Antimicrobials

Antimicrob Agents Chemother, 1995 Dec, 39(12), 2827 - 8
Clarithromycin is inactive against Mycobacterium tuberculosis; Truffot-Pernot C et al.; When 10% oleic acid-albumin-dextrose-catalase-enriched Mueller-Hinton agar medium was employed, the MICs of clarithromycin (CLARI) at which 50 and 90% of 12 strains of Mycobacterium tuberculosis were inhibited were 64 and > 128 micrograms/ml, respectively, which are significantly greater than the achievable peak CLARI concentrations in serum and in lung tissue in humans . In two different mouse experiments, 4 to 6 weeks of treatment with CLARI at 200 mg/kg of body weight six times weekly produced neither bactericidal nor bacteriostatic effects against M . tuberculosis . Therefore, we conclude that CLARI as a single drug is inactive against M . tuberculosis.

Mikrobiol Z, 1995 Nov-Dec, 57(6), 63 - 78
{Cytokines and nonviral infections}; Grabchenko NI et al.; Cytokines (interferons, tumour necrosis factor and interleukin-1) with marked polyfunctional properties are described . They are synthesized by different cells of both immune and non-immune systems of organism and are able to stimulate, induce or inhibit various immunological and biological reactions and processes . The effect exerted by these cytokines on the course of bacterial infections is analyzed . The cytokines possess protective properties which are demonstrated in activation of neutrophils, intensification of bactericidal and phagocytic activity of macrophages and natural cells-killers.

Int Immunol, 1995 Nov, 7(11), 1753 - 61
Human glycoprotein HGP92 induces cytokine synthesis in mouse mononuclear phagocytes; Briend E et al.; HGP92 has been shown to enhance in vitro and in vivo the bactericidal and tumoricidal activity of mouse macrophages . In this study we investigated the effect of HGP92 on the accumulation of cytokine mRNA in mouse inflammatory, peritoneal macrophages and the monocytic cell line J774 . HGP92 significantly enhanced the level of cytokine mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha and GM-CSF during the first 24 h of the incubation . This effect triggered by HGP92 was comparable to that obtained with lipopolysaccharide (LPS), which is a strong cytokine inducer . This accumulation of cytokine mRNA in macrophages was correlated with secretion of IL-6 and TNF-alpha in cell supernatant . The release of IL-6 was HGP92 concentration dependent over a range of 0.3-10 micrograms/ml with a maximum production obtained after a 24 h incubation of inflammatory macrophages with HGP92 . This effect was shown not to be due to contamination of HGP92 by LPS since inflammatory macrophages from C57BL/6 mice were responsive to HGP92 pretreated with polymyxin B sulfate and unresponsive to heated HGP92 . Stimulating activity of HGP92 was confirmed using macrophages from C3H/HeJ mice . These results suggest that HGP92 might modulate the immune responses by increasing cytokine production by macrophages.

Hepatology, 1995 Nov, 22(5), 1499 - 506
Endotoxin and interleukin-1 related hepatic inflammatory response promotes liver failure after partial hepatectomy; Boermeester MA et al.; Impairment of various functions of the liver and concomitantly increased levels of parameters of liver damage, a clinical entity termed liver failure, is commonly seen after partial hepatectomy . We investigated in a rat model whether damage of the remnant liver was due to local inflammatory responses, and related to endotoxin or interleukin-1 (IL-1) . To address this question, the effects of partial hepatectomy on infiltration of immunocompetent cells and expression of major histocompatibility complex (MHC) class II antigen of macrophages in the remnant liver was studied using immunohistochemical techniques . Specific intervention with recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23) to neutralize endotoxin and with IL-1 receptor antagonist (IL-1ra) to block IL-1 activity was used to examine the respective roles of endotoxin and IL-1 . After partial hepatectomy, we found an influx of neutrophils, an increased expression of MHC class II antigens, and morphologic changes of Kupffer cells consistent with activation . These inflammatory events coincided with increased serum levels of markers of liver damage (aspartate aminotransferase, alanine aminotransferase, ammonia) . Both neutralization of endotoxin and blocking of IL-1 activity reduced hepatic inflammation and reduced serum levels of aminotransferases and ammonia . In addition, liver cell proliferation as assessed by staining for proliferating cell nuclear antigen (PCNA) expression was significantly enhanced when either endotoxin or IL-1 effects were blocked . Thus, our results suggest that local hepatic inflammatory responses inhibit liver cell proliferation and promote liver failure, presumably by affecting the functional capacity of the remnant liver.

Am J Pathol, 1995 Nov, 147(5), 1428 - 40
Liver failure induces a systemic inflammatory response . Prevention by recombinant N-terminal bactericidal/permeability-increasing protein; Boermeester MA et al.; The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation . However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking . Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations . In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs . Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response . Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions . Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23 . Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23.

FEMS Microbiol Lett, 1995 Oct 15, 132(3), 189 - 94
Invasion of HeLa cells by Mycoplasma penetrans and the induction of tyrosine phosphorylation of a 145-kDa host cell protein; Andreev J et al.; The ability of Mycoplasma penetrans to invade eukaryotic cells was studied using a HeLa cell line . The bactericidal antibiotic, gentamicin, in combination with low concentrations of Triton X-100, was utilized to kill mycoplasmas that had not entered the cells, allowing the quantitation of internalized organisms . The intracellular location of the mycoplasma was also documented by transmission electron microscopy . The actin polymerization inhibitor cytochalasin-D markedly inhibited the internalization process, whereas the tyrosine phosphorylation inhibitors, staurosporin and genistein had only a slight effect . As against the invasion of enteropathogenic Escherichia coli which depends on tyrosine phosphorylation of a 90-kDa (Hp90) HeLa cell protein, internalization of M . penetrans by HeLa cells was independent of the phosphorylation of Hp90 . Nonetheless, tyrosine phosphorylation of a 145-kDa HeLa cell protein was found to be associated with the interaction of M . penetrans with HeLa cells.

Indian J Lepr, 1995 Oct-Dec, 67(4), 375 - 82
In vivo activities of novel benzoxazinorifamycins against Mycobacterium leprae; Dhople AM et al.; Among the four newly synthesized benzoxazinorifamycin derivatives, KRM-1648 and KRM-2312 completely inhibited the multiplication of rifampicin-sensitive as well as rifampicin-resistant strains of M . leprae in the foot-pads of mice . Both were found to be more potent than rifampicin and were bactericidal . In combination with ofloxacin, another potent bactericidal drug against M . leprae, both KRM-1648 and KRM-2312 exhibited synergism . Thus, combination of one of these benzoxazinorifamycin derivatives and ofloxacin in multidrug regimens is worth evaluating in clinical trials.

Diabet Med, 1995 Oct, 12(10), 916 - 20
Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control; Gallacher SJ et al.; Neutrophil bactericidal activity was assessed in patients with type 1 (n = 45) and Type 2 diabetes mellitus (n = 68) and non-diabetic control subjects (n = 40) by measurement of whole blood chemiluminescence . Though chemiluminescence values tended to be highest in the non-diabetic subjects these differences were not statistically significant (mean +/- SD) (2.73 +/- 1.65 mV (controls), 2.33 +/- 1.41 mV (Type 1 diabetes) and 2.38 +/- 1.12 mv (Type 2 diabetes), F = 1.12, p = 0.33) . Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (rs = -0.35, p = 0.005 (Type 1), rs = -0.45, p = 0.002 (Type 2), fructosamine (rs = -0.36, p = 0.003 (Type 1), r = -0.42, p = 0.004 (Type 2)), and random blood glucose (rs 0 -0.25, p = 0.04 (Type 1), rs = -0.48, p = 0.001 (Type 2)) . Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days . Serum fructosamine concentrations fell significantly over this time (524 +/- 58 mumol l-1 to 405 +/- 47 mumol l-1, p < 0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 +/- 0.38 mV to 1.60 +/- 0.91 mV, S = 4.24, df = 5, p = 0.52) . These results suggested that impaired neutrophil bactericidal function is associated with poor blood glucose control . While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.

Shock, 1995 Oct, 4(4), 298 - 306
The recombinant 23-kDa N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) decreases Escherichia coli-induced mortality and organ injury during immunosuppression-related neutropenia; Lechner AJ et al.; Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ injury in conscious rats during Escherichia coli (EC) bacteremia despite antibiotics and fluid administration . We hypothesized that such shock and inflammatory organ injury would be mitigated by rBPI23's microbicidal activity and/or binding of EC endotoxins . Four days after 100 mg cyclophosphamide/kg, catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the irrelevant 22 kDa protein thaumatin {3.3-6.6 mg/kg, i.v . in 0.9% NaCl (NS)} 5 min before graded i.v . infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype 055:B5 ending at t = 0 . Posttreatment with each protein continued (3.3-6.6 mg/kg in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t = 1.5 and 8 h . Arterial samples were obtained before pretreatment and at t = 1.5, 4.5, 8, and 24 h when animals were necropsied . One of eight thaumatin + 5 x 10(9) EC rats and none of six thaumatin + 10(10) EC rats survived 24 h . In contrast, rBPI23 significantly reduced mortality after either inoculum, improved bacterial clearance, and led to renormalization of early EC-induced hypotension, hypothermia, tachypnea, hyperoxemia, and hypocarbia . Compared with thaumatin, however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic tumor necrosis factor-alpha . Sepsis-induced severe neutropenia (< 50 PMNs/microL) evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5 h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Clin Pharmacol, 1995 Oct, 40(4), 347 - 60
The pharmacokinetics of 8-methoxypsoralen following i.v . administration in humans; Billard V et al.; 1 . 8-methoxypsoralen (8-MOP) is a naturally occurring photoreactive substance which, in the presence of u.v . light, forms covalent adducts with pyrimidine bases in nucleic acids . For many years, 8-MOP has been used in PUVA therapy for treatment of psoriasis . Recently, the drug has been found to inactivate effectively bacteria spiked into platelet concentrates . The purpose of this study was to determine the pharmacokinetics and safety of 8-MOP administered intravenously in the bactericidal dosage range . 2 . Eighteen volunteers were divided into three treatment groups to receive, respectively, 5, 10, and 15 mg 8-MOP infused over 60 min . Frequent arterial samples were gathered, and the blood and plasma were assayed for 8-MOP concentration . The pharmacokinetic parameters were determined by moment and compartmental population analysis, the latter performed with the program NONMEM . Haemodynamics, ventilatory pattern, and subjective effects were recorded throughout the study . 3 . The intravenously administered 8-MOP was well tolerated in all individuals, and no acute toxicity was observed . 4 . The pharmacokinetics of 8-MOP were best described by a three-compartment mammillary model in which the volumes and clearances were proportional to weight . The mean pharmacokinetic parameters for the plasma concentrations were: V1 = 0.045 1 kg-1, V2 = 0.57 1 kg-1, V3 = 0.15 1 kg-1, CL1 (systemic) = 0.010 1 kg-1 min-1, CL2 = 0.0067 1 kg-1 min-1, CL3 = 0.012 1 kg-1 min-1 . The mean pharmacokinetic parameters for the blood concentrations were: V1 = 0.061 1 kg-1, V2 = 1.15 1 kg-1, V3 = 0.21 1 kg-1, CL1 (systemic) = 0.015 1 kg-1 min-1, CL2 = 0.011 1 kg-1 min-1 and CL3 = 0.015 1 kg-1 min-1 . 5 . The plasma pharmacokinetic model described the observations with a median absolute error of 17%, and the blood pharmacokinetic model described the observations with a median absolute error of 18% . Analysis of the relative concentration of 8-MOP between plasma and red blood cells suggested concentration-dependent partitioning . 6 . The addition of 7.5 mg 8-MOP to 300 ml platelet concentrate would produce bactericidal concentrations of 25 micrograms ml-1 . Simulations based upon our data show that intravenous administration of 7.5 mg over 60 min would result in systemic concentrations of 8-MOP similar to those observed with conventional PUVA therapy . We conclude that the extensive safety history established in PUVA therapy will be applicable to this new application of 8-MOP.

J Pept Sci, 1995 Sep-Oct, 1(5), 295 - 302
The immunosuppressive mini-domain of human lactoferrin; Siemion IZ et al.; It has been found that the disulphide-bridged 231-245 pentadecapeptide loop of the lactoferrin (LF) N-lobe contains a region of immunosuppressive activity . The activity resides within a thymopentin-like sequence (Arg-Lys-Pro-Val-Asp) of the loop . Peptides related to the 575-589 loop of the LF C-lobe differ in their immunomodulatory activity from those related to the 231-245 loop . We ascribe this difference to the replacement of the Asp residue in the 231-245 loop by Thr in the 575-589 loop . Two other fragments of LF which were studied, 27-34 and 309-315, do not manifest any activity in the DTH test (cellular immune response), but, on testing in vivo, stimulate the humoral immune response . The 27-34 fragment is related to the bactericidal and immunostimulative region of LF identified by Bellamy et al . {1} . Our results show that the LF molecule contains, not only the known immunostimulating mini-domain, but also a region endowed with immunosuppressive activity.

Riv Eur Sci Med Farmacol, 1995 Sep-Oct, 17(5), 197 - 202
{The treatment of decubitus lesions}; Fugazza G et al.; The authors present a plan for pharmacological treatment of pressure sores in patients affected by neurological pathologies: cerebrovascular accidents, head injuries, spinal cord injuries . This plan is easily applicable to all pressure sores included between first and third degree of the Reuler and Cooney classification . Authors identified some drugs specifically usefull in different cutaneous lesion degrees . Skin lesions and employed medicines are described as follows: Erythema: semi occlusive bandage with porous adsorbing membrane . This dressing must be left in for five days at least . Excoriation: bactericidal or bacteriostatic medicines if it's situated in a non pressed area while the same dressing utilized for erythema if it's localized in a pressed area . Pressure sores: if there is local infection cleanse the wound from bacterial defilement using topic antibiotics apply compresses with vitamin C if the cutaneous lesion is larger than deeper, Cadexomero lodico if it's deeper than larger . Fistulas: wadding with tablets of collagen . Necrobiosis: complete or partial surgical removal of eschar preceded by the use of enzymatic drugs when eschar is firmly adherent to subcutaneous tissues . The first group collects 9 patients with stroke and head injury: 8 with sacral and 1 with heel pressure sores . First degree pressure sores heal within 45 days and third degree lesions within 160 days . The second group collects 10 spinal cord injury patients mostly with complete lesion among which: 7 sacral, 1 heel, 1 ischiatic and 1 malleolar lesions . First degree pressure sores heal within 30 days, third degree pressure sores heal within 200 days . Healing time are considered acceptable . Pressure sores recovery swiftness can be related to different factors such as pressure sores sterness, neurological pathology and arising of clinical complication (hyperthermia, infections, low serum albumin values, etc).

Zentralbl Veterinarmed A, 1995 Sep, 42(7), 461 - 6
Evaluation of the effect of experimental cow endometritis on bactericidal capability of phagocytizing cells isolated from the blood and uterine lumen; Klucinski W et al.; Studies were undertaken to assess the bactericidal activity of phagocytes isolated from blood and the uterine lumen of clinically healthy cows after ovulation, and from cows in which endometritis was induced experimentally . Experiments were carried out on 28 clinically healthy cows of the black and white lowland breed . Animals were aged 5 years and were used between the 2nd and 8th day after spontaneous ovulation . Cows were divided into four groups . Group I comprised animals in which cell-mediated type immune reaction was induced in the left uterine horn by intrauterine challenge with tuberculin . Cows in this group were initially vaccinated with M . bovis via the intrauterine route . In group II, Arthus type immune reaction was induced by challenging immunized animals with C . fetus ssp . veneralis through intrauterine instillation . The non-specific inflammatory process was initiated in the uterus of animals in group III by one instillation of lipopolysaccharide from S . abortus equi . Animals in group IV were set as control and received a phosphate buffered saline instillation into the uterine lumen . The cells from the left uterine horn were washed out 6 h after induction . Neutrophils were isolated from blood samples collected from all animals within the same time . The bacterial activity of cells from the uterine lumen and blood was assessed with the nitro-blue tetrazolium reduction test . Results are presented as increase in optical density resulting from a constant number of phagocytizing cells (delta OD/10(6) cells) . Induction of cell-mediated immune reaction or Arthus type immune reaction in the uterus significantly boosts the intracellular capability of uterine cells to kill bacteria through the oxidation system . Experimentally induced non-specific endometritis weakens the bactericidal activity of uterine phagocytes, while peripheral blood phagocytes efficiently kill the engulfed bacteria.

Am Fam Physician, 1995 Sep 1, 52(3), 919 - 24
Acute focal bacterial pyelonephritis; Boam WD et al.; Acute focal bacterial pyelonephritis is a renal inflammatory disease that has similarities to both pyelonephritis and renal abscess . The diagnosis is based on clinical symptoms of pyelonephritis and renal abnormalities detected on radiologic imaging studies (ultrasonography and computed tomographic scanning) . Ultrasonographic examination demonstrates mass lesions in the renal cortex that resolve after appropriate antibiotic therapy . Computed tomographic studies reveal localized, wedge-shaped or circular, poorly enhancing, hypodense areas and/or swelling of the superior pole of the kidney . A voiding cystourethrogram should be done to rule out reflux as an underlying cause . Magnetic resonance imaging is not required for diagnosis or follow-up evaluation . Escherichia coli is the most common etiologic agent . All reported cases have responded to conservative therapy with extended courses of oral bactericidal antibiotics . Resolution is typically complete in one to three months . A follow-up evaluation with ultrasonography is required to document resolution.

Gut, 1995 Sep, 37(3), 367 - 73
Respiratory burst of intestinal macrophages in inflammatory bowel disease is mainly caused by CD14+L1+ monocyte derived cells; Rugtveit J et al.; Macrophages play a crucial role in intestinal mucosal defence, forming dense subepithelial aggregates, particularly in the colon . One of their important bactericidal mechanisms is production of oxygen radicals but this may damage the intestinal epithelium, perhaps as an early step in inflammatory bowel disease (IBD) . The potential for release of oxygen radicals from mucosal macrophages in IBD was measured and whether a difference exists between newly arrived (CD14+L1+) monocyte-like cells and resident macrophages (CD14(-)L1-), without or with additional priming in vitro, was investigated . Lamina propria mononuclear cells from six patients with IBD and five with a normal intestine were isolated with an ethylenediaminetetra acetic acid/collagenase/dispase technique and cultured for three days . The cells were tested with or without interferon gamma (200 U/ml) priming in the presence or absence of lipopolysaccharide (1 microgram/ml) for the last 48 hours in cultures . Samples from inflamed IBD mucosa depleted of CD14+ cells by immunomagnetic beads were compared with their undepleted counterparts and with samples from virtually normal mucosa from the same patients . The production of oxygen radicals was measured as the amount of reduced cytochrome C 2.5 hours after triggering with phorbol 12-myristate 13-acetate . The oxygen radical production in macrophages from moderately or severely inflamed mucosa was reduced by median 69% (range 22%-79%, p < 0.027) after depletion of CD14+ cells, reaching a level similar to that found for virtually normal samples from the same IBD patients . Furthermore, this production did not increase significantly in mucosal macrophages from normal reference mucosa and from virtually normal or inflamed IBD mucosa after priming with interferon gamma with or without addition of lipopolysaccharide . Upregulation of a respiratory burst in subepithelial resident macrophages os not a likely pathogenetic step in IBD . The increased oxygen radical production shown by macrophages from IBD lesions can, however, be ascribed to recently extravasated CD14+L1+ monocyte-like cells . Inhibition of extravasation of these reactive cells may form part of a therapeutic approach in the future.

Boll Chim Farm, 1995 Sep, 134(8), 413 - 33
{Gas sterilization with gas hydrogen peroxide: a new technology in the pharmaceutical industry}; Manzati C; This article shows the bactericidal capacity of hydrogen peroxide vapor, particularly if used through VHP vaporizer (Vaporizer Hydrogen Peroxide) which was recently developed and used in the pharmaceutical sector . After a short description technologies and of the characteristics of the chemical agents used in these technics, will illustrate the machine (VHP), its functioning and its possible application fields . The review ends with the illustration of a number of experiments, tests and validation trials which stand out from technical point of view.

J Med Entomol, 1995 Sep, 32(5), 646 - 9
Effects of seven antibiotics on the growth and development of Phaenicia sericata (Diptera: Calliphoridae) larvae; Sherman RA et al.; Maggot therapy is used for patients with severe tissue destruction, who often receive antibiotics concurrently . Therefore, we studied the effects on maggots of ampicillin, cefazolin, ceftizoxime, clindamycin, gentamicin, mezlocillin, and vancomycin in concentrations of 1, 10, 100, and 1,000 times the average minimum bactericidal or bacteriostatic concentration against highly susceptible organisms . There was a reduction in larval survival in media with gentamicin at concentrations of 1,000 times the average pharmacologic level, or 4,000 micrograms/ml (2.7% survival), versus lower concentrations (80-88% survival) . Maturation of the surviving pupae to adults also was decreased at this concentration . Media with cefazolin concentrations of 100 times the average bacteristatic level, or 800 micrograms/ml, also led to a significant decrease in larval survival (70% versus 80-88%) . There were no differences in larval survival, rate of maturation, or pupal weights for organisms reared on media containing ampicillin, ceftizoxime, clindamycin, mezlocillin, or vancomycin . P . sericata matured normally--and thus can be used therapeutically--when exposed to standard pharmacologic levels of the 7 antibiotics tested . Furthermore, the methods employed herein may be helpful to forensic entomologists attempting to develop models for drug ingestion by maggots.

Diabetes Res Clin Pract, 1995 Aug, 29(2), 121 - 7
Respiratory burst activity of monocytes from patients with non-insulin-dependent diabetes mellitus; Chang FY et al.; Monocytes from patients with poorly controlled non-insulin-dependent diabetes mellitus (NIDDM) show a decrease in intracellular bactericidal function . To determine whether this reduced bactericidal function is mediated by an impaired oxygen-dependent mechanism, we assayed the production of superoxide (O2-) and hydrogen peroxide (H2O2) by monocytes from poorly controlled NIDDM patients (n = 12), well controlled NIDDM patients (n = 12) and healthy subjects (n = 16) . Using phorbol myristate acetate (PMA) as stimulant, the production of O2- by fresh monocytes was significantly decreased in poorly controlled NIDDM patients (231 +/- 30 nmol/mg protein/2-h) as compared with that of well controlled NIDDM patients (430 +/- 81 nmol/mg protein/2-h) and that of healthy subjects (399 +/- 61 nmol/mg protein/2-h), respectively (P < 0.05) . Using opsonized zymosan (OZ) as stimulant, the production of O2- by fresh monocytes was also notably decreased in patients with poorly controlled NIDDM (312 +/- 42 nmol/mg protein/2-h) as compared with that of patients with well controlled NIDDM (688 +/- 92 nmol/mg protein/2-h) and that of healthy subjects (539 +/- 96 nmol/mg protein/2-h), respectively (P < 0.05) . Poorly controlled NIDDM patients had a significant decrease in the production of H2O2 by monocytes, either stimulated by PMA or OZ, as compared with that of well controlled NIDDM patients and that of healthy subjects, respectively (P < 0.05) . Enhancement of the production of O2- and H2O2 occurred in healthy subjects (150% increase) as well as NIDDM patients (170% increase) after a preincubation of monocytes with interferon-gamma (IFN-gamma 100 U/ml) for 48 h . The respiratory burst activity of both fresh and cultured monocytes from well controlled NIDDM patients was not significantly different from that of healthy subjects . This study suggests that both, strict metabolic control and in vitro culture with IFN-gamma may improve the monocyte oxygen-dependent bactericidal mechanism in NIDDM patients.

Arch Biochem Biophys, 1995 Aug 1, 321(1), 153 - 9
Fumarate reductase: a target for therapeutic intervention against Helicobacter pylori; Mendz GL et al.; The potential of fumarate reductase as a therapeutic target against the human pathogen Helicobacter pylori was investigated by studying the cytotoxicity of morantel, oxantel, and thiabendazole, known to inhibit the enzyme in parasitic worms . Nuclear magnetic resonance spectroscopy was employed to investigate the effects of the inhibitors on the fumarate reductase activity of laboratory-adapted and wild-type bacterial strains . Production of succinate from fumarate in H . pylori cells was inhibited by morantel, oxantel, and thiabendazole . Cell growth and viability techniques were used to examine the bacteriostatic and bactericidal effects of the three anthelmintics . Each of the antiparasites arrested growth and produced cell death in liquid cultures, although the minimal inhibitory and bactericidal concentrations of these compounds are such that they would not be of therapeutic use . The strength of the effects as measured by minimal inhibitory and bactericidal concentrations was oxantel > thiabendazole > morantel . The findings suggested that fumarate reductase is an essential component of the metabolism of H . pylori and as such constitutes a possible target for therapeutic intervention in the treatment of the bacterium.

Nippon Sanka Fujinka Gakkai Zasshi, 1995 Aug, 47(8), 713 - 23
{The viewpoints of viral vertical transmission from fetal neonatal immunologic aspects}; Ichijo M; A . The development of fetal Immune system 1 . Complement: Alternative pathway is dominant in the development of fetal complement . 2 . Neutrophil function: Phagocytosis in full term infants was increased to be adult-level, but bactericidal function was decreased . 3 . NK activity: NK activity in full-term infants was significantly lower than in adults, however, IL-2-augmented NK activity did not indicate any significant difference with levels in adults . In pre-32 week infants both NK and IL-2-augmented NK activity were further decreased as opposed to in full-term infants . 4 . LAK activity: LAK activity was fully developed already in 19 week infants, indicating that auto-monitoring of mutant cells is already under control from the early stages of fetal development . 5 . Antibody production: Antibody production in infants was significantly decreased in comparison to adults . Reduced cytokine (IL-1, BCDF) production were considered to be the causal factors . 6 . IL-2, IL-2R: In IL-2 production, no difference was recognized between normal neonates and adult subjects . In contrast, a significantly higher value of IL-2 production was observed for premature neonates born between 16 and 36 GW, compared with adults . IL-2 production and IL-2R system is fully developed at 22 weeks . 7 . BCDF gamma, BCDF mu: Reduced compared to that of adults . 8 . IL-6, IL-8, G-CSF: Much higher levels were found in cases of intrauterine infection, particularly in cases of premature delivery . The cytokine levels were 20-to-30-fold higher in chorioamnitis-positive premature delivery group . 9 . M-CSF: M-CSF is increased, M-CSF may play a role in decidual function and placental function by the autocrine and paracrine system . 10 . IL-1 alpha, IL-1 beta, IL-6: These production by macrophages was diminished in aborted fetuses, premature infants and IUGR infants . However, in the infants of mother with intrauterine infection, cytokine production was elevated to the level in full term infants and adults . 11 . IFN gamma: Production of IFN gamma by memory T cells was diminished in premature infants . B . The vertical transmission of HTLV-I . The routes of vertical transmission of HTLV-I are intrauterine, intra-birth canal and via breast milk . Bottle-feeding is an effective way of avoiding mother-to-child infection . However breast milk is necessary for optimal infant nourishment, so we use -20 degrees C for 12 hours freeze-thawing of breast milk.(ABSTRACT TRUNCATED AT 400 WORDS)

FEBS Lett, 1995 Jul 10, 368(1), 173 - 6
hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules; Cowland JB et al.; A 19 kDa protein was identified in specific granules of human neutrophils . A full-length cDNA clone was isolated from a human CML cDNA library, based on amino-acid sequences of isolated tryptic fragments . This clone includes the recently identified cDNA for FALL-39/CAP-18 . Aminoacid sequences of proteolytic fragments derived both from the conserved N-terminal cathelin-like region and the highly variable C-terminal region characteristic of this family of bactericidal, LPS binding proteins, were in complete agreement with the sequence deduced from the cDNA . Thus, the 19 kDa protein is hCAP-18, stored as a 'pro-peptide' in specific granules.

Proc Natl Acad Sci U S A, 1995 Jul 3, 92(14), 6419 - 23
Liquid-phase combinatorial synthesis; Han H et al.; A concept termed liquid-phase combinatorial synthesis (LPCS) is described . The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer . To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin . The peptide-based library was synthesized by a recursive deconvolution strategy {Erb, E., Janda, K . D . & Brenner, S . (1994) Proc . Natl . Acad . Sci . USA 91, 11422-11426} and several ligands were found within this library to bind a monoclonal antibody elicited against beta-endorphin . The non-peptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy . The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.

J Antimicrob Chemother, 1995 Jul, 36(1), 101 - 8
Lack of bactericidal effect of antibiotics except aminoglycosides on Bartonella (Rochalimaea) henselae; Musso D et al.; Bartonella (Rochalimaea) henselae is a cause of peliosis hepatis and bacillary angiomatosis, and one of the putative agents of cat scratch disease . Specific therapy for B . henselae infections is not available . Treatment failures and relapses are frequent, especially following brief antibiotic courses, and this contrasts with the in-vitro susceptibility of B . henselae to most antibiotics . We decided to test the antibiotic susceptibility of B . henselae associated with murine macrophage-like cells (P388 D1) and a human endothelial cell line . We carried out a bactericidal assay in this model and in axenic broth . In both models, only aminoglycosides were bactericidal . These results suggest that aminoglycosides may be effective in the treatment of B . henselae infections.

J Infect Dis, 1995 Jul, 172(1), 144 - 51
Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein; von der Mohlen MA et al.; To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature . The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23 . The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

J Periodontal Res, 1995 Jul, 30(4), 290 - 3
In vitro activity of tetracyclines, macrolides, quinolones, clindamycin and metronidazole against periodontopathic bacteria; Miyake Y et al.; We re-evaluated several antibiotics including newer ones, for their in vitro killing activity, as well as their inhibitory activity, against clinical isolates of periodontopathic bacteria . Tetracyclines were active against Porphyromonas gingivalis, and were highly active against Prevotella intermedia, but demonstrated only a low killing activity against Actinobacillus actinomycetemcomitans . Rokitamycin, a new macrolide, and clindamycin were highly active against P . gingivalis and P . intermedia, but showed very weak killing activity against A . actinomycetemcomitans . Quinolones demonstrated excellent bactericidal activity against A . actinomycetemcomitans, and good inhibitory and bactericidal activity against P . gingivalis and P . intermedia . Metronidazole had an activity almost equivalent to quinolones against P . gingivalis and P . intermedia; but it was the least active against A . actinomycetemcomitans.

Shock, 1995 Jul, 4(1), 74 - 8
rBPI23 attenuates endotoxin-induced cardiovascular depression in awake rabbits; Koyama S et al.; We determined the effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) on hemodynamic and renal sympathetic responses to lethal endotoxemia in unanesthetized rabbits . Endotoxin was continuously infused intravenously (200 micrograms/kg/h) over 120 min with simultaneous infusion of either rBPI23 (3 mg/kg bolus followed by 6 mg/kg/h over 120 min; n = 6) or thaumatin (the same dose as rBPI23), a control cationic protein with a molecular weight and isoelectric point similar to that of rBPI23 (n = 9) . Tissue blood flow was also determined using colored microspheres to the left ventricle, renal cortex, liver, and skeletal muscle . Seven of nine animals treated with endotoxin and thaumatin died between 45 and 120 min after start of the infusion, whereas all animals with rBPI23 treatment were alive throughout the entire 2 h experimental period . A transient increase in renal sympathetic nerve activity was observed in the thaumatin-treated animals followed by sympathoinhibition with concomitant decreases in heart rate, blood pressure, and cardiac output . Tissue blood flow to all measured organs gradually decreased in animals receiving endotoxin and thaumatin . However, rBPI23 abolished all these deleterious responses to endotoxin . In conclusion, rBPI23 attenuates the acute lethal sympathoinhibitory and hemodynamic effects of endotoxemia in awake rabbits.

Antimicrob Agents Chemother, 1995 Jul, 39(7), 1574 - 9
Influence of pentoxifylline and its derivatives on antibiotic uptake and superoxide generation by human phagocytic cells; Hand WL et al.; Pentoxifylline modulates multiple activities of stimulated polymorphonuclear neutrophils (PMNs), including the respiratory burst response and membrane transport of certain substances (e.g., nucleosides) . We found that several weakly basic antibiotics are highly concentrated by human PMNs and that these drugs also inhibit the respiratory burst response (by a mechanism different from that of pentoxifylline) . Since both pentoxifylline and antibiotics will be administered to some patients with serious infections, we have evaluated several types of interactions between these drugs and human PMNs and have attempted to identify the mechanisms that produce alterations in cellular function . Roxithromycin, dirithromycin, and clindamycin were avidly concentrated by PMNs . Pentoxifylline and two derivatives (HWA-448 {torbafylline} and HWA-138 {albifylline}) increased the uptake of these antibiotics by PMNs, both in the resting state and during phagocytosis . Pentoxifylline, HWA-448, HWA-138, and the highly concentrated antibiotics each exerted an inhibitory effect on the stimulated respiratory burst response in PMNs . The combination of both pentoxifylline and a modulatory antibiotic (roxithromycin or clindamycin) inhibited superoxide production to a greater extent than either agent alone . This additive effect might be expected, since pentoxifylline and the modulatory antibiotics influence the respiratory burst activation pathway at different sites . The ability of pentoxifylline to augment the entry of antibiotics into neutrophils has important therapeutic implications . The consequences of this phenomenon might include improved intracellular bactericidal activity as well as efficient antibiotic delivery and release at sites of infection.

Antimicrob Agents Chemother, 1995 Jul, 39(7), 1499 - 504
Activities of oral and parenteral agents against penicillin-susceptible and -resistant pneumococci; Pankuch GA et al.; This study examined bacteriostatic and bactericidal activities of oral and parenteral antibiotics for penicillin-susceptible and intermediately and fully penicillin-resistant pneumococci . beta-Lactamase inhibitors did not affect beta-lactam results . The activities of ampicillin, amoxicillin +/- clavulanate, WY-49605, cefuroxime, cefpodoxime, cefdinir, cefixime, and cefaclor against two penicillin-susceptible, two intermediately penicillin-resistant, and two fully penicillin-resistant pneumococcal strains were tested . For all three groups, bacteriostatic values of amoxicillin and WY-49605 were lower than were those of other beta-lactams tested . Of the cephalosporins, cefdinir, cefuroxime, and cefpodoxime yielded the lowest bacteriostatic values . All beta-lactams were bactericidal (reduced original counts by > or = 3 log10 CFU/ml) at 1 dilution above bacteriostatic values, except for cefpodoxime (bactericidal at 2 dilutions above bacteriostatic values for one susceptible strain and one intermediately resistant strain), cefuroxime (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain), and ampicillin (bactericidal at 2 dilutions above bacteriostatic values for one intermediately resistant strain) . The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftriaxone, ceftazidime, and ciprofloxacin against four penicillin-susceptible, two intermediately penicillin-resistant, and four fully penicillin-resistant pneumococcal strains were evaluated . Bacteriostatic values of piperacillin, ampicillin, and ceftriaxone for all groups were lower than were those of ticarcillin and ceftazidime . Bacteriostatic values of ciprofloxacin were unaffected by penicillin susceptibility . All beta-lactams were bactericidal at 1 dilution above the bacteriostatic value, except for piperacillin (bactericidal at 2 dilutions above the bacteriostatic value for one intermediately resistant strain), ticarcillin (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain and one resistant strain), ampicillin (bactericidal at 2 dilutions above the bacteriostatic value for two resistant strains), ceftriaxone (bactericidal at 2 dilutions above the bacteriostatic value for one resistant strain), and ceftazidime (bactericidal at 2 dilutions above the bacteriostatic value for one susceptible strain).

Cas Lek Cesk, 1995 Jun 28, 134(13), 399 - 403
{Hyperbaric oxygen therapy}; Dolezal V; Oxygen inhalation in a chamber at the pressure exceeded 0.2 MPa produces some positive effects, that are explored for therapeutic purposes at about 30 years . Oxygen increases bactericidal capacity of leukocytes, reduces tissue edema, protects intracellular ATP, maintain tissue oxygenation even in the absence of hemoglobin . Stimulates fibroblast replication, increases collagen production, stimulates arborisation of capillaries into ischemic tissue, protects from lipid peroxidation . These properties of oxygen are exploit in acute, life threatened conditions and in various chronic ischemias . Hyperbaric oxygen therapy as an adjuvant together with conservative and invasive therapy methods helps to decrease morbidity, work incapability, invalidisation and mortality in oclusive and inflammatory arteriities, diabetic gangrene and other forms of clinical leg ischemia . The use of hyperbaric oxygenation will become increasingly common as more hyperbaric facilities are established.

Mol Microbiol, 1995 Jun, 16(6), 1059 - 66
Colicin import and pore formation: a system for studying protein transport across membranes?
Lazdunski CJ.
Pore-forming colicins are a family of protein toxins (M(r) 40-70 kDa) produced by Escherichia coli and related bacteria . They are bactericidal by virtue of their ability to form ion channels in the inner membrane of target cells . They provide a useful means of studying questions such as toxin action, polypeptide translocation across and into membranes, voltage-gated channels and receptor function . These colicins bind to a receptor in the outer membrane before being translocated across the cell envelope with the aid of helper proteins that belong to nutrient-uptake systems and the so-called 'Tol' proteins, the function of which has not yet been properly defined . A distinct domain appears to be associated with each of three steps (receptor binding, translocation and formation of voltage-gated channels) . The Tol-dependent uptake pathway is described here . The structures and interactions of TolA, B, Q and R have by now been quite clearly defined . Transmembrane alpha-helix interactions are required for the functional assembly of the E . coli Tol complex, which is preferentially located at contact sites between the inner and outer membranes . The number of colicin translocation sites is about 1000 per cell . The role and the involvement of the OmpF porin (with colicins A and N) have been described in a recent study on the structural and functional interactions of a colicin-resistant mutant of OmpF . The X-ray crystal structure of the channel-forming fragment of colicin A and that of the entire colicin la have provided the basis for biophysical and site-directed mutagenesis studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Lab Invest, 1995 Jun, 72(6), 696 - 706
The role of macrophage colony-stimulating factor in the differentiation and proliferation of Kupffer cells in the liver of protein-deprived mice; Honda Y et al.; BACKGROUND: Protein calorie malnutrition is known to induce various macrophage dysfunctions, such as the impairment of their phagocytic function, proliferative capacity, and bactericidal activity . However, little is known about the behavior of Kupffer cells under protein calorie malnutrition in vivo . EXPERIMENTAL DESIGN: To investigate the behavior of Kupffer cells under protein calorie malnutrition, we fed mice on a low protein (protein-derived) diet for 4 weeks and examined the number, cytologic changes, and proliferative capacity of their Kupffer cells . To detect macrophage precursor cells, colony-forming assays were performed in the bone marrow, spleen, and liver of the mice . To investigate the relationship of Kupffer cells to CSF, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor were measured by ELISA, and the expression of macrophage colony-stimulating factor (M-CSF) mRNA in the liver was determined by Northern blot analysis . The recovery processes of Kupffer cells in the protein-deprived mice after normal protein feeding or daily recombinant human macrophage colony-stimulating factor administration were also investigated . RESULTS: In the protein-deprived mice, Kupffer cells decreased in number to two-thirds that of the normally fed (nondeprived) mice, showed the cytologic and ultrastructural features of maturation failure, and had reduced proliferative capacity . After normal protein feeding or recombinant human macrophage colony-stimulating factor administration, the number, morphology, and proliferative capacity of the Kupffer cells in the liver returned to normal, and they matured as in the nondeprived mice . In the protein-deprived mice, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor increased, and the expression of M-CSF mRNA in the liver was reduced . In the bone marrow, the granulocyte-macrophage colony-forming cells and macrophage colony-forming cells were increased, and the influx of monocytes into the liver was temporarily enhanced; however, the number of monocytes in the peripheral blood was decreased . CONCLUSIONS: These results suggest that the reduced production of M-CSF in the liver of protein-deprived mice results in numerical reduction, maturation failure, and decreased proliferative capacity of Kupffer cells.

Proc Soc Exp Biol Med, 1995 Jun, 209(2), 112 - 7
Superoxide radical: controversies, contradictions, and paradoxes; McCord JM; The study of free radical biology has engendered a great deal of controversy and apparently conflicting observations, particularly with regard to the use of the antioxidant enzyme superoxide dismutase as a protective or therapeutic agent . Slowly, the reasons behind the confusion are beginning to emerge . The superoxide radical, O2.-, has a number of paradoxical physiological and pathophysiological roles . Several examples of the radical's schizophrenic behavior include its roles in bactericidal action versus inflammation, as a modulator of cell division versus malignant transformation and apoptosis, and as both an initiator and a terminator of lipid peroxidation.

J Appl Bacteriol, 1995 Jun, 78(6), 655 - 62
Bactericidal effect of bovine normal and immune serum, colostrum and milk against Helicobacter pylori; Korhonen H et al.; Serum and colostrum but not post-colostral milk from non-immunized Friesian cows was found highly bactericidal for Helicobacter pylori NCTC 11637 . This bactericidal activity was destroyed by heating at 56 degrees C for 30 min and restored by the addition of fetal calf serum as a source of complement, indicating that the bacterial effect was probably dependent on an antibody-complement system . Systemic, serial immunization of non-lactating, pregnant cows with H . pylori resulted in high specific antibody titres in serum and colostrum . No titres were found in post-colostral milk, even after booster-immunization during lactation . Immunization did not enhance the bactericidal activity of serum and colostrum, but increased it in post-colostral milk . The bactericidal activity was not correlated with titres of specific antibody or with IgG concentrations.

Ostomy Wound Manage, 1995 Jun, 41(5), 18 - 20, 22-4, 26-7
Physical modalities in wound management: UVC, therapeutic heating and electrical stimulation; Kloth LC; In spite of efforts to create an optimum wound environment for healing, there are times that a wound may not heal, may heal very slowly, or may worsen . In these cases, a series of treatments with an appropriate physical agent can be added to the patient's care plan to augment tissue reparative processes . Three modalities that have received support in the literature for use in wound healing are ultraviolet "C" radiation (UVC), therapeutic heating, and electrical stimulation . Treatment goals for UVC are hyperplasia and enhanced re-epithelialization or desquamation of the leading edge of periulcer epidermal cells, granulation tissue formation, sloughing of necrotic tissue, and bactericidal effects . Treatment goals for therapeutic heating are increased blood perfusion with subsequent increased delivery of oxygen to the tissues (avoiding the dessication of wound tissues) . The treatment goal for electrical stimulation is to attract negatively or positively charged cells into the wound area, such as neutrophils, macrophages, epidermal cells and fibroblasts that in turn will contribute to wound healing processes by way of their individual cellular activities.

FEMS Immunol Med Microbiol, 1995 Jun, 11(3), 207 - 11
Complement resistance is a virulence factor of Branhamella (Moraxella) catarrhalis; Hol C et al.; The purpose of this study was to investigate complement resistance in Branhamella (Moraxella) catarrhalis isolated from healthy schoolchildren or sputum-producing adult patients . Two techniques were used: a serum bactericidal assay as the gold standard and an easier 'culture and spot' test . Children (age 4-13; n = 303) and patients (n = 1047) showed high colonization/infection rates with B . catarrhalis (31% and 19%, respectively) . Complement resistance or intermediate sensitivity occurred frequently in patient isolates (62% and 27%, respectively) and less often in children (33% and 8.5%, respectively; P << 0.0001) . In young children (age 4-5 years), the proportion of complement-resistant strains was around 50% . Complement resistance in B . catarrhalis is associated with illness and may hence be considered a virulence factor.

Antimicrob Agents Chemother, 1995 Jun, 39(6), 1386 - 7
In vitro antibiotic susceptibility testing of clinical isolates of Mycoplasma penetrans from patients with AIDS; Hayes MM et al.; In vitro susceptibilities of Mycoplasma penetrans were determined . MICs and MBCs were determined . The MICs at which 50% of the isolates are inhibited (micrograms per milliliter) for broth dilution testing were as follows: azithromycin, 0.039; chloramphenicol, 0.625; ciprofloxacin, 0.156; clindamycin, 0.078; doxycycline, 0.312; erythromycin, 0.312; gentamicin . > 10; levofloxacin, 0.078; lincomycin, 0.625; streptomycin, > 10; and tetracycline, 1.25 . Bactericidal activity was significant only for ciprofloxacin (MBC at which 50% of the isolates are killed, 0.312 microgram/ml) and levofloxacin (MBC at which 50% of the isolates are killed, 0.312 microgram/ml).

Antimicrob Agents Chemother, 1995 Jun, 39(6), 1295 - 9
Bacterial activity of a new antiulcer agent, ecabet sodium, against Helicobacter pylori under acidic conditions; Shibata K et al.; Helicobacter pylori NCTC 11637, which is nonviable at pH 3.0, became viable after addition of 10 mM urea owing to ammonia production by urease . In a buffer supplemented with urea, ecabet sodium decreased both the production of ammonia and the number of viable cells of H . pylori NCTC 11637 and changed the bacteria from the bacilliform to the horseshoe or doughnut shape in a concentration-dependent manner . In particular, ecabet sodium (2 and 4 mg/ml) decreased the number of viable cells below the control level . Benzohydroxamic acid, a urease inhibitor, also caused a decrease in ammonia production accompanied by a decrease in the number of viable cells and changed the morphological form at pH 3.0, but the number of viable cells was not lowered below the control level . In buffers at various pHs without urea, ecabet sodium showed a concentration-dependent bactericidal effect on H . pylori at pHs 4.0 and 5.0 but not at pHs 6.0 and 7.0 while benzohydroxamic acid caused only a slight decrease in the number of viable cells at pH 4.0 . These results suggest that ecabet sodium has strong bactericidal activity in addition to its urease-inhibiting activity under acidic conditions.

J Vet Med Sci, 1995 Jun, 57(3), 493 - 5
Effects of vitamin B2 on neutrophil functions in cattle; Osame S et al.; Vitamin B2 was intramuscularly administered to Holstein cattle and the ensuing changes in peripheral blood neutrophil function were investigated . The neutrophil count displayed a significant increase at 1-2 days after administration, while nitroblue tetrazolium reducing activity and phagocytic bactericidal activity were enhanced at 1-4 days after administration in calves and at 1-6 days after administration in adult cows . The increases in the neutrophil count and the activation of neutrophil functions were observed, being manifested at dosages of 10 mg/kg or greater for calves and 5 mg/kg or greater for adult cows.

Inflammation, 1995 Jun, 19(3), 389 - 404
Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein; Huang K et al.; Endothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation . E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h . rBPI21, a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), inhibited LPS-induced E-selectin expression when added at the same time as, and up to 6 h after, LPS . Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B . Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was already activated, addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h . These results indicate that endothelial activation requires continuous presence of LPS, and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal.

Biochemistry, 1995 May 30, 34(21), 7258 - 63
Point mutagenesis of positively charged amino acids of cholesteryl ester transfer protein: conserved residues within the lipid transfer/lipopolysaccharide binding protein gene family essential for function; Jiang XC et al.; The cholesteryl ester transfer protein (CETP) binds to plasma lipoproteins and transfers neutral lipids between them . Previous studies showed that lipoprotein binding involves ionic interactions between CETP and lipoproteins, with increased binding of CETP to lipoproteins carrying increased negative charge . In order to understand the molecular determinants of lipoprotein binding in CETP, site-directed mutagenesis was carried out on positively charged amino acids within and outside regions of conserved sequence in the putative family of lipid transfer/lipopolysaccharide (LPS) binding proteins (LT/LBP) . Within the conserved regions, two mutant proteins, K233A and R259D, were well secreted by the transfected cells but showed markedly reduced cholesteryl ester transfer activity . Separating the bound from free CETP by gel filtration after incubation with HDL, HDL binding by K233A was found to be impaired, suggesting that the binding deficiency of the mutant may be responsible for decreased transfer activity . Kinetic analysis showed a marked increase in the apparent Km but no change in Vmax, consistent with a lipoprotein binding defect . Thus, within CETP, K233 and R259 play an essential role in cholesteryl ester transfer activity probably by mediating binding of CETP to lipoproteins . Sequence alignment of CETP, phospholipid transfer protein, LPS binding protein, and bactericidal permeability-inducing protein showed that K223 and R259 were strictly conserved as positively charged amino acids, suggesting a common function within the LT/LBP gene family.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1995 May, 11(3), 197 - 201
{The role of complement in inhibition of intracellular bactericidal activity to P . aeruginosa of PMN in seriously burnt patients}; Wang Z et al.; 129 PMN-samples from the peripheral blood of 70 burnt patients were collected, and ICBA, SG and O2- were dynamically studied . The harmful effects on patients' plasma on normal human PMN, and specific blocking effect of anti-human C3 . C5 serum (AHC3C5S) on the above harmful effects were also observed . The results: 1) All the parameters values showed a significant decrease in seriously or moderately burnt patients as compared with normal values; the decrease was most marked on 1st-6th postburn days when deep burn surface exceeded 45% . 2) ICBA was significantly correlated with SG and O2- . 3) Patients' plasma greatly reduced the reserves of ICBA, SG and O2- in normal PMN, while AHC3C5S might lessen the reduction in term of net reserve rates: ICBA (67.33) > SG (51.60) > O2- (46.68) . The findings suggest: ICBA levels are reversely related with DBSA and fragments of C3 and C5 are the main factors in reduction of ICBA.

Indian Pediatr, 1995 May, 32(5), 533 - 8
Furazolidone in typhoid fever--correlation of clinical efficacy with serum bactericidal activity; Kumar AS et al.; Treatment of typhoid fever with furazolidone produces a high cure rate . This is a clinical curiosity, as furazolidone is described to be poorly absorbed . The present study examined whether furazolidone could produce unequivocal clinical response and, if so whether this was due to the drug producing bactericidal levels in the serum . Twenty one patients selected by defined criteria were treated with furazolidone and evaluated for definite clinical response in 5-7 days . Bactericidal activity of pre dose and post dose sera were estimated in seven patients showing definite clinical response . All the seven patients had a clinical cure without the drug producing significant bactericidal levels in the blood . Hence we concluded that the major site of action of furazolidone was in the intestine . It is our postulate that the organisms reaching the intestine in large numbers from bile are prevented from gaining re-entry into the circulation by the action of furazolidone in the intestine . After repeated cycles of entry of organisms into the intestine from bile and the simultaneous prevention of its re-entry into the circulation, the number of organisms remaining in circulation comes down considerably, thus helping the immune system to bring about a cure.

Pharmacotherapy, 1995 May-Jun, 15(3), 297 - 316
Single daily dosing of aminoglycosides; Preston SL et al.; To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles . Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974 . The advantages of this regimen include optimum concentration-dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance . Because of longer dosing intervals, toxicity may also be delayed or reduced . Costs may be reduced due to decreased monitoring and administration . Clinically, the regimen has been implemented in various patient populations with reported success . Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia . More clinical experience with this method in large numbers of patients has to be published . Pharmacists can be instrumental in monitoring patients receiving once-daily therapy and by educating health care professionals as to the rationale behind the therapy.

Clin Diagn Lab Immunol, 1995 May, 2(3), 365 - 8
Assessment of complement-mediated killing of Moraxella (Branhamella) catarrhalis isolates by a simple method; Verduin CM et al.; Recently, we showed that complement resistance is an important virulence factor of Moraxella (Branhamella) catarrhalis . Our study used a serum bactericidal assay to determine complement resistance in M . catarrhalis . Although the serum bactericidal assay is considered the "gold standard" for determining complement resistance, it is laborious and time-consuming and therefore not well suited for large-scale studies . Using a large number (n = 324) of M . catarrhalis isolates obtained from the sputa of patients with lower respiratory tract infections (n = 200) and young carriers (n = 124), we assessed the value of a simple "culture-and-spot" test as an alternative to the serum bactericidal assay . For both groups of isolates, the degree of concordance between the two tests used was very significant (P < 0.0001) . The agreement between the two assays was estimated to be "excellent beyond chance" (as determined by Cohen's kappa test) . The culture-and-spot assay is a valuable alternative to the serum bactericidal assay, not only for screening purposes as shown here but also for studying the mechanism of complement resistance in M . catarrhalis at the molecular level.

J Invest Surg, 1995 May-Jun, 8(3), 155 - 62
Penetration of ciprofloxacin into bone: a new bioabsorbable implant; Overbeck JP et al.; The implantation of antibiotic-containing cement beads became standard adjuvant local antibiotic therapy of chronic osteomyelitis . The new developed bioabsorbable drug carrier system of polyglycolic acid with the antibiotic Ciprofloxacin was tested in vitro and in vivo . The goal of this study was to determinate the penetration depth of Ciprofloxacin into bone cortex and marrow . Two monofil, PGA cylinders, 3.2 x 5 mm in size, containing 3 mg of Ciprofloxacin each, were implanted into the proximal part of both femora of 18 rabbits (New Zealand white) . After sacrifice, the concentration of Ciprofloxacin in micrograms/g cortex and marrow was measured with high-performance liquid chromatography in relation to the distance from the test material at day 2, as well as at 1, 2, 3, 4, and 6 weeks postimplantation . For a distance up to 5 mm, marrow levels of the drug exceeded cortical levels at day 2 (5000 to 240 micrograms/g) . At a distance of 5-10 mm, cortex levels were similar to marrow levels after 2 weeks and were higher than marrow levels at week 3 . This observation could be made at a distance between 10 and 15 mm only after 2 days . Later, marrow concentrations again exceeded that in cortex . At a distance of more than 15 mm, antibiotic levels were low and approximated . After 6 weeks, at 5 mm distance, a bactericidal drug concentration of about 2 micrograms/g in bone marrow could be measured . Drug penetration into cortical bone in bactericidal concentrations of about 2 micrograms/g was achieved at up to 30 mm in the first few days.(ABSTRACT TRUNCATED AT 250 WORDS)

Proc Soc Exp Biol Med, 1995 May, 209(1), 46 - 53
Rapid induction of mRNA for nitric oxide synthase II in rat alveolar macrophages by intratracheal administration of Mycobacterium tuberculosis and Mycobacterium avium; Greenberg SS et al.; Mycobacterium avium complex (MAC) organisms are among the most common bacterial cause of disseminated infection in patients with acquired immune deficiency syndrome (AIDS) . An increase in the incidence of virulent Mycobacterium tuberculosis (MTB) is also occurring throughout the world . In vitro data suggest that nitric oxide (NO) may be important in restricting the growth of MAC . However, the ability of MTB to stimulate NO production and the susceptibility of MTB to the bactericidal activity of NO produced by murine alveolar macrophages (AM) is controversial . This study tested the hypothesis that in vivo administration of heat-killed MAC (strain 100 and 101) and human virulent MTB (strain F1) to rats stimulated NO production by rat AM, ex vivo . We show that heat-killed MTB instilled into rat lungs rapidly induced mRNA for NO synthase (iNOS) II in AM obtained by bronchoalveolar lavage (BAL) . In contrast, expression of AM iNOS mRNA was only found in 40% of the rats given MAC . Moreover, the change in iNOS mRNA in the AM obtained from rats given MTB and MAC correlated with the production of the reactive nitrogen intermediates (RNI) NO2- and NO3- in BAL fluid, lung homogenate, and the spontaneous generation of RNI by isolated AM ex vivo and occurred without measurable increases in BAL fluid tumor necrosis factor-alpha (TNF-alpha) . L-NG-monomethylarginine (50 mg/kg, ip) given 30 min before MAC or MTB attenuated the increase in RNI in lung homogenates and BAL fluid . This is the first demonstration that in vivo exposure to MTB results in rapid upregulation of gene expression for iNOS which is associated with functional RNI production by rat AM . These results show that MTB human virulent strain 1 has the ability to rapidly upregulate iNOS mRNA in AM . If human AM generate NO from L-arginine by either iNOS or other NADPH oxidases then NO may play a role in the overall host-defense response of the lung to MAC and MTB.

Biochem Biophys Res Commun, 1995 Apr 6, 209(1), 111 - 6
Signals from the IL-1 receptor homolog, Toll, can activate an immune response in a Drosophila hemocyte cell line; Rosetto M et al.; The Toll gene encodes an interleukin 1 receptor-like protein that mediates dorsoventral polarity in the Drosophila embryo . The possible involvement of Toll or Toll-like proteins also in the Drosophila immune response was investigated by overexpressing Toll10B, a constitutively active mutant protein, in the Drosophila blood cell line mbn-2 . Induction of the Cecropin A1 (CecA1) gene, coding for a bactericidal peptide, was used as an indicator for the immune response . Toll10B was found to increase CecA1 transcription, as detected with a cotransfected CecA1-lacZ reporter gene construct . This effect depends on the presence of a kappa B-like site in the CecA1 promoter . The endogenous Toll gene is expressed in mbn-2 cells, indicating that this gene may normally play a role in Drosophila blood cells.

Infect Immun, 1995 Apr, 63(4), 1362 - 8
Prolonged expression of lipopolysaccharide (LPS)-induced inflammatory genes in whole blood requires continual exposure to LPS; Dedrick RL et al.; Blood-borne lipopolysaccharide (LPS) is thought to be a major inducer of sepsis; however, it remains controversial whether an ongoing exposure to LPS is required to maintain the underlying systemic inflammatory response . To address this question, we have studied the expression of tumor necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), and the procoagulant protein tissue factor induced by LPS ex vivo in whole human blood . The addition of a 1-ng/ml bolus of LPS to blood rapidly induced mRNA expression of all three genes . The mRNA levels peaked after 1 to 2 h, depending on the gene, and then declined to baseline after approximately 5 h . The decline in mRNA expression was not caused by a loss of responsiveness of the blood cells to LPS but rather correlated with the neutralization of LPS inflammatory activity by plasma components . Furthermore, administering a 1-ng/ml dose of LPS in six hourly aliquots of 167 pg/ml greatly prolonged the expression of mRNAs and induced a much greater release of TNF-alpha and IL-1 beta protein than did a single bolus . Dosing by repeated additions was more effective than a single bolus in inducing secretion of TNF-alpha and IL-1 beta at LPS levels of < or = 10 ng/ml, which corresponded to the LPS neutralization capacity of plasma . Finally, both mRNA expression and protein secretion induced by repeated administration of LPS were rapidly reversed by the addition of the LPS-neutralizing protein, bactericidal/permeability-increasing protein, even after several hours of stimulation . These results indicate that continuous or repeated exposure to LPS is required to maintain the expression of inflammatory genes and that the activated state is rapidly reversed with LPS neutralization.

Antimicrob Agents Chemother, 1995 Apr, 39(4), 878 - 81
Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice; Struillou L et al.; The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice . In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043 . For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment . Mice were infected with the MO-1 strain . Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection . At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens . Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo.

Ann Surg, 1995 Apr, 221(4), 398 - 405
Pathogenesis of hemorrhage-induced bacteria/endotoxin translocation in rats . Effects of recombinant bactericidal/permeability-increasing protein; Yao YM et al.; OBJECTIVES: This study was conducted to determine the role of gut-derived bacteria/endotoxin in the pathogenesis of the multiple-organ damage and mortality, the possible beneficial effect of recombinant bactericidal/permeability-increasing protein (rBPl21), and whether neutralizing endotoxemia by rBPl21 treatment influences tumor necrosis factor (TNF) formation in rats after hemorrhagic shock and resuscitation . SUMMARY BACKGROUND DATA: Hypovolemic shock might be associated with bacterial or endotoxin translocation as well as systemic sepsis . Similar to bactericidal/permeability-increasing (BPl) protein, rBPl21 has been found to bind endotoxin and inhibit TNF production . METHODS: A rat model of prolonged hemorrhagic shock (30 to 35 mm Hg for 180 min) followed by adequate resuscitation was employed . Recombinant bactericidal/permeability-increasing protein was administered at 5 mg/kg intravenously . The control group was treated similarly to the BPl group, but received thaumatin as a protein-control preparation in the same dose as rBPl21 . RESULTS: Immediately after resuscitation (230 min), plasma endotoxin levels in the control group (61.0 +/- 16.3 pg/mL) were almost neutralized by rBPl21 treatment (13.8 +/- 4.8 pg/mL, p < 0.05) . Plasma TNF levels were not significantly influenced by rBPl21 treatment . The 48-hour survival rate was 68.8% in the treatment group versus 37.5% in the control group (p = 0.08) . Microscopic histopathologic examination revealed relatively minor damage to various organs in the treatment group . CONCLUSIONS: These data suggest that hemorrhagic shock may lead to bacterial/endotoxin translocation with concomitant TNF formation, endogenous endotoxemia may play an important role in the pathogenesis of multiple-organ failure after shock and trauma, TNF formation at an early stage might be related mainly to mechanisms other than Kupffer's cells activation via lipopolysaccharide, and rBPl21 might be a useful therapeutic agent against endogenous bacteria/endotoxin related disorders in severe hemorrhagic shock.

J Clin Invest, 1995 Apr, 95(4), 1947 - 52
Protection against endotoxic shock by bactericidal/permeability-increasing protein in rats; Jin H et al.; Bactericidal/permeability-increasing protein (BPI) is a neutrophil primary granule protein that inhibits effects of LPS in vitro . The current study examined the effects of BPI on hemodynamics, mortality, and circulating endotoxin and cytokines in conscious rats with endotoxic shock . Catheters were implanted into the right femoral artery and vein . 1 d later, human recombinant BPI (10 mg/kg) or vehicle was intravenously injected immediately, 30 min, or 2 h after intravenous injection of LPS (7.5 mg/kg) . Mean arterial pressure (MAP) and heart rate were monitored and blood was collected before and after injection . BPI given immediately or 30 min after LPS prevented the LPS-induced reduction in MAP at 4-8 h and markedly reduced mortality . BPI given 2 h after LPS injection had no protective effect . BPI treated immediately after LPS reduced the circulating levels of endotoxin and IL-6 but increased the circulating levels of TNF . We propose that BPI exerts its protective effect through a TNF-independent mechanism, by inhibiting endotoxin-stimulated production of IL-6.

Vet Immunol Immunopathol, 1995 Apr, 45(3-4), 333 - 45
Natural hemolytic and bactericidal activities of sea bream Sparus aurata serum are effected by the alternative complement pathway; Sunyer JO et al.; Sea bream serum displayed bactericidal and hemolytic activities . These activities were depleted when serum was incubated with different activators of the alternative complement pathway (ACP) . Ethylenediaminetetraacetic acid (EDTA) inhibited both the hemolytic and bactericidal activities, while ethyleneglycol-bis (B-aminoethyl ether)-N, N, N'-tetraacetic acid (EGTA) was not inhibitory . An antibody against the putative third component of sea bream component (C3) was produced . It was observed by immunoelectrophoresis that the sea bream C3 and human C3 migrated in the same position . Crossed immunoelectrophoresis showed that sea bream C3 exhibited a similar pattern of activation when compared with its human counterpart . The anti-sea bream C3 antibody inhibited both bactericidal and hemolytic activities . It was concluded that both serum actions were displayed by the ACP . The best conditions for the sea bream ACP titration were investigated . Of all mammal erythrocytes tested, rabbit erythrocytes (RaRBC) were found to be the best ACP activators and thus were used for the titration . Sea bream showed very high ACP titers when compared with those of mammals . Absorption of naturally occurring antibodies against rabbit RaRBC did not influence the ACP titers . Enzymatic removal of sialic acid from different mammalian erythrocytes increased the sensitivity of these cells to hemolysis mediated by the sea bream ACP.

Bull Acad Natl Med, 1995 Apr, 179(4), 767 - 74; discussion 775-6
{Contribution of the experimental model of bacterial endocarditis}; Carbon C; Bacterial endocarditis is a difficult to cure infection, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action . The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans, remains of great importance due to the difficulties encountered in clinical trials . The advantage of the experimental model is that besides the fact that is closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens . The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on therapeutic outcome . Two main aspects are discussed for their relevance to human therapy and represent our recent contribution: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis . This animal model has also helped to define the importance of antibiotic dosing strategies to achieve in vivo synergism and to outline the predictive value of some drug pharmacokinetic and dynamic properties on the in vivo response to therapy.

Arch Mal Coeur Vaiss, 1995 Apr, 88(4), 511 - 5
{Coxiella burnetii endocarditis on a mechanical valvular prosthesis . Apropos of 2 cases}; Stchepinsky O et al.; The authors report two cases of prosthetic valve endocarditis due to Coxiella burnetii . The histories were chronic and complex suggesting an auto-immune disease: prolonged recurrent fever despite antibiotic therapy with a biological inflammatory syndrome whilst blood cultures remained negative . The first patient presented with prosthetic valve dehiscence and acute glomerulonephritis . The second patient had coagulation defects with prosthetic valve thrombosis, mesenteric adenopathy and congestive cardiac failure without prosthetic valve dysfunction . In suspected endocarditis with negative blood cultures, serological tests should be extended to intracellular pathogens difficult to identify and justifying specific and prolonged bactericidal therapy (fluoroquinolones, cyclines, rifampincine) . Long-term serological surveillance is essential even when the outcome could have led to the termination of antibiotic therapy . Usually, antibiotic therapy provides a bacteriological cure, but treatment has to be continued for at least 3 years, and, in some patients, all their lives . Valve replacement is reserved for haemodynamic complications of the pathology which determine the ultimate prognosis.

Int J Clin Pharmacol Ther, 1995 Apr, 33(4), 232 - 9
Comparative bioavailability of metronidazole formulations (Vagimid) after oral and vaginal administration; Hoffmann C et al.; Bioavailability of Vagimid 500 tablets (film coated, 500 mg metronidazole) and absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets (100 mg metronidazole) relative to respective listed references were studied in 16 female healthy volunteers (age 21-37 years, weight 45-67 kg, height 158-179 cm) . Metronidazole and its main hydroxylated metabolite were measured using an HPLC-method with detection limits of 0.025 and 0.25 micrograms/ml (for vaginal and oral studies), respectively . Extent of absorption was assessed by AUC0-infinity (bioequivalence range 0.80-1.25), rate of absorption by Cmax/AUC0-infinity (bioequivalence range 0.70-1.43) . Geometric means and 90%-confidence intervals of the ratios of these primary characteristics were calculated using a multiplicative model . Vagimid 500 tablets were bioequivalent to the reference formulation with regard to extent and rate of absorption of metronidazole because of AUC0-infinity = 0.995 (0.84-1.18) and Cmax/AUC0-infinity = 1.11 (0.94-1.30) . The absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets caused maximal serum concentrations between 433 and 1,156 ng/ml after 8-20 h which are bactericidal only for the most susceptible anaerobic germs and which are most likely only of marginal importance for drug safety.

Pathol Biol (Paris), 1995 Apr, 43(4), 284 - 8
{Extra and intracellular activity of dirithromycin against Mycobacterium avium}; Gevaudan MJ et al.; The in vitro activity of dirithromycin alone and in combination with clofazimin, ethambutol and rifabutin was tested against thirty strains of Mycobacterium avium isolated from patients . Extracellular activity of dirithromycin was assessed by determining MICs using the radiometric methodology in 7H12 broth at two pHs 6.8 and 7.4 . The MICs obtained at pH 7.4 were 3 to 4 more dilutions lower than those obtained at pH 6.8 . Activity of pairs of antibiotics was measured using the FIC indices . Dirithromycin-clofazimin combination demonstrated the most important additive effects and even produced synergic effect against 5 of 30 strains . Studies of intracellular bacteria showed that the most effective bactericidal combination was dirithromycin, clofazimin and ethambutol together.

Eur J Immunol, 1995 Apr, 25(4), 1101 - 4
Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines; Modolell M et al.; Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase . Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline . NO is important in the bactericidal and cytotoxic activities of macrophages . An equivalent functional role of arginase and its products is not known . We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-gamma (IFN-gamma), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E2 (PGE2) . We find that PGE2 and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase . In contrast, the TH1 cytokine IFN-gamma does not induce arginase . Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase . Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase . Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase . The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena . The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH1 and TH2 cytokines, respectively.

Microb Pathog, 1995 Apr, 18(4), 269 - 78
The construction and characterization of colanic acid deficient mutants in an extraintestinal isolate of Escherichia coli (O4/K54/H5); Russo TA et al.; Extraintestinal strains of Escherichia coli possess a variety of virulence factors that enable them to cause disease . These strains express a group 2 capsular polysaccharide which is important in the pathogenic process . Extraintestinal strains evaluated to date are also capable of producing the group 1 capsular polysaccharide colanic acid . The blood isolate CP9 (O4/K54/H5) constitutively produces the group 2, K54 capsule but can be induced to produce colanic acid . In this report we assess whether colanic acid contributes to the pathogenesis of this extraintestinal pathogen . CP9 and its derivatives that are deficient in their ability to produce colanic acid (TR94), the K54 group 2 capsule +/- colanic acid (CP9.137, TR1374) and the O4 specific antigen +/- colanic acid (CP921,CP925) were used to test whether the group 1 capsule colanic acid conferred protection against the bactericidal effects of serum and recombinant bactericidal/permeability-increasing protein (rBPI-23) in vitro . Additionally, CP9, CP9.137 and TR94 were evaluated in the rat granuloma pouch, an in vivo model for localized infection, and by intraperitoneal inoculation into mice, a systemic infection model . In summary, the inability of CP9 to produce colanic acid in the presence or absence of its K54 and O4 antigens had no effect on its ability to survive these host defenses in vitro and did not affect its virulence in these two in vivo models of infection.

J Infect Dis, 1995 Mar, 171(3), 739 - 43
Presence of bactericidal/permeability-increasing protein in disease: detection by ELISA; Dentener MA et al.; A sandwich ELISA was developed specific for human bactericidal/permeability-increasing protein (BPI), using Mg++ ions to abrogate disturbance by lipopolysaccharide of BPI measurement and to prevent aspecific adherence of BPI to solid phase . In fresh EDTA or heparinized plasma of healthy volunteers BPI was not detectable, whereas in serum BPI was present, indicating that coagulation activates polymorphonuclear leukocytes to release BPI . Furthermore, BPI was present in plasma of critically ill intensive care unit (ICU) patients, in bronchoalveolar lavage fluid of patients suspected of having pneumonia, in wound fluid, and in pleural fluid . In sub-groups of samples with culture-proven bacteria, mean BPI levels were increased compared with subgroups without bacteria, although the differences were only significant in EDTA plasma of ICU patients . These findings indicate the presence of BPI during pathologic conditions . The physiologic role of the released BPI has to be further elucidated.

J Immunol, 1995 Mar 1, 154(5), 2351 - 7
Substrate specificities of the protease of mouse serum Ra-reactive factor; Ogata RT et al.; Ra-reactive factor (RaRF) is a serum bactericidal factor whose function seems to be to activate C in a manner similar to that of C1, but with activation triggered by binding to bacterial polysaccharides instead of to immune complexes . It is composed of multiple polysaccharide-binding subunits associated with a novel serine protease, and its overall structural organization is similar to that of C1 . This similarity extends to the serine protease component, which shares a similar modular construction and about 40% sequence identity with the C1r and C1s subcomponents of C1 . In this study, we examined the substrate specificity of mouse RaRF by assaying its ability to cleave C components C3, C4, and C5, and its activity against the murine C4 isotype, sex-limited protein . Our results revealed that RaRF preferentially cleaves the C4 alpha-chain with specific activities 20- to 100-fold greater than either human or murine C1s, and that RaRF also cleaves the C3 alpha-chain, but with a lower efficiency than C4 alpha . We also found that RaRF is much less sensitive than C1s to mutations near the proteolytic site and that the two proteases show different reactivities against synthetic substrates . Hence, although the RaRF protease and C1s have similar structures and play similar roles in C activation, they also display clear differences in substrate range and in the details of their substrate recognition mechanisms . Finally, we found that RaRF does not cleave sex-limited protein even at a level 100-fold higher than necessary for C4 cleavage.

Antimicrob Agents Chemother, 1995 Mar, 39(3), 725 - 30
Therapy of Mycobacterium avium complex infections in beige mice with streptomycin encapsulated in sterically stabilized liposomes; Gangadharam PR et al.; Mycobacterium avium complex (MAC) causes serious opportunistic infections in AIDS patients . Previous studies with MAC-infected beige mice have indicated that weekly administration of liposome-encapsulated streptomycin can reduce significantly the CFU in the liver and spleen . We examined whether streptomycin encapsulated in recently developed sterically stabilized liposomes with prolonged circulation times would have a therapeutic effect in this animal model . Two liposome types with prolonged circulation (polyethyleneglycol-distearoylphosphatidylethanolamine {PEG-DSPE}-distearoylphosphatidylcholine {DSPC}-cholesterol {chol} or phosphatidylinositol {PI}-DSPC-chol) and conventional liposomes (phosphatidylglycerol {PG}-phosphatidylcholine {PC}-chol) encapsulating streptomycin and administered twice weekly were bactericidal to MAC strain 101 in the spleen when the level of infection after treatment was compared with the level of infection before treatment . PI-DSPC-chol and PG-PC-chol liposomes encapsulating streptomycin were bactericidal in the liver . Although PG-PC-chol or PEG-DSPE-DSPE-chol liposomes encapsulating streptomycin were not bactericidal in the lungs, they reduced the level of MAC infection by more than 3 orders of magnitude compared with the level of MAC infection in untreated controls.

Antimicrob Agents Chemother, 1995 Mar, 39(3), 608 - 12
Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model; Lounis N et al.; Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice . Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alone . Four other combined regimens, CLARI combined with ethambutol (EMB), rifabutin (RBT), or both EMB and RBT during the entire 16 weeks of treatment or with AMIKA administered in an initial 2-week course showed bactericidal activity not significantly greater than that of CLARI alone . After 16 weeks of treatment, CLARI-resistant mutants were isolated from the majority of mice that had been treated with CLARI alone, CLARI-RBT, CLARI-EMB, or CLARI-EMB-RBT, as was the case for untreated controls, but the frequencies of occurrence of mutants were significantly greater in the groups treated with these combinations or CLARI alone . On the other hand, no CLARI-resistant mutants were isolated from the mice that had been treated with the combination of CLARI plus an initial 4 or 8 weeks of AMIKA and were isolated from only a tiny proportion of mice that had been treated with CLARI plus an initial 2 weeks of AMIKA . Therefore, only treatment with CLARI combined with an initial 4 or 8 weeks of AMIKA but not combined with RBT or EMB or both, could enhance the activity of the drug treatment and prevent the selection of CLARI-resistant mutants.

Antimicrob Agents Chemother, 1995 Mar, 39(3), 593 - 7
Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits; Nau R et al.; Using a rabbit model of pneumococcal meningitis, we compared the pharmacokinetics and bactericidal activities in cerebrospinal fluid (CSF) of older (ciprofloxacin, ofloxacin) and newer (levofloxacin, temafloxacin, CP-116,517, and Win 57273) quinolones with those of the beta-lactam ceftriaxone . All quinolones penetrated into the inflamed CSF better than ceftriaxone, and the speed of entry into CSF was closely related to their degrees of lipophilicity . At a dose of 10 mg/kg.h, which in the case of the quinolones already in use in clinical practice produced concentrations attainable in the sera and CSF of humans, ciprofloxacin had no antipneumococcal activity (delta log10 CFU/ml.h, +0.20 +/- 0.14) . Ofloxacin (delta log10 CFU/ml.h, -0.13 +/- 0.12), temafloxacin (delta log10 CFU/ml.h, -0.19 +/- 0.18), and levofloxacin (delta log10 CFU/ml.h, -0.24 +/- 0.16) showed slow bactericidal activity (not significantly different from each other), while CP-116,517 (delta log10 CFU/ml.h, -0.59 +/- 0.21) and Win 57273 (delta log10 CFU/ml.h, -0.72 +/- 0.20) showed increased bactericidal activities in CSF that was comparable to that of ceftriaxone at 10 mg/kg.h (delta log10 CFU/ml.h, -0.80 +/- 0.17) . These improved in vivo activities of the newer quinolones reflected their increased in vitro activities . All quinolones and ceftriaxone showed positive correlations between bactericidal rates in CSF and concentrations in CSF relative to their MBCs . Only when this ratio exceeded 10 did the antibiotics exhibit rapid bactericidal activities in CSF . In conclusion, in experimental pneumococcal meningitis the activities of new quinolones with improved antipneumococcal activities were comparable to that of ceftriaxone.

Eur J Anaesthesiol, 1995 Mar, 12(2), 141 - 6
The effects of thiopentone, etomidate, ketamine and midazolam on several bactericidal functions of polymorphonuclear leucocytes in vitro; Krumholz W et al.; Polymorphonuclear leucocytes (PMNL) are an essential component of the defence system against invading bacteria . There is evidence that some anaesthetics are able to suppress PMNL functions, promoting, perhaps, perioperative infection . We studied the effects of thiopentone, etomidate, ketamine, and midazolam on the generation of bactericidal agents (superoxide anion, hydrogen peroxide, and myeloperoxidase) by PMNL in vitro . Thiopentone inhibited superoxide anion (P < or = 0.01) as well as hydrogen peroxide production (P < or = 0.001) . However, there was no statistically significant effect on myeloperoxidase release . Neither etomidate nor ketamine influenced the PMNL functions tested to any extent . Midazolam suppressed superoxide anion generation (P < or = 0.01) but only if a concentration far beyond clinical relevance was used.

Biomaterials, 1995 Mar, 16(5), 355 - 60
Influence of soluble suture factors on in vitro macrophage function; Uff CR et al.; Suture materials may interact with immune competent cells and thereby affect localized immunity . Macrophages are central to the inflammatory response and coordinate wound healing . They are also involved in the clearance of foreign material, bacteria and malignant cells . We studied the influence of soluble factors associated with silk, steel, nylon, polyglactin, polydioxanone and chromic catgut sutures on macrophage adherence, phagocytosis and the production of lysozyme and tumour necrosis factor . Soluble factors from suture materials influenced macrophage behaviour in vitro causing cellular activation, functional impairment and alterations in secreted levels of the cytokine tumour necrosis factor and the bactericidal agent lysozyme . Of the six materials studied, polyglactin had the most extreme effect, causing significant inhibition of cell adherence and lysozyme production . Silk also exerted a considerable effect on macrophages, significantly inhibiting adherence . In contrast, steel and polydioxanone media caused minimal inhibition of macrophage function although, as with all materials, they did activate the cells . This study has demonstrated that sutures release immunotoxic factors which considerably influence macrophage behaviour in vitro . These effects may have important clinical implications.

Vopr Kurortol Fizioter Lech Fiz Kult, 1995 Mar-Apr, (2), 14 - 6
{Changes in the immunity indices of children suffering from inflammatory lung diseases undergoing cold exposures}; Iarosh AM et al.; Cooling and heating the feet in children with pulmonary inflammatory diseases in remission improved immunity . Air baths in addition to stimulating immunity enhanced bactericidal potential of blood neutrophils . Cool and warm showers decreased this potential.

Biochim Biophys Acta, 1995 Feb 16, 1265(1), 40 - 8
Interleukin-4 suppresses the expression of macrophage NADPH oxidase heavy chain subunit (gp91-phox); Zhou Y et al.; The production of superoxide anion by NADPH oxidase is a principal nonspecific bactericidal activity of macrophages and neutrophils in host defense . However, exuberant production of superoxide anion also damages host tissues . Cloning and DNA sequencing of the 91 kDa subunit (gp91-phox) open reading frame indicated a high degree of sequence conservation, greater than 90% in nucleotide and amino acid sequences, between the porcine and human cDNAs . We show in pigs that interleukin-4 (IL-4), a T lymphocyte cytokine which plays a major role in mediating antibody responses to pathogens, suppresses superoxide anion production in macrophages by specifically reducing the level of mRNA encoding gp91-phox . Messenger RNA levels are suppressed approx . 70% within 4 h and persist for 24 h without any change in the rate of mRNA turnover . Nuclear run-on analysis showed that IL-4 did not alter the rate of gp91-phox gene transcription under conditions in which IL-1 beta transcription was inhibited . These results indicate that IL-4 suppresses the inflammatory response of macrophages by mechanisms that include post-transcriptional regulation of the 91 kDa catalytic subunit of NADPH oxidase, and transcriptional regulation of inflammatory cytokine expression.

Genomics, 1995 Feb 10, 25(3), 757 - 9
Localization of the genes for the 100-kDa complement-activating components of Ra-reactive factor (CRARF and Crarf) to human 3q27-q28 and mouse 16B2-B3; Takada F et al.; Human and mouse genes for the complement-activating component (P100) of Ra-reactive factor, a novel bactericidal factor (CRARF and Crarf), were mapped to R-banded metaphase chromosomes by fluorescence in situ hybridization with human and mouse P100 cDNA 2.7 and 2.0 kb long, respectively . The localization of fluorescent signals showed that CRARF and Crarf mapped to human 3q27-q28 and mouse 16B2-B3, respectively . This evidence is consistent with the previous assumption that the distal portion of the long arm of human chromosome 3 is homologous to the proximal portion of mouse chromosome 16.

APMIS, 1995 Feb, 103(2), 154 - 60
Inhibitory effect of lactoferrin on the adhesion of Actinobacillus actinomycetemcomitans and Prevotella intermedia to fibroblasts and epithelial cells; Alugupalli KR et al.; Adhesion of the periodontitis-associated bacteria Actinobacillus actinomycetemcomitans and Prevotella intermedia to monolayers of fibroblasts, HEp-2, KB and HeLa cells was quantified with radiolabeled bacteria . Bacterial adhesion was also examined microscopically with Giemsa-stained non-radioactive preparations . The degree of bacterial adherence was dependent on the growth phase of the bacteria . Strains at the exponential phase adhered to a greater extent than those at the stationary phase of growth . Both human and bovine lactoferrins competitively inhibited the adhesion of A . actinomycetemcomitans and P . intermedia to all tested cell monolayers . The inhibitory effect was dose-dependent in the concentration range 0.5-2500 micrograms/ml and not related to the bacterial growth phase . In the presence of lactoferrin, decreased association of bacteria with the cell monolayers was also found by microscopic examination of the preparations . The present findings indicate that lactoferrin may prevent the establishment of bacteria in periodontal tissues through adhesion-counteracting mechanisms in addition to its bacteriostatic and bactericidal properties.

Kansenshogaku Zasshi, 1995 Feb, 69(2), 151 - 7
{Bactericidal effect of chlorine on strains of Legionella species}; Yabuchi E et al.; We have previously reported that the hot water of 17 (42.5%) out of 40 thermal baths were contaminated with legionellae . Our recent investigation revealed that legionellae inhabited 39 (66.1%) of the 59 thermal bath water, and their viable counts were at the level of 10(4) CFU/100 ml in 5 baths and 10(5) CFU/100 ml in another 5 . Accordingly, the bactericidal effects of free chlorine on 102 strains of 22 Legionella species were tested, in order to find a method of controlling legionellae in thermal bath water . The test strains were the type strains of 22 species, 35 strains of 4 species from patients with Legionella pneumonia in Japan, and 45 strains of 4 species from thermal bath water . Viable cells of all 102 strains suspended at the concentration of 10(5) CFU/100 ml in sodium hypochloride solution with 0.4 mg/l free chlorine became undetectable within 15 min.

Antimicrob Agents Chemother, 1995 Feb, 39(2), 467 - 75
Tobramycin uptake in Escherichia coli membrane vesicles; Leviton IM et al.; The uptake of tobramycin was measured in Escherichia coli membrane vesicles prepared in KMES {K(+)-2-(N-morpholino)ethanesulfonic acid} buffer at pH 6.6 . Uptake occurred in vesicles energized with ascorbic acid and phenazine methosulfate, in which the electrical potential (delta psi) was -120 mV, but not in vesicles energized with D-lactate (delta psi = -95 mV) . The addition of nigericin to vesicles energized with D-lactate did not induce tobramycin uptake despite an increase in delta psi to -110 mV . However, when delta psi was increased or decreased by the addition of nigericin or valinomycin, respectively, uptake in vesicles energized with ascorbic acid and phenazine methosulfate was stimulated or inhibited, respectively, confirming studies with whole cells showing that uptake of aminoglycosides is gated by delta psi rather than by proton motive force (delta microH+) or delta pH . N-ethylmaleimide prevented uptake, suggesting that the aminoglycoside transporter is a cytoplasmic membrane protein with accessible sulfhydryl groups . The observation that uptake is gated in vesicles as well as in whole cells suggested that diffusion occurs through a voltage-gated channel . In vesicles preloaded with tobramycin, no efflux occurred after the addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone . In susceptible cells, aminoglycosides themselves decreased the magnitude of delta psi . We propose a mechanism of aminoglycoside-induced killing in which aminoglycosides themselves close the voltage-gated channel by decreasing the magnitude of delta psi . Channel closure causes aminoglycosides accumulated prior to the fall in delta psi to be trapped, which in turn causes irreversible uptake and subsequent bactericidal effects.

Adv Dent Res, 1995 Feb, 9(1), 63 - 6
Identification of CG-1, a natural peptide antibiotic derived from human neutrophil cathepsin G; Miyasaki KT et al.; Cathepsin G is a neutral serine protease of the granzyme B family which is found in human PMN, cells known to be important in the defense of the periodontium against periodontal bacteria . We propose that cathepsin G serves as a "pro-antibiotic" containing peptide domains which express selective antibiotic properties . In this study, we used HPLC to separate the low-molecular-weight peptides derived from the ultrafiltrate of a granule extract from unstimulated PMN . One of the peptides exhibited intense bactericidal activity as determined by radial diffusion overlay assay (against Escherichia coli ML-35P), an amino-terminal sequence "RVSSFLPWIR...", and a 3.1-kDa molecular mass determined by electrospray ionization-mass spectrometry . The sequence and mass are consistent with the C-terminus of cathepsin G deduced by cDNA analysis . These findings support the hypothesis that antibiotic peptides derived from cathepsin G occur naturally in human PMN . Since this is the first naturally occurring antibiotic peptide derived from cathepsin G, we designate it "CG-1".

Med Hypotheses, 1995 Feb, 44(2), 127 - 31
Inhibition of cell wall synthesis--is this the mechanism of action of penicillins?
Ghooi RB, Thatte SM.
Penicillins have been shown to inhibit bacterial cell wall synthesis, and interact with penicillin binding proteins, leading to bacterial lysis . These two mechanisms, the former more than the latter are believed to be responsible for their therapeutic potential . It has further been demonstrated that only actively multiplying cells are susceptible to bactericidal effects of the antibiotic, which is in accordance with the suggested mechanism of action . Bacterial growth takes place in terms of size and number, both requiring additional cell wall . An increase in bacterial size is due to an increase in the volume of cytosol and area of the cell wall . Presently there is no proof that the former is the cause of the latter or vice versa . Penicillin by inhibiting cell wall synthesis would inhibit both growth and multiplication . Since the antibiotic is bactericidal to rapidly multiplying cells, its effect on cell wall would interfere with its bactericidal action . As per the present understanding penicillin acts principally by inhibiting cell wall synthesis . There is however a discrepancy between its observed effects and what should logically be expected, which forces us to reexamine the mechanism of action of penicillin . We believe that the present understanding of the action of penicillin is incomplete if not outright faulty . It would be expedient to radically modify the same in view of its implication, for example on drug development.

Arch Biochem Biophys, 1995 Jan 10, 316(1), 327 - 34
The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli; Brunelli L et al.; The reactivity and toxicity of nitric oxide is modest in comparison to oxidants derived from nitric oxide . Exposure of Escherichia coli to 1 mM nitric oxide under aerobic or anaerobic conditions did not decrease viability of the bacteria . Peroxynitrite (1 mM), the reaction product of superoxide and nitric oxide, was completely bactericidal after 5 s . The nitrovasodilator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), slowly decomposes to release both nitric oxide and superoxide and thereby produces peroxynitrite . SIN-1 killed E . coli in direct proportion to its concentration with an LD50 of 0.5 mM . Copper, zinc superoxide dismutase (50-400 units/ml) provided substantial but not complete protection against SIN-1 killing . Catalase (500-10,000 units/ml) partially protected in direct proportion to its concentration, while inactivated catalase was not protective . Superoxide dismutase and catalase together completely protected E . coli against SIN-1 toxicity . Oxy-hemoglobin eliminated both SIN-1 and peroxynitrite toxicity . The bactericidal activity of SIN-1 was further enhanced by pterin plus xanthine oxidase . Pterin plus xanthine oxidase alone or together with Fe3+ ethylenediamine tetraacetate produced no significant decrease in E . coli viability . Hydrogen peroxide was not directly toxic to the bacteria, but E . coli pretreated with hydrogen peroxide were more susceptible to peroxynitrite, SIN-1, and the aerobic oxidation products of nitric oxide . Hydrogen peroxide pretreatment did not increase significantly the toxicity of nitric oxide under anaerobic conditions . Our results suggest that peroxynitrite is far more toxic to E . coli than nitric oxide or its by products from aerobic oxidation.

Crit Rev Oncog, 1995, 6(3-6), 327 - 56
Effects of benzalkonium salts on eukaryotic and microbial G-protein-mediated processes and surface membranes; Patarca R et al.; Benzalkonium salts comprise a group of positively charged surface-active alkylamine biocides with the general formula alkyldimethylbenzylammonium chloride or bromide . They interact with guanine nucleotide triphosphate-binding proteins (G proteins), thereby affecting signal transduction in a variety of cell types and processes . The present report reviews the known and potential basic science research and clinical applications and manifestations of benzalkonium salts . Benzalkonium salts have antiproliferative effects on a variety of cells through G-protein-dependent pathways, affect cytokine gene expression, and are also effective bactericidal, fungicidal, and virucidal agents with multisite (direct and immunologically-mediated) inhibitory activity against many pathogens, including the human immunodeficiency virus (HIV), papillomavirus, and herpesviruses . Therefore, benzalkonium salts not only appear to be effective as disinfectants and spermicides but may also prove useful in the prevention and treatment of neoplasias and other disease, particularly those linked to viruses and originating at the skin or mucosal surface.

Microbios, 1995, 84(340), 195 - 9
Effect of essential oils on the viability and morphology of Escherichia coli (SP-11); Pattnaik S et al.; The four essential oils (aromatic plant products) from palmarosa (Pm), lemongrass (Lg), peppermint (Pt) and eucalyptus (Eu) plants were found to be bactericidal to Escherichia coli strain SP-11, at a concentration of 1.66 (Pm, Lg and Eu) or 2.5 (Pt) microl ml-1 . This effect was observed both at 37 degrees C and 4 degrees C and was not prevented by immediate tenfold dilution or by the presence of 0.5 M sucrose . Pm and Pt but not Lg or Eu induced the formation of elongated filamentous forms, some measuring 60-70 micrometers long.

Microbiol Immunol, 1995, 39(9), 647 - 54
Temperature effects on Legionella pneumophila killing by and multiplication in phagocytes of guinea pigs; Miyamoto H et al.; We examined the effects of temperature on the interaction between Legionella pneumophila and phagocytes of guinea pigs . The body temperatures of guinea pigs infected with a sublethal dose (1.2 x 10(4) CFU) or a lethal dose (1.0 x 10(5) CFU) of L . pneumophila elevated from 38.4 +/- 0.15 C to 40.2 +/- 0.42 C or 40.3 +/- 0.62 C, respectively . The intracellular bacterial killing by and bacterial proliferation in the phagocytes were examined at 33, 37, 40, and 42 C, using in vitro culture systems of peritoneal macrophages or polymorphonuclear leukocytes (PMN) of guinea pigs . In all the macrophages incubated at different temperatures, significant intracellular bacterial killings were observed at 4 hr after in vitro phagocytosis . After 24 hr of incubation, there was about a 100-fold increase of CFU and the number reached a maximum after 48 hr of incubation in the macrophages incubated at 42 C as well as 37 and 40 C, suggesting that macrophages support the intracellular bacterial growth in hyperthermia . In the PMN, L . pneumophila CFU 4 hr or 12 hr after the infection were significantly lower at 42 C than those at 37 C (P < 0.05), indicating that the bactericidal capacity of PMN was enhanced at 42 C compared to 37 C . However, in all the PMN incubated at different temperatures, there were about 10-fold increases of CFU 24 hr after the infection, suggesting that PMN as well as macrophages support intracellular bacterial growth in hyperthermia . The extracellular bacterial growth was examined at 33, 37, 40, and 42 C in buffered yeast extract (BYE) broth or RPMI 1640 medium containing 50% guinea pig serum as a permissive or non-permissive liquid medium for the bacterial growth, respectively . Inhibition of bacterial growth in BYE broth at 42 C, and a decrease of CFU in RPMI 1640 medium containing 50% guinea pig serum at 42 C were observed . In conclusion, hyperthermia may be beneficial by restricting extracellular bacterial survival, but it exerts no beneficial effect on the restriction of intracellular bacterial growth in phagocytes, though PMN showed enhanced initial killing at 42 C . These results suggest that fever, or hyperthermia itself, may not largely contribute as a nonspecific host defense early in the course of legionellosis.

Nephron, 1995, 71(2), 176 - 9
Antioxidant enzymes activity in polymorphonuclear leukocytes in chronic renal failure; Shurtz-Swirski R et al.; In the present study, activity of polymorphonuclear leukocyte (PMNL) intracellular antioxidant enzymes, i.e . catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), was assessed in CRF patients on hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) and in healthy controls . The activity of SOD and GPX was reduced in HD and in CAPD (SOD: by 34.2 and 42%, respectively, and GPX 66 vs . 42%, respectively, taking the activity in normal controls as 100%) . Catalase activity, on the other hand, was significantly augmented (298 and 175%, respectively) as compared to the healthy controls . This impairment in antioxidant enzymes activity, involved in the respiratory burst and phagocytosis, may contribute to the understanding of the reduced bactericidal ability of PMNL activity found in these patients.

Annu Rev Nutr, 1995, 15, 93 - 110
Lactoferrin: molecular structure and biological function; Lonnerdal B et al.; Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears . It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis . The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced . Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria . Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses . Additionally, lactoferrin may function in ways not related to iron-binding, e.g . as a growth factor and as a bactericidal agent . This review attempts to evaluate these proposed functions and their biological significance in more detail.

C R Seances Soc Biol Fil, 1995, 189(3), 389 - 400
{Does nitric oxide stress exist?}; Torreilles J et al.; Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism . This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment . Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress . Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion . However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation . Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy . stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production . inhibition of ribonucleotide reductase: extensive inhibition of this key enzyme in DNA synthesis in the presence of large amounts of NO could lead to important antiproliferative effects; inhibition of cytochrome P450-dependent metabolism: in Kupffer cells and hepatocytes, LPS-induced overproduction of NO has been shown to inhibit cytochrome P450-dependent metabolism and to mediate the suppression of hepatic metabolism . Moreover, NO synthetized in the peripheral nervous system is known to mediate nonadrenergic noncholinergic (NANC) neurotransmission . Overstimulation of NO synthases might therefore contribute to pathophysiological states such as: gastrointestinal motility, reflux oesophagitis, asthma, adult respiratory distress syndrome (ARDS) and chronic pulmonary artery hypertension . To these NO-mediated biological functions, one could add the biological effects of NO-derivatives such as N-nitrosocompounds, which act as carcinogenic agents, or C-nitrosocompound which were recently used as "zinc-ejecting" agents to inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Nippon Kyobu Geka Gakkai Zasshi, 1995 Jan, 43(1), 69 - 73
{Successful surgical treatment of active infective endocarditis associated with perforation of aortic wall}; Noji S et al.; A 69-year-old man was transferred to our hospital because of severe progressive heart failure, eyeground hemorrhage due to embolism and uncontrollable inflammation . Emergent operation was suggested . Aortic valve replacement with a 23 mm Carpentier-Edwards bioprosthesis and patch closure of perforation using Dacron double velore was successfully performed . Vegetation was observed from the commissure between left and non coronary cusp to the aortic wall . Perforation (3 mm in diameter) and a moderate amount of bloody pericardial effusion were recognized . However periannular abscess was not detected . Postoperative course was uneventful and no recurrence of infection has been seen . We believe that surgical treatment for active infective endocarditis should be recommended when the bactericidal agents are ineffective and before the hemodynamics is suddenly deteriorated and the embolism occurs to the other organs.

J Dent Res, 1995 Jan, 74(1), 323 - 30
Reduction of infection-stimulated periapical bone resorption by the biological response modifier PGG glucan; Stashenko P et al.; Pulpal and periodontal diseases are bacterial infections which result in local connective tissue and bone destruction . Effective host resistance to these infections is primarily mediated by neutrophils and other phagocytic cells . PGG glucan (poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan) is a biological response modifier which stimulates the production of neutrophils and upregulates their phagocytic and bactericidal activity . In the present studies, the effect of PGG glucan on infection-stimulated alveolar bone resorption was tested in an in vivo model . Periapical bone resorption was induced in Sprague-Dawley rats by surgical pulp exposure and subsequent infection from the oral environment . Animals were administered PGG glucan (0.5 mg/kg) or saline (control) subcutaneously the day before and on days 2, 4, 6, 9, 11, 13, 16, and 18 following the pulp exposure procedure . PGG glucan enhanced the number of circulating neutrophils and monocytes and increased neutrophil phagocytic activity approximately two-fold . PGG glucan-treated animals had significantly less infection-stimulated periapical bone resorption than control animals, as determined radiographically (-48.0%; p < 0.001) and by histomorphometry (-40.8% and -42.4% for first and second molars, respectively; p < 0.001) . PGG glucan-treated animals also had less soft tissue destruction, as indicated by decreased pulpal necrosis . Only 3.3% of the first molar pulps from PGG glucan-treated animals exhibited complete necrosis, as compared with 40.6% of pulps from controls . Finally, PGG glucan had no effect on either PTH- or IL-1-stimulated bone resorption in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Dtsch Tierarztl Wochenschr, 1995 Jan, 102(1), 40 - 3
{The immune response in edema disease of weaned piglets measured with a recombinant B subunit of shiga-like toxin II}; Wieler LH et al.; An outbreak of edema disease (ED) was monitored in 80 piglets after weaning over a period of 4 weeks . The shedding of Shiga-like toxin-IIe) producing Escherichia coli strains, the serum bactericidal activity (SBA) against SLTEC-IIe, and the antibody response against SLT-IIe were investigated . The antibody response was monitored by utilizing a glutathione-S-transferase (GST) + SLT-IIe B/SUB fusion protein (FRANKE et al., in press) for immunoblot assays . E . coli-strain GO15III (0141:K85ac) was diagnosed as SLT-IIe-producing E . coli by polymerase chain reaction, DNA hybridization and cytotoxicity assays . Maximum excretion of GO15III appeared between days 8 and 15 after weaning . On day 1 after weaning no piglet shed GO15III, while the number increased on day 8 to 53 (66.2%) and on day 15 to 59 (73.8%) of the piglets . 4 week after weaning, GO15III was only isolated from 23 (28.8%) of the piglets . In parallel, serum bactericidal activity against GO15III increased significantly in the sera of 73 (91.2%) piglets, reaching a stable maximum from day 15 on . During the first two weeks after weaning, no piglet yielded detectable SLT-IIe-IgG . However, the number of SLT-IIe-IgG positive piglets increased steadily from day 15 . On day 15, 5 (6.2%) piglets were positive in SLT-IIe immunoblot analysis and 29 days after weaning the number increased to 31 (38.8%) . These data represent the first serological monitoring of a natural outbreak of edema disease in piglets after weaning by using a recombinant fusion protein (GST+SLT-IIe B/SUB) . The recombinant protein proved to be a useful diagnostical tool for monitoring the specific antibody status of piglets.

Biol Trace Elem Res, 1995 Jan-Mar, 47(1-3), 37 - 50
Effect of iron and phagocytosis on murine macrophage activation in vitro; Gauthier YP et al.; Iron-exposed murine macrophages have a modified bactericidal activity as shown by previous observations . In order to assess the role of iron in macrophage activation, as measured by free radical production and by intracellular bacterial killing, murine peritoneal macrophages were cultivated in the presence of various sources of iron, human iron-saturated transferrin and ammonium ferric citrate, or iron chelators, Desferal, and human Apo-transferrin, and were infected with an enteropathogenic strain of E . coli . The release of nitrite (NO2-), and the production of superoxide anion (O2-) and hydrogen peroxide (H2O2) by the phagocytes were measured and compared to the production by uninfected macrophages . The synergistic action with murine r.IFN-gamma was also studied in the radical production reaction and for the bactericidal activity of macrophages . Our results show that in vitro phagocytosis of E . coli induced elevated production of NO2- and H2O2 by macrophages, and that oxygen derivatives were released independently of the presence of added iron or chelator . Despite a phagocytosis-related enhancement of NO2- release, reactive nitrogen intermediates (RNI) are not directly involved in the bactericidal mechanism, as revealed by increased intracellular killing owing to RNI inhibitors . Moreover, bacterial killing may depend on oxygen derivatives, as suggested by the effect of the antioxidant sodium ascorbate leading to both a diminished H2O2 production and a decreased bactericidal activity of macrophages.

Eur J Appl Physiol Occup Physiol, 1995, 70(2), 187 - 91
Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects; Benoni G et al.; In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects . Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects . Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise . In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production . In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations.

Acta Orthop Belg, 1995, 61(1), 10 - 3
Utility of measurement of gentamicin release from PMMA beads in wound drainage fluid after in-vivo implantation; Jenny JY et al.; Acute or chronic osteomyelitis in 188 patients was treated by surgical debridement and filling of the cavity with gentamicin-PMMA beads . The gentamicin concentration was measured in the total drainage fluid of the first postoperative day . There was no correlation between this concentration and the amount of implanted beads . It is impossible to predict preoperatively the gentamicin concentration which will be obtained in situ . The measurement of gentamicin concentration in the total drainage fluid of the first postoperative day and its comparison to the minimal bactericidal concentration of responsible pathogens, allow very early assessment of the effectiveness of the local antibiotherapy and if necessary, adaptation, of systemic antibiotherapy.

Surg Today, 1995, 25(4), 302 - 6
Factors related to impaired bactericidal activity in patients with esophageal cancer; Shigemitsu Y et al.; We examined the possible factors that could contribute to the impairment of polymorphonuclear neutrophil (PMN) bactericidal activities in patients with esophageal cancer, based on the discovery that a depression of the intracellular killing (KI) activity, with an elevation of the superoxide anion-producing capacity (SOP), of PMN is associated with the occurrence of infectious complications following surgery for esophageal cancer . KI, SOP, and myeloperoxidase (MPO) activity were measured in 30 patients with esophageal cancer and 33 patients with gastric cancer . Sex, age, and cancer stage were not significantly associated with impaired bactericidal activities; however, malnutrition was significantly correlated with both a depression in KI (r = 0.58, P < 0.001) and an elevation in SOP (r = -.36, P < 0.05) in the patients with esophageal cancer, but not in those with gastric cancer . The incidence of chronic obstructive pulmonary disease (COPD) was significantly higher in the esophageal cancer patients whose SOP was elevated, at 39% versus 0% (P < 0.05) . These results suggest that malnutrition and probably also latent infections associated with COPD contribute to the impaired bactericidal activities of PMN in patients with esophageal cancer.

Life Sci, 1995, 57(5), 443 - 7
A novel bacteristatic action of bovine and porcine serum that is reversed by norepinephrine; Lenard J et al.; A previously unreported anti-bacterial activity against Escherichia coli has been found in porcine and bovine sera, but not in human or chicken sera . The activity is not affected by heat inactivation of the complement system, and is bacteriostatic rather than bactericidal . Growth inhibition is reversible by addition of norepinephrine.

Nephron, 1995, 70(1), 21 - 4
Parathyroid hormone and the cellular immune system; Shurtz-Swirski R et al.; Parathyroid hormone (PTH) is the main hormone controlling calcium concentration in the extracellular fluid (ECF) through its biological activity on bone, kidney and intestine . However, data published over the last two decades indicate that PTH may act as an immunomodulator . The purpose of the present review is to summarize the effects of PTH on various immune functions . Polymorphonuclear leukocytes of patients with chronic renal failure (CRF) and elevated blood levels of PTH showed impaired migration, reduced phagocytic and bactericidal activity, and inhibited granulocyte chemotaxis . Antibody production and T and B lymphocyte proliferation are affected by PTH, both in vivo and in vitro . Possible implications of the involvement of PTH and its fragments in CRF are discussed.

Wien Med Wochenschr, 1995, 145(7-8), 162 - 5
{Growth inhibition of Borrelia burgdorferi sensu lato by antibodies . A contribution to understanding the pathogenesis and improving diagnosis of Lyme borreliosis}; Sadziene A et al.; Phenomenon of growth inhibition of Borrelia burgdorferi sensu lato (BBSL), the agent of Lyme disease, by antiborrelial antibodies was observed and investigated . Some of the antiborrelial antibodies were bactericidal in the absence of complement and phagocytes . Based on growth inhibition phenomenon we developed and evaluated the function-oriented in vitro growth inhibition assay (GIA) . GIA proved to be more strain-specific and a better predictor of protection against infectious challenge than matrix-based assays, such as ELISA and Western blot . Growth inhibition phenomenon was also applied as a tool for selection of antibody-resistant BBSL mutants . All BBSL isolates characterized to date have one or a combination of several major outer surface proteins (Osps) . Mutants of BBSL with altered or absent Osps were selected with polyclonal or monoclonal antibodies (mAbs) at a frequency of 10(-2) to 10(-6) . Based on PAGE and Western blot analysis all examined mutants were catalogued into 4 classes . Some of these mutants were later employed in studies of functional importance of Osps in immunopathogenesis of BBSL . Several studies revealed some possible functions of Osp proteins in borrelias . In one study, Osp-lacking mutant was distinguished from its Osp-bearing parent by autoaggregation and slower growth rate, diminished capacity to adhere to human umbilical vein endothelial cells, decreased plating efficiency on solid medium as well as serum and complement sensitivity . Mutant also was unable to evoke a detectable immune response after intradermal live cell immunization even though mutant cells survived in mouse skin for the same duration as wild type cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Annu Rev Pharmacol Toxicol, 1995, 35, 213 - 33
Nitric oxide in the nervous system; Zhang J et al.; Nitric oxide (NO) has only recently been appreciated as a normal biologic substance with a role in signal transduction . It was first identified as endothelial-derived relaxing factor in blood vessels and as the mediator of the tumoricidal and bactericidal actions of macrophages . NO's role as a neural messenger may be even more prominent . Biosynthesis of NO involves oxidation of the guanidine group of arginine with stoichiometric formation of citrulline . NO synthase is one of the most extensively regulated enzymes in biology . In the periphery, NO is a likely transmitter of nonadrenergic, noncholinergic neurons . In the brain, NO neurons mediate action of glutamate acting at N-methyl-D-aspartate (NMDA) receptors . Excess release of NO appears to account for a major portion of neural damage following vascular stroke.

J Clin Gastroenterol, 1995, 20 Suppl 2, S44 - 6
Quality of peptic ulcer healing induced by lansoprazole and roxatidine; Fujino MA et al.; This study reports preliminary results of a controlled, multicenter trial on the quality of ulcer healing induced by lansoprazole (LPZ) or roxatidine (R) in gastric ulcer (GU) or duodenal ulcer (DU) patients . Group A received LPZ 30 mg q.d . and group B received R 75 mg b.i.d . All drugs were given for 8 weeks in GU and for 6 weeks in DU . Endoscopy and gastric biopsy were performed to detect Helicobacter pylori before and on completion of treatment . The healing rates of groups A and B were 100 and 69.2%, respectively, in GU and 100 and 70.0%, respectively, in DU . This difference (p < 0.01) was significant between the two groups in GU . There was no significant difference between the two groups in the S2 stage shift rate in GU and DU . The H . pylori clearance rates of groups A and B were 33.3 and 20.0%, respectively, in GU and 62.5 and 33.3%, respectively, in DU . The differences in treatment response (healing rates and S2 shift rates) between the LPZ group and the R group may be related to the differences in suppression of acid secretion and in bactericidal effects on H . pylori.

J Infect Dis, 1994 Dec, 170(6), 1483 - 9
Characterization of two monoclonal antibodies directed against bactericidal/permeability-increasing protein; Dentener MA et al.; In this study the production and characterization of two monoclonal antibodies (MAbs), 4E3 and 5D7, against the bactericidal/permeability-increasing protein (BPI) were described . Using ELISAs, both 4E3 and 5D7 were shown to detect recombinant (r) BPI . Furthermore, natural BPI present in polymorphonuclear leukocytes (PMNL) was detected by both 4E3 and 5D7 . The use of both MAbs in flow cytometry revealed that PMNL expressed low levels of cell-surface BPI . Lipopolysaccharide (LPS) was shown to block the interaction between anti-BPI MAb and rBPI . In addition, the MAbs blocked biologic activity of rBPI . The inhibition by BPI of LPS activation of the limulus amebocyte lysate assay and of LPS-induced tumor necrosis factor-alpha release by monocytes was prevented by 4E3 and 5D7 . Both MAbs are specifically directed against BPI and can inhibit BPI bioactivity.

Infect Immun, 1994 Dec, 62(12), 5419 - 23
Difference in Legionella pneumophila growth permissiveness between J774.1 murine macrophage-like JA-4 cells and lipopolysaccharide (LPS)-resistant mutant cells, LPS1916, after stimulation with LPS; Kura F et al.; To elucidate the role of the oxidative burst in macrophage resistance to Legionella infection, we examined a murine macrophage-like cell line, J774.1, for permissiveness to Legionella growth, using a mutant that has a selective defect in the oxidative burst after lipopolysaccharide (LPS) stimulation . Legionella pneumophila serogroup 1 was infected into J774.1 monolayers, and then the extent of bacterial growth was estimated by a CFU assay . Both the parental cell line, JA-4, and the LPS-resistant mutant, LPS1916, were permissive for Legionella growth but became nonpermissive after pretreatment with gamma interferon . However, pretreatment of LPS1916 cells with LPS failed to inhibit bacterial growth, although LPS-treated JA-4 cells exhibited inhibited multiplication of the bacteria . The bacterial growth inhibition in JA-4 and mutant LPS1916 cells was correlated with the extent of the oxidative burst in the cells, as judged by cytochrome c reduction but not nitrite production . Neither transferrin receptor expression nor the iron content in JA-4 and LPS1916 cells, with or without LPS treatment, was correlated with suppression of Legionella growth . These results suggest that the restriction of Legionella growth in J774.1 cells is due to a bactericidal effect of the oxidative burst rather than reduction of the iron supply to the intracellular bacteria and that the effectors are reactive oxygen intermediates and not reactive nitrogen intermediates.

Infect Immun, 1994 Dec, 62(12), 5296 - 304
The PapG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bactericidal activity; Tewari R et al.; Compared with Escherichia coli ORN103, a nonfimbriated K-12 strain, P-fimbriated E . coli ORN103/pPAP5 was found to interact poorly with human neutrophils and resist their bactericidal activity in vitro . PapG, the Gal alpha(1-->4)Gal binding moiety located at the distal end of the P fimbrial filament, appeared to be responsible for this effect because an isogenic PapG- mutant, E . coli ORN103/pPAP24, exhibited binding interactions with neutrophils that were similar to nonfimbriated E . coli ORN103 . Although no direct evidence is available, the poor adherence mediated by PapG could be related to its electrostatic properties because the isolated PapG protein had a pI of 5.2, which indicated that in the physiological pH range it possessed a net negative charge . Antibodies against PapG overcame the protective effect of PapG and markedly enhanced the interactions of P-fimbriated E . coli with neutrophils resulting in bacterial killing . When a P-fimbriated clinical E . coli strain or its isogenic PapG- derivative was injected into the peritoneal cavities of mice, a similar number of neutrophils was recruited to the site of injection . After 2 h, the number of P-fimbriated E . coli organisms that survived the neutrophil influx in the mouse peritoneum was approximately four times more than the number of surviving PapG- bacteria . This result demonstrates that the PapG protein, which is strategically located at the distal region of the P-fibrillum structure, protects E . coli from the bactericidal action of neutrophils.

Environ Health Perspect, 1994 Dec, 102 Suppl 10, 43 - 4
Aspects of the release of superoxide by leukocytes, and a means by which this is switched off; Karnovsky ML et al.; Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (O2-), it is possible that a component or components, might have been overlooked . Furthermore, O2- production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells . It is important, therefore, that a biologic mechanism exist to turn off O2- production by stimulated leukocytes . This article offers evidence that methoxatin (PQQ), a redox-cycling orthoquinone, might be involved in O2- production by leukocytes . This is based on the fact that inhibitors of O2- production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance . Addition of PQQ to cells blocked with the inhibitors partially restored O2- release . With respect to turning off cellular O2- release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old) . Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked O2- release . This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes . It was partially purified by column (sizing) chromatography and HPLC . It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.

Leukemia, 1994 Dec, 8(12), 2188 - 93
Effect of ubenimex on the proliferation and differentiation of U937 human histiocytic lymphoma cells; Murata M et al.; We investigated the effect of ubenimex on the growth and differentiation of U937 cells, a histiocytic lymphoma cell line . Ubenimex is a dipeptide ((2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine) and an inhibitor of aminopeptidase B produced by Streptomyces olivoreticuli . Ubenimex inhibited the proliferation of U937 cells in a dose-dependent manner . Ubenimex-treated U937 cells showed condensation of nuclear chromatin, increase of cytoplasmic vacuoles and more intense nonspecific esterase staining compared with untreated U937 cells . Expression of CD13 and CD68 detected by monoclonal antibodies My7 and EBM11, respectively, was enhanced by ubenimex, but the expression of CD4 detected by MT310 was significantly decreased . The effects of ubenimex on U937 cell growth inhibition and enhancement of monocytic cell surface marker expression on U937 cells were reversible when cultivated without ubenimex for more than 6 days . In addition, the bactericidal activity of U937 cells was increased by ubenimex treatment, and was further enhanced by treatment with macrophage colony-stimulating factor (M-CSF) . Furthermore, ubenimex augmented the expression of M-CSF receptors by U937 cells and enhanced the tyrosine kinase activity of cellular pp60c-src . These findings indicated that ubenimex inhibited the proliferation of U937 cells and induced morphological, cytochemical and functional differentiation into monocyte/macrophages.

J Trauma, 1994 Dec, 37(6), 909 - 12
Augmentation of alveolar macrophage phagocytic activity by granulocyte colony stimulating factor and interleukin-1: influence of splenectomy; Hebert JC et al.; The use of cytokines and other naturally occurring substances as biopharmaceuticals for modulating the host response to trauma and infection offers new therapeutic possibilities . Cytokine pretreatment protects animals in a variety of experimental models, including splenectomized mice following pneumococcal aerosol challenge . Since splenectomy appears to affect alveolar macrophage function, we postulated that pretreatment with interleukin 1 (IL-1) and granulocyte colony stimulating factor (G-CSF) improved survival in mice following aerosol challenge of live pneumococci by activating alveolar macrophages . Alveolar macrophage bactericidal and phagocytic function was slightly, but consistently, depressed following splenectomy . Interleukin-1 and G-CSF pretreatment had pronounced effects on macrophage phagocytic and bactericidal activity, and these effects were quite different depending upon whether the mice were eusplenic or asplenic . Splenectomy augmented the effects of IL-1 on alveolar macrophage bactericidal function compared with eusplenic mice (p < 0.001), while more pronounced effects on macrophage function following G-CSF treatment were seen in mice with intact spleens (p < 0.001) . The use of cytokines and other substances to modify the host response to infection has great potential . Individuals with deficits such as splenectomy will have a different net response to therapy . It is important that we be able to predict these responses accurately in most patients in order to use these substances more effectively.

Am J Respir Crit Care Med, 1994 Nov, 150(5 Pt 1), 1355 - 62
Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice; Chapuis L et al.; The effectiveness of intermittent administration of rifapentine (RPT), with or without isoniazid (INH), for preventive therapy of tuberculosis was evaluated in immunocompetent (normal) and nude mice . After infection with a small inoculum of Mycobacterium tuberculosis H37Rv, normal mice developed a chronic and nonfatal infection, and the bacterial population became relatively stable after an initial period of limited multiplication . On the other hand, nude mice developed an acute and fatal infection, and all untreated mice died within 5 wk, with very high colony-forming-unit (CFU) counts in their organs . Various degrees of bactericidal activity were shown in normal mice after daily treatment with rifampin (RMP) plus pyrazinamide (PZA) for 13 wk, INH daily for 26 wk, or RPT once weekly for 13 or 26 wk or once fortnightly for 26 wk . The activity of RPT was significantly enhanced when INH was added at the same dosing frequency . In nude mice the response of M . tuberculosis infection to certain regimens was less favorable than that in normal mice, suggesting that preventive therapy may be less effective in severely immunodeficient hosts even during treatment . After chemotherapy was stopped, virtually all nude mice relapsed within 12 wk regardless of the regimen administered, whereas no or very few relapses were observed in normal mice that had been treated with RMP+PZA daily for 13 wk, or RPT alone or RPT+INH once weekly for 26 wk . The latter three regimens and RPT+INH once weekly for 13 wk may be applied for fixed-duration preventive therapy in human immunodeficiency virus (HIV)-negative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Vet Surg, 1994 Nov-Dec, 23(6), 442 - 7
Effects of 0.05% chlorhexidine lavage on the tarsocrural joints of horses; Wilson DG et al.; In six horses, a 0.05% solution of chlorhexidine diacetate was used to lavage one tarsocrural joint; the contralateral control joint was lavaged with lactated Ringer's solution . Horses were evaluated daily for lameness . Synovial fluid samples were collected on days 1, 4, and 8 for determination of protein concentration, total and differential leukocyte counts, and mucin clot formation . After death on day 8, synovium and osteochondral samples were collected from the tarsocrural joints for examination of morphology and proteoglycan staining . Lavage with chlorhexidine solution caused lameness that was reduced but still evident at day 8 . Synovial protein concentration was significantly increased by chlorhexidine lavage; the greatest increase occurred on day 1 . Joint lavage increased synovial leukocyte counts on day 1, primarily by increasing polymorphonuclear (PMN) cell counts . Although total synovial leukocyte counts returned to normal by day 4, PMN cell counts remained elevated through day 8; PMN cell counts for chlorhexidine-lavaged joints were typically twice that of control joints . Chlorhexidine lavage caused synovial ulceration, inflammation, and abundant fibrin accumulation . Consistent differences in proteoglycan staining were not detected between control and chlorhexidine-lavaged joints . Joint lavage with 0.05% chlorhexidine diacetate, the lowest known bactericidal concentration, is not recommended for equine joints.

Agents Actions, 1994 Nov, 43(1-2), 24 - 8
Interactions of P 1507, a new antioxidant agent, with phagocyte functions; Meloni F et al.; Toxic oxygen free radicals are believed to play a role in the pathogenesis of a number of respiratory diseases . In particular, pulmonary emphysema may occur because of the oxidative impairment of alpha 1-proteinase inhibitor (alpha 1-PI) . We report in vitro data on a new thiol agent, P 1507 {N-5-(thioxo-L-prolyl)-L-cysteine}, obtained in a series of experiments designed in view of its therapeutic potential in these clinical conditions . We found that P 1507 at the concentration of 5 x 10(-6) M was able to almost fully abolish the PMA-triggered PMN-induced oxidative impairment of alpha 1-PI . Protection may be due to the radical scavenger ability of P 1507, that markedly reduced superoxide anion production from PMNs . We also found that P 1507 did not significantly impair other defence mechanisms of PMNs (i.e . phagocytosis, chemotaxis and bactericidal activity) . The release of cytokines (TNF-alpha, IL-6 and IL-8) from monocytes was not altered in the presence of P 1507 . We conclude that the compound P 1507 may be considered for treatment of clinical conditions characterized by overload of oxidants, on the basis of its ability in preventing the oxidative damage of alpha 1-PI and of a lack of unwanted inhibitory effects towards defence mechanisms of phagocytes.

J Antimicrob Chemother, 1994 Nov, 34(5), 613 - 27
Antibiotic susceptibility testing by flow cytometry; Pore RS; The first significant development in antibiotic susceptibility testing in recent years may be the flow cytofluorometric susceptibility test (FCST) . The advanced analytical capability of the flow cytometer has provided the means to measure microbial diversity in culture . Membrane integrity and other indicators of microbial viability can be evaluated on a cell-by-cell basis . The FCST measures subtle dosage-response effects as well as the conventional minimum inhibitory and minimum bactericidal concentrations, simultaneously, in rapid tests which have the potential to supersede conventional techniques in terms of sensitivity and reproducibility.

J Wound Ostomy Continence Nurs, 1994 Nov, 21(6), 224 - 31
A rational approach to the use of topical antiseptics; Doughty D; The proper application of antiseptics to the open wound is controversial . With the goal of creating an optimal environment for wound repair, consideration of a topical antiseptic includes both its bactericidal activity and its potential cytotoxicity when applied to the healing wound in varying concentrations . This discussion reviews the events of wound healing, including the key cells that mediate this process, the significance of bacteria in the wound bed, and the impact of infection . Specific antiseptics, including povidone-iodine, hydrogen peroxide, acetic acid, and Dakin's solution are reviewed, emphasizing their bactericidal potential and their cytotoxic properties.

Alcohol, 1994 Nov-Dec, 11(6), 539 - 47
Ethanol suppresses LPS-induced mRNA for nitric oxide synthase II in alveolar macrophages in vivo and in vitro; Greenberg SS et al.; Alcohol abuse increases the incidence and severity of opportunistic lung infections and pneumonias . Inducible nitric oxide (NO) synthase (iNOS II) and NO may be a pivotal system in the intracellular bactericidal activity of macrophages . We tested the hypothesis that acute administration of ethanol (ETOH) suppressed Escherichia coli endotoxin lipopolysaccharide (LPS) mediated upregulation of the iNOS II system in the lung of the rat, in vivo . We also tested the effect of ETOH on alveolar macrophage (AM) production of free NO using microelectrodes . Male Sprague-Dawley rats were given ETOH (5.5 g/kg, IP) 30 min . before giving intratracheal sterile phosphate buffered saline solution (PBS, 0.5 ml) or LPS (1 mg/kg in a total volume of 0.5 ml PBS) . The isolated lungs were subjected to bronchoalveolar lavage (BAL) 3.5 hr . later . Aliquots of the BAL fluid were assayed for tumor necrosis factor alpha TNF alpha and reactive nitrogen intermediates (nitrate and nitrite) (RNI) with chemiluminescence . Aliquots of AM were incubated 1 hr ex vivo for spontaneous production of RNI or frozen and assayed for iNOS II mRNA with competitor exchange reverse transcriptase polymerase chain reaction (cERT-PCR) . The lung was homogenized and assayed for RNI . LPS increased BAL fluid TNF alpha and RNI, lung RNI, and the spontaneous production of RNI by AM, ex vivo . These effects were inhibited by in vivo administration of inhibitors of iNOS II . LPS increased iNOS mRNA in AM . This was unaffected by iNOS inhibitors . ETOH suppressed LPS-induced BAL fluid TNF, iNOS mRNA and RNI production by AM and the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

J Biol Chem, 1994 Oct 21, 269(42), 26331 - 7
Structural determinants of the action against Escherichia coli of a human inflammatory fluid phospholipase A2 in concert with polymorphonuclear leukocytes; Weiss J et al.; Extracellular 14-kDa phospholipases A2 (PLA2) in inflammatory exudates can contribute to bacterial phospholipid (PL) degradation during phagocytosis of Escherichia coli by polymorphonuclear leukocytes (PMN) and are highly active toward E . coli treated with the bactericidal/permeability-increasing protein (BPI) purified from PMN . PLA2 activity toward BPI-treated E . coli varies greatly among members of this conserved family of enzymes and apparently depends on a cluster of basic residues in a variable surface region near the NH2 terminus for recognition of this biological target (Weiss, J., Wright, G.W., Bekkers, A.C.A.P.A., van den Bergh, C.J., and Verheij, H.M . (1991) J . Biol . Chem . 266, 4162-4167) . We have examined by site-specific mutagenesis of a recombinant PLA2 that is identical to an enzyme in human synovial fluid (containing His-6, Arg-7, Lys-10, and Lys-15 and a global net charge of +15) the role of basic residues in this region in PLA2 action against PLA-deficient (pldA-) E . coli . Substitution of Ser for Arg-7 +/- Gln for Lys-15 caused, respectively, about a 10- and 25-fold reduction in BPI-dependent PLA2 binding and activity to E . coli, but had no effect on hydrolysis of PL of autoclaved E . coli or dispersions of purified PL . PL degradation during phagocytosis was increased after pretreatment of E . coli (or PMN) with wild-type PLA2 followed by removal of unbound PLA2 . Thus, the PLA2 binds to cells before phagocytosis followed by internalization of the enzyme along with E . coli and intracellular action . Mutant (e.g . R7S +/- K15Q) PLA2 show the same BPI-independent binding to E . coli as the wild-type enzyme but 10-30-fold reduced activity during phagocytosis, reflecting lower intracellular activity of these enzymes . Thus, structural determinants first implicated in PLA2 action toward E . coli treated with purified BPI apparently are also important in the intracellular action of PLA2 during phagocytosis by PMN.

Int J Sports Med, 1994 Oct, 15(7), 441 - 5
Suppressed PMA-induced oxidative burst and unimpaired phagocytosis of circulating granulocytes one week after a long endurance exercise; Gabriel H et al.; Ten endurance athletes performed two exhaustive intensive endurance exercises (Ex1: 21 +/- 7 min; Ex2: 18 +/- 6 min) on a cycle ergometer at 110% of their individual anaerobic threshold (maximal lactate concentration at Ex1: 9.7 +/- 2.3 mmol.1-1, Ex2: 9.5 +/- 2.2 mmol.l-1) . Ex1 was performed two weeks before, Ex2 8 or 9 days after a long endurance competition (duration: 762 +/- 74 min), respectively . At both exercises before, at the 10th, during the last two and 60 minutes after exercise venous blood samples were taken to determine rat and activity of phagocytosis (FITC-conjugated, opsonized E . coli) and oxidative burst (intracellular oxidation of dihydrorhodamine123 to rhodamine123 after induction by phorbol-myristate-acetate) was measured in circulating granulocytes by flow cytometry . Statistical analysis was performed with procedures of ANOVA . Neither at Ex1 nor at Ex2 rate or activity of phagocytosis changed significantly over time, a difference between Ex1 and Ex2 was not observed . In contrast to Ex1, at Ex2 the bactericidal capacity of granulocytes decreased significantly by 37% at the end of exercise . This effect at Ex2 was reversible within the first hour of recovery . The observed transient and partial suppression of the oxydative burst was not accompanied by clinically apparent infections . Therefore, we conclude that the observed in vitro effect is without major clinical importance in healthy subjects.

Clin Infect Dis, 1994 Oct, 19(4), 774 - 6
Transient exacerbation of tuberculous lymphadenitis during chemotherapy in patients with AIDS; Hill AR et al.; We describe three men with disseminated, drug-sensitive tuberculosis and advanced human immunodeficiency virus disease (CD4+ lymphocyte count, < 50/mm3) who had flares of tuberculous lymphadenitis with suppuration during the initial weeks of successful chemotherapy . Bactericidal drugs may kindle these transient exacerbations, which involve neutrophils but apparently do not require normal helper T cell function . In patients with AIDS, as in immunocompetent individuals, treatment-related flares of lymphadenitis are usually not an adverse sign, provided that drug resistance and nonadherence have been excluded.

Immunobiology, 1994 Oct, 191(4-5), 478 - 92
T cell helper types and endocrines in the regulation of tissue-damaging mechanisms in tuberculosis; Rook GA et al.; The necrotising immunopathology, which is accompanied by very little mycobactericidal activity, is probably the key to the pathogenesis of tuberculosis . Conventional chemotherapy fails to correct this immunoregulatory anomaly, so the host response does little to assist the drugs in the removal of the "persister" subpopulation of bacteria . Therefore chemotherapy must be prolonged for at least 6 months, with consequent problems of cost, resistance, and compliance . If we can learn to switch off the necrotising pathway, and replace it with bactericidal mechanisms, treatment of the disease will be enormously improved and shortened . One problem is that we do not know the mechanism of cell-mediated immunity to tuberculosis in man . On the other hand, we are gaining some insights into the mechanism of the necrosis, and there are encouraging indications that it can indeed be separated from immunity, and that it can be suppressed by suitable immunotherapy . We present here some evidence that when a TH2 response is superimposed upon a pre-existing TH1 response, the resulting cell-mediated inflammatory site becomes exquisitely sensitive to cytokine-mediated damage . There is clear evidence for a TH2 component in the immune response of tuberculosis patients . This inappropriate TH1 to TH2 shift may result from subtle endocrinological changes brought about by M . tuberculosis and the response to it . Immunotherapy should aim to switch off this TH2 component.

J Mol Biol, 1994 Sep 30, 242(4), 351 - 63
The complex of DNA gyrase and quinolone drugs with DNA forms a barrier to transcription by RNA polymerase; Willmott CJ et al.; The effects of DNA gyrase and quinolone drugs on in vitro transcription of a template containing a preferred gyrase cleavage site have been investigated . We have found that gyrase-quinolone complexes with DNA lead to blocking of transcription by Escherichia coli and bacteriophage T7 RNA polymerases . Either gyrase or quinolone alone has no effect on transcription . With DNA gyrase containing a point mutation in the gyrase A protein, known to confer quinolone resistance, blocking was found to occur only at much higher concentrations of the drug . Other agents that inhibit gyrase-catalysed supercoiling (novobiocin and 5'-adenylyl-beta,gamma-imidodiphosphate) do not arrest transcription in the presence of gyrase . Mapping of the transcription termination sites in the presence of gyrase and quinolones shows that blocking occurs about 10 to 20 base-pairs upstream of the gyrase cleavage site . Analysis of transcription in the absence of drug suggests that RNA polymerase does not displace gyrase from the template . These results are discussed in the light of models for the bactericidal effects of quinolone drugs.

Infect Immun, 1994 Sep, 62(9), 3930 - 6
Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury; Arditi M et al.; Bactericidal/permeability-increasing protein (BPI), a human neutrophil granule protein, has been shown to bind lipopolysaccharide (LPS) and neutralize LPS-mediated cytokine production in adherent monocytes and the whole-blood system . In this study we investigated the ability of recombinant human BPI (rBPI) to inhibit LPS-induced vascular endothelial cell (EC) injury and activation . rBPI inhibited significantly both rough and smooth LPS-mediated injury for cultured bovine brain microvessel ECs, as measured by lactic dehydrogenase release, and blocked the LPS-induced interleukin-6 (IL-6) release from human umbilical vein ECs in a dose-dependent manner . BPI was able to inhibit LPS-mediated EC injury or activation whether it was added before or at the same time with LPS, but delaying the time of addition of rBPI resulted only in a partial inhibition . BPI also inhibited LPS-induced tumor necrosis factor alpha, IL-1 beta, and IL-6 release from human whole blood . This inhibition of tumor necrosis factor alpha, IL-1 beta, and IL-6 release from whole blood was maximal when BPI was premixed with LPS before addition to blood and was partial when BPI was added simultaneously with LPS, but no inhibition was observed when the addition of rBPI was delayed for 5 min . These findings suggest that rBPI is a potent inhibitor of LPS-mediated responses in ECs and whole blood and underscore the potential use of BPI in treatment or prevention of endotoxic shock . In contrast, the anti-lipid A monoclonal antibodies HA-1A and E5 were ineffective in inhibiting LPS-mediated EC injury and activation as well as LPS-induced cytokine release in whole blood.

J Immunol, 1994 Sep 1, 153(5), 2110 - 21
Resistance of Actinobacillus pleuropneumoniae to bactericidal antibody and complement is mediated by capsular polysaccharide and blocking antibody specific for lipopolysaccharide; Ward CK et al.; Actinobacillus pleuropneumoniae is resistant to complement-mediated killing, even in the presence of specific Ab . Our studies focused on identifying the mechanism(s) responsible for this resistance . Encapsulated A . pleuropneumoniae was susceptible to killing in precolostral calf serum (PCS) but not in normal serum as a complement source in the presence of anti-capsular polysaccharide (CP) IgG . In contrast, two capsule-deficient mutants were sensitive to killing in normal serum and one was sensitive to killing in PCS alone . Electron microscopy demonstrated that A . pleuropneumoniae serotype 5a synthesized a thick, adherent CP that bound anti-CP Ab distant from the outer membrane . The CP of A . pleuropneumoniae did not prevent complement activation or the attachment of C3 to the cell surface . However, the CP did limit the amount of C9, a component of the membrane attack complex, that bound to A . pleuropneumoniae in PCS . A second mechanism of serum resistance was a result of an LPS-specific Ab present in the IgG fractions of normal swine serum, swine anti-K17 serum, and guinea pig anti-K17 LPS that blocked anti-CP IgG complement-mediated killing of A . pleuropneumoniae . Incubation of swine anti-K17 IgG with purified K17 LPS depleted Abs specific for K17 LPS but not for K17 proteins and removed all blocking activity . Immune swine serum containing this blocking Ab reduced the deposition of C9 on A . pleuropneumoniae in the presence of anti-CP IgG and also directed the deposition of C9 to sites on the bacteria in which the bound C9 was easily eluted . Thus, CP and anti-LPS Ab may act synergistically or at different stages of infection to limit the ability of complement to eliminate A . pleuropneumoniae.

Int J Lepr Other Mycobact Dis, 1994 Sep, 62(3), 359 - 64
Activity of two doses of rifampin against Mycobacterium leprae; Husser JA et al.; In the course of a clinical trial designed to re-examine the bactericidal efficiency of 600-mg doses of rifampin (RMP) against Mycobacterium leprae, two doses of RMP, either 600 mg or 1200 mg, were administered 28 days apart to 29 previously untreated patients with lepromatous or borderline leprosy . Seven, 28, and 35 days after the start of the trial, skin biopsies were performed and immunologically normal mice were inoculated with 5 x 10(3) or 10(4) M . leprae in each hind foot pad . The patients assigned to the two regimens did not differ significantly in terms of sex, age, disease classification, bacterial index, or the concentration of M . leprae in the skin lesion biopsied for the inoculation of mice . The concentrations of organisms in the skin-biopsy specimens did not change significantly over the course of the trial among the patients, whether they were being treated by the first or the second regimen . The M . leprae recovered from specimens obtained from 21 of the patients, before beginning treatment, multiplied in a majority of the mice inoculated . The results of mouse inoculation confirmed the rapid bactericidal effects of RMP against M . leprae: a single dose of RMP rendered the organisms obtained from all but two of the patients incapable of multiplying in mice . No significant difference was demonstrated between the two regimens, nor was an additional effect of the second dose of RMP observed.

Indian Pediatr, 1994 Sep, 31(9), 1075 - 8
Pulmonary cavitatory tuberculosis in children; Vijayasekaran D et al.; This study was undertaken to analyse children with pulmonary cavitatory tuberculosis which is a rare and infectious condition . The pretreatment characteristics, course and response to three different anti-tuberculous regimes in 27 children with cavitary pulmonary lesions registered at the TB Clinic, Institute of Child Health, are described . Male:Female ratio was 1.2:4 . Thirty per cent of affected children were below 3 years of age and had predominant lower lobe involvement whereas in older children the upper lobes were affected . Eighty five per cent of children had definite history of contact with an adult with tuberculosis . Tuberculin test was positive in 70% of children . Cavitary lesion were observed in the right lung in 66% of cases . Follow up and surveillance was carried out in 23 children who completed the anti tuberculous treatment . Regimes with isoniazid, rifampicin, pyrazinamide and streptomycin were given to different groups . Response and compliance was also monitored . Eleven out of 23 children had persistence of radiological lesions even after completion of 9 months of therapy . Inclusion of streptomycin with 2 or 3 bactericidal drugs in the intensive phase showed a better response.

J Antimicrob Chemother, 1994 Sep, 34(3), 421 - 4
Bacteriostatic and bactericidal activities of paromomycin against Mycobacterium avium complex isolates; Piersimoni C et al.; The MICs and MBCs of paromomycin for 32 Mycobacterium avium complex (MAC) strains isolated from patients with the acquired immunodeficiency syndrome were determined by a radiometric broth dilution method . The MICs for the majority of strains were either 8 or 16 mg/L and the MBCs were four- to eight-fold higher . Paromomycin merits further evaluation as oral prophylaxis against disseminated MAC infection.

Nat Struct Biol, 1994 Sep, 1(9), 597 - 604
The domain structure of the ion channel-forming protein colicin Ia; Ghosh P et al.; Colicin Ia undergoes a transition from a soluble to a transmembrane state, forming an ion channel to effect its bactericidal activity . The X-ray crystal structure of soluble colicin Ia at an effective resolution of 4 A reveals that the molecule is highly alpha-helical and has an unusually elongated 'Y'-shape . The stalk and two arms of the 'Y' form three discrete structural domains which most likely correspond to the three functional regions identified for the channel-forming colicins . The channel-forming region of colicin Ia can be located to the larger of the two arms, the insertion domain, by its structural similarity to the ten alpha-helix motif found for the ion channel-forming fragments of colicins A and E1 . The domain arrangement found in this structure provides novel insights into the mechanism of membrane insertion of colicin Ia.

Urol Nefrol (Mosk), 1994 Sep-Oct, (5), 24 - 7
{The preoperative anti-inflammatory and postoperative therapy of patients with calculous pyelonephritis and prostatic adenoma with chronic prostatitis under outpatient polyclinic conditions}; Shabad AL et al.; Such wide-spread urological diseases as nephrolithiasis and prostatic adenoma requiring surgical management are often associated with chronic infection or inflammation (pyelonephritis, prostatitis, adenomitis) . Relevant antiinflammatory treatment as a rule is conducted after the patient hospitalization which may induce unwanted emotional stress, occasional hospital infection, additional material expenditures . The authors have the experience of bactericidal and antiinflammatory treatment of the kidneys (143 patients with nephrolithiasis) and prostate (287 patients with adenoma) in the outpatient setting . Three-stage system of the patients' care is recommended: district outpatient clinic-consultative outpatient department of the Research Urological Center-Hospital of the above Center . Such an approach noticeably improved the treatment outcomes: the frequency of inflammatory postoperative complications reduced 2-fold, no more lethal outcomes occurred, the duration of the hospital stay decreased two-fold . The authors suggest to introduce the above three-stage system of pre- and posthospital outpatient antiinfectious and antiinflammatory treatment of nephrolithiasis-affected kidney and prostate in adenoma into the practice of all national, regional and local urological centers.

Antimicrob Agents Chemother, 1994 Sep, 38(9), 1959 - 65
Assessment of mycobacterial viability by RNA amplification; van der Vliet GM et al.; We investigated whether the presence of intact RNA is a valuable indicator of viability of mycobacteria with Mycobacterium smegmatis . M . smegmatis was exposed to various concentrations of rifampin and ofloxacin suspended in broth for different periods of time . The NASBA nucleic acid amplification system was used because of its rapid, sensitive, and specific detection of 16S rRNA . During drug exposure, the viability of the mycobacteria, expressed by the number of CFU, was compared with the presence of 16S rRNA as determined by NASBA and with the presence of DNA coding for 16S rRNA as determined by PCR . Both NASBA and PCR were shown to have a detection limit of approximately 5 x 10(2) CFU/ml . The intensity of the NASBA signal corresponded well with the number of CFU, and the lack of NASBA signal coincided with a loss of viability, which was reached after 3 days of exposure to bactericidal concentrations of both drugs . The presence of mycobacterial DNA, as determined by the intensity of the PCR signal, and the viability of M . smegmatis were not related, but an increase in the number of cells and intensity of PCR signal correlated well . Bacterial viability may thus be assessed by a rapid, sensitive, and specific, and semiquantitative technique by using NASBA . This system of viability testing provides the potential for rapid evaluation of drug susceptibility testing.

Ann N Y Acad Sci, 1994 Aug 15, 730, 26 - 36
Identification of genes involved in the resistance of mycobacteria to killing by macrophages; Mundayoor S et al.; The survival of M . leprae and M . tuberculosis in the human host is dependent upon their ability to produce gene products that counteract the bactericidal activities of macrophages . To identify such mycobacterial genes and gene products, recombinant DNA libraries of mycobacterial DNA in E . coli were passed through macrophages to enrich for clones carrying genes that endow the normally susceptible E . coli bacteria with an enhanced ability to survive within macrophages . Following three cycles of enrichment, 15 independent clones were isolated . Three recombinants were characterized in detail, and each confers significantly enhanced survival on E . coli cells carrying them . Two of the cloned genetic elements also confer enhanced survival onto M . smegmatis cells . Further characterization of these genes and gene products should provide insights into the survival of mycobacteria within macrophages and may identify new approaches of targets for combatting these important pathogens.

Hepatology, 1994 Aug, 20(2), 326 - 30
Impaired ability of neutrophils to produce oxygen-derived free radicals in patients with chronic liver disease and hepatocellular carcinoma; Uehara M et al.; To evaluate whether neutrophil bactericidal function, the ability to produce oxygen-derived free radicals, is altered in patients with chronic liver disease, we measured chemiluminescence amplified by a luciferin analog (Cypridina luciferin analog-dependent chemiluminescence) and luminol (luminol-dependent chemiluminescence) in response to N-formyl-Met-Lue-Phe by neutrophils from patients with chronic liver diseases due to C and/or B type hepatitis: chronic active hepatitis, cirrhosis and hepatocellular carcinoma . Both Cypridina luciferin analog-dependent chemiluminescence and luminol-dependent chemiluminescence were significantly decreased in neutrophils from patients with chronic liver disease (hepatocellular carcinoma < cirrhosis < chronic active hepatitis) when they were compared with normal healthy subjects . The reduction of Cypridina luciferin analog-dependent chemiluminescence in chronic active hepatitis and cirrhosis was more sensitive than Cypridina luciferin analog-dependent chemiluminescence; however, in hepatocellular carcinoma, luminol-dependent chemiluminescence was more reduced than luminol-dependent chemiluminescence . Although there were not significant correlations between glutamic pyruvic transaminase and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence, there were significant negative correlations between total bilirubin and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence . Furthermore, there were significant positive correlations between albumin/prothrombin time and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence . These data suggest that an impaired ability to produce oxygen-derived free radicals may contribute to the susceptibility to infection in patients with chronic liver disease.

J Immunol, 1994 Aug 1, 153(3), 1171 - 9
Bovine parainfluenza-3 virus selectively depletes a calcium-independent, phospholipid-dependent protein kinase C and inhibits superoxide anion generation in bovine alveolar macrophages; Dyer RM et al.; Bovine parainfluenza-3 (PI-3) virus inhibits oxygen-dependent bacterial killing by phagocytes, a key pulmonary defense, thus predisposing the host to intrapulmonary bacterial superinfection . PI-3 virus inhibited opsonized zymosan or PMA-activated superoxide anion (O2-) generation in bovine alveolar macrophages . The respiratory virus influenza also inhibits O2- generation by phagocytes, however, the mechanisms(s) of viral inhibition differs from PI-3 . PI-3 did not trigger O2- generation before inhibition, whereas influenza triggered O2- generation before desensitization of ligand-initiated respiratory burst . PI-3 modified the twin signals of calcium and protein kinase C in alveolar macrophages . PI-3 infection increased macrophage membrane permeability to extracellular calcium, but did not inhibit calcium mobilization triggered by opsonized zymosan . These effects further distinguish bovine PI-3 from human influenza, which triggers mobilization of cell-associated calcium and inhibits calcium mobilization activated by physiologic ligands . Macrophages possessed two classes of PKC activity, a calcium/phosphatidylserine/diglyceride (Ca/PS/DG))-dependent activity and a Ca-independent, PS/DG-dependent histone IIIS phosphorylating activity . PI-3 infection selectively depleted the Ca-independent, PS/DG-dependent kinase activity but not the classical Ca/PS/DG-dependent activity . Inhibition of Ca-independent, PS/DG-dependent kinase activity and inhibition of O2- generation by PI-3 occurred at a similar viral dose and time frame, suggesting a role for this kinase in activating the respiratory burst . Inhibition of the oxygen-dependent bactericidal function of alveolar macrophages and disturbances in signal transduction may contribute to the immunosuppression and bacterial superinfection accompanying viral respiratory disease.

Inflammation, 1994 Aug, 18(4), 419 - 26
Impact of intravenous infusions of low and high doses of gamma globulins (IVIG) on phagocytic functions in adults with primary humoral immunodeficiency; Van T et al.; Twelve adult patients with primary humoral immunodeficiency were treated for at least six months with IVIG 200 mg/kg/mo and then crossed over to a high dose of 600 mg/kg/mo . Polymorphonuclear and mononuclear cells of these patients were tested after the third infusion in the low-dose cycle and then after the third infusion in the high-dose cycle, each time a day before, four days after, and 14 days after intravenous infusion . Each time, patients' cells and normal cells were tested using normal sera and patients' sera . IVIG infusions led to a significant increase in the level of circulating IgG, which was much more prominent in the high-dose group . Phagocytosis, phagocytic index, intracellular bactericidal activity and chemotaxis of polymorphonuclear cells (PMNs) were at least as active as in healthy controls . Actually in both cycles patients' PMN's had slightly higher phagocytic activity than normal cells . Patients' serum in the high dose cycle supported chemotaxis better than normal serum . Efficient phagocytic activity was maintained throughout the cycle; however, it was more active (P < 0.0125) in the midcycle in the high-dose cycle . Superoxide generation was normal in all conditions . Monocytic function was also normal in all conditions tested . It may be concluded that as far as cellular phagocytic functions are concerned, the high dose of IVIG does not protect the host more efficiently than the low dose.

Trends Microbiol, 1994 Aug, 2(8), 284 - 8
Mechanisms of persistence of mycobacteria; Britton WJ et al.; Pathogenic mycobacteria use a variety of mechanisms to survive and replicate within mononuclear phagocytic cells, including avoidance of early direct activation of macrophages, interference with gamma-interferon-mediated activation and inhibition of bactericidal products . Developments in genetic manipulation should allow the genes involved in mycobacterial virulence and intracellular survival to be identified . Understanding these mechanisms may lead to more effective treatment and prevention of mycobacterial infections.

Lett Appl Microbiol, 1994 Aug, 19(2), 102 - 4
Antagonists of bacitracin; Podlesek Z et al.; Three groups of substances were identified which inhibit the bactericidal activity of bacitracin . Beside two divalent metals, Mg2+ and Ca2+, and a metabolite with chelating properties, citrate, the most pronounced effect was observed with pyrophosphate . Metals probably prevent access of bacitracin to the lipid carrier whereas metabolites with chelating properties deprive the bacitracin of a metal ion needed for its binding to the lipid carrier . Pyrophosphate, effective as an antagonist at very low concentrations, may intercept the binding of bacitracin to the pyrophosphate part of the target molecule.

Aliment Pharmacol Ther, 1994 Aug, 8(4), 425 - 31
The effect of tripotassium dicitrato bismuthate on the rat stomach; Waldum HL et al.; BACKGROUND: Bismuth has been used as symptomatic treatment of dyspepsia for many years . It promotes healing of peptic ulcers and reduces their recurrence . The beneficial effect of bismuth on duodenal ulcer disease is thought to be due to an effect on Helicobacter pylori, although it has a rather weak bactericidal effect on H . pylori in vitro . Eradication of H . pylori in duodenal ulcer patients by a combination of bismuth, tetracycline and metronidazole has been reported to increase the density of somatostatin-producing D cells in the antrum . A reduced D cell density in the antral mucosa of duodenal ulcer patients could explain their exaggerated gastrin release . AIMS/METHODS: To test the possibility that bismuth could affect the neuroendocrine cells independently of the presence of H . pylori or not, we gave rats a diluted tripotassium dicitrato bismuthate solution by gastric gavage for 14 days . RESULTS: Tripotassium dicitrato bismuthate treatment did not affect maximal pentagastrin-stimulated acid secretion or histamine release in isolated rat stomachs or the density of argyrophil cells in the oxyntic and antral mucosa . However, it significantly reduced the duodenal concentration of gastrin and calcitonin gene-related peptide, and the density of G cells in the antrum and duodenum . CONCLUSION: The effect of tripotassium dicitrato bismuthate on the G cell may be of significance for its beneficial effect on duodenal ulcer disease.

J Immunol, 1994 Jul 15, 153(2), 743 - 52
Molecular cloning, characterization, and tissue distribution of rat lipopolysaccharide binding protein . Evidence for extrahepatic expression; Su GL et al.; LPS binding protein (LBP) is a glycoprotein present in normal serum that becomes markedly elevated during acute phase responses . LBP has been reported to greatly potentiate host responses to endotoxin or LPS . Therefore, LBP may play a critical role in the body's response to injury and infection . Little is known about the factors regulating production of LBP . To investigate the regulation of LBP expression, we have cloned the full-length cDNA for rat LBP . The deduced amino acid sequence of rat LBP was highly homologous with that reported for rabbit and human LBP . The sequence of rat LBP further refines the conserved regions found within the family of proteins that bind LPS; this family is comprised of bactericidal permeability-increasing protein and LBP from multiple species . Use of the rat LBP cDNA clone for Northern blot analysis reveals that LBP mRNA levels are markedly up-regulated in liver during acute phase responses . However, in contrast to previous reports, we also find evidence of extrahepatic expression of LBP under these induced conditions . The presence of LBP mRNA in activated tissues other than liver suggests that LBP may play a larger role in local tissue responses to LPS than previously appreciated.

J Submicrosc Cytol Pathol, 1994 Jul, 26(3), 405 - 14
Estrogen induced peroxidase secretion from the endometrial epithelium: a possible function for the luminal enzyme; Wang G et al.; Estrogen induced peroxidase (EIP) activity revealed as a diaminobenzidine-H2O2 product in electron micrographs is apparent within cisternae of the RER and in large dilated apical vesicles, of which only a few have been seen to open into the uterine lumen . EIP activity is infrequently present in the trans cisternae of the rather diminutive Golgi complex in uterine epithelial cells from 12-72 h after treatment with estrogen . EIP activity is, however, prominent on the surface of microvilli of epithelial cells and as deposits in the lumen . Desalted uterine fluid (72 h) isolated by rotofor (Biorad) and analysed on isoelectric focusing gels that were stained with the diaminobenzidine-H2O2 reaction, reveal the existence of at least 6 peroxidase isoelectric variants with isoelectric points between pI 3.5 and pI 5.0 . In similar preparations doubly-stained by diaminobenzidine-H2O2 and silver, peroxidase positive bands are enhanced, along with other isoelectric variants in the acidic pI range . In SDS-PAGE preparations, five prominent proteins ranging from 29-115 kD are present in 72 h uterine fluid . Luminal EIP coats the surface microvilli of the reproductive tract cells, and of viable spermatozoa incubated in uterine fluid . Peroxidase coated bacteria appear to be in the process of decay, and enzyme activity is present on the surface of most spermatozoa . It is not yet determined if EIP has bactericidal, spermicidal or capacitation functions.

Ann Hematol, 1994 Jul, 69(1), 33 - 40
Hematologic aspects of end-stage renal failure; Zachee P et al.; Renal dysfunction may give rise to a variety of hematologic disturbances, including anemia, leukocyte dysfunction, and coagulopathy . The anemia of renal failure has been attributed to a relative deficiency of erythropoietin, but absolute deficiencies of iron or folate may also play a role . Other contributing factors include heavy-metal toxicity, blood loss, and a reduction in red cell survival induced by toxic radicals . The treatment of the anemia of renal disease has advanced with the development of recombinant human erythropoietin . At subcutaneous doses of 50-75 IU/kg triweekly in selected patients, normalization of hemoglobin is presently possible . The coagulopathy of renal disease consists of an acquired qualitative platelet defect, best remedied by dialysis but also treated successfully by rHuEPO, cryoprecipitate or DDAVP, and conjugated estrogens . Uremia-induced leukocyte dysfunctions include diminished granulocyte chemotaxis, phagocytosis, and bactericidal activity . Cell-mediated immune defects and hypogammaglobulinemia have also been described . The pathophysiology of the hematologic manifestations of uremia is discussed . Therapeutic recommendations for dealing with anemia, bleeding, and infectious complications of renal failure are described.

Ann Surg, 1994 Jul, 220(1), 77 - 85
Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI; Rogy MA et al.; OBJECTIVE: The in vivo neutralizing activities of an anti-lipopolysaccharide (LPS) antibody HA-1A (Centoxin {Centocor, Malvern, PA}), a human immunoglobulin M monoclonal antibody, and of bactericidal/permeability-increasing protein (BPI), an endogenously produced human LPS-neutralizing protein, were studied in a primate model of lethal Escherichia coli bacteremia . SUMMARY BACKGROUND DATA: HA-1A has been used with variable success against LPS activity in some animal models and in a recently reported clinical trial . However, no data assessing the efficacy of this agent in subhuman primates is available . Bactericidal/permeability-increasing protein is a product of polymorphomononuclear cells (PMNs) that is stored in azurophilic granules and exhibits LPS-neutralizing activity in vitro and in some in vivo models . METHODS: Immediately after E . coli infusion and in a blinded fashion, three baboons were treated with BPI (5 mg/kg bolus infusion and 95 micrograms/kg/min infusion over 4 hr) . Three animals received 3 mg/kg BW of HA-1A, whereas another three baboons received a placebo treatment . RESULTS: The BPI-treated animals demonstrated significantly (p < 0.03) lower circulating LPS-limulus amoebocyte lysate (LAL) activity compared with the control animals, but this reduction in LPS-LAL activity was not associated with improved survival . HA-1A treatment did not reduce LPS-LAL activity . However, both BPI and HA-1A treatment did attenuate the pro-inflammatory cytokine response . CONCLUSION: The current data suggests that incomplete neutralization of endotoxin activity does not alter mortality from severe bacteremia . Given the diversity of mediator production under such circumstances, a strategy of combination therapy in the form of anti-lipopolysaccharide and anticytokine treatment may be necessary to achieve optimal survival.

Am J Respir Cell Mol Biol, 1994 Jul, 11(1), 114 - 22
Aggregation and opsonization of type A but not type B Hemophilus influenzae by surfactant protein A; McNeely TB et al.; The ability of surfactant protein A (SP-A) to aggregate and opsonize type a and b Hemophilus influenzae was investigated . Type a, but not type b, was aggregated by SP-A . Aggregation was maximal at 24 micrograms SP-A/ml and was Ca(2+)-dependent . Aggregation of type a was inhibited by D-glucosyl-BSA but not by high concentrations of monosaccharides (D-mannose, D-galactose, D-glucose, or L-fucose) or by sialic acid, purified type a capsular polysaccharide, or type IV collagen . In Western blots, 125I-labeled SP-A bound to the major outer membrane protein (putatively P2) of type a hemophilus by a Ca(2+)-dependent mechanism . This binding was competitively inhibited by excess unlabeled SP-A . 125I-labeled SP-A also bound to the major membrane protein of type b, but at less than 5% of the level observed for type a . SP-A did not bind to lipooligosaccharides of either type a or type b . SP-A increased association of type a, but not type b, hemophilus with alveolar macrophages . After opsonization with SP-A, type a hemophilus were killed by alveolar macrophages, as indicated by bactericidal assays and the release of soluble, radiolabeled products from leukocytes . It is concluded that SP-A aggregated and opsonized type a hemophilus, but not type b, possibly because SP-A bound to the P2 outer membrane protein of type a to a greater extent.

Antimicrob Agents Chemother, 1994 Jul, 38(7), 1651 - 4
Clinical trial of fusidic acid for lepromatous leprosy; Franzblau SG et al.; Fusidic acid was assessed for antileprosy activity in nine lepromatous leprosy patients . Patients received fusidic acid at either 500 mg/day for 12 weeks or 750 mg/day for 4 weeks followed by 500 mg/day for 8 weeks . All patients showed time-dependent clinical improvement and decreases in bacillary morphological index, radiorespirometric activity and PCR signal, and in serum phenolic glycolipid I . Fusidic acid appears to be a weakly bactericidal antileprosy agent which may have a role in the multidrug treatment of leprosy pending an evaluation of lepra-reaction-suppressive activity.

Indian J Med Res, 1994 Jul, 100, 1 - 4
Early bactericidal action of pulsed exposure to rifampicin, ethambutol, isoniazid & pyrazinamide in pulmonary tuberculosis patients; Paramasivan CN et al.; The bactericidal action of two therapeutic regimens on Mycobacterium tuberculosis was assessed by viable counts in serial sputum samples in 49 pulmonary tuberculosis patients being treated with rifampicin (R), ethambutol (Emb), isoniazid (I) and pyrazinamide (Z) together in a single dose thrice weekly (REmbIZ3) or with REmb and IZ on alternate days (REmb3IZ3alt) . In both groups of patients, there was a significant reduction (P < or = 0.02) in the colony forming units (cfu) of M . tuberculosis per ml of sputum during the first two days of treatment itself . This early bactericidal action (EBA) as well as the reduction in counts during the subsequent days of treatment were similar (P > 0.2) for both REmbIZ3 and REmb3IZ3alt regimens indicating that splitting up REmbIZ into REmb on one day and IZ on the next day in short course chemotherapy (SCC) regimens may not affect the bactericidal action of the regimens.

Dev Comp Immunol, 1994 Jul-Aug, 18(4), 277 - 86
Inhibition of in vitro replication of the oyster parasite Perkinsus marinus by the natural iron chelators transferrin, lactoferrin, and desferrioxamine; Gauthier JD et al.; The mammalian iron-binding proteins transferrin and lactoferrin, the bactericidal peptide lactoferricin B, and the bacterial siderophore desferrioxamine were tested for their ability to inhibit the in vitro replication of the oyster parasite Perkinsus marinus . All three chelators were effective in reducing the parasite proliferation in a dose-dependent manner . Lactoferricin B, a peptide of lactoferrin that exhibits bactericidal properties unrelated to iron chelation, had no inhibitory activity on the parasite . When the chelators were partially or completely saturated with the appropriate iron equivalents, their inhibitory effects on the parasite proliferation were diminished or abolished accordingly, confirming that this activity was related to the chelator's capacity for iron sequestration . Our results indicate that the parasite has a strong requirement for soluble iron and its growth rates are correlated with iron availability . We propose that excess iron accumulation in the host Crassostrea virginica promotes parasite proliferation . P . marinus may avoid oxidative damage that would compromise its intracellular survival by exhaustion the host's intracellular selected iron pools required for superoxide and hydroxyl radical production.

Comp Biochem Physiol Biochem Mol Biol, 1994 Jul, 108(3), 375 - 84
Serotransferrin, ovotransferrin and metallothionein levels during an immune response in chickens; Hallquist NA et al.; Extracellular iron-binding proteins function in iron transport, iron scavenging and bactericidal activity . To determine whether the levels of chicken iron-binding proteins are altered during an immune challenge, young broiler chicks and 40-week-old hens were injected with lipopolysaccharide (LPS) . Serum transferrin and liver mRNA for serum transferrin increased at 24 hr after injection . Increased levels of serum transferrin and hepatic mRNA for serum transferrin define chicken serum transferrin as an acute-phase protein . Magnum mRNA for ovotransferrin decreased 24 hr after the immune challenge in hens . Hens had also stopped ovulating, suggesting that synthesis of all egg proteins was decreased.

J Biol Chem, 1994 Jul 1, 269(26), 17411 - 6
Bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding protein . LPS binding properties and effects on LPS-mediated cell activation; Wilde CG et al.; We have previously shown that human bactericidal/permeability-increasing protein (BPI) is able to inhibit serum-dependent lipopolysaccharide (LPS)-mediated activation of human monocytes and neutrophils in vitro, and to counteract the lethal effects of LPS challenge in vivo . Lipopolysaccharide-binding protein (LBP) is a serum protein which participates in LPS-mediated activation of cells (Tobias, P . S., Mathison, J., Mintz, D., Lee, J . D., Kravchenko, V., Kato, K., Pugin, J., and Ulevitch, R . J . (1992) Am . J . Respir . Cell . Mol . Biol . 7, 239-245) . We have proposed that BPI functions in a negative feedback loop which opposes this activation (Marra, M . N., Wilde, C . G., Collins, M . S., Snable, J . L., Thornton, M . B., and Scott, R . W . (1992) J . Immunol . 148, 532-537) . We have now cloned and expressed recombinant forms of human BPI and LBP . Here we demonstrate that purified recombinant human LBP can replace the serum requirement for both LPS binding to human monocytes and LPS-mediated secretion of tumor necrosis factor alpha from these cells . These activities of LBP are inhibited by a neutralizing anti-CD14 monoclonal antibody . We further demonstrate that purified recombinant human BPI can inhibit LBP-mediated LPS binding to cells and their subsequent activation . Comparison of the LPS binding properties of BPI and LBP in enzyme-linked immunosorbent type assays and in the Limulus amebocyte lysate assay suggest that BPI has a stronger affinity for LPS than does LBP . Direct competition between BPI and LBP for LPS may explain the inhibition by BPI of the proinflammatory effects of LBP in the presence of LPS.

Immunobiology, 1994 Jun, 190(4-5), 399 - 410
Mannan-binding protein-like activity in the sera of newborn piglets; Dlabac V et al.; The mechanism of the antibody-independent bactericidal activity of the sera of newborn piglets deprived of colostrum was studied using rough strains of E . coli and S . typhimurium . Although all strains were invariably killed by all newborn piglet sera tested, two different mechanisms of killing were encountered . Using specific anti-pig C1q antiserum, strains S . typhimurium LT2Ml and E . coli K-12, strain Gal 23 were found to be killed by a C1q-dependent mechanism, while the killing of E . coli S 16, E . coli K-12, strain W 3100 and E . coli B 41 could not be inhibited by anti-C1q antiserum . In order to test whether a mannan-binding protein is responsible for the bactericidal effect in the latter group of strains, we examined the inhibitory activity of two types of mannans isolated from S . cerevisiae and H . capsulata, respectively . The use of a purified rabbit mannan-binding protein showed that only strains killed by the C1q-independent mechanism were sensitive to the MBP-dependent mechanism of killing, the inhibitory activities of both mannans were found to be equal . As expected, the inhibitory effect of mannan on the bactericidal activity of newborn piglet sera was also detected only in strains killed by the C1q-independent mechanism . Surprisingly, only the phosphomannan isolated from H . capsulata was found to be an effective inhibitor of the bactericidial activity of piglet sera against E . coli S 16 and E . coli K-12, strain W 3100, while the mannan isolated from S . cerevisiae was inactive . Hence the factor present in newborn piglet sera is either MBP with slightly different binding properties, or a completely different protein.

Am J Vet Res, 1994 Jun, 55(6), 810 - 4
Inhibition of complement-mediated killing of Brucella abortus by fluid-phase immunoglobulins; Hoffmann EM et al.; Bovine immunoglobulin preparations from normal serum and from sera containing antibodies against Brucella abortus interfered with the brucellacidal action of bovine serum, whereas unfractionated normal serum and antisera were not inhibitory . The inhibitory property of immunoglobulin appeared to be attributable to some anticomplementary property because it also interfered with serum-mediated hemolysis of antibody-coated erythrocytes . The supernatant phase obtained after ultracentrifugation of bovine anti-B abortus immunoglobulin did not inhibit brucellacidal activity of normal bovine serum . Results of this study indicate that bovine anti-B abortus immunoglobulin preparations contain microaggregates of protein that can inhibit the ability of bovine serum to kill B abortus . The most likely mechanism is nonspecific activation of complement by microaggregated immunoglobulin, which consumes complement and makes it unavailable for bactericidal activity.

Int J Biomed Comput, 1994 Jun, 36(1-2), 59 - 67
Animal models of endocarditis; Carbon C; Bacterial endocarditis is a difficult infection to cure, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action . The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans remains of great importance due to the difficulties encountered in clinical trials . The advantage of the experimental model is that besides the fact that it closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens: number of bacteria per gram of tissue, frequency of emergence of resistance, positivity of blood cultures, death vs . survival rates, and percentage of relapses after treatment has been stopped . All these parameters are more sensitive and more easy to study than in humans . The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on the therapeutic outcome . Two main aspects are discussed for their relevance to human therapy: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters with respect to antibiotic dosing regimens and length of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Biomed Comput, 1994 Jun, 36(1-2), 121 - 5
Pharmacokinetic parameters of vancomycin for therapeutic regimens in neutropenic adult patients; Le Normand Y et al.; Vancomycin (V) is widely used in neutropenic patients, though its kinetics are known in this type of patient . In the present study, ten patients were included: all of them received an intensive therapy for non-Hodgkin malignant lymphoma, Hodgkin disease, myeloma, acute leukemia, followed by an autologous bone marrow transplantation in 6 cases . All patients were neutropenic (100/mm3) . The pharmacokinetic study was done at the first V administration: 1000 mg V were injected as a 1-h infusion . Plasma V concentrations were measured by an enzyme immunoassay (EMIT, Syva, France) . V maximal and minimal concentrations were 61.3 +/- 38.6 micrograms/ml and 1.69 +/- 0.77 microgram/ml, respectively . Total V clearance was 158 +/- 51 ml/min, with a creatinine clearance of 141.2 +/- 36.2 ml/min on test day . V plasma kinetics can be described by a biexponential model, with the following parameters: {table: see text} These data show a 3-fold increase of initial volume of distribution and a shortened (3-fold) T1/2 beta, if compared to values obtained in normal subjects . Because the bactericidal effect is time dependent, there can be a risk of insufficient antibiotic effect throughout the day . Our data suggest that new therapeutic regimens are needed for these patients.

Int J Biomed Comput, 1994 Jun, 36(1-2), 117 - 9
Teaching individualized antibiotic dosage regimens by means of two computer-assisted learning programs; Le Normand Y et al.; We developed two multidisciplinary tutorial programs (TOBRA-DIDACT and VANCO-DIDACT) for teaching the basic principles of antibiotic drug monitoring by simulation of repeated administrations to fictitious patients whose physio-pathologic characteristics were pre-defined in the programs . To illustrate the two types of bactericidal kinetics, we have chosen one time-dependent (vancomycin) and one concentration-dependent (tobramycin) antibiotic . These computer-assisted programs operate on an interactive mode . In each of them, three main steps are connected: (1) Various types of clinical cases are submitted to the student: for each of them, case report includes clinical characteristics, location of infection, bacterial strain and minimal bactericidal concentration . These data must be taken into account during the following steps . (2) The student has to establish the treatment schedule: route of administration, dose for each injection, intervals between injections and duration of infusion . (3) The result of the dosage scheme proposed by the student is represented by a simulation of plotting antibiotic plasma concentrations vs . time during the first 4 days of treatment . These curves are obtained by a monoexponential (TOBRA-DIDACT) or biexponential (VANCO-DIDACT) pharmacokinetic model . Peak and trough concentrations are calculated at steady-state . An expert system provides a commentary with each result to evaluate the efficacy of the treatment and to assist the student in improving his prescription . TOBRA-DIDACT and VANCO-DIDACT illustrate the influence of age, obesity, renal impairment, location of infection and bacterial strain on antibiotic therapy . They also show the role of route of administration, dosing and intervals between injections on therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS)

J Immunol, 1994 May 15, 152(10), 5070 - 6
Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes . Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein; Leeuwenberg JF et al.; Previously we demonstrated that two soluble(s) tumor necrosis factor receptors, TNF-R55 as well as sTNF-R75, are constitutively released in vitro by monocytes, and that this release was markedly enhanced after activation . Because LPS is an important activator of monocytes, we investigated the effect of LPS on sTNF-R release by monocytes . It was found that release of sTNF-R75, but not (or minimally) release of sTNF-R55, was enhanced after activation with LPS, reaching plateau levels after approximately 2 days . CD14, one of the membrane receptors for LPS, is an intermediate in this process, as shown in experiments using mAb directed against CD14 . Under serum-free conditions, LPS-induced sTNF-R75 release was less as compared with release in the presence of serum, suggesting involvement of serum proteins . Addition of LPS binding protein (LBP) enhanced the LPS-induced sTNF-R75 release under serum-free conditions, but had no effect in the presence of serum . On the other hand, bactericidal/permeability-increasing protein (BPI), known to possess LPS neutralizing activity, inhibited LPS-induced sTNF-R75 release . Furthermore, cell surface expression of both types of TNF-R was shown to be controlled by LPS, LBP, and BPI . LPS caused, within 1 h, a complete reduction of TNF-R55 as well as TNF-R75 expression, followed by enhanced re-expression of both receptors after 24 h . The down-modulation of expression was increased by LBP, whereas BPI counteracted the LPS-induced down-regulation . The LPS-enhanced release of sTNF-R75, capable of inactivation of TNF, as well as LPS-induced initial down-modulation of TNF-R expression leading to postulated temporary unresponsiveness to TNF may share in a physiological mechanism to carefully control the effects of TNF.

J Leukoc Biol, 1994 May, 55(5), 633 - 41
Induction of mycobacterial proteins during phagocytosis and heat shock: a time interval analysis; Alavi MR et al.; Mycobacterium tuberculosis survives macrophage bactericidal activities by mechanisms that may include induction of stress proteins . We sought to determine whether the synthesis of any mycobacterial proteins is increased during phagocytosis and whether any of these proteins are also up-regulated during heat shock . Protein synthesis by M . tuberculosis H37Ra during phagocytosis by the mouse macrophage cell line IC-21, and during heat shock at 45 and 48 degrees C, was monitored at various time intervals using 35S-labeled methionine/cysteine and sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Our data suggest the existence of certain common elements in the stress response of mycobacteria to the three stress stimuli . This apparent similarity was best characterized by the up-regulation of a 25-kDa protein after exposure to each of the stress conditions . Furthermore, this 25-kDa protein and a 37-kDa protein that was also synthesized during phagocytosis appeared to be extracellular because they were preferentially solubilized when infected macrophages were lysed with 0.5% NP-40.

Immunopharmacol Immunotoxicol, 1994 May, 16(2), 261 - 80
Decrease of phagocytic functions in hypertensive rats; Serio M et al.; The present investigation was aimed to examine non-specific immunologic capabilities of spontaneously hypertensive rats (SHR) during the development of hypertension . In vitro phagocytosis and oxidative killing exerted by monocytes, polymorphonuclear cells (PMN) and splenic macrophages (SpM0) were evaluated in SHR at 5-, 8-, and 24-weeks of age . Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls . Results showed that in pre-hypertensive stage (5-wk) there was no difference between SHR and WKY rats with regard to non-specific immunologic functions . Statistically significant differences in both phagocytosis and oxidative killing arose in early hypertensive stage (8-wk) and became more marked in adult SHR with established hypertension (24-wk) . In conclusion, our data provide evidence of novel immunologic abnormalities in SHR in terms of ingestion and bactericidal phagocytic capabilities . The mechanisms responsible for these impaired immunologic functions may depend on various suppressive factors which will be object of discussion.

Anal Biochem, 1994 May 1, 218(2), 377 - 81
A method for screening hypochlorous acid scavengers by inhibition of the oxidation of 5-thio-2-nitrobenzoic acid: application to anti-asthmatic drugs; Ching TL et al.; Neutrophils use a bactericidal mechanism through the release of the enzyme myeloperoxidase which catalyzes the formation of the powerful oxidant hypochlorous acid (HOCl) from H2O2 and Cl- . HOCl can inactivate alpha 1-antiproteinase (alpha 1-AP) which causes increased proteolytic activity at sites of pulmonary inflammation . The search for possible HOCl scavengers usually involves time-consuming enzyme assays (e.g., alpha 1-AP and elastase) . We developed a method in which the compound 5-thio-2-nitrobenzoic acid could easily be oxidized by HOCl . The inhibition of this oxidation by a test compound is a measurement of its HOCl scavenging activity . To illustrate the method we tested some well-known HOCl scavengers such as S-methylated glutathione and oxidized lipoate . Finally several anti-asthmatic drugs such as terbutaline, isoproterenol, salbutamol, cromoglycate, theophylline, and dexamethasone were evaluated . Only the drug terbutaline acted as a HOCl scavenger.

Antimicrob Agents Chemother, 1994 May, 38(5), 1186 - 9
Rifampin for therapy of experimental pneumococcal meningitis in rabbits; Nau R et al.; Rifampin at a maximally effective dose was less active than ceftriaxone (both drugs at 10 mg/kg of body weight.h) in a rabbit model of pneumococcal meningitis (delta log10 CFU/ml.h, -0.40 +/- 0.13 versus -0.77 +/- 0.18; P < 0.01) . The bactericidal activity of rifampin decreased at concentrations in cerebrospinal fluid greater than those that are clinically achievable, and use of rifampin in combination with ofloxacin had no synergistic or additive effect.

Isr J Med Sci, 1994 May-Jun, 30(5-6), 331 - 5
Some aspects of the humoral immunity and the phagocytic function in newborn infants; Wolach B et al.; Newborn infants, particularly those born prematurely, are prone to develop life-threatening pyogenic infections . Different studies have demonstrated impairment of various aspects of the humoral immunity and the phagocytic activity of neutrophils in newborns . We conducted a comprehensive study evaluating the complement function (CH50 and AP50) and the level of the vast majority of the complement components (Clq, Clr, Cls, C2-C9, FB and properdin) in preterm and full-term newborn infants as compared to adults . Furthermore, we investigated the effect of autologous and heterologous serum on the bactericidal activity of neutrophils, by crossing newborn serum with adult cells and vice versa . Results showed that preterm and full-term newborns have an impaired complement activity as compared to adults (CH50 P < 0.05, AP50 < 0.01) and significantly reduced complement components except for C7, which was found to be normal in full-term infants and in most appropriate-for-gestational age preterm newborns at 34-36 weeks . A statistically significant correlation was found between gestational age and the level of most of the complement components . CH50 and AP50 also showed a positive trend which, however, was not statistically significant . No correlation was found between birthweight and complement activity or complement component levels . The neutrophil bactericidal activity of full-term newborns was about one-third that of adults (P < 0.001) . Adult serum improved the bactericidal activity of newborn neutrophils by 93%, indicating a considerable neonatal humoral defect . Conversely, neonatal serum blunted the adult bactericidal activity by 86% . Our results support the fact that both humoral and phagocytic functions in newborn infants are impaired, which may possibly account for their increased tendency to develop severe pyogenic infections.

Int J Immunopharmacol, 1994 May-Jun, 16(5-6), 445 - 9
Influence of synthetic adjuvants on nonspecific resistance to infections; Parant M; Among the numerous synthetic compounds of the MDP series capable of acting as adjuvants of vaccines, some can also stimulate the resistance of mice to experimental bacterial infections when given alone as a single dose before the challenge . This increase in nonspecific resistance appears to be mainly related to a priming effect on phagocytic cells leading to an enhancement in responses to the bacterial challenge, such as bactericidal activity and release of cytokines . The mediators produced by monocytes and macrophages (TNF, IL-1) are known to exert a protective effect when given early at the beginning of infection . Moreover, TNF and muramyl peptides could exert a synergistic activity against a bacterial or fungal challenge.

Pathol Biol (Paris), 1994 May, 42(5), 412 - 8
{Evaluation of the extra- and intracellular activity of clarithromycin against Mycobacterium chelonae}; Gevaudan MJ et al.; The in vitro activity of clarithromycin alone and in combination with amikacin, ethambutol and rifabutin was tested against twelve strains of M . chelonae abscessus and eight strains of M . chelonae chelonae isolated from patients . Extracellular activity of clarithromycin was assessed by determining MICs using the 1 p . cent proportion method in Middlebrook 7H11 agar media compared to the radiometric methodology in 7H12 broth at two pHs 6.8 and 7.4 . The MICs obtained at pH 7.4 were 2 to 4 more dilutions lower than those obtained at pH 6.8 . By both methods, clarithromycin appeared more active against isolates of M . chelonae chelonae than against isolates of M . chelonae abscessus . Clarithromycin- amikacin combination demonstrated the most important additive effect . The use of three drugs in association resulted in syngergistic effect . Studies of intracellular bacteria showed that the most effective bactericidal combination was clarithromycin amikacin and ethambutol together.

Infect Immun, 1994 May, 62(5), 2037 - 45
A bactericidal antibody to Borrelia burgdorferi is directed against a variable region of the OspB protein; Sadziene A et al.; Borrelia burgdorferi, an agent of Lyme disease, is killed by some monoclonal antibodies in the absence of complement or phagocytes . In the present study, the bactericidal action of monoclonal antibodies against B . burgdorferi and B . hermsii, a cause of relapsing fever, was further characterized . H6831, an antibody recognizing the OspB proteins of some B . burgdorferi strains, and H4825, an antibody specific for one serotype of B . hermsii, were purified, and Fab fragments of the antibodies were prepared . In time-kill studies, more than 99.9% of strain B31 B . burgdorferi cells were killed after 30 min of exposure to H6831 Fab fragments . The MBC of the Fab fragments was 10 micrograms/ml . Electron microscopy revealed that the bactericidal Fab fragments produced numerous blebs and cell lysis of the borrelias for which they were specific . To identify the epitope for H6831, the OspB sequences of H6831-susceptible and -resistant strains and mutants were determined . The deduced OspB proteins of all H6831-resistant strains and mutants differed from the strain B31 OspB at residue 253 . Murine antisera raised against a 21-mer synthetic peptide representing the region around residue 253 were specific for strain B31 by Western blot (immunoblot) and growth inhibition assays . Furthermore, the antipeptide serum inhibited the binding of H6831 to whole borrelias . These findings indicated that the linear component of the bactericidal antibody's epitope was located at or near residue 253.

Blood, 1994 May 1, 83(9), 2516 - 25
Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein; Meszaros K et al.; Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia . In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades . In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity . We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo . Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (> or = 10 pg/mL) . The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum . Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP . Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23 . The expression of tumor necrosis factor showed qualitatively similar changes . Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

Clin Infect Dis, 1994 Apr, 18 Suppl 3, S233 - 6
Assessment of new therapies for infection due to the Mycobacterium avium complex: appropriate use of in vitro and in vivo testing; Grosset JH; Laboratory testing is a prerequisite to predictions about the potential value of human clinical trials--the gold standard for the assessment of new therapies for infection with the Mycobacterium avium complex (MAC) . These laboratory assessments must be made in the proper sequence, with appropriate models and methodology used to obtain data valid in determining whether clinical trials are warranted . In vitro testing permits measurements of minimal inhibitory and minimal bactericidal concentrations, identification of the synergism or antagonism of various agents, definition of an agent's pharmacokinetic properties (e.g., hydrophilicity or lipophilicity), and evaluation of a drug's intracellular penetration and activity against intracellular organisms . The most appropriate animal model for in vivo testing of activity against MAC is the beige mouse . Experiments in this model provide important data on an agent's minimal effective dose and on its optimal dose, dosing frequency, and route(s) of administration . Evaluations in the beige mouse also document whether the agent is bactericidal or bacteriostatic, whether it selects drug-resistant mutants, and whether its use in combination with other agents is beneficial.

Am J Surg, 1994 Apr, 167(4), 391 - 5
Effectiveness of ceftriaxone versus cefoxitin in reducing chest and wound infections after upper abdominal operations; Morris WT; A controlled randomized trial with blind assessment of end results is described comparing the efficacy of 1 g of intravenous ceftriaxone at induction of anesthesia with 1 g of intravenous cefoxitin (three times) administered every 8 hours starting at induction in preventing pulmonary and wound infection after upper abdominal operations . There were 150 adults who underwent biliary or gastroduodenal operations who were randomized to each protocol . A total of 123 patients completed the protocol--59 received ceftriaxone and 64 cefoxitin . Chest infection was defined as pyrexia plus clinical and/or radiologic signs of consolidation or the production of purulent sputum . Wound infection was defined as purulent wound discharge . There was a significant reduction (19% versus 42%, P < 0.05) in chest complications and in wound infection (0% versus 8%, P < 0.05) in the ceftriaxone group compared with the cefoxitin group . It is concluded that for biliary and gastroduodenal operations, 1 g of ceftriaxone is superior to 1 g of cefoxitin (three times) administered every 8 hours and that this effect is likely to be due to the prolonged bactericidal blood levels produced by a single dose of ceftriaxone.

J Inorg Biochem, 1994 Apr, 54(1), 67 - 74
Organomercury(II) complexes of kojic acid and maltol: synthesis, characterization, and biological studies; Marwaha SS et al.; A number of organomercury(II) complexes of kojic acid (HL1, I) and maltol (HL2, II) of the type p-XC6H4HgL1 (III) and p-XC6H4HgL2 (IV) {X = Me, MeO, NO2} have been synthesized and characterized . {formula: see text} Conductance measurements indicate the nonelectrolyte behavior of the complexes . From IR and UV studies, the bonding modes of the ligands to the organomercury(II) moieties have been elucidated . The 1H and 13C NMR spectra support the stoichiometry of the complexes . The fragmentation pattern has been analyzed on the basis of mass spectra . From thermal studies (TG and DTA), various kinetic and thermodynamic parameters for thermal degradation have been enumerated . The complexes have been screened against some pathogenic bacterial strains . The bactericidal activity has been correlated with the thermal data.

J Biol Chem, 1994 Apr 1, 269(13), 9721 - 8
Bactericidal potency of hydroxyl radical in physiological environments; Wolcott RG et al.; Rates of radiolytic inactivation of bacteria suspended in N2O-saturated solutions were dramatically increased over normal background levels when the media contained chloride or bicarbonate ions . The bacteria could be protected from this enhanced toxicity by the addition of free radical scavengers (ethanol, ascorbate, hydrogen peroxide, mannitol, glucose, EDTA, picolinic acid), indicating that the lethal reactions were extracellular in origin . Prior irradiation of chloride-containing solutions led to formation of hypochlorous acid, which was identified by detection of ring-chlorinated products when reacted with fluorescein . Prolonged irradiation of other solutions did not lead to accumulation of bactericidal agents; however, irradiation of bicarbonate-containing solutions in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) led to formation of the EPR-detectable DMPO.CO3- adduct . The results are interpreted in terms of formation of secondary radicals, among which the carbonate and chlorine radicals are uniquely toxic to bacteria . From rate comparisons of the solution components, it was concluded that the reactions involving chloride ion are unlikely to be expressed in biological environments, but that the CO3- radical could be an important intermediary oxidant in peroxide-inflicted cellular damage, particularly in spatially confined environments such as the leukocyte phagosome.

Crit Care Med, 1994 Apr, 22(4), 559 - 65
Endotoxin-binding and -neutralizing properties of recombinant bactericidal/permeability-increasing protein and monoclonal antibodies HA-1A and E5; Marra MN et al.; OBJECTIVE: To compare the endotoxin-binding and -neutralizing properties of bactericidal/permeability-increasing protein, the human monoclonal antiendotoxin antibody HA-1A, and the murine antiendotoxin antibody E5 . DESIGN: Prospective, randomized, placebo-controlled laboratory study . SETTING: Biotechnology company research laboratory . SUBJECTS: Female CD-1 mice . INTERVENTIONS: Recombinant bactericidal/permeability-increasing protein, HA-1A, a human immunoglobulin M monoclonal antibody raised against Escherichia coli J5 (Rc) endotoxin, and E5, a murine immunoglobulin M monoclonal antibody raised against E . coli J5 endotoxin, were compared in the following assays: a) binding to rough lipopolysaccharide immobilized onto microtiter plates; b) inhibition of lipopolysaccharide activity in the limulus amebocyte lysate assay; c) inhibition of lipopolysaccharide-induced cytokine release in whole blood; and d) protection against lethal endotoxin challenge in CD-1 mice . MEASUREMENTS AND MAIN RESULTS: The binding affinity of bactericidal/permeability-increasing protein for immobilized lipopolysaccharide is apparently greater than the binding affinity of HA-1A or E5 . Bactericidal/permeability-increasing protein neutralized lipopolysaccharide activity in the chromogenic limulus amebocyte lysate assay, while neither monoclonal antibody inhibited lipopolysaccharide activity . Similarly, bactericidal/permeability-increasing protein reduced lipopolysaccharide-mediated tumor necrosis factor production in human whole blood in vitro, whereas monoclonal antibodies had slight (HA-1A) or no (E5) effect on lipopolysaccharide activity in this system . Administration of bactericidal/permeability-increasing protein gave > 90% protection against an LD60 dose of endotoxin in CD-1 mice, while treatment with HA-1A or E5 did not improve survival rate . CONCLUSIONS: Neither monoclonal antibody was as effective as bactericidal/permeability-increasing protein at binding or neutralizing endotoxin in vitro or in vivo . The potent endotoxin-binding and -neutralizing properties of bactericidal/permeability-increasing protein indicate that it might be useful in the treatment of endotoxin-related disorders in humans.

Crit Care Med, 1994 Apr, 22(4), 553 - 8
Human neutrophil bactericidal/permeability-increasing protein reduces mortality rate from endotoxin challenge: a placebo-controlled study; Fisher CJ Jr et al.; OBJECTIVES: To study the toxicology and pharmacology of the endotoxin-neutralizing agent, bactericidal/permeability-increasing protein . DESIGN: Prospective, randomized, placebo-controlled laboratory study . SETTING: Academic research laboratory . SUBJECTS: CD-1 mice (n = 259); Sprague Dawley rats (n = 26); New Zealand White rabbits (n = 19) . INTERVENTIONS: Pharmacokinetics of intravenously injected bactericidal/permeability-increasing protein was assessed in mice . Toxicology was tested in mice and rats . Efficacy of intravenously administered bactericidal/permeability-increasing protein as an endotoxin-neutralizing agent was tested in mice, rats, and rabbits . MEASUREMENTS AND MAIN RESULTS: Administration of a single 10-mg/kg bolus injection of bactericidal/permeability-increasing protein resulted in no alterations in hematologic, renal, or hepatic function, activity level, or weight gain in animals observed over a 7-day study period . A single bolus injection (10 mg/kg) of bactericidal/permeability-increasing protein protected 15 of 16 mice from a lethal endotoxin challenge (mortality rate 1/16 {6.25%}) compared with a 100% (16/16) mortality rate in the saline-treated controls (p < .001) . Bactericidal/permeability-increasing protein administered up to 1 hr after endotoxin provided significant protection against lethal endotoxin challenge . Furthermore, bactericidal/permeability-increasing protein reduced the induration and dermal necrosis observed in the localized dermal Shwartzman reaction . CONCLUSIONS: Bactericidal/permeability-increasing protein is a potent antiendotoxin that neutralizes endotoxin in vivo and prevents mortality in animal models of lethal endotoxemia.

Antimicrob Agents Chemother, 1994 Apr, 38(4), 662 - 7
Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy; Ji B et al.; Twenty-four patients with newly diagnosed lepromatous leprosy were allocated randomly to three groups and treated for 56 days with 400 mg of ofloxacin daily, 800 mg of ofloxacin daily, or 400 mg of ofloxacin, 100 mg of dapsone, and 50 mg of clofazimine daily plus 300 mg of clofazimine once every 28 days . The patients in all three groups demonstrated remarkable clinical improvements, accompanied by rapid decline of the morphological index in skin smears during treatment . More than 99, > 99.99, and > 99.99% of the viable Mycobacterium leprae organisms had been killed by 14, 28, and 56 days of treatment, respectively, as measured by inoculation into the footpads of immunocompetent and nude mice of organisms recovered from skin biopsy specimens obtained before and during treatment . Mild to moderate elevations of the serum glutamic pyruvic transaminase level were observed in four patients, all after 28 days of treatment, which returned to normal after the trial had been completed . Clinical improvement, bactericidal activity, and hepatotoxicity did not differ significantly among the three groups . Ofloxacin displayed powerful bactericidal activity against M . leprae in leprosy patients and may be an important component of new multidrug regimens for the treatment of leprosy . Its optimal dosage appears to be 400 mg daily, and combination with dapsone and clofazimine does not enhance its activity.

Rinsho Ketsueki, 1994 Apr, 35(4), 381 - 5
{Analysis of platelet-derived factors that modulate functions of polymorphonuclear leukocytes}; Sasada M et al.; Interactions between platelets and polymorphonuclear leukocytes (PMN) modulate their functions and play a role in the development of pathogenesis of some disease . Platelets secret various kinds of factors that affect PMN functions . They seemed to have important role in vivo, but little has been elucidated on exact mechanism of action and physiological meaning of each factor in relation to PMN functions . We studied the effects of platelets and released substances from activated platelets on the functions of PMN . Results were as follows . 1) Platelets enhanced bactericidal activities of PMN against E.coli . 2) Platelets had effects on the generation of superoxide anion (O2-) of PMN . Their effects were quite different according to the assay condition of PMN, that is, platelets inhibited O2- generation when PMN were at rest or stimulated slightly and they enhanced O2-generation of PMN that were stimulated with optimal condition . 3) Thrombin-activated platelets and their supernatant elicited a transient elevation of {Ca2} of PMN . The activity of the supernatant decreased by treating with hexokinase that decomposed ATP . Further treatment with trypsin abolished its activity almost completely . Considering with our additional experiments, factors that induced {Ca2+} elevation of PMN were ATP, beta-thromboglobulin and some trypsin-sensitive factor(s) . 4) Supernatant of thrombin-activated platelets decreased random migration and chemokinesis of PMN.

J Cardiovasc Pharmacol, 1994 Apr, 23(4), 664 - 8
Tetrachlorodecaoxygen, a wound healing agent, produces vascular relaxation through hemoglobulin-dependent inactivation of serotonin and norepinephrine; Wolin MS et al.; We investigated the vasoactive actions of the wound-healing agent tetrachlorodecaoxygen (TCDO) . TCDO (20 microM) had no direct effect on tone in isolated calf pulmonary arteries precontracted with potassium with or without 1 microM reduced hemoglobin under O2 or N2 atmosphere . However, TCDO, in a reduced hemoglobin-dependent manner, attenuated contraction produced by serotonin, associated with spectral changes consistent with destruction of serotonin . The loss of tone induced by serotonin catalyzed by TCDO plus reduced hemoglobin was not altered in the presence of superoxide dismutase (SOD) plus catalase . TCDO plus reduced hemoglobin also produced rapid relaxation of isolated rabbit aorta precontracted with norepinephrine (NE), whereas with phenylephrine (PE)-induced bone, the observed relaxation was slow to develop . Neither did TCDO, with or without reduced hemoglobin, alter soluble guanylate cyclase activity in pulmonary artery . Thus, a highly reactive species produced by interaction of TCDO with reduced hemoglobin appears to attenuate the contractile actions of serotonin, NE, and PE, selectively potentially by destroying these vasoactive agents . The vasodilator actions of TCDO (plus reduced hemoglobin) may contribute to wound healing by increasing nutrient blood flow and O2 delivery needed for repair processes and bactericidal activity.

J Biol Chem, 1994 Mar 25, 269(12), 9388 - 91
Complete cDNA encoding human phospholipid transfer protein from human endothelial cells; Day JR et al.; Phospholipid transfer protein, with an apparent molecular mass of 81 kDa, was purified from human plasma . The NH2-terminal amino acid sequence of a 51-kDa proteolytic fragment obtained from phospholipid transfer protein allowed degenerate primers to be designed for polymerase chain reaction and the eventual isolation of a full-length cDNA from a human endothelial cDNA library . The cDNA is 1,750 base pairs in length and contains an open reading frame of 1,518 nucleotides encoding a leader of 17 amino acids and a mature protein of 476 residues . Northern blot analysis shows a single mRNA transcript of approximately 1.8 kilobases with a wide tissue distribution . The gene was mapped to chromosome 20 using a human/rodent somatic cell hybrid mapping panel . Phospholipid transfer protein was found to be homologous to human cholesteryl ester transfer protein, human lipopolysaccharide-binding protein, and human neutrophil bactericidal permeability increasing protein (20, 24, and 26% identity, respectively).

Prehospital Disaster Med, 1994 Apr-Jun, 9(2 Suppl 1), S35 - 7
Epidemic of surgical wound infections in wartime Sarajevo; Ler Z et al.; BACKGROUND: An epidemic of surgical wound infections observed at the State Hospital of Sarajevo during June-September 1992 is reported . METHODS: A cross-sectional survey of 138 surgical patients with wound infection treated by the Department of Surgery of the State Hospital of Sarajevo was performed in mid-September and again in mid-November 1992 . A preliminary evaluation of the bactericidal effectiveness of a new antiseptic preparation called DI-ASEPT also was done . RESULTS: The frequency of wound infections was 24.4% in September and 19.2% in November . Pseudomonas species was the primary etiologic agent in this epidemic . DI-ASEPT was as effective as povidone-iodine in producing wound asepsis . CONCLUSIONS: Because of limited resources, large numbers of casualties, and an extremely adverse environment as a result of war that has affected hygienic conditions at the State Hospital of Sarajevo, a high frequency of contaminated or dirty operations were performed . This was the primary reason for the observed increase in wound infections . After hygienic conditions were restored, the epidemic of wound infections was terminated.

Antimicrob Agents Chemother, 1994 Mar, 38(3), 515 - 7
Clinical trial of clarithromycin for lepromatous leprosy; Chan GP et al.; Clarithromycin was administered to nine previously untreated lepromatous leprosy patients . Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy . Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks . The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I . Clarithromycin was well tolerated, with only minor side effects noted in two patients . Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses . Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy-derived M . leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens . Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks . Significant clinical improvement was evident after 4 weeks of treatment . All analyses indicate that clarithromycin is rapidly bactericidal for M . leprae in humans.

J Crit Care, 1994 Mar, 9(1), 47 - 71
Role of neutrophil-endothelial cell adhesion in inflammatory disorders; Korthuis RJ et al.; Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens . However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions . Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions . Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma . NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria . The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.

J Clin Immunol, 1994 Mar, 14(2), 120 - 33
The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock; Rogy MA et al.; Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS) . The in vivo LPS neutralizing activity of exogenous BPI was studied in a model of lethal Escherichia coli bacteremia . Five baboons were treated with BPI (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 hr), while four additional animals received a genetically engineered variant of BPI (NCY103) . Five animals received a placebo treatment and served as controls . Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels of LPS throughout an 8-hr evaluation period following live bacterial challenge . Two hours following E . coli administration, LPS levels peaked in the controls, at 6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group and 2.04 +/- 1.18 ng/ml in the NCY103 group . Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 levels likewise were attenuated in the treatment groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in the BPI group . Leukocytopenia and granulocytopenia were significantly (P < 0.02) lessened in the BPI group, by an average of 59% leukocytopenia and 65% granulocytopenia, respectively . This study supports the concept of E . coli LPS neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in peak LPS-LAL activity is sufficient to alter some hematologic and cytokine manifestations of bacteremia.

J Immunol, 1994 Mar 1, 152(5), 2308 - 16
A 100-kDa protein in the C4-activating component of Ra-reactive factor is a new serine protease having module organization similar to C1r and C1s; Takayama Y et al.; Ra-reactive factor (RaRF), a C-dependent bactericidal factor in mice, is composed of one polysaccharide-binding component and one C4/C2-activating component . The former is an oligomer of 28-kDa protein corresponding to the mannose-binding protein of mice . The 100-kDa protein, P100, has been shown to be present in the C4/C2-activating component . This protein generates 29- and 70-kDa polypeptide chains when reduced . In this study, we determined the nucleotide sequence of cDNA coding for P100 . cDNAs were prepared by reverse transcription PCR and cassette-ligation-mediated PCR on mRNA from BALB/c mouse liver, using primers synthesized by reference to the sequence determined in a previous study . The results of cDNA sequencing indicate that the precursor protein of P100 containing a 24-residue signal peptide consists of 704 amino acid residues . Taking the results of the previous electrophoretic study into consideration, it is thought that the cleavage of mature P100 protein generates a 29-kDa chain of 251 residues and a 70-kDa chain of 429 residues . Although homology in the amino acid sequence of P100 with that of human C1r and C1s subcomponents of C was less than 40%, a striking similarity in domain organization was found among these proteins, indicating that P100 is a new C4-activating serine protease structurally similar to C1r and C1s . Northern hybridization showed that the liver was the primary site of the expression of the P100 gene.

Zentralbl Bakteriol, 1994 Mar, 280(4), 433 - 8
Host defense abnormalities as causes of increased susceptibility to infections in children with HIV infection; Roilides E; Infection with human immunodeficiency virus (HIV) is followed by an increased susceptibility to a series of opportunistic and common pathogenic organisms that can be viruses, bacteria, fungi or protozoa . This increased susceptibility has been associated with multiple defects underlying the whole spectrum of host defenses . Numerical and functional deficiencies in CD4+ T lymphocytes are the hallmark of progression of the disease . In addition, B cells become affected as evidenced by a spontaneous hyperproduction of immunoglobulins which are, however, dysfunctional, and an impaired production of specific antibodies in response to a variety of antigens . Natural killer cell cytotoxicity is also defective . Both monocytes/macrophages and neutrophils are affected by HIV and exhibit defective chemotactic and bactericidal function as well as defective antibody dependent cellular cytotoxicity and certain antifungal activities . These defects may explain the heightened frequency of infections in this population of patients, especially in children . Restoration of them with specific immunotherapeutic agents may decrease the incidence of infections.

Pol Arch Med Wewn, 1994 Mar, 91(3), 185 - 91
{Comparison of selected indices of nonspecific immunity estimated in peripheral blood of patients with untreated duodenal ulcer and after treatment with ranitidine}; Hrycek A et al.; In 20 patients (8 women and 12 men) aged of 20-56 years (38 years on the average) with the yet untreated duodenal bulb ulcer selected indices of nonspecific immunity in peripheral blood (total leukocytes number and absolute neutrophils (N) number, N adherence to fibre, spontaneous leukocytes migration in a 3 hour test, N phagocytic activity and bactericidal activity of plasma and leukocytes) were estimated . Those indices were again estimated after two week of treatment with ranitidine, 150 mg every 12 hours . After ranitidine treatment reduction of the total leukocytes number and absolute N number was found, as compared with the pretreatment results . In addition to that treatment an increase of N adherence and their phagocytic activity was observed with unchanged leukocyte capacity for spontaneous migration . No statistically significant difference was observed in bactericidal activity of plasma and leukocytes . The following conclusions were reached . 1 . Two-week treatment of duodenal ulcer patients with 150 mg ranitidine every 12 hours was followed by reduction of the total leukocytes and N numbers in peripheral blood, and by augmentation of their adherence and phagocytic activity . 2 . Bactericidal activity of plasma and leukocytes and leukocytes capacity for spontaneous migration did not show any changes after two-week ranitidine treatment of duodenal patients.

Z Kardiol, 1994 Mar, 83(3), 188 - 93
{Brain abscess in patients with cyanotic heart defects}; Piper C et al.; As a result of hypoxia following right-to-left shunts, cerebral bacterial spreading and an altered blood-brain-barrier permeability, brain abscesses (BA) are typical complications in patients with cyanotic congenital heart disease . In 483 prospectively followed patients the incidence of BA was 0.45%/year . It was higher (0.57%/year) for patients with tetralogy of Fallot where the cumulative risk within the first two decades of life was 12.1 +/- 1.7% . The risk of BA complicating cyanotic heart disease is inconstant and continuously increasing up to approximately age 12 (instantaneous risk at that time: 1.75 +/- 0.12%), decreasing thereafter . With respect to etiology, infectious endocarditis, infections per continuitatem, bacterial meningitis, bacterial lung diseases with intrapulmonary shunts, and thromboembolic complications of systemic infections have to be differentiated . The stepwise diagnosis includes CCT to demonstrate the typical contrast enhancement and a lumbar puncture which shows granulocytic pleocytosis . If the cerebral spinal fluid fails to demonstrate the typical findings, cerebral angiography may be necessary to exclude a malignant vascularized neoplasma . In cases of doubt, stereotactic cerebral biopsy should be performed . Optimal antibiotic therapy after determining the minimal bactericidal concentration and combination of antibiotics is of utmost prognostic significance . Cranial computed tomography should be repeated after 6, 14, and 24 days . Infections resistant to antibiotics may necessitate local instillation of antibiotics.

J Biol Chem, 1994 Feb 18, 269(7), 5059 - 63
Enhanced bactericidal action of lysozyme to Escherichia coli by inserting a hydrophobic pentapeptide into its C terminus; Ibrahim HR et al.; The mechanism of the enhanced bactericidal action to Escherichia coli of the lysozyme having a hydrophobic pentapeptide (Phe-Phe-Val-Ala-Pro) at its C terminus was investigated . The modified lysozyme, hydrophobic pentapeptide-fused lysozyme (HLz), was secreted in the culture medium from yeast harboring the expression plasmid, in which a synthetic DNA fragment encoding a hydrophobic pentapeptide was introduced to the 3'-end of the coding region of the lysozyme cDNA . Although CD analysis showed that HLZ was considerably different from wild-type lysozyme (WLz) in the secondary and tertiary structures, it retained 76% of the lytic activity of WLz . When E . coli cells were exposed to the WLz or HLz, the survival cells were significantly reduced only in the case of HLz . Periplasmic proteins from the HLz-treated cells were released to an extent similar to that from the WLz-treated cells, indicating that HLz has nearly the same action as WLz with respect to the disruption of the outer membrane and peptidoglycan . Experiments with E . coli phospholipid liposomes revealed that HLz dissipated the valinomycin-induced transmembrane electrochemical potential, but WLz did not . These results suggest that the enhanced bactericidal action of HLz to E . coli is due to disruption of the electrochemical potential of the inner membrane in cooperation with the inherent function of the lysozyme to the outer membrane and peptidoglycan.

Anal Biochem, 1994 Feb 15, 217(1), 7 - 11
Chiral separation by capillary affinity zone electrophoresis using an albumin-containing support electrolyte; Arai T et al.; Chiral separations of some pharmaceutical compounds were studied by capillary affinity zone electrophoresis . Bovine serum albumin (BSA) was used as a chiral selector and added to electrolyte . For the chiral separation of new quinolone bactericidal reagents, phosphate buffer was more appropriate than borate buffer solution as the support electrolyte . The effects of BSA concentration, albumin type, pH, chiral additive, and voltage on separation were observed . As a result, chiral separations were performed in the pH range 7-8 . The migration and stereoselectivities of enantiomers were changed by varying the protein concentration (more than 0.2% w/v) and voltage and by adding amino acids as chiral modifiers . This procedure is easily applicable to other compounds for chiral separation or for studies of protein binding interaction.

Infect Immun, 1994 Feb, 62(2), 722 - 5
Analysis of protective and nonprotective monoclonal antibodies specific for Bordetella pertussis lipooligosaccharide; Shahin RD et al.; In this study, it has been determined that immunoglobulin G1 (IgG1) and IgG3 monoclonal antibodies directed to the lipooligosaccharide A of Bordetella pertussis were able to protect mice from fatal aerosol infection . No correlation was found between the bactericidal activity in vitro in the presence of complement and the protection in mice, since a bactericidal IgG3 did not elicit protection . In addition, no significant difference in protective capacity was observed with bactericidal and nonbactericidal IgG1 antibodies, indicating that bactericidal activity is not a requirement for protection mediated by certain anti-lipooligosaccharide A antibodies . A reduction in protection in C5-deficient mice was observed, suggesting a significant role for complement in certain host defense mechanisms against B . pertussis infection.

J Dairy Sci, 1994 Feb, 77(2), 560 - 5
Vitamin concentration and function of leukocytes from dairy calves supplemented with vitamin A, vitamin E, and beta-carotene in vitro; Eicher SD et al.; Blood neutrophils and pulmonary alveolar macrophages, isolated from calves at 3 and 6 wk of age, were cultured in medium without added vitamins or supplemented with 100 micrograms/dl of vitamin A, 1000 micrograms/dl of vitamin E, 100 micrograms/dl of vitamin A plus 1000 micrograms/dl of vitamin E, or .25 micrograms/dl of beta-carotene plus 1000 micrograms/dl of vitamin E . Macrophage bactericidal activity improved with supplementation of vitamins A plus E compared with supplementation of beta-carotene plus E or vitamin E at wk 3 . Neutrophil bactericidal activity decreased with all vitamin E treatments at wk 3 and with vitamins E or A plus E at wk 6 . Neutrophil phagocytosis improved at wk 3 with supplementations of vitamins A, E, and A plus E . The chemotactic index improved with beta-carotene and vitamin E compared with vitamin E alone at wk 3 and at wk 6 with vitamin E compared with vitamin A and control treatments . Retinol content of neutrophils varied at wk 3, but, by wk 6, cells supplemented with vitamins A, E, or A plus E had greater retinol concentrations than control cells . Neutrophil alpha-tocopherol concentrations at wk 3 increased from those of controls with supplementation of vitamin E or beta-carotene and vitamin E, but, at wk 6, vitamin E-supplemented cells were different only from vitamin A-supplemented cells . These data suggest that optimal plasma concentrations of vitamins A and E exist for leukocyte function.

Nippon Rinsho, 1994 Feb, 52(2), 451 - 5
{Cardiac infection}; Fukayama M; Cardiac infection usually refers to infective endocarditis (IE) and purulent pericarditis . Though, IE was initially observed in patients with congenital or rheumatic heart disease, currently, persons with prosthetic cardiac valves and with degenerative heart disease account for the majority of the cases and there has been a significant trend toward an increase in the age of patients . Echocardiography, especially, transesophageal echocardiography, has provided valuable information for diagnosis . Since cure requires eradication of all the organisms, bactericidal agents must be used sufficient period to sterilize the vegetation . Overall mortality from recent reports is 10% . Purulent pericarditis almost always occurs in the setting of other serious disease and it's specific signs are often absent, so the disease still carries a high mortality.

Nippon Rinsho, 1994 Feb, 52(2), 389 - 94
{Diabetes mellitus with intractable bacterial infections}; Sato A et al.; Infections complicating diabetes mellitus are often severe and persist, becoming intractable . As the mechanism of the intractability, cell function involved in the defense against infection was evaluated . The function of peripheral blood neutrophils in diabetes mellitus was markedly decreased compared with the control group . In the bronchoalveolar lavage fluid (BALF) in diabetes mellitus, alveolar macrophages (AM) were increased, and especially, the appearance of foamy AM was characteristic . Among the functions of AM, chemotactic ability and bactericidal ability were significantly decreased, and the decreases were more marked in IDDM than in the NIDDM . The function of AM did not recover even after improvement in the blood glucose level . Thus, the effects of metabolic abnormalities in diabetes mellitus extended to the cellular level in the lungs.

Nippon Rinsho, 1994 Feb, 52(2), 378 - 83
{Treatment-resistant bacterial infection in specific bacterial species and developmental movement of new antibiotics--Mycobacterium}; Shiraishi T et al.; Mycobacterium tuberculosis and atypical mycobacteriosis are potent diseases which had not been curable before . Progress of chemotherapy has a marked effect but not enough results . We are now waiting for the appearance of a new medicine . Other rifamycim derivatives are developed as antimycobacterial agents, which have a mainframe of 3'-hydroxy-5'-alkylpiperazinyl-benzoxazinorifamycins (KRMs) . KRMs exceeds RFP in bacteriostatic function, and also have already established in vivo in chemotherapeutic efficacy . Another study will also reveal a higher of bactericidal function . We expect possibility of much more powerful and short-term initial chemotherapy.

J Chemother, 1994 Feb, 6(1), 39 - 43
Do Escherichia coli susceptibilities to various antibiotics decrease in the presence of polyunsaturated fatty acids? A preliminary report; Giamarellos-Bourboulis EJ et al.; Polyunsaturated fatty acids (PUFAs) constitute an ingredient of the daily diet and therefore they might be in close contact with the polymicrobial gastrointestinal flora . In order to study the interaction of bacteria and PUFAs, eight Escherichia coli strains were cultured in the presence of docosahexaenoic acid (DHA) at a concentration of 100 micrograms/ml, and six of the latter eight at 75 micrograms/ml whereas nine other E . coli strains were cultured in the presence of 50 micrograms/ml gamma-linolenic acid (GLA) . DHA provoked > or = 4-fold increases in the minimum inhibitory and bactericidal concentrations of various antibiotics in six strains at 100 micrograms/ml and in three strains at 75 micrograms/ml, which were not antibiotic-specific and involved mainly aminoglycosides . GLA provoked in four strains > or = 4-fold increases in MICs-MBCs of ampicillin . The clinical relevance of these observations require further study.

Circ Shock, 1994 Feb, 42(2), 68 - 75
Bactericidal antibiotics increase tumor necrosis factor-alpha and cardiac output in rats after cecal ligation and puncture; Stockwell JA et al.; We hypothesized that treatment of experimental sepsis with bactericidal antibiotics, known to enhance microbial toxin release, would alter tumor necrosis factor-alpha production and the hemodynamic response to the syndrome . In the rat, after cecal ligation and puncture (CLP), elevated serum TNF levels and cardiac output were observed following antibiotic treatment . TNF and cardiac output were elevated to a greater extent in bactericidal-treated than bacteriostatic-treated or antibiotic-untreated rats . Animals treated with bactericidal antibiotics also had significantly greater cardiac outputs than untreated rats . Despite increases in circulating TNF with antibiotic administration, the mortality rate at 96 hr decreased after either bactericidal or bacteriostatic antibiotics . We conclude that elevated TNF after CLP in rats treated with antibiotics is associated with enhanced hemodynamic responses to CLP, but does not increase early mortality . In this model of polymicrobial sepsis, bactericidal and bacteriostatic antibiotics led to different hemodynamic effects without compromising survival.

Shock, 1994 Feb, 1(2), 81 - 6
A recombinant amino-terminal fragment of bactericidal/permeability increasing protein (rBPI23) inhibits soluble CD14-mediated lipopolysaccharide-induced endothelial adherence for human neutrophils; Huang K et al.; Exposure of cultured human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) or interleukin 1 (IL-1) causes increased expression of adhesion molecules such as E-selectin and CD54 by HUVEC and consequently increased adherence of peripheral blood neutrophils . A recombinant aminoterminal fragment of bactericidal/permeability increasing protein (rBPI23) was shown to specifically block the LPS-induced adhesiveness of HUVEC for neutrophils . rBPI23 also prevented the LPS- but not IL-1 beta-induced upregulation on HUVEC of E-selectin and CD54 . Furthermore, this inhibition was evident even when the endothelial cells were exposed to LPS for up to 1-2 h prior to rBPI23 addition . The inhibitory effects of an anti-CD14 monoclonal antibodies (mAb) were similar to those of rBPI23 . Combination of the anti-CD14 mAb and rBPI23 resulted inhibition greater than either one used alone . These studies demonstrate that rBPI23 acts as a specific and potent inhibitor of soluble CD14-mediated LPS induction.

J Immunol Methods, 1994 Jan 3, 167(1-2), 227 - 35
Measurement of bactericidal/permeability-increasing protein in human body fluids by sandwich ELISA; White ML et al.; A sensitive sandwich ELISA has been developed to measure levels of native bactericidal/permeability-increasing protein (BPI) as well as two recombinant forms of BPI (rBPI and rBPI23) in human body fluids . The linear range for the rBPI and rBPI23 standard curves were 100-6000 pg/ml and 25-800 pg/ml respectively . Recovery of different concentrations of rBPI spiked into pooled human plasma samples averaged 83% and ranged from 65% at 300 ng/ml to 97% at 3 ng/ml . Recovery of rBPI23 averaged 56% and ranged from 30% at 0.5 ng/ml to 90% at 50,000 ng/ml . Because LBP is present in normal human plasma and shares sequence homology with BPI, the effects of rLBP on the BPI ELISA were also evaluated . Under standard assay conditions, rLBP caused minimal interference with BPI detection . At 100 micrograms/ml, rLBP generated a signal equivalent to 3 ng/ml of rBPI and 0.6 ng/ml of rBPI23 . Matched serum and plasma samples were collected from 20 healthy adults to measure endogenous levels of BPI . The range of BPI concentrations was < 0.2-2.1 ng/ml in plasma and 4.9-72.1 ng/ml in serum . Western blot analysis indicated that the BPI ELISA immunoreactivity in plasma and serum correlated with the presence of a protein doublet (M(r) approximately 60,000), which comigrated with native BPI extracted from human neutrophils . These data demonstrate that low levels of holo-BPI are present in plasma, and suggest that additional quantities of BPI were released from neutrophils during the process of coagulation.

Life Sci, 1994, 54(2), 61 - 70
Nitric oxide: a signal for ADP-ribosylation of proteins; Brune B et al.; Nitric oxide (NO), a highly reactive gas, is now established as a major messenger molecule regulating blood vessel dilation, immune functions and serving as a neurotransmitter in brain and peripheral nervous system . NO can also act as a tumoricidal and bactericidal molecule . The effect of NO to dilate blood vessels is largely explained by stimulation of soluble guanylate cyclase (a heme-iron containing protein) leading to formation of cGMP and protein phosphorylation . This is considered to be the main physiological signaling mechanism of NO . NO also binds to non-heme iron-containing proteins and this has been considered as a pathophysiological or cytotoxic action of NO . Furthermore, NO, more correctly nitrosonium (NO+) which can be formed by the removal of one electron, reacts with protein SH-groups to cause the S-nitrosylation of proteins . We have recently established a link between NO and the S-nitrosylation and mono-ADP-ribosylation of the enzyme glyceraldehyde 3-monophosphate dehydrogenase, which adds a further protein modification mechanism for NO action . This links the formation of the second messenger molecule NO to post-translational protein modification and adds a new dimension to NO in the communication of intracellular signals.

Infect Immun, 1994 Jan, 62(1), 1 - 8
Reduction in superoxide anion secretion and bactericidal activity of neutrophils from aged rats: reversal by the combination of gamma interferon and growth hormone; Fu YK et al.; Polymorphonuclear neutrophils (PMN) from bone marrow of 24-month-old rats kill Escherichia coli less efficiently than PMN from 3-month-old rats . Secretion of O2- and killing of E . coli by PMN from both young and old rats can be significantly augmented by preincubation with either 250 U of gamma interferon (IFN-gamma) or 250 ng of growth hormone (GH) per ml . This priming is specific, because neutralizing monoclonal antibodies against either IFN-gamma or GH completely abrogate the enhanced O2- secretion by PMN from young rats . However, in contrast to PMN from young rats, PMN from aged rats are not primed to kill E . coli by 10-fold-lower concentrations of either IFN-gamma (25 U/ml) or GH (25 ng/ml) . To explore the mechanism for the reduction in bacterial killing by PMN from old rats, a syngeneic GH-secreting pituitary cell line (GH3) was implanted in vivo . PMN from GH3-treated aged rats, but not control aged rats, could now be primed in vitro for O2- secretion by IFN-gamma (25 U/ml) . Although PMN from aged rats do not respond to the lower doses of either IFN-gamma or GH, the combination of both reagents totally restores the ability of PMN to secrete O2- and to kill E . coli . This synergistic priming is observed with PMN from aged rats, but not with those from young rats, and can be detected when both reagents are added simultaneously or when they are added in either sequence . Furthermore, addition of a monoclonal antibody against either IFN-gamma or GH abrogates the synergism of these two molecules . Collectively, these data identify an important alteration in myeloid cells from aged rodents by showing that their PMN are intrinsically unable to respond to low concentrations of IFN-gamma by secreting O2- and killing bacteria . The results also define a previously unrecognized synergism in PMN from aged animals by showing that GH synergizes with IFN-gamma both in vivo and in vitro to restore these suppressed responses.

Nutrition, 1994 Jan-Feb, 10(1), 32 - 6
Influence of dietary fiber on microbial growth in vitro and bacterial translocation after burn injury in mice; Nelson JL et al.; Translocation of enteric bacteria from the gut to the mesenteric lymph nodes and beyond can cause life-threatening infection and multiple-organ failure in immunocompromised and traumatized patients . One of the conditions that promotes bacterial translocation is disruption of the normal gut flora, which results in bacterial overgrowth . In vitro methods were used to determine whether the fibers pectin, cellulose, chitosan, kaolin, lignin, or soy had bactericidal properties . Our results indicated that only chitosan and lignin significantly reduce microbial growth in vitro . A burned mouse model (20% total-body surface area) was used to study the effects of dietary lignin, cellulose, pectin, and chitosan on burn-induced bacterial translocation . Animals were fed a standard mouse diet containing no fiber, pectin, cellulose, lignin, or chitosan (10% of diet) for 14 days ad libitum . On day 14, all animals were burned . Four hours later the animals were killed and the mesenteric lymph nodes, spleen, liver, and cecum were aseptically harvested for determination of quantitative aerobic microbial growth . The animals which received chitosan, and lignin to a lesser extent, added to their diet had significantly lower levels of bacteria in the cecum, mesenteric lymph nodes, and liver . We suggest that addition of chitosan and possibly lignin to the diet may reduce the amount of bacterial translocation after burn injury, presumably by reducing the bacterial population of the cecum.

Probl Tuberk, 1994, (1), 40 - 2
{Ultrastructure of epithelioid cells in the dynamics of forming tubercular granules}; Shkurupii VA et al.; As shown by ultrastructural findings in epithelioid cells, their number and differentiation degree increase in granulomas of animals with chronic generalized tuberculosis . Isoniazid treatment stimulated differentiation of the monocytes into epithelioid cells and differentiation of the latter . A large number of epithelioid cells with adequate lysosomal apparatus may denote a risk of the destructive process in the affected organs . The efforts in the search for new potent anti-tuberculous drugs should be focused on their lysosomotropy, ability to stay long in the lysosomal apparatus being bactericidal and bacteriostatic, and to stimulate plastic processes in the macrophages.

Microbios, 1994, 77(311), 121 - 31
Antagonism between bactericidal activities of 4-quinolones and coumarins gives insight into 4-quinolone killing mechanisms; Howard BM et al.; At concentrations exceeding their MICs, novobiocin and coumermycin antagonised the bactericidal activities of nalidixic acid, ciprofloxacin, ofloxacin and norfloxacin against Escherichia coli KL16 . The sensitivities to killing by ciprofloxacin of four mutant derivatives of KL16 carrying gyrA, nalB, nal24 or nal31 alleles were also antagonised by novobiocin . The activities of drug combinations were tested in nutrient broth, which allowed expression of 4-quinolone killing mechanisms A, B and C . They were also tested in nutrient broth plus rifampicin to inhibit mechanisms A and C of the 4-quinolones, and in phosphate-buffered saline, which inhibited mechanism A . Results showed that novobiocin antagonised mechanism C, but not B, of both ciprofloxacin and ofloxacin, but did not antagonise mechanism C of norfloxacin . A review of these and other data indicates that mechanism B may result from the activities of SOS error-prone DNA repair on an irreversibly-bound drug-gyrase-DNA complex, and that mechanism C is mediated via drug interaction with the B subunit of DNA gyrase.

J Appl Bacteriol, 1994 Jan, 76(1), 49 - 54
An in-vitro meat model for the immediate bactericidal effect of lactic acid decontamination on meat surfaces; van Netten P et al.; An in-vitro model of the lactic acid decontamination (LAD) of meat is described . As LAD is a disinfection rather than a preservation process the model is based on the inactivation kinetics of bacteria in a suspension of pork skin . The model takes account of interfering factors present in nature, such as microbial interactions, leaching of organic material from the meat surfaces and buffering activity.

Antimicrob Agents Chemother, 1994 Jan, 38(1), 61 - 5
Clinical trial of sparfloxacin for lepromatous leprosy; Chan GP et al.; Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans . The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M . leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum . Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity . After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was > 99% . Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays . Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.

Jikken Dobutsu, 1994 Jan, 43(1), 101 - 3
{Investigation of nitroblue tetrazolium reduction of neutrophils in the dog infected with Hepatozoon canis}; Murata T et al.; Investigation of nitroblue tetrazolium (NBT) reduction of neutrophils was performed in the dog infected with Hepatozoon canis . No positive reactions were observed in the parasitized neutrophils by the resting and the stimulated NBT reduction tests . However, results of resting and stimulated NBT reduction tests apparently made no differences between non-parasitized neutrophils of the infected dogs and neutrophils of the non-infected dogs . These findings show that the parasitized neutrophil has no oxidative bactericidal capacity and the infected dogs had no-change in the host protective mechanism.

Dev Comp Immunol, 1994 Jan-Feb, 18(1), 57 - 66
Effect of temperature on macrophage activation and the production of macrophage activating factor by rainbow trout (Oncorhynchus mykiss) leucocytes; Hardie LJ et al.; Production of macrophage activating factor (MAF) by rainbow trout leucocytes has been shown to be temperature dependent in vivo and in vitro . Cells from fish held at 14 degrees C and stimulated to produce MAF immediately after isolation were capable of secreting MAF down to 6 degrees C (the lowest temperature tested) . However, after 48 h at 6 degrees C, these leucocytes show impaired MAF secretion . Acclimation of fish to low temperatures (7 degrees C) did not recover the inhibitory effects of low in vitro temperatures on MAF production, but if these leucocytes were preincubated at 10 or 18 degrees C for 48 h, MAF was produced from these cells . Interestingly, macrophages isolated from fish kept at 7 or 14 degrees C and cultured at low temperatures (6 degrees C) were responsive to MAF-containing supernatants, and showed a higher relative increase in respiratory burst activity compared with their counterparts cultured at 10 and 18 degrees C . Such observations clearly demonstrate that a major impairment of bactericidal activity at low temperatures resides within the specific immune compartment of fish . The implications for fish health are discussed.

Am J Nephrol, 1994, 14(3), 182 - 6
Imipenem/cilastatin sodium in the treatment of continuous ambulatory peritoneal dialysis-associated peritonitis; Lui SF et al.; Imipenem/cilastatin sodium is a new thienamycin class of antibiotic with a broad spectrum of bactericidal activities . It may be a suitable single first-line therapy for the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients . Fifty episodes of CAPD peritonitis were treated with imipenem/cilastatin sodium . On presentation, all patients were given an intravenous loading dose of 1 g of imipenem/cilastatin sodium followed by intraperitoneal imipenem/cilastatin sodium for 10 days . During 1989 (30 episodes), 20 mg imipenem/cilastatin sodium was added to each 2-liter bag of peritoneal dialysis (PD) fluid for 10 days . The primary response rate as defined by polymorphonuclear neutrophils < 100/ml in PD fluid was 90% . Unfortunately, 17% of the peritonitis relapsed within 14 days of stopping antibiotic . The complete cure rate without relapse was therefore 73% . During 1990 (20 episodes), 100 mg imipenem/cilastatin sodium was added to each 2-liter bag of PD fluid for 10 days . The primary response rate was 95%, the complete cure rate without relapse was 85% . Imipenem/cilastatin sodium is an effective single first-line antibiotic for the treatment of peritonitis in CAPD.

Akush Ginekol (Mosk), 1994, (6), 18 - 21
{Increase of nonspecific resistance of the body in normal pregnancy}; Shmagel' KV; The phagocytic function of blood neutrophils, hemolytic activity of the complement, levels of blood serum total IgG and of IgG-containing circulating immune complexes (CIC) were studied in 87 somatically healthy nonpregnant and pregnant women . A normal course of pregnancy was found to be associated with a marked increase of neutrophilic absorption capacity and bactericidal potential, as well as with increased activity of the complement . Despite a decrease of the concentration of total IgG in the IInd and IIIrd gestation trimesters, the level of IgG-containing CIC was unreliably, though constantly increased over the entire course of pregnancy, in comparison with that in nonpregnant women . Hence, stimulation of nonspecific resistance of the body permits pregnant women cope with the antigenic loading of a fetal origin.

Eur J Clin Microbiol Infect Dis, 1994, 13 Suppl 2, S41 - 6
Effects of granulocyte-macrophage colony-stimulating factor on wound contraction; Robson M et al.; The effect of topical recombinant murine and human GM-CSF, 1 or 10 micrograms/cm2 for one to ten days, on the contraction and healing of acute and chronic granulating wounds infected with Escherichia coli was studied in Sprague-Dawley rats . Bacterial contamination of wounds produced significant inhibition of wound contraction . Application of GM-CSF at either dose level to infected wounds markedly increased the rate of wound closure compared to the rate in infected untreated controls . Ten days treatment was found to be more effective than a single application . An advanced stage of wound healing was observed at ten days in the GM-CSF-treated rats compared with controls . Bacterial counts decreased in the GM-CSF-treated wounds which may suggest bactericidal activity . Topical treatment with GM-CSF was shown to effectively inhibit the retardation of wound closure produced by bacterial contamination and may therefore be useful in the management of patients with infected wounds.

Microbiol Immunol, 1994, 38(9), 753 - 6
Complement-mediated killing of Borrelia garinii--bactericidal activity of wild deer serum; Isogai E et al.; The susceptibility of Borrelia garinii to fresh wild deer sera was determined by incubating strain SIKA2 at 10% serum concentration for 1 hr at 37 C in an in vitro bactericidal assay . Each serum showed bactericidal effects at various levels . The effect was dependent on the concentration of antibody to the spirochetes . Complement was essential in the bactericidal assay because the inactivated deer serum showed greatly decreased activity . Our results suggest that B . garinii is sensitive to deer serum, in the presence of antibody and the bactericidal effect is important for preventing Lyme disease in wild sika deer.

Microbiol Immunol, 1994, 38(9), 741 - 5
Augmentation of host resistance against bacterial infection by treatment with leustroducsin B, a new CSF inducer; Kohama T et al.; We tested the in vivo activity of leustroducsin B (LSN B), a new colony-stimulating factor (CSF) inducer isolated from the culture broth of Streptomyces platensis, with mice infected with Escherichia coli . Treatment with LSN B augmented the host resistance to lethal infection of E . coli at doses between 0.1 mg/kg and 1 mg/kg . Serum interleukin-6 (IL-6) levels were found to increase after this treatment, and superoxide anion generation of neutrophils was enhanced in vivo, suggesting that LSN B augmented the host resistance at least in part by inducing IL-6, which subsequently enhanced the bactericidal activity of the neutrophils.

Probl Khig, 1994, 19, 97 - 105
{A comparative evaluation of the toxic and cumulative properties of the Takal drug group}; Mikhailova A et al.; The acute oral and dermal toxicity was studied as well as subacute oral toxicity {30 successive days} and skin irritating effect on experimental animals of new drug form "Takal 9", "Takal 14" and "Takal 16" with proved bactericidal and virucidal activity . A complex of toxicometric, unspecific, haematological, biochemical and histological studies were performed . The compositions "Takal 9", "Takal 14" and "Takal 16" are slightly toxic at oral and dermal application . LD50 for "Takal 9" and "Takal 16" is above 15,000 mg/kg-1 while for preparation "Takal 14" is not reached . At unrepeated dermal application LD50 for the examined group of preparations surpasses 5000 mg/kg-1 . The products have no skin-irritative effect . No cumulative effect is established in the conditions of a 30-day oral treatment . On the background of no changes in the serum indices an activation of the aerobic and anaerobic oxidation in the liver is registered in animals treated with ethyl alcohol, "Takal 9" and "Takal 16" . These deviations are due, most probably, to the participation of ethyl alcohol as solvent, in "Takal 9" and "Takal 16" . On the basis of the experiments, as most suitable for use, is established the preparation "Takal 14".

Rocz Panstw Zakl Hig, 1994, 45(3), 237 - 40
{The effect of temperature on bactericidal activity of certain disinfectants}; Janowska J et al.; Increase of the temperature by 10 degrees C (on the temperature range 22-32 degrees C) grows up the bactericidal activity of the disinfectants like Laurosept, Chloramine, Sterinol and Jodoseptan against E . coli and S . aureus . It has not observed the influence on the bactericidal activity of Septyl against S . aureus . Surface-active agents are more effective at higher temperature against S . aureus, phenolic disinfectants and Chloramine against E . coli.

Digestion, 1994, 55(6), 417 - 24
Orally administered phospholipids inhibit abdominal rubber-drain-induced bacterial translocation in the rat; Guo W et al.; In order to determine the influence of phospholipid on abdominal biomaterial-induced bacterial translocation (BT), phsophatidylcholine (PC) or phosphatidylinositol (PI) was administered orally or intraperitoneally in rats with intraperitoneal implantation of 7-cm2 rubber drain pieces . Two days after surgery, the incidence of translocation to mesenteric lymph nodes and liver significantly decreased, the adherence of 3H-labeled Escherichia coli to the ileal mucosa was significantly inhibited and the phagocytic and bactericidal capacity of peritoneal macrophages increased in animals with PC or PI administered orally, but not intraperitoneally, as compared with rats without phospholipid administration . Scanning electron microscopy revealed a coating layer on the surface of the intestinal mucosa in phospholipid-gavaged rats . Thus, the results in the present study imply that oral, but not intraperitoneal, PC of PI administration reduces enteric BT induced by intraperitoneal drain implantation.

Stem Cells, 1994, 12 Suppl 1, 37 - 44; discussion 44-5
Signal transduction through homo- or heterodimers of gp130; Kishimoto T; One of the characteristic features of cytokines is their functional pleiotropy and redundancy which can now be explained on the molecular basis of the cytokine receptor system . The cytokine receptor system usually consists of two polypeptide chains, a ligand specific receptor and a common signal transducer . The IL-6 receptor system consists of an 80 kDa IL-6 receptor and a gp130 which functions as a signal transducer not only for IL-6R but also for LIF, OSM, ciliary neurotrophic factor (CNTF), and IL-11 receptors . Interaction of IL-6 and IL-6 receptor induces homodimerization of gp130 which interacts and activates an intracytoplasmic tyrosine kinase, JAK-1 kinase . A downstream substrate of JAK kinase in hepatocytes is acute phases responsive factor (APRF)/STAT3 . After tyrosine specific phosphorylation of APRF, it translocates into nuclei, binds to type 2 IL-6 responsive element and induces acute phase gene expression . In order to study in vivo roles of the signaling molecules, targeted disruptions of the genes encoding gp130 and NF IL-6 were carried out . The result revealed the essential role of gp130 in hemopoiesis and heart muscle development . NF IL-6 was shown to be essential for bactericidal function of macrophages.

Med Dosw Mikrobiol, 1994, 46(4), 349 - 55
{Opsonizing activity of human immunoglobulin preparations for intravenous use (IVIG)}; Banach W et al.; It was shown that all the examined immunoglobulin preparations (IVIG) enhance growth of opsonization of S . aureus, S . epidermidis, E . coli which was studied using the chemiluminescence method . However, no opsonization growth was observed of P . aeruginosa rods with the participation of IVIG (except for Sandoglobulin and the specific immunoglobulin Pseudomonas) . We assume that such a result was due to the P . aeruginosa strain's susceptibility to lysis factors of the human serum used in the experiment as the complement source . It was confirmed that phagocytosis with the participation of IVIG measured by the chemiluminescence test requires the presence of a complement . The bactericidal test showed that all IVIG preparations, Pentaglobin in particular, are bactericidal and active against P . aeruginosa . Basing on the results obtained, we believe that the biological activity of the Polish preparation is comparable with the investigated IVIG preparations from foreign firms.

J Egypt Soc Parasitol, 1993 Dec, 23(3), 649 - 57
Selective intestinal decontamination in patients with schistosomal hepatic fibrosis and low-protein ascites; el Aggan HA et al.; Selective intestinal decontamination (SID) for 7 days with norfloxacin (NF) was performed in 15 patients with schistosomal hepatic fibrosis (SHF) and low-protein ascites . Changes in ascitic fluid (AF) opsonic activity and complement3 (C3), complement4 (C4), total protein (TP) and albumin concentrations after NF therapy were compared with those of a control group composed of 15 untreated patients with similar characteristics . After oral NF administration, the mean % changes of AF opsonic activity & AF C3 & TP concentrations showed significant increases and were significantly higher than those in the control group . There were direct correlations between mean % changes in AF opsonic activity and C3 concentrations (r = 0.62) . AF opsonic activity and TP concentrations (r = 0.54) and AF C3 and TP concentrations (r = 0.57) in the NF group . On the other hand, the AF C4 and albumin concentrations were not significantly changed in any group at the end of the study . Based on the results of the present study, it can be concluded that short-term NF therapy in patients with SHF and low-protein ascites increased AF opsonic activity and AF C3 and TP concentrations and hence, AF bactericidal activity . Study of larger numbers of patients for longer periods will determine if these beneficial effects on NF translate into a decreased incidence of spontaneous bacterial peritonitis in patients with chronic liver disease and high-risk of infection.

Am Rev Respir Dis, 1993 Dec, 148(6 Pt 1), 1547 - 51
Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis; Kennedy N et al.; The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis . Two randomized prospective studies were performed in Northern Tanzania . In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days . Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed . In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC) . Sputum colony counts were performed for 8 wk . Patients were tested for antibodies to human immunodeficiency virus (HIV)-1 . The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid . When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE . The difference in outcome was most marked in HIV-1 positive patients . The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.

J Bacteriol, 1993 Dec, 175(23), 7617 - 23
An extraintestinal, pathogenic isolate of Escherichia coli (O4/K54/H5) can produce a group 1 capsule which is divergently regulated from its constitutively produced group 2, K54 capsular polysaccharide; Russo TA et al.; We are studying an O4/K54/H5 Escherichia coli bacteremic isolate (CP9) as a model pathogen for extraintestinal infection . Its group 2, K54 capsular polysaccharide is an important virulence determinant and confers serum resistance . In this study the effect of the group 1 capsule regulators, RcsA, RcsB, and Lon protease, on the regulation of CP9's capsular polysaccharides was assessed . It was established that in the presence of multicopy rcsA or with disruption of lon, CP9 can be induced to produce a group 1 capsule . RcsA, RcsB, and Lon are present in this K54 background and regulate group 1 capsule expression in a fashion similar to that described for K-12 strains . Two independent group 2 capsule gene protein fusions (cl1.29::TnphoA and cl1.137::TnphoA) were used to evaluate the effects of these regulators on group 2 K54 capsule production . Disruption of lon resulted in 1.9-fold (TR293 {cl1.29::TnphoA lon-146}) and 3.4-fold (TR1373 {cl1.137::TnphoA lon-146}) decreases in fusion activity at 28 degrees C, relative to the baseline level . However, decreases in fusion activity at 42 degrees C were only 1.2- and 1.4-fold, respectively . Inactivation of both lon and rcsA or lon and rcsB restored fusion activity to baseline levels at 28 degrees C, but only a partial restoration of activity was seen at higher temperatures . To assess whether these differences in fusion activity reflected a functional change in capsule production, the effects of 80% normal human serum (NHS) were tested against CP9 and TR93 (lon-146) . Since the group 2 K54 capsule protects against the bactericidal activity of 80% NHS, a decrease in its production results in an increase in serum sensitivity . Viable counts of CP9 increased 10-fold in 80% NHS over 3 h at 28 degrees C, as expected . In contrast to CP9, TR93 (lon-146) incurred a 10-fold loss in viability under the same conditions . The levels of RcsA are increased in TR93 (lon 146) as consequence of lon disruption; therefore, these results in conjunction with the cl1::TnphoA protein fusion data establish RcsA as a negative regulator of the group 2 K54 capsular polysaccharide . Furthermore, these results also suggest existence of another Lon-sensitive negative regulator of group 2 K54 capsule production, which is active higher temperatures.

Int J Lepr Other Mycobact Dis, 1993 Dec, 61(4), 605 - 8
Activity of sparfloxacin against Mycobacterium leprae measured by the proportional bactericidal test; McDermott-Lancaster RD et al.; The activity of 25 mg/kg and 50 mg/kg sparfloxacin was measured against Mycobacterium leprae in normal (immunocompetent) mouse foot pads by the proportional bactericidal test . This was compared with the action of 25, 50, and 150 mg/kg ofloxacin by the same method . Sparfloxacin, at both concentrations, was found to be strongly bactericidal by this method, comparable to 150 mg/kg ofloxacin.

J Antimicrob Chemother, 1993 Dec, 32(6), 867 - 75
The early bactericidal activity of rifabutin in patients with pulmonary tuberculosis measured by sputum viable counts: a new method of drug assessment; Sirgel FA et al.; The activity of rifabutin and rifampicin against rapidly growing, extra-cellular Mycobacterium tuberculosis in cavity walls was measured by counting colony-forming units (cfu) in the sputum of 74 patients with newly diagnosed, severe pulmonary tuberculosis during the first 2 days of daily chemotherapy . The fall in counts, (log10 cfu/mL sputum/day), was termed the early bactericidal activity (EBA) . The EBA, a highly reproducible measure within groups of 10-13 patients, was -0.015 for a low EBA reference group (who received no chemotherapy) and 0.495 for a high EBA reference group (who received 300 mg isoniazid daily) . The EBAs in patients receiving 300 and 600 mg rifabutin were 0.014 and 0.075, and for those taking 150, 300 and 600 mg rifampicin 0.021, 0.150 and 0.204, respectively . Weight-for-weight, the ratio rifabutin to rifampicin producing the same EBA was estimated to be 2.73 (95% confidence limits 1.96-3.78) . Determination of the EBA is a rapid and economical method of comparing the potency in human lesions of drugs of the same type before embarking on a conventional clinical trial.

Clin Perinatol, 1993 Dec, 20(4), 761 - 89
Other uses of surfactant; Brown DL et al.; Surfactant is found not only in the alveoli but in bronchioles and small airways . Along with its important role in surface-tension reduction in alveoli, surfactant has several other properties . Any condition characterized by mucus abnormality, mucociliary transport deficiency, airway obstruction, or bronchoalveolar collapse could potentially benefit from exogenous surfactant therapy . Anti-inflammatory and bactericidal properties of surfactant could provide additional benefit in a variety of diseases.

Vet Microbiol, 1993 Dec, 38(1-2), 139 - 55
Virulence factors associated with F165-positive Escherichia coli strains isolated from piglets and calves; Harel J et al.; In this study, 91 F165-positive Escherichia coli isolated from calves and piglets with diarrhea or septicemia were characterized with respect to receptor binding specificity, presence of the aerobactin system, production of colicin V, resistance to the bactericidal effects of serum . Although most F165-positive isolates shared similar DNA sequences with pap operon sequences, less than half of these isolates demonstrated MRHA to P antigen of human red blood cells and Forssman antigen of sheep red blood cells recognized by P and F (or Prs) adhesins respectively . Certain F165-positive isolates sharing similar DNA sequences with both pap and sfa operon sequences demonstrated mannose-resistant hemagglutination of sheep erythrocytes, as observed in human uropathogenic E . coli possessing the prs operon . Most isolates caused mannose-resistant, neuraminidase-resistant hemagglutination of human, equine, feline, and bovine erythrocytes . Thus, F165-positive isolates express one or more adhesins with different receptor binding specificities . An association was observed between the various receptor binding specificities and serogroup . Most F165-positive isolates possessed the aerobactin system and were resistant to the bactericidal effects of serum, but only 38.5% isolates produced colicin V.

Clin Nephrol, 1993 Dec, 40(6), 346 - 51
Plasma levels of bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) during hemodialysis; Schindler R et al.; Several proteins modify the biological response to lipopolysaccharide (LPS) . Both bactericidal/permeability-increasing factor (BPI), a protein stored in neutrophils, and the acute phase protein LPS-binding protein (LBP) bind to LPS; however, BPI inhibits while LBP enhances binding of LPS to leukocytes and subsequent induction of cytokines . We investigated plasma levels of BPI, LBP, elastase and C5a before, during and after hemodialysis (HD) . Six patients were dialysed with Cuprophane (Cup) and polysulfone (PS) low-flux dialyzers on two consecutive HD sessions . There was a significant, 10.9 +/- 2.8-fold increase in BPI after 4-hour HD compared to predialysis and a 4.4 +/- 1.6-fold increase in elastase after 4-hour HD using Cup . Plasma levels of BPI and elastase decreased rapidly after the dialysis session . HD with PS resulted in a smaller, but still significant rise in BPI (3.7 +/- 1.6-fold at 4 hours) and elastase (1.69 +/- 0.2-fold at 4 hours) . Levels for BPI and elastase were similar in the arterial and venous blood lines of the dialyzer . Plasma levels of LBP did not change during or after the HD session . These data indicate that BPI, but not LBP is released during HD with Cup and to a lesser extent with PS . Activation of neutrophils and release of BPI during HD may influence the biological response to bacterial products possibly introduced during HD.

Res Vet Sci, 1993 Nov, 55(3), 292 - 7
Maturation of cellular defence in the respiratory tract of young calves; Yeo SP et al.; The maturation of respiratory tract defence was investigated in a longitudinal study of calves during the first 100 days of life . From day 7, the proportions of the cell types identified in bronchoalveolar lavage (BAL) fluid were similar to those found in adults, with a predominance of alveolar macrophages over polymorphonuclear neutrophils (PMNs) and lymphocytes . Functionally, bactericidal activity of BAL cells was defective and for the first 21 days they supported intracellular bacterial growth . At 24 hours of life, the movement of peripheral blood neutrophils to a chemotactic source was poor, but this increased rapidly during the first week of life . Like BAL cells, peripheral blood PMNs supported intracellular bacterial growth for the first two weeks of life . These studies suggest that cellular defence mechanisms may be compromised during the first week of life.

Clin Ther, 1993 Nov-Dec, 15(6), 1108 - 19
A review of the safety profile of cefixime; Wu DH; Data are reviewed for safety from worldwide clinical trials of 4000 patients and postmarketing studies of 38,000 patients treated with cefixime, a broad-spectrum, bactericidal, beta-lactam stable, third-generation cephalosporin . Adverse experiences were similar in adults and children in all groups, with the most frequent side effects being gastrointestinal in nature . The reported frequency of gastrointestinal adverse experiences was higher in patients in US clinical trials when compared with French, German, or Canadian clinical trials or Canadian or US postmarketing studies . The overall incidence of side effects ranged from 2.7% to 48.2%, and the incidence of gastrointestinal events reported in these studies ranged from 1.4% to 38.6% . Patients infrequently discontinued treatment due to adverse events . The design and methods of data collection in US clinical trials may have resulted in higher frequencies of adverse experiences being reported in US trials when compared with the experiences reported in postmarketing studies and in clinical trials conducted outside of the United States . This is because of the more rigorous methodology used to elicit patient reporting of adverse events in US clinical trials compared with the methodology in postmarketing studies and foreign clinical trials.

Rev Paul Med, 1993 Nov-Dec, 111(6), 472 - 6
Chronic granulomatous disease of childhood: differential diagnosis and prognosis; Grumach AS et al.; Of a total of 111 children with primary immunodeficiency, 20 had phagocytic disorders (18%) and 10 of them (8 boys and 2 girls) were diagnosed as chronic granulomatous disease (CGD) . The children presented with repeated infections already during the first months of life . The main clinical findings were: abscess (n = 8), otitis (n = 8), pneumonia (n = 8), lymphadenitis and pyodermitis (n = 6) and septicemia (4), NBT reduction was almost absent in all the children, except one of them . Bactericidal activity against S . aureus and phagocytosis were impaired in CGD patients . Different patterns of laboratory tests and prognosis were observed and girls had a better evolution.

Kansenshogaku Zasshi, 1993 Nov, 67(11), 1094 - 100
{Influence of granulocyte colony-stimulating factor on bactericidal activities of macrophages and polymorphonuclear leukocytes}; Kawahara M; We investigated the influence of granulocyte colony-stimulating factor (G-CSF) on bactericidal activities of macrophages and polymorphonuclear leukocytes (PMNs) from experimental pyelonephritis in leukocytopenic rats, in order to clarify the usefulness of G-CSF for opportunistic pyelonephritis . We prepared three groups of experimental pyelonephritis, i.e., G-CSF administration group (group-1), cyclophosphamide (CPA) administration group (group-2), and CPA and G-CSF administration group (group-3) . And we measured the active oxygen generation of peritoneal macrophages and PMNs in each group . On the other hand, we produced pseudomonal pyelonephritis in each group, and compared the survival rate of each group for 7 days . G-CSF enhanced active oxygen generation of peritoneal macrophages and PMNs, significantly . Furthermore, G-CSF improved the survival rate of pseudomonal pyelonephritis in leukocytopenic rats . These results indicate that G-CSF enhanced bactericidal activities of macrophages and PMNs in vivo, and prevents dissemination of infections.

Nippon Sanka Fujinka Gakkai Zasshi, 1993 Nov, 45(11), 1320 - 4
{Effect of rG-CSF on the morphology and function of neutrophils in ovarian cancer chemotherapy}; Hoshino T et al.; The combined use of rG-CSF in ovarian cancer chemotherapy prevents a decrease in the number of neutrophils and promotes their recovery . rG-CSF also protects against infections, enhancing chemotherapeutic effectiveness . It is reported that neutrophils produced by rG-CSF not only increase in number but also in function . Some clinicians, however, doubt whether neutrophils mobilized or produced by rG-CSF have sufficient ability to function practically in clinical cases . We therefore examined, by means of flow cytometry, the neutrophils' phagocytosis and bactericidal ability and we found both normal . No morphological abnormalities were seen in these neutrophils . In our observations, moreover, no effect was exerted on the leukocyte-membrane antigen . It was concluded that (a) rG-CSF was very effective in protecting against the diminution of neutrophils by chemotherapy and (b) in promoting their recovery, and (c) also the function, morphology and leukocyte-membrane antigen of these neutrophils were normal.

Biochem Biophys Res Commun, 1993 Oct 29, 196(2), 1003 - 9
A new member of the C1s family of complement proteins found in a bactericidal factor, Ra-reactive factor, in human serum; Takada F et al.; The Ra-reactive factor (RaRF) found in vertebrate sera activates the C4 and C2 components of complement . The C4/C2-activating component of mouse RaRF has been found to contain a 100-kDa serine protease called P100 . In the present study, we cloned a cDNA with cDNA of mouse RaRF P100 as a probe from a human liver cDNA library . An open reading frame of 2097 nucleotides encoding a protein of 699 residues was found in the cloned cDNA of 4489 nucleotides . This protein exhibits 87.4% amino acid homology with mouse P100, and 36.4% and 37.1% homologies with that of the C1r and C1s subcomponents of human complement, respectively . The characteristic nodules and domain of C1r and C1s were highly conserved in this protein . This indicates that the P100, together with the C1r and C1s, forms a unique protein family having the same module/domain constitution.

J Immunol, 1993 Oct 15, 151(8), 4258 - 65
Antagonistic effects of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein on lipopolysaccharide-induced cytokine release by mononuclear phagocytes . Competition for binding to lipopolysaccharide; Dentener MA et al.; Serum proteins play an important role in LPS-induced cell activation . The LPS binding protein (LBP) enhances cellular responses to LPS, whereas the polymorphonuclear leukocyte product bactericidal/permeability-increasing protein (BPI) inhibits LPS-induced cell activation . In this study the influences of LBP and BPI, two proteins with opposite effects, but with considerable sequence homology, on LPS-induced mononuclear phagocytic cell cytokine release was studied . LBP was shown to enhance LPS-induced TNF-alpha, IL-6, and IL-8 release by mononuclear phagocytic cells, whereas BPI inhibited the release of these cytokines . Furthermore, the effects of LBP and BPI on LPS-induced cytokine release by mononuclear phagocytic cells were shown to be counteractive . BPI interfered with the enhancing effect of LBP on the LPS-induced cytokine release . At high LBP to BPI ratios, BPI could no longer inhibit LBP-induced enhancement . In accordance, increasing concentrations of BPI abrogated the LBP effect . Next, it was shown that LBP and BPI compete for binding to LPS by using an assay system that detects binding of free BPI to an anti-BPI mAb . LPS prevented binding of BPI to anti-BPI mAb, whereas preincubation of LPS with LBP prevented the LPS-induced inhibition . Also, it was observed that both BPI and LBP inhibited LPS activity in the chromogenic LAL assay . We conclude from this study that LBP and BPI have counteractive effects on LPS-induced mononuclear phagocytic cell cytokine release by competing for binding to LPS.

Infect Immun, 1993 Oct, 61(10), 4523 - 6
The 39-kilodalton protein of Borrelia burgdorferi: a target for bactericidal human monoclonal antibodies; Scriba M et al.; Three human monoclonal immunoglobulin M antibodies against Borrelia burgdorferi, obtained from in vitro-stimulated peripheral blood lymphocytes, reacted in Western blots (immunoblots) with a prominent 39-kDa peptide and a faint band of approximately 66 kDa . Two of these antibodies showed bactericidal activity without addition of complement . All three antibodies were reactive in an enzyme immunoassay with cloned P39 (W.J . Simpson, M.E . Schrumpf, and T.G . Schwan, J . Clin . Microbiol . 28:1329-1337, 1990), suggesting that the target molecule of these antibodies is identical to the P39 protein . In addition, the majority of supernatants from human lymphocytes stimulated in vitro with crude B . burgdorferi antigen reacted in this assay, demonstrating that P39, although a minor component of B . burgdorferi, is an immunodominant antigen in these spirochetes . A fourth monoclonal antibody, reacting with OspA, also exhibited bactericidal activity.

Eur J Surg, 1993 Oct, 159(10), 551 - 4
Restoration of bactericidal activity of peritoneal fluid by cimetidine but not ranitidine or famotidine in burned mice; Altaca G et al.; OBJECTIVE: To find out the effect of 20%, third degree burns and H2 receptor antagonists on peritoneal bactericidal activity . DESIGN: Animal experiment . SETTING: Research laboratory of university school of medicine . SUBJECTS: 52 mice in five groups . INTERVENTIONS: Sham burn (n = 5, group I), burned, and received subcutaneous injections of saline (0.3 ml/kg day, n = 14, group II); ranitidine (10 ml/kg/day, n = 15, group III); cimetidine (10 mg/kg/day, n = 8, group IV); or famotidine (0.7 mg/kg/day, n = 10, group V); for 14 days . MAIN OUTCOME MEASURE: Peritoneal bactericidal activity in all groups measured 15 days after the burn . RESULTS: There was a significant difference in peritoneal bactericidal activity between the control and burned mice, but no significant difference between the control group and the burned mice that were given cimetidine and famotidine . CONCLUSION: Peritoneal bactericidal activity is suppressed in mice after 20% third degree burns and this effect may be partly reversed by cimetidine and famotidine.

Eur J Surg, 1993 Oct, 159(10), 521 - 4
Effect of povidone-iodine lavage on peritoneal defence mechanisms in rats; Abbasoglu O et al.; OBJECTIVE: To assess the effect of povidone iodine lavage on peritoneal defence mechanisms in rats . DESIGN: Randomised study . MATERIAL: 90 Wistar albino rats . INTERVENTION: Rats were divided in three groups of 30 . All rats underwent midline laparotomy, and 20 rats in each group had peritoneal lavage with 20 ml 1% povidone iodine, samples being taken before lavage in 10 and after lavage in 10 . MAIN OUTCOME MEASURES: Effect of povidone-iodine lavage compared with laparotomy alone on bactericidal activity of peritoneal fluid (group 1); chemotactic indices of polymorphonuclear leucocytes (PMNL) (group 2); and total cell counts, cell types, and peritoneal phagocytic activity (group 3) . RESULTS: Lavage with povidone-iodine increased the total peritoneal cell count/washing from 10.4 x 10(6) to 12.4 x 10(6) (p < 0.005), peritoneal bactericidal activity from 69.2% to 92.7% (p < 0.05), and peritoneal phagocytic activity from 58.9% to 73.7% (p < 0.05) at the end of four hours . Chemotactic indices of peritoneal PMNL before and after lavage were 1.90 and 1.89, respectively . Among the cells in the peritoneal fluid, the proportion of PMNL increased, whereas those of macrophages, lymphocytes, and mast cells decreased (p < 0.005) . CONCLUSIONS: These results differ from those that we found previously after saline lavage . Lavage with 1% povidone-iodine does not increase the detrimental effect of saline lavage; on the contrary, it may even enhance peritoneal defence mechanisms . Any detrimental effects of povidone-iodine lavage should be attributed to systemic rather than local toxicity.

Cesk Farm, 1993 Oct, 42(5), 228 - 31
{Testing for immunomodulating effects of ethanol-water extracts of the above-ground parts of the plants Echinaceae (Moench) and Rudbeckia L.}; Bukovsky M et al.; Ethanolic extracts of aerial parts of the plants Echinacea angustifolia DC, Echinacea purpurea L . (Moench), Rudbeckia fulgida var . sullivantii, Boyton et Beadle, and Rudbeckia speciosa Wenderoth show immunomodulating activity . The mice were treated in vivo for 5 days and the activity was tested for and observed on day 7 . An immunostimulatory effect was observed on the phagocytic, metabolic and bactericidal activities of peritoneal macrophages . The ethanolic extracts of both Echinacea plants also increased the total weight of the spleens as compared to the effect of the Rudbeckia plants and the control group which received saline.

Stomatologiia (Mosk), 1993 Oct-Dec, 72(4), 22 - 5
{A clinico-laboratory assessment of the efficacy of dalargin in treating acute suppurative-inflammatory processes in the maxillofacial area}; Bazhanov NN et al.; Dalargin effects on the immune status parameters were studied in patients with acute pyoinflammatory processes of the soft tissues of the face . Tsen . lymphocyte subpopulation was found to be increasing in all the patients during therapy, whatever the clinical course of the underlying disease . Another finding was a significant elevation of the functional activity of the peripheral blood polymorphonuclear neutrophils . These data were confirmed in vitro when dalargin was added to a leukocyte suspension, though it was known to exert no bactericidal activity . These results permit recommending dalargin for the correction of the immunity status of patients with grave pyoinflammatory diseases of the soft maxillofacial tissues.

Antibiot Khimioter, 1993 Oct-Nov, 38(10-11), 40 - 3
{Protegentin--a combined preparation for the local treatment of suppurative infection}; Pozdniakova VP et al.; Protegentin is a formulation in the form of an ointment for local application . Its high efficacy was demonstrated in the treatment of wounds in the 1st phase of the process, extended decubitus, trophic ulcers, wounds of various genesis not healing for prolonged periods, urogenital infections, abscesses, maxillofacial phlegmon and abscessing parodontosis . The ointment showed good draining, proteolytic and bactericidal effects . The tolerance was good . The positive results were observed in 97 per cent of the cases.

J Postgrad Med, 1993 Oct-Dec, 39(4), 183 - 6
Biochemical changes in polymorphonuclear leucocytes in diabetic patients; Sawant JM; A study on the functional ability of polymorphonuclear leucocytes (PMNL) indicates that the total lysosomal enzyme levels viz . Beta-glucuronidase, lysozyme, acid phosphatase and alkaline phosphatase were not altered in diabetics, compared to that in control subjects . However, the findings also reveal that the release of these lysosomal enzymes in response to a particulate stimulus is impaired in diabetics . This suggests that the bactericidal capacity of these cells, which are involved in phagocytosis, is impaired in diabetics, making them more vulnerable to infections.

Arzneimittelforschung, 1993 Oct, 43(10), 1125 - 9
4-Quinolone bactericidal mechanisms; Howard BM et al.; The bactericidal activity of nalidixic acid against Escherichia coli strain KL16 in nutrient broth was abolished by the addition of rifampicin . Cells suspended in phosphate-buffered normal saline (PBS) were also not killed by nalidixic acid . Experiments with modern 4-quinolones showed their activities varied according to the conditions under which they were tested . Rifampicin did not affect the concentration at which ofloxacin became bactericidal in nutrient broth, but did limit the extent of ofloxacin-induced death . However, rifampicin produced a 10-fold increase in the concentration at which ciprofloxacin became bactericidal in nutrient broth, and completely abolished the bactericidal activity of norfloxacin . Unlike nalidixic acid all of the modern 4-quinolones killed cells suspended in PBS . Based on these results it was possible to differentiate 3 processes by which 4-quinolones induced death . Mechanism A was only active against dividing bacteria and required RNA and protein synthesis; it was therefore not active against bacteria suspended in PBS and was inhibited in nutrient broth by the addition of rifampicin . Mechanism B required neither RNA nor protein synthesis and was also active against non-dividing bacteria; it was therefore not inhibited by rifampicin nor by suspending bacteria in PBS . Mechanism C killed non-dividing bacteria, but required protein and RNA synthesis: it therefore functioned in PBS, but was inhibited by rifampicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Chin Med J (Engl), 1993 Sep, 106(9), 703 - 6
Study on neutrophil enzymes in atopic disease; Xue ZY et al.; Neutrophils (PMN) from 20 patients with atopic disease (atopy), the parents of 8 of the patients and 10 normal controls were studied by light-microscopic cytochemistry . The results revealed that myeloperoxidase (MPO) and acid phosphatase (ACP) activities in PMN in all cases significantly decreased and alkaline phosphatase activity was normal . Parents or parent of 7 of those patients had PMN enzyme deficiency similar to that of the patients . The results indicated that a primary combined and partial deficiency of MPO and ACP in PMN azurophilic granule existed in atopy . It is postulated that the deficiency led to reduction of PMN bactericidal power and delay of bactericidal action . Foreign bodies which were partially degraded could possess antigenic property . This is believed to be the important cytobiological mechanism of the tendency toward infections and formation of sensitive antigen in atopy.

J Dairy Sci, 1993 Sep, 76(9), 2795 - 803
Role of vitamin E and selenium in host defense against mastitis; Hogan JS et al.; Vitamin E and Se are essential nutrients that share common biological activities . Deficiencies in either of these micronutrients have been related in increased incidence and severity of mastitis . A known physiological consequence of alpha-tocopherol or Se deficiency is reduced neutrophil activity . Vitamin E and the Se-containing enzyme, glutathione peroxidase, and antioxidants that protect neutrophils from the destructive action of toxic oxygen molecules necessary for intracellular kill of ingested pathogens . Dietary supplementation of cattle with Se results in a more rapid neutrophil influx into milk following intramammary bacterial challenge and increased intracellular kill of ingested bacteria by neutrophils . Dietary supplementation of early lactation cows with vitamin E results in increased bactericidal activity by bovine blood neutrophils . Recently completed trials have shown that subcutaneous injections of vitamin E approximately 10 and 5 d prior to calving successfully elevated neutrophil alpha-tocopherol concentrations during the periparturient period and negated the suppressed intracellular kill of bacteria by neutrophils that is commonly observed at calving.

J Pharm Pharmacol, 1993 Sep, 45(9), 779 - 83
Distribution of free and liposome-encapsulated cefoxitin in experimental intra-abdominal sepsis in rats; Kresta A et al.; The distributions of radiolabelled free cefoxitin (FC) and liposome-encapsulated cefoxitin (LC) were compared in an animal model of intra-abdominal sepsis . Intraperitoneally administered LC was initially retained in the peritoneal cavity with subsequent preferential drug targeting to the liver (14% injected LC) and spleen (6% injected LC) by 3 h post-injection . Differing patterns of liposomal drug and lipid retention indicated that drug release from the liposome complex occurred within the peritoneum, liver and spleen . Intraperitoneal FC was rapidly taken up into the systemic circulation, with peak recovery in the blood (9% injected FC) and liver (5% injected FC) at 1 h post-injection . FC was also rapidly eliminated; 7% of the injected drug was recovered in the kidney 1 h post-injection . A negligible amount of FC was recovered in the spleen and very little FC or LC was found in the lungs of treated animals . Unlike FC, LC was found to provide a sustained bactericidal drug level (> 40 micrograms mL-1) in the peritoneal fluid for up to 5 h post-injection . LC also achieved significantly higher drug levels, compared with FC, within the liver at 3 and 5 h post-injection . Since severe intra-abdominal sepsis is often characterized by the presence of intraphagocytic bacteria in hepatic and splenic reticuloendothelial systems, the enhanced delivery of liposome-encapsulated anti-microbial agents, such as cefoxitin, to the liver and spleen may provide a more effective treatment for the septic condition.

Biochem Biophys Res Commun, 1993 Aug 16, 194(3), 1161 - 6
Antibodies specific for human albumin function as blocking antibodies when attached to erythrocyte-bound albumin; Houle JJ et al.; Albumin is shown to be firmly bound to human red blood cells using the techniques of flow cytometry, immunoblotting, and complement fixation . The interactions between antibodies attached to the cell bound albumin and the complement system are examined . Antibodies specific for human serum albumin bind to albumin on erythrocytes and activate both homologous and heterologous complement in the absence of hemolysis . Moreover, treatment of erythrocytes with anti-albumin antibodies renders the cells resistant to classical pathway mediated lysis initiated by a passive lysis system . Thus, erythrocyte-bound anti-albumin antibodies appear to function in a manner similar to "blocking" antibodies described in some bactericidal systems.

Can J Anaesth, 1993 Aug, 40(8), 770 - 4
The influence of intravenous anaesthetics on polymorphonuclear leukocyte function; Krumholz W et al.; Polymorphonuclear leukocytes (PMNL) play a vital role in the defence against invading bacteria . It is known that some anaesthetics inhibit PMNL function and, thus, possibly enhance perioperative infection . We investigated the effect of methohexitone, flunitrazepam, and droperidol on three bactericidal PMNL functions, i.e., superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase, in vitro . Approved photometrical assays were used . Superoxide anion was measured by the reduction of cytochrome C, hydrogen peroxide by the horse radish peroxidase catalysed oxidation of phenol red, and myeloperoxidase by the turnover of 2,2'-azino-di(3-ethylbenzthiazoline) sulfonic acid . Methohexitone (P < or = 0.001) and flunitrazepam (P < or = 0.01) inhibited superoxide anion production, and methohexitone (P < or = 0.01) reduced hydrogen peroxide generation but only at concentrations beyond clinical relevance . Droperidol did not cause any alteration of the PMNL functions tested . Consequently, it seems unlikely that the usual doses of methohexitone, flunitrazepam, or droperidol promote bacterial infections in vivo by impairing the activity of myeloperoxidase or by inhibiting the generation of superoxide anion or hydrogen peroxide.

J Vet Med Sci, 1993 Aug, 55(4), 627 - 30
Protective effect of dihydroheptaprenol in combination with vaccine to experimental Actinobacillus pleuropneumoniae infection in guinea pigs and pigs; Kimura M et al.; We investigated the effects of dihydroheptaprenol (DHP) on resistance of guinea pigs and pigs inoculated with Actinobacillus pleuropneumoniae (Apn) vaccine to subsequent challenge with Apn . Guinea pigs with complement-fixation (CF) antibody titers of 1:8 and 1:16 after intramuscular (i.m.) inoculation with inactivated Apn vaccine showed enhanced resistance to intraperitoneal (i.p.) infection with a homologous Apn strain (5 x 10(10) CFU/animal) when injected with DHP (20 mg/kg, i.m.) on the day before infection . The survival rates of the control, vehicle (lecithin solution without DHP), and DHP groups were 33%, 37%, and 63%, respectively, and that of the DHP group was significantly higher than the rates of the other groups (P < 0.05) . Pigs with CF antibody titers of 1:8 and 1:16 after i.m . inoculation with inactivated Apn vaccine showed enhanced resistance to intratracheal infection with 5 x 10(10) CFU of Apn when injected with DHP (1, 2.5, or 5 mg/kg, i.m.) on the day before infection . The survival rates of the control, vehicle, DHP 1 mg/kg, DHP 2.5 mg/kg, and DHP 5 mg/kg groups were 37%, 38%, 47%, 60%, and 73%, respectively, and pigs given DHP at a dose of 5 mg/kg showed a significantly higher survival rate than the vaccinated control pigs (P < 0.05) . The protective effect of DHP in vaccinated guinea pigs and pigs suggests that phagocytosis and bactericidal activity may be enhanced by this agent, depending on some opsonification effect on Apn antibody.

Br J Ind Med, 1993 Aug, 50(8), 732 - 5
Effect of quartz and alumina dust on generation of superoxide radicals and hydrogen peroxide by alveolar macrophages, granulocytes, and monocytes; Gusev VA et al.; Phagocytosis of quartz particles by rabbit alveolar macrophages and monocytes and human granulocytes and monocytes was accompanied by stimulation of substrate free reduction of nitroblue tetrazolium to formazan . This reflects activation of an oxygen dependent bactericidal system of phagocytes and total (exogenic and endogenic) generation of active oxygen species . Low fibrogenic and cytotoxic alumina dust tended to increase formazan production by comparison with quartz dust . During phagocytosis of quartz dust by alveolar macrophages and monocytes there was no exogenic generation of superoxide radicals and hydrogen peroxide by these cells . By contrast, incubation of human granulocytes with quartz dust caused a significant increase in exogenic generation of superoxide radicals and hydrogen peroxide . Under such conditions, low fibrogenic alumina dust had no effect on hydrogen peroxide generation and substantially decreased the level of superoxide radical generation by human granulocytes . During incubation of rabbit granulocytes with quartz dust, an increase in the level of superoxide radical generation was also detected . It is considered that the differences between alveolar macrophages and granulocytes in their response to quartz dust are important from a physiological point of view . Alveolar macrophages are permanently present in pulmonary alveolae in large quantities; therefore their uncontrolled generation of superoxide radicals and hydrogen peroxide might immediately cause damage to pulmonary parenchyma . At the same time, destruction products from alveolar macrophages that died during phagocytosis of quartz particles contain a factor attracting granulocytes . Presence of a significant number of granulocytes in bronchopulmonary lavage fluid in cases of silicosis indicates development of a pathological process . This agrees well with the data obtained on exogenic generation of superoxide radicals and hydrogen peroxide by granulocytes, and on stimulation of this process due to phagocytosis of the quartz dust.

Infect Immun, 1993 Aug, 61(8), 3578 - 82
TnphoA-mediated disruption of K54 capsular polysaccharide genes in Escherichia coli confers serum sensitivity; Russo TA et al.; To assess whether non-K1, group 2 capsular serotypes are important in conferring serum resistance to extraintestinal isolates of Escherichia coli, a K54 blood isolate (CP9) was evaluated as a model pathogen . Transposon mutagenesis (TnphoA) was used to generate isogenic capsule-negative mutants . CP9 was resistant to the bactericidal effects of serum, growing in 80% serum . In contrast, all of the capsule-negative mutants had an increased sensitivity to 80% normal human serum, undergoing a 2- to 3-log kill over 3 h when starting inocula of 10(4) to 10(7) CFU/ml were used . The killing of the capsule-negative strains was mediated through the alternative complement pathway and not by lysozyme or beta-lysins . The protective effect of the K54 capsule against the bactericidal activity of serum was not through inhibition of the complement cascade, nor did it appear to be through a difference in the binding of C3.

J Dent Res, 1993 Aug, 72(8), 1194 - 7
Long-term effects of Meridol and chlorhexidine mouthrinses on plaque, gingivitis, staining, and bacterial vitality; Brecx M et al.; The aim of the present study was to compare the effect on plaque growth and gingival response of Meridol, an amine/stannous fluoride solution, during a three-month investigation, with those of a placebo preparation as a negative control and a chlorhexidine solution as a positive control, in a double-blind study . After having their teeth professionally cleaned, 36 volunteers continued their usual oral hygiene for a period of two weeks . Their teeth were then polished again (month 0) after which they rinsed twice daily (morning and evening) with one of the three mouthrinses in addition to their habitual toothcleaning . After three months of rinsing, plaque indices remained lowest in the chlorhexidine group, although the subjects using Meridol had indices significantly lower than those of individuals rinsing with the placebo solution . The gingival index scores in the Meridol group were higher than in the chlorhexidine group and lower than in the placebo group . The plaque vitality scores showed a bactericidal effect in vivo with chlorhexidine and Meridol during the entire experiment . The use of Meridol resulted in more toothstaining than with the placebo, but significantly less than with chlorhexidine . This study demonstrated that Meridol reduced plaque accumulation, retarded gingivitis development, possessed a definite bactericidal action, and produced only slight toothstaining.

J Chemother, 1993 Aug, 5(4), 223 - 7
In vivo potentiation of polymorphonuclear leukocyte function by ciprofloxacin; Lianou PE et al.; Ciprofloxacin was administered to 10 healthy volunteers at a dose of 250 mg orally . Serum and polymorphonuclear leukocytes (PMNLs) were obtained from all subjects before the administration of the drug and 12 hours after the administration . In addition serum was obtained from all subjects at 24 and 48 hours after ciprofloxacin administration . All sera and PMNLs were used for the chemotactic, phagocytic and killing determinations of the PMNLs . The results demonstrated that serum obtained 12 hours after the administration of ciprofloxacin potentiates PMNL chemotactic activity (chemotactic index (CI) = 33.0 +/- 4.2 microns (means +/- S.D.)) as compared to the chemotactic activity generated by serum obtained prior to administration of the drug, CI = 20.4 +/- 4.4 microns (p < 0.01) . Serum obtained 24 and 48 hours after ciprofloxacin administration did not stimulate PMNL function . The administration of ciprofloxacin did not have any direct influence on the PMNLs in terms of their chemotactic response . Furthermore, serum obtained after the administration of ciprofloxacin markedly enhanced PMNL phagocytosis and killing of all organisms tested . Ciprofloxacin also acted directly on the PMNLs and increased their bactericidal activity . These results demonstrate that ciprofloxacin potentiates PMNL function in vivo which may be of potential clinical benefit.

Indian J Med Res, 1993 Jul, 97, 145 - 50
Bactericidal action of pulsed exposure to rifampicin, ethambutol, isoniazid & pyrazinamide on Mycobacterium tuberculosis in vitro; Paramasivan CN et al.; The bactericidal action of pulsed exposure to rifampicin (R), ethambutol (Emb), isoniazid (I) and pyrazinamide (Z) together on alternate days (REmbIZ) and as REmb and IZ separately on alternate days (REmb/IZ) on M.tuberculosis H37Rv, two isolates of M.tuberculosis sensitive to these drugs, as well as four isolates resistant to one or more drugs, was studied using an in vitro method . The experimental duration was 6 days . REmbIZ and REmb/IZ appeared to have equally good bactericidal action on M.tuberculosis strains in the in vitro system . The results suggest that splitting REmbIZ into REmb and IZ on alternate days in short course chemotherapy regimens for tuberculosis may not affect the bactericidal action of the regimens.

J Infect Dis, 1993 Jul, 168(1), 120 - 7
Down-regulation of chemotaxis of polymorphonuclear leukocytes following thermal injury involves two distinct mechanisms; Bjornson AB et al.; Thermal injury induces a depression of major effector functions of polymorphonuclear leukocytes (PMNL) that contributes to the increased susceptibility to bacterial infection associated with severe injury . In a study on chemotactic alterations in PMNL induced by thermal injury in a well-characterized guinea pig model, a concomitant reduction in the chemotactic response of PMNL to zymosan-activated serum (ZAS) and FMLP was seen early after thermal injury in temporal association with the previously reported bactericidal defect and depression of superoxide anion production . Unlike the bactericidal defect, the chemotactic alterations were not directly linked to the marked elevation of intracellular cAMP in PMNL associated with thermal injury . Two mechanisms (adaptation and desensitization) were shown to be involved in the reduction of chemotactic responses of PMNL to FMLP and ZAS, respectively . Adaptation appears to be a protective response of PMNL to thermal injury unassociated with receptor down-regulation.

New Microbiol, 1993 Jul, 16(3), 251 - 8
Effect of intravenous immunoglobulin on opsonic activity and TNF production in patients at high risk for sepsis syndrome; Nazzari C et al.; In a randomized double blind study, we analyzed the efficacy of IVIG in the infectious complications in patients at high risk of developing sepsis syndrome . Two groups of twenty patients were enrolled, one receiving 250 mg/Kg of IVIG on the first and seventh day after admission and the other receiving sterile saline as placebo . Serum samples were drawn before IVIG administration and 24, 48 and 72 hours afterwards . The same schedule was used for patients treated with placebo . Sera pooled from healthy donors served as controls . On all the samples, opsonic and bactericidal activity as well as C3, total IgG and serum TNF content were tested . IVIG did not significantly affect total IgG and C3 content . Similarly, opsonic and bactericidal activity tested against E . coli 06 :K-, E . coli 0111 and SAC I was not modified ranging within HPS values . Furthermore, IVIG administration did not change the TNF level . A lower incidence of bacteremia in IVIG treated patients was observed.

J Infect Dis, 1993 Jul, 168(1), 188 - 90
Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy; Ji B et al.; Thirty-six patients with newly diagnosed lepromatous leprosy were allocated randomly to three groups and treated for 56 days with minocycline (100 mg daily), clarithromycin (500 mg daily), or clarithromycin (500 mg) plus minocycline (100 mg daily) . All groups had rapid and remarkable clinical improvement and significant decline of the bacterial and morphologic indices in skin smears during treatment . More than 99% and > 99.9% of the viable Mycobacterium leprae had been killed by 28 and 56 days of treatment, respectively, as measured by inoculation of organisms recovered from skin samples, taken before and during treatment, into the footpads of immunocompetent and nude mice . Clinical improvement and bactericidal activity did not differ significantly among the three groups . Adverse reactions were rare and mild, and no laboratory abnormality was detected during the trial . Both clarithromycin and minocycline displayed powerful bactericidal activities against M . leprae in leprosy patients and may be considered important components of new multidrug regimens for the treatment of multibacillary leprosy.

J Antimicrob Chemother, 1993 Jul, 32(1), 93 - 9
Comparative study of the bactericidal activity of ampicillin/sulbactam and erythromycin against intracellular Legionella pneumophila; Ramirez JA et al.; Intracellular bactericidal activity of ampicillin/sulbactam and erythromycin was determined with a human macrophage-like (U-937) cell line infected with Legionella pneumophila . Cell monolayers inoculated with L . pneumophila were treated with erythromycin, ampicillin, sulbactam, or ampicillin/sulbactam during the logarithmic phase of bacterial growth . Intracellular bacterial counts were determined at 2-h intervals for 8 h from the time that antibiotics were added . The number of viable intracellular bacteria increased during this time by 0.9 x log10 cfu/mL (P < 0.05) in the control culture, did not change significantly in the cultures treated with ampicillin or sulbactam, decreased by 0.8 x log10 cfu/mL (P < 0.05) with erythromycin, and decreased by 1.8 x log10 cfu/mL with ampicillin/sulbactam (P < 0.05) . The number of cfu/mL was significantly less after incubation with ampicillin/sulbactam than with erythromycin (P < 0.05) . Ampicillin/sulbactam appeared to have greater bactericidal activity against intracellular L . pneumophila than erythromycin in this in-vitro model . The bactericidal action of ampicillin/sulbactam was significantly greater than would be expected from the additive effects of ampicillin plus sulbactam, suggesting synergic bactericidal activity.

Indian J Exp Biol, 1993 Jul, 31(7), 590 - 4
Growth response of Pseudomonas stutzeri RS34 to ethylenediaminetetraacetic acid (EDTA) and its interaction with zinc; Bhagat R et al.; Pseudomonas stutzeri RS34 is a less sensitive member of pseudomonads to toxic effect of EDTA, the effect of EDTA is more bacteristatic than bactericidal, and can be reversed by divalent cations . Zn2+ provides more specific protection than Mg2+ . EDTA-treated cells show higher sensitivity to lysozyme confirming the chelating mode of action of EDTA that leads to destabilization of the outer membrane . Such metal resistant bacteria can be profitably employed in the removal of metals from polluted ecosystems.

Indian Pediatr, 1993 Jul, 30(7), 883 - 90
Polymorphonuclear leukocyte functions in children with cyanotic and acyanotic congenital heart disease; Parikh S et al.; Eighteen cyanotic congenital heart disease (CCHD) and 17 acyanotic congenital heart disease (ACHD) patients in the age range of 2 months to 10 years along with their age and nutrition matched controls were studied for bactericidal, chemotactic and phagocytic functions . Bactericidal and phagocytic functions were significantly depressed in CCHD (p < 0.001) as well as ACHD group (p < 0.001) compared with controls . Chemotactic function was not significantly affected in either . Arterial oxygen content (as a measure of hypoxia) was calculated for each patient and correlated with each immune parameter by univariate linear regression analysis . In CCHD patients linear correlation of borderline significance (p = 0.07) was found between arterial oxygen content and bactericidal activity, but no correlation could be established with phagocytic and chemotactic functions . No correlation was obtained between hematocrit and any of the immune parameters . In ACHD patients no correlations were obtained between the immune parameters and arterial oxygen content or hematocrit . Iron deficiency anemia, known to affect bactericidal function, did not seem to affect the immune parameters in CCHD and ACHD groups . Altered oxygen content of the blood owing to hypoxia in CCHD patients may be an important etiological factor in the genesis of bacteremia and cerebral abscess . The affection of immune functions in ACHD cannot be adequately explained.

Zh Mikrobiol Epidemiol Immunobiol, 1993 Jul-Aug, (4), 99 - 103
{The functional activity of the peripheral blood neutrophils in patients with chronic brucellosis}; Suleimanov AK et al.; The functional activity of peripheral blood neutrophils was studied by their main functional and metabolic parameters . The group of chronic brucellosis patients under study included 32 patients . The control group consisted of 35 practically healthy donors . The complex of methods, used for the evaluation of the functional activity of peripheral blood neutrophil leukocytes, included the determination of adhesion, activity of nitro blue tetrazolium reduction, enzymatic activity of myeloperoxidase and acid phosphatase, the level of cation protein and the production of active forms of oxygen (AFO) by these cells . Chronic brucellosis patients were found to have disturbances in the adhesive capacity of phagocytizing cells and the production of highly bactericidal AFO . These disturbances in the activity of phagocytizing cells may be one of the mechanisms contributing to incomplete phagocytosis in chronic brucellosis in humans.

Vestn Khir Im I I Grek, 1993 Jul-Dec, 151(7-12), 13 - 5
{The use of low-frequency ultrasound in the surgical treatment of pulmonary echinococcosis}; Islambekov ES et al.; A convincing evidence is given that the low-frequency ultrasound (26.4-26.6 kHz) has pronounced parasiticidal and bactericidal effects and can completely replace the drugs commonly used for disinfection . The low-frequency ultrasound used for treatment of the parasitic cyst bed allows the indication for organ preserving operations to be wider, the complicated forms of the disease included.

J Pharm Pharmacol, 1993 Jul, 45(7), 658 - 62
Function of the SOS process in repair of DNA damage induced by modern 4-quinolones; Howard BM et al.; The recA13 mutant of Escherichia coli strain K-12, which lacks recombination and SOS error-prone DNA repair is hypersensitive to nalidixic acid and to the newer 4-quinolones ciprofloxacin, norfloxacin and ofloxacin . However, whereas recombination-proficient but SOS repair-deficient strains, such as those carrying the lexA3 or recA430 alleles are no more sensitive to nalidixic than the lexA+ recA+ parent, they are more sensitive to the newer quinolones, although not as sensitive as the recA13 derivative . Nalidixic acid possesses only bactericidal mechanism A (which requires RNA and protein synthesis and is only effective on actively dividing cells), whereas the newer 4-quinolones exhibit additional mechanisms B (which does not require RNA and protein synthesis and is effective on bacteria unable to multiply) and C (which requires RNA and protein synthesis but does not depend on cell division) . Results obtained with bacteria suspended in phosphate-buffered saline, which inhibits mechanism A, and with bacteria suspended in nutrient broth plus rifampicin, which inhibits mechanisms A and C, showed that the lexA3 mutant was still more sensitive than the lexA+ parent under these conditions . The results suggest that, unlike bactericidal mechanism A, DNA damage that results from bactericidal mechanisms B and C of the newer 4-quinolones is subject to SOS error-prone (mutagenic) repair.

Ann Surg, 1993 Jun, 217(6), 644 - 53; discussion 653-4
Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance . The role of nitric oxide; Gianotti L et al.; OBJECTIVE: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression . SUMMARY BACKGROUND DATA: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined . METHODS: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow . In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury . Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega-Nitro-L-arginine (NNA) before gavage and burn . The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E . coli from the intestine and the ability of the host to kill translocated organisms was also investigated . Mice were fed and received transfusion, gavage, and burn as above . Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn . RESULTS: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02) . After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01) . In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001) . Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group . However, there was no difference in translocation to the liver and spleen related to dietary group . Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine . Treatment with NNA reversed the beneficial effects of arginine on immune defense . CONCLUSIONS: The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 16 - 20
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Selecting the antibiotic; Craig WA; Variations in antibiotic pharmacokinetics and pharmacodynamics allow therapy to be readily adapted to the outpatient setting . Factors to be taken into account when designing an outpatient parenteral regimen include minimal inhibitory and bactericidal concentrations, post-antibiotic effect, half-life, protein binding, drug stability, IM versus i.v . administration, and continuous versus intermittent infusion.

J Infect Dis, 1993 Jun, 167(6), 1351 - 7
Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes; Heumann D et al.; The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)-mediated activation of monocytes . Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock . To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD14 of monocytes, rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP . Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNF alpha) synthesis from monocytes . LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23 . Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNF alpha release, but this inhibition vanished with delaying the time of addition of rBPI23 . These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS.

Infect Immun, 1993 Jun, 61(6), 2532 - 6
Facilitation of complement-dependent killing of the Lyme disease spirochete, Borrelia burgdorferi, by specific immunoglobulin G Fab antibody fragments; Kochi SK et al.; In the absence of specific antibody, Borrelia burgdorferi is resistant to the bactericidal action of complement, despite the capacity of the spirochete to activate complement . Complement-mediated killing of B . burgdorferi requires the presence of antiborrelial immunoglobulin G (IgG) . The effect of bactericidal IgG takes place after formation of the C5 convertase . Therefore, we examined the ability of Fab fragments from bactericidal IgG to mediate killing of B . burgdorferi by complement . The complement-activating domain of IgG, the Fc fragment, was not required for killing of borreliae, as monovalent Fab fragments prepared from immune IgG were also able to mediate killing . However, the killing efficiency of the Fab fragments was less than that of intact IgG, suggesting that the bactericidal activity of IgG is enhanced by divalency . IgG Fab-mediated killing occurred without increased complement activation or C3 fluid-phase consumption . Cell killing proceeded via the classical complement pathway, as no killing of Fab fragment-sensitized cells was observed in human serum deficient in C2 . These results demonstrate directly that the bactericidal effect of anti-B . burgdorferi IgG is independent of the complement-activating properties of the antibody.

Int J Hematol, 1993 Jun, 57(3), 213 - 9
Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders; Tsurumi H et al.; We analyzed active oxygen (hydroperoxide; H2O2) production by peripheral neutrophils in various hematological diseases by flow cytometry . One hundred microliters of heparinized fresh blood was sequentially incubated at 37 degrees C with 2',7'-dichlorofluorescein diacetate and with or without phorbol myristate acetate (PMA) . After hemolysis, the pelleted white blood cells were subjected to flow cytometry, and the neutrophil fraction was gated on the cytogram . Production of H2O2 by the fraction was estimated by determining the increase in the relative intensity of fluorescence emitted from the fraction in response to stimulation by PMA . In controlled chronic myelogenous leukemia (CML) (WBC < 1 x 10(10)/1), H2O2 production was normal, while in uncontrolled CML (WBC > or = 1 x 10(10)/1), it was reduced . In myelodysplastic syndrome (MDS), H2O2 production was also reduced, but no significant difference was observed among FAB classification disease types in MDS patients . In untreated acute non-lymphocytic leukemia (ANLL), H2O2 production was reduced, while in the complete remission stage of ANLL, its level was normal, suggesting recovery from normal clones . In aplastic anemia, the H2O2 production level was normal . Steroid therapy might be responsible for the reduction of H2O2 production in non-Hodgkin's lymphoma and multiple myeloma . The production of H2O2 is closely related to the oxygen-dependent bactericidal activity of neutrophils, and, hence, can be utilized as an index to indicate susceptibility to infection . This neutrophil function can be determined easily in ordinary clinical facilities by using flow cytometry, and care should be taken to prevent infection when H2O2 production is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Dis Clin North Am, 1993 Jun, 7(2), 445 - 59
Bactericidal testing; Stratton CW; Recognition of the importance of bactericidal activity in certain clinical settings has generated a great deal of interest in bactericidal testing . Indeed, bactericidal testing can be of great use in a number of settings, but it also has the potential for being overutilized . Moreover, there are biologic and technical pitfalls inherent in bactericidal testing . This article addresses these issues and summarizes the progress toward standardization of these methods . Thoughtful and deliberate application of standardized bactericidal testing should make this controversial test much more useful in the future.

J Reprod Med, 1993 Jun, 38(6), 459 - 64
Effect of the HELLP syndrome on maternal immune function; Cunningham DS et al.; The HELLP syndrome occurs in less than 1% of gravidas and is characterized by hemolysis, elevated liver enzymes and low platelet count . The status of immune function in these high-risk patients is not known but may be of great importance in better understanding the basis, if any, of immune dysfunction in pregnancy-associated hypertensive disorders and from the potential compounding effect of infection upon an already debilitated patient . We assessed maternal immune status in patients with the HELLP syndrome using conventional in vitro techniques . The results of these studies clearly show a depression of both T and B cell potential and impaired monocyte handling of intracellular pathogens (up to 33%, 11% and 17% of control values, respectively) . The onset of this immunosuppression occurred before the clinical diagnosis of HELLP syndrome was made and persisted for at least 14 days after clinical resolution . Results of cell admixture studies suggest that these effects are mediated by accessory cells or their products and do not represent true lymphocyte dysfunction . The risk of opportunistic infections may therefore be increased in the patient with the HELLP syndrome because of this generalized immunosuppression and profound decrease in monocyte phagocytic and bactericidal activity.

Acta Stomatol Belg, 1993 Jun, 90(2), 103 - 27
Anatomy of the human temporomandibular joint . An updated comprehensive review; Piette E; This article is an in-depth review of the current knowledge on human temporomandibular joints (TMJ's) . All aspects of joint anatomy are described with emphasis on adaptability to biochemical stimuli throughout life . Each TMJ is a pressure-bearing compound double synovial joint . TMJ's are unique in having a movement not only controlled by the morphology of the joint per se but also by the dentition at the other end of the lever system . During life the temporal, condylar and discal articular surfaces undergo remodelling . The synovium is an important joint component which contributes to nourish and lubricate the avascular surfaces and has bactericidal properties . The joint capsule has privileged relationships anteriorly with the lateral pterygoid muscle . This muscle has two heads that show functionally reciprocal activation . The exact insertion and role of the superior head of the lateral pterygoid muscle remains controversial . The disc has a very low coefficient of friction and compensates for the lack of congruence between articular surfaces . Biomechanically it is stabilized between condyle and articular eminence by its thick rim which has special viscoelastic properties . Apart from the viscoelastic deformations the other important mechanism of disc stabilization seems to be related with the structure of some of the disc attachments.

Pol Tyg Lek, 1993 May 3-10, 48(18-19), 401 - 3
{Activity of bactericidal peripheral granulocytes in blood of workers employed in production of ferromanganese alloys}; Misiewicz A; We estimated bactericidal activity of peripheral blood neutrophils, using nitrotetrazolium blue reduction test (NBT), in metallurgists producing ferromanganese alloys . We didn't find essential changes in neutrophils metabolic activity in metallurgists comparing with the control group . Only spontaneous reduction index mean values were lower in metallurgists working over 10 years, and higher in metallurgists who smoked more cigarettes . Chronic bronchitis increased the index of stimulated reduction NBT.

Antimicrob Agents Chemother, 1993 May, 37(5), 1001 - 3
Postantibiotic effects of amikacin and ofloxacin on Mycobacterium fortuitum; Tsui SY et al.; A study of postantibiotic effects (PAE) in vitro of amikacin and ofloxacin on Mycobacterium fortuitum isolates from sternotomy wounds by use of the dilution method for drug removal showed that both drugs exhibited good bactericidal activities, with the PAE of amikacin lasting from 13.5 to 27.6 h and the PAE of ofloxacin lasting from 1.2 to 5.0 h . These laboratory results concur with our experience of the efficacy of once-daily dosing with these drugs in the treatment of infections caused by M . fortuitum . These data may have therapeutic implications in guiding the scheduling of the administration of drugs in these infections, which require a long duration of therapy.

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