Antimicrob Agents Chemother, 2000 Apr, 44(4), 1019 - 28 Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae; Brophy VH et al.; There is a pressing need for drugs effective against the opportunistic protozoan pathogen Cryptosporidium parvum . Folate metabolic enzymes and enzymes of the thymidylate cycle, particularly dihydrofolate reductase (DHFR), have been widely exploited as chemotherapeutic targets . Although many DHFR inhibitors have been synthesized, only a few have been tested against C . parvum . To expedite and facilitate the discovery of effective anti-Cryptosporidium antifolates, we have developed a rapid and facile method to screen potential inhibitors of C . parvum DHFR using the model eukaryote, Saccharomyces cerevisiae . We expressed the DHFR genes of C . parvum, Plasmodium falciparum, Toxoplasma gondii, Pneumocystis carinii, and humans in the same DHFR-deficient yeast strain and observed that each heterologous enzyme complemented the yeast DHFR deficiency . In this work we describe our use of the complementation system to screen known DHFR inhibitors and our discovery of several compounds that inhibited the growth of yeast reliant on the C . parvum enzyme . These same compounds were also potent or selective inhibitors of the purified recombinant C . parvum DHFR enzyme . Six novel lipophilic DHFR inhibitors potently inhibited the growth of yeast expressing C . parvum DHFR . However, the inhibition was nonselective, as these compounds also strongly inhibited the growth of yeast dependent on the human enzyme . Conversely, the antibacterial DHFR inhibitor trimethoprim and two close structural analogs were highly selective, but weak, inhibitors of yeast complemented by the C . parvum enzyme . Future chemical refinement of the potent and selective lead compounds identified in this study may allow the design of an efficacious antifolate drug for the treatment of cryptosporidiosis. Antimicrob Agents Chemother, 2000 Apr, 44(4), 938 - 42 In vivo characterization of the pharmacodynamics of flucytosine in a neutropenic murine disseminated candidiasis model; Andes D et al.; In vivo pharmacodynamic parameters have been characterized for a variety of antibacterial agents . These parameters have been studied in correlation with in vivo outcomes in order to determine (i) which dosing parameter is predictive of outcome and (ii) the magnitude of that parameter associated with efficacy . Very little is known of the pharmacodynamics of antifungal agents . We used a neutropenic murine model of disseminated candidiasis to correlate the pharmacodynamic parameters (percentage of time above the MIC, area under the concentration-time curve {AUC}/MIC and peak level/MIC) for flucytosine (5-FC) in vivo with efficacy as measured by organism number in homogenized kidney cultures after 24 h of therapy . The pharmacokinetics of 5-FC in infected mice were linear . Serum half-lives ranged from 0.36 to 0.43 h . Infection was achieved by intravenous inoculation of 10(6) CFU of yeast cells per ml via the lateral tail vein of neutropenic mice . Groups of mice were treated with fourfold escalating total doses of 5-FC ranging from 1.56 to 400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24 h . Increasing doses produced minimal concentration-dependent killing ranging from 0 to 0.9 log(10) CFU/kidneys . 5-FC did, however, produce a dose-dependent suppression of growth after levels in serum had fallen below the MIC . The fungistatic dose increased from 6 to 8 mg/kg with dosing every 3 and 6 h to 70 mg/kg at with dosing every 24 h . Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy . Time above the MIC was the parameter best predictive of outcome, while AUC/MIC was only slightly less predictive (time above MIC, R(2) = 85%; AUC/MIC, R(2) = 77%; peak level/MIC, R(2) = 53%) . Maximal efficacy was observed when levels exceeded the MIC for only 20 to 25% of the dosing interval . If one considers drug kinetics in humans, these results suggest reevaluation of current dosing regimens. Arch Surg, 2000 Mar, 135(3), 309 - 14 Chlorhexidine lavage in the treatment of experimental intra-abdominal infection; Bondar VM et al.; HYPOTHESIS: Closed postoperative peritoneal lavage (CPPL) with chlorhexidine gluconate reduces the number of intraperitoneal bacteria and improves the outcome of intra-abdominal infection . DESIGN: Laboratory animal trial . INTERVENTIONS: Intra-abdominal infection was produced in mice by the cecal ligation and puncture technique . After 16 to 18 hours, the animals underwent relaparotomy and placement of an intra-abdominal catheter for CPPL . In the first experiment animals were randomly divided into 4 groups: no lavage (served as a control), CPPL with chlorhexidine . CPPL with cefoxitin, and CPPL with lactated Ringer solution (LR) . Lavage was continued intermittently every 8 hours for 24 hours . All animals received systemic cefoxitin every 8 hours for 7 days . Mortality was recorded every 8 hours for 10 days . In the second experiment, animals were divided into 3 groups: no lavage (served as a control), CPPL with chlorhexidine, and CPPL with LR . Lavage was continued intermittently every 8 hours for 24 hours . The animals were killed 48 hours after reoperation . Bacterial counts from peritoneal fluid and biopsy specimens, as well as peritoneal white blood cell counts, were measured before and after lavage . RESULTS: Closed postoperative peritoncal lavage with chlorhexidine reduced mortality from 71% in a control group to 37% (P = .003) . There was no survival benefit in either the CPPL with cefoxitin (91% mortality) (P = .14) or CPPL with LR groups (90% mortality) (P = .17) . The statistically significant findings of analysis of variance evaluation demonstrated a decrease in bacterial counts after cecal excision in all 3 groups . There was a greater reduction in bacterial counts in the chlorhexidine group compared with the control group (P<.05) . Bacterial counts decreased in peritoneal fluid, as well as in tissue biopsy specimens, after cecal excision . White blood cell counts significantly decreased after cecal excision in all 3 groups . There was no difference in white blood cell counts between the groups . Correlation analyses demonstrated weak interaction between bacterial and white blood cell counts before or after treatment in all the groups . Pearson r ranged from -0.37 to +0.35, none of which were statistically significant . CONCLUSIONS: In our experiments chlorhexidine lavage resulted in a 50% reduction in mortality and a significant reduction in bacterial counts compared with the control group . There was no survival benefit from lavage with either cefoxitin or LR . There was no reduction in bacterial counts in the LR group relative to the control group . Thus, the survival benefit and the reduction in bacterial numbers are attributed to the antibacterial properties of chlorhexidine rather than to the mechanical washing of the abdominal cavity . Closed postoperative peritoneal lavage with 0.05% chlorhexidine gluconate might be useful in the multimodal treatment of intra-abdominal infection. Drugs, 2000 Jan, 59(1), 115 - 39 Moxifloxacin: a review of its clinical potential in the management of community-acquired respiratory tract infections; Balfour JA et al.; Moxifloxacin is an extended-spectrum fluoroquinolone which has improved coverage against gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, while retaining good activity against gram-negative bacteria . The antibacterial spectrum of moxifloxacin includes all major upper and lower respiratory tract pathogens; it is one of the most active fluoroquinolones against pneumococci, including penicillin- and macrolide-resistant strains . In in vitro studies, emergence of bacterial resistance was less common with moxifloxacin than with some other fluoroquinolones, but this requires confirmation in large-scale clinical studies . As with other fluoroquinolones, moxifloxacin achieves good penetration into respiratory tissues and fluids . It shows a low potential for drug interactions and dosage adjustment is not required for patients of advanced age or those with renal or mild hepatic impairment . The efficacy of oral moxifloxacin has been demonstrated in large, well-designed clinical trials in patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis . Moxifloxacin 400 mg once daily achieved bacteriological and clinical success rates of approximately 90% or higher . It was as effective as, or more effective than, comparators including clarithromycin, cefuroxime axetil and high dose amoxicillin in these trials . The most commonly reported adverse events in patients receiving moxifloxacin are gastrointestinal disturbances . Moxifloxacin is also associated with QTc prolongation in some patients; there are, as yet, no data concerning the possible clinical sequelae of this effect in high-risk patients . Moxifloxacin has a low propensity for causing phototoxic reactions relative to other fluoroquinolones, and animal data suggest that it has a low potential for causing excitatory CNS and hepatotoxic effects . Conclusions: As an extended-spectrum fluoroquinolone, moxifloxacin offers the benefits of excellent activity against pneumococci, once daily administration and a low propensity for drug interactions . Although studies are needed regarding its tolerability in at-risk patients with QT interval prolongation, available data suggest that moxifloxacin is likely to become a first-line therapy option for the treatment of community-acquired lower respiratory tract infections, particularly in areas where drug-resistant S . pneumoniae or H . influenzae are common. Int J Antimicrob Agents, 2000 Feb, 14(1), 33 - 7 Use of antibiotics in an Italian children's hospital, 1993-1995; clinical and economic considerations; Bassetti M et al.; Antibiotic consumption and expenditure was studied during 1993 and 1995 in G . Gaslini children's hospital, an Italian 400-bed paediatric hospital, to see if any changes in use had occurred . There was an increase in the cost of antibacterial agents from 1993 to 1995, with a decrease in the daily cost of antibiotics and in the consumption of antiviral, antifungal and antiparasitic agents . There was a notable increase in the use of glycopeptides and carbapenems between 1995 and 1993 especially in specialities such as onco-haematology and intensive care . We suggest a basis for an antibiotic management programme aimed at reducing costs while still providing a high standard of care for patients. Biochemistry, 2000 Mar 21, 39(11), 3091 - 6 Reactions of glutamate 1-semialdehyde aminomutase with R- and S-enantiomers of a novel, mechanism-based inhibitor, 2,3-diaminopropyl sulfate; Contestabile R et al.; Glutamate semialdehyde aminomutase is a recognized target for selective herbicides and antibacterial agents because it provides the aminolevulinate from which tetrapyrroles are synthesized in plants and bacteria but not in animals . The reactions of the enzyme with R- and S-enantiomers of a novel compound, diaminopropyl sulfate, designed as a mechanism-based inhibitor of the enzyme are described . The S-enantiomer undergoes transamination without significantly inactivating the enzyme . The R-enantiomer inactivates the enzyme rapidly . Inactivation is accompanied by the formation of a 520 nm-absorbing chromophore and by the elimination of sulfate . The inactivation is attenuated by simultaneous transamination of the enzyme to its pyridoxamine phosphate form but inclusion of succinic semialdehyde to reverse the transamination leads to complete inactivation . The inactivation is attributed to further reactions arising from generation of an external aldimine between the pyridoxal phosphate cofactor and the 2,3-diaminopropene that results from enzyme-catalyzed beta-elimination of sulfate. Bioorg Med Chem Lett, 2000 Feb 21, 10(4), 333 - 6 Synthesis and antibacterial activity of 2alpha-functionalized 1beta-methylcarbapenems related to KR-21012; Kwak HJ et al.; The 2alpha-functionalized 1beta-methylcarbapenems 3 were synthesized from the 2-formyl 1beta-methylcarbapenem intermediate 5 . The best compound in the series of 2alpha-(hydroxy)alkylcarbapenems, KR-21012, displayed well balanced in vitro and in vivo activity as a parent compound of oral carbapenem. J Periodontol, 2000 Feb, 71(2), 202 - 8 Fluoroquinolones in the treatment of Actinobacillus actinomycetemcomitans-associated periodontitis; Kleinfelder JW et al.; BACKGROUND: Periodontitis patients harboring Actinobacillus actinmycetemcomitans (Aa) are prime candidates for systemic antibiotic therapy . Besides tetracycline and the combination of metronidazole and amoxicillin the fluoroquinolones are also believed to have antibacterial activity against Aa . The aim of the present study was to evaluate systemic ofloxacin therapy as adjunct to flap surgery . METHODS: Twenty-five adult periodontitis patients with subgingival detection of Aa were treated with 2x200 mg/d ofloxacin for 5 days as adjunct to open flap surgery (test) . Another 10 patients received only flap surgery (control) . Probing depth (PD) and clinical attachment level (CAL) was recorded and subgingival plaque samples were cultivated on TSBV agar for detection of Aa at baseline as well as 3 and 12 months following therapy . RESULTS: At 3 and 12 months following therapy mean PD at monitored sites in the test group changed from 6.8 mm (+/-1.3) to 3.6 mm (+/-1.0), 3.8 mm (+/-1.1) and CAL from 7.5 mm (+/-1.4) to 5.4 mm (+/-1.4), 5.5 mm (+/-1.3) . In the control group PD changed from 6.5 mm (+/-0.7) to 4.0 mm (+/-1.7), 4.1 mm (+/-1.6) and CAL from 7.5 mm (+/-1.0) to 6.3 mm (+/-1.7), 6.4 mm (+/-1.8) . P was <0.05 for CAL between groups . Three and 12 months following adjunctive systemic ofloxacin therapy, Aa was suppressed below detectable levels in 22 of 22, test patients, whereas Aa could not be recovered in only 2 of the 10 controls . (P<0.0001) . CONCLUSIONS: Systemic ofloxacin as adjunct to open flap surgery is able to suppress A . actinomycetemcomitans below detectable level in patients harboring this organism at baseline. Khirurgiia (Mosk), 2000, (2), 38 - 40 {Endobronchial laser therapy in complex preoperative preparation of patients with lung diseases}; Uspenskii LV et al.; The method of endobronchial laser therapy with the use of photosensitiser-photosense (phthalocyanine aluminum)--was used since 1998 for the first time in faculty surgical clinic, as preoperative preparation in 36 patients with surgical diseases of the lungs (malignant and benign tumors and chronic inflammatory diseases) . The method aimed at elimination of postoperative pyogenous complications and improvement of the respiratory system functional . The method consists in introduction into the organism by various ways the photosensitizing preparation photosence, followed by irradiation of the right and left parts of bronchial tree by low intensity laser light, (wave length 675 mm) through dispersing light guide, introduced through the flexible bronchoscope to the areas of the ostia of the lobar bronchi . 3 ways of introduction of the photosensitizer were used: endobronchial (9 patients); aerosol (22 patients); combination of the endobronchial lavage and intravenous injection (5 patients) . The duration of the procedure of irradiation made up 5 min . at each side of the bronchial tree, the power density being 85 mV/cm2 . The procedure was repeated twice for 2 days . The following results were obtained: antibacterial effect; reduction of endoscopic and morphological features of inflammation of the bronchial mucosa; stimulation of local immunity; decrease of the tumor aggression (according to histological examination); the appearance of the tumor destruction areas; lavering of Ki-67 and bcl-2, increase of c-bax; the improvement of the respiratory system functional; positive dynamics of clinical status (a decrease of cough, dispnea, quantity of mucus discharge and haemoptysis) . The perspectiveness of the method is stressed as a preoperative preparation in patients with surgical diseases of the lungs. Int Endod J, 1999 Nov, 32(6), 430 - 5 The shear bond strength of glass ionomer cement sealers to bovine dentine conditioned with common endodontic irrigants; Lalh MS et al.; AIM: The aim of this in vitro study was to evaluate the shear bond strength of commercially available and experimental glass ionomer cement (GIC) sealers to dentine exposed to common endodontic irrigants . METHODOLOGY: The enamel of 90 bovine incisor crowns, randomly divided into nine equal groups, was ground to expose the superficial dentine layer . The exposed surface was conditioned with either: (i) distilled H2O; (ii) 2.6% NaOCl; or (iii) 17% EDTA followed by 2.6% NaOCl . Five cc of each irrigant was applied over a 30-second period . The following GIC sealers were tested: (i) Ketac-Endo; (ii) KT-308, an experimental sealer; and (iii) ZUT, a combination of KT-308 and an antibacterial agent (0.2% by weight) . The test sealers were applied to form cylinders with a standardized contact surface area (17.8 mm2) on the conditioned dentine surfaces . Specimens were bench set for 90 min and stored in distilled water at 37 degrees C for 48 h, then tested to failure for shear bond strength (MPa) in an Instron machine . RESULTS: KT-308 and ZUT had significantly higher MPa values than Ketac-Endo (two-factor ANOVA, P < 0.0001), regardless of the dentine conditioning . All specimens conditioned with 17% EDTA and 2.6% NaOCl combined had significantly lower MPa values than those conditioned with water or 2.6% NaOCl alone (P < 0.02) . CONCLUSIONS: It was concluded that the experimental sealers KT-308 and ZUT bonded better to bovine dentine than Ketac-Endo, and that the bond of all three GIC sealers was better with the smear layer present. Therapie, 1999 Nov-Dec, 54(6), 763 - 5 Screening of antibacterial and antiparasitic activities of six Moroccan medicinal plants; Larhsini M et al.; The extracts of six plants selected on the basis of folk-medicine reports were examined for their antibacterial effects against eight pathogenic bacteria . The results showed that n-butanol extract of Calotropis procera proved to be the most effective against the bacteria tested using the paper disc diffusion method . The antiprotozoal activity was also examined and showed that ethyl ether extract of Sium nodiflorum exhibits a parasiticidal effect against Trichomonas intestinalis and vaginalis. Therapie, 1999 Nov-Dec, 54(6), 753 - 8 Antitumour principles from Peganum harmala seeds; Lamchouri F et al.; From ancient times, Peganum harmala was claimed to be an important medicinal plant . Its seeds were known to possess hypothermic, and essentially hallucinogenic properties . Various authors have undertaken studies on the antibacterial, antifungal and antiviral effects of Peganum harmala seeds, but studies on the antitumour activity are not to be found in the literature . In Moroccan traditional medicine, seed powder is sometimes used on skin and subcutaneous tumours . This work was designed to investigate some aspects of the antineoplastic properties of the plant Peganum . Varying concentrations (10 to 120 micrograms/ml) of total alkaloid extracts of Peganum harmala seeds (collected in Morocco) were tested in vitro on four tumoural cell-lines: Med-mek and UCP-Med carcinoma, UCP-Med sarcoma and Sp2/O-Ag14 . In vivo experiments were performed with the Sp2/O cell-line grafted subcutaneously in syngenic BALB/c mice . In vitro, proliferation of tumoural cell lines was significantly reduced by all tested concentrations of the Peganum alkaloid extracts during the first 24 h of contact . A cell lysis effect occurred after 24 h and progressed to complete cell death within 48 to 72 h depending on the alkaloid concentration . Results obtained indicate that alkaloids of Peganum have a high cell toxicity in vitro . The active principle at a dose of 50 mg/kg given orally to mice for 40 days was found to have significant antitumoural activity . Peganum harmala alkaloids thus possess significant antitumour potential, which could prove useful as a novel anticancer therapy. Drug Metabol Drug Interact, 1999, 15(2-3), 187 - 95 Synthesis and antibacterial activity of 1-(3-hydroxy-2-naphthoyl)-4-substituted thiosemicarbazides; Dogan HN et al.; 1-(3-Hydroxy-2-naphthoyl)-4-substituted thiosemicarbazides were obtained by the addition of 3-hydroxy-2-naphthoic acid hydrazide to various isothiocyanates . The structures of the synthesized compounds were confirmed using UV and 1H-NMR spectral methods together with elemental analysis. Chemosphere, 2000 Apr, 40(7), 731 - 9 Algal toxicity of antibacterial agents used in intensive farming; Halling-Sorensen B; The growth inhibiting effects of eight antibiotics used either therapeutically or as growth promoters in intensive farming on two species of micro algae, Microcystis aeruginosa (freshwater cyanobacteria) and Selenastrum capricornutum (green algae) were investigated . The effects of the antibiotics benzylpenicillin (penicillin G) (BP), chlortetracycline (CTC), olaquindox (O), spiramycin (SP), streptomycin (ST), tetracycline (TC), tiamulin (TI) and tylosin (TY) were tested in accordance with the ISO 8692 (1989) standard protocol . Algal growth was measured as increase in chlorophyll concentration by extraction with ethanol followed by measurement of fluorescence . Results were quantified in terms of growth rates using the Weibull equation to describe the concentration response relationship . The toxicity (EC50 value, mg/l) in alphabetic order were BP (0.006); CTC (0.05); O (5.1); SP (0.005); ST (0.007); TC (0.09); TI (0.003) and TY (0.034) for M . aeruginosa . BP (NOEC = 100); CTC (3.1); O (40); SP (2.3); ST (0.133); TC (2.2); TI (0.165) and TY (1.38) for S . capricornutum . In this investigation M . aeruginosa is found to be about two orders of magnitude more sensitive than S . capricornutum . It was observed that most of the compounds were unstable during the test period due to hydrolysis and photolysis. Mediators Inflamm, 1999, 8(3), 147 - 51 Production of secretory leucocyte protease inhibitor (SLPI) in human pancreatic beta-cells; Nystrom M et al.; Secretory leucocyte protease inhibitor (SLPI) is a potent inhibitor of granulocyte elastase and cathepsin G, and also an inhibitor of pancreatic enzymes like trypsin, chymotrypsin and pancreatic elastase . SLPI has also been shown to inhibit HIV-1 infections by blocking viral DNA synthesis . Since SLPI is an inhibitor of pancreatic proteases we wished to investigate whether SLPI was also actually produced in the pancreas . M-RNA from human pancreatic tissue showed evidence of SLPI production using the reverse transcriptase polymer chain reaction technique (RT-PCR) . Using immunohistochemical methods SLPI was demonstrated in the beta-cells of the islets of Langerhans . The function could be local protease/antiprotease regulation or antiviral/antibacterial defence in the close vicinity of the cell surface, or even inside the beta-cell itself. Vopr Onkol, 1999, 45(6), 660 - 2 ¿The use of Neupogen in prevention of purulent septic complications after radical surgery for esophageal cancerv; Drukin EIa et al.; To prevent purulent complications, a granulocyte-colony stimulating factor--filgrastim-neupogen (200 or 480 mg) was injected during radical surgery and for the following 6 weeks in 26 patients with esophageal tumors and gastric cancer disseminated to the esophagus . A significant rise in leukocyte levels which potentiated antibacterial therapy was recorded in all patients . Purulent septic complication was registered in one case. J Periodontal Res, 1999 Nov, 34(8), 437 - 44 Cysteine protease inhibitory activity and levels of salivary cystatins in whole saliva of periodontally diseased patients; Baron AC et al.; The 3 human salivary cystatins S, SA and SN are multifunctional proteins that possess a cysteine protease inhibitory property, but their ability to act as such is very different (SN > SA >> S) . One form, S, also appears to possess antibacterial properties towards the bacterium Porphyromonas gingivalis, often associated with periodontal diseases . In this study we measured the total cystatin inhibitory activity and the levels of each salivary cystatin in the whole saliva of 8 periodontally diseased patients and 2 groups of control subjects (n = 6 and n = 10) . The total cystatin inhibitory activity and the total salivary cystatin concentration in the periodontally diseased patients were found to be lower than the controls (p < or = 0.005) . The concentration of S was depleted to levels that would not allow it to be an effective antibacterial agent, and the concentration of SA, although depleted in some cases, was still present at sufficient levels to allow it to act as an effective physiological inhibitor of cathepsin L . The concentration of cystatin SN was also depleted in the periodontally diseased patients, but was still present in sufficient quantities to act as an effective physiological cysteine protease inhibitor of cathepsins H and L . In comparison, the concentration of all 3 salivary cystatins in the control subjects were sufficient to enable these proteins to be both effective physiological cysteine protease inhibitors and antibacterial agents. Prep Biochem Biotechnol, 2000 Feb, 30(1), 69 - 78 Preliminary study on the cleavage of fusion protein GST-CMIV with palladium(II) complex; Dou F et al.; A novel method for post-treatment of gene-engineered proteins is reported . A coden of Cys-His unit is introduced into the N-terminal of cecropin CMIV by using PCR . The gene is expressed in E . coli fused with GST . After purification, the fusion protein is cleaved by {Pd(en)(H2O)2}2+ at the His-Arg bond and the cecropin CMIV with antibacterial activity is obtained . The preliminary results held some promise of success for application of the palladium(II) complex as cleavage agent for the production of peptide drugs from gene-engineering fusion proteins. Eur Respir J, 2000 Jan, 15(1), 62 - 7 Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages; Kohri K et al.; There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties . In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro . The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting . Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA . The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cefaclor . These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor . These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation. J Invest Dermatol, 2000 Mar, 114(3), 569 - 75 Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice; Ohshima A et al.; Quinolone antibacterial agents are well known to cause photoallergy as a side-effect . Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells . In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells . Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells . In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody . Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional . There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity . Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy. Antibiot Khimioter, 2000, 45(1), 16 - 20 {The in-vitro effect of the leukocytic cationic protein preparation Intercide on Escherichia coli}; Bukharin OV et al.; Intercide is a cationic protein with the molecular weight of 11.0-11.5 kD from human leukocytes . The in vitro effect of its different concentrations (0.6 to 1.8 mg/ml) on populations of Escherichia coli M17 and K12 and 120 E.coli isolates from various sources such as water, feces of healthy humans and patients with extraintestinal escherichiosis was studied . The experiments with the bacterial suspensions and broth cultures demonstrated that Intercide had an antibacterial action on both the stationary and growing cells . However, some strains of E.coli were resistant to the lethal effect of Intercide . It was observed for the first time that in a concentration of 1.8 mg/ml Intercide was able to stimulate the biomass growth of some E.coli strains in broth culture . The factor analysis showed that the Intercide stimulating effect was more often evident with respect to extraintestinal escherichiosis pathogens with high anti-Intercide and antilysozyme activities. Ugeskr Laeger, 2000 Feb 7, 162(6), 773 - 7 {Invasive aspergillosis in hematological patients}; Rask CU et al.; An increasing incidence of invasive aspergillosis over the last decades is well documented in patients with haematological malignancies and is the most significant fungal infection in patients undergoing bone marrow transplantation and in aplastic anaemia . The diagnosis is difficult as clinical signs and symptoms usually are non-specific, but can be supported by frequent radiological examinations of the chest and sinuses and successive demonstrations of Aspergillus antigen in serum . The prognosis depends on the course of the underlying disease . A regeneration of the neutrophil granulocyte number is a condition for successful treatment . Early antifungal therapy is often necessary in neutropenic patients with fever and a lung infiltrate that does not remit following broad spectrum antibacterial treatment . Because of the risk of relapse after successful treatment these patients should receive prophylactic antifungal treatment during subsequent neutropenic episodes. Vaccine, 2000 Feb 25, 18(16), 1712 - 6 Enhancement of immunocompetence in tuberculosis by DNA vaccination; Lowrie DB et al.; Our studies in mice show that DNA vaccines, initially designed to prevent infection, can have a dramatic therapeutic action too . In heavily infected mice, simply by giving DNA vaccination, the immune response can be caused to switch from one that is relatively inefficient and gives bacterial stasis to one that kills the bacteria, and persistent bacteria can be eliminated . Adoptive transfer of protection with T cell clones and in vitro tests of clone function indicate that the effects are probably mainly mediated by antigen specific CD8+/CD4-/CD44hi T cells that both produce gamma-interferon and kill the bacteria during granule-dependent lysis of infected macrophages . We can speculate that application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in man . Furthermore, similar vaccines used prophylactically and therapeutically might be able to both prevent establishment of this persistent state and eliminate it if it is already established. Dev Comp Immunol, 2000 Jan, 24(1), 1 - 12 Gender differences and individual variation in the immune system of the scorpionfly Panorpa vulgaris (Insecta: Mecoptera); Kurtz J et al.; From investigations of the vertebrate immune system gender specific differences in individual immunocompetence are well known . In general, females seem to possess more powerful immune systems than males . In invertebrates, the situation is much less clear . Therefore, we investigated the immune system of an invertebrate species, the scorpionfly Panorpa vulgaris . We found a high degree of individual variation in both traits studied, the lysozyme-like antibacterial activity of hemolymph and the capacity for in vitro phagocytosis of artificial particles . These two immune traits were positively correlated . As expected, hemolymph derived from females had higher lysozyme-like activity and hemocytes from females phagocytosed more particles . The difference in phagocytosis was mainly based on higher total hemocyte counts and higher proportions of phagocytically active cells in females, while the average number of ingested particles per active phagocyte was not significantly different . The observed gender differences are discussed in the context of reproductive strategies and parasite-mediated sexual selection. Proc Natl Acad Sci U S A, 2000 Feb 29, 97(5), 2241 - 6 Isolation of peptide aptamers that inhibit intracellular processes; Blum JH et al.; We have developed a method for isolation of random peptides that inhibit intracellular processes in bacteria . A library of random peptides expressed as fusions to Escherichia coli thioredoxin (aptamers) were expressed under the tight control of the arabinose-inducible P(BAD) promoter . A selection was applied to the library to isolate aptamers that interfered with the activity of thymidylate synthase (ThyA) in vivo . Expression of an aptamer isolated by this method resulted in a ThyA(-) phenotype that was suppressed by simultaneous overexpression of ThyA . Two-hybrid analysis showed that this aptamer is likely to interact with ThyA in vivo . The library also was screened for aptamers that inhibited growth of bacteria expressing them, and five such aptamers were characterized . Four aptamers were bacteriostatic when expressed, whereas one showed a bactericidal effect . Introduction of translational stop codons into various aptamers blocked their activity, suggesting that their biological effects were likely to be due to protein aptamer rather than RNA . Combinatorial aptamers provide a new genetic and biochemical tool for identifying targets for antibacterial drug development. Audiol Neurootol, 2000 Jan-Feb, 5(1), 3 - 22 Aminoglycoside antibiotics; Forge A et al.; In the 50 years since their discovery, the aminoglycoside antibiotics have seen unprecedented use . Discovered in the 1940s, they were the long-sought remedy for tuberculosis and other serious bacterial infections . The side effects of renal and auditory toxicity, however, led to a decline of their use in most countries in the 1970s and 1980s . Nevertheless, today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost . This review first summarizes the history, chemistry, antibacterial actions and acute side effects of the drugs . It then details the pathophysiology of aminoglycoside ototoxicity including experimental and clinical observations, risk factors and incidence . Pharmacokinetics, cellular actions and our current understanding of the underlying molecular mechanisms of ototoxicity are discussed at length . The review concludes with recent advances towards therapeutic intervention to prevent aminoglycoside ototoxicity . Fertil Steril, 2000 Feb, 73(2), 353 - 8 Evaluation of the antifertility effect of magainin-A in rabbits: in vitro and in vivo studies; Reddy VR et al.; OBJECTIVE: To evaluate the safety and contraceptive potential of magainin-A in rabbits . DESIGN: Controlled laboratory study . SETTING: Department of Immunology, Institute for Research in Reproduction, Mumbai, Parel, India . ANIMAL(S): Forty-eight female New Zealand white rabbits . INTERVENTION(S): The effect of magainin-A on sperm motility (in vitro and in vivo studies) and on vaginal epithelium (histologic study) was assessed along with serum and liver biochemical profiles . MAIN OUTCOME MEASURE(S): Suitability of magainin-A for contraceptive use . RESULT(S): Magainin-A arrested sperm motility, and 1 mg of magainin-A administered intravaginally blocked conception . No histopathologic abnormalities in the vaginal tissue or any changes in serum biochemical profiles were observed . CONCLUSION(S): Magainin-A may be used as an effective and safe intravaginal contraceptive compound that also has antibacterial properties. Hua Xi Yi Ke Da Xue Xue Bao, 1998 Jun, 29(2), 122 - 6 {Partially purified antibacterial polypeptides from granules of human large granular lymphocytes}; Huang N et al.; This was a study on the antibacterial activity of human large granular lymphocytes (LGL) . In our previous work, three antibacterial fractions named HLP-1, HLP-2 and HLP-3 had been identified from the acid-soluble extracts of the granules of LGL by using the gel overlay technique . The present study demonstrated that HLP-1, HLP-2 and HLP-3 separated by preparative acid-urea polyacrylamide gel electrophoresis were potently bactericidal against E . coli MI-35P, S . aureus ATCC 25923, P . aeruginosa ATCC 27853 when tested for their antibacteiral activities by using both agarose radial diffusion assay and gel overlay technique . SDS-PAGE analysis showed that the HLP-3 was almost purified with the molecular weight of 7 kd . The HLP-1 and HLP-2 were more complex, and the ranges of molecular weight were 5.6-13 kd and 5.6-8.8 kd respectively . Our study suggests that the granules of human LGL might contain some low molecular weight antibiotic peptides which play an important role in human innate immunity. Hua Xi Yi Ke Da Xue Xue Bao, 1998 Mar, 29(1), 25 - 8 {Isolation of antibacterial polypeptides of human cervical mucus}; Huang N et al.; The acid-soluble extract of human cervical mucus was obtained by solving mucus with 5% acetic acid in the presence of protease inhibitor . The antibacterial activity of the acid-soluble extract was analyzed by gel overlay technique . The result showed that two protein bands which were designated human cervical protein-1 (Hcp-1), human cervical protein-2(Hcp-2) were potently antibacterial against E . coli 25922 and S . aureus 25923 . Tricine-SDS-PAGE analysis indicated that Hcp-1, Hcp-2 actually contained three and four protein bands respectively . The molecular weights of Hcp-1 were 6.7 kd, 10 kd, 15.4 kd; these of Hcp-2 were 4.4 kd, 6.7 kd, 9 kd, 15.4 kd . Our studies suggested that human cervical mucosa might secrete some currently-unknown antibacterial polypeptides which play an important role in the cervical defense against infection. Curr Opin Microbiol, 2000 Feb, 3(1), 60 - 4 Bacterial adaptation to host innate immunity responses; Rhen M et al.; Several recent reports show that different bacterial components trigger innate and inflammatory responses in host organisms . In parallel, selected bacterial virulence factors have been identified that interfere with corresponding responses . In many cases, this involves interference with host proinflammatory signal transduction pathways, whereas in selected cases bacterial virulence factors interfere with host antibacterial mechanisms . This indicates that bacteria, besides activating cellular responses, also have the capacity to directly interact with branches of the innate defence. Antimicrob Agents Chemother, 2000 Mar, 44(3), 602 - 7 Antibacterial and antimembrane activities of cecropin A in Escherichia coli; Silvestro L et al.; The ability of cecropin A to permeabilize and depolarize the membranes of Escherichia coli ML-35p bacteria has been compared to its bactericidal activity in an extension of earlier studies performed on synthetic lipid vesicle membranes (L . Silvestro, K . Gupta, J . H . Weiser, and P . H . Axelsen, Biochemistry 36:11452-11460, 1997) . Our results indicate that differences in the concentration dependences of membrane permeabilization and depolarization seen in synthetic vesicles are not manifested in whole bacteria . The concentration dependences of both phenomena roughly correlate with bactericidal activity, suggesting that the bactericidal mechanism of cecropin A is related to membrane permeabilization. Antimicrob Agents Chemother, 2000 Mar, 44(3), 511 - 21 Effect of proinflammatory cytokines on the interplay between roxithromycin, HMR 3647, or HMR 3004 and human polymorphonuclear neutrophils; Vazifeh D et al.; Cytokines, the hallmarks of infectious and inflammatory diseases, modify phagocyte activities and thus may interfere with the immunomodulating properties of antibacterial agents . We have investigated whether various proinflammatory cytokines (interleukin 1 {IL-1}, IL-6, IL-8, gamma interferon, tumor necrosis factor alpha {TNF-alpha}, and granulocyte-macrophage colony-stimulating factor {GM-CSF}) modify two macrolide properties, i.e., inhibition of oxidant production by polymorphonuclear neutrophils (PMN) and cellular uptake . Roxithromycin and two ketolides, HMR 3647 and HMR 3004, were chosen as the test agents . TNF-alpha and GM-CSF (but not the other cytokines) decreased the inhibitory effect of HMR 3647 only on oxidant production by PMN . Fifty percent inhibitory concentrations were, however, in the same range in control and cytokine-treated cells (about 60 to 70 microgram/ml), suggesting that HMR 3647 acts downstream of the priming effect of cytokines . In contrast, the impairment of oxidant production by roxithromycin and HMR 3004 was unchanged (or increased) in cytokine-treated cells . This result suggests that HMR 3004 (the strongest inhibitory drug, likely owing to its quinoline side chain) and roxithromycin act on a cellular target upstream of cytokine action . In addition, TNF-alpha and GM-CSF significantly (albeit moderately) impaired (by about 20%) the uptake of the three molecules by PMN . The inhibitory effect of these two cytokines seems to be related to activation of the p38 mitogen-activated protein kinase . Our data also illuminate the mechanism underlying macrolide uptake: protein kinase A- and tyrosine kinase-dependent phosphorylation seems to be necessary for optimal uptake, while protein kinase C activation impairs it . The relevance of our data to the clinical setting requires further investigations, owing to the complexity of the cytokine cascade during infection and inflammation. J Chromatogr B Biomed Sci Appl, 1999 Dec 24, 736(1-2), 299 - 303 Simple and efficient method for the detection of diethylenetriaminepentaacetic acid; Weber C et al.; Diethylenetriaminepentaacetic acid (DTPA) is a commonly used chelating agent . Its antiviral, antibacterial and immunomodulatory effects are well documented . DTPA forms a highly stable complex with lead (II) with an increased absorption coefficient and a bathochromic shift of the absorption maximum compared to pure DTPA . Based on this complex a high-performance liquid chromatographic method for the quantitative detection of DTPA in biological fluids was developed . A calibration curve was prepared and linearity was shown in the concentration range between 10 mg l(-1) and 1000 mg l(-1) DTPA . The recovery in water and in human plasma showed the method to be suitable for routine use. J Clin Periodontol, 2000 Jan, 27(1), 53 - 60 Concentration of 3 tetracyclines in plasma, gingival crevice fluid and saliva; Sakellari D et al.; BACKGROUND: Systemically-administered tetracyclines have been used widely for treatment of periodontal diseases with little understanding of their delivery characteristics to periodontal tissues . This study was designed to measure concentrations of 3 tetracyclines in gingival crevice fluid (GCF), plasma and saliva of following systemic administration . METHOD: The concentration of tetracycline (TC), minocycline (MN) and doxycycline (DX) was measured in gingival crevice fluid (GCF), plasma and saliva of 20 subjects following single sequential standard oral systemic doses . Gingival crevice fluid concentration was measured at 4 sites (2 shallow and 2 deep) before administration, and at 1 h and 2 h following administration . Plasma and saliva concentrations were measured from in samples at the same time points . No antibacterial activity was detected before administration . The highest concentrations were measured 2 h after administration . RESULTS: The average concentrations at 2 h were highest in plasma (TC = 1.02, MN=2.18, DX=2.35 microg/ml) . Intermediate concentrations were measured in GCF (TC=0.61, MN= 1.49, DX= 1.65 microg/ml) . Saliva concentrations (TC=0.09 MN=0.31, DX=0.47 microg/ml) were the lowest of the 3 fluids monitored . Data are presented indicating that the average GCF concentration of systemically administered tetracyclines is less than the that of plasma concentration . The concentration of tetracyclines in GCF was strongly associated with plasma concentration, indicating a primary role of drug absorption in the delivery of these systemically administered antibiotics to the site of action in periodontal therapy . The average GCF concentration in individuals varied widely (between 0 and 8 microg/ml) with approximately 50% of samples not achieving levels of 1 microg/ml . CONCLUSION: These observations suggest that poor absorption of orally-administered tetracyclines in many individuals may account for much of the variability in clinical response to antibiotics observed in practice. J Clin Periodontol, 2000 Jan, 27(1), 37 - 40 Comparative effects of quaternary ammonium mouthrinses on 4-day plaque regrowth; Moran J et al.; BACKGROUND: Quaternary ammonium compounds constitute a large group of antibacterial chemicals with a potential for inhibiting plaque and gingivitis . One compound, benzalkonium chloride (BC), may be of value, although there is a dearth of evidence to support efficacy . The aim of this study was to measure the ability of 2 BC mouthrinses (0.05% and 0.1%) to inhibit de novo plaque reformation . METHOD: A 4-day plaque regrowth model . For comparative purposes, a commercial mouthrinse containing cetyl pyridinium chloride (CPC) and a positive control chlorhexidine (CX) mouthrinse were also evaluated . RESULTS: Compared to water control, a reduction in plaque scores of 52% was noted for the CX mouthrinse, 22.5% for CPC and 5% and 6% for the 2 BC rinses . For plaque area, reductions of 84%, 47%, 16% and 15% were found for CX, CPC, and the 2 BC rinses, respectively . Significant reductions in plaque area compared to the water rinse were also seen with the 2 BC rinses (p<0.05) . However, for both plaque score and plaque area, the CX and CPC rinses significantly reduced plaque compared to the BC rinses (p<0.0001) . CONCLUSIONS: These findings would suggest that the 2 benzalkonium rinses would only have a limited value at inhibiting plaque formation. Bioorg Med Chem Lett, 2000 Jan 17, 10(2), 161 - 5 Coumarin inhibitors of gyrase B with N-propargyloxy-carbamate as an effective pyrrole bioisostere; Periers AM et al.; The synthesis and biological profile in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3' of noviose is presented . Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity . Analysis of crystal structures of coumarin antibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides a rational for the excellent inhibitory potency of C-3' N-alkoxycarbamates. Bioorg Med Chem Lett, 2000 Jan 17, 10(2), 143 - 5 Multi gram synthesis of UDP-N-acetylmuramic acid; Dini C et al.; As part of an effort to discover novel antibacterial agents, a new and efficient synthesis was established in order to provide a large amount of UDP-N-acetylmuramic acid (UDP-MurNAc). Bioorg Med Chem Lett, 2000 Jan 17, 10(2), 95 - 9 Synthesis and antibacterial activity of new carbapenems containing isoxazole moiety; Kang YK et al.; The synthesis and biological activity of a series of new 1beta-methylcarbapenems 1a-g containing 5'-isoxazolopyrrolidin-3'-ylthio derivatives as C-2 side chain are described . Most compounds exhibited potent and well-balanced antibacterial activity as well as high stability to DHP-I comparable to that of meropenem . 1e and 1c showed the best combination of antibacterial activity and stability to DHP-I, respectively. Dermatol Nurs, 1999 Jun, 11(3), 205 - 8 Update on acne therapy; O'Donoghue MN; Current therapy of acne vulgaris is very effective . It consists of a combination of topical comedolytic agents, antibacterial agents, and combinations of both . The use of systemic therapy with antibiotics, isotretinoin, and hormones is necessary for cystic acne . The management of patients with the various combinations of topical and systemic medications is discussed. Zentralbl Chir, 1999, 124 Suppl 4, 9 - 12 {Perioperative infection prophylaxis in gastrointestinal surgery}; Schwarz M et al.; Antibiotic perioperative prophylaxis is known to reduce postoperative infections and is generally administered as single-dose regimen today . Effective prophylaxis requires plasma- and tissue concentrations above the MIC of the expected bacterial spectrum throughout the whole operation from skin incision to wound closure . In longlasting operations a second dose after 4 hours is recommended . Indications for antibiotic prophylaxis are clean-contaminated or contaminated procedures according to Cruse and in patients with elevated risk of infection . Generally antibiotic prophylaxis is administered intravenously . Chinolons achieving high tissue- and plasmalevels and showing a broad antibacterial spectrum seem appropriate to be used for oral prophylaxis . In a prospective study in 36 patients pharmocokinetics of ofloxacin were measured perioperatively and proper plasma- and tissue concentrations were attained . A following prospective randomized study in 56 patients undergoing colonic or pancreatic resections oral prophylaxis did not show a higher infection rate compared with a standard intravenous prophylaxis . Therefore oral prophylaxis seems to be an attractive option, its effectivity needs to be proven by studies with sufficiently high patient numbers. J Med Chem, 2000 Feb 10, 43(3), 467 - 74 Acid-catalyzed degradation of clarithromycin and erythromycin B: a comparative study using NMR spectroscopy; Mordi MN et al.; One of the major drawbacks in the use of the antibiotic erythromycin A is its extreme acid sensitivity, leading to degradation in the stomach following oral administration . The modern derivative clarithromycin degrades by a different mechanism and much more slowly . We have studied the pathway and kinetics of the acid-catalyzed degradation of clarithromycin and of erythromycin B, a biosynthetic precursor of erythromycin A which also has good antibacterial activity, using (1)H NMR spectroscopy . Both drugs degrade by loss of the cladinose sugar ring and with similar rates of reaction . These results suggest that erythromycin B has potential as an independent therapeutic entity, with superior acid stability compared with erythromycin A and with the advantage over clarithromycin of being a natural product. Farmaco, 1999 Nov-Dec, 54(11-12), 826 - 31 5-Nitroimidazole derivatives as possible antibacterial and antifungal agents; Gunay NS et al.; Some novel 1-{2-{{5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl{thio{ethyl{-2-methyl-5-nitro-1H-imidazoles (3), 1-{3-{{5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl{-thio}-2-hydroxypropyl{-2-methyl-5-nitro-1H- imidazoles (5) and 1-{3-{(N,N-disubstituted thiocarbamoyl)-thio{-2-hydroxypropyl}-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity . Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml). Therapie, 1999 Sep-Oct, 54(5), 637 - 44 {Synthesis of benzimidazole derivatives by amino acid action on ortho-phenylenediamine, variously substituted in positions 4 and 5}; Zniber R et al.; As part of the synthesis of the benzimidazole derivative heterocyclique system, we are interested in studying the condensation of the o-phenylenediamines with amino-acids such as aspartic acid, serine and histidine . The interest that these present is based mainly on their pharmacological properties . They have, in fact anti-inflammatory, antidepressive, antibacterial and antihistamine properties . On the other hand, it should be noted that 5,6-dimethyl-1-(alpha-D-ribofuranosyl) benzimidazole constitutes part of vitamin B12 . Taken together, these results led us to pursue our research in this domain while focusing on new methods of benzimidazolic derivative synthesis . It should be said that the obtaining of these compounds depends on the quantity of the amino-acid . All synthesized products have been characterized by infrared, nuclear magnetic resonance and mass spectrometry. J Dent, 2000 Jan, 28(1), 61 - 7 Cytotoxic effects of composite restorations employing self-etching primers or experimental antibacterial primers; Imazato S et al.; OBJECTIVE: The aim of this study was to investigate the cytotoxic effects of composites which employ proprietary self-etching primers or experimental primers containing an antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on human pulpal cells by in vitro dentine barrier tests . METHODS: Experimental primers were prepared by the addition of MDPB to each of two control proprietary primers at 1, 2 and 5% . Direct and indirect composite specimens were placed using each primer on one side of a dentine disk assembled in a simple pulp chamber device . Human pulp cells were incubated on the other side of the disk . After 48 h of incubation, the uptake of {3H}-thymidine by the cells was compared with that for negative controls using wax . Tests were repeated four times for each material . The diffusion of monomers from each specimen was determined using the same device . RESULTS: The specimens with control primers showed 26-35% reduction in cell activity . There were no significant differences in cytotoxicity between the control and experimental primers-specimens (Kruskal-Wallis test, p > 0.05) . 2-Hydroxyethyl methacrylate at more than 1 mg ml-1 diffused from all specimens and was considered to be the cause of cytotoxic effects . The concentrations of MDPB diffused from the experimental primers-specimens were less than the toxic level, even for 5% MDPB-containing specimens . CONCLUSIONS: The results demonstrate that composites employing proprietary self-etching primers produced cytotoxic effects on human pulpal cells in vitro, although the toxicity was not severe . Incorporation of MDPB into a proprietary primer of up to 5% had no significant influence on the cytotoxicity observed. Graefes Arch Clin Exp Ophthalmol, 2000 Jan, 238(1), 45 - 52 Quality of salivary tears following autologous submandibular gland transplantation for severe dry eye; Geerling G et al.; BACKGROUND: This study aimed to characterise the composition of the pre-ocular fluid after transplantation of the autologous submandibular gland (SMG) for patients with severe dry eye . METHODS: Stimulated and unstimulated pre-ocular fluid from 15 patients (17 eyes) with a viable SMG graft ("SMG-salivary tears"), as well as normal tears and SMG saliva (20 normal subjects/ 20 eyes), was sampled . As global tear parameters, fern pattern analysis and SDS gel electrophoresis were performed . As specific quality parameters, total protein content, secretory immunoglobulin A (SIgA), lysozyme, amylase, sodium, potassium and osmolality were measured using routine laboratory methods . The flow rate of SMG-salivary tears was determined in 5 patients by means of sequential scintillography . RESULTS: The fern pattern of SMG-salivary tears was coarse and thus more similar to normal SMG saliva than tears . SDS gel electrophoresis of the SMG-salivary tears showed albumin and two unidentified proteins in addition to the normal tear pattern . Osmolality and total protein content of SMG-salivary tears were higher than in normal SMG saliva, but still lower than in normal tears . High activities of normal tear antibacterial proteins (SIgA, lysozyme and amylase) were detected in the salivary tears . Stimulation of the secretion did not alter the composition of SMG-salivary tears . The flow rate of SMG-salivary tears was closer to that of normal tears than normal SMG saliva . CONCLUSION: Salivary tears resulting from SMG-transplantation represent condensed SMG saliva . Thus their quality is intermediate between normal tears and normal SMG saliva . High levels of secretory proteins demonstrate that the gland maintains an active function . Surgical denervation and residual tear components from the ocular surface are the most likely factors to cause the complex differences between normal SMG saliva and SMG-salivary tears . The effects of this secretion on the ocular surface are currently being evaluated in a clinical and laboratory study. Immunogenetics, 2000 Feb, 51(2), 92 - 8 Independent evolution of Toll and related genes in insects and mammals; Luo C et al.; Toll and Toll-related proteins play an important role in antibacterial innate immunity in insect, plants, and mammals . We present the first comprehensive phylogenetic analyses of Toll-related genes from both insects and mammals . Drosophila melanogaster contains Toll and a highly homologous gene, Tehao . The protein, Dm Tehao, comprises 795 amino acid residues and its cytoplasmic domain shares a striking 61% identity with Dm Toll . Two Toll homologues were found in another dipteran of medical importance, Anopheles gambiae, a vector for human malaria . One Toll-like gene each was identified from Aedes aegypti and Glossina palpalis palpalis, vectors for yellow fever and trypanosomiasis, respectively . Phylogenetic analyses revealed separate clustering of Toll and related proteins from insects and mammals, suggesting independent evolution of the Toll family of proteins and of innate immunity in arthropods and vertebrates . These results also provide new avenues to understanding the function of Toll proteins in insect innate immunity against bacteria, fungi, and protozoans. J Hosp Infect, 2000 Feb, 44(2), 147 - 50 Comparison of in-vivo antibacterial activity of two skin disinfection procedures for insertion of peripheral catheters: povidone iodine versus chlorhexidine; Traore O et al.; Skin disinfection is a key step in the prevention of nosocomial infections especially prior to invasive procedures such as the insertion of peripheral catheters . Alcohol-based antiseptics improve bactericidal activity and decrease the time needed for skin disinfection in emergencies . A randomized study was performed in two groups of 22 volunteers to compare the in vivo bactericidal effect of two rapid disinfection procedures using povidone iodine (PVP-I) in scrub formulation followed by alcoholic PVP-I, or chlorhexidine in scrub formulation followed by alcoholic chlorhexidine . Bacteria were recovered using the cylinder scrub method . Comparison of reductions in the aerobic and anaerobic flora from baseline levels to each of the three sampling times (30 sec, 3 min, 2 h) showed no significant difference between the two procedures Log(10)reduction after 30 seconds was around 1.5 for the aerobic flora and 1.1 for the anaerobic flora . After 3 minutes the corresponding values were 2.1 and 1.8, and after 2 hours 2.0 and 1.3 . The products were well tolerated in both groups . The two procedures had comparable rapid bactericidal activity in vivo . Pharmacoeconomics, 1999 Nov, 16(5 Pt 2), 551 - 61 Cost effectiveness of ciprofloxacin plus metronidazole versus imipenem-cilastatin in the treatment of intra-abdominal infections; Walters DJ et al.; OBJECTIVE: To compare the cost effectiveness of sequential intravenous (i.v.) to oral ciprofloxacin plus metronidazole (CIP/MTZ i.v./PO) with that of i.v . ciprofloxacin plus i.v . metronidazole (CIP/MTZ i.v.) and i.v . imipenem-cilastatin (IMI i.v.) in patients with intra-abdominal infections . DESIGN AND PARTICIPANTS: Patients enrolled in a double-blind randomised clinical trial were eligible for inclusion into this cost-effectiveness analysis . Decision analysis was used to characterise the economic outcomes between groups and provide a structure upon which to base the sensitivity analyses . 1996 cost values were used throughout . SETTING: The economic perspective of the analysis was that of a hospital provider . MAIN OUTCOME MEASURES AND RESULTS: Among 446 economically evaluable patients, 176 could be switched from i.v . to oral administration . The 51 patients randomised to CIP/MTZ i.v./PO who received active oral therapy had a success rate of 98%, mean duration of therapy of 9.1 days and mean cost of $US7678 . There were 125 patients randomized to either CIP/MTZ i.v . or IMI i.v . who received oral placebo while continuing on active i.v . antibacterials; their success rate was 94%, mean duration of therapy was 10.1 days and mean cost was $US8774 (p = 0.029 vs CIP/MTZ i.v./PO) . Of the 270 patients who were unable to receive oral administration, 97 received IMI i.v . and had a success rate of 75%, mean duration of therapy of 13.8 days and a mean cost of $US12,418, and 173 received CIP/MTZ i.v . and had a success rate of 77%, mean duration of therapy of 13.4 days and mean cost of $US12,219 (p = 0.26 vs IMI i.v.) . CONCLUSIONS: In patients able to receive oral therapy, sequential i.v . to oral treatment with ciprofloxacin plus metronidazole was cost effective compared with full i.v . courses of ciprofloxacin plus metronidazole or imipenem-cilastatin . In patients unable to receive oral therapy, no difference in mean cost was found between i.v . imipenem-cilastatin or i.v . ciprofloxacin plus i.v . metronidazole. Pharmacoeconomics, 1999 Nov, 16(5 Pt 1), 499 - 520 Economic evaluation of ciprofloxacin compared with usual antibacterial care for the treatment of acute exacerbations of chronic bronchitis in patients followed for 1 year; Torrance G et al.; OBJECTIVE: To undertake a 1-year prospective economic evaluation of ciprofloxacin compared with usual antibacterial care (any antibacterial other than a quinolone) for the treatment of acute exacerbations of chronic bronchitis (AECB) in adults presenting with a type I or type II AECB . DESIGN: Patients entered the study with an initial AECB and were randomised to the ciprofloxacin group or the usual care group . The following measurements were taken at the end of each AECB and every 3 months: resource utilisation, St . George's Respiratory Questionnaire, Nottingham Health Profile and Health Utilities Index (HUI) . The following additional measurements were taken after each AECB: AECB-symptom days and willingness to pay to avoid the AECB . Economic evaluations were performed from the societal viewpoint and the viewpoint of a major third-party payer . Cost-effectiveness analysis was based on cost per AECB-symptom day averted; cost-utility analysis (CUA) was based on cost per quality-adjusted life-year (QALY) gained using the HUI as the basis for calculating QALYs . Cost-benefit analysis was based on the willingness-to-pay (WTP) data . SETTING: This was a study of outpatients enrolled from 46 family physicians and 2 respirologists in Ontario (29 sites) and Quebec (19 sites), Canada, between November 1993 and June 1994 . PATIENTS AND PARTICIPANTS: 240 adult male and female patients aged > or = 18 years with chronic bronchitis . MAIN OUTCOME MEASURES AND RESULTS: WTP data did not pass scope tests for reasonableness . Ciprofloxacin was more costly and provided better outcomes compared with usual antibacterial care . The base-case results are as follows (1994/1995 values): the incremental annual cost was 578 Canadian dollars ($Can) from the societal viewpoint and $Can840 for the third-party payer; the cost-effectiveness ratio per AECB-symptom day averted was $Can209 from the societal viewpoint and $Can304 for the third-party payer; the cost-utility ratio per QALY gained was $Can18,600 from the societal viewpoint and $Can27,000 for the third-party payer . According to Laupacis criteria, these CUA results are strong evidence in favour of adoption from the societal viewpoint and moderate evidence in favour from the viewpoint of the third-party payer . A subgroup analysis suggests that ciprofloxacin may be particularly cost effective, even 'win-win', in patients with more severe disease . CONCLUSIONS: The sensitivity analyses indicate that the results are relatively robust . Nevertheless, the statistical uncertainty in the results is sufficient that the findings cannot be accepted unequivocally . A further study with a larger sample size would be useful to confirm (or deny) the findings of this study. Jpn J Antibiot, 1999 Nov, 52(11), 661 - 6 {Levofloxacin concentrations in serum, sputum and lung tissue: evaluation of its efficacy according to breakpoint}; Fujita A et al.; The levels of levofloxacin (LVFX) in the serum, sputum and lung tissue were measured by a high-performance liquid chromatography method, and the penetration ratio of LVFX into respiratory tissue was investigated . The subjects of this study were 23 patients under pulmonectomy or brochoscopy . LVFX at the dose of 200 mg was given orally and specimens were collected as follows; serum at 2, 3 and 5 hours after, sputum at 2 hours after, and lung tissue at 3 and 5 hours after the administration, respectively . The mean level of LVFX in lung tissue at 3 hours was 3.91 +/- 2.33 micrograms/g, and those in sputum and in serum at 2 hours were 0.71 +/- 0.63 and 2.08 +/- 1.01 micrograms/ml, respectively . A very strong correlation was demonstrated between the level of LVFX in lung tissue and that in serum (p < 0.0001), but correlation between those in sputum and in serum was not significant . The penetration ratio of LVFX into lung tissue was 217.2% and that into sputum was 4.05% . Based on the results of this study, the breakpoints (BPs) of LVFX for pneumonia and chronic respiratory tract infections were calculated to be 4 micrograms/ml and 1 microgram/ml, respectively . It was concluded that penetration of LVFX into lung tissue was satisfactory, and the tissue level of LVFX exceeded greatly the MIC90s against the typical pathogenic bacteria of respiratory tract infections . Taking the excellent BP for pneumonia, 4 micrograms/ml, into consideration, it was thought that LVFX is an effective antibacterial agent against pneumonia and other respiratory tract infections. J Antibiot (Tokyo), 1999 Nov, 52(11), 1029 - 41 Semisynthetic derivatives of madurahydroxylactone and their antibacterial activities; Heinisch L et al.; Madurahydroxylactone is a secondary metabolite from Nonomuria rubra (former Actinomadura rubra) with in vitro activity against gram-positive bacteria and belongs to the family of benzo{a}naphthacenequinones . A series of derivatives of madurahydroxylactone were synthesized to investigate the effect on the antibacterial activity . Reaction with alcohols and amines gave cyclic acetals or aminals derived from the lactone form, whereas other amino reagents like hydroxylamines and acyl or sulfonyl hydrazides led to the corresponding imine derivatives of the aldehyde . Hydrazine, alkyl and aryl hydrazines react with madurahydroxylactone under cyclization to give compounds of the new heterocyclic basic structure naphthaceno{1,2-g}phthalazine . Some new compounds strongly inhibit gram-positive bacteria, in part stronger than the parent compound. Biomaterials, 2000 Feb, 21(4), 393 - 8 Antibacterial silver-containing silica glass prepared by sol-gel method; Kawashita M et al.; Recently, various inorganic antibacterial materials containing silver have been developed and some of them are in commercial use . Colorless and more chemically durable materials which slowly release the silver ion for a long period are, however, desirable to be developed for medical applications such as composite resin for dental restoration . In the present study, Si(OC2H5)4, Al(NO3)3 x 9H2O, AgNO3, HNO3, C2H5OH and H2O solutions with various Al/Ag atomic ratios under a constant Si/Ag atomic ratio of 1/0.023 were kept at 40 degrees C for gelation and drying . Thus obtained gels were pulverized into fine powders with average particle size of approximately 10 microm and then heat-treated at 900-1000 degrees C for 2 h . For the composition Al/Ag = 0, a yellow-colored glass was formed, since the silver existed in the form of metallic colloids in the glass . However, for the compositions Al/Ag > or = 1, colorless glasses were successfully obtained, since the silver existed in the form of Ag+ ions in the glasses . For the composition Al/Ag = 0, the silver ions got released rapidly into the water, whereas, for the compositions Al/Ag > or = 1, they gradually got released into the water at a controlled rate . A composite of the obtained powders with Al/Ag atomic ratio of 1 with Bis-GMA/TEGDMA in 70:30 weight ratio showed excellent antibacterial property . The sol-gel derived silica glass powders containing silver with compositions Al/Ag > or = 1 are believed to be useful as an antibacterial material for medical applications such as filler of composite resin for dental restoration. J Toxicol Sci, 1999 Dec, 24(5), 383 - 91 Novel action of quinolones on osteoclast-like cells; Fukuishi N et al.; Quinolones have a broad antibacterial spectrum against Gram-negative and Gram-positive bacteria . The compounds, however, have a few adverse effects, such as convulsion and toxicity to articular cartilage . We observed that some quinolones such as Naldixic acid, Ofloxacin, and Norfloxacin have osteoclast-inducing effects . All quinolones we tested produced tumor necrosis factor-alpha and prostaglandin E2, and have potency as osteoclast inducers to cultured cells . These results suggest that some quinolones affect osteoclast induction or activation, and this may be related to the production of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Yakugaku Zasshi, 2000 Jan, 120(1), 132 - 5 {Molecular cloning of cDNAs coding Sarcophaga diptericin family}; Baba K et al.; We purified an antibacterial protein named sarcotoxin III from the hemolymph of injured larvae of Sarcophaga peregrina (Baba K., et al., J . Biochem., 102, 69-74 (1987)) . In this report we determined the partial amino acid sequence of sarcotoxin III and tried to conduct the cloning of sarcotoxin III cDNA . As a result we obtained two clones coding a protein similar to sarcotoxin III in sequence . Their primary structures are highly homologous to N-terminal sequences of an antibacterial protein from Phormia, diptericin, and another 8 kD antibacterial protein purified from Sarcophaga peregrina . These results suggested that sarcotoxin III is one of the proteins forming a diptericin family in Sarcophaga peregrina as well as newly obtained clone-coded products and 8 kD protein. Mol Hum Reprod, 2000 Feb, 6(2), 191 - 6 Presence of secretory leukocyte protease inhibitor in human endometrium and first trimester decidua suggests an antibacterial protective role; King AE et al.; Secretory leukocyte protease inhibitor (SLPI) is a neutrophil elastase inhibitor which also has antibacterial and anti-inflammatory properties . It is found associated with mucosal membranes . Although SLPI has been reported in the cervix it has not thus far been reported in human endometrium . This study investigates the presence of SLPI in endometrium, first trimester decidua and trophoblast . Cultured first trimester decidua was found to produce 4 . 7 +/- 2.0 ng/mg/24 h of SLPI . Endometrium and trophoblast were both found to secrete significantly lower amounts of SLPI (P < 0.01) although endometrial expression was menstrual cycle dependent with increased secretion in the secretory phase . Although relatively low concentrations of SLPI were released from the endometrium during culture, most of the SLPI remained associated with the tissue and could be recovered with mild acid extraction . This is in agreement with the high isoelectric point (pI) for SLPI, associated with high solubility at low pH . The main site of SLPI synthesis in endometrium and decidua was found to be the glandular epithelium . An antibiotic role for SLPI in the endometrium and decidua during implantation and pregnancy would be consistent with the expression profile and localization of SLPI. Virus Res, 2000 Jan, 66(1), 51 - 63 Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells; Ikeda M et al.; We recently found that bovine lactoferrin (bLF), a milk glycoprotein belonging to the iron transporter family, prevented hepatitis C virus (HCV) infection in human hepatocyte PH5CH8 cells, that are susceptible to HCV infection, and demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF and HCV . In this study we further characterized the anti-HCV activity of bLF and the mechanism by which bLF prevents HCV infection . We found that bLF inhibited viral entry to the cells by interacting directly with HCV immediately after mixing of bLF and HCV inoculum . The anti-HCV activity of bLF was lost by heating at 65 degrees C, and other milk proteins (mucin, beta-lactoglobulin and casein) did not prevent HCV infection, indicating that bLF prevented HCV infection in a rather specific manner . Furthermore, we found that bovine lactoferricin, a basic N-terminal loop of bLF that is an important region for antibacterial activity, did not exhibit any anti-HCV activity, suggesting that some other region is involved in anti-HCV activity . We confirmed that prevention of HCV infection by bLF was a general phenomenon, because bLF inhibited HCV infection with all five inocula examined, and bLF inhibited HCV infection in human MT-2C T-cells, that were susceptible to HCV infection . In addition, infection with hepatitis G virus, which is distantly related to HCV, was prevented also by bLF . In conclusion, lactoferrin is a natural glycoprotein which effectively protects against HCV infection in hepatocytes and lymphocytes by neutralizing the virus. J Am Dent Assoc, 2000 Jan, 131(1), 67 - 71 Formation of a facial hematoma during endodontic therapy; Mehra P et al.; BACKGROUND: Sodium hypochlorite, or NaOCl, is one of the most commonly used irrigating solutions in endodontic practice . Its clinically proven antibacterial, solvent and lubricating properties make it a very appealing choice as an intracanal medicament . CASE DESCRIPTION: The authors present a case of facial hematoma formation after an inadvertent injection of NaOCl into the periapical tissues . The NaOCl solution caused extensive tissue destruction . Management of the condition required the hospitalization, intravenous antibiotic therapy and multiple intraoral surgical incisions to facilitate drainage . CLINICAL IMPLICATIONS: Use of NaOCl must be confined to the root canal system . This report reviews this intracanal medicament's potential toxicity and emphasizes the need for clinicians to remain cognizant of possible problems while using the solution. Phytochemistry, 1999 Dec, 52(8), 1469 - 71 Antibacterial and antifungal flavanones from Eysenhardtia texana; Wachter GA et al.; An activity-guided fractionation of a methanol-dichloromethane extract obtained from the aerial parts of Eysenhardtia texana led to the isolation of two novel antibacterial and antifungal flavanones together with a known flavanone . Their structures were established as 4',5,7-trihydroxy-8-methyl-6-(3-methyl-{2-butenyl})-(2S)-flavanone, 4',5,7-trihydroxy-6-methyl-8-(3-methyl-{2-butenyl})-(2S)-flavanone and 4',5-dihydroxy-7-methoxy-6-(3-methyl-{2-butenyl})-(2S)-flavanone on the basis of their UV, 1D and 2D-NMR spectra. Drug Saf, 2000 Jan, 22(1), 83 - 8 Assessment of infant development during an 18-month follow-up after treatment of infections in pregnant women with cefuroxime axetil; Manka W et al.; BACKGROUND: Choices of antibacterial for infections in pregnancy are limited because of potential risks to the fetus, particularly in the early months . However, infections may result in preterm labour or other problems and so treatment is needed . Increasingly, resistance is reported among common pathogens to older agents, such as ampicillin or amoxicillin, that have been widely used in pregnancy . OBJECTIVE: To assess the safety and efficacy of cefuroxime axetil in the treatment of infections during pregnancy . DESIGN: This was a retrospective analysis of case records for women who were treated with cefuroxime axetil at some point during pregnancy . SETTING: Patients were treated at one centre in Lubliniec, Poland in 1996 and 1997 . PATIENTS AND PARTICIPANTS: The study included 78 women aged 19 to 38 years (mean 26 years) and their 80 infants . MAIN OUTCOME MEASURES AND RESULTS: Efficacy in treating maternal infections was assessed, and the physical and mental development of children born to treated mothers was evaluated for at least 18 months after birth . 13 women were treated in the first trimester, 19 in the second trimester and 46 in the third trimester . There were no abnormalities causing concern in terms of physical or mental development in any of the children, and no abnormality that was attributable to the treatment the mother had received . CONCLUSIONS: The results add clinical support for the use of cefuroxime axetil in pregnancy if an antibacterial is needed, thus offering an alternative if antibacterial resistance to older agents is an issue for the pregnant mother. J Urol, 2000 Feb, 163(2), 481 - 2 Long-term experience with salvage of infected penile implants; Mulcahy JJ; PURPOSE: The effectiveness of treating patients with an infected penile implant by removing the device, cleansing the wound with a series of antiseptic solutions and placing a new device at the same procedure was assessed . MATERIALS AND METHODS: A total of 65 patients were included in the study . All foreign material was removed from the infected wound followed by copious wound irrigations with a protocol of 7 antibacterial solutions . A new prosthesis was inserted and the patient was placed on antibiotics . RESULTS: Followup ranged from 6 to 93 months . Recent status was determined in 85% of cases (55 of 65) . Of the 55 patients 45 (82%) showed no sign of infection . In 5 patients recurrent infection was documented and in 5 others erosion of parts to the exterior possibly related to infection was noted . CONCLUSIONS: Salvage of an infected penile implant has been successful and is gaining in popularity among urologists to reduce morbidity associated with infection. Arch Insect Biochem Physiol, 2000 Feb, 43(2), 64 - 71 Insect immunity: a genetic factor (hrtp) is essential for antibacterial peptide expression in Drosophila after infection by parasitoid wasps; Benassi V et al.; We have used a parasitoid wasp Drosophila melanogaster system to investigate the relationship between the humoral and cellular immune responses in insects . Expression of the gene encoding diptericin, an antibacterial peptide in various D . melanogaster strains parasitized by several species of parasitoid wasps, was studied by Northern blot . These strains have the capacity to encapsulate parasitoid eggs . Two strains appeared to produce diptericin mRNA after parasitoid challenge, regardless of their cellular immune reaction to the wasp species . This suggests that a specific genetic factor, or factors, here designated humoral response to parasitoid (hrtp), is present in these two strains of D . melanogaster and is implicated in the expression of the antibacterial gene after parasite infection . This hrtp genetic factor is recessively expressed and located on the second chromosome, suggesting that it is monofactorial . The transgenic strain Dipt.2.2-lacZ:1, in which the transgene is present on the first chromosome, is normally susceptible to the parasitoid wasp . The chromosome bearing the hrtp factor was transferred to this transgenic strain, which then became reactive when triggered by wasp infection . The hrtp factor appears necessary for the activation of diptericin by the parasitoid wasp . No correlation between the cellular immune capacity and the humoral response was observed, suggesting that the two components of insect immunity are regulated independently . Arch . Acta Trop, 2000 Jan 5, 74(1), 33 - 8 Disinfectants/antiseptics in the management of guinea worm ulcers in the rural areas; Ogunniyi TA et al.; The effectiveness of trichlorophenol (TCP), chlorhexidine gluconate plus cetrimide (Savlon) and Izal in inhibiting the growth of bacterial isolates from guinea worm ulcers was investigated . Using an adaptation of the method of Russell and Furr (Russell, A.D., Furr, J.R., 1977 . The antibacterial activity of a new chloroxylenol preparation containing ethylenediamine tetraacetic acid . J . Appl . Bacteriol . 43, 253-260) the minimum inhibitory concentration (MIC) values of the three anti-microbial agents for each of the isolated bacteria was determined . Water drawn from the rural guinea worm endemic sites was autoclaved and used for the various dilutions of the anti-microbial agents . At the manufactures' recommended use-dilutions in cases of wounds/cuts/sores, Savlon showed greater effectiveness than Izal and TCP in this order . Probable organic and inorganic inhibitors in water that is usually employed in diluting anti-microbial agents in the rural areas for the dressing of guinea worm ulcers very likely had greatest effect(s) on TCP and least effect(s) on Savlon. Bone Marrow Transplant, 1999 Dec, 24(11), 1207 - 11 Oral ciprofloxacin as antibacterial prophylaxis after allogeneic bone marrow transplantation: a reappraisal; Yeh SP et al.; The efficacy of ciprofloxacin as antibacterial prophylaxis for allogeneic bone marrow transplantation has been well documented, and it virtually eliminated bacteremias caused by gram-negative pathogens in early reports . Ciprofloxacin was therefore incorporated into the prophylactic antibiotic regimen during allogeneic bone marrow or peripheral blood stem cell transplantation at Veterans General Hospital, Kaohsiung from February 1997 . In 12 consecutive patients receiving allogeneic bone marrow or peripheral blood stem cell transplantation, ciprofloxacin-resistant Escherichia coli bacteremia developed in three (25%) . In addition to our data, increasing evidence suggests that the widespread use of a fluoroquinolone is associated with the emergence of resistant isolates as well as documented infections caused by these resistant strains . The incidence of Escherichia coli bacteremia in our transplant patients was 25%, which was similar to that in patients not receiving preventive therapy or in those receiving trimethoprim-sulfamethoxazole prophylaxis . The prophylactic efficacy of ciprofloxacin in allogeneic bone marrow transplant or peripheral blood stem cell transplant recipients should therefore be reassessed. Toxicol Appl Pharmacol, 2000 Jan 15, 162(2), 86 - 92 Lung mucin production is stimulated by the air pollutant residual oil fly ash; Longphre M et al.; Human and animal exposure to particulate air pollution is correlated with airway mucus hypersecretion and increased susceptibility to infection . Seeking clues to the mechanisms underlying this pathology, we examined the effect of the particulate air pollutant residual oil fly ash (ROFA) on production of the major component of mucus, mucin, and the major antibacterial protein of the respiratory tract, lysozyme . We found that following in vitro exposure to ROFA, epithelial cells showed an increase in mucin (MUC5AC) and lysozyme (LYS) steady state mRNA . This upregulation was controlled at least partly at the level of transcription as shown by reporter assays . Experiments testing the ability of the major components of ROFA to mimic these effects showed that vanadium, a metal making up 18.8% by weight, accounted for the bulk of the response . A screen of signaling inhibitors showed that MUC5AC and LYS induction by ROFA are mediated by dissimilar signaling pathways, both of which are, however, phosphotyrosine dependent . Recognizing that the ROFA constituent vanadium is a potent tyrosine phosphatase inhibitor and that mucin induction by pathogens is phophotyrosine dependent, we suggest that vanadium-containing air pollutants trigger disease-like conditions by unmasking phosphorylation-dependent pathogen resistance pathways . Acta Pol Pharm, 1999 Jul-Aug, 56(4), 283 - 8 Synthesis and antibacterial activities of some 1,2,4-triazole derivatives; Ikizler AA et al.; Reactions of 3-amino-1,2,4-triazole with some dicarboxylic acid anhydrides and diketones were studied . The structural assignments of the compounds obtained from the reactions are based on elemental analyses and spectral data . The compounds were screened for their in vitro antibacterial activities. Insect Mol Biol, 1999 Nov, 8(4), 545 - 50 FST, a female-specific transcript from the medfly Ceratitis capitata (Diptera: Tephritidae); Rosetto M et al.; We report here the sequence of a novel cDNA clone (FST, female-specific transcript), isolated by differential screening during a search for sexually mature accessory gland-specific transcripts from the medfly Ceratitis capitata . It contains an open reading frame (ORF) with a potential translational start site encoding a putative precursor peptide of 100 amino acids . The FST gene is expressed only in the female reproductive accessory glands . Like the accessory gland-specific antibacterial peptides ceratotoxins, its expression reaches the maximum level when sexual maturity is achieved . However, in contrast to ceratotoxins, it is expressed at a basal level in newly emerged females, and its expression does not increase after mating. J Periodontal Res, 1999 Aug, 34(6), 290 - 5 Quantitative comparison of cytocidal effects of tetracyclines and fluoroquinolones on human periodontal ligament fibroblasts; Omori N et al.; The cytocidal effects of tetracyclines and fluoroquinolones on human periodontal ligament fibroblasts (Pel cells) were studied . Pel cells were treated for 24 h with tetracycline (TC), demeclocycline (DMC), minocycline (MINO), chlortetracycline (CTC), tosufloxacin (TFLX), enoxacin (ENX), sparfloxacin (SPFX), lomefloxacin (LFLX) or ofloxacin (OFLX), and allowed to form colonies . The cytocidal effects of the antibacterial agents, as determined by a decrease in colony-forming efficiency, increased as the dose increased . However, CTC was an exception . As a quantitative measure of the cytocidal effect, LD50, the concentration which results in a 50% decrease in colony-forming efficiency relative to control cells, was extrapolated from the dose-response curves . The rank-order of cytocidal effects (LD50) was DMC {symbol: see text} MINO {symbol: see text} TC >> CTC . DMC, MINO and TC were at least 5.6-6.6 times more cytocidal than CTC . The cytocidal effects of the fluoroquinolones were in the following order: TFLX > ENX > SPFX > LFLX > OFLX . TFLX, ENX, SPFX and LFLX were 36.3, 11.4, 7.7 and 3.1 times more cytocidal than OFLX, respectively . Little cytocidal effect was observed when the cells were treated with either < or = 0.03 mM tetracyclines or < or = 0.01 mM fluoroquinolones . The results provide useful estimates concerning the relative toxicities against human periodontal ligament of antibacterial agents used to treat periodontitis. Bioorg Med Chem, 1999 Nov, 7(11), 2465 - 71 Studies on 6-aminoquinolones: synthesis and antibacterial evaluation of 6-amino-8-ethyl- and 6-amino-8-methoxyquinolones; Cecchetti V et al.; From our quantitative structure-activity relationship (QSAR) study on a large set of 6-aminoquinolones, which indicated that a group larger than methyl could be allocated at C-8 position, we have synthesized two new series of 6-aminoquinolones characterized by the presence of an ethyl or a methoxy group at C-8 position . The antibacterial evaluation shows that, while the 8-ethyl derivatives were devoid of any antibacterial activity, the introduction of methoxy group gave compounds with good antibacterial activity, especially against gram-positive bacteria . A tentative explanation of the different behaviours among the 8-substituted analogues is given taking into account both the length and electronic properties of the C-8 groups. Biochemistry, 2000 Jan 18, 39(2), 442 - 52 Membrane binding and pore formation of the antibacterial peptide PGLa: thermodynamic and mechanistic aspects; Wieprecht T et al.; The antibacterial peptide PGLa exerts its activity by permeabilizing bacterial membranes whereas eukaryotic membranes are not affected . To provide insight into the selectivity and the permeabilization mechanism, the binding of PGLa to neutral and negatively charged model membranes was studied with high-sensitivity isothermal titration calorimetry (ITC), circular dichroism (CD), and solid-state deuterium nuclear magnetic resonance ((2)H NMR) . The binding of PGLa to negatively charged phosphatidylcholine (PC)/phosphatidylglycerol (PG) (3:1) vesicles was by a factor of approximately 50 larger than that to neutral PC vesicles . The negatively charged membrane accumulates the cationic peptide at the lipid-water interface, thus facilitating the binding to the membrane . However, if bulk concentrations are replaced by surface concentrations, very similar binding constants are obtained for neutral and charged membranes (K approximately 800-1500 M(-)(1)) . Membrane selectivity is thus caused almost exclusively by electrostatic attraction to the membrane surface and not by hydrophobic insertion . Membrane insertion is driven by an exothermic enthalpy (DeltaH approximately -11 to -15 kcal/mol) but opposed by entropy . An important contribution to the binding process is the membrane-induced random coil --> alpha-helix transition of PGLa . The peptide is random coil in solution but adopts an approximately 80% alpha-helical conformation when bound to the membrane . Helix formation is an exothermic process, contributing approximately 70% to the binding enthalpy and approximately 30% to the free energy of binding . The (2)H NMR measurements with selectively deuterated lipids revealed small structural changes in the lipid headgroups and in the hydrocarbon interior upon peptide binding which were continuous over the whole concentration range . In contrast, isothermal titration calorimetry of PGLa solutions with PC/PG(3:1) vesicles gave rise to two processes: (i) an exothermic binding of PGLa to the membrane followed by (ii) a slower endothermic process . The latter is only detected at peptide-to-lipid ratios >17 mmol/mol and is paralleled by the induction of membrane leakiness . Dye efflux measurements are consistent with the critical limit derived from ITC measurements . The endothermic process is assigned to peptide pore formation and/or lipid perturbation . The enthalpy of pore formation is 9.7 kcal/mol of peptide . If the same excess enthalpy is assigned to the lipid phase, the lipid perturbation enthalpy is 180 cal/mol of lipid . The functional synergism between PGLa and magainin 2 amide could also be followed by ITC and dye release experiments and is traced back to an enhanced pore formation activity of a peptide mixture. Planta Med, 1999 Dec, 65(8), 740 - 3 New triterpenoids with antibacterial activity from Zizyphus joazeiro; Schuhly W et al.; The stem bark of the Brazilian medicinal plant Zizyphus joazeiro C . Mart . was phytochemically investigated . Three known compounds (betulinic, ursolic and alphitolic acid) and three new derivatives of betulinic acid, 7 beta-(4-hydroxybenzoyloxy)-betulinic acid, 7 beta-(4-hydroxy-3'-methoxybenzoyloxy)-betulinic acid and 27-(4-hydroxy-3'-methoxybenzoyloxy)-betulinic acid which showed a considerable activity against Gram-positive bacteria were isolated from the dichloromethane extract . The structures were established on the basis of NMR spectroscopy and mass spectrometry. Spectrochim Acta A Mol Biomol Spectrosc, 1999 Nov, 55A(13), 2745 - 51 Molecular complexes of iron violurate with donor amines; Belal AA et al.; The acceptor character of iron violurate complex was studied by examining the electronic, vibrational and 1H-nmr spectra of the charge transfer molecular complexes formed between the iron violurate as pi-acceptor and some amines as n-donors . Elemental analysis and spectral results establishes 1:2 stoichiometry of the adducts . The study has been conducted at different temperatures . Values of delta G degree, delta H degree and delta S degree have been calculated from the self-consistent values of the formation constants (KCT) . Ionization potentials of the donors have been calculated and the solvent effect on the KCT values is discussed . The antibacterial and antifungal effects of the molecular complexes were studied. Arch Otolaryngol Head Neck Surg, 2000 Jan, 126(1), 75 - 8 Histopathologic features of the temporal bone in patients with cystic fibrosis; Yildirim N et al.; OBJECTIVES: To investigate the lower than expected incidence of otitis media in patients with cystic fibrosis (CF) through histopathologic evaluation of temporal bones and to document pathologic findings in the inner ears of patients with CF who received long-term administration of antibacterial and diuretic agents . DESIGN: Clinical records of patients who died of CF were reviewed . Their temporal bones were sectioned, stained with hematoxylin-eosin, and examined histologically . Additional sections were stained with Alcian blue and periodic acid-Schiff for comparison of goblet cell densities from middle ears and auditory tubes of patients with CF with those of control temporal bones . Results were analyzed using the t test . SUBJECTS: Twenty-one temporal bones from 11 patients with CF and 13 bones from 8 age-matched patients without CF were selected . RESULTS: All temporal bones with CF had well-pneumatized mastoids . Temporal bones from 2 patients (3 ears) revealed histological findings of chronic otitis media with effusion . There was a statistically significant reduction in the density of goblet cells in the medial (P = .002) and lateral (P = .05) walls in patients with CF who had no otitis media histologically compared with control temporal bones . Two patients with CF who had otitis media had increased densities of goblet cells . Inner ear damage, due to ototoxic drugs, was seen in most of the temporal bones from patients with CF . CONCLUSION: Low densities of goblet cells in temporal bones with CF may contribute reduced amounts of viscous mucus, which can lead to a low incidence of otitis media. Clin Orthop, 1999 Sep, (366), 239 - 47 Antibiotic loaded chitosan bar . An in vitro, in vivo study of a possible treatment for osteomyelitis; Aimin C et al.; A biodegradable drug delivery system of a gentamicin loaded chitosan bar with sustained antibiotic effect is described . Chitosan has proven to be a biocompatible aminopolysaccharide and a matrix for controlled release of pharmaceuticals . Combined crosslinking, solvent evaporation, and a cylinder model cutting technique was used to prepare the chitosan bar . Sustained diffusion of gentamicin into the surrounding medium was seen using a release test in vitro . Approximately 11% gentamicin was released from the bar in the first 24 hours . The gentamicin released from the bar showed significant antibacterial activity . The bar implanted in the proximal portion of the rabbit tibia produced a low blood concentration of gentamicin, but a much higher concentration was produced in local bone and in the hematoma . In all bone tissue around the bar, the gentamicin concentration exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for approximately 8 weeks . The implant caused no systemic side effects . Based on these test results together with the chitosan characteristics of biodegradable, antibiotic, and immunologic activity, the gentamicin loaded chitosan bar seems to be a clinically useful method for the treatment of bone infection . This system has an advantage over other systems in that it avoids a second operation for removal of the carrier. Lik Sprava, 1999 Sep, (6), 37 - 9 {The effect of the regimen for administering antibacterial therapy on the manifestations of endogenous intoxication in patients operated on for lung cancer}; Mykhailovych IuI; It is shown, that tumour and progression of the tumour process cause a change in the normal microflora of the tracheobronchial tree . Highlighted in the article are causes making for an origination of inflammatory processes, infectious complications in those patients presenting with oncological diseases . Regimens of antibacterial therapy are given . The following methods of investigation into bodily endogenous intoxication have been developed: malonic dialdehyde, superoxiddismutase, and coefficient K . Toxic effects of antibiotics on the organism were found out to be dependent on the regimen of their administration . Perioperative antibiotic prophylaxis was proved to be superior from the standpoint of the clinical practice to the postoperative one. Pharmacol Res, 2000 Feb, 41(2), 211 - 9 Adverse testicular effects of some quinolone members in rats; Abd-Allah AR et al.; In the last few years, a marked decrease in male fertility has been reported . Environmental factors were recently suspected for this effect . Among those factors is the misuse of drugs and in particular antibiotics . Quinolones are a group of antibacterial agents with broad-spectrum activity . Testicular impairment of some quinolone members is controversial; a matter which stimulated our attention to investigate the adverse testicular effects of the most familiar quinolone members, namely: ofloxacin, ciprofloxacin and pefloxacin . They were given to rats in doses of 72, 135 and 72 mg kg(-1) day(-1) p.o., respectively, for 15 consecutive days . Ofloxacin was also used to establish a dose-response relationship in doses of 36, 72 and 360 mg kg(-1) day(-1) p.o . for 15 consecutive days . Results revealed that ofloxacin, ciprofloxacin and pefloxacin reduced testicular LDH-X activity by 39.8%, 62.7% and 60.7%, respectively . Moreover, sperm count, motility and daily sperm production were markedly decreased . Ofloxacin induced a dose-dependent decrease in testicular LDH-X activity, sperm count and motility . Furthermore, daily sperm production showed a marked reduction which amounted to 26.1% and 40 . 0% following administration of ofloxacin (72, 360 mg kg(-1) day(-1) x 15 days), respectively . Moreover, administration of ofloxacin resulted in marked testicular histopathological changes . It is concluded that, ofloxacin, ciprofloxacin and pefloxacin significantly impaired both testicular function and structure in rats . Pharmacoeconomics, 1999 Oct, 16(4), 343 - 53 Clinical and economic considerations of empirical antibacterial therapy of febrile neutropenia in cancer; Dranitsaris G; Febrile neutropenia is a condition that can develop in patients with cancer following the administration of myelosuppressive chemotherapy or radiation therapy . The current standard of patient management involves the empirical use of a combination of antibacterials or a single broad spectrum agent to offer extensive antibacterial coverage of both Gram-positive and Gram-negative micro-organisms . Over the past 25 years, febrile neutropenia has changed from a condition that was fatal in over 50% of patients to a condition with an infection-related mortality rate of less than 10% . A major reason behind these extraordinary advances in patient care has been the many well-designed randomised trials of empirical antibacterial therapy that have been conducted over this period of time . In contrast to this finding, a review of the literature revealed limited economic data on the empirical treatment of febrile neutropenia in patients with cancer . Therefore, there is a definite need to conduct more pharmacoeconomic research in this area and to develop methods of implementing the findings of such studies. Mol Cell, 1999 Nov, 4(5), 827 - 37 Relish, a central factor in the control of humoral but not cellular immunity in Drosophila; Hedengren M et al.; The NF-kappa B-like Relish gene is complex, with four transcripts that are all located within an intron of the Nmdmc gene . Using deletion mutants, we show that Relish is specifically required for the induction of the humoral immune response, including both antibacterial and antifungal peptides . As a result, the Relish mutants are very sensitive to infection . A single cell of E . cloacae is sufficient to kill a mutant fly, and the mutants show increased susceptibility to fungal infection . In contrast, the blood cell population, the hematopoietic organs, and the phagocytic, encapsulation, and melanization responses are normal . Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response. Pediatrics . 2000 Jan;105(1):e7. Granulocyte colony-stimulating factor is present in human milk and its receptor is present in human fetal intestine; Calhoun DA et al.; OBJECTIVE: Human milk provides neonates with a meaningful degree of protection from infection, but the responsible mechanisms are not well understood . Discovering these mechanisms is important, because of the possibility of supplementing infant formulas with factors that simulate human milk's protective capacity . We postulated that granulocyte colony-stimulating factor (G-CSF), a cytokine known to augment antibacterial defenses through its salutory effect on neutrophil production, might be one such factor . To test this hypothesis, we quantified G-CSF in milk of healthy women and those with intraamniotic infection, and sought the presence of functional G-CSF receptors (G-CSF-R) in fetal/neonatal intestinal villi . STUDY DESIGN: G-CSF was measured by enzyme-linked immunoassay in 126 milk samples obtained from breast-feeding women, and the concentrations were analyzed according to gestational age, postpartum day of collection (first 2 days vs greater 2 days), and the presence versus absence of intraamniotic infection . G-CSF-R messenger ribonucleic acid transcripts were sought from fetal/neonatal intestine using reverse transcriptase polymerase chain reaction, and localized using in situ RT-PCR . G-CSF-R protein, and specific intracellular signaling proteins (Janus tyrosine kinase-1, Janus tyrosine kinase-2, and tyrosine kinase-2), were sought by immunohistochemistry . RESULTS: All milk samples contained G-CSF, and significantly more G-CSF was contained in milk collected during the first 2 postpartum days than during subsequent days . Milk from women who delivered prematurely had less G-CSF during the first 2 postpartum days than milk from women who delivered at term . When intraamniotic infection was present, the concentration of G-CSF in milk was elevated significantly compared with concentrations in milk of noninfected women . G-CSF concentrations were also higher in milk collected during the first 2 postpartum days from women who had received intrapartum recombinant G-CSF treatment, compared with milk obtained from women with intraamniotic infection, regardless if they delivered prematurely or at term . G-CSF-R messenger ribonucleic acid and protein were expressed on fetal villus enterocytes, and Janus tyrosine kinase-1, Janus tyrosine kinase-2, and tyrosine kinase-2 were present within the cytoplasm of these cells . CONCLUSIONS: Human milk contains substantial quantities of G-CSF . G-CSF-R are abundant on villus enterocytes, and specific proteins associated with G-CSF-R signaling are present in these cells. J Biol Chem, 2000 Jan 7, 275(1), 135 - 40 Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues . The role of the 2-amino function in catalysis; Bearne SL et al.; Glucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source . Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents . The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis . The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described . Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1 . 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition . Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding . Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding . Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively. Postgrad Med J, 1999 Sep, 75(887), 571 - 3 Ciprofloxacin-induced bone marrow depression; Dutta TK et al.; Ciprofloxacin, a broad-spectrum fluoroquinolone antibacterial agent, is generally considered to be a safe drug . However, occasionally it may have life-threatening complications . Two instances of bone marrow failure following use of ciprofloxacin are reported . In one case, the bone marrow reverted to normal following withdrawal of the drug . In the other case, the patient succumbed to irreversible bone marrow depression leading to severe thrombocytopenia and uncontrolled bleeding . This could have been an idiosyncratic reaction. Arch Pharm Res, 1999 Dec, 22(6), 579 - 84 Synthesis and in vitro antibacterial activity of quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety; Chung IH et al.; Several oxazolidinones having amine moiety were prepared to form a quaternary ammonium salt with cephalosporin nucleus, and antibacterial activity of the quaternary ammonium cephalosporin derivatives bearing oxazolidinone moiety were examined particularly with expectation of dual activity . However, the cephalosporin-oxazolidinone compounds revealed rather weaker antibacterial activity in vitro than their parent oxazolidinone and cephalosporin without showing any characteristic activity as expected. Med Pediatr Oncol, 2000 Jan, 34(1), 39 - 42 Monocyte deactivation and its reversal in a patient with chemotherapy-induced leukopenia and severe systemic infection; Bonig H et al.; BACKGROUND: Serious infections constitute a major problem for patients with cancer, and new approaches must be found in dealing with these . The pathophysiology of neutropenic infection is not well understood, although there is some evidence that, as in sepsis in the primarily immunocompetent host, a pro- and an antiinflammatory phase can be discriminated . In the recent literature is described a series of nonneutropenic patients with sepsis in whom interferon-gamma was successfully administered during the immunoparalytic phase, a concept that might possibly be extended to immunocompromised hosts . PROCEDURE: A 14-year-old patient with RAEB-T/hypoplastic M2 and chemothera py-induced neutropenia developed a severe infection and continued to deteriorate clinically despite maximum supportive measures, including broad antibacterial and antifungal coverage . On the basis of monocyte de-activation this patient was considered to be in the immunoparalytic phase of sepsis and consequently treated with 60 microg/m(2) of interferon-gamma per day for 10 days . RESULTS: The patient made a rapid clinical recovery, and biochemical markers of infection improved promptly . At the same time, the fraction of activated monocytes normalized rapidly and stably . We hypothesize that treatment with interferon-gamma effected this rapid restoral of monocyte activation and that monocyte reactivation might have contributed to the patient's prompt recovery from his severe infection . Interferon-gamma treatment was well tolerated . CONCLUSIONS: Immunostimulation with interferon-gamma might prove to be a valuable adjuvant treatment for patients with chemotherapy-induced neutropenia during the rare scenario of infection with immunoparalysis . Mol Cell Biol, 2000 Jan, 20(2), 594 - 603 An antitumor drug-induced topoisomerase cleavage complex blocks a bacteriophage T4 replication fork in vivo; Hong G et al.; Many antitumor and antibacterial drugs inhibit DNA topoisomerases by trapping covalent enzyme-DNA cleavage complexes . Formation of cleavage complexes is important for cytotoxicity, but evidence suggests that cleavage complexes themselves are not sufficient to cause cell death . Rather, active cellular processes such as transcription and/or replication are probably necessary to transform cleavage complexes into cytotoxic lesions . Using defined plasmid substrates and two-dimensional agarose gel analysis, we examined the collision of an active replication fork with an antitumor drug-trapped cleavage complex . Discrete DNA molecules accumulated on the simple Y arc, with branch points very close to the topoisomerase cleavage site . Accumulation of the Y-form DNA required the presence of a topoisomerase cleavage site, the antitumor drug, the type II topoisomerase, and a T4 replication origin on the plasmid . Furthermore, all three arms of the Y-form DNA were replicated, arguing strongly that these are trapped replication intermediates . The Y-form DNA appeared even in the absence of two important phage recombination proteins, implying that Y-form DNA is the result of replication rather than recombination . This is the first direct evidence that a drug-induced topoisomerase cleavage co