Nutr Cancer, 2002, 43(1), 76 - 81 Antineoplastic activity of Solidago virgaurea on prostatic tumor cells in an SCID mouse model; Gross SC et al.; Solidago virgaurea (goldenrod) has traditionally been used as an anti-inflammatory herbal medicine for the treatment of various symptoms, including prostatic diseases . The plant has also been reported to have antibacterial, spasmolytic, and carminative properties . During the course of our screening for antineoplastic activities in various herbal plants, we found that the extract of S . virgaurea exhibits strong cytotoxic activities on various tumor cell lines . The active component mostly resides in the leaves of the plant and is soluble in water . When the extract was fractionated by a Sephadex G-100 column, the active fraction corresponded to a molecular weight of approximately 40,000 . This cytotoxic activity is effective on various tumor cell lines, including human prostate (PC3), breast (MDA435), melanoma (C8161), and small cell lung carcinoma (H520) . To examine the effect of the cytotoxic activity on tumor cells in vivo, we used the rat prostate cell line (AT6.1) and an SCID mouse model . AT6.1 cells were injected into the flank of SCID mice, and then the G-100 fraction of S . virgaurea was administered intraperitoneally or subcutaneously every 3 days . The size of the tumor was measured for up to 25 days . The growth of the tumor was significantly suppressed by the G-100 fraction at 5 mg/kg without any apparent side effects . Therefore, S . virgaurea is considered to be promising as an antineoplastic medicine with minimal toxicities. Acta Pharmacol Sin, 2002 Dec, 23(12), 1127 - 41 Morinda citrifolia (Noni): a literature review and recent advances in Noni research; Wang MY et al.; Morinda citrifolia L (Noni) has been used in folk remedies by Polynesians for over 2000 years, and is reported to have a broad range of therapeutic effects, including antibacterial, antiviral, antifungal, antitumor, antihelmin, analgesic, hypotensive, anti-inflammatory, and immune enhancing effects . In order to reveal the nutritional and medicinal value of the Noni plant, and to summarize scientific evidence that supports the Polynesians' claim, a literature review and recent advances in Noni research is given below. Nat Prod Lett, 2002 Dec, 16(6), 407 - 13 Steroid and antibacterial steroidal glycosides from marine green alga Codium iyengarii Borgesen; Ali MS et al.; The ethyl acetate soluble part of methanolic extract of marine green alga Codium iyengarii collected from Karachi coast of Arabian Sea afforded a new steroid ({structure: see text}, iyengadione) and two new steroidal glycosides {iyengaroside-A ({structure: see text}) and B ({structure: see text})} along with clerosterol galactoside ({structure: see text}) . Their structures were elucidated with the aid of 1D-NMR spectroscopy and reconfirmed through HMBC experiments . The bactericidal activity of {structure: see text} was also explored and found positive response from iyengaroside-A ({structure: see text}) and clerosterol galactoside ({structure: see text}). Curr Drug Targets Infect Disord, 2002 Jun, 2(2), 109 - 19 Antibacterial drug discovery in the post-genomics era; Lerner CG et al.; Antibacterial research has evolved dramatically over the past five decades . Early work relied on serendipity of finding drug-like molecules, usually natural products that had desirable antibacterial and nontoxic properties without regard to mechanism of action . In the past decade, however, significant technological advances in the fields of genomics, molecular biology, high-throughput screening, and structural biochemistry have led to a fundamentally new paradigm in the pursuit of novel antibacterial agents . The new methods promise to lead to the discovery of novel drug-target pairs that will be useful in the continuing battle against drug-resistant bacterial infections . This review describes this new paradigm, the technologies on which it is based, and the current status of this approach in drug discovery. J Antimicrob Chemother, 2002 Dec, 50(6), 883 - 8 Activity against Plasmodium falciparum of cycloperoxide compounds obtained from the sponge Plakortis simplex; Fattorusso E et al.; There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs . In the last few years, artemisinin, the endoperoxide sesquiterpene lactone derived from Artemisia annua, and its derivatives proved to be very active against Plasmodium falciparum . These compounds are characterized by an endoperoxide pharmacophore that is critical for their antimalarial activity . There are several reports, from our group and others, that marine organisms can be another natural source of stable cyclic peroxides, with selective antifungal or antibacterial activity . With the aim of identifying new bioactive molecules, we evaluated in vitro the antimalarial activity of the major cycloperoxides extracted from the sponge Plakortis simplex . The six-membered endoperoxide compounds plakortin and dihydroplakortin, but not the five-membered cycloperoxide plakortide E, inhibited the growth of cultured P . falciparum parasites, both chloroquine-sensitive D10 strain and chloroquine-resistant W2 strain . The IC50 values were similar for both compounds and in the range of 1263-1117 nM against D10, and 735-760 nM against W2, using the colorimetric parasite lactate dehydrogenase assay . The activity of plakortin and dihydroplakortin was significantly higher against chloroquine-resistant than chloroquine-susceptible parasites, following a pattern similar to that of artemisinin, although they were 50-fold less active . Moreover, plakortin and dihydroplakortin showed an additive effect when used in combination with chloroquine . These results support further studies on cycloperoxides of marine origin to characterize their mechanism of action and identify/synthesize new compounds with stronger antimalarial activity. Biochemistry (Mosc), 2002 Oct, 67(10), 1152 - 8 L-Lysine alpha-oxidase: physicochemical and biological properties; Lukasheva EV et al.; This review summarizes data on the properties of L-lysine alpha-oxidase, an enzyme that belongs to the group of oxidases of L-amino acids . This enzyme acts virtually only on L-lysine with a rather low Km yielding alpha-keto-epsilon-aminocaproic acid . The decrease in the level of the essential amino acid L-lysine and the formation of hydrogen peroxide during the reaction possibly provide the basis for the unique properties of L-lysine alpha-oxidase: cytotoxic, antitumor, antimetastatic, antiinvasive, antibacterial, and antiviral activities, as well as an immunomodulating effect . Native L-lysine alpha-oxidase and its immobilized forms are promising tools for determination of concentration of L-lysine in various biological materials. J Chromatogr A, 2002 Oct 18, 974(1-2), 53 - 89 Liquid chromatographic-mass spectrometric methods for analyzing antibiotic and antibacterial agents in animal food products; Di Corcia A et al.; Public health agencies in many countries rely on detection by mass spectrometry for unambiguous identification of residues of antibiotic and antibacterial agents in animal food products for human consumption . The introduction of relatively inexpensive and robust LC-MS systems has given a strong impulse to develop determinative and confirmatory methods for the above medicines in foodstuffs . This impulse has been also dictated by thermal instability and lack of volatility of many antibiotics and antibacterials that makes the GC-MS technique of difficult application . Analytical methods developed for analyzing components of the major classes of the medicines mentioned above are here reviewed . The discussion is focused on both sample treatment and final LC-MS analysis. Phytother Res, 2002 Dec, 16(8), 762 - 4 Antibacterial effect of Melia azedarach flowers on rabbits; Saleem R et al.; A methanol extract of Melia azedarach flowers showed potent antibacterial action in rabbits suffering from a skin infection produced by Stapyhlococcus aureus . The healing effects were found comparable to neomycin . Curr Drug Targets Infect Disord, 2001 Aug, 1(2), 181 - 99 The discovery of linezolid, the first oxazolidinone antibacterial agent; Ford CW et al.; The emergence of new antibiotic-resistance in the significant Gram-positive pathogens in the last decade created a substantial medical need for new classes of antibacterial agents . Pharmacia Corporation scientists initiated a discovery research program in oxazolidinone chemistry and biology . Indanone-, tetralone-, and indoline-subunit oxazolidinones provided proof-of-concept interim improvements in antibacterial activity and safety SAR for the program . A method for enantiomeric enrichment of analogs was developed and intensive synthesis and evaluation efforts were undertaken with three oxazolidinone subclasses; the piperazine, indoline, and tropones . Members of the piperazinyl-phenyloxazolidinones possessed the most suitable chemical characteristics and biologic activity of the three subclasses . The monofluorophenyl congener eperezolid and the morpholino analog linezolid emerged as the first clinical candidates from the piperazine oxazolidinones . Linezolid was selected for continued human clinical evaluation based upon its' superior pharmacokinetic profile . Microbiologic testing revealed that linezolid compared very favorably against comparator antibiotics in vitro and in animal infection models . Linezolid possessed a unique mechanism of action in that it inhibited functional 70S initiation complex formation and did not cross-react with existing bacterial resistance . Oral bioavailability in humans was determined to be 100% and twice daily dosing in humans resulted in blood levels which even at trough values were in excess of the MIC90 for significant Gram-positive pathogens . The preclinical promise of linezolid was realized in human clinical trials where linezolid was highly efficacious in the treatment of medically significant Gram-positive infections. Curr Drug Targets Infect Disord, 2001 Aug, 1(2), 91 - 106 Lipopolysaccharide as a target for the development of novel therapeutics in gram-negative bacteria; Yethon JA et al.; Lipopolysaccharide (LPS) constitutes the lipid portion of the outer leaflet of Gram-negative bacteria, and is essential for growth . LPS is also known to be responsible for the variety of biological effects associated with Gram-negative sepsis . In recent years, tremendous progress has been made in determining the exact chemical structure of this highly complex macromolecule, and recent advances have elucidated much of the enzymology involved in its biosynthesis . Using this knowledge, a number of inhibitors to LPS biosynthesis have been developed: some of these compounds have antibacterial properties, while others show excellent in vitro activity and are undergoing further investigation . This review summarizes the main features of LPS structure, function, and biosynthesis, highlighting the potential target reactions that have been or might be exploited for therapeutic intervention. Curr Drug Targets Infect Disord, 2001 May, 1(1), 63 - 77 Molecular mechanisms of antibiotic resistance in gram-positive pathogens; Dessen A et al.; The widespread and uncontrolled use of antibiotics, both for human consumption and animal feed, has encouraged the development of drug resistance in a variety of pathogenic bacteria . Gram-positive species employ resistance mechanisms which include the modification of the antibiotic structure, mutagenesis of key amino acids in the macromolecular targets of specific chemotherapeutics, or drug efflux from the cell, among others . These three main mechanisms have been identified in resistance profiles for systems involved in protein biosynthesis, nucleic acid replication, and bacterial cell wall generation . This work will review how Gram-positive bacteria have manipulated all three classes of targets in the generation of resistance . Upcoming and recently approved antibacterials for human consumption will also be highlighted. Mol Cell, 2002 Nov, 10(5), 1033 - 43 The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition; Goetz DH et al.; First identified as a neutrophil granule component, neutrophil gelatinase-associated lipocalin (NGAL; also called human neutrophil lipocalin, 24p3, uterocalin, or neu-related lipocalin) is a member of the lipocalin family of binding proteins . Putative NGAL ligands, including neutrophil chemotactic agents such as N-formylated tripeptides, have all been refuted by recent biochemical and structural results . NGAL has subsequently been implicated in diverse cellular processes, but without a characterized ligand, the molecular basis of these functions remained mysterious . Here we report that NGAL tightly binds bacterial catecholate-type ferric siderophores through a cyclically permuted, hybrid electrostatic/cation-pi interaction and is a potent bacteriostatic agent in iron-limiting conditions . We therefore propose that NGAL participates in the antibacterial iron depletion strategy of the innate immune system. Am J Trop Med Hyg, 2002 Oct, 67(4), 430 - 5 The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan; Luby S et al.; We conducted a study to determine if soap containing 1.2% triclocarban would be effective in reducing the incidence of impetigo . We randomized 162 households in a low-income neighborhood of Karachi, Pakistan, to receive a regular supply of 1.2% triclocarban-containing soap (n = 81) or an identically appearing placebo (n = 81); 79 households in a nearby neighborhood were enrolled as standard practice controls . After adjustment for household clustering and covariates, the incidence of impetigo among children living in households receiving triclocarban-containing soap (1.10 episodes per 100 person-weeks) was 23% lower than in households receiving placebo soap (P = 0.28) and 43% lower than the standard habit and practice controls (P = 0.02) . The routine use of triclocarban-containing soap by children living in a community with a high incidence of impetigo was associated with a reduced incidence of impetigo. J Pept Sci, 2002 Oct, 8(10), 570 - 7 Parallel and antiparallel dimers of magainin 2: their interaction with phospholipid membrane and antibacterial activity; Mukai Y et al.; Magainin 2 (M2) forms pores by associating with several other M2 molecules in lipid membranes and shows antibacterial activity . To examine the effect of M2 dimerization on biological activity and membrane interaction, parallel and antiparallel M2 dimers were prepared from two monomeric precursors . Antibacterial and haemolytic activities were enhanced by dimerization . CD measurements showed that both dimers and monomers have an alpha-helical structure in the presence of lipid vesicles . Tryptophan fluorescence shift and KI quenching studies showed that all the peptides were more deeply embedded in acidic liposomes than in neutral liposomes . Experiments on dye-leakage activity and membrane translocation of peptides suggest that dimers and monomers form pores through lipid membranes, although the pore formation may be accompanied by membrane disturbance . Although dimerization of M2 increased the interaction activity with lipid membranes, no appreciable difference between the activities of parallel and antiparallel M2 dimers was observed. Biosci Biotechnol Biochem, 2002 Oct, 66(10), 2236 - 8 Synthesis and biological activity of isoamoenylin, a metabolite of Dendrobium amoenum; Venkateswarlu S et al.; Isoamoenylin (6), a dihydrostilbene from Dendrobium amoenum, was synthesised from 3,4,5-trimethoxybenzaldehyde (1) in four steps with an overall yield of 60% . The spectral data for synthetic 6 are in good agreement with those of the natural product . Isoamoenylin showed moderate antioxidative and weak antibacterial activities. Am J Hematol, 2002 Dec, 71(4), 260 - 7 Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation; Koh LP et al.; Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT) . The optimal approach for prophylactic antifungal therapy has yet to be determined . To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT . Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven . High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections . From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB . Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs . AmB 34, P > 0.05) . The incidence of proven fungal infections (FL 12% vs . AmB 12.8%), suspected fungal infections (FL 4% vs . AmB 2.3%), superficial fungal infections (FL 1% vs . AmB 4.6%) did not show any significant difference . The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs . AmB 70%, P = 0.254) . Death attributable to fungal infections was similar in both groups (6% vs . 7%, P > 0.05) . We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation . J Invertebr Pathol, 2002 Oct, 81(2), 94 - 102 Antibacterial activity in Strongylocentrotus droebachiensis (Echinoidea), Cucumaria frondosa (Holothuroidea), and Asterias rubens (Asteroidea); Haug T et al.; A search for antibacterial activity in different body parts of the green sea urchin Strongylocentrotus droebachiensis, the common starfish Asterias rubens, and the sea cucumber Cucumaria frondosa was conducted . Antibacterial activity was detected in extracts from several tissues in all species tested, but mainly in the coelomocyte and body wall extracts . Relatively high antibacterial activity could also be detected in gastrointestinal organs and eggs from A . rubens and in eggs from C . frondosa . Differences between active extracts regarding hydrophobicity and sensitivity to heat and proteinase K treatment indicated that several different compounds were responsible for the antibacterial activities detected . Lysozyme-like activity could be detected in several tissues from A . rubens . Haemolytic activity could be detected in all species tested, especially in the body wall extracts . Results from the current study suggest that marine echinoderms are a potential source for the discovery of novel antibiotics. J Clin Periodontol, 2002 Oct, 29(10), 944 - 54 The efficacy of amine fluoride/stannous fluoride in the suppression of morning breath odour; Quirynen M et al.; BACKGROUND: Breath odour is a complaint encountered worldwide, often linked to microbial overload in the oral cavity . This double blind, crossover, randomised study assessed the efficacy of several antiseptic mouthrinses or slurry vs . a control solution in the prevention of morning bad breath during an experimental period of 7 days without mechanical plaque control . Methods: Sixteen dental students with a healthy periodontium abolished, after a thorough professional cleaning, all means of mechanical plaque control during five experimental periods of 7 days, interleaved by washout periods of at least 3 weeks . During each experimental period, as the only oral hygiene measure, the students rinsed twice a day with one of the following formulations (in a randomised order): a 0.2% chlorhexidine-alcohol mouthrinse (CHX-Alc), a 0.05% CHX + 0.05% cetylpyridinium chloride + 0.14% zinc lactate mouthrinse (CHX-CPC-Zn), an amine fluoride/stannous fluoride (125 ppm F-/125 ppm F-) containing mouthrinse (AmF/SnF2Mr), a slurry of a tooth paste (AmF/SnF2Sl) containing amine fluoride (350 ppm F-) and stannous fluoride (1050 ppm F-) and a placebo solution (placebo) . At days 0, 3 and 7, morning breath was scored via VSC level measurements of the mouth air, and organoleptic ratings of the mouth air and tongue coating . At the same visits both the degree of gingival inflammation and the de novo plaque formation were rated . At the end of each period a questionnaire for subjective ratings was completed and microbiological samples were taken from the tongue dorsum, the saliva and the supragingival plaque for anaerobic and aerobic culturing . Results: Although oral hygiene during the experimental periods was limited to rinsing, bad breath parameters systematically improved (P < 0.001) with the three mouthrinses (CHX-Alc, CHX-CPC-Zn, AmF/SnF2Mr), with a superiority of the CHX-CPC-Zn solution when only VSC values were considered (P < 0.003) . The AmF/SnF2 slurry and the placebo solution showed only minor changes with time . The three mouthrinses reduced significantly (P < 0.001) the bacterial load (aerobic & anaerobic) in the saliva (>or= 0.5 log reduction with a superiority (P < 0.005) for the CHX-Alc when compared to the two others) . Changes in the bacterial load on the tongue dorsum could only be detected for the CHX-Alc solution (0.5 log) . The antibacterial effect of the placebo solution and the slurry were negligible . The composition of microflora on the other hand did not reveal significant changes . The de novo supragingival plaque formation was significantly (P < 0.05) inhibited by the three mouthrinses with a slight superiority for the CHX-Alc solution . The degree of gingival inflammation at day 7 remained low (< 0.16) for all products . The CHX-Alc solution scored significantly worse for the subjective evaluation (questionnaires) concerning taste and sensitivity of tongue) . CONCLUSIONS: The results of this study demonstrate that morning breath odour can be successfully reduced by the sole twice daily use of CHX-Alc, CHX-CPC-Zn or AmF/SnF2Mr mouthrinses, which all significantly reduced the bacterial load in the saliva and retarded the de novo plaque formation. J Org Chem, 2002 Nov 29, 67(24), 8699 - 702 Mild method for cleavage of dehydroalanine units: highly efficient conversion of nocathiacin I to nocathiacin IV; Regueiro-Ren A et al.; Thiazolyl peptide antibacterial nocathiacin I (1) was converted to nocathiacin IV (4) in high yield using iodomethane and hydriodic acid in THF at 45 degrees C . Several simplified dehydroalanine-containing systems undergo dehydroalanine cleavage under the same conditions, although in these cases iodomethane is not needed for efficient conversion . The mild reaction conditions are in contrast with other methods described in the literature. Bioorg Med Chem Lett, 2002 Dec 16, 12(24), 3605 - 9 A simple and rapid method for the differentiation of C-13 manoyl oxide epimers in biologically important samples using GC-MS analysis supported with NMR spectroscopy and computational chemistry results; Demetzos C et al.; There is confusion in the literature related to the characterization of biologically important C13 manoyl oxide epimers by using their mass spectrometric data . Furthermore a method for calculating the epimeric purity has not been established . In this work mixtures of manoyl oxide C13 epimers and pure ent-13-epi-manoyl oxide have been isolated from plant extracts . The GC-MS analysis allows the characterization of each stereoisomer in a sample of natural origin: the ratio of intensities of peaks m/z 275 : 257 is lower in ent-13-epi-manoyl oxide than in manoyl oxide . NMR spectroscopy is used to give experimental evidence and simple calculations were performed to support the MS data . On the basis of these results the characterization of the two stereoisomers and the calculation of their ratio in plant extracts and essential oils can be done in a routine basis . The biological activity evaluation of mixtures with different epimeric composition of manoyl oxide showed that the ratio of the two epimers is important for their antibacterial activity . Ent-13-epi-manoyl oxide seems to be more active than its epimeric congener against Gram-positive bacteria. Bioorg Med Chem Lett, 2002 Dec 16, 12(24), 3595 - 9 Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the metal binding group; Smith HK et al.; A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised . Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone. Bioorg Med Chem Lett, 2002 Dec 16, 12(24), 3569 - 72 17S,20S-Methanofusidic acid, a new potent semi-synthetic fusidane antibiotic; Duvold T et al.; A novel fusidic acid type antibiotic having the side chain linked to the tetracyclic ring system via a spiro-cyclopropane system is described . 17S,20S-Methanofusidic acid is obtained by an efficient synthetic route including cyclopropanation of the Delta17(20) bond with attack solely from the least hindered alpha-face . The spiro-cyclopropane system orients the side chain into a bioactive conformational space . The new 17S,20S-methanofusidic acid exerts antibacterial activity against several Gram-positive species with potency essentially equal to natural fusidic acid. Arzneimittelforschung, 2002, 52(10), 725 - 30 Clinical effects of nifuratel in vulvovaginal infections . A meta-analysis of metronidazole-controlled trials; Mendling W et al.; Nifuratel (CAS 4936-47-4) displays a strong antiprotozoarian and antibacterial activity and is provided with certain fungicidal effect, but it is not active against the physiologic flora . Its therapeutic effectiveness has been evaluated in more than 12,000 patients . The wide clinical experience with nifuratel confirms that the drug is safe and effective for the treatment of trichomoniasis, bacterial vaginosis, candidosis, and, particularly, in patients suffering from mixed vaginal infection . A meta-analysis of clinical trials comparing nifuratel and metronidazole (CAS 443-48-1) in vulvovaginal infections was performed . All parallel-group metronidazole-controlled trials carried out in patients with vulvovaginal infections have been included, complying with the following criteria: 1) cure assessed both as disappearance of symptoms and signs, and negative microbiological findings; 2) microbiological tests performed with valid methods still used in current practice . Seven clinical trials have been selected, including overall 1767 patients, 832 out of whom were treated with nifuratel and 935 with metronidazole . The results of the meta-analysis confirmed the equivalence between nifuratel and metronidazole: overall proportion of cured patients in the two groups were 88.5% and 90.0%, respectively, in the presence of homogeneity among studies (p = 0.342) . In the fixed and random effect analyses, the confidence interval of Odds ratio included 1 and the p values for testing the hypothesis of no difference between treatments were 0.656-1.266, p = 0.582 (fixed effects) and 0.643-1.290, p = 0.599 (random effects), respectively, indicating equivalence . Furthermore, some controlled studies and the wide clinical experience showed that the cure rate of nifuratel in patients with mixed infections due to Trichomonas vaginalis + Candida or Trichomonas vaginalis + bacteria or with bacterial vaginosis and mixed bacterial flora is higher than that of metronidazole, due to the wide spectrum of action of nifuratel. Z Naturforsch {C}, 2002 Sep-Oct, 57(9-10), 797 - 800 The chemical constituents and biological activity of essential oil of Lavandula stoechas ssp . stoechas; Goren A et al.; The composition of essential oil of the leaves of Lavandula stoechas ssp . stoechas, was analyzed by means of capillary GC-MS . The main components of L . stoechas ssp . stoechas oil were pulegone (40.4%), menthol (18.1%), menthone (12.6%) . The essential oil of the plant was evaluated for antibacterial and a panel cytotoxic activities. J Wound Ostomy Continence Nurs, 2002 Nov, 29(6), 295 - 300 Honey: a potent agent for wound healing? Lusby PE, Coombes A, Wilkinson JM. Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized . Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing . The physicochemical properties (eg, osmotic effects and pH) of honey also aid in its antibacterial actions . Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound . The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds . It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey) . This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types. Infect Immun, 2002 Dec, 70(12), 6896 - 903 Role of caspase 1 in murine antibacterial host defenses and lethal endotoxemia; Joshi VD et al.; Sepsis is thought to result from an exaggerated innate immune response to microbial components such as lipopolysaccharide (LPS), but the involvement of a specific mechanism(s) has not been identified . We studied the role of caspase 1 (Cas-1) in the murine innate immune response to infection with gram-negative bacteria and to nonlethal and lethal doses of LPS . cas-1(-/-) and Cas-1 inhibitor (Ac-YVAD-CHO)-treated cas-1(+/+) mice were two- to threefold more susceptible to lethal Escherichia coli infection than cas-1(+/+) mice . Administration of Cas-1 products, interleukin-18 (IL-18) or IL-1beta, protected three of three and six of seven mice, respectively, from lethal infection with E . coli compared to none of six of untreated mice (P = 0.0082) . Therefore, cas-1 is essential for antibacterial host defense . Nonlethal (75 micro g) and lethal (500 micro g) doses of LPS induce different patterns of gamma interferon, IL-1beta, and IL-18 expression . Consequently, the role of Cas-1, which cleaves pro-IL-18 and pro-IL-1beta to their active forms, was investigated in these disparate conditions by using enzymatic assay and reverse transcription-PCR . At 75 micro g, LPS induced a transient increase in IL-1beta and IL-18 levels in serum, whereas at 500 micro g it induced a 1.5-fold-higher IL-18 level in serum, which increased till death . At 75 micro g of LPS, splenic cas-1 mRNA expression remained unchanged at all time points, but activity increased transiently at 3 h . In lethally treated mice, Cas-1 activity remained elevated until death; however, cas-1 mRNA levels increased at 3 h and decreased to basal levels by 8 h . Treatment with Cas-1 inhibitor protected mice from lethal endotoxemia . Thus, Cas-1 is essential for innate antibacterial host defenses and may represent a mechanism of innate immunity that upon excessive stimulation by microbial components may lead to endotoxic shock. Ann Clin Microbiol Antimicrob . 2002 Oct 22;1(1):5 {Epub ahead of print} Quinine sulfate and bacterial invasion; Wolf R et al.; BACKGROUND: As many patients who receive antimalarial drugs for treatment of noninfectious, inflammatory diseases are also immunosuppressed and might have a concomitant bacterial infection, we studied the effectiveness of these drugs against bacterial infections, to find out whether they could protect against (and even treat) such conditions and obviate the need for an additional antibiotic drug . METHODS: Effect of QS on bacterial growth: Escherichia coli (E . coli) HB101 pRI203 were cultured overnight at 37 degrees C in TSB and inoculated (approx 1 x 107 cells /ml) in MEM in the presence of QS at various concentrations (0, 50 and 100 &mgr;M).The effect of QS at concentration of 50 and 100 &mgr;M on the entry process of E . coli HB101 pRI203 into HeLa cells was studied under different experimental conditions: 1 . QS was incubated with 3 x 105 HeLa cells for 60 min at 37 degrees C prior to infection . 2 . QS was added to HeLa cell monolayers during the infection period . RESULTS: QS showed no antibacterial activity after 24 h of incubation.The invasive efficiency of the bacteria was significantly inhibited at a dose-dependent manner, when QS was added to HeLa cells for 60 min at 37 degrees C prior to infection (condition 1), and to a lesser extent when added during the period of infection (condition 2) . CONCLUSIONS: Although the antimalarials are generally regarded as being inactive against most extracellular bacterial species, our results indicate that QS significantly inhibited the internalization/invasion efficacy of E . coli in the host cells. Nat Prod Lett, 2002 Oct, 16(5), 351 - 7 Structure and biological activity of a new rotenoid from Pongamia pinnata; Simin K et al.; Pongarotene (1), a new rotenoid and karanjin (2), a known flavonol, were isolated from the seeds of Pongamia pinnata . The structure determination of these compounds were based on spectral analyses including 2D-NMR . The antifungal, antibacterial and phytotoxicity results of pure compounds 1 and 2 as well as of the methanol (M) and ethyl acetate (E) crude extracts are also being reported. Immunity, 2002 Nov, 17(5), 575 - 81 The Drosophila immune defense against gram-negative infection requires the death protein dFADD; Naitza S et al.; Drosophila responds to Gram-negative infections by mounting an immune response that depends on components of the IMD pathway . We recently showed that imd encodes a protein with a death domain with high similarity to that of mammalian RIP . Using a two-hybrid screen in yeast, we have isolated the death protein dFADD as a molecule that associates with IMD . Our data show that loss of dFADD function renders flies highly susceptible to Gram-negative infections without affecting resistance to Gram-positive bacteria . By genetic analysis we show that dFADD acts downstream of IMD in the pathway that controls inducibility of the antibacterial peptide genes. Anal Chem, 2002 Nov 1, 74(21), 5455 - 62 Determination of fluoroquinolone antibacterial agents in sewage sludge and sludge-treated soil using accelerated solvent extraction followed by solid-phase extraction; Golet EM et al.; A method for the quantitative determination of humanuse fluoroquinolone antibacterial agents (FQs) ciprofloxacin and norfloxacin in sewage sludge and sludge-treated soil samples was developed . The accelerated solvent extraction was optimized with regard to solvents and operational parameters, such as temperature, pressure, and extraction time . A 50 mM aqueous phosphoric acid/ acetonitrile mixture (1:1) was found to be optimum in combination with an extraction temperature of 100 degrees C at 100 bar, during 60 and 90 min for sewage sludge and sludge-treated soil samples, respectively . A cleanup step using solid-phase extraction substantially improved the selectivity of the method . Overall recovery rates for FQs ranged from 82 to 94% for sewage sludge and from 75 to 92% for sludge-treated soil, with relative standard deviations between 8 and 11% . Limits of quantification were 0.45 and 0.18 mg/kg of dry matter for sewage sludge and sludge-treated soils, respectively . The presented method was successfully applied to untreated and anaerobically digested sewage sludges and sludge-treated soils . Ciprofloxacin and norfloxacin were determined in sewage sludges from several wastewater treatment plants with concentrations ranging from 1.40 to 2.42 mg/kg of dry matter . Therefore, contrary to what may be expected for human-use pharmaceuticals, FQs may reach the terrestrial environment as indicated by the occurrence of FQs in topsoil samples from experimental fields, to which sewage sludge had been applied. Int Immunopharmacol, 2002 Oct, 2(11), 1541 - 9 Immunomodulatory activity of a protein isolated from garlic extract on delayed type hypersensitivity; Ghazanfari T et al.; Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant . One major protein has been isolated and purified; it is the 14-kDa glycoprotein . This protein has shown to have immunomodulatory effects . In this study, two sources of garlic (freshly prepared and commercial tablet) were used . Both sources of garlic were augmented delayed type hypersensitivity (DTH) response, the optimum enhancement were detected at 20 mg/kg . Histological studies indicate that 20 mg/kg caused a hyperplasia and hypertrophy of periarteriolar lymphoid sheath of spleen and paracortical zone of lymph nodes . Partial purified fraction could increase the DTH response comparing to garlic extract, and purified protein could highly increase the DTH response comparing to both garlic extract and partial purified fraction . Garlic at all doses employed did not exhibit any effect on enhancement of antibody titer to SRBC. Int J Hematol, 2002 Aug, 76 Suppl 2, 253 - 7 Pathogen inactivation of blood components: current status and introduction of an approach using riboflavin as a photosensitizer; Corbin F 3rd; Riboflavin is a naturally occurring compound and an essential human nutrient . Studies in the 1960s and 70s showed that it could be effective, when exposed to visible or UV light, in inactivating viruses and bacteria . This suggested to us that it could act as a photosensitizer useful in the inactivation of pathogens found in blood products, because of its nucleic acid specificity and its limited tendency toward indiscriminate oxidation . The riboflavin molecule is a planar, conjugated ring structure with a sugar side chain that confers water solubility . The planar portion is capable of intercalating between the bases of DNA or RNA . Light activated riboflavin oxidizes guanine in nucleic acids, preventing replication of the pathogen's genome . Gambro BCT is developing processes using riboflavin and light to inactivate pathogens in plasma, platelet, and red cell products . We call these Pathogen Eradication Technology (PET) processes . Riboflavin is non-toxic; it must be present in the body for good health . The photo-byproducts formed in the PET processes are lumichrome and protein adducts . The photodegradation of riboflavin in the body is clearly shown by the decrease in its concentration in neonates who are treated with intense visible light to break down circulating bilirubin, which their immature livers cannot yet handle . A definitive lookback study showed no difference in cancer rates between the 55,000 children receiving this therapy in Denmark from 1977 through 1989 and nonirradiated controls . Gambro BCT is developing specific riboflavin-based PET processes for platelet concentrates, fresh frozen plasma, and packed red blood cells . In each, the process is being optimized to achieve high levels of inactivation of specific pathogens, while maintaining acceptable levels of product quality and activity . Extra- and intracellular HIV, BVDV (a model for HCV), and pseudorabies virus (a herpes virus) have been used to guide process development and validation . We have demonstrated 4 to 7 log10 reductions in the titers of these viruses, when they are spiked into blood products and irradiated in the presence of riboflavin . Porcine parvovirus, a tight-capsid, nonenveloped virus is more resistant, a finding in all experimental inactivation approaches . A range of bacteria implicated in platelet and red cell transfusion injuries and deaths, including S . aureus, E . coli, K . pneumoniae, and Y . enterocolitica, are being used to validate antibacterial efficacy . The PET platelet process involves the addition of riboflavin to platelets in plasma, illumination of the product, storage of the product and transfusion without further manipulation . The lack of toxicity of the treatment byproducts permits this ease of use . Quality of the platelets throughout storage has been assessed by pH, PO2, lactate, hypotonic shock response, morphology, glucose, and GMP-140 expression . In vitro function is well maintained . The levels seen are within the range of those reported in commonly transfused products . Radiolabeled transfusion studies of treated platelets have been carried out in primates to determine a preliminary measure of their in-vivo circulation . The in vivo recoveries and survivals of treated and control platelets did not differ . This work suggests that an endogenous photosensitizer, riboflavin, which has an extremely good safety profile, can inactivate high levels of a broad range of viruses and bacteria in platelet concentrates, fresh frozen plasma, and in red blood cells, preserving the activity and functionality of the components . Planned animal and clinical studies are expected to solidify this suggestion into a well-characterized process which can be safely and readily applied to reduce the risks of transfusion transmitted disease. Chem Commun (Camb), 2002 Oct 21, (20), 2312 - 3 A flexible strategy for the divergent modification of pleuromutilin; Bacque E et al.; The complex antibacterial natural product, pleuromutilin, can be directly modified by the radical addition reaction of various xanthates to the unactivated terminal olefin present on C-12. J Agric Food Chem, 2002 Nov 20, 50(24), 7182 - 6 Tea enhances insulin activity; Anderson RA et al.; The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity . The objective of this study was to determine the insulin-enhancing properties of tea and its components . Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay . Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity . High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate . For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds . Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins . Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities . Addition of lemon to the tea did not affect the insulin-potentiating activity . Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90% . Nondairy creamers and soy milk also decreased the insulin-enhancing activity . These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate. Thromb Haemost, 2002 Nov, 88(5), 705 - 10 Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants; Visser LE et al.; BACKGROUND: Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation . Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications . OBJECTIVE: To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins . Design: Population-based cohort study in a sample of the Rotterdam Study . SUBJECTS: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available . METHODS: Patients were followed until an INR >/= 6.0, the end of their treatment, death or end of the study period . Proportional hazards regression analysis was used to estimate the risk of an INR >/= 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure . RESULTS: Of the 1,124 patients in the cohort, 351 developed an INR >/= 6.0 . The incidence rate was 6.9 per 10,000 treatment days . Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9) . Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs . CONCLUSION: In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation . Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications. Ostomy Wound Manage, 2002 Nov, 48(11), 28 - 40 Re-introducing honey in the management of wounds and ulcers - theory and practice; Molan PC; Dressing wounds with honey, a standard practice in past times, went out of fashion when antibiotics came into use . Because antibiotic-resistant bacteria have become a widespread clinical problem, a renaissance in honey use has occurred . Laboratory studies and clinical trials have shown that honey is an effective broad-spectrum antibacterial agent that has no adverse effects on wound tissues . As well as having an antibacterial action, honey also provides rapid autolytic debridement, deodorizes wounds, and stimulates the growth of wound tissues to hasten healing and start the healing process in dormant wounds . Its anti-inflammatory activity rapidly reduces pain, edema, and exudate and minimizes hypertrophic scarring . It also provides a moist healing environment for wound tissues with no risk of maceration of surrounding skin and completely prevents adherence of dressings to the wound bed so no pain or tissue damage is associated with dressing changes . Using appropriate dressing practice overcomes potential messiness and handling problems. J Bacteriol, 2002 Dec, 184(23), 6725 - 9 DNA microarray analysis of the expression profile of Escherichia coli in response to treatment with 4,5-dihydroxy-2-cyclopenten-1-one; Phadtare S et al.; We carried out DNA microarray-based global transcript profiling of Escherichia coli in response to 4,5-dihydroxy-2-cyclopenten-1-one to explore the manifestation of its antibacterial activity . We show that it has widespread effects in E . coli affecting genes encoding proteins involved in cell metabolism and membrane synthesis and functions . Genes belonging to the regulon involved in synthesis of Cys are upregulated . In addition, rpoS and RpoS-regulated genes responding to various stresses and a number of genes responding to oxidative stress are upregulated. Braz J Med Biol Res, 2002 Oct, 35(10), 1133 - 7 Epub 2002 Oct 13. Exhaled nitric oxide collected with two different mouthpieces: a study in asthmatic patients; Leme AS et al.; Techniques for collecting exhaled nitric oxide (ENO) recommend the use of antibacterial filters of 0.3 m . The aim of the present study was to compare the measurements of ENO obtained with two different filtering devices . Air samples from 17 asthmatic and 17 non-asthmatic subjects were collected by a recommended off-line technique using two different mouthpieces: 1) the Sievers disposable tool (A) under a breathing pressure of 18 cmH2O, and 2) a mouthpiece containing a HEPA filter (B) under a breathing pressure of 12 cmH2O . The nitric oxide samples were collected into an impermeable reservoir bag . Values for ENO were compared using two-way repeated measures ANOVA followed by the Tukey test . Agreement was assessed by Bland-Altman analysis . ENO values obtained with mouthpieces A and B were comparable for asthmatic (mean +/- SEM, 42.9 +/- 6.9 vs 43.3 +/- 6.6 ppb) and non-asthmatic (13.3 +/- 1.3 vs 13.7 +/- 1.1 ppb) subjects . There was a significant difference in ENO between asthmatics and non-asthmatics using either mouthpiece A (P<0.001) or B (P<0.001) . There was a positive correlation between mouthpiece A and mouthpiece B for both groups . The Bland-Altman limits of agreement were considered to be acceptable . Mouthpiece B was less expensive than A, and these data show that it can be used without compromising the result . Our data confirm reports of higher ENO values in the presence of airway inflammation. Toxicol In Vitro, 2002 Dec, 16(6), 683 - 93 In vitro phototoxic properties of new 6-desfluoro and 6-fluoro-8-methylquinolones; Miolo G et al.; A representative set of potent antibacterial 6-desfluoro-8-methylquinolones, in which the C-6 fluorine atom is replaced by -NH(2) or -H, and their 6-fluoro counterparts, were investigated to evaluate their phototoxic potential and to explore the mechanism behind their phototoxicity . The capacity to photosensitize biological substrates (lipids, proteins, DNA) has been analyzed, as well as their photocytotoxicity on red blood cells and 3T3 murine fibroblasts . The results obtained show that the quinolones studied are able to photosensitize red blood cell lysis in an oxygen-dependent way and induce a high decrease in cell viability after UVA irradiation . A major correlation with phototoxicity lies in the structure of the individual antibacterials and their hydrophobicity; in particular, 6-amino derivatives are less phototoxic than corresponding unsubstituted and fluorinated compounds . Cellular phototoxicity was inhibited by the addition of free radical and hydroxyl radical scavengers (BHA, GSH and DMTU), suggesting the involvement of a radical mechanism in their cytotoxicity . A good correlation was observed between lipid peroxidation and phototoxicity, indicating that the test compounds exert their toxic effects mainly in the cellular membrane . Preliminary experiments on pBR322 DNA show that these derivatives do not photocleave DNA, differently from the two photogenotoxic fluoroquinolones, ciprofloxacin and lomefloxacin, used as reference compounds. J Vet Pharmacol Ther, 2002 Oct, 25(5), 343 - 50 Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v . administration of enrofloxacin to mares; Papich MG et al.; Enrofloxacin was administered i.v . to five adult mares at a dose of 5 mg/kg . After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h . The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography . In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively . Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL . In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h . Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h . The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively . For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively . We concluded that plasma concentrations achieved after 5 mg/kg i.v . are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria . Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria. Am J Rhinol, 2002 Sep-Oct, 16(5), 261 - 4 The influence of the size of the maxillary sinus ostium on the nasal and sinus nitric oxide levels; Kirihene RK et al.; BACKGROUND: Nitric oxide (NO) is produced in significant quantities in the nasal sinuses and is thought to have a beneficial effect on the mucociliary transport of the sinuses and nose and to have significant antibacterial properties that contribute to the health of the sinuses . Recently, the concept of "mini-functional endoscopic sinus surgery" has been introduced where the uncinate is removed without enlargement of the maxillary ostium . Although no scientific evidence has been published, enlargement of the ostium is thought to possibly disrupt the mucociliary pathway and decrease the concentration of NO in the nose and sinuses . The aim of this study was to establish the effect of enlargement of the maxillary ostium on sinus and nasal NO . METHODS: Twenty-nine patients who were post-endoscopic sinus surgery were included with 52 who were maxillary sinus ostia cannulated . There were 22 large maxillary sinus ostia and 30 small ostia . Smoking, allergy status, and topical steroid use were recorded . NO levels were measured in the nose and maxillary sinus after decongestion with patients mouth breathing and breath holding . RESULTS: This study shows that enlargement of the maxillary sinus ostium above its normal size (20 mm2) produces a significant decrease in both the maxillary sinus and the nasal cavity NO levels . In addition, the size of the ostium showed a significant correlation to the sinus NO level . Use of topical nasal steroid sprays and topical decongestants were shown to effect NO levels in the sinuses and nasal cavity . The lowered levels of NO were found irrespective of the technique of measurement of the NO . CONCLUSIONS: The effect of this lowered NO level on the susceptibility of the maxillary sinuses to recurrent infection is yet to be determined. Antibiot Khimioter, 2002, 47(6), 38 - 41 {Fibrin-collagen substance as a vehicle for local application of antibacterial agents}; Gorskii VA et al.; Inhibitory activity of fibrin-collagen substance (FCS) impregnated by various antibacterial agents against various microorganisms was investigated . It was demonstrated that antibacterials bind well with FCS, providing its sufficient antibacterial activity . Determination of growth-inhibition zones showed that antibacterial agents diffuse into medium well and demonstrated the same activity as discs with antibiotics . For clinical practice it is recommended to use for impregnation the following drugs: gentamycin, meropenem, cefriaxone and ciprofloxacin. Acta Biochim Pol, 2002, 49(3), 721 - 34 Comparison of serological specificity of anti-endotoxin sera directed against whole bacterial cells and core oligosaccharide of Escherichia coli J5-tetanus toxoid conjugate; Lukasiewicz J et al.; The rough mutants of Gram-negative bacteria are widely used to induce protective antisera but the nature of the target epitope for such antibodies is not precisely defined . Endotoxin is one of several antigens present on the surface of bacterial cells, which are able to elicit specific antibodies . We studied the specificity of antibodies produced against a conjugate of E . coli J5 endotoxin core oligosaccharide with tetanus toxoid . The use of chemically defined antigen for immunisation excludes the possibility of production of antibodies against other cell surface antigens . A comparison of this monospecific anti-endotoxin serum with antiserum against E . coli J5 whole cells was performed in order to distinguish the role that endotoxin core oligosaccharide plays in the interaction with humoral host defences from that of other potentially important Gram-negative bacterial surface antigens . The reactivity of both sera with smooth and rough lipopolysaccharides was determined in ELISA, immunoblotting and by flow cytometry . Both antisera reacted with similar specificity with most lipopolysaccharides of identical or related core type . Less distinct reactions with endotoxins of the antibacterial serum in comparison with the anti-conjugate serum were found in all serological tests . LPS of E . coli O100 that showed the strongest reactions with both sera was used to stimulate IL-6, TNFalpha and nitric oxide production by the J-774A.1 cell line . Both sera were used to inhibit that stimulation and no inhibitory effects of the examined sera in comparison with non-immune serum were observed. Insect Mol Biol, 2002 Dec, 11(6), 611 - 8 Antibacterial peptide defensin is involved in midgut immunity of the soft tick, Ornithodoros moubata; Nakajima Y et al.; Two defensin genes A and B were previously demonstrated to be up-regulated by blood feeding in the soft tick, Ornithodoros moubata {Nakajima et al . (2001) Two isoforms of a member of the arthropod defensin family from the soft tick, Ornithodoros moubata (Acari: Argasidae) . Insect Biochem Mol Biol 31: 747-751} . In this study, two defensin isoforms C and D similar to defensins A and B were newly cloned . A total of four defensins have been identified in O . moubata . All four Ornithodoros defensins are coded as prepro-defensins . Ornithodoros defensin genes consist of four exons and three introns, an organization reported in mussel defensins but not insect defensins . Ornithodoros defensin C and D genes are predominantly expressed in the midgut and up-regulated in response to blood feeding . The mature peptide of the previously cloned Ornithodoros defensin A was purified from the midgut lumen, indicating defensin is secreted into the midgut . These findings confirm the involvement of Ornithodoros defensin in midgut immunity. CNS Drugs, 2002, 16(12), 799 - 802 Antibacterial therapy of neurosyphilis: lack of impact of new therapies; Ali L et al.; Neurosyphilis is caused by the spirochete Treponema pallidum . These organisms divide slowly, requiring long exposure to antibacterials for treatment success . In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance . Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis. Biol Pharm Bull, 2002 Nov, 25(11), 1432 - 5 Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4(3H) ones; Alagarsamy V et al.; A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid . The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities . All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium. Can J Anaesth, 2002 Nov, 49(9), 942 - 5 Xenon preserves neutrophil and monocyte function in human whole blood; De Rossi L et al.; PURPOSE: Most volatile anesthetics are known to inhibit the oxidative and phagocytic function of neutrophils . In the present study, we investigated the effect of xenon on phagocytosis and respiratory burst activity of neutrophils and monocytes in human whole blood . METHODS: Heparinized whole blood from 22 healthy volunteers was incubated for 60 min in the presence of 65% xenon . Sixty-five percent nitrous oxide was used as a positive control to prove the reliability of our in vitro system . Phagocytosis of fluorescein isothiocyanate labelled, opsonized Escherichia coli (E . coli) by neutrophils and monocytes was measured using flow cytometry . After induction with either N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-12-myristate-13-acetate or opsonized E . coli, respiratory burst activity was assessed by measuring the oxidation of dihydrorhodamine 123 to rhodamine 123 with a flow cytometer . RESULTS: Exposure of human whole blood to xenon increased the percentage of neutrophils showing phagocytosis (94 +/- 3% vs 92 +/- 4%; P < 0.01), and the amount of ingested bacteria (P < 0.01) . Respiratory burst activity in neutrophils and monocytes was not affected by xenon . Nitrous oxide significantly reduced the percentage of neutrophils showing respiratory burst after FMLP stimulation . Furthermore, E . coli-induced stimulation resulted in a decreased number of reacting neutrophils (84 +/- 15% vs 95 +/- 5%; P < 0.05) and monocytes (70 +/- 22% vs 83 +/- 11%; P < 0.05) as well as a reduced production of hydrogen peroxide in both cell lines compared to control . CONCLUSION: In contrast to nitrous oxide, xenon preserves neutrophil and monocyte antibacterial capacity in vitro. J Ocul Pharmacol Ther, 2002 Oct, 18(5), 445 - 53 Penetration of topically administered ofloxacin and trimethoprim into aqueous humor; Price FW Jr et al.; Ocular penetration of two topical antibiotics used to treat bacterial conjunctivitis was assessed in adult volunteers scheduled for cataract surgery . In this randomized, parallel-group study, patients instilled trimethoprim sulfate 0.1%/polymyxin B (n = 23) or ofloxacin 0.3% (n = 25) QID for 3 days, plus 4 instillations in the hour before surgery . Analysis of aqueous humor samples obtained during surgery showed a 2.4-fold greater concentration of ofloxacin over trimethoprim (1.135 micro g/ml vs 0.470 micro g/ml; P <.0001) . The greater concentration of ofloxacin in ocular tissue coupled with its superior antibacterial activity profile supports its use as an alternative to trimethoprim/polymyxin B for treatment of bacterial conjunctivitis. Int Dent J, 2002 Oct, 52(5), 337 - 45 Mouthrinses and dental caries; FDI Commission; Mouthrinsing for the prevention of dental caries in children and adolescents was established as a mass prophylactic method in the 1960s and has shown average efficacy of caries reduction between 20-50% . Commonly, weekly or twice monthly rinsing procedures using neutral 0.2% NaF solutions have been used in schools or institutions in areas with low fluoride concentrations in the drinking water . Today, when dental caries has declined substantially in the western countries, and relatively few individuals are suffering from caries, the efficiency of large scale mouthrinsing is questioned and more individual approaches of caries prevention strategies are needed . For this reason individual caries risk assessments are necessary, utilising diagnostic tools with the aim of explaining the main causes of the caries disease . Therefore in high risk patients, daily mouthrinses using 0.05% NaF can be recommended combined with other selective preventive measures such as sugar restriction, improved oral hygiene, antibacterial treatments, and so forth . Mouthrinsing solutions have therefore been combined with antiplaque agents like chlorhexidine and other agents which can improve the caries preventive effect not only in high caries risk patients, including those with dry mouth problems and root caries . Other agents than sodium fluoride have been used, such as stannous and amine fluoride with proven clinical effects . However, although a series of new formulas of mouthrinses containing fluoride combined with different antiplaque agents have shown promising antibacterial and antiplaque efficacy, their long-term clinical effects are sparsely documented . Acute and chronic side effects from established and recommended mouthrinsing routines are extremely rare but ethanol containing products should not be recommended to children for long-term use or to individuals with alcohol problems . Patients with dry mouth problems should avoid mouthrinses containing high concentration of detergent components which reduce the substantivity of the agent and worsen the dry mouth effect . For the future, patients, dentists and public health officials will welcome new and safe, controlled and self-administrated mouthrinsing procedures with not only high efficacy, but also high effectivity and efficiency. Respir Med, 2002 Nov, 96(11), 862 - 71 Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis; Aubier M et al.; This randomized, double-blind study evaluated the efficacy and safety of a short, 5-day course of telithromycin, a new ketolide antibacterial, compared with a standard 10-day course of amoxicillin/clavulanate, in the treatment of acute exacerbations of chronic bronchitis (AECB) . The study enrolled 325 adult patients with AECB and a history of chronic obstructive pulmonary disease (COPD) . Patients received either telithromycin 800 mg once daily (qd) for 5 days (followed by placebo for 5 days) or amoxicillin/clavulanate 500/125 mg three times daily (tid) for 10 days . Clinical cure rates for telithromycin post-therapy (Days 17-21, test-of-cure) and late post-therapy (Days 31-36) were 86.1 and 78.1%, respectively; 82.1 and 75.0% for amoxicillin/clavulanate . Excellent clinical cure rates were also observed for high-risk patients . Bacteriologic outcome was satisfactory for 69.2% of telithromycin recipients vs 70.0% for amoxicillin/clavulanate recipients . Both treatments were generally well tolerated, although the frequency of drug-related adverse events was almost two-fold higher for amoxicillin/clavulanate (25.0 vs . 13.1%) . Thus, a 5-day course of telithromycin 800 mg qd is an effective and well-tolerated alternative to a standard 10-day course of amoxicillin/clavulanate 500/125 mg tid for first-line empiric treatment of AECB in adults with COPD. J Dairy Sci, 2002 Oct, 85(10), 2571 - 5 Efficacy of systemic ceftiofur as a therapy for severe clinical mastitis in dairy cattle; Erskine RJ et al.; The objectives of this study were to determine the efficacy of intramuscular administration of ceftiofur to reduce the incidence of case-related death and culling following severe clinical mastitis in lactating dairy cattle . A total of 104 cows with severe clinical mastitis (systemic signs) were enrolled in the study and randomly assigned to one of two treatment groups . Immediately after detection of the case, one group was administered 2.2 mg/kg of ceftiofur intramuscularly, and the dose repeated at 24-h intervals for a total of five doses . The second group of cows did not receive systemic antibacterial therapy . Additionally, all cows in both treatment groups received intramammary pirlimycin (Pirsue) in the affected quarter every 24 h for a total of up to three doses . Also at the onset of the case, all cows on the trial were administered a supportive therapeutic regimen of fluids and anti-inflammatory agents that varied from farm to farm, but was standard within each herd at the discretion of the herd manager and veterinarian . Of all cases 14/104 (13.5%) resulted in a lost cow (died or culled) . The proportion of cases that resulted in a lost cow and were treated with ceftiofur (4/51; 7.8%) did not statistically differ from cows that were not treated with ceftiofur (10/53; 18.9%) . However, the proportion of cases that resulted in lost cows was higher for those cases that yielded a coliform organism on culture (14/56; 25.0%) than cases that did not yield coliforms (0/48; 0.0%; P < 0.001) . Thus, among coliform cases, cows that were not treated with ceftiofur were more likely to be culled or die (10/27, 37.0%; P < 0.05) than cows treated with ceftiofur (4/29, 13.8%) . We conclude that intramuscular administration of ceftiofur did not affect the outcome of severe clinical mastitis when all etiologic agents are included in the analysis . However, for severe clinical mastitis cases caused by coliform organisms, ceftiofur therapy reduced the proportion of cases that resulted in cow death or culling . This benefit may be realized because of the amelioration of bacteremic-related pathogenesis. Bioorg Med Chem, 2002 Dec, 10(12), 3905 - 13 Straightforward syntheses of furanomycin derivatives and their biological evaluation; Kazmaier U et al.; Several types of furanomycin analogues were synthesized and investigated with respect to their antibacterial activity . Two different synthetic pathways were developed, based on aldol reactions/ring closing metathesis and an ester enolate Claisen rearrangement . Only the natural product and its desmethyl derivative showed antibacterial activity, pointing towards a narrow structure-activity relationship. Zhonghua Yu Fang Yi Xue Za Zhi, 2002 Mar, 36(2), 114 - 6 Effect of ambient conditions on the antibacterial activity of antibacterial agent based on sodium titanium phosphate; Yan J et al.; OBJECTIVE: To investigate the effects of ambient conditions on the antibacterial activity of inorganic antibacterial agent based on sodium titanium phosphate . METHODS: The number of live E . Coli ATCC 44113 was counted after the suspension was shaken and incubated in flask with antibacterial agent under ambient conditions . RESULT: The number of live bacteria increased when the concentration of bacteria increased in the range of 1.2 x 10(2) to 1.2 x 10(8) cfu/ml . The antibacterial activity increased with the increase of ambient temperature in the range of 16 approximately 46 degrees C, showing good antibacterial activity at human body temperature . With the increase of the concentrations of co-existing NaCl and protein, the antibacterial activity was found to decrease at first and level off at 0.01 g/ml and 0.0005 g/ml respectively . CONCLUSION: The antibacterial agent has to be used together with organic antibacterial agent in order to achieve good antibacterial effect when the ambient bacterial concentration is high . The antibacterial agent is promising to be used in the preparation of antibacterial cloth because it is highly effective at body temperature and expected to remain antibacterial in perspiration. Phytother Res, 2002 Nov, 16(7), 680 - 2 Studies on essential oils: part 10; antibacterial activity of volatile oils of some spices; Singh G et al.; The essential oils extracted from the seeds of seven spices, Anethum graveolens, Carum capticum, Coriandrum sativum, Cuminum cyminum, Foeniculum vulgare, Pimpinella anisum and Seseli indicum have been studied for antibacterial activity against eight pathogenic bacteria, causing infections in the human body . It has been found that the oil of C . capticum is very effective against all tested bacteria . The oil of C . cyminum and A . graveolens also gave similar results . These oils are equally or more effective when compared with standard antibiotics, at a very low concentration . Phytochemistry, 2002 Nov, 61(5), 561 - 6 Antibacterial cyclopeptide alkaloids from the bark of Condalia buxifolia; Morel AF et al.; The cyclopeptide alkaloid, named condaline-A, was isolated from the root bark of Condalia buxifolia Reissek (Rhamnaceae), along with the known compounds adouetine-Y', scutianine-B, and scutianine-C . Their structures were determined by spectroscopic analyses, with their antibacterial activities being evaluated by use of a direct bioautography method. Biophys Chem, 2002 Nov 6, 99(3), 271 - 9 Concentration-dependent behavior of nisin interaction with supported bilayer lipid membrane; Huang W et al.; Nisin is a positively charged antibacterial peptide that binds to the negatively charged membranes of gram-positive bacteria . The initial interaction of the peptide with the model membrane of negatively charged DPPG (dipalmitoylphosphatidylglycerol) was studied by cyclic voltammetry and a.c . impedance spectroscopy . Nisin could induce pores in the supported bilayer lipid membrane, thus, it led to the marker ions Fe(CN)(6)(3-/4-) crossing the lipid membrane and giving the redox reaction on the glassy carbon electrode (GCE) . Experimental results suggested that the pore formation on supported bilayer lipid membrane was dependent on the concentration of nisin and it included three main concentration stages: low, middling, high concentration. J Pharm Biomed Anal, 2002 Nov 7, 30(4), 1411 - 6 Method development for determining the antibacterial linezolid in human serum by micellar electrokinetic capillary chromatography; Kitahashi T et al.; A precise method for determining linezolid concentration in human serum by micellar electrokinetic capillary chromatography has been developed and validated . Serum was deproteinized with acetonitrile and etofylline was used as an internal standard . A borate buffer (pH 10.0; 25 mM) containing sodium dodecyl sulfate (80 mM) was used as a running buffer . Detection was performed at UV253 nm by applying 25 kV voltage to a fused-silica capillary tube . Migration time of linezolid was approximately 14 min . Good linearity (0-100 mg/l) was obtained and the limit of detection was 0.5 mg/l (S/N=3) . This technique covered the clinical concentration (4 mg/l) measurement of this drug enough . The intra- and inter-day reproducibility was good . Serum recovery was 95-102% . No interference from other anti-microbial agents was observed . Linezolid after serum deproteinization showed high stability . This method was easy to operate as well as economical as a method for determining linezolid in serum. Am J Respir Crit Care Med, 2002 Nov 15, 166(10), 1375 - 81 Epub 2002 Oct 11. Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets; Goldstein I et al.; Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli . AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8) . Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens . The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge . After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01) . Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units . g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001) . In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration. J Biochem Biophys Methods, 2002 Oct-Nov, 53(1-3), 25 - 36 Chiral separation of bioactive cyclic Mannich ketones by HPLC and CE using cellulose derivatives and cyclodextrins as chiral selectors; Grobuschek N et al.; The chiral separation of cyclic Mannich ketones of potential pharmaceutical interest is investigated using HPLC and CE . These Mannich ketones show a marked antibacterial and antifungal activity . In HPLC, stationary phases containing cellulose derivatives or beta-cyclodextrin were used and in CE different cyclodextrins, such as beta-CD, gamma-CD, carboxymethyl-beta-CD and succinyl-beta-CD were added to the background electrolyte as chiral selectors. Chembiochem, 2002 Nov 4, 3(11), 1105 - 11 A non-antibacterial oxazolidinone derivative that inhibits epithelial cell sheet migration; Mc Henry KT et al.; We have developed a high-throughput assay for screening chemical libraries for compounds that affect cell sheet migration during wound closure in epithelial cell monolayers . By using this assay, we have discovered a new inhibitor of cell sheet migration . This compound (UIC-1005) is a 3,4-disubstituted oxazolidinone that bears an electrophilic alpha,beta-unsaturated N-acyl group required for activity . UIC-1005 also inhibits growth in an epithelial cell proliferation assay . The molecule does not display general toxicity at concentrations at which it potently inhibits cell sheet migration and growth . Unlike certain 3,5-disubstituted oxazolidinones, it exhibits no antibacterial activity . UIC-1005 therefore represents a new class of bioactive oxazolidinone derivative that may prove useful as a probe for signaling pathways leading to cell motility. J Hepatol, 2002 Nov, 37(5), 592 - 600 Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: epidemiological and clinical features, and exposure to drugs; Ibanez L et al.; BACKGROUND/AIMS: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is uncommon . Many drugs have been implicated . Data on its epidemiology are scarce . We performed a population-based prospective study of acute serious liver disease in Catalonia (Spain) . METHODS: A collaborating hospital network was set up . All patients with acute serious liver disease and negative viral hepatitis serological markers, without an obvious cause of liver disease, were included . RESULTS: The incidence of acute serious liver disease was 7.4 per 10(6) inhabitants per year (95% CI; 6.0-8.8), which increased with age . The incidence of hepatocellular acute serious liver disease (3.84 per 10(6) per year) was greater than that of cholestatic and mixed patterns . The case-fatality ratio was 11.9% and mortality 0.8 per million person-years . The risk of death was similar among patients with hepatocellular and cholestatic patterns . Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most frequently used drugs . CONCLUSIONS: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is rare . Its incidence increases with age . The prognosis of cholestatic acute serious liver disease does not significantly differ from that of the hepatocellular pattern . Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most common drugs likely to be responsible for acute liver disease . J Nat Prod, 2002 Oct, 65(10), 1412 - 6 Bioactive constituents from Iryanthera megistophylla; Ming DS et al.; Activity-guided fractionation of the 95% ethanol extract from the stem bark of Iryanthera megistophylla led to the isolation of two new compounds, named megislignan {2,3-dimethyl-4-(4-methoxyphenyl)-6-hydroxynaphthalene} (1) and megislactone {(2R,3R,4R)-3-hydroxy-4-methyl-2-(hexacos-17-enyl)butanolide} (2), along with seven known compounds, grandinolide (3), iryantherin K (4), iryantherin L (5), cinchonain I b (6), cinchonain I a (7), procyanidin B-2 (8), and cinchonain IIa (9) . The structures of the new compounds were elucidated by spectral data interpretation . Isolates were evaluated for their antibacterial, antifungal, antiviral, and antiacetylcholinesterase activities. J Zoo Wildl Med, 2002 Jun, 33(2), 108 - 11 In vitro drug susceptibility pattern of Mycoplasma alligatoris isolated from symptomatic American alligators (Alligator mississippiensis); Helmick KE et al.; A recently described mycoplasma, Mycoplasma alligatoris, was isolated from dead American alligators (Alligator mississippiensis) that had demonstrated clinical signs of lethargy, anorexia, bilateral ocular discharge, edema . paraparesis, and polyarthritis . The in vitro minimum inhibitory concentration for nine antibacterial agents was determined through serial dilution in broth and plate culture for M . alligatoris isolates . The inhibitory concentration obtained for doxycycline, enrofloxacin, sarafloxacin, oxytetracycline, tilmicosin, and tylosin (< 1 microg/ml) was lower than that of clindamycin (1-8 microg/ml), chloramphenicol (8-16 microg/ml), and erythromycin (32-138 microg/ml). Arch Pharm (Weinheim), 2002 Aug, 335(8), 389 - 94 Synthesis and antibacterial activity of fused 1, 2, 4-triazolo{4, 3-a}quinoxaline and oxopyrimido{2', 1':5, 1}-1, 2, 4-triazolo{4, 3-a}quinoxaline derivatives; Nasr MN; A new series of potential antibacterial agents having tricyclic 1, 2, 4-triazolo-{4, 3-a} quinoxaline fused with one or more heterocyclic rings was synthesized via several routes . The tricyclic 1-amino-4-chloro-1, 2, 4-triazolo{4, 3-a} quinoxaline (2 ) and tetracyclic 1, 6-diamino-bis-1, 2, 4-triazolo{4, 3-a:3, 4-c} quinoxaline (3) were synthesized from 2, 3-dichloroquinoxaline (1) with two or four equivalents of thiosemicarbazide, respectively . Compound 2 was allowed to react with different aldehydes, alkoxides, cyclic amines, phenyl isothiocyanate, and t-butyl isocyanate to afford the corresponding quinoxaline derivatives . Moreover, compound 2 reactedwithhydrazine hydrate to give compound 4 which was cyclized by carbondisulfide inalcoholic potassium hydroxide to give the tetracyclic compound 5 . Compound 2 was subjected to another cyclocondensation reaction using diethyl ethoxymethylene malonate (DEMM), dimethyl acetylenedicarboxylate (DMAD), and ethyl cyanoacetate to give the tetracyclic compounds 18, 20, and 21, respectively . All the synthesized compounds were evaluated in vitro for antibacterial activity; compounds 18 and 20 were found to display the greatest antibacterial activities . Structural identification was provided by elemental analyses, IR, and (1)H-NMR spectroscopy. J Spinal Disord Tech, 2002 Oct, 15(5), 425 - 30 An immunocompetent patient with primary Scedosporium apiospermum vertebral osteomyelitis; Levine NB et al.; Scedosporium apiospermum, the asexual anamorph of Pseudallescheria boydii, is a ubiquitous saprophytic fungus that usually causes cutaneous/subcutaneous infection but may manifest as an invasive disease, often in immunocompromised hosts . Following an extensive literature review, we think that this case represents the first documented report of a primary infection of the spine in an immunocompetent patient . Despite extensive surgical debridement and itraconazole therapy, the patient died of multisystem organ failure of unknown etiology . Our case and three previously reported cases of P . boydii vertebral osteomyelitis highlight the importance of obtaining repeat cultures in patients with culture-negative vertebral osteomyelitis who fail to adequately respond to empiric standard antibacterial and/or antimycobacterial therapy . Combined surgical debridement and antifungal therapy have been required for eradication of P . boydii spinal infections in two previously reported immunocompromised patients, although the optimal antifungal regimen for this infection has not been established. Biochim Biophys Acta, 2002 Dec 12, 1588(3), 232 - 40 Antibacterial peptide PR-39 affects local nitric oxide and preserves tissue oxygenation in the liver during septic shock; Madhani M et al.; The effects of the antibacterial peptide PR-39 on nitric oxide (NO) and liver oxygenation (pO(2)) in a mouse model of endotoxaemia have been explored . In vivo electron paramagnetic resonance (EPR) spectroscopy was used to make direct measurements of liver NO and pO(2) . Measurements of pO(2) were made at two different anatomical locations within hepatic tissue to assess effects on blood supply (hence oxygen supply) and lobule oxygenation; selectively from the liver sinusoids or an average pO(2) across the liver lobule . PR-39 induced elevated levels of liver NO at 6 h following injection of lipopolysaccharide (LPS) as a result of increased iNOS expression in liver, but had no effect on eNOS or circulatory NO metabolites . Sinusoidal oxygenation was preserved, and pO(2) across the hepatic tissue bed improved with PR-39 treatment . We propose that the beneficial effects of PR-39 on liver in this septic model were mediated by increased levels of local NO and preservation of oxygen supply to the liver sinusoids. Mol Pharmacol, 2002 Nov, 62(5), 1036 - 42 Modulation of the hydrophobic domain of polymyxin B nonapeptide: effect on outer-membrane permeabilization and lipopolysaccharide neutralization; Tsubery H et al.; Polymyxin B nonapeptide (PMBN), a cationic cyclic peptide derived from the antibacterial peptide polymyxin B, is capable of specifically increasing the permeability of the outer membrane (OM) of Gram-negative bacteria toward hydrophobic antibiotics . In this study, we evaluated the contribution of the hydrophobic segment of PMBN (i.e., D-Phe(5)-Leu(6)) to this activity . Accordingly, we synthesized four analogs of PMBN by replacing D-Phe(5) with either with D-Trp or D-Tyr and Leu(6) with Phe or Ala and evaluated their ability to bind cell-free lipopolysaccharide (LPS) and increase bacterial OM permeability . Compared with PMBN, {D-Tyr(5)}PMBN and {Ala(6)}PMBN possessed reduced LPS affinity (IC(50) = 2.5, 25, and 12 microM, respectively) and significantly reduced OM permeability and LPS neutralization activity . {Phe(6)}PMBN exhibited rather similar affinity to cell-free LPS (IC(50) = 5 microM) and the same OM permeability capacity as PMBN . However, {D-Trp(5)}PMBN, despite its similar affinity to cell-free LPS (IC(50) = 4 microM), had moderately reduced OM permeability capacity . These results demonstrate the significant role of the PMBN hydrophobic segment in promoting biological activity. Perspect Biol Med, 2002 Fall, 45(4), 529 - 38 Fleming's Unfinished; Wainwright M; It is often suggested that, soon after he discovered penicillin, Alexander Fleming lost interest in what became the most important of all the antibiotics . Fleming's notebooks, however, show that he continued working with penicillin throughout the 1930s, even to the point when Florey and Chain became interested in it . During this period, Fleming isolated new airborne molds and checked them for their ability to produce antibacterial agents, and he also investigated other examples of microbial antagonism, such as bacteriophages . Unfortunately, none of this work was published . What follows is a simulation, based largely upon Fleming's notebooks, of a paper that he might have written in early 1940 . This version of "Fleming's Unfinished" should once and for all dismiss the view that he failed fully to recognize the significance of his famous discovery. Lancet, 2002 Oct 12, 360(9340), 1144 - 9 Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study; Putsep K et al.; BACKGROUND: Antibacterial peptides, such as defensins and LL-37, are natural bactericidal components similar in potency to classic antibiotics . These peptides are produced at mucosal linings in the body and the skin, and by leucocytes such as neutrophils and natural killer cells . Patients with morbus Kostmann-a severe congenital neutropenia-are treated by recombinant granulocyte-colony stimulating factor, which restores their levels of neutrophils . Despite this treatment, patients still have recurrent infections and periodontal disease . Our aim was to investigate if defensins and LL-37 are deficient in patients with morbus Kostmann . METHODS: We studied samples of neutrophils, plasma, and saliva from six patients with congenital neutropenia and 22 healthy controls for presence of antibacterial peptides . Neutrophils were analysed by high-performance liquid chromatography and mass spectrometry for alpha-defensins . All samples were analysed by western blot for cathelin-LL-37 (precursor of LL-37) and LL-37 . Neutrophils were also tested for lactoferrin and ability to produce oxidative burst . FINDINGS: Neutrophils from patients with morbus Kostmann were deficient in cathelin-LL-37 and had reduced concentrations of a-defensins HNP1-3 . No cathelin-LL-37 could be detected in plasma and saliva from patients . One patient with morbus Kostmann who had had bone-marrow transplantation had almost normal concentrations of LL-37 . Lactoferrin concentrations and oxidative burst were normal in all patients . All patients with morbus Kostmann had severe periodontal disease, apart from the individual who had had a bone-marrow transplant, whose dental status was normal . INTERPRETATION: Antibacterial peptides are a vital part of the first line of antibacterial immune defence . Deficiency in saliva LL-37 accords with occurrence of periodontal disease in patients with morbus Kostmann. J Cardiovasc Surg (Torino), 2002 Oct, 43(5), 741 - 6 Sternal cyanoacrylate gluing in mediastinitis . Effects on infection, stability and bone healing; Ogus TN et al.; BACKGROUND: It is crucial to determine stability, histocompatibility and antibacterial properties of the cyanoacrylate used for sternal fixation . METHODS: Clinical study: in 17 cases of mediastinitis, debridement and rewiring the sternum, was applied as the treatment method (Group I) . Eighteen cases of mediastinitis were treated with the same method added sternal cyanoacrylate gluing (Group II) . A comparative study was done; the follow-up period was 36.7+/-4 and 18.5+/-6.9 months in Group I and II, respectively . Animal study: in 10 rats, upper sternotomy was done and the sternal bone was contaminated . Direct wound closure was done in 4 rats (Group A), in 6 animals, wounds were closed after applying cyanoacrylate in sternal split (Group B) . In this prospective study, all rats alive were sacrificed at the 3rd and 8th weeks and sternums were examined histologically . RESULTS: Clinical study: in Group I, 6 patients required additional interventions due to recurrent sternal detachment and osteomyelitis (35.3%) . In Group II neither osteomyelitis nor sternal detachment occurred, 3 patients required re-intervention related to cyanoacrylate histotoxicity . Hospital stay was higher in Group I than Group II (24.06+/-4.7 vs 14.16+/-3.98 days, respectively) . Experimental study: all of the animals in Group A died of sepsis . In Group B all rats survived the procedure . At the 3rd week histologic evaluations showed that cyanoacrylate was not degraded, and no infection or foreign body reaction was observed . At the 8th week histologic examination showed that cyanoacrylate was completely degraded and replaced by connective tissue . CONCLUSIONS: Cyanoacrylate is effective in diminishing sternal wound complications and related cost and hospital stay of mediastinitis. Fitoterapia, 2002 Oct, 73(6), 526 - 8 Antibacterial compounds from the flowers of Alangium salviifolium; Anjum A et al.; 1-Methyl-1H-pyrimidine-2,4-dione and 3-O-beta-D-glucopyranosyl-(24beta)-ethylcholesta-5,22,25-triene, isolated from the flowers of Alangium salviifolium, showed remarkable antibacterial activities against a number of Gram-positive and Gram-negative bacterial species . J Biotechnol, 2002 Nov 13, 99(3), 175 - 85 Targets and assays for discovering novel antibacterial agents; Donadio S et al.; The increasing frequency of nosocomial infections due to multi-resistant pathogens exerts a significant toll and calls for novel and better antibiotics . Different approaches can be used in the search for novel antibiotics acting on drug-resistant bacterial pathogens . We present some considerations on valid bacterial targets to be used for searching new antibiotics, and how the information from bacterial genome sequences can assist in choosing the appropriate targets . Other factors to be considered in target selection are the chemical diversity available for screening and its uniqueness . We will conclude discussing our strategy for searching novel antibacterials . This is based on a large collection of microbial extracts as a source of chemical diversity and on the use of specific targets essential for the viability of bacterial pathogens . Two assay strategies have been implemented: a pathway-based assay, where a series of essential bacterial targets is screened in a single assay; and a binding assay, where many targets can be screened individually in the same format. Int J Antimicrob Agents, 2002 Sep, 20(3), 227 - 9 Interaction between 3,5-diacetyl-1,4-dihydropyridines and ampicillin, and erythromycin on different E . coli strains; Gunics G et al.; Eleven analogues of nifedipine (NP) showed synergistic interactions with ampicillin (Ap) and erythromycin (Er) on Escherichia coli K12LE140/F'lac . The antibacterial effect of Ap was enhanced by most analogues but compound (G9) and (+/-)-verapamil (VP) were antagonistic . Two of the 11 compounds (G7, G8) were synergistic with Er and four were additive . With a sensitive clinical isolate of E . coli Gy-1/Ap(sens)Er(res), compound G1 antagonized the antibacterial effect of Ap and a synergistic effect was found in the combination of Er with G4, G5, G6 or G7 . None of the drugs had any effect on a multidrug resistant (MDR) clinical isolate of E . coli Gy-2/Ap(res)Er(res) . Gene, 2002 Sep 4, 297(1-2), 197 - 208 Cloning and characterization of a polyketide synthase gene cluster involved in biosynthesis of a proposed angucycline-like polyketide auricin in Streptomyces aureofaciens CCM 3239; Novakova R et al.; A new polyketide gene cluster, aur1, was identified in Streptomyces aureofaciens CCM3239 by using genes for the spore-pigment polyketide synthase of the Streptomyces coelicolor whiE operon as a probe . Sequence analysis of three overlapping DNA fragments (encompassing 15,100 bp) revealed 15 open reading frames, the majority of which showed high similarity to the previously characterized type II polyketide synthase genes . The highest similarity was to three Streptomyces polyketide gene clusters involved in biosynthesis of angucycline antibiotics, jadomycin, urdamycin and landomycin . The proposed S . aureofaciens ketosynthase (Aur1D) was phylogenetically more related to all known ketosynthases for polyketide antibiotics in Streptomyces than to spore-pigment ketosynthases . Interestingly, the aur1 gene cluster contained a gene encoding a proposed malonyl-CoA:ACP transacylase that has not been identified in any of the previously characterized type II polyketide synthase cluster . Transcriptional analysis of aur1 revealed a single promoter upstream the first open reading frame (the aur1A gene) that was active in all stages of differentiation with increased activity at the time of aerial mycelium formation . The aur1 gene cluster was disrupted by a homologous recombination, replacing the three genes (aur1B,C,D) including ketosynthase, with antibiotic resistance marker gene in S . aureofaciens chromosome . Disruption did not affect growth and differentiation; disrupted strain produced spores with wild-type gray-pink pigmentation . The biochromatographic analysis of the culture extracts from S . aureofaciens wild-type and aur1-disrupted strains revealed an antibacterial compound that was missing in the mutant . The results indicated a role of the S . aureofaciens aur1 gene cluster in biosynthesis of a polyketide secondary metabolite (which we named auricin), and not in the spore pigment biosynthesis. Peptides, 2002 Oct, 23(10), 1869 - 71 A new synthetic all-D-peptide with high bacterial and low mammalian cytotoxicity; Ryadnov MG et al.; Using the synthetic alpha-helical peptide ((RLA)(2)R)(2) as a model the effect of net charge, helicity, and epimeric nature of the peptide on bactericidal potency has been examined . Both the nature and the extent of the net charge were shown to be relatively important for antibacterial activity . The loss of the structured character of the peptide resulted in reducing the activity . The all-D-peptide appeared to be a remarkably strong bacteriostatic agent with MIC <1 microM against Escherichia coli . The peptide was neither hemolytic nor cytotoxic, which in conjunction with data on its stability to enzymatic degradation makes this peptide very attractive in terms of designing new bactericidal agents on the basis of (D)((RLA)(2)R)(2). J Med Chem, 2002 Oct 24, 45(22), 4828 - 37 Comparative binding energy (COMBINE) analysis of OppA-peptide complexes to relate structure to binding thermodynamics; Wang T et al.; The periplasmic oligopeptide binding component (OppA) of the oligopeptide permease found in Gram-negative bacteria acts as a receptor for peptide transport across the cell membrane and is a potential target for antibacterial drug design . OppA exhibits broad specificity, binding to diverse peptides of 2-5 amino acid residues length . Crystallographic and calorimetric measurements have been carried out by Tame et al . of the binding of 28 peptides of sequence K-X-K to OppA, where X is a natural or nonnatural amino acid . Despite this extensive experimental characterization, a clear relationship between structural and thermodynamic parameters could not be readily identified, with a complicating factor being the observation of varying numbers of water molecules at the binding interface in the different complexes . Consequently, we have applied COMparative BINding Energy (COMBINE) analysis to derive quantitative structure-activity relationships (QSARs) for these 28 OppA-tripeptide complexes . This is the first application of COMBINE analysis to predict binding enthalpies and entropies, and predictive QSAR models were obtained for these quantities as well as for binding free energies . These QSAR models highlight several protein residues and bound water molecules in the binding site, as well as the electrostatic desolvation energies of the protein and the peptides, as responsible for most of the differences in binding thermodynamics between the peptides studied . The QSAR models aid rationalization of the determinants of binding affinity of the OppA:peptide complexes and provide guides for further ligand design . This study also points to the general applicability of COMBINE analysis to estimating thermodynamic parameters for protein-peptide complexes. Genes Dev, 2002 Oct 15, 16(20), 2662 - 71 Activation of the innate immunity in Drosophila by endogenous chromosomal DNA that escaped apoptotic degradation; Mukae N et al.; Apoptotic cell death is accompanied by degradation of chromosomal DNA . Here, we established in Drosophila a null mutation in the gene for inhibitor of caspase-activated DNase (ICAD) by P-element insertion . We also identified a loss-of-function mutant in Drosophila for DNase II-like acid DNase . The flies deficient in the ICAD gene did not express CAD, and did not undergo apoptotic DNA fragmentation during embryogenesis and oogenesis . In contrast, the deficiency of DNase II enhanced the apoptotic DNA fragmentation in the embryos and ovary, but paradoxically, the mutant flies accumulated a large amount of DNA, particularly in the ovary . This accumulation of DNA in the DNase II mutants caused the constitutive expression of the antibacterial genes for diptericin and attacin, which are usually activated during bacterial infection . The expression of these genes was further enhanced in flies lacking both dICAD and DNase II . These results indicated that CAD and DNase II work independently to degrade chromosomal DNA during apoptosis, and if the DNA is left undigested, it can activate the innate immunity in Drosophila. Clin Nutr, 2002 Oct, 21(5), 385 - 8 Indirect calorimetry in patients with active respiratory infection--prevention of cross-infection; Schwenk A et al.; BACKGROUND: Measurement of resting energy expenditure in patients with active respiratory infection is hampered by the risk of contamination of indirect calorimeters and connecting tubes that cannot be sterilized . This validation study tested whether the use of disposable standard-bore air tubes and an antibacterial filter, by reducing air flow, introduces an error due to recirculation of expired air in the canopy . METHODS: Eleven healthy volunteers underwent indirect calorimetry twice in random order, using a Deltatrac calorimeter either with standard wide-bore tubing or with a disposable standard-bore air tube and filter . Methods were compared by Bland-Altman plots and by calculating trends over time . RESULTS: The new tube and filter reduced air flow by 40% . Measured resting energy expenditure did not differ significantly between methods, with limits of agreement -135 to +188 kcal/d . Carbon dioxide flow (VCO(2)) and respiratory quotient (RQ), but not oxygen flow decreased slowly over time with both methods . CONCLUSIONS: The use of an air filter and standard-bore tubes do not introduce a systematic error into indirect calorimetry . Although trends in VCO(2) and RQ are consistent with minor recirculation of exhaled air, this modified Deltatrac system can be safely and reliably used to measure resting energy expenditures in patients with active tuberculosis and other airborne infection. J Agric Food Chem, 2002 Oct 23, 50(22), 6276 - 80 Effect of phosphorus concentration of the nutrient solution on the volatile constituents of leaves and bracts of Origanum dictamnus; Economakis C et al.; The chemical composition of the essential oils obtained from the leaves and bracts of hydroponically cultivated Origanum dictamnus were analyzed by GC-MS techniques . Three different concentrations of phosphorus (5, 30, and 60 mg/L) in the nutrient solution were used for the cultivation, using the nutrient film technique (NFT) . A total of 46 different compounds were identified and significant differences (qualitative and quantitative) were observed between the samples . Carvacrol and p-cymene were identified as the main compounds in all samples analyzed, whereas thymoquinone was found in higher percentage in the leaves than in bracts . The essential oils were tested for their antibacterial activity against Gram-positive and Gram-negative bacteria . The oils obtained from the bracts were found to be more active . The results obtained from GC-MS analyses were submitted to chemometric analysis. J Bacteriol, 2002 Nov, 184(21), 5912 - 25 A single nucleotide exchange in the wzy gene is responsible for the semirough O6 lipopolysaccharide phenotype and serum sensitivity of Escherichia coli strain Nissle 1917; Grozdanov L et al.; Structural analysis of lipopolysaccharide (LPS) isolated from semirough, serum-sensitive Escherichia coli strain Nissle 1917 (DSM 6601, serotype O6:K5:H1) revealed that this strain's LPS contains a bisphosphorylated hexaacyl lipid A and a tetradecasaccharide consisting of one E . coli O6 antigen repeating unit attached to the R1-type core . Configuration of the GlcNAc glycosidic linkage between O-antigen oligosaccharide and core (beta) differs from that interlinking the repeating units in the E . coli O6 antigen polysaccharide (alpha) . The wa(*) and wb(*) gene clusters of strain Nissle 1917, required for LPS core and O6 repeating unit biosyntheses, were subcloned and sequenced . The DNA sequence of the wa(*) determinant (11.8 kb) shows 97% identity to other R1 core type-specific wa(*) gene clusters . The DNA sequence of the wb(*) gene cluster (11 kb) exhibits no homology to known DNA sequences except manC and manB . Comparison of the genetic structures of the wb(*)(O6) (wb(*) from serotype O6) determinants of strain Nissle 1917 and of smooth and serum-resistant uropathogenic E . coli O6 strain 536 demonstrated that the putative open reading frame encoding the O-antigen polymerase Wzy of strain Nissle 1917 was truncated due to a point mutation . Complementation with a functional wzy copy of E . coli strain 536 confirmed that the semirough phenotype of strain Nissle 1917 is due to the nonfunctional wzy gene . Expression of a functional wzy gene in E . coli strain Nissle 1917 increased its ability to withstand antibacterial defense mechanisms of blood serum . These results underline the importance of LPS for serum resistance or sensitivity of E . coli. Adv Cancer Res, 2002, 86, 195 - 225 The life and death of a B cell; Defrance T et al.; Regulation of apoptosis in the B cell lineage has implications for homeostasis, quality control of the antibody response, and tolerance . In this chapter we examine the different checkpoints that control life and death decisions of B cells during the antigen-independent and antigen-dependent phases of their development . We discuss the cell death mechanism involved in elimination of unwanted B cells at different stages of their development as well as the signals that trigger or repress the apoptotic process . At the steady state, before or after development of an immune response, B cell apoptosis ensures that the antigen receptor (BCR) on newly produced B cells is functional and does not recognize self-antigens with high avidity . It also ensures that the size of the peripheral B cell compartment remains constant in spite of the continuous input of B cells from the bone marrow . All these processes are controlled by the mitochondrial death pathway and are thus perturbed by overexpression of the antiapoptotic members of the bcl-2 gene family . By contrast, the death receptor pathway plays a prominent role during the antigen-dependent phase of B cell development . Three sets of membrane molecules stand as crucial regulators of B cell survival . First, the BCR which plays a central but ambiguous role . On the one hand, it triggers death of B cells that recognize self-antigens or have been exposed to repeated antigenic stimulations . On the other hand, it promotes survival of the peripheral mature B cell pool and protects activated B cells from CD95-induced killing . Second, the death receptor Fas/CD95 which is instrumental in censoring B cells activated in a bystander fashion at the initiation of the response to T-dependent antigens . It also drives elimination of low-affinity and self-reactive B cell clones that arise through the process of somatic mutations during the germinal center reaction . As such, it contributes to the affinity maturation of the antibody response . Finally, three membrane receptors (TACI, BCMA, and BAFF-R) which bind a newly discovered member of the tumor necrosis factor family named BAFF . BAFF acts specifically on peripheral B cells but its cellular targets seem to be restricted to two splenic B cell populations: (i) transitional immature B cells and (ii) marginal zone B cells, known to be responsible for the response to thymus-independent type 2 antigens . This suggests its possible implication in positive selection of peripheral B cells and in the antibacterial B cell responses. J Infect Chemother, 2002 Sep, 8(3), 211 - 7 Properties of extended-spectrum beta-lactamases constructed by site-directed mutagenesis; Takenouchi T et al.; Plasmids carrying three types of TEM-type extended-spectrum beta-lactamase (ESBL) genes, encoding TEM-3, TEM-5, and TEM-9, respectively, were constructed by site-directed mutagenesis . ESBL producers were prepared by transformation of Escherichia coli JM109 with a plasmid carrying one gene of either the three TEM types, an SHV-type, or a Toho-1 group gene . This strategy with the same vector and host strain can exclude the contribution of other factors to susceptibility, and is useful in Japan, where few TEM-type ESBL producers have been isolated . In vitro antibacterial activities of 23 beta-lactam antibiotics were tested against the ESBL producers by the agar dilution method, and the results were compared . The minimum inhibitory concentrations (MICs) of penicillins tested were more than 32 micro g/ml against both the parental RTEM and ESBL producers, but they were substantially decreased by a combination with beta-lactamase inhibitors . Compared with the MICs against the ESBL-nonproducing host strain, the MICs of the cephalosporins tested for the ESBL producers were increased more than eight times in most cases and in several cases soared to more than 2048 times against a Toho-1 ESBL producer . On the other hand, the MICs of carbapenem, cephamycin, and penem antibiotics were generally comparable to those against the host strain, and were increased by 32 times at most . Kinetic analysis revealed that extended-spectrum cephalosporins were hydrolyzed only slightly to moderately by the TEM-type ESBLs, while carbapenems and a cephamycin were scarcely hydrolyzed, and rather inhibited or inactivated the mutant enzymes. Bioorg Med Chem Lett, 2002 Nov 4, 12(21), 3033 - 6 An efficient and practical method for solid-phase synthesis of tripeptide-bearing glycopeptide antibiotics: combinatorial parallel synthesis of carboxamide derivatives of chloroorienticin B; Yasukata T et al.; An efficient and practical method was established for solid-phase parallel synthesis of the peptide-bearing carboxamide derivatives of chloroorienticin B, and over 80 compounds were synthesized simultaneously . Among the derivatives prepared, compounds having both tryptophan and tyrosine residues (1-3) were found to possess potent antibacterial activity against VRE. Clin Exp Dermatol, 2002 Sep, 27(6), 464 - 6 Fixed drug eruption following metronidazole therapy and the use of topical provocation testing in diagnosis; Short KA et al.; Fixed drug eruption is characterized by recurrent well-defined lesions appearing in the same location each time the drug responsible is taken . A number of agents have been implicated . Metronidazole, a nitroimidazole agent widely used for its antibacterial and antiprotozoal activity, has been reported only rarely as the causative agent . We describe a patient with FDE due to metronidazole in whom we were able to induce the clinical and histological features of FDE by topical provocation testing . In agreement with the published literature we commend the use of topical provocation testing as a possible first-line investigation in the diagnosis of FDE . This may avoid the need for subsequent oral provocation testing and therefore the prevention of possible adverse sequelae. Drug Metabol Drug Interact, 1994, 11(3), 201 - 35 The toxicity of phenothiazine; Mitchell SC; Phenothiazine, the parent compound of a multitude of present-day drugs, has been employed on an extensive scale for its insecticidal, fungicidal, antibacterial and anthelmintic properties . Almost a