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 t