Bactericidal

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 . Initial effects include selective OmpR-dependent changes in the synthesis of outer membrane porins (OmpF and OmpC) . Because OmpR is a global transcriptional regulator, we have examined its possible role in responses of E . coli to sublethal injury caused by BPI . Early (<15 min) reversible effects of BPI on bacterial colony-forming ability and outer membrane permeability were virtually identical in isogenic wild-type (wt) and ompR- E . coli . Both strains could repair the outer membrane permeability barrier after Mg2+-induced displacement of bound BPI . However, OmpR was essential for the ability of E . coli to tolerate low doses of BPI and escape the progression of sublethal to lethal damage . Scanning electron microscopy revealed that BPI treatment produced greater membrane perturbations in the ompR- strain, apparent even before lethal injury . These findings suggest that the fate of E . coli exposed to BPI depends on both OmpR-independent mechanisms engaged in outer membrane repair and OmpR- dependent processes that modulate porin synthesis and retard progression of injury from the outer to the inner membrane.

Am J Dent, 2001 Dec, 14(6), 387 - 96
The biocompatibility of glass-ionomer cement materials . A status report for the American Journal of Dentistry; Sidhu SK et al.; Since their introduction in the market, some 30 yrs ago, the biocompatibility aspects of glass-ionomer cements (GICs) have been intensively studied . In general, cytotoxicity of fully set conventional preparations in previous studies was shown to be minimal . However, a resin-modified preparation proved to be cytotoxic under these conditions . This product was also observed to be mutagenic, but data in this area are sparse and difficult to interpret . There is also evidence that certain GICs exert some antibacterial properties which is claimed to be related to the fluoride release; however, the mechanisms for this fluoride release are still unclear . Pulp response studies have shown conflicting results . However, unfavorable initial reactions, if present, resolved with time if a bacterial layer under the restoration and pulp exposures were prevented . Pain reactions after cementation of cast restorations with GICs have been reported in the past but there are no such reports in the more recent literature.

J Laryngol Otol, 2002 Apr, 116(4), 264 - 8
Immunocytochemical localization of lysozyme and lactoferrin attached to surface bacteria of the palatine tonsils during infectious mononucleosis; Stenfors LE et al.; Bacterial samples were obtained from the tonsillar surfaces of seven patients (four males, three females; median age 18 years, range 15 to 21 years) suffering from acute infectious mononucleosis with concomitant pharyngotonsillitis, and from five healthy controls . By using gold-labelled antiserum to human lysozyme and lactoferrin, micro-organisms on the tonsillar surfaces coated with these antibacterial substances could be identified by tracing the gold particles in the transmission electron microscope . In healthy individuals, most of the bacteria were coated with lysozyme and significantly more bacteria were coated with lysozyme than with lactoferrin (p < 0.01) . In patients there was a non-significant reduction in lysozyme-coating of the bacteria, whereas lactoferrin-coating was significantly increased (p < 0.01) . Changes in the lysozyme and/or lactoferrin coating of the tonsillar surface bacteria on the palatine tonsils during infectious mononucleosis cannot explain the tendency to immense local bacterial colonization with commensals and proneness to bacterial penetration into the epithelial cells.

Curr Pharm Des, 2002, 8(11), 995 - 1005
Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection; Caradonna L et al.; Endotoxins or lipopolysaccharides (LPS), major components of the cell wall of Gram-negative bacteria, once released from the bacterial outer membrane bind to specific receptors and, in particular, to a membrane-bound receptor, the CD14 (mCD14) and the toll-like receptor 4 present on monocytes/ macrophages . In turn, LPS-activated monocytes/ macrophages release in the host tissue an array of so-called proinflammatory cytokines and, among them, Tumor Necrosis Factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-12 are the major mediators . Before therapy (To) and at the end of 6-month interferon (IFN)-alpha/Ribavirin (RIB) treatment (T6), circulating endotoxin levels were measured in responder and non responder HCV+ patients . At T0, 57% of the non responders were endotoxin-positive and had, on average, 54 pg/ml of plasma LPS while in 50% of the responder patients endotoxin were found with an average of 29 pg/ml . At T6, in responders LPS were no longer detectable, while in 42% of the non responders LPS were found (average levels 45 pg/ml) . In terms of serum cytokine concentration, at T6 IFN-gamma levels when compared to those detected at T0 were increased in both endotoxin-positive and endotoxin-negative patients . However, at T6 IL-10 concentration was significantly increased only in the group of endotoxin-negative subjects (responder patients), in comparison to T0 values . The origin of endotoxemia in HCV+ patients seems to be multifactorial, likely depending on impaired phagocytic functions and reduced T-cell mediated antibacterial activity . In these patients, however, one cannot exclude the passage of LPS from the gut flora to the blood stream, owing a condition of altered intestinal permeability . At the same time, a less efficient detoxification of enteric bacterial antigens at the hepatic level should be taken into consideration . Finally, novel therapeutic attempts aimed to neutralize LPS in the host are discussed.

Curr Med Chem, 2002 Feb, 9(4), 471 - 98
Recent developments in depsipeptide research; Ballard CE et al.; This review focuses on the major developments in depsipeptide research since 1995 . Depsipeptides are bio-oligomers composed of hydroxy and amino acids linked by amide and ester bonds . Many depsipeptides show very promising biological activities, including anticancer, antibacterial, antiviral, antifungal, anti-inflammatory, and anti-clotting or anti-antherogenic properties . In this report depsipeptides exhibiting these properties are discussed . Their isolation, structural determination, and notable structural features are discussed, but their biological properties and therapeutic potentials are emphasized . Depsipeptides have shown the greatest therapeutic potential as anticancer agents . Four depsipeptides have entered clinical trials for cancer treatment . Among the antiviral compounds discovered, the callipeltins and the quinoxapeptins are particularly promising due to their inhibitory activities against HIV . These compounds have the potential to be developed as anti-AIDS drugs or to serve as lead compounds for the discovery of structurally related anti-AIDS compounds . Antifungal compounds, such as the jaspamides, may lead to therapies against many of the opportunistic infections that accompany AIDS . Anti-inflammatory compounds such as SCH217048 act as neurokinin antagonists and may lead to anti-inflammatory treatments . Some depsipeptides such as micropeptins and A90720A have been found to be effective plasmin inhibitors, which have implications as treatments for cardiovascular diseases . Compounds such as SCH58149 help control the levels of HDL and LDL.

Biochem Biophys Res Commun, 2002 Apr 12, 292(4), 964 - 8
L-Methionine-gamma-lyase, as a target to inhibit malodorous bacterial growth by trifluoromethionine; Yoshimura M et al.; Methyl mercaptan is a major component responsible for oral malodor . This compound arises from the bacterial metabolism of methionine . Here we show that the growth of Porphyromonas gingivalis, a periodontal microorganism that produces large amounts of methyl mercaptan, was strongly inhibited by l-trifluoromethionine (TFM), a fluorinated derivative of methionine . In contrast, TFM had no effect on the growth of bacteria which do not produce methyl mercaptan . In addition, the survival rate of P . gingivalis-infected mice was remarkably increased by the co-injection of TFM . These results suggest that TFM is a promising antibacterial agent specific to the malodorous oral bacteria . (c)2002 Elsevier Science (USA).

Klin Khir, 2002 Jan, (1), 40 - 1
{Experience of application of meronem in the treatment of severe purulent sepsis in children}; Sleptsov VP et al.; Results of antibacterial therapy with application of meropenem (meronem by firm Astra Zeneca, Great Britain) in 29 childs with severe purulent-septic state, including 5 with toxic peritonitis, in 2--with sepsis, in 3 newborn childs--with esophageal atresia and in 19--with the blood disease (nonhodgkin's lymphoma, an acute lymphoblastic or myeloblastic leucosis, reccurrent of acute lymphoblastic leucosis, nephroblastoma).

Lancet Infect Dis, 2002 Mar, 2(3), 171 - 9
Role of lipoteichoic acid in infection and inflammation; Ginsburg I; Lipoteichoic acid (LTA) is a surface-associated adhesion amphiphile from Gram-positive bacteria and regulator of autolytic wall enzymes (muramidases) . It is released from the bacterial cells mainly after bacteriolysis induced by lysozyme, cationic peptides from leucocytes, or beta-lactam antibiotics . It binds to target cells either non-specifically, to membrane phospholipids, or specifically, to CD14 and to Toll-like receptors . LTA bound to targets can interact with circulating antibodies and activate the complement cascade to induce a passive immune kill phenomenon . It also triggers the release from neutrophils and macrophages of reactive oxygen and nitrogen species, acid hydrolases, highly cationic proteinases, bactericidal cationic peptides, growth factors, and cytotoxic cytokines, which may act in synergy to amplify cell damage . Thus, LTA shares with endotoxin (lipopolysaccharide) many of its pathogenetic properties . In animal studies, LTA has induced arthritis, nephritis, uveitis, encephalomyelitis, meningeal inflammation, and periodontal lesions, and also triggered cascades resulting in septic shock and multiorgan failure . Binding of LTA to targets can be inhibited by antibodies, phospholipids, and specific antibodies to CD14 and Toll, and in vitro its release can be inhibited by non-bacteriolytic antibiotics and by polysulphates such as heparin, which probably interfere with the activation of autolysis . From all this evidence, LTA can be considered a virulence factor that has an important role in infections and in postinfectious sequelae caused by Gram-positive bacteria . The future development of effective antibacteriolitic drugs and multidrug strategies to attenuate LTA-induced secretion of proinflammatory agonists is of great importance to combat septic shock and multiorgan failure caused by Gram-positive bacteria.

Proc Natl Acad Sci U S A, 2002 Apr 16, 99(8), 5638 - 42 Epub 2002 Apr 09.
Mechanism of plasmid-mediated quinolone resistance; Tran JH et al.; Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV . Widespread use of these agents has contributed to the rise of bacterial quinolone resistance . Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes . Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones . We have cloned the plasmid-quinolone resistance gene, termed qnr, and found it in an integron-like environment upstream from qacE Delta 1 and sulI . The gene product Qnr was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17 . Qnr had pentapeptide repeat domains of 11 and 28 tandem copies, separated by a single glycine with a consensus sequence of A/C D/N L/F X X . Because the primary target of quinolones is DNA gyrase in Gram-negative strains, we tested the ability of Qnr to reverse the inhibition of gyrase activity by quinolones . Purified Qnr-His(6) protected Escherichia coli DNA gyrase from inhibition by ciprofloxacin . Gyrase protection was proportional to the concentration of Qnr-His(6) and inversely proportional to the concentration of ciprofloxacin . The protective activity of Qnr-His(6) was lost by boiling the protein and involved neither quinolone inactivation nor independent gyrase activity . Protection of topoisomerase IV, a secondary target of quinolone action in E . coli, was not evident . How Qnr protects DNA gyrase and the prevalence of this resistance mechanism in clinical isolates remains to be determined.

Recenti Prog Med, 2002 Mar, 93(3), 200 - 11
{Piperacillin-tazobactam in the treatment of severe nosocomial infections}; Venditti M et al.; Epidemiology and clinical manifestations of nosocomial infections have been progressively evolving through last three decades . New pathogens, often associated to multiple antibiotic-resistances, are now among the leading etiologies in a patient population mainly represented by individuals debilitated by serious underlying diseases, immunosuppressive treatments and multiple diagnostic and therapeutic invasive procedures . Under these circumstances, when an infectious complication develops, prompt initiation of empiric antibiotic therapy, based on general and/or local epidemiology of nosocomial infections, may be crucial for survival of more critically ill patients . Based on recent data, the antibiotics of choice for treatment of nosocomial infections should have not only a bactericidal activity and a broad antibacterial spectrum, but also poor propensity to induce antibiotic-resistance and a satisfactory pharmacoeconomy profile . After a detailed description of the above mentioned context, the pre-eminent role of piperacillin-tazobactam in the treatment of nosocomial infections is reviewed and discussed.

J Biol Chem, 2002 Jun 21, 277(25), 22131 - 9 Epub 2002 Apr 08.
Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression; Hsu HY et al.; Lipopolysaccharide (LPS) stimulates macrophages to release inflammatory cytokines, interleukin-1 beta (IL-1), and tumor necrosis factor (TNF) . LPS-induced TNF suppresses scavenger receptor functions in macrophages (van Lenten, B . J., and Fogelman, A . M . (1992) J . Immunol . 148, 112-116), which is regulated by TNF-mediated protein kinases (Hsu, H . Y., and Twu, Y . C . (2000) J . Biol . Chem . 275, 41035-41048) . To examine the molecular mechanism for LPS induction of IL-1 in macrophages, we demonstrated that LPS quickly stimulated reactive oxygen species (ROS), and 3 h later induced prointerleukin-1 beta (pro-IL-1, precursor of IL-1) production and IL-1 secretion . LPS stimulated pro-IL-1 message/protein between 3 and 10 h; however, there was a 40% reduction of pro-IL-1 in preincubation of the antioxidant, N-acetylcysteine (NAC) . Moreover, NAC moderated LPS-induced IL-1 secretion partially via interleukin 1-converting enzyme . The maximal activity of LPS-induced ERK, JNK, and p38 was 12- (30 min), 5- (30 min), and 16-fold (15 min), respectively . In contrast, NAC reduced ERK activity to 60% and decreased p38 activity to the basal level, but JNK activity was induced 2-fold . Furthermore, the pharmacological antagonists LY294002, SB203580, curcumin, calphostin C, and PD98059 revealed the diverse roles of LPS-mediated protein kinases in pro-IL-1 . On the other hand, NAC and diphenyleneiodonium chloride partially inhibited LPS-induced Rac activity and protein-tyrosine kinase (PTK), indicating that LPS-mediated ROS and NADPH oxidase correspond to Rac activation and IL-1 expression . Our findings establish for the first time that LPS-mediated PTK/phosphatidylinositol 3-kinase/Rac/p38 pathways play a more important role than pathways of PTK/PKC/MEK/ERK and of PTK/phosphatidylinositol 3-kinase/Rac/JNK in the regulation of pro-IL-1/IL-1 . The findings also further elucidate the critical role of LPS-mediated ROS in signal transduction pathways . Our results suggest that understanding LPS-transduced signals in IL-1 induction upon the antibacterial action of macrophages should provide a therapeutic strategy for aberrant inflammatory responses leading to severe cellular injury or concurrent multiorgan septic damage.

J Clin Periodontol, 2002 Mar, 29(3), 207 - 10
Anti-plaque effect of tempered 0.2% chlorhexidine rinse: an in vivo study; Konig J et al.; OBJECTIVES: The aim of this in vivo study was to compare the anti-plaque effect of warm and cold chlorhexidine gluconate irrigation on matured human plaque . METHODS: In a split-mouth design, the antibacterial effect of 47 degrees C "warm" 0.2% chlorhexidine solution was compared with that of 18 degrees C "cold" rinse at the same concentration on newly-formed supragingival plaque that had been left undisturbed for 72 h . Before and 1 h after a 1-min rinse procedure, plaque was sampled from 10 test persons and vitality determined using vital fluorescence technique . RESULTS: Cold and warm 0.2% chlorhexidine solution reduced plaque vitality significantly from 99.63% to 77.81% (p=0.014) and from 98.98% to 51.77% (p<0.001), respectively . Rinsing with warm chlorhexidine solution reduced plaque vitality to a significantly greater degree (p=0.003) than did cold chlorhexidine . CONCLUSION: In this study, warm 0.2% chlorhexidine rinse showed a significantly more intensive anti-plaque effect than cold chlorhexidine solution at the same concentration.

Yao Xue Xue Bao, 1998, 33(4), 269 - 74
{Studies on synthesis and bioactivity of 2-alkenyl-4(1H)-quinolone}; Tang Y et al.; Three 2-alkenyl-4(1H)-quinolone compounds(I-III) were synthesized by two methods . III is a new compound from Evodia rutaecarpa and was synthesized through the reaction of the aldehyde intermediate(5) with Wittig reagent . The other two compounds were synthesized for the first time . These compounds showed vasodilating and antibacteria effects in pharmacological tests.

Int Immunol, 2002 Apr, 14(4), 421 - 6
Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway; Niyonsaba F et al.; Mast cells are known to accumulate at the sites of inflammation in response to chemoattractants generated in the local milieu . Since human beta-defensin-2 (hBD-2) is generated in several epithelial tissues where mast cells are present and because we have recently reported that this human antibacterial peptide induces mast cell degranulation, we thus hypothesized that hBD-2 could be a mast cell chemotaxin . Here we report that hBD-2 directly and specifically induces mast cell migration with an optimal concentration of 3 microg/ml . Checkerboard analysis showed that the migration was more chemotactic rather than chemokinetic . Moreover, Scatchard analysis using 125I-labeled hBD-2 revealed that mast cells have at least two classes of receptors, high- and low-affinity receptors, for this peptide . Moreover, the competitive binding assay suggested that hBD-2 is unlikely to utilize CCR6, a functional receptor for hBD-2-mediated dendritic and T cell migration, on mast cells . In addition, treatment of mast cells with G protein inhibitor, pertussis toxin, and phospholipase C inhibitor, U-73122, abolished the cell chemotaxis in response to hBD-2, indicating that the G protein-phospholipase C signaling pathway is involved in hBD-2-induced mast cell activation . Thus, we suggest that hBD-2, which was originally believed to be involved in innate host defense, may participate in the recruitment of mast cells to inflammation foci.

Bioorg Med Chem Lett, 2002 Apr 22, 12(8), 1209 - 13
Synthesis of sub-micromolar inhibitors of MraY by exploring the region originally occupied by the diazepanone ring in the liposidomycin structure; Dini C et al.; The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described . These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY . Thus, inhibitory activity was improved from 5300 to 140 nM . This improvement was correlated with the length and lipophilicity of substituents, but was found to be independent of the nature of the chemical bond generated . In addition, some of these inhibitors presented encouraging antibacterial activities.

Pathol Biol (Paris), 2002 Mar, 50(2), 109 - 17
{Local treatment of burns}; Dhennin C; Local burn care is one among the components of the total burn care . However since local wounds initiate and maintain the systemic disorders and provoke the aesthetic and functional sequellae, its significance must be stressed . The quality of the results relies upon teams trained and organized to control infection hazards in centres specifically designed . Closure of the wounds, through spontaneous healing of superficial burns or surgical techniques in deep ones, represents the aim of local care which includes the cleaning and dressing of superficial wounds and deep ones before and after grafting, with topical antibacterial (or not) agents, and also excision and grafting procedures . Today skin autografts remain the basic technique for closing deep burns . However because of the inadequacy between donor and wound areas either they must be meshed or other methods are added especially skin allografts, keratinocytes cultures or artificial skin . Local care does not come to an end when wound closure is achieved because of the lengthy rehabilitation cares such as massages, wearing of custom-fitted pressure garments, cures at specialized spas and some patients also need secondary surgery . Burn injuries remain one of the most devastating ordeal that a human being can sustain, because most of them provoke permanent and severe after-effects, whatever their extend and areas, that initial local care must aim at minimizing.

J Inorg Biochem, 2002 Apr 10, 89(1-2), 89 - 96
15-MC-5 manganese metallacrowns hosting herbicide complexes . Structure and bioactivity; Dendrinou-Samara C et al.; Interaction of manganese with salicylhydroxamic ligands leads to the formation of a series of 15-membered metallacrown Mn(II)(L)(2){15-MC(Mn(III)N(shi))-5}(py)(6) (L=alkanoato ligand) . The crystal structure contains a neutral 15-membered metallacrown ring of the type {15-MC(Mn(III)N(shi))-5} . The metallacrown core consists of five Mn(III) and five shi(-3) ligands . The 15-membered metallacrown ring is formed by the succession of five structural moieties of the type {Mn(III)-N-O} . The diversity in the configuration (planar or propeller) for the ring Mn(III) ions gives to the metallacrown core flexibility and simultaneously allows the encapsulation of the sixth Mn(II) . The encapsulated Mn(II) is seven-coordinate and is bound to the five hydroximate oxygen donors provided by the metallacrown core, and two oxygen atoms from the carboxylate herbicide ligands . Antibacterial screening data showed that among all the compounds tested, manganese metallacrowns are more active than the simple manganese herbicide or carboxylate complexes while an increase in the efficiency of {15-MC(Mn(III)N(shi))-5} towards the analogous {12-MC(Mn(III)N(shi))-4} can be observed.

J Pharm Biomed Anal, 2002 Apr 15, 28(2), 217 - 25
Voltammetric studies of the interaction of lumazine with cyclodextrins and DNA; Ibrahim MS et al.; The interaction of lumazine, an antibacterial drug, with alpha-, beta-cyclodextrins and DNA in aqueous solution was studied by differential pulse stripping voltammetry and cyclic voltammetry as well as UV-vis spectroscopy . The electrochemical and absorption spectral data indicated a 1:1 complex formation of lumazine with alpha-, beta-cyclodextrins and DNA . The nature of the process, taking place at the hanging mercury drop electrode, was clarified . It was found that the complexation of lumazine molecules enhances the stacking interactions which might facilitate the formation of a perpendicularly stacked layer of lumazine-alpha-cyclodextrin complex on the electrode surface . Based on the variations in the current or absorbance, the formation constants and consequently, the Gibbs energy of these complexes were determined . The small size cavity of alpha-cyclodextrin was found to have a greater affinity for lumazine than the beta-cyclodextrin . Moreover, the interactions of lumazine-alpha-cyclodextrin or lumazine-beta-cyclodextrin inclusion complex with DNA have been investigated by means of voltammetry . The results suggest that lumazine displayed high affinity for DNA and the inclusion complex decomposed when it binds to DNA.

Pharmacoeconomics, 2002, 20(3), 153 - 68
Acute exacerbations of chronic bronchitis: a pharmacoeconomic review of antibacterial use; Morris S et al.; Chronic bronchitis is a common problem affecting a large proportion of the adult population . People with chronic bronchitis are subject to recurrent attacks of bronchial inflammation called acute exacerbations of chronic bronchitis (AECBs) . In patients with AECBs, symptoms may worsen due to a bacterial infection; the exacerbation is then known as an acute bacterial exacerbation of chronic bronchitis (ABECB) . ABECBs are thought to be controllable through the use of antibacterial agents . In this paper we review current evidence on the cost of chronic bronchitis and AECBs, the cost effectiveness of antibacterials in the management of ABECB, and the factors that may affect the cost-effectiveness of antibacterials in the management of ABECB . We find that the number of economic evaluations conducted in this area is small . Of the few economic evaluations that have been conducted there has been only one prospective economic evaluation based on a clinical trial . The remainder are simple decision analysis-based modelling studies or retrospective database studies . Our principle findings are as follows: a key factor affecting the cost-effective use of antibacterials in the management of ABECB is the definitive diagnosis of the condition . Unfortunately, diagnosing a bacterial cause of an AECB is difficult, which presents problems in ensuring that antibacterials are not prescribed unnecessarily;current evidence suggests but does not prove that use of more effective but more costly first-line antibacterials may be relatively cost effective and may minimise overall expenditure by reducing the high costs associated with treatment failure;chronic bronchitis and AECB have a significant and negative physical and psychological effect on health-related quality of life . In conclusion, the small number of economic evaluations conducted in this area, coupled with the nature of the design of these studies, precludes a definitive statement recommending which specific antibacterial should be preferred on cost-effectiveness grounds for the management of ABECB . On the basis of our findings we suggest some topics for further research.

Int J Clin Pract, 2002 Mar, 56(2), 132 - 9
An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole; Bown RL; Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion in a dose-dependent manner via inhibition of H+/K+-adenosine triphosphatase in gastric parietal cells . It also exhibits antibacterial activity against Helicobacter pylori in vitro . During almost 10 years of clinical use, lansoprazole has proved effective and well tolerated in a wide range of acid-related disorders, including gastro-oesophageal reflux disease (GORD), duodenal ulcers, gastric ulcers, non-steroidal anti-inflammatory drug-related ulcers, as well as non-ulcer dyspepsia and acid hypersecretion . It is also used, in combination with antibiotics, for H . pylori eradication . In the above indications, lansoprazole has generally proved to be superior to the histamine H2-receptor antagonists, and is at least as effective as the other currently available proton pump inhibitors . This review aims to evaluate the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole in acid-related disorders, with particular emphasis on its use in GORD and H . pylori eradication regimens.

Z Naturforsch {C}, 2002 Jan-Feb, 57(1-2), 21 - 8
New triterpenoidal alkaloids from Buxus sempervirens; Ata A et al.; Phytochemical studies on the ethanolic extract of the roots of Buxus sempervirens of Turkish origin have resulted in the isolation of two new triterpenoidal alkaloids, (+)-16a, 31-diacetylbuxadine (1), (-)-Nb-demethylcyclomikuranine (2) along with three known natural products, (-)-cyclomikuranine (3), (-)-cyclobuxophylline-K (4) and (+)-buxaquamarine (5) isolated for the first time from this species of genus Buxus . The structures of these new natural products were established on the basis of extensive spectroscopic studies . Compound 1 exhibited antibacterial activity against human pathogenic bacteria and weak phytotoxic activity against Lemna minor Linn.

Invest Ophthalmol Vis Sci, 2002 Apr, 43(4), 1182 - 8
An in vitro study of ceftazidime and vancomycin concentrations in various fluid media: implications for use in treating endophthalmitis; Kwok AK et al.; PURPOSE: To investigate the precipitation process of a mixture of vancomycin and ceftazidime by equilibrium dialysis and determine its subsequent effect on the level of free antibiotics for treatment of endophthalmitis . METHODS: Concentrations of vancomycin and ceftazidime in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography . Normal saline (NS), balanced salt solution (BSS), and vitreous were used separately as the medium of dialysis . RESULTS: Precipitation of ceftazidime occurred at 37 degrees C but not at room temperature and did not affect the pH of the medium . It formed precipitate on its own or when mixed with vancomycin in all the three media of NS, BSS, and vitreous . More precipitation was formed if ceftazidime was initially prepared in BSS than in NS . After 168 hours in the dialysis chambers, ceftazidime prepared in NS precipitated to 54% of that in vitreous, compared with 88% if prepared in BSS . At 48 hours, ceftazidime prepared in NS decreased from an initial concentration of 137.5 to 73.4 microg/mL in vitreous medium and to 6.3 microg/mL if prepared in BSS . Precipitation of vancomycin was negligible . CONCLUSIONS: Based on this in vitro investigation, ceftazidime precipitates in vitreous at body temperature, regardless of the presence of vancomycin . NS is preferred to BSS as a preparation medium for antibiotics for intravitreal injection, because the extent of ceftazidime precipitation is less . However, due to precipitation, the concentration of free ceftazidime in vitreous may not be sufficiently high for antibacterial activity against most common organisms.

J Infect Dis, 2002 Mar 15, 185(6), 805 - 11 Epub 2002 Feb 19.
Bacterial endosymbionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions; Keiser PB et al.; Treatment of onchocerciasis with diethylcarbamazine (DEC) or ivermectin is associated with a posttreatment reaction characterized by fever, tachycardia, hypotension, lymphadenopathy, and pruritus . To investigate the role of the Wolbachia bacterial endosymbiont of Onchocerca volvulus in these reactions, serum samples collected before and after treatment with either anthelmintic were assessed for evidence of Wolbachia DNA . By use of real-time quantitative polymerase chain reaction, Wolbachia DNA was detected in both groups-with significantly higher levels in those who received DEC (P <.0001) . In the ivermectin group, there was a significant correlation between levels of bacterial DNA and serum tumor necrosis factor-alpha (P =.013) . Peak DNA levels correlated with reaction scores (P =.048) . Significant correlations were also seen between Wolbachia DNA and the antibacterial peptides calprotectin (P =.021) and calgranulin B (P <.0001) . These findings support a role for Wolbachia products in mediating the inflammatory responses seen following treatment of onchocerciasis and suggest new targets for modulating these reactions.

Med Hypotheses, 2001 Dec, 57(6), 764 - 9
Are superoxide and/or hydrogen peroxide responsible for some of the beneficial effects of hyperbaric oxygen therapy?
Hink J, Jansen E.
The basic mechanisms behind the pharmacologic effects of hyperbaric oxygen therapy are not clear . Reactive oxygen metabolites are generally associated with the adverse reactions to hyperbaric oxygen exposure but they are also believed to be involved in the antibacterial effects of this therapy . The possibility that reactive oxygen metabolites are responsible for some of the other reported beneficial effects of hyperbaric oxygen therapy has not been investigated . This hypothesis paper briefly reviews the literature suggesting that the pharmacologic actions underlying some of the beneficial effects of hyperbaric oxygen therapy may be caused by superoxide and/or hydrogen peroxide . Elucidation of the pharmacologic mechanisms is fundamental in order to fully exploit the therapeutic potential of hyperbaric oxygen and we incite experimental research to be done within this area.

J Antibiot (Tokyo), 2002 Jan, 55(1), 25 - 9
CJ-21,058, a new SecA inhibitor isolated from a fungus; Sugie Y et al.; A new equisetin derivative, CJ-21,058 (I) was isolated from the fermentation broth of an unidentified fungus CL47745 . It shows antibacterial activity against Gram-positive multi-drug resistant bacteria by inhibiting ATP-dependent translocation of precursor proteins across a bacterial cell membrane.

Med Arh, 2002, 56(1), 43 - 8
{Hexetidine--an oral antiseptic}; Kapic E et al.; Hexetidine is very safe oral antiseptic with broad antibacterial and antifungal activity in vivo and in vitro . It has local-anesthetics, astringent and deodorant activity . Also, it has very strong antiplac effects . Resistention of microorganisms on hexetidine is short and transient . These characteristics give important therapeutic role in treatment of oral infections.

J Am Chem Soc, 2002 Apr 3, 124(13), 3229 - 37
Design of novel antibiotics that bind to the ribosomal acyltransfer site; Haddad J et al.; The structure of neamine bound to the A site of the bacterial ribosomal RNA was used in the design of novel aminoglycosides . The design took into account stereo and electronic contributions to interactions between RNA and aminoglycosides, as well as a random search of 273 000 compounds from the Cambridge structural database and the National Cancer Institute 3-D database that would fit in the ribosomal aminoglycoside-binding pocket . A total of seven compounds were designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA . Indeed, all synthetic compounds were found to bind to the target RNA comparably to the parent antibiotic neamine, with dissociation constants in the lower micromolar range . The synthetic compounds were evaluated for antibacterial activity against a set of important pathogenic bacteria . These designer antibiotics showed considerably enhanced antibacterial activities against these pathogens, including organisms that hyperexpressed resistance enzymes to aminoglycosides . Furthermore, analyses of four of the synthetic compounds with two important purified resistance enzymes for aminoglycosides indicated that the compounds were very poor substrates; hence the activity of these synthetic antibiotics does not appear to be compromised by the existing resistance mechanisms, as supported by both in vivo and in vitro experiments . The design principles disclosed herein hold the promise of the generation of a large series of designer antibiotics uncompromised by the existing mechanisms of resistance.

Nature, 2002 Apr 11, 416(6881), 644 - 8 Epub 2002 Mar 24.
Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E . coli; Ramet M et al.; The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans . Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages, suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity . We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis . These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor . This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria . Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified . Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo . Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E . coli), but not Gram-positive, bacterial infection . Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria . Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis.

Am J Vet Res, 2002 Mar, 63(3), 349 - 53
Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses; Peck KE et al.; OBJECTIVE: To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses . ANIMALS: 5 donkeys, 5 mules, and 3 horses . PROCEDURE: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg) . Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations . Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables . RESULTS: Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses . In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours) . Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys . Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys . CONCLUSIONS AND CLINICAL RELEVANCE: Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules . Donkeys eliminate the drugs rapidly, compared with horses . Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules.

Chem Pharm Bull (Tokyo), 2002 Mar, 50(3), 415 - 8
Syntheses of 1beta-methylcarbapenems bearing 5-methyl-4-hydroxypyrrolidinone; Pyun do K et al.; A new series of 1beta-methylcarbapenems 1a-d bearing 5-methyl-4-mercaptopyrrolidinone rings has been prepared and evaluated for in vitro antibacterial activity and pharmacokinetic parameters . Most compounds showed excellent antibacterial activity and high stability to dehydropeptidase-1 . We have synthesized optically active 5-methyl-4-hydroxypyrrolidinones from enantiomerically pure aziridine esters.

Chem Pharm Bull (Tokyo), 2002 Mar, 50(3), 413 - 4
Megistoquinones I and II, two quinoline alkaloids with antibacterial activity from the bark of Sarcomelicope megistophylla; Fokialakis N et al.; Two alkaloids, megistoquinone I (1) and megistoquinone II (2), were isolated from the bark of Sarcomelicope megistophylla . Their structures have been elucidated on the basis of MS and NMR data . Both belong to quinoline alkaloid series and should be considered as oxidation products of a furo{2,3-b}quinoline precursor . The two alkaloids showed antibacterial properties with minimum inhibitory concentration (MIC) ranging from 2.35 to 5.25 mg/ml for 1 and 0.73 to 1.23 mg/ml for 2.

Ceska Slov Farm, 2002 Jan, 51(1), 11 - 6
{Pharmaceutical importance of Allium sativum L . 2 . Antibacterial effects}; Sovova M et al.; The communication summarizes mainly newly obtained experimental findings confirming the antibacterial effect of garlic preparations (powders, extracts, juice, essential oil, oil macerate) and their individual components . It also reports the effectiveness of substances newly isolated from the oil macerate (iso-E-10-devinylajoene, Z-10-devinylajoene, and three, or five thiosulfinates) . The effect on the tested bacteria included here is, according to new evidence, indisputable . The paper has purposefully excluded the action of garlic against the widely distributed bacteria Helicobacter pylori, which causes chronic gastritis, gastric and duodenal ulcers . The findings concerning this matter will be published in the following communication.

Protein Sci, 2002 Apr, 11(4), 974 - 9
Acyl group specificity at the active site of tetrahydridipicolinate N-succinyltransferase; Beaman TW et al.; Tetrahydrodipicolinate N-succinyltransferase (DapD) catalyzes the succinyl-CoA-dependent acylation of L-2-amino-6-oxopimelate to 2-N-succinyl-6-oxopimelate as part of the succinylase branch of the meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green algae, and plants . This pathway provides meso-diaminopimelate as a building block for cell wall peptidoglycan in most bacteria, and is regarded as a target pathway for antibacterial agents . We have solved the X-ray crystal structures of DapD in ternary complexes with pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor analog, succinamide-CoA . These structures define the binding conformation of the cofactor succinyl group and its interactions with the enzyme and place its thioester carbonyl carbon in close proximity to the nucleophilic 2-amino group of the acceptor, in support of a direct attack ternary complex mechanism . The acyl group specificity differences between homologous tetrahydrodipicolinate N-acetyl- and N-succinyltransferases can be rationalized with reference to at least three amino acids that interact with or give accessible active site volume to the cofactor succinyl group . These residues account at least in part for the substrate specificity that commits metabolic intermediates to either the succinylase or acetylase branches of the meso-diaminopimelate/lysine biosynthetic pathway.

BioDrugs, 2002, 16(1), 57 - 62
Bacteriophages: potential treatment for bacterial infections; Duckworth DH et al.; Bacteriophages (phages) are viruses of bacteria that can kill and lyse the bacteria they infect . After their discovery early in the 20th century, phages were widely used to treat various bacterial diseases in people and animals . After this enthusiastic beginning to phage therapy, problems with inappropriate use and uncontrolled studies and ultimately the development of antibacterials caused a cessation of phage therapy research in the West . However, a few institutions in Eastern Europe continued to study and use phages as therapeutic agents for human infections . The alarming rise in antibacterial resistance among bacteria has led to a review of the Eastern European studies and to the initiation of controlled experiments in animal models . These recent studies have confirmed that phages can be highly effective in treating many different types of bacterial infections . The lethality and specificity of phages for particular bacteria, the ability of phages to replicate within infected animal hosts, and the safety of phages make them efficacious antibacterial agents . Although there are still several hurdles to be overcome, it appears likely that phage therapy will regain a role in both medical and veterinary treatment of infectious diseases, especially in the scenario of emerging antibacterial resistance.

J Nat Prod, 2002 Mar, 65(3), 334 - 8
Oligomeric acylphloroglucinols from myrtle (Myrtus communis); Appendino G et al.; The dimeric nonprenylated acylphloroglucinol semimyrtucommulone (6) was obtained from the leaves of myrtle (Myrtus communis) as a 2:1 mixture of two rotamers . The known trimeric phloroglucinol myrtucommulone A (1) was also isolated and characterized spectroscopically as a silylated cyclized derivative (5) . Myrtucommulone A showed significant antibacterial activity against multidrug-resistant (MDR) clinically relevant bacteria, while semimyrtucommulone was less active.

J Nat Prod, 2002 Mar, 65(3), 290 - 4
Benzoylphloroglucinol derivatives from Hypericum scabrum; Matsuhisa M et al.; Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum . Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS) . Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).

Ann Dermatol Venereol, 2001 Dec, 128(12), 1305 - 7
{Lyell syndrome in Senegal: responsibility of thiacetazone}; Mame Thierno D et al.; INTRODUCTION: Toxic epidermal necrolysis is a severe disease often leading to death or to mucosal, particularly ocular, after effects . The principle drugs responsible are antibacterial sulfonamides, anti-epileptics, non-steroid anti-inflammatories, allopurinol and chlormezanone . We report a series of 38 cases of toxic epidermal necrolysis, observed in Dakar, imputable to thiacetazone and lethal in 60 percent of cases . PATIENTS AND METHODS: Our study was retrospective . Diagnosis of toxic epidermal necrolysis was made in patients presenting more than 30 p . 100 of the epidermis of their total body surface stripped off, multi-orificial mucosal damage and epidermal necrosis revealed on histological examination . Drug imputability was established on classical criteria . Treatment was composed of reanimation and antibiotics . RESULTS: Among the 38 cases of toxic epidermal necrolysis counted, 24 were imputable to thiacetazone . All the patients presented typical clinical features, confirmed histologically . Evolution was lethal in 60 p . 100 of cases . The causes of death were frequently hypovolemic shock during the first week and septic shock during the second . The deceased were generally aged over 50, had more than 50 p . 100 of total epidermis stripped off, presented evolving tuberculosis at the time of the accident and HIV infection at the AIDS stage . After effects were vaginal synechia and 2 cases of blindness . COMMENTS: Our series is exceptional in that a) the drug responsible: thiacetazone, an economic tuberculostatic of minor efficacy, was systematically introduced after 2 months of intensive treatment with 4 major anti-tuberculosis agents; b) the 60 percent mortality rate, two-fold greater that that usually observed . Other than the known elements of poor prognosis in our patients, the treatment conditions of this dermatological emergency explain this high rate of mortality.

Nat Rev Immunol, 2001 Oct, 1(1), 20 - 30
How can immunology contribute to the control of tuberculosis?
Kaufmann SH.
Tuberculosis poses a significant threat to mankind . Multidrug-resistant strains are on the rise, and Mycobacterium tuberculosis infection is often associated with human immunodeficiency virus infection . Satisfactory control of tuberculosis can only be achieved using a highly efficacious vaccine . Tuberculosis is particularly challenging for the immune system . The intracellular location of the pathogen shields it from antibodies, and a variety of T-cell subpopulations must be activated to challenge the bacterium's resistance to antibacterial defence mechanisms . A clear understanding of the immune responses that control the pathogen will be important for achieving optimal immunity, and information provided by functional genome analysis of M . tuberculosis will be vital in the design of a future vaccine.

J Pharm Pharmacol, 2002 Mar, 54(3), 341 - 7
Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue; Hopkins AM et al.; Triple therapy using proton-pump inhibitors (PPIs) in combination with oral antibiotics for the treatment of Helicobacter pylori-associated gastritis has shown increased efficacy for reasons that are still poorly understood . Possible explanations include a direct antibacterial effect of the PPIs or a PPI-mediated increase in bacterial susceptibility to antibiotics . Using an in-vitro model of rat gastric mucosa, we examined fluxes of a radiolabelled marker molecule through the interepithelial tight junctions under normal conditions and under the influence of an acid secretagogue (50 microM histamine) and a PPI (100 microM omeprazole) . Paracellular fluxes of the radiolabel (represented by calculation of apparent permeability coefficients) were linear over 2 h . Fluxes of the marker increased significantly after treatment with histamine followed by omeprazole, but were unaltered in paired preparations exposed to the same drugs given in reverse order . Enhancements in paracellular permeability were mirrored in separate experiments using a detergent (Triton X-100), a bile salt (deoxycholate) and an agent that disrupts the cytoskeleton (cytochalasin D) to interfere with tight junctional integrity . The results suggest that exposure of acid-secreting gastric mucosa to omeprazole widens the interepithelial spacing in a manner that may facilitate enhanced macromolecular transport . Increases in antibiotic delivery from the blood to the gastric lumen via such a mechanism may account for the greater eradication rates observed with PPI-based triple therapy in H . pylori-associated gastritis.

Farmaco, 2002 Jan, 57(1), 63 - 9
Synthesis and antibacterial activity of pyridazino{4,3-b}indole-4-carboxylic acids carrying different substituents at N-2; Palluotto F et al.; The synthesis and the in vitro evaluation of antibacterial activity of new pyridazino{4,3-b}indole-4-carboxylic acids 2-4, 6 against some selected representative of Gram-positive and Gram-negative bacteria are reported . The role of the lipophilicity in the modulation of the antibacterial activity of the tested compounds is discussed . All the synthesized compounds appear quite weak against Gram-positive bacteria, whereas have no significant activity against Gram-negative bacteria . Only derivative 2g possesses an interesting activity against Gram-positive bacteria.

Ned Tijdschr Geneeskd, 2002 Mar 2, 146(9), 400 - 4
{Constitutional eczema; the possibilities of local treatment}; Sillevis Smitt JH; Atopic dermatitis is a common skin disease with a major impact on the quality of life . The cause of this disease is unknown and the diagnosis is made using a set of diagnostic features . In very moderate cases topical treatment of the dry skin may be sufficient . In more severe cases topical treatment with corticosteroids is recommended . Dependent on the steroid used and the severity of the eczema, different application schemes and treatment methods may be used . In exceptional cases, tar derivatives, topical antibacterial compounds and non-steroidal anti-inflammatory drugs may be applied . In the near future, the limited therapeutic arsenal of topically effective substances will almost certainly be extended to include drugs such as tacrolimus and pimecrolimus with an inhibiting effect on inflammatory cytokines.

Expert Opin Ther Targets, 2002 Feb, 6(1), 1 - 19
The bacterial cell wall as a source of antibacterial targets; Green DW; This review focuses on target-based approaches for developing new chemical classes of antibacterial agents aimed at the bacterial cell wall . The clinical success of antibiotics such as beta-lactams and glycopeptides validates this chemotherapeutic strategy and emerging resistance to these agents warrants the development of new antibacterial drugs . Understanding the mechanism of action and resistance to beta-lactams and glycopeptides at a molecular level has supported the development of new agents that prevent transpeptidation and transglycosylation reactions of peptidoglycan polymerisation . The enzymes involved in the synthesis of the peptidoglycan structural unit have also been targeted for antibacterial discovery . The influence of bacterial genetics and genomics, structural biology, assay development and the properties of known inhibitors on these approaches will be discussed in the context of drug discovery.

Klin Med (Mosk), 2002, 80(2), 60 - 2
{Effectiveness of sparfloxacin (sparflo) in the treatment of complicated forms of pyelonephritis and prostatitis}; Derevianko II; A novel difluoroquinolone drug sparfloxacine has a wide antibacterial spectrum . It is active both against gram-negative and gram-positive flora . Sparfloxacine was tried in 43 patients with pyelonephritis and prostatitis complicated with urolithiasis, diabetes mellitus, nephroptosis, anomalous kidneys, etc . The drug was given according to its pharmacokinetics for 7-14 days in a daily dose 400 mg (day 1) then 200 mg/day . The effectiveness of sparfloxacine in complicated pyelonephritis and prostatitis was rather high: clinical response reached 83.7%, bacteriological one--78.7%.

Klin Med (Mosk), 2002, 80(2), 27 - 31
{Neurological complications of infectious endocarditis}; Tiurin VP et al.; Of 204 patients with infectious endocarditis (IE) treated in the hospital in 1980-2000, 43(21.2%) developed neurological complications . These were: ischemic stroke (72.1%), hemorrhagic stroke (9.3%), both (7%), abscess and subarachnoidal hemorrhage (2.3% for each), meningitis (7%), toxic encephalopathy (11.6%) . Neurological complications of IE arose prior to treatment and within the first week of antibacterial therapy in 63% cases, more frequently in the left carotid territory . Neurological complications in IE debute manifested acutely, pareses were more frequent than paralyses, with elevated temperature, low hemoglobin and red cell levels, leukocytosis . MRT detected 8 +/- 4.6 foci in the brain, CT--2 +/- 1.1, on the average . Lethality of IE patients with neurological complications reached 58.1% and was significantly higher than in those without such complications (14.9%, p < 0.001) . Overall acturial survival 1 year after the discharge from the hospital was 94.4%, 5-year survival--61.1%, 10-year survival--11%.

J Cutan Med Surg, 2002 Jan-Feb, 6(1), 19 - 22 Epub 2002 Jan 09.
Herpetic folliculitis; Al-Dhafiri SA et al.; BACKGROUND: Although herpetic skin infection is very common, herpetic folliculitis is infrequently reported in the literature . It has varied presentations, some of which are clinically atypical requiring histopathological confirmation of follicular involvement . OBJECTIVE: We describe an otherwise healthy young adult male with extensive herpetic sycosis of the beard area, which is a variant of herpetic folliculitis . The diagnosis was confirmed by typical herpetic cytopathic changes in Tzanck smear and positive viral culture for HSV-1 . METHOD: This article includes a case report and a literature review of herpetic (simplex and varicella/zoster) folliculitis . Conclusions: More cases of herpetic folliculitis should be reported to improve our understanding of this disease entity . Physicians should consider herpetic or other viral etiology in patients with folliculitis even if they were healthy, especially if they show resistance to antibacterial and antifungal therapy.

Curr Opin Investig Drugs, 2001 Aug, 2(8), 1028 - 34
Delivering novel targets and antibiotics from genomics; Payne DJ et al.; Recent advances in DNA sequencing technology have made it possible to elucidate the sequences of the entire genomes of pathogenic bacteria and concomitant advancements in bioinformatic tools have driven comparative studies of these genome sequences . These evaluations are significantly 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-essentiality technologies amenable to pathogenic organisms liave enabled new genes and gene products critical to bacterial growth and pathogenicity to be uncovered at an unprecedented rate . This review will describe how aspects of the above capabilities are impacting the discovery and characterization of known and novel antibacterial targets using specific examples taken from a variety of important, diverse bacterial processes.

J Chemother, 2002 Feb, 14(1), 65 - 70
Antibiotic prescribing for dental conditions: a community-based study in southern Italy; Mazzaglia G et al.; The aim of this study was to investigate for which conditions antibiotics are being used in community dental practice, and which clinical features represent the most common reason for an antibacterial approach to the treatment of dental conditions . The study was carried out from November 1998 to June 1999 . Dentists were selected according to the different areas of southern Italy, from a list provided by the Italian Society of Dentists . Out of 87 selected dentists, 33 agreed to participate and filled in 1615 questionnaires for each therapeutic intervention ending with antibiotic treatment . Analysis of data indicated that alveolar-gingival abscesses were the most commonly treated infection, accounting for 23.6% of total treatments, followed by acute periodontitis (20.6%) and disodontiasis of the 3rd molar (18.5%) . Parenteral antibiotics were chosen in 7.8% of cases . Penicillins were the most commonly used group, 40.1% of total treatments, followed by macrolides (30.2%) and cephalosporins (13.4%) . Moreover, penicillins were widely used for post-surgery therapy (52.1%) and disodontiasis of the 3rd molar (50.8%), while macrolides were the most commonly used group for gingivitis (44.1%) and parodontal diseases (55.0%) . The choice of parenteral antibiotics was related to severe general symptoms (odds ratios {OR}, 4.4; 95% CI: 2.2-9.0), pain (OR, 2.7; 95% CI: 1.2-6.1) and lymphonodal involvement (OR, 6.4; 95% CI: 2.7-15.1) . In conclusion, our study demonstrates that antibiotic treatment is often based on the eradication of as many microorganisms as possible, and on the clinical assessment of the patients, rather than on any knowledge of the pathogens involved.

Drug Ther Bull, 2002 Feb, 40(2), 15 - 6
{symbol: see text}Quinupristin + dalfopristin for infections; Pharmacological and phytochemical screening of two Hyacinthaceae species: Scilla natalensis and Ledebouria ovatifolia; Research Centre for Plant Growth and Development, School of Botany and Zoology, University of Natal Pietermaritzburg, Private Bag X01, 3209, Scottsville, South AfricaAqueous, ethanolic, dichloromethane and n-hexane extracts of Scilla natalensis Planch . and Ledebouria ovatifolia (Bak.) Jessop bulbs (Hyacinthaceae) were screened for antibacterial, anti-inflammatory, antischistosomic, anticancer and anthelmintic activity . Poor antibacterial activity against both Gram-positive and Gram-negative bacteria was shown with S . natalensis extracts . Good antibacterial activity was shown by the ethanolic and dichloromethane extracts of L . ovatifolia against Gram-positive bacteria . In the anti-inflammatory screening, the dichloromethane and hexane extracts of S . natalensis resulted in good inhibition against both COX-1 and COX-2 . Ethanolic extracts had the highest inhibitory effect against nematodes in the anthelmintic assays . Poor anti-inflammatory and anthelmintic activity was found with L . ovatifolia . Aqueous extracts of S . natalensis had good activity against Schistosoma haematobium, with a minimum inhibitory concentration of 0.4 mg ml(-1) . Aqueous extracts of fresh L . ovatifolia bulb material were found to be lethal to S . haematobium at a concentration of 1.6 mg ml(-1) . The phytochemical screening of S . natalensis bulbs revealed the presence of saponins and bufadienolides within the bulbs . Bulbs of L . ovatifolia contained bufadienolides.

J Ethnopharmacol, 2002 Apr, 80(1), 91 - 4
Isolation and identification of antibacterial compounds from Vernonia colorata leaves; Rabe T et al.; Vernonia colorata (Compositae) is used throughout Africa for a variety of ailments . This prompted the screening of this plant for biological activity . Previous experiments carried out in our laboratory revealed that the leaves possessed high antibacterial activity . Through conventional chromatographic techniques and bioassay-guided fractionation, the following sesquiterpene lactones were isolated and identified by spectroscopic data; vernolide (1), 11beta, 13-dihydrovernolide (2) and vernodalin (3) . Only 2 is a novel compound, although its antibacterial activity is low compared to compounds 1 and 3 which had minimum inhibitory concentrations of 0.1-0.5 mg/ml against Gram-positive bacteria.

Helicobacter, 2002 Feb, 7(1), 67 - 70
The presence of immunoglobulins in the gastric juice of patients infected with Helicobacter pylori is related to a reduced secretion of acid; Meining A et al.; BACKGROUND: It has been reported that treatment with proton pump inhibitors (PPI) leads to partial elimination and suppression of Helicobacter pylori . In theory, since acid is known to denature immunoglobulins, this antibacterial activity of PPI may be due to a reduction in the acid output favouring humoral immunity . MATERIALS AND METHODS: We analysed prospectively fasting gastric juice in 54 consecutive patients attending upper endoscopy for pH and levels of IgG, IgA and IgM . In addition, two antral and two corpus biopsies were obtained and histologically examined for the presence of H . pylori . RESULTS: 41/54 patients were infected with H . pylori . Immunoglobulines in the gastric juice of these patients were found in 25/41 (IgG), 27/41 (IgA), and 29/41 (IgM) patients . There was a highly significant difference in the gastric pH when H . pylori infected patients with measurable IgG, IgA, or IgM were compared with those in whom no immunoglobulines were found (median pH: 6 vs . 2 in each group; p <.001) CONCLUSIONS: There is a close correlation between a high gastric pH and the presence of IgG, IgA, and IgM antibodies . Hence, it may be speculated that the efficacy of humoral immunity following H . pylori infection depends on a high pH such as resulting from PPI treatment.

Helicobacter, 2002 Feb, 7(1), 39 - 45
Antibacterial activities of beta-lactamase inhibitors associated with morphological changes of cell wall in Helicobacter pylori; Horii T et al.; BACKGROUND: Recent study has demonstrated that beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam have an vitro antibacterial effect on Helicobacter pylori . Here we describe the relationship between viability and cell profiles of H . pylori exposed to beta-lactamase inhibitors and some antibiotics in a short-time course . MATERIALS AND METHODS: The antibacterial effects of beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam on the bacterial viability of and morphological changes in H . pylori ATCC43504 were examined . RESULTS: The beta-lactamase inhibitors such as clavulanate and sulbactam alone decreased the viable counts of H . pylori, depending on the antibiotic concentrations . Exposure to these beta-lactamase inhibitors resulted in morphological changes of cell shape, cell-wall disintegration and cell lysis . Among these beta-lactamase inhibitors, clavulanate was the most active, causing a decrease in viable counts and morphological changes such as short filamentous to sphaeroplast formation and lysis . One x minimum inhibitory concentration (MIC) of amoxicillin plus 1 x MIC of clavulanate decreased viable counts effectively compared with 1 x MIC of amoxicillin or 1 x MIC of clavulanate alone, and induced morphological changes of cell shape and cell wall . CONCLUSION: Our results suggest that the beta-lactamase inhibitors alone have concentration-dependent antibacterial activities against H . pylori and affect the morphology of the cell shape and the cell wall in vitro.

Jpn J Pharmacol, 2001 Nov, 87(3), 231 - 4
A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia; Hagiwara T et al.; We examined the effects of ten fluoroquinolone antibacterial agents, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin, tosufloxacin, gatifloxacin, grepafloxacin, moxifloxacin and sparfloxacin, on action potentials recorded from guinea pig ventricular myocardia . Sparfloxacin prolonged action potential duration (APD) by about 8% at 10 microM and 41% at 100 microM . Gatifloxacin, grepafloxacin and moxifloxacin also prolonged APD at 100 microM by about 13%, 24% and 25%, respectively . In contrast, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin and tosufloxacin had little or no APD-prolonging effect at concentrations as high as 100 microM . These findings suggest that there are differences in potency to prolong QT interval among the fluoroquinolones.

J Med Chem, 2002 Mar 14, 45(6), 1383 - 6
Synthesis and antimycobacterial activity of 6-arylpurines: the requirements for the N-9 substituent in active antimycobacterial purines; Gundersen LL et al.; 6-Arylpurines carrying a variety of substituents in the 9-position were prepared by Stille coupling between appropriately substituted 6-chloropurines and aryl(tributyl)tin, and the compounds were screened for antibacterial activity against Mycobacterium tuberculosis H(37)Rv . The lowest minimum inhibitory concentration value, 0.78 microg/mL, was found for 9-benzyl-2-chloro-6-(2-furyl)purine . This compound exhibited relatively low cytotoxicity, and it was active against several singly drug-resistant strains of M . tuberculosis.

Stomatologiia (Mosk), 2001, 80(6), 28 - 30
{Analysis of antibacterial activity of a new antiseptic for the treatment of maxillofacial inflammations}; Kuznetsova LI et al.; Clinical and experimental studies of polydimethyldiallylammonium chloride (PDMDAAC) were carried out in order to select the optimal concentration and composition of the preparation . 1% PDMDAAC solution showed high antiseptic activity and can be used for local therapy of the periodontal inflammations and infected posttraumatic wounds.

Bioorg Khim, 2002 Jan-Feb, 28(1), 72 - 80
{Antibiotic N',N''-dibenzyleremomycin with reduced 1,2-peptide bond}; Printsevskaia SS et al.; Eremomycin derivatives with benzylated amino groups of both residues of eremosamine and with (R) or (S)-2-amino-4-methylpentyl substituted for N-methyl-D-Leu, the first amino acid residue of its heptapeptide, were synthesized to study the role of the peptide bond between the first and the second amino acid residues of the heptapeptide moiety of the antibiotic in its interaction with the precursors of the bacterial cell wall peptidoglycan and exhibition of its antibacterial activity . Comparison of the antibacterial activities of N',N"-dibenzyleremomycin, de-(N-methyl-D-Leu)-N',N"-dibenzyleremomycin, and its N-(2-amino-4-methylpentyl)-derivative (1,2-deoxo-N',N"-dibenzyleremomycin) demonstrated that cleavage or replacement of the first amino acid residue by the corresponding aminoalkyl residue results in a decrease in its antibacterial activity towards both vancomycin-sensitive and vancomycin-resistant strains of microorganisms . The English version of the paper.

Science, 2002 Apr 12, 296(5566), 359 - 62 Epub 2002 Feb 28.
Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila; Choe KM et al.; Components of microbial cell walls are potent activators of innate immune responses in animals . For example, the mammalian TLR4 signaling pathway is activated by bacterial lipopolysaccharide and is required for resistance to infection by Gram-negative bacteria . Other components of microbial surfaces, such as peptidoglycan, are also potent activators of innate immune responses, but less is known about how those components activate host defense . Here we show that a peptidoglycan recognition protein, PGRP-LC, is absolutely required for the induction of antibacterial peptide genes in response to infection in Drosophila and acts by controlling activation of the NF-kappaB family transcription factor Relish.

Appl Environ Microbiol, 2002 Mar, 68(3), 1211 - 9
Production of penicillin by fungi growing on food products: identification of a complete penicillin gene cluster in Penicillium griseofulvum and a truncated cluster in Penicillium verrucosum; Laich F et al.; Mycobiota growing on food is often beneficial for the ripening and development of the specific flavor characteristics of the product, but it can also be harmful due to the production of undesirable compounds such as mycotoxins or antibiotics . Some of the fungi most frequently isolated from fermented and cured meat products such as Penicillium chrysogenum and Penicillium nalgiovense are known penicillin producers; the latter has been shown to be able to produce penicillin when growing on the surface of meat products and secrete it to the medium . The presence of penicillin in food must be avoided, since it can lead to allergic reactions and the arising of penicillin resistance in human-pathogenic bacteria . In this article we describe a study of the penicillin production ability among fungi of the genus Penicillium that are used as starters for cheese and meat products or that are frequently isolated from food products . Penicillium griseofulvum was found to be a new penicillin producer and to have a penicillin gene cluster similar to that of Penicillium chrysogenum . No other species among the studied fungi were found to produce penicillin or to possess the penicillin biosynthetic genes, except P . verrucosum, which contains the pcbAB gene (as shown by hybridization and PCR cloning of fragments of the gene) but lacks pcbC and penDE . Antibacterial activities due to the production of secondary metabolites other than penicillin were observed in some fungi.

Toxicol Lett, 2002 Mar 10, 128(1-3), 117 - 27
Extrathyroidal actions of antithyroid thionamides; Bandyopadhyay U et al.; Some compounds having thionamide structure inhibit thyroid functions . Such antithyroid thionamides include mercaptomethylimidazole (methimazole), thiourea and propylthiouracil, of which mercaptomethylimidazole is widely used to treat hyperthyroidism . Undesirable side effects develop from these drugs due to extrathyroidal actions . Antithyroid thionamides inhibit lactoperoxidase which contributes to the antibacterial activities of a number of mammalian exocrine gland secretions that protect a variety of mucosal surfaces . These drugs stimulate both gastric acid and pepsinogen secretions, thereby augmenting the severity of gastric ulcers and preventing wound healing . Increased gastric acid secretion is partially due to the H2 receptor activation, and also through the stimulation of the parietal cell by intracellular generation of H2O2 following inactivation of the gastric peroxidase-catalase system . Severe abnormalities may develop in blood cells and the immune system after thionamide therapy . It causes agranulocytosis, aplastic anemia, and purpura along with immune suppression . Olfactory and auditory systems are also affected by these drugs . Thionamide affects the sense of smell and taste and also causes loss of hearing . It binds to the Bowman's glands in the olfactory mucosa and causes extensive lesion in the olfactory mucosa . Thionamides also affect gene expression and modulate the functions of some cell types . A brief account of the chemistry and metabolism of antithyroid thionamides, along with their biological actions are presented.

Heredity, 2001 Nov, 87(Pt 5), 511 - 21
Seminal fluid-mediated fitness traits in Drosophila; Chapman T; The seminal fluid of male Drosophila contains a cocktail of proteins that have striking effects on male and female fitness . In D . melanogaster, seminal fluid proteins affect female receptivity, ovulation, oogenesis, sperm storage, sperm competition and mating plug formation . In addition, the seminal fluid contains antibacterial peptides and protease inhibitors . Some seminal fluid-encoding genes also show high rates of evolutionary change, exhibiting both significant between-species divergence and within-species polymorphism . Seminal fluid protein genes are expressed only in males, begging the question of how and why the reproductive processes of females are influenced by males . In this review I address these issues by bringing together evidence for the function, evolution, diversification, and maintenance of variation in, seminal fluid-mediated traits.

Clin Microbiol Infect, 1997 Jun, 3 Suppl 3, S62 - S68
Decision-making in otitis media in children, Part I: epidemiologic data and definitions for a reliable cost-effectiveness analysis; Grenier B; There is a gap between the medical and economic weight of acute otitis media and the imprecise knowledge and irrational attitude towards diagnosis and treatment . The wide variations among prescribers need to be analyzed . Precise definitions are proposed for acute otitis media and endpoints for outcomes being estimated . An empirical antibiotic treatment gives a greater cure rate than a conservative approach with antipyretic and analgesic drugs . The incremental efficacy expected from more extended-spectrum antibacterials is not clinically significant.

Clin Microbiol Infect, 1997 Jun, 3 Suppl 3, S43 - S48
Antibiotic treatment in acute otitis media: 'in vivo' demonstration of antibacterial activity; Dagan R et al.; The ultimate goal in antibiotic treatment of acute otitis media (AOM) is eradication of the pathogens from the middle ear fluid (MEF) . To test the ability of an antibiotic to achieve this goal, the best available method is to obtain MEF by aspiration before initiating antibiotics and to repeat this procedure during treatment, a method which was termed the 'in vivo sensitivity test' . This advantageous method is difficult to perform and thus only a few groups were able to conduct such large-scale studies . The available information is discussed in the present manuscript, as well as some preliminary results suggesting that oral beta-lactam antibiotics may not be the ideal drugs to date, due to the emergence of resistant pneumococci.

Skin Pharmacol Appl Skin Physiol, 2002 Mar-Apr, 15(2), 112 - 9
Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy; Pierard-Franchimont C et al.; BACKGROUND: Some antibiotics represent a mainstay in acne treatment . However, studies comparing their efficacies are rare . AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages . METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks . Evaluations were made at the screening visit and at five on-treatment visits . They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings . RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules . By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments . There were less live and more dead bacteria . CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg .

Phytochemistry, 2002 Mar, 59(6), 649 - 54
Coumarins and gamma-pyrone derivatives from Prangos pabularia: antibacterial activity and inhibition of cytokine release; Tada Y et al.; The n-hexane and ethyl acetate extracts of the stems and the ethyl acetate extracts of roots from Prangos pabularia afforded an gamma-pyrone derivative and furanocoumarin derivatives with three glucose and gamma-pyrone (pabularin A, B and C), along with 26 previously known compounds (18 coumarins, six terpenoids and two glycosides) . Their structures were established on the basis of spectroscopic studies . Of these, 16 coumarin derivatives isolated from P . pabularia were tested for antibacterial activity and inhibition of cytokine release.

J Am Chem Soc, 2002 Mar 6, 124(9), 1854 - 5
Diazo group electrophilicity in kinamycins and lomaiviticin A: potential insights into the molecular mechanism of antibacterial and antitumor activity; Laufer RS et al.; Theoretical and chemical studies of the reactivity of isoprekinamycin, the kinamycins, and the lomaiviticins support the proposal that these natural products exhibit enhanced diazonium salt character and may owe their antitumor antibiotic properties to their ability to act as electrophilic azo-coupling agents in vivo.

Nucleic Acids Res, 2002 Mar 1, 30(5), 1169 - 75
RNase 8, a novel RNase A superfamily ribonuclease expressed uniquely in placenta; Zhang J et al.; We report the identification and characterization of the gene encoding the eighth and final human ribonuclease (RNase) of the highly diversified RNase A superfamily . The RNase 8 gene is linked to seven other RNase A superfamily genes on chromosome 14 . It is expressed prominently in the placenta, but is not detected in any other tissues examined . Phylogenetic analysis suggests that RNase 7 is the closest relative of RNase 8 and that the pair likely resulted from a recent gene duplication event in primates . Further analysis reveals that the RNase 8 gene has incorporated non-silent mutations at an elevated rate (1.3 x 10(-9) substitutions/site/year) and that orthologous RNase 8 genes from 6 of 10 primate species examined have been deactivated by frameshifting deletions or point mutations at crucial structural or catalytic residues . The ribonucleolytic activity of recombinant human RNase 8 is among the lowest of members of this superfamily and it exhibits neither antiviral nor antibacterial activities characteristic of some other RNase A ribonucleases . The rapid evolution, species-limited deactivation and tissue-specific expression of RNase 8 suggest a unique physiological function and reiterates the evolutionary plasticity of the RNase A superfamily.

Aliment Pharmacol Ther, 2002 Feb, 16(2), 275 - 80
Effect of Helicobacter pylori eradication on duodenal ulcer scar in patients with no clinical history of duodenal ulcer; Kim JS et al.; BACKGROUND: Helicobacter pylori eradication has become the standard treatment for duodenal ulcer . However, there is no relevant evidence for antibacterial treatment of the white scar stage of duodenal ulcer (duodenal ulcer scar) in patients with no past history of duodenal ulcer . AIM: To investigate whether H . pylori eradication could decrease duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer . PATIENTS AND METHODS: We prospectively enrolled 66 patients with duodenal ulcer scar: 53 were H . pylori-positive and 13 were H . pylori-negative . H . pylori-positive patients were randomly assigned into two groups (two-to-one allocation): 36 patients were assigned to the treatment group and 17 to the follow-up group . Thirteen H . pylori-negative patients were followed up according to the study protocol . Follow-up endoscopy was performed to evaluate ulcer scar changes and H . pylori status 6 weeks after anti-H . pylori treatment and then every 6 months for up to 30 months . RESULTS: Active duodenal ulcer recurrence was identified in seven of 23 H . pylori-positive/non-cured patients (30%) . There was no duodenal ulcer recurrence in 43 H . pylori-negative/cured patients (0%), which was significantly different in terms of duodenal ulcer recurrence (P=0.001) . CONCLUSIONS: H . pylori eradication is effective at preventing active duodenal ulcer recurrence in patients with duodenal ulcer scar and no past history of duodenal ulcer.

J Chromatogr A, 2002 Feb 1, 945(1-2), 1 - 24
Analysis of quinolone residues in edible animal products; Hernandez-Arteseros JA et al.; A comprehensive review on the analysis of quinolone antibacterials is presented . The review covers most of the methods described for the determination of quinolone residues in edible animal products . Sample handling, chromatographic conditions and detection methods have been discussed . A summary of the most relevant information about the analytical procedures has been included.

Prog Urol, 2001 Dec, 11(6), 1331 - 4
{Tendinopathy associated with fluoroquinolones: individuals at risk, incriminated physiopathologic mechanisms, therapeutic management}; Saint F et al.; The use of fluoroquinolones in urology has grown considerably over recent years . Unfortunately, although these molecules are not associated with severe life-threatening complications, they have nevertheless been associated with tendon lesions responsible for functional disability . The frequency of these complications is probably underestimated . There is a variable lag-time (3 to 5 days) between introduction of the antibacterial and onset of pain . The symptom most frequently reported is pain over the tendon affected and the tendons most frequently affected are those submitted to high constraints . Bilateral lesions are present in 66% of cases . Although Pefloxacin is associated with the highest frequency of tendon complications (2.7% versus 0.2-0.3% for other fluoroquinolones), the duration of treatment appears to be important in every case, with a peak frequency after a fortnight of treatment . Although these complications were considered for a long time to be associated with patients presenting certain risk factors (age, steroid therapy, renal failure), they can also occur suddenly, in young adult sportsmen or non-sportsmen, with no known tendon disease . Several hypotheses have been proposed to explain the development of these cases of tendinopathy: immuno-allergic mechanisms, direct toxicity of the molecule on collagen fibres, cell-mediated oxidative aggression, or tendon necrosis due to vascular mechanisms . The outcome remains favourable in 75% of cases of tendinitis and in 49% of cases for tendon rupture . Contraindications must therefore be identified and the duration of treatment must be adapted, as the functional handicap can be long and particularly severe.

Med Sci Monit, 2002 Feb, 8(2), RA27 - 31
Tonal nitric oxide and health: anti-bacterial and -viral actions and implications for HIV; Benz D et al.; Nitric oxide has been shown to have important physiological regulatory roles, i . e, vasodilation, neurotransmitter release, etc . Now, we review its role as an antibacterial and antiviral agent . Nitric oxide has also been identified as an important factor in the development of non-specific immunity . And accordingly, nitric oxide synthase (NOS), the catalytic enzyme producing nitric oxide, is a key element in the protective activities of nitric oxide . The expression of inducible (i) NOS is regulated by cytokines . iNOS-derived nitric oxide was found to contribute to both early and late phases of antibacterial activity . Enzymes, such as proteases (reverse transciptases, and ribonucleotide reductase, etc.) containing cysteine residues, appear to be targets for nitric oxide nitrosylation, as well as viral-encoded transcription factors that are involved in viral replication . It would appear that this multifunctional signaling molecule is not only involved with signaling between cells, it also appears to maintain the immediate environment free of microbial agents.

Phytochemistry, 2002 Mar, 59(5), 537 - 42
Non-glycosidic iridoids from Cymbaria mongolica; Dai JQ et al.; Six non-glycosidic iridoids, i.e . (1R,4S,4aS,7S,7aS)-7-hydroxyl-4-hydroxy- methyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta{e}pyran-3-one (1), (1S,4R,4aS,7S,7aS)-7-hydroxyl-4-hydroxymethyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta{e}pyran-3-one (2), (1R,4R,4aS,7S,7aS)-7-hydroxyl-4-hydroxy-methyl-7-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta{e}pyran-3-one (3), (1R, 4R, 4aS, 7aS)-4,7-dihydroxymethyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta-6-ene{e}pyran-3-one (4), (1R, 4R, 4aS, 7aS)-4,7-dihydroxymethyl-1-hydroxyl-1,4,4a, 7a-tetrahydrocyclopenta-6-ene{e}pyran-3-one (5), (1R, 4S, 4aS, 7aS)-4,7-dihydroxy-methyl-1-methoxyl-1,4,4a,7a-tetrahydrocyclopenta-6-ene{e}pyran-3-one (6), as well as five known non-glycosidic iridoids mussaenin A (7), gardendiol (8), isoboonein (9), 4-epi-alyxialactone (10) and rehmaglutin D (11) have been isolated from the Chinese medicinal plant Cymbaria mongolica . Their structures were elucidated by spectroscopic methods . These compounds exhibit significant antitumor and antibacterial activity.

Semin Dial, 2001 Nov-Dec, 14(6), 446 - 51
Central venous dialysis catheters: catheter-associated infection; Saad TF; Tunneled dialysis catheters (TDC) are extensively used for long-term venous hemodialysis access and their use is frequently associated with infectious complications . Catheter-related bacteremia (CRB) is the most common and important infection associated with TDC use and may be caused by a wide variety of Gram-positive or Gram-negative organisms . Prevention of CRB can be difficult despite use of rigorous infection-control techniques for catheter insertion and access . A number of antibacterial catheter-packing solutions hold promise for reduction of CRB . Treatment of CRB with antibiotics alone yields poor results and may increase the risk for other infectious complications, especially endocarditis . In selected cases where initial infection control can be achieved with antibiotics, guidewire exchange of the TDC results in cure rates equivalent to those of TDC removal and subsequent replacement . Dialysis programs should monitor TDC infections with attention to incidence, bacteriology, and outcomes.

Antimicrob Agents Chemother, 2002 Mar, 46(3), 625 - 9
1H nuclear magnetic resonance study of oxazolidinone binding to bacterial ribosomes; Zhou CC et al.; The oxazolidinones are a novel class of antibiotics that inhibit initiation of protein synthesis in bacteria . In order to investigate their novel mechanism of action, the interactions of several oxazolidinones with bacterial 70S ribosomes, 50S subunits, and 30S subunits have been characterized by (1)H nuclear magnetic resonance (NMR) line-broadening analyses and transferred nuclear Overhauser enhancement (TRNOE) experiments . PNU-177553 and PNU-100592 (eperezolid) and their corresponding enantiomers, PNU-184414 and PNU-107112, were studied . The dissociation constants were determined to be 94 +/- 44 microM and 195 +/- 40 microM for PNU-177553 and eperezolid, respectively . There was a approximately 4-fold decrease in affinity for their corresponding enantiomers . The NMR-derived dissociation constants are consistent with their antibacterial activity . PNU-177553 and eperezolid were found to bind only to the 50S subunit, with similar affinity as to the 70S ribosome, and to have no affinity for the 30S subunit . Specific binding of PNU-177553 was further confirmed in TRNOE experiments in which positive NOEs observed for the small molecule alone were changed to negative NOEs in the presence of bacterial 70S ribosomes . The observed NOEs indicated that PNU-177553 did not adopt a significantly different conformation when bound to the 70S ribosome, compared to the extended conformation that exists when free in solution . Since this is likeliest the case for each of the four compounds included in this study, the A ring C5 side chain may be positioned in the proper orientation for antibacterial activity in PNU-177553 and eperezolid but not in their inactive enantiomers.

Bioorg Chem, 2001 Dec, 29(6), 380 - 6
Microwave induced synthesis and antibacterial activity of cephalosporin derivatives using solid support; Kidwai M et al.; Reaction of 7-amino-3-{5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl}cephalo-sporanic acid with heterocyclic amines using basic alumina under microwave irradiation (MWI) afforded new cephalosporin analogs in shorter reaction time with improved yield as compared to conventional heating . All the synthesised compounds were tested for their in vitro antibacterial activity, using cefotaxime and cephalothin as reference drugs . All compounds showed significant in vitro antibacterial activity against E . herbicola, P . vulgaries, and Z . mobilis .

J Periodontol, 2002 Jan, 73(1), 13 - 9
Controlled local delivery of tetracycline with polymer strips in the treatment of periodontitis; Friesen LR et al.; BACKGROUND: Several antibacterial agents have been studied as a means to produce bactericidal or bacteriostatic activity as an adjunct to mechanical treatment of periodontal disease . The primary purpose of this study was to evaluate the efficacy of tetracycline strips administered singly or in multiples in conjunction with root planing, versus root planing alone, or to an untreated control . Secondary purposes were to compare gingival crevicular fluid (GCF) volume and GCF concentrations of tetracycline in pockets treated with strips; to evaluate strip insertion time; and to compare ease of placement for single or multiple strips . METHODS: Using a 4-quadrant design, 4 test teeth in 24 patients were treated with either root planing and single strip application; root planing and multiple strip application; root planing alone; or an untreated control . RESULTS: Single and multiple strip placement resulted in a significant reduction in probing depth (P = 0.033) compared to root planing and untreated groups . The multiple strip group significantly decreased bleeding on probing (P = 0.05) compared to all other treatment groups . There was no treatment effect on GCF; however, there was a significant reduction in the GCF volume over time (P = 0.001) . The time required for placement was, on average, 1.9 minutes for single strips and 3.25 minutes for multiple strips . CONCLUSIONS: Our data suggest that multiple strips are superior to a single strip in reducing bleeding on probing, and that local delivery of tetracycline is superior to root planing alone in reducing probing depth.

Bioorg Med Chem Lett, 2002 Feb 25, 12(4), 561 - 5
Total synthesis and semi-synthetic approaches to analogues of antibacterial natural product althiomycin; Zarantonello P et al.; Numerous analogues of the naturally occurring antibiotic althiomycin have been synthesised exploiting both total- and semi-synthetic methodologies . The antibacterial activity of these derivatives has been determined in whole cell assays and indicates the natural product exhibits a restricted SAR.

J Eur Acad Dermatol Venereol, 2001, 15 Suppl 3, 57 - 61
Endocrinological evaluation and hormonal therapy for women with difficult acne; Thiboutot DM; Acne vulgaris is the most common skin condition observed in the medical community . Convention is to treat this condition with a combination of comedolytics, anti-inflammatory and antibacterial topical agents, or if indicated, oral antibiotics or retinoids . In addition to these therapies, hormonal therapy is potentially an option in women whose acne is not responding to conventional treatment or if signs of endocrine abnormalities are present . This paper focuses on the use of hormonal therapy in women with severe or recalcitrant acne . After a brief description of the pathogenesis of acne vulgaris, and the conventional treatment modalities, indications for hormonal therapy are discussed . This is followed by an outline of a suggested endocrine evaluation, and interpretation of the evaluation test results . Various options for hormonal therapy are then described, including a further discussion of oral contraceptives (OCs) in the treatment of acne.

Planta Med, 2002 Jan, 68(1), 91 - 4
New norsesquiterpenoids from Cucubalus baccifer; Cheng YX et al.; The chemical investigation of Cucubalus baccifer L . afforded three new norsesquiterpenoids, cucubalol, cucubalactone and drummondol-11-O-beta-D-glucopyranoside together with two known related compounds, drummondol and 5,7{E}-megastigmadiene-3 beta,4 alpha,9 xi-triol . Their structures were established based on spectral and chemical evidence . No activity was observed in anti-cancer (CDC25), antibacterial (PEPT) and antifungal (YNG) assays.

Nat Prod Lett, 2001, 15(5), 307 - 14
A new antibacterial diterpene from the roots of Salvia caespitosa; Ulubelen A et al.; From the roots of Saliva caespitosa Montbret and Aucher ex . Bentham a new diterpene 6beta-hydroxyisopimaric acid (1) has been isolated together with four known diterpenes, one new triterpenoid, 3-acetylvergatic acid (2), as well as five known triterpenoids, two steroids and a flavone . The structures of the compounds were established by spectroscopic analyses . The isolated compounds were tested against standard bacterial strains . Only the new diterpene, 6beta-hydroxyisopimaric acid has strong activity (MIC 9 microg/ml) against S . aureus and (MIC 18 microg/ml) against S . epidermidis as well as against B . subtilis (MIC 9 microg/ml).

Ugeskr Laeger, 2002 Jan 21, 164(4), 488 - 92
{Trimethoprim-sulfamethoxazole as antibacterial prophylaxis during induction therapy of children with acute lymphatic leukemia}; Agger KE et al.; INTRODUCTION: Children with acute lymphoblastic leukaemia (ALL) are treated with intensive chemotherapy, which results in profound immunosuppression . Treatment with trimethoprim/sulphamethoxazole (TMP-SMX) is therefore used in some departments as prophylaxis against infections with both bacteria and Pneumocystis carinii . The use of TMP/SMX for prophylaxis during the induction therapy is not uniform in the four departments of paediatric oncology in Denmark . This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy . MATERIAL AND METHODS: Between 1 January 1992 and 31 December 1997, 210 children were diagnosed with ALL in Denmark . From a retrospective review of the medical charts, the number of children with fever (> 38 degrees C), the number of febrile days, days of antibiotic treatment, and the number of positive blood cultures were registered for each febrile episode . RESULTS: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not . Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) vs . 60/76 (79%), p < 0.01) and significantly fewer children who received the prophylaxis had positive blood cultures before the start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p < 0.001)) . Nineteen different species were isolated from the blood stream before the start of antibiotic treatment . In the non-prophylaxis group there were a preponderance of isolates with Staph . aureus, Str . pneumoniae, E . coli, and P . aeruginosa . There was no difference in the mortality between the two groups (p = 0.44) . There were no cases of P . carinii pneumonia in the period of induction therapy . DISCUSSION: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteraemias and febrile illness.

Z Naturforsch {C}, 2001 Nov-Dec, 56(11-12), 1112 - 5
Antibacterial activity and chemical composition of Turkish propolis; Keskin N et al.; The antibacterial activities of propolis samples have been examined in vitro, according to the principles accepted for the determination of a similar activity of antibiotics with the use of solid and liquid media . It has been found that propolis extracts showed antibacterial activity through a range of commonly encountered gram positive cocci (S . aureus, beta hem . Streptococus), but had weak activity against gram negative bacteria (E . coli, P . aeruginosa) . GC/MS analysis showed that propolis samples contain a variety of chemical compounds including aromatic compounds, fatty acid esters and sesquiterpenes.

Z Naturforsch {C}, 2001 Nov-Dec, 56(11-12), 1108 - 11
The first glycosides isolated from propolis: diterpene rhamnosides; Popova M et al.; Two diterpene glycosides, ent-8(17)-labden-15-O-alpha-L-rhamnoside and ent-8(17)-labden-15-O-(3'-O-acetyl)-alpha-L-rhamnoside (new natural compounds) were isolated from propolis from El Salvador . The compounds showed significant antibacterial activity and moderate toxicity to Artemia salina nauplii . These are the first glycosides reported in bee glue.

Z Naturforsch {C}, 2001 Nov-Dec, 56(11-12), 1008 - 14
Chemical composition and biological activities of the Black Sea algae Polysiphonia denudata (Dillw.) Kutz . and Polysiphonia denudata f . fragilis (Sperk) Woronich; De Rosa S et al.; The two investigated algae had almost identical sterol composition, but there were significant differences in the composition of the polar components and especially in the composition of the volatiles . P . denudata f . fragilis extracts possessed a stronger biological activity (antibacterial, antifungal and toxicity against Artemia salina) . Despite the minute morphological differences between the two algae, we recommend P . denudata f . fragilis to be regarded as P . denudata subsp . fragilis.

J Dermatol, 2002 Jan, 29(1), 23 - 7
Therapeutic effects of antibacterial treatment for intractable skin diseases in Helicobacter pylori-positive Japanese patients; Sakurane M et al.; In order to understand the pathogenic relationship between Helicobacter pylori (H . pylori) and skin diseases, we examined the serum levels of IgG antibody against H . pylori and then performed gastroscopic examinations in Japanese patients with chronic skin diseases . These H . prylori-positive patients were treated with antibacterial eradication therapy, and therapeutic efficacy was evaluated . A total of 198 patients who were resistant to conventional therapies were randomly selected . They included 50 cases with chronic urticaria, 32 with pruritus cutaneous, 74 with atopic dermatitis, 15 with nummular dermatitis, 17 with prurigo chronica multiformis, 6 with psoriasis vulgaris, and 4 with erythroderma . Positive anti-H . pylori antibody was detected in 102 out of these 198 patients; more than half of the ones with chronic urticaria, pruritus cutaneous, nummular dermatitis, and prurigo chronica multiformis had positive antibodies . Gastroscopy was then performed in 48 cases with positive antibodies . Eradication therapy was effective in 60% of the patients with chronic urticaria, in 58% with pruritus cutaneous, in 54% with nummular dermatitis, and in 50% with prurigo chronica multiformis . In chronic skin diseases, persistent infection with H . pylori may be an eruption trigger and may cause deterioration of the disease into an in tractable and chronic form.

Pharmazie, 2002 Jan, 57(1), 34 - 40
Synthesis and biological activity of chiral tetrahydrofuranyl amino acids as building moieties of pamamycin analogues; Kruger-Velthusen E et al.; A new synthetic route to chiral tetrahydrofuranyl amino acids is described starting with D-glucose . The 17-step and a 20-step procedures, respectively, furnished compounds of the general formulas 1 and 2 mimicking the dimethylamino carboxylic acid part of pamamycin (3) . In comparison with the absolute stereochemistry of 3 the acyclic compounds 1a-c and 2a-c are enantiomers . Despite of the presence of a dimethylamino function they showed neither antibacterial activity nor protonophoric effects on an artificial bilayer membrane suggesting that the macrodiolide ring of 3 forms an indispensable prerequisite for the known interaction of this antibiotic with biological systems.

Peptides, 2002 Mar, 23(3), 413 - 8
Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and analogs:structural and disulfide bridge requirements for activity; Mandal M et al.; Structure and biological activities of synthetic peptides corresponding to bovine neutrophil beta-defensin BNBD-12, GPLSC(1)GRNGGVC(2)IPIRC(3) PVPMRQIGTC(4) FGRPVKC(5) C(6)RSW with disulfide connectivities C(1)-C(5), C(2)-C(4) and C(3)-C(6) and its variants with one, two and three disulfide bridges have been investigated . Selective protection of cysteine thiols was necessary in the four and six cysteine containing peptides for the formation of disulfide connectivities as observed in BNBD-12 . Circular dichroism (CD) spectra indicate that in aqueous medium, only a small fraction of molecules populate turn-like conformations . In the presence of micelles and lipid vesicles, the single, two and three disulfide containing peptides adopt beta-hairpin or beta-sheet structures . Antibacterial activity was observed for all the peptides, irrespective of the number of disulfide bridges or how they were connected . Our results suggest that a rigid beta-sheet structure or the presence of three disulfide bridges does not appear to be stringent requirements for antibacterial activity in beta-defensins.

J Pharm Sci, 2002 Feb, 91(2), 467 - 81
Structural relationships, thermal properties, and physicochemical characterization of anhydrous and solvated crystalline forms of tetroxoprim; Caira MR et al.; Six distinct phases of the antibacterial tetroxoprim (TXP) have been isolated by recrystallization from various solvents . These comprise two polymorphs, forms I and II, and four solvates with the following solvents and TXP solvent stoichiometric ratios: chloroform (3:2), water (3:2), methanol (2:1), and ethanol (2:1) . Thermal and infrared spectral data showed that forms I and II are enantiotropically related with form II being stable below the transition temperature of 118 degrees C and form I melting at 159 degrees C . The crystal structure of form I contains three crystallographically independent TXP molecules arranged in layers formed by extensive base pairing between the 2,4-diaminopyrimidine rings . This species invariably results upon heating the solvates of TXP . Thermogravimetry and differential scanning calorimetry respectively showed one-step mass losses and progressively increasing desolvation temperatures for the solvates with chloroform, water, ethanol, and methanol . X-ray diffraction studies revealed that the latter three solvates are isostructural, belonging to the class of "isolated site" solvates . Extensive base pairing maintains the common TXP crystalline framework . Thermal data for the desolvation of these phases are reconciled with the observed crystal packing features . Experimental and computed powder X-ray patterns for form I and the solvates with water, methanol, and ethanol are presented .

J Pharm Pharmacol, 2002 Jan, 54(1), 99 - 104
Spasmolytic effects of baccharis conferta and some of its constituents; Weimann C et al.; The Nahua of the Mexican state of Veracruz use Baccharis conferta in the treatment of a variety of gastrointestinal illnesses, especially diarrhoea associated with gastrointestinal cramps . The aerial parts of B . conferta were investigated phytochemically and pharmacologically using the guinea pig ileum assay as a model (histamine, KCI and electric stimulation) . The crude ethanolic extract showed a dose-dependent antispasmodic effect that was particularly strong in flavonoid-rich fractions (e.g . IC50 value for fraction E.3.1 from the ethyl acetate fraction, in histamine-induced contraction, 10 microg mL(-1)) . Several flavonoids (apigenin-4',7-dimethylether, naringenin-4',7-dimethylether, pectolinarigenin and cirsimaritin) were isolated, while others were identified in complex fractions by GC-MS . The flavonoids play an important role in the antispasmodic activity of this indigenous drug . Additionally, oleanolic acid and its methyl ester as well as erythrodiol were isolated . Oleanolic acid methyl ester shows weak antibacterial activity against M . luteusand E . coli (20 microg/spot in a TLC assay) . The phytochemical as well as the pharmacological data provide some in-vitro evidence forthe use of B . conferta in thetreatment of gastrointestinal cramps.

Farmaco, 2001 Dec, 56(12), 919 - 27
Studies on nitrophenylfuran derivatives part Xii . synthesis, characterization, antibacterial and antiviral activities of some nitrophenylfurfurylidene-1,2,4-triazolo{3,4-b}-1,3,4-thiadiazines; Holla BS et al.; Synthesis of four 1-aryl-3-{5-(p-nitrophenyl)-2-furyl}-2-propen-1-ones starting from substituted acetophenones and p-nitrophenylfurfuraldehyde is described . These propenones were then converted into corresponding dibromo derivatives which on dehydrobromination afforded alpha-bromopropenones rather than acetylenic ketones . Condensation of these dibromopropanones with 4-amino-5-mercapto-1,2,4-triazoles yielded a new class of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines . The structures of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines were established on the basis of analytical, IR, NMR and mass spectral studies . The formation of 1,2,4-triazolo{3,4-b}-1,3,4-thiadiazines rather than 1,2,4-triazolo{3,4-b}-1,3,4-thiadiazepines in the above condensation was unambiguously confirmed by X-ray crystallographic analysis of one of them . A possible mechanism is proposed to account for the formation of nitrophenylfurfurylidene-1,2,4-triazolo{3,4-b}-1,3,4-thiadiazines . Some of the newly synthesized triazolothiadiazines were screened for their antibacterial and antiviral properties.

Farmaco, 2001 Dec, 56(12), 899 - 903
Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis-(thiadiazolotriazinyl) alkanes; Holla BS et al.; 4-Amino-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with dicarboxylic acids 2 to yield bis-(4-oxo-4H-1,3,4-thiadiazolo{2,3-c}-1,2,4-triazin-7-yl)alkanes (3b-d,f-h,j-l,n-p) and bis-thiadiazolotriazines (3a,e,i,m) . All the newly synthesised compounds were characterised by analytical, IR, NMR and mass spectral studies . Some of the newly synthesised compounds were screened for their antibacterial and antifungal properties . Among the tested compounds, compound 7,7'-(1,4-butanediyl)-his-(3-t-butyl-4-oxo-4H-1,3,4-thia-diazolo{2,3-c}-1,2,4-triazine (3p) exhibited highest degree of antifungal activity.

Jpn J Antibiot, 2001 Nov, 54(11), 571 - 9
{Comparative antibacterial activity of carbapenems against P . aeruginosa (1)}; Hikida M et al.; Comparative antibacterial activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM) and biapenem (BIPM) was determined against 288 clinical isolates of P . aeruginosa collected from various hospitals in 2000 . The order of activity by comparison of MIC50/MIC80/MIC90 was: MEPM (1/4/8 micrograms/ml) > BIPM (1/4/16 micrograms/ml) > IPM (2/4/16 micrograms/ml) > PAPM (8/16/32 micrograms/ml) . Moreover, the order of activity against 75 strains of P . aeruginosa (MIC of CAZ, AZT was > or = 16 micrograms/ml and MIC of IPM, MEPM was < or = 8 micrograms/ml) by comparison of MIC50/MIC80/MIC90 was: BIPM (1/2/8 micrograms/ml) > or = MEPM (1/4/8 micrograms/ml) > or = IPM (2/2/8 micrograms/ml) > PAPM (8/16/16 micrograms/ml) . Judging from both correlation between the MICs of carbapenems and relationship between class C beta-lactamase activity and drug susceptibility of carbapenems, it becomes apparent that carbapenems, especially BIPM and MEPM will be useful for treatment of antipseudomonal cephem resistant pseudomonas infection.

J Antibiot (Tokyo), 2001 Nov, 54(11), 917 - 25
New pyrrolizidinone antibiotics CJ-16,264 and CJ-16,367; Sugie Y et al.; Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457 . These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi . Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coli with altered permeability (imp) . Comparison of an antibacterial profile between the two compounds suggested that the gamma-lactone portion of I is important for the activity.

Boll Chim Farm, 2001 Nov-Dec, 140(6), 428 - 32
Synthesis and biological studies of some imidazolinone derivatives; Kalluraya B et al.; A Series of 4-(1-Aryl-5-oxo-2-phenyl-2-imidazolin-4-yl) metheno-5-chloro-3-methyl-1-phenyl-3-pyrazole) were synthesised and tested for their antibacterial, antiinflammatory and analagesic activities . Some of the compounds showed significant antiinflammatory properties.

Boll Chim Farm, 2001 Nov-Dec, 140(6), 411 - 6
Synthesis and antibacterial activity of some novel N-substituted piperazinyl-quinolones; Foroumadi A et al.; A series of N-substituted-piperazinyl-quinolones were synthesized and evaluated for in vitro antibacterial activity . Compounds with a 2-(2,4-dichlorophenyl)-2-oxoethyl group attached to the piperazine ring (5a-c) had similar antibacterial activity to the reference drugs, ciprofloxacin, norfloxacin and enoxacin against both Gram-positive and Gram-negative bacteria . The oximes 6a-c and 6g-i were almost less active than corresponding ketones against the tested microorganisms, however the 2,4-difluorophenyl analogues (6g-i) were more active than 2,4-dichlorophenyl derivatives (6a-c) . If the hydrogen of oxime is replaced with a benzyl group (6d-f & 6j-l), in-vitro antibacterial activity was decreased against both Gram-positive and Gram-negative bacteria . Generally ciprofloxacin derivatives were more active than norfloxacin and enoxacin derivatives.

J Biochem (Tokyo), 2002 Feb, 131(2), 277 - 81
Participation of two N-terminal residues in LPS-neutralizing activity of sarcotoxin IA; Okemoto K et al.; Sarcotoxin IA is a cecropin-type antibacterial peptide of flesh fly . Using a mutant sarcotoxin IA lacking two N-terminal residues, we demonstrated that these residues are indispensable for its antibacterial activity against Escherichia coli and LPS-binding . Contrary to the native sarcotoxin IA, the mutant sarcotoxin IA could not neutralize various biological activities of LPS . It was suggested that sarcotoxin IA firmly binds to the lipid A core of LPS via these two N-terminal residues and forms a stable binding complex that exhibits no appreciable biological activity like native LPS.

Invest Ophthalmol Vis Sci, 2002 Feb, 43(2), 503 - 9
Differential effects of bactericidal/permeability-increasing protein (BPI) analogues on retinal neovascularization and retinal pericyte growth; Rauniyar RK et al.; PURPOSE: Bactericidal/permeability-increasing protein (BPI), an antibacterial and lipopolysaccharide-neutralizing protein, also has an antiangiogenic effect . To evaluate the therapeutic role of BPI in ischemic retinopathies, the antiangiogenic activity of a human recombinant 21-kDa modified N-terminal fragment of BPI (rBPI(21)), which has the biological properties of the holoprotein, and a peptidomimetic (XMP.Z) derived from BPI were examined . METHODS: The effects of rBPI(21) and XMP.Z on VEGF-induced growth of bovine retinal microvascular endothelial cells (BRECs) and on serum-induced growth of bovine retinal pericytes (BRPs) and retinal pigment epithelial cells (BRPECs) were evaluated by determining total DNA content . The neonatal mouse model of retinopathy of prematurity (ROP) was used to study the effect of XMP.Z in vivo . Intraperitoneal injections of the peptidomimetic (10 mg/kg) were administered every 24 hours for 5 days (postnatal {P}12-P17) during induction of neovascularization . Retinal neovascularization was evaluated using flatmounts of fluorescein-dextran-perfused retinas and quantitated by counting retinal cell nuclei anterior to the internal limiting membrane . RESULTS . VEGF (25 ng/mL) increased the total DNA per well of BRECs by 120% +/- 50% (P < 0.001), which was inhibited by addition of rBPI(21) or XMP.Z, with decreases of 77% +/- 15% (P < 0.05) and 107% +/- 19% (P < 0.01) at maximum effective doses of 75 and 15 microg/mL rBPI(21) and XMP.Z, respectively . In contrast, rBPI(21) at 75 microg/mL enhanced the total DNA per well of BRP 53% +/- 14% (P < 0.001) in the presence of 5% fetal bovine serum (FBS), whereas XMP.Z enhanced BRP growth by 27% +/- 7% (P < 0.001) at 5 microg/mL . In the presence of 10% FBS, rBPI(21) and XMP.Z increased BRP growth by 91% +/- 35% (P < 0.001) and 43% +/- 18% (P < 0.01), respectively . In the oxygen-induced ROP neonatal mouse model, retinal neovascularization was decreased by 40% +/- 16% (n = 5, P < 0.01) when animals were treated with XMP.Z . CONCLUSIONS: Two BPI-derived compounds, rBPI(21) and XMP.Z, significantly suppressed VEGF-induced BREC growth in vitro, while conversely enhancing the growth of BRPs, even above that induced by 20% FBS . When tested in animals, XMP.Z also suppressed ischemia-induced retinal neovascularization in mice . These data suggest that BPI-derived compounds may have unique therapeutic potential for proliferative retinal diseases such as diabetic retinopathy, if physiological levels can be achieved in clinical settings.

Drugs, 2002, 62(2), 309 - 17
Intravenous/oral sequential therapy in patients hospitalised with community-acquired pneumonia: which patients, when and what agents?
Vogel F.
Cost and pharmacoeconomic aspects are becoming more and more important in antibacterial therapy . Nevertheless, antibacterial therapy is curative and initial use of the right antibacterial with high activity and low resistance rates against the relevant pathogens can help to save costs . A new trend in antibacterial therapy is sequential therapy (intravenous/oral) in hospitalised patients with moderate to severe infections . Large studies comparing intravenous therapy with sequential therapy (intravenous/oral) have shown equivalence in clinical and bacteriological outcome . One main indication investigated is community-acquired pneumonia (CAP) . CAP requires prompt and effective antibacterial treatment and conventional therapy for patients hospitalised with CAP has typically been parenteral antibacterial therapy for 7 to 10 days . However, clinical evidence shows that in most patients the objective and subjective indicators of infection are substantially improved within the first 2 to 3 days of treatment . Today a large number of clinical trials in patients with CAP have been undertaken and sequential therapy with appropriate antibacterials used in suitable patients has been proven as a treatment option . This demonstrates pharmacoeconomic benefits without compromising antibacterial efficacy . Recommended antibacterials for intravenous/oral sequential therapy in patients with CAP are second- and third- generation cephalosporins, aminopenicillins plus a beta-lactamase inhibitor, and new fluoroquinolones.

Indian J Gastroenterol, 2001 Nov-Dec, 20(6), 247 - 8
Port-site infection with Mycobacterium chelonei following laparoscopic appendicectomy; Bhandarkar DS et al.; We report a 14-year-old girl who developed port-site infection with Mycobacterium chelonei following laparoscopic appendicectomy . She was treated with local exploration and excision of sinuses that developed at the site, followed by antibacterial agents for six months . She has had no recurrence of infection at two years.

J Pharm Biomed Anal, 2002 Feb 1, 27(5), 845 - 9
Determination and pharmacokinetic study of ferrocene-A in blood serum of rabbits; Pochkhidze MSh et al.; Ferrocene-A (ferrocenyl-1-phenyl-1-dioxy-1,4-butin-2) has significant antitumour and antibacterial properties . This study was designed to estimate main pharmacokinetic parameters of ferrocene-A (FC-A) . These parameters are very important from the standpoint to elucidate the mechanism of pharmacological action of ferrocene-A . Examined substance was administrated intramuscularly and orally to rabbits . For determination of small quantities of ferrocene-A in a blood plasma liquid-liquid extraction and reversed-phase high performance liquid chromatography (HPLC) method was applied . Kinetic parameters were estimated using the one-compartment linear pharmacokinetic model.

J Infect Chemother, 1999 Dec, 5(4), 206 - 207
beta-Lactamase inhibitors have antibacterial activities against Helicobacter pylori; Horii T et al.; Recently, it was reported that amoxicillin-clavulanate has slightly higher activity than amoxicillin against Helicobacter pylori . In this study, we evaluated the in-vitro antibacterial activity of beta-lactamase inhibitors against H . pylori . We investigated the susceptibility of 30 H . pylori strains to beta-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam . In short-term bactericidal studies, a clinical isolate of H . pylori NU27 was exposed to 1 x minimum inhibitory concentration (MIC) of the beta-lactamase inhibitors, amoxicillin, clarithromycin, and amoxicillin-clavulanate for 3 and 6 h . The MICs90 for these beta-lactamase inhibitors were 2, 4, and 2 mg/l, respectively . The short-term bactericidal studies showed that these beta-lactamase inhibitors decreased viable counts of H . pylori during 6-h exposure at 1 x MIC . Our results suggest that beta-lactamase inhibitors have in-vitro antibacterial activity against H . pylori . Amoxicillin and clavulanate used in combination resulted in increased antibacterial activity.

J Food Prot, 2002 Jan, 65(1), 106 - 10
Consumer acceptance of raw apples treated with an antibacterial solution designed for home use; McWatters KH et al.; An antibacterial treatment consisting of 1.5% lactic acid plus 1.5% hydrogen peroxide at 40 degrees C for 15 min was effective in reducing foodborne bacterial pathogens on raw apples . However, the effects of this treatment on an apple's sensory characteristics and the extent of consumers' willingness to use the treatment at home were not known . This study was undertaken to determine the sensory acceptability and chemical characteristics (pH, soluble solids, and total acidity) of apples subjected to the sanitizing treatment and to obtain information on consumers' purchase behavior, apple handling and consumption practices, and willingness to use an antibacterial treatment . Untrained consumers (n = 80) evaluated the appearance, color, aroma, flavor, texture, and overall appeal of untreated (control) and treated Red Delicious apples that had been stored at 5 degrees C for 0, 6, and 10 days . Panelists used a nine-point hedonic scale (1 = "dislike extremely"; 5 = "neither like nor dislike"; 9 = "like extremely") to evaluate sensory acceptability . Treatment and storage had no significant effect on the appearance, color, or aroma of the samples . Flavor ratings ranged from 6.2 ("like slightly") to 7.0 ("like moderately") . There was no significant difference among any of the control and treated apples stored for 0 days or among those stored for 6 days . Although apples stored for 10 days received the lowest ratings (6.2 to 6.3), they still had an acceptable flavor (6, "like slightly"), and panelists could not perceive differences between the control samples and the treated samples on day 10 . The same trends were noted in texture ratings and in overall liking ratings . Treatment and storage had a minimal effect on pH (range, 3.96 to 4.02), soluble solids (range, 11.8 to 12.9 degrees Brix), and total acidity (range, 0.20 to 0.23% malic acid), which are important for apple flavor . Many consumers (87%) were concerned about fruit safety, and 53.2% were willing to try an antibacterial treatment at home . However, 74% would not be willing to use it if a 15-min heating-and-soaking step were required . Implementation of the treatment may be more feasible in the packinghouse than in the home.

J Chemother, 2001 Dec, 13(6), 611 - 4
Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori; Marone P et al.; In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori . The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay . Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml . The influence of sub-MBCs of mastic gum on the morphologies of H . pylori was evaluated by transmission electron microscopy . The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H . pylori cells.

J Chromatogr A, 2001 Dec 21, 939(1-2), 49 - 58
Determination of the metabolites of nitrofuran antibiotics in animal tissue by high-performance liquid chromatography-tandem mass spectrometry; Leitner A et al.; A LC-MS-MS method is presented to analyse simultaneously the metabolites of four nitrofuran antibacterial agents, furazolidone, furaltadone, nitrofurazone and nitrofurantoin in animal muscle tissue . Sample clean-up and analyte enrichment was performed by solid-phase extraction (SPE) with a polystyrene sorbent following combined hydrolysis of the protein-bound drug metabolites and derivatisation of the homogenised tissue with 2-nitrobenzaldehyde . Limits of detection of 0.5-5 ng g(-1) tissue and limits of determination of 2.5-10 ng g(-1) tissue were achieved using electrospray ionisation in positive mode . Analyte identification and quantification was performed according to EU guidelines, using multiple reaction monitoring (MRM) with one precursor ion and two product ions as identifiers . The use of an internal standard in combination with the simplified sample preparation led to a sensitive and reliable analysis method . The yield of the derivatisation reaction was between 66 and 74% and the recovery of SPE reached 92-105% for all values between 10 and 500 ng g(-1) . The developed analytical protocol has been applied to contaminated tissue samples of furazolidone- and furaltadone-treated pigs and allowed unequivocal identification and quantification of the metabolites.

Zhonghua Jie He He Hu Xi Za Zhi, 2001 Jan, 24(1), 52 - 5
{Observations of properties of the L-form of M . tuberculosis induced by the antituberculosis drugs}; Wang H et al.; OBJECTIVES: To investigate the mechanism of generation of L-form of M . tuberculosis and its significance on the development, diagnosis and treatment of tuberculosis . METHODS: M . tuberculosis was inoculated into the non-high osmotic medium with rifampin, isoniazid or ethambutol and then the L-form was observed by microscopy daily . The cultures were filtrated to get the pure cultures of stable L-form by subculture with the non-high osmotic medium and characteristics of morphology, growth, susceptibilities to the antibacterial drugs and the special gene of M . tuberculosis were observed when the pure subcultures of the L-form were isolated . RESULTS: L-form of M . tuberculosis was induced by the concentrations of routine inhibition test of rifampin, isoniazid or ethambutol . The L-form would not be susceptible to the above mentioned antituberculosis drugs but susceptible to streptomycin, erythromycin, ofloxacin, norfloxacin and others . The morphologies of L-form were irregular or spherical with single, paired or chain form, and growth under the bottom of the medium but not movement or adhere to the glass . The L-form was negative by acid-fast stain and negative or positive by Gram stain . The gene of L-form reacted with the PCR kit for the M . tuberculosis and showed the same band . CONCLUSIONS: M . tuberculosis could be killed by rifampin, isoniazid or ethambutol but also could be induced to become the L-form by these antituberculosis drugs, and it is one of the important factor that affecting the effect of treatment of the tuberculosis . The cell wall deficient variants of M . tuberculosis could be determined by the PCR of M . tuberculosis . It is recommended that the L-forms should be noticed during the treatment with the antituberculosis drugs and combination treatment with antituberculous drugs to which the L-forms were susceptible, is also very important.

Int J STD AIDS, 2002 Jan, 13(1), 55 - 7
Candida dubliniensis candidaemia in an HIV-positive patient in Ireland; Boyle BM et al.; Candida dubliniensis was first identified in Dublin in 1995 in oral isolates recovered from human immunodeficiency virus (HIV)-infected individuals . Although C . dubliniensis has been primarily recovered from the oral cavities of HIV-infected individuals, the number of reports describing its isolation from HIV-negative individuals, including cases of candidaemia, is growing . To date there has only been one report of C . dubliniensis candidaemia in an HIV-infected patient, in this case from the USA . In the present study, 2 Candida isolates recovered from blood samples were presumptively identified as C . dubliniensis on the basis of their dark green coloration on CHROMagar Candida medium and lack of growth at 45 degrees C . This identification was confirmed by carbohydrate assimilation profile analysis and by polymerase chain reaction (PCR) analysis with C . dubliniensis-specific PCR primers . Both isolates were susceptible to fluconazole . The isolates were found retrospectively to be from a single HIV-infected patient who was receiving broad-spectrum antibacterials at the time of isolation of C . dubliniensis from blood . This study represents the first documented case of C . dubliniensis bloodstream infection in Ireland and is only the second case of C . dubliniensis bloodstream infection identified in an HIV-infected individual anywhere in the world.

Zhonghua Nei Ke Za Zhi, 1999 Feb, 38(2), 98 - 100
{The serum bactericidal activity of domestic fleroxacin and lomefloxacin}; Zhao M et al.; OBJECTIVE: To evaluate antibacterial activities in vivo and in vitro of fleroxacin and lomefloxacin . METHODS: Minimal inhibitory concentration (MIC) and serum bactericidal activity (SBA) domestic fleroxacin and lomefloxacin were determined by agar disk dilution method and microplate method respectively . A clinical observation of fleroxacin and lomefloxacin for treating acute bacillary dysentery was carried out . RESULTS: MIC(90) of fleroxacin against E . coli, K . pneumoniae, S . dysenteriae, S . aureus was 0.25-2 mg/L, being the same as that of ofloxacin . However, MIC(90) of lomefloxacin against the above mentioned species was twice or fourfold as that of ofloxacin and fleroxacin . The percent age of peak SBA > or = 1:8 with ofloxacin, fleroxacin and lomefloxacin against E . coli, K . pneumoniae, S . dysenteriae was 80%-100%, 90%-100% and 50%-80% respectively (P < 0.01) . The clinical cure rates of acute bacillary dysentery were 93.3%, 100% and 100% and the bacterial clearance rates were 93.3%, 100% and 100% in the lomefloxacin, fleroxacin and ofloxacin group respectively . CONCLUSION: The antibacterial activity in vivo and in vitro of fleroxacin against E . coli, K . pneumoniae, S . dysenteriae was similar to that of ofloxacin and stronger than that of lomefloxacin.

Zhonghua Nei Ke Za Zhi, 1999 Jan, 38(1), 22 - 6
{A randomized controlled clinical study of sparfloxacin versus ofloxacin in the treatment of bacterial infections}; Hu P et al.; OBJECTIVE: To evaluate the efficacy and safety of sparfloxacin in the treatment of bacterial infections . METHODS: A randomized controlled multi-centre clinical trial was conducted . Ofloxacin used as the control drug . A total of 212 patients entered the study, with 106 in the sparfloxacin group and the remaining 106 in the ofloxacin group . Both compounds were given by oral administration . RESULTS: The cure rate of sparfloxacin and ofloxacin was 74.5% and 69.8% respectively and the overall efficacy rate was 91.5% and 88.7% respectively . The bacterial clearance rate was 90.7% in the sparfloxacin group and 90.8% in the ofloxacin group . The adverse drug reaction rate of sparfloxacin and ofloxacin was 9.43% and 8.49% respectively . There was no statistical significant difference between the two groups for the above results . The results of in vitro activity of sparfloxacin as compared with other 5 antibacterial agents showed that sparfloxacin had good activity against many Gram-negative organisms and was similar to those of ofloxacin . The activity against Gram-positive organisms (MIC(90) <or= 0.25 mg/L) was generally higher than that of ofloxacin . CONCLUSION: Sparfloxacin is a highly effective and safe broad-spectrum antibacterial agent for the treatment of bacterial infections . It is also effective in the treatment of infections caused by Gram-positive organisms.

Infect Immun, 2002 Feb, 70(2), 569 - 76
Host defense functions of proteolytically processed and parent (unprocessed) cathelicidins of rabbit granulocytes; Zarember KA et al.; Members of the cathelicidin family are present in all mammals studied . Generally, these proteins contain a conserved N-terminal domain and a structurally and functionally divergent C-terminal region that expresses antibacterial or other activities when proteolytically released . Rabbit granulocytes produce CAP18, a cathelicidin that conforms to this structural and functional organization, and also 15-kDa protein isoforms (p15s) that share several key structural features with other cathelicidins but apparently do not undergo processing with release of an active peptide . To further define the importance of proteolysis in the antibacterial activities of these proteins, we have purified from granulocytes proCAP18, its C-terminal peptide (CAP18p), and two p15 isoforms to apparent homogeneity . Of these four polypeptides, only CAP18p was independently cytotoxic to encapsulated Escherichia coli (90% inhibitory concentration, approximately 600 nM) but it was approximately 50-fold less potent on a molar basis than the bactericidal/permeability-increasing protein (BPI) . However, all four cathelicidin species, notably including proCAP18, exhibited antibacterial synergy with BPI, and the p15s also displayed synergy with CAP18p in the absence of BPI . Subnanomolar concentrations of proCAP18 blocked lipopolysaccharide-induced chemiluminescence of human leukocytes, showing a molar potency more than 100-fold greater than that of CAP18p ( approximately 20 nM) or BPI ( approximately 50 nM) . Thus, while independent bactericidal activity of cathelicidins requires processing, other host-defense functions do not and are more potently expressed by the unprocessed protein than by the C-terminal peptide.

Drug Dev Ind Pharm, 2001 Nov, 27(10), 1017 - 30
Characterization of the solubility and dissolution properties of several new rifampicin polymorphs, solvates, and hydrates; Henwood SQ et al.; Based on reports that tuberculosis is on the increase, this investigation into the physicochemical properties of rifampicin when recrystallized from various solvent systems was undertaken . Rifampicin is an essential component of the currently recommended regimen for treating tuberculosis, although relatively little is known about its solubility and dissolution behavior in relation to its solid-state properties . A rifampicin monohydrate, a rifampicin dihydrate, two amorphous forms, a 1:1 rifampicin:acetone solvate, and a 1:2 rifampicin:2-pyrrolidone solvate were isolated and characterized using spectral, thermal, and solubility measurements . The crystal forms were relatively unstable because except for the 2-pyrrolidone solvate, all the hydrated or solvated materials changed to amorphous forms after desolvation . Fourier transform infrared (FTIR) analysis confirmed the favorable three-dimensional organization of the pharmacophore to ensure antibacterial activity in all the crystal forms except the 2-pyrrolidone solvate . In the 2-pyrrolidone solvate, the strong IR signals of 2-pyrrolidone interfered with the vibrations of the ansa group . The 2-pyrrolidone solvate was the most soluble in phosphate buffer at pH 7.4 . This solvate also had the highest solubility (1.58 mg/ml) and the fastest dissolution in water . In 0.1 M HCl, the dihydrate dissolved the quickest . A X-ray amorphous form (amorph II) was the least soluble and had the slowest dissolution rate because the powder was poorly wettable and very electrostatic.

Klin Khir, 2001 Aug, (8), 52 - 4
{Treatment of the diabetic foot in general surgery}; Turaev PI et al.; Experience of treatment of disorders of peripheral blood circulation in 120 patients with diabetes mellitus was summarized . Conservative treatment, conducted in 85 patients, included insulinization, preparations of sulfanilurea and glibenclamids, antibacterial therapy (beta-lactams, aminoglycosides, metronidazole) during 7-10 days, acidum acetylsalicylicum, trental, solcoseryl, vitamins . Amputation of lower extremity was done 35 patients, in 15 of them--on the hip level . Good result was noted in the treatment of diabetic foot with pronounced trophic changes in the third stage of ischemia when fraxiparine was applied locally.

Klin Khir, 2001 Aug, (8), 42 - 7
{Antibacterial therapy of purulent necrotic foot lesions in patients with diabetes mellitus}; Podpriatov SIe et al.; Efficacy of antibacterial therapy was analyzed in 266 patients with diabetes mellitus and purulent-necrotic affection of the foot . In presence of affection of bones and joints good effect was achieved while conduction of antibacterial therapy and in the cases of open wound--while local administration of systemic antibacterial preparations.

Klin Khir, 2001 Aug, (8), 14 - 6
{Peculiarities of the occurrence of soft tissue disorders and prospects of their closure in patients with diabetes mellitus}; Driuk MF et al.; Cause and mechanisms of the foot soft tissues defect (FSTD) and efficacy of its closure were analyzed in 62 patients with diabetes mellitus . FSTD presented as chronic infected (in 7 observations) or uninfected (in 4) ulcer of foot or it occurred acutely immediately after excision of necrotized tissues (in 32) and after the operation due to disordered healing of wound or to necrosis of her edge (in 12) . In presence of osteoarthropathy, purulent inflammation as a consequence of trauma or isolated affection of toes II or III the conduction of intensive antibacterial therapy permits to eliminate purulent inflammation during 4-7 days and than to close FSTD using existing methods . Occurrence of FSTD on background of disordered blood supply of foot forces to conduct not only systemic, but intensive local antibacterial therapy as well, yet it is not possible to achieve clearing of all the wound . In such a case it is expedient to perform staged closure of little-infected places of wound and sawn surfaces of the bones, what reduces the wound cachexia of patient and promotes the foot stump preservation . Closure of chronic ulcer of the foot by the cutaneous flap transposition must be done on background of alprostan injections.

Comp Biochem Physiol C Toxicol Pharmacol, 2000 Mar, 125(3), 287 - 97
Antibacterial properties and partial cDNA sequences of cecropin-like antibacterial peptides from the common cutworm, Spodoptera litura; Choi CS et al.; The antibacterial properties and cDNA sequences of two types of antibacterial peptides from the haemolymph of immunized common cutworm, Spodoptera litura larvae, were determined . Since the primary structures of peptides deduced from cDNA sequences showed significant homologies to cecropins A and B, they were named as Spodoptera cecropins A and B . Spodoptera cecropins were broadly effective against Gram-positive and negative bacteria . They also retained antibacterial activities in all conditions tested (at pH 5.6-8.0 and in the presence of 50-150 mM NaCl) that was adapted to confirm the antibacterial properties of Spodoptera cecropins . These results indicate that the change of pH and the increase of salt concentration in the media do not influence the activities of Spodoptera cecropins . For the reverse transcription (RT)-polymerase chain reaction (PCR) to obtain the complete primary sequence, the primer designed according to the conserved region of the cecropin leader sequences was used, which was determined by the comparison of the cDNA sequences of known cecropins . The results from RT-PCR presented that the partial cDNAs of Spodoptera cecropins A and B encode 57 and 58 amino acids, including the sequences of mature peptides, respectively . In addition, Northern blot analysis with (32)P-labeled PCR product coding for Spodoptera cecropin A revealed that Spodoptera cecropin genes are expressed in immunized fat body, but not in normal fat body.

Drugs, 2002, 62(1), 71 - 106
Zanamivir: an update of its use in influenza; Cheer SM et al.; Zanamivir is a potent competitive inhibitor of the neuraminidase glycoprotein, which is essential in the infective cycle of influenza A and B viruses . Zanamivir (10mg by inhalation via the Diskhaler twice daily, or 10mg inhaled plus 6.4mg intranasally two or four times daily, for 5 days) reduced the median time to alleviation of major influenza symptoms by up to 2.5 days compared with placebo . Significant reductions of 1 to 2.5 days versus placebo were observed with inhaled zanamivir in phase III trials involving otherwise healthy adults, high-risk patients or children aged 5 to 12 years . Accelerated return to normal activities, and reduced interference with sleep, consumption of relief medication and incidence of complications leading to antibacterial use were also observed with zanamivir . When used for prophylaxis, inhaled zanamivir 10 to 20 mg/day for 10 days to 4 weeks (plus 6.4 mg/day intranasally in one trial) prevented influenza A in 67% of recipients in a university community, significantly reduced the number of families with new cases of influenza compared with placebo or prevented new cases of influenza in long-term care facilities . The tolerability of inhaled or intranasal zanamivir was similar to that of placebo in otherwise healthy adults, high-risk and elderly patients, and children . Recommended dosages of zanamivir did not adversely affect pulmonary function in patients with respiratory disorders in a well-controlled trial, although there have been rare reports of bronchospasm and/or a decline in respiratory function . CONCLUSION: Zanamivir (used within 48 hours of symptom development) reduces the duration of symptomatic illness, causes accelerated return to normal activities or reduces complications requiring antibacterial use in adults, high-risk individuals and children with influenza . Vaccination remains the intervention of choice for prophylaxis in selected populations . However, the efficacy, good tolerability profile and lack of resistance with zanamivir make it a useful option, particularly in those not covered or inadequately protected by vaccination, who are able to use the inhalation device . The use of zanamivir in patients with respiratory disorders remains unclear because of concerns regarding its potential for bronchospasm . Prospective cost-effectiveness analyses and investigations of efficacy in preventing serious complications of influenza, particularly in high-risk patients, are required . Zanamivir shows potential for prophylaxis in persons for whom vaccination is contraindicated or ineffective, in elderly or high-risk patients in long-term care facilities and in households.

Aust Vet J, 2001 Nov, 79(11), 740 - 6
Systemic antibacterial drug use in dogs in Australia; Watson AD et al.; A survey of veterinarians' use of antibacterial drugs was conducted by distributing a questionnaire to Australian practitioners . Respondents were asked to indicate their general patterns of use of various systemic antibacterial drugs and drug combinations in dogs and their approach to certain specified clinical disorders . Overall, antibacterials of the beta-lactam type (penicillins and cephalosporins) were most commonly used . Other antibacterials with substantial use were doxycycline, sulphonamide-trimethoprim, metronidazole, fluoroquinolones and clindamycin . Drug selection for different disorders was generally appropriate when compared with recommendations in recent texts, although inappropriate use was evident in some circumstances.

Infection, 2001 Dec, 29 Suppl 2, 3 - 10
Barriers to the effective management of respiratory tract infections in the community; Saginur R; The treatment of respiratory tract infections (RTIs) continues to challenge the knowledgeable and conscientious physician . Upper RTIs such as sinusitis and tonsillitis/pharyngitis - while not generally life-threatening - are associated with personal cost and suffering, while infections of the lower respiratory tract, including community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB), represent a more serious clinical challenge and account for almost half of all community-acquired infections . Moreover, such infections may be fatal . Laboratory tests for etiologic agents of RTIs are often insensitive and slow and identify the causative pathogen in only a minority of cases . Therapy for RTIs is, therefore, generally presumptive and instituted before there is a clear understanding of etiology . Such an approach requires antibacterials that possess a spectrum of activity which covers both the common and atypical/intracellular pathogens associated with RTIs to enable physicians to confidently prescribe treatment . A major barrier to the confident prescribing of empiric therapies for RTIs is the increasing prevalence of resistance to existing antibacterial agents among respiratory tract pathogens . Increasing levels of antibacterial resistance now threaten the utility of existing agents, primarily the beta-lactams and macrolides, and continue to drive the search for newer agents which retain activity against drug-resistant respiratory tract pathogens . This need is emphasized by recent evidence that bacterial resistance may be associated with poorer clinical outcomes, particularly for patients with severe infections . There is enormous concern and uncertainty about the factors that contribute to increasing bacterial resistance and treatment strategies that should be adopted to minimize this problem . The arguments have raged particularly around recent Infectious Diseases Society of America (IDSA) guidelines on the treatment of CAP, which have advocated a greater role for fluoroquinolones . One school of thought - driven in part by concerns over cost of therapy - advocates the use of older agents such as amoxicillin, in the hope that any resistance that is incurred will be to these agents, leaving the newer agents for select cases with acquired resistance . Advocates of the newer agents argue that this approach represents a false economy and that there is a greater likelihood of first-line success with newer agents, so that patients are less likely to require a second physician visit and a second course of antibacterial therapy.

Infection, 2001 Dec, 29 Suppl 2, 11 - 5
Predicting antibacterial response from pharmacodynamic and pharmacokinetic profiles; Nicolau DP; The aim of antibacterial chemotherapy is to achieve sufficient drug concentrations at the site of infection for an adequate length of time to ensure bacterial eradication and optimize clinical success . Whether the desired outcome is achieved or not depends on a number of pathogen-, drug- and patient-related factors . Neither microbiologic activity nor antibacterial pharmacokinetic data alone can adequately describe the complex interaction between pathogen, host and antibacterial during the disease process . A relatively new discipline - pharmacodynamics - seeks to integrate both microbiologic and pharmacokinetic data . The particular model that best predicts clinical outcome depends on the pattern of microbial killing and the persistence of antibacterial effects after plasma concentrations have fallen below the minimum inhibitory concentration (MIC) for the target pathogen (post-antibiotic effect {PAE}) . The beta-lactams, for example, exhibit time-dependent bacterial killing with minimal persistent effects . Time above MIC (T(MIC)) is therefore the parameter that best correlates with clinical efficacy for these agents and that, in turn, necessitates multiple daily dosing to optimize the duration of exposure . The macrolides erythromycinA and clarithromycin exhibit a similar pharmacokinetic/pharmacodynamic relationship to that of the beta-lactams, although for clarithromycin the area under the concentration-time curve (AUC) also correlates with clinical outcome (reflecting the more prolonged PAE of this agent) . Azithromycin, ketolides, such as telithromycin (HMR 3647), streptogramins and fluoroquinolones exhibit concentration-dependent killing and have prolonged persistent effects, such that the AUC:MIC or Cmax:MIC ratio correlates most closely with clinical efficacy . For these agents the aim is to maximize drug concentrations to which the target pathogen is exposed and this may require higher doses and hence enable longer dosing intervals to be used . In summary, pharmacodynamic models provide a unique approach to determining likely in vivo activity of individual antibacterial agents and prediction of clinical outcomes.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 1999 Apr, 19(4), 212 - 4
{Clinical study on acute upper respiratory tract infection treated with qingkailing injection}; Li C et al.; OBJECTIVE: To explore the effect of Qingkailing injection (QKLI) in treating acute fever . METHODS: Four hundred cases of acute upper respiratory tract infection were divided into three groups treated with QKLI 120 ml/d, 160 ml/d and 200 ml/d respectively, and compared with a control group treated with lincomycin 1.8 g/d . RESULTS: The markedly effective rate of QKLI was 84.14% which was better than that of lincomycin (75.83%) . The mean initial time of QKLI (12.6 h) was shorter than that of lincomycin (17.6 h) . Effect of QKLI on patients with disease course within one day was better than that within 3 days . No significant difference revealed between effects in groups treated with different dosage of QKLI . The effect of QKLI in lowering white blood cell count was similar to that of lincomycin . For patients with positive throat swab culture of pathogenic bacteria, QKLI displayed good antibacterial action in vivo . CONCLUSION: QKLI is a highly effective with rapid action drug for treatment of acute respiratory infection.

Med Sci Monit, 2002 Jan, 8(1), PI1 - 7
Comparative study of cefaclor AF vs . cefuroxime axetil in acute exacerbations of chronic bronchitis; Haczynski J et al.; BACKGROUND: Acute exacerbations of chronic bronchitis (AECB) are the most common complication of chronic bronchitis . The majority of AECB are caused by infection . The choice of appropriate antibacterial therapy for AECB is becoming more difficult and is usually empirically . Cefaclor and cefuroxime are used for ambulatory treatment of AECB . MATERIAL/METHODS: This multicenter, randomized, single blind study was undertaken in order to compare efficacy and safety of cefaclor AF (500 mg BID) and cefuroxime axetil (250 mg BID) in 10 days treatment of ambulatory patients with AECB . 170 adults were enrolled into the study . Clinical responses were assessed on 17th-24th day after randomization . RESULTS: Both antibiotics had high over 97% effectiveness in the treatment of AECB . There was statistically significant 1.7 times higher rate of patients with cough release after cefaclor treatment compared to cefuroxime (p<0.03) . There was a significantly 2.25 higher rate of patients with AECB symptoms release like: increasing dyspnea, sputum volume and sputum purulence or cough in cefaclor group compared to cefuroxime (p<0.0187) . Both treatments resulted in significant improvement of pulmonary peak expiratory flow (PEF) . There were no differences between the rates of gastrointestinal and other side effects in both groups . CONCLUSIONS: 1 . Cefaclor and cefuroxime have similar high efficacy and safety in 10 days treatment of patients with AECB . 2 . Cefaclor treatment significantly higher 2.25 times reduces the rate of principle symptoms of AECB compared to cefuroxime . 3 . Both antibiotics treatment significantly increase PEF, with higher tendency observed in after cefaclor treatment.

J Clin Gastroenterol, 2002 Feb, 34(2), 135 - 40
A comparative study between conventional and laparoscopic cholecystectomy: evaluation of phagocytic and T-cell-mediated antibacterial activities; Altamura M et al.; Over the past few years, many reports have pointed out that open, but not minimally invasive, cholecystectomy was associated with reduced immune functions . Also, after laparoscopic surgery, a reduced impairment of T cell functions and lower levels of proinflammatory cytokines, epinephrine, and norepinephrine were found in comparison with those detected in patients who underwent conventional cholecystectomy . We investigated polymorphonuclear cell- and monocyte-mediated phagocytosis and killing and T-cell-mediated antibacterial activity in 12 patients who underwent open cholecystectomy versus another group of 12 patients who underwent laparoscopic cholecystectomy . Our data show that polymorphonuclear and monocyte killing activities are preserved or are less affected in patients who undergo laparoscopy when compared with patients who undergo conventional operation . On the other hand, in both groups of patients, T-cell-mediated antibacterial activity was significantly reduced in the preoperative period, and, therefore, we could not draw conclusions on the effects of the surgical techniques used on the above immune parameter . The overall data suggest that laparoscopic cholecystectomy is a valid alternative to open surgery because of the moderate postoperative immune suppression and decreased risk of postsurgical infections.

Neuro Endocrinol Lett, 2001 Dec, 22(6), 467 - 74
Neuroimmunology of opioids from invertebrates to human; Salzet M; There is today growing evidence that the nervous and the immune systems can exchange information, mainly through small molecules, either cytokines or neuropeptides . Furthermore, it appears that some so-called neurotransmitters like neuropeptides can function as endogenous messengers of the immune system, and that they most likely participate in an important part in the regulation of the various components of the immune response . In this context, it is widely accepted that all organisms have processes that maintain their state of health . Failure of these processes, such as those involving naturally occurring antibacterial peptides, may lead to pathological events . The presence of antibacterial peptides on both proenkephalin invertebrate (Leeches) and vertebrate (Human) neuropeptide precursors such like enkelytin, peptide B, further supports the hypothesis that some of neuropeptide precursors are implicated in immune response . Indeed, their peptides, with their high antibacterial activities further associate opioid peptides with immune related activities . We surmise that immune signalling molecule may lead to enhanced proenkephalin proteolytic processing by prohormone convertase freeing both opioid peptides and antibacterial peptides during innate immune response . However, because it is necessary to modulate inflammation, invertebrates like leeches are also able to synthesize panoply of messengers that modulate inflammation e.g . endocannabinoids, opiates and pro-opiomelanocortin derived peptides such like adenocorticotrophin and melanostimulating hormone . This demonstrates that the equilibrium between the stimulation and the inhibition of the immune response has evolved sooner that it can be thought.

J Ind Microbiol Biotechnol, 2001 Sep, 27(3), 144 - 8
Simocyclinones: diversity of metabolites is dependent on fermentation conditions; Schimana J et al.; Simocyclinones, a novel group of angucyclinone antibiotics, are produced by Streptomyces antibioticus Tu 6040 . The compounds show antibacterial and antitumor properties . In submerged cultivation, the production of simocyclinones is strongly dependent on the carbon and nitrogen sources used in a chemically defined medium . Productivity of distinct components and diversity of simocyclinone compounds are influenced by the medium composition . Four series of simocyclinone compounds were detected by high-performance liquid chromatography (HPLC) diode array detector (DAD) and HPLC electrospray ionization (ESI) mass spectrometry (MS) analysis, isolated and the structures determined by nuclear magnetic resonance (NMR) techniques . Under optimized conditions, simocyclinone D8 was produced in an amount of 300 mg l(-1) and simocyclinone C4 in a concentration up to 50 mg l(-1).

Vet Clin North Am Equine Pract, 2001 Dec, 17(3), 479 - 89, vii
Toxic feed constituents in the horse; Hall JO; Poisoning cases in horses associated with dietary exposures can encompass a wide variety of etiologies that can be caused by natural or man-made components . Feed mixing errors and ingestion of feed formulated for other species are the most common means by which poisonings from man-made materials occur . Ionophore feed additives and antibacterial agents are especially toxogenic to horses . Effects of ionophores in horses include clinical, clinicopathologic, and pathologic changes associated with cardiac, muscular, and neurologic tissues involvement . The acute effects of ionophores, however, can result in long-term cardiac dysfunction . Antibacterial effects are associated with changed microbial populations in the digestive tract that results in bacterial toxin liberation . These bacterial toxins damage the mucosa, and they result in systemic effects . For either type of feed-associated poisoning, it is critical that samples be analyzed for an accurate diagnosis.

Infect Dis Clin North Am, 2001 Dec, 15(4), 1227 - 61
Antifungal susceptibility testing . New technology and clinical applications; Pfaller MA et al.; The state of the art for susceptibility testing of yeasts is comparable with that of bacteria . Standardized methods for performing antifungal susceptibility testing are reproducible, accurate, and available in clinical laboratories . The development of quality control limits and interpretive criteria for a limited number of antifungal agents provides a basis for the application of this testing in the clinical laboratory . A proficiency testing program is available as a quality assurance measure for laboratories and has documented steady improvement among laboratories using the NCCLS method . As with antibacterial agents, surveillance programs are now in place using reference quality testing methods to monitor antifungal resistance trends on a global scale . It is clear that antifungal susceptibility testing can predict outcome in several clinical situations . Susceptibility testing is most helpful in dealing with infection caused by non-albicans species of Candida, and susceptibility testing of azoles is increasingly important in the management of candidiasis in critically ill patients . Susceptibility testing also has been standardized for filamentous fungi that cause invasive infections . Studies are ongoing to further refine this approach and evaluate the in vivo correlation with the in vitro data for molds . Future efforts must be directed toward establishing and validating interpretive break-points for licensed antifungals such as amphotericin B, and for new antifungals that are not yet licensed . Finally, procedures must be optimized for testing non-Candida yeasts (e.g., C . neoformans) and molds.

J Neuroimmunol, 2002 Jan, 122(1-2), 65 - 73
Differentiated Th1 autoreactive effector cells can induce experimental autoimmune encephalomyelitis in the absence of IL-12 and CD40/CD40L interactions; Mendel I et al.; IL-12 plays a critical role in the priming of Th1 responses to bacterial/parasitic antigens and autoantigens . Several studies have demonstrated a dependency on CD40/CD40L interactions and IL-12 for maintenance of both antibacterial/parasitic and autoreactive Th1 cells in vivo . However, it is still unclear if fully differentiated Th1 effectors require continued stimulation by IL-12 . We demonstrate that the proliferative response and IFN-gamma production by a fully differentiated T cell line specific for myelin oligodendrocyte glycoprotein are completely independent of IL-12 and CD40/CD40L interactions . The capacity of this line to adoptively transfer experimental autoimmune encephalomyelitis is also independent of IL-12 and CD40/CD40L . These results have important implications regarding the therapeutic usefulness of blockade of IL-12 or the CD40/CD40L pathway for treatment of autoimmune disease.

Yakushigaku Zasshi, 2001, 36(1), 10 - 7
{Wood creosote: a historical study and its preparation in combination with herbal drugs}; Baba T et al.; Two kinds of creosote have been found based on historical evidence of the medicinal uses and origins . One is wood creosote, and distillate of wood-tar containing guaiacol and creosol . The other type of creosote is coal-tar creosote, obtained from coal-tar, containing naphthalene and anthracene as the major constituents . Wood creosote was prepared for the first time in Germany in 1830 and was used for medicinal purposes . It had been listed officially in the German, American, and Japanese Pharmacopoeia as an antibacterial agent for the treatment of pulmonary tuberculosis, diarrhea, and external injury . In recent days, it has been deleted from the Pharmacopoeia in Western countries and not officially used for medicinal purposes . However, wood creosote is still been listed in the Japanese Pharmacopoeia and is used for the treatment of diarrhea . Since the interest of common people in herbal medicines and self-medication has been increasing, the use of wood creosote has also been modified in combination with some herbal drugs, "Seiro-gan" especially is quite popular in Japan as a self-medication for digestive trouble, including food poisoning or diarrhea.

J Antibiot (Tokyo), 2001 Oct, 54(10), 771 - 82
Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2; Vertesy L et al.; The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone . The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide . The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro . This proline-rich peptide is a subsequence of beta-casein . From the observed absence in the literature of any other highly significant sequence homologues, memnopeptide A can be assumed to arise from metabolic products of the fungus with direct incorporation of constituents of the nutrient medium . The formation of memnopeptide A suggests this may be a mechanism for storage of amines by the fungus . Memnopeptide A has weak antibacterial activity against gram-positive bacteria and effects half-maximal activation of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) at a concentration of 12.5 microM.

J Comput Aided Mol Des, 2001 Sep, 15(9), 819 - 33
Electrostatic and structural similarity of classical and non-classical lactam compounds; Coll M et al.; Various electrostatic and structural parameters for a series of classical and non-classical beta-lactams were determined and compared in order to ascertain whether some specific beta-lactams possess antibacterial or beta-lactamase inhibitory properties . The electrostatic parameters obtained, based on the Distributed Multipole Analysis (DMA) of high-quality wavefunctions for the studied structures, suggest that some non-classical beta-lactams effectively inhibit the action of beta-lactamases . As shown in this work, such electrostatic parameters provide much more reliable information about the antibacterial and inhibitory properties of beta-lactams than do structural parameters.

Shokuhin Eiseigaku Zasshi, 2001 Oct, 42(5), 322 - 8
{Migrants from disposable gloves and residual acrylonitrile}; Wakui C et al.; Disposable gloves made from polyvinyl chloride with and without di(2-ethylhexyl) phthalate (PVC-DEHP, PVC-NP), polyethylene (PE), natural rubber (NR) and nitrile-butadiene rubber (NBR) were investigated with respect to evaporation residue, migrated metals, migrants and residual acrylonitrile . The evaporation residue found in n-heptane was 870-1,300 ppm from PVC-DEHP and PVC-NP, which was due to the plasticizers . Most of the PE gloves had low evaporation residue levels and migrants, except for the glove designated as antibacterial, which released copper and zinc into 4% acetic acid . For the NR and NBR gloves, the evaporation residue found in 4% acetic acid was 29-180 ppm . They also released over 10 ppm of calcium and 6 ppm of zinc into 4% acetic acid, and 1.68-8.37 ppm of zinc di-ethyldithiocarbamate and zinc di-n-butyldithiocarbamate used as vulcanization accelerators into n-heptane . The acrylonitrile content was 0.40-0.94 ppm in NBR gloves.

J Egypt Soc Parasitol, 2001 Dec, 31(3), 893 - 904 + 1p plate
Evaluation of the effect of a plant alkaloid (berberine derived from Berberis aristata) on Trichomonas vaginalis in vitro; Soffar SA et al.; Berberine is a quaternary alkaloid derived from the plant Berberis aristata having antibacterial, antiamoebic, antifungal, antihelminthic, leishmanicidal and tuberculostatic properties . The effect of berberine sulphate salt on the growth of Trichomonas vaginalis in vitro was compared to the efficacy of metronidazole as a reference drug . Results showed that berberine sulphate was comparable to metronidazole as regards potency with the advantage of being more safe and possible replacement in metronidazole resistant cases.

Zhonghua Kou Qiang Yi Xue Za Zhi, 1998 Jul, 33(4), 219 - 21
{Effect of guchijianzhou decoction on antioxidation in aged mice}; Xu Z et al.; OBJECTIVE: To observe the antioxidation effect of Guchijianzhou decoction in aged mice . METHODS: The Guchijianzhou decoction was given to aged mice by gastric intubation and compared with a group of young mice and a group of aged mice giving tape water . The LPO, SOD and CAT level were examined . RESULTS: There were significant differences as the experimental group was campared with the control groups . CONCLUSION: The results show that Guchijianzhou decoction is effective in antioxidation and against danage by free radical . It can reinforce antibacterial function and is benificial in the restoration of periodontal health.

FASEB J, 2002 Feb, 16(2), 261 - 3 Epub 2001 Dec 28.
Antiangiogenic activity of aeroplysinin-1, a brominated compound isolated from a marine sponge; Rodriguez-Nieto S et al.; (+)-aeroplysinin-1, an antibacterial brominated compound produced by certain sponges, was selected during a blind high-throughput screening for new potential antiangiogenic compounds obtained from marine organisms . In a variety of experimental systems, representing the sequential events of the angiogenic process, aeroplysinin-1 treatment of endothelial cells resulted in strong inhibitory effects . Aeroplysinin-1 inhibited the growth of endothelial cells in culture and induced endothelial cell apoptosis . Capillary tube formation on Matrigel was completely abrogated by addition of aeroplysinin-1 at the low micromolar range . Aeroplysinin-1 also exhibited a clear inhibitory effect on the migration capabilities of endothelial cells . Zymographic assays showed that aeroplysinin-1 treatment produced a decrease in the concentration of matrix metalloproteinase-2 and urokinase in conditioned medium from endothelial cells . Finally, aeroplysinin-1 exhibited a dose-dependent inhibitory effect on the in vivo chorioallantoic membrane assay, showing potent apoptosis-inducing activity in the developing endothelium . The in vivo inhibition of angiogenesis by aeroplysinin-1 was confirmed by the Matrigel plug assay . Together, our data indicate that aeroplysinin-1 is a compound that interferes with key events in angiogenesis, making it a promising drug for further evaluation in the treatment of angiogenesis-related pathologies.

Drug Saf, 2001, 24(15), 1143 - 54
Profiles of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolone antibacterials: experience from large cohorts from the Drug Safety Research Unit Prescription-Event Monitoring database; Clark DW et al.; OBJECTIVE: To investigate how frequently serious dysrhythmic cardiovascular, and hepatotoxic events are reported during routine clinical use of fluoroquinolones (quinolones) in general practice . DESIGN: Cohorts prescribed quinolones (cohort sizes: ciprofloxacin 11 477; enoxacin 2790; ofloxacin 11 033 and norfloxacin 11 110; mean age in each cohort of 48.6 to 57.0 years) were selected from the Drug Safety Research Unit's Prescription-Event Monitoring (PEM) database . The monitoring periods were November 1988 to January 1989 for ciprofloxacin; April 1989 to January 1991 for enoxacin; May 1991 to December 1991 for ofloxacin and October 1990 to October 1991 for norfloxacin . Data collected over the total PEM surveillance period on selected gastrointestinal events were extracted and reviewed to identify possible hepatic events, together with selected cardiovascular events associated with dysrhythmias . For each quinolone, times to onset of the event and patient-months of observation (denominator values) were calculated . The analysis was based on two observation periods: rate of event during the first 7 days following dispensing of a prescription for each drug (W(1)), and rate of event during the second to sixth week inclusive (W(2)) . RESULTS: Scrutiny of original green forms revealed no evidence of drug-induced hepatic dysfunction within 42 days of drug administration for any of the quinolones monitored . No evidence was found of drug-induced dysrhythmic events associated with enoxacin within 42 days of drug administration . Of the other quinolones, 'atrial fibrillation' was reported most often within 42 days following ciprofloxacin administration, with no change in event rate over that time, crude relative risk (CRR){W(1)/W(2)} 1.0 {95% confidence interval (CI) 0.02 to 8.92} . Other less serious events associated with dysrhythmia were reported with varying incidence within 42 days of quinolone administration . The crude rate of palpitation did not change significantly over that time for ciprofloxacin, ofloxacin and norfloxacin: CRR 0.83 (95% CI 0.02 to 6.86), 2.00 (95% CI 0.19 to 12.20) and 4.99 (95% CI 0.06 to 391.94), respectively . Syncope and tachycardia were also reported for ofloxacin {CRR 9.99 (95% CI 0.52 to 589.49 for both events)} and ciprofloxacin {1.0 (95% CI 0.02, 8.92)} and 2.50 (95% CI 0.04, 47.96) for syncope and tachycardia, respectively} . CONCLUSION: It cannot be ruled out that some rare hepatic and dysrhythmic events associated with quinolones may be drug related . The primary purpose of PEM is signal generation . Compared with the other quinolones, ciprofloxacin was associated with the highest number of reports of dysrhythmic cardiovascular events occurring within 42 days of administration . This requires further investigation by other types of epidemiological study.

Drugs Aging, 2001, 18(11), 827 - 35
Diagnosis and treatment of allergic skin disorders in the elderly; Nedorost ST et al.; Allergic skin disorders in the elderly may arise from contact with or ingestion of offending allergens . Itching associated with skin allergy must be distinguished from other causes of itching in the elderly such as xerosis, itching due to systemic disease and bullous disease . Although elderly people have somewhat decreased cell-mediated immunity and may be harder to sensitise under experimental conditions, they have had many years to acquire allergic responses, and therefore develop contact dermatitis frequently . Patch testing is a valuable tool to diagnose contact allergy and should be used often in the elderly, particularly in patients at high risk of contact dermatitis, such as those with chronic lower extremity dermatitis or ulcers due to venous stasis . When prescribing topical medications to high risk patients, a knowledge of the common sensitisers is important . In addition to allergy to medicaments and dressings used to treat stasis ulcers, contact allergy to dental prostheses and medications used to treat ocular disease are common in the elderly as a result of increased usage and exposure . Rash caused by ingested allergens is much more commonly due to medications than to food in the elderly . Allergic noneczematous dermatoses in the elderly are commonly drug-induced . Urticarial skin reactions are often associated with the administration of antibacterials, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants or opioids . Morbilliform rashes are a common sign of systemic reaction to anticonvulsants, gold, allopurinol or diuretics . Phototoxic reactions may be associated with the administration of tetracyclines, diuretics, NSAIDs and antihyperglycaemic agents . Patient-specific variables such as HLA type and concomitant medication may affect the likelihood of an allergic response to medication . Many elderly patients take multiple medications, which can make diagnosis of drug allergy difficult because diagnosis is most commonly accomplished by observing clinical response once the medication is withdrawn . In the case of lichenoid cutaneous reactions, clinical improvement may take several months after withdrawal of the offending drug . Laboratory tests to detect drug-induced allergic skin disorders may be available in the future.

Biochemistry, 2002 Jan 8, 41(1), 21 - 30
Overexpression and structural study of the cathelicidin motif of the protegrin-3 precursor; Sanchez JF et al.; Numerous precursors of antibacterial peptides with unrelated sequences share a similar prosequence of 96-101 residues, referred to as the cathelicidin motif . The structure of this widespread motif has not yet been reported . The cathelicidin motif of protegrin-3 (ProS) was overexpressed in Escherichia coli as a His-tagged protein to facilitate its purification . The His tag was then removed by thrombin cleavage . In addition, the complete proprotegrin-3 (ProS-PG-3) (120 residues) was overexpressed in baculovirus-infected insect cells . As it contained the antibacterial peptide protegrin-3 in its C-terminal part, ProS-PG-3 contained four disulfide bonds . At neutral pH, ProS and ProS-PG-3 adopted two slowly exchanging conformations that existed in a ratio of 55/45 . This ratio was progressively modified at acidic pH to reach a 90/10 value at pH 3.0, suggesting that electrostatic interactions are involved in such a conformational change . Therefore, the structural study of the main conformer was undertaken at pH 3.0 by circular dichroism, mass spectrometry, and homo- and heteronuclear NMR . In parallel, a model for the ProS structure was built from the X-ray structure of the chicken cystatin . ProS and the chicken cystatin share two conserved disulfide bonds as well as a high conservation of hydrophobic residues . The ProS model features the conservation of a hydrophobic core made of the interface between the N-terminal helix and the wrapping beta-sheet . Although the full assignment of the main conformer of ProS could not be obtained, available NMR data validated the presence of the N-terminal helix and of a four-stranded beta-sheet, in agreement with the cystatin fold . Moreover, we clearly demonstrated that ProS and ProS-PG-3 share the same global structure, suggesting that the presence of the highly constrained beta-hairpin of protegrin does not significantly modify the structure of the cathelicidin motif of the protegrin precursor.

Biomaterials, 2002 Feb, 23(3), 887 - 92
Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity; Bosetti M et al.; The most significant complication in external fixation is pin tract infection causally related to the highly adaptive ability of bacteria to colonise the surfaces of "inert" biomaterials or of adjacent damaged tissue cells . The hypothesis that coating a pin with a silver-containing compound will decrease bacterial colonisation and/or pin tract infection has been confirmed in other studies in vitro and in vivo experiments . In this work, biocompatibility of silver-coated orthopaedic external fixation pins was compared with stainless steel controls in an in vitro study . Human peripheral blood lymphocytes were used to assess the possible genotoxic effect of silver, studying the frequency of sister-chromatid exchanges and micronuclei while fibroblasts (NIH 3T3) and osteoblast-like cells were used for cytotoxicity and cytocompatibility studies . These studies have shown that silver is neither genotoxic nor cytotoxic as compared to stainless steel, a material in wide use as a metal implant . At 4 days cells cultured on the silver-coated material evidenced good cell spreading and a higher cell count with respect to the uncoated material . It appears that the addition of silver onto implantable medical devices could be beneficial when specific biological properties, such as antibacterial behaviour, are required . Based on these and the previous bacterial studies it seems like the toxicity towards bacteria was quite a bit greater than that towards the human cells.

Acta Pharm Hung, 2001, 71(1), 44 - 56
{Microbiological research for the Hungarian pharmaceutical industry}; Ambrus G; A survey is presented on the last 50 years of biotechnological R & D activities in the Institute for Drug Research, Budapest . In the 1950s and 1960s this Institute played an important role in the industry of antibiotics in Hungary, contributing to the development of manufacturing processes for streptomycin, oxytetracycline, neomycin and nystatine . In the late 1950s a microbial screening program was initiated, which led to the discovery of several new antibiotics and the isolation of microorganisms producing medically important, known antibiotics and other therapeutical agents of microbial origin from natural sources . In the 1970s and 1980s the biotechnological research group elaborated new industrial processes for the production of several antibacterial antibiotics, such as gentamycin C, sisomicin, tobramycin, apramycin, kanamycin B and mupirocin and the antitumor antibiotic daunomycin . In the last 15 years new processes have been developed for manufacturing the immunosuppressants cyclosporin A and mycophenolic acid and the hypocholesterolemic agents mevinolin and pravastatin as well as recombinant hirudin, a thrombin inhibitor . Research on steroid bioconversions has also been continued from the mid 1950s up to now . In the early 1960s manufacturing processes were developed for the anti-inflammatory prednisolone and the anabolic drug methandrostenolone . The results on microbial transformations (stereoselective reduction, hydroxylation) were utilized in the synthesis of contraceptive drugs . Since the mid 1960s several new microbial processes have been discovered for the selective side chain cleavage of natural sterols, resulting in various key intermediates for the synthesis of a wide variety of steroid drugs.

Drug Resist Updat, 2001 Jun, 4(3), 145 - 51
The apicoplast as an antimalarial drug target; Ralph SA et al.; Resistance to commonly used malaria drugs is spreading and new drugs are required urgently . The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds . The apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host thereby presenting ideal strategies for drug therapy . Indeed, many compounds targeting these plastid pathways are antimalarial and have favourable profiles based on extensive knowledge from their use as antibacterials.

Dan Med Bull, 2001 Nov, 48(4), 275 - 7
Antibacterial prophylaxis with trimethoprim-sulfamethoxazole during induction treatment for acute lymphoblastic leukemia; Schroder H et al.; BACKGROUND AND PURPOSE: Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression . Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments . The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark . This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy . MATERIAL AND METHODS: Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark . Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode . RESULTS: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not . Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)) . Nineteen different species were isolated from the blood stream before start of antibiotic treatment . In the non-prophylaxis group there was a preponderance of isolates with Staph . aureus, Str . pneumoniae, E . coli and P . aeruginosa . There was no difference in the mortality between the two groups (p=0.44).There were no cases of P carinii pneumonia in the period of induction therapy . CONCLUSION: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness.

Biol Pharm Bull, 2001 Dec, 24(12), 1395 - 9
The influence of commonly prescribed synthetic drugs for peptic ulcer on the pharmacokinetic fate of glycyrrhizin from Shaoyao-Gancao-tang; He JX et al.; The influence of synthetic drugs prescribed for peptic ulcer on the pharmacokinetic fate of glycyrrhizin (GL) from Shaoyao-Gancao-tang (SGT, a traditional Chinese formulation, Shakuyaku-Kanzo-to in Japanese) was investigated in rats . Co-administration of histamine H2-receptor antagonist (cimetidine) and anticholinergic drug (scopolamine butyl bromide) with SGT didn't influence the area under the plasma concentration-time curves (AUC) of glycyrrhetic acid (GA), an active metabolite derived from GL in SGT . The AUC of GA from SGT were significantly reduced by co-administration of synthetic drugs commonly used for peptic ulcer in a triple therapy (OAM), a combination of a proton pump inhibitor (omeprazole) and two antibiotics (amoxicillin and metronidazole) . We found that the reduction of AUC in OAM treatment was due to the antibacterial effect of amoxicillin and metronidazole on intestinal bacteria in rat which lead to the decrease of GL-hydrolysis activity . The present study suggests that it may not be a proper way to use triple therapy containing antibiotics simultaneously with SGT for healing of chronic ulcers.

Chem Pharm Bull (Tokyo), 2001 Dec, 49(12), 1660 - 1
Synthesis and antibacterial activity of new 1beta-methylcarbapenems having the potential for intramolecular nonbonded S...O interactions; Nagao Y et al.; Mercaptoacetyliminothiadiazoline derivatives (19, 20) useful for the pendant moiety of 1beta-methylcarbapenem antibiotics were efficiently synthesized . Acetyl derivative (18) of 20 was submitted to X-ray analysis, and a significant nonbonded S...O close contact was recognized in the crystallographic structure . New 1beta-methylcarbapenems (5, 6) were synthesized by exploiting 19 and 20, and exhibited considerable antibacterial activities in vitro.

Curr Opin Pharmacol, 2001 Oct, 1(5), 470 - 6
Oxazolidinones: a new class of antibacterials; Zurenko GE et al.; The oxazolidinones represent the first truly new class of antibacterial agents to reach the marketplace in several decades . They have a unique mechanism of action involving inhibition of the initiation step of protein synthesis and are not cross-resistant to other classes of antibiotics . The first marketed member of that class, linezolid (Zyvox), shows good efficacy with an impressive antibacterial spectrum (including activity against gram-positive organisms resistant to other drugs), and a pharmacodynamic/pharmacokinetic relationship best characterized by time above the minimum inhibitory concentration . The agent is effective by both the intravenous and oral route of administration . Although technically classified as bacteriostatic against a number of pathogens in vitro, linezolid behaves in vivo like a bactericidal antibiotic.

Curr Opin Pharmacol, 2001 Oct, 1(5), 451 - 8
Beta-lactamase-inhibitor combinations in the 21st century: current agents and new developments; Miller LA et al.; Combinations of beta-lactams and beta-lactamase inhibitors have become one of the most successful antibacterial strategies in our global battle against bacterial infections . The success of these agents is particularly emphasized by the continued efficacy of Augmenting (amoxicillin and clavulanate) after nearly 20 years of clinical use . The clinical situation now dictates that second-generation beta-lactamase inhibitors capable of encompassing both class A and class C beta-lactamases would combat emerging resistance and provide a vital addition to our armory of hospital antibiotics . This realization has generated a renewed interest in beta-lactamase inhibitors and improved the prospects for the delivery of such agents in the future.

Ter Arkh, 2001, 73(10), 48 - 53
{Immune correction by polyoxidonium in chronic alcoholics with renal impairement}; Tarasova NS et al.; AIM: To study clinical effectiveness and immunocorrective properties of polyoxidonium in chronic alcoholics with renal impairment . MATERIAL AND METHODS: The trial enrolled 62 chronic alcoholics with chronic pyelonephritis (CP) . Group 1 comprised 28 patients (mean age 39.9 +/- 2.4 years) with severe chronic alcoholism (CA) in long abstinence and grave CP; 16 moderate CA patients of group 2 (mean age 42.2 +/- 1.2 years) with moderate CP in drinking period; the control group consisted of 11 severe CA patients (mean age 39.2 +/- 1.2 years) in short-term abstinence and moderate CP . CP was the only visceral damage in the examinees . All the patients were examined clinically . Biochemical blood tests, ultrasound, x-ray examinations, radionuclide investigation of the kidneys, immunological examination were made before and after the treatment . Patients of groups 1 and 2 received polyoxidonium (12 mg once a day, i.m., each other day, a course dose 0.084 g) in combination with penicillin and nistatin . Patients of group 3 received placebo in combination with the same antibacterial therapy . RESULTS: Remission with normalization of laboratory and immunological parameters was achieved in 75% of group 1 patients . No response was seen in 7.1% . In group 2 remissions were absent while immunological changes were insignificant . Group 3 patients exhibited clinical response in 48.2% but no remission was achieved . CONCLUSION: Polyoxidonium immunocorrection was effective in CA patients with renal affection only in long-term abstinence being a failure in drinking period.

Am J Vet Res, 2001 Dec, 62(12), 1979 - 89
Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration; Aliabadi FS et al.; OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of danofloxacin in goats and the concentrations required to induce bacteriostasis, bactericidal activity, and bacterial elimination . ANIMALS: 6 healthy British Saanen goats . PROCEDURE: Danofloxacin (1.25 mg/kg of body weight) was administered i.v . and i.m . in a cross-over design with 14 days between treatments . A tissue cage was used for evaluation of drug distribution into transudate and exudate . The ex vivo antibacterial activity of danofloxacin in serum, exudate, and transudate against a caprine isolate of Mannheimia haemolytica was determined . Pharmacokinetic and pharmacodynamic data were integrated to determine the ratio of the area under the concentration versus time curve to the minimum inhibitory concentration of danofloxacin (AUIC) . RESULTS: Elimination half-lives of danofloxacin in serum were 4.67 and 4.41 hours after i.v . and i.m . administration, respectively . Volume of distribution was high after administration via either route, and bioavailability was 100% after i.m . administration . Rate of penetration into exudate and transudate was slow, but elimination half-lives from both fluids were approximately twice that from serum . Drug concentrations in serum, exudate, and transudate for 9 to 12 hours after administration induced marked ex vivo antibacterial activity . For serum, AUIC24h values required for bacteriostasis, bactericidal effect, and bacterial elimination were 22.6, 29.6, and 52.4, respectively . Similar values were obtained for exudate and transudate . CONCLUSIONS AND CLINICAL RELEVANCE: Integration of danofloxacin pharmacokinetic and pharmacodynamic data obtained in goats may provide a new approach on which to base recommendations for therapeutic dosages.

Ann N Y Acad Sci, 2001 Nov, 946, 179 - 99
Drugs and cardiotoxicity in HIV and AIDS; Fantoni M et al.; The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance . Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used . Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50% . Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk . Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile . Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a life-threatening ventricular arrhythmia . Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway . Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART . Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms . Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy . The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug-related cardiac effects.

Biol Trace Elem Res, 2001 Nov, 83(2), 149 - 67
Dietary titanium and infant growth; Schwietert CW et al.; Dietary titanium as TiO2+ improved animal growth during infancy while inhibiting the metabolism of intestinal bacteria . TiO2+ was also found capable of inhibiting human cytomegalovirus in tissue culture . These and other findings indicate TiO2+ improves infant growth by acting as an antibacterial and antiviral agent . The behavior of TiO2+ stands in contrast to that of TiO2, which is inert.

Biosci Biotechnol Biochem, 2001 Oct, 65(10), 2193 - 9
Chemistry of zerumbone . 2 . Regulation of ring bond cleavage and unique antibacterial activities of zerumbone derivatives; Kitayama T et al.; Further investigation of the chemistry of the eleven-membered cyclic sesquiterpene, zerumbone, the major component of the wild ginger, Zingiber zerumbet Smith, has revealed a new selective epoxidation process, a further example of a novel Favorskii-initiated double ring contraction, and a regiospecific fragmentation of zerumbone dibromide derivatives . Several zerumbone derivatives were found to be selective inhibitors of the growth of gram-positive bacteria.

Dent Mater, 2002 Mar, 18(2), 103 - 10
Disinfection procedures: their effect on the dimensional accuracy and surface quality of irreversible hydrocolloid impression materials and gypsum casts; Taylor RL et al.; OBJECTIVES: This study primarily investigated the effect of disinfection procedures (Perform and sodium hypochlorite) on the dimensional accuracy and surface quality of four irreversible hydrocolloid impression materials and the resultant gypsum casts . The antibacterial efficacy of the procedures was also studied . METHODS: Dimensional accuracy was determined from the mean percentage deviation of six measurements taken from casts made from disinfected impressions compared with corresponding measurements from the master model and controls . Statistical analysis of data was determined by analysis of variance . Surface quality was determined using a stainless steel test block in accordance with ISO 1563 . RESULTS: The dimensional accuracy of the impression materials tested were of a comparable standard following disinfection . The surface quality of casts taken from Blueprint Cremix impressions were unaffected by the disinfection procedures . The remaining impression materials studied showed greater surface deterioration on casts following disinfection with sodium hypochlorite than immersion in Perform . All disinfection procedures selected proved appropriate for antibacterial purposes . SIGNIFICANCE: Individual analysis of impression materials is required to determine their suitability to a given disinfection protocol.

Rev Esp Quimioter, 2001 Sep, 14(3), 269 - 74
{Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections}; Casellas JM et al.; Telithromycin was the first ketolide to be approved in Europe and is in the approval process in the United States . It is structurally related to the macrolides; it has a keto group in the C3 position rather than cladinose . A carbamate group is also present at C11-C12 . As a result, it has a reduced induction of the MLSB resistance mechanism (erm gene), it is not affected by the flux mechanism (mef gene), it has higher stability at low pH and has increased intrinsic activity compared with clarithromycin and azithromycin . Phase III studies have shown telithromycin to be effective in the treatment of community-acquired upper and lower respiratory tract infections . Its long half-life allows for oral once-daily dosing . From a pharmacokinetic point of view, its activity has been shown to be AUC(24h)/MIC dependent . It is active against bacteria involved in atypical pneumonia . The aim of our study was to determine the activity of telithromycin in isolates with defined resistance phenotypes obtained from community-acquired respiratory tract infections . Twelve centers in Argentina, Chile, Paraguay and Uruguay participated in the study . Each center collected three strains of the following species and resistance patterns: S . pyogenes, S . pneumoniae with resistance or intermediate resistance to oxacillin, erythromycin-resistant S . pneumoniae, clindamycin-resistant S . pneumoniae, oxacillin-susceptible S . aureus, erythromycin-resistant S . aureus, ampicillin-susceptible and -resistant M . catarrhalis and H . influenzae . Agar diffusion susceptibility tests with NeoSensitabs tablets (Rosco, Denmark) were carried out at each center . Isolates were sent to the coordinating center, where MICs were determined using agar microdilution and the Seppala test was used to determine the resistance mechanism to macrolides . The 327 isolates received were susceptible to telithromycin . Eighty percent of the erythromycin-resistant S . pneumoniae isolates were likely resistant due to a flux mechanism, and all those resistant to clindamycin were resistant due to the erm inducible mechanism . Only 20 out of 36 strains of clindamycin-resistant S . pneumoniae and 25 of the 36 ampicillin-resistant H . influenzae strains could be collected, thereby showing that these resistance patterns are less common in the participating South American countries than in other areas . The in vitro activity of telithromycin suggests that it is a promising antibacterial drug for the treatment of community-acquired respiratory tract infections.

Mutagenesis, 2002 Jan, 17(1), 89 - 93
Detection of micronuclei, cell proliferation and hyperdiploidy in bladder epithelial cells of rats treated with o-phenylphenol; Balakrishnan S et al.; o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA . Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variable results . This difference has been attributed to the presence of the sodium salt . To determine cellular and genetic alterations in the rat bladder and the influence of the sodium salt, F344 rats were administered 2% OPP, 2% NaCl and 2% NaCl + 2% OPP in their diet for 14 days . Twenty-four hours before being killed the animals were administered 5-bromo-2'-deoxyuridine (BrdU) by i.p . injection . Bladder cells were isolated, stained with DAPI and scored for the presence of micronuclei and incorporation of BrdU into replicating cells . To determine changes in chromosome number, we used fluorescence in situ hybridization (FISH) with a DNA probe for rat chromosome 4 . Significant increases in the frequency of micronuclei and BrdU incorporation were seen in bladder cells of rats from all treatment groups . In contrast, the frequency of hyperdiploidy/polyploidy in treated animals was not increased over that seen in controls . A high control frequency of cells with three or more hybridization signals was seen, probably due to the presence of polyploid cells in the bladder . The presence of polyploid cells combined with cytotoxicity and compensatory cell proliferation makes it difficult to determine whether OPP is capable of inducing aneuploidy in the rat urothelium . In summary, these studies show that OPP can cause cellular and chromosomal alterations in rat bladder cells in the absence of the sodium salt . These results also indicate that at high concentrations the sodium salt can enhance chromosomal damage in the rat urothelium.

Antimicrob Agents Chemother, 2002 Jan, 46(1), 184 - 7
Efficacies of BMS 284756 against penicillin-sensitive, penicillin-resistant, and quinolone-resistant pneumococci in experimental meningitis; Cottagnoud P et al.; BMS 284756 penetrated well into inflamed meninges (44% +/- 11%) and produced good bactericidal activity (-0.82 +/- 0.22 Delta log(10) CFU/ml . h) in the treatment of experimental meningitis in rabbits due to a penicillin-sensitive strain . BMS 284756 monotherapy had a greater potency than the standard regimen of ceftriaxone and vancomycin (-0.49 +/- 0.08 Delta log(10) CFU/ml . h) against a penicillin-resistant strain (MIC, 4 mg/liter) . Even against a penicillin- and quinolone-resistant strain, BMS 284756 showed good bactericidal activity (-0.52 +/- 0.12 Delta log(10) CFU/ml . h) . The antibacterial activity of BMS 284756 was confirmed by time-killing assays over 8 h in vitro.

Curr Opin Struct Biol, 2001 Dec, 11(6), 746 - 51
Bacterial and mammalian HMG-CoA reductases: related enzymes with distinct architectures; Istvan ES; The committed step in the biosynthesis of isoprenoids is catalyzed by HMG-CoA reductase . Recently determined structures of the distantly related bacterial and mammalian HMG-CoA reductases have revealed two distinct classes of the protein with differently formed active sites and oligomeric states . An appreciation of the remarkable differences in the active site architecture may ultimately lead to the development of novel antibacterial agents.

Phytother Res, 2001 Nov, 15(7), 593 - 7
Chemical and biological investigations on Zizyphus spina-christi L; Shahat AA et al.; Different extracts and fractions of the leaves, fruits and seeds of Zizyphus spina-christi L . grown in Egypt were investigated in vitro for their antiviral, antifungal and antibacterial activities . The flavonoids quercetin, hyperoside, rutin and quercetin-3-O-{beta-xylosyl-(1-2)-alpha-rhamnoside} 4'-O-alpha- rhamnoside) were isolated .

J Ethnopharmacol, 2002 Jan, 79(1), 133 - 8
Antibacterial activity of some Peruvian medicinal plants from the Callejon de Huaylas; Neto CC et al.; Extracts of eight medicinal plants from the Callejon de Huaylas in Peru were screened for antibacterial activity in eighteen bacterial strains by the agar-diffusion method; six of these were active against a variety of bacteria.

Anal Biochem, 2002 Jan 1, 300(1), 34 - 9
A scintillation proximity assay amenable for screening and characterization of DNA gyrase B subunit inhibitors; Gevi M et al.; DNA gyrase is the target of coumarin and cyclothialidine antibacterials, which bind to the B subunit of the enzyme (GyrB) . Currently available GyrB inhibitors have not been clinically successful, but their high in vitro potency against DNA gyrase has raised interest in the development of novel noncoumarin antibacterials acting at the same site . We report the development of a simple scintillation proximity assay (SPA) for the study of binding interactions between coumarin or noncoumarin antibacterials and GyrB, which prevents the needs of separation steps and can be run in microtiter plate formats . The assay is based on the detection of the binding of a radioligand, {3H}dihydronovobiocin, to a biotin-labeled 43-kDa fragment of GyrB (biotin-GyrB43), which is captured by streptavidin-coated SPA beads . The typical assay was conducted in 96-well microtiter plates, with final concentration of 10 nM for biotin-GyrB43, 20 nM for {3H}dihydronovobiocin, and 33 microg of SPA beads/well . From saturation experiments, an equilibrium dissociation constant (K(d)) for dihydronovobiocin of 8.10 nM was found . Displacement studies gave 50% inhibitory concentrations (IC(50)) of 42, 64, and 11 nM for novobiocin, dihydronovobiocin, and the cyclothialidine analogue GR122222X, respectively, consistent with previous findings . The assay was found to be robust to dimethyl sulfoxide up to 5% (v/v) and can be used for high-throughput screens of large chemical collections in the search of novel DNA gyrase inhibitors . (c)2002 Elsevier Science.

Phytochemistry, 2001 Dec, 58(8), 1305 - 9
Glyceroglycolipids from Serratula strangulata; Dai JQ et al.; The rhizomes of Serratula strangulata yielded three glyceroglycolipids, i.e . 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-(6-amine-6-deoxy-alpha-D-glucosyl)-glycerol, 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-(6-p-hydroxy-phenyl-propionamido-6-deoxy-alpha-D-glucosyl)-glycerol and 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-{alpha-D-glucose(1-6)-beta-D-allose}-glycerol, as well as a known sesquiterpene lactone and three known phytoecdysones . Their structures were elucidated on the basis of spectral data, especially by 2D NMR spectroscopic methods and chemical conversion . These compounds exhibited significant antibacterial and antitumor activities.

J Clin Periodontol, 2001 Dec, 28(12), 1121 - 6
Effect of a polyhexamethylene biguanide mouthrinse on bacterial counts and plaque; Rosin M et al.; OBJECTIVES: For various clinical applications, polyhexamethylene biguanide (PHMB) has been used for many years as an antiseptic in medicine . Little is known, however, of its antibacterial activity in the oral cavity and its ability to inhibit plaque formation . In this study, a 0.04% PHMB mouthrinse (A) was compared with a negative control placebo rinse (10% ethanol, flavour) (B) and 2 positive control chlorhexidine rinses, one of which was a 0.12% aqueous solution (C) and the other a commercially available mouthrinse (Skinsept mucosa) diluted to a chlorhexidine concentration of 0.12% (D) . MATERIAL AND METHODS: The study was a double-blind, randomised 4-replicate 4 x 4 Latin square cross-over design . Plaque regrowth was assessed with the Turesky et al . modification of the Quigley and Hein plaque index . The in vivo antibacterial effect was assessed by taking bacterial counts from the tooth surface (smears from the lingual surface of 16) and mucosa (smears from the buccal mucosa) 4 h after the 1st rinse with the preparations on day 1 and prior to the clinical examination on day 5 . 16 volunteers participated, and on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed 2x daily with the allocated mouthrinse . On day 5, plaque was scored and smears were collected according to the protocol . Washout periods were 9 days . Data were analysed using ANOVA with Tukey HSD adjustment for multiple comparisons (significance level alpha=0.05) . RESULTS: Mouthrinses A, C, and D were significantly more effective in inhibiting plaque than the placebo (B) . Mouthrinse C was significantly better than mouthrinses A and D, while mouthrinses D and A were equally effective in inhibiting plaque . Bacterial count reductions on the tooth surface with mouthrinse C were significantly greater compared to mouthrinse A and the placebo (B) . The reduction of bacterial counts on the mucosa with C was significantly greater than with A and B after 4 h and significantly greater than with A, B and D after 5 days . Mouthrinse A reduced bacteria on the mucosa significantly more effectively than the placebo (B) after 4 h and 5 days, while mouthrinse D was more effective than the placebo (B) after 4 h . CONCLUSION: The results indicate that a 0.04% PHMB mouthwash inhibits plaque regrowth and reduces oral bacterial counts, and may be used in preventive applications in the oral cavity.

Eur J Clin Invest, 2001 Oct, 31(10), 876 - 9
Oral nitric oxide during plaque deposition; Carossa S et al.; BACKGROUND: Nitric oxide (NO) is one of the most powerful antibacterial compounds . We investigated if NO oral production increases during dental plaque deposition . MATERIALS AND METHODS: Oral NO and salivary nitrite were measured in 31 healthy subjects - 11 smokers and 20 nonsmokers - with natural healthy teeth, in the morning after tooth cleaning (baseline), after withdrawal of oral hygiene for 24 h and again after tooth cleaning . RESULTS: NO and nitrite were significantly higher during plaque deposition than with clean teeth: mean NO values +/- SEM were 44.3 +/- 4.9 parts per billion (ppb) at baseline, 58.8 +/- 3.7 ppb with plaque and 43.6 +/- 3.7 ppb after tooth cleaning, P < 0.05; nitrite values were 32.9 +/- 5.5 microm at baseline, 66.4 +/- 8.2 with plaque and 37.5 +/- 5.5 after tooth cleaning, P < 0.01 . During plaque deposition, oral NO was significantly directly related to salivary nitrite (r = 0.497, P = 0.002) and so were their respective changes after tooth cleaning (r = 0.577, P < 0.001) . Smokers had significantly lower oral NO than nonsmokers, with both clean and dirty teeth (P < 0.001), and higher bacteria counts in the plaque (38.6 +/- 11.5 vs . 19.9 +/- 2.3, P = 0.046) . CONCLUSIONS: Oral NO production increases during de novo deposition of dental plaque . NO might be an early host defence mechanism against bacterial proliferation in the plaque . Such a mechanism is inhibited by cigarette smoking.

Drugs, 2001, 61(14), 2087 - 96
Pyelonephritis in pregnancy: treatment options for optimal outcomes; Wing DA; Acute pyelonephritis is one of the most common indications for antepartum hospitalisation . When acute pyelonephritis is diagnosed, conventional treatment includes intravenous fluid and parenteral antibacterial administration . There are limited data by which to assess the superiority of one antibacterial regimen over the other in terms of efficacy, patient acceptance and safety for the developing fetus . There is a small body of evidence to support the ambulatory treatment of pregnant women with pyelonephritis in the first and early second trimesters.

Pharmacol Res, 2001 Dec, 44(6), 451 - 4
Anti-inflammatory capabilities of macrolides; Zalewska-Kaszubska J et al.; Macrolide antibiotics play a significant role in clinical practise due not only to their antibacterial activity, but also to their accompanying anti-inflammatory effect that is independent of their antibiotic action . Several studies reported in literature show that macrolides affect several inflammatory processes, such as migration of neutrophils, the oxidative burst in phagocytes and production of pro-inflammatory cytokines, although the precise mechanisms are not clear . They also inhibit eosinophilic inflammation and may be useful in the treatment of patients with steroid-dependent asthma . Macrolides are also effective in diffuse panbronchiolitis, chronic sinusitis and inflammatory skin diseases .

Langenbecks Arch Surg, 2001 Nov, 386(6), 397 - 401 Epub 2001 Oct 27.
Efficacy of oral ofloxacin for single-dose perioperative prophylaxis in general surgery--a controlled randomized clinical study; Schwarz M et al.; BACKGROUND: Perioperative antibiotic prophylaxis surely reduces surgical infection rate . Pharmacokinetic data of oral ofloxacin in combination with its antibacterial spectrum suggest effective protection against perioperative infection . In addition, costs, adverse effects, and induction of microbial resistance are low . Therefore we performed a controlled randomized study comparing oral and intravenous single dose prophylaxis . METHODS: A total of 61 patients undergoing colonic or pancreatic resection randomly received either a single dose standard intravenous prophylaxis or ofloxacin 400 mg and metronidazole 500 mg orally 2 h before surgery . Postoperative infections were recorded for 3 weeks . RESULTS: Groups were very well comparable regarding age, overweight, concomitant disease, type and duration of surgery, blood loss, and volume support . Infectious complications occurred in 14.8% after parenteral and 3.3% after enteral antibiotic prophylaxis . There was no difference in post-operative hospital stay . CONCLUSION: The data demonstrate that single-dose oral ofloxacin is at least as effective as a standard intravenous prophylaxis in patients with colonic or pancreatic resection . It offers significant advantages regarding costs and ease of administration.

Fitoterapia, 2001 Dec, 72(8), 927 - 9
Antibacterial activity of Urena lobata root; Mazumder UK et al.; The methanol extract of Urena lobata root showed a broad spectrum of antibacterial activity.

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