Acta Crystallogr C, 2002 Jun, 58(Pt 6), o323 - 4 Epub 2002 May 11. The natural diterpenoid kamebanin; Sun CR et al.; Kamebanin, alternatively called rel-(-)-(1R,4R,8S,9R,10S,13S,16R)-2,8,16-trihydroxy-5,5,9-trimethyl-14-methylenetetracyclo{11.2.1.0(1,10).0(4,9)}hexadecan-15-one, C(20)H(30)O(4), is a natural diterpenoid which has cytotoxic and antibacterial activity . The molecule is composed of three six-membered rings, which all adopt chair conformations, and one five-membered ring, which adopts an envelope conformation . The conjugated alpha-methylenecyclopentanone ring is the active part in the molecule due to the ring strain . All three hydroxy groups serve as hydrogen-bond donors and acceptors, forming a continuous two-dimensional network. Vestn Khir Im I I Grek, 2002, 161(1), 19 - 22 {Change in lymphatic circulation of lower extremities and prospects for lymphotrophic therapy in trophic ulcers of venous etiology}; Petrov SV et al.; Investigations of the lymphatic bed of lower extremities by the method of rentgen-contrast lymphography were performed in 64 patients with trophic ulcers of lower extremities and postthrombotic disease . The data obtained by lymphography allowed formation of a group of patients perspective for treatment by lymphotropic antibacterial therapy . The lymphotropic therapy using Gentamycin and Cefazolin resulted in a more rapid arresting of local inflammatory alterations and development of reparative processes in the trophic ulcer area and in normalization of the main clinico-laboratory parameters. Fitoterapia, 2002 Jun, 73(3), 255 - 60 Antibacterial, antifungal activities of Barringtonia asiatica; Khan MR et al.; The crude methanolic extract of Barringtonia asiatica (leaves, fruits, seeds, stem and root barks) and the fractions (petrol, dichloromethane, ethyl acetate, butanol) exhibited a very good level of broad spectrum antibacterial activity . A number of fractions demonstrated antifungal activity against a number of fungi. Fitoterapia, 2002 Jun, 73(3), 251 - 4 Antibacterial activity of Hygrophila stricta and Peperomia pellucida; Khan MR et al.; The crude methanolic extracts of Hygrophila scricta and Peperomia pellucida were fractionated into petrol, dichloromethane, ethyl acetate and butanol . All the crude extracts and the fractions exhibited a very good level of broad spectrum antibacterial activity . The fractions were more active than the crude extracts . The petrol fraction of H . stricta and the butanol fraction of P . pellucida were particularly good . No activity was noticed for the moulds tested. Fitoterapia, 2002 Jun, 73(3), 244 - 50 Antibacterial properties of Thymus pubescens and Thymus serpyllum essential oils; Rasooli I et al.; Antibacterial properties of essential oils of Thymus pubescens and Thymus serpyllum collected at pre and flowering stages were studied . The oils were found to possess bactericidal activities. Helicobacter, 2002 Jun, 7(3), 183 - 91 Additive effect of pronase on the efficacy of eradication therapy against Helicobacter pylori; Gotoh A et al.; BACKGROUND: Helicobacter pylori (H . pylori) colonizes not only the surface of the surface mucous cells but also the surface mucous gel layer (SMGL) . Thus, we examined the possible value of pronase, a mucolytic agent, as a potential eradication therapy . MATERIALS AND METHODS: One hundred and thirty-five patients were randomly assigned to two treatment groups . Sixty-eight patients received 30 mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole thrice daily for 2 weeks (LAM group), while the other 67 patients received the same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily for 2 weeks (LAMP group) . Eradication was assessed 4-6 weeks after treatment by immunohistochemical tests and cultures . We also determined the in vitro activity of pronase against H . pylori, and evaluated the synergistic effects between pronase and the other three drugs . To investigate the effect of pronase on the structure of the SMGL, surgically removed stomachs obtained from patients who had taken pronase were examined histopathologically . RESULTS: The cure rates for H . pylori infection in the LAMP group were significantly higher than those in the LAM group (intention to treat analysis: 94.0 vs . 76.5%, p =.0041) . Pronase exhibited no antibacterial activity against H . pylori., and no in vitro synergistic effects were observed . In the patients who took pronase before surgery, the SMGL was thinner than in the patients who did not take pronase, and the structure of the SMGL was markedly disrupted . CONCLUSIONS: Pronase has an additive effect in curing H . pylori infection . Pronase has no apparent in vitro activity against H . pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL. Insect Biochem Mol Biol, 2002 Jul, 32(7), 795 - 801 Trichoplusia ni gloverin, an inducible immune gene encoding an antibacterial insect protein; Lundstrom A et al.; By using differential display PCR, we obtained a cDNA clone encoding a gloverin homologue from the cabbage looper, Trichoplusia ni . The expression of the gene was induced by bacterial infections . The gene codes for a 174 amino acid residue protein, including a signal sequence and a prosegment . The deduced mature protein is 14 kDa and shows 58% and 49% identity to P2 from Helicoverpa armigera and to Hyalophora gloveri gloverin, respectively . The protein was detected in hemolymph and hemocytes from bacteria-immunized animals . We expressed gloverin using the baculovirus expression system . N-terminal amino acid sequence analysis showed that the purified protein contained a propart . This progloverin inhibited the growth of E . coli and the activity is comparable to that of H . gloveri mature gloverin . Processing of progloverin was possible in vitro, using human furin. Biochemistry, 2002 Jun 11, 41(23), 7217 - 23 DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose; Lafitte D et al.; DNA gyrase is a major bacterial protein that is involved in replication and transcription and catalyzes the negative supercoiling of bacterial circular DNA . DNA gyrase is a known target for antibacterial agents since its blocking induces bacterial death . Quinolones, coumarins, and cyclothialidines have been designed to inhibit gyrase . Significant improvements can still be envisioned for a better coumarin-gyrase interaction . In this work, we obtained the crystal costructures of the natural coumarin clorobiocin and a synthetic analogue with the 24 kDa gyrase fragment . We used isothermal titration microcalorimetry and differential scanning calorimetry to obtain the thermodynamic parameters representative of the molecular interactions occurring during the binding process between coumarins and the 24 kDa gyrase fragment . We provide the first experimental evidence that clorobiocin binds gyrase with a stronger affinity than novobiocin . We also demonstrate the crucial role of both the hydroxybenzoate isopentenyl moiety and the 5'-alkyl group on the noviose of the coumarins in the binding affinity for gyrase. J Chemother, 1991 Jan, 3 Suppl 1, 51 - 3 Evaluation of pefloxacin activity against recent clinical isolates; Lembo M et al.; The in-vitro antibacterial activity of pefloxacin, a new quinolone carboxylic acid, was tested against 1140 bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations . Comparisons were made with other quinolones (enoxacin, norfloxacin, flumekin, oxolinic acid, pipemidic acid) and other drugs (piperacillin, cefotaxime, ceftazidime, gentamicin, tobramycin, amikacin) widely used for the treatment of bacterial infections . Pefloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean of MICs, a MIC 50 and MIC 90 of 0.27, 0.12 and 4 microg/ml respectively. J Chemother, 1991 Jan, 3 Suppl 1, 39 - 42 Microbiological profile of teicoplanin; Covelli I et al.; The in-vitro antibacterial activity of teicoplanin, a new glycopeptide antibiotic, previously named teichomycin A2, was tested against 258 gram-positive anaerobic bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations . Comparisons were made with other drugs, clindamycin, rifampicin, netilmicin, enoxacin, vancomycin, widely utilized for the treatment of bacterial infections . Teicoplanin was very active against the tested species and showed the highest activity against all the tested strains, with a geometric mean of MICs, a MIC 50 and MIC 90 of 0.125, 0.12 and 0.5 microg/ml, respectively. J Chemother, 1991 Jan, 3 Suppl 1, 182 - 9 Antibiotics and mucous membrane: pharmacokinetic aspects; Fraschini F et al.; The penetration of chemoantibiotic agents across the mucous membrane is affected by several factors, some of which are related to the drug and others to the membrane . Molecular weight can influence the penetration of chemoantibiotic agents into mucous membranes . Liposolubility is another factor which can enhance the penetration of chemoantibiotic agents . Factors related to the membrane can affect diffusion of the antibiotic . Inflammation of the mucous membrane enhances the volume of blood circulating within tissues and, as a consequence, the rate of drug penetration into them . This condition, however, can be counterbalanced by a high binding rate of the drug to tissues . The pH affects the action of antibacterial agents . Acid pH range enhances the antibacterial activity of beta-lactams, an alkaline range that of macrolides . Besides purely physiochemical factors, there are others able to interfere with the diffusion of a chemoantibiotic agent into and through the mucous membranes . The diffusion into bronchial membrane and the penetration through the hematobronchial barrier seems to occur substantially by means of a passive transfer . There is therefore an establishment of a proportionality relationship between the concentrations in the two blood-bronchial fluid compartments . Exceptions to this rule seem to be some drugs like macrolides, even if a real active transfer mechanism has not yet been demonstrated . A precise knowledge of its pharmacokinetic parameters is an indispensable condition for the characterization of a molecule which penetrates the mucous membranes. Arzneimittelforschung, 2002, 52(4), 286 - 93 Syntheses, antibacterial, cytotoxic and antifungal effects of new 3-carboxy-l-phenacylpyridinium salts; Khan KM et al.; Thirteen pyridine-3-carboxylic acid salt derivatives with various substituted phenacyl residues were prepared and their cytotoxicity, antibacterial and antifungal activities tested . Compounds 5 and 11 proved to be active in the brine shrimp bioassay, compounds 7, 9-12 and 14 showed promising antibacterial activities, whereas none of the compounds tested against 15 fungal cultures proved to be active . Extensive spectroscopic techniques were employed to confirm the structure of the synthetic products. Rheumatol Int, 2002 Apr, 21(6), 227 - 33 Predominance of IgG1 and IgG3 subclasses of autoantibodies to neutrophil cytoplasmic antigens in patients with systemic lupus erythematosus; Manolova I et al.; The IgG subclasses displayed by antibodies to four neutrophil cytoplasmic antigens were studied in 20 patients with systemic lupus erythematosus (SLE) by solid-phase enzyme immunoassays and monoclonal antibodies to human IgG subclasses . The IgG subclass reactivity of antineutrophil cytoplasmic antibodies (ANCA) was measured in six sera containing antiproteinase3 (PR3) antibodies, in five sera containing antimyeloperoxidase (MPO) antibodies, in sera containing antibactericidal/permeability-increasing protein (BPI) antibodies, and in ten sera containing antilactoferrin (LF) antibodies . The IgG subclass distribution of anti-dsDNA antibodies in eight sera was examined as well . IgGI was the predominant subclass for MPO-ANCA and LF-ANCA, whereas IgG1/IgG3 contributed mainly to anti-PR3, anti-BPI antibodies, and anti-dsDNA antibodies . In addition, we found elevated levels of the total IgG1 and IgG3 isotypes in the sera of our patients . Our results demonstrated a predominance of IgG1/IgG3 ANCA in SLE, suggesting that the isotype distribution of ANCA is a feature of antibody production in this disease. Chem Pharm Bull (Tokyo), 2002 May, 50(5), 594 - 9 A cosolvency model to predict solubility of drugs at several temperatures from a limited number of solubility measurements; Jouyban A et al.; A cosolvency model to predict the solubility of drugs at several temperatures was derived from the excess free energy model of Williams and Amidon . The solubility of oxolinic acid, an antibacterial drug, was measured in aqueous (water+ethanol) and non-aqueous (ethanol+ethyl acetate) mixtures at several temperatures (20, 30, 35, 40 degrees C) . Oxolinic acid displays a solubility maximum in each solvent mixture at solubility parameter values of 32 and 22 MPa(1/2) . The temperature and heat of fusion were determined from differential scanning calorimetry . The solvent mixtures do not produce any solid phase change during the solubility experiments . The experimental results and those from the literature were employed to examine the accuracy and prediction capability of the proposed model . An equation was obtained to represent the drug solubility changes with cosolvent concentration and temperature . The model was also tested using a small number of experimental solubilities at 20 and 40 degrees C showing reasonably accurate predictions . This is important in pharmaceutics because it save experiments that are often expensive and time consuming. Mutat Res, 2002 May 27, 517(1-2), 113 - 21 In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation; Itoh S et al.; The photochemical clastogenic potential of 12 quinolone antibacterial agents with or without light irradiation was assessed by an in vitro chromosomal aberration test using cultured CHL cells . Exposure to all test compounds, except for DK-507k, increased the incidence of cells with structural aberrations excluding gap (TA) following light irradiation . Test compounds used in the present study under light irradiation were divided into three groups based on their ED(50) values, doses inducing chromosomal aberrations in 50% of cells . The first group with ED(50) values below 30 microg/ml includes sparfloxacin (SPFX), clinafloxacin (CLFX), gemifloxacin (GMFX), lomefloxacin (LFLX), sitafloxacin (STFX), grepafloxacin (GPFX) and fleroxacin (FLRX); the second group with ED(50) values of 100 microg/ml, enoxacin (ENX) and levofloxacin (LVFX); the third group with little or no potency, moxifloxacin (MFLX), trovafloxacin (TVFX) and DK-507k . The photochemical clastogenicity of these compounds correlates well with their reported in vivo phototoxic potentials . In the chemical structure and clastogenicity relationships, substitution of a methoxy group at the C-8 position in the quinolone nucleus was confirmed to reduce not only photochemical clastogenicity, but also the clastogenic potential of quinolone antibacterial agents. J Inorg Biochem, 2002 Jun 7, 90(3-4), 113 - 26 Synthesis, characterization and X-ray structures of new antiproliferative and proapoptotic natural aldehyde thiosemicarbazones and their nickel(II) and copper(II) complexes; Belicchi Ferrari M et al.; Synthesis and characterization of new thiosemicarbazones derived from natural aldehydes (1-9) have been investigated in order to develop a research program aimed at the development of compounds with antiviral, antibacterial, and antitumor properties . These substances contain both a chain with N and S nucleophilic centers with tuberculostatic activity, and an alkyl or terpenic moiety . In addition, a few nickel(II) and copper(II) complexes (10-18), derived also from the previously studied ligands, were synthesized and characterized by means of NMR and IR techniques . The trans-2-octenal N(1)-phenylthiosemicarbazone and its nickel complex were also characterized by X-ray diffractometry . Biological studies, performed with some of these compounds, have involved both inhibition of cell proliferation and apoptosis tests in vitro on human leukemia cell line U937 to deepen our knowledge on the way these substances interfere with biological processes in leukemic cells. Dev Comp Immunol, 2002 Jul, 26(6), 495 - 503 An azurocidin-like protein is induced in Trichoplusia ni larval gut cells after bacterial challenge; Kang D et al.; Trichoplusia ni immune genes up-regulated in response to bacterial infection have been isolated using differential display polymerase chain reaction . Here we report the cloning and characterisation of a gut-specific immune gene encoding an azurocidin-like protein . The deduced protein is 317 amino acid residues long with a hydrophobic C-terminus and a predicted 17-residue signal peptide . The mature T . ni protein shows 30% identity to human azurocidin, an antibacterial protein . Like azurocidin, the T . ni protein contains two amino acid substitutions in the active site triad normally present in serine proteases . The T . ni protein was synthesised with a six-histidine C-terminal extension using the baculovirus expression system . Sequencing of the recombinant azurocidin-like protein confirmed the predicted cleavage of the signal peptide . Northern blots show that T . ni azurocidin-like protein is expressed solely in the larval gut and that expression is up-regulated by injecting or feeding bacteria . Expression reaches its highest level at 10 h after bacteria injection. J Nat Prod, 2002 May, 65(5), 714 - 7 New eremophilenolides from Ligulariopsis shichuana; Wang W et al.; Four new eremophilenolides, 1-4, have been isolated from the whole plant of Ligulariopsis shichuana . Their structures were elucidated by spectroscopic methods, including 2D NMR experiments . Structures of compounds 1 and 2 were unequivocally established by X-ray diffraction experiments . All of these sesquiterpenes have eremophilane skeletons with 7(11)-en-8(12) lactone units . Compounds 1 and 2 showed moderate antibacterial activities against E . coli and B . subtilis. Acta Pol Pharm, 2002 Jan-Feb, 59(1), 77 - 9 Synthesis and tumoricidal activity evaluation of new morin and quercetin sulfonic derivatives; Krol W et al.; Flavonoids are a group of naturally occurring compounds with interesting medical properties, such as antiinflammatory, antiallergic, antiviral, antibacterial and antitumor activities . In our experiments we were trying to examine the tumoricidal activity of newly synthesized derivatives of two flavonoids: 3,5,7,2',4'-pentahydroxyflavone (morin) and 3,5,7,3',4'-pentahydroxyflavone (quercetin) . These derivatives were: natrium salt of morin-5'-sulfonic acid (NaMSA), natrium salt of quercetin-5'-sulfonic acid (NaQSA), complex of Mg2+ with quercetin-5'-sulfonic acid (QSA), complex of iron(II) with QSA . The antitumor activity of these agents was tested in vitro on two cell lines: L1210--murine lymphocytic leukaemia and P-815--murine mastocytoma . Our experiments showed that sulfonic derivatives of these two flavonoids were less potent than the original agents in their cytostatic and cytotoxic activities . However, their solubility in water was greater than that of the original agents and higher culture medium concentration of these derivatives was obtained . The results indicate that the ability of flavonoids to act tumoricidally is reciprocally correlated with their lipophilicity. Hindustan Antibiot Bull, 1999 Feb-Nov, 41(1-4), 17 - 21 Activity of some plant extracts against dermatophytes; Lachoria R et al.; The occurrence of fungal diseases is a serious problem of the present medicine because of the development of drug resistance against the antifungal activities in the pathogen . As compared to antibacterial antibiotics, there are only a few antibiotics which are used against fungal infection besides there is a serious problem of the development of resistance in fungal pathogen against the known antifungals, hence there seems a great demand of some alternative chemotherapeutic agent . The possibility of getting certain active principle in plants are immense, earlier workers have shown the presence of antifungal activity in various plants of varied nature suggest that the search for antifungal of plant origin should continue to explore their potential. Klin Khir, 2002 Feb, (2), 15 - 8 {Pharmacotherapeutic aspects of early postoperative period in patients with complicated gastroduodenal ulcer}; Korotkyi VM et al.; There were analyzed the immediate and remote results of treatment of 556 patients with complicated gastroduodenal ulcer, in whom radical operation and ulcer excision with various variants of medicinal correction in early postoperative period were performed . The best immediate result was achieved after performance of radical operation (vagotomy, thrifty gastric resection) . But in 5-10 years after vagotomy performance the ulcer recurrency have occurred in 11.3% of observations . Excision of the ulcer morphological substratum in combination with antiulcer medicinal therapy in early postoperative period constitutes an alternative method of treatment of such patients . Important role of Helicobacter pylori in the ulcer complications occurrence was established, demanding application of antibacterial preparations . Of many schemes of antibacterial therapy existing preference should be given to combination of macrolides (clarythromycine) with nitroimidazole (tinidazole) and the proton pump inhibitors (pylobact) as most secure and quite effective one. Acta Paediatr, 2002, 91(3), 339 - 47 Off-label use of drugs in Italy: a prospective, observational and multicentre study; Pandolfini C et al.; The aims of the study were to measure the paediatric, off-label use of drugs in the Italian hospital setting and to reveal areas for priority intervention by investigating the therapeutic indications most involved . Prescriptions given to all children admitted to nine general paediatric hospital wards from December 1998 to February 1999 were analysed . In total, 4265 prescriptions were given to 1461 children, 10 of which were unlicensed and excluded from further analysis . Sixty percent of prescriptions (range between centres: 44-71%) were off-label and concerned 89% of children receiving medications (80-96%) . The main drug classes were antibacterials, antiasthmatics and analgesics, and represented 56% of off-label prescriptions . Paracetamol (385 prescriptions) and beclomethasone (339) were the generic substances most often used off-label . The most common off-label categories were dosage/frequency (50% of prescriptions), indication and lack of paediatric licence (7% each) . Fifty-four per cent of all indications that led to off-label prescribing involved only respiratory problems, fever, respiratory tract infections and bronchospasm . CONCLUSIONS: Despite prescription profile differences among centres, off-label use was high everywhere . Immediate action for more rational drug use is necessary and requires not only regulatory intervention but also a more evidence-based, therapeutic approach. Curr Pharm Biotechnol, 2002 Jun, 3(2), 63 - 75 Bifunctional penicillin-binding proteins: focus on the glycosyltransferase domain and its specific inhibitor moenomycin; Di Guilmi AM et al.; Beta-lactams and glycopeptides antibiotics directed against enzymes involved in bacterial cell wall synthesis have generated bacterial resistance . Search for new antibiotic molecules is widely focused on bifunctional Penicillin-Binding Proteins (PBPs), with particular emphasis on their glycosyltransferase activity . This function catalyzes glycan chain polymerization of the cell wall peptidoglycan . This review summarizes recent results about biochemical characterization of bifunctional PBPs and enzymatic properties of the glycosyltransferase domain . Moenomycin, a well studied glycosyltransferase activity inhibitor has provided useful informations about lipid binding properties and about cellular role of bifunctional PBPs . These enzymes were shown to be a part of the multienzymatic complex involved in peptidoglycan biosynthesis . Furthermore, bifunctional PBPs are also present in the protein complex located at the site of septation during cell division . The glycosyltransferase domain of bifunctional PBPs remains unsufficently characterized: the structural analysis may lead to the development of novel antibacterials and to the understanding of the enzymatic properties, while genetic and cellular studies focused on bifunctional PBPs will provide a wealth of knowledge regarding cell growth and division. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2002 May, 34(3), 305 - 10 {Purification and characterization of L-amino acid oxidase from Agkistrodon halys pallas venom}; Liu JW et al.; L-amino acid oxidase (LAO, EC 1.4.3.2) is widely found in snake venoms and is thought to contribute to the toxicity in envenoming . By using of Sephadex G-150, DEAE-Sepharose CL-6B and FPLC Superose 12 chromatography, a protein with L-amino acid oxidase activity was purified and characterized from Agkistrodon haly Pallas venom . Its molecular mass was 57 kD as determined by SDS-PAGE analysis under both reducing and non-reducing conditions, and its pI was about 4.9.The protein catalysed the stereospecific oxidative deamination of L-amino acid substrate . It inhibited the platelet aggregation induced by ADP and collagen dose-dependently, even at low concentrations of 0.2 micromol/L and 0.08 micromol/L, respectively . The LAO had antibacterial effect to E.coli K12D31, and the effective concentration was as low as 0.03 g/L . Furthermore, the LAO showed cytotoxicity in crystal violet assay and apoptosis-inducing activity in the A549 cells . After 24h treatment with 5 mg/L LAO, the typical DNA fragmentation pattern of apoptotic cells was observed by using of agrose gel electrophoresis. Yao Xue Xue Bao, 1998 May, 33(5), 392 - 5 {Synthesis and antibacterial activity of 7-substituted-1-ethyl(2-fluoro-ethyl)-6,8-difluoro-1,4-dihydro-4- oxoquinoline-3-carboxylic acid}; Yan L et al.; Eighteen 7-substituted-1-ethyl (2-fluoroethyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid were designed and synthesized . The results of preliminary antibacterial test showed that most of the compounds exhibited definite activities in test against pathogenic bacteria . Especially, compound 17 and 18 showed better activities and surpassed fleroxacin when compared in vitro. Yao Xue Xue Bao, 1998 Jul, 33(7), 498 - 501 {Studies on QSAR of the antibacterial agents quinolones: changing the parent nucleus influenced the activity}; Li J et al.; By the method of AM1, quantum chemistry indexes of 16 compounds of quinoline, 1,8-naphthyridine and pyrido(2,3-C)pyridazine analogues were calculated and 4 QSAR equations were obtained . The results showed that the net charge of 4-carbonyl oxygen is highly correlated with the antibacterial activity in vitro, the correlation coefficient of the regressions are high(R > or = 0.96) . The antibacterial activity in vitro is strongly influenced by the coplanarity of 3-carboxylic acid and the parent nucleus . In light of this study, a new parent nucleus of isothiazoleannexed quinolizine was proposed, which is expected to have much higher activity. Yao Xue Xue Bao, 1998 Sep, 33(9), 675 - 81 {Studies on pyridonecarboxylic acids as antibacterial agents . XIV . Synthesis and structure-activity relationships of 7,8-disubstituted-1-cyclopropyl-6-methyl-1,4-dihydro-4-oxo-3-quinoline carboxylic acids}; Wang H et al.; Eighteen pyridonecarboxylic acids, characterized by a methyl group at the C6-position instead of the usual fluorine atom, cyclopropyl at the N1-position, substituted amino groups at the C7-position, and some substituted groups (hydrogen, chlorine, nitro and amino) at the C8-position, were synthesized . The in vitro antibacterial activity of these compounds were tested, and the structure-activity relationships were also discussed . The results of the study showed that the activity of compounds 22 and 24 were less potent than that of ciprofloxacin against S . aureus, S . epidermidis, E . coli and P . aeruginosa, while they were 2-100 times more potent than ciprofloxacin against K . pneumoniae, S . marcescens, A . calcoacetous, E . aerogenes, S . typhi and S . typhimurium. Morfologiia, 2001, 120(6), 37 - 41 {Morphological variants of neutrophilic granulocytes in blood of practically normal humans}; Saprykin VP et al.; Verification of presumed inertness of blood neutrophil granulocytes revealed their morphological heterogeneity in practically healthy donors . At light microscopic level it was expressed as a varying degree of cell cytoplasm granularity--58% of the cells were highly granular, 30% contained moderate amount of granules and 12% were completely devoid of granules . According to the ultrastructural analysis, neutrophils were subdivided into four groups: intact cells (60%), cells with slight (26%), moderate (12%) and severe (2%) changes . The criteria for this classification included changes in neutrophil shape and ultrastructure during its activation: formation of pseudo- and lobopodia, spatial redistribution of organelles, degranulation etc . Presence of neutrophils with the signs of activation in the circulation suggests that the neutrophil system normally is not inert, but is in a state of so-called working tone, thus providing high antibacterial resistance of the macroorganism exposed to natural bacterial environment. Drug Saf, 2002, 25(5), 345 - 72 Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management; Moore DE; The interaction of sunlight with drug medication leads to photosensitivity responses in susceptible patients, and has the potential to increase the incidence of skin cancer . Adverse photosensitivity responses to drugs occur predominantly as a phototoxic reaction which is more immediate than photoallergy, and can be reversed by withdrawal or substitution of the drug . The bias and inaccuracy of the reporting procedure for these adverse reactions is a consequence of the difficulty in distinguishing between sunburn and a mild drug photosensitivity reaction, together with the patient being able to control the incidence by taking protective action . The drug classes that currently are eliciting a high level of adverse photosensitivity are the diuretic, antibacterial and nonsteroidal anti-inflammatory drugs (NSAIDs) . Photosensitising chemicals usually have a low molecular weight (200 to 500 Daltons) and are planar, tricyclic, or polycyclic configurations, often with heteroatoms in their structures enabling resonance stabilisation . All absorb ultraviolet (UV) and/or visible radiation, a characteristic that is essential for the chemical to be regarded as a photosensitiser . The photochemical and photobiological mechanisms underlying the adverse reactions caused by the more photoactive drugs are mainly free radical in nature, but reactive oxygen species are also involved . Drugs that contain chlorine substituents in their chemical structure, such as hydrochlorthiazide, furosemide and chlorpromazine, exhibit photochemical activity that is traced to the UV-induced dissociation of the chlorine substituent leading to free radical reactions with lipids, proteins and DNA . The photochemical mechanisms for the NSAIDs that contain the 2-aryl propionic acid group involve decarboxylation as the primary step, with subsequent free radical activity . In aerated systems, the reactive excited singlet form of oxygen is produced with high efficiency . This form of oxygen is highly reactive towards lipids and proteins . NSAIDs without the 2-arylpropionic acid group are also photoactive, but with differing mechanisms leading to a less severe biological outcome . In the antibacterial drug class, the tetracyclines, fluoroquinolones and sulfonamides are the most photoactive . Photocontact dermatitis due to topically applied agents interacting with sunlight has been reported for some sunscreen and cosmetic ingredients, as well as local anaesthetic and anti-acne agents . Prevention of photosensitivity involves adequate protection from the sun with clothing and sunscreens . In concert with the preponderance of free radical mechanisms involving the photosensitising drugs, some recent studies suggest that diet supplementation with antioxidants may be beneficial in increasing the minimum erythemal UV radiation dose. Anticancer Res, 2002 Mar-Apr, 22(2A), 809 - 14 The effect of taurolidine on brain tumor cells; Stendel R et al.; BACKGROUND: Although an inhibiting effect of the antibacterial substance taurolidine on several tumor cell lines was suggested in 1990, no specific research has been performed concerning its effect on brain tumor cells . MATERIALS AND METHODS: Monolayers of rat-derived C6 glioma, mouse-derived HT22 neuronal tumor, and human-derived U373 astrocytoma/glioblastoma cell lines were cultured and incubated with 1 microg/ml to 4 mg/ml of taurolidine . Neuronal and glial brain cells were obtained from rat fetuses at day 15 of gestation and incubated with taurolidine to investigate its effect on normal brain cells . RESULTS: Following incubation with taurolidine, the tumor cells started to shrink and to become denser . Ultrastructurally, shrinkage of cytoplasm and condensation and marginalization of chromatin could be observed . Exposure to taurolidine at concentrations of 2.8 microg/ml to 2 mg/ml led to cell death of the evaluated tumor cell types . Results of flow cytometry suggested a fragmentation of DNA . Phosphatidylserine expression increased from 6% to 25% following exposure to taurolidine at a concentration of 25 microg/ml . Normal brain cells did not show any significant changes following incubation with taurolidine . CONCLUSION: The characteristics identified by light and electron microscopy and the data obtained by flow cytometry indicate an apoptotic mechanism of cell death via currently unknown pathways . Taurolidine was found to have a direct and selective antineoplastic effect on glial and neuronal brain tumor cells in vitro. J Antibiot (Tokyo), 2002 Mar, 55(3), 322 - 36 Synthesis and anti-Helicobacter pylori activity of pyloricidin derivatives I . Structure-activity relationships on the terminal peptidic moiety; Hasuoka A et al.; The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori . In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H . pylori activity . The derivatives bearing alpha-D-, beta- and gamma-amino acids or peptidemimetics showed drastically decreased activity . On the other hand, the derivatives with a-L-amino acids were found to maintain the activity . Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H . pylori activity, with an MIC value of less than 0.006 microg/ml against H . pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C. Ann Med, 2002, 34(1), 19 - 27 The antiangiogenic properties of bactericidal/permeability-increasing protein (BPI); van der Schaft DW et al.; Inhibition of angiogenesis is regarded as a promising tool in the treatment of diseases such as cancer, arthritis and atherosclerosis . This fact has led to the search for novel endogenous or synthetic angiogenesis inhibitors . Recently, antiangiogenic properties were ascribed to an endogenous molecule that until only recently was known for its antibacterial effects . This molecule, bactericidal/permeability-increasing protein (BPI), that was discovered as a bacterial permeabilizing and lipopolysaccharide-neutralizing protein, was found to inhibit angiogenesis by specific induction of apoptosis in endothelial cells . This paper gives a short introduction on angiogenesis and reviews the current knowledge on BPI as an angiogenesis inhibitor . In addition, the issue of commonality between antibacterial and antiangiogenic functions will be addressed. Dermatology, 2002, 204 Suppl 1, 92 - 5 Ocular applications of povidone-iodine; Isenberg SJ et al.; Ocular infections can have devastating consequences and may lead to blindness . Povidone-iodine (PVP-I) has many potential advantages over the currently used drugs, including a broader antibacterial spectrum, it turns the surface of the eye brown for a few minutes, bacterial resistance has not been seen and it is cheaper than other agents . PVP-I has made a significant contribution to pre- and postoperative ocular surgical prophylaxis, ophthalmia neonatorum prophylaxis and treatment of bacterial conjunctivitis . Scientific support for these applications includes studies conducted over the past 17 years, which are reviewed . Infect Immun, 2002 Jun, 70(6), 3164 - 9 Mice lacking monocyte chemoattractant protein 1 have enhanced susceptibility to an interstitial polymicrobial infection due to impaired monocyte recruitment; Chae P et al.; Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces monocyte recruitment in a number of different pathologies, including infection . To investigate the role of MCP-1 in protecting a host from a chronic interstitial polymicrobial infection, dental pulps of MCP-1(-/-) mice and controls were inoculated with six different oral pathogens . In this model the recruitment of leukocytes and the impact of a genetic deletion on the susceptibility to infection can be accurately assessed by measuring the progression of soft tissue necrosis and osteolytic lesion formation . The absence of MCP-1 significantly impaired the recruitment of monocytes, which at later time points was threefold higher in the wild-type mice than in MCP-1(-/-) mice (P < 0.05) . The consequence was significantly enhanced rates of soft tissue necrosis and bone resorption (P < 0.05) . We also determined that the MCP-1(-/-) mice were able to recruit polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls and to produce equivalent levels of Porphyromonas gingivalis-specific total immunoglobulin G (IgG) and IgG1 . These results point to the importance of MCP-1 expression and monocyte recruitment in antibacterial defense and demonstrate that antibacterial defense is not due to an indirect effect on PMN recruitment or modulation of the adaptive immune response. Drugs, 2002, 62(8), 1143 - 72 Sickle cell anaemia: progress in pathogenesis and treatment; Ballas SK; The phenotypic expression of sickle cell anaemia varies greatly among patients and longitudinally in the same patient . It influences all aspects of the life of affected individuals including social interactions, intimate relationships, family relations, peer interactions, education, employment, spirituality and religiosity . The clinical manifestations of sickle cell anaemia are protean and fall into three major categories: anaemia and its sequelae;pain and related issues; andorgan failure including infection . Recent studies on the pathogenesis of sickle cell anaemia have centred on the sequence of events that occur between polymerisation of deoxy haemoglobin (Hb) S and vaso-occlusion . Cellular dehydration, inflammatory response and reperfusion injury seem to be important pathophysiological mechanisms . Management of sickle cell anaemia continues to be primarily palliative in nature, including supportive, symptomatic and preventative approaches to therapy . Empowerment and education are the major aspects of supportive care . Symptomatic management includes pain management, blood transfusion and treatment of organ failure . Pain managment should follow certain priniciples that include assessment, individualisation of therapy and proper utilisation of opioid and nonopioid analgesics in order to acheive adequate pain relief . Blood selected for transfusion should be leuko-reduced and phenotypically matched for the C, E and Kell antigens . Exchange transfusion is indicated in patients who are transfused chronically in order to prevent or delay the onset of iron-overload . Acute chest syndrome is the most common form of organ failure and its management should be agressive, including adequate ventilation, multiple antibacterials and simple or exchange blood transfusion depending on its severity . Preventitive therapy includes prophylactic penicillin in infants and children, blood transfusion (preferably exchange transfusion) in patients with stroke, and hydroxyurea in patients with frequent acute painful episodes . Bone marrow and cord blood transplantation have been successful modalities of curative therapy in selected children with sickle cell anaemia . Newer approaches to preventative therapy include cellular rehydration with agents that inhibit the Gardos channel or the KCl co-transport channel . Curative gene therapy continues to be investigational at the level of the test tube and transgenic mouse models. Bioelectrochemistry, 2002 May 15, 56(1-2), 53 - 5 Reduction of lapachones and their reaction with L-cysteine and mercaptoethanol on glassy carbon electrodes; Oliveira-Brett AM et al.; The electrochemical reduction of beta-lapachone and its 3-sulphonic salt was studied by cyclic, square wave and differential pulse voltammetry in aqueous media using a glassy carbon electrode . These compounds have a wide range of biological activities, including antibacterial, cytotoxic, antifungal, trypanocidal and anticancer action . The reduction of beta-lapachone in the presence of L-cysteine and 2-mercaptoethanol was studied and the results, together with others already published, suggest that the anticancer mechanism of beta-lapachones can be explained via interaction with topoisomerase. Int J Med Microbiol, 2002 Mar, 291(8), 605 - 14 The role of motility as a virulence factor in bacteria; Josenhans C et al.; Many bacteria that cause diseases of humans, animals and plants use flagella to move . This review summarises recent studies that have analysed the role of motility and chemotaxis in the host-parasite relationship of pathogenic bacteria . These studies have shown that for many pathogens, motility is essential in some phases of their life cycle and that virulence and motility are often intimately linked by complex regulatory networks . Possibilities to exploit bacterial motility as a specific therapeutic antibacterial target to cure or prevent disease are discussed. Int J Antimicrob Agents, 2002 May, 19(5), 405 - 11 Cefpirome sulphate for gynaecological infections and prophylaxis of non-laparotomy surgery in patients with benign disease; Hayashi H et al.; We organized a study group to conduct a clinical trial in patients with various gynaecological infections, and we also assessed the efficacy of a single dose of cefpirome sulphate as prophylaxis after vaginal hysterectomy . Cefpirome sulphate (CROM) was administered to 100 patients with gynaecological infections and the clinical and antibacterial efficacy was evaluated in 88 patients . The improvement rate was 77.0% (67/87) and the bacterial eradication rate 67.8% (40/59) . Nineteen of the 210 patients enrolled in the comparison of CROM with cefmetazole sodium (CMET) prophylaxis developed postoperative infections . The incidence of infection showed no significant difference between the CROM group (n=11, 10.6%) and the CMET group (n=8, 7.5%) (P=0.56) . Although these results suggest that CROM may be effective for the treatment of gynaecological infections and has a good safety profile, it was not superior to CMET as prophylaxis in women undergoing non-laparotomy procedures at our hospital. J Photochem Photobiol B, 2002 May, 67(1), 64 - 70 Active oxygen species (1O2, O2*-) generation in the system of TiO2 colloid sensitized by hypocrellin B; Xu S et al.; TiO2 semiconductor colloids have been successfully employed in environmental clean-up, antibacterial and bactericidal action under ultraviolet light due to its strong redox ability and high yield of active oxygen species (1O2, O2*-), *OOH) generation . Hypocrellin B, isolated from Hypocrella bambusae (B.et.Br) Sacc, a natural pigment with strong and broad absorption over the visible light region, was used in our work in an attempt to extend the photoresponse of TiO2 to visible light and maintain the high generation of active oxygen under visible light illumination . The formation of the HB-TiO2 chelate was characterized by UV-Vis and surface enhanced raman spectroscopy (SERS) and it was found that the chelate still had high efficiency of active oxygen generation . The possible generation mechanism was explored by Electron Paramagnetic Resonance (EPR) and time-resolved transient spectra techniques, showing that singlet oxygen (1O2) and superoxide radical anion (O2*-)) were produced via energy transfer and electron transfer, respectively . The application of HB-TiO2 chelate in environment protection and bacteria sterilization was implied. Structure (Camb), 2002 Mar, 10(3), 357 - 67 Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design; Kumar A et al.; Peptide deformylase catalyzes the deformylation reaction of the amino terminal fMet residue of newly synthesized proteins in bacteria, and most likely in Plasmodium falciparum, and has therefore been identified as a potential antibacterial and antimalarial drug target . The structure of P . falciparum peptide deformylase, determined at 2.8 A resolution with ten subunits per asymmetric unit, is similar to the bacterial enzyme with the residues involved in catalysis, the position of the bound metal ion, and a catalytically important water structurally conserved between the two enzymes . However, critical differences in the substrate binding region explain the poor affinity of E . coli deformylase inhibitors and substrates toward the Plasmodium enzyme . The Plasmodium structure serves as a guide for designing novel antimalarials. J Pept Res, 2001 Dec, 58(6), 504 - 14 Antibacterial, antitumor and hemolytic activities of alpha-helical antibiotic peptide, P18 and its analogs; Shin SY et al.; The alpha-helical antibiotic peptide (P18: KWKLFKKIPKFLHLAKKF-NH2) designed from the cecropin A(1-8)-magainin 2 (1-12) hybrid displayed strong bactericidal and tumoricidal activity without inducing hemolysis . The effect of the Pro9 residue at central position of P18 on cell selectivity was investigated by Pro9 --> Leu or Pro9 --> Ser substitution . Either substitution markedly reduced the antibacterial activity of P18 and increased hemolysis, although it did not significantly affect cytotoxicity against human transformed tumor and normal fibroblast cells . These results suggest that a proline kink in alpha-helical antibiotic peptide P18 serves as a hinge region to facilitate ion channel formation on bacterial cell membranes and thus plays an important role in providing high selectivity against bacterial cells . Furthermore, to investigate the structure-antibiotic activity relationships of P18, a series of N- or C-terminal deletion and substitution analogs of P18 were synthesized . The C-terminal region of P18 was related to its antibiotic activity and alpha-helical conformation on lipid membranes rather than N-terminal one . Higher alpha-helicity of the peptides was involved in the hemolytic and antitumor activity rather than antibacterial activity . Except for {L9}-P18 and {S9}-P18, all the designed peptides containing a Pro residue showed potent antibacterial activity, although they did not induce a cytolytic effect against human erythrocyte and normal fibroblast cells at the concentration required to kill bacteria . In particular, P18 and some analogs (N-1, N-2, N-3, N-3L and N-4L) with potent bactericidal and tumoricidal activity and little or no normal cell toxicity may serve as an attractive candidate for the development of novel anti-infective or antitumor agents. J Org Chem, 2002 May 17, 67(10), 3387 - 97 Design and synthesis of a novel class of constrained tricyclic pyrrolizidinone carboxylic acids as carbapenem mimics; Hanessian S et al.; A series of tricyclic pyrrolizidinone carboxylic acids harboring an angular methano group were synthesized as mimics of carbapenems and carbapenams . A key reaction involved a novel intramolecular cyclopropanation mediated by a trimethylstannylmethyl group and an adjacent iminium ion . Enolate chemistry on a tricyclic lactam ring unit allowed the introduction of various substituents . Further elaboration afforded tricyclic pyrrolidinone carboxylic acids, which were found to be inactive as inhibitors against a panel of bacterial strains . However, the antibacterial activity of ceftazidine was enhanced in the presence of the tricyclic analogues. Anaesth Intensive Care, 2002 Apr, 30(2), 179 - 82 Inhibition of bacterial growth by lignocaine in propofol emulsion; Ozer Z et al.; Contamination of propofol, in an emulsion formulation, has been associated with infective complications . Local anaesthetics,some of which are known to have antibacterial properties, are frequently added to the solution to reduce pain on injection . We examined the growth rates of E . coli, S . aureus, S . epidermidis and P . aeruginosa in propofol with and without lignocaine 0.1%-2% after incubation for 2, 5 and 24 hours at 37 degrees C . Growth of microorganisms in each solution was compared by counting the number of colony forming units (CFU) . Propofol supported the growth of all microorganisms . An increase in the number of CFUs was observed in all drug combinations 2, 5 and 24 hours after inoculation except for S . aureus (P<0.05) . No difference was found in CFU numbers between 2 and 5 hours for this microorganism . With E . coli, a significant decline in colony counts was observed in mixtures of 1% and 2% lignocaine (P<0.05) . With the other microorganisms only 2% lignocaine showed a significant reduction in the number of CFUs (P<0.05) . We conclude that lignocaine in recommended clinical doses (0.05%-0.1%) did not exhibit adequate antibacterial activity to prevent infective complications. Res Vet Sci, 2002 Feb, 72(1), 61 - 8 Effect of in-feed inclusion of a natural zeolite (clinoptilolite) on certain vitamin, macro and trace element concentrations in the blood, liver and kidney tissues of sows; Papaioannou DS et al.; The study was conducted to evaluate, under field conditions, the effect of the long-term dietary use of a natural zeolite (clinoptilolite, CLI) and antibacterials (chlortetracycline, CTC) on the concentrations of certain vitamins (vitamin A and vitamin E) and minerals (K, Na, P, Ca, Mg, Cu and Zn) in blood and body tissues of the sow . Twenty-four sows were assigned to two main experimental groups and four subgroups, depending on the presence or absence of CLI and CTC in their feed, respectively . CLI was provided to the sows from weaning, during the service, gestation and lactation periods and up to the date of the next service, while CTC was administered for a 2-week period post-service, as well as for a 2-week period following the allocation of the sows in the farrowing house, around 5 days prior to the expected parturition . Blood samples were collected on the starting day of the trial, on the 30th and the 90th day of each pregnancy, on the day of each parturition and on the day of each weaning . Furthermore, 20 sows were similarly distributed in the same experimental groups and subgroups and at the end of the trial they were slaughtered and liver and kidney samples were collected for biochemical analysis . Neither CLI nor CTC supplementation of the diets had any significant effect on vitamins' and minerals' uptake and their distribution in the body, since there was no alteration in their blood serum and liver/kidney concentrations . Furthermore, no CLI x CTC interaction was noticed. Res Vet Sci, 2002 Feb, 72(1), 51 - 9 A field study on the effect of in-feed inclusion of a natural zeolite (clinoptilolite) on health status and performance of sows/gilts and their litters; Papaioannou DS et al.; The study was conducted to evaluate the effect of the long-term dietary use of a natural zeolite (clinoptilolite, NZ) on health status and reproductive performance of sows/gilts and performance of their litters, along with its compatibility with antibacterials (chlortetracycline, CTC) periodically used in medication programmes . Two hundred and forty sows/gilts and their litters were assigned to two main experimental groups and four subgroups, depending on the inclusion of NZ and CTC in their feed . During the trial, frequent sampling of pregnancy feed for mycotoxicological analysis revealed a high contamination level with zearalenone . No adverse or side effects attributed to NZ were noticed . Furthermore, the combined use of NZ and CTC revealed no clinically apparent interactive effect on the availability of the latter . Reproductive performance was significantly improved by the dietary inclusion of both NZ and CTC . The results also suggested that the beneficial effect of NZ could be additionally considered as an indicator of the amelioration of zearalenone exposure consequences. Infect Control Hosp Epidemiol, 2002 Apr, 23(4), 212 - 6 Skin colonization by Malassezia in neonates and infants; Ashbee HR et al.; OBJECTIVE: To identify the timing, pattern, and determinants of colonization of neonates by Malassezia . DESIGN: Prospective observational study . SETTING: A neonatal medical and surgical unit consisting of 10 special care, 10 high-dependency, 10 intensive care, and 10 surgical cots . PARTICIPANTS: All neonates (< or = 28 days of age) or infants (> 28 days of age) admitted to the unit during the 20-week period from October 1995 to March 1996 . METHODS: All infants or neonates were swabbed on the day of admission and every third day thereafter and risk factors were collected for every day on the unit . RESULTS: During the study period, 245 neonates and 42 infants were sampled for their entire duration of stay on the unit . Of these, 41 infants (97.6%) were colonized with Malassezia on admission to the unit and thereafter, as assessed by subsequent samples . Within the neonate population, 78 (31.8%) became colonized, but none were colonized immediately after birth . Univariate analysis showed that many factors appeared to be significantly associated with colonization in the neonates, including use of ventilation, presence of central venous catheters, use of parenteral nutrition, and use of antibacterial or antifungal drugs . However, when the data were analyzed by multivariate logistic regression to control for confounding variables, only gestational age and length of stay on the unit were found to be significantly associated with colonization . CONCLUSION: Colonization of infants is not as unusual as previously thought and many infants have established a cutaneous Malassezia commensal flora by the age of 3 to 6 months . Factors that predispose to colonization in neonates may not be the same as those that predispose to infection. J Craniofac Surg, 2002 Mar, 13(2), 212 - 8; discussion 219-23 Holding power of bioabsorbable ciprofloxacin-containing self-reinforced poly-L/DL-lactide 70/30 bioactive glass 13 miniscrews in human cadaver bone; Leinonen S et al.; Antibiotics-plus bioactive glass-containing bioabsorbable self-reinforced (SR) polylactide screws have been developed for antibacterial osteoconductive bone fixation . The aim of the present study was to test the pullout properties of these recently developed miniscrews . Ciprofloxacin-plus bioactive glass-containing SR-polylactide miniscrews (BC) were compared with miniscrews made of neat SR-polylactide (A), SR-polylactide with bioactive glass (B), and ciprofloxacin-containing SR-polylactide (C) . BC miniscrews and their controls (A, B, C) (all of length 6.0 mm, core diameter 1.45 mm, thread diameter 2.0 mm) were applied to one pair of cadaveric fibulae . Pullout force was measured using a materials testing machine . We carried out 49-50 pullout tests for each implant type . The Mann-Whitney test and Student's t-test were used for statistical evaluation . The pullout force for BC miniscrews was 114.9 +/- 34.0 (SD) N . Pullout forces for control miniscrews were 162.7 +/- 37.8 N (A), 99.1 +/- 16.2 N (B), and 142.9 +/- 26.9 N (C) . Differences between the four groups were statistically significant (p < 0.001) . Ciprofloxacin-plus bioactive glass-containing polylactide miniscrews have good holding power to human cadaver fibulae . However, adding bioactive glass and ciprofloxacin components to neat SR-polylactide results in lower pullout values. Insect Mol Biol, 2002 Jun, 11(3), 257 - 65 cDNA cloning, characterization and gene expression of nitric oxide synthase from the silkworm, Bombyx mori; Imamura M et al.; Molecular cloning and nucleotide sequencing of cDNA encoding Bombyx mori nitric oxide synthase (BmNOS) was conducted to analyse its possible role in insect immunity . The amino acid sequence deduced from the BmNOS cDNA showed 84%, 54% and 53% identity with those of NOSs from Manduca sexta, Drosophila melanogaster and Rhodonius prolixus . Recombinant BmNOS produced in insect cells using baculovirus was found to require NADPH, Ca2+, calmodulin and tetrahydrobiopterin (BH4) for its activity . The BmNOS gene was constitutively expressed at a low level in the larval fat body, haemocyte, Malpighian tubule and midgut, and adult antenna, and induced strongly in the fat body by lipopolysaccharide (LPS), suggesting that the BmNOS gene plays different physiological roles in different tissues . Injection of NO donors that produce NO in vivo induced the gene expression of an antibacterial peptide, cecropin B, strongly suggesting that NO produced by BmNOS following LPS stimulation is involved in signal transduction as a signalling molecule for immune gene expression. J Appl Microbiol, 2002, 92 Suppl, 35S - 45S Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria; Denyer SP et al.; The principal targets for antibacterial agents reside at the cytoplasm and cytoplasmic membrane, damage to other structures often arising from initial events at these loci . The Gram-negative bacteria offer a complex barrier system to biocides and antibiotics, regulating, and sometimes preventing, their passage to target regions . Routes of entry differ between hydrophobic and hydrophilic agents, often with a structure dependency; specialized uptake mechanisms are exploited and portage transport can occur for pro-drug antibacterials . Uptake isotherms offer insight into the sorption process and can sometimes shed light on biocide mechanisms of action . The multi-component barrier system of Gram-negative bacteria offers opportunities for phenotypic resistance development where partitioning or exclusion minimizes the delivery of an antibacterial agent to the target site . Active efflux processes are recognized as increasingly relevant mechanisms for resistance, potentially offering routes to biocide:antibiotic cross-resistance . These mechanisms may be targeted directly in an attempt to compromise their role in microbial survival. J Appl Microbiol, 2002, 92 Suppl, 28S - 34S Novel targets for the future development of antibacterial agents; McDevitt D et al.; Recent advances in DNA sequencing technology have made it possible to elucidate the entire genomes of pathogenic bacteria, and advancements in bioinformatic tools have driven comparative studies of these genome sequences . These evaluations are dramatically increasing our ability to make valid considerations of the limitations and advantages of particular targets based on their predicted spectrum and selectivity . In addition, developments in gene knockout technologies amenable to pathogenic organisms have enabled new genes and gene products critical to bacterial growth and pathogenicity to be uncovered at an unprecedented rate . Specific target examples in the areas of cell wall biosynthesis, aromatic amino acid biosynthesis, cell division, two component signal transduction, fatty acid biosynthesis, isopreniod biosynthesis and tRNA synthetases illustrate how aspects of the above capabilities are impacting on the discovery and characterization of novel antibacterial targets . An example of a novel inhibitor of bacterial fatty acid biosynthesis discovered from high throughput screening processes is described, along with its subsequent chemical optimization . Furthermore, the application and importance of technologies for tracking the mode of antibacterial action of these novel inhibitors is discussed. J Appl Microbiol, 2002, 92 Suppl, 4S - 15S Exploiting current understanding of antibiotic action for discovery of new drugs; Chopra I et al.; The introduction of antibiotics for the chemotherapy of bacterial infections has been one of the most important medical achievements of the past 50 years . However, the emergence of bacterial resistance to antibiotics undermines the therapeutic utility of existing agents, creating a requirement for the discovery of new antibacterial drugs . Several drug discovery strategies have emerged, including incremental improvements to existing antibiotics by chemical manipulation and the search for novel drug targets based on genomic approaches . An alternative strategy seeks to exploit opportunities for drug discovery arising from an understanding of the mode of action of existing antibiotics . Thus biochemical pathways or processes inhibited by antibiotics already in clinical use may nevertheless contain key functions that represent unexploited targets for further drug discovery . A major benefit of employing pathways or processes that are already known to contain drug targets is that proof of principle for drug intervention is already established . This approach to drug discovery is illustrated by reviewing target sites for existing antibiotics and considering how this information might be applied for the discovery of new agents inhibiting peptidoglycan synthesis, tRNA synthesis, transcription and DNA replication J Wound Care, 2002 Apr, 11(4), 125 - 30 Silver . I: Its antibacterial properties and mechanism of action; Lansdown AB; Silver products have two key advantages: they are broad-spectrum antibiotics and are not yet associated with drug resistance . This article, the first in a two-part series, describes the main mechanism of action of this metallic element. FEBS Lett, 2002 May 8, 518(1-3), 33 - 8 Solution structure of moricin, an antibacterial peptide, isolated from the silkworm Bombyx mori; Hemmi H et al.; A novel antibacterial peptide, moricin, isolated from the silkworm Bombyx mori, consists of 42 amino acids . It is highly basic and the amino acid sequence has no significant similarity to those of other antibacterial peptides . The 20 structures of moricin in methanol have been determined from two-dimensional 1H-nuclear magnetic resonance spectroscopic data . The solution structure reveals an unique structure comprising of a long alpha-helix containing eight turns along nearly the full length of the peptide except for four N-terminal residues and six C-terminal residues . The electrostatic surface map shows that the N-terminal segment of the alpha-helix, residues 5-22, is an amphipathic alpha-helix with a clear separation of hydrophobic and hydrophilic faces, and that the C-terminal segment of the alpha-helix, residues 23-36, is a hydrophobic alpha-helix except for the negatively charged surface at the position of Asp30 . The results suggest that the amphipathic N-terminal segment of the alpha-helix is mainly responsible for the increase in permeability of the membrane to kill the bacteria. Drug Saf, 2002, 25(4), 263 - 86 Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview; De Ponti F et al.; The long and growing list of non-antiarrhythmic drugs associated with prolongation of the QT interval of the electrocardiogram has generated concern not only for regulatory interventions leading to drug withdrawal, but also for the unjustified view that QT prolongation is usually an intrinsic effect of a whole therapeutic class {e.g . histamine H(1) receptor antagonists (antihistamines)}, whereas, in many cases, it is displayed only by some compounds within a given class of non-antiarrhythmic drugs because of an effect on cardiac repolarisation . We provide an overview of the different classes of non-antiarrhythmic drugs reported to prolong the QT interval (e.g . antihistamines, antipsychotics, antidepressants and macrolides) and discusses the clinical relevance of the QT prolonging effect . Drug-induced torsade de pointes are sometimes considered idiosyncratic, totally unpredictable adverse drug reactions, whereas a number of risk factors for their occurrence is now recognised . Widespread knowledge of these risk factors and implementation of a comprehensive list of QT prolonging drugs becomes an important issue . Risk factors include congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia, hypocalcaemia), impaired hepatic/renal function, concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions (e.g . azole antifungals, macrolide antibacterials and class I or III antiarrhythmic agents) . This review provides insight into the strategies that should be followed during a drug development program when a drug is suspected to affect the QT interval . The factors limiting the predictive value of preclinical and clinical studies are also outlined . The sensitivity of preclinical tests (i.e . their ability to label as positive those drugs with a real risk of inducing QT pronglation in humans) is sufficiently good, but their specificity (i.e . their ability to label as negative those drugs carrying no risk) is not well established . Verapamil is a notable example of a false positive: it blocks human ether-a-go-go-related (HERG) K(+) channels, but is reported to have little potential to trigger torsade de pointes . Although inhibition of HERG K(+) channels has been proposed as a primary test for screening purposes, it is important to remember that several ion currents are involved in the generation of the cardiac potential and that metabolites must be specifically tested in this in vitro test . At the present state of knowledge, no preclinical model has an absolute predictive value or can be considered as a gold standard . Therefore, the use of several models facilitates decision making and is recommended by most experts in the field. J Hosp Infect, 2002 Jan, 50 Suppl A, S17 - 21 New perspectives in antibiotic prophylaxis for intra-abdominal surgery; Sganga G; Effective management of intra-abdominal infections requires a combination of preoperative preparation, antibiotic prophylaxis and appropriate surgical technique . Antibacterial prophylaxis should provide coverage of all likely pathogens, including aerobic and anaerobic organisms . Whereas antibacterial combination therapy is appropriate in certain situations, single-agent prophylaxis is appropriate for the majority of patients and ampicillin/sulbactam, with its broad-spectrum anti-aerobic/anti-anaerobic activity, is an attractive prophylactic option . Surgery involving the gastrointestinal tract provides a special challenge by virtue of its high, predominantly anaerobic, bacterial load . However, the requirement for prophylaxis varies depending upon the precise site of intervention . Biliary tract surgery requires prophylaxis in high-risk patients only, whereas hepatobiliary or pancreatic surgery requires prophylaxis in all patients . Gastroduodenal operations require prophylaxis in the presence of risk factors, such as abnormal gastric acidity or bleeding . Colorectal procedures present a high risk of anaerobic infection and sepsis, and require adequate prophylaxis combined with a thorough preoperative preparation designed to reduce considerably the bacterial load of the bowel . Where peritonitis does follow intra-abdominal surgery, patients should receive antibacterial therapy commensurate with the risk of serious infection . A small proportion of patients will be at risk of severe infection and will require triple-agent therapy . However, most patients are likely to develop mild-to-moderate infections only and can be treated with a single, broad-spectrum antibiotic agent, such as ampicillin/sulbactam, a beta-lactam/beta-lactamase inhibitor. Folia Parasitol (Praha), 2002, 49(1), 73 - 7 Bacterial colonisation in the gut of Phlebotomus duboseqi (Diptera: Psychodidae): transtadial passage and the role of female diet; Volf P et al.; Bacteria isolated from the gut of different developmental stages of Philebotomus duboseqi Neveu-Lcmaire, 1906 belonged almost all to aerobic or facultatively anaerobic gram-negative rods . In females, the highest bacterial counts were observed two days after bloodfeeding; seven days after bloodfeeding the bacterial counts returned to pre-feeding levels . Most isolates were identified phenotypically as Ochrobactrum sp . The distinctiveness and homogeneity of the phenotypic and genotypic characteristics of Ochrobactrum isolates indicated that they belonged to a single strain (designated AK) . This strain was acquired by larvae from food and passaged transtadially: it was isolated from the guts of fourth-instar larvae shortly before pupation, from pupae as well from newly emerged females . Most other bacteria found in females were acquired from the sugar solution fed to adults . To determine if the midgut lectin activity may serve as antibacterial agent females were membrane-fed on blood with addition of inhibitory carbohydrates . No significant differences in bacterial infections were found between experimental and control groups and we suppose that the lectin activity has no effect on gram-negative bacteria present in sandfly gut. J Cutan Med Surg, 2002 Mar-Apr, 6(2), 128 - 50 Epub 2002 Feb 13. A review of antibiotics in dermatology; Carrasco DA et al.; BACKGROUND: Since the early 1930s when antibiotics were first introduced, they have revolutionized the way physicians treat infections . Skin conditions from acne to leprosy, which were once shunned by society, are now easily treated with oral antibiotics . OBJECTIVE: Antibiotics are chemicals derived from bacteria and fungi that uniquely have antibacterial action . The most notable example is penicillin, which is derived from a mold . With hundreds of antibiotics available to the practicing physician, improper use of these drugs has become widespread and expensive and has spawned resistant strains . For the dermatologist, antibiotics are vital weapons in the drug armamentarium for treating various skin conditions . CONCLUSION: This review explores the newest and most common oral, parenteral, and topical antibiotics used in dermatology, their indications, adverse effects, dosage, and spectrum of activity . Furthermore, systemic antibacterial prophylaxis and vaccines pertinent to dermatology are discussed . The penicillins, cephalosporins, tetracyclines, macrolides, fluoroquinolones, sulfonamides, aminoglycosides, lincosamides, folate inhibitors, and a new synthetic class of drugs, the oxazolidinones, are reviewed . These antibiotics are used to treat a variety of organisms. Nucleosides Nucleotides Nucleic Acids, 2002, 21(3), 231 - 41 Synthesis and in vitro antibacterial activity of novel 5'-O-analog derivatives of zidovudine as potential prodrugs; Moroni GN et al.; An efficient, short synthesis of four potential prodrugs of 3'-azido-3'-deoxythymidine (AZT) and their antibacterial activity are reported . The 5'-OH group of AZT was functionalized with oxalyl chloride obtaining an acyl chloride derivative (AZT-Ox), which by further transformation with leucine, isoleucine and valine amino acids led to the corresponding AZT analogs, namely AZT-Leu, AZT-iLeu and AZT-Val . A carboxyl acid derivative (AZT-Ac) was also obtained by hydrolysis of AZT-Ox . These compounds, which exhibit anti HIV activity, have killed collection and clinical strains of some opportunistic infectious agents in AIDS-related complex . Thus, the clinical strains, K . oxytoca, S . typhi and K . pneumoniae, and collection strain K . pneumoniae ATCC 10031 showed sensitivity to antibiotics . The activity order for the studied compounds against the most sensitive strain (K . pneumoniae ATCC 10031) was AZT-Leu > AZT-iLeu > AZT-Val > AZT-Ac > AZT . On the other hand, the activity order for the second most sensitive strain (K . oxytoca) was AZT-Leu > AZT-Val = AZT-Ac > AZT-iLeu > AZT . The most effective antibacterial drug AZT-Leu, M.I.C.=0.125 microgmL(-1)) was 16 times more active than AZT (AZT, M.I.C.=2 microg mL(-1)) against K. J Neurosurg, 2002 Apr, 96(4), 760 - 9 Polyester meshes and adhesive materials in the brain: comparative research in rats to optimize surgical strategy; Quester R et al.; OBJECT: The goal of this study was to determine the biocompatibility of polyester mesh electrode carriers for auditory brainstem implants with and without adhesives in a rat model . METHODS: Physical properties of the meshes were evaluated within the fourth ventricle region, both without (Group A) and with adhesives (muscle, Group B; oxidized regenerated cellulose {ORC}, Group C; and fibrin glue, Group D) . The stability of the mesh position, the healing process, and host defense reaction after 2 to 60 days were examined in series of tissue sections in which meshes were preserved in situ . The cellular reaction was further evaluated using electron microscopy . Although otherwise pliable, polyester meshes were too rigid when used with adhesives, especially fibrin glue or muscle . Also, the sharp edges of the meshes presented a risk of brainstem and cerebellar lesions . Regardless of the material, meshes induced persistent inflammatory tissue reactions characterized by numerous macrophages and foreign-body giant cells . After 14 days, the cellular response had resulted in sufficient fibroblast and collagen fiber encapsulation of the meshes and remained essentially unchanged thereafter . No influence of adhesives on the healing process was observed, and, unexpectedly, these substances did not reduce the risk of dislocation prior to adequate cellular encasement . In some rats in Groups A and C, purulent inflammation, in part with Gram-positive bacteria, occurred after 2 to 14 days . The ORC exhibited persistent swelling, introducing the risk of occlusive hydrocephalus and/or brainstem compression . CONCLUSIONS: Polyester meshes and various adhesives exhibited acceptable biocompatibility in terms of local tissue reaction . Adhesives reduced pliability of the meshes, however, and were ineffective in reducing the risk of dislocation . Handling characteristics could be improved by better mesh designs, and risk of infection could be reduced by both improved designs and surface treatment of the meshes with antibacterial agents. Anal Sci, 2001 Oct, 17(10), 1145 - 8 Determination of lomefloxacin, an antibacterial drug, in pharmaceutical preparations based on its polarographic catalytic wave in the presence of 2-iodoacetamide; Song JF et al.; In a 0.125 mol/L phosphate (pH 6.6)/2.5 x 10(-4) mol/L 2-iodoacetamide solution, lomefloxacin yields a response of a polarographic catalytic current . The second-order derivative peak current of the catalytic wave of lomefloxacin is proportional to its concentration in the range of 1.0 x 10(-8)-1.0 x 10(-6) mol/L (r = 0.998) . The sensitivity of the catalytic wave is 25-times higher than that of the corresponding reduction wave for 5.0 x 10(-7) mol/L lomefloxacin . The proposed method was applied to the determination of lomefloxacin in pharmaceutical preparations . The polarographic reduction wave is ascribed to a one-electron reduction of the C=C bond of lomefloxacin zwitterion accompanied by an acid-base equilibrium . The catalytic wave should be caused by regeneration of the lomefloxacin molecule at electrode surface due to the one-electron reduction product being further oxidized by electroreductive intermediate products of 2-iodoacetamide. Farmaco, 2002 Apr, 57(4), 273 - 83 Synthesis of new C-6 alkyliden penicillin derivatives as beta-lactamase inhibitors; Di Giacomo B et al.; New penicillin, penicillin sulfone and sulfoxide derivatives bearing a C-6-alkyliden substituent were prepared . Their chemical synthesis, in vitro antibacterial activity and inhibition properties against two selected enzymes representing Class A and C beta-lactamases are reported . Compounds 3a-c, 7a-c were able to inhibit either TEM-1 (a Class A enzyme, from Escherichia coli) or P-99 (a Class C enzyme, from E . cloacae), or both enzymes, when tested in competition experiments using nitrocefin as the reporter substrate . However, when tested in combination with amoxicillin, the same compounds did not show synergistic effects against E . coli and E . cloacae strains producing TEM-1 and P99 enzymes, respectively . This finding is most likely related to poor penetration through the bacterial cell wall, as shown by using a more permeable isogenic E . coli strain . Interestingly, a synergistic effect against a strain of S . aureus which produces PC1-enzyme (a Class A beta-lactamase) was observed for compound 3a when used in combination with amoxicillin. Planta Med, 2002 Apr, 68(4), 361 - 3 Antibacterial diterpenoids from Fabiana densa var . ramulosa; Erazo S et al.; A biologically monitored fractionation of the resinous exudate of Fabiana densa Remy var . ramulosa Wedd . led to the isolation of the two new diterpenes: ent-beyer-15-en-18-O-succinate and ent-beyer-15-en-18-O-oxalate as the unique compounds responsible for the observed antibacterial activity of this extract . Their structures were determined by 1D and 2D NMR spectroscopy. Ophthalmology, 2002 May, 109(5), 835 - 42; quiz 843 Indecision about corticosteroids for bacterial keratitis: an evidence-based update; Wilhelmus KR; PURPOSE: To quantify the effect of topical corticosteroids on bacterial keratitis . CLINICAL RELEVANCE: Bacterial keratitis is an economically important infection affecting 1 in 10,000 Americans annually . The predisposing factors, prior ocular health, infecting microorganisms, inflammatory severity, and therapeutic choices can affect the course and outcome . Antibacterial treatment is often curative but does not guarantee good vision . Because many treated patients develop a sight-limiting corneal problem, antiinflammatory therapy has sometimes been recommended . LITERATURE REVIEWED: Publications from 1950 to 2000 that evaluated the effect of corticosteroids on bacterial keratitis in animal experiments, case reports and series, case-comparison and cohort studies, and clinical trials were systematically identified by electronic and manual search strategies . RESULTS: The use of a topical corticosteroid before the diagnosis of bacterial keratitis significantly predisposed to ulcerative keratitis in eyes with preexisting corneal disease (odds ratio {OR}, 2.63; 95% confidence limits {CL}, 1.41, 4.91) . Once microbial keratitis occurred, prior corticosteroid use significantly increased the odds of antibiotic treatment failure or other infectious complications (OR, 3.75; 95% CL, 2.52, 5.58) . However, the effect of a topical corticosteroid with antibiotics after the onset of bacterial keratitis was unclear . Experimental models suggested likely advantages, but clinical studies did not show a significant effect of topical corticosteroid therapy on the outcome of bacterial keratitis (OR, 0.62; 95% CL, 0.25, 1.54) . CONCLUSIONS: Topical corticosteroids increase the risk of infectious complications affecting the cornea but may or may not have an effect during antibacterial therapy . The unproven role of corticosteroids in the adjunctive treatment of bacterial keratitis highlights the need to collect prospective information that would guide appropriate management for this common eye disease. J Pept Res, 2002 Mar, 59(3), 95 - 104 Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and analogs with one, two and three disulfide bridges; Mandal M et al.; Structure and biological activities of synthetic peptides corresponding to human alpha-defensin HNP-1, AC1YC2RIPAC3IAGERRYGTC4IYQGRLWAFC5C6 with the S-S connectivities: C1-C6, C2-C4, C3-C5, and its variants with one, two and three disulfide bridges were investigated . Oxidation of synthetic, reduced HNP-1 yielded a peptide with S-S connectivities C1-C3, C2-C4 and C5-C6, and not with the S-S linkages as in naturally occurring HNP-1 . Selective protection of cysteine sulfhydryls was necessary for the formation of S-S bridges as in native HNP-1 . Likewise, oxidation of peptide encompassing the segment from C2 to C5, resulted in the S-S linkages C2-C3 and C4-C5 instead of the expected linkage C2-C4 and C3-C5 . Antibacterial activities were observed for all peptides, irrespective of how the S-S bridges were linked . Linear peptides without S-S bridges were inactive . Circular dichroism (CD) spectra suggest that peptides constrained by one and two S-S bridges do not form rigid beta-sheet structures in an aqueous environment . The spectrum of HNP-1 in an aqueous environment suggests the presence of a beta-hairpin conformation . In the presence of lipid vesicles, the S-S constrained peptides tend to adopt a beta-structure . Although the S-S connectivities observed in HNP-1 may be necessary for other physiological activities, such as chemotaxis, they are clearly not essential for antibacterial activity. Chem Biol, 2002 Apr, 9(4), 455 - 63 Aminoglycosides modified by resistance enzymes display diminished binding to the bacterial ribosomal aminoacyl-tRNA site; Llano-Sotelo B et al.; Understanding the basic principles that govern RNA binding by aminoglycosides is important for the design of new generations of antibiotics that do not suffer from the known mechanisms of drug resistance . With this goal in mind, we examined the binding of kanamycin A and four derivatives (the products of enzymic turnovers of kanamycin A by aminoglycoside-modifying enzymes) to a 27 nucleotide RNA representing the bacterial ribosomal A site . Modification of kanamycin A functional groups that have been directly implicated in the maintenance of specific interactions with RNA led to a decrease in affinity for the target RNA . Overall, the products of reactions catalyzed by aminoglycoside resistance enzymes exhibit diminished binding to the A site of bacterial 16S rRNA, which correlates well with a loss of antibacterial ability in resistant organisms that harbor these enzymes. Int J Antimicrob Agents, 2002 Apr, 19(4), 333 - 9 How predictive is PK/PD for antibacterial agents? Frimodt-Moller N. The pharmacodynamic (PD) parameters most often used in studies of antibiotic effect include the following relationships between the antibiotic concentration curve in serum as a surrogate marker for the antibiotic concentration at the infection site, the peak/minimal inhibitory concentration (MIC) ratio, the area under the curve (AUC)/MIC ratio and the duration of time the concentration exceeds the MIC (T(>MIC)) . The MIC plays an important role also as a PD marker, and its precision in this respect is discussed . The predictive role of T(>MIC) is important for drugs showing minimal concentration dependent effect such as the beta-lactam antibiotics, the macrolides and others . The time can be calculated as the chronological time measured or as the (cumulative) per cent of the dosing interval covered by the dose . Several clinical studies have confirmed this relationship . It can be deduced from experimental as well as clinical studies that there is a minimal effective time (MET), which needs to be covered by the antibiotic concentration at the site of infection in order to achieve cure . Dosing according to this MET will result in the least antibiotic needed for the shortest duration . In several cases a single dose will suffice to cover the MET . If this is not possible the antibiotic should be dosed in a way, that each dose will surpass the MIC for at least 40-50% of the dosing interval . For antibiotics with a clear concentration-dependent bacterial killing effect the most important pharmacokinetic/pharmacodynamic (PK/PD) index is the peak/MIC ratio (or the AUC/MIC ratio) . This is the case for aminoglycosides and fluoroquinolones, and for both classes a peak/MIC ratio of at least 10 within the first 24 h of treatment has been shown to result in around 90% bacteriological as well as clinical cure . One consequence of clinical dosing has been the once-a-day (OD) dosing for aminoglycosides, which is the standard mode of therapy in many countries . Clinical studies in the field of antibacterial PD are still relatively scarce, and much information is needed to enable relevant dosing strategies for all types of antibiotics against all common infections and micro-organisms. Int J Antimicrob Agents, 2002 Apr, 19(4), 291 - 8 Developments in PK/PD: optimising efficacy and prevention of resistance . A critical review of PK/PD in in vitro models; MacGowan A et al.; In vitro pharmacokinetic models are excellent tools with which to study an antibacterial's pharmacodynamics (pD), being flexible, adaptable, low cost, and correlating well with animal and human systems . They can be used to perform simple descriptive studies on antibacterial effect, determine the dominant pD factor and its magnitude for antibacterial effect, and finally be used to assess the effect of dosing on emergence of resistance . A wide range of model designs are used and some standardisation maybe of value in the near future, however it is clear that in vitro models in conjunction with animal studies and human trials offer an excellent way of studying drug dosing to optimise outcomes. Int J Antimicrob Agents, 2002 Apr, 19(4), 285 - 90 Rational dosing of antibiotics: the use of plasma concentrations versus tissue concentrations; Liu P et al.; At the moment, the most common pharmacokinetic/pharmacodynamic (PK/PD) approaches for anti-infective agents, such as time above MIC, C(max)/MIC and AUC(24)/MIC, rely on plasma concentration as the PK input value and minimum inhibitory concentration (MIC) as the PD input value . However, only the free tissue concentrations of antibiotics at the target site are responsible for the therapeutic effect . Using plasma concentrations frequently overestimates the target site concentrations and therefore clinical efficacy . Microdialysis is a new technique that allows direct measurement of unbound tissue concentrations . Furthermore, a better PD approach, bacterial time-kill curves, can offer more detailed information about the antibacterial activity as a function of time and antibiotic concentration than MICs. Am J Clin Dermatol, 2002, 3(3), 149 - 58 Clinical management of pyoderma gangrenosum; Wollina U; Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that usually starts with sterile pustules which rapidly progress to painful ulcers of variable depth and size with undermined violaceous borders . In 17 to 74% of cases, pyoderma gangrenosum is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatological or hematological disease or malignancy . Diagnosis of pyoderma gangrenosum is based on a history of an underlying disease, typical clinical presentation and histopathology, and exclusion of other diseases that would lead to a similar appearance . Randomized, double-blinded prospective multicenter trials investigating the treatment of pyoderma gangrenosum are not available . The treatments with the best clinical evidence are systemic corticosteroids (in the initial phase usually 100 to 200 mg/day) and cyclosporine (mainly as a maintenance treatment) . Combinations of corticosteroids with cytotoxic drugs such as azathioprine, cyclophosphamide or chlorambucil are used in patients with disease that is resistant to corticosteroids . The combination of corticosteroids with sulfa drugs, such as dapsone, or clofazimine, minocycline and thalidomide, has been used as a corticosteroid-sparing alternative . Limited experience has been documented with methotrexate, colchicine, nicotine, and mycophenolate mofetil, among other drugs . Alternative treatments include local application of granulocyte-macrophage colony-stimulating factor, intravenous immunoglobulins and plasmapheresis . Skin transplants (split-skin grafts or autologous keratinocyte grafts) and the application of bioengineered skin is useful in selected cases in conjunction with immunosuppression . Topical therapy with modern wound dressings is useful to minimize pain and the high risk of secondary infection . The application of topical antibacterials cannot be recommended because of their potential to sensitize and their questionable efficacy, but systemic antibacterial therapy is mandatory when infection is present . Despite recent advances in therapy, the prognosis of pyoderma gangrenosum remains unpredictable. Jpn J Antibiot, 2002 Feb, 55(1), 77 - 88 {Pharmacokinetic study of penetration of meropenem into pleural effusion in patients with pleurisy}; Makino J et al.; Complication by secondary infection is observed in not only bacterial pleurisy but also other pleurisy, and the appropriate administration of antibacterial agents is necessary . It is very important to secure a smooth penetration of systemically administered antibacterial agents to pleural effusion in infection therapy . In this study, we investigated the pharmacokinetics of a carbapenem antibiotic, meropenem (MEPM), in blood and pleural effusion in patients with an accumulation of pleural effusion caused by pleurisy, who underwent placement of an indwelling thoracic drain and received intravenous drip administration of MEPM for pneumonia or other respiratory tract infection . The blood pharmacokinetic parameters of MEPM after an intravenous drip administration of 0.5 g MEPM in six patients were: area under the blood concentration-time curve (AUCx), 37.9 +/- 6.2 (hr.mg/L); volume of distribution (Vd), 27.3 +/- 4.4 (L); total clearance (CLtotal), 13.4 +/- 1.8 (L/hr); elimination half life (t1/2), 0.50 +/- 0.08 (hr-1); and elimination rate constant (kel), 1.42 +/- 0.22 (hr) . The pharmacokinetic parameters in pleural effusion were: AUCx, 35.7 +/- 7.1 (hr.mg/L); mean retention time (MRT), 5.00 +/- 3.25 (hr); variance of retention time (VRT), 29.9 +/- 44.6 (hr2); kel, 0.34 +/- 0.27 (hr-1); and t1/2, 3.14 +/- 2.36 (hr) . The penetration rate calculated from the ratio of pleural concentration to blood concentration in each patient was 46.5 +/- 26.1%, showing good penetration comparable or superior to those of other antibacterial agents previously reported . From these results, it was suggested that MEPM was rapidly penetrated to the pleural effusion and was retained for a more prolonged time in the pleural effusion than in the blood of patients with accumulated pleural effusion, and it suggested the usefulness of MEPM in antibacterial therapy for patients with pleurisy causing accumulation of pleural effusion. Sheng Wu Gong Cheng Xue Bao, 2002 Jan, 18(1), 10 - 5 {Bioactive compounds from marine sponges and cell culture of marine sponges}; Zhang XY et al.; Presented a survey of bioactive compounds discovered from marine sponges in the recent five years, including the classes, distribution and their potential pharmaceutical uses . In particular, the compounds with antitumor, antivirus and antibacteria activity were discussed with their originating marine sponge species . Whereas the "Supply Problems" were identified to hinder the clinical tests and commercial applications of most of the sponge bioactive compounds . In vitro cell culture of marine sponges is one of the most promising approaches to solve this problem . The state-of-the art of marine sponge cell culture and the challenging areas were discussed . A brief summary of the R&D status was also given on the bioactive compounds from marine sponges in Chinese oceans . It is crucial to invest more efforts on studying marine sponges and their bioactive compounds in our country in order to develop new marine drugs of independent intellectual property. Acta Crystallogr D Biol Crystallogr, 2002 May, 58(Pt 5), 864 - 6 Epub 2002 Apr 26. Crystallization and preliminary X-ray crystallographic analysis of UDP-N-acetylglucosamine acyltransferase from Helicobacter pylori; Lee BI et al.; Lipid A, a constituent of lipopolysaccharides, is essential for the growth and virulence of most Gram-negative bacteria . This makes its biosynthetic enzymes potential targets for development of new antibacterial agents . The first step of lipid A biosynthesis is catalyzed by the enzyme UDP-N-acetylglucosamine acyltransferase (LpxA) . LpxA from the pathogenic bacterium Helicobacter pylori has been overexpressed in Escherichia coli and crystallized at 297 K using ammonium sulfate and sodium/potassium tartrate as precipitants in the presence of a detergent . Diffraction data to 2.1 A resolution have been collected from a native crystal . The crystal belongs to space group P6(3)22, with unit-cell parameters a = b = 90.69, c = 148.20 A . The asymmetric unit contains one subunit of LpxA, with a crystal volume per protein mass (V(M)) of 2.87 A(3) Da(-1) and a solvent content of 57.1%. J Nat Prod, 2002 Apr, 65(4), 611 - 3 Derrisin, a new rotenoid from Derris malaccensis plain and anti-Helicobacter pylori activity of its related constituents; Takashima J et al.; A new rotenoid, derrisin (1), together with 10 known rotenoids (2-11) were isolated from the roots of Derris malaccensis Plain . The structure of 1 was elucidated by spectroscopic analysis . Nine of the isolated rotenoids (3-11) showed antibacterial activity against Helicobacter pylori. Pest Manag Sci, 2002 Mar, 58(3), 297 - 302 Potential of a novel antibiotic, 2-methylheptyl isonicotinate, as a biocontrol agent against fusarial wilt of crucifers; Bordoloi GN et al.; Screening for newer bioactive compounds from microbial metabolites resulted in the isolation of a novel antibiotic from the culture filtrate, Streptomyces sp 201, of a soil . The bioactive compound, with antifungal and antibacterial activity, was identified as 2-methylheptyl isonicotinate . The antifungal activity of live culture, culture broth and the isolated bioactive compound showed marked inhibition against dominant soil-borne phytopathogens such as Fusarium oxysporum Schlect, F moniliforme Sheldon, F semitectum Berkeley & Ravenel, F solani (Martius) Sacc and Rhizoctonia solani Kuehn . The compound had no effect on seed germination and seedling development as displayed by root and stem growth of the test plant species . In pot experiments with seedlings of cruciferous plants such as Raphanus sativus L (radish), Brassica campestris L (yellow mustard), Brassica oleracea var botrytis L (cauliflower), the antibiotic compound showed promising protective activity of 92% when seeds of the test plants were treated at a dose of 50 micrograms ml-1 prior to sowing . Seed treatment with a spore suspension (3 x 10(8) spores ml-1) of the Streptomyces sp 201 displayed protective activity in the range of 56-60% . Seeds coated with 2.5% methyl cellulose-amended spores of the antagonist showed protective activity in the range of 64-72% . Further, seed treatment with the culture filtrate of the antagonist also showed promising protective activity in the range of 64-84%. Immunology, 2002 May, 106(1), 20 - 6 A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis; Niyonsaba F et al.; The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body . During inflammation, an increase in the number of mast cells in the local milieu occurs, and such accumulation requires directed migration of this cell population . As it has previously been reported that the human cathelicidin-derived antibacterial peptide, LL-37, stimulates the degranulation of mast cells, we hypothesized that LL-37 could be a mast cell chemotaxin . The present study shows that LL-37 is a potent chemotactic factor for mast cells . The chemotactic response was dose-dependent and bell-shaped, reaching an optimal concentration of 5 microg/ml . In addition, checkerboard analysis showed that cell migration towards this peptide was chemotactic rather than chemokinetic . Moreover, Scatchard analysis using 125I-labelled LL-37-derived peptide revealed that LL-37 has at least two classes of receptors, namely high- and low-affinity receptors, on mast cells . Furthermore, the competitive binding assay suggested that LL-37 is unlikely to utilize formyl peptide receptor-like 1 (FPRL1), a functional LL-37 receptor for neutrophil and monocyte migration, on mast cells . In addition, the treatment of cells with pertussis toxin and phospholipase C inhibitor, U-73122, inhibited LL-37-mediated migration, indicating that LL-37 induces mast cell chemotaxis through a Gi protein-phospholipase C signalling pathway . These results show that besides its antibacterial activities, LL-37 may have the potential to recruit mast cells to inflammation foci. Nurs Stand, 2000 Nov 29-Dec 5, 15(11), 63 - 8 The use of honey in wound management; Dunford C et al.; Honey has been used as a wound treatment for more than 2,000 years . Greater scientific understanding of how it works, particularly as an antibacterial agent, has led practitioners to reconsider the therapeutic value of honey . Once honey is commercially available as a regulated product in the UK, practitioners will have access to an effective, alternative wound treatment . Specific, sterilised honeys intended for wound care will provide a safe natural product to manage colonised or infected wounds that would otherwise remain unresponsive to treatment. Yakugaku Zasshi, 2002 Apr, 122(4), 291 - 4 {Antibacterial constituents against Helicobacter pylori of Brazilian medicinal plant, Pariparoba}; Isobe T et al.; Four known compounds have been isolated from the aerial parts of the Brazilian medicinal plant Pariparoba (Pothomorphe umbellata) . They were an alkaloid, a flavone, a dihydrocalcone, and a steroid . The chemical structures were established to be N-benzoylmescaline, wogonin, uvangoletin, and beta-sitosterol glucoside using spectral methods . Among these compounds, the main component N-benzoylmescaline showed significant antibacterial activity against Helicobacter pylori. J Mol Evol, 2002 May, 54(5), 665 - 70 Rapid evolution of the male-specific antibacterial protein andropin gene in Drosophila; Date-Ito A et al.; Andropin, which encodes an antibacterial protein, is closely linked to the Cecropin gene cluster of D . melanogaster . Andropin and Cecropins are considered to have originated from one common ancestor . However, the expression pattern of Andropin is distinct from that of Cecropins, being restricted to the adult male ejaculatory duct . To elucidate the evolutionary process of Andropin, we have sequenced Andropin genes from D . melanogaster and its closely related species . In D . melanogaster, the nucleotide diversity of Andropin is remarkably low compared to that of Cecropin . In contrast, nonsynonymous substitutions of Andropin are conspicuously frequent between species . From genomic Southern analysis, Andropin-like genes are present in at least the melanogaster species subgroup . The series of present results suggests that Andropin was born in the course of constructing the Drosophila Cecropin gene family and then started to evolve rapidly, in contrast to Cecropins. Curr Opin Infect Dis, 2001 Jun, 14(3), 289 - 93 The role of C-reactive protein in the resolution of bacterial infection; Du Clos TW et al.; C-reactive protein is an acute phase protein in man and an important component of the innate immune system . C-reactive protein activates the classical pathway of complement, which is one of its main mechanisms in providing host defense . It has recently been recognized that C-reactive protein interacts with the cells of the immune system by binding to Fc gamma receptors . It may thus bridge the gap between innate and adaptive immunity and provide an early, effective antibacterial response . Furthermore, as it protects against the damaging inflammatory response to lipopolysaccharide and cytokines, it may prevent the lethal side-effects of bacterial products . The recent identification of the interaction of C-reactive protein with Fc gamma receptors will lead to an enhanced understanding of C-reactive protein and its role in both the innate and acquired immune systems. Curr Opin Infect Dis, 2000 Apr, 13(2), 171 - 176 Acute exacerbations of chronic bronchitis; Ball P; Acute exacerbations of chronic bronchitis are one of the major public health challenges . New data suggest that they will remain so for many years . Although the role of bacteria in the initiation and maintenance of bronchial inflammation, both during and between exacerbations, is well recognized, studies of the long-term effects of therapy are few and inadequate, and the nature of the relationship with disease progression is largely unknown . Data are beginning to emerge that firmly link bacterial inflammation and progressive disease with physiological and functional disability . Methods are being developed to provide integrated, uncomplicated and reproducible assessments of health-related quality of life . These may prove fundamental to the proper investigation of new treatment modalities . Among the newer antibacterial agents, fluoroquinolones have received most investigative attention, regrettably usually without providing clinical confirmation of their obvious superiority in vitro and of their pharmacokinetic and related pharmacodynamic properties . New trial designs need to address an integrated outcome analysis, with the assessment of long-term benefit and pharmaco-economic monitoring . More antibacterial agents are available at the millennium than ever before . After 50 years, it would be preferable if we knew a little more about their role in this complex disease. Curr Opin Allergy Clin Immunol, 2001 Aug, 1(4), 327 - 35 Chemistry of drug allergenicity; Baldo BA et al.; Of the very large number and variety of drugs used in medicine, those that are frequently implicated in immediate allergic reactions are relatively small in number and include neuromuscular blocking drugs used in anaesthesia, beta-lactam antibiotics, some other antibacterial agents including broad-spectrum antibiotics and quinolones and, less often, some narcotics . Structure-activity and immunochemical investigations have been most numerous and detailed for neuromuscular blocking drugs and beta-lactams, particularly penicillins . For the former group of drugs, morphine is proving to be a useful agent for the in-vitro detection of clinically relevant neuromuscular blocking drug-- as well as morphine- and fentanyl-reactive IgE antibodies . The employment of so-called 'major' and 'minor' determinants for a range of different penicillins and cephalosporins has revealed previously unsuspected heterogeneity in patient recognition responses, and has reinforced findings on the allergenic importance of side-chain groups . Many reports have been published on anaphylaxis to chlorhexidine, and progress in identifying allergenic determinants is reviewed together with the still inadequately understood subject of IgE antibody recognition of quinolone antibacterial agents. Gynecol Obstet Invest, 2002, 53(2), 93 - 9 Effects of ondansetron, granisetron, ramosetron, and azasetron on human neutrophil functions; Mikawa K et al.; Neutrophil functions play an important role in the antibacterial or antitumor host defense system . Ondansetron, granisetron, ramosetron, and azasetron are often used in gynecological patients as a prophylaxis against postoperative emesis or chemotherapy-induced emesis . In this study, using an ex vivo system, we have shown that these antiemetics at clinically relevant concentrations had no effect on superoxide (O(-)(2)) and hydrogen peroxide (H(2)O(2)) production of neutrophils, although high doses of these drugs significantly inhibited it to a similar degree . The drugs failed to impair chemotaxis or phagocytosis and to scavenge O(-)(2) or H(2)O(2) generated by an acellular system . Inhibition of the reactive oxygen species production may be due to attenuation of calcium elevation in neutrophils with these antiemetics . Our findings suggest that we are able to use these antiemetics in gynecological patients with cancer or those undergoing surgery without great caution . Antimicrob Agents Chemother, 2002 May, 46(5), 1607 - 9 Gemifloxacin is efficacious against penicillin-resistant and quinolone-resistant pneumococci in experimental meningitis; Cottagnoud P et al.; In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log(10) {Deltalog(10)} CFU/ml/h, -0.68 +/- 0.30 {mean and standard deviation}), even superior to that of the standard regimen of ceftriaxone plus vancomycin (-0.49 +/- 0.09 deltalog(10) CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) . Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (-0.48 +/- 0.16 deltalog(10) CFU/ml/h) . The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro. Bioorg Med Chem Lett, 2002 Mar 25, 12(6), 857 - 9 Synthesis and antibacterial activity of linezolid analogues; Yu D et al.; Several new compounds of oxazolidinone class were designed and synthesized referring to the structure-activity relationship studies and the synthesis of Linezolid, and their antibacterial activity was studied. Bioorg Med Chem Lett, 2002 Mar 25, 12(6), 849 - 52 Antibacterial activity of G6-quaternary ammonium derivatives of a lipophilic vancomycin analogue; Blizzard TA et al.; A series of G6-amino derivatives of a lipophilic vancomycin analogue was prepared . Antibacterial activity of the analogues was inversely proportional to the degree of substitution of the G6-nitrogen . The fully substituted (quaternary) analogues were essentially inactive against vanA phenotype VREF strains but retained substantial activity against other bacteria, a profile reminiscent of teicoplanin. Appl Microbiol Biotechnol, 2002 Apr, 58(5), 582 - 94 Epub 2002 Feb 15. Biotechnological applications and potential of wood-degrading mushrooms of the genus Pleurotus; Cohen R et al.; The genus Pleurotus comprises a group of edible ligninolytic mushrooms with medicinal properties and important biotechnological and environmental applications . The cultivation of Pleurotus spp is an economically important food industry worldwide which has expanded in the past few years . P . ostreatus is the third most important cultivated mushroom for food purposes . Nutritionally, it has unique flavor and aromatic properties; and it is considered to be rich in protein, fiber, carbohydrates, vitamins and minerals . Pleurotus spp are promising as medicinal mushrooms, exhibiting hematological, antiviral, antitumor, antibiotic, antibacterial, hypocholesterolic and immunomodulation activities . The bioactive molecules isolated from the different fungi are polysaccharides . One of the most important aspects of Pleurotus spp is related to the use of their ligninolytic system for a variety of applications, such as the bioconversion of agricultural wastes into valuable products for animal feed and other food products and the use of their ligninolytic enzymes for the biodegradation of organopollutants, xenobiotics and industrial contaminants . In this Mini-Review, we describe the properties of Pleurotus spp in relation to their biotechnological applications and potential. Int J Pediatr Otorhinolaryngol, 2002 Apr 25, 63(2), 111 - 8 A preventive measure for otitis media in children with upper respiratory tract infections; Mora R et al.; Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages . Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population . The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications . Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections . Eighty-four paediatric patients of both sexes (range: 4-14 years) with otitis were enrolled in the study . Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study . The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month . Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions . Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost . The reduction in the incidence of infectious episodes became significant vs . placebo . A significantly improved outcome vs . placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies . Immucytal treatment was associated with significant changes in both immunological and auditory function parameters . Serum concentrations of immunoglobulins were significantly increased in Immucytal . For both evaluations, a significant difference between treatment groups was found (P>0.001) . Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach. Mol Microbiol, 2002 Mar, 43(6), 1493 - 504 OmpR-dependent and OmpR-independent responses of Escherichia coli to sublethal attack by the neutrophil bactericidal/permeability increasing protein; Prohinar P et al.; Bactericidal/permeability-increasing protein (BPI) of neutrophils is a lipopolysaccharide (LPS)-binding antibacterial protein with specificity for Gram negative bacteria . BPI binding to the bacterial surface rapidly triggers potentially reversible bacterial growth inhibition and alterations of the outer membrane and, later, disruption of the inner membrane and lethal injury