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| 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 activity against both Gram-positive and Gram-negative bacteria (MIC = 0.7-12 microg/mL). Gerodontology, 2003 Jul, 20(1), 3 - 8 Developing an instrument to support oral care in the elderly; Sumi Y et al.; BACKGROUND: The dramatic increase in the number of dependent elderly in developed countries has created a great need for their improved oral care . However, optimal oral care by caregivers is not possible because of time constraints, difficulty involved in brushing other individuals' teeth, lack of co-operation, and the lack of perceived need . Therefore, the development of an effective instrument simplifying and supporting oral care to relieve the strain on caregivers is a matter of some urgency . PURPOSE: In order to clean the mouths of elderly dependent patients, we have developed a new oral care support instrument (an electric toothbrush in combination with an antibacterial-agent supply and suction system) . The purpose of the present study was to develop and evaluate a new oral care support instrument . METHODS: a) Plaque removal study: The plaque- removing ability of this new instrument in 70 outpatients was compared with the Plak Control D9011 (Braun Gillette Japan Inc.) as a control by means of the Turesky modification of the Quigley and Hein plaque index . b) Clinical study: The subjects were 10 dependent elderly who received oral care using the new oral care support instrument for two weeks . The plaque and gingival indices were used for clinical evaluations . RESULTS: a) Plaque removal study: Brushing with the new oral care support instrument removed significantly more plaque than with the Plak Control D9011 . b) Clinical study: The new oral care support instrument allows a more effective removal of dental plaque and shows a significant improvement in the gingival indices in dependent elderly . CONCLUSION: It is concluded that the new oral care support instrument is effective and can be recommended for oral care in the dependent elderly. Clin Microbiol Infect, 2003 Jul, 9(7), 691 - 703 Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia; Carbon C et al.; OBJECTIVE: This open, multinational study examined the efficacy and tolerability of telithromycin (HMR 3647), the first ketolide antibacterial agent, at an oral dose of 800 mg once daily for seven to ten days (further validated using pharmacokinetic analysis) as an empiric therapy in adults with mild to moderate community-acquired pneumonia (CAP) . METHODS: A total of 240 patients (aged 18-79 years; median 40 years) with clinical signs and symptoms of CAP (radiologically confirmed) were enrolled in the study and received at least one dose of study medication . Sputum and blood samples for bacteriologic documentation were collected within 48 h prior to enrollment . Clinical and bacteriological outcomes were assessed 17-21 days (test of cure visit) and 31-36 days (late post-therapy visit) after treatment initiation . Adverse events were assessed by spontaneous reporting and investigator observation . RESULTS: At the test of cure visit, 92.9% (95% CI: 88.4-96.1; n= 197) of patients achieved clinical cure in the per-protocol (PP) population . In the modified intent-to-treat (mITT) population, the cure rate was 79.6% (95% CI: 73.9-84.5; n= 240), including 12.5% of undetermined cases categorized as failures . Clinical cure (PP population) remained high in patients >/=65 years (85.7%), and in patients with a Fine score >/=III (92.1%) . Among those patients for whom bacteriologic data were available, the majority had a satisfactory outcome (88.9% in the bacteriologic PP; n= 45) . Bacterial eradication rates were similarly high (85.5% and 82.7% for the mITT and PP populations, respectively) . All patients with infections as a result of atypical/intracellular pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila had a clinical outcome of cure . Treatment was well tolerated . Adverse events were mainly gastrointestinal in origin and mild in intensity . CONCLUSION: An oral dose of telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated first-line treatment for mild to moderate CAP in adults. Cas Lek Cesk, 2003, 142(6), 356 - 64 {Multiresistant tuberculosis in the Czech Republic (1999-2001)}; Havelkova M et al.; BACKGROUND: Multidrug-resistant (MDR) tuberculosis, defined as a disease caused by Mycobacterium tuberculosis strains, which are resistant to more antituberculous drugs (at least to isoniazid and rifampicin), is a problem frequently discussed in the Czech Republic . Cases of specific disease refractive to causal antituberculous therapy are associated with the risk of the spread of the causative agent among the population . METHODS AND RESULTS: The National Reference Laboratory for Mycobacteria collected 2813 Mycobacterium tuberculosis strains isolated by Czech mycobacteriological laboratories in 1999 to 2001 . All strains were tested for susceptibility to basic antituberculous drugs and then the MDR strains were further tested for susceptibility/resistance to other antituberculous and antibacterial drugs . The MDR strains were studied by DNA analysis (DNA fingerprinting restriction analysis, RFLP-Restriction Fragment Length Polymorphism) as well . Thirty-nine patients who had MDR tuberculosis were excretors of 56 Mycobacterium tuberculosis strains . In average, MDR tuberculosis accounted for 1.96% (1.7-2.4) of all cases of bacillary tuberculosis . The most frequent type of the multidrug resistance was that resistant to four basic antituberculous drugs (isoniazid, rifampicin, ethambutol and streptomycin) . It was confirmed in 48.2% multidrug resistant strains . CONCLUSIONS: Isepamicin, clofazimin, capreomycin and amikacin are considered to be the most promising antituberculosis drugs . Based on RFLP profiles, 61.5% of strains were placed into 8 clusters while the other strains remained unclustered . No significant differences in geographical distribution and population structure were found between the excretors of clustered strains and those of unclustered strains . Preliminary comparison with restriction profiles of the MDR Mycobacterium tuberculosis strains in the international database suggests the uniqueness of Czech strains showing the profiles not found elsewhere to date. Heart, 2003 Sep, 89(9), 1055 - 61 Incidence of embolism and paravalvar leak after St Jude Silzone valve implantation: experience from the Cardiff Embolic Risk Factor Study; Ionescu A et al.; BACKGROUND: Silver coating of the sewing ring (Silzone) was introduced as a modification of the St Jude Medical standard valve to provide antibacterial protection, but the valve has recently been withdrawn . OBJECTIVE: To study patients with these prostheses to assess possible adverse effects, and to guide their follow up . DESIGN: Prospective observational study of risk factors for stroke after valve replacement . SETTING: Cardiology and cardiac surgery departments in a tertiary centre . PATIENTS: There were 51 patients with Silzone and 116 with St Jude Medical standard valves . Patients undergoing aortic valve replacement were well matched for stroke risk factors . Silzone patients with mitral valve replacement were younger (mean (SD) age 61 (10) v 66 (7) years), more likely to be female (95% v 65%), and had more pulmonary arterial hypertension (100% v 78%), but fewer coronary artery bypass grafts (5% v 33%) than patients with standard mitral valve replacements (all p < 0.05) . RESULTS: Follow up was 100% in the Silzone group (mean duration 3.0 (0.9) years) and 97.4% in the standard group (4.7 (1.4) years) . Survival, morbidity, and anticoagulant control were documented over 682 follow up years (153 for Silzone and 529 for standard) . There were six embolic strokes and one peripheral embolism in the Silzone group, all within three months after operation, and five embolic strokes and one peripheral embolism in the standard group . Freedom from major thromboembolism at three months was 65% in the Silzone mitral valve replacement group and 100% in the standard mitral valve replacement group (difference 35%, 95% confidence interval 8% to 62%) . There was one reoperation for paravalvar leak in the standard group, but none in the Silzone group (NS) . Anticoagulant control in the two groups was similar . CONCLUSIONS: Patients with Silzone mitral valves had a high rate of early postoperative embolism but no excess paravalvar leak. Drugs, 2003, 63(17), 1799 - 812 Pharmacological prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis; Pande H et al.; The incidence of clinically significant pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) ranges from 1-13.5% . It is more common after therapeutic procedures such as sphincterotomy or balloon dilatation of the sphincter, and diagnostic procedures such as biliary or pancreatic manometry . The severity of post-ERCP pancreatitis may vary from very mild to extremely severe disease with multiple organ failure and fatal outcome . Several factors including papillary oedema, injection of hyperosmolar contrast-material, introduction of previously activated enzymes during repeated cannulation, bacterial contamination and thermal injury from endoscopic sphincterotomy have been implicated as triggering factors that initiate the sequential cascade of pancreatic autodigestion and release of proinflammatory cytokines leading to acute pancreatitis . Recovery from post-ERCP pancreatitis is usually rapid when the injury is confined to the pancreas . However, systemic production of inflammatory mediators may lead to the development of more serious manifestations including multiorgan failure.A wide range of pharmacological agents has been tested in experimental and clinical trials, but the results have been largely disappointing . Several drugs are discussed in this review, but only somatostatin and gabexate (gabexate mesilate) have consistently shown a moderate beneficial effect . In clinical trials, both gabexate and somatostatin appear equally effective in reducing the incidence of pancreatitis by two-thirds compared with controls . However, both drugs need to be given by continuous infusion for about 12 hours and this makes them less cost-effective than conventional treatment . One potential strategy is to reserve these drugs for high-risk patients undergoing ERCP . Preliminary studies have shown encouraging results with nitroglycerin, antibacterials and heparin . However, these observations need to be corroborated in a rigorous fashion in large, randomised, double-blind, controlled trials . If these drugs are found to be effective in further trials, it may become cost-effective to use them routinely for the prevention of post-ERCP pancreatitis . Despite the theoretical benefits, interleukin-10 has not shown a consistent benefit in clinical trials . It is probable that other cytokine inhibitors or modulators may become available for future trials to prevent pancreatitis or more probably, to reduce the severity of pancreatitis . Further research also should focus on developing newer molecules or the use of a combination of currently available drugs to prevent pancreatitis in high-risk patients undergoing therapeutic ERCP procedures. Am J Respir Cell Mol Biol, 2004 Feb, 30(2), 184 - 92 Epub 2003 Aug 14. Purification and characterization of PLUNC from human tracheobronchial secretions; Campos MA et al.; To study proteins secreted into the airway, we used secretions from primary human airway epithelial cells, re-differentiated at the air-liquid interface, and from patients intubated during surgery . A major protein of the cultured cell secretions was ethanol soluble . This protein was purified, analyzed by Edman degradation, matrix-assisted laser-desorption ionization time-of-flight mass spectroscopy of tryptic digests, and Western blots of two-dimensional electrophoresis gels using antisera against the purified preparation . The protein was identified as palate, lung, nasal epithelium clone protein (PLUNC) . The protein had multiple truncated molecules, a pattern also seen in tracheal aspirates . PLUNC was poorly soluble in water (50 microg/ml) or in 50 mM NaCl but was more soluble in 75% ethanol (> 380 microg/ml) . PLUNC secretion dramatically increased during the second week in air-liquid interface culture and continued to increase over time . Immunohistochemistry showed that PLUNC was expressed in human airway epithelium and submucosal glands . Although PLUNC is in the lipopolysaccharide (LPS)-binding protein (LBP) and bactericidal/permeability-increasing protein family of antibacterial host defense proteins, purified PLUNC failed to compete with LBP for the binding of LPS, whereas polymyxin B, a known inhibitor of LPS-LBP binding, did interfere with binding . This study showed that plunc gene product is expressed both in vivo and in vitro, detailed a method for its purification and provided basic information on its biochemical properties in secretions. Dermatol Ther, 2003, 16(2), 106 - 13 From medical herbalism to phytotherapy in dermatology: back to the future; Dattner AM; Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy . They serve as therapeutic alternatives, safer choices, or in some cases, as the only effective treatment . Folk medicine tradition provides different indicators for use than the medical disease model . Advantages of multiple synergistic components of crude extracts are discussed, as well as herbs already used in dermatology . Bitter digestive stimulants are used for vitiligo . Bioflavinoids from buckwheat and horse chestnut are used for varicose veins, and silymarin is used for liver protection . Gotu kola and sarsaparilla are used for inflammatory skin conditions . Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties which make the crude extract useful in acne . Philosophical differences in herbology compared to medicine exist in the application of science toward improving elimination and strengthening the host as opposed to destroying the vector or manifestation of the disease. Boll Chim Farm, 2003 May, 142(4), 146 - 50 Synthesis and antibacterial activity of 1,3-diarylpyrimido{4,5-d}pyrimidines; Cieplik J et al.; This paper describes the synthesis of 4,5-diaminoderivatives of pyrimidine and pyrimido {4,5-d} pyrimidines and evaluation of their antibacterial activity on 9 selected bacterial species relatif the changes in the chemical structure to an increase in the bioactive properties. Anesteziol Reanimatol, 2003 May-Jun, (3), 57 - 60 {The enteral feeding during the treatment of appendicular peritonitis in children}; Bagaev VG et al.; A total of 65 patients, aged 3 to 14, with different forms of appendicular peritonitis, in whom the intestinal insufficiency syndrome (IIS), stage 2, was diagnosed, were investigated . 35 patients were in the main group, and 30 patients were in the control group; the subjects of the latter group had a similar form of peritonitis, i.e . IIS, stage 2, it was confirmed clinically and by ultrasound examinations . The laparoscopic operations were carried out in all patients . The patients of both groups received postoperatively a similar therapy, i.e . the antibacterial, metabolic and infusive ones, as well as vitamins and parenteral feeding (daily caloric values--50-120 kcal/kg, protein--2-3 g/kg/day) according to a child's age and a clinical course of peritonitis . All children of the main group received postoperatively an early enteral therapy (EET), which involved 4 stages . Stage 1: introduction of the salt solution with added glutamine through the naso-gastric probe by increasing volumes and with respect to an individual tolerability of a patient; stage 2: introduction of semi-element mixtures; stage 3: introduction of 10% solutions of polymer balanced mixture; stage 4: introduction of 20% solutions of polymer mixtures . Ultrasound scanning and clinical methods were used to assess the efficiency of the recovery of intestinal peristalsis . The conducted investigations showed that the mean duration of the gastric-type EET amounted to 3-4 days, and the IIS was, on the average, arrested by days 6 or 7 . The duration of infusive therapy and parenteral feeding went down, in the main group, by 2 days . A trend towards an increase of the erythrocyte level was noted in these patients . No differences were registered in the values of concentrations of total protein and albumin in the blood serum of patients in both groups from the 1st to 7th postoperative days, however, the infusions of plasma and albumin were made by 2 times more often in the main group as compared to the control one . The EET technique preserved the gastric mucous tunic intact, which cut the postoperative complications 2-fold, and consequently, it reduced the stay of patients in hospital on the average by 8 days . A conclusion was made, on the basis of the conducted study, that EET is a pathophysiologically substantiated treatment method for IIS, stage 2, in children with appendicular peritonitis; EET ensures a rapid recovery of gastric-tract functions, it reduces the frequency rate of postoperative complications and cuts the length of both the infusive therapy and of the patients' stay in hospital. Cochrane Database Syst Rev . 2003;(3):CD003066. G-CSF and GM-CSF for treating or preventing neonatal infections; Carr R et al.; BACKGROUND: The colony stimulating factors (CSFs), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF), are naturally occurring cytokines that stimulate the production and antibacterial function of neutrophils and monocytes . Two strategies have been adopted for exploring whether CSFs can provide clinical benefit for preterm infants . The first has investigated their use as a treatment to improve outcome in established systemic infection, especially when complicated by a low neutrophil count . The alternative strategy has been to use CSFs prophylactically, to prevent sepsis prospectively through stimulation of neutrophil production and bactericidal function . OBJECTIVES: To determine the efficacy and safety of the haemopoietic colony stimulating factors (G-CSF or GM-CSF) in newborn infants, when used for:a) treatment of suspected or proven systemic infection to reduce mortality, orb) prophylaxis, to prevent systemic infection in infants at high risk of nosocomial infection.To determine, in subgroup analysis, the influence of pre-existing or high risk of neutropenia on the outcome of therapy . SEARCH STRATEGY: PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) were searched in April 2003 using the keywords: G-CSF, GM-CSF, infant newborn, with and without the limit Clinical Trial . In addition, reference lists of identified RCTs, meta-analyses and personal files were searched . SELECTION CRITERIA: The criteria used to select studies for inclusion were:Design: RCT.Subjects: Newborn infants in intensive care.Interventions: G-CSF or GM-CSF given as treatment in conjunction with antibiotics for suspected or microbiologically proven systemic infection . G-CSF or GM-CSF given as prophylaxis with the aim of reducing the incidence of systemic infection . Outcomes: Treatment studies reporting all cause mortality . Prophylaxis studies reporting subsequent incidence of sepsis and / or mortality . DATA COLLECTION AND ANALYSIS: Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) using the fixed effect model are reported . Number needed to treat (NNT) was calculated for the outcomes that showed a statistically significant reduction in RR . MAIN RESULTS: Seven treatment studies of 257 infants with suspected systemic bacterial infection and three prophylaxis studies comprising 359 neonates are analysed.Treatment studies: There is no evidence that the addition of G-CSF or GM-CSF to antibiotic therapy in preterm infants with suspected systemic infection reduces immediate all cause mortality . No significant survival advantage was seen at 14 days from the start of therapy {typical RR 0.71 (95% CI 0.38,1.33); typical RD -0.05 (95% CI -0.14, 0.04)} . However all seven of the treatment studies were small, the largest recruiting only 60 infants . The subgroup analysis of 97 infants from three treatment studies who, in addition to systemic infection, had clinically significant neutropenia (< 1.7 x 10(9)/l) at trial entry, does show a significant reduction in mortality by day 14 {RR 0.34 (95% CI 0.12, 0.92); RD -0.18 (95% CI -0.33, -0.03); NNT 6 (95% CI 3-33)}.Prophylaxis studies have not demonstrated a significant reduction in mortality in neonates receiving GM-CSF {RR 0.59 (95% CI 0.24,1.44); RD -0.03 (95% CI -0.08,0.02)} . The identification of sepsis as the primary outcome of prophylaxis studies has been hampered by inadequately stringent definitions of systemic infection . However, data from one study suggest that prophylactic GM-CSF may provide protection against infection when given to preterm infants who are neutropenic or at high risk of developing postnatal neutropenia . REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to support the introduction of either G-CSF or GM-CSF into neonatal practice, either as treatment of established systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates . No toxicity of CSF use was reported in any systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates . No toxicity of CSF use was reported in any study included in this review . The limited data suggesting that CSF treatment may reduce mortality when systemic infection is accompanied by severe neutropenia should be investigated further in adequately powered trials which recruit sufficient infants infected with organisms associated with a significant mortality risk. J Antimicrob Chemother, 2003 Sep, 52(3), 497 - 9 Epub 2003 Aug 13. In vitro activity of cethromycin, a novel antibacterial ketolide, against Chlamydia pneumoniae; Miyashita N et al.; OBJECTIVES: To investigate the in vitro activity of cethromycin, a new ketolide, against Chlamydia pneumoniae . METHODS: The in vitro activity of cethromycin against 20 isolates of C . pneumoniae was compared with the activities of telithromycin, erythromycin A, azithromycin and clarithromycin against those isolates . RESULTS: The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of the isolates were killed by cethromycin were both 0.016 mg/L (range 0.016-0.031 mg/L) . Cethromycin was the most active antibiotic tested in this study . CONCLUSIONS: Our results appear to indicate that cethromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C . pneumoniae. Chem Pharm Bull (Tokyo), 2003 Aug, 51(8), 990 - 3 Two new bromotyrosine-derived metabolites from the sponge Psammaplysilla purpurea; Goud TV et al.; Two new bromotyrosine-derived metabolites (1, 2) have been isolated along with the known compounds 3,5-dibromo-4-methoxyphenylacetonitrile, 3-bromo-4-methoxyphenylacetonitrile, 3-bromo-4-hydroxyphenylacetonitrile, 1-hydroxyuracil, 1-methoxyhemibastadin 2, purpuramine H and a steroid 5alpha,8alpha-epidioxycholest-6-en-3beta-ol from the sponge Psammaplysilla purpurea . Compounds 1 and 2 were characterized by interpretation of their spectral data . The antibacterial activity of these compounds is summarized. Arch Intern Med, 2003 Aug 11-25, 163(15), 1801 - 7 Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids; van der Linden PD et al.; BACKGROUND: In several case reports, the occurrence of Achilles tendon rupture has been attributed to the use of quinolones, but the epidemiologic evidence for this association is scanty . METHODS: We conducted a population-based case-control study in the General Practice Research Database in the United Kingdom during the period 1988 through 1998 . Cases were defined as all persons who had a first-time recording of an Achilles tendon rupture, and who had at least 18 months of valid history before the index date . As a control group, we randomly sampled 50 000 patients with at least 18 months of valid history who were assigned a random date as index date . RESULTS: We identified 1367 cases that met the inclusion criteria . The adjusted odds ratio (OR) for Achilles tendon rupture was 4.3 (95% confidence interval {CI}, 2.4-7.8) for current exposure to quinolones, 2.4 (95% CI, 1.5-3.7) for recent exposure, and 1.4 (95% CI, 0.9-2.1) for past exposure . The OR of Achilles tendon rupture was 6.4 (95% CI, 3.0-13.7) in patients aged 60 to 79 years and 20.4 (95% CI, 4.6-90.1) in patients aged 80 years or older . In persons aged 60 years and older, the OR was 28.4 (95% CI, 7.0-115.3) for current exposure to ofloxacin, while the ORs were 3.6 (95% CI, 1.4-9.1) and 14.2 (95% CI, 1.6-128.6) for ciprofloxacin and norfloxacin, respectively . Approximately 2% to 6% of all Achilles tendon ruptures in people older than 60 years can be attributed to quinolones . CONCLUSIONS: Current exposure to quinolones increased the risk of Achilles tendon rupture . The risk is highest among elderly patients who were concomitantly treated with corticosteroids. Przegl Epidemiol, 2003, 57(2), 329 - 34 {Occurrence of insect pests in hospitals in Poland}; Gliniewicz A et al.; The prevalent synantropic species present in hospitals in Poland was the German cockroach (Blattella germanica L.), found in about 70% hospitals . It was followed by Oriental cockroach (Blatta orientais L.) and Pharaoh's ant (Monomorium pharaonis L.) occurred in 40% and 17% of hospitals respectively . Kitchens, laundries and lavatories were the most often infested places . Preliminary investigation of German cockroaches caught in hospitals in Poland showed on their body surfaces presence of bacteria known as these causing nosocomial infection . Several strains were resistant to antibacterial drugs widely used for treatment and showed insensitivity to chemical disinfectants used for surface treatment . Additional risk elements in Poland could be high resistance levels to many insecticides used for insect control in hospitals. J Pharm Biomed Anal, 2003 Aug 21, 32(6), 1235 - 41 Physicochemical compatibility between ketoprofen lysine salt injections (Artrosilene) and pharmaceutical products frequently used for combined therapy by intravenous administration; Anacardio R et al.; Ketoprofen lysine salt (Artrosilene) Fiale) is a non-steroidal anti-inflammatory agent frequently administered by intravenous infusion in association regimen with other drugs, such as steroidal anti-inflammatory, anti-hemorrhagic, anti-spastic, anti-ulcer, and antibacterial drugs . The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt (Artrosilene) Fiale) and other injectable drugs frequently used in association . Physicochemical properties of ketoprofen lysine salt mixtures with different drugs, including colour, clarity, pH and drug content were observed or measured before and after (up to 5 h) mixing at room temperature and under light protection . Results show that the association of Artrosilene Fiale with different drugs does not cause, up to 5 h from mixing, any significant variation in the physicochemical parameters mentioned above . In conclusion, the results obtained demonstrated the physicochemical compatibility of ketoprofen lysine salt (Artrosilene) Fiale) with several drugs. Structure (Camb), 2003 Aug, 11(8), 899 - 900 The final player in the coenzyme A biosynthetic pathway; O'Toole N et al.; The determination of the crystal structure of human phosphopantothenoylcysteine synthetase completes our knowledge of the enzyme structures involved in all steps of coenzyme A biosynthesis . This structure provides insight into the differences between bacterial and mammalian forms of the enzyme and may guide the structure-based development of novel antibacterial compounds. Nucleic Acids Symp Ser, 2000, (44), 75 - 6 Design and synthesis of curcumin-bioconjugates to improve systemic delivery; Kumar S et al.; Di-O-glycinoyl curcumin (I), di-O-glycinoyl-C4-glycyl-curcumin (II), 5'-deoxy-5'-curcuminyl thymidine (5'-cur-T) (III) and 2'-deoxy-2'-curcuminyl uridine (2'-cur-U) (IV) have been synthesized and characeterised by elemental analysis & 1H NMR . The antibacterial activities of these four bioconjugates has been tested particularly for multiresistant micro-organisms . Best results are shown by I & IV . These bioconjugates serve dual purpose of systemic delivery as well as therapeutic agents against viral diseases. Lancet Infect Dis, 2003 Aug, 3(8), 501 - 6 Antibacterial cleaning and hygiene products as an emerging risk factor for antibiotic resistance in the community; Aiello AE et al.; Antibiotic resistance within the community setting is an emerging public-health concern . Infection with antibiotic-resistant organisms in the community among people lacking traditional risk factors has been reported . In addition, prevalence studies have identified individuals carrying antibiotic-resistant organisms in the absence of known risk factors . These studies strongly suggest the presence of contributing factors that have yet to be identified . In this paper we review the burden of antibiotic resistance and known risk factors within the community setting, assess the potential role of antibacterial cleaning and hygiene products containing triclosan in the emergence of resistance, and recommend future research on the assessment of household cleaning and hygiene products containing triclosan. Zhonghua Yi Xue Za Zhi, 2003 Jun 25, 83(12), 1018 - 22 {Epidemiologic features, clinical diagnosis and therapy of first cluster of patients with severe acute respiratory syndrome in Beijing area}; Zhou XZ et al.; OBJECTIVE: Investigate the features of outbreak epidemic, clinical disease progression of the first SARS cases in Beijing and evaluate the efficacy of therapeutic regimen . METHODS: Twenty-nine patients (11 men and 18 women, 20 - 74 years old age range) were diagnosed with infectious SARS and admitted in our hospital from the March 5th to April 14th, 2003 in this study . The data of clinical presentation and disease progression of all the patients including index subject as the infectious SARS resource patient, her family infected members and 21 health care workers were abstracted . RESULTS: The first SARA outbreak in Beijing was characterized with the cluster feature of resource patient family members and health care providers . The incubation period ranged from 2 to 14 days . All the patients had a fever (temperature > 38 degrees C for over 24 hours) and other manifestations as reported before . Serial chest radiographs showed progressive pathologic air-space disease . Twenty patients showed the severe syndrome with various time ranged from 1 day to 14 days . Two patients died of progressive acute respiratory distress disease . The histologic analysis of one death patient showed diffuse alveolar damage in the two lungs . Twenty-six patients receiving the combined therapy including use of corticosteroid, antiviral ribavirin agents after the onset of symptoms and showed they had an acute self-limited disease course . The oldest patient (74 year old, male) received the healthy convalescent plasma infusion (50 ml) from recovered SARS subject and completely recovered within 21 days, having a shorter disease course . CONCLUSION: SARS is a kind of new self-limited and acute infectious disease . Early diagnosis, early isolation, early antiviral therapy for patients and efficient prevention for health care providers are urgently recommended . In particular, a combinational therapy of use of antiviral agents, preventive antibacterial antibiotics and pulsed dosage of corticosteroid can efficiently raise the clinical recovery rate and decrease mortality of SARS patients. Biochemistry, 2003 Aug 12, 42(31), 9307 - 15 Single disulfide and linear analogues corresponding to the carboxy-terminal segment of bovine beta-defensin-2: effects of introducing the beta-hairpin nucleating sequence d-pro-gly on antibacterial activity and Biophysical properties; Krishnakumari V et al.; Mammalian defensins (alpha as well as beta forms) have a beta-hairpin structural motif spanning approximately 20 residues at the carboxy-terminal end . We have investigated the antibacterial activity and biophysical properties of synthetic peptides corresponding to the carboxy-terminal segment of bovine beta-defensin-2 (BNBD-2): VRNHVTC(1)RINRGFC(2)VPIRC(3)PGRTRQIGTC(4)FGPRIKC(5)C(6)RSW (positions of disulfide bonds are C(1){bond}C(5), C(2){bond}C(4), and C(3){bond}C(6)) . The parent sequence chosen was RCPGRTRQIGTIFGPRIKCRSW (P1), which spans the carboxy-terminal region of BNBD-2 . Since the dipeptide sequence D-Pro-Gly favors nucleation of beta-hairpin structures even in acyclic peptides, analogues of P1 with one D-Pro-Gly at the central portion and two D-Pro-Gly segments near the N- and C-terminal ends were generated . An analogue in which GP (residues 14 and 15) in P1 was switched to PG was also synthesized . It was observed that the cyclic form as well as their linear forms exhibited antibacterial activity . Circular dichroism and theoretical studies indicated that while the beta-hairpin conformation is populated, there is conformational plasticity in the cyclic and linear peptides . The mode of bacterial killing was by membrane permeabilization . The entire mammalian defensin sequence does not appear to be essential for manifestation of antibacterial activity . Hence, short peptides corresponding to the C-terminal segments of mammalian defensins could have potential as therapeutic agents. Planta Med, 2003 Jul, 69(7), 675 - 7 Antibacterial new clerodane diterpenes from the surface of Haplopappus foliosus; Urzua A et al.; A biologically monitored fractionation of the resinous exudate extract of Haplopappus foliosus DC . is reported . Purification of the two active fractions yielded 2-alpha-hydroxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (1) and 2-alpha-acetoxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (2), two new clerodane diterpenes. Int J Dermatol, 2003 Sep, 42 Suppl 1, 23 - 7 Interdigital tinea pedis (dermatophytosis simplex and complex) and treatment with ciclopirox 0.77% gel; Gupta AK et al.; The most common presentation of tinea pedis (athlete's foot) is that involving the interdigital spaces . Tinea pedis interdigitalis may present as asymptomatic dermatophytosis simplex or dermatophytosis complex, which is symptomatic, with secondary bacterial infection . In the dermatophytosis complex presentation there may be inflammation, maceration and odor, with bacterial involvement . Ciclopirox gel offers advantages in the treatment of tinea pedis, especially in the dermatophytosis complex presentation, with antifungal, antibacterial, and anti-inflammatory activity; furthermore, the gel formulation is fast drying, which is an advantage when the toe web area is moist. Int J Dermatol, 2003 Sep, 42 Suppl 1, 3 - 9 Ciclopirox for the treatment of superficial fungal infections: a review; Gupta AK et al.; Ciclopirox is a broad-spectrum antifungal agent that also exhibits anti-inflammatory and antibacterial activity . The lotion and cream formulations of ciclopirox are effective in many types of infection, including tinea corporis/cruris, tinea pedis, cutaneous candidiasis, pityriasis (tinea) versicolor, and seborrheic dermatitis . The new ciclopirox gel 0.77% formulation is also indicated for the treatment of seborrheic dermatitis of the scalp, interdigital tinea pedis and tinea corporis. Paediatr Drugs, 2003, 5(8), 525 - 31 New and emerging therapies for short bowel syndrome in children; Vanderhoof JA et al.; This review provides an overview of traditional as well as emerging therapies useful in the management of pediatric short bowel syndrome . Pediatric short bowel syndrome is relatively uncommon; however, when it does occur, it presents a unique challenge to medical care providers . The use of parenteral and enteral nutrition to maximize growth and enhance intestinal adaptation so as to increase absorptive surface area has been the primary focus of therapy . In recent years, the advent of pharmacologic advances, including the use of antibacterial drugs, anti-motility drugs and hormonal therapies, has had a significant impact on this condition . At times, surgery may be indicated for dealing with complications, or providing alternative therapy such as transplantation . With ongoing research, it is likely that improved pharmacologic therapy will be available for enhanced intestinal adaptation, control of gut motility, treatment of small bowel bacterial overgrowth, and treatment of rejection following small intestinal transplantation. J Org Chem, 2003 Aug 8, 68(16), 6079 - 82 Cytosporacin, a highly unsaturated polyketide: application of the ACCORD-ADEQUATE experiment to the structural determination of natural products; He H et al.; Cytosporacin (1), a novel antibacterial polyketide containing naphthopyranone and isochromandione moieties, was isolated from the fermentation broth of the fungus Cytospora rhizophorae . A (1)H-detected ACCORD-ADEQUATE pulse sequence that distinguished (2)J(CH) from (3)J(CH) correlations provided critical information for structural determination . NOE studies established the relative configuration and revealed the presence of two rotamers . A biosynthetic (13)C-labeling experiment indicated that cytosporacin was derived from acetate origin. Fish Shellfish Immunol, 2003 Sep, 15(3), 249 - 62 Structural and functional characterisation of the blood cells of the bivalve mollusc, Scrobicularia plana; Wootton EC et al.; Light and electron microscopical studies were carried out in order to characterise the blood cells of the bivalve mollusc, Scrobicularia plana . Three types of haemocytes were recognised: eosinophilic granular haemocytes, basophilic granular haemocytes and basophilic agranular haemocytes . The eosinophilic granulocytes were vesicular and contained large granules whereas the basophilic granulocytes were found to contain small granules and glycogen 'lakes' . The basophilic agranular haemocytes were significantly smaller than the granular haemocytes and had a high nucleus to cytoplasm ratio . Functional characterisation of the blood cells identified activity for the lysosomal enzymes: acid phosphatase, beta-glucuronidase, non-specific esterase and arylsulphatase . There was also a weak staining reaction for phenoloxidase and peroxidase activities . Phagocytosis of Gram-positive bacteria was demonstrated by the haemocytes and antibacterial activity was shown by cell-free haemolymph . Assays to determine release of reactive oxygen species from the haemocytes did not detect any reactive oxygen generation. Yao Xue Xue Bao, 2003 Apr, 38(4), 264 - 7 {Synthesis and antibacterial activity of 7-(4-acylamino-thiocarbamoyl-1-piperazinyl) fluoroquinolone analogues in vitro}; Qu LB et al.; AIM: To synthesize new fluoroquinolone analogues as antibacterial compounds . METHODS AND RESULTS: By reaction of acryl chloride(chloro-carbonic ester) with sodium sulfocyanate, acyl isosulfocyanic ester were easily obtained . Twelve 7-(4-acylamino-thiocarbamoyl-1-piperazinyl) fluoroquinolone analogues (1-12) were synthesized through modifying the 7-piperazine of norflorxacin and ciprofloxacin with isosulfocyanic ester synthesized above . The structures of synthesized compounds were characterized by 1HNMR, IR and elemental analysis . CONCLUSION: Antibacterial activities of the new compounds were evaluated in vitro compared with norflorxacin . Compounds 5, 7, 10 and 12 showed antibacterial activities. Yao Xue Xue Bao, 2003 Apr, 38(4), 260 - 3 {Synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol}; Ye FQ et al.; AIM: To study the synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol . METHODS: Pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol were synthesized primarily from 2-methyl-5-nitroimidazol, norfloxacin, ciprofloxacin, enoxacin via nucleophilic substitution and esterification . The antibacterial activity of the nine target compounds were tested . RESULTS: Nine new compounds were synthesized (IIa-c and IIIa-f) . The structure of the title compounds were identified by 1HNMR, MS as well as elementary analysis . CONCLUSION: Compounds IIa, IIb and IIc showed antibacterial activity, and were worth further studying. J Biomed Mater Res A, 2003 Aug 1, 66(2), 266 - 74 Preparation of antibacterial silver-doped silica glass microspheres; Kawashita M et al.; Various types of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized . Colorless and chemically durable materials that slowly release silver ions are, however, still need to be developed . The present authors have previously shown that when a silica glass doped with silver and aluminium ions is prepared using the sol-gel method, the resultant product is colorless, chemically durable, and slowly releases silver ions into water over a long period . The doped silica glass takes a form of microspheres <1 microm in diameter, it is easily mixed with organic polymers, and the mixture can be formed into a thin film or fine fibers, etc . We report on the preparation of silver doped silica glass microspheres having a diameter =1 microm, using the sol-gel method . Initially, tetraethoxysilane was partially prehydrolyzed by water in ethanol, and then aluminium triisopropoxide was added to the solution to form Si-O-Al bonds . Finally, an ammonia solution containing silver nitrate was added to form silica microspheres doped with silver ion together with aluminium ions . The results show monodispersed microspheres 0.4-0.6 microm in diameter were obtained with nominal compositions of Si/Al/Ag = 1/0.01-0.03/0.003-0.03, with a molar ratio of Al/Ag = 1-3.3 . The microspheres were colorless, showed a high chemical durability, and slowly released silver ions into water at 37 degrees C . Microspheres with the composition Si/Al/Ag = 1/0.01/0.01 showed excellent antibacterial activity against Escherichia coli . The minimum inhibitory concentration (MIC) of the microspheres was 400, which is less than the MIC value (800) of commercial antibacterial materials . J Inorg Biochem, 2003 Aug 1, 96(2-3), 393 - 400 Antifertility, antibacterial, antifungal and percent disease incidence aspects of macrocyclic complexes of manganese(II); Chaudhary A et al.; Macrocyclic complexes of Mn(II) were synthesized by template condensation using 2,6-diaminopyridine and diethylenetriamine with malonic, succinic, glutaric and adipic acids . The reaction proceeded smoothly to completion . These 16- to 24-membered N(6), but behaving as tetradentate, macrocyclic complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray spectral analyses . The elemental analyses are consistent with the formation of complexes {Mn(N(6)L(n))Cl(2)} . All the complexes are stable and monomeric in nature, as indicated by the molecular weight determinations . The spectral studies confirmed the proposed framework of the new macrocyclic complexes and indicated an octahedral geometry around the central metal atom . The complexes were screened in vitro against a number of pathogenic fungi and bacteria to assess their growth-inhibiting potential . The testicular sperm density, sperm morphology, sperm motility, density of cauda epididymis, spermatozoa and fertility in mating trials and the biochemical parameters of the reproductive organs of the rat were examined and are discussed. Anim Biotechnol, 2003 May, 14(1), 7 - 12 Molecular characterization of lysozyme type II gene in rainbow trout (Oncorhynchus mykiss): evidence of gene duplication; Mitra A et al.; Rainbow trout (Oncorhynchus mykiss) have two types of lysozyme . Type II lysozyme differs from type I by only one amino acid, but only type II lysozyme has significant bactericidal activity . Due to this novel antibacterial property, lysozyme type II appears to be a candidate gene for enhancing disease resistance in fish as well as livestock species . Using polymerase chain reaction the lysozyme type II gene was amplified from genomic DNA isolated from rainbow trout . Two amplified fragments of 2041 and 2589 bp were observed . Sequencing revealed both amplicons were lysozyme genes having nearly identical nucleotide sequences, except the longer fragment has 548 base pairs inserted in intron 2 at nucleotide position 513 and a few point mutations within intron 2 . Both versions of trout lysozyme type II gene were comprised of four exons and three introns . We also demonstrated that trout lysozyme is most likely encoded by these two different genes. Zh Mikrobiol Epidemiol Immunobiol, 2003 May-Jun, (3), 43 - 50 {Detection of Treponema pallidum DNA and RNA in clinical material from patients with syphilis at different stages}; Rodionova EN et al.; The results of the development and approval of methods for the detection of T . pallidum DNA and 16S rRNA in clinical material (blood plasma, serous exudates) are presented . T . pallidum DNA was detected with the use of primers to the gene coding protein with a moleculat weight of 47 kD and T . pallidum RNA, with the primers to gene 16S rRNA . The isolation, reverse transcription and amplification of DNA and RNA was carried out in the presence of inner DNA and RNA control respectively . The analytical sensitivity of the developed method was 400 DNA copies per ml . The characteristics of analytical and diagnostic specificity were 100% . The specimens of blood plasma, taken from 292 patients with syphilis at different stages before specific antibacterial therapy, were tested by the PCR . The detection rate of T . pallidum DNA and RNA in blood plasma was, respectively, 91% and 100% in primary seropositive syphilis, 68% and 79% in secondary early syphilis, 19% and 26% in latent unverified syphilis . In secondary relapsing syphilis T . pallidum DNA and RNA were detected in 92% and in latent early syphilis, in 14% of patients . T . pallidum nucleic acids were detected in 1 patient at the seronegative period of primary syphilis . No positive result was obtained in the PCR analysis in any of the patients with diagnosed seroresistance, latent late syphilis and tertiary syphilis . In the study of material taken from chancres of 11 syphilis patients the data obtained by dark-field microscopy and the PCR analysis completely coincided. FEBS Lett, 2003 Jul 31, 548(1-3), 5 - 10 Transferrins selectively cause ion efflux through bacterial and artificial membranes; Aguilera O et al.; Serum transferrin, ovotransferrin and lactoferrin constitute the most notable members of the transferrin family . Among their multiple biological functions, they possess an important antibacterial activity . These proteins can permeate the Escherichia coli outer membrane, reaching the inner membrane where they selectively cause permeation of ions, resulting in dissipation of the electrical potential without affecting the pH gradient . Similar results were obtained using artificial liposomes, suggesting a direct action of the proteins on the lipid bilayer, which was mediated by detectable conformational changes in their structures. Clin Pharmacokinet, 2003, 42(10), 863 - 81 Bone as an effect compartment : models for uptake and release of drugs; Stepensky D et al.; "Bone-seeking agents" are drugs characterised by high affinity for bone, and are disposed in bone for prolonged periods of time while maintaining remarkably low systemic concentrations . As a consequence, the bone becomes a reservoir for bone-seeking agents, and a site of both desirable and adverse effects, depending on the pharmacological activities of the specific agent . For some agents, significant systemic effects may also be produced following their prolonged release from bone, a process that is governed mostly by the rate of bone remodelling . This review covers the pharmacokinetic and pharmacodynamic features of bone-seeking agents with different pharmacological properties, including drugs (bisphosphonates, drug-bisphosphonate conjugates, radiopharmaceuticals and fluoride), bone markers (tetracycline, bone imaging agents) and toxins (lead, chromium, aluminium) . In addition, drugs that do not possess bone-seeking properties but are used for therapy of bone diseases (such as antibacterials for treatment of osteomyelitis) are discussed, along with targeting of these drugs to the bone by conjugation to bone-seeking agents, local delivery systems, and other approaches.The pharmacokinetic and pharmacodynamic behaviour of bone-seeking agents is extremely complex due to heterogeneity in bone morphology and physiology . This complexity, accompanied by difficulties in human bone research caused by ethical and other limitations, gave rise to modelling approaches to study bone drug disposition . This review describes the pharmacokinetic models that have been proposed to describe the pharmacokinetic behaviour of bone-seeking agents and predict bone concentrations of these agents for different doses and patient populations . Models of different types (compartmental and physiologically based) and of different complexity have been applied, but their relevance to drug effects in the bone tissue is limited since they describe the behaviour of the "average" drug molecule . Understanding of the cellular and molecular processes responsible for the heterogeneity of bone tissue will provide better comprehension of the influence of microenvironment on drug bone disposition and the resulting pharmacological response. Biomed Chromatogr, 2003 Jul, 17(5), 297 - 305 The benefit of the retrofitting of a conventional LC system to micro LC: a practical evaluation in the field of bioanalysis with fluorimetric detection; Roy S et al.; The interests in liquid micro-chromatography (higher column efficiencies, increase in sensitivity) are now well established . The enhancement of fluorimetric response induced by the reduction of the inner diameter of columns (4.6, 3.0, 1.0 and 0.3 mm respectively) coupled with adapted detection cells to control the loss of efficiency (8 micro L for the two first columns and 100 nL for the two smaller ones) has been studied in the bioanalytical field, using the plasma determination of native fluorescent antibacterial agents: fluoroquinolones . Ten-fold enhancement of the signal can easily be obtained when substituting a 0.3 mm i.d . column and 100 nL detection cell for a 4.6 mm i.d . column, and 8 micro L detection cell . In addition to inner diameter reduction, the detection cell geometry appears to be an essential parameter to obtain the best enhancement of the recorded signal . Hence, the enhancement of signal with micro-chromatography with fluorimetric detection appears to be a compromise between column inner diameter and flow cell volume reduction . J Pharm Sci, 2003 Aug, 92(8), 1648 - 53 Uptake, distribution and release of 14C-triclosan in human gingival fibroblasts; Mustafa M et al.; Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is an antibacterial agent included in dentifrices and mouth rinses . Previously, we reported that triclosan reduces the production of the inflammatory mediators in gingival fibroblasts . The aim of this study was to investigate the uptake, distribution, and release of (14)C-triclosan in gingival fibroblasts . Time-course studies showed that the uptake of (14)C-triclosan in cytoplasmic and nuclear fraction started within the first minute of incubation, increased gradually, and reached constant levels after 1 h in the nuclear fraction and slightly increased in the cytoplasmic fraction between 3 and 24 h . The distribution of (14)C-triclosan in the cytoplasmic and the nuclear fractions was, on an average, 84 and 16%, respectively . Autoradiographic results based on transmission electron microscopy confirmed the distribution of (14)C-triclosan in the cytoplasm and nucleus of the cell . The release of (14)C-triclosan showed that the radioactivity of the agent in the medium gradually increased during the first hour of incubation and then reached steady-state levels . After repeated washing of preloaded fibroblasts, the level of (14)C-triclosan in the cytoplasmic fraction decreased by 77% whereas the level in the nuclear fraction remained unchanged . Our results demonstrate that triclosan is distributed in the cytoplasm and remains associated with the nucleus of gingival fibroblasts, suggesting that the agent may affect the intracellular signal pathways involved in the production of inflammatory mediators . Eur J Clin Microbiol Infect Dis, 2003 Jul, 22(7), 397 - 407 Epub 2003 Jun 26. Antifungal activity of nonantifungal drugs; Afeltra J et al.; The antifungal activity of synthetic, nonchemotherapeutic compounds, antineoplastic agents and antibacterial drugs, such as sulphonamides, has been known since the early 20th century (1932) . In this context, the term "nonantifungal" is taken to include a variety of compounds that are employed in the management of pathological conditions of nonfungal infectious etiology but have been shown to exhibit broad-spectrum antifungal activity . In this review, the antifungal properties of compounds such as chlorpromazine, proton pump inhibitors, antiarrhythmic agents, cholesterol-lowering agents, antineoplastic and immunosuppressive agents, antiparasitic drugs and antibiotics are described . Since fungi are eukaryotic cells, they share many pathways with human cells, thus increasing the probability of antifungal activity of "nonfungal drugs" . The potential of these drugs for treatment of fungal infections has been investigated sporadically using the drugs alone or in combination with "classic" antifungal agents . A review of the literature, supplemented with a number of more recent investigations, suggests that some of these compounds enhance the activity of conventional antifungal agents, eliminate natural resistance to specific antifungal drugs (reversal of resistance) or exhibit strong activity against certain fungal strains in vitro and in animal models . The role of these agents in the epidemiology and in the clinical manifestations of fungal infections and the potential of certain drugs for treatment of invasive fungal infections require further investigation. Biotechnol Lett, 2003 Feb, 25(3), 213 - 8 High expression of a human lactoferrin in transgenic tobacco cell cultures; Choi SM et al.; Transgenic Nicotiana tabacum cell lines were developed expressing the human lactoferrin gene driven by the oxidative stress-inducible peroxidase (SWPA2) promoter . Western blot analysis showed the accumulation of both the full-length human lactoferrin protein as well as a immuno-reactive truncated fragment . Accumulation of human lactoferrin as monitored by ELISA increased proportionally to cell growth and reached a maximal (up to 4.3% of total soluble proteins) at the stationary phase of growth . Protein extracts from transgenic tobacco cells exhibited antibacterial activity. Antimicrob Agents Chemother, 2003 Aug, 47(8), 2526 - 37 Unique biological properties and molecular mechanism of 5,6-bridged quinolones; Macinga DR et al.; We have characterized an early series of 5,6-bridged dioxinoquinolones which behaved strikingly different from typical quinolones . The 5,6-bridged dioxinoquinolones inhibited Escherichia coli DNA gyrase supercoiling activity but, unlike typical quinolones, failed to stimulate gyrase-dependent cleavable complex formation . Analogous unsubstituted compounds stimulated cleavable complex formation but were considerably less potent than the corresponding 5,6-bridged compounds . Consistent with a previous report (M . Antoine et al., Chim . Ther . 7:434-443, 1972) and contrary to established quinolone SAR trends, a compound with an N-1 methyl substitution (PGE-8367769) was more potent than its analog with an N-1 ethyl substitution (PGE-6596491) . PGE-8367769 was shown to antagonize ciprofloxacin-mediated cleavable complex formation in a dose-dependent manner, suggesting an interaction with the gyrase-DNA complex that overlaps that of ciprofloxacin . Resistance to PGE-8367769 in E . coli was found to arise through missense mutations in gyrA, implicating DNA gyrase as the primary antibacterial target . Notably, only 1 of 15 distinct mutations selected on PGE-8367769 (D87G) has previously been implicated in quinolone resistance in E . coli . The remaining 14 mutations (E16V, G31V, R38L, G40A, Y50D, V70A, A84V, I89L, M135T, G173S, T180I, F217C, P218T, and F513C) have not been previously reported, and most were located outside of the traditional quinolone resistance-determining region . These novel GyrA mutations decreased sensitivity to 5,6-bridged dioxinoquinolones by four- to eightfold, whereas they did not confer resistance to other quinolones such as ciprofloxacin, clinafloxacin, or nalidixic acid . These results demonstrate that the 5,6-bridged quinolones act via a mechanism that is related to but qualitatively different from that of typical quinolones. Int Arch Allergy Immunol, 2003 Jul, 131(3), 195 - 200 Sera from patients with multiple drug allergy syndrome contain circulating histamine-releasing factors; Asero R et al.; BACKGROUND: A subset of drug-intolerant patients show a marked propensity to react to several chemically unrelated antibacterial drugs . This condition is termed multiple drug allergy syndrome (MDAS) . The pathogenesis of MDAS is still unclear . A possible mechanism is that a nonspecific patient-related factor leading to direct histamine release from mast cells and basophils is involved . We investigated whether a patient-related facilitating factor such as the clinically unapparent presence of circulating histamine-releasing factors may represent a nonspecific mechanism underlying drug-induced histamine release in patients with MDAS . METHODS: 38 otherwise healthy adults with a history of acute urticaria following the ingestion of antibacterial drugs {18 subjects with MDAS (patients) and 20 monosensitive subjects (drug-allergic controls) on the basis of both clinical history and single-blind peroral challenges with alternative substances} and 20 subjects without a history of drug allergy (normal controls) underwent an autologous serum skin test (ASST) . IgE specific for beta-lactams was measured in sera from 25 subjects (11 patients and 14 drug-allergic controls) with a history of amoxicillin intolerance . Sera from 13 patients and 5 drug-allergic controls (all positive on ASST) were used in the in vitro histamine release assay using basophils from 3 normal donors . RESULTS: 17 of 18 patients (94%) versus 8 of 20 drug-allergic controls (40%) showed an unequivocal wheal-and-flare reaction on ASST (p < 0.05) . Skin reactions were generally more intense in the patient group . In one MDAS patient, the ASST was not assessable due to dermographism . No normal control was positive on ASST . Sera from 3 of 13 patients (23%) versus 0 of 6 drug-allergic controls (not significant) induced significant histamine release from basophils of normal donors . IgE specific for beta-lactams was detected in sera from 1 of 11 patients (9%) versus 5 of 14 drug-allergic controls (36%) (not significant) . CONCLUSION: Most patients with MDAS and more than one third of subjects with a history of hypersensitivity to a single antibacterial drug were characterized by the presence of circulating histamine-releasing factors . Such factors might play a role in drug-induced adverse reactions observed in these patients . Farmaco, 2003 Aug, 58(8), 569 - 72 Synthetic and antibacterial studies on some new furanopeptides; Poojary B et al.; A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent . Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis . Some of the selected compounds are also tested for their antibacterial properties. Klin Med (Mosk), 2003, 81(6), 61 - 5 {Principles of antibacterial therapy of sepsis}; Igonin AA et al.; For the last decade understanding of sepsis pathogenesis has changed much . A significant role pathogenesis of sepsis is assigned to systemic inflammatory reaction provoking imbalance in different links of antiinfection protection . Antibiotics remain the only available group of drugs which can improve prognosis in sepsis . The authors consider general principles of empiric choice of antibiotics in sepsis and its complications. Bioorg Med Chem Lett, 2003 Aug 18, 13(16), 2805 - 8 Synthesis and evaluation of ether and halogenated derivatives of mannopeptimycin glycopeptide antibiotics; Sum PE et al.; A number of 6-O-ether and 4-O-ether derivatives of mannopeptimycin-alpha with different steric bulk and lipophilicity were synthesized for structure-activity relationship study . Novel iodo and bromo mannopeptimycin-alpha were also prepared . These compounds were synthesized via electrophilic aromatic substitution . Many of the new ether derivatives exhibited potent antibacterial activity against Gram-positive resistant strains including VRE, MRSA, and PRSP. Bioorg Med Chem Lett, 2003 Aug 18, 13(16), 2715 - 8 Structure--activity relationships of the peptide deformylase inhibitor BB-3497: modification of the P2' and P3' side chains; Davies SJ et al.; Structural modifications to the peptide deformylase inhibitor BB-3497 are described . In this paper, we describe the initial SAR around this lead for modifications to both the P2' and P3' side chains . Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2' and P3' positions of the inhibitor backbone . The data from this study highlights the potential for modification at the P2' and P3' positions to optimise the physicochemical properties. Bioorg Med Chem Lett, 2003 Aug 18, 13(16), 2709 - 13 Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain; Davies SJ et al.; Structural modifications to the peptide deformylase inhibitor BB-3497 are described . In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain . Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit . Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile. Bioorg Med Chem Lett, 2003 Aug 18, 13(16), 2641 - 5 Pyrimidinone antibiotics--heterocyclic analogues with improved antibacterial spectrum; Brands M et al.; We report the synthesis and pharmacological evaluation of new derivatives of the natural dipeptide antibiotic TAN 1057 A,B containing heterocycles either in the beta-amino acid side chain or as mimics of the urea function . In the course of this program, we identified novel analogues that display activity towards a broader panel of Gram-positive bacteriae. Biochemistry, 2003 Jul 29, 42(29), 8663 - 70 Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity; Gaczynska M et al.; Substrate-specific inhibition of the proteasome has been unachievable despite great interest in proteasome inhibitors as drugs . Recent studies demonstrated that PR39, a natural proline- and arginine-rich antibacterial peptide, stimulates angiogenesis and inhibits inflammatory responses by specifically blocking degradation of IkappaBalpha and HIF-1alpha by the proteasome . However, molecular events involved in the PR39-proteasome interaction have not been elucidated . Here we show that PR39 is a noncompetitive and reversible inhibitor of the proteasome function . This effect is achieved by a unique allosteric mechanism allowing for specific inhibition of degradation of selected proteins without affecting total proteasome-dependent proteolysis . Atomic force microscopy (AFM) studies demonstrate that 20S and 26S proteasomes treated with PR39 or its derivatives exhibit serious perturbations in their structure and their normal allosteric movements . These effects are universal for proteasomes from yeast to human . The shortest functional sequence derived from PR39 still showing the allosteric inhibitory effect consists of eleven NH(2)-terminal residues containing essential three NH(2)-terminal arginines . The noncompetitive and reversible in vitro action of PR39 and its truncated derivatives is matched by the ability of the peptides to induce angiogenesis in vivo . We postulate that PR39 changes conformational dynamics of the proteasomes by interactions with the noncatalytic subunit alpha7 in a way that prevents the enzyme from cleaving the substrates of unique structural constraints. Curr Opin Allergy Clin Immunol, 2003 Aug, 3(4), 275 - 81 Quinolone hypersensitivity; Campi P et al.; PURPOSE OF REVIEW: Quinolones are potent antibacterial agents that can cause drug hypersensitivity reactions affecting different organs . A better understanding of the underlying mechanism and the level of crossreactivity within different quinolones is needed to handle and prevent these diseases . RECENT FINDINGS: The adverse side-effects caused by quinolones are the result of different immunological mechanisms and cause quite different diseases . The development of an assay detecting quinolone-specific IgE revealed specific antibodies in more than 50% of patients with immediate-type reactions, and the majority of sera also reacted with related compounds . In maculopapular drug exanthemas caused by ciprofloxacin, specific T cells could be detected and cloned . They reacted with ciprofloxacin directly, and crossreactivity to related compounds was detected in approximately 50% of the clones . SUMMARY: Quinolones can cause drug hypersensitivity reactions by different immunological mechanisms . In-vitro analysis suggests that crossreactivity is common. Am J Clin Dermatol, 2003, 4(8), 561 - 72 Differential diagnosis of severe cutaneous drug eruptions; Bachot N et al.; Adverse cutaneous reactions to drugs are frequent, mostly secondary to antibacterials, however, serious adverse cutaneous reactions are infrequent . Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of the same disease . They are the more severe drug eruptions, with a mortality around 30% for TEN . The confusion between erythema multiforme major and SJS means that erythema multiforme major is the main differential diagnosis . Skin disorders involving desquamation, in particular after pustulosis, are also common differential diagnoses . Mechanical or autoimmune blistering are also potential misdiagnoses of TEN/SJS . Hypersensitivity Syndrome (HSS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous drug reaction with often a long duration of eruption and serious other organ involvement . Exfoliative dermatitis, whether caused by psoriasis, dermatitis or lymphoma, can be thought of as a differential diagnosis of DRESS/HSS . Angio-immunoblastic lymphadenopathy, viral eruption and vasculitis are other differential diagnoses of DRESS/HSS . Prompt recognition of a severe drug reaction and withdrawal of the culprit drug is often the most important therapeutic action . Alternatively, a delay in starting a specific treatment for a disease misdiagnosed as a drug eruption could be deleterious. Zhong Yao Cai, 2003 Jan, 26(1), 21 - 2 {Studies on chemical constituents of mycelium of fungus Cephalosporium sp . AL031(II)}; Bi Y et al.; Three compounds were isolated from the mycelium of the fungus Cephalosporium sp . AL031 whose metabolites have been proven to possess antifungal and antibacterial activities . Based on the spectral data and elemental analysis, they were identified as 3-hydroxy-ergosta-7,22-dien-6-one(A), penicillic acid(B), 4-hydroxy-3,6-dimethyl-2-pyrone(C) . All of these compounds were obtained from the culture medium of this fungus for the first time. Akush Ginekol (Sofiia), 2003, 42(3), 31 - 2 {Our experience with cedax (ceftibuten) in the obstetrical and gynecological practice}; Lazarov L et al.; Cedax is an oral third generation cephalosporin for use with a wide spectrum of antibacterial activity . It has been made a comparative study between Cedax and other third generation cephalosporins in 40 pregnant women with asymptomatic bacteriuria . The authors made a conclusion Cedax is a preferred antibacterial drug for treatment of similar infections of pregnancy because of his easy application way and the absence of side effects. Electrophoresis, 2003 Jun, 24(12-13), 2111 - 8 Determination of low-molecular-mass quaternary ammonium compounds by capillary electrophoresis and hyphenation with mass spectrometry; Buchberger W et al.; The determination of quaternary ammonium ions by capillary electrophoresis (CE) is reviewed . The analytes include tetraalkylammonium and alkylbenzyldimethylammonium compounds frequently used as antiseptic and antibacterial agents as well as in various household products, several plant growth regulators and herbicides, by-products in bile acid sequestrants, and a range of anticholinergic drugs . Besides direct and indirect UV detection, hyphenation with electrospray mass spectrometry is particularly suited for quaternary ammonium ions and may lower the detection limits by two orders of magnitude . In comparison with established liquid chromatographic techniques, CE may exhibits superior separation efficiency . Applications in routine analysis have demonstrated that CE is reliable and robust enough to represent a real alternative to chromatography. Am J Chin Med, 2003, 31(2), 321 - 6 Effect of apitherapy in piglets with preweaning diarrhea; Choi SH et al.; This study was designed to examine the therapeutic effect of honeybee (Apis mellifera L.) venom in piglets with bacterial diarrhea Comparison between bee venom- and drug-treated groups was our main concern in the present study . Preweaning piglets were assigned to treated and non-treated control groups . In the treated group, 47 piglets were acupunctured with the worker honeybee once a day for three consecutive days . Two acupoints, GV-1 (Jiao-chao) and ST-25 (Hai-men), were selected for apitherapy . In the control group, 44 piglets were intramuscularly injected with a standard dose of a known antibacterial drug, colistin sulfate (300,000 IU/kg of body weight), and an antidiarrheal drug (berberine, 2 ml/kg) once a day for three consecutive days . At post-treatment, 90.9% of the control piglets and 93.6% of piglets in the treated group recovered from bacterial diarrhea . Bee acupuncture therapy did not show any side effects such as allergy, intoxication, hemorrhage or infection . It is concluded that bee venom therapy was effective in controlling bacterial diarrhea in preweaning piglets. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2003 Jun, 20(2), 255 - 9, 280 {Expression of recombinant human beta-defensin-2 gene with C terminal of double marks of Myc and poly-histidine in transfected COS-7 cells}; Cai S et al.; The aim of this study is to explore the possibility and technical itinerary of establishing an mammal engineering cell line in which hBD-2 can be effectively expressed, secreted, detected, separated and purified . The full hBD2 cDNA was inserted into the multi clone site of a eukaryotic expressive plasmid pcDNA3.1/Myc-His(+) and located closely at the upstream of two tag gene (myc and 6 Poly-histidines) so as to construct another recombinant eukaryotic expressive vector of hBD-2 gene: rpcDNA3.1/Myc-His/hBD-2 . By the use of RT-PCR with special primers, a band of 240 bp was amplified from COS-7 cells transfected by this recombinant plasmid, which matched full length of cDNA coding hBD2 plus myc epitope and 6 poly-histidines tags . Western blot analysis with specific anti-histidines antibody revealed that the lysate of COS-7 cells transfected by rpcDNA3.1/Myc-His/hBD-2 had a strong band with molecular weight of about 10 Kd that was approximate to the size of chiasmic peptide . Antibacterial activity assay showed that obvious bacterial inhibition occurred in both lysate and supernatant of COS-7 cells transfected by rpcDNA3.1/Myc-His/hBD-2. Biol Reprod, 2003 Nov, 69(5), 1593 - 9 Epub 2003 Jul 09. Temporal regulation of gene expression during the expected window of receptivity in the rhesus monkey endometrium; Okulicz WC et al.; Progesterone has been shown to regulate a number of genes and gene networks in the primate endometrium . This action of progesterone is essential to provide an appropriate milieu for embryo-endometrial communication that can lead to implantation and the successful initiation of pregnancy . A temporal regulation of endometrial genes is most likely required to achieve an appropriate state of receptivity in the primate endometrium . Using simulated menstrual cycles in the rhesus monkey, endometrial tissue was harvested at days that encompass the expected window of receptivity (4-10 days after the estradiol surge) and subsequently converted to cycle day-specific cDNA populations . Using differential display reverse transcriptase-polymerase chain reaction, 12 cDNA fragments were isolated and sequenced whose mRNA levels were elevated during this time frame . The temporal expression patterns of these mRNAs were confirmed by semiquantitative polymerase chain reaction . Two of these fragments exhibited high homology to previously characterized human genes: 1) secretory leukocyte protease inhibitor, also known as antileukoprotease, an endometrial neutrophil elastase inhibitor with antibacterial and anti-inflammatory properties; and 2) syncytin, also known as endogenous retrovirus W envelope protein, a highly fusogenic membrane glycoprotein that induces formation of giant syncytia and is believed to be important in decidual and placental development . The temporal regulation of these genes by progesterone supports their likely role in the orchestration of molecular and cellular events that are required to achieve a state of receptivity in the primate endometrium. J Med Chem, 2003 Jul 17, 46(15), 3371 - 81 Tethered dimers as NAD synthetase inhibitors with antibacterial activity; Velu SE et al.; The solution-phase parallel synthesis of tethered dimers was employed to identify lead inhibitors of bacterial NAD synthetase . Active dimers contained two aromatic end groups joined by a polymethylene linker, with one end group containing a permanent positive charge . Effective inhibitors of NAD synthetase also inhibited the growth of Gram-positive (but not Gram-negative) bacteria, including antibiotic-resistant strains . The desmethyl precursors of active inhibitors lacked a permanent positive charge and were inactive as either enzyme inhibitors or antibacterial agents . Similarly, a close structural analogue of the most active inhibitors contained two additional ether oxygens in the tether and was inactive in both assays . These results are consistent with the premise that NAD synthetase inhibition is responsible for the antibacterial actions and support further studies on NAD synthetase as a new target for antibacterial agents. Gastroenterology, 2003 Jul, 125(1), 47 - 57 Crohn's disease and the NOD2 gene: a role for paneth cells; Lala S et al.; BACKGROUND & AIMS: The NOD2 gene, which is strongly associated with susceptibility to Crohn's disease (CD) of the terminal ileum, interacts with bacterial lipopolysaccharide (LPS), inducing cellular activation . However, the mechanisms by which NOD2 mutations cause terminal ileitis are unknown, and NOD2 is expressed most highly by peripheral blood monocytes, which are distributed ubiquitously and readily respond to LPS via cell-surface receptors . Paneth cells on the other hand, are most numerous in the terminal ileum, are critically important in enteric antibacterial defense, and respond to LPS through as yet undefined pathways . We therefore determined if these specialized intestinal epithelial cells also expressed the NOD2 gene . METHODS: In situ hybridization, immunohistochemistry, and laser-capture microdissection were used to determine RNA and protein expression in tissue sections, and real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to quantitate gene expression in intestinal epithelial cells and peripheral blood mononuclear cells . RESULTS: NOD2 was detected readily in monocytes, but not in mature macrophages in the lamina propria or within granulomas, and levels declined as monocytes differentiated into macrophages in vitro, so that Caco-2 cells expressed more NOD2 mRNA than macrophages . NOD2 mRNA was enriched in crypts compared with villi, and in situ, Paneth cells were the most prominent cells expressing NOD2 in normal and CD-affected intestinal tissue, where they also strongly expressed tumor necrosis factor alpha (TNFalpha) RNA . CONCLUSIONS: The NOD2 gene product is most abundant in Paneth cells in the terminal ileum, which could therefore play a critical and hitherto unrecognized role in the pathogenesis of NOD2-associated CD. Life Sci, 2003 Aug 1, 73(11), 1401 - 12 Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-alpha, iNOS, and IL-12 production in LPS-stimulated macrophages; Lee DU et al.; Berberine, a major alkaloidal component of Coptidis Rhizoma, has antibacterial activity, anti-inflammatory effect, antitumor and antimotility actions . We suggested that one of possible mechanisms of anti-bacterial activity of berberine may be based on the production of interleukin (IL)-12 . Recently 13-alkyl-substituted berberines were shown to be better activity than berberine against certain bacteria species and human cancer cell lines . In the present study, therefore, the effects of 13-methylberberine (13-MB) and 13-ethylberberine (13-EB) on the production of IL-12 and expression of iNOS, TNF-alpha and COX-II were investigated using macrophages in culture . In LPS-stimulated RAW 264.7 cells, these alkaloids decreased the nitrites, concentration-dependently . The concentration of 50% inhibition of NO production (IC50) by 13-MB and 13-EB was 11.64 and 9.32 microM, respectively . The suppressed expression of iNOS protein was responsible for the reduction of NO production . Neither the expression of mRNA of iNOS, COX-II and TNF- alpha nor protein of COX-II and TNF-alpha was affected by both 13-MB and 13-EB, but production of PGE2 in LPS-stimulated RAW 264.7 cells was significantly reduced . Another striking finding of the present study is that 13-MB and 13-EB increased production of IL-12 in LPS-treated splenic macrophages . These results indicate that posttranscriptional regulatory mechanism of iNOS gene expression by 13-MB and 13-EB is involved, and COX-II activity is inhibited by 13-MB and 13-EB, respectively . In conclusion, the present study demonstrates that 13-methyl- and 13-ethylberberine alkaloids can be useful as an immunotherapeutic compound for induction of IL-12, which is potentially applicable for tumors, infectious disease, and airway inflammation. Microbes Infect, 2003 Jul, 5(9), 781 - 8 Outer membrane protein A deficient Escherichia coli activates neutrophils to produce superoxide and shows increased susceptibility to antibacterial peptides; Fu H et al.; The outer membrane protein A (OmpA) of Gram-negative bacteria has been ascribed multiple functions including maintenance of structural membrane integrity and porin activity . OmpA has also been implicated in various host defense processes in that it contributes to bacterial serum resistance and activates certain immune cells . Recently, OmpA was shown to be the molecular target for neutrophil elastase (NE), and Escherichia coli mutants lacking OmpA were resistant to the bactericidal effects of NE . In addition to NE, neutrophils use a variety of other antibacterial effector molecules such as oxygen radicals and bactericidal peptides or proteins . The aim of this study was to investigate the role of E . coli OmpA regarding susceptibility to other neutrophil-derived defense systems . We found that OmpA-deficient (OmpA(-)), but not wild-type isogenic, E . coli activated human neutrophils to produce oxygen radicals intracellularly . This activation was found to require an intact neutrophil cytoskeleton but was independent of bacterial phagocytosis . Furthermore, we found that the OmpA(-) strain was more susceptible to membrane-acting bactericidal peptides than the wild-type strain, although the susceptibility to different oxygen radicals was independent of the presence of OmpA . Taken together, these data suggest an important role for OmpA in the context of bacteria vs . host interactions. Biochem J, 2003 Oct 15, 375(Pt 2), 405 - 13 Lipid binding and membrane penetration of polymyxin B derivatives studied in a biomimetic vesicle system; Katz M et al.; Understanding membrane interactions and cell-wall permeation of Gram-negative bacteria is of great importance, owing to increasing bacterial resistance to existing drugs and therapeutic treatments . Here we use biomimetic lipid vesicles to analyse membrane association and penetration by synthetic derivatives of polymyxin B (PMB), a potent naturally occurring antibacterial cyclic peptide . The PMB analogues studied were PMB nonapeptide (PMBN), in which the hydrophobic alkyl residue was cleaved, PMBN diastereomer containing D-instead of L-amino acids within the cyclic ring (dPMBN) and PMBN where the hydrophobic alkyl chain was replaced with an Ala6 repeat (Ala6-PMBN) . Peptide binding measurements, colorimetric transitions induced within the vesicles, fluorescence quenching experiments and ESR spectroscopy were applied to investigate the structural parameters underlying the different membrane-permeation profiles and biological activities of the analogues . The experiments point to the role of negatively charged lipids in membrane binding and confirm the prominence of lipopolisaccharide (LPS) in promoting membrane association and penetration by the peptides . Examination of the lipid interactions of the PMB derivatives shows that the cyclic moiety of PMB is not only implicated in lipid attachment and LPS binding, but also affects penetration into the inner bilayer core . The addition of the Ala6 peptide moiety, however, does not significantly promote peptide insertion into the hydrophobic lipid environment . The data also indicate that the extent of penetration into the lipid bilayer is not related to the overall affinity of the peptides to the membrane. Acta Pol Pharm, 2003 Jan-Feb, 60(1), 75 - 9 Synthesis and antibacterial properties of 4-sulfonamidopyrimidine derivatives; Cieplik J et al.; The synthesis of derivatives of 4-aryl-6-methyl-sulfonamido-2-phenyl-5-carboxypyrimidine acid was presented and antibacterial activity of the obtained compounds was investigated. Acta Pol Pharm, 2003 Jan-Feb, 60(1), 41 - 4 Synthesis and biological action of 3-R-4-substituted-delta2-1,2,4-triazoline-5-thione; Dobosz M et al.; In the reaction of hydroiodide of methyl ester of 3-thiocarbazic acid with diethylamine and morpholine hydroiodide of 2-amino-1-substituted-guanidine {I-II} were obtained . These compounds were then converted to respective 3-R-4-substituted-delta2-1,2,4-triazoline-5-thione {III-X} in the reaction with isothiocyanates . Some of these compounds were screened for their antibacterial activities. Drug Ther Bull, 2003 Jun, 41(6), 43 - 6 Dilemmas when managing cellulitis; The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma; Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The NetherlandsGenes controlling antibacterial resistance may be important in the hygiene hypothesis, which states that lack of bacterial infections during childhood would favor development of allergic disease . We, therefore, studied whether Nramp1 (Slc11a1) alleles, which determine susceptibility (Nramp1(s)) or resistance (Nramp1(r)) to intracellular bacteria, affect the efficacy of heat-killed Mycobacterium vaccae in the treatment of allergic asthma in a mouse model . Treatment of OVA-sensitized Nramp1(s) mice with M . vaccae suppressed airway hyperresponsiveness, airway eosinophilia, Ag-specific IgE, and IL-4 and IL-5 production after OVA aerosol challenge . In contrast, M . vaccae hardly affected these parameters in Nramp1(r) mice . In addition, The Nramp1 gene affected both T cell-mediated responses to M . vaccae in vivo and the level of macrophage activation after stimulation with M . vaccae in vitro . In conclusion, the efficacy of M . vaccae in preventing allergic and asthmatic manifestations in a mouse model is strongly affected by Nramp1 alleles . These findings could have important implications for the future use of mycobacteria and their components in the prevention or treatment of allergic asthma . A new link is described between genes, the environment, and the development of allergy, in which the Nramp1 gene fine tunes the hygiene hypothesis. Ann Dermatol Venereol, 2003 May, 130(5), 519 - 21 {Adverse cutaneous reaction to celecoxib: 6 cases}; Murr D et al.; INTRODUCTION: Our objective was to characterize adverse cutaneous reactions to celecoxib, a new non steroidal anti-inflammatory drug . PATIENTS AND METHODS: A retrospective study of 6 consecutive patients . RESULTS: The average delay before the onset of the reaction was 10.2 days for patients taking the medication for the first time and 48 hours for one patient taking the drug for the second time . Two patients had fever . Patients presented with an exanthema and in most cases an edema of the face . Buccal mucosa was involved in two patients, and one patient had minimal blister lesions . In five of the six patients, minor and transitory biological abnormalities were found . The intrinsic imputability of the celecoxib was I3 (C3S2) in all the cases . DISCUSSION: Our cases are similar to those reported by the French drug regulatory agency (Pharmacovigilance) . Usually the adverse cutaneous reactions were not too severe, with maculo-papulo exanthema and edema of the face . The reactions due to celecoxib are more frequent than those due to other non steroidal anti-inflammatory drugs (7.5% versus 4.1%), but severe cases are rarely reported . Besides, an allergic history to sulphonamide contraindicates celecoxib . However celecoxib does not have the aromatic amine common to antibacterial sulphonamides, and there is no proof of cross reactions between these two families . Furthermore, this amine is usually associated with drug reaction severity, which could explain why severe cases due to celecoxib are rare. Chem Pharm Bull (Tokyo), 2003 Jul, 51(7), 870 - 1 Jatrophenone, a novel macrocyclic bioactive diterpene from Jatropha gossypifolia; Ravindranath N et al.; A novel macrocyclic diterpene, jatrophenone, has been isolated from the whole plant of Jatropha gossypifolia . The structure of the compound was established by detailed studies of its one- and two-dimensional (1D and 2D) NMR spectra . The compound possesses significant antibacterial activity. Eur J Gastroenterol Hepatol, 2003 Jun, 15(6), 627 - 34 Crohn's disease: a defensin deficiency syndrome? Fellermann K, Wehkamp J, Herrlinger KR, Stange EF. This comprehensive review promotes the novel concept that a defensin deficiency, i.e . lack of mucosal peptide antibiotics, may play a pivotal role in the aetiopathogenesis of Crohn's disease . Such an impaired function of this chemical barrier is consistent with the epidemiological relationship of good domestic hygiene with the incidence of inflammatory bowel diseases . The disregulated adaptive immune system, formerly believed to be the major cause in the development of Crohn's disease, may reflect only the primary break of the mucosal defence since the immune response is mostly directed against lumenal bacteria . Recent work has identified five different defensins expressed in colonic mucosa . In contrast to ulcerative colitis, Crohn's disease is characterised by an impaired induction of human beta defensins 2 and 3 . This deficient induction may be due to changes in the intracellular transcription by NFkappaB and the intracellular peptidoglycan receptor NOD2, mutated in Crohn's disease . These findings are consistent with the mucosal attachment of lumenal bacteria in inflammatory bowel diseases and the frequent occurrence of other infectious agents . The hypothesis of an impaired mucosal antibacterial activity is also consistent with the benefit from antibiotic or probiotic treatment in certain inflammatory bowel disease states. Patol Fiziol Eksp Ter, 2003 Apr-Jun, (2), 15 - 7 {Effectiveness and mechanism of action of a new plant complex drug in nonspecific inflammatory processes in the bronchopulmonary system}; Aleksandrova AE et al.; The elixir Bronchofit is an aqueous-alcoholic extract from 7 kinds of plants . It is a balanced compound, rich in biologically active substances including essential oils and flavonoids, possessing a wide spectrum of pharmacological activity . On the model of frog's palate the elixir enhanced the transport function of the ciliated epithelium . On the model "karragenin edema" bronchofit showed a marked anti-inflammatory activity . A noticeable therapeutic effect was registered in rats with induced bronchopulmonary inflammation . Bronchial secretion contained reduced content of glycosaminoglycans while bronchial lavage did of histamine . Also, bronchofit demonstrated a prominent antioxidative activity, an antibacterial action in relation to Str . pyogenes and Bac . cereus . By a total complex of the activities bronchofit is a promising medicine against bronchopulmonary inflammation. Mikrobiyol Bul, 2002 Jul-Oct, 36(3-4), 259 - 69 {Bactericidal effects of commonly used antiseptics/disinfectants on nosocomial bacterial pathogens and the relationship between antibacterial and biocide resistance}; Ficici SE et al.; Bactericidal efficacy of seven different disinfectants (chlorhexidine gluconate, povidone-iodine, glutaraldehyde, benzalkonium chloride, sodium hypochloride, ethoxydiamino acridine, the mixture of "12% ethandiol + 0.5% pentanediol + 7.5% didecyldimethylammonium cloride") commonly used at Osmangazi University, Medical Faculty Hospital, was investigated against frequent nosocomial bacterial pathogens (19 Gram-negative and 25 Gram-positive strains) by using modified Kelsey-Sykes method . Chlorhexidine gluconate, povidone-iodine and glutaraldehyde were determined as the most effective disinfectants against all of the pathogens . There was no significant difference in terms of biocide resistance between antibiotic sensitive and resistant strains . All of the P . aeruginosa strains were found to be resistant to 0.01% benzalkonium chloride and 0.25%, 0.5% and 1% concentrations of "12% ethandiol + 0.5% pentanediol + 7.5% didecyldimethyl ammonium cloride" mixture . One vancomycin resistant E . faecium strain and one extended spectrum beta-lactamase (ESBL) positive K . pneumoniae strain were found to be resistant to 0.55% sodium hypochloride . Ethoxydiamino acridine showed little or no activity against all tested strains. Res Microbiol, 2003 Jun, 154(5), 345 - 52 Isolation, purification and partial characterization of antibacterial activities produced by a newly isolated Streptomyces sp . US24 strain; Mellouli L et al.; A new actinomycete strain designated US24 producing antibacterial activities against Gram-positive and Gram-negative bacteria was isolated from Tunisian soil . Culture characteristic studies strongly suggested that the US24 strain belonged to the genus Streptomyces . Analysis of the nucleotide sequence of the 16S rRNA gene of the Streptomyces sp . US24 strain showed high similarity (98%) with the 16S rRNA gene of Streptomyces caelestis which produces two antibiotics, niddamycin and celesticetin . Study of the influence of different nutritional compounds on antibiotic biosynthesis showed that the highest antibacterial activities were obtained when starch at 1% (w/v) was used as sole carbon source in the presence of traces of mineral oligoelements . Application to the supernatant culture of the Streptomyces sp . US24 strain of various separation steps led to isolation of two pure active molecules having a retention time of 34 and 37.26 min, respectively . P(34 min) possessed antibacterial activity against Gram-positive and Gram-negative bacteria, whereas P(37.26 min) inhibited only Gram-positive bacteria . Partial characterization of the P(34 min) molecule using spectroscopic studies showed that this active molecule is different from the two antibiotics produced by the S . caelestis strain. Dent Mater, 2003 Sep, 19(6), 449 - 57 Antibacterial properties of resin composites and dentin bonding systems; Imazato S; This paper reviews the research conducted on the evaluation of antibacterial properties of commercial composites and adhesive systems, in addition to the discussion on many attempts to achieve antibacterial composites or adhesives . With regard to composites, commercially available products including fluoride-releasing materials have no antibacterial effect after being cured, which may explain why composites accumulate more plaque than other filling materials . The attempts to provide composites with antibacterial properties involve alterations to the resin components and filler components, and the trials can be subsequently classified into two groups based on the release profile of antibacterial components; agent-releasing or non-agent-releasing materials . Each type of antibacterial composite has advantages and disadvantages, and further modifications are needed to achieve clinically useful materials . Among proprietary dentin bonding systems (DBS), the products which contain glutaraldehyde or have an acidic property exhibit some antibacterial effects . However, the antibacterial properties shown by these products are only side-effects which are derived from the constituents included to produce superior bonding characteristics, and appear to be unreliable . Inclusion of antibacterial components into DBS has also been attempted using several methods, and the results of in vitro tests indicate that some of the trials seem promising . It is worthy of continuing the attempts to develop DBS which can inhibit invading bacteria after the placement of restoration as well as residual bacteria in the cavity . Achievement of bio-functional composites or DBS with therapeutic effects would contribute to prevent secondary caries. Fitoterapia, 2003 Jul, 74(5), 501 - 5 Antibacterial activity of Artocarpus heterophyllus; Khan MR et al.; The crude methanolic extracts of the stem and root barks, stem and root heart-wood, leaves, fruits and seeds of Artocarpus heterophyllus and their subsequent partitioning with petrol, dichloromethane, ethyl acetate and butanol gave fractions that exhibited a broad spectrum of antibacterial activity . The butanol fractions of the root bark and fruits were found to be the most active . None of the fractions were active against the fungi tested. Fitoterapia, 2003 Jul, 74(5), 469 - 72 Antibacterial and antifungal activity of Xylopia aethiopica, Monodora myristica, Zanthoxylum xanthoxyloi;des and Zanthoxylum leprieurii from Cameroon; Tatsadjieu LN et al.; The essential oils of Xylopia aethiopica, Monodora myristica, Zanthoxylum xanthoxyloides and Z . leprieurii, four Cameroonian plants used as spices in local food, showed antibacterial and antifungal activity. Paediatr Drugs, 2003, 5(7), 457 - 61 Evaluation of the child who convulses with fever; Rosman NP; Febrile seizures result from age-dependent hyperexcitability of the brain that is induced by fever . Although there are important genetic influences that render a febrile child more likely to develop seizures, it is the fever per se that causes the seizure.Of primary importance in the diagnostic assessment of such children are efforts directed at finding the cause of the fever . Once found, the cause should be treated specifically, e.g . antibacterials for otitis media, and/or symptomatically, e.g . antipyretics for viral pharyngitis . It is essential to exclude underlying meningitis in all children with febrile seizures, either clinically or, if any doubt remains, by lumbar puncture . In as many as one child in six with meningitis, seizures are the presenting sign, and in one-third of these patients, meningeal signs and symptoms may be lacking . The great majority of such cases of meningitis are bacterial in origin, and delay in diagnosis can result in serious neurologic morbidity, and even death.In the child who convulses with fever, it is always important to consider that something in addition to the fever has caused the child to have a seizure . Infection that has gone unnoticed, such as meningitis or encephalitis, as well as a systemic illness, head trauma, intoxication, electrolyte imbalance, low blood sugar, or a phakomatoses, can cause seizures . One must also consider the possibility that the child with a febrile seizure has epilepsy, and that fever has simply triggered a seizure recurrence in a child who also experiences unprovoked seizures.Thus, based on the specifics of each case, the diagnostic evaluation of the child with a febrile seizure can be very limited or moderately comprehensive . Imaging studies are necessary only in selected cases . The electroencephalogram is of limited value . The primary concern is always the need to exclude meningitis . Therefore, a lumbar puncture should be carried out, except in those cases where the possibility of CNS infection seems truly remote. Paediatr Drugs, 2003, 5(7), 443 - 55 Outpatient management of febrile neutropenia in children with cancer; Holdsworth M et al.; The objectives of this article are to review the studies that have examined the safety and feasibility of outpatient management for children with febrile neutropenia, and to provide recommendations as to which patient populations and treatment strategies are most appropriate for this approach . The outpatient strategies have included either complete outpatient management or employment of early discharge, with the latter methodology predominating in most published studies . Common criteria relied upon to identify children with febrile neutropenia at low risk of serious infections included evidence of hematopoietic recovery and/or an absolute monocyte count >/=100/mm(3), and the absence of both comorbidity and culture positivity . A wide variety of different antibacterial regimens have been employed, with some trials investigating either early discontinuation of treatment or conversion to an oral administration strategy . Trials performed to date among this low risk population indicate a very low rate of readmission and/or complications . Some studies have also estimated substantial overall cost savings with this approach . However, many of these trials are significantly underpowered to detect the low rate of serious complications in the pediatric population with febrile neutropenia . At present, the available evidence indicates that a carefully chosen subpopulation of children with febrile neutropenia can be safely managed on an outpatient basis . Regardless of setting, current clinical guidelines for febrile neutropenia management indicate that all children with febrile neutropenia should be managed with appropriate antibacterial therapy until resolution of febrile neutropenia . Treatment with either an oral antibacterial regimen as initial therapy, or early discontinuation of antibacterial therapy in the outpatient setting should remain investigational at the present time. Eur J Clin Microbiol Infect Dis . 2003 Jun 26; {Epub ahead of print} Antifungal Activity of Nonantifungal Drugs; Afeltra J et al.; The antifungal activity of synthetic, nonchemotherapeutic compounds, antineoplastic agents and antibacterial drugs, such as sulphonamides, has been known since the early 20(th) century (1932) . In this context, the term "nonantifungal" is taken to include a variety of compounds that are employed in the management of pathological conditions of nonfungal infectious etiology but have been shown to exhibit broad-spectrum antifungal activity . In this review, the antifungal properties of compounds such as chlorpromazine, proton pump inhibitors, antiarrhythmic agents, cholesterol-lowering agents, antineoplastic and immunosuppressive agents, antiparasitic drugs and antibiotics are described . Since fungi are eukaryotic cells, they share many pathways with human cells, thus increasing the probability of antifungal activity of "nonfungal drugs" . The potential of these drugs for treatment of fungal infections has been investigated sporadically using the drugs alone or in combination with "classic" antifungal agents . A review of the literature, supplemented with a number of more recent investigations, suggests that some of these compounds enhance the activity of conventional antifungal agents, eliminate natural resistance to specific antifungal drugs (reversal of resistance) or exhibit strong activity against certain fungal strains in vitro and in animal models . The role of these agents in the epidemiology and in the clinical manifestations of fungal infections and the potential of certain drugs for treatment of invasive fungal infections require further investigation. Drugs, 2003, 63(14), 1481 - 8 Acute exacerbations in chronic obstructive pulmonary disease: current strategies with pharmacological therapy; Hall CS et al.; In acute exacerbation of chronic obstructive pulmonary disease (AECOPD), short-acting inhaled bronchodilators, such as salbutamol (albuterol) and ipratropium bromide, have proven useful . In patients who are refractory to these agents, intravenous aminophylline should be considered . Corticosteroids should also be used, either in the outpatient or inpatient setting . The duration of corticosteroids should probably not exceed 2 weeks and the optimum dosage is yet to be determined . Antibacterials, especially in patients with purulent or increased sputum, should be used, guided by the local antibiogram of the key microbes . Controlled oxygen therapy improves outcome in hypoxaemic patients and arterial blood gases should be performed to ensure hypercarbia is not becoming excessive . Should patients be in distress despite the above measures or if there is acidaemia or hypercarbia, noninvasive positive pressure ventilation could be used to improve outcomes without resorting to invasive mechanical ventilation . Mucous-clearing drugs and chest physiotherapy have no proven beneficial role in AECOPD. Klin Khir, 2003 Mar, (3), 33 - 5 {Ways of optimization for the plan of treatment of acute appendicitis}; Bondarenko NM et al.; Results of surgical treatment of 318 patients with an acute appendicitis, using principles of antibioticoprophylaxis and antibacterial therapy, new medicinal preparations, were analyzed. J Physiol Pharmacol, 2003 Jun, 54(2), 283 - 90 Physiological and chemical characteristics of antibacterial activity of pancreatic juice; Laubitz D et al.; Attempts were made to find and characterize an antibacterial activity (ABA) factor in porcine pancreatic juice (PJ) . Its isolation requires several steps . Since ABA factor was found to be heat resistant, the first step was heating for 30 min at 65 degrees C . Afterwards column chromatography, ethanol precipitation and polyacrylamide gel electrophoresis were involved . Finally, we obtained a pancreatic juice fraction with antibacterial activity against Escherichia coli strain AB1157 . In the presence of this fraction the number of living bacterial cells in overnight culture decreased about 10,000 fold and a spot-test gave clearly positive results . The results of analysis suggest that the antibacterial factor is a polypeptide active in a pH range 8.0-8.5, that migrates in polyacrylamide gel electrophoresis as a band under 14,000 Da . Mass spectroscopy analysis of active fraction showed high concentration of porcine pancreatic spasmolytic polypeptide (PSP) . In conclusion, a polypeptide controlling bacterial homeostasis has been found in the porcine pancreatic juice. J Pharm Pharmacol, 2003 May, 55(5), 593 - 601 Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin; Fang JY et al.; Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity . The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model . The enhancers selected in this study included terpenes, flavonoids and cholestanol . The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations . Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers . Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation . Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control . The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers. Pharmacogenomics, 2003 Jul, 4(4), 511 - 8 Anadys Pharmaceuticals, Inc; Basbaum A; The people of Anadys are committed to advancing patient care by discovering, developing, and commercializing novel and powerful anti-infective medicines . Anadys is focused on the discovery and development of small molecule therapeutics for the treatment of infectious disease, including hepatitis C and bacterial infections . The company's lead program for the treatment of hepatitis C is currently in Phase IB testing . Anadys also has a broad portfolio of antiviral and antibacterial programs directed at novel targets, intervention points and mechanisms of action . With an integrated suite of technologies and capabilities, including Riboproteomics, ATLAS and structure-based drug design through a world-class medicinal chemistry team, Anadys is capable of quickly optimizing lead compounds for use in preclinical and clinical testing . The company's goal is to build a strong and continual pipeline of novel and powerful drug candidates directed to advance patient care. Environ Sci Technol, 2003 Jun 1, 37(11), 2421 - 30 Oxidative transformation of triclosan and chlorophene by manganese oxides; Zhang H et al.; The antibacterial agents triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) and chlorophene (4-chloro-2-(phenylmethyl)phenol) show similar susceptibility to rapid oxidation by manganese oxides (delta-MnO2 and MnOOH) yielding Mn(II) ions . Both the initial reaction rate and adsorption of triclosan to oxide surfaces increase as pH decreases . The reactions are first-order with respect to the antibacterial agent and MnO2 . The apparent reaction orders to H+ were determined to be 0.46 +/- 0.03 and 0.50 +/- 0.03 for triclosan and chlorophene, respectively . Dissolved metal ions (Mn(II), Zn(II), and Ca(II)) and natural organic matter decrease the reaction rate by competitively adsorbing and reacting with MnO2 . Product identification indicates that triclosan and chlorophene oxidation occurs at their phenol moieties and yields primarily coupling and p-(hydro)quinone products . A trace amount of 2,4-dichlorophenol is also produced in triclosan oxidation, suggesting bond-breaking of the ether linkage . The experimental results support the mechanism that after formation of a surface precursor complex of the antibacterial agent and the surface-bound Mn(IV), triclosan and chlorophene are oxidized to phenoxy radicals followed by radical coupling and further oxidation to form the end products . Compared to several structurally related substituted phenols (i.e., 2-methyl-4-chlorophenol, 2,4-dichlorophenol, 3-chlorophenol, and phenol), triclosan and chlorophene exhibit comparable or higher reactivities toward oxidation by manganese oxides . The higher reactivities are likely affected by factors including electronic and steric effects of substituents and compound hydrophobicity . Once released into the environment, partitioning of triclosan and chlorophene to soils and sediments is expected because of their relatively hydrophobic nature . Results of this study indicate that manganese oxides in soils will facilitate transformation of these antibacterial agents. Trends Mol Med, 2003 Jun, 9(6), 269 - 76 Molecular targeted treatments for fungal infections: the role of drug combinations; Lupetti A et al.; Invasive mycoses are associated with a high mortality rate, and their incidence is increased in immunologically deficient patients . From a diagnostic and therapeutic perspective, these infections represent a significant challenge to medicine . In addition to new antifungal agents, drug combinations are an important therapeutic resource, which might be exploited clinically, owing to the multiplicity of fungal targets against which currently available agents are active . In this review, we examine the experimental data regarding the combination of conventional antifungal agents with cytokines, antibacterial agents, calcineurin inhibitors and drugs under development characterized by novel mechanisms of action. Bioorg Med Chem Lett, 2003 Jul 21, 13(14), 2413 - 8 N- and C-terminal modifications of negamycin; Raju B et al.; Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program . An orthogonally protected beta-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support . This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies . The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity . The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC(50)=2.3 microM), has antibacterial activity (Escherichia coli, MIC=16 microgram/mL), and is efficacious in an E . coli murine septicemia model (ED(50)=16.3mg/kg). Bioorg Med Chem Lett, 2003 Jul 21, 13(14), 2373 - 5 Synthesis and biological testing of non-fluorinated analogues of levofloxacin; Gray JL et al.; Quinolones without the usual 6-fluorine substituent have been recently described as potent antibacterial agents . A series of non-fluorinated analogues of the antibacterial quinolone Levofloxacin were synthesized and tested. Bioorg Med Chem Lett, 2003 Jul 21, 13(14), 2311 - 3 Synthesis and antibacterial activity of oxazolidinone containing sulphonyl group; Cui Y et al.; A series of oxazolidinone derivatives carrying sulphonyl group was synthesized and their antibacterial activity was evaluated in vitro . Many of such compounds demonstrated potent antibacterial activity . The activity of a novel compound (YC-20) was 2-4-fold more potent than that of linezolid. Arch Pharm (Weinheim), 2003 Jun, 336(3), 159 - 64 Synthesis of novel isoxazolidine derivatives and their antifungal and antibacterial properties; Kumar KR et al.; The synthesis of some biologically interesting isoxazolidine derivatives has been accomplished by the cycloaddition reaction of C-(4-biphenyl)-N-(3-methylphenyl) nitrone and C-(4-biphenyl)-N-(3-chlorophenyl) nitrone to monosubstituted alkenes . The compounds were screened for their antibacterial and antifungal activities . Among the tested compounds 3a (ii), 3a (vii), 3a (viii), 3b (iv), 3b (vii), and 3b (viii) showed significant antifungal activity comparable with that of the standard drug Nystatin against Botrydiplodia theobromae. Phytother Res, 2003 Jun, 17(6), 599 - 604 Antibacterial activity of medicinal plant extracts against periodontopathic bacteria; Iauk L et al.; This study was performed to evaluate the antibacterial activity of Althaea officinalis L . roots, Arnica montana L . flowers, Calendula officinalis L . flowers, Hamamelis virginiana L . leaves, Illicium verum Hook . fruits and Melissa officinalis L . leaves, against anaerobic and facultative aerobic periodontal bacteria: Porphyromonas gingivalis, Prevotella spp., Fusobacterium nucleatum, Capnocytophaga gingivalis, Veilonella parvula, Eikenella corrodens, Peptostreptococcus micros and Actinomyces odontolyticus . The methanol extracts of H . virginiana and A . montana and, to a lesser extent, A . officinalis were shown to possess an inhibiting activity (MIC < or = 2048 mg/L) against many of the species tested . In comparison, M . officinalis and C . officinalis extracts had a lower inhibiting activity (MIC > or = 2048 mg/L) against all the tested species with the exception of Prevotella sp . Illicium verum methanol extract was not very active though it had a particular good activity against E . corrodens . The results suggest the use of the alcohol extracts of H . virginiana, A . montana and A . officinalis for topical medications in periodontal prophylactics . Proc Natl Acad Sci U S A, 2003 Jul 8, 100(14), 8146 - 50 Epub 2003 Jun 20. Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis; Whittington DA et al.; The outer leaflet of the outer membrane of the Gram-negative bacterium serves as a permeability barrier and is composed of lipopolysaccharide, also known as endotoxin . The membrane anchor of lipopolysaccharide is lipid A, the biosynthesis of which is essential for cell viability . The first committed step in lipid A biosynthesis is catalyzed by UDP-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase . Here we report the crystal structure of LpxC from Aquifex aeolicus, which reveals a new alpha+beta fold reflecting primordial gene duplication and fusion, as well as a new zinc-binding motif . The catalytic zinc ion resides at the base of an active-site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid . This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents . Notably, simple inhibitors designed to target interactions in the hydrophobic tunnel bind with micromolar affinity, thereby representing a step toward the structure-based design of a potent, broad-spectrum antibacterial drug. J Antibiot (Tokyo), 2003 Apr, 56(4), 399 - 414 Synthesis and biological evaluation of novel leucomycin analogues modified at the C-3 position . I . Epimerization and methylation of the 3-hydroxyl group; Furuuchi T et al.; The synthesis and biological evaluation of sixteen-membered macrolides modified at the C-3 position are described . 3-Epi-leucomycin A7 (9), 3-O-acyl-3-epi-leucomycin A7 analogues (11a-11e), 3-O-acylleucomycin A7 analogues (13b-13e) and 3-O-methylleucomycin analogues (16a, 16b and 22) were synthesized via fully protected intermediates (7, 5a, 5b and 20) . After appropriate modification, subsequent deprotections were performed to furnish a variety of leucomycin analogues . Methylation of the 3-hydroxyl group was found to improve the pharmacoprofile of leucomycin antibiotics . 3-O-Methylrokitamycin (16b) showed enhanced antibacterial activity in vitro and 3,3''-di-O-methyl-4''-O-(3-methylbutyl)leucomycin V (22) exhibited improved metabolic stability in rat plasma in vitro. J Antibiot (Tokyo), 2003 Apr, 56(4), 379 - 91 An innovative classification of, and a new structure-activity-relationship approach to degradation kinetics of cephalosporins: an attempt to enhance the therapeutic activity; Akaho E et al.; Degradation kinetics of cephalosporins was innovatively classified into six groups according to its mechanism that is based on the attached functional and/or substituent groups . 3-Position plays an important role in the degradation kinetics, and they are classified into three major groups; one with a 3-acetoxy group, another with a 3-deacetoxy group, and the other without a 3-acetoxy group . Each group is further subdivided depending on whether it contains 7-x-amino group or not . The order of the alkaline hydrolysis of cephalosporins coincided with the order of the degree of their antibacterial activities . This provides an evidence to support the hypothesis that the biological activity of beta-lactam antibiotics depends upon the reactivity of the beta-lactam moiety . At the same time, the compound should be stable, and the stability is often related to the reactivity of 3-position . Combination products of biodegradable cephalosporins and acid-stable cephalosporins are desired products . An example of such products produced by chemical modifications stated above will be the one with a good leaving group at the 3-position that is not hydrolyzed. Am J Clin Dermatol, 2003, 4(7), 473 - 92 Topical acne drugs: review of clinical properties, systemic exposure, and safety; Akhavan A et al.; This review examines the commonly available topical acne agents and factors that determine their percutaneous absorption . Reported and theoretical adverse effects from systemic exposure are detailed . The topical retinoid class, which includes tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin and erythromycin, are regulated by prescription in most countries . Used appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of active ingredient into the circulation . Clear-cut links to systemic toxicity in humans are practically nonexistent, except in the case of topical clindamycin, which has been associated with diarrhea rarely, and there have been 2 cases of pseudomembranous colitis reported . Birth defects have occurred in two patients treated with tretinoin and one patient treated with adapalene, but causation was not proven . Another prescription drug, 20% azelaic acid, is associated with relatively high systemic exposure, which is presumed innocuous because it is a normal dietary constituent whose endogenous levels are not altered by topical use . Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are available in concentrations of 2% or more in over-the-counter acne treatments and some prescription products . All of these agents are known to exhibit some degree of percutaneous absorption . They remain largely unregulated because, other than skin irritation, only local allergic contact dermatitis from benzoyl peroxide in about 2.5% of patients and rare local and systemic hypersensitivity reactions from sodium sulfacetamide have been reported . Salicylism has occurred using methyl salicylate ointments and high concentrations of salicylic acid on widespread areas of hyperkeratotic skin, but there are no known cases resulting from salicylic acid acne products . Caution is advised in special circumstances, such as during childhood, pregnancy, lactation and concomitant therapy with other drugs, because relevant studies are lacking . Animal data support avoidance of many topical agents, particularly known teratogens such as retinoids and salicylic acid, in pregnant women . Salicylate avoidance is advised during lactation, because aspirin use carries the risk of bleeding disorders in nursing infants. Am J Clin Dermatol, 2003, 4(7), 467 - 71 Dermabrasion in dermatology; Gold MH; Dermabrasion has been used for a number of years to treat a variety of dermatologic conditions, including facial skin resurfacing and scar revision . The popularity of this procedure has diminished with the advent of newer procedures including chemical exfoliation, laser resurfacing, non-ablative laser resurfacing, and microdermabrasion . Dermabrasion found its niche in treating acne and traumatic facial scars, and in cosmetic facial resurfacing . Small, portable hand-held dermabraders are the most popular units available today and are able to generate rotation speeds of 18,000-35,000 revolutions per minute . End pieces, including wire brushes, diamond fraises and serrated wheels, attach to the end of the dermabrader to allow precise resurfacing and treatment . As with all cosmetic surgical procedures, appropriate patient selection and room preparation (with appropriate lighting and monitoring equipment) are essential to assure optimal outcomes with the dermabrasion procedure . Patients must understand all of the potential risks, benefits and limitations associated with the procedure . Patients must also be aware of alternative therapies that are available . Dermabrasion is technique-dependent and the surgeon should be well versed on the technique prior to performing this therapy . Gentian violet solution is used to delineate the areas to be treated . Refrigerant topical anesthesia is used to freeze the skin prior to the procedure . Holding the skin taut, the dermabrasion procedure occurs in a routine manner, treating one anatomic unit at a time . Postoperatively, patients may have an open or closed dressing system . Postoperative medical treatment is also recommended, including the use of antiviral agents, antibacterials and corticosteroids . The re-epithelialization process is usually complete in 5-7 days and residual erythema is common for up to 4 weeks . Adequate sun protection is essential following dermabrasion . Dermabrasion has also been used in combination with other dermatologic procedures, including chemical exfoliation, soft tissue augmentation and laser procedures, to enhance the results of dermabrasion . Dermabrasion remains a useful facial skin resurfacing and scar revision technique, particularly when performed by a trained and skilled surgeon . Most dermatologic surgeons argue that pure dermabrasion is a useful modality in skilled surgical hands and should be considered when appropriate. Acta Pharm Hung, 2002, 72(4), 223 - 30 {Reactions of derivatives of beta-lactam antibiotics with non-antibacterial biological activity}; Gunda T; Beyond the well-known antibacterial and beta-lactamase enzyme inhibiting properties of the different beta-lactam antibiotics and their modified derivatives there are a number of beta-lactam (azetidine-2-one) compounds possessing different biological activities . Most of them have been shown to inhibit a variety of cysteine or serine protease enzymes comprising plants, viruses, protozoa, bacteria and mammalian species . This review article covers the biologically active beta-lactam compounds but beta-lactam antibiotics or beta-lactamase inhibitors, and including a few chemically related gamma- or delta-lactams or azetidines presumably having the same site and mechanism of action . These include viral protease inhibitors, protozoan enzymes (e.g . cruzain, falcipain), plant enzymes (papain) . Of the mammal enzymes the most important ones are cholesterol absorption inhibitors and human leucocyte (neutrophyle) elastase inhibitors, but mention must be made on thrombin, chymotrypsin, cathepsin, prostata specific antigen and tumor necrosis factor inhibitors, as potential future remedies of cardio vascular and inflammatory diseases. Commun Dis Intell, 2003, 27 Suppl, S89 - 91 Low levels of fluoroquinolone resistance in Escherichia coli . A five-year trend in Australia measured through the use of TSN Database Australia; Turnidge J et al.; In many countries, fluoroquinolones are among the most commonly used antibacterial drugs . Concerns about bacterial resistance to these and other frequently used drugs have been raised by the medical and scientific communities . While fluoroquinolone resistance has not yet developed among many bacteria, emergence of resistance in Escherichia coli would be a problem as multiple resistances to other antibiotics is now a common problem . This paper examines trends in resistance to fluoroquinolones in Escherichia coli through analysis of data collected from Australian institutions between 1997 and 2001 . During the study period, norfloxacin and ciprofloxacin were the most frequently tested fluoroquinolones in Australian laboratories . An examination of results for strains tested simultaneously against both drugs indicated that testing against either drug accurately predicted resistance or susceptibility for the other (99.7% agreement) . Over 400,000 tests were performed to determine the fluoroquinolone susceptibility of E . coil . Data were analysed by the test method used (Calibrated Dichotomous Sensitivity (CDS) or National Committee for Clinical Laboratory Standards (NCCLS)) . The data indicate that fluoroquinolone resistance in E . coli has not yet emerged as a significant problem in Australia, but there are some indications of low level increases in resistance rates . Norfloxacin results are likely to be a better guide to fluoroquinolone resistance in this species using this method of surveillance. Boll Chim Farm, 2003 Apr, 142(3), 99 - 101 {Commentary about the 16th National Symposium of Medicinal Chemistry Italian Chemical Society--Sorrento, September 18-22, 2002}; Passarotti C; The Congress was been structured on four main sections: 1) receptors chemistry; 2) developments in pharmaceutical analysis; 3) computational molecular design; 4) antineoplastic, antiviral, antibacteric and cytostatic agents . In the present review we summarize the more important communications, and we emphasize that all the communications were of a high standard. J Altern Complement Med, 2003 Apr, 9(2), 267 - 73 The effect of dilution on the rate of hydrogen peroxide production in honey and its implications for wound healing; Bang LM et al.; OBJECTIVE: Honey is an effective antiseptic wound dressing, mainly the result of the antibacterial activity of hydrogen peroxide that is produced in honey by the enzyme glucose oxidase . Because the rate of production of hydrogen peroxide is known to vary disproportionately when honey is diluted, and dilution of honey dressings will vary according to the amount of wound exudate, it is important to know more about the production of hydrogen peroxide at different concentrations of honey . DESIGN: The rates of hydrogen peroxide production by honey with respect to honey dilution were measured in eight different samples of honey from six different floral sources . SETTINGS: Honey Research Unit, Waikato University, Hamilton, New Zealand . MAIN RESULTS: The maximum levels of accumulated hydrogen peroxide occurred in honey solutions diluted to concentrations between 30% and 50% (v/v) with at least 50% of the maximum levels occurring at 15-67% (v/v) . This is equivalent to a 10 cm x 10 cm dressing containing 20 mL of honey becoming diluted with 10 to 113 mL of wound exudate . Maximum levels of hydrogen peroxide reached in the diluted honeys were in the range of 1-2 mmol/L . CONCLUSION: Significant antibacterial activity can be maintained easily when using honey as a wound dressing, even on a heavily exuding wound . Concentrations of hydrogen peroxide generated are very low in comparison to those typically applied to a wound, thus, cytotoxic damage by hydrogen peroxide is very low. J Chromatogr Sci, 2003 Apr, 41(4), 173 - 6 Determination of antibacterial flomoxef in serum by capillary electrophoresis; Kitahashi T et al.; A determination method of flomoxef (FMOX) concentration in serum by capillary electrophoresis is developed . Serum samples are extracted with acetonitrile . After pretreatment, they are separated in a fused-silica capillary tube with a 25 mM borate buffer (pH 10.0) as a running buffer that contains 50mM sodium dodecyl sulfate . The FMOX and acetaminophen (internal standard) are detected by UV absorbance at 200 nm . Linearity (0-200 mg/L) is good, and the minimum limit of detection is 1.0 mg/L (S/N = 3) . The relative standard deviations of intra- and interassay variability are 1.60-4.78% and 2.10-3.31%, respectively, and the recovery rate is 84-98% . This method can be used for determination of FMOX concentration in serum. Appl Microbiol Biotechnol, 2004 Jan, 63(4), 335 - 43 Epub 2003 Jun 12. The challenge of multidrug resistance: actual strategies in the development of novel antibacterials; Schmidt FR; Bacterial resistance against established antibiotics is becoming an increasingly important global healthcare problem . Despite enormous efforts, the number of therapeutically useful compounds that emerge from chemical derivatisation programs, which aim at circumventing mechanisms of resistance, is continuously decreasing and no truly novel class of compound has been introduced into therapy for nearly four decades . Hopes are now set on a thorough elucidation of bacterial cell functions to identify new bacterial target sites, and on the development of novel compounds with alternative modes of action . The pursuit of these strategies is rendered possible by employment of biotechnologically based methods such as in vivo modification of biosynthetic routes in antibiotic-producing organisms, large-scale screening assays with isolated bacterial targets, the molecular profiling of bacterial genomes and proteomes, and the development and clinical use of biochips as diagnostic tools for rapid identification and characterization of pathogenic strains . As one of the most promising class of compounds known to date with unique modes of action that escape most known mechanisms of resistance, peptic agents have recently came under the focus of anti-infective research, just as extracellular signalling molecules (autoinducer) have emerged as new bacterial target sites. J Med Chem, 2003 Jun 19, 46(13), 2755 - 64 Antiretroviral activity of semisynthetic derivatives of glycopeptide antibiotics; Balzarini J et al.; A variety of semisynthetic derivatives of natural antibacterial glycopeptide antibiotics such as vancomycin, eremomycin, ristocetin A, teicoplanin A(2)-2, DA-40926, their aglycons, and also the products of their partial degradation with a destroyed or modified peptide core show marked anti-retroviral activity in cell culture . In particular, aglycon antibiotic derivatives containing various substituents of a preferably hydrophobic nature displayed activity against human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine sarcoma virus at a 50% inhibitory concentration in the lower micromolar (1-5 microM) concentration range while not being cytostatic against human lymphocytic cells at 250 microM or higher . The mode of anti-HIV action of the antibiotic aglycon derivatives could be ascribed to inhibition of the viral entry process. J Med Chem, 2003 Jun 19, 46(13), 2706 - 15 Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives; Tanikawa T et al.; A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated . These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H . influenzae . 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H . influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests . However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides. Bioorg Med Chem Lett, 2003 Jul 7, 13(13), 2239 - 40 Enantiotracin; McDougal PG et al.; The enantiomer of the antibiotic bacitracin A was prepared by solid-phase total synthesis . ent-Bacitracin A was found to be equally potent to the natural enantiomer in in vitro susceptibility assays . This supports the notion that bacitracin exerts its antibacterial effects through interaction with bactoprenylpyrophosphate, an achiral ligand. J Gastroenterol Hepatol, 2003 Jul, 18(7), 787 - 95 Rabeprazole treatment attenuated Helicobacter pylori-associated gastric mucosal lesion formation in Mongolian gerbils; Suzuki H et al.; BACKGROUND AND AIM: Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H . pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium . In the present study, we investigated the effect of RPZ on H . pylori-associated gastric mucosal lesion formation . METHODS: Sixty-two male Mongolian gerbils were inoculated with H . pylori (ATCC43504) (Hp group) and 60 gerbils with the culture media alone (control group) . Some gerbils in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for 7 days) at the 5th week . Gerbils were evaluated at the 12th, 24th and 48th weeks . RESULTS: In the Hp group, all gerbils were persistently infected for 24 weeks, but 36% became negative for H . pylori at the 48th week . In the Hp + RPZ group, 18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week, became negative for H . pylori . The level of neutrophil infiltration was significantly decreased in the Hp + RPZ group in comparison to the Hp group, possibly through the effects of RPZ on initial bacterial colonization and resultant inflammation . Even in the gerbils that became H . pylori-negative, the level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp group . RPZ treatment significantly increased the level of the reduced form of glutathione (GSH) at the 48th week . The elevated levels of the reduced form of GSH may have been reduced by an antioxidation process in the H . pylori-positive Hp + RPZ group . CONCLUSION: Administration of RPZ not only inhibited gastric H . pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH . BMC Pharmacol . 2003 Jun 06;3(1):6. In vitro antileishmanial effects of antibacterial diterpenes from two Ethiopian Premna species: P . schimperi and P . oligotricha; Habtemariam S; BACKGROUND: Three antibacterial diterpenes: (5R,8R,9S,10R)-12-oxo-ent-3,13(16)-clerodien-15-oic acid (1), 16-hydroxy-clerod-3,13(14)-diene-15,16-olide (2) and ent-12-oxolabda-8,13(16)-dien-15-oic acid (3) were previously isolated form Premna schimperi and P . oligotricha . Since andrographolide and other structurally related diterpenes were shown to have antileishmanial activity, the aim of the present study was to assess the in vitro effect of premna diterpenes against Leishmania aethiopica; the causative agent of cutaneous leishmaniasis in Ethiopia . RESULTS: The diterpenes showed potent concentration-dependant suppressive effect on the viability of axenically cultured amastigotes of L . aethiopica . The clerodane diterpenes 1 and 2 were most active (LD50 values 1.08 and 4.12 microg/ml respectively) followed by andrographolide and 3 . Compounds 1 and 2 appear to be over 20 and 10-times respectively more selective to leishmania amastigotes than the permissive host cell line, THP-1 cells or the promastigotes stage of the parasites . CONCLUSION: The clerodane diterpenes (1, 2) which were more potent and selective than labdanes (andrographolide and 3) are promising for further studies and/or development. Compend Contin Educ Dent, 2002 Oct, 23(10 Suppl), 12 - 20 Dental caries: risk assessment and treatment solutions for an elderly population; Anusavice KJ; Caries remains one of the top three most common infectious diseases in the world today . Although caries prevalence decreased markedly in children and in adults up to age 40 between 1975 and 2000, the overall risk for caries in older age groups (45 to 64, 65 to 84, and > 85 years of age) has not decreased appreciably . In fact, the risk for caries in individuals 70 years of age and older has increased . The increase in restorative work needed between 1990 and 2030 will be highest in adults over the age of 44 years . Root caries prevalence and the number of restored teeth will be greatest in the elderly population . Approximately 30% of individuals over the age of 65 will have no permanent teeth . It is also apparent that additional caries risk factors are associated with a significant proportion of the older population, including reduced saliva flow, inadequate oral hygiene, frequent sugar intake, Asian ethnicity, and the presence of partial dentures . The principles of modern caries management focus on risk assessment, risk reduction, monitoring noncavitated carious lesions, and the assignment of specific treatment options according to risk . Because a relatively high proportion of elderly patients will remain at high risk for caries, therapeutic regimens for managing caries as an infectious disease must focus on the use of antibacterial treatment; high-fluoride dentifrices; supplementary low-dose, high-frequency fluoride rinses; patient education; and shorter recall intervals. Med Res Rev, 2003 Sep, 23(5), 535 - 58 Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents; Supuran CT et al.; The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others . A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties . Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties . Some of these compounds are currently being evaluated in clinical trials . The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types . Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported . Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome . Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke . Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity . Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs . Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs . J Clin Periodontol, 2003, 30 Suppl 5, 19 - 21 Additional properties and uses of essential oils; Seymour R; Much evidence has been published supporting the use of mouthwashes in a number of crucial areas of oral health . These areas include antibacterial activity, home irrigation, maintenance of implant health, postsurgery uses, reduction of bacteria in dental aerosols and bacteraemia reduction . Although other commonly used mouthwashes (e.g . chlorhexidine) have been reviewed in other articles in this Supplement, this article concentrates solely on data supporting essential-oil mouthwash use in these oral health areas. Indian J Pathol Microbiol, 2002 Jul, 45(3), 307 - 10 Evaluation of antibacterial activity of Mangifera indica on anaerobic dental microglora based on in vivo studies; Bairy I et al.; The present study was carried out to compare the subgingival plaque microflora in mango leaf users . Fifty subjects of both sexes, 25 of them used tooth brush and 25 used mango leaf as their home care hygiene device were included in the study . The microbiological evaluation for specific bacterial counts of Actinobacillus actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum and Peptostreptococcus micros were carried out for all subject . Specific microbial evaluation revealed significant decrease in the proportion of P . intermedia and P . gingivalis in mango leaf users compared to tooth brush users . It shows that mangiferin possesses antibacterial activity in vivo against specific periodontal pathogens such as P . intermedia and P . gingivalis . Use of mango leaf in conjunction with a tooth brush will be a good home care device for maintenance of oral hygiene. Shock, 2003 Jun, 19(6), 577 - 81 Neutralization of endotoxin in vitro and in vivo by Bac7(1-35), a proline-rich antibacterial peptide; Ghiselli R et al.; Lipopolysaccharides (LPS), or endotoxins, are structural components of gram-negative bacteria implicated in the pathogenesis of septic shock . In this study the antiendotoxin activity of Bac7(1-35), a synthetic peptide based on the sequence of a proline-rich antibacterial peptide from bovine neutrophils, was investigated in vitro and in an experimental rat model of gram-negative septic shock . The ability of Bac7(1-35) to bind LPS from Escherichia coli O111:B4 was determined using a sensitive Limulus chromogenic assay . In the in vivo study, adult male Wistar rats were given an intraperitoneal injection of 1 x 10(9) colony-forming units of E . coli ATCC 25922 . All animals were randomized to receive intraperitoneally 1 mg/kg Bac7(1-35), or isotonic sodium chloride solution (control group C1), 60 mg/kg of piperacillin and 1 mg/kg polymyxin B, 1 mg/kg of polymyxin B plus 60 mg/kg of piperacillin, and 1 mg/kg of Bac7(1-35) plus 60 mg/kg of piperacillin . Each group included 15 animals . Bac7(1-35) was found to completely inhibit the LPS procoagulant activity at approximately 10 microM peptide concentration, as determined by in vitro LAL chromogenic assay . Treatment with Bac7(1-35) resulted in significant decrease in plasma endotoxin levels and lethality rates compared with saline injected control animals . No statistically significant differences were noted between Bac7(1-35) and polymyxin B in reducing all variables measured . These results provide evidence for the ability of Bac7(1-35) to effectively bind LPS and protect animals from lethal effects of this molecule, and point to its potential use for the treatment of endotoxin-induced septic shock. Biosci Biotechnol Biochem, 2003 Apr, 67(4), 803 - 8 Relationship between response to and production of the aerial mycelium-inducing substances pamamycin-607 and A-factor; Hashimoto M et al.; Respectively, exogenous pamamycin-607 and A-factor restored or stimulated aerial mycelium formation in 30 (67%) and 6 (13%) of 45 Streptomyces strains, and both restored or stimulated it in 5 strains (11%) . Pamamycin-607 production was detected in 3 of those strains that responded to pamamycin-607 . These findings indicate that pamamycin-607 acts on the common regulatory system for aerial mycelium formation in Streptomyces spp . but is not a universal autoregulator . Increased or decreased antibacterial production occurred in 5 strains in association with aerial mycelium formation by pamamycin-607 or A-factor. Skin Pharmacol Appl Skin Physiol, 2003 Jul-Aug, 16(4), 252 - 8 Aminoglycosides suppress tRNA processing in human epidermal keratinocytes in vitro; Tekos A et al.; The ever-growing resistance of pathogens to antibiotics and the lack of potent antibacterial drugs constitute major problems in the treatment of infectious diseases . Thus, the better understanding of the mode of action of antibiotics at the molecular level is of essential importance . Accumulating evidence points towards RNA as being a crucial target of antibacterial and antiviral drugs . Interestingly, aminoglycosides, one of the most important families of antibiotics, apart from their inhibitory effect on ribosome function, reportedly interfere with various RNA molecules and in vitro suppress the proliferation of human keratinocytes . In this study we investigated the effect of the aminoglycosides neomycin B, paromomycin, tobramycin and gentamycin on ribonuclease P activity from normal human epidermal keratinocytes . All aminoglycosides tested revealed a dose-dependent inhibition of tRNA maturation, which was reduced by increasing Mg(2+) ion concentrations, indicating competition of the cationic aminoglycosides with magnesium ions required for catalysis . Our in vitro findings suggest that the inhibitory effects of aminoglycosides on tRNA processing may be implicated in the mechanisms of their antiproliferative action on human epidermal keratinocytes . Fitoterapia, 2003 Jun, 74(4), 404 - 6 Antibacterial activity of Tagetes terniflora; Tereschuk ML et al.; Methanol extracts of the leaves of Tagetes terniflora and ethyl acetate and aqueous fractions showed different degrees of activity against Gram positive and Gram negative strains. Fitoterapia, 2003 Jun, 74(4), 401 - 3 Antibacterial activity of embelin; Chitra M et al.; Embelin, a benzoquinone-derivative isolated from Embelia ribes, when tested for its antibacterial potential exhibited significant inhibition against five and moderate activity against three strains of the 12 bacteria tested. Fitoterapia, 2003 Jun, 74(4), 387 - 9 Antibacterial and antifungal activity of Erigeron breviscapus; Liu H et al.; The antibacterial and antifungal properties of the ethanol extract of Erigeron breviscapus whole plant was evaluated . The extract showed a moderate antibacterial activity and a high antifungal activity. Fitoterapia, 2003 Jun, 74(4), 384 - 6 Antifungal activity of some Cuban Zanthoxylum species; Dieguez-Hurtado R et al.; Ethanolic extracts of the trunk bark of Zanthoxylum fagara, Z . elephantiasis and Z . martinicense showed activity against different species of fungi . No antibacterial activity was detected. Toxicol In Vitro, 2003 Jun, 17(3), 301 - 10 In vitro cytotoxic and anti-inflammatory effects of myrrh oil on human gingival fibroblasts and epithelial cells; Tipton DA et al.; Limited scientific studies suggest that myrrh (Commiphora molmol) has antibacterial and anti-inflammatory activities . This study determined myrrh oil (MO) cytotoxicity to human gingival fibroblasts and epithelial cells and its effect, measured by ELISA, on interleukin (IL)-1beta-stimulated IL-6 and IL-8 production . Cell viability and cytotoxicity were determined by metabolic reduction of a tetrazolium salt to a formazan dye (MTT assay) and by release of lactate dehydrogenase (LDH) from membrane damaged (LDH release assay) cells, respectively . Based on the MTT assay, 24- and 48-h exposures to </=0.001% MO had little effect on fibroblast and epithelial cell (24-h only) viability . At 48 h, 0.0005-0.001% MO decreased epithelial cell viability 30-50% . After 24 and 48 h, MO, at >/=0.005%, maximally decreased viability of all cell lines . In the LDH release assay, exposure to </=0.0001% MO caused <10% cytotoxicity to all cells . At 24 h, >/=0.0025% MO caused maximal cytotoxicity; </=0.001% MO caused 10-70% cytotoxicity . At longer exposure times, epithelial cells were more susceptible to cytotoxic effects of MO . There was little or no detectable IL-1beta-stimulated production of IL-6 or IL-8 by cells exposed to >/=0.0025% MO, probably reflective of loss of viability . At subtoxic MO levels (0.00001-0.001%), there was a significant reduction of IL-1beta-stimulated IL-6 and IL-8 production by fibroblasts, but not by epithelial cells. Zhongguo Zhong Yao Za Zhi, 2001 Nov, 26(11), 765 - 7 {Studies on constituents of the leaves of Lindera aggregata (Sims) Kosterm}; Zhang CF et al.; OBJECTIVE: To study the antibacterial and anti-inflammatory constituents of the leaves of Lindera aggrega . METHOD: Compounds were isolated by colum chromatography, and the structures were identified by spectroscopic methods . RESULT: Six compounds were isolated and identified as mixture of 6-Acetyllindenanolide B-1 and B-2(I), dehydrolindestrenolide (II), hydroxylinderstrenolide (III), linderalactone (IV), kameofero (V), beta-sitosterol (VI) . CONCLUSION: These compounds were obtained from the leaves of Lindera aggregata for the first time. Nat Rev Drug Discov, 2003 Jun, 2(6), 489 - 97 The prospect for bacteriophage therapy in Western medicine; Merril CR et al.; Bacteriophage (phage) have been used for clinical applications since their initial discovery at the beginning of the twentieth century . However, they have never been subjected to the scrutiny--in terms of the determination of efficacy and pharmacokinetics of therapeutic agents--that is required in countries that enforce certification for marketed pharmaceuticals . There are a number of historical reasons for this deficiency, including the overshadowing discovery of the antibiotics . Nevertheless, present efforts to develop phage into reliable antibacterial agents have been substantially enhanced by knowledge gained concerning the genetics and physiology of phage in molecular detail during the past 50 years . Such efforts will be of importance given the emergence of antibiotic-resistant bacteria. Probl Tuberk Bolezn Legk, 2003, (4), 39 - 41 {Enhancing the efficiency of treatment in patients with multidrug resistant pulmonary tuberculosis by a combination of surgery and adequate chemotherapy}; Erimbetov KD; The outcomes of surgical treatment were analyzed in 68 patients with multidrug-resistant pulmonary tuberculosis . Of them, 38 patients (Group 1) received preoperative and postoperative chemotherapy with antibacterial drugs by the WHO standard treatment regimens, 30 patients (Group 2) used reserve antibacterial drugs . Chemotherapy and surgical interventions yielded the following results: 84.3 and 93.3% of clinical efficiencies in Group 1 and 2, respectively . The use of reserve antibiotics enhances the efficiency of surgical treatment in patients with multidrug-resistant pulmonary tuberculosis. Rapid Commun Mass Spectrom, 2003, 17(11), 1146 - 56 Confirmatory analysis of sulfonamide antibacterials in bovine liver and kidney: extraction with hot water and liquid chromatography coupled to a single- or triple-quadrupole mass spectrometer; Bogialli S et al.; A simple, specific, and rapid confirmatory method for determining 12 sulfonamide (SAs) antibacterials in bovine liver and kidney is presented . This method is based on the matrix solid-phase dispersion technique with hot water as extractant followed by liquid chromatography/mass spectrometry (LC/MS) with an electrospray ion source . The method was tailored for use with both single-quadrupole MS (I) and triple-quadrupole MS (II) instruments . After acidification and filtration of the aqueous extract, a 250-microL aliquot was injected into instrument I while only 25 microL was analyzed by instrument II . With instrument I MS data acquisition was performed in the selected ion monitoring (SIM) mode, selecting at least three ions for each target compound . With instrument II the selected reaction monitoring (SRM) mode with three fragmentation reactions for each compound was chosen . With the exception of sulfaquinoxaline (SQX), recovery of the analytes at the 50 ppb level in both liver and kidney was 72-96% with relative standard deviations (RSDs) ranging between 3 and 11% . The very poor recovery of SQX was due to its rapid enzymatic oxidation when in contact with the two tissues . With instrument I, limits of quantification (LOQs, S/N = 10) were 5-14 ppb of SAs . Even lower LOQs (1-8 ppb) were estimated by using instrument II, even though the extract volume analyzed was ten times lower than that with instrument I . With both matrices and using instrument I, severe ion signal suppression was experienced for the early-eluted SAs when trying to fractionate analytes by using a short chromatographic run time . This effect was traced to polar endogenous co-extractives eluted in the first part of the chromatographic run that interfered with gas-phase ion formation for SAs . Adopting more selective chromatographic conditions minimized this effect . Chem Biol, 2003 May, 10(5), 431 - 41 A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin; Sun Y et al.; The PKS genes for biosynthesis of the polyether nanchangmycin are organized to encode two sets of proteins (six and seven ORFs, respectively), but are separated by independent ORFs that encode an epimerase, epoxidase, and epoxide hydrolase, and, notably, an independent ACP . One of the PKS modules lacks a corresponding ACP . We propose that the process of oxidative cyclization to form the polyether structure occurs when the polyketide chain is still anchored on the independent ACP before release . 4-O-methyl-L-rhodinose biosynthesis and its transglycosylation involve four putative genes, and regulation of nanchangmycin biosynthesis seems to involve activation as well as repression . In-frame deletion of a KR6 domain generated the nanchangmycin aglycone with loss of 4-O-methyl-L-rhodinose and antibacterial activity, in agreement with the assignments of the PKS domains catalyzing specific biosynthetic steps. J Insect Physiol, 1997 Nov, 43(12), 1161 - 1167 Juvenile hormone regulates the expression of the gene encoding ceratotoxin a, an antibacterial peptide from the female reproductive accessory glands of the medfly Ceratitis capitata; Dallai R et al.; Ceratotoxin A is an antibacterial peptide produced by the reproductive female accessory glands of the medfly Ceratitis capitata . To investigate whether ceratotoxin A gene expression was affected by juvenile hormone, which has gonadotropic functions in adult insects, newly emerged female medflies were treated with precocene II, an antiallotropin compound capable of inhibiting juvenile hormone biosynthesis . Daily treatment of newly emerged flies with precocene II blocked ceratotoxin A gene expression in a dose-dependent manner . Ceratotoxin A gene expression could be recovered after withdrawl of precocene II treatment . Moreover, the effect of precocene II on ceratotoxin A gene expression could be countered by simultaneous treatment with methoprene, a juvenile hormone analogue . The effects of precocene II and methoprene treatments on the growth of both ovaries and accessory glands was also investigated . Our data suggest that ceratotoxin A gene expression is modulated by juvenile hormone. J Insect Physiol, 1997 Apr, 43(4), 383 - 391 Isolated Apolipophorin III from Galleria mellonella Stimulates the Immune Reactions of This Insect; GOTZ P et al.; Apolipophorin III (apoLp-III) was isolated from the haemolymph of last instar larvae of Galleria mellonella . The ultraviolet (u.v.) spectrum and the N-terminal amino acid sequence reveal high similarities with the apoLp-III from Manduca sexta . The protein is heat-stable . The molecular mass of apoLp-III was determined to be 18 077 Da using mass spectrometry . The heat treatment (90 degrees C, 30 min) resulted in a pI shift from 6.6 for the non-heated to 6.1 for the heat-treated apoLp-III without change in the molecular mass, indicating that a conformational change might have been caused by the heat treatment, rather than covalent alterations . Intrahaemocoelic injection of pure apoLp-III into last instar G . mellonella larvae is followed by a dose-dependent increase of antibacterial activity in cell-free haemolymph of treated larvae 24 h after injection . Furthermore, pure apoLp-III enhances the phagocytic activity of isolated haemocytes in vitro . The newly discovered role of apoLp-III in inducing immune-related functions in insects is discussed in regard to the known features of this molecule in lipid metabolism . Arylphorin, another heat-stable protein in G . mellonella haemolymph, was likewise isolated in this study . The protein was identified by N-terminal protein sequencing, the sequence obtained exactly matches the known sequence data for this protein . Curr Pharm Des, 2003, 9(16), 1257 - 75 Antibacterial and antiviral effects of milk proteins and derivatives thereof; Florisa R et al.; Milk forms a rich source of biologically interesting components . In particular, its protein fraction is known to encompass many kinds of biological functions . In this review we focus on antibacterial and antiviral properties of milk proteins and milk protein derivatives . The latter include chemically modified proteins and enzymatically induced peptides . If such peptides are released by enzymes present within the digestive tract (e.g . trypsin or pepsin), it is likely that they play a role in the health defense system . This is especially the case when the active fragments can survive the intestinal conditions long enough to arrive at the right place to exert their beneficial function . In the first part of this paper attention is paid to the antibacterial proteins lactoferrin, lactoperoxidase, and lysozyme . Furthermore, antibacterial peptides originating from caseins and whey proteins are described . The second part reports on studies of antiviral effects of milk proteins and derivatives thereof . Special focus is directed to the antiviral action towards the human immunodeficiency virus (HIV) and the human cytomegalovirus (HCMV) . Unmodified milk proteins are generally not active against these viruses . An exception is lactoferrin, which shows significant antiviral activity against both HIV and HCMV . Several other milk proteins tested showed strong antiviral effects only after chemical modification, i.e . by making them polyanionic (for anti-HIV activity) or polycationic (for anti-HCMV activity) . In a number of cases, conclusions are drawn concerning possible relationships between antibacterial/antiviral activity and molecular structure of the components described. Biotechnol Bioeng, 2003 Jul 20, 83(2), 168 - 72 Mechanism of bactericidal and fungicidal activities of textiles covalently modified with alkylated polyethylenimine; Lin J et al.; Our previous studies have led to a novel "nonrelease" approach to making materials bactericidal by covalently attaching certain moderately hydrophobic polycations to their surfaces . In the present work, this strategy is extended beyond the heretofore-used nonporous materials to include common woven textiles (cotton, wool, nylon, and polyester) . Pieces of such cloths derivatized with N-hexylated+methylated high-molecular-weight polyethylenimine (PEI) are strongly bactericidal against several airborne Gram-positive and Gram-negative bacteria . In contrast, the immobilized and N-alkylated PEIs of low molecular weight have only a weak, if any, bactericidal activity . These findings support a mechanism of the antibacterial action whereby high-molecular-weight and hydrophobic polycationic chains penetrate bacterial cell membranes/walls and fatally damage them . The bactericidal textiles prepared herein are lethal not only to pathogenic bacteria but to fungi as well . Biochem Biophys Res Commun, 2003 Jun 13, 305(4), 997 - 1001 Crystallization and characterization of polyphosphate kinase from Escherichia coli; Zhu Y et al.; Linear polyphosphate chains have been found to play a key role in bacterial responses to stresses and nutritional depletion, and are necessary for host infection of various pathogens . Polyphosphate kinase (PPK) is a critical enzyme responsible for polyphosphate synthesis in bacteria . PPK knockout mutations in several Gram-negative pathogens identify PPK as an ideal drug target for the development of a new class of antibacterial drugs . To reveal the catalytic mechanism and provide a structural basis for drug discovery, we have purified and crystallized full-length Escherichia coli PPK and its complex with AMP-PNP . The crystals diffract to a resolution of 2.5A and belong to the space group P4(2)2(1)2 with unit-cell parameters a=152.0, b=152.0, and c=150.0 A . Crystal structure of PPK is being determined by the Se-Met MAD experiment. Am Heart J . 2003 May;145(5):E20. Antibiotics in primary prevention of myocardial infarction among elderly patients with hypertension; Brassard P et al.; BACKGROUND: Given the premise that certain bacteria (such as Chlamydia pneumoniae) may play a role in the etiology of atherosclerosis, subjects treated with antibiotics that have antibacterial activity against C pneumoniae may be at lower risk for the development of an acute myocardial infarction (MI) than untreated subjects . METHODS: A case-control design, nested within a cohort of 29,937 elderly subjects in whom antihypertensive therapy was initiated (1982-1995) was used, in which each subject who was hospitalized with a primary discharge diagnosis of MI between 1987 and 1995 (n = 1047) was matched on calendar time to 5 randomly selected control subjects for exposure contrasts . Conditional logistic regression analyses were conducted to adjust for predisposing factors for MI . RESULTS: Although no clear consistent effect of antibiotics use was found in relation to MI, a trend was observed for a decreased risk of acute MI in patients receiving a prescription for antichlamydial antibiotics in the preceding 3 months (odds ratio 0.68, 95% CI 0.46-1.00) . Antibiotics without antichlamydial activity showed no benefit in MI risk . CONCLUSION: The beneficial effect of certain antichlamydial antibiotics in reducing the risk of MI cannot be excluded on the basis of this representative cohort of elderly patients in a routine clinical care setting . Larger prospective studies are required to confirm the usefulness of antibiotics in the primary prevention of MI. Paediatr Drugs, 2003, 5(6), 363 - 72 Diagnosis, treatment, and prevention of Lyme disease in children; Eppes SC; The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience . In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi . This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD . Issues specifically related to the management of children will be identified . Controversies regarding treatment approaches will be examined in some detail . Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment . Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans . Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete . Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody . Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range.Early localized disease responds well to oral antibacterial therapy . Early disseminated disease, often associated with neurologic findings, may require parenteral therapy . The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery . Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children . Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy . Tick avoidance has long been the mainstay for preventing LD . Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain . Vaccines designed to prevent infection have also been developed. Toxicol Lett, 2003 Apr 30, 142(1-2), 103 - 9 Transplacental pharmacokinetics of the new fluoroquinolone DW-116 in pregnant rats; Kim JC et al.; DW-116 is a newly developed fluoroquinolone antibacterial with a broad spectrum against both gram-positive and gram-negative bacteria . Recently, we have reported that DW-116 induces a significant developmental toxicity in rat . The present study was undertaken to characterize the placental transfer and pharmacokinetics of DW-116 in Sprague-Dawley rats . Pregnant females were given a single oral dose of 500-mg {14C}DW-116/kg on gestational day 18 . Maternal and fetal tissues were collected at 0.17, 0.5, 1, 2, 4, 8 and 24 h after dosing . The {14C}DW-116-derived radioactivity was rapidly distributed to the fetus and slowly eliminated from the tissue . The radioactivity in both maternal plasma and fetal tissue reached its peak within 1 h and maintained the level of radioactivity up to 16-28% of the peak level until 24 h after dosing . Radioactivity in whole fetus was higher than those in the maternal plasma and placenta . The T(1/2)abs, T(1/2)beta, AUC, Tmax and Cmax in the maternal plasma were approximately 6 min, 13.3 h, 1620 microg h/ml, 0.5 h and 136 microg/ml, respectively . Those in the placenta were approximately 20 min, 12.3 h, 2150 microg h/ml, 1.0 h and 172 microg/ml, respectively . Those in the whole fetus were 13 min, 12.8 h, 2549 microg h/ml, 1 h and 191 microg/ml, respectively . In the amniotic fluid of maternal uterus, the T(1/2)abs, T(1/2)beta, AUC, Tmax and Cmax were approximately 1.3 h, 9.3 h, 2508 microg h/ml, 4.4 h, and 135 microg/ ml, respectively . While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid . These results indicate that (1) total radioactivity appeared rapidly in maternal plasma and fetuses; (2) the elimination of total radioactivity is slow; and (3) DW-116 or relevant metabolites could cross the blood-placenta barrier in pregnant rats. J Inorg Biochem, 2003 Jun 1, 95(2-3), 199 - 207 Interactions of oxovanadium(IV) and the quinolone family member--ciprofloxacin; Turel I et al.; The interactions of quinolone ciprofloxacin (cfH) and oxovanadium(IV) were studied by various methods . Green crystals of a complex {V(IV)O(cf)(2)(H(2)O)} were isolated and the molecular connectivities established, although the crystal structure was not perfectly refined due to the instability of the crystals . Based on a plausible interpretation of the data sets, two cf anions bidentately coordinate to a vanadyl cation through carboxylate and carbonyl oxygen atoms; in addition, there is a water molecule in the coordination sphere . Solution techniques (cyclic voltammetry, electronic and electron paramagnetic resonance spectroscopy, potentiometric measurements) confirmed the presence of various species in the solution, the composition of which strongly depends on the conditions in the system . The antibacterial activity of the complex against various microorganisms was tested and it was established that its activity is similar to that of free ciprofloxacin. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1991 - 4 Stability and antibacterial activity of cefepime during continuous infusion; Sprauten PF et al.; The stability of cefepime during simulated continuous infusion was determined with a motorized portable infusion pump worn over a period of 24 to 36 h . Susceptibility testing on cefepime solutions over time indicates that the degradation products do not exhibit antibacterial activity . Cefepime stability at 24 h following continuous infusion was 94.3% +/- 1.0%, which supports the use of continuous infusion. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1943 - 7 Activities of ertapenem, a new long-acting carbapenem, against penicillin-sensitive or -resistant pneumococci in experimental meningitis; Cottagnoud P et al.; The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively . Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 +/- 0.17 and 0.59 +/- 0.22 log(10) CFU/ml x h, respectively, in the viable cell counts in the cerebrospinal fluid . The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain) . In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains . Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro. Antimicrob Agents Chemother, 2003 Jun, 47(6), 1836 - 41 Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo; Wang AM et al.; Antioxidant therapy protects against aminoglycoside-induced ototoxicity in animal models . A clinically suitable antioxidant must not affect the therapeutic efficacy of aminoglycosides or exhibit any side effects of its own . In addition, the treatment should be inexpensive and convenient in order to be implemented in developing countries where the use of aminoglycosides is most common . Standardized Salviae miltiorrhizae extracts (Danshen) are used clinically in China and contain diterpene quinones and phenolic acids with antioxidant properties . We combined in vitro and in vivo approaches to investigate the effect of a clinically approved injectable Danshen solution on aminoglycoside-induced free radical generation and ototoxicity . In vitro, Danshen inhibited gentamicin-dependent lipid peroxidation (formation of conjugated dienes from arachidonic acid), as well as the gentamicin-catalyzed formation of superoxide (in a lucigenin-based chemiluminescence assay) and hydroxyl radicals (oxidation of N,N-dimethyl-p-nitrosoaniline) . Danshen extracts were then administered to adult CBA mice receiving concurrent treatment with kanamycin (700 mg/kg of body weight twice daily for 15 days) . Auditory threshold shifts induced by kanamycin (approximately 50 dB) were significantly attenuated . Danshen did not reduce the levels in serum or antibacterial efficacy of kanamycin . These results suggest that herbal medications may be a significantly underexplored source of antidotes for aminoglycoside ototoxicity . Such traditional medicines are widely used in many developing countries and could become an easily accepted and inexpensive protective therapy. J Antibiot (Tokyo), 2003 Mar, 56(3), 280 - 8 Isolation and structure of a new macrolide antibiotic, erythromycin G, and a related biosynthetic intermediate from a culture of Saccharopolyspora erythraea; Cevallos A et al.; The new naturally occurring erythromycin G (4), formally derived from erythromycin B by hydroxylation of the C-16 methyl group, and 3-O-mycarosylerythronolide B (5), an erythromycin biosynthetic intermediate previously obtained only from microorganisms blocked in erythromycin biosynthesis, were isolated from a concentrate of mother liquors derived from a culture of Saccharopolyspora erythraea . The structure of erythromycin G was defined by spectroscopic data and X-ray crystallographic analysis . Theoretical calculation of 4 has been performed at MM2 level, and the low-energy conformations have been compared with X-ray data: both theoretical and experimental approaches give similar three-dimensional shapes . Antibacterial activity of 4 against both gram-positive and gram-negative organisms has been evaluated . A simple method for the isolation of large amounts of erythromycins B (2) and D is provided as well. Eur J Biochem, 2003 May, 270(10), 2207 - 17 The antibiotic activity of cationic linear amphipathic peptides: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes; Beven L et al.; Peptides composed of leucyl and lysyl residues ('LK peptides') with different compositions and sequences were compared for their antibacterial activities using cell wall-less bacteria of the class Mollicutes (acholeplasmas, mycoplasmas and spiroplasmas) as targets . The antibacterial activity of the amphipathic alpha-helical peptides varied with their size, 15 residues being the optimal length, independent of the membrane hydrophobic core thickness and the amount of cholesterol . The 15-residue ideally amphipathic alpha helix with a +5 positive net charge (KLLKLLLKLLLKLLK) had the strongest antibacterial activity, similar to that of melittin . In contrast, scrambled peptides devoid of amphipathy and the less hydrophobic beta-sheeted peptides {(LK)nK}, even those 15-residue long, were far less potent than the helical ones . Furthermore, the growth inhibitory activity of the peptides was correlated with their ability to abolish membrane potential . These data are fully consistent with a predominantly flat orientation of LK peptides at the lipid/water interface and strongly supports that these peptides and probably the linear polycationic amphipathic defence peptides act on bacterial membranes in four main steps according to the 'carpet' model: (a) interfacial partitioning with accumulation of monomers on the target membrane (limiting step); (b) peptide structural changes (conformation, aggregation, and orientation) induced by interactions with the lipid bilayer (as already shown with liposomes and erythrocytes); (c) plasma membrane permeabilization/depolarization via a detergent-like effect; and (d) rapid bacterial cell death if the extent of depolarization is maintained above a critical threshold. Infect Dis Clin North Am, 2003 Mar, 17(1), 113 - 34, viii Fungal infections in the recipients of solid organ transplantation; Singh N; The advent of effective antibacterial and antiviral prophylatic and therapeutic strategies has led to the emergence of opportunistic mycoses as a principal cause of infection-related mortality in organ transplant recipients . Candida and Aspergillus species have accounted for most invasive fungal infections in organ transplant recipients . Epidemiologic trends within the last decade, however, are notable for the emergence of mycelial fungi other than Aspergillus as increasingly important pathogens in these patients . This article reviews the epidemiology, clinical manifestations, pathogenetic basis, diagnosis, and management of invasive fungal infections after organ transplantation in context of emerging trends and new developments in these areas. Eur J Med Chem, 2003 Apr, 38(4), 345 - 9 Inhibitors of phosphopantetheine adenylyltransferase; Zhao L et al.; Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in Coenzyme A biosynthesis . Because bacterial PPAT and mammalian PPAT are dissimilar, this enzyme is an attractive antibacterial target . Based on the structure of the substrate, 4-phosphopantetheine, a dipeptide library was designed, synthesised and tested against Escherichia coli PPAT . The most potent inhibitor PTX040334 was co-crystallised with E . coli PPAT . With this structural information, a rational iterative medicinal chemistry program was initiated, aimed at increasing the number of inhibitor-enzyme interactions . A very potent and specific inhibitor, PTX042695, with an IC(50) of 6 nM against E.coli PPAT, but with no activity against porcine PPAT, was obtained. Phytother Res, 2003 May, 17(5), 558 - 9 Antibacterial efficacy of Rumex nepalensis Spreng . roots; Ghosh L et al.; The antibacterial property of Rumex nepalensis Spreng . was evaluated against some strains of bacteria . The methanol extract of the roots (tested at 200-1000 micro g/disc) showed significant concentration-dependent antibacterial activity . Lancet, 2003 May 10, 361(9369), 1615 - 7 Development of a standard treatment protocol for severe acute respiratory syndrome; So LK et al.; A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone . Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone . One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone . Four patients required short periods of non-invasive ventilation . No patient required intubation or mechanical ventilation . There was no mortality or treatment morbidity in this series. J Periodontol, 2003 Apr, 74(4), 501 - 5 A pilot study on antiplaque effects of mastic chewing gum in the oral cavity; Takahashi K et al.; BACKGROUND: Chemical plaque control is a useful aid in mechanical oral hygiene, and various chemical agents have been evaluated as antiplaque agents . It has been shown that mastic chewing gum has antibacterial effects on Helicobacter pylori . In this study, the antiplaque effect of mastic chewing gum was investigated . METHODS: Twenty dental students who were both systemically and periodontally healthy participated in this study . The effects of mastic gum were assessed from 2 double-blinded, randomized studies . In the first trial, after mechanical toothbrushing, the inhibitory effect of mastic gum on bacteria in saliva following its use was compared to a placebo gum . Saliva samples were collected at the end of 1, 2, 3, and 4 hours; diluted; inoculated onto 10% horse blood chocolate agar plates; and cultured anaerobically at 37 degrees C for 48 hours . The total number of bacterial colonies on each plate was calculated (n = 20) . In the second trial, the effects of mastic gum on de novo plaque formation on tooth surfaces and gingival inflammation were evaluated over a 7-day period without mechanical oral hygiene following random use of either mastic or placebo chewing gum . The degree of plaque accumulation and gingival inflammation were compared between the 2 groups (n = 10) . RESULTS: The total number of bacterial colonies was significantly reduced during the 4 hours of chewing mastic gum compared to the placebo gum (P < 0.05, Student t test) . The mastic group showed a significantly reduced plaque index (2.69 +/- 0.29 versus 3.15 +/- 0.24; P = 0.001, Student t test) and gingival index (0.44 +/- 0.15 versus 0.66 +/- 0.23, P = 0.021, Student t test) compared to the placebo group . CONCLUSION: These results suggest that mastic chewing gum is a useful antiplaque agent in reducing the bacterial growth in saliva and plaque formation on teeth. J Perinat Med, 2003, 31(2), 176 - 83 Impaired CD14-dependent and independent response of polymorphonuclear leukocytes in preterm infants; Henneke P et al.; Preterm newborn infants are especially susceptible to Gram-negative sepsis that is associated with a lethality of up to 40% . AIMS: We tested whether polymorphonuclear leukocytes (PMN) from preterm infants exhibit an impaired antibacterial response upon stimulation with lipopolysaccharide (LPS) from Escherichia coli when compared to full term newborns or adults . METHODS: We studied the effect of LPS on the expression of the surface proteins CD11b and CD14 and the secretion of elastase by PMN from preterm infants, term infants and adults ex vivo . RESULTS: We found a significantly reduced antibacterial activity of PMN from preterm infants upon stimulation with LPS as indicated by low surface expression of the adhesion molecule CD11b and the reduced secretion of PMN elastase . LPS-induced CD11b expression was dependent on binding of LPS to the surface protein CD14 as CD14 antibodies inhibited LPS dependent CD11b upregulation . Furthermore CD14 expression was lower on PMN from preterm infants than from adults . In addition, CD14 independent upregulation of CD11b in response to tumor necrosis factor (TNF-alpha), N-formyl peptides (FMLP) and phorbol ester (PMA) was impaired . CONCLUSION: PMN from preterm infants are distinctly hyporesponsive to LPS, which may explain the predisposition of these children to invasive disease due to gramnegative bacteria. Probl Tuberk, 2003, (3), 40 - 1 {Results of studying of the pathomorphism of pulmonary tuberculosis in Iakutiia}; Basharin KG; The paper summarizes the results of studies into the pathological anatomy and pathomorphism of pulmonary tuberculosis in Yakutia, which have been conducted by the Department of Anatomy, Yakutsk State University Medical Institute, over 36 years . A morphological comparative analysis of autopsies of individuals who died from different forms in the pre-antibacterial and antibacterial periods and surgical materials were used as a major source of data . More than 1,000 autopsies made it possible to define a wide range of behavioral patterns and the morphological features of pulmonary tuberculosis under the extreme climatic conditions of the Far North . These findings have made a significant contribution to the development of the new scientific school Northern Phthisiology. Neuro Endocrinol Lett, 2003 Feb-Apr, 24(1-2), 39 - 45 Antibacterial properties of hemerythrin of the sand worm Nereis diversicolor; Deloffre L et al.; OBJECTIVES: To investigate the immune defense of the annelid Nereis diversicolor and the key role of a oxygen-binding protein, the metalloprotein MPII animals were subjected to bacteria infection . METHODS AND RESULTS: Using RACE-PCR, we have cloned the complete cDNA coding for the MPII related to the hemerythrin family in the sand worm Hediste diversicolor . This cDNA (883 pb) codes for a polypeptide of 119 amino acid residues with no signal peptide . Previous works have identified this protein as a cadmium scavenger . We here clearly demonstrated that this protein is also involved in the worm defence towards bacteria growth by its iron scavenger ability . This protein is expressed and produced in a haematopoietic center that floats freely in the coelomic fluid before stored in a particular hemocyte type: the granulocyte type 1 . During bacterial challenge, this protein contained in these cells is discharged into the blood stream 3-4 hours after the infection and remains active for approximately 10 hours . This time period blocks progression of the pathogen and its attachment to tissues . CONCLUSION: These results reflect that MPII in conjunction with others partners like lysozyme act as defence molecule for the sand worm. Antiviral Res, 2003 Apr, 58(2), 159 - 65 Synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro; van der Strate BW et al.; Human cytomegalovirus (HCMV) causes severe morbidity and mortality in immunocompromised patients . Treatment of HCMV infections with conventional antiviral drugs like ganciclovir and cidofovir has major drawbacks (i.e . serious side effects) . Therefore, combination therapies using drugs with different antiviral mechanisms should be envisaged . Potential synergy between lactoferrin (LF), an antibacterial, antimycotic and antiviral protein, and the antiviral drugs acyclovir, ganciclovir, foscarnet and cidofovir was investigated, using an in vitro test system with the recombinant RC256 HCMV strain . RESULTS: Combination of LF with acyclovir and foscarnet resulted in antagonism . When LF and ganciclovir were combined, neither synergy nor antagonism was observed . Strikingly, the combination of LF with cidofovir resulted in marked synergy . The synergistic effect could be explained by inhibition of two subsequent steps in the viral replication cycle: HCMV penetration into the target cells and intracellular synthesis of HCMV DNA . In conclusion, LF might be a potential candidate for combination therapy with cidofovir. J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Jun 15, 789(2), 211 - 8 Highly sensitive quantification of vancomycin in plasma samples using liquid chromatography-tandem mass spectrometry and oral bioavailability in rats; Shibata N et al.; We developed a highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS-MS) for a glycopeptide antibacterial drug, vancomycin (VCM), in rat plasma . After precipitating 100 micro l of plasma with 300 micro l of 10% trifluoroacetic acid-methanol (2:1, v/v), the supernatant was diluted with 300 micro l of distilled water and was passed through a filter . LC-MS-MS equipped with electrospray ionization in the positive ion mode used a pair of ions at 725/144 m/z for VCM in the multiple reaction-monitoring mode with a sample injection volume of 20 micro l . The calibration curve had a linear range from 0.01 to 20 micro g/ml when linear least square regression was applied to the concentration versus peak area plot . The drug in the sample was detected within 5 min . Precision, accuracy and limit of quantitation indicated that this method was suitable for the quantitative determination of VCM in rat plasma . Using this method, we defined for the first time that the oral bioavailability of VCM in rats was 0.069% . This method can be applied to basic pharmacokinetic and pharmaceutical studies in rats. J Clin Pediatr Dent, 2003 Spring, 27(3), 251 - 6 Antibacterial and conventional self-etching primer system: morphological evaluation of intact primary enamel; Daronch M et al.; The aim of this study was to analyze the etching effect of a new dental adhesive system that uses an antibacterial and self-etching primer agent . Non-carious primary human molars were divided into three groups: 35% phosphoric acid etching (3M-ESPE), self-etching primer (Clearfil SE Bond--Kuraray) and antibacterial self-etching primer (ABF experimental system--Kuraray) for SEM evaluation of surface, resin replicas and interface . Both self-etching primers produced shallow grooves and no defined etching morphologies . Phosphoric acid produced definite etching patterns at the enamel surface. Kansenshogaku Zasshi, 2003 Apr, 77(4), 219 - 26 {Clinical evaluation of performance of a new diagnostic method for deep mycosis by measuring beta-glucan concentration in the blood}; Moro H et al.; beta-Glucan Test MARUHA for high sensitive diagnosis of deep mycosis which was developed recently detects (1-->3)-beta-D-glucan, a component of the cell wall . The performance of beta-Glucan Test MARUHA is evaluated in this report . Although existing methods to detect (1-->3)-beta-D-glucan have trouble with sulfa drugs, hemolysis, and immunoglobulin G (IgG), these problems were overcome by the beta-Glucan Test MARUHA: No effect was observed for beta-Glucan Test MARUHA at lower than 200 micrograms/ml, 500 mg/dl, and 6,000 mg/dl of sulfa drugs, hemoglobin, and IgG, respectively . The effect of drugs administrated on the measurement value of beta-glucan Test MARUHA was checked at several concentrations . However, almost no effect of drugs, such as, 5 kinds of antifungals, 8 kinds of antibiotics, a kind of antibacterial, 2 kinds of infusions, and a kind of contrast media was observed at the practical concentrations. Nat Prod Res, 2003 Jun, 17(3), 189 - 94 GC-MS analysis and bioactivity testing of the volatile oil from the leaves of the toothbrush tree Salvadora persica L; Alali F et al.; Upon GC-MS analysis of the volatile oil extracted from Salvadora persica L . leaves, we were able to identify benzyl nitrile, eugenol, thymol, isothymol, eucalyptol, isoterpinolene, and beta-caryophyllene . Toxicity of the aroma was evaluated using brine shrimp lethality test which gave an LC50 > 1,000 ppm . Using Disc Diffusion Test, it was found that the extract of the leaves has a considerable antibacterial effect on several different oral aerobic bacteria with comparable results to known antibiotics . The extract can be used effectively as a natural tool for teeth cleaning and as a natural analgesic for the disturbing toothache. Cell Mol Life Sci, 2003 Mar, 60(3), 599 - 606 Ascaris nematodes from pig and human make three antibacterial peptides: isolation of cecropin P1 and two ASABF peptides; Andersson M et al.; Organisms co-habiting with bacteria have developed efficient bactericidal agents to control their microbe-rich environment . The Ascaris nematode lives in its final development stages in the gut of its host and is believed to feed on bacteria . Ascaris suum survive in pig intestine while A . lumbricoides is the principal species in humans . Here we show that A . suum and A . lumbricoides both produce linear (cecropin P1) and cysteine-rich (ASABF) peptides with activity against either gram-negative or gram-positive bacteria, respectively . Thus nematodes rely in part on a peptide-based antibacterial system for digestion of bacteria, which may also confer protection against infection . Cecropin P1 was previously isolated from pig intestine but we can now conclude that was due to contaminating nematodes. Methods Find Exp Clin Pharmacol, 2003 Mar, 25(2), 131 - 43 Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori; Furuta T et al.; Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ) . PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver . The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs . Eradication rates by PPI-based therapies are also affected by this genotype, as well as bacterial resistance to antibiotics . An individualized treatment strategy based on CYP2C19-related pharmacogenetics or pharmacogenomics and bacterial resistance is expected to increase the cure rate of the initial treatment . It is also necessary to recognize that there is a possible drug-drug interaction between some of the drugs used in this treatment regimen. Bioorg Med Chem Lett, 2003 May 19, 13(10), 1669 - 72 Identification of 2-aminobenzimidazole dimers as antibacterial agents; Seth PP et al.; The preparation and evaluation of 2-aminobenzimidazole dimers as antibacterial agents is described . Biological screening of the dimers indicated that compounds with multiple chloro substituents possessed optimal antibacterial activity. Fitoterapia, 2003 Apr, 74(3), 305 - 7 Biological activity of Euonymus europaeus; Kumarasamy Y et al.; The n-hexane, dichloromethane and methanol extracts of the seeds of Euonymus europaeus have been screened for antibacterial and free radical scavenging activity . General toxicity (brine shrimp lethality assay) of these extracts has also been assessed. FEMS Immunol Med Microbiol, 2003 May 15, 36(1-2), 9 - 17 Antibacterial actions of fatty acids and monoglycerides against Helicobacter pylori; Sun CQ et al.; The bactericidal potencies of saturated and unsaturated fatty acids (FAs) and monoglycerides (MGs) against Helicobacter pylori were determined following short incubations with freshly harvested cells over a range of pHs . FAs and their derivatives with an equivalent-carbon number of 12 were the most potent: lauric acid had a minimum bactericidal concentration (MBC) at pH 7.4 of 1 mM, myristoleic and linolenic acid were the most potent unsaturated FAs (MBCs of 0.5 mM, pH 7.4), and monolaurin was the most potent MG (MBC 0.5 mM) . Potencies of saturated FAs were increased sharply by lowering pH, and a decrease of only 0.5 pH units can cause a change from non-lethal to lethal conditions . Conversely, the bactericidal action of monolaurin was not pH-dependent . The bactericidal potencies of unsaturated FAs increased with degree of unsaturation . When more than one FA or FA plus MGs were present, their combined action was additive . Urea and endogenous urease did not protect H . pylori from the bactericidal action of FAs . These results suggest that H . pylori present in the stomach contents (but not necessarily within the mucus barrier) should be rapidly killed by the millimolar concentrations of FAs and MGs that are produced by pre-intestinal lipase(s) acting on suitable triglycerides such as milk fat. Ann Surg, 2003 May, 237(5), 677 - 85; discussion 685 Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing; Ikeda S et al.; OBJECTIVE: To determine the influence of route of nutrition on gut mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) expression and the effect of MAdCAM-1 blockade on gut-associated lymphoid tissue (GALT) lymphocyte populations and established respiratory antibacterial immunity . SUMMARY BACKGROUND DATA: Lymphocytes, sensitized to antigens in Peyer's patches, migrate via mesenteric lymph nodes and home to intestinal lamina propria . MAdCAM-1 located on endothelial cells regulates this trafficking . Experimentally, parenteral nutrition (PN) decreases GALT cell mass and mucosal immunity when compared with enteral feeding . METHODS: In experiment 1, MAdCAM-1 expression was quantified in 32 mice after 4 days of feeding chow, a complex diet, intragastric (IG)-PN, or PN . In experiment 2, MAdCAM-1 was measured in 102 mice 0, 4, 8, 12, 24, 48, or 72 hours after starting PN and at 0, 4, 8, 12, 24, or 48 hours after reinstituting chow following 5 days of PN . In experiment 3, 56 mice received chow, PN, chow + MECA-367 (anti-MAdCAM-1 mAb), or chow + Isotype control Ab (IsoAb) for 5 days, followed by Peyer's patches, lamina propria, and intraepithelial lymphocyte yield with respiratory and intestinal IgA levels . In experiment 4, 10 days after Pseudomonas immunization, mice received chow + MECA-367 or chow + IsoAb for 4 days followed by 1.2 x 108 Pseudomonas intratracheally . RESULTS: Diet and route affect MAdCAM-1 expression (chow > complex diet > IG-PN > PN) . Decreased MAdCAM-1 expression occurred within hours of starting PN in Peyer's patches, but not mesenteric lymph nodes or the intestine, and recovered quickly with enteral refeeding . MAdCAM-1 blockade reduced all GALT populations . Blockade had little effect on IgA levels and partially impaired the late response of established respiratory immunity . CONCLUSIONS: Enteral feeding affects MAdCAM-1 expression . Complete MAdCAM-1 blockade reduces GALT lymphocytes to PN levels, but the chow feeding stimulus preserves IgA and early antibacterial resistance, implying the existence of non-MAdCAM-1 mechanisms to preserve mucosal immunity. J Med Chem, 2003 May 8, 46(10), 1795 - 8 Synthesis and antibacterial activity of 6-O-arylbutynyl ketolides with improved activity against some key erythromycin-resistant pathogens; Keyes RF et al.; A series of novel 6-O-substituted homopropargyl ketolides was synthesized and evaluated against various erythromycin-resistant pathogens . Promising in vitro antibacterial activity was demonstrated for compounds bearing this structural motif. Support Care Cancer, 2003 Jun, 11(6), 356 - 61 Epub 2003 Apr 26. Resource utilization and cost of episodes of febrile neutropenia in children with acute leukemias and lymphomas; Costa VC et al.; The resource utilization and cost of 51 episodes of febrile neutropenia in children with leukemia and lymphomas who were admitted to the Pediatric Oncology Institute (GRAAC) of the Federal University of Sao Paulo were analyzed . Patients aged 60 days to 21 years with confirmed diagnoses of acute myeloid leukemia, acute lymphoid leukemia, non-Hodgkin lymphoma, or Hodgkins disease who presented axillary temperature above 38 degrees C at least once episode, or between 37.5 degrees C and 38 degrees C on three occasions during a 24-h period, neutrophil count below 500/mm(3), or between 500/mm(3)and 1,000/mm(3) but expected to fall below 500/mm(3) were included in the study . The patients' ages varied between 1 and 15.6 years, and 67% of the patients were male . The median cost per treated episode was US dollars 2,660 (2,039) . Hospitalization costs accounted for 62% of the total cost of the treatment, antibacterials accounting for 23% . Episodes in patients with documented infections had a higher median direct cost than episodes in patients with fever of unknown origin (P=0.018) . There was a trend for a higher median direct cost in episodes among patients with a worse prognostic factor, such as type of underlying disease, presence of documented infection, and longer duration of neutropenia . This is the first study to evaluate the economics of febrile neutropenia episodes in Brazil, and serves as a basis for resource utilization and costs incurred in the treatment of such patients in this country. Proc Natl Acad Sci U S A, 2003 May 13, 100(10), 6009 - 14 Epub 2003 Apr 28. Antigens in tea-beverage prime human Vgamma 2Vdelta 2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses; Kamath AB et al.; Human gammadelta T cells mediate innate immunity to microbes via T cell receptor-dependent recognition of unprocessed antigens with conserved molecular patterns . These nonpeptide alkylamine antigens are shared by tumor cells, bacteria, parasites, and fungi but also by edible plant products such as tea, apples, mushrooms, and wine . Here we show that priming of gammadelta T cells with alkylamine antigens in vitro results in a memory response to these antigens . Such priming results also in a nonmemory response to whole bacteria and to lipopolysaccharide, characterized by IL-12-dependent secretion of IFN-gamma by gammadelta T cells and by gammadelta T cell proliferation . Drinking tea, which contains l-theanine, a precursor of the nonpeptide antigen ethylamine, primed peripheral blood gammadelta T cells to mediate a memory response on reexposure to ethylamine and to secrete IFN-gamma in response to bacteria . This unique combination of innate immune response and immunologic memory shows that gammadelta T cells can function as a bridge between innate and acquired immunity . In addition, these data provide an explanation for the health benefits of tea. J Biol Chem, 2003 Jul 18, 278(29), 26497 - 504 Epub 2003 Apr 28. Polymerization of mycobacterial arabinogalactan and ligation to peptidoglycan; Yagi T et al.; The cell wall of Mycobacterium spp . consists predominately of arabinogalactan chains linked at the reducing ends to peptidoglycan via a P-GlcNAc-(alpha1-3)-Rha linkage unit (LU) and esterified to a variety of mycolic acids at the nonreducing ends . Several aspects of the biosynthesis of this complex have been defined, including the initial formation of the LU on a polyprenyl phosphate (Pol-P) molecule followed by the sequential addition of galactofuranosyl (Galf) units to generate Pol-P-P-LU-(Galf)1,2,3, etc . and Pol-P-P-LU-galactan, catalyzed by a bifunctional galactosyltransferase (Rv3808c) capable of adding alternating 5- and 6-linked Galf units . By applying cell-free extracts of Mycobacterium smegmatis, containing cell wall and membrane fragments, and differential labeling with UDP-{14C}Galp and recombinant UDP-Galp mutase as the source of {14C}Galf for galactan biosynthesis and 5-P-{14C}ribosyl-P-P as a donor of {14C}Araf for arabinan synthesis, we now demonstrate sequential synthesis of the simpler Pol-P-P-LU-(Galf)n glycolipid intermediates followed by the Pol-P-P-LU-arabinogalactan and, finally, ligation of the P-LU-arabinogalactan to peptidoglycan . This first time demonstration of in vitro ligation of newly synthesized P-LU-arabinogalactan to newly synthesized peptidoglycan is a necessary forerunner to defining the genetics and enzymology of cell wall polymer-peptidoglycan ligation in Mycobacterium spp . and examining this step as a target for new antibacterial drugs. J Coll Physicians Surg Pak, 2003 Apr, 13(4), 195 - 7 Furuncular myiasis by tumbu fly; Mashhood AA; OBJECTIVE: To study cases of furuncular myiasis by tumbu fly (Cordylobia anthropophaga) among Pakistani troops in Sierra Leone, Africa . DESIGN: Observational study . PLACE AND DURATION OF STUDY: Pakistani troops in Sierra Leone, Africa . The duration of the study was 1 year, from July 2001 to August 2002 . SUBJECTS AND METHODS: Two hundred and forty-eight cases of furuncular myiasis were observed among Pakistani soldiers . All the patients were male . The lesions were treated by removal of the larva followed by twice daily application of an antibacterial ointment . The extraction was done by injecting 2% xylocaine over the base of the nodule . Care was exercised in not damaging the larva while extracting . RESULTS: The ages were from 22 to 43 years . Mean age was 29.42 years . The patients presented with a solitary lesion (178 out of total 248 cases, 71.8%) or multiple lesions (70 out of 248 cases, 28.2%) . The lesions were almost always on the non-exposed parts of the body (239 cases out of total 248 cases, 96.37%) . One case presented with a lesion on the face and 8 cases had lesions over dorsum of hands or feet . CONCLUSION: This disease is common in tropical Africa . The knowledge of the disease, its management and prevention is necessary for all the individuals who are planning to visit tropical Africa. Paediatr Drugs, 2003, 5(5), 335 - 49 The management of idiopathic nephrotic syndrome in children; Hodson E; Childhood nephrotic syndrome is a rare condition with an incidence of 1-2 per 100000 children aged below 16 years . Untreated idiopathic nephrotic syndrome (INS) is associated with increased risks of life-threatening infection, thromboembolism, lipid abnormalities, and malnutrition . The aim of the management of INS in children is to induce and maintain complete remission with resolution of proteinuria and edema without serious adverse effects of therapy.The majority of children have corticosteroid sensitive idiopathic nephrotic syndrome (CSINS), and in these children, corticosteroid therapy is the mainstay of therapy to induce remission . Data from a meta-analysis of randomized controlled trials (RCTs) indicate that prolonged courses of corticosteroids (up to 7 months) given in the first episode of CSINS reduce the risk of relapse . Nevertheless, many children relapse, and are at risk of corticosteroid toxicity if frequent courses of corticosteroids are required . Data from RCTs supports the use of alkylating agents (cyclophosphamide, chlorambucil), cyclosporine, and levamisole in these children to achieve prolonged periods of remission . The specific management of corticosteroid-resistant idiopathic nephrotic syndrome (CRINS) is more difficult since few therapies are consistently effective, and data from RCTs are limited . In such children, cyclosporine, alkylating agents, and high dose intravenous methylprednisone may be used.In addition to specific therapies for INS, supportive therapies are commonly used to control edema (loop diuretics, aldosterone antagonists, albumin infusions, angiotensin-converting enzyme inhibitors), reduce the risk of infection (antibacterials, pneumococcal vaccination) and thromboembolism (aspirin {acetylsalicylic acid}), and to control hyperlipidemia (HMG-CoA reductase inhibitors), especially in children with CRINS. Heredity, 2003 May, 90(5), 382 - 9 The ceratotoxin gene family in the medfly Ceratitis capitata and the Natal fruit fly Ceratitis rosa (Diptera: Tephritidae); Rosetto M et al.; Ceratotoxins (Ctxs) are a family of antibacterial sex-specific peptides expressed in the female reproductive accessory glands of the Mediterranean fruit fly Ceratitis capitata . As a first step in the study of molecular evolution of Ctx genes in Ceratitis, partial genomic sequences encoding four distinct Ctx precursors have been determined . In addition, anti-Escherichia coli activity very similar to that of the accessory gland secretion from C . capitata was found in the accessory gland secretion from Ceratitis (Pterandrus) rosa . SDS-PAGE analysis of the female reproductive accessory glands from C . rosa showed a band with a molecular mass (3 kDa) compatible with that of Ctx peptides, also slightly reacting with an anti-Ctx serum . Four nucleotide sequences encoding Ctx-like precursors in C . rosa were determined . Sequence and phylogenetic analyses show that Ctxs from C . rosa fall into different groups as C . capitata Ctxs . Our results suggest that the evolution of the ceratotoxin gene family might be viewed as a combination of duplication events that occurred prior to and following the split between C . capitata and C . rosa . Genomic hybridization demonstrated the presence of multiple Ctx-like sequences in C . rosa, but low-stringency Southern blot analyses failed to recover members of this gene family in other tephritid flies. Bioorg Med Chem, 2003 May 15, 11(10), 2313 - 9 Design, synthesis and biological evaluation of oxazolidinone-quinolone hybrids; Hubschwerlen C et al.; Oxazolidinone-quinolone hybrids that combine the pharmacophores of a quinolone and an oxazolidinone were synthesised and shown to be active against a variety of resistant and susceptible Gram-positive and fastidious Gram-negative organisms . The best compounds in this series overcome all types of resistance in relevant clinical Gram-positive pathogens . The nature of the spacer greatly influences the antibacterial activity . The dual mode of action could be demonstrated for compounds having a piperazinyl spacer . Antibacterial activity was higher at acidic pH. Anal Chem, 2003 Apr 15, 75(8), 1798 - 804 A liquid chromatography-mass spectrometry assay for analyzing sulfonamide antibacterials in cattle and fish muscle tissues; Bogialli S et al.; A simple and rapid method able to determine residues of 12 sulfonamide (SAs) antibacterials in cattle and trout muscle tissues is presented . This method is based on the matrix solid-phase dispersion technique with hot water as extractant followed by liquid chromatography-mass spectrometry (LC-MS) . The LC-MS instrumentation was equipped with an electrospray source and a single quadrupole . After 0.8 g of a flesh sample containing the analytes is deposited on sand (crystobalite), this material is packed into an extraction cell . SAs are extracted by flowing 4 mL of water through the cell heated at 80 degrees C . A 0.5-mL aliquot of the bovine tissue extract is then directly injected into the LC column, while the fish tissue extract is filtered prior to LC-MS analysis . MS data acquisition was performed in the positive-ion mode and monitoring at least three ions for each target compound . Confirmatory ions were produced by the in-source collision-induced dissociation process . At the tolerance levels issued by the EU and U.S . Food and Drug Administration, i.e., 100 ppb, recovery of the analytes in bovine and trout muscle tissues was 75-98% with RSDs ranging between 1 and 8% . Estimated limits of quantification (S/N = 10) were 6-15 ppb for SAs in bovine muscle tissue and 3-13 ppb in trout fillet . When trying to reduce the analysis time by using a short chromatographic run time, severe ion signal suppression was experienced for the early-eluted SAs . This effect was traced to competition effects by polar endogenous coextractives, maybe proteinaceous species, which are eluted in the first part of the chromatographic run . This unwelcome effect was removed by simply adopting more selective chromatographic conditions.
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