Antimicrobials

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 catholicon, its widespread use in animals and man has led to the uncovering of many adverse reactions encompassing effects on blood elements, neuromuscular problems and photosensitization . The high lipophilicity of phenothiazine and the formation of two redox systems amongst its many metabolites can facilitate the occurrence of generalised macromolecular disruption . Information from the literature has been garnered and appraised in this review to enable an insight into the possible mode(s) of interaction of phenothiazine with living systems.

Mini Rev Med Chem, 2001 Nov, 1(4), 409 - 16
Peptides neutralizing lipopolysaccharide - structure and function; Pristovsek P et al.; Lipopolysaccharide (LPS) induced Gram-negative sepsis and septic shock remain lethal in up to 60 % of cases, and LPS antagonists that neutralize its endotoxic action are the subject of intensive research . In the last decade peptidic antagonists have become increasingly important in providing leads for treatment of LPS-mediated diseases . In this review an overview of the sources, functions and structures of antiseptic and antibacterial peptides that interact with LPS is presented.

Curr Med Chem, 2002 Nov, 9(21), 1871 - 92
Drug evolution: p-aminobenzoic acid as a building block; Kluczyk A et al.; The core or the building block is an important component in drug development . In this article, we propose and review p-aminobenzoic acid (PABA) as a building block used in the design of drugs or drug candidates . PABA is frequently found as a structure moiety in drugs . For example, in a database of 12,111 commercial drugs, 1.5% (184 drugs) were found to contain the PABA moiety . These drugs have a wide range of therapeutic uses, such as: sun-screening, antibacterial, antineoplastic, local anesthetic, anticonvulsant, anti-arrhythmic, anti-emetic, gastrokinetic, antipsychotic, neuroleptic, and migraine prophylactic . This article reviews the molecular targets and the mechanisms of these activities . Drugs containing PABA also show a wide range of structural diversity . Of the 184 PABA containing drugs identified, 95 different substitutions were found at the carboxylic group and 61 were found at the amino group of the building block . Substitution on the aromatic ring was also diverse . 13, 3, and 13 different side chains were found to modify positions 2, 3 and 5 of the aromatic ring respectively . In some drugs, the amino group is further substituted to form tertiary amine (4 different side chains) . Substitutions at the carboxyl and amino groups of PABA are particularly suitable for the generation of combinatorial libraries . Just by reshuffling the identified side chains of the 184 PABA containing drugs, 4.5 million compounds can be generated . Consequently, PABA fits well as a building block for a general chemical library of "drug-like" molecules with a wide range of functional and structural diversity.

Curr Med Chem, 2002 Nov, 9(21), 1859 - 69
BM 212 and its derivatives as a new class of antimycobacterial active agents; Biava M; During our investigation in pyrrole antibacterial area we have identified a subclass with a good potent in vitro activity against mycobacteria and fungi . We have individuated the salient structural feature and BM 212 as lead for the class . SAR studies allowed us to synthesize several analogue derivatives . Some of them revealed more active than BM 212 against mycobacteria, but they lost antifungal activity . In particular the Protection Index (PI) was very interesting for some derivatives, comparable to that of reference compounds, Isoniazid (INH), Streptomycin (SM) and Rifampin (RF) . Many of the synthesized compounds revealed active against intracellular mycobacteria and they showed to be inhibitory to drug-resistant mycobacteria of clinical origin . On the base of microbiological results we have hypothesized a pharmacophore model that was also optimized . The rational design, and the evaluation of the in vitro activity against mycobacteria are described.

Drug Metabol Drug Interact, 1994, 11(2), 85 - 109
Imidazolidinones structurally-related to penicillins: synthesis, molecular modeling and biological evaluation; Marchand-Brynaer J et al.; Several bicyclic imidazolidinones structurally-related to penicillins have been prepared from penam precursors . The compounds were compared to benzylpenicillin as active reference, using the methods of theoretical chemistry . Structures 7 and 8, in which the acyl group of the side-chain was anchored, via a "one-atom spacer", at position N-7 of the imidazolidinone ring, appeared as good penicillin mimics . However, they were found devoid of significant antibacterial activity.

J Dairy Res, 2002 Aug, 69(3), 419 - 31
Purification, characterization, antibacterial activity and N-terminal sequencing of buffalo-milk lysozyme; Priyadarshini S et al.; Lysozyme from buffalo milk was purified to homogeneity and its N-terminal amino acid sequence, biochemical properties and antibacterial spectrum were determined . The purification procedure, comprising ion-exchange chromatography using CM-cellulose and size-exclusion chromatography using Sephadex G-50, conferred 8622-fold purification and 39.3% recovery of lysozyme . The purified enzyme migrated as a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and native PAGE . Immunological purity of lysozyme preparation was confirmed by immuno-electrophoresis . Molecular weight of buffalo-milk lysozyme as determined by SDS-PAGE was 16 kDa and its amino acid composition was determined by reverse phase high performance liquid chromatography (HPLC) . The sequence of 23 amino acid residues at the N-terminal end showed 56.5% homology with bovine milk lysozyme and 30.4% with equine milk lysozyme . The specific activity of buffalo milk lysozyme was ten-times that of bovine milk lysozyme . Buffalo-milk lysozyme was active over a wide range of pH and its activity was strongly influenced by molarity of the medium . Antibacterial activity of buffalo-milk lysozyme was determined against 11 species of bacteria; out of seven Gram-positive bacteria tested, four were inhibited, while Gram-negative bacteria were resistant.

Acta Pol Pharm, 2002 Mar-Apr, 59(2), 127 - 32
Pyrrole analogues of chloramphenicol . III . Synthesis and antibacterial activity of DL-threo-1-(1-methylsulfonylpyrrole-3-yl)-2-dichloroacetamidopropane-1,3-diol; Krajewska D et al.; A seven-stage synthesis of a pyrrole analogue of chloramphenicol (9) is described . The compound exhibits a significant antibacterial activity, over the 3% to 50% range of the chloramphenicol activity: over the 6% to 100% range of the thiamphenicol activity and florfenicol.

Biotechnol Prog, 2002 Sep-Oct, 18(5), 1082 - 6
Bactericidal properties of flat surfaces and nanoparticles derivatized with alkylated polyethylenimines; Lin J et al.; We previously discovered that covalently coating glass and plastic slides with certain long poly(vinyl-N-alkylpyridinium) chains enables the resultant surfaces to kill a variety of airborne and waterborne bacteria on contact . In the present study, these findings have been extended to an unrelated polymer class, polyethylenimines (PEIs) . Alkylated PEIs attached to flat macroscopic surfaces and to those of nanoparticles make these materials highly bactericidal toward both Gram-positive and Gram-negative pathogenic bacteria . Systematic chemical modifications of the immobilized PEI conducted herein shed light on the relationship between the structure of the polymer and the antibacterial efficiency of the resultant coating.

Microb Drug Resist, 2002 Fall, 8(3), 193 - 200
Clonal diversity and metallo-beta-lactamase production in clinical isolates of Stenotrophomonas maltophilia; Mercuri PS et al.; Stenotrophomonas maltophilia is a nosocomial pathogen with an intrinsic broad-spectrum resistance to beta-lactam compounds and other antibacterial agents . It produces two chromosomal beta-lactamases: a clavulanic acid-sensitive class A (L2) and a tetrameric carbapenemase (L1 or BlaS) . We screened 40 S . maltophilia multidrug-resistant clinical isolates recovered between 1995 and 1998 in the Varese Hospital (Italy) for the presence of the metallo-beta-lactamase . The isolates were investigated by phenotypic profiling (enzymatic activity and antibiotic resistance pattern) and molecular methods such as PCR and pulsed-field gel electrophoresis (PFGE) to reveal intraspecies diversity . For the tested S . maltophilia strains, we showed that the beta-lactamase production could be induced by the presence of imipenem (50 microg/ml) in the culture media . Addition of 1 mM dipicolinic acid completely inhibited the hydrolysis of imipenem but decreased that nitrocefin in a strain-dependent manner . Full activity of crude extract towards imipenem could be restored by addition of 1 mM ZnCl2 . Finally, the gene encoding the carbapenem-hydrolyzing beta-lactamase from S . maltophilia ULA-511 and 39/95, a clinical strain, were isolated and sequenced . These two strains have a different profile of multidrug resistance . The two metallo-beta-lactamases were found to be isologous . The difference of sensitivity of these two strains was associated to the level of production of the metallo-beta-lactamase.

J Dairy Sci, 2002 Sep, 85(9), 2065 - 74
Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells; Roy MK et al.; To determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF) and related compounds on the growth of leukemic cells, human myeloid leukemic cells (HL-60) were exposed to bovine lactoferrin (bLF) and proteolytic hydrolysates of bLF . Pepsin hydrolysates of bLF showed a greater growth suppressive effect than tryptic hydrolysates or mature bLF . Four peptides with proliferation inhibition activity were purified from pepsin hydrolysates by ion-exchange chromatography, reverse-phase HPLC, and gel-filtration . All peptides were from the N-terminal end, in a region where lactoferricin B (Lfcin B), an antibacterial peptide, is located . Among the four peptides, peptide 1 (pep1) was found to exhibit highest activity and corresponded to residues 17 to 38 of bLF, with a molecular weight of 2753.88 . The IC50 value of this peptide was 6.3 micrograms/ml . Three other peptides were less active and corresponded to sequences 1 to 16 and 45 to 48, linked by disulfide-bridge (pep2, molecular mass of 2430.13), 1 to 15 and 45 to 46 linked by disulfide bridge (pep3, molecular mass of 2017,92) and from residues 1 to 13 (pep4, molecular mass of 1558.73) . Cell proliferation inhibition activity of the peptides was thought to be due to induction of apoptosis, which was evaluated by DNA ladder formation, DNA fragmentation, enhanced expression of phosphatidyl serine, and morphological changes . The IC50 values of the three peptides were confirmed using synthetic peptides and were consistent with those of purified peptides.

Farmaco, 2002 Aug, 57(8), 693 - 6
Synthesis of some new biologically active thiadiazolotriazinones--part III; Holla BS et al.; 4-Amino-6-arylmethyl/tert-butyl-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with arylfuroic acids (2) to yield 7-(5-aryl-2-furyl)-3-arylmethyl/tert-butyl-4H-1,3,4-thiadiazolo{2,3-c}-1,2,4-triazin-4-ones (3) . The newly synthesized compounds exhibited antibacterial activity comparable to that of nitrofurazone . In addition, two compounds displayed in vitro antitumor activity with moderate growth inhibition against a panel of 60 tumor cell lines.

J Antimicrob Chemother, 2002 Oct, 50(4), 547 - 52
In vivo action of novel alkyl methyl quinolone alkaloids against Helicobacter pylori; Tominaga K et al.; Previously purified and isolated compounds of novel alkyl methyl quinolone alkaloids (AM quinolones) from Gosyuyu (Wu-Chu-Yu), a Chinese herbal medicine, have a strong and highly selective antibacterial activity against Helicobacter pylori in vitro . To clarify the antibacterial mechanism(s) of AM quinolones, we examined the effects of AM quinolones on respiration of H . pylori in vitro . One week after treatment with AM quinolones alone (2, 10 or 20 mg/kg/day, orally) or combinations of AM quinolones and omeprazole (30 mg/kg/day) for H . pylori (1 x 10(8) cfu)-infected Mongolian gerbils, we checked viable H . pylori and myeloperoxidase (MPO) activity in the gastric tissues . AM quinolones decreased the number of H . pylori and inhibited H . pylori respiration in a dose-dependent manner . AM quinolones decreased the number of viable H . pylori (AM quinolones alone: 46.0 +/- 22.6 x 10(4), 17.3 +/- 4.9 x 10(4) and 8.1 +/- 6.6 x 10(4) cfu/stomach, respectively; and combinations of AM quinolones and omeprazole: 8.0 +/- 5.6 x 10(4), 4.2 +/- 2.5 x 10(4) and 5.5 +/- 2.7 x 10(4) cfu/stomach) compared with the vehicle-treated group (control: 359.9 +/- 180.3 x 10(4) cfu/stomach) . AM quinolones significantly decreased MPO activity of H . pylori-inoculated gastric tissues . These findings suggest that AM quinolones have a potent antibacterial effect against H . pylori through respiratory inhibition, and reduced bacterial growth in vivo . AM quinolones might be novel therapeutic agents for H . pylori eradication.

Indian J Pediatr, 2002 Aug, 69(8), 679 - 82
Mupirocin vs terbinafine in impetigo; Ciftci E et al.; OBJECTIVE: Terbinafine is an antifungal drug known to have also antibacterial activity against certain Gram-positive and Gram-negative bacteria . It seems that antibacterial and antifungal activity of terbinafine may have an advantage in the treatment of mixed fungal and bacterial superficial skin infections . Nevertheless, clinical relevance of the antibacterial part of its action has not been investigated efficiently . To compare the efficacy and safety of terbinafine with those of mupirocin, which has already proven antibacterial action, in the treatment of impetigo . METHODS: Children clinically diagnosed as having impetigo were treated with topical mupirocin or topical terbinafine in a randomized fashion . Patients' lesions were examined clinically on days 0, 4, 7, 10 and bacteriologic cultures were obtained on days 0 and 10 . RESULTS: A total of 62 patients were included in the study . Forty-eight of these patients were eligible for the efficacy and safety analysis . Twenty-five and 23 patients were treated with mupirocin and terbinafine, respectively . The clinical cure rates were 100% for the mupirocin group and 70% for the terbinafine group (p < 0.05) . The bacteriological eradication rate for mupirocin-treated children was 100% and that for terbinafine-treated children was 78% (p < 0.05) . Presence of bullous lesions appeared to be a factor for poor clinical outcome in the terbinafine group . Mild local adverse effects were noted in a small percentage of patients in each group . CONCLUSION: Antibacterial activity of terbinafine is not strong enough to be an alternative in the treatment of impertigo . It is advisable that terbinafine could be used in combination with an antibacterial drug for superficial skin infections caused by both fungi and bacteria.

Eur J Immunol, 2002 Oct, 32(10), 2721 - 5
Antibody-dependent macrophage-mediated activity against Helicobacter pylori in the absence of complement; Peppoloni S et al.; Helicobacter pylori is a Gram-negative bacterium, which chronically infects the stomach . Little is known about the immune mechanisms limiting the spread of infection and/or contributing to protection after experimental immunization . In this study, we investigated the hypothesis that specific antibodies and host cells cooperate in the immunity against H . pylori . Antibody-dependent cellular activity against H . pylori was assessed using specific immune serum, or purified IgG, in an in vitro assay, with peritoneal cells as effector cells . The natural antibacterial activity of peritoneal cells was significantly augmented by H . pylori-specific antibodies in a dose-dependent manner . A novel finding was that this killing effect did not require functional complement . Most of the bactericidal activity was associated with cells that were adherent, DX5(-), CD19(-), CD11c(-), Thy-1.2(-), CD11b(+) and CD16/32(+), indicating that the main effector population was represented by macrophages . Similar antibacterial killing was obtained with the macrophage cell line GG2EE . Cytochalasin D significantly impaired this antibacterial activity, suggesting that phagocytosis plays a major role in the antibody-mediated H . pylori killing.

Eur J Biochem, 2002 Oct, 269(19), 4799 - 810
Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa; Moerman L et al.; Two novel pore-forming peptides have been isolated from the venom of the South-African scorpion Opistophtalmus carinatus . These peptides, designated opistoporin 1 and 2, differ by only one amino acid and belong to a group of alpha-helical, cationic peptides . For the first time, a comparison of the primary structures of alpha-helical pore-forming peptides from scorpion venom was undertaken . This analysis revealed that peptides in the range of 40-50 amino acids contain a typical scorpion conserved sequence S(x)3KxWxS(x)5L . An extensive study of biological activity of synthesized opistoporin 1 and parabutoporin, a pore-forming peptide previously isolated from the venom of the South-African scorpion Parabuthus schlechteri, was undertaken to investigate an eventual cell-selective effect of the peptides . Opistoporin 1 and parabutoporin were most active in inhibiting growth of Gram-negative bacteria (1.3-25 micro m), while melittin and mastoparan, two well-known cytolytic peptides, were more effective against Gram-positive bacteria in the same concentration range . In addition, the peptides showed synergistic activity with some antibiotics commonly used in therapy . Opistoporin 1 and parabutoporin had hemolytic activity intermediate between the least potent mastoparan and the highly lytic melittin . Furthermore, all peptides inhibited growth of fungi . Experiments with SYTOX green suggested that this effect is related to membrane permeabilization.

J Biomol Struct Dyn, 2002 Oct, 20(2), 291 - 9
Preferential binding of quinolones to DNA with alternating G, C / A, T sequences: a spectroscopic study; Jain A et al.; The binding of quinolones, nalidixic acid (Nal), oxolinic acid (Oxo) with double stranded polynucleotides was undertaken by using UV-melting, UV-Vis absorption, fluorescence and CD spectroscopic techniques . The binding of Nal or Oxo to the polynucleotides under low-salt buffer conditions were determined for poly (dA).(dT), poly {d(A-T)}, poly (dG).(dC), poly {d(G-C)} and E . coli DNA . The fluorescence data were analyzed using a previously established two step mechanism with two different DNA-Drug complexes {Rajeswari et al., Biochemistry 26, 6825-31 (1987)} . The first complex {DN}(1) with a binding constant K(1), is formed where the interactions are 'nonspecific' and complex {DN}(2) with a binding constant K(2), is formed where the interactions are "specific" which involve (additional) hydrophobic type of interactions like 'stacking' of the drug and the overall association constant is represented as K(=K(1)K(2)) . The order of binding for Nal and Oxo is: poly {d(G-C)} > poly {d(A- T)} > E . coli > poly (dG).(dC) > poly (dA).(dT) . Interaction of quinolones seems to be preferential in the alternating G, C or A, T stretches of DNA than those of non-alternating . Within any alternating or non-alternating in DNA sequences the G, C rich sequences have distinctly greater binding than A, T sequences . The overall association constant data (K) reveal higher binding of Oxo to DNA compared to Nal to any given polynucleotide investigated; which also explains the higher antibacterial potency of Oxo . Changes in the absorption difference spectra and in circular dichroic spectra also manifest these results . As the melting temperatures of the polynucleotides were only marginally raised in presence of the quinolone, we rule out the possibility of 'classical intercalation' of the drug . Amino group of guanine facilitates the binding of quinolones and therefore has the greater binding with the DNA . However, poly (dG).(dC) is known to exist in 'A' conformation which is not adopted by quinolones as in the case of poly (dA).(dT) . Present results suggest that Nal or Oxo bind to DNA in a non-classical fashion which is partially stacking in nature.

Acta Derm Venereol, 2002, 82(3), 204 - 5
Herpes simplex virus infection in a hyper-IgE patient: appearance of unusual mass lesions; Hershko K et al.; A 7-year-old girl presented with large soft masses rising from the nostril and from behind the ear . She had previously been diagnosed as suffering from hyper-IgE syndrome . The presence of herpes simplex virus infection within these lesions was confirmed by biopsy and immunohistochemical studies . The mass lesions did not respond to antibacterial therapy with cefazolin, but improved promptly under antiviral therapy with acyclovir . Immunological studies revealed a mild decrease in the CD4 cell population . Based on our results and on the relevant literature we propose an immunological mechanism for this unique manifestation of herpes simplex virus infection in hyper-IgE syndrome.

Eksp Klin Gastroenterol, 2002, (3), 66 - 7, 121
{Pariet in eradication therapy plans}; Minushkin ON et al.; In the article the results of the eradication therapy by Pariet in the patients suffering from the duodenal ulcer disease, associated with Helicobacter pylori (HP), are estimated . Four schemas with use 40 and 20 mg of Pariet per day in a combination with two antibacterial preparations were evaluated . The therapy duration was 7 days . The ulcer cicatrisation has occurred in 100% of the patients . The eradication was achieved in 100% of cases at use of a dose 40 mg of Pariet per day . At use of the schemas with a dose 20 mg of Pariet per day the eradication was observed in 67% of patients . Pariet is considered as the high efficient preparation in the eradication and cicatrisation of the ulcer.

Eur J Med Chem, 2002 Sep, 37(9), 743 - 54
Synthesis and antibacterial activity of 1beta-methyl-2-(5-substituted thiazolo pyrrolidin-3-ylthio)carbapenem derivatives; Oh CH et al.; The synthesis of a new series of 1beta-methylcarbapenems having the substituted thiazolopyrrolidine moiety is described . Their in vitro antibacterial activities against both Gram-positive including MRSA and Gram-negative bacteria were tested and the effect of substituent on the thiazole ring was investigated . A particular compound (28c) having 4'-amide substituted thiazole moiety showed the most potent antibacterial activity .

Ahfad J, 1995 Jun, 12(1), 74 - 86
Grandmothers' influence on mother and child health; Bedri NM; PIP: This study is based on interviews with grandmothers during July-September 1992-93 in Sudan . The study shows that grandmothers play a significant role in health education and child care within families in the Sudan . Grandmothers, who are not aware of the changes in knowledge, also promote harmful traditions . The authors recommend that health education be directed to elderly women and grandmothers in order to change beliefs and practices that continue to be harmful to children and mothers . Grandmothers were found to give sound advice on child birth, such as movement during labor, breast feeding immediately after birth, and birth intervals of 2-4 years . Grandmothers also gave sound advice on good nutritional practices during pregnancy and use of fermented cereals as weaning foods . Grandmothers recommended use of fenugreek for lactating mothers and use of mint and haharaib for stomach upsets, remedies that are beneficial . Babul is useful after an episiotomy for its antibacterial effects . Harmful advice includes recircumcision after delivery, short birth intervals, and avoidance of contraception . Female genital mutilation (FGM) is a major practice that exposes girls and mothers to a greater risk of mortality during childbirth and pregnancy . The sample of grandmothers agreed on the importance of sex education for a girl before marriage . Unfortunately, 57% of grandmothers recommended 14 years as a suitable age for marriage . Grandmothers generally believed wrongly that riding bicycles, drinking coffee, and wearing trousers by girls would increase their sexual desires . Grandmothers explained menstruation to granddaughters and offered home-made remedies for cramps . 45% believed that there were no disadvantages to FGM and recommended FGM at ages 2-5 years . Most viewed fevers as a danger that required a doctor's care . Advice varied among grandmothers according to socioeconomic class .

Curr Opin Pharmacol, 2002 Oct, 2(5), 513 - 22
New (and not so new) antibacterial targets - from where and when will the novel drugs come?
Projan SJ.
Although the need for new antibacterial therapies and strategies is greater than it has been in a quarter of a century and despite considerable effort, little progress has been observed in the development of agents . Target-based screening for new antibacterial agents has been particularly disappointing, despite a plethora of potential targets, enhanced screening methodologies and considerable investment . Recent efforts are coalescing around tried and true biosynthetic pathways like cell wall biosynthesis and the less well exploited pathway for fatty acid biosynthesis . Novel crystal structures for components of the replication complex and the ribosome have fuelled efforts at screening for novel replication and translation inhibitors . And target-based screening appears to have scored at least a modest success with inhibitors of peptide deformylase . More problematic are strategies targeting virulence and regulation of gene expression; despite considerably better understanding of these processes, there is no clear path to the use of inhibitors of host-pathogen interactions and/or regulation . In targeting the expression of resistance itself, it appears that staying one step ahead of the beta-lactamases is an overly optimistic goal; the best that can be expected is to avoid falling too far behind . Targeting multidrug efflux pumps may be more edifying in the long run.

Environ Sci Technol, 2002 Sep 1, 36(17), 3645 - 51
Environmental exposure and risk assessment of fluoroquinolone antibacterial agents in wastewater and river water of the Glatt Valley Watershed, Switzerland; Golet EM et al.; The mass flows of fluoroquinolone antibacterial agents (FQs) were investigated in the aqueous compartments of the Glatt Valley Watershed, a densely populated region in Switzerland . The major human-use FQs consumed in Switzerland, ciprofloxacin (CIP) and norfloxacin (NOR), were determined in municipal wastewater effluents and in the receiving surface water, the Glatt River . Individual concentrations in raw sewage and in final wastewater effluents ranged from 255 to 568 ng/L and from 36 to 106 ng/L, respectively . In the Glatt River, the FQs were present at concentrations below 19 ng/L . The removal of FQs from the water stream during wastewater treatment was between 79 and 87% . During the studied summer period, FQs in the dissolved fraction were significantly reduced downstream in the Glatt River (15-20 h residence time) (66% for CIP and 48% for NOR) . Thus, after wastewater treatment, transport in rivers causes an additional decrease of residual levels of FQs in the aquatic environment . Refined predicted environmental concentrations for the study area compare favorably with the measured environmental concentrations (MEC) obtained in the monitoring study . Total measured FQ concentrations occurring in the examined aquatic compartments of the Glatt Valley Watershed were related to acute ecotoxicity data from the literature . The risk quotients obtained (MEC/PNEC < 1) following the recommendations of the European guidelines or draft documents suggest a low probability for adverse effects of the occurring FQs, either on microbial activity in WWTPs or on algae, daphnia, and fish in surface waters.

AIDS Wkly Plus . 1998 Oct 19;:10.
International award received recognizing anti-HIV spermicide; Sexually transmitted diseases (STD) in infertile males attending the andrology clinic at Ga-Rankuwa Hospital; Sexually transmitted diseases (STDs) affect the physiology of male/female reproduction . Chronic bacterial infection of semen is uncommon, but may be a cause of male infertility . Antibacterial treatment results in improvement in sperm quality, once the infection is eradicated . Little is known about how infection with Mycoplasma hominis affects semen quality, but treatment with antibiotics improves motility and decreases the percentage of coiled tails . Chlamydia trachomatis is not frequently isolated from the urethral cultures of normal men, but is a major cause of nongonococcal urethritis and epididymitis . Chlamydia is an important cause of epididymal and oviductal obstruction . Trichomonas vaginalis most frequently colonizes the vagina and cervix of women and the anterior urethra of the male sexual partners . The highest prevalence is in sexually active men and women and Trichomoniasis may well be the most common STD . Syphilis may be an important cofactor in facilitating transmission of the human immunodeficiency virus (HIV) . A history of syphilis or a positive serologic test for syphilis is associated with HIV seropositivity in men . In South Africa, the seropositivity in pregnant black women ranges from 11-20% . Ga-Rankuwa Hospital is the referral center for 40 peripheral hospitals and over 4 million people . Since the inception of the Andrology Laboratory in June 1985, more than 5300 semen analyses have been performed on 2000 patients.

Eksp Klin Gastroenterol, 2002, (1), 37 - 9, 191
{Microflora of the peri-ulcer zone in patients with ulcer disease and its sensitivity to antibacterial agents}; Chervinets VM et al.; The investigations carried out on 126 patients with ulcer disease has shown that from bioptates of periulcer mucosa it is possible to elicit 21 kinds of microorganisms including H . pylori, in quantity 2.8-5.76 lg KOE in 1 gr of bioptate in a combination from 2 to 6 various microbial cultures . They have hemocatheretic, lecithin, urease, gelatinous, DRNA, RNA, katalase activity and cytotoxic properties, what makes the microbiological characteristics of ulcer defect close to parameters of contaminated wound . The given circumstance allows to conclude that in treatment of ulcer relapse it is necessary to suppress the activity not only H . pylori, but also another high pathogenic microbial flora . The testing of various antibacterial medications to microorganisms of periulcer zone has shown, that Ampicillin had the greatest effect in a combination with Gentamicin or Ofloxacin.

Chem Phys Lipids, 2002 Oct, 119(1-2), 33 - 9
A MAS-NMR study of the location of (+)-totarol, a diterpenoid bioactive molecule, in phospholipid model membranes; Bernabeu A et al.; (+)-Totarol, a diterpenoid isolated from Podocarpus spp., is a potent antioxidant and antibacterial agent . Although the mechanism of action of this hydrophobic molecule is poorly understood, recent work from our laboratories suggests that it could be due to membranotropic interactions . The location of (+)-totarol in membranes and its interaction with membrane components is therefore of considerable interest . High resolution magic angle spinning (MAS) natural abundance 13C nuclear magnetic resonance studies were undertaken to assess the location of (+)-totarol in model membranes composed of egg yolk phosphatidylcholine (EYL) . 13C spin-lattice relaxation times (T(1)) of both the phospholipid and (+)-totarol molecules in the presence of Gd(3+) were measured to obtain information on molecular distances . Our results indicate that (+)-totarol is situated in the upper region of the membrane, with its hydroxyl group located in the vicinity of the C-3/4 carbon atoms of the phospholipid acyl chain, and nearly perpendicular with respect to the phospholipid acyl chain axis . Such a location of (+)-totarol in the membrane would be expected to compromise the functional integrity of the membrane and account, at least in part, for its antibacterial effects.

Biochemistry, 2002 Oct 1, 41(39), 11779 - 85
The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions; Hiasa H; DNA gyrase and topoisomerase IV (Topo IV) are cellular targets of quinolone antibacterial drugs . The Ser-80 and the Glu-84 of the ParC subunit have been identified as mutational hotspots for quinolone resistance . Mutant Topo IV proteins containing a quinolone resistance-conferring mutation have been constructed, and the effects of these mutations on Topo IV are assessed . Both S80L and E84K mutations abolish the ability of quinolones to trap covalent Topo IV-DNA complexes, demonstrating that both the Ser-80 and the Glu-84 of ParC are essential for Topo IV-quinolone interaction . In addition, the E84K mutation greatly reduces the catalytic activity of Topo IV . Covalent Topo IV-DNA complexes formed with Topo IV containing the E84K mutation are more stable than those formed with the wild-type protein . Interestingly, the E84P mutation confers quinolone resistance to Topo IV without affecting its catalytic activity . The E84P mutation inhibits the formation of covalent Topo IV-DNA complexes when Mg(2+), but not Ca(2+), is used as a cofactor . These results show that the Glu-84 plays an important role in Topo IV-DNA interaction . Thus, the Glu-84 of ParC is critical for the interactions of Topo IV with both the quinolone drug and the DNA in topoisomerase-quinolone-DNA ternary complexes.

Bull Haffkine, 1977 Dec, 5(3), 94 - 6
N'N'-disubstituted piperazine derivatives as antifilarial antiamoebic and spermicidal agents; Sonurlikar UA et al.; PIP: 4 derivatives of N',N'-piperazine were tested for spectra of activity against filaria, amoeba, and sperm, in addition to bacteria . All 4 of the desubstituted piperazines stopped movements of sperms within 10 minutes at a concentration of 15.6 mg/ml . 2 of the compounds, coded R-3504 and R-3536, showed activity within 2 minutes . Antifilarial activity was exhibited by all 4 compounds within 5 minutes at 15.6 and 31.2 mg/ml against L . carinii and W . bancroft, respectively, in vitro . 3 of the compounds showed activity against E . histolytica at 5 mg/ml; and R-2916 showed antiamoebal activity at 50 mg/ml in vitro . Up to 200 mg/ml, all 4 compounds exhibited no antibacterial activity against S . typhi, S . aureus, and V . cholerae when tested in vitro . The compounds R-2768, R-3504, and R-3536 inhibited the motility of the microfilariae of W . bancrofti and L . carinii; E . histolyica; and human sperms . This was not due to cytotoxic activity but was specific activity since the compounds did not exhibit any antibacterial activity .

Exp Parasitol, 2002 May, 101(1), 77 - 81
Brugia malayi: effects of antibacterial agents on larval viability and development in vitro; Rao RU et al.; Recent studies have suggested that intracellular Wolbachia bacteria are necessary for reproduction and survival of adult filarial worms . We now report results of in vitro studies of effects of antibacterial antibiotics (tetracycline, rifampicin, chloramphenicol, azithromycin, and doxycycline) on Brugia malayi infective larvae (L3) motility and molting . All of the antibiotics tested except chloramphenicol decreased L3 motility by 50% or more at 10 days, with minimal effective concentrations (MECs) of 20-100 microg/ml . Tetracyclines, rifampicin, and chloramphenicol inhibited L3 to L4 molting by 12 days in a concentration- and time-dependent manner, with MECs in the range of 1-20 microg/ml . These studies show that antibiotics active against Rickettsiaceae inhibit B . malayi L3 molting at low concentrations in vitro; higher concentrations kill the larvae . While it is possible that antibiotics directly affect filarial L3, we believe it is more likely that the effects seen are indirect effects related to bacterial killing.

J Otolaryngol, 2002 Aug, 31 Suppl 1, S38 - 40
Anti-inflammatory effects of the macrolides; Davidson R et al.; Since their introduction into clinical practice, the macrolides have played an important role in the treatment of both upper and lower respiratory tract disease . In addition to their antibacterial effects, increased evidence is mounting to suggest that the macrolides possess other clinically relevant properties, such as anti-inflammatory and immunomodulatory activities . Several in vitro and clinical trials have been published supporting this hypothesis . This article reviews some of the evidence.

J Vet Med B Infect Dis Vet Public Health, 2002 Aug, 49(6), 289 - 93
Determination of intracellular concentrations of free and two types of liposome-encapsulated enrofloxacin in anatolian shepherd dog monocytes; Bas LA et al.; In this study, it was evaluated the accumulation of free and two types of liposome-encapsulated enrofloxacin (LEE) at the doses of 0.25, 0.5 and 1 microg/ml, which were clinically relevant concentrations into monocytes of healthy Anatolian shepherd dogs . Enrofloxacin was encapsulated with two different types of liposome in multilamellar large vesicles (MLV) . Type A MLV composed of 15 mg egg phosphatidylcholine and 35 mg cholesterol, Type B MLV composed of phosphatidylcholine (PC), cholesterol and enrofloxacin, in a molar ratio of 1 : 1 : 1 . The mean sizes of Type A and Type B liposome were found to be 7.65 and 4.27 microm, respectively . However, the mean encapsulation rate determined of Type A (13 +/- 2%) was found lower than Type B liposome (44 +/- 3%) . The amounts of intracellular enrofloxacin concentrations were determined by high performance liquid chromatography . Type B LEE accumulated significantly higher level into monocytes when compared to free drug or Type A liposome . This study showed that Type B LEE markedly concentrated within monocytes and may improve the antibacterial efficacy of the antibiotic.

Burns, 2002 Oct, 28 Suppl 1, S40 - 4
Postal survey on the use of glycerol-preserved allografts in clinical practice; Mackie D; Glycerol-preserved allografts (GPAs) are in widespread use throughout Europe in the management of burns injury . However, little is known of the clinical usage and effectiveness of GPA . To gain more insight into clinical practice, The Euro Skin Bank (ESB), which is the main provider of GPA, sent a questionnaire to 62 burn centres which had received GPA from the ESB in the last 5 years . Replies from 37 centres were received, of which 31 contained useful information . Ninety percent of correspondents used GPA regularly, although 24% of centres would prefer to use cryo-preserved allografts and 16% preferred fresh allografts . Three principal indications for GPA were identified: its use as a temporary cover on freshly excised wounds; its use as an overlay on widely expanded autografts and its use to improve the quality of the wound bed prior to autografting . Twenty-five percent of correspondents used GPA as a biological dressing for partial thickness injuries.Pre-operative topical therapy consisted of semi-closed wound treatment with frequent dressing changes and application of silver sulfadiazine (SSD) or SSD with 1% cerium nitrate . Twenty percent of correspondents also used povidone iodine.The surgical approach of early excision and wound coverage (autograft or allograft) were followed by all correspondents . Graft fixation was achieved by staples alone or in combination with fibrin glue or adhesive dressings . Post-operative care comprised frequent dressing changes . Few clinicians used topical antibacterial agents and peri-operative antibiotics were prescribed by a third of correspondents.Few complications were reported following GPA use . Around 50% of clinicians reported "occasional" wound infection; around 50% of clinicians reported "occasional" graft failure . In general, GPA appeared to perform well in clinical practice.

Proc Natl Acad Sci U S A, 2002 Oct 1, 99(20), 12628 - 32 Epub 2002 Sep 16.
Antiviral and antitumor peptides from insects; Chernysh S et al.; Insects can rapidly clear microbial infections by producing a variety of immune-induced molecules including antibacterial and/or antifungal peptides/polypeptides . In this report, we present the isolation, structural characterization, and biological properties of two variants of a group of bioactive, slightly cationic peptides, referred to as alloferons . Two peptides were isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina (Diptera), with the following amino acid sequences: HGVSGHGQHGVHG (alloferon 1) and GVSGHGQHGVHG (alloferon 2) . Although these peptides have no clear homologies with known immune response modifiers, protein database searches established some structural similarities with proteins containing amino acid stretches similar to alloferon . In vitro experiments reveal that the synthetic version of alloferon has stimulatory activities on natural killer lymphocytes, whereas in vivo trials indicate induction of IFN production in mice after treatments with synthetic alloferon . Additional in vivo experiments in mice indicate that alloferon has antiviral and antitumoral capabilities . Taken together, these results suggest that this peptide, which has immunomodulatory properties, may have therapeutic capacities . The fact that insects may produce cytokine-like materials modulating basic mechanisms for human immunity suggests a source of anti-infection and antitumoral biopharmaceuticals.

Fitoterapia, 2002 Jul, 73(4), 331 - 5
Antibacterial, antifungal activity of Harpullia petiolaris; Khan MR et al.; The methanol extracts of Harpullia petiolaris, leaves, stem and root barks and heartwoods were fractionated into petrol, dichloromethane, ethyl acetate and butanol . All fractions exhibited antibacterial activity.

Fitoterapia, 2002 Jul, 73(4), 327 - 30
Antibacterial and antifungal activities of Dracontomelon dao; Khan MR et al.; The crude methanolic extracts of the leaves, stem and root barks of Drancantomelon dao and their subsequent partitioning (petrol, dichloromethane, ethyl acetate, butanol) gave fractions which demonstrated a very good level of broad spectrum antibacterial activity . The dichloromethane and butanol fractions of the leaf were the most active . Only the leaf fractions had antifungal activity, particularly the dichloromethane and butanol.

Chem Res Toxicol, 2002 Sep, 15(9), 1142 - 9
Type II guanine oxidation photoinduced by the antibacterial fluoroquinolone Rufloxacin in isolated DNA and in 2'-deoxyguanosine; Belvedere A et al.; The role played by type I (radical) and type II (singlet oxygen) mechanisms in the Rufloxacin (RFX)-photoinduced production of 8-hydroxy-2'-deoxyguanosine in DNA has been evaluated . This fluoroquinolone drug has been shown to be able to photoinduce increased levels of some DNA base oxidation products, such as 8-OH-dGuo, that are indicative of mutagenic and carcinogenic events, with probable implications in aging processes . The relative weight of the two photosensitization mechanisms was obtained via determination of two different photoproducts of 2'-deoxyguanosine (dGuo), which are diagnostic of the two different pathways, namely, (4R)- and (4S)-4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine and 2,2-diamino-4-{(2-deoxy-beta-D-erythro-pentofuranosyl)amino}-2,5-dihydrooxazol-5-one . The observed predominance of type II reaction is in agreement with the fact that the triplet state of RFX is able to transfer with high efficiency its energy to molecular oxygen, giving rise to singlet oxygen . Photophysical measurements suggest that hydrated electrons produced by Rufloxacin photoionization react with dGuo, Thd, and DNA, whereas these biomolecules quench the RFX triplet state with low efficiency . Static quenching of Rufloxacin fluorescence indicates an interaction of this drug both with DNA and with dGuo . On the basis of these experimental data, Rufloxacin photosensitization of DNA is proposed to occur by a type II mechanism.

Stomatologiia (Mosk), 2002, 81(3), 20 - 3
{Lymphotropic antibacterial therapy for preventing inflammatory complications of mandibular fractures}; Iaremenko NV et al.; We propose a new method of preventing infectious and inflammatory complications of mandibular fractures crossing the dental arch . The method was based on regional lymphotropic administration of antibacterial drugs to the mastoid region of the temporal bone . This technique was applied in combined therapy of 51 patients . Comparative analysis with the control group revealed high efficacy of the given method . Basing upon clinical experience we worked out indications to the regional lymphotropic antibacterial therapy as a part of complex prophylaxis of posttraumatic mandible osteomyelitis.

Stomatologiia (Mosk), 2002, 81(3), 14 - 6
{Analysis of antibacterial activity of a new antiseptic for therapy of maxillofacial inflammations}; Leont'ev VK et al.; Clinical and experimental studies of polydimethyldiallylammonium chloride (PDMDAAC) experimentally validated the choice of optimal concentration and composition of this agent . The results indicate a high antiseptic activity of 1% PDMDAAC and the possibility of using it in local therapy of periodontitis and posttraumatic infection.

Expert Opin Ther Targets, 2002 Jun, 6(3), 257 - 74
Quorum sensing: an emerging target for antibacterial chemotherapy?
Williams P.
The emergence of bacterial strains exhibiting resistance to multiple antibiotic classes poses a major threat to medicine and public health . This has been compounded over the last few decades by the failure of drug discovery programmes to provide new broad spectrum antibacterials with novel modes of action . As a consequence, there is renewed interest in antibacterial targets which disrupt the capacity of pathogenic bacteria to cause infection by attenuating virulence . In this respect, one crucial feature of almost all bacterial infections is that the pathogen must attain a critical cell population density sufficient to overwhelm the host defences . Many pathogens are now known to regulate diverse physiological processes, including virulence, in a cell density dependent manner through cell-cell communication . This phenomenon, which relies upon the interaction of a diffusible signal molecule with a sensor kinase or response regulator, has become known as 'quorum sensing' . This review considers the molecular basis of quorum sensing and whether it constitutes a potential therapeutic target for the design of small molecule antagonists capable of controlling infection by attenuating adaptation to the host environment.

Expert Opin Ther Targets, 2002 Aug, 6(4), 507 - 16
Peptide ligands in antibacterial drug discovery: use as inhibitors in target validation and target-based screening; Lapan KA et al.; There is an urgent need to develop novel classes of antibiotics to counter the inexorable rise of resistant bacterial pathogens . Modern antibacterial drug discovery is focused on the identification and validation of novel protein targets that may have a suitable therapeutic index . In combination with assays for function, the advent of microbial genomics has been invaluable in identifying novel antibacterial drug targets . The major challenge in this field is the implementation of methods that validate protein targets leading to the discovery of new chemical entities . Ligand-directed drug discovery has the distinct advantage of having a concurrent analysis of both the importance of a target in the disease process and its amenability to functional modulation by small molecules . VITA is a process that enables a target-based paradigm by using peptide ligands for direct in vitro and in vivo validation of antibacterial targets and the implementation of high-throughput assays to identify novel inhibitory molecules . This process can establish sufficient levels of confidence indicating that the target is relevant to the disease process and inhibition of the target will lead to effective disease treatment.

Microbiol Immunol, 2002, 46(7), 475 - 82
Antibacterial effect of Kampo herbal formulation Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang) on Helicobacter pylori infection in mice; Yan X et al.; Because Helicobacter pylori (H . pylori) infection is a major cause of gastroduodenal diseases in humans, the eradication of H . pylori using antibiotics is very effective for the treatment of gastroduodenal diseases . However, it has recently been reported that resistance to these antibiotics is developing . In the present study, the antibacterial effect of a Kampo (traditional Japanese medicine) herbal formulation, Hochu-ekki-to (RET; Formula repletionis animalis et supletionis medii), against H . pylori was examined in vitro and in vivo . HET inhibited the growth of antibiotic-resistant strains of H . pylori as well as antibiotic-sensitive strains at a dose of 2.5 mg/ml in vitro . When 1,000 mg/kg of HET was administered orally to C57BL/6 mice for 7 days before or after inoculation with H . pylori, H . pylori in the stomach was significantly reduced in the HET-pre-treatment group compared with the control group . Furthermore, HET in combination with antibiotics completely eradicated the bacteria in mice . The expression of interferon (IFN)-gamma was induced in the gastric mucosa of the mice pre-treated with HET . There were no significant differences between the colonization of H . pylori in the control and HET treatment groups in IFN-gamma gene-deficient mice . These results suggest that the antibacterial effect of HET may be partly due to IFN-gamma induction, and that HET may be clinically useful for treatment of H . pylori infection.

Allergy Asthma Proc, 2002 Jul-Aug, 23(4), 271 - 3
Hot tub-related Mycobacterium avium intracellulare pneumonitis; Mery A et al.; Atypical Mycobacteria have been widely known to cause opportunistic infections in patients with AIDS . Recently, cases have been reported of patients colonized with atypical Mycobacteria who are only partially responsive to antibacterial treatment . It is thought that perhaps these cases represent a clinically different subset of patients that not only have underlying infection, but hypersensitivity disease as well, which may be responsive to concomitant treatment with oral corticosteroids.

Anesteziol Reanimatol, 2002 May-Jun, (3), 52 - 6
{Diprivan-EDTA--choice in favor of patients safety}; Ovechkin AM et al.; Use of propofol in anesthesiology increases with every year . On the other hand, some data indicate a risk of postoperative complications caused by bacterial contamination of propofol solution in the course of its utilization . The probability of these complications reaches 6.3% . A modified formula of propofol (diprivan-EDTA) has been developed, which is characterized by antibacterial (bacteriostatic) effect towards 20 most prevalent microorganisms . Preliminary results of clinical evaluation of diprivan-EDTA safety indicate its positive effect on the incidence of severe postoperative complications and mortality of patients in intensive care wards.

Odontostomatol Trop, 2002 Jun, 25(98), 32 - 4
{An in vitro study of the action of kola nitida on bacterial strains implicated in dental caries and periodontal diseases}; Kamagate A et al.; The Nitida Kola is a substance extracted from the kolanut . In West Africa its use by chewing is widespread among the Manding people . It's said to have tonic, stimulant and aphrodisiac characteristics and even recent studies have shown that it has antibacterial characteristics . The aim of this study is to make an estimation of the Nitida Kola's effects on different bacterial species involved in the two main oral and dental pathologies (teeth decays and periodontal illnesses) . The obtained results indicate that the kola extract is not effectual against the tried-out bacteria at regular dose used by chewing.

J Control Release, 2002 Sep 18, 83(1), 23 - 8
Water flea Moina macrocopa as a novel biocarrier of norfloxacin in aquaculture; Wiwattanapatapee R et al.; The potential of using water flea Moina macrocopa as a novel live drug carrier to freshwater aquatic animals has been evaluated . The incorporation of antibacterial, norfloxacin into Moina and subsequently into fish was quantified . The efficiency of drug incorporation into water flea depends on both drug concentration in enrichment medium and incubation time . The maximum drug level in Moina following bioencapsulation technique was reached at 4 h of exposure at drug concentrations of 10-20% (w/w) (0.70-0.90 mg/g dry weight of water flea) . Significant higher drug uptake was obtained (1.902+/-0.228 mg/g dry weight of water flea) in 2 h at the drug concentration of 40% . A marked decrease of norfloxacin percentage level upon storage of the Moina in water was observed and the survival of the Moina up to 2 h was satisfactory . It was suggested that medicated water flea should be either administered freshly enriched to fish or after short duration of storage . Following oral administration of medicated water flea to fish, the level of drug in fish body tissue increased as the number of doses increased, and the drug level was highest after a three-dose feeding . This primary food source appears to be a promising drug delivery system to aquatic animals .

Dev Comp Immunol, 2002 Oct, 26(8), 707 - 13
Comparative study on characteristics of lysozymes from the hemolymph of three lepidopteran larvae, Galleria mellonella, Bombyx mori, Agrius convolvuli; Yu KH et al.; Lysozymes were purified from the hemolymph of three immunized Lepidopteran larvae, Galleria mellonella, Bombyx mori, Agrius convolvuli to compare their physico-chemical properties and antibacterial activities with those of chicken lysozyme . Four lysozymes including the one from chicken had similar molecular masses and chromatographic behavior on reverse phase-high pressure liquid chromatography . Western blotting analysis using an antibody raised against G . mellonella revealed that lysozyme cross-reacted with two other insect lysozymes but not with commercial chicken lysozyme . Antibacterial activities of lysozymes were measured in two types of tests: radial diffusion assay and colony count assay . Our antibacterial tests revealed that all lysozymes have strong activities against Gram-positive bacteria and three insect lysozymes still retain a little potency against Gram-negative bacteria, while chicken lysozyme has no activity against Gram-negative bacteria . Taken together, we conclude three Lepidopteran lysozymes have a common distinct structure and have an antibacterial activity, which is absent in chicken lysozyme, against Gram-negative bacteria.

Cell Biol Toxicol, 2002, 18(4), 259 - 69
Ozone-mediated cytotoxicity after short-term exposure and its relation to the production of cellular metabolites (NO, H2O2); Klestadt D et al.; Alveolar macrophages secrete numerous mediators, playing an important role in host defence . Among these mediators, nitric oxide (NO) and hydrogen peroxide (H2O2) are both involved in bactericidal killing and trigger the release of other cellular metabolites . We have analyzed the effect of an atmosphere polluted with ozone (0.03-0.5 ppm v/v) on the monocytic cell line THP-1, as a model for alveolar macrophages, in vitro . NO and H2O2 were chosen to evaluate cell response to ozone . Cell injury was evaluated using lactate dehydrogenase (LDH) liberation into the medium . An exposure to 0.5 ppm ozone proved to be more toxic to the cells, than 0.1 or 0.03 ppm, evidenced by more LDH being liberated and cytotoxicity reaching values up to 64% . For all ozone concentrations, H2O2 production reached a peak value after 10-15 min of exposure, after which the concentration of extracellular H2O2 production diminished rapidly . The highest NO concentrations were measured with 0.5 ppm ozone, reaching a maximum value of 1460 nmol/L per 5 x 10(6) cells, which is 1.55 times higher than for nonexposed cells . Lower concentrations barely induced higher NO concentrations compared to nonexposed cells . The results indicate that ozone effects not only the viability of human monocytes but also the release of antibacterial and defense signaling molecules and suggest that ozone-mediated cytotoxicity may be related to the secretion of NO and H2O2.

Nature, 2002 Sep 5, 419(6902), 77 - 81
Protective role of phospholipid oxidation products in endotoxin-induced tissue damage; Bochkov VN et al.; Lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, interacts with LPS-binding protein and CD14, which present LPS to toll-like receptor 4 (refs 1, 2), which activates inflammatory gene expression through nuclear factor kappa B (NF kappa B) and mitogen-activated protein-kinase signalling . Antibacterial defence involves activation of neutrophils that generate reactive oxygen species capable of killing bacteria; therefore host lipid peroxidation occurs, initiated by enzymes such as NADPH oxidase and myeloperoxidase . Oxidized phospholipids are pro-inflammatory agonists promoting chronic inflammation in atherosclerosis; however, recent data suggest that they can inhibit expression of inflammatory adhesion molecules . Here we show that oxidized phospholipids inhibit LPS-induced but not tumour-necrosis factor-alpha-induced or interleukin-1 beta-induced NF kappa B-mediated upregulation of inflammatory genes, by blocking the interaction of LPS with LPS-binding protein and CD14 . Moreover, in LPS-injected mice, oxidized phospholipids inhibited inflammation and protected mice from lethal endotoxin shock . Thus, in severe Gram-negative bacterial infection, endogenously formed oxidized phospholipids may function as a negative feedback to blunt innate immune responses . Furthermore, identified chemical structures capable of inhibiting the effects of endotoxins such as LPS could be used for the development of new drugs for treatment of sepsis.

J Med Chem, 2002 Sep 12, 45(19), 4359 - 70
Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal binding groups; Pirrung MC et al.; UDP-3-O-{R-3-hydroxymyristoyl}-GlcNAc deacetylase (LpxC) is a zinc amidase that catalyzes the second step of lipid A biosynthesis in Gram negative bacteria . Known inhibitors of this enzyme are oxazolines incorporating a hydroxamic acid at the 4-position, which is believed to coordinate to the single essential zinc ion . A new structural class of inhibitors was designed to incorporate a more stable and more synthetically versatile isoxazoline core . The synthetic versatility of the isoxazoline allowed for a broad study of metal binding groups . Nine of 17 isoxazolines, each incorporating a different potential metal binding functional group, were found to exhibit enzyme inhibitory activity, including one that is more active than the corresponding hydroxamic acid . Additionally, a designed affinity label inhibits LpxC in a time-dependent manner.

J Med Chem, 2002 Sep 12, 45(19), 4264 - 70
N-{(2-Sulfo)-9-fluorenylmethoxycarbonyl}(3)-gentamicin C(1) is a long-acting prodrug derivative; Shechter Y et al.; Most low-molecular-weight drugs are short-lived species in the circulatory system, being rapidly eliminated by glomerular filtration in the kidney . However, binding to human serum albumin (HSA) can slow clearance and prolong lifetime profile in vivo . In this study, we have engineered a gentamicin derivative with affinity to albumin by linking three (2-sulfo)-9-fluorenylmethoxycarbonyl (FMS) to three amino groups of gentamicin C(1) . FMS(3)-gentamicin associates with HSA with a K(a) value of (1.31 +/- 0.2) x 10(5) M(-1) . It has less than 1% the antibacterial potency of native gentamicin . Upon incubation at pH 8.5 and 37 degrees C, the FMS moieties from FMS(3)-gentamicin undergo slow hydrolysis (t(1/2) = 8.0 +/- 0.2 h), leading to a linear regeneration of the antibacterial potency with a t(1/2) value of 11 +/- 0.7 h . FMS(3)-gentamicin is a long-lived species in the rat circulatory system . Following a single subcutaneous or intravenous administration, it maintains a prolonged pharmacokinetic profile with a peak and a "through" concentration of immuno/antibacterial active gentamicin exceeding 4-5 times the duration obtained by administered native gentamicin . To sum up, an approach aimed at elongating the lifetime of low-molecular-weight drugs in vivo has been examined here with gentamicin . Two to three FMS per mole of compound are to be introduced to obtain an albumin associating affinity of K(d) = 7.6-9.2 microM and, hence, to significantly extend the drug's lifetime in situ following administration . By use of this technology, the loss of pharmacological potency with derivatization is of no consequence, since FMS moieties are hydrolyzed and activity is generated at physiological conditions.

Zhongguo Zhong Yao Za Zhi, 2000 Feb, 25(2), 107 - 10
{Studies on antitussive, antiasthmatic, expectorant and anti-inflammatory effects of Jin'an kechuan granules}; Chen GL et al.; OBJECTIVE: To study the pharmacologic effect of Jin'an Kechuan granules . METHOD: Routine antitussive, antiasthmatic and expectorant methods were used . RESULT: Jin'an Kechuan granules in the doses of 16, 8, 4 g.kg-1 ig could significantly decrease the frequency of cough caused by ammonia water in mice, and increase the secretion of phenol red from mouse tracheas in a dose-dependent manner . The granules also help increase the threshold voltage to induce cats to cough, prolong the latent period of asthma induced by histamine and acetylcholine mixture, and antagonize the contraction of isolated trachea strips induced by histamine and acetylcholine in guinea pigs . Jin'an Kechuan granules had inhibitory effects on common bacteria in the respiratory tract as well as on the swelling of acute inflammation in mice and rats . CONCLUSION: Jin'an Kechuan granules have antitussive, antiasthmatic, expectorant and anti-inflammatory, antibacterial effects.

Arch Pharm (Weinheim), 2002 May, 335(5), 200 - 6
Synthesis and antibacterial activity of 1beta-methylcarbapenems having a 2, 2-disubstituted-1, 3-diazabicyclo{3.3.0}octan-4-one moiety and related compounds . Part III; Oh CH et al.; The synthesis of new series of 1beta-methylcarbapenems having a 2, 2-disubstituted-1, 3-diazabicyclo{3.3.0}octan- and -{4.3.0}nonan-4-one moiety is described.Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of the substituent of the bicyclic ring was investigated . A particular compound (16 f) bearing a hydroxymethyl group showed the most potent antibacterial activity and the compound (17 a) with a 1, 3-diazabicyclo{4.3.0}nonane moiety exhibited excellent stability against renal dehydropeptidase-I (DHP-I) to Meropenem.

Biomed Chromatogr, 2002 Aug, 16(5), 356 - 60
Liquid chromatographic resolution of gemifloxacin mesylate on a chiral stationary phase derived from crown ether; Hyun MH et al.; A new racemic fluoroquinolone antibacterial agent, gemifloxacin mesylate, has been successfully resolved on a chiral stationary phase (CSP) derived from (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid . Compared to the Crownpak CR(+) column, the CSP used in this study was more effective for the resolution of racemic gemifloxacin mesylate, especially in terms of analytical time . The resolution of gemifloxacin mesylate enantiomers on the CSP was found to be dependent on the type and content of organic and acidic modifiers in the aqueous mobile phase and the column temperature .

Eur J Pharmacol, 2002 Aug 30, 450(3), 277 - 289
Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects; Culic O et al.; Effects on human neutrophils and circulating inflammatory mediators were studied in 12 volunteers who received azithromycin (500 mg/day, p.o.) for 3 days . Blood was taken 1 h before treatment, 2.5, 24 h and 28 days after the last dose . An initial neutrophil degranulating effect of azithromycin was reflected in rapid decreases in azurophilic granule enzyme activities in cells and corresponding increases in serum . The oxidative response to a particulate stimulus was also acutely enhanced . These actions were associated with high plasma and neutrophil drug concentrations . A continuous fall in chemokine and interleukin-6 serum concentrations, within the non-pathological range, accompanied a delayed down-regulation of the oxidative burst and an increase in apoptosis of neutrophils up to 28 days after the last azithromycin dose . Neutrophils isolated from blood at this time point still contained detectable drug concentrations . Acute neutrophil stimulation could facilitate antibacterial effects of azithromycin, while delayed, potentially anti-inflammatory activity may curtail deleterious inflammation.

FEMS Microbiol Lett, 2002 Aug 27, 214(1), 133 - 6
Transformation of cinoxacin by Beauveria bassiana; Parshikov IA et al.; The ability of the fungus Beauveria bassiana ATCC 7159 to transform the antibacterial agent cinoxacin was investigated . Cultures in sucrose-peptone broth were dosed with cinoxacin, grown for 20 days, and then extracted with ethyl acetate . Two metabolites were detected and purified by high-performance liquid chromatography . The major metabolite was identified by mass and proton nuclear magnetic resonance spectra as 1-ethyl-1,4-dihydro-3-(hydroxymethyl){1,3}dioxolo{4,5-g}cinnolin-4-one and the minor metabolite was identified as 1-ethyl-1,4-dihydro-6,7-dihydroxy-3-(hydroxymethyl)cinnolin-4-one . B . bassiana also reduced quinoline-3-carboxylic acid to 3-(hydroxymethyl)quinoline.

J Clin Microbiol, 2002 Sep, 40(9), 3146 - 54
Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens; Lorenzo-Pajuelo B et al.; Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial . A case of cavitary pneumonia caused by B . bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated . B . bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter . Unlike previous work reporting the involvement of B . bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate . Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele . Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point . Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable . We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts.

Org Lett, 2002 Sep 5, 4(18), 3039 - 42
Nagahamide A, an antibacterial depsipeptide from the marine sponge Theonella swinhoei; Okada Y et al.; {structure: see text} An antibacterial depsipeptide, nagahamide A (1), has been isolated from the marine sponge Theonella swinhoei . Its structure was determined on the basis of spectral and chemical methods . Absolute configuration of amino acid residues was determined by Marfey's analysis, and relative stereochemistry of the polyketide moiety was assigned by comparison of NMR data with those of a model compound.

Fish Shellfish Immunol, 2002 Jul, 13(1), 69 - 83
Gene expression in haemocytes of kuruma prawn, Penaeus japonicus, in response to infection with WSSV by EST approach; Rojtinnakorn J et al.; Gene expression in haemocytes of the kuruma prawn (Penaeus japonicus) was investigated using an expressed sequence tag (EST) approach . Partial nucleotide sequences of cDNA library clones constructed from normal and white spot syndrome virus (WSSV)--infected P . japonicus haemocytes were determined . Of 635 clones obtained from the normal library, 284 (44.7%) significantly matched sequences in GenBank, and of 370 clones obtained from WSSV-infected library, 174 (47.0%) significantly matched sequences in the database . One hundred fifty-two deduced proteins were newly identified . Of these, 28 types were involved in biodefence . For the prophenoloxidase system, there are prophenoloxidase, coagulation factor G-beta chain precursor, factor D, Masquarade-like protease, transglutaminase (TGase), clottable protein and eight types of protease inhibitors (two types of antileukoproteinase, alpha-2-macroglobulin, chelonianin, elastase inhibitor, two types of Kazal inhibitor and Kunitz-type inhibitor) . For antibacterial peptides, there are bactinecin 11, penaeidin-2 precursor and lysozyme c type . The others defence-related proteins are basophil leukocyte interleukin-3-regulated protein, natural killer enhancing factor (NK-EF), integral membrane protein (CD34+), ESM-1, Notch homologue and Drac homologue . For the adhesion proteins, there are beta-integrin, cell adhesion molecule (CAM) and three types of collagens . All ESTs representing protease inhibitors and tumour-related proteins were found only in the WSSV-infected library . Those encoding for apoptotic peptides were expressed at high levels in infected library . The putative defence proteins accounted for 2.7% of total ESTs in a normal shrimp library and 15.7% of the total ESTs in an infected library.

Jpn J Antibiot, 2002 Jun, 55(3), 270 - 80
{Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin mesilate, a new quinolone antibacterial agent for intravenous use: convulsions in mice after intravenous or intracerebroventricular administration}; Fukuda H et al.; Convulsant activity of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, in combination with nonsteroidal anti-inflammatory drug (NSAID) was investigated in mice after intravenous or intracerebroventricular administration . Following results were obtained . 1 . In combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg . Reference quinolones induced convulsions at the following intravenous doses: Enoxacin (ENX), 3.13 mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX), 6.25 mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX) and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200 mg/kg . 2 . PZFX mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice after oral administration of any of 14 kinds of NSAIDs . It induced convulsions at 200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did not with the other 13 kinds of NSAIDs . 3 . Convulsion-inducing dose of PZFX mesilate after intracerebroventricular administration was 100 mg/body, which was higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX, levofloxacin, ofloxacin, FLRX and SPFX) and beta-lactam antibiotics (penicillin G, cefazoline, imipenem/cilastatin and panipenem/betamipron) . In addition, concurrent dosing of BPAA (1 microgram/body) did not reduce the convulsion-inducing dose of PZFX mesilate . These results suggest that PZFX mesilate has remarkably weak convulsant activity.

BioDrugs, 2002, 16(4), 303 - 11; discussion 313-4
Anakinra; Cvetkovic RS et al.; Anakinra, a recombinant human interleukin-1 (IL-1) receptor antagonist, is the first biological agent approved to block the pro-inflammatory effects of IL-1 in patients with rheumatoid arthritis . In a double-blind, randomised trial in 472 patients with active, severe or very severe rheumatoid arthritis, recipients of subcutaneous anakinra 150 mg/day achieved higher response rates {assessed using the American College of Rheumatology (ACR) composite score} and accumulated more mean productivity days after 6 months than placebo recipients . However, the response rates and accumulated productivity days of patients receiving subcutaneous anakinra 30 or 75 mg/day for 6 months were similar to those of placebo . With respect to the total Genant radiographic scores, the same study showed that all anakinra treatment regimens slowed disease progression after 6 months to a greater extent than placebo . In double-blind, randomised trials in patients with rheumatoid arthritis, combined treatment with anakinra and methotrexate was associated with higher ACR 20, 50 and 70 response rates than with methotrexate alone . Anakinra, used alone or in combination with methotrexate, was generally well tolerated, with the most frequent adverse event being a mild injection-site reaction of transient duration . Infections requiring antibacterial therapy or hospitalisation occurred more commonly in anakinra recipients than in placebo recipients, but were a rare cause for discontinuation of anakinra therapy (approximately 1%) in clinical trials.

J Immunol, 2002 Sep 1, 169(5), 2536 - 44
IL-18 levels and the outcome of innate immune response to lipopolysaccharide: importance of a positive feedback loop with caspase-1 in IL-18 expression; Joshi VD et al.; LPS enhanced antibacterial host defenses (ABHD) when given at low (75 micro g) doses (16 of 19 mice survived 3x LD(50) Escherichia coli vs 3 of 19 LPS-naive mice; p = 0.0001), but induced lethal inflammation at high (500 micro g) doses (5 of 5 died) . Differences in the cytokine profiles induced by these LPS doses may provide insight into the mechanism(s) of transition from beneficial to lethal LPS responses . The 75 micro g LPS induced 5.9 +/- 0.9 ng/ml serum IL-18 at 8 h, which decreased to 2.3 +/- 0.4 ng/ml by 24 h, whereas 500 micro g LPS induced 11.1 +/- 1.6 ng/ml serum IL-18 levels at 8 h, which increased until death . Compared with 75 micro g, higher but sublethal (150 micro g) doses of LPS induced greater serum IL-18 levels and less effectively induced ABHD (3 of 8 survived) . Reduction of serum IL-18 with neutralizing Ab improved the ABHD induced by 150 micro g, but reduced that produced by 75 micro g LPS, suggesting an optimal range of serum IL-18 level was essential for efficient ABHD . Increased expression of caspase-1 mRNA in response to the higher IL-18 levels induced at the 150 and 500 micro g, but not at the 75 micro g doses of LPS may represent a positive feedback regulatory loop leading to sustained serum IL-18 levels . We conclude that the regulation of serum IL-18 expression is critical to the outcome of innate immune responses to LPS.

Protein Sci, 2002 Sep, 11(9), 2158 - 67
Plasticity in structure and interactions is critical for the action of indolicidin, an antibacterial peptide of innate immune origin; Nagpal S et al.; The comparative analysis of two cationic antibacterial peptides of the cathelicidin family-indolicidin and tritrypticin-enabled addressing the structural features critical for the mechanism of indolicidin activity . Functional behavior of retro-indolicidin was found to be identical to that of native indolicidin . It is apparent that the gross conformational propensities associated with retro-peptides resemble those of the native sequences, suggesting that native and retro-peptides can have similar structures . Both the native and the retro-indolicidin show identical affinities while binding to endotoxin, the initial event associated with the antibacterial activity of cationic peptide antibiotics . The indolicidin-endotoxin binding was modeled by docking the indolicidin molecule in the endotoxin structure . The conformational flexibility associated with the indolicidin residues, as well as that of the fatty acid chains of endotoxin combined with the relatively strong structural interactions, such as ionic and hydrophobic, provide the basis for the endotoxin-peptide recognition . Thus, the key feature of the recognition between the cationic antibacterial peptides and endotoxin is the plasticity of molecular interactions, which may have been designed for the purpose of maintaining activity against a broad range of organisms, a hallmark of primitive host defense.

J Med Chem, 2002 Aug 29, 45(18), 3953 - 62
Synthesis of conformationally constrained analogues of linezolid: structure-activity relationship (SAR) studies on selected novel tricyclic oxazolidinones; Selvakumar N et al.; In an effort to discover potent antibacterials based on the entropically favored "bioactive conformation" approach, we have designed and synthesized a series of novel tricyclic molecules mimicking the conformationally constrained structure of the oxazolidinone antibacterial, Linezolid 1 . The structure 3 obtained by this approach was synthesized and found to be moderately active against a panel of Gram-positive organisms tested . Further introduction of a fluorine atom in the aromatic ring of compound 3 as in Linezolid resulted in some excellent compounds possessing potent antibacterial activity . The thus obtained lead molecule 16 was further fine-tuned by structure-activity relationship studies on the amide functionality leading to a number of novel tricyclic oxazolidinone derivatives . Some particularly interesting compounds include the thioamides 36 and 37, thiocarbamate 41, and thiourea 45 . The in vitro activity results of amide homologues of 16 (compounds 25-30) revealed that compounds up to four carbon atoms on the amide nitrogen retain the activity . In general, thioamides and thiocarbamates are more potent when compared to the corresponding amides and carbamates.

Pol J Vet Sci, 2002, 5(2), 51 - 6
Characterization of Escherichia coli strains associated with canine pyometra; Wernicki A et al.; The purpose of this study was to characterize E . coli isolates from canine pyometra which were isolated in pure culture . The E . coli strains were obtained in 128 cases, from 143 animals which were submitted to ovariohisterectomy . Biochemical analysis of all strains examined was possible on separation of 10 primary biotypes . The majority of the strains (87.5%) belonged to biotype 9, 1, 13 and 15 . Dulcitol was fermented by 93% of all isolates . Haemolysin and colicin production was found in 53.9% and 26.6% of the strains, respectively . Approximately 37% of strains expressed resistance to two or more antibacterial agents . No plasmid was detected in 4.6% of the isolates . Plasmid profiles of all plasmid-containing isolates revealed plasmid bands corresponding to molecular weight ranging from 1 kb to 160 kb . Many of the strains examined had a single plasmid of 110 kb (46.1%), or two plasmids 110:65 kb (18.8%) . Both plasmids appearing alone or in combination with other plasmids were detected in 90.1% of isolates with plasmid content . It was established that among haemolytic, colicinogenic and motile strains, the presence of both plasmids was 91.3, 94.1 and 91.4%, respectively . The appearance of both plasmids among dulcitol-positive and raffinose-negative strains was estimated at 88.2 and 88.3%, respectively . In a group of colicinogenic strains the presence of a single plasmid of molecular weight 110 kb was estimated at 5.9% . When both plasmids were present (profile 110:65), the percentage of these strains was 70.6%.

Clin Rheumatol, 2002 Aug, 21(4), 330 - 4
Seronegative Lyme arthritis caused by Borrelia garinii; Dejmkova H et al.; A case of a female patient suffering from Lyme arthritis (LA) without elevated antibody levels to Borrelia burgdorferi sensu lato is reported . Seronegative Lyme arthritis was diagnosed based on the classic clinical manifestations and DNA-detected Borrelia garinii in blood and synovial fluid of the patient, after all other possible causes of the disease had been ruled out . The disease was resistant to the first treatment with antibacterial agents . Six months after the therapy, arthritis still persisted and DNA of Borrelia garinii was repeatedly detected in the synovial fluid and the tissue of the patient . At the same time, antigens or parts of spirochaetes were detected by electron microscopy in the synovial fluid, the tissue and the blood of the patient . The patient was then repeatedly treated by antibiotics and synovectomy has been performed.

Curr Cancer Drug Targets, 2002 Mar, 2(1), 55 - 75
Sulfonamides and sulfonylated derivatives as anticancer agents; Casini A et al.; The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others . A host of structurally novel sulfonamide derivatives have recently been reported to show substantial antitumor activity in vitro and/or in vivo . Although they have a common chemical motif of aromatic/heterocyclic sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle arrest in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others . Some of these compounds selected via elaborate preclinical screenings or obtained based on computer-aided drug design, are currently being evaluated in clinical trials . This review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed ultimately as effective tumor cell growth inhibitors, or for the treatment of different types of cancer.

Ceska Slov Farm, 2002 Jul, 51(4), 168 - 72
{Pharmaceutical importance of Allium sativum L . 3 . Antibacterial effects on Helicobacter pylori}; Sovova M et al.; The paper points out the risk factors which render possible the outbreak of infections due to the bacterium Helicobacter pylori manifesting itself as chronic gastritis . In a great extent it results in peptic and duodenal ulcers and can even lead to the development of adenocarcinoma and lymphoma of the stomach . The paper mentions the efficacy of previous and contemporary therapy . Possible use of garlic in the treatment of these infections is intensively investigated . At present mainly in vitro experiments showing promising results are performed . A minimum of experiments carried out with out-patients produced negative results . As they do not fulfill the parameters of clinical experiments, this question still remains open.

Antimicrob Agents Chemother, 2002 Sep, 46(9), 2735 - 46
Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone action; Strumberg D et al.; We report that point mutations causing alteration of the fourth alpha-helix (alpha4-helix) of the CAP homology domain of eukaryotic (Saccharomyces cerevisiae) type II topoisomerases (Ser(740)Trp, Gln(743)Pro, and Thr(744)Pro) change the selection of type II topoisomerase-mediated DNA cleavage sites promoted by Ca(2+) or produced by etoposide, the fluoroquinolone CP-115,953, or mitoxantrone . By contrast, Thr(744)Ala substitution had minimal effect on Ca(2+)- and drug-stimulated DNA cleavage sites, indicating the selectivity of single amino acid substitutions within the alpha4-helix on type II topoisomerase-mediated DNA cleavage . The equivalent mutation in the gene for Escherichia coli gyrase causing Ser(83)Trp also changed the DNA cleavage pattern generated by Ca(2+) or quinolones . Finally, Thr(744)Pro substitution in the yeast type II topoisomerase rendered the enzyme sensitive to antibacterial quinolones . This study shows that the alpha4-helix within the conserved CAP homology domain of type II topoisomerases is critical for selecting the sites of DNA cleavage . It also demonstrates that selective amino acid residues in the alpha4-helix are important in determining the activity and possibly the binding of quinolones to the topoisomerase II-DNA complexes.

Bioorg Med Chem Lett, 2002 Sep 16, 12(18), 2591 - 4
DNA binding ligands with excellent antibiotic potency against drug-resistant gram-positive bacteria; Burli RW et al.; An efficient synthesis of DNA binding molecules consisting of four heterocyclic carboxamide units and various substituents at both termini is described . The minor-groove binding ligands showed excellent activity against a broad range of Gram-positive bacteria; no cross-resistance to known antibacterial drugs was observed.

Aliment Pharmacol Ther, 2002 Aug, 16(8), 1481 - 90
Effects of ABT-229, a motilin agonist, on acid reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease; Netzer P et al.; AIM: The effect of ABT-229, a new macrolide with no antibacterial activity, on gastro-oesophageal reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease was investigated . METHODS: Twenty-one patients were treated with a placebo and ABT-229 (2.5, 5 or 10 mg b.d.) in a randomized, incomplete crossover study design . Ambulatory 24-h pH manometry was performed and gastric emptying was assessed by the 13C-octanoic acid breath test on the seventh day of treatment . RESULTS: A significant decrease was found in the mean (+/- s.e.) percentage of reflux time (intra-oesophageal pH < 4) for ABT-229 5 mg b.d . and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo . For ABT-229 5 mg, it was 8.5 +/- 0.5% vs . 10.7 +/- 0.7% (P < 0.038) and, for ABT-229 10 mg, it was 6.6 +/- 0.5% vs . 8.4 +/- 0.5% (P < 0.019) . There were no significant differences in any of the analysed manometric parameters . In addition, the gastric half-emptying time for all doses of ABT-229 did not differ significantly from that after placebo . CONCLUSIONS: ABT-229 is able to reduce slightly, but significantly, acid reflux in patients with gastro-oesophageal reflux disease . This effect does not appear to be due to a measurable improvement in oesophageal motility or gastric emptying.

J Food Prot, 2002 Aug, 65(8), 1221 - 6
Consumer acceptance of fresh-cut iceberg lettuce treated with 2% hydrogen peroxide and mild heat; McWatters LH et al.; An antibacterial treatment consisting of 2% hydrogen peroxide at 50 degrees C for 60 s was evaluated for its effects on the sensory quality of fresh-cut iceberg lettuce . Treated lettuce was packaged in polyethylene film by a protocol used in the fresh-cut produce industry and then stored along with untreated controls for 3, 10, and 15 days at 5 degrees C . Gas chromatographic analysis confirmed that the desired initial volume (approximately 6 liters) and oxygen gas content (approximately 10%) were maintained during storage . Consumers from the local community who were the primary shoppers for their households and who purchased and ate lettuce regularly evaluated the appearance, color, aroma, flavor, and texture of the lettuce and their overall liking of the lettuce . Forty consumers were recruited to evaluate processing replication 1 on 26 April, and another 40 were chosen to evaluate processing replication 2 on 3 May . Because replication differences were observed in instrumental color measurements and in mean sensory ratings, replications were not pooled for the two test dates . Lettuce purchased for processing replication 2 was considerably greener than that used in replication 1 . Overall, the antibacterial treatment was more effective than the control treatment in maintaining sensory quality over 15 days of storage, provided that the lettuce was initially intensely green . Three-fourths of the participants indicated that they would be willing to buy precut packaged lettuce that had already been treated at the packinghouse or processing plant with an antibacterial solution, and of these participants, 62.5% indicated that they would be willing to pay 5 to 10 cents more per bag.

Klin Med (Mosk), 2002, 80(7), 54 - 9
{Systemic lupus erythematosus and sepsis}; Volkova SIu et al.; Features of clinical course and symptoms of systemic lupus erythematosus are analysed in SLE patients with sepsis (n = 11) which was defined as a systemic inflammatory reaction to verified infection with polyorganic insufficiency . Statistic analysis was made with the program MS Excel 7.0 . Sepsis, activating factors, antibacterial and immunosuppressive therapy are discussed . Outcomes are described . Differential diagnosis with paraneoplastic syndrome is illustrated.

Am J Clin Dermatol, 2002, 3(7), 489 - 96
The management of rosacea; Rebora A; Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment . Flushing is better prevented rather than treated, and its etiology investigated . Beta-blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea . Currently, clonidine is the only drug available for the treatment of flushing . Treatment for erythrosis includes topical and systemic therapies . Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema . The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea . However, this role is still being debated . Eradication of H . pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks {omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)} . Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases . Both systemic and topical remedies may be used to treat the papulopustules of rosacea . Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel . The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not . Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D . folliculorum . Oral or topical ivermectin may also be useful in such cases . Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials . Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures . Decortication and various types of lasers can also be used . Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.

J AOAC Int, 2002 Jul-Aug, 85(4), 848 - 52
Determination of sulfonamide residues in eggs by liquid chromatography; Furusawa N; A method was developed for determining residual sulfonamide antibacterials such as sulfamethazine (SMZ), sulfamonomethoxine (SMM), sulfadimethoxine (SDM), and sulfaquinoxaline (SQ) in eggs using liquid chromatography with a photodiode array detector . The spiked and blank samples were cleaned up by using an Ultrafree-MC/PL centrifugal ultrafiltration unit . A Mightysil RP-4 GP column and a mobile phase of 28% (v/v) ethanol-H2O with a photodiode array detector were used for the determination . Average recoveries from eggs spiked with each drug at 0.1, 0.2, 0.4, and 1.0 ppm were > or = 80.9%, with relative standard deviations between 1.3 and 4.7% . The limits of quantitation were 0.060 ppm for SMZ, 0.045 for SMM, 0.044 for SDM, and 0.093 for SQ . The analysis of one sample required < 30 min and < 5 mL ethanol as solvent.

Biochim Biophys Acta, 2002 Aug 31, 1564(2), 359 - 64
Antibacterial peptide pleurocidin forms ion channels in planar lipid bilayers; Saint N et al.; Pleurocidin, a 25-residue alpha helical cationic peptide, isolated from skin mucous secretions of the winter flounder, displays a strong anti-microbial activity and appears to play a role in innate host defence . This peptide would be responsible for pore formation in the membrane of bacteria leading to lysis and therefore death . In this study, we investigated the behaviour of pleurocidin in different planar lipid bilayers to determine its mechanism of membrane permeabilisation . Macroscopic conductance experiments showed that pleurocidin did not display a pore-forming activity in neutral phosphatidylcholine/phosphatidylethanolamine (PC/PE) lipid bilayers . However, in 7:3:1 PC/PE/phosphatidylserine (PS) lipid bilayers, pleurocidin showed reproducible I/V curves at different peptide concentrations . This activity is confirmed by single-channel experiments since well-defined ion channels were obtained if the lipid mixture was containing an anionic lipid (PS) . The ion channel characteristics such as-no voltage dependence, only one unitary conductance, linear relation ship current-voltage-, are not in favour of the membrane permeabilisation according to the barrel model but rather by the toroidal pore formation.

Anticancer Res, 2002 Jul-Aug, 22(4), 1959 - 64
The antibacterial drug taurolidine induces apoptosis by a mitochondrial cytochrome c-dependent mechanism; Han Z et al.; The antibacterial agent taurolidine (TRD) has been used as a lavage antibiotic to prevent development of peritonitis in patients after surgery . We recently showed that TRD induced growth arrest and apoptosis of a variety of cultured cell lines derived from human solid tumors and also significantly inhibited the growth of human ovarian tumors in a mouse model . In this report, we present data to show that TRD, at concentrations below the doses that are used to treat patients in the clinic, induces apoptosis of human leukemia HL-60 cells by a mitochondrial cytochrome c-dependent pathway.

Curr Med Chem, 2002 Sep, 9(18), 1655 - 65
Acridine derivatives as chemotherapeutic agents; Denny WA; Acridine derivatives are one of the oldest classes of bioactives, widely used as antibacterial and antiprotozoal agents . Some work in these areas continues, but recent research has focused mainly on their use as anticancer drugs, because of the ability of the acridine chromophore to intercalate DNA and inhibit topoisomerase enzymes.

Prog Lipid Res, 2002 Nov, 41(6), 437 - 56
New advances in the chemistry of methoxylated lipids; Carballeira NM; Methoxylated lipids have been reviewed emphasizing the alkylglycerol ethers and fatty acids bearing the methoxy group in the alkyl chain . The literature on methoxylated lipids and their derivatives has been divided into four main groups, namely 2-methoxylated alkyl glycerols, omega-methoxylated fatty acids, mid-chain methoxylated fatty acids, and alpha-methoxylated fatty acids . The natural occurrence, biological activity, and synthesis of this interesting group of lipids are discussed . Most of these compounds have been isolated from either bacterial or marine sources, but others are mainly of synthetic origin . Among the interesting biological activities displayed by these compounds the most important are antibacterial, antifungal, antitumor, and antiviral.

Nat Prod Lett, 2002 Aug, 16(4), 283 - 90
Isolation and structure elucidation of three glycosides and a long chain alcohol from Polianthes tuberosa Linn; Kha KM et al.; Three glycosides and a long chain alcohol were isolated from the bulbs of Polianthes tuberosa, these were identified as 3,29-dihydroxystigmast-5-ene-3-O-beta-D-galactopyranoside (1), ethyl beta-D-galactopyranoside (2), ethyl-alpha-D-galactopyranoside (3), and 1-tricosanol (4) . The structures were determined by extensive spectroscopic and chemical methods . All four isolated compounds were screened for their cytotoxicity, antibacterial and antifungal activities, none of the compounds showed any significant activity.

Pharmazie, 2002 Jul, 57(7), 448 - 52
Syntheses and reactions of some new 2-arylidene-4-(biphenyl-4-yl)-but-3-en-4-olides with a study of their biological activity; Khan MS et al.; 2-Arylidene-4-(biphenyl-4-yl)but-3-en-4-olides also known as 3-arylidene-5-(biphenyl-4-yl)-2(3H)-furanones were prepared from 3-(4-phenyl-benzoyl) propionic acid and aromatic aldehydes . Some of the selected butenolides were reacted with ammonia and benzylamine to give corresponding pyrrolones and N-benzylpyrrolones respectively, which were characterized on the basis of 1H NMR and MS data and elemental analysis results . These compounds were tested for anti-inflammatory and anti-microbial actions . A few compounds were found to have promising anti-inflammatory activity while a fair in number of compounds showed a good anti-fungal activity and a promising antibacterial activity against S . aureus and E . coli.

Fitoterapia, 2002 Aug, 73(5), 439 - 41
Antibacterial activity of the essential oil from Aristolochia indica; Shafi PM et al.; The essential oil of Aristolochia indica, containing beta-caryophyllene and alpha-humulene as major constituents, was found to show a moderate antibacterial activity.

Fitoterapia, 2002 Aug, 73(5), 414 - 6
Antibacterial activity of Syzygium cumini and Syzygium travancoricum leaf essential oils; Shafi PM et al.; The leaf essential oils of Syzygium cumini and Syzygium travancoricum were tested for their antibacterial property . The activity of S . cumini essential oil was found to be good, while that of S . travancoricum was moderate.

J Altern Complement Med, 2002 Jun, 8(3), 325 - 32
The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I . An in vitro agar assay; Reagor L et al.; OBJECTIVES: Grapefruit-seed extract (GSE) Citricidal has, in recent reports, been reported to be successful in combating a variety of common infectious agents . In our study, drops of concentrated grapefruit-seed extract were tested for antibacterial properties against a number of gram-positive and gram-negative organisms . DESIGN: Sixty-seven (67) distinct biotypes were tested for their susceptibilities to the GSE as well as to 5 other topical antibacterials (Silvadene, Sulfamylon, Bactroban, Nitrofurazone, and Silvadene, Nystatin) . Wells were punched into Mueller-Hinton agar plates, which were then inoculated with the organism to be tested; each well was then inoculated with one of the antibacterial agents . After an overnight incubation period, the plates were checked for zones of bacterial susceptibility around the individual wells, with a measured susceptibility zone diameter of 10 mm or more considered a positive result . RESULTS: The GSE was consistently antibacterial against all of the biotypes tested, with susceptibility zone diameters equal to or greater than 15 mm in each case . CONCLUSIONS: Our preliminary data thus suggest an antibacterial characteristic to GSE that is comparable to that of proven topical antibacterials . Although the GSE appeared to have a somewhat greater inhibitory effect on gram-positive organisms than on gram-negative organisms, its comparative effectiveness against a wide range of bacterial biotypes is significant.

Clin Exp Pharmacol Physiol, 2002 Sep, 29(9), 741 - 53
Ion channel formation and membrane-linked pathologies of misfolded hydrophobic proteins: the role of dangerous unchaperoned molecules; Kourie JI et al.; 1 . Protein-membrane interaction includes the interaction of proteins with intrinsic receptors and ion transport pathways and with membrane lipids . Several hypothetical interaction models have been reported for peptide-induced membrane destabilization, including hydrophobic clustering, electrostatic interaction, electrostatic followed by hydrophobic interaction, wedge x type incorporation and hydrophobic mismatch . 2 . The present review focuses on the hypothesis of protein interaction with lipid membranes of those unchaperoned positively charged and misfolded proteins that have hydrophobic regions . We advance the hypothesis that protein misfolding that leads to the exposure of hydrophobic regions of proteins renders them potentially cytotoxic . Such proteins include prion, amyloid beta protein (AbetaP), amylin, calcitonin, serum amyloid and C-type natriuretic peptides . These proteins have the ability to interact with lipid membranes, thereby inducing membrane damage and cell malfunction . 3 . We propose that the most significant mechanism of membrane damage induced by hydrophobic misfolded proteins is mediated via the formation of ion channels . The hydrophobicity based toxicity of several proteins linked to neurodegenerative pathologies is similar to those observed for antibacterial toxins and viral proteins . 4 . It is hypothesized that the membrane damage induced by amyloids, antibacterial toxins and viral proteins represents a common mechanism for cell malfunction, which underlies the associated pathologies and cytotoxicity of such proteins.

Pharmacol Ther, 2002 Jul, 95(1), 1 - 20
Rational identification of new antibacterial drug targets that are essential for viability using a genomics-based approach; Chalker AF et al.; In the last two decades, the search for completely novel antibacterial agents has acquired a new sense of urgency due to the remarkable rise of antibiotic resistance among key bacterial pathogens . More recently, the advent of bacterial genomics has provided investigators with the data and bioinformatic tools to rationally identify novel antibacterial targets and the genome-scaled methodologies to validate them . Only 6 years have elapsed since the publication of the first complete bacterial genome sequence, but more than 50 complete microbial genome sequences are now available . This review will discuss the advantages and limitations of the existing bacterial genome dataset for the rational identification of novel antibacterial targets . Since the ability to rapidly identify essential genes where loss of function is coincident with loss of viability is the most important task of genomics-based target validation, essentiality testing methodologies (in which molecular genetic techniques are used to determine whether or not a gene product is required for viability of the parent cell) will be surveyed and their amenability to genome-scaled analysis assessed . Finally, we will discuss the impact of bacterial genomics to date on the development of novel and effective antibiotics.

Clin Pharmacokinet, 2002, 41(10), 741 - 50
Clinical role of protein binding of quinolones; Bergogne-Berezin E; Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness . Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibacterial classes, showing that wide variations of the degree of protein binding occur even in the same antibacterial class, as with beta-lactams . As the understanding of protein binding grew, the complexity of the binding system was increasingly perceived and its dynamic character described . Studies of protein binding of the fluoroquinolones have shown that the great majority of these drugs exhibit low protein binding, ranging from approximately 20 to 40% in plasma, and that they are bound predominantly to albumin . The potential role in pharmacokinetics-pharmacodynamics of binding of fluoroquinolones to plasma, tissue and intracellular proteins has been analysed, but it has not been established that protein binding has any significant direct or indirect impact on therapeutic effectiveness . Regarding the factors influencing the tissue distribution of antibacterials, physicochemical characteristics and the small molecular size of fluoroquinolones permit a rapid penetration into extravascular sites and intracellularly, with a rapid equilibrium being established between intravascular and extravascular compartments . The high concentrations of these drugs achieved in tissues, body fluids and intracellularly, in addition to their wide antibacterial spectrum, mean that fluoroquinolones have therapeutic effectiveness in a large variety of infections . The tolerability of quinolones has generally been reported as good, based upon long experience in using pefloxacin, ciprofloxacin and ofloxacin in clinical practice . Among more recently developed molecules, good tolerability has been reported for levofloxacin, moxifloxacin and gatifloxacin, but certain other new compounds have been removed from the market because of renal, hepatic and cardiac toxicity . To what extent the protein binding of fluoroquinolones can play a role in their tolerability is unclear . In terms of drug-drug interactions, the role of protein binding is questionable: several drug combinations can be responsible for toxicity, such as with beta-lactams, metronidazole, theophylline, nonsteroidal anti-inflammatory agents or a series of drugs used for cardiac diseases, but protein binding does not seem to be involved in these interactions . In conclusion, protein binding of fluoroquinolones appears to be a complex phenomenon, but has no clear role in therapeutic effectiveness or toxicity.

Comp Biochem Physiol C Toxicol Pharmacol, 2002 Jul, 132(3), 315 - 39
Marine pharmacology in 1999: compounds with antibacterial, anticoagulant, antifungal, anthelmintic, anti-inflammatory, antiplatelet, antiprotozoal and antiviral activities affecting the cardiovascular, endocrine, immune and nervous systems, and other miscellaneous mechanisms of action; Mayer AM et al.; This review, a sequel to the 1998 review, classifies 63 peer-reviewed articles on the basis of the reported preclinical pharmacological properties of marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria . In all, 21 marine chemicals demonstrated anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis or antiviral activities . An additional 23 compounds had significant effects on the cardiovascular, sympathomimetic or the nervous system, as well as possessed anti-inflammatory, immunosuppressant or fibrinolytic effects . Finally, 22 marine compounds were reported to act on a variety of molecular targets, and thus could potentially contribute to several pharmacological classes . Thus, during 1999 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads in the ongoing global search for therapeutic agents for the treatment of multiple disease categories.

Bioorg Med Chem Lett, 2002 Sep 2, 12(17), 2431 - 4
Synthesis and SAR of azalide 3,6-ketal aromatic derivatives as potent Gram-positive and Gram-negative antibacterial agents; Cheng H et al.; 3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics . The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.

J Med Dent Sci, 1997 Dec, 44(4), 75 - 80
A prospective, randomized clinical trial of preoperative bowel preparation for elective colorectal surgery--comparison among oral, systemic, and intraoperative luminal antibacterial preparations; Yabata E et al.; During a one year and six month period, 137 patients undergoing elective colorectal surgery for carcinoma were randomly allocated to three groups . Patients in group A received oral tobramycin and metronidazole for three days prior to surgery . Patients in groups B and C received systemic antibiotic, a second generation cephem cefmetazole, every 3 hours during surgery . Patients in group C also received a luminal preparation of tobramycin during surgery . All patients received mechanical bowel preparation in the same manner . The incidence of postoperative wound sepsis was 10.9% in group A, 9.8% in group B, and 10.0% in group C . There were no significant differences in postoperative wound sepsis among the three groups . The oral antibiotic regimen induced a greater change in intestinal flora and was associated with more frequent postoperative diarrhea . Although the preoperative bowel preparation taken for patients in group A could not sufficiently reduce the intestinal bacterial count, systemic antibiotic prophylaxis was simple and cost-effective . There was no additional advantage in combining the systemic and luminal antibiotic preparations . Therefore, for elective colorectal surgery, we recommend intravenous infusion of second generation cephem cephmetazole with mechanical bowel preparation.

J Infect, 2002 Feb, 44 Suppl A, 17 - 23
Pharmacodynamic rationale for short-duration antibacterial therapy; Nicolau DP; With the global spread of antibacterial resistance, selecting appropriate therapy for respiratory tract infections (RTIs) presents a major challenge . Current opinion favours short-duration chemotherapy, which can improve patient compliance, thereby reducing potential resistance, minimize toxicodynamic profiles and decrease treatment costs . Neither microbiological nor pharmacokinetic (PK) data alone can determine whether a drug is suitable for short-duration therapy . Pharmacodynamics (PD) seeks to integrate PK and microbiological data into models that can then be used to predict clinical outcomes and to guide rational dosing strategies . Telithromycin is the first ketolide antibacterial to undergo clinical development . Its novel structure provides enhanced microbiological activity, even against beta-lactam and macrolide-resistant pathogens, and the potential to minimize the selection of resistance . PK profiling of telithromycin reveals that once-daily oral administration of 800 mg achieves plasma concentrations that exceed the MICs of key respiratory pathogens throughout most of the dosing period . PK-PD modelling indicates that the AUC:MIC ratio is predictive of outcome for this antibacterial . Telithromycin achieves high AUC:MIC ratios, has a prolonged postantibiotic effect, shows excellent penetration into respiratory and inflammatory tissues and has a long elimination half-life from these tissues . These variables strongly suggest that telithromycin is suitable for short-duration therapy and a once-daily dosing regimen.

J Cutan Pathol, 2002 Feb, 29(2), 93 - 5
The histopathology of folliculitis in HIV-infected patients; Holmes RB et al.; BACKGROUND: Cutaneous disease referable to human immunodeficiency virus (HIV) infection has become less common with the advent of widespread administration of antiretroviral medications, particularly the protease inhibitors . Pruritic eruptions that fall into the general categorization of folliculitis continue to be problematic . METHODS: In this report, we describe 33 skin biopsy samples prospectively obtained of follicular papules and pustules from 33 HIV-infected individuals with the clinical diagnosis of HIV-related folliculitis . RESULTS: The histopathologic findings were stratified as follows: (i) acute folliculitis with bacteria and/or yeast (n = 9); (ii) lymphocytic perifolliculitis (n = 7); (iii) eosinophilic folliculitis (n = 5); (iv) perifolliculitis with mixed inflammation (n = 11); (v) follicular rupture with predominant granulomatous inflammation (n = 1) . Demodex organisms were found in 10 specimens scattered among these categories . CONCLUSIONS: The histopathology of folliculitis in HIV-infected patients is protean . No single factor could be identified as the cause, making targeted antibacterial or antifungal therapy unlikely to be successful across a wide range of patients.

J Am Soc Mass Spectrom, 2002 Jul, 13(7), 804 - 12
In vivo labeling: a glimpse of the dynamic proteome and additional constraints for protein identification; Ogorzalek Loo RR et al.; Identities ascribed to the intact protein ions detected in MALDI-MS of whole bacterial cells or from other complex mixtures are often ambiguous . Isolation of candidate proteins can establish that they are of correct molecular mass and sufficiently abundant, but by itself is not definitive . An in vivo labeling strategy replacing methionine with selenomethionine has been employed to deliver an additional constraint for protein identification, i.e., number of methionine residues, derived from the shift in mass of labeled versus unlabeled proteins . By stressing a culture and simultaneously labeling, it was possible to specifically image the cells' response to the perturbation . Because labeled protein is only synthesized after application of the stress, it provides a means to view dynamic changes in the cellular proteome . These methods have been applied to identify a 15,879 Da protein ion from E . coli that was induced by an antibacterial agent with an unknown mechanism of action as SpY, a stress protein produced abundantly in spheroplasts . It has also allowed us to propose protein identities (and eliminate others from consideration) for many of the ions observed in MALDI (and ESI-MS) whole cell profiling at a specified growth condition.

J Appl Microbiol, 2002, 93(2), 302 - 9
Antibacterial activity of surfactants against Escherichia coli cells is influenced by carbon source and anaerobiosis; Ishikawa S et al.; AIMS: In order to clarify the involvement of an energy-yielding system in the antibacterial action of surfactants, the effects of carbon source and anaerobiosis during the growth period on the surfactant sensitivity of Escherichia coli cells were investigated . METHODS AND RESULTS: Cetyltrimethylammonium bromide (CTAB) and N-dodecyl-N,N-dimethylglycine, at relatively low concentrations, caused a delay in growth of E . coli cells . Cells grown in M9 medium supplemented with glycerol, succinate or acetate as a carbon source were more sensitive to surfactants and had a higher respiratory activity than those grown with glucose . Cultivation under anaerobiosis made cells resistant to CTAB . CONCLUSIONS: Bacterial sensitivity to surfactants was affected by carbon source and anaerobiosis . SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained should be helpful in determining suitable conditions of treatment in the practical use of surfactants for bacterial decontamination.

Chemosphere, 2002 Jul, 48(3), 351 - 61
Determination of the distribution coefficient (log Kd) of oxytetracycline, tylosin A, olaquindox and metronidazole in manure; Loke ML et al.; Olaquindox (log Kow = -2.3) and metronidazole (log Kow = -0.1) both have low tendencies to sorp to particles in manure . This corresponds with the negative log Kow values of these antibiotics . Tylosin (log Kow = 1.63) and oxytetracycline (log Kow = -1.12) sorp relatively strongly to the manure particles and have log Kd values between 1.5 and 2.0 . The tendency to bind to manure was ranked after increasing binding as follows: metronidazole < olaquindox << tylosin A and oxytetracycline . This order of ranking is consistent with results of sorption in soil . Our experiments illustrate that for some antibacterial agents estimation of the partitioning coefficients, Kd, cannot be made from Kow and f(oc) alone . Sorption of oxytetracycline to manure is much higher than expected from the negative log Kow value of the compound . It is believed that sorption of oxytetracycline to manure is influenced by ionic binding to divalent metal ions as such Mg2+ and Ca2+ as well as other charged compounds in the matrix . Binding of oxytetracycline to soil is stronger than the binding to manure . This is most likely due to the strong mineral related metal complexes formed between soil, metal ion and oxytetracycline . These complexes are not known to exist in manure . The relatively strong sorption of tylosin A to manure corresponds with data found for soil sorption of tylosin . Tylosin has a log Kow value of 2.5, thus it is not surprising that this drug binds strongly to manure.

Clin Infect Dis, 2002 Aug 15, 35(4), 434 - 41 Epub 2002 Jul 16.
Recent advances in the treatment of Acanthamoeba keratitis; Kumar R et al.; Infection of the eye caused by Acanthamoeba species constitutes a burgeoning and unsolved problem . Of individuals with Acanthamoeba keratitis, 85% wear contact lenses; abrasion of the cornea is implicated . Corneal infection often can be prevented by good lens care and hygiene . Severe Acanthamoeba keratitis often can be very difficult to treat; surgery can be less than successful and may lead to further problems . The encysted stage in the life cycle of Acanthamoeba species appears to cause the most problems; many biocides are ineffective in killing the highly resistant cysts . Combination therapy--that is, use of 2 or 3 biocides, sometimes with antibacterial antibiotics--appears to work best . Recurrence is common if treatment is stopped prematurely . Immunologic methods are being investigated as a form of prevention, and oral immunization of animals recently has been successful in the prevention of Acanthamoeba keratitis by inducing immunity before infection occurs . Immunization thus may eventually become the best approach for reduction of the incidence of amebic infection in humans.

Planta Med, 2002 Jul, 68(7), 626 - 30
Sesquiterpene lactone glycosides, eudesmanolides, and other constituents from Carpesium macrocephalum; Yang C et al.; Two new sesquiterpene lactone glycosides and two new eudesmanolides, along with twelve known compounds were isolated from seeds of Carpesium macrocephalum . The structures of these new compounds were elucidated as 2alpha- O-beta- D-glucopyranosyl-5alpha, 11alpha H-eudesma-4(15)-en-12,8beta-olide ( 1), 2alpha- O-beta- D-glucopyranosyl-5alpha H-eudesma-4(15),11(13)-dien-12,8beta-olide ( 2), 2alpha-acetoxy-5alpha-hydroxy-11alpha H-eudesma-4(15)-en-12,8beta-olide ( 3) and 2alpha,5alpha-dihydroxy-11alphaH-eudesma-4(15)-en-12,8beta-olide ( 4) by spectroscopic methods including 2D NMR techniques ( (1)H- (1)H COSY, (1)H- (1)H NOESY, HMQC, HMBC) and chemical transformations . Compounds 1, 6, 8, 9 and 10 exhibited moderate antibacterial activity, while compound 4 showed appreciable cytotoxic activity against cultured SMMC-7721 (human hepatoma cell).

J Med Chem, 2002 Aug 1, 45(16), 3430 - 9
New inhibitors of bacterial protein synthesis from a combinatorial library of macrocycles; Jefferson EA et al.; A mixture-based combinatorial library of 14-membered macrocycles was synthesized to target ribosomal RNA and uncover a new class of antibacterial agents . High-throughput screening identified a macrocyclic mixture that inhibited cell-free-coupled transcription/translation in Escherichia coli-derived extracts, with an IC(50) value in the 25-50 microM range . In a follow-up library of 64 single macrocycles, 8 gave IC(50) values ranging from 12 to 50 microM in the cell-free protein synthesis inhibition assay . Some of the macrocycles were screened in a translation inhibition assay, and IC(50) values generally paralleled those obtained in the uncoupled transcription/translation assay . Additional analogues were prepared in a preliminary structure-activity relationship study, and more potent macrocycles were identified with low micromolar activity (IC(50) values = 2-3 microM) . Some of these macrocycles displayed antibacterial activity against lipopolysaccharide mutant E . coli bacterial cells (IC(50) values = 12-50 microM).

J Antibiot (Tokyo), 2002 May, 55(5), 462 - 6
Novel alpha-glucosidase inhibitors, CKD-711 and CKD-711a produced by Streptomyces sp . CK-4416 . II . Biological properties; Kwon YI et al.; CKD-711 and CKD-711a are aminooligosaccharide alpha-glucosidase inhibitors discovered during the bioactive material screening for antibacterial agent . Their inhibitory activities were studied and compared with those of acarbose in vitro and in vivo with animals . In in vitro study, CKD-711 showed similar effects to acarbose on porcine intestinal maltase and sucrase, IC50s of 2.5 and 0.5 microg/ml, respectively, whereas it had about 2 fold lower alpha-amylase inhibitory activity (IC50, 78.0 microg/ml) than acarbose (IC50, 36 microg/ml) . CKD-711a showed less inhibitory activity than CKD-711 against all the enzymes tested . In rat fed on starch and sucrose meals, the dose of CKD-711 which reduced the postprandial blood glucose increment by 50 percent in comparison to control rats (ED50) were 3.07 and 1.15 mg/kg, respectively, and acarbose had ED50s of 1.94 and 1.15 mg/kg, respectively . CKD-711 and CKD-711a also showed antibacterial activity against Comamonas terrigena.

Klin Med (Mosk), 2002, 80(6), 7 - 12
{Side effects of current anti-Helicobacter therapy}; Maev IV et al.; The article deals with side effects of present-day antihelicobacter therapy including side effects of some drugs with antisecretory and antibacterial action and complications observed in using combined treatment of helicobacteriosis (triple and quadrotherapy).

Klin Med (Mosk), 2002, 80(6), 57 - 62
{Exacerbation of chronic obstructive pulmonary disease: current approaches to antibacterial therapy}; Sinopal'nikov AI et al.; The article outlines current approaches to empiric antibacterial therapy of patients who had exacerbation of chronic obstructive pulmonary disease (COPD) . The choice of the antibiotics should be made basing on the frequency of exacerbations, COPD duration, severity of bronchial obstruction, age of the patient, concomitant visceral lesions . Common errors in antibacterial therapy are analysed: wrong choice of the antibiotic, mode of drug administration, dose, dose regimen, duration of treatment (too long); simultaneous intake of antibiotics and nistatine; frequent change of antibiotics throughout the treatment.

Genetika, 2002 Jun, 38(6), 758 - 72
{Production of bacteriocins by gram-positive bacteria and the mechanisms of transcriptional regulation}; Kotel'nikova EA et al.; The mechanisms of production of bacteriocins in Gram-positive bacteria and the main distinctions of these bacteriocins from the bacteriocins of Gram-negative bacteria (colicins) are outlined . A classification of antibacterial peptides is presented, and most of known class I and II peptides are pointed out . In Gram-positive bacteria, the cases of bacteriocin-associated quorum sensing are examined . For these cases, the structure of loci containing the genes of regulatory systems, transport, immunity, processing, and posttranslational modification of antibacterial peptides are described . All known regulatory sites for class II bacteriocins are presented . A description of the putative regulatory sites found by us and their classification are provided . The evolutionary tree of transcriptional response regulators is shown to correspond to the tree of their recognition sites.

Acta Biochim Pol, 2002, 49(1), 185 - 95
Synthesis, antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives; Kazimierczuk Z et al.; Two series of benzimidazole derivatives were sythesised . The first one was based on 5,6-dinitrobenzimidazole, the second one comprises 2-thioalkyl- and thioaryl-substituted modified benzimidazoles . Antibacterial and antiprotozoal activity of the newly obtained compounds was studied . Some thioalkyl derivatives showed remarkable activity against nosocomial strains of Stenotrophomonas malthophilia, and an activity comparable to that of metronidazole against gram-positive and gram-negative bacteria . Of the tested compounds, 5,6-dichloro-2-(4-nitrobenzylthio)-benzimidazole showed the most distinct antiprotozoal activity.

Yakugaku Zasshi, 2002 Jul, 122(7), 487 - 94
{Identification of chemical structure of antibacterial components against Legionella pneumophila in a coffee beverage}; Dogasaki C et al.; We previously reported that certain constituents in brewed coffee exhibited antibacterial activities against a strain of Legionella pneumophila . The constituents showing antibacterial activities were included only in extracts cold with water or hot water . To determine the antibacterial substances in coffee extract, the extract was fractionated by HPLC using a UV/photodiode array detector . The optimum HPLC conditions for analysis were UV wavelength of 250 nm and eluents of methanol/acetic acid (10/90), pH 3.0 . When several fractions separated by HPLC were investigated for antibacterial activities against L . pneumophila, it was found that three peak fractions exhibited strong antibacterial activities . Each product from these fractions was analyzed by NMR and LC-mass spectrometry, and the chemical structure of each was determined . It was shown that the antibacterial substances was were protocatechuic acid (3,4-dihydroxy benzoic acid), chlorogenic acid, and caffeic acid.

Eur J Clin Pharmacol, 2002 Jul, 58(4), 275 - 83 Epub 2002 Jun 07.
A Swedish case-control network for studies of drug-induced morbidity--acute pancreatitis; Blomgren KB et al.; OBJECTIVE: To evaluate risk factors - notably drugs - for developing acute pancreatitis . METHODS: A population-based, case-control study, encompassing 1.4 million inhabitants aged 20-85 years from four regions in Sweden between 1 January 1995 and 31 May 1998 . A total of 462 cases were hospitalised in surgical departments with their first episode of acute pancreatitis without previously known biliary stone disease . From a population register, 1781 controls were randomly selected . Information was obtained from medical records and through telephone interviews . RESULTS: Fifty-seven percent of the cases were males . An expert group found evidence for biliary stones in 50% of the cases, alcohol intake in 23%, but in 29% neither of these factors were present . In all, "other" factors, e.g . drugs, could have contributed to the development of acute pancreatitis in 52% of the cases . In a multivariate analysis, the adjusted odds ratios (ORs) for H(2) antagonists were 2.4 (95% CI 1.2-4.8) for proton pump inhibitors (PPIs), 2.1 (1.2-3.4) for non-steroidal anti-inflammatory drugs (NSAIDs), 2.3 (1.3-4.0) for those derived from acetic acid and 1.9 (1.1-3.2) for antibacterials for systemic use . Significant ORs were found for a history of gastrointestinal tract disorders {1.5 (1.1-1.9)} and inflammatory bowel disease (IBD) {3.4 (1.5-7.9)} . Smoking was significantly associated with acute pancreatitis {1.7 (1.2-2.1)} and, for those smoking more than 20 cigarettes per day, the OR was 4.0 (2.2-7.5) . Alcohol in moderate amounts did not increase the risk, but for those drinking more than 420 g alcohol per week the OR was 4.1 (2.2-7.5) . CONCLUSION: In addition to cholelithiasis, smoking and heavy alcohol use, drugs may be an important risk factor for acute pancreatitis.

Boll Chim Farm, 2002 Mar-Apr, 141(2), 105 - 9
Synthesis, characterization and antibacterial activities of some N-bridged heterocycles containing triazole, quinoline and nitrofuran moieties; Holla BS et al.; A series of 2-(2-furyl)4-quinolinecarboxylic acids (3), 2-(5-nitro-2-furyl)4-quinolinecarboxylic acids (6), 4-(3-aryloxymethyl-1,2,4-triazolo{3,4-b}-1,3,4-thiadiazolo-6-yl)-2-(furyl)quinolines (5) and 4-(3-aryloxymethyl-1.2,4-triazolo{3,4-b}-1,3,4-thiadiazolo-6-yl)-2-(5-nitro-2-furyl)quinolines (7) were synthesized . The structures of the newly synthesized compounds are confirmed on the basis of elemental analysis, IR, 1H-NMR and mass spectral data . The newly synthesized compounds are evaluated for their antibacterial activities . Compounds containing nitrofuran moiety showed excellent antibacterial activity . Results of such studies are disscussed in this paper.

J Chem Inf Comput Sci, 2002 Jul-Aug, 42(4), 869 - 78
Structure-based classification of antibacterial activity; Cronin MT et al.; The aim of this study was to develop a simple quantitative structure-activity relationship (QSAR) for the classification and prediction of antibacterial activity, so as to enable in silico screening . To this end a database of 661 compounds, classified according to whether they had antibacterial activity, and for which a total of 167 physicochemical and structural descriptors were calculated, was analyzed . To identify descriptors that allowed separation of the two classes (i.e . those compounds with and without antibacterial activity), analysis of variance was utilized and models were developed using linear discriminant and binary logistic regression analyses . Model predictivity was assessed and validated by the random removal of 30% of the compounds to form a test set, for which predictions were made from the model . The results of the analyses indicated that six descriptors, accounting for hydrophobicity and inter- and intramolecular hydrogen bonding, provided excellent separation of the data . Logistic regression analysis was shown to model the data slightly more accurately than discriminant analysis.

Curr Opin Infect Dis, 2002 Aug, 15(4), 377 - 82
Treatment of febrile neutropenia: what is new?
Viscoli C, Castagnola E.
PURPOSE OF THE REVIEW: To identify the more recent challenges in the treatment of patients with febrile neutropenia following antineoplastic chemotherapy or bone marrow transplant published in the English language in the period late 2000-early 2002 regarding: changes in etiology of bacteremia in neutropenic patients; new options for initial empirical antibacterial therapy; factors associated with the risk of developing infection in cancer patients; prediction of prognosis in febrile neutropenia; oral therapy; need for a specific anti-Gram-positive coverage in persistently febrile and neutropenic patients . RECENT FINDINGS: Findings may be summarized according with the identified topics as follows: many centers are reporting an increase in the incidence of Gram-negative bacteremias; piperacillin-tazobactam could be safely administered as monotherapy of febrile neutropenia; congenital factors and intensity of chemotherapy and other medical interventions, such as antifungal prophylaxis, are recognized as of increasing importance in the determination of infectious risk; it is now possible to identify patients with a good prognosis (low risk) by means of validated scoring systems; oral therapy is feasible in low risk patients; the empirical addition of a glycopeptide in persistently febrile neutropenic patients is not indicated . SUMMARY: Many of the identified points may have a great impact in the daily management of febrile granulocytopenic patients . However, all recent epidemiological and therapeutical studies underline the absoloute need for the knowledge of the pattern of infecting organisms in each center.

Biochem Biophys Res Commun, 2002 Jul 26, 295(4), 884 - 9
Enzymatic properties of a new peptide deformylase from pathogenic bacterium Leptospira interrogans; Li Y et al.; Peptide deformylase (LiPDF), a target protein for antibacterial agents from pathogenic bacteria Leptospira interrogans was identified and purified . Enzymatic studies including kinetics and inhibition revealed new inspiring highlights . The purified active enzyme was a dimer and showed a hyperbolic progress plot when the substrate was low but an excess substrate inhibition effect in higher substrate concentration . Variants on the metal-binding ligand-Cys102 were constructed to verify the indispensable attribute . Also the variant, LiPDF with the insertion residues (R(70)Y(71)P(72)G(73)T(74) P(75)D(76)V(77)) between the conserved motif 1 and motif 2 excised, was constructed and displayed no marked changes on enzymatic features . The results of atom absorbance proved that it contains a tightly bound Zn2+ rather than Fe2+ in E . coliPDF that is an essential cofactor for its high catalytic activity.

Curr Biol, 2002 Jun 25, 12(12), 996 - 1000
Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults; Leulier F et al.; In Drosophila, the immune deficiency (Imd) pathway controls antibacterial peptide gene expression in the fat body in response to Gram-negative bacterial infection . The ultimate target of the Imd pathway is Relish, a transactivator related to mammalian P105 and P100 NF-kappaB precursors . Relish is processed in order to translocate to the nucleus, and this cleavage is dependent on both Dredd, an apical caspase related to caspase-8 of mammals, and the fly Ikappa-B kinase complex (dmIKK) . dTAK1, a MAPKKK, functions upstream of the dmIKK complex and downstream of Imd, a protein with a death domain similar to that of mammalian receptor interacting protein (RIP) . Finally, the peptidoglycan recognition protein-LC (PGRP-LC) acts upstream of Imd and probably functions as a receptor for the Imd pathway . Using inducible expression of dFADD double-stranded RNA, we demonstrate that dFADD is a novel component of the Imd pathway: dFADD double-stranded RNA expression reduces the induction of antibacterial peptide-encoding genes after infection and renders the fly susceptible to Gram-negative bacterial infection . Epistatic studies indicate that dFADD acts between Imd and Dredd . Our results reinforce the parallels between the Imd and the TNF-R1 pathways.

Chest Surg Clin N Am, 2002 May, 12(2), 397 - 416
Perioperative care of the lung transplant patient; Duarte AG et al.; Improvements in the perioperative management of lung transplant recipients have produced a 90% survival in the first 30 days following surgery . Detailed attention to donor organ procurement and preservation of the allograft are important in ensuring an early successful outcome . Early antibacterial administration based on donor or pretransplant cultures and antiviral therapy in CMV-negative recipients assist in avoiding early infectious complications . Development of hypoxemia or hemodynamic instability in the perioperative period requires a rapid, systematic evaluation with attention to mechanical, immunologic, or infectious causes . Nonpulmonary complications are not infrequent in lung transplant recipients.

Int J Infect Dis, 2002 Jun, 6(2), 103 - 7
The decision-making process in antibacterial treatment of pediatric upper respiratory infections: a national prospective office-based observational study; Boccazzi A et al.; BACKGROUND: The identification of patient management practices and the sources of medical information is crucial for rationalizing the treatment of respiratory tract infections, whose high incidence, especially in children, makes them one of the maior areas of unnecessary health expenditure . MATERIALS AND METHODS: This national prospective study was designed to investigate the diagnostic and prescribing habits of 100 office-based pediatricians managing upper respiratory tract infections in 1111 pediatric patients (604 males, mean age 6.7962.77 years; 507 females, mean age 6.7362.8 years) sequentially enrolled when an antibiotic treatment was deemed necessary . RESULTS: The most frequently diagnosed diseases were acute tonsillopharyngitis (56.2%) and acute otitis media (18.1%) . Penicillins were prescribed in 34.3% of the cases, cephalosporins in 38.1%, and macrolides in 26.1%: oral drugs accounted for 92.2% of the prescriptions . The treatments were administered once or twice daily in 75.8% of the patients, and prescribed for 8 days in more than 80%; 76.7% also received supportive or symptomatic treatment (antipyretics, corticosteroids, cough suppressants and non-steroidal anti-inflammatory drugs) . Laboratory or radiologic investigations were rarely requested . The main sources of medical information indicated by the participating pediatricians were pharmaceutical companies (35.6%) and meeting or congress reports (27.3%) . CONCLUSIONS: The results indicate that more active education is still needed to improve the decision-making processes of office-based pediatricians.

Proc Natl Acad Sci U S A, 2002 Jul 23, 99(15), 9978 - 83 Epub 2002 Jul 15.
Characterization of three alternatively spliced isoforms of the Rel/NF-kappa B transcription factor Relish from the mosquito Aedes aegypti; Shin SW et al.; The Rel/NF-kappa B transcription factor Relish performs a central role in the acute-phase response to microbial challenge by activating immune antibacterial peptides . We cloned and molecularly characterized the gene homologous to Drosophila Relish from the mosquito Aedes aegypti . Unlike Drosophila Relish, Aedes Relish has three alternatively spliced transcripts encoding different proteins . First, the predominant Aedes Relish transcript of 3.9 kb contains both the Rel-homology domains and the inhibitor kappa B (I kappa B)-like domain, which is similar to Drosophila Relish and to the mammalian p105 and p100 Rel/NF-kappa B transcription factors . Second, Aedes Relish transcript contains Rel-homology domains identical to those of the major transcript but it completely lacks the I kappa B-like domain-coding region, which has been replaced by a unique 3'-untranslated region sequence . In the third transcript, a deletion replaces most of the N-terminal sequence and Rel-homology domains; however, the I kappa B-like domain is intact . All three Aedes Relish transcripts were induced by bacterial injection but not by blood feeding . In vitro-translated protein from the Rel-only construct specifically binds to the kappa B motif from Drosophila cecropin A1 and Aedes defensin genes . PCR and Southern blot hybridization analyses show that these three transcripts originated from the same large inducible mRNA encoded by a single Relish gene.

Mol Plant Microbe Interact, 2002 Jul, 15(7), 701 - 8
Sensitivity of bacterial and fungal plant pathogens to the lytic peptides, MSI-99, magainin II, and cecropin B; Alan AR et al.; In vitro and leaf disk assays of bacterial and fungal plant pathogens were conducted using three cationic lytic peptides, MSI-99, magainin II (MII), and cecropin B (CB) . Growth of bacterial organisms was retarded or completely inhibited by low concentrations of these lytic peptides . The peptides also significantly reduced germination of fungal spores and growth of mycelia; however, higher concentrations of peptides were needed to inhibit fungal growth compared with those needed to inhibit bacteria . The relative efficacy of the peptides depended on the microorganism tested, but CB was the most inhibitory to the majority of the bacteria and fungi assayed . MSI-99, a synthetic derivative of MII with increased positive charge, showed equal or two- to fivefold higher antibacterial activity compared to MII in the in vitro assays . MSI-99 was also superior to MII against the oomycete, Phytophthora infestans but was slightly inferior to MII in assays with the true fungi, Penicillium digitatum and Alternaria solani . In the leaf disk assays, pretreating spores of Alternaria solani and Phytophthora infestans with the peptides at concentrations as low as 10 microg per ml led to significant reductions in the size of early blight lesions and prevented development of any late blight lesions on tomato leaf disks . Our results from in vitro and leaf disk assays suggest that MSI-99 can be used as a transgene to generate tomato lines with enhanced resistance to bacterial and fungal diseases of this crop.

Biotechnol Bioeng, 2002 Aug 20, 79(4), 465 - 71
Polymer surfaces derivatized with poly(vinyl-N-hexylpyridinium) kill airborne and waterborne bacteria; Tiller JC et al.; A facile methodology has been developed for covalently derivatizing the surfaces of common materials with a designed antibacterial polycation, poly(vinyl-N-pyridinium bromide), wherein the first, key step involves surface coating with a nanolayer of silica . Various commercial synthetic polymers derivatized in this manner become bactericidal-they kill up to 99% of deposited, from either an aerosol or an aqueous suspension, Gram-positive and Gram-negative bacteria on contact .

Am J Ther, 2002 Jul-Aug, 9(4), 275 - 80
In vivo evaluation of interaction between aqueous seed extract of Garcinia kola Heckel and ciprofloxacin hydrochloride; Esimone CO et al.; The effect of Garcinia kola seed extract (100 mg/kg) on the pharmacokinetic and antibacterial effects of ciprofloxacin hydrochloride (40 mg/kg) was studied . The results (mean +/- SEM) indicated that concurrent administration of both agents significantly (P < 0.05) decreased average serum concentration, peak serum concentration, and elimination rate of ciprofloxacin HCl, whereas the half-life and clearance rate were increased . The decrease in clearance rate was not significant . There was no difference in time to peak plasma concentration of ciprofloxacin HCl in both groups (n = 5), which occurred at 1 hour . However, the peak plasma concentration of ciprofloxacin HCl was 46.90 +/- 9.50 microg/mL in the group that received ciprofloxacin HCl alone as against 35.80 +/- 9.30 microg/mL noted in the group that received both agents (difference of 22.24%) . At 2.5 hours and longer, the values were higher in the group that received both agents, but these were not statistically significant . The reciprocal serum inhibitory titer (SIT) was 33.33 and 50.00% higher in group that received ciprofloxacin HCl alone at 1 and 2.5 hours, respectively; the highest value for both groups being at 1 hour . In contrast, at 4 hours, the value of reciprocal SIT was 66.67% higher in the group that received both agents and at 24 hours, the value was zero for both groups . The observed pharmacokinetic and antibacterial interactions at various time interval indicate biphasic interaction . The interaction was antagonistic at 1 and 2.5 hours, but exhibited potentiation at 4 hours . The precise mechanism underlying the observed biphasic interaction is not fully understood.

Microsc Res Tech, 2002 Jun 15, 57(6), 421 - 31
Phagocytosis--the mighty weapon of the silent warriors; Djaldetti M et al.; Professional phagocytes, comprising polymorphonuclear neutrophils and monocyte/macrophage cells, play an important role in the host defense . Any defect in their function exposes the organism to microbial intruders terminating in fatal diseases . The functional responses of the phagocytes to bacterial and fungal infections include chemotaxis, actin assembly, migration, adhesion, aggregation, phagocytosis, degranulation, and reactive oxygen species production . Superoxide generation by phagocytic NADPH oxidase is an imperative step toward bacterial killing . Phagocytes participate in inflammatory reactions and exert tumoricidal activity . They are supported by serum factors such as immunoglobulins, cytokines, complement, the acute phase reactant C-reactive protein, production of antibacterial proteins, and others . In addition to their principal task to eliminate bacteria, they are engaged in removing damaged, senescent, and apoptotic cells . Engulfed cell debris, large particles such as latex beads, fat, and oil droplets, are examples of phagocytic activity illustrated in the present review with transmission and scanning electron microscope micrographs . Numerous factors, such as diseases and stressful conditions, affect the engulfing activity of the professional phagocytes . Our experience regarding the impaired phagocytic capacity of cells in patients with diabetes and chronic renal failure is discussed . The results obtained in our laboratory from experiments detecting the effect of strenuous physical exercise, hypothermia, fasting, and abdominal photon irradiation on the phagocytic capacity of human polymorphonuclear neutrophils and rat peritoneal macrophages are hereby summarized and the reports on those subjects in the recent literature are reviewed . A variety of assays are applied for quantifying phagocytosis . Flow cytometry based on incubation of phagocytic cells with fluorescent conjugated particles and measuring the amount of fluorescence as an indicator of the engulfing capacity of the cells is a useful method . A direct visualization of the ingested particles using light or electron microscopy is a valuable tool for estimation of phagocytic function . In our hands, the use of semithin sections of embedded phagocytes following their incubation with latex particles provided satisfactory results for measuring the total number of phagocytic cells, as well as the internalizing capacity of each individual cell . Microbiological assays, the nitroblue tetrazolium test, quantitation of antibody- and antigen-mediated phagocytosis, as well as methods reviewed in detail in other reports are additional applications for determination of this intricate process .

Arch Pharm (Weinheim), 2002 Apr, 335(4), 152 - 8
Synthesis and antibacterial activity of 1beta-methyl-2-(5-substituted thiazolidinopyrrolidin-3-ylthio)carbapenems and related compounds; Oh CH et al.; The synthesis of a new series of 1beta-methylcarbapenems containing the substituted thiazolidinopyrrolidine moiety is described . Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the thiazolidine ring was investigated.A particular compound (18 c) having a 2-amide substituted thiazolidine moiety showed the most potent antibacterial activity.

Bioessays, 2002 Jul, 24(7), 637 - 48
The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery; Bermingham A et al.; The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been acknowledged for many years and validated by the clinical use of several drugs . Recently, the crystal structures of all but one of the enzymes in the pathway from GTP to dihydrofolate have been determined . Given that structure-based drug design strategies are now widely employed, these recent developments have prompted a re-evaluation of the potential of each of the enzymes in the pathway as a target for development of specific inhibitors . Here, we review the current knowledge of the structure and mechanism of each enzyme in the bacterial folic acid biosynthesis pathway from GTP to dihydrofolate and draw conclusions regarding the potential of each enzyme as a target for therapeutic intervention .

Insect Biochem Mol Biol, 2002 Aug, 32(8), 881 - 7
Protein purification, cDNA cloning and gene expression of attacin, an antibacterial protein, from eri-silkworm, Samia cynthia ricini; Kishimoto K et al.; Attacin was isolated from immunized larval hemolymph of the wild silkmoth, Samia cynthia ricini . The antibacterial effect of the attacin was limited to some species of Gram-negative bacteria . Two cDNA clones encoding attacin A and B, respectively, were isolated by screening the cDNA library from immunized fat body . The two cDNAs encoded the same length of precursor protein with 233 amino acid residues . The 46-residue prepropeptides of the two attacins were identical to each other, but 4 out of 187 residues of the mature proteins were different in each other . The two attacins show 98% identity at the amino acid level, while 92% identity at the nucleotide level . Both of the mature proteins were highly homologous to cecropia basic attacin with identity of 96% . The attacin transcripts were detected at significant level in fat body, hemocytes and Malpighian tube after injection with peptidoglycan, but not in the midgut and the silkgland . The induction of attacin gene expression was elicited most effectively by peptidoglycan and UV-killed bacteria in the fat body.

Biochimie, 2002 Apr, 84(4), 329 - 34
Molecular characterization and action of usnic acid: a drug that inhibits proliferation of mouse polyomavirus in vitro and whose main target is RNA transcription; Campanella L et al.; Usnic acid is a normal component of lichen cells . This natural compound has shown different biological and physiological activities that might have a great relevance in pharmacology and clinics . For instance, usnic acid is known for its antibacterial and antiparasitic action . Also, the drug has a potential interest in cancer therapy because of its antimitotic and antiproliferative action . The molecular structure of usnic acid has been validated and further explored in this investigation . Many biological properties of this drug are known; however its potential antiviral action has not yet been evaluated . In this paper, we demonstrate that usnic acid is a potent inhibitor of the proliferation of mouse polyomavirus . Its action is not exerted at the level of virion entry into the host cell . Moreover, the abolition of viral DNA replication is an indirect consequence of the drastic inhibition of RNA transcription.

J Antimicrob Chemother, 2002 Jul, 50(1), 133 - 6
Effect of plaunotol in combination with clarithromycin or amoxicillin on Helicobacter pylori in vitro and in vivo; Koga T et al.; Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori . The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H . pylori . When combined with clarithromycin, plaunotol showed synergic activity against 11 of 14 strains, and additive activity against the other three strains, by chequerboard titration . When combined with amoxicillin, plaunotol showed additive activity against 10 of 14 strains . No antagonistic effects were seen against any of the strains tested . The interactions between plaunotol and either clarithromycin or amoxicillin were determined by time-kill assay against the Sydney Strain (strain SS1) of H . pylori . The combination of plaunotol with clarithromycin showed synergic activity and with amoxicillin showed additive activity . In a C57BL/6 mouse gastritis model infected with H . pylori SS1, the plaunotol-clarithromycin and plaunotol-amoxicillin combinations both exhibited synergic effects, which allowed the effective dose of clarithromycin to be reduced when co-administered with plaunotol . These results suggest that plaunotol may have a useful role in combination with anti-H . pylori drugs in the treatment of H . pylori-associated diseases.

J Antimicrob Chemother, 2002 Jul, 50(1), 129 - 32
In vitro anti-Helicobacter pylori activity of BAS-118, a new benzamide derivative; Kobayashi I et al.; The antibacterial activity of BAS-118, a new benzamide derivative, against Helicobacter pylori and other species of bacteria was investigated, as was the in vitro ability of the compound to induce drug resistance in H . pylori . The MICs of BAS-118 for 155 isolates of H . pylori, including 30 clarithromycin (CAM)-resistant isolates (MIC > or= 1.56 mg/L) and 25 metronidazole (MNDZ)-resistant isolates (MIC >or = 6.25 mg/L), and 29 reference strains of other genera were determined by an agar dilution method . The MIC(50), MIC(90) and MIC range of BAS-118 for 100 randomly selected isolates of H . pylori were <or =0.003, 0.013 and < or =0.003-0.025 mg/L, respectively, with similar values obtained for CAM- and MNDZ-resistant isolates . Furthermore, MICs of BAS-118 for five H . pylori strains increased no more than two-fold after 10 serial passages in the presence of subinhibitory concentrations . BAS-118 exhibited a low antibacterial activity against the 29 non-H . pylori strains, with MICs of >or =8 mg/L . In summary, BAS-118 is a novel anti-H . pylori agent with a potent and selective antibacterial activity, which includes CAM- and MNDZ-resistant isolates . Furthermore, BAS-118 does not appear to induce drug resistance readily in vitro.

Int Immunopharmacol, 2002 May, 2(6), 807 - 13
Inmunoferon, a glycoconjugate of natural origin, regulates the liver response to inflammation and inhibits TNF-alpha production by an HPA axis-dependent mechanism; Brieva A et al.; In this report, we have examined the mechanism of action of Inmunoferon, a patented glycoconjugate (GC) of natural origin with immunomodulatory properties, in the regulation of TNF-alpha expression induced by LPS challenge in a rodent model . GC was found to be dependent on a normal HPA response to exert its regulatory effect on TNF-alpha expression . Adrenalectomized mice were unresponsive to the drug in terms of TNF-alpha levels after LPS challenge, whereas control mice showed lower serum TNF-alpha levels when treated with GC than vehicle-treated animals . GC treatment also induced the expression of acute phase proteins but it did not alter the normal metabolism or viability of hepatic cells . These data suggested the employment of GC as a novel adjuvant during antibacterial treatment without disadvantages such as side effects in the metabolism of the liver, thus, acting as an enhancer of the host response against infection.

J Pharm Biomed Anal, 2002 Jul 31, 29(5), 795 - 801
Electrochemical analysis of sparfloxacin in pharmaceutical formulation and biochemical screening of its Co(II) complex; Jain S et al.; Simple and sensitive, direct current polarographic (DCP) and differential pulse polarographic (DPP) methods have been developed for the qualitative as well as quantitative analysis of 5-amino-1-cyclopropyl-7 (cis-3,5 dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (sparfloxacin) . The developed methods have been standardized for the determination of the drug in pharmaceutical formulation for quality control purposes . The observed data has been subjected to statistical analysis, which revealed high reliability and precision . Sparfloxacin forms a complex with Co(II) which has been characterized on the basis of elemental analysis, IR spectral, polarographic and amperometric analysis . The analytical results indicated a 1:1 (M:L) stoichiometry for the Co(II)-sparfloxacin complex . The antibacterial studies on the drug and its complex were carried out against various pathogenic bacteria . The results revealed that the complex is more potent compared to the pure drug.

Drugs Aging, 2002, 19(5), 355 - 63
Treatment of inflammatory bowel disease in the elderly: an update; Pardi DS et al.; Inflammatory bowel disease (IBD) is most common in young adults, but it can also present in the elderly . Furthermore, with the aging of the population, the number of elderly patients with IBD is expected to grow . Other conditions, such as diverticulitis and ischaemic colitis, may be more common in the elderly and need to be considered in the differential diagnosis . Management of elderly patients with IBD follows the same principles as in younger patients, with a few exceptions . For patients with mild-to-moderate colitis, a 5-aminosalicylate drug is often used (sulfasalazine, olsalazine, mesalazine, balsalazide) . Topical therapy may be sufficient for those with distal colitis, whereas an oral preparation is used for more extensive disease . In those with more severe or refractory symptoms, corticosteroids are used, although the elderly appear to be at increased risk for corticosteroid-associated complications . For patients with corticosteroid-dependent or corticosteroid-refractory disease, immunosuppression with azathioprine or mercaptopurine may help avoid surgery . In patients with Crohn's disease, a similar approach is followed, with the additional consideration that the formulation of drug used must ensure delivery of drug to the site of inflammation . In fistulising Crohn's disease, antibacterials, immunosuppressive drugs, infliximab and surgery are often used in combination . Controlled trials and clinical experience have shown that infliximab is a significant addition to the therapeutic armamentarium for patients with Crohn's disease.

J Clin Pharmacol, 2002 Jul, 42(7), 806 - 11
Impairment of ciprofloxacin absorption by calcium polycarbophil; Kato R et al.; The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study . In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure . In the in vivo study, male ST Wistar rats and male volunteers were employed . First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats . Second, a volunteer study was employed and a randomized crossover design with twophases was used . In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2) . The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography . The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions . The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1 . AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1 . In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1 . In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1 . These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes . Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.

Rev Med Chir Soc Med Nat Iasi, 2001 Jan-Mar, 105(1), 11 - 8
{The role of oxidative stress in normal and pathological adaptive reactions}; Haulica I et al.; After a brief presentation of the data concerning the mechanism of production of oxidative stress as an expression of cellular and molecular stressing aggression, the main actions and functional implications of the excess of free radicals at the level of the main tissues and organs are presented . Emphasis is made on the nuclear, cytosolic and membrane alterations produced by the lipid peroxidation phenomena and the cell protein degradation induced by the oxidative stress . Special attention is given to the beneficial and harmful properties of the free radical species of oxygen and nitrogen, beginning with their involvement in the production of the normal adaptive reactions and ending with their involvement in the pathogenesis of various pathological states . In the group of beneficial effects are included along with the antibacterial and antiviral properties of the free radicals and their participation in the autoregulation of the local arteriolar-capillary circulation network . As harmful properties are mentioned the cellular destructive phenomena produced by the free radicals, which are considered as the generators of a true radicals pathology (senescence, atherogenesis, cancerogenesis, neurodegenerative diseases, etc).

Pol Merkuriusz Lek, 2002 Apr, 12(70), 304 - 5
{Pneumoperitoneum and peritonitis in a child treated by continuous ambulatory peritoneal dialysis}; Czupryniak A et al.; Pneumoperitoneum is a rare complication of peritoneal dialysis, which in most cases occurs soon after the implantation of the peritoneal catheter and does not need any specific treatment . In contrast, pneumoperitoneum due to visceral perforation represents a serious clinical problem and usually needs an urgent surgical intervention . We present a case of a 10-year old girl treated by peritoneal dialysis for 7 months who was admitted to hospital with symptoms of peritonitis and pneumoperitoneum . On admission her condition was severe and visceral perforation was strongly suspected . As her parents did not give consent to surgical treatment, only conservative management was introduced . Peritoneal dialysis was continued and the girl responded well to antibacterial therapy . The final outcome was favourable.

Reumatismo, 2001, 53(4), 309 - 311
{Chronic osteomyelitis: a new therapeutical idea}; Carlino G et al.; We studied the case of a male patient aged 43 affected by post-traumatic chronic osteomyelitis with frequent relapses . Having supposed an insufficiency of the arterial and venous microcirculation in perilesional bone and soft tissue we decided for a therapy with iloprost and antibacterial drugs . After 15 months of treatment the patient hasn't showed any clinically evident relapsing episodes and we have not reported any side effects related to the therapy.

Nat Biotechnol, 2002 Jul, 20(7), 713 - 6
Genetic engineering of aminodeoxyhexose biosynthesis in Streptomyces fradiae; Butler AR et al.; The antibacterial properties of macrolide antibiotics (such as erythromycin, tylosin, and narbomycin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones . Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose) . Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as narbomycin) have only single sugar substituents . As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses . Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the narbomycin producer Streptomyces narbonensis . This engineered S . fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.

Curr Opin Immunol, 2002 Aug, 14(4), 452 - 7
Control of Mycobacterium tuberculosis through mammalian Toll-like receptors; Stenger S et al.; An efficient immune response against the intracellular pathogen Mycobacterium tuberculosis is critically dependent on rapid detection of the invader by the innate immune response and the activation of the adaptive immune response . Toll-like receptors (TLRs) contribute to innate immunity by the detection of Mycobacteria-associated molecular patterns and mediating the secretion of antibacterial effector molecules . TLRs influence the adaptive immune response by upregulation of immunomodulatory molecules supporting the development of a Th1-biased T cell response . In this manner, activation of TLRs contributes to defense against microbial infection.

J Nat Prod, 2002 Jun, 65(6), 916 - 9
Decipinin A and decipienolides A and B: new bioactive metabolites from the coprophilous fungus Podospora decipiens; Che Y et al.; Decipinin A (1), a new compound with antifungal and antibacterial activity, has been isolated from liquid cultures of the coprophilous fungus Podospora decipiens (JS 270) . Two new tetracyclic sesquiterpene lactones, decipienolides A (2) and B (3), were also obtained from this isolate as an inseparable mixture of epimers that showed antibacterial activity . The structures of 1-3 were elucidated by analysis of 1D and 2D NMR data, aided by chemical shift comparisons to related compounds.

J Nat Prod, 2002 Jun, 65(6), 876 - 82
Biologically active polyketide metabolites from an undetermined fungicolous hyphomycete resembling Cladosporium; Holler U et al.; Eight new polyketide-derived metabolites {cladoacetals A and B (1 and 2), 3-(2-formyl-3-hydroxyphenyl)propionic acid (3), 3-deoxyisoochracinic acid (4), isoochracinol (5), 7-hydroxy-3-(2,3-dihydroxybutyl)-1(3H)-isobenzofuranone (6), (+)-cyclosordariolone (10), and altersolanol J (11)} and six known metabolites {two isomeric 1-(1,3-dihydro-4-hydroxy-1-isobenzofuranyl)butan-2,3-diols (7a/b), 7-hydroxy-1(3H)-isobenzofuranone (8), isoochracinic acid (9), altersolanol A (12), and macrosporin (13)} have been isolated from solid-substrate fermentation cultures of an undetermined fungicolous isolate (NRRL 29097) that resembles Cladosporium sp . All structures were assigned primarily by analysis of 1D and/or 2D NMR data . Five of the compounds showed antibacterial activity.

Klin Med (Mosk), 2002, 80(5), 13 - 8
{Effectiveness of ulcer treatment with electromagnetic radiation of extremely high frequency (EHF therapy) and some mechanism of its therapeutic action}; Tsimmerman IaS et al.; A clinical response to and some mechanisms of therapeutic action of extremely high frequency (EHF) therapy were studied in 132 patients with exacerbation of duodenal ulcer vs routine pharmacological treatment . EHF-therapy was used alone and in combination with famotidin (antisecretory drug) and norfloxacine (antibacterial drug) . EHF monotherapy proved highly effective in duodenal ulcer exacerbation . It normalizes secretory and motor functions of the stomach, suppresses initially high activity of free radical lipid oxidation, corrects abnormal vegetative and psychoemotional status of the patients, moderately potentiates the antihelicobacter effect of antibacterial drugs . These effects are produced due to specific action of EHF therapy: mobilisation of sanogenesis mechanisms, correction of mechanisms of adaptive regulation and self regulation at different levels . Additional administration of antisecretory and antibacterial drugs improved immediate but deteriorates long-term response to EHF-therapy.

Infez Med, 2001 Dec, 9(4), 193 - 211
{Role of parenteral cephalosporins for outpatients treatment of infections}; Esposito S et al.; OPAT (Outpatient Parenteral Antibiotic Therapy) arose in the early !980s in the USA and later in many other countries from the primary consideration that outpatient treatment is more cost-effective than hospitalisation . Currently, several thousand patients undergo OPAT programmes all over the world and several different bacterial infections are included in the list of treatable diseases, especially those requiring long-term parenteral treatment such as osteomyelitis and soft tissue infections . All injectable antibiotics are suitable for OPAT according to their microbiological spectrum, although clearly some pharmacological properties make one antibiotic more preferable than another . Beta-lactams represent more than half of the antibiotic world market and two-thirds of them are cephalosporins . Such a widespread use of cephalosporins is certainly due to their wide antibacterial spectrum and good tolerability . Among third-generation cephalosporins, covering the majority of micro-organisms responsible for community-acquired infections, ceftriaxone is the only one with an 8-hour half-life, thereby permitting a single daily dose, which represents a great advantage when undertaking an OPAT programme . Analysis of antibiotic consumption used for OPAT therapies, based on data collected from the International OPAT Registry project, with the participation of many countries (USA, Canada, Britain, Argentina, etc.) including Italy, shows that ceftriaxone is the most widely used antibiotic for home therapy, clearly due to the above-mentioned properties.

Biomed Sci Instrum, 2002, 38, 245 - 50
A new method of tightening halo orthosis pins that reduces initial pin force variation; Klingenberg J et al.; The halo orthosis is a medical device used to immobilize the cervical spine when an injury to the region is sustained . This device consists of a halo vest, support rods, a ring, and four pins that contact the skull . The halo is applied to the patient by securing the halo ring to the skull with four pointed pins that are threaded into a halo ring . In an effort to produce a desired initial force in each pin, a specified torque (typically 0.9 N-m) is applied to the pin . One problem associated with the existing method is that it produces a wide range of initial pin forces despite a constant applied torque . The existing method is particularly sensitive to the presence of medical agents (e.g . antibacterial ointments or hydrogen peroxide) that may change frictional characteristics at the pin site or at the threaded hole in the halo ring . Variability in initial forces from an applied torque of 0.9 N-m (8 in-lbf) have been reported in the literature . These forces vary from 620 N (140 lbf) when hydrogen peroxide is applied to the threads and pin site up to 980 N (220 lbf) when antibacterial ointment is applied to the threads and pin site . We present a new method of tightening halo pins that reduces the variability of the initial pin force . Using the new method, a known force is applied to the pin to provide a preload . Once the appropriate preload is applied, the halo pin is secured in place relative to the halo ring and the applied force is removed leaving the pin in the final configuration . We compare the existing method and the new proposed method by examining a single pin site . The pin force data display less sensitivity to lubricants using the new direct loading technique.

Eur J Pharm Biopharm, 2002 Jul, 54(1), 51 - 8
Determination of lipophilicity of two quinolone antibacterials, ciprofloxacin and grepafloxacin, in the protonation equilibrium; Sun J et al.; The objective of this study was to compare protonation equilibrium and lipophilicity of two quinolone antibacterials, grepafloxacin (GPFX) and ciprofloxacin (CPFX), in order to give an insight into effects on the physicochemical properties by slight structural motifs . The protonation equilibrium was investigated by a spectrophotometry . Macro- and micro-dissociation constants were simultaneously determined, based on nonlinear regression analysis using the MULTI program, and then microspecies distribution could be described accordingly . Zwitterionic microspecies predominated at isoelectrical point (pI) for both drugs, and the concentration ratio of neutral to zwitterionic forms was near 4-fold greater for GPFX than that for CPFX . The apparent partition coefficient (D(O/B,pH)) versus pH profiles had the shape of a parabolic curve in an n-octanol/buffer system, and reached the maximum around pI for both, respectively . Moreover, two introduced methyl groups in GPFX increased not only intrinsic lipophilicity but also neutral microspecies fraction relative to CPFX, and D(O/B,pH) of GPFX was consequently far higher than that of CPFX . The results emphasized that there were significant differences in protonation equilibrium and lipophilicity between GPFX and CPFX, which conduced to explaining their different behavior in terms of antibacterial activities and pharmacokinetics.

Biochim Biophys Acta, 2002 Jul 18, 1587(2-3), 145 - 54
Sequence-specific interactions of drugs interfering with the topoisomerase-DNA cleavage complex; Palumbo M et al.; DNA-processing enzymes, such as the topoisomerases (tops), represent major targets for potent anticancer (and antibacterial) agents . The drugs kill cells by poisoning the enzymes' catalytic cycle . Understanding the molecular details of top poisoning is a fundamental requisite for the rational development of novel, more effective antineoplastic drugs . In this connection, sequence-specific recognition of the top-DNA complex is a key step to preferentially direct the action of the drugs onto selected genomic sequences . In fact, the (reversible) interference of drugs with the top-DNA complex exhibits well-defined preferences for DNA bases in the proximity of the cleavage site, each drug showing peculiarities connected to its structural features . A second level of selectivity can be observed when chemically reactive groups are present in the structure of the top-directed drug . In this case, the enzyme recognizes or generates a unique site for covalent drug-DNA binding . This will further subtly modulate the drug's efficiency in stimulating DNA damage at selected sites . Finally, drugs can discriminate not only among different types of tops, but also among different isoenzymes, providing an additional level of specific selection . Once the molecular basis for DNA sequence-dependent recognition has been established, the above-mentioned modes to generate selectivity in drug poisoning can be rationally exploited, alone or in combination, to develop tailor-made drugs targeted at defined loci in cancer cells.

Transfusion, 2002 May, 42(5), 603 - 11
Characterization and functional analysis of granulocyte concentrates collected from donors after repeated G-CSF stimulation; Joos K et al.; BACKGROUND: Neutropenic patients often develop bacterial or fungal infections not responding to broad-spectrum antibacterial or antifungal agents . Clinical efforts were made with transfusion of granulocyte concentrates; however, functions of granulocytes after multiple G-CSF stimulations and after apheresis are not yet investigated and described sufficiently . STUDY DESIGN AND METHODS: The aim of this study was to characterize functional and immunologic variables of granulocytes in blood samples drawn from donors before and after each stimulation episode with G-CSF, in the resulting granulocyte concentrates and in the patients 8 hours after transfusion . RESULTS: Chemotaxis was not influenced, neither by G-CSF application nor by apheresis . Multiple G-CSF stimulations enhanced oxidative burst and phagocytosis of Escherichia coli in donor granulocytes . These values returned to basal levels in granulocyte concentrates . Expression of granulocytic surface antigens was downregulated after application of G-CSF but returned to normal and in part enhanced values in concentrates . A clinically relevant increase of proinflammatory cytokines could not be detected . Leukotriene B4 production was reduced after the fourth G-CSF stimulation in the donor blood and enhanced in the granulocyte concentrate after apheresis . Results in recipients indicate that changes of granulocyte function noted in concentrates were only transient . CONCLUSION: Stimulation of healthy donors with repeated G-CSF injections and subsequent granulocyte apheresis does not dramatically change decisive functions of granulocytes.

Expert Opin Pharmacother, 2002 Jul, 3(7), 857 - 63
Current treatment options for chronic granulomatous disease; Goldblatt D; Chronic granulomatous disease is a rare inherited disorder of phagocytic cells which results in a susceptibility to infections of catalase-positive bacteria and fungi (especially Aspergillus species), as well as granuloma formation . The mainstay of therapy is antibacterial and antifungal prophylaxis . Trimethoprim sulfamethoxazole is the drug of choice for the prevention of bacterial infection, while itraconazole is most widely used for the prevention of fungal infection . Immunomodulatory agents, such as IFN-phi, have a role in the prevention and treatment of intractable infection . New antifungal agents provide the promise of improved cure rates for invasive Aspergillus, while bone marrow transplants and gene therapy may offer the promise of complete cure.

Jpn J Cancer Res, 2002 Jun, 93(6), 677 - 84
Clinicopathologic comparison between the API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type; Nakamura T et al.; Little is known about the clinicopathological differences between API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type . The aim of this study was to clarify those differences in gastric MALT lymphoma . Twenty-three patients with gastric MALT lymphoma were enrolled in a unicenter study . Helicobacter pylori (H . pylori) infection status and clinical stages were investigated . Antibacterial treatment was performed for every patient . Responsiveness of MALT lymphoma to this treatment was assessed by means of regular follow-up endoscopy combined with biopsy . All cases were examined for API2-MALT1 chimeric transcript by means of RT-PCR and sequencing analyses . H . pylori infection status was assessed as positive in 20 patients and negative in three . With regard to responsiveness to antibacterial treatment, complete remission was observed in two patients, partial remission in 12 and no change in nine . API2-MALT1 chimeric transcript was detected in seven patients, all of whom showed no change in response to antibacterial treatment . API2-MALT1 positivity was found to be significantly correlated with responsiveness to antibacterial treatment (P = 0.0001), absence of H . pylori infection (P = 0.0198), and gross cobblestone mucosa observed endoscopically (P = 0.0198) . For the other factors (age, sex, dominant site of lesion, high-grade component, infiltrated layer of gastric wall, nodal involvement or clinical stages), there were no differences between API2-MALT1 chimeric transcript-positive and -negative cases . Gastric API2-MALT1 chimeric transcript-positive MALT lymphoma generally features unresponsiveness to antibacterial treatment, and is thought to be unrelated to H . pylori infection in its pathogenesis . Our findings indicate the presence of different clinical subtypes in gastric MALT lymphomas.

Acta Orthop Scand, 2002 Apr, 73(2), 165 - 9
Bacterial contamination of femoral head allografts from living donors; Vehmeyer SB et al.; We analyzed the bacterial contamination rate of femoral head allografts from living donors and determined the true bacterial load with cultures from the grafts in their entirety in a specially prepared medium . During 4 years we took swab cultures from 2,679 grafts of which 2,414 (90%) were negative . In a period of 12 months, grafts rejected for reasons other than infectious disease were cultured in their entirety to determine the true bacterial load . Of the 106 grafts included, 15 were contaminated . Microorganisms were isolated from 10 of the 91 initially swab culture-negative grafts (9%) and from only 5 of the 15 swab culture-positive grafts, most of which were normal skin contaminants . Swab culture negative grafts apparently may still be contaminated . It seems wise to subject all femoral head allografts from living donors to antibacterial processing.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1998 Feb, 16(1), 26 - 8
{In vitro sensitivity of oral gram-negative bacteria to the bactericidal activity of defensins}; Zhong D et al.; Oral gram-negative bacteria, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga sputigena, Provotella intermedius, Provotella melaninogenicus, have been associated with destructive periodontal infection . An ultrasensitive antibacterial assay was applied to determine the sensitivity of a battery of oral gram-negative bacteria to the bactericidal effects of the isolated human neutrophil defensins (HNP) and two kinds of rabbit defensins NP1 and NP2 . All species tested were killed by HNP, NP1 and NP2 except that porphyromonas gingivalis was resistant to HNP . However, there was strain-to-strain variation in sensitivity . It was concluded that the oral gram-negative bacteria were sensitive to the cidal mechanism involved in defensinmediated bacterial killing.

J Antimicrob Chemother, 2002 Jul, 50 Suppl, 19 - 22
Interstitial tissue concentrations of cefpodoxime; Liu P et al.; Microdialysis is a technique that allows the measurement of concentrations of free antibiotic in tissue . The free antibiotic concentration is responsible for the antibacterial effect at the target site . We used microdialysis in animal and human studies to investigate the tissue penetration of cefpodoxime . In the animal study, total plasma and free muscle and lung concentrations of cefpodoxime were measured after male Wistar rats had received either 10 mg/kg or 20 mg/kg i.v . cefpodoxime over 5 h or a continuous i.v . infusion of 260 microg/h cefpodoxime after a loading dose of 6 mg/kg . Free muscle concentrations of cefpodoxime were similar to free lung concentrations and therefore provided a surrogate measure of cefpodoxime concentrations at the pulmonary target site . In an open, randomized, two-way crossover, single-dose study in six healthy male volunteers, total plasma and free muscle concentrations were measured after a single oral dose of cefpodoxime 400 mg or cefixime 400 mg . The total plasma concentrations of each antibiotic were similar and higher than free muscle concentrations . The tissue penetration of cefpodoxime was, however, greater than that of cefixime, as shown by two-fold higher peak free muscle concentrations after dosing with cefpodoxime than with cefixime (2.1 mg/L versus 0.9 mg/L) . In addition, the area under the curve for tissue (AUC(t)) of cefpodoxime (400 mg) was more than double that of cefixime (400 mg), based on free antibiotic concentrations (15.4 mg x h/L versus 7.3 mg x h/L) . These findings indicate that, taking into account pharmacokinetic/pharmacodynamic considerations, cefpodoxime is likely to be more efficacious than cefixime, due to its greater tissue penetration.

Orv Hetil, 2002 May 26, 143(21), 1207 - 10
{Orbital phlegmone caused by acute exacerbation of chronic fungal pansinusitis in a child}; Fucsek M et al.; INTRODUCTION: Invasive fungal rhinosinusitis is an aggressive, destructive process most commonly affecting immunocompromised hosts with mortality rate of approximately 60-80% . AIM OF STUDY: The authors present a child's recovery of orbital phlegmone due to acute exacerbation of chronic fungal pansinusitis . They call the attention to the possibility of ever more frequent fungal sinusitis in our country . METHODS: Retrospective case report of an 8 years old boy presented with photos . RESULTS: The recovery was promoted by supposing the chance of fungal origin in time . No orbital abscess was found by surgery despite of typical clinical appearance and MRI results . After beginning of antibacterial treatment and functional endoscopic sinus surgery (FESS) the even worsening clinical status of orbital phlegmone raised the possibility of fungal origin, which was verified by mycological examination . The antimycotic treatment, which had been started in time was followed by complete recovery . Due to scarring in the medial rectus muscle, diplopia was the only complication which needs further ophthalmological controls . CONCLUSIONS: Supposition and verification of chance of fungal origin is essential in cases of chronic inflammation of paranasal sinus and/or their complications for complex recovery.

Cornea, 2002 Jul, 21(5), 519 - 23
Fungal keratitis caused by Scedosporium apiospermum: report of two cases and review of treatment; Wu Z et al.; PURPOSE: We report our experience in treating two cases of Scedosporium apiospermum keratitis and provide a review of basic scientific and clinical data regarding the treatment of this visually devastating disease . METHOD: We present a case report and literature review . RESULTS: A 35-year-old woman and a 73-year-old man both reported pain, redness, and a foreign body sensation in the eye after trauma . They were initially treated with antibacterials . When cultures were positive for S . apiospermum, the first patient was treated with fluconazole and amphotericin with good results . The second was treated with fluconazole and natamycin, but the infection persisted and the eye was eventually enucleated . Review of the literature showed variable responsiveness of S . apiospermum to antifungal treatment . CONCLUSIONS: It is difficult to predict how S . apiospermum keratitis will respond to treatment, but miconazole appears to be useful in conjunction with other antifungals . Voriconazole shows promise as an effective alternative.

J Am Coll Nutr, 2002 Jun, 21(3 Suppl), 218S - 221S
Expression of human milk proteins in plants; Lonnerdal B; Human milk proteins are believed to have a multitude of biological activities benefiting the newborn infant . Such functions include antibacterial and antiviral activities, enhancement of the immune system and increased nutrient absorption . To date, only breast-fed infants have been exposed to these proteins . However, by using genetic engineering it is now possible to express these proteins in plants, such as rice, at very high levels . Recombinant human milk proteins can subsequently be added to infant formula and baby foods . Prior to such addition, safety tests and efficacy trials need to be conducted . The safety tests will initially be done in rats and then in humans . The efficacy trials should also evaluate stability against heat treatment (processing), pH (stomach conditions) and proteolytic enzymes (digestion) . To date, we have expressed recombinant human lactoferrin, lysozyme and alpha1-antitrypsin in rice at very high expression levels . These recombinant proteins showed a stability and activities similar to those of the native milk proteins, suggesting that they may be able to exert biological activities in infants when added to formula or baby foods.

Schweiz Arch Tierheilkd, 2002 May, 144(5), 215 - 21
Antifungal effect of Australian tea tree oil on Malassezia pachydermatis isolated from canines suffering from cutaneous skin disease; Weseler A et al.; The lipophilic yeast Malassezia pachydermatis is part of the normal skin flora of most warm-blooded organisms . In a number of surveys it could be demonstrated that this yeast species might be involved in different skin diseases like seborrhoeic dermatitis, especially in dogs and cats . In order to look for an alternative therapeutic agent to the commonly used antimycotic and antiseptic synthetic substances the in vitro activity of Australian tea tree oil, the essential oil of Melaleuca alternifolia, against several strains of Malassezia pachydermatis was examined . All tested strains showed remarkably high susceptibility to tea tree oil . With these results the excellent antibacterial activity of tea tree oil is extended to a new group of fungal pathogens colonizing mainly mammals' skin . During the last ten years there was an increasing popularity of tea tree oil containing human health care products . The presented data open up new horizons for this essential oil as a promising alternative agent for topical use in veterinary medicine as well.

Scand J Infect Dis, 2002, 34(5), 359 - 61
Benefits of management strategy adjustments during an outbreak of enterovirus meningitis in adults; Tattevin P et al.; Enteroviruses (EVs) are the most common identifiable cause of the aseptic meningitis syndrome . Widespread seasonal outbreaks of EV meningitis result in a high financial cost to the community, in part because of the difficulty of discriminating between viral and bacterial meningitis . During a nationwide outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis that a management strategy including early testing of cerebrospinal fluid (CSF) by means of EV PCR in all adult patients with acute aseptic meningitis on admission might reduce the duration of hospitalization and thus the expenditure on health resources . We compared the characteristics of adult patients with acute aseptic meningitis seen in our institution before (n = 21) and after (n = 27) implementation of this strategy . The strategy was cost-effective in that it significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h; p = 0.02) . Systematic testing of CSF in adult patients with aseptic meningitis by means of EV PCR may be cost-effective during an outbreak of EV meningitis.

Bioorg Med Chem Lett, 2002 Jul 8, 12(13), 1723 - 6
A convenient synthetic pathway for multivalent assembly of aminoglycoside antibiotics starting from amikacin; Tanaka H et al.; Vinylpolymers carrying a kanamycin cluster at the side chain were prepared via regioselective N-acylation of amikacin with N-succinimidyl p-vinylbenzoate, followed by radical homo- and co-polymerization with acrylamide . Two independent biological assays disclosed that the polyvalent kanamycin models showed neither antibacterial activity nor inhibitory activity against rRNA-based protein synthesis, suggesting that the multivalency-binding approach is not valid for integrating the potential of aminoglyoside anitibiotics.

Hautarzt, 2002 May, 53(5), 316 - 21
{St . John's wort (Hypericum perforatum L.) . A plant with relevance for dermatology}; Schempp CM et al.; Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective in the treatment of mild to moderate depression . In traditional folk medicine, oily extracts of St . John's wort are used for topical treatment of wounds, burns and myalgia . The lipophilic phloroglucin-derivative hyperforin has antibacterial and antiinflammatory effects . These effects could be of relevance in topical treatment of infected wounds and other dermatoses, but no studies have been conducted so far . The naphtodianthrone hypericin is a photodtodynamic active substance that kills tumor cells via the induction of apoptosis . Hypericin also displays antiviral activity in vitro . In vivo, intravenous or oral treatment with hypericin of HIV-infected subjects did not result in a reduction of the virus load . Most of the patients treated with hypericin experienced phototoxicity . Similar phototoxic symptoms ("hypericism") have been observed in grazing animals ingesting large amounts of St . John's wort . In contrast, antidepressant medication with St . John's wort usually does not produce phototoxic symptoms . Recent pharmacokinetic studies suggest that the phototoxic threshold level of hypericin is not reached with dosages used for the oral treatment of depression . However, very recent reports demonstrated interactions of St . John's wort with other drugs such as digoxin, indinavir and cyclosporin . Blood levels of these drugs were dramatically decreased by St . John's wort . This should be considered in the treatment of skin conditions with antiviral drugs or cyclosporin.

J Pharm Biomed Anal, 2002 Jun 20, 29(1-2), 51 - 9
Second derivative spectrophotometric determination of trimethoprime and sulfamethoxazole in the presence of hydroxypropyl-beta-cyclodextrin (HP-beta-CD); Granero G et al.; An easy and rapid second-derivative spectrophotometric method for the simultaneous analysis of trimethoprime (TMP) and sulfamethoxazole (SM) is described . These drugs have been used as antibacterial against a wide spectrum of organisms and combinations of these drugs are commonly used for the treatment of a variety of infections . The most advantageous approach of this method is the use of HP-beta-CD, which allows to improve the performance of the second-derivative ultraviolet spectrophotometry . For both compounds, a shift of the absorption bands and variations of their intensity were observed . The calibration graphs were linear in the concentration range of TMP (1.92-19.2 microg ml(-1)) and SM (1.60-16.5 microg ml(-1)), the correlation coefficient for the calibration graphs was better than 0.9994 and the precision was satisfactory (CV%< 4.96) in HP-beta-CD solutions . The proposed method was successfully applied to the assay of commercial tablets . The results were compared to those obtained by second-derivative ultraviolet spectrophotometry in the absence of HP-beta-CD . Thereby, the details of the statistical treatment of the analytical data are also presented.

J Pharm Biomed Anal, 2002 Jun 20, 29(1-2), 17 - 33
Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC; Robatel C et al.; Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) . However, there are limited data available to substantial rational dosing decisions in this condition . In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF . The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients . The clean-up procedure involved a SPE on C18 cartridge . Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4 . Meropenem and UK-1a were subsequently desorbed with MeOH . The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4 . Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm . The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min . Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998 . The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a . In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a . The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a . The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations . The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure . The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients . The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.

Pharmacol Biochem Behav, 2002 Jul, 72(4), 953 - 64
Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm); Kennedy DO et al.; Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent . It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease . To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans . The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M . officinalis . Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M . officinalis (Pharmaton) or a matching placebo at 7-day intervals . Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter . In vitro IC(50) concentrations for the displacement of {3H}-(N)-nicotine and {3H}-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated . Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors . Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose . Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.

J Inorg Biochem, 2002 Apr 28, 89(3-4), 203 - 11
Synthesis, cytotoxicity, antibacterial and antitumor activity of platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin; Kushev D et al.; New platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin (achsh) were prepared and characterized . Ab initio calculation of the structure and the measurements of IR and NMR spectra of {Pt(NH(3))(achsh)Cl(2)} were also performed . Quantum-chemical and spectroscopic studies indicated a cis-square planar structure with a hydantoin ligand coordinated via the NH(2) group . The complexes were evaluated for in vitro cytotoxicity in murine erythroleukemia (MEL) cells, clone F4N, as well as for in vivo antitumor activity toward murine L1210 leukemia . The complexes exerted significantly lower in vitro and in vivo toxicities compared with those of cisplatin (cis-diamminedichloroplatinum(II), DDP) . The complex {Pt(NH(3))(achsh)Cl(2)} exhibited antitumor activity against L1210 leukemia, comparable to that of cisplatin, resulting at a dose of 72 mg/kg in a %T/C (increased survival time) of 191% . This complex, as well as cisplatin, induced apoptosis in F4N cells, and exerted antibacterial activity as assessed in 10 bacterial strains.

Surg Today, 2002, 32(5), 414 - 7
Aortocaval fistula complicated with bacteremia due to Escherichia coli: report of a case; Inoguchi H et al.; We herein report a case of aortocaval fistula complicated with bacteremia due to Escherichia coli in a 78-year-old man who underwent an emergency operation . A surgical resection of the abdominal aortic aneurysm with a closure of the fistula, and reconstruction with an expanded polytetrafluoroethylene bifurcated graft and wrapping with an omental flap, were performed followed by a 9-week continuous administration of antibiotics . Thereafter, antifungal agents were administered and the results were good . Both an early diagnosis and prompt surgery are important for such patients, and long-term administration of antibacterial agents is also necessary.

Odontostomatol Trop, 2002 Mar, 25(97), 5 - 10
{In vitro study of chlorhexidine resistance in subgingival bacteria}; Kamagate A et al.; Chlorhexidine is an antibacterial agent of the bisguanide family . It's the most effectual molecule of all antiseptics for oral use . Because of its so frequent use, we have elaborated a protocol in order to estimate the resistance of the sub-gingival flora bacteria to its actions . We have determined the minimal inhibitory concentration of the different observed bacteria species and, have from that stage, progressively increased the concentration at a rate of 5 micrograms/ml . The obtained results show that the bacteria can undergo structural and/or biochemical alterations to adapt to more significant concentrations.

FASEB J, 2002 Aug, 16(10), 1295 - 7 Epub 2002 Jun 07.
Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent Tetrocarcin-A; Tinhofer I et al.; The T-ALL cell lines CCRF-CEM and Jurkat were studied for their sensitivity toward apoptosis induced by tetrocarcin-A (TC-A), an antibacterial and antitumor agent isolated from the actinomycete Micromonospora . This substance promoted cell death via a mitochondrial signaling pathway, that is, by activation of Bid and Bax, loss of the mitochondrial transmembrane potential, release of cytochrome c, and activation of effector caspases, even under conditions of Bcl-2 overexpression . Furthermore, sensitivity to TC-A was not dependent on expression of wild-type caspase-8 . In contrast, this apoptotic pathway was inhibited markedly by pretreatment of cells with cycloheximide, an inhibitor of de novo protein synthesis . cDNA microarray chip analysis revealed that TC-A induced a significant up-regulation of members of the heat shock protein family known to be involved in the endoplasmic reticulum (ER)-stress-induced apoptotic program . The activation of caspase-12, the central inducer caspase involved in ER-stress by TC-A treatment, is in concordance with this result . These results show that, in T-ALL cells, TC-A induces an apoptotic machinery via mitochondrial and ER signaling, which is not inhibited by aberrant expression/function of important regulators of death receptor- and drug-induced apoptosis.

Planta Med, 2002 May, 68(5), 416 - 9
In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots; Friis-Moller A et al.; Licochalcone A, extracted and purified from Chinese licorice roots, showed in vitro inhibitory effect on human pathogenic Mycobacteria species and Legionella species . M . tuberculosis, M . bovis and BCG were inhibited by < 20 mg/l licochalcone A, whereas all non- M . tuberculosis complex species were resistant to > 20 mg/l Legionella pneumophila (serogroups 1 - 7) and L . bozemanii, L . dumoffii, L . feelei, L . longbeacheae and L . wadsworthii were inhibited by licochalcone A 1 - 4 mg/l, whereas L . gormanii and L . micdadei were inhibited by licochalcone A 500 - 1000 mg/l . These data indicate that licochalcone A might be of interest as a new class of antibacterial drug in the treatment of severe lung-infections.

J Immunol, 2002 Jun 15, 168(12), 6232 - 43
Prostaglandin D2 and its metabolites induce caspase-dependent granulocyte apoptosis that is mediated via inhibition of I kappa B alpha degradation using a peroxisome proliferator-activated receptor-gamma-independent mechanism; Ward C et al.; Many inflammatory mediators retard granulocyte apoptosis . Most natural PGs studied herein (e.g., PGE(2), PGA(2), PGA(1), PGF(2 alpha)) either delayed apoptosis or had no effect, whereas PGD(2) and its metabolite PGJ(2) selectively induced eosinophil, but not neutrophil apoptosis . This novel proapoptotic effect does not appear to be mediated via classical PG receptor ligation or by elevation of intracellular cAMP or Ca(2+) . Intriguingly, the sequential metabolites Delta(12)PGJ(2) and 15-deoxy-Delta(12,) Delta(14)-PGJ(2) (15dPGJ(2)) induced caspase-dependent apoptosis in both granulocytes, an effect that did not involve de novo protein synthesis . Despite the fact that Delta(12)PGJ(2) and 15dPGJ(2) are peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activators, apoptosis was not mimicked by synthetic PPAR-gamma and PPAR-alpha ligands or blocked by an irreversible PPAR-gamma antagonist . Furthermore, Delta(12)PGJ(2) and 15dPGJ(2) inhibited LPS-induced I kappa B alpha degradation and subsequent inhibition of neutrophil apoptosis, suggesting that apoptosis is mediated via PPAR-gamma-independent inhibition of NF-kappa B activation . In addition, we show that TNF-alpha-mediated loss of cytoplasmic I kappa B alpha in eosinophils is inhibited by 15dPGJ(2) in a concentration-dependent manner . The selective induction of eosinophil apoptosis by PGD(2) and PGJ(2) may help define novel therapeutic pathways in diseases in which it would be desirable to specifically remove eosinophils but retain neutrophils for antibacterial host defense . The powerful proapoptotic effects of Delta(12)PGJ(2) and 15dPGJ(2) in both granulocyte types suggest that these natural products control the longevity of key inflammatory cells and may be relevant to understanding the control and resolution of inflammation.

Curr Opin Investig Drugs, 2002 Jan, 3(1), 61 - 8
Antibiotics as anti-inflammatory agents; Labro MT; Although the empirical use of some antibacterial agents in various inflammatory diseases has proved beneficial in the past, it is only recently that the therapeutic anti-inflammatory potential of cyclines and macrolides has received attention worldwide . Other drugs like fosfomycin and some quinolones are also contenders for this role . Owing to the complexity of the inflammatory process, which involves many redundant cellular effectors and soluble mediators, and the obscure etiopathogenesis of many inflammatory diseases (some of which may be secondary to persistent infections), the precise mechanisms underlying the therapeutic benefit of anti-inflammatory antibiotics remain to be elucidated . Structure-activity relationships are the key to developing new anti-inflammatory agents derived from antibacterial drugs.

Mutat Res, 2002 Jun, 511(2), 133 - 44
Is metronidazole carcinogenic?
Bendesky A, Menendez D, Ostrosky-Wegman P.
Metronidazole (MTZ, 1-{2-hydroxyethyl}-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs . MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals . However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans . As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor . Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.

Curr Pharm Des, 2002, 8(13), 1091 - 8
Genomics and the prospects for the discovery of new targets for antibacterial and antifungal agents; Isaacson RE; The current increase in the number of microbes resistant to antibacterial or antifungal agents represents a potential crisis in human and veterinary medicine . Some believe that we are entering a post-antibiotic era where most antibiotics no longer will be efficacious . Therefore, it is important that new antibiotics be developed . However, because of the potential for cross-resistance, new targets for the discovery of antibiotics are needed particularly where resistance does not currently exist . The results obtained from the sequencing of genomes from pathogenic bacterial and fungal microbes provide an opportunity to ameliorate this problem . Genomic sequence data can be used to identify new genes that could be used as targets for new antibiotic discoveries . Viable new target genes might represent those that are widely distributed among pathogens or that have homologs and are essential for the viability of the organism . Chemical compounds that attack such targets would be expected to have classical antibiotic activities . Less widely distributed genes still could be valuable targets for narrow spectrum antibiotics . While many of these genes will have known or putative functions based on DNA sequence homology, the most interesting genes are the newly discovered genes with unknown functions . In this paper, it is suggested that novel, non-traditional targets also will be found through the analysis of genome sequences: those that are involved in disease pathogenesis and those that are involved in adaptation and growth in infection sites . The advantage of the non-classical targets is that targeting these sites may not result in the same degree of selective pressure that encourages resistance, and these could have a longer therapeutic life time.

Curr Top Med Chem, 2002 Jul, 2(7), 717 - 31
Cephalosporins in veterinary medicine - ceftiofur use in food animals; Hornish RE et al.; Cephalosporins are an important class of antibacterial agents in use today for both humans and animals . Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin . The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans . A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle . A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use . Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle . Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle . Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults . This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment . The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment . The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals.

Pharmacogenomics, 2002 May, 3(3), 315 - 23
The role of genomics in the discovery of novel targets for antibiotic therapy; Ji Y; The emergence of antibiotic resistance and multi-drug resistance in bacterial pathogens underscores the need for the development of novel classes of antibiotics . The availability of complete genome sequence data from many important human pathogens provides a wealth of fundamental information . This allows us to define each gene and thus to better understand molecular pathogenesis . New techniques have enabled the identification and characterization of genes that are critical for bacterial growth and survival during infection . The combination of genome sequence data and new technologies make it possible to systematically explore the function of each open reading frame in a genome and identify any potential molecular targets for drug discovery . With particular emphasis on antibacterial therapy, this review discusses genome-based technologies and their important applications to anti-infective drug discoveryPublication Types:

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