Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Oct, 96(4), 492 - 8 Cytokines in periradicular lesions: the effect of linezolid treatment; Danin J et al.; OBJECTIVE: The purpose of this study was to quantify the cytokines interleukin (IL)-1 receptor antagonist (RA), IL-6, and transforming growth factor beta(1) found in extracts of inflammatory periapical tissues and to study the effect of a new antibiotic (linezolid) on the levels of these cytokines . STUDY DESIGN: Twenty-two patients with root-filled teeth with persisting periapical pathoses were randomly divided into a control group or an antibiotic group . One tooth from each of the patients was resected at the root-end, and the periapical tissue was collected . IL-1RA, IL-6, and TGF-beta(1) were quantified in tissue extracts through the use of enzyme-linked immunosorbent assays . RESULTS: Measurable amounts of all 3 cytokines were found in all extracts . A statistically significant reduction in IL-1RA per milliliter was observed in the linezolid group in comparison with the control group (P <.05) . The difference in variation of IL-1RA in the treatment and control groups was also highly statistically significant (P <.001) . CONCLUSIONS: Although drawn from a limited sample size, the results indicate that IL-1RA is a sensitive indicator of the effect of antibacterial treatment on the immune response in periapical inflammatory tissues. Eur J Med Chem, 2003 Sep, 38(9), 851 - 4 Synthesis and in vitro antibacterial evaluation of N-{5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl} piperazinyl quinolones; Foroumadi A et al.; A series of N-{5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl}piperazinyl quinolones (7a-c) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria . The antibacterial data revealed that compounds 7a-c had strong and better activity against tested Gram-positive organisms than the reference quinolones such as ciprofloxacin, norfloxacin and enoxacin . However, all three compounds were nearly inactive against Gram-negative bacteria . Compound 7a (ciprofloxacin analogue) was the most active compound against Gram-positive bacteria (MIC=0.008-0.015 mug mL(-1)). Eur J Med Chem, 2003 Sep, 38(9), 841 - 50 Synthesis and biological activity of 1beta-methyl-2-{5-(2-N-substituted aminoethylcarbamoyl)pyrrolidin-3-ylthio}carbapenem derivatives; Oh CH et al.; The synthesis of a new series of 1beta-methylcarbapenems having the substituted aminoethylcarbamoylpyrrolidine moiety is described . Their in vitro antibacterial activities against both Gram-positive including MRSA and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated . In particular, the compound 11g having piperazinyl urea moiety showed the most potent antibacterial activity and 11k exhibited excellent anti-MRSA. Curr Drug Targets Inflamm Allergy, 2003 Sep, 2(3), 224 - 31 Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells; Niyonsaba F et al.; Antibacterial peptides function as effectors for defense in innate immunity . In mammals, they are implicated in the barrier protection of epithelia where their expression can be induced during infection and inflammation . Over a dozen of antibacterial peptides have been identified in humans . Among these, defensins and cathelicidins have been well characterized . Two types of defensins (alpha- and beta-defensins) are recognized based on the presence of their conserved six cysteine residues, whereas cathelicidins are characterized by a homologous cathelin sequence in the pro-region and a variable antibacterial C-terminal sequence . Human beta-defensins and cathelicidin hCAP18/LL-37 are mainly expressed in epithelial tissues where mast cells are present . Here we review the structure of human beta-defensins and cathelicidin, and describe their multiple activities on mast cells to induce chemotaxis, degranulation and prostaglandin D(2) production, acting through receptors coupled to G-protein-phospholipase C pathway . Thus, in addition to their bactericidal activities, epithelial cell-derived antibacterial peptides may modulate the inflammatory responses by recruiting mast cells to inflammation foci and inducing the degranulation as well as prostaglandin production from this cell population. Rev Environ Contam Toxicol, 2004, 180, 1 - 91 Veterinary medicines in the environment; Boxall AB et al.; The impact of veterinary medicines on the environment will depend on a number of factors including physicochemical properties, amount used and method of administration, treatment type and dose, animal husbandry practices, manure storage and handling practices, metabolism within the animal, and degradation rates in manure and slurry . Once released to the environment, other factors such as soil type, climate, and ecotoxicity also determine the environmental impact of the compound . The importance of individual routes into the environment for different types of veterinary medicines varies according to the type of treatment and livestock category . Treatments used in aquaculture have a high potential to reach the aquatic environment . The main routes of entry to the terrestrial environment are from the use of veterinary medicines in intensively reared livestock, via the application of slurry and manure to land, and by the use of veterinary medicines in pasture-reared animals where pharmaceutical residues are excreted directly into the environment . Veterinary medicines applied to land via spreading of slurry may also enter the aquatic environment indirectly via surface runoff or leaching to groundwater . It is likely that topical treatments have greater potential to be released to the environment than treatments administered orally or by injection . Inputs from the manufacturing process, companion animal treatments, and disposal are likely to be minimal in comparison . Monitoring studies demonstrate that veterinary medicines do enter the environment, with sheep dip chemicals, antibiotics, sealice treatments, and anthelmintics being measured in soils, groundwater, surface waters, sediment, or biota . Maximum concentrations vary across chemical classes, with very high concentrations being reported for the sheep dip chemicals . The degree to which veterinary medicines may adsorb to particulates varies widely . Partition coefficients (K(d)) range from low (0.61 L kg(-1)) to high (6000 L kg(-1)) . The variation in partitioning for many of the compounds in different soils was significant (up to a factor of 30), but these differences could be not be explained by normalization to the organic carbon content of the soils . Thus, to arrive at a realistic assessment of the availability of veterinary medicines for transport through the soil and uptake into soil organisms, the K(oc) (which is used in many of the exposure models) may not be an appropriate measure . Transport of particle-associated substances from soil to surface waters has also been demonstrated . Veterinary medicines can persist in soils for days to years, and half-lives are influenced by a range of factors including temperature, pH, and the presence of manure . The persistence of major groups of veterinary medicines in soil, manure, slurry, and water varies across and within classes . Ecotoxicity data were available for a wide range of veterinary medicines . The acute and chronic effects of avermectins and sheep dip chemicals on aquatic organisms are well documented, and these substances are known to be toxic to many organisms at low concentrations (ng L(-1) to microg L(-1)) . Concerns have also been raised about the possibility of indirect effects of these substances on predatory species (e.g., birds and bats) . Data for other groups indicate that toxicity values are generally in the mg L(-1) range . For the antibiotics, toxicity is greater for certain species of algae and marine bacteria . Generally, toxicity values for antibacterial agents were significantly higher than reported environmental concentrations . However, because of a lack of appropriate toxicity data, it is difficult to assess the environmental significance of these observations with regard to subtle long-term effects. Di Yi Jun Yi Da Xue Xue Bao, 2003 Oct, 23(10), 1066 - 8 {Effects of the antibacterial peptide cecropins from Chinese oak silkworm, Antheraea pernyi on 1, 2-dimethylhydrazine-induced colon carcinogenesis in rats}; Zhang WM et al.; OBJECTIVE: To gain insight into the putative anticancer effect of the antibacterial peptides, cecropins, from Chinese oak silkworm, Antheraea pernyi, on the cancer cells and 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats . METHODS: Growth inhibitory effect of the cecropins on normal human gastric epithelial cell line (GES-1) and human colon adenocarcinoma cell line (LS-174T) was observed using a microculture tetrazolium (MTT) colorimetric methods . Male Wistar rats were divided into 4 groups . Group1 was given on a weekly basis cecropins from Antheraea pernyi (3,000 Ua/ml) by gavage at 2 doses of 10 ml/kg body weight and exposed to subcutaneous injection of DMH at the dose of 20 mg/kg body weight . Group 2 was received weekly DMH only . Group 3 was given the cecropins by gavage at the same dose as in group 1 . Group 4 was weekly exposed to subcutaneous injection of EDTA (1 mmol/L) . All treatments were completed in a course of 18 weeks and the experiment was finished at week 33 . RESULTS: MTT assay showed selective cytotoxic activity of the cecropins against the human colon adenocarcinoma cells line . The viability of the cancer cells was about 54% and 100% for the normal cells . There was a significantly lower incidence of large intestinal tumors in rats gavaged with cecropins (65%, P<0.01), but the tumor burden (tumors/tumor-bearing animal) and tumor mass index were comparable between the groups (P>0.05) . CONCLUSION: The cecropins possess effective anti-tumor activity with no cytotoxicity against normal eukaryotic cells, and impede the neoplastic process in murine large intestines. Curr Opin Pharmacol, 2003 Oct, 3(5), 502 - 7 Targeting metalloenzymes: a strategy that works; White RJ et al.; Faced with a wealth of antibacterial drug discovery targets as a result of bacterial genomics, we need to carefully select which ones to work with . Choosing bacterial metalloenzymes is one possible approach that can increase the probability of success . Metalloenzymes can be identified through specific motif searches of bacterial genomes . Current state-of-the-art medicinal chemistry allows for the design of inhibitor libraries targeting metalloenzymes and the efficient optimization of leads identified . This approach has been successfully applied to the discovery of in vivo active antibacterial agents that are inhibitors of bacterial peptide deformylase and UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase . Other bacterial metalloenzymes are open to the same approach. Eur J Clin Pharmacol, 2003 Nov, 59(8-9), 689 - 95 Epub 2003 Oct 14. Absolute contraindications in relation to potential drug interactions in outpatient prescriptions: analysis of the first five million prescriptions in 1999; Guedon-Moreau L et al.; OBJECTIVES: Adverse drug interactions increase morbidity and mortality . To prevent these, situations leading to adverse prescriptions must be clarified . This study quantifies and analyses prescriptions with potential adverse drug interactions in primary health care in the north of France over a 3-month period . METHODS: All prescriptions administered between 1 January and 31 March 1999 were analysed to identify potential interactions amongst drugs appearing on the same prescription sheet . The regional French healthcare database was compiled to further classify contra-indications . RESULTS: There were 5,358,374 prescriptions administered to 44% of the overall population of the Nord-Pas de Calais area (1,754,372 patients/3,990,167 general population) . There were 14,390 prescriptions classified as either absolute (26%) or relative contraindications (74%) . Nine drug categories accounted for most of the absolute contraindications: dopaminergic antiparkinsonians, neuroleptic agents, migraine treatments (such as ergot alkaloids, sumatriptan and other triptan derivatives), prokinetic drugs (cisapride), antibacterial drugs (macrolides), antifungals (imidazoles), antiarrhythmics, betablockers and analgesics (opioids and floctafenine) . In 54% of patients exposed, the incurred risk was either QT prolongation/Torsade de Pointes or antagonism of dopaminergic antiparkinson agents with dopamine receptor antagonists prescribed as antipsychotic agents . CONCLUSIONS: Among a non-selected population of ambulatory outpatients, the number of quarterly prescriptions with contra-indications with potentially harmful drug interaction was 27 in 10,000 prescriptions . This would extrapolate to nearly 200,000 contra-indications on the same-prescription sheets in France in the first quarter of 1999. Chirality, 2003 Nov, 15(9), 731 - 42 Link between biological signaling and increased enantioseparations of acids using glycopeptide antibiotics; Reilly J et al.; The vancomycin analog A82846B has been shown to provide excellent selectivity as a chiral recognition agent for some acidic test analytes in capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) . In both modes A82846B outperforms vancomycin as a chiral selector . A82846B has enhanced antibacterial activity data in comparison to vancomycin, which is probably due to the increased dimerization constant of over 100 in magnitude in comparison to vancomycin . The link between the electrophoretic and chromatographic separations observed and the biological activity of A82846B is discussed . Dimerization of A82846B in solution was proposed as a theory as to why A82846B gave such enhanced separations for acidic racemates . Further literature and experimental studies support the theory . J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Oct 25, 796(1), 155 - 64 Development of a liquid chromatography method for the determination of linezolid and its application to in vitro and human microdialysis samples; Buerger C et al.; Linezolid is a new, promising antibacterial agent to treat severe infections . A rapid HPLC assay using UV detection for the determination in microdialysate and human plasma was developed . After sample preparation, using acetonitrile for plasma and water for microdialysate, 20 microl was injected and separated on a RP-18 column . Overall, the assay exhibited good precision and accuracy . The diffusion properties of linezolid investigated in in vitro microdialysis experiments revealed a mean relative recovery of 77.5% (CV: 5.4%; delivery and recovery experiments) . Following characterization of linezolid in in vitro microdialysis, the setting is suitable for application in clinical studies. Bioorg Med Chem Lett, 2003 Nov 3, 13(21), 3747 - 51 QSAR study on antibacterial activity of sulphonamides and derived Mannich bases; Joshi S et al.; The paper describes synthesis and comparative study on antibacterial activities of sulphonamides and Mannich bases derived from them . The compounds were screened for their antibacterial activity against various gram-positive and gram-negative bacteria and were analyzed statistically . The results have shown that the compounds are quiet active against pathogens under study and were nontoxic. Nutr Rev, 2003 Sep, 61(9), 295 - 305 Nutritional and physiologic significance of alpha-lactalbumin in infants; Lonnerdal B et al.; alpha-Lactalbumin is the major protein in breast milk (20-25% of total protein) and has been described to have several physiologic functions in the neonatal period . In the mammary gland, it participates in lactose synthesis, thereby creating an osmotic "drag" to facilitate milk production and secretion . alpha-Lactalbumin binds divalent cations (Ca, Zn) and may facilitate the absorption of essential minerals, and it provides a well-balanced supply of essential amino acids to the growing infant . During its digestion, peptides appear to be transiently formed that have antibacterial and immunostimulatory properties, thereby possibly aiding in the protection against infection . A novel folding variant ("molten globule state") of multimeric alpha-lactalbumin has recently been discovered that has anti-infective activity and enhances apoptosis, thus possibly affecting mucosal cell turnover and proliferation . Cow milk also contains alpha-lactalbumin, albeit less than human milk (2-5% of total protein in bovine milk), and protein fractions enriched with alpha-lactalbumin may now be added to infant formula to provide some of the benefits of human alpha-lactalbumin. Eur J Pharm Sci, 2003 Oct, 20(2), 173 - 9 Convergent synthesis and antibacterial activity of pyrazole and pyrazoline derivatives of diazepam; Berghot MA et al.; Polysubstituted pyrazoles (5)(a-l), pyrazolines (7)(a-c), (8)(a-c) and pyrazolotriazine (10) derivatives of diazepam were synthesized . The structures of hitherto unknown compounds were established by analytical and spectral methods . Some of these compounds were screened to test their antibacterial activity against gram-positive (B . subtilis) and gram-negative (P . aeruginosa) . All compounds showed potent activity against these bacteria. Biotechnol Adv, 2001 Apr 1, 19(2), 109 - 18 Polymerized lipid vesicles as colorimetric biosensors for biotechnological applications; Jelinek R et al.; Supramolecular chemical assemblies composed of polydiacetylene (PDA) exhibit rapid colorimetric transitions upon specific interactions with a variety of biological analytes in aqueous solutions . Among the analytes that give rise to the unique blue-red color changes are lipophilic enzymes, antibacterial peptides, ions, antibodies, and membrane penetration enhancers . The chemical assemblies include conjugated PDA, responsible for the chromatic transitions, and the molecular recognition elements, which are either chemically or physically associated with the PDA . Thus, by incorporation of specific recognition elements, the system can be designed in ways allowing for highly selective identification of analytes . In particular, receptors and epitopes can be incorporated within the sensor assembly, which then determine the specificity of the colorimetric transitions . The PDA-based molecular assemblies are robust and can be readily applied to diagnosis of physiological molecules and for rapid screening of chemical and biological libraries, for example, in 96 well-plate platforms. Biotechnol Adv, 2002 May, 20(2), 91 - 100 Applications of natural silk protein sericin in biomaterials; Zhang YQ; Silk sericin is a natural macromolecular protein derived from silkworm Bombyx mori . During the various stages of producing raw silk and textile, sericin can be recovered for other uses . Also, sericin recovery reduces the environmental impact of silk manufacture . Sericin protein is useful because of its properties . The protein resists oxidation, is antibacterial, UV resistant, and absorbs and releases moisture easily . Sericin protein can be cross-linked, copolymerized, and blended with other macromolecular materials, especially artificial polymers, to produce materials with improved properties . The protein is also used as an improving reagent or a coating material for natural and artificial fibers, fabrics, and articles . The materials modified with sericin and sericin composites are useful as degradable biomaterials, biomedical materials, polymers for forming articles, functional membranes, fibers, and fabrics. Khirurgiia (Mosk), 2003, (9), 28 - 32 {Healing of purulent wounds of soft tissues in local treatment}; Stoliarov EA et al.; GOALS: To improve results of treatment of patients with purulent wounds of soft tissues of various etiology and location . METHODS: Developed method of local treatment was used in patients with purulent wounds of soft tissues . Efficacy of the treatment was evaluated with clinical, cytological, bacteriologic and bacterioscopic methods . RESULTS: When proposed antibacterial drugs were used, cleaning of wounds in inflammatory phase procedea 2 times faster compared to local treatment with standard drugs . Collagen wound covering Lioplast promoted in phases of regeneration and epithelisation 1.5 times faster reparative processes in the wound and prevention of secondary contamination of the wound . CONCLUSION: This method permits to improve results of treatment and to shorten hospital stay of patients. Ann Rheum Dis, 2003 Nov, 62 Suppl 2, ii37 - 42 Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF; Ehlers S; Studies in mouse infection models clearly demonstrate tumour necrosis factor (TNF) to be a critical component of both the antibacterially protective and the inflammatory immune response to Mycobacterium tuberculosis . It is therefore not surprising that treatment of patients-for example, those with rheumatoid arthritis-with biological agents interfering with TNF activity have shown an increased risk of reactivating tuberculosis . However, conceivably, TNF targeting biological agents can be developed that because of their particular mode of action and their specific pharmacodynamics may be less likely to have this side effect. J Exp Med, 2003 Oct 6, 198(7), 977 - 85 Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids; Wittamer V et al.; Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity . ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types . Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids . Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor . Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins . Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens . Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner . Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs. Curr Med Chem Anti-Canc Agents, 2003 Nov, 3(6), 439 - 50 The quinolone family: from antibacterial to anticancer agents; Sissi C et al.; The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent . Indeed, a distinctive feature of drugs based on the quinolone structure is their remarkable ability to target different type II topoisomerase enzymes . In particular, some congeners of this drug family display high activity not only against bacterial topoisomerases, but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and in vivo tumor models . Hence, these cytotoxic quinolones represent an exploitable source of new anticancer agents, which might also help addressing side-toxicity and resistance phenomena . Their ability to bind metal ion co-factors represents an additional means of modulating their pharmacological response(s) . Moreover, quinolones link antibacterial and anticancer chemotherapy together and provide an opportunity to clarify drug mechanism across divergent species. Comb Chem High Throughput Screen, 2003 Sep, 6(6), 501 - 12 Expanding the scope of aromatic polyketides by combinatorial biosynthesis; Kantola J et al.; Combinatorial biosynthesis is a technology for mixing genes responsible for the biosynthesis of secondary metabolites, in order to generate products for compound libraries serendipitously or to cause desired modifications to natural products . Both of these approaches are extremely useful in drug discovery . Streptomyces and related species are abundant in bioactive secondary metabolites and were therefore the first microbes to be used for combinatorial biosynthesis . Polyketides are the most abundant medicinal agents among natural products . Structural diversity and a wide scope of bioactivities are typical of the group . However, the common feature of polyketides is a biosynthetic process from simple carboxylic acid residues . In molecular genetics, polyketides are sub-classified as types I and II, called modular and aromatic polyketides respectively . The best-known bioactivities of aromatic polyketides are their antibacterial and antitumor effects . Genetic analysis of aromatic polyketides has resulted in almost 30 cloned and identified biosynthetic gene clusters . Several biosynthetic enzymes are flexible enough to allow their use in combinatorial biosynthesis to create high diversity compound libraries . This review describes the state of the art of combinatorial biosynthesis, giving anthracyclines as examples . Contiguous DNA sequences for antibiotics, cloned from four different anthracycline producers, provide tools for rapid lead optimization or other structural modification processes, and not only for anthracyclines . Two gene cassettes enabling fast and flexible structural modification of polyketides are introduced in this paper. Boll Chim Farm, 2003 Jun, 142(5), 223 - 5 Preparation and antibacterial evaluation of some nitrone derivatives with Ge(IV) and Sn(IV) chloride complexes; Khallow KI et al.; New complexes of the general formula MCl3.L where L1 = {N-p-chlorophenyl)-alpha-(2-xanthatonaphthol)nitrone, L2 = {N-(p-anisole)-alpha-(2-xanthatonaphthol)nitrone}; M = Ge(IV) and Sn(IV) have been synthesized and characterized by elemental analyses, i.r . and molar conductances . The antibacterial activities of these ligands and their complexes have been studied against six species of bacteria in vitro at concentration ranging from 1-10 micrograms/ml . No activity were observed for the both ligands while a remarkable activities were exhibited by some complexes of both ions Ge(IV) and Sn(IV) against S . aureus, B . subtilis and P . mirabilis even more than the effect of antibacterial used in this study. Comp Biochem Physiol C Toxicol Pharmacol, 2003 Sep, 136(1), 95 - 102 Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats; Shin HC et al.; We investigated maternal and fetal tissue distribution of DW-116, a newly developed fluoroquinolone with a broad antibacterial spectrum against both G(+) and G(-) bacteria, in pregnant rats . After oral administration of {14C}-DW-116 (labeled 1 mg and unlabeled 500 mg/kg) to female rats on the 18th day of gestational, groups of three rats were killed at various time points up to 24 h, and plasma and tissues were collected, processed and analyzed . {14C}-DW-116 was rapidly absorbed, and distributed into the maternal and fetal tissues, and it declined in a biphasic manner with elimination half-lives (t(1/2)) of 10-15 h and mean residence times (MRT(0-24 h)) of 4-9 h . The radioactivity in most tissues of both dams and fetus reached its peak within 1 h and radioactivity levels of up to 10-25% of the peak level were maintained until 24 h after dosing . Among various tissues, the radioactivity in the maternal lungs was the highest (27 times that of plasma) at the C(max) . Radioactivity in other tissues including liver, kidney, heart, lung, brain, spleen, mammary gland, placenta, ovary and uterus was higher than that in the maternal plasma (one- to three-fold) . The tissue-to-plasma partition coefficient (K(p), AUC(0-24 h,tissue)/AUC(0-24 h,plasma)) of {14C}-DW-116 in maternal tissues was highest in the lung (K(p)=3.7), followed by the spleen (2.2), kidney (2.0), liver (1.8), heart (1.5), placenta (1.3), brain (1.3), ovary (1.1), uterus (1.1), and mammary gland (1.0) . The tissue-to-plasma partition coefficient values in fetal tissues were heart (K(p)=2.2), kidney (2.1), liver (1.9), lung (1.6) and brain (1.4) . When lactating rats were given a single oral dose of {14C}-DW-116, the radioactivity was rapidly secreted into the milk with K(p) of 1.7 at T(max) (0.5 h) . These results indicate that DW-116 or its related metabolite(s) rapidly cross the blood-placenta and blood-milk barrier, extensively distribute into the fetal tissues, and are eliminated from the body in a prolonged manner . This study sheds insights into the maternal and fetal tissue distribution of DW-116 and will be useful for assessing both therapeutic and toxicological relevance of DW-116 in pregnant subjects. J Antimicrob Chemother, 2003 Nov, 52(5), 796 - 800 Epub 2003 Sep 30. Development of a microdilution method to evaluate Mycobacterium tuberculosis drug susceptibility; Banfi E et al.; A new rapid microdilution method, employing the dye resazurin as an indicator of mycobacterial growth, was developed to evaluate drug susceptibility of Mycobacterium tuberculosis reference strain H37Rv and of 13 M . tuberculosis susceptible or multidrug-resistant clinical strains . Different growth conditions were evaluated . The MICs of isoniazid, rifampicin, streptomycin and ethambutol were determined by the Microdilution Resazurin Assay (MRA) and the results compared with those obtained by the agar proportion method; complete agreement was always obtained . MRA resulted in a rapid, reliable, simple and inexpensive coloured method suitable for testing the susceptibility of M . tuberculosis clinical strains to first-line drugs; its employment in evaluating new antibacterial molecules is also suggested. J Morphol, 2003 Nov, 258(2), 239 - 48 Morphology of the midgut trunk in the penaeid shrimp, Sicyonia ingentis, highlighting novel nuclear pore particles and fixed hemocytes; Martin GG et al.; The morphology of the midgut trunk (MGT) in the penaeid shrimp Sicyonia ingentis was examined by light and scanning and transmission electron microscopy . Although the function of the MGT is poorly understood, it is not involved with the digestion and absorption of nutrients, and it appears to be the surface of a shrimp least protected from penetration by potential pathogens . As described for other decapod crustaceans, the MGT in shrimp is composed of a simple columnar epithelium separated from a layer of connective tissue by a thick basal lamina . Beneath the basal lamina is a previously unreported layer of hemocytes, exclusively of the granulocyte variety, embedded in a matrix continuous with the basal lamina and extending into the connective tissue . This layer was observed in four other species of penaeid shrimp . Granulocytes in circulation can phagocytose and encapsulate foreign material and the granules contain antibacterial molecules, lysosomal enzymes, and prophenoloxidase . We suggest that the granulocytes associated with the basal lamina have matured at this site and are well positioned to fight potential pathogens that have penetrated the epithelial layer of the MGT . A second observation is the presence of clusters of cylinders bound to the nuclear pores of the epithelial cells . The possibility that these clusters are viruses, organelles, or abnormal organelles induced by disease or toxic materials is discussed . These unique particles were observed in S . ingentis but none of the other penaeid shrimp we examined . Biotechnol Lett, 2003 Aug, 25(15), 1263 - 6 Improved bactericidal activity of silver-loaded zirconium phosphate in the presence of Cl- by combining with hydroxyapatite; Nishioka M et al.; Silver-loaded zirconium phosphate (AgZ) was combined with hydroxyapatite (HA) to prepare an antibacterial composite (AgZ/HA) with improved activity in the presence of Cl- . When Escherichia coli cells were deactivated in 154 mM NaCl, the bacterial survival ratio at 90 min for AgZ/HA was 3.9 x 10(-4) compared to 1.2 x 10(-1) for AgZ itself . Because the bactericidal activity of AgZ/HA decreased with increasing phosphate ion up to 10 mM, cell adsorption onto the combined HA moiety probably compensated for the Cl- -induced deterioration in the activity of the silver-based bactericide. J Am Acad Dermatol, 2003 Oct, 49(4), 730 - 2 Scar-localized argyria secondary to silver sulfadiazine cream; Fisher NM et al.; Silver sulfadiazine cream is a topical antibacterial agent that combines the antibacterial effects of both silver and sulfadiazine . Its reported cutaneous side effects include hypersensitivity reactions, allergic contact dermatitis, erythema multiforme, and systemic argyria . We report the case of a patient who had localized argyria develop in a scar after the use of silver sulfadiazine cream . In this case, the silver sulfadiazine cream was applied to and argyria developed within a postsurgical wound and area of severe contact dermatitis. J Nat Prod, 2003 Sep, 66(9), 1175 - 80 Cytotoxic sesquiterpene lactones from the root of Saussurea lappa; Sun CM et al.; Bioassay-directed fractionation of Saussurea lappa led to the isolation of a novel lappadilactone (1) and seven sesquiterpene lactones (2-8) as cytotoxic principles against selected human cancer cell lines . Lappadilactone (1), dehydrocostuslactone (2), and costunolide (5) exhibited the most potent cytotoxicity with CD50 values in the range 1.6-3.5 microg/mL in dose- and time-dependent manners . The cytotoxicities were not specific and showed similar activities against HepG2, OVCAR-3 and HeLa cell lines . The structure-activity relationship showed that the alpha-methylene-gamma-lactone moiety is necessary for cytotoxicity, and activity is reduced with the presence of a hydroxyl group . In addition, seven noncytotoxic compounds (9-15) were also isolated, including two novel sesquiterpenes, a guaianolide-type with a C17 skeleton, lappalone (13), and 1beta,6alpha-dihydroxycostic acid ethyl ester (14) . The structures of the new compounds were elucidated from spectroscopic and/or X-ray data interpretations . Some representative compounds were also tested for antibacterial activity; however, only marginal activities were observed . Therefore, compounds 1-8 are potential cytotoxic agents but without significant antibacterial effect. Acta Biomed Ateneo Parmense, 2003 Aug, 74(2), 81 - 7 Prophylaxis for acute exacerbations of chronic bronchitis using an antibacterial sublingual vaccine obtained through mechanical lysis: a clinical and pharmacoeconomic study; Cogo R et al.; Chronic obstructive bronchitis (COB) complicated by acute exacerbations, or exacerbations, triggered by episodes of infection is the most demanding respiratory disease in our country today, to the extent that the implementation of every possible prevention strategy, in terms of both behaviour and prophylactic vaccination, is fully justified . From this point of view, in addition to the classic anti-viral vaccines, increasing importance is also being placed on antibacterial vaccines obtained by mechanically crushing pathogen bacteria (without the use of chemicals to denature the antigenic structures), which can be sublingually administered . In this study, conducted on 57 patients aged over 75 suffering from COB and affected by at least one exacerbation over the past 12 months, we evaluated the incidence of these exacerbations during a follow-up period, subsequent to prophylaxis with polyvalent bacterial mechanical lysate . As well as the absolute number of episodes, we also evaluated the seriousness of the episodes, the length of any antibiotic therapy and the overall cost of this therapy and of the prophylactic treatment . We then compared this data with that of the same period for the previous year, during which time no antibacterial prophylaxis had been administered . Both the absolute number of exacerbations, their length and seriousness were shown to be significantly reduced during the period of treatment compared to the control period . Similarly, the need to use antibiotic treatments, as well as the overall cost of the treatment of these patients, were shown to be reduced during the period of treatment compared to the control period. Curr Opin Investig Drugs, 2003 Aug, 4(8), 926 - 36 Antibacterial agents: patent highlights January to June 2003; Phillips OA; This review presents an overview of 38 patents published between January and June 2003 on different classes of antibacterial agents . Patent disclosures on novel oxazolidinone and macrolide derivatives with strong antibacterial activity continue to dominate patent publications in recent years . A use patent of a linezolid formulation for ear infections in infants and pre-operative procedure is highlighted . Disclosures on novel dual action oxazolidinone-quinolone hybrids designed to overcome bacterial resistance and new macrolide derivatives with antimycobacterial activity are also presented . Patents on beta-lactam and quinolone antibiotics focus on the development of new processes and formulations to improve cost, purity and stability of existing agents in clinical use . Novel antibacterial agents (DNA polymerase and D-glutamate racemase inhibitors) as potential lead compounds are also presented. Org Lett, 2003 Oct 2, 5(20), 3575 - 8 A new class of branched aminoglycosides: pseudo-pentasaccharide derivatives of neomycin B; Fridman M et al.; {reaction: see text} The clinically important antibiotic neomycin B was modified at position C5' ' by adding one extra sugar ring in the beta-configuration, and the observed pseudo-pentasaccharides were tested against various bacterial strains, including pathogenic and resistant strains . The designed antibiotics show antibacterial activity superior to that of neomycin B against pathogenic and resistant bacterial strains. Farmaco, 2003 Oct, 58(10), 1011 - 5 Synthesis of two and antibacterial activity of one novel oxime ether derivatives of erythromycin A; Dondas HA et al.; The synthesis of novel erythromycin A 9-O-(2-ethenesulfony-ethyl)-oxime and erythromycin A 9-O-(3-oxo-butyl)-oxime from erythromycin A (EA) by the Michael reaction is described and to describe the effects of transformation of ketone in position 9 of EA to an oxime ether . This transformation occurred in a single step without protecting of any functional moiety of erythromycin oxime and zero waste manner in good yield . The antibacterial screen of EA 9-O-(2-ethenesulfony-ethyl)-oxime is also reported. Chemotherapy, 2003 Sep, 49(5), 213 - 21 Synthesis, structural analysis and antibacterial activity of a butyl ester derivative of ampicillin; Bartzatt R et al.; BACKGROUND: Ester groups placed on medicinal agents have been found to increase lipophilicity (more positive log p value) . Alterations in a partition coefficient may affect medicinal activity . Formation of an ester group such as -C(O)OCH(2)CH(2)CH(2)CH(3) from a carboxyl group {-C(O)OH} can be efficiently accomplished utilizing diazoalkanes and produces a prodrug-like structure of ampicillin (a bipartate drug carrier) . Formation of an ester group may produce beneficial changes in medicinal parameters such as log P, log BB, and molecular polar surface area (TPSA) . METHODS: An ester of ampicillin was synthesized by replacing the carboxyl group with a butyl ester group . The ester formed was synthesized utilizing diazobutane, which is a gas at room temperature and reacts with the acidic hydrogen of the carboxylic acid . The ampicillin ester was dissolved into LB agarose media at levels of 0.228 and 0.180 mg/ml, and its antibacterial activity was compared to that of normal ampicillin . Medicinal parameters such as log P, solubility, polar surface area, log BB, molecular dipole, Clog P, intestinal absorption and the 'Rule of 5' were determined . RESULTS: The ampicillin ester consisted of yellow crystals that were stable for >12 weeks at 0 degrees C . The ester has reduced hydrogen bonding capacity and increased lipophilic character (by log P) compared to the parent structure . Each concentration of the ester tested induced 100% growth inhibition of ampicillin-susceptible but streptomycin-resistant Escherichia coli bacteria, and >30% growth inhibition of an ampicillin-resistant E . COLI . This ester compound of ampicillin showed zero violations of the 'Rule of 5', which indicates good bioavailability and good bioactivity . Intestinal absorption indicated by TPSA value showed moderate absorption activity for both parent and ester compounds . The lipophilic substituent constant for the butyl ester is +0.941, which indicates increased lipophilicity . The ester group improves log BB and dermal permeability of ampicillin . CONCLUSION: The butyl ester of ampicillin inhibited the growth of susceptible and resistant E . COLI . Favorable values for parameters such as TPSA, log P, log BB, and zero violations of the 'Rule of 5' suggest good bioavailability and good bioactivity . J Chem Inf Comput Sci, 2003 Sep-Oct, 43(5), 1423 - 33 On the physical interpretation of QSAR models; Stanton DT; Multidimensional quantitative structure-activity models (QSAR) developed using molecular structure descriptors and regression analysis techniques have found wide utility and acceptance . However, it is often difficult to extract a physical interpretation of such models because of the types of descriptors involved and the multidimensional nature of the model . The work described here illustrates a method of model interpretation that employs partial least squares (PLS) analysis . Structure-activity relationship information is derived from the positions of specific sets of structures in the PLS score plots and the weights for each variable in the PLS components . Using these data, information regarding major structure-activity trends, trend exceptions, and unique or outlying observations is easily obtained . Examples of this methodology are illustrated using QSAR equations developed for the inhibition of quinolone-resistant bacterial DNA gyrase and human topoisomerase-II inhibition by a series of quinolone antibacterial agents. J Burn Care Rehabil, 2003 Sep-Oct, 24(5), 289 - 96 Pain control in a randomized, controlled, clinical trial comparing moist exposed burn ointment and conventional methods in patients with partial-thickness burns; Ang E et al.; Conventional management of partial-thickness burn wounds includes the use of paraffin gauze dressing, frequently with topical silver-based antibacterial creams . Some creams form an overlying slough that renders wound assessment difficult and are painful upon application . An alternative to conventional management, moist exposed burn ointment (MEBO), has been proposed as a topical agent that may accelerate wound healing and have antibacterial and analgesic properties . One hundred fifteen patients with partial-thickness burns were randomly assigned to conventional (n = 58) or MEBO treatment (n = 57) . A verbal numerical rating score of pain was made in the morning, after burn dressing, and some 8 hours later . Patient pain profiles were summarized by locally weighted regression smoothing technique curves and the difference between treatments estimated using multilevel regression techniques . Mean verbal numerical rating scale pain levels (cm) in week 1 for all patients were highest at 3.2 for the after dressing assessment, lowest in the evening at 2.6, and intermediate in the morning at 3.0 . This pattern continued at similar levels in week 2 and then declined by a mean of 0.5 in all groups in week 3 . There was little evidence to suggest a difference in pain levels by treatment group with the exception of the postdressing pain levels in the first week when those receiving MEBO had a mean level of 0.7 cm (95% confidence interval, 0.2 to 1.1) lower than those on conventional therapy . MEBO appeared to bring greater pain relief for the postdressing assessment during the first week after burns . This initial relief, together with comparable pain levels experienced on other occasions, indicates that MEBO could be an alternative to conventional burns management. Infect Immun, 2003 Oct, 71(10), 5598 - 604 Augmentation of Actinobacillus actinomycetemcomitans invasion of human oral epithelial cells and up-regulation of interleukin-8 production by saliva CD14; Takayama A et al.; It has recently been shown that human salivary glands constitutively express CD14, an important molecule in innate immunity, and that a soluble form of CD14 is secreted in saliva . The concentration of CD14 in parotid (a serous gland) saliva was comparable to that in normal serum and 10-fold the amount in whole saliva, although the physiological function of saliva CD14 remained unclear . Actinobacillus actinomycetemcomitans is a periodontopathic bacterium and is able to invade oral epithelial cells . The present study showed that upon exposure to live A . actinomycetemcomitans Y4 for 2 h, human oral epithelial HSC-2 cells produced interleukin-8 (IL-8) for a further 24 h and whole saliva augmented the production induced by A . actinomycetemcomitans Y4 . Parotid saliva showed a more pronounced effect on the production of IL-8 than whole saliva . Neither saliva preparation itself had IL-8-inducing activity . Parotid saliva exhibited antibacterial activity against a low concentration of A . actinomycetemcomitans Y4, but recombinant CD14 did not show the activity . The internalization of A . actinomycetemcomitans Y4 into HSC-2 cells was inhibited by cytochalasin B, indicating that the process was actin dependent, and depletion of CD14 from parotid saliva inhibited the invasion and, as a consequence, inhibited production of IL-8 . Furthermore, human recombinant CD14 augmented invasion and IL-8 production . These results suggest that saliva CD14 promoted the invasion of oral epithelial cells by A . actinomycetemcomitans and consequently augmented the production of IL-8, playing an important role in innate immunity in the oral cavity. Peptides, 2003 Jul, 24(7), 945 - 53 In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines; Kim S et al.; In order to develop peptide agents with reduced length and enhanced tumoricidal activity, we have designed gaegurin 6 (GGN6) derivatives through deletions and/or substitutions of amino acids . The deletion of hydrophobic amino terminal region completely abolished antitumor activity whereas the deletion of carboxy terminal region had little influence on antitumor activity . Antitumor activity of the PTP peptides did not correlate with antibacterial activity . PTP7, the most potent derivative, was found to have comparable antitumor activity to GGN6 in spite of reduced number of amino acids which is about half the size of gaegurin 6; furthermore, it showed little cytotoxicity on PBMCs and RBCs . GGN6 and PTP7 also showed equivalent cytotoxicity against drug sensitive (MCF-7) and multidrug-resistant cell lines (MCF-7/DOX) . Plasma membrane blebbing and DNA fragmentation of peptide-treated tumor cells indicated that the peptides could induce apoptosis in tumor cells . These results suggest that GGN6 and its derivatives can be developed as new anticancer agents and may provide a new strategy for overcoming MDR which is a major problem in cancer therapy. BioDrugs, 2003, 17(5), 355 - 67 Ribosomal immunostimulation: assessment of studies evaluating its clinical relevance in the prevention of upper and lower respiratory tract infections in children and adults; Bellanti J et al.; OBJECTIVE: To review the efficacy of the ribosomal immunostimulant Ribomunyl in preventing upper and lower respiratory tract infections . DESIGN AND SETTING: Review of studies of 3 and 6 months' duration comprising part of the international registration file . PATIENTS: Data from 2117 patients (1215 children and 902 adults); ribosomal immunostimulant n = 1062, placebo n = 1055 . RESULTS: Nineteen randomised, double-blind, placebo-controlled clinical trials were performed between 1983 and 1994 in Europe . In children with ear-nose-throat (ENT) infections, 3 months' ribosomal immunostimulant treatment significantly decreased the mean number of recurrences (27-68% reduction), and reduced the duration of infection (28-66% reduction) and antibacterial requirement (29-60% reduction) . Ribosomal immunostimulant was similarly effective in children with ENT and bronchopulmonary infections, reducing the mean number of recurrences by 32-61% compared with placebo . In children with otitis media, ribosomal immunostimulant reduced recurrences by 10-53% and also reduced the duration of infection, antibacterial use and local surgery requirement . Results obtained from studies of 6 months' duration confirmed or extended these results . In adult patients with ENT or mixed respiratory infections, ribosomal immunostimulant produced similar reductions to those seen in children for recurrent infections (54-78% reduction), duration of infection (42-79% reduction) and antibacterial use (38% reduction) . CONCLUSIONS: These results clearly demonstrate that ribosomal immunostimulant is effective in preventing and in reducing upper and lower respiratory tract infections in children and adults. Phytother Res, 2003 Sep, 17(8), 973 - 5 Cytotoxicity and antibacterial activity of Sida rhombifolia (Malvaceae) grown in Bangladesh; Islam ME et al.; The cytotoxicity and antibacterial activities of crude extracts from the leaves of Sida rhombifolia were investigated . The ethyl acetate extract showed potent cytotoxicity with LC50 values (5.41 ppm) comparable to the reference standard, gallic acid . All the extracts showed weak antibacterial activity against both Gram-positive and Gram-negative test organisms . J Perinatol, 2003 Sep, 23(6), 493 - 7 Effect of recombinant granulocyte colony-stimulating factor on blood neutrophil concentrations among patients with "idiopathic neonatal neutropenia": a randomized, placebo-controlled trial; Juul SE et al.; OBJECTIVES: We previously described a severe, prolonged, idiopathic, but self-resolving, variety of neutropenia among preterm neonates . In the present study, we sought to assess the marrow neutrophil reserves of these patients by serially measuring blood neutrophils following the administration of recombinant granulocyte colony-stimulating factor (rG-CSF) or placebo . STUDY DESIGN: Prospective, randomized trial of rG-CSF vs placebo for infants with "idiopathic neonatal neutropenia" . RESULTS: During 36 consecutive months, 2407 neonates were admitted to the neonatal intensive care unit; 429 weighed less than 1500 g at birth, 14 of these were later diagnosed with "idiopathic neonatal neutropenia"; 10 were enrolled in this trial . The five rG-CSF recipients had an immediate, marked increase in blood neutrophil concentration, indicating adequate rG-CSF-mobilizable marrow neutrophil reserves . This effect persisted to day 5, but counts were not different from those of the five placebo recipients on days 12 and 15 . CONCLUSIONS: Patients with "idiopathic neonatal neutropenia" have a substantial rG-CSF-mobilizable marrow neutrophil reserve . On that basis, we speculate that this variety of neonatal neutropenia does not constitute a significant deficiency in antibacterial defense. Int J Antimicrob Agents, 2003 Sep, 22(3), 279 - 83 Phenothiazines as potent modulators of yeast multidrug resistance; Kolaczkowski M et al.; Active efflux of antifungal, antibacterial and anticancer drugs by broad-specificity multidrug resistance (MDR) transporters are major obstacles to successful chemotherapy of infectious diseases and cancer . We evaluated the growth inhibitory and MDR modulatory effect of a series of 36 phenothiazines and related compounds, against Saccharomyces cerevisiae strains exhibiting different levels of expression of MDR transporters Pdr5p, Snq2p and Yor1p . Several newly synthesized derivatives were identified as substrates of Pdr5p as their growth inhibitory properties were potentiated by deletion of PDR5 . They were synergistic with the antifungal ketoconazole at micromolar concentrations . The most active phenothiazines contained the amino group at the end of the alkylene chain substituent. Pharmacoeconomics, 2003, 21(14), 1001 - 24 Cystic fibrosis: cost of illness and considerations for the economic evaluation of potential therapies; Krauth C et al.; Cystic fibrosis (CF) is the most common life-shortening inherited disease of the Caucasian race, with a prevalence of around 1 in 2500 live births . Advances in the treatment and management of respiratory and pancreatic disorders have dramatically increased the life expectancy of patients with CF . This article presents an overview of cost-of-illness studies of CF, identifies deficits in the available health economic analyses of CF and discusses which specific factors are essential for the economic evaluation of potential therapies, based on a critical review of the health economic literature on two main therapeutic strategies . Cost-of-illness studies of CF have predominantly been restricted to direct costs . According to the literature, direct costs amount to between 6200- 16300 US dollars (1996 values) per patient per year . As most studies likely underestimated the actual costs (e.g . by disregarding provision of certain healthcare services), real healthcare costs tend to be at the upper end of the cost range . Healthcare costs depend on the patient's age (for adults, costs are approximately twice as high as for children), the grade of severity (the cost relationship of severe to mild CF is between 4.5 and 7.1) and other factors . Lifetime direct costs of CF are estimated at 200 000-300000 US dollars (at 1996 values and a discount rate of 5%) . Home intravenous (IV) antibacterial therapy and recombinant human DNase (rhDNase; dornase alfa) treatment are the two main therapeutic strategies most often evaluated in health economic studies of CF . While home IV antibacterial therapy (compared with inpatient IV antibacterial therapy) is assumed to be cost saving, rhDNase treatment is a very cost-intensive therapy intended to efficiently achieve health improvements . Health economic analyses of future CF therapeutic technologies should present explicit data regarding healthcare services provision, resource consumption and unit costs . Indirect costs and patient costs should be considered more often than they have to date, particularly when they are significantly influenced by novel CF technologies . The perspective of health economic studies should be stated explicitly and always include the societal perspective . More economic studies should be based on a controlled, and preferably randomised, design . The observation period must be long enough to identify long-term effects of interventions . A greater number of effectiveness studies should be performed to determine costs and outcomes of therapies applied under everyday life conditions for patients with CF . Finally, international comparison studies should identify the influence of different healthcare systems on the costs and outcomes of interventions. Insect Mol Biol, 2003 Oct, 12(5), 491 - 9 Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phagocytosis, endocytosis and infection of West Nile virus; Mizutani T et al.; We recently cloned a c-Jun amino-terminal kinase (JNK) sequence from the C6/36 cell line, derived from the mosquito Aedes albopictus . We showed that SP600125, an inhibitor of JNK proteins, inhibits phagocytosis by C6/36 cells, suggesting that the JNK-like protein regulates phagocytosis . Here, we show that C6/36 cells constitutively express low levels of mRNA encoding the antibacterial peptides, cecropin and defensin, but that these mRNAs were up-regulated upon stimulation by lipopolysaccharide (LPS) . Thus, the C6/36 cells have properties similar to those of mammalian macrophages . To characterize further the functional properties of C6/36 cells, we have assayed the role of the JNK-like protein in phagocytosis, endocytosis, and viral infection . C6/36 cells phagocytosed bacteria and artificial beads, and this was only slightly up-regulated following LPS stimulation, suggesting that newly stimulated JNK-like protein was not necessary for phagocytosis . SP600125 inhibited the acidification of intracellular compartments, including those involved in the endocytic pathway . Pretreatment of C6/36 cells with SP600125 or bafilomycin A1, but not cytochalasin D, inhibited the entry of West Nile virus (WNV), suggesting that WNV is internalized mainly by endocytosis, and that the JNK signalling pathway is important for endocytic entry . These findings indicate that the JNK-like protein regulates basic physiological functions, including phagocytosis and endocytosis and infection of WNV. Toxicol Ind Health, 2002 Apr, 18(3), 109 - 60 Organic mercury compounds: human exposure and its relevance to public health; Risher JF et al.; Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes, and the effects of such exposure depend upon both the type of mercury to which exposed and the magnitude of the exposure . In general, the effects of exposure to organic mercury are primarily neurologic, while a host of other organ systems may also be involved, including gastrointestinal, respiratory, hepatic, immune, dermal, and renal . While the primary source of exposure to organic mercury for most populations is the consumption of methylmercury-contaminated fish and shellfish, there are a number of other organomercurials to which humans might be exposed . The antibacterial and antifungal properties of organomercurials have resulted in their long use as topical disinfectants (thimerosal and merbromin) and preservatives in medical preparations (thimerosal) and grain products (both methyl and ethyl mercurials) . Phenylmercury has been used in the past in paints, and dialkyl mercurials are still used in some industrial processes and in the calibration of certain analytical laboratory equipment . The effects of exposure to different organic mercurials by different routes of exposure are summarized in this article. Cent Afr J Med, 2002 May-Jun, 48(5-6), 68 - 71 A study of human bite injuries to the face; Obukwe ON; OBJECTIVES: To analyse human bites injuries of the face as seen in Benin City, Nigeria and to compare the results with similar studies . DESIGN: Prospective cross sectional study . SETTING: Department of Oral and Maxillofacial Surgery, University of Benin Teaching Hospital, Benin City, Nigeria . SUBJECTS: Twenty patients with human bites to the face . RESULTS: The patients had a mean age of 36.0 years (range: 26 to 48 years), with a female to male ratio of 4:1 . Matrimonial conflict related to polygamy was the commonest reason for assault, with females predominating as assailants . The lower lip was the commonest site of injury with 15 cases (75%) . Eighteen patients (90.0%) presented at the clinic within 48 hours of injury with only 14 (70.0%) undergoing surgical repair within two to four days . Financial constraints accounted for the time lapse . None of the bite injuries became infected . This was attributed to early local wound care and systemic antibacterial therapy . None of the victims planned to seek legal redress for the bite injuries . CONCLUSION: This study showed that assaults during matrimonial conflicts led to most human bites to the face . It also showed that the Nigerian female was most often the victim and the assailant in such cases . Financial constraints were identified as the major cause of delay in the treatment of these injuries . However, delay in repair did not adversely affect the outcome of these injuries. Haematologica, 2003 Sep, 88(9), 1022 - 8 Risk factors for the development of bacterial infections in multiple myeloma treated with two different vincristine-adriamycin-dexamethasone schedules; Cesana C et al.; BACKGROUND AND OBJECTIVES: We evaluated bacterial infections (BIs) in patients with multiple myeloma (MM) treated with two different schedules of vincristine-adriamycin-dexamethasone (VAD) . DESIGN AND METHODS: Ninety-seven patients were studied during 340 VAD cycles . VAD was given by either continuous intravenous infusion (CII) to hospitalized patients or rapid intravenous infusion (RII) to outpatients . The characteristics of patients and VAD schedules were retrospectively analyzed to detect correlations with the incidence of BI . RESULTS: By analyzing each VAD cycle, we found that profound hypogammaglobulinemia (p=0.06) and post-treatment neutropenia (p=0.08) were associated with a trend for a higher risk of infection, while renal function impairment was significantly correlated with BI risk at both univariate (p<0.02) and multivariate (p<0.002) analyses . Evaluating only the first 4 months of therapy, characterized by a significantly higher incidence of BI than the later period (p<0.0001), previously untreated disease was significantly correlated with BI risk (p<0.04), while male sex (p=0.06), CII schedule (p=0.07), and profound hypogammaglobulinemia (p=0.1) were associated with a tendency to a higher risk of infection; however, at multivariate analysis the latter two parameters independently predicted BI probability (p<0.015 and p<0.03, respectively) as did previously untreated disease (p<0.025) . The high probability of CII-related infection was demonstrated to depend on the frequent development of nosocomial infections . INTERPRETATION AND CONCLUSIONS: Patients with profound hypogammaglobulinemia who receive VAD as first line treatment are at a major risk of BI up to the completion of the fourth month of therapy . In this setting hospitalization should be avoided and, if patients require admission, antibacterial prophylaxis with intravenous immunoglobulins could be appropriate and effective. J Appl Microbiol, 2003, 95(4), 677 - 85 Application of sucrose-gradient centrifugation for selective isolation of Nocardia spp . from soil; Yamamura H et al.; AIMS: To devise and evaluate a method for selective isolation of the less abundant actinomycetes, Nocardia spp . in soil . METHODS AND RESULTS: This newly developed method is based on differentiating Nocardia from other actinomycete taxa by centrifugation . A water suspension of air-dried soil is centrifuged through a gradient consisting of 10, 20, 30, 40 and 50% sucrose at 240 x g for 30 min . The 20% sucrose layer, which is enriched with Nocardia spp., is then diluted and plated on humic acid-vitamin agar supplemented with antibacterial agents . The proposed method consistently achieved selective isolation of Nocardia spp . in all 14 soil samples tested, which accounted for 5-89% of the total microbial population recovered . Tentative taxonomic characterization based on a restriction fragment length polymorphism (RFLP) analysis of the 16S ribosomal DNA suggested that many of the soil isolates could belong to N . asteroides, N . salmonicida or N . uniformis . CONCLUSIONS: Differential centrifugation can successfully and efficiently isolate soil Nocardia populations that are suppressed by conventional dilution plating approaches . SIGNIFICANCE AND IMPACT OF THE STUDY: The development and application of new methodologies with which to isolate less-explored actinomycete taxa is important for improving our knowledge about their taxonomy, ecology and industrial applications. Vopr Pitan, 2003, 72(4), 42 - 6 {Biologically active substances in garlic (Allium sativum L.) and their application in nutrition for humans}; Ryzhenkov VE et al.; Reviewed above is chemical composition of garlic and its biological Hypolipidemic, antioxidative, antibacterial and antitumorogenic properties of preparations were elucidated in experimental, clinical and epidemiological observations . It has been concluded that garlic are useful for prevention and combined treatment of most chronical diseases. Zh Mikrobiol Epidemiol Immunobiol, 2003 Jul-Aug, (4), 3 - 8 {Bacterial interactions}; Bukharin OV et al.; The review deals with specific features of interactions in microbial biocenoses . The subdivision of the mechanisms of microbial interactions in associations into direct and indirect ones is proposed . The formation of intercellular contacts and matrix belongs to one group of mechanisms, the second group includes the products of metabolism (changes in the physical and chemical composition of the medium, specific growth regulators) and secreted factors (antibacterial substances, pheromones and signal molecules, vitamins, specific mediators) . The applied aspects of the knowledge of microbial interactions in the human body are presented. Arch Ophthalmol, 2003 Sep, 121(9), 1229 - 33 Influence of fluoroquinolone susceptibility on the therapeutic response of fluoroquinolone-treated bacterial keratitis; Wilhelmus KR et al.; OBJECTIVE: To estimate how a corneal isolate's minimal inhibitory concentration for a fluoroquinolone agent affects the rate of clinical response of bacterial keratitis to fluoroquinolone therapy . DESIGN: Prospective cohort study . METHODS: Six hundred sixty-three individuals with suspected bacterial keratitis underwent diagnostic corneal scraping and were treated with topical 0.3% ciprofloxacin solution or ointment . Of 407 patients with culture-confirmed bacterial keratitis, improvement and cure rates with ciprofloxacin monotherapy were estimated for 391 who had in vitro ciprofloxacin susceptibility of the principal corneal isolate . MAIN OUTCOME MEASURES: Slitlamp biomicroscopic assessment for clinical improvement of corneal inflammation and for clinical cure with complete reepithelialization . RESULTS: Adjusted rates of improvement and of cure were reduced, respectively, by 43% (95% confidence limits, 8%, 64%) and by 29% (95% confidence limits, 0%, 49%) among corneal infections having a ciprofloxacin minimal inhibitory concentration above 1.0 micro g/mL compared with those with more sensitive isolates . CONCLUSIONS: Corneal infection by relatively ciprofloxacin-resistant bacteria responds more slowly to ciprofloxacin therapy . Antibacterial susceptibility testing of corneal cultures may predict the fluoroquinolone therapeutic response rate of bacterial keratitis. J Ethnopharmacol, 2003 Oct, 88(2-3), 181 - 8 Ethnobotany and antibacterial activity of some plants used in traditional medicine of Zapotitlán de las Salinas, Puebla (México); Hernandez T et al.; The village of Zapotitlan de las Salinas is situated in the Valley of Tehuacan-Cuicatlan, Puebla, Mexico . Plant species used by the local inhabitants to treat gastrointestinal diseases were identified using ethnobotanical, ethnographic and taxonomic methods . Out of 119 interviews, 44 plant species were registered, of which the following are the most frequently used (listed in descending order): Lippia graveolens H.B . et K . (Verbenaceae), Lantana achyranthifolia Desf . (Verbenaceae), Turnera diffusa (Willd.) ex Schult . (Turneraceae), Lippia oaxacana Rob . et Greenm . (Verbenaceae), Gymnolaena oaxacana (Greenm.) Rydb . (Asteraceae), Cordia curassavica (Jacq.) Roem . et Schult . (Boraginaceae), Lantana camara L . (Verbenaceae) and Acalypha hederacea Torrey (Euphorbiaceae) . From these plants, hexane, chloroform and ethanol extracts were prepared in order to assess their antibacterial activity against 14 bacterial strains causing the most common gastrointestinal diseases in Mexican population . All hexane extracts showed antibacterial activity against Gram-positive and Gram-negative bacteria . There is a correlation between the frequency of mention (of plant use) and the antibacterial activity . In conclusion, the knowledge of plants most frequently used for gastrointestinal infections in Zapotitlan de las Salinas is supported by scientific rationale. Biochemistry, 2003 Sep 16, 42(36), 10569 - 78 Role of ionic interactions in ligand binding and catalysis of R67 dihydrofolate reductase; Hicks SN et al.; R67 dihydrofolate reductase (DHFR), which catalyzes the NADPH dependent reduction of dihydrofolate to tetrahydrofolate, belongs to a type II family of R-plasmid encoded DHFRs that confer resistance to the antibacterial drug trimethoprim . Crystal structure data reveals this enzyme is a homotetramer that possesses a single active site pore . Only two charged residues in each monomer are located near the pore, K32 and K33 . Site-directed mutants were constructed to probe the role of these residues in ligand binding and/or catalysis . As a result of the 222 symmetry of this enzyme, mutagenesis of one residue results in modification at four related sites . All mutants at K32 affected the quaternary structure, producing an inactive dimer . The K33M mutant shows only a 2-4-fold effect on K(m) values . Salt effects on ligand binding and catalysis for K33M and wildtype R67 DHFRs were investigated to determine if these lysines are involved in forming ionic interactions with the negatively charged substrates, dihydrofolate (overall charge of -2) and NADPH (overall charge of -3) . Binding studies indicate that two ionic interactions occur between NADPH and R67 DHFR . In contrast, the binding of folate, a poor substrate, to R67 DHFR.NADPH appears weak as a titration in enthalpy is lost at low ionic strength . Steady-state kinetic studies for both wild type (wt) and K33M R67 DHFRs also support a strong electrostatic interaction between NADPH and the enzyme . Interestingly, quantitation of the observed salt effects by measuring the slopes of the log of ionic strength versus the log of k(cat)/K(m) plots indicates that only one ionic interaction is involved in forming the transition state . These data support a model where two ionic interactions are formed between NADPH and symmetry related K32 residues in the ground state . To reach the transition state, an ionic interaction between K32 and the pyrophosphate bridge is broken . This unusual scenario likely arises from the constraints imposed by the 222 symmetry of the enzyme. J Chemother, 2003 Aug, 15(4), 350 - 6 Interaction of macrolides and ketolides with the phagocytic cell line PLB-985; Abdelghaffar H et al.; Interactions between antibacterial agents and polymorphonuclear neutrophils (PMNs) are a major focus of investigation . Owing to the variable drug susceptibility of PMNs from different individuals, in vitro studies require samples from large panels of healthy volunteers to reach statistical significance . Here, we used a phagocytic cell line, PLB-985, which can differentiate into mature PMNs in vitro, for the study of cellular interactions (drug uptake and antioxidant effects) of two macrolides (azithromycin and roxithromycin) and four ketolides {HMR 3004, HMR 3647 (telithromycin), HMR 3562 and HMR 3787} . The oxidative burst of differentiated (D) cells was inhibited by macrolides and ketolides . IC50% values (concentrations impairing the oxidative burst by 50%), determined after 30 min of incubation, were as follows for azithromycin, roxithromycin, HMR 3004, telithromycin, HMR 3562 and HMR 3787, respectively: 40, 39, 15, 23, 26, and 33 mg/l (fMLP stimulation) and 37, 86, 39, 43, 14, and 31 mg/l (PMA stimulation) . These values were similar to those obtained with PMNs . Uptake of the two macrolides was significantly lower in non-differentiated (ND) cells than in D cells and PMNs . The cellular/extracellular (C/E) concentration ratios at 60 min for PMNs, D and ND PLB were respectively 67, 25 and 11 (roxithromycin) and 159, 137 and 48 (azithromycin) . Ketolide uptake by ND-PLB was also significantly lower than that obtained with PMNs (C/E ratios at 60 min were about 75 versus 265 (HMR 3004), 36 vs 230 (telithromycin), 75 vs 235 (HMR 3562) and 20 vs 130 (HMR 3787) . Although the active carrier system seemed to be present in ND cells, its activation pathway was not functional . Thus, the PLB-985 cell line is a good in vitro model for studying drug-PMN interactions . The use of ND and D cells may shed light on the nature and activation pathways of macrolide transport systems present on the PMN membrane. Mayo Clin Proc, 2003 Sep, 78(9), 1113 - 24 Ketolides: a new class of antibacterial agents for treatment of community-acquired respiratory tract infections in a primary care setting; Clark JP et al.; Pathogens implicated in community-acquired respiratory tract infections are becoming increasingly resistant to anti-bacterial therapies . Thus, there is an urgent need for new agents with activity against current resistant respiratory tract pathogens and a low potential to select for resistance or induce cross-resistance to existing antibacterial agents . Telithromycin, the first ketolide antibacterial agent to undergo clinical development, has enhanced binding to bacterial ribosomal RNA . Through its unique structure, telithromycin retains activity against resistant respiratory pathogens and has shown high efficacy in the treatment of respiratory tract infections . On the basis of phase 3 clinical trial experience, telithromycin appears safe and well tolerated across various patient populations, including high-risk groups. Acta Pol Pharm, 1990, 47(1-2), 71 - 3 Alkaloids in the tissue culture of Holarrhena antidysenterica; Dohnal B et al.; In the present study the tissue culture of a medicinal plant Holarrhena antidisenterica was established . Phytochemical analysis revealed a presence of a few alkaloids in the callus tissues . Two of them were determined by TLC as conessine and conimine . A screening of antibacterial activity of alkaloid extract was performed. Front Biosci, 2003 Sep 01, 8, s1157 - 65 Inteins as targets for potential antimycobacterial drugs; Paulus H; Protein splicing is a self-catalyzed process mediated by inteins . The observation that inteins occur only in microorganisms and that they often interrupt genes that play an essential role in nucleic acid metabolism makes them attractive as potential antibacterial targets . Because mycobacteria are the only intein-containing bacteria associated with human hosts, inteins would represent highly specific antimycobacterial targets . In Mycobacterium tuberculosis, two important proteins of DNA repair and replication, RecA and DnaB, respectively, are interrupted by inteins that must be excised by protein splicing before these proteins can function . This review describes the screening systems for the detection of mutations or inhibitors that interfere with proteins splicing that have been developed and published to date . In three of these experimental system, inteins have been inserted into proteins that are toxic under certain conditions . Protein splicing therefore leads to conditional growth inhibition or cell death and its inhibition can be monitored in terms of bacterial growth . A fourth assay for protein splicing and its inhibition is based on purified proteins and measures the formation of Green Fluorescent Protein or its inhibition . The advantages of inteins as antimycobacterial targets are discussed. Int J Cardiol, 2003 Aug, 90(2-3), 141 - 5; discussion 145-6 An open label crossover trial of effects of metronidazol on hyperlipidaemia; Shamkhani K et al.; Metronidazole, a synthetic derivative of tile nitroimidazole class, is a known antibacterial and antiprotozoal agent . Following an anecdotal observation of hypolipidemic effect of metronidazole, a randomized open trial of 250 mg three times daily was conducted in 30 subjects . This open label crossover trial was performed in three stages-14 days each-as challenge, wash out and re-challenge on 30 subjects, including six male and 24 female in the age limits of 40 to 73 years (mean 58.7+/-10.6 years) . Results of this trial revealed that metronidazole 750 mg daily in divided doses for 14 days decreased the average of total blood cholesterol in 30 cases by 46+/-27 mg/dl (14.6%, P=0.025) and LDL cholesterol by 39+/-28 mg/dl (22%, P=0.005) . Decrease in total and LDL cholesterol and increase in HDL cholesterol by 3.8+/-4.1 mg/dl also accompanied fall of triglyceride level cases by 68+/-13 mg/dl . This study suggests that metronidazole or its derivatives may form a new class of lipid lowering compounds. Eur J Pharm Biopharm, 2003 Sep, 56(2), 223 - 9 Protonation equilibrium and lipophilicity of olamufloxacin (HSR-903), a newly synthesized fluoroquinolone antibacterial; Sun J et al.; This study was performed to characterize the protonation equilibrium at the molecular level and pH-dependent lipophilicity of olamufloxacin . The deprotonation fraction of the carboxyl group as a function of pH was specifically calculated at the critical wavelength 294 nm, where UV pH-dependent absorbance of olamufloxacin was independent of the ionized state of the aminopyrrolidinyl amino group but heavily depended on that of the carboxyl moiety . Accordingly, micro-protonation equilibrium could be described using a nonlinear least-squares regression program MULTI . In contrast, macro-protonation equilibrium was depicted at most wavelengths where olamufloxacin absorbance was influenced by ionized states of both proton-binding groups, results coinciding with the former . Furthermore, distribution features of four microspecies in aqueous phase were assessed . The apparent partition coefficient versus pH profile of olamufloxacin showed a parabolic curve in n-octanol/buffer system which reached peak near pH 8, agreeing with the above determined isoelectric point (pI) . Ion-pair effect was observed for olamufloxacin under an acidic condition, eliciting experimental values higher than those theoretically calculated, which was similar to ciprofloxacin but not levofloxacin due to amino group type . Moreover, olamufloxacin was moderately lipophilic in comparison with other quinolones, with an apparent partition coefficient of 1.95 at pH 7.4. Arch Immunol Ther Exp (Warsz), 2003, 51(4), 237 - 44 Phage therapy: a reappraisal of bacteriophages as antibiotics; Inal JM; The concept of phage therapy to treat bacterial infections was born with the discovery of the bacteriophage almost a century ago . After a chequered history, its current renaissance is fueled by the dangerous appearance of antibiotic-resistant bacteria on a global scale . As a mark of this renewed interest, the unanswered problems of phage therapy are now being addressed, especially for human use . Phage therapy in the agricultural, food-processing and fishery industries is already being successfully applied, and this review, whilst being aware of the potential drawbacks, emphasizes the need for further carefully controlled empirical data on its efficacy and safety in treating human and animal disease, especially in view of its numerous advantages over antibiotics . Finally the potential of phage therapy against bioterrorism and the emergence of second generation phage antibacterials based on phage-derived single-protein lysis systems are addressed. Dermatol Clin, 2003 Jul, 21(3), 431 - 62 Treatments of tinea pedis; Gupta AK et al.; The severity of tinea pedis infection determines the course of treatment required . Mild infections may be resolved using a topical agent . More severe presentations (eg, dermatophytosis complex) may require treatment that eliminates the bacterial and fungal infection . Some topical monotherapies may exhibit both antifungal and antibacterial activity . In other instances, it may be necessary to combine an antifungal agent with an antibacterial agent . If inflammation is present, an agent with known anti-inflammatory action may need to be used . The chronic presentation of tinea pedis (dry type) sometimes does not respond well to topical therapy . In such instances, systemic antifungal therapy is required to ensure that adequate concentrations of the therapeutic agent are present at the site of infection. Int Dent J, 2003 Aug, 53(4), 237 - 42 Combined effect of zinc ions and cationic antibacterial agents on intraoral volatile sulphur compounds (VSC); Young A et al.; OBJECTIVE: Volatile sulphur compounds (VSC) are major components of oral malodour . As both zinc ions and cationic antibacterial agents inhibit the formation of oral VSC, this study aimed to determine whether these agents combined have synergistic anti-VSC actions . METHODS: Baseline oral VSC measurements of mouth air from 10 volunteers following cysteine rinsing (6mM, pH 7.2) were obtained using gas chromatography (GC) . Subjects rinsed for 1 min with 10ml of the test solutions, 0.3% zinc acetate (Zn), 0.025% chlorhexidine (CHX), 0.025% cetyl pyridinium (CPC), and the combinations Zn+CHX and Zn+CPC . Cysteine rinses were repeated at 1h, 2h and 3h and VSC measurements recorded . Three subjects rinsed with the Zn+CHX combination and fasted for 9h, undergoing cysteine rinses and VSC measurements at 3h intervals . 10 microl of the test solutions were also added to 1ml aliquots of human whole saliva (n=8) . Following incubation at 37 degrees C for 24h VSC levels in the saliva headspace were measured by GC . Inhibition of VSC formation and the fractional inhibitory index indicating synergy were calculated . RESULTS: Zn+CHX mouthrinse had a synergistic anti-VSC effect, and was effective for at least 9h . Zn+CPC mouthrinse was less effective . Both combinations showed a synergistic inhibiting effect in-vitro . CONCLUSIONS: Synergy between Zn and the antibacterial agents confirms different mechanisms of operation. J Pept Sci, 2003 Aug, 9(8), 510 - 7 Enhanced antitumour activity of 15-residue bovine lactoferricin derivatives containing bulky aromatic amino acids and lipophilic N-terminal modifications; Eliassen LT et al.; In a structure-antibacterial activity relationship study of a peptide fragment of bovine lactoferricin consisting of FKCRRWQWRMKKLGA (LFB 17-31), it was revealed that the two Trp residues were important for antibacterial activity . It has further been demonstrated that the size, shape and the aromatic character of the side chains were even more important than the Trp itself . In this study the antitumour effect of a series of LFB 17-31 derivatives are reported, in which the two Trp residues in position 6 and 8 were replaced with the larger non-coded aromatic amino acids Tbt, Tpc, Bip and Dip . The counterproductive Cys in position 3 was also substituted with these larger aromatic residues . In addition, the effect of introducing lipophilic groups of different size and shape in the N-terminal of the LFB 17-31 sequence was addressed . The resulting peptide derivatives were tested for activity against three human tumour cell lines and against normal human umbilical vein endothelial cells and fibroblasts . High antitumour activity by several of the peptides demonstrated that Trp successfully could be substituted by the bulky aromatic residues, and peptides containing the large and rigid Tbt residue in position 6 and/or 8 in LFB 17-31 were the most active candidates . The antitumour effect was even more increased by the Tbt-modified peptides when the three counterproductive amino acids Cys3, Gln7 and Gly14 were replaced by Ala . Enhanced antitumour activity was also obtained by modifying the N-terminal of LFB 17-31 with either long-chained fatty acids or bulky moieties . Thus, our results revealed that the size and shape of the lipophilic groups and their position in the peptide sequence were important for antitumour activity. Chem Pharm Bull (Tokyo), 2003 Sep, 51(9), 1081 - 4 Two new macrocyclic diaryl ether heptanoids from Boswellia ovalifoliolata; Lakshmi Niranjan Reddy V et al.; The stems of Boswellia ovalifoliolata BAL . & HENRY (Burseraceae) afforded two new macrocyclic diaryl ether heptanoids, ovalifoliolatin A (1) and B (2) together with three known compounds; acerogenin C (3), 3 alpha-hydroxyurs-12-ene (4), and sitost-4-en-3-one (5) . The structures were established by means of spectroscopic analysis and compounds 1, 3-5 were evaluated for their antibacterial activity. Bioorg Med Chem Lett, 2003 Oct 6, 13(19), 3305 - 9 Synthetic dihydropacidamycin antibiotics: a modified spectrum of activity for the pacidamycin class; Boojamra CG et al.; Dihydropacidamycins having an antibacterial spectrum modified from that of the natural product pacidamycins and mureidomycins have been synthesized . Synthetic dihydropacidamycins with noteworthy antibacterial activity against wild-type and resistant Escherichia coli have been identified (MIC=4-8 microg/mL) . Some dihydropacidamycins are shown to have activity against multi-resistant clinical strains of Mycobacterium tuberculosis . Compounds of this class are inhibitors of the cell wall biosynthetic enzyme, MraY. Bioorg Med Chem Lett, 2003 Oct 6, 13(19), 3273 - 6 Synthesis and PDF inhibitory activities of novel benzothiazolylidenehydroxamic acid derivatives; Takayama W et al.; A novel series of benzothiazolylidenehydroxamic acid derivatives has been designed and synthesized as PDF inhibitors . Some of this novel class of PDF inhibitors exhibited micromolar order enzyme inhibitory activity and antibacterial activity. Helicobacter, 2003 Aug, 8(4), 294 - 9 Gastric juice, gastric tissue and blood antibiotic concentrations following omeprazole, amoxicillin and clarithromycin triple therapy; Nakamura M et al.; BACKGROUND: Amoxicillin and clarithromycin are key antibiotics in proton pump inhibitor-based Helicobacter pylori eradication therapies . AIMS: To study gastric mucus and tissue concentrations and collect basic data about optimal antibacterial doses . METHODS: Plasma, gastric mucosa and gastric juice antibiotic concentrations were measured following either low- or high-dose amoxicillin (750 or 1000 mg b.i.d.) and clarithromycin (400 or 500 mg b.i.d.) given in combination with omeprazole 20 mg bid to 12 male volunteers in an open crossover design . Gastric juice and mucosal biopsy collection was performed either 2 (n=6) or 6 hours (n=6) after dosing . RESULTS: Amoxicillin concentrations 2 hours after high dosage were gastric juice > gastric body > antral mucosa > plasma . At 6 hours, plasma and gastric juice concentrations were still above the MIC for amoxicillin-susceptible bacteria but no antibiotic was detectable in mucosa samples . Clarithromycin concentrations after high dosage were gastric juice > mucosa > serum; all above the MIC for clarithromycin-susceptible bacteria at both 2 and 6 hours . CONCLUSIONS: Both dosage regimens provided effective antibiotic concentrations in gastric juice at 2 hours . After dosing, both antibiotics demonstrated high gastric tissue concentrations via local diffusion while clarithromycin also provided sustained delivery (6 hours) via gastric mucosa penetration. Sichuan Da Xue Xue Bao Yi Xue Ban, 2003 Apr, 34(2), 214 - 6 {Isolation and purification of an antibacterial polypeptide from human cervical mucus}; Yang H et al.; OBJECTIVE: This study was made to isolate and purify antibacterial polypeptides from human cervical mucus . METHODS: Human cervical mucus was collected from human healthy subjects, and the acid-soluble extract was obtained by solving the mucus with 5% acetic acid in the presence of protease inhibitor . By using gel overlay technique, one protein band that was potently antibacterial against E . coli ML-35P was identified . To purify the antibacterial polypeptide, the preparative acid-urea gel electrophoresis and Reverse Phase HPLC were performed . RESULTS: A purified antibacterial polypeptide was obtained and named HCP-1 . Tricine-SDS-PAGE indicated that the relative molecular mass of HCP-1 was around 14 x 10(3) . Agar radial diffusion assay showed that the purified polypeptide had antibacterial activities against E . coli ML-35P and Pseudomanas aeruginosa ATCC65922 . CONCLUSION: HCP-1 may be a new effector molecule of human cervical mucus. Fitoterapia, 2003 Sep, 74(6), 609 - 12 Biological activity of serotonin conjugates from the seeds of Centaurea nigra; Kumarasamy Y et al.; Two serotonin conjugates, N-(trans-p-coumaroyl)-serotonin (1) and N-(trans-feruloyl)-serotonin (maoschamine, 2), isolated from the methanol extract of the seeds of Centaurea nigra, have been assessed for antibacterial and free radical scavenging activities . The general toxicity of 1 and 2 has also been determined by the brine shrimp lethality bioassay. Fitoterapia, 2003 Sep, 74(6), 603 - 5 Antibacterial activity of Pterocarpus indicus; Khan MR et al.; The leaves, root and stem barks of Pterocarpus indicus were successively partitioned with petrol, dichloromethane, ethyl acetate, butanol and methanol . All the fractions exhibited a wide spectrum of antibacterial activity . The activity was more pronounced in the butanol and methanol fractions . None were active against the moulds. Fitoterapia, 2003 Sep, 74(6), 592 - 6 Antibacterial and antifungal activity of Indonesian ethnomedical plants; Goun E et al.; Methylene chloride and methanol extracts of 20 Indonesian plants with ethnomedical uses have been assessed for in vitro antibacterial and antifungal properties by disk diffusion method . Extracts of the six plants: Terminalia catappa, Swietenia mahagoni Jacq., Phyllanthus acuminatus, Ipomoea spp., Tylophora asthmatica and Hyptis brevipes demonstrated high activity in this bioassay system . These findings should stimulate the search for novel, natural product such as new antibacterial and antifungal agents. Drug Deliv, 2003 Jul-Sep, 10(3), 185 - 91 Ion-activated in situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride; Balasubramaniam J et al.; The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac . Our present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, CPH, based on the concept of ion-activated in situ gelation . Gelrite gellan gum, a novel ophthalmic vehicle that gels in the presence of mono or divalent cations, present in the lacrimal fluid was used alone and in combinations with sodium alginate as the gelling agent . The developed formulations were therapeutically efficacious and provided sustained release of the drug over an 8-hr period in vitro. Phytochemistry, 2003 Sep, 64(2), 395 - 9 Cardioactive and antibacterial terpenoids from some Salvia species; Ulubelen A; Seven Salvia species were investigated recently for their chemical and biological activities . Some terpenoidal compounds exhibited cardiovascular and antibacterial activities . A number of new diterpenoids were obtained and their structures were established through extensive spectral analysis. Clin Exp Rheumatol, 2003 Jul-Aug, 21(4), 515 - 21 Efficacy of empirically prescribed amoxicillin and amoxicillin + clavulanic acid in children's reactive arthritis: a randomised trial; Astrauskiene D; OBJECTIVE: To evaluate the efficacy of early empiric prescription of amoxicillin and amoxicillin + clavulanic acid in children with reactive arthritis (ReA) when the arthritis-triggering microorganism is not identified . METHODS: 138 children, ranging in age from 2 to 16 years, with ReA of up to 3 months duration were randomly assigned to 3 groups and either prescribed antibacterial treatment with amoxicillin or amoxicillin + clavulanic acid (amoxicillin-potassium clavulanate combination) or were not given antibiotics (control group) . Patients in all 3 groups were prescribed the usual treatment with nonsteroidal antiinflammatory drugs . Both groups of patients under antibacterial treatment were randomised into 2 subgroups: patients given a 10- to 14-day or a 28-day-duration antibacterial course . The results of the study were evaluated after 1 and 3 months of observation by determining the percentage of patients that had no clinical or laboratory signs of disease activity . RESULTS: After 1 month of observation no signs of disease activity were found in 48.0% of patients who were prescribed amoxicillin, in 58.5% of patients treated with amoxicillin + clavulanic acid, and only in 13.0% of patients from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group) . After 3 months of observation no disease activity was found in 92.0% of patients who used amoxicillin, in 95.1% of those treated with amoxicillin + clavulanic acid, and in 58.7% of children from the control group (p < 0.001 for either antibacterial treatment in comparison with the control group) . There was no significant difference in the efficacy of amoxicillin and amoxicillin + clavulanic acid . The duration of the antibacterial course showed no influence on the results of treatment . CONCLUSION: Amoxicillin or amoxicillin + clavulanic acid in 10- to 14-day courses are advisable, in addition to the antirheumatic treatment, for children in the early stage of ReA when the arthritis-triggering microorganism is not identified. Vestn Khir Im I I Grek, 2003, 162(3), 27 - 30 {Surgical strategy in oncologic diseases of organs of the pancreatobiliary zone complicated by mechanical jaundice}; Iarema IV et al.; In patients operated upon for oncological diseases of organs of the pancreatobiliary zone complicated by mechanical jaundice the lethality was decreased in a group of patients with purulent cholangitis and high biliary hypertension by means of using a two-stage method of operative treatment, use of the dosaged decompression of the bile ducts with a gradually increased diameter of the drain from 4 to 7-8 mm being most effective . A good effect of the application of complex antibacterial therapy was also noted when using a direct endolymphatic administration and intracholedochal perfusion of antibiotics . It allowed twice as quick to arrest the inflammatory process in the bile ducts, to normalize the biochemical indices of blood, and to prepare the patient for the main stage of operation. Med Res Rev, 2003 Nov, 23(6), 697 - 762 Structure and function of "metalloantibiotics"; Ming LJ; Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin . The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics . Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics . Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review . Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities . In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics." Saudi Med J, 2003 Aug, 24(8), 842 - 5 Does regular garlic intake affect the prevalence of Helicobacter pylori in asymptomatic subjects? Salih BA, Abasiyanik FM. OBJECTIVE: The in vitro antibacterial activity of garlic against Helicobacter pylori (H.pylori) is well documented and the potential for its use in vivo was suggested . Garlic intake, a traditional habit by the Taskopru population in Turkey for decades, was examined for its effect on the prevalence of H . pylori and compared with the non garlic consuming group . METHODS: Eighty-one garlic consuming asymptomatic subjects in Kastamonu province in Turkey (68 males, 13 females) of 23-82 years of age (average 46) were selected on a very restricted bases in regards to the garlic intake (raw or cooked, or both), amount, duration and other criteria . Control group (non-garlic consuming) of 81 asymptomatic subjects (66 males, 15 females) of 23-90 years of age (average 43) were enrolled for comparison with the garlic consuming group . Serum samples were collected from both groups during the period from September 2001 through to April 2002 and examined by the enzyme linked immunoassay test for anti H.pylori antibodies . RESULTS: An overall H.pylori prevalence of 79% and 81% was detected in the garlic and non garlic consuming groups . A significantly lower average antibody titer was detected in the garlic consuming group than that of the control group and similarly in those who consumed mixture of raw plus cooked garlic as compared to those who consumed raw or cooked garlic alone . CONCLUSION: Garlic intake for long durations (years) did not appear to have an effect on the prevalence of H.pylori infection . Garlic consuming subjects had a significantly lower average antibody titer than non garlic consuming groups, which might suggest an indirect inhibitory effect on the reproduction of H.pylori and possibly progression to more serious peptic ulcer diseases. J Exp Med, 2003 Sep 1, 198(5), 725 - 36 Epub 2003 Aug 25. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation; Prass K et al.; Infections are a leading cause of death in stroke patients . In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections . 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia . Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production . Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden . Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis . Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke . These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke. Z Naturforsch {C}, 2003 Jul-Aug, 58(7-8), 541 - 6 Dacrymenone and VM 3298-2--new antibiotics with antibacterial and antifungal activity; Mierau V et al.; Two new antibiotic metabolites, dacrymenone (1) and VM 3298-2 (2), were isolated from fermentations of a Dacrymyces sp., and their structures were determined by spectroscopic techniques . Dacrymenone (1) is a new eremophilane sesquiterpenoid while VM 3298-2 (2) is a bis-enol ether between methyl pyruvate and 4,6-dihydroxycyclohexan-1,3-dione . Dacrymenone (1) shows weak antibacterial and antifungal activity while VM 3298-2 (2) exhibits cytotoxic and antifungal activities. Z Naturforsch {C}, 2003 Jul-Aug, 58(7-8), 527 - 32 Antibacterial and cytotoxic activity of prenylated bicyclic acylphloroglucinol derivatives from Hypericum amblycalyx; Winkelmann K et al.; Two new bicyclic acylphloroglucinol derivatives, hypercalyxone A (1-{5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl}-2-methyl-propan-1-one, 1) and B (1-{5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl}-2-methyl-butan-1-one, 2), have been isolated from the petroleum ether extract of the aerial parts of Hypericum amblycalyx, together with two further compounds (1-{5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl}-2-methyl-propan-1-one, 3 and 1-{5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl}-2-methyl-butan-1-one, 4), which have been described only as semi-synthetic products . In addition, the known triterpene lup-20(29)-en-3-one was obtained . Structure elucidation was based on 1D and 2D NMR studies, as well as on data derived from mass spectrometry . The four acylphloroglucinol derivatives were evaluated for their cytotoxic and antibacterial activity . All compounds showed moderate cytotoxic activity against KB and Jurkat T cancer cells . Especially compounds 3 and 4 exhibited a strong antibacterial activity against different Gram-positive strains. J Chromatogr A, 2003 Jul 18, 1006(1-2), 251 - 60 Mass transfer effects in preparative chromatography of eremomycin on polymeric sorbents; Polyakova IV et al.; This work is devoted to the study of the regularities of the sorption of the new antibacterial antibiotic eremomycin on carboxylic sorbents . The main sorption kinetic equilibrium and dynamic parameters for realization of one-act preparative chromatographic process were determined and the difference between gel-like and structurally segregated carboxylic cation exchangers was analyzed . The optimal conditions for sorption and complete desorption of eremomycin were found. Drug News Perspect, 2000 Aug, 13(6), 366 - 77 Progress in antibacterial and antifungal chemotherapy; Fromtling RA; European Society of Clinical Microbiology and Infectious Diseases; The European Society of Clinical Microbiology and Infectious Diseases sponsored the 10th European Congress on Clinical Microbiology and Infectious Diseases in Stockholm, Sweden, May 28-31, 2000 . At the ECMID, well-attended sessions were held which focused on the pathogenesis and therapy of viral, bacterial and fungal diseases . This report focuses on new information on resistance to antibacterial agents, including data from recent surveillance studies, and the in vitro and investigational clinical activity of new antibacterial (moxifloxacin, telithromycin) and antifungal (fluconazole, itraconazole, voriconazole, amphotericin B, liposomal formulations of amphotericin B, terbinafine and the candins) drugs. Am J Clin Nutr, 2003 Sep, 78(3 Suppl), 579S - 583S Spicing up a vegetarian diet: chemopreventive effects of phytochemicals; Lampe JW; Thousands of chemical structures have been identified in plant foods . Many are found in spices . Typically, spices are the dried aromatic parts of plants-generally the seeds, berries, roots, pods, and sometimes leaves-that mainly, but not invariably, grow in hot countries . Given the wide range of botanical species and plant parts from which spices are derived, they can contribute significant variety and complexity to the human diet . In the past, the medicinal uses of spices and herbs were often indistinguishable from their culinary uses, and for good reason: people have recognized for centuries both the inherent value, as well as the potential toxicity, of phytochemicals in relation to human health . Plants have the capacity to synthesize a diverse array of chemicals, and understanding how phytochemicals function in plants may further our understanding of the mechanisms by which they benefit humans . In plants, these compounds function to attract beneficial and repel harmful organisms, serve as photoprotectants, and respond to environmental changes . In humans, they can have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of the immune system, reduction of inflammation, modulation of steroid metabolism, and antibacterial and antiviral effects . Embracing a cuisine rich in spice, as well as in fruit and vegetables, may further enhance the chemopreventive capacity of one's diet. Chem Commun (Camb), 2003 Aug 21, (16), 2062 - 3 First synthesis of the antifungal and antibacterial agent cladobotryal; Clive DL et al.; The antifungal and antibacterial agent cladobotryal (1) was synthesized by a convergent route from lactone 5 and aldehyde 12, a key step in the elaboration of the pyridinone ring being conversion of a t-BuOC(O) group on nitrogen into an i-Pr3SiOC(O) group. Infect Immun, 2003 Sep, 71(9), 4917 - 24 Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis; Gyurko R et al.; Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing . Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS(-/-)) mice with P . gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P . gingivalis infection . iNOS(-/-) mice inoculated with P . gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice . Chamber fluid from iNOS(-/-) mice possessed significantly more P . gingivalis than that of WT mice . The immunoglobulin G responses to P . gingivalis in serum was similar in WT and iNOS(-/-) mice, and the inductions of tumor necrosis factor alpha, interleukin-1 beta and interleukin-6, and prostaglandin E(2) were comparable between the two mouse strains . Although no differences in total leukocyte counts in chamber fluids were observed between iNOS(-/-) and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS(-/-) mouse chamber fluids than that of WT samples . Interestingly, casein-elicited PMNs from iNOS(-/-) mice released more superoxide than did WT PMNs when stimulated with P . gingivalis . These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P . gingivalis. Eur J Med Chem, 2003 Jul-Aug, 38(7-8), 751 - 8 Synthesis and antibacterial activity of 1beta-methyl-2-{5-(N-substituted-2-hydroxy iminoethyl)pyrrolidin-3-ylthio}carbapenem derivatives; Oh CH et al.; The synthesis of a new series of 1-methylcarbapenems having the substituted thiazolopyrrolidine moiety is described . Their in vitro antibacterial activities against both gram-positive and gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated . In particular, compounds 12b and 12k showed the most potent antibacterial activity. Br J Dermatol, 2003 Aug, 149(2), 354 - 62 The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial; Berger RS et al.; BACKGROUND: Recent studies of antidandruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit . OBJECTIVES: The purpose of this 6-month, 200-patient, randomized, investigator-blinded, parallel-group clinical study was to assess the hair growth benefits of a 1% pyrithione zinc shampoo . The efficacy of a 1% pyrithione zinc shampoo (used daily), was compared with that of a 5% minoxidil topical solution (applied twice daily), a placebo shampoo and a combination of the 1% pyrithione zinc shampoo and the 5% minoxidil topical solution . METHODS: Two hundred healthy men between the ages of 18 and 49 years (inclusive) exhibiting Hamilton-Norwood type III vertex or type IV baldness were enrolled . Total hair counts, the primary efficacy measure, were obtained using fibre-optic microscopy and a computer-assisted, manual hair count method . Secondary measures of efficacy included assessments of hair diameter, as well as patient and investigator global assessments of improvement in hair growth . These were based on photographs of the scalp using both midline and vertex views . RESULTS: Hair count results showed a significant (P < 0.05) net increase in total visible hair counts for the 1% pyrithione zinc shampoo, the 5% minoxidil topical solution, and the combination treatment groups relative to the placebo shampoo after 9 weeks of treatment . The relative increase in hair count for the 1% pyrithione zinc shampoo was slightly less than half that for the minoxidil topical solution and was essentially maintained throughout the 26-week treatment period . No advantage was seen in using both the 5% minoxidil topical solution and the 1% pyrithione zinc shampoo . A small increase in hair diameter was observed for the minoxidil-containing treatment groups at week 17 . Assessments of global improvements by the patients and investigator generally showed the benefit of 5% minoxidil . The benefit of the 1% pyrithione zinc shampoo used alone tended (P < 0.1) to be apparent only to the investigator . CONCLUSIONS: Hair count results show a modest and sustained improvement in hair growth with daily use of a 1% pyrithione zinc shampoo over a 26-week treatment period. J Intern Med, 2003 Sep, 254(3), 197 - 215 Antibacterial peptides: basic facts and emerging concepts; Boman HG; Antibacterial peptides are the effector molecules of innate immunity . Generally they contain 15-45 amino acid residues and the net charge is positive . The cecropin type of linear peptides without cysteine were found first in insects, whilst the defensin type with three disulphide bridges were found in rabbit granulocytes . Now a database stores more than 800 sequences of antibacterial peptides and proteins from the animal and plant kingdoms . Generally, each species has 15-40 peptides made from genes, which code for only one precursor . The dominating targets are bacterial membranes and the killing reaction must be faster than the growth rate of the bacteria . Some antibacterial peptides are clearly multifunctional and an attempt to predict this property from the hydrophobicity of all amino acid side chains are given . Gene structures and biosynthesis are known both in the fruit fly Drosophila and several mammals . Humans need two classes of defensins and the cathelicidin-derived linear peptide LL-37 . Clinical cases show that deficiencies in these peptides give severe symptoms . Examples given are morbus Kostmann and atopic allergy . Several antibacterial peptides are being developed as drugs. J Med Chem, 2003 Aug 28, 46(18), 3771 - 4 Structure-based design of a macrocyclic inhibitor for peptide deformylase; Hu X et al.; A macrocyclic, peptidomimetic inhibitor of peptide deformylase was designed by covalently cross-linking the P1' and P3' side chains . The macrocycle, which contains an N-formylhydroxylamine side chain as the metal-chelating group, was synthesized from a diene precursor via olefin metathesis using Grubbs's catalyst . The cyclic inhibitor showed potent inhibitory activity toward Escherichia coli deformylase (K(I) = 0.67 nM) and antibacterial