Altern Med Rev, 1998 Dec, 3(6), 422 - 31 Botanical influences on cardiovascular disease; Miller AL; Several botanicals, including Crataegus oxycantha, Terminalia arjuna, Inula racemosa, and Astragalus membranaceus, have been found to have therapeutic benefit for the treatment of cardiovascular disease . Crataegus oxycantha has been used traditionally as a cardiac tonic and current uses include treatment for angina, hypertension, arrhythmias, and congestive heart failure . Animal studies have also indicated that Crataegus extracts may also have potential use as anti-ischemic and lipid-lowering agents . The bark of the Terminalia arjuna tree has a long history of use as a cardiac tonic as well, and has been indicated in the treatment of coronary artery disease, heart failure, hypercholesterolemia and for relief of anginal pain . Additionally, it has been found to have antibacterial and antimutagenic properties . Inula racemosa, also known as Pushkarmoola, is another traditional Ayurvedic botanical that has potential cardioprotective benefit . In human trials, a combination of Inula racemosa and Commiphora mukul was shown to be superior to nitroglycerin in reducing the chest pain and dyspnea associated with angina . Astragalus membranaceus, a Chinese herb, is often used as a "Qi tonifier" and has been studied for its therapeutic benefit in treatment of ischemic heart disease, myocardial infarction, heart failure, and relief of anginal pain . Clinical studies have indicated that its in vitro antioxidant activity is the mechanism by which it affords its cardioprotective benefit. Pharmacotherapy, 1998 Nov-Dec, 18(6), 1255 - 63 A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis; Adelglass J et al.; A multicenter, investigator-blinded, randomized, parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis . Of 216 adult outpatients randomized to treatment, 190 were evaluable for efficacy . The primary efficacy measure was clinical response, based on resolution of signs and symptoms 2-5 days after therapy . A secondary efficacy measure was relapse rate 1 month after therapy . Among evaluable patients, clinical success rates (cured or improved) were 96.0% and 93.3% for levofloxacin (L) and clarithromycin (C), respectively (95% CI -9.2%, 3.7%) . The confidence interval (CI) for treatment difference (C-L) included zero and its upper limit was less than 15%, indicating that levofloxacin was as effective as clarithromycin . In all, 4.1% of patients receiving levofloxacin and 7.2% receiving clarithromycin had a relapse of symptoms 1 month after therapy (95% CI-12.2%, 3.2%) . Long-term success (initial success, absence of relapse at 1 month, no further antibacterial therapy 2-5 days after therapy) was 79.2% in the levofloxacin group and 76.4% in the clarithromycin group (95% CI -14.7%, 9.0%) . Based on investigator-assessed treatment-emergent adverse events, overall tolerability of the drugs was similar, except for a higher frequency of taste perversion and diarrhea in the clarithromycin group . Levofloxacin had an advantage over clarithromycin based on two quality-of-life (QOL) parameters: number of times taking other drugs for targeted medical conditions and mean total cost of these drugs . No statistical significance was found in other QOL variables . These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis. Dent Update, 1998 Jul-Aug, 25(6), 247 - 50, 252-3 A review of dentifrices; Preston AJ; Dentifrices have a role to play in the prevention of certain oral diseases, such as dental caries and gingivitis . The use of fluoridated dentifrices has had a dramatic effect on the caries rate in the western world over the last 30 years, and antibacterial, desensitizing and anticalculus dentifrice formulations have recently been developed . This paper provides a brief overview of the dentifrices currently available. Int J Mol Med, 1998 Jan, 1(1), 77 - 82 Drosophila antibacterial protein, cecropin A, differentially affects non-bacterial organisms such as Leishmania in a manner different from other amphipathic peptides; Akuffo H et al.; The effects of the antibacterial protein Drosophila cecropin A on developmental forms of Leishmania were compared with the effect of Hyalophora cecropin A in vitro . Both cecropins had a potent lytic activity on the promastigotes at concentrations not far from those occurring in vivo in the respective insect . Drosophila cecropin A had strong differential effects on the two maturation forms of Leishmania aethiopica at high concentrations: inhibiting intracellular amastigotes and stimulating extracellular promastigotes to take up thymidine . Hyalophora cecropin A also inhibited amastigotes by up to 50% at concentrations of 0.250 mg/ml, and inhibited promastigotes at high concentrations but had no enhancing effects at any of the concentrations tested . In contrast to the results with Leishmania, Drosophila cecropin A had no discernible effect on any developmental stage of P . falciparium and showed no lytic effects on haemocytes . The two enantiomers of a synthetic amphipathic peptide, D- and L-KALA, were also tested . D- and L-KALA had some in vitro antimalarial effects at 0.025 and 0.05 mg/ml respectively but both forms were haemolytic at 0.1 mg/ml . Potential uses of naturally occurring proteins and their derivatives in the control of insect born infections and topical use of cecropins against leishmaniasis are discussed. J Leukoc Biol, 1998 Dec, 64(6), 845 - 52 Evaluation of the expression of human CAP18 gene during neutrophil maturation in the bone marrow; Nagaoka I et al.; To understand the gene expression of CAP18 (18-kDa cationic antibacterial protein), a member of cathelicidins, we evaluated mRNA and protein expression of CAP18 using human bone marrow cells and mature neutrophils . Northern blot analysis revealed that CAP18 mRNA was expressed more abundantly in bone marrow cells than mature neutrophils, whereas Western blot analysis indicated that CAP18 protein was more abundant in mature neutrophils than bone marrow cells . Consistent with this, in situ hybridization using bone marrow cells demonstrated that the expression of CAP18 mRNA was neutrophil lineage-specific and was observed primarily in myelocytes (>95%) with limited expression in more immature cells (promyelocytes) and mature cells (metamyelocytes, band cells, and segmented neutrophils) . Furthermore, immunohistochemical study indicated that, coincident with the increase of CAP18 mRNA levels, CAP18-positive cells increased markedly at myelocyte stage, and the increased levels remained almost constant (>95%) in metamyelocytes, band cells, and segmented neutrophils, although the mRNA levels were remarkably reduced in these cells . Together these observations indicate that CAP18 gene transcription likely occurs lineage- and stage-specifically at the myelocyte stage of neutrophil maturation in the bone marrow and results in the synthesis and cytoplasmic accumulation of CAP18, which is present in the subsequent stages of neutrophil maturation. FEBS Lett, 1998 Nov 13, 439(1-2), 41 - 5 Synthesis and structure-function study about tenecin 1, an antibacterial protein from larvae of Tenebrio molitor; Lee KH et al.; Tenecin 1, an inducible antibacterial protein secreted in the larvae of Tenebrio molitor, has a long N-terminal loop and common structural feature of insect defensin family corresponding to cysteine stabilized alpha/beta motif . To study the function of the N-terminal loop and disulfide bridges, N-terminal loop deleted tenecin 1, reduced tenecin 1 and tenecin 1 were chemically synthesized and their activities were measured . N-terminal loop deleted tenecin and reduced tenecin 1 did not show antibacterial activity . Circular dichroism (CD) spectroscopy data revealed that the alpha-helical content of tenecin 1 and the other proteins increased in the presence of 50% (v/v) trifluoroethanol (TFE) and the alpha-helical content of tenecin 1 was much higher than that of the other proteins in buffer with or without 50% (v/v) TFE . These results suggest that disulfide bridges are necessary for the activity structure and the N-terminal loop plays an important role in the increase of alpha-helix in the membrane mimetic environment and the activity. Transpl Immunol, 1998 Sep, 6(3), 183 - 92 Expression and modulation of ICAM-1, TNF-alpha and RANTES in human alveolar macrophages from lung-transplant recipients in vitro; Fattal-German M et al.; Alveolar macrophages (AMs) play a central role in pulmonary inflammation in response to local stimuli . As a model for investigating anti-inflammatory drugs, we studied the effects of the cyclohexadepsipeptide antibiotic, fusafungine, and that of the glucocorticoid dexamethasone on the expression of ICAM-1, TNF-alpha and RANTES, induced in vitro by rIFN-gamma in human AMs freshly isolated from bronchoalveolar lavage fluid (BAL) obtained in lung-transplanted patients . ICAM-1 antigen expression, induced on AMs after 24 h of culture, was significantly inhibited by fusafungine in a concentration-dependent manner, as measured by flow cytometry analysis using an anti-CD54 monoclonal antibody . TNF-alpha production, but not RANTES release (measured by ELISA), was significantly inhibited . mRNA studies, by means of polymerase chain reaction amplification of complementary deoxyribonucleic acids (RT-PCR), showed no significant modification of mRNA levels, suggesting that fusafungine acts mainly at a post-transcriptional level . In the same conditions, dexamethasone significantly inhibited the release both of TNF-alpha and RANTES by AMs, mainly acting at the mRNA level, but had no effect on ICAM-1 expression . Assessment of the cellular and molecular targets of anti-inflammatory drugs in this model of human AM activation should lead to more appropriate treatment of inflammatory process of the respiratory tract . By virtue of its anti-inflammatory effects on alveolar macrophages, combined with its antibacterial properties, fusafungine should prove particularly suitable for local treatment of bacterial infections of the respiratory tract. J, Mar . Biotechnol. . 1998 Aug, 6(3), 136 - 41 Quinolones from a bacterium and tyrosine metabolites from its host sponge, Suberea creba from the Coral Sea; Debitus C et al.; A marine bacterium, identified as a pseudomonad, isolated from Suberea creba Bergquist, 1995 (Porifera, Dictyoceratida, Verongida, Aplysinellidae) collected along the eastern coast of New Caledonia, gave in culture phenazine-alpha-carboxamide, 2-n-heptylquinol-4-one, 2-n-nonylquinol-4-one, 2-n-(1'E-nonenyl)quinol-4-one, 3-n-heptyl-3-hydroxyquinolin-2,4-dione, a N-oxide-2-n-heptylquinoline derivative, and a benzyldiketopiperazine . None of these products could be detected, at the HPLC-UV sensitivity level, in the sponge extracts, which contained instead (+)-aerothionin, homoaerothionin, (+)-aeroplysinin-1, dibromo-, bromochloro-, and dichloroverongiaquinol . 2-n-Heptylquinol-4-one, (+)-aeroplysinin-1, and dibromoverongiaquinol showed strong antibacterial activity in vitro . The latter also proved promising for mariculture, rivaling chloramphenicol as an antibacterial agent in cultures of Pecten maximus larvae, while being nontoxic according to the Artemia salina test. Vestn Ross Akad Med Nauk, 1998, (10), 29 - 32 {Study of antiinfectious potential of recombinant tumor necrosis factor-alpha}; Kalinin IuT et al.; Tumor necrosis factor-alpha (TNF) was shown to have an antiinfectious effect on murine and rat models of viral, bacterial and parasitic infections . The effective antiinfectious dose of TNF was determined to be 10(2)-10(3) U/kg body weight . TNF, interferon, and antibiotics were demonstrated to potentiate the antibacterial effect of each . Clinical trials of TNF in the treatment of slowly progressive, latent, and chronic infections and in the emergency prevention of acute infections are advisable. J Biolumin Chemilumin, 1998 Sep-Oct, 13(5), 279 - 83 Chemiluminometric beta-galactosidase detection as a basis for a tetracycline screening test in milk; D'Haese E et al.; The observation that tetracyclines inhibit the biosynthesis of beta-galactosidase in Escherichia coli to a greater extent than other antibacterials was exploited for the development of a chemiluminometric method to detect residues of this class of antibiotics in milk . The procedure involves the incubation of a milk sample with 10(7) CFU/ml of an E . coli strain in the presence of IPTG, an inducer of beta-galactosidase, and of EGTA, a chelator of calcium ions, followed by a 1000-fold dilution and measurement of the residual enzymatic activity using the chemiluminogenic substrate Galacton . Chemiluminometry proved an essential tool in this procedure because the extensive dilution of the sample, necessary to avoid light quenching by turbidity, results in an insufficient level of beta-galactosidase activity to be measurable by colorimetry . This tetracycline galactosidase (TG) test has been validated and compared in the field to existing commercial screening assays for antibiotics . Its detection limit for tetracyclines ranges between 40 and 65 micrograms/kg, which is below the European maximum residue limit (MRL = 100 micrograms/kg) in milk . No other antibacterials, at concentrations commonly expected in milk, were found to interfere with the TG test . Strategies to avoid false positive reactions possibly arising from very high somatic cell counts will be reported elsewhere. Indian J Exp Biol, 1998 Aug, 36(8), 808 - 10 Antibacterial property of goat milk lactoperoxidase; Jacob BM et al.; The goat milk lactoperoxidase was purified using CM sephadex C-50 and sephadex G 100 . The purity of protein was confirmed by SDS-PAGE . The purified protein was found to have antibacterial action against most of the disease causing bacteria. J Biol Chem, 1998 Dec 11, 273(50), 33517 - 23 Solution conformation of the synthetic bovine proenkephalin-A209-237 by 1H NMR spectroscopy; Kieffer B et al.; Proenkephalin-A has been described to generate enkephalins, opoid peptides, and several derived peptides, which display various biological effects, including antinociception and immunological enhancement . Recently, we have isolated from bovine chromaffin granules a new antibacterial peptide, named enkelytin, which corresponds to the bisphosphorylated form of PEAP209-237 (Goumon, Y., Strub, J . M., Moniatte, M., Nullans, G., Poteur, L., Hubert, P., Van Dorsselaer, A., Aunis, D., and Metz-Boutigue, M . H . (1996) Eur . J . Biochem . 235, 516-525) . In this paper, the three-dimensional solution structure of synthetic PEAP209-237 was investigated by NMR . These studies indicate that this peptide, which is unstructured in water, folds into an alpha-helical structure in trifluoroethanol/water (1/1) . NMR data revealed two possible three-dimensional models of PEAP209-237 . In both models, the proline residue Pro-227 induces a 90 degrees hinge between two alpha-helical segments (Ser-215 to Ser-221 and Glu-228 to Arg-232) leading to an overall L-shaped structure for the molecule . The negative charge of PEAP209-237 and the low amphipathy of the two alpha-helical segments imply new mechanisms to explain the antibacterial activity of enkelytin. J Biol Chem, 1998 Dec 11, 273(50), 33115 - 8 Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37; Wang Y et al.; The antibacterial and cytotoxic activity of the human cathelicidin peptide LL-37 is inhibited by plasma . Because LL-37 does not undergo rapid degradation in human plasma, we postulated that this inhibition results from binding of LL-37 to unidentified proteins . An LL-37 binding plasma protein has now been isolated by affinity chromatography . SDS-polyacrylamide gel electrophoresis of proteins that bound to an LL-37 column revealed one band with a molecular mass of about 26 kDa, and amino acid sequence analysis identified the protein as apolipoprotein A-I (apoA-I) . Biomolecular interaction analysis using surface plasmon resonance showed that LL-37 and isolated apoA-I bind with an apparent Kd in the low micromolar range . 50 microM of apoA-I inhibits the antibacterial activity of 50 microM LL-37 by about 50% of the inhibition exhibited by plasma . In addition, anti-apoA-I IgG completely blocks the plasma inhibition of LL-37 antibacterial activity up to a peptide concentration of 25 microM and blocks most of the plasma inhibition at higher LL-37 concentrations . These results indicate that apoA-I is the main LL-37 binding protein in human plasma and may work as a scavenger of LL-37, thus suggesting a novel mechanism involved in the regulation of a cathelicidin peptide. Jpn J Antibiot, 1998 Aug, 51(8), 501 - 8 {Clinical evaluation of cefozopran for infections associated with hematological malignancies}; Sasai Y et al.; Cefozopran (CZOP) was used as an initial antibacterial therapy for infections in patients with hematological malignancies . CZOP was given at a daily dose of 4 g by drip intravenously to patients who were febrile over 38 degrees C and were suspected as having bacterial infections . As underlying diseases, 8 patients had acute lymphoblastic leukemia (ALL), 9 acute myeloblastic leukemia (AML), 2 aplastic anemia (AA), 2 adult T cell leukemia/lymphoma (ATLL), 28 non Hodgkin lymphoma (NHL), and 2 multiple myeloma (MM) . Bacterial infections diagnosed were sepsis in 7 patients, suspected sepsis in 32, bronchitis in 6, pneumonia in 5 and acute peritonitis in 1 . Clinical responses among 51 evaluable cases were excellent in 14, good in 15, fair in 3, poor in 19 and the overall response rate was 57% . The overall response rates for AML, ALL, AA, ATLL, NHL and MM were 56%, 63%, 100%, 50%, 50%, and 100%, respectively . Those for sepsis, suspected sepsis, bronchitis, pneumonia and acute peritonitis were 14%, 63%, 100%, 40%, and 0%, respectively . This therapy was effective in 53% (9/17) of patients whose granulocyte count remained below 500/microliter throughout the course of CZOP therapy . Six bacterial and one fungal strains were isolated from blood and sputum of six patients including five sepsis cases; two bacteria were eradicated and bacterial change was observed in one case . As side adverse effects, 10 patients had liver dysfunction, 1 anemia, 2 proteinemia, 1 indirect bilirubinemia, 2 thrombocytopenia, and 1 eosinophilia . We tried to establish a scoring system for the severities of patients with their infections, underlying diseases, treatments for the underlying disease, and granulocyte counts in order to evaluate the efficacy of CZOP more precisely . This scoring system was consisted of three grades; severe, moderate, and mild . CZOP was effective on mild and moderate grades . These results indicate that the initial antibacterial therapy by CZOP is useful for the treatment of mild and moderate grade infections complicated with hematological malignancies. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3153 - 6 Antibacterial effects of levofloxacin, erythromycin, and rifampin in a human monocyte system against Legionella pneumophila; Baltch AL et al.; The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular Legionella pneumophila L-1033, serogroup 1, were studied . In an in vitro system utilizing adherent human monocytes, L . pneumophila L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods . The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (P < 0.01) . The decrease in CFU with rifampin was first observed at 48 h (P < 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin . Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (P < 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not . Removal of levofloxacin after 24 h of incubation resulted in regrowth of L . pneumophila L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin . At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin . Levofloxacin had a significantly higher bactericidal activity against L . pneumophila L-1033 than erythromycin or rifampin . In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin. J Inorg Biochem, 1998 Sep, 71(3-4), 171 - 9 Anti-inflammatory drugs interacting with Zn(II), Cd(II) and Pt(II) metal ions; Dendrinou-Samara C et al.; Complexes of Zn(II), Cd(II) and Pt(II) metal ions with the anti-inflammatory drugs, 1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid (Tolmetin), alpha-methyl-4-(2-methylpropyl)benzeneacetic acid (Ibuprofen), 6-methoxy-alpha-methylnaphthalene-2-acetic acid (Naproxen) and 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid (indomethacin) have been synthesized and characterized . In the structurally characterized Cd(naproxen)2 complex the anti-inflammatory drugs acts as bidentate chelate ligand coordinatively bound to metal ions through the deprotonated carboxylate group . Crystal data for 1: {C32H26O8Cd}, orthorhombic, space group P22(1)2(1), a = 5.693(2) (A), b = 8.760(3) (A), c = 30.74(1) (A), V = 1533(1) A3, Z = 2 . Antibacterial and growth inhibitory activity is higher than that of the parent ligands or the platinum(II) diamine compounds. Arch Environ Contam Toxicol, 1999 Jan, 36(1), 1 - 6 Algal toxicity of antibacterial agents applied in Danish fish farming; Lutzhoft HH et al.; Algal toxicity of antibacterial agents applied in fish farming was investigated . The growth-inhibiting effects of amoxicillin (A), flumequine (F), oxolinic acid (OA), oxytetracycline hydrochloride (OT), sarafloxacin hydrochloride (SF), sulfadiazine (SD), and trimethoprim (T) were investigated by a modified test procedure based on the procedure described in the ISO 8692 (1989) protocol on three algal species: the freshwater cyanobacteria Microcystis aeruginosa, the freshwater green alga Selenastrum capricornutum, and the marine cryptophycean Rhodomonas salina . Algal growth was measured as increased chlorophyll concentration by extraction with ethanol followed by measurement of fluorescence . Results were quantified in terms of growth rates using the Weibull equation to describe the concentration response relationship . M . aeruginosa showed higher sensitivity compared to both R . salina and S . capricornutum, whereas the results for the latter two were more or less identical . The toxicity (EC50 value, mg/L) in decreasing order were A (0.0037), SF (0.015), SD (0.135), F (0.159), OA (0.180), OT (0.207), and T (112) for M . aeruginosa; OT (1.6), OA (10), T (16), F (18), SF (24), SD (403), and A (3108) for R . salina; and OT (4.5), F (5.0), SD (7.8), OA (16), SF (16), T (130), and A (NOEC > 250) for S . capricornutum . Applying this test procedure the toxicity of antibacterial agents, being mono- or polyprotic compounds, may be underestimated because of partitioning between ionized and unionized forms. Nature, 1998 Nov 12, 396(6707), 186 - 90 Crystal structure of a bacterial signal peptidase in complex with a beta-lactam inhibitor; Paetzel M et al.; The signal peptidase (SPase) from Escherichia coli is a membrane-bound endopeptidase with two amino-terminal transmembrane segments and a carboxy-terminal catalytic region which resides in the periplasmic space . SPase functions to release proteins that have been translocated into the inner membrane from the cell interior, by cleaving off their signal peptides . We report here the X-ray crystal structure of a catalytically active soluble fragment of E . coli SPase (SPase delta2-75) . We have determined this structure at 1.9 A resolution in a complex with an inhibitor, a beta-lactam (5S,6S penem), which is covalently bound as an acyl-enzyme intermediate to the gamma-oxygen of a serine residue at position 90, demonstrating that this residue acts as the nucleophile in the hydrolytic mechanism of signal-peptide cleavage . The structure is consistent with the use by SPase of Lys 145 as a general base in the activation of the nucleophilic Ser90, explains the specificity requirement at the signal-peptide cleavage site, and reveals a large exposed hydrophobic surface which could be a site for an intimate association with the membrane . As enzymes that are essential for cell viability, bacterial SPases present a feasible antibacterial target: our determination of the SPase structure therefore provides a template for the rational design of antibiotic compounds. Cancer Detect Prev, 1998, 22(6), 506 - 15 Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis; Kimoto T et al.; Artepillin C was extracted from Brazilian propolis . Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) has a molecular weight of 300.40 and possesses antibacterial activity . When artepillin C was applied to human and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearly inhibited . The artepillin C was found to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation in vitro . When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma . Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 microg of artepillin C three times a week . In addition to suppression of tumor growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells . These findings indicate that artepillin C activates the immune system, and possesses direct antitumor activity. J Med Chem, 1998 Nov 19, 41(24), 4681 - 5 Syntheses of new isodethiaazacephems as potent antibacterial agents; Hwu JR et al.; New isodethiaazacephems (+/-)-3, (+/-)-4, and (+/-)-10 as well as the 4-sulfonylated isodethiaazacepham (+/-)-5 were synthesized by chemical methods and found to possess biological activity against five pathogenic microorganisms in vitro . The mesylate and the triflate functionalities in (+/-)-3 and (+/-)-4, acting as effective leaving groups, enhanced remarkably the biological activity in comparison with the parent 3-hydroxyisodethiaazacephem (+/-)-10 . The mode of action related to (+/-)-3 and (+/-)-4 can be explained by a {1,4}-elimination process. J Med Microbiol, 1998 Nov, 47(11), 1015 - 8 Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro; Portelli J et al.; The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus . These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture . Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides . While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus . Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk . The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula . Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus. J Pharm Pharmacol, 1998 Oct, 50(10), 1183 - 6 Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens; Fernandez MA et al.; Different species of the Scrophularia genus (Scrophulariaceae) have been reported to have bacteriostatic and anti-inflammatory properties . In previous studies the anti-inflammatory and antibacterial activity of different extracts from Scrophularia frutescens were investigated and p-coumaric, caffeic, ferulic gentisic, protocatechuic, syringic and isovanillic acids were isolated and identified . In this work the anti-inflammatory activity of these compounds, administered orally, has been studied against carrageenan-induced rat paw oedema and, administered topically, against tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema . The compounds' myeloperoxidase activity in inflamed ear was also investigated . Some of the phenolic acids were remarkably active in the TPA test (protocatechuic 71.59% inhibition, P < 0.001; syringic 74.43%, P < 0.001; ferulic 71.02% P < 0.001) and all significantly inhibited mouse ear oedema . They were only moderately active, or were without activity, in the carrageenan test . These results imply that the phenolic acids assayed are more effective topically than as oral anti-inflammatory agents and that their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue . This study has also enabled us to make some observations on the possible relationship between the chemical structure and anti-inflammatory activity of the compounds assayed. Acta Pol Pharm, 1998 Jul-Aug, 55(4), 323 - 7 Comparison of drug utilization of most commonly used drugs in Poland and Czech Republic; Ruszczynska E et al.; Utilization of drugs from the following groups: antibacterial, cardiovascular, gastrointestinal and respiratory tract diseases in Poland and Czech Republic was analyzed . The most commonly sold drugs were among antibacterial drugs, viz., doxycycline (4.5DDD/1000 inh./day in Poland; 3.3 in Czech Republic), co-trimoxazole (Poland-2.9; Czech Republic 2.5), ampicilline and amoxicilline; among gastrointestinal drugs, ascorbic acid (Poland 42.2; Czech Republic 59.3), among respiratory drugs, sodium cromoglicate in Poland and bromhexine in Czech Republic, and among cardiovascular drugs, enalapril in Poland and diuretics with potasium sparing drug in Czech Republic . In general, the leading drugs in Poland and Czech Republic, were the same . All drugs with highest utilization were on the Essential Drug List . Some differences in drug utilization between these two countries could result from the prevalence of particular diseases in each population and physician's prescribing patterns. Ter Arkh, 1998, 70(9), 35 - 41 {Whipple's disease: results of long-term follow-up}; Loginov AS et al.; AIM: To analyze clinical, diagnostic and therapeutic aspects of Whipple's disease . MATERIALS AND METHODS: Diagnostic and therapeutic data are available for 7 patients registered in 1990-1997 . The diagnosis was made using intestinoscope SIF-10L ("Olympus") . Biopsies were obtained from the jejunal, duodenal and gastric mucosa . The patients received tetracycline, erythromycin, biceptol, on demand--prednisolone . RESULTS: Whipple's disease was diagnosed 6 years on the average following the first clinical symptoms . In most patients the intestinal symptoms were preceded or accompanied by such extraintestinal symptoms as enlargement of the lymph nodes, lowering of hemoglobin, hypoproteinemia, ESR increase to 40-60 mm/h . To study biopsies from the distal duodenum is the only measure needed for diagnosis of Whipple's disease . In untreated patients PAS-positive macrophages are detectable also in gastric body mucosa . The immediate treatment outcome is favorable . The recurrence was observed only in one patient who had given up taking tetracycline . CONCLUSION: Long-term antibacterial therapy brings the recovery . Primary disorder of the cellular immunity responsible for the disease onset necessitates long-term follow-up of the patients . Control biopsy should be examined once a year. J Antibiot (Tokyo), 1998 Sep, 51(9), 872 - 9 A novel glycopeptide carrying a 3-oxazolin-5-one ring obtained by intra-molecular cyclization; Panzone G et al.; The structure of a product, isolated during the synthesis of the semisynthetic glycopeptide MDL 63,246, was elucidated on the basis of spectroscopic methods and proved to be a novel glycopeptide containing a 3-oxazolin-5-one ring between positions 36 and 38 . Subjected to acid hydrolysis this compound gave the corresponding pseudo aglycone and aglycone derivatives which maintained the original oxazolinone structure . Tested for antibacterial activity, these compounds showed a moderate activity against Gram-positive and inactive against Gram-negative bacteria. J Antibiot (Tokyo), 1998 Sep, 51(9), 816 - 22 Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species; Daferner M et al.; The antifungal and cytostatic compound strobilurin M (1) is a new variant of the strobilurins produced by Mycena sp . 96097, a tropical basidiomycete . The same fungus was found to produce tetrachloropyrocatechol (3a) and tetrachloropyrocatechol methyl ether (3b), new natural products, which exhibit antifungal, antibacterial and cytotoxic activities. J Photochem Photobiol B, 1998 Aug 21, 45(1), 51 - 9 Photocleavage of DNA by the fluoroquinolone antibacterials; Martinez L et al.; We have determined the relative efficiencies for the formation of single strand breaks (ssbs) after the UVA irradiation of pBR322 DNA and various fluoroquinolone (fleroxacin, lomefloxacin, norfloxacin) and naphthyridine (nalidixic acid, enoxacin) antibacterials . After correcting for the differences in absorption, the relative order for DNA photocleaving activity under anaerobic conditions is: fleroxacin, lomefloxacin > nalidixic acid >> norfloxacin > enoxacin . In general, fluoroquinolones having fluorine substituents at the C-6 and C-8 positions (lomefloxacin and fleroxacin) are 10-fold more efficient in generating ssbs than those having only a C-6 fluorine atom (norfloxacin) . The effect of oxygen on photoinduced DNA damage caused by these antibacterials is complex, but our data imply that active oxygen species are not necessary for DNA scission by these molecules, and indeed, may sometimes inhibit it . Lomefloxacin ethyl ester, which cannot undergo decarboxylation, is as active as lomefloxacin itself . Thus the free radical generated by decarboxylation is unlikely to be the active species involved in photoinduced fluoroquinolone DNA cleavage . For lomefloxacin and fleroxacin, DNA damage probably results from the generation of a carbene at C-8 as a result of photoinduced loss of their F8 atom as fluoride upon UVA irradiation . Fluoroquinolones lacking a C-8 fluorine atom must operate by a different mechanism . While photocleavage of pBR322 DNA does not necessarily mean that duplex DNA will be cleaved under the same conditions, nevertheless lomefloxacin and fleroxacin, the two most photogenotoxic fluoroquinolones, did cause the most damage to the plasmid DNA. Mol Gen Mikrobiol Virusol, 1998, (3), 16 - 9 {Formation of M . hominis and A . laidlawii resistance to fluoroquinolones}; Govorun VM et al.; Mycoplasma hominis and Acholeplasma laidlawii cultures resistant to antibacterial fluoroquinolone drugs ciprofloxacin (Cpf), ofloxacin (Ofl), and lomefloxacin (Lmf) were prepared by selection in liquid nutrient medium with ascending concentrations of Cpf . Resistant mycoplasma clones contained point mutations in the gyrase . A gene region determining quinolone resistance (QRDR gyrA): M . hominis contained C-->T transition resulting in substitution of Ser(83) for Leu and A . laidlawii G-->A resulting in substitution of Asp (91) for Asn . The phenomena of mutation formation during mycoplasma culturing in the presence of fluoroquinolones is studied . In the presence of Cpf in culture medium in concentrations of up to 10 micrograms/ml (for M . hominis) and 1 microgram/ml (for A . laidlawii) the mycoplasma populations contained cells with both altered and wild genotype . Culturing in the presence of higher Cpf concentrations resulted in elimination of cells nonmutant for QRDR gyrA . Besides in vitro studies, we analyzed clinical strains of M . hominis in the presence of different Cpf concentrations . M . hominis clones resistant to Cpf varying in genotypes were detected . These data permit a conclusion that the mechanism of fluoroquinolone resistance formation in mycoplasma includes several stages. J Travel Med, 1995 Dec 1, 2(4), 229 - 231 Antibrucella Activity of Quinolone Sparfloxacin; Qadri SMH et al.; Background: Sparfloxacin is a new fluoroquinolone with excellent in vitro activity against a variety of Gram-positive and Gram-negative bacteria . Methods: In vitro antibacterial activity of this new drug was tested against 139 strains of Brucella melitensis . These strains were isolated from 138 patients at a major tertiary care referral center in Riyadh, Saudi Arabia . Results: Seven percent of the strains were inhibited by 0.06 mg per L and 99% by 0.12 mg per L of sparfloxacin . Of the five other fluoroquinolones tested, ciprofloxacin, norfloxacin, pefloxacin, and fleroxacin exhibited comparable or slightly higher minimal inhibitory concentrations values . They inhibited the growth of 138 of the 139 isolates at 0.25-0.5 mg per L . Rufloxacin required 2-8 mg per L to inhibit 138 of the 139 strains tested . One of the isolates, which had previously developed resistance to ciprofloxacin during therapy with this drug, with a rise in MIC from 0.06 mg per L to >5.0 mg per L, exhibited cross-resistance to sparfloxacin and other fluoroquinolones . Conclusion: Sparfloxacin exhibited excellent in vitro activity against clinical isolates of Brucella . Clinical trials are warranted to determine its potential in the treatment of brucellosis. Zentralbl Bakteriol, 1995 Nov, 283(1), 69 - 78 Imipenem inhibits in vitro activity of amphotericin B directed against Aspergillus fumigatus; Rath PM et al.; A decrease of the susceptibility of Aspergillus fumigatus strains to amphotericin B was found when tested in combination with high concentrations (128-2048 mg/l) of the antibacterial agent imipenem by checkerboard titration and agar diffusion assay . Only bacteriologically active imipenem showed the antagonism . The mechanism of action is unknown . However, imipenem and amphotericin B did not react directly, as shown by checkerboard titration with bacterial strains as well as by HPLC analysis . It is concluded that imipenem medication may influence the efficacy of amphotericin B treatment in aspergillosis. Planta Med, 1998 Oct, 64(7), 675 - 6 Composition and antibacterial activity of the essential oils of Helichrysum rupestre and H . ambiguum growing in the Balearic Islands (Part III) Roussis V, Tsoukatou M, Chinou IB, Ortiz A. The chemical compositions of the essential oils obtained from the aerial parts of Helichrysum rupestre and H . ambiguum were analysed by GC and GC/MS . From the forty-five identified constituents representing 90.21% and 93.90% of the two oils, respectively, manoyl oxide, dodecanal, nonanal, p-cymene, alpha-pinene, and 2,4,6-tris(1,1-dimethylethyl)benzoic acid, were found to be the major components . Furthermore, the oils were tested against six Gram (+/-) bacteria and it was found that one of them exhibited significant antibacterial activity. J Pharmacol Exp Ther, 1998 Nov, 287(2), 672 - 8 Transport of quinolone antibacterial drugs in a kidney epithelial cell line, LLC-PK1; Matsuo Y et al.; The transport of quinolone antibacterial drugs by LLC-PK1 monolayers was examined to characterize the renal tubular secretion of these drugs . The transcellular transport of levofloxacin and grepafloxacin from the basolateral to apical side was larger than the transport in the opposite direction . The basal-to-apical transcellular transport and uptake from the basolateral side of levofloxacin showed concentration dependent saturation with an apparent Michaelis constant (Km) of 0.6 and 13 mM, respectively . Various quinolones (1 mM) inhibited the transcellular transport of levofloxacin, and this inhibition was accompanied by a marked increase of cellular accumulation . These results indicated that quinolones interacted more strongly with the transport system on the apical than the basolateral membrane . Neither tetraethylammonium nor cyclosporin A affected the basal-to-apical transcellular transport and accumulation of levofloxacin . The basal-to-apical transcellular transport of levofloxacin was not influenced by either lowering the pH of the apical side or pretreatment of apical membrane with p-chloromercuribenzene sulfonate . These findings indicate that quinolones are specifically transported from the basolateral to apical side by LLC-PK1 monolayers and have higher affinity for the transport system in the apical membrane, a system distinct from H+/organic cation antiport system. FEBS Lett, 1998 Oct 16, 437(1-2), 153 - 7 Molecular characterization of an exceptionally acidic lysozyme-like protein from the protozoon Entamoeba histolytica; Nickel R et al.; The protozoan parasite Entamoeba histolytica contains a second antibacterial protein with lysozyme-like properties . The newly recognized bacteriolytic protein was purified from extracts of amoebic trophozoites to allow amino-terminal sequencing . Subsequent molecular cloning revealed that it is an isoform of the amoeba lysozyme described previously but also demonstrated a substantial sequence divergence of the two forms . As lysozymes typically are basic proteins, the novel amoebic protein differs markedly in having a pI of 4.5 . There is no significant similarity of both amoeba lysozymes with any bacteriolytic protein of other organisms reported so far; however, striking sequence identity is found with predicted gene products of unknown function derived from the bacteria-feeding nematode Caenorhabditis elegans. Bioorg Med Chem, 1998 Sep, 6(9), 1555 - 61 Mg(2+)-mediated binding of 6-substituted quinolones to DNA: relevance to biological activity; Sissi C et al.; The interaction of a number of novel 6-substituted quinolone derivatives with DNA in the presence/absence of magnesium ions has been investigated by fluorometric techniques . The drug-single-stranded nucleic acid interaction is invariantly mediated by the metal ion . In all cases optimal complex formation is found at physiological Mg2+ concentration . From titrations at different {Mg2+} the binding constant for the ternary drug-DNA-Mg2+ complex (KT) has been evaluated . Interestingly, a good relationship is found between KT and gyrase poisoning activity of the test quinolones (IC50), which confirms that DNA-affinity of the quinolone, modulated by Mg2+, plays an important role in poisoning the cleavable gyrase-DNA complex and, consequently, in eliciting antibacterial activity in this family of drugs . The results obtained with different 6-substituted compounds supports the idea that position 6 of the drug, besides playing a pharmacokinetic role, is involved in recognition of the enzyme pocket . Our data do not support a mechanism of action based upon quinolone intercalation into B-DNA. Boll Chim Farm, 1998 Jul-Aug, 137(7), 233 - 8 Studies on arylfuran derivatives- Part VIII . Synthesis, characterization and antibacterial activities of some 1-aminomethyl-3-substituted-4-{5-(4-nitrophenyl-2-furfurylidene)} amino-1,2,4-triazole-5-thiones; Holla BS et al.; A series of 4-{5-(4-nitrophenyl-2-furfurylidene)}amino-5- mercapto-3-substituted-s-triazoles (3) and their Mannich bases (4) are synthesized . The structures of these compounds are established on the basis of elemental analysis, IR, NMR and mass spectral data . The newly synthesized compounds are screened for their antibacterial activities. Khirurgiia (Mosk), 1998, (7), 17 - 9 {Endolymphatic therapy of peritonitis}; Akhundov IT; Effectiveness of lymphological methods of treatment (LT) of endogenic intoxication (EI) developed by the author (endolymphatic anticoagulatory, improving rheology and microcirculation, antibacterial, detoxicating, enzyme-inhibiting, myo- and lymphostimulating, immunomodulating and hepatotropic) was studied in 210 patients with peritonitis divided into two groups of 105 patients each: in the control group a conventional postoperative treatment was carried out, in the study group--LT . Toxicity of the blood was determined by the level of medium-size molecules and leukocytic index of intoxication on postoperative day 1, 3, 5, 7 and 14 . It was established that LT which creates conditions for simultaneous sanation of blood and lymphatic bed, interstitial space, the inflammation focus promotes total detoxication of the body with almost complete elimination of EI on postoperative day 5-7 . In conventional treatment EI persisted for 7-14 days after operation. Antibiot Khimioter, 1998, 43(9), 24 - 8 {Characteristics of etiotropic therapy of plaque infection induced by atypical strains of F1- phenotype plaque microbe}; Ryzhko IV et al.; The efficacy of various group antibacterial drugs: aminoglycosides, quinolones, 3rd generation cephalosporins, doxycycline, rifampicin, ampicillin and azthreonam was estimated in the treatment of experimental plague of albino mice induced by antigen complete and atypical strains of the F1- phenotype plague microbe . The in vitro experiments showed that all the strains of the plague microbe irrespective of the phenotype (F1+ or F1-) were highly susceptible to the drugs . The animal experiments demonstrated that aminoglycosides (streptomycin, kanamycin, tobramycin, gentamicin and amikacin) and cephalosporins (ceftriaxone and ceftazidim) were highly efficient in the prophylaxis and treatment of plague due to F1+ and F1- strains . In experimental plague due to F1- phenotype plague microbe the prophylactic effects of cefotaxime, cefoperazone, sulbactam/ampicillin, azthreonam, ciprofloxacin and rifampicin were lower . However, increase of the daily doses of the drugs and prolongation of the treatment course up to 7 days made it possible to increase the protective effects up to 80-100 per cent . Doxycycline and ampicillin were not sufficiently efficient even when used for 10 days in the prophylaxis of plague due to F1- strains. J Wound Care, 1998 Jul, 7(7), 332 - 6 A povidone-iodine medicated dressing; Lawrence JC; The iodine content of a tulle gras-type dressing medicated with povidone-iodine (Poviderm) has been measured and its potential efficacy in wound care explored by means of laboratory models . Simple tests demonstrated the ready diffusibility and antibacterial activity of povidone-iodine . Wound models clearly showed that the limiting factor for useful dressing life is extent of exudation . It seems likely that this dressing would provide good topical antibacterial prophylaxis and may reduce the bacterial burden of colonised wounds . The dressing should help contain wound bacteria and thus assist infection control. Comp Biochem Physiol B Biochem Mol Biol, 1998 Apr, 119(4), 769 - 76 Ascidian phenoloxidase: its release from hemocytes, isolation, characterization and physiological roles; Hata S et al.; Hemocytes of the solitary ascidian Halocynthia roretzi released phenoloxidase in response to sheep red blood cells and yeast cells but not to latex beads . Phenoloxidase was also released from the hemocytes by treatments with zymosan and lipopolysaccharides but not with beta 1-3 glucan . EDTA scarcely inhibited the activity of phenoloxidase but inhibited the release of the enzyme . Phenoloxidase was purified from H . roretzi hemocytes by SP-Sephadex chromatography and Sephadex G-100 gel filtration . The molecular weight of the purified enzyme was estimated to be 62,000 . Phenoloxidase activity was strongly inhibited by diethyldithiocarbamate, phenylthiourea and reducing agents . H . roretzi phenoloxidase was characterized as a metalloenzyme that required copper ions for the expression of full activity . The phenoloxidase showed antibacterial activity in the presence of L-(3,4-dihydroxy)-phenylalanine and H . roretzi plasma . Thus, it can be concluded that phenoloxidase released from H . roretzi hemocytes functions as a humoral factor in the defense system of H . roretzi. Klin Khir, 1998, (5), 28 - 30 {Complications after the surgery for spinal cord tumor and their prevention}; Ermol'ev AI; The experience of surgical treatment of 200 patients with spinal cord tumor was summarized . After the operation the neurological symptoms had become more severe in 45% of patients, bronchopulmonary complications occurred in 23%, and purulent-inflammatory--in 12% . For the complications prophylaxis the antioedematious preparations application is recommended as well as hemodilution, anticoagulants, hemodilution agents, antibacterial prophylaxis therapy, the inspiration deepening training. Clin Pharmacokinet, 1998 Sep, 35(3), 223 - 46 Pharmacokinetic optimisation of the treatment of bacterial central nervous system infections; Nau R et al.; Central nervous system (CNS) infections caused by bacteria with reduced sensitivity to antibacterials are an increasing worldwide challenge . In successfully treating these infections the following conditions should be considered: (i) Antibacterials do not distribute homogeneously in the central nervous compartments {cerebrospinal fluid (CSF), extracellular space of the nervous tissue, intracellular space of the neurons, glial cells and leucocytes} . Even within the CSF, after intravenous administration, a ventriculo-lumbar concentration gradient is often observed . (ii) Valid parameters of drug entry into the CSF are the CSF: serum concentration ratio in steady state and the CSF: serum ratio of the area under the concentration-time curves (AUCCSF/AUCS) . Frequently, the elimination half-life (t1/2 beta) in CSF is longer than t1/2 beta in serum . (iii) For most antibacterials, lipophilicity, molecular weight and serum protein binding determine the drug entry into the CSF and brain tissue . With an intact blood-CSF and blood-brain barrier, the entry of hydrophilic antibacterials (beta-lactam antibacterials, glycopeptides) into the CNS compartments is poor and increases during meningeal inflammation . More lipophilic compounds {metronidazole, quinolones, rifampicin (rifampin) and chloramphenicol} are less dependent on the function of the blood-CSF and blood-brain barrier . (iv) Determination of the minimal inhibitory concentrations (MIC) of the causative organism is necessary for optimisation of treatment . (v) For rapid sterilisation of CSF, drug concentrations of at least 10 times MIC are required . The minimum CSF concentration: MIC ratio ensuring successful therapy is unknown . Strategies to achieve optimum antibacterial concentrations in the presence of minor disturbances of the blood-CSF and blood-brain barrier include, the increased use of low toxicity antibacterials (e.g., beta-lactam antibiotics), the use of moderately lipophilic compounds, and the combination of intravenous and intraventricular administration . Antibacterials which do not interfere with bacterial cell wall synthesis delay and/or decrease the liberation of proinflammatory bacterial products, delay or inhibit tumour necrosis factor release, and may reduce brain oedema in experimental meningitis . Conclusive evidence of the reduction of neuronal damage by this approach, however, is lacking. Leuk Res, 1998 Nov, 22(11), 1037 - 48 Identification of an upstream enhancer containing an AML1 site in the human myeloperoxidase (MPO) gene; Austin GE et al.; Myeloperoxidase (MPO) is an important antibacterial enzyme found only in granulocytes and monocytes . The human MPO gene is transcribed early during myelogenesis but MPO RNA synthesis ceases at the end of the promyelocyte stage of myeloid maturation . We recently identified a basal MPO promoter and several adjacent cis-elements in the proximal 5'-flanking region of this gene . Transfection studies using constructs containing several kb of 5'-flanking MPO DNA revealed the presence of a DNA segment located between bp (base pair) -4200 and bp -3800 with enhancer activity for the endogenous basal MPO promoter . Deletion studies revealed the core enhancer activity to lie between bp -4100 and bp -3844 . The percentage enhancement of promoter activity is greater in MPO-expressing myeloid cells than in MPO-non-expressing myeloid cells or non-myeloid cells . Furthermore . the enhancer confers TPA- or DMSO-responsiveness upon either endogenous or exogenous promoters . DNase I footprinting and transfection experiments identified an AML1 site as a functionally important element within the enhancer . Gelshift competition and supershift experiments demonstrated the binding of the alpha subunit of the transcription factor AML1 to this site in HL-60 cells . This distal enhancer appears likely to play an important role in the control of MPO transcription during myeloid differentiation. Pediatr Hematol Oncol, 1998 Sep-Oct, 15(5), 459 - 62 Necrotizing otitis externa, otitis media, peripheral facial paralysis, and brain abscess in a thalassemic child after allogeneic BMT; Tezcan I et al.; Severe infection is one of the major complications in the early and late post-bone marrow transplantation period . The authors report a thalassemic child who developed necrotizing otitis externa and otitis media, a very rare complication after bone marrow transplantation, and then peripheral facial nerve paralysis and brain abscess in the early period of bone marrow transplantation despite antibacterial and antifungal prophylaxis . Necrotizing otitis media is characterized by necrosis and sloughing of considerable areas in the middle ear and adjacent tissues and is an unusual disorder because of today's antibiotics . Granulocytopenia and background ear tissue exposed to previous repeated otitis media attacks may be the predisposing factors in this case . The authors conclude that the children with previous histories of recurrent otitis media should be prepared and monitored very carefully during bone marrow transplantation because of the risk of necrotizing otitis media, especially in the granulocytopenic period. Ostomy Wound Manage, 1998 Aug, 44(8), 68 - 78; discussion 77-8 Hand eczema; Sibbald RG; Hand eczema is a common disorder of healthcare providers . The pattern of eczema can help to distinguish endogenous (dyshidrosis, atopy) causes from exogenous (contact irritant and allergic dermatitis) and the common differential diagnoses (psoriasis, fungus infections) . Appropriate strength topical steroids, moisturizers, antibacterials, and systemic agents are all used to treat hand eczema depending on the type of eczema and its severity . Patients with contact allergic eczema should be assessed for possible latex allergy. Ginekol Pol, 1997 Oct, 68(10), 492 - 8 {The analysis of rationale in antibiotic usage in certain maternity and gynecological wards and analogous outpatient clinics}; Swierzy H et al.; The aim of this work was the analysis of the correctness of therapeutic and preventive use of chemotherapeutic agents by the gynaecologists in their hospital and outpatient treatment . 1774 orders concerning chemotherapy or antibacterial chemoprophylaxis in 4 chosen health institutions (2 maternity-gynaecological wards and 2 analogous out-patient departments) were analysed . While evaluating each course indications for chemotherapy, choice of drug, each dose, way and time of administration were considered . In analysed health institutions 22.1-40.1% of used chemotherapeutics were applied without reasonable indications . In 11.3-27.7% of indicated cases the right chemotherapeutic was not chosen properly . Improper dosage concerned 0.0-23.7% of analysed courses of chemotherapy . It was no reservation for the ways of administration of the drugs . The inappropriate time of usage referred to 5.6-21.4% of analysed courses. Drugs, 1998 Sep, 56(3), 447 - 86 Omeprazole . A review of its use in Helicobacter pylori infection, gastro-oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti-inflammatory drugs; Langtry HD et al.; Omeprazole is a well studied proton pump inhibitor that reduces gastric acid secretion . This review examines its use in Helicobacter pylori infection, gastro-oesophageal reflux disease (GORD) with or without oesophagitis and gastrointestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) . Optimal omeprazole regimens for anti-H . pylori therapy are those that administer the drug at a dosage of 40 mg/day (in 1 or 2 divided doses) for 7, 10 or 14 days in combination with 2 antibacterial agents . As a component of 3-drug regimens in direct comparative studies, omeprazole was at least as effective as lansoprazole, pantoprazole, bismuth compounds and ranitidine . However, a meta-analysis suggests that triple therapies with omeprazole are more effective than comparable regimens containing ranitidine, lansoprazole or bismuth . Omeprazole also appears to be successful in triple therapy regimens used in children with H . pylori infection . In patients with acute GORD with oesophagitis, omeprazole is at least as effective as lansoprazole or pantoprazole in promoting healing, and superior to ranitidine, cimetidine or cisapride in oesophagitis healing and symptom relief . Omeprazole was similar to lansoprazole and superior to ranitidine in preventing oesophagitis relapse in patients with all grades of oesophagitis, but may be superior to lansoprazole or pantoprazole in patients with more severe disease . More patients with symptomatic GORD without oesophagitis experienced symptom relief after short term treatment with omeprazole than with ranitidine, cisapride or placebo, and symptoms were more readily prevented by omeprazole than by cimetidine or placebo . Omeprazole was effective in healing and relieving symptoms of reflux oesophagitis in children with oesophagitis refractory to histamine H2 receptor antagonists . Omeprazole is superior to placebo in preventing NSAID-induced gastrointestinal damage in patients who must continue to take NSAIDs . It is also similar to misoprostol and superior to ranitidine in its ability to heal NSAID-induced peptic ulcers and erosions, and superior to misoprostol, ranitidine or placebo in its ability to prevent relapse . In long and short term studies, omeprazole was well tolerated, with diarrhoea, headache, dizziness, flatulence, abdominal pain and constipation being the most commonly reported adverse events . Usual omeprazole dosages, alone or combined with other agents, are 10 to 40 mg/day for adults and 10 to 20 mg/day for children . CONCLUSIONS: Omeprazole is a well studied and well tolerated agent effective in adults or children as a component in regimens aimed at eradicating H . pylori infections or as monotherapy in the treatment and prophylaxis of GORD with or without oesophagitis or NSAID-induced gastrointestinal damage. Drugs, 1998 Sep, 56(3), 307 - 35 Proton pump inhibitors . Pharmacology and rationale for use in gastrointestinal disorders; Richardson P et al.; Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use . There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders . Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers . Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks) . There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing . For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H . pylori in over 90% of cases and significantly reduce ulcer recurrence . Patients with H . pylori-positive gastric ulcers should be managed similarly . PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) . In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment . For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates . There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration . In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion. Rev Med Interne, 1998 Apr, 19(4), 255 - 61 {New macrolides}; Lecomte F et al.; INTRODUCTION: Following their use for a few years, the place of new macrolides can be assessed . CURRENT KNOWLEDGE AND KEY POINTS: "New macrolides", ie, roxithromycin, clarithromycin, azithromycin and dirithromycin, are derivated from erythromycin and defined by different pharmacokinetic parameters: longer half time with better oral administration and shorter duration of treatment, better tissue concentrations with reduction of dosages and better tolerance, high cellular concentration with good activity . However, new macrolides and erythromycin do not show major differences in their antibacterial spectrum against usual pyogenic strains . Clinical use of new macrolides extends to opportunistic infections, such as atypical mycobacterial infections or toxoplasmosis, occurring in the course of HIV infection . New macrolides are also recommended for the treatment of Helicobacter pylori-related gastroduodenal ulcer . FUTURE PROSPECTS AND PROJECTS: New macrolides have opened new avenues in the development of anti-infectious strategies . Due to their good efficacy against Chlamydia pneumoniae which is suspected of inducing vascular diseases, the upcoming use of ketolids and the development of their non-antibiotic effects, the future of macrolides is favorable. Mol Cell, 1998 Sep, 2(3), 397 - 403 Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro; Zabner J et al.; Cystic fibrosis (CF) is caused by the loss of functional CFTR Cl- channels . However, it is not understood how this defect disrupts salt and liquid movement in the airway or whether it alters the NaCl concentration in the thin liquid film covering the airway surface . Using a new approach, we found that CF airway surface liquid had a higher NaCl concentration than normal . Both CF and non-CF epithelia absorbed salt and liquid; however, expression of CFTR Cl- channels was required for maximal absorption . Thus, loss of CFTR elevates the salt concentration in CF airway surface liquid and in sweat by related mechanisms; the elevated NaCl concentration is due to a block in transcellular Cl- movement . The high NaCl may predispose CF airways to bacterial infections by inhibiting endogenous antibacterial defenses. Parasitology, 1998 Sep, 117 ( Pt 3), 201 - 8 Active resistance of entomophagous rhabditid Heterorhabditis bacteriophora to insect immunity; Jarosz J; A specific extracellular proteinase, degrading selectively the cecropin-based defence system of insects, is secreted into the larval body during parasitism of the greater wax moth by the Heterorhabditis bacteriophora/Photorhabdus luminescens complex and by phase 1 of P . luminescens . The proteolytic digestion of insect inducible cecropin-like immune molecules was demonstrated by the disappearance of the Galleria mellonella cecropins and purified Hyalophora cecropin B peptide PAGE bands upon exposure to infected extracts, and a similar abrogation of antibacterial activity using an agar diffusion assay . Proteolytic activity of infected extracts produced by nematode/bacterial complex and phase 1 variant of P . luminescens was shown to be correlated with cecropin-inhibitory activity, suggesting that this anti-cecropin agent may be responsible for the ability of bacteria to establish infection and the insecticidal nature of H . bacteriophora . Antibacterial activity of Galleria lysozyme and that of chicken egg-white lysozyme to which P . luminescens is insensitive, was unaffected by H . bacteriophora proteinase. Zhonghua Yi Xue Za Zhi, 1997 May, 77(5), 336 - 9 {Observation of 212 cases of typhoid fever treated with FQNS}; Jiang S et al.; OBJECTIVES: To treat 212 cases of typhoid fever with Seven kinds of fluoroquinolones (FQNS) and to evaluate their clinical efficacy, bacterial susceptibility and adverse drug reaction (ADR) . METHODS: All the cases were hospitalized and uniantibiotic treated in which NFX group (n = 43) was compared with CP group (n = 28) . RESULTS: 204/212 (96.23%) cases were positively cultured . All except 9 (S . paratyphi) were S . typhi . Of the 212 clinically isolated strains, 194(91.51%) were susceptible to FQNS with K-B assay . The MIC except 1 (6.25 mg/L) were all < or = 4 mg/L . The results of MIC detection with 20 strains of clinically isolated bacteria in 1994 and 1995 showed that FQNS were apparently superior to other antityphoid fever antibiotics as chloramphenicol and cefoperazone . When FQNS were used the overall clinical cure rate was 98.11%, the bacterial clear rate was 99.51%, and the rate of ADR was 11.3% . No difference was found between the NFX group and CP group in defervescent days and the cure rates and bacterial carrier state in recovery . The rate of recurrence and ADR in the NFX group was lower than that in the CP group . With the improvement of pharmacokinetics, new FQNS can be administered once or twice a day, and the therapy course shortened from 14 to 7 days . It is considered that FQNS are currently the first choice of antibacterials in treating typhoid fever. Anesteziol Reanimatol, 1998 Jul-Aug, (4), 16 - 9 {A strategy and procedure for the antibacterial therapy of abdominal sepsis}; Gel'fand BR et al.; Offers a protocol of antibacterial therapy of abdominal sepsis in surgical patients . Analyzes the principal etiological agents of abdominal septic complications . Presents optimal schemes of antibacterial therapy of abdominal sepsis . Pays special attention to choice of antibiotics in different clinical situations. J Antibiot (Tokyo), 1998 Aug, 51(8), 786 - 94 Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates; Poras H et al.; The first synthesis of siderophore conjugates of two macrolide antibiotics, spiramycin 1 and neospiramycin 2, which are unable to penetrate the outer membrane of gram-negative bacteria are described . These novel conjugates were prepared by regioselective acylation of a hydroxyl function of 1 and 2 with a dihydroxybenzoic Fe(III) complexing ligand linked via a carboxyl group containing spacer to the macrolide antibiotics . The preliminary biological evaluation of these novel conjugates under standard and iron depleted conditions has shown that their antibacterial activity was comparable to that of spiramycin 1 and neospiramycin 2. J Antibiot (Tokyo), 1998 Aug, 51(8), 771 - 85 Cladinose analogues of sixteen-membered macrolide antibiotics . VI . Synthesis of metabolically programmed, highly potent analogues of sixteen-membered macrolide antibiotics; Kurihara KI et al.; Five novel 3-hydroxyl derivatives of sixteen-membered macrolide possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar moiety were synthesized by using a combination of structurally stable silyl acetal protection and selective hydrogenolysis of a 3"-methylthiomethyl ether to a 3"-OMe group . Several derivatives having n-butyryl, i-butyryl and n-valeryl substituent at the 4"-OH group exhibited significant antibacterial activity in vitro . One of them, 4"-O-n-butyryl-3"-O-methylleucomycin V, showed improved therapeutic effect in mice. J Antibiot (Tokyo), 1998 Aug, 51(8), 757 - 70 Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains; Ishikawa K et al.; The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied . Two types of new carbapenem derivatives have been synthesized . These 1beta-methylcarbapenems, one type having a (2S,4S)-2-{1,1-dimethyl-2-(1-piperazinyl)carbonyl}pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I . The in vivo potency of these two carbapenems was compared with that of meropenem . The structure-activity relationships leading to these carbapenems are also described. J Biol Chem, 1998 Oct 16, 273(42), 27668 - 77 The mechanism of inhibition of topoisomerase IV by quinolone antibacterials; Khodursky AB et al.; Topoisomerase IV (Topo IV) is a mediator of quinolone toxicity in bacteria . In this work, we demonstrate that norfloxacin, a model quinolone, converts Escherichia coli Topo IV into a poisonous adduct on DNA as opposed to inhibiting topoisomerase activity . Norfloxacin inhibition of Topo IV induces a slow decline in DNA synthesis that parallels cell death . Treatment of cells with a lethal concentration of the antibacterial did not block chromosome segregation, the phenotype of catalytic inhibition of Topo IV . Instead, norfloxacin causes DNA damage, as evidenced by the induction of the SOS pathway for DNA repair; the increase in susceptibility to the drug by mutations in genes for DNA repair pathways including recA, recB, and uvrD; and the efficient detergent-induced linearization of plasmid DNA in drug-treated cells . Wild-type and drug-resistant alleles of Topo IV are co-dominant, but we find that mutations in recA, seqA, or gyrB result in unconditional dominance of the sensitive allele, the characteristic of a poisoning mode of inhibition . These mutations either compromise chromosome integrity or force Topo IV to play a more active role in DNA unlinking in front of the replication fork . We interpret our results in terms of distinct but complementary roles of Topo IV and gyrase in DNA replication. J Biol Chem, 1998 Oct 16, 273(42), 27438 - 48 The dependence of membrane permeability by the antibacterial peptide cecropin B and its analogs, CB-1 and CB-3, on liposomes of different composition; Wang W et al.; A natural antibacterial peptide, cecropin B (CB), and designed analogs, CB-1 and CB-3, were synthesized . The three peptides have different structural characteristics, with CB having one hydrophobic and one amphipathic alpha-helix, CB-1 having two amphipathic alpha-helices, and CB-3 having two hydrophobic alpha-helices . These differences were used as the rationale for a study of their efficacy in breaking liposomes with different combinations of phosphatidic acid and phosphatidylcholine . Biosensor binding measurements and encapsulating dye leakage studies showed that the higher binding affinity of CB and CB-1 to the polar heads of lipids is not necessary for the peptides to be more effective at lysing lipid bilayers, especially when liposomes have a higher phosphatidic acid content . Kinetic studies, by intrinsic and extrinsic fluorescence stopped-flow measurements, revealed two transitional steps in liposome breakage by CB and CB-1, although only one kinetic step was found for CB-3 . Circular dichroism stopped-flow measurements, monitoring the formation of secondary structure in the peptides, found one kinetic step for the interaction of all of the peptides with the liposomes . Also, the alpha-helical motif of the peptides was maintained after interacting with the liposomes . Based on these results, the mechanisms of liposome lysis by CB, CB-1, and CB-3 are discussed. Farmaco, 1998 Jun 30, 53(6), 395 - 8 Synthesis of some new biologically active thiadiazolotriazinones; Holla BS et al.; 4-Amino-6-arylmethyl-3-mercapto-1,2,4-triazin-5(4H)-ones 1 are condensed with aromatic carboxylic acids, aryloxyacetic acids and anilinoacetic acids 2 to yield 7-substituted-3-arylmethyl-4H-1,3,4-thiadiazolo{2,3-c}-1,2,4-tr iazin-4-ones 3 . Phosphorus oxychloride is used as cyclizing agent . Some of the newly synthesized compounds are screened for their antibacterial activities. Int J Infect Dis, 1998 Apr-Jun, 2(4), 230 - 6 Catheter-related infection: an update on diagnosis, treatment, and prevention; Capdevila JA; Catheter-related infection (CRI) accounts for a large percentage of nosocomial infections, and related bacteremia is a common complication . Bacteremia arises in approximately 1 of 15 episodes of CRI and causes considerable morbidity and occasional mortality, as well as increased medical costs . The diagnosis of CRI and catheter-related bacteremia (CRB) is still a challenge for practitioners treating catheterized patients . Semiquantitative tip culture by the roll-plate method is the cornerstone for diagnosis of CRI in routine practice . However, there is a great deal of interest in the alternative methods for diagnosing CRI without catheter withdrawal, since treatment of the patient can be successfully completed with the infected device maintained in place . The conservative management of CRI includes perfusion of antibiotics through the infected catheter and the antibiotic-lock technique (ALT) . Catheter-related infection prevention is accomplished mainly by strict adherence to hygienic practices in insertion and manipulation of the catheter . However, knowledge of the pathophysiology of CRI has led to the development of new sophisticated catheters and hubs that incorporate mechanical and antibacterial barriers. Naturwissenschaften, 1998 Aug, 85(8), 359 - 68 Intracellular bacteria in protozoa; Gortz HD et al.; Intracellular bacteria in humans are typically detrimental, and such infections are regarded by the patients as accidental and abnormal . In protozoa it seems obvious that many bacteria have coevolved with their hosts and are well adapted to the intracellular way of life . Manifold interactions between hosts and intracellular bacteria are found, and examples of antibacterial resistance of unknown mechanisms are observed . The wide diversity of intracellular bacteria in protozoa has become particularly obvious since they have begun to be classified by molecular techniques . Some of the bacteria are closely related to pathogens; others are responsible for the production of toxins. Biophys Chem, 1998 Aug 24, 74(2), 107 - 15 Calculation of concentrations of equilibrium components in an in vitro activity test of vancomycin antibiotics and the possible mode of action; Yan H et al.; The vancomycin group of antibiotics is considered to act by binding the bacterial cell wall mucopeptide precursor terminating in -L-Lys-D-Ala-D-Ala . The dimerization of these antibiotics is also believed to play a role in the action . In this paper, we analyzed the equilibria in the in vitro antibacterial activity test of the vancomycin antibiotics both with and without the cell wall precursor analogue di-acetyl-L-Lys-D-Ala-D-Ala (DALAA) . Based on the equilibria and concentration balance, we obtained 10 equations (seven quadratic equations and three linear equations) containing 10 equilibrium concentrations which relate to the antibiotic, cell wall precursor and DALAA . A computer program was written to solve these equations from known dimerization constant and the binding constants (both monomer and dimer) with DALAA of the antibiotic . The concentrations in the test for vancomycin and eremomycin were obtained . The antibiotic activity of these antibiotics may be quantitatively correlated with their dimerization constants and the binding constants through the calculation . By analyzing the calculated results, we concluded that the cell wall-bound dimer may be the major contributor to the antibiotic activity in the case of eremomycin, while the cell wall-bound monomer is possibly the determinant for the activity of vancomycin. Eur J Biochem, 1998 Sep 1, 256(2), 404 - 10 Solution structure of thanatin, a potent bactericidal and fungicidal insect peptide, determined from proton two-dimensional nuclear magnetic resonance data; Mandard N et al.; Thanatin is the first inducible insect peptide that has been found to have, at physiological concentrations, a broad range of activity against bacteria and fungi . Thanatin contains 21 amino acids including two cysteine residues that form a disulfide bridge . Two-dimensional (2D) 1H-NMR spectroscopy and molecular modelling have been used to determine its three-dimensional (3D) structure in water . Thanatin adopts a well-defined anti-parallel beta-sheet structure from residue 8 to the C-terminus, including the disulfide bridge . In spite of the presence of two proline residues, there is a large degree of structural variability in the N-terminal segment . The structure of thanatin is quite different from the known structures of other insect defence peptides, such as antibacterial defensin and antifungal drosomycin . It has more similarities with the structures of various peptides from different origins, such as brevinins, protegrins and tachyplesins, which have a two-stranded beta-sheet stabilized by one or two disulfide bridges . Combined with activity test experiments on several truncated isoforms of thanatin, carried out by Fehlbaum et al . {Fehlbaum, P., Bulet, P., Chernysh, S., Briand, J . P., Roussel, J . P., Letellier, L., Hetru, C . & Hoffmann, J . (1996) Proc . Natl Acad . Sci . USA 93, 1221-1225}, our structural study evidences the importance of the beta-sheet structure and also suggests that anti-Gram-negative activity involves a site formed by the Arg20 side-chain embedded in a hydrophobic cluster. Otolaryngol Pol, 1997, 51 Suppl 25, 161 - 4 {Zinnat in ambulatory treatment of acute pharyngitis and otitis media in adult patients}; Olszewski J et al.; The aim of this work was the assessment of therapeutic efficacy of antibiotic Zinnat (Cefuroksym Aksetyl) in ambulatory treatment of acute pharyngitis and otitis media in 20 adult patients, aged 21-36 . The efficacy of Zinnat was assessed on the basis of the smear from the throat and external auditory meatus to examine the culture and antibiogram, fever chart and self-assessment chart of symptoms which were assessed from 0 to 4 . It was shown that Zinnat is an effective antibiotic in ambulatory treatment of acute pharyngitis and otitis media . It shows a wide range of antibacterial effect comprising most often occurring pathogens bringing about acute pharyngitis and otitis media. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2674 - 7 In vivo efficacy of ABT-255 against drug-sensitive and -resistant Mycobacterium tuberculosis strains; Oleksijew A et al.; Current therapy for pulmonary tuberculosis involves 6 months of treatment with isoniazid, pyrazinamide, rifampin, and ethambutol or streptomycin for reliable treatment efficacy . The long treatment period increases the probability of noncompliance, leading to the generation of multidrug-resistant isolates of Mycobacterium tuberculosis . A treatment option that significantly shortened the course of therapy, or a new class of antibacterial effective against drug-resistant M . tuberculosis would be of value . ABT-255 is a novel 2-pyridone antibacterial agent which demonstrates in vitro potency and in vivo efficacy against drug-susceptible and drug-resistant M . tuberculosis strains . By the Alamar blue reduction technique, the MIC of ABT-255 against susceptible strains of M . tuberculosis ranged from 0.016 to 0.031 microg/ml . The MIC of ABT-255 against rifampin- or ethambutol-resistant M . tuberculosis isolates was 0.031 microg/ml . In a murine model of pulmonary tuberculosis, 4 weeks of oral ABT-255 therapy produced a 2- to 5-log10 reduction in viable drug-susceptible M . tuberculosis counts from lung tissue . Against drug-resistant strains of M . tuberculosis, ABT-255 produced a 2- to 3-log10 reduction in viable bacterial counts from lung tissue . ABT-255 is a promising new antibacterial agent with activity against M . tuberculosis. J Inorg Biochem, 1998 Aug, 71(1-2), 53 - 60 Antibacterial tests of bismuth(III)-quinolone (ciprofloxacin, cf) compounds against Helicobacter pylori and some other bacteria . Crystal structure of (cfH2)2{Bi2Cl10}.4H2O; Turel I et al.; The antibacterial tests of two bismuth(III)-ciprofloxacin (cf) compounds against Helicobacter pylori (H . pylori) and some other bacteria were performed . The results have shown that the activity of both compounds is comparable to that of ciprofloxacin hydrochloride . The crystal structure of (cfH2)2{Bi2Cl10}.4H2O (cfH2 = doubly protonated molecule of cf) is presented and discussed . The compound was isolated from acidic medium where quinolone is protonated and thus no bonding between quinolone and bismuth was observed . The bismuth(III) ions are coordinated by chloride ions forming dinuclear {Bi2Cl10}4- anions . The charge of this ion is compensated with protonated quinolone molecules (ionic interactions). Jpn J Antibiot, 1998 Jul, 51(7), 488 - 93 {In vitro antibacterial activity of vancomycin in combination with panipenem against carbapenem-resistant MRSA}; Sato S et al.; The synergistic relationship between vancomycin (VCM) and carbapenem (CRB) has been reported in antibacterial activity against CRB-resistant strains of MRSA . The purpose of this study is to investigate the antibacterial activity against CRB-resistant MRSA using VCM, panipenem (PAPM), and a combination of both . 8 strains of CRB-resistant MRSA were used to examine the effects of these antibiotics by the broth microdiluton technique . The effect of pH (pH 6, 7, 8) on MIC of VCM alone was not observed in 7 out of 8 strains; MICs were between 1.0-2.0 micrograms/ml . PAPM alone, however, showed an enhancing tendency in alkaline condition in 6 out of 8 strains . There was no influence of pH on MICs in the combination use of VCM and PAPM, showing additive effect in 1 strain and synergistic in 6 strains . Killing-curves against PAPM-resistant MRSA were examined under the following drug combinations; 1/4 MIC of VCM (0.5 micrograms/ml) plus 1/4 MIC of PAPM (16 micrograms/ml), and 1/4 MIC of VCM plus 1/8 MIC of PAPM (8 micrograms/ml) . The former drug combination showed synersistic effect; decrease from 1.05 x 10(5) to 6.45 x 10(4) CFU/ml after 6 hours' incubation and to less than 10 CFU/ml after 24 hours . The latter drug combination showed synergistic activity (2.68 x 10(2) CFU/ml) after 24 hours' incubation, but lost antibacterial activity after 48 hours . In conclusion, PAPM in combination with VCM showed synergistic effects on CRB-resistant MRSA . This combination therapy should be evaluated for the treatment of MRSA infection in patients with renal dysfunction. Scand J Gastroenterol, 1998 Aug, 33(8), 847 - 52 Impairment of phagocytic and T-cell-mediated antibacterial activity and plasma endotoxins in patients with untreated gastrointestinal cancer; Amati L et al.; BACKGROUND: Cancer patients have multiple immune deficits, and mediators, such as prostaglandins, transforming growth factor-beta, and interleukin (IL)-10, may play a role in the pathogenesis of these immune dysfunctions . METHODS: Fifty-six patients with gastrointestinal cancer (11 gastric cancer, 7 papilla of Vater cancer, and 38 colorectal cancer) were enrolled for this study, before starting conventional treatments . Phagocytosis and killing exerted by polymorphonuclear cells and monocytes, peripheral blood mononuclear cell absolute numbers, T-cell-mediated antibacterial activity, serum levels of IL-10 and interferon (IFN)-gamma, and plasma bacterial endotoxin concentration were evaluated . RESULTS: Data show an impaired phagocytic and T-cell-mediated antibacterial activity in all cancer patients, whereas only in subjects with gastric cancer were IFN-gamma serum levels reduced . Circulating endotoxins were detected in 17 patients . CONCLUSIONS: In untreated gastrointestinal cancer patients the capacity of phagocytes and T-cells to clear pathogens is reduced . This dysfunction may increase the risk of becoming infected and may account for the presence of endotoxin in 30% of patients. Ophthalmology, 1998 Sep, 105(9), 1721 - 6 Diffuse lamellar keratitis . A new syndrome in lamellar refractive surgery; Smith RJ et al.; OBJECTIVE: This study aimed to describe a syndrome that the authors call diffuse lamellar keratitis that follows laser in situ keratomileusis (LASIK) and related lamellar corneal surgery . DESIGN: Noncomparative case series and record review . PARTICIPANTS: Thirteen eyes of 12 patients in whom infiltrates developed in the interface after lamellar refractive surgery were studied . INTERVENTION: Topical antibiotics or corticosteroids or both were administered . MAIN OUTCOME MEASURES: Corneal infiltrate appearance, focality, location, and clinical course were measured . RESULTS: Patients presented between 2 and 6 days after surgery with pain, photophobia, redness, or tearing . Ten cases directly followed either myopic keratomileusis or LASIK . Three cases followed enhancement surgery without the use of a microkeratome . All 13 cases had infiltrates that were diffuse, multifocal, and confined to the flap interface with no posterior or anterior extension . The overlying epithelium was intact in each case . Cultures were negative in the two cases cultured . Ten eyes were treated with antibacterial agents; two eyes had fluorometholone four times daily added to the routine postoperative antibacterial regimen, and one eye had the antibacterial agent discontinued and was treated with topical fluorometholone alone . All infiltrates resolved without sequelae . CONCLUSIONS: A distinct syndrome of unknown cause of noninfectious diffuse infiltrates in the lamellar interface is described . It can be distinguished from infectious infiltrates by clinical presentation and close follow-up . Patients with the syndrome should be spared the more invasive treatment of infectious keratitis. Ceska Gynekol, 1998 Aug, 63(4), 279 - 82 {Treatment of chlamydial urogenital infections}; Masata J et al.; Chlamydia trachomatis is the most frequent sexually transmitted bacterial pathogen in developed countries {3, 12, 13} . The position is similar in the Czech Republic . Depending on the group of examined women active Chlamydia infection varies between 10 and 23% . The increasing incidence of urogenital Chlamydia infections and improving diagnostic possibilities call for adequate treatment . Correct treatment of urogenital infections caused by Chlamydia trachomatis is very important for the prevention of undesirable sequelae of inflammations of the lesser pelvis, subsequent risk of GEU, sterility, prevention of premature delivery and possible infection of the neonate . When starting treatment, selecting a suitable antibiotic and deciding on the therapeutic strategy it is important to select an antibiotic with regard to its efficacy, the epidemiological situation, regional sensitivity of the infectious agent, toxicity and tolerance of the antibiotic, to its bacteriostatic or bactericide action, and last not least, also its price . Despite selection of a suitable antibiotic sometimes treatment fails . For treatment of urogenital chlamydial infections tetracyclin and macrolid antibiotics are recommended or quinolone chemotherapeutic agents of the third generation . Tetracyclines are broad spectrum antibiotics with bacteriostatic action . As to oral forms doxycycline, tetracycline and oxytetracycline are used . The most frequent undesirable effects during treatment are nausea, vomiting, diarrhoea and abdominal pain . Tetracycline antibiotics are contraindicated in children under 8 years, during pregnancy and lactation and in case of sensitivity to this group of drugs . Macrolids are antibiotics with a medium broad antibacterial spectrum with bacteriostatic action . Macrolids of the first generation have a low antibacterial activity . They have a short biological half-life, not always a good tolerance, and serious clinically important drug interactions may develop . The most frequently used preparations of the first generation include erythromycin, josamycina and spiramycin . Macrolids of the second generation, azitromycin, roxitromycin and claritromycin lack the above negative properties . The most frequent undesirable effects after administration of macrolids include nausea and vomiting . Considerable differences were found in particular between different preparations containing erythromycin . Macrolids of the second generation have only slight undesirable gastrointestinal effects . Macrolid antibiotics are contraindicated in case of sensitization to this group, in severe hepatic disorders and great care must be taken in the treatment of pregnant women . Quinolone chemotherapeutic agents of the third generation, ciprofloxacine, enoxacine, ofloxacine and pefloxacine are synthetic drugs with a broad antibacterial spectrum which act on systemic infections . On oral administration they are rapidly absorbed and the blood and tissue concentrations are sufficiently effective . In the treatment of urogenital Chlamydia infections they are useful in the treatment of chronic infections after failure of previous macrolid and tetracycline therapy . The most frequent undesirable side-effects include nausea, vomiting, meteorism, diarrhoea, tinnitus, headache, changes of mood, allergic skin reaction . They are contraindicated in hypersensitivity to quinolone chemotherapeutic preparations, in children and adolescents under 18 years, during pregnancy and lactation . The objective of the present study was to evaluate different therapeutic patterns, their efficacy and tolerance. Biochim Biophys Acta, 1998 Oct 1, 1400(1-3), 339 - 47 Bacteriophage T4, a model system for understanding the mechanism of type II topoisomerase inhibitors; Kreuzer KN; Bacteriophage T4 provides a simple model system for analyzing the mechanism of action of antitumor agents that inhibit DNA topoisomerases . The phage-encoded type II topoisomerase is sensitive to many of the same antitumor agents that inhibit mammalian type II topoisomerase, including m-AMSA, ellipticines, mitoxantrone and epipodophyllotoxins . Results from the T4 model system provided a convincing demonstration that topoisomerase is the physiological drug target and strong evidence that the drug-induced cleavage complex is important for cytotoxicity . The detailed molecular steps involved in cytotoxicity, and the mechanism of recombinational repair of inhibitor-induced DNA damage, are currently being analyzed using this model system . Studies with the T4 topoisomerase have also provided compelling evidence that topoisomerase inhibitors interact with DNA at the active site of the enzyme, with each class of inhibitor favoring a different subset of cleavage sites based on DNA sequence . Finally, analysis of drug-resistance mutations in the T4 topoisomerase have implicated certain regions of the protein in drug interaction and provided a strong link between the mechanism of action of the antibacterial quinolones, which inhibit DNA gyrase, and the various antitumor agents, which inhibit mammalian type II topoisomerase. Biochim Biophys Acta, 1998 Oct 1, 1400(1-3), 185 - 94 DNA sequence selectivity of topoisomerases and topoisomerase poisons; Capranico G et al.; Chemical agents able to interfere with DNA topoisomerases are widespread in nature, and some of them have clinical efficacy as antitumor or antibacterial drugs . Drugs which have as a target DNA topoisomerases could be divided into two categories: poisons and catalytic inhibitors . Classical topoisomerase poisons stimulate cleavage in a sequence-selective manner, yielding drug-specific cleavage intensity pattern . The mechanisms of drug interaction with DNA topoisomerases, the DNA sequence selectivity of the action of topoisomerase II poisons and the identification of structural determinants of their activity have suggested that topoisomerase II poisons may fit into a specific pharmacophore, constituted by a planar ring system with DNA intercalation or intercalation-like properties, and protruding side chains interfering with the protein side of the covalent enzyme-DNA complex . The complete definition of the diverse pharmacophores of topoisomerase II poisons will certainly be of value for the design of new agents directed to specific genomic sites, and more effective in the treatment of human cancer. J Nat Prod, 1998 Sep, 61(9), 1171 - 3 Novel betaines from the marine sponge Agelas dispar; Cafieri F et al.; Three novel betaine alkaloids, called aminozooanemonin (1), pyridinebetaine A (2), and pyridinebetaine B (3), have been isolated from the Caribbean sponge Agelas dispar . Their structures were determined by FABMS, IR, UV, and 1D and 2D NMR spectroscopic experiments . Aminozooanemonin and pyridinebetaine A showed moderate antibacterial activity. J Nat Prod, 1998 Sep, 61(9), 1115 - 9 New p-terphenyl and polyketide metabolites from the sclerotia of Penicillium raistrickii; Belofsky GN et al.; Three new p-terphenyls (1-3), a new xanthone derivative (4), and two known fungal metabolites (5 and 6) have been isolated from the sclerotia of Penicillium raistrickii (NRRL 2039) . The structures for 3,3"-dihydroxy-6'-desmethylterphenyllin (1); 3'-demethoxy-6'-desmethyl-5'-methoxycandidusin B (2); 6'-desmethylcandidusin B (3); and 1,3,5, 6-tetrahydroxy-8-methylxanthone (4) were determined on the basis of HRMS and NMR data . Although compounds 1 and 4 exhibited mild antiinsectan and antibacterial activity, griseofulvin (5) was responsible for most of the activity of the sclerotial extract in dietary assays against the corn earworm Helicoverpa zea. J Dermatol Sci, 1998 Sep, 18(1), 1 - 10 Quinolone photoallergy: photosensitivity dermatitis induced by systemic administration of photohaptenic drugs; Tokura Y; Quinolone antibacterial agents are well known to elicit photosensitivity as a side effect . The photoallergenicity of fluoroquinolones, the representative quinolone derivatives, is mainly derived from their photohaptenic moiety . When epidermal cells are irradiated with ultraviolet A light in the presence of fluoroquinolones, quinolone photoadducts are formed in the treated cells . This photomodification is thought to be an initial step for sensitization and elicitation of this photoallergy, and quinolone-photoderivatized Langerhans cells are capable of stimulating immune T cells in mice . In the murine model, fluoroquinolone photoallergy is mediated by Th1 cells bearing T cell receptor Vbeta 13 . There is a broad photoantigenic cross-reactivity among fluoroquinolones in recognition by T cells and immunoglobulins . Therefore, it is most likely that fluoroquinolones carry the same photoantigenic epitope, which is recognized by Vbetal3+ T cells, leading to fluoroquinolone photosensitivity and cross-reactivity. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1994 Aug, 27(3), 120 - 32 Lipopolysaccharide binding and antibacterial activities of a synthetic peptide representing amino acids 90-101 of bactericidal/permeability-increasing protein; Yeh TM et al.; The bactericidal/permeability-increasing protein (BPI) of polymorphonuclear leukocytes is a potent antibacterial agent specific for gram-negative bacteria . BPI can bind to lipopolysaccharide (LPS) and neutralize its toxicity . However, little is known about the specific site and mechanisms of the BPI involved in this LPS binding and antibacterial activities . This study compared the amino acid sequences among BPI, cecropin A, magainin 2, and polymyxin B, and identified a common structure among these four bactericidal agents . They share a basic amphipathic alpha helix motif (Baah) . A short peptide that represents amino acids 90-101 of BPI was then synthesized to test if it possessed any LPS binding and antibacterial activities . Results from in vitro lymphocyte culture indicated this peptide was able to inhibit LPS-induced lymphocyte proliferation, suggesting that it may interact with LPS . This LPS binding ability of BPI peptide 90-101 was further supported by the results from HPLC assays which showed the mobility of the peptide shifted in the presence of LPS . Furthermore, the antibacterial spectra of this peptide and cecropin peptide 1-11 were very similar to that of polymyxin B, even though the antibacterial activities of these two peptides were less potent than that of polymyxin B . In addition, the antibacterial activities of these two peptides and polymyxin B were inhibited by free LPS or a high concentration of MgCl2 . These results thus suggest that a common structure (Baah) and antibacterial mechanism may be involved in these antibacterial agents. Jpn J Antibiot, 1997 Jul, 50(7), 591 - 6 {The drug sensitivity of enterohemorragic Escherichia coli and antibiotics treatment for hemorrhagic enterocolitis--from an outbreak of enterocolitis in Sakai city}; Moriguchi N et al.; In July, 1996, a massive outbreak of hemorrhagic enterocolitis involving more than 5,000 people was caused by enterohemorragic Escherichia coli (EHEC) O157:H7 occurred mainly among elementary school children of Sakai City, Japan . The antibacterial activities in vitro against EHEC from stool specimens were determined . Norfloxacin showed the highest antibacterial activity, and fosfomycin, kanamycin, ampicillin, cefaclor were considered as effective drugs . But doxycycline showed lower antibacterial activities compared to other examined drugs, and it appears necessary to take antibiotic resistance of Escherichia coli into consideration when a treatment regimen is determined . As a result of the oral administration of fosfomycin to 95 patients of hemorrhagic enterocolitis and carrier, no patients developed complications with hemolytic uremic syndrome (HUS) . However, a study of 17 patients with HUS demonstrated the fact that most of them were subjected to intravenous administration of fosfomycin . It may be needed to consider oral administration route of effective antibiotics in the treatment of enterocolitis in order to maintain high concentrations of a drug in the intestine. J Clin Epidemiol, 1998 Aug, 51(8), 703 - 8 Skin reactions to antibacterial agents in general practice; van der Linden PD et al.; OBJECTIVES: To quantify the risk of skin reactions to antibacterial drugs under everyday circumstances in a large population with automated data from general practitioners (GP) . DESIGN: A retrospective cohort study in a dynamic population . SETTING: Data came from the Integrated Primary Care Information (IPCI) database . The IPCI database consists of all data on consultations, morbidity, and prescriptions and other interventions, as registered by the GP in a source population of approximately 150,000 persons . METHODS: The study period started on April 1, 1994, and ended on September 30, 1995 . All patients who were treated with an antibacterial drug were enrolled on the first day of starting treatment until the end of the study period or until the occurrence of one or more of the following diagnoses within the risk period: allergic reaction, rash, erythema, pruritus and urticaria, or a notification of a skin reaction in the free text . Subsequently, patient profiles were assessed by two authors who were blinded to exposure . The risk period was defined as the legend duration of the antibacterial drug plus 14 days to control for carry-over of drug effects and delay in patient presentation . Age, gender, and comedication were examined as potential confounders . RESULTS: In the study period 13,679 patients received 19,961 prescriptions of an antibacterial drug . It concerned 5330 men (39.0%) and 8349 (61.0%) women with a mean age of 41 and 42 years, respectively . One hundred thirty-five patients developed a skin reaction in the risk period . Rash, pruritus, urticaria, and miscellaneous skin reactions were encountered in 76 (56.3%), 18 (13.3%), 19 (14.1%), and 22 (16.3%) patients, respectively . The three most frequently reported causes of skin reactions were combinations of trimethoprim with sulfonamides (2.1% of users; incidence density {ID}: 2.1/1000 exposed days), fluoroquinolones (1.6% of users; ID: 1.5/1000 person days), and penicillins (1.1% of users; ID: 1.3/1000 person days) . Compared to tetracyclines, the broad-spectrum penicillins showed an incidence density ratio (IDR) of 3.7, the combination of amoxicillin with clavulanic acid of 3.3, the fluoroquinolones of 2.8, and the combination of trimethoprim with sulphonamides of 4.4 . The presence of infectious mononucleosis increased the risk of rash in amoxicillin users with a factor of 58 . CONCLUSIONS: We found that the frequency of skin reactions to antibacterial drugs in general practice is around 1% and highest for the combination of trimethoprim with sulphonamides, penicillins, and fluoroquinolones . The outpatient incidence for skin reactions is probably lower than the incidence in hospitalized patients . Although this may be partly explained by negative misclassification, it is also likely that the actual incidence is lower as some hospitalized patient groups may be more prone to develop a skin reaction. J Control Release, 1998 Apr 30, 53(1-3), 235 - 47 Controlled delivery of antibacterial proteins from biodegradable matrices; Kuijpers AJ et al.; Prosthetic valve endocarditis is an infrequent, but serious complication of cardiac valve replacement . The infection is caused by the adherence of bacteria to the prosthetic valve or to tissue at the site of implantation . Recently it was shown that antibacterial peptides from blood platelets are involved in clearance and killing of bacteria adhering to vegetations induced in a model for prosthetic valve endocarditis using rabbits . The application of these antibacterial proteins in a release system, incorporated in the Dacron sewing ring of the prosthetic heart valve would diminish the incidence of endocarditis . In this study a release system for small cationic proteins based on cross-linked gelatin was developed and characterised . Furthermore, the system was evaluated with respect to the uptake and in vitro release of lysozyme, a small cationic protein that was chosen as a model protein for small cationic antibacterial proteins . Variation of gelatin type (A and B), and cross-link density resulted in differences in swelling, thermal behaviour, and number of charged groups . Lysozyme uptake was proportional to swelling, but was governed by the number of anionic groups . The latter was also observed for the release profiles: when the amount of free carboxylic acids is higher (gelatin B compared to gelatin A), the lysozyme release lasts for a longer time period . The release into solidified agarose medium, as a model for heart muscle tissue, was measured . After 50 h, 40-100% of the lysozyme was released, which is in accordance with the aimed release period of 24-48 h . The adsorption experiments in vitro suggest an influence of the electrostatic interactions between lysozyme and gelatin . This hypothesis was validated with a mathematical model which takes both diffusion and adsorption interactions into account. Antimicrob Agents Chemother, 1998 Sep, 42(9), 2359 - 64 Absence of effect of rufloxacin on theophylline pharmacokinetics in steady state; Kinzig-Schippers M et al.; Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration . A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline . Both drugs were administered at steady state . Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only . During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction . Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods . To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period . These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1 . 02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05) . In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state . Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events. Antimicrob Agents Chemother, 1998 Sep, 42(9), 2232 - 4 In vitro effectiveness of povidone-iodine on Acanthamoeba isolates from human cornea; Gatti S et al.; Acanthamoeba keratitis is a severe ocular infection secondary to accidental macro- or microscopic trauma of the cornea . Starting in 1985, a dramatic increase of this infection was recorded along with the spread of contact lens use . This protozoal disease is difficult to treat because of the scarcity of efficacious topical and systemic drugs . We evaluated the in vitro effectiveness of povidone-iodine (PVP-I {Betadine}), an agent with broad antibacterial and antiviral activity, compared to that of chlorhexidine (CXD), a cationic antiseptic, on Acanthamoeba isolates from patients with amebic keratitis . The results showed that PVP-I solution from 0.5 to 2.5% has a better antiamebic activity both on trophic and cystic stages of Acanthamoeba spp . than does CXD. Biochem Biophys Res Commun, 1998 Sep 8, 250(1), 1 - 4 Disassembly of the post-termination complex and reduction of translational error by ribosome recycling factor (RRF)-A possible new target for antibacterial agents; Kaji A et al.; In this paper, we briefly review RRF (ribosome recycling factor, previously called ribosome releasing factor) (for recent reviews covering historical background see (1, 2)) . Chem Pharm Bull (Tokyo), 1998 Aug, 46(8), 1254 - 60 Antibacterials and antimycotics: Part 1: Synthesis and activity of 2-pyrazoline derivatives; Nauduri D et al.; A series of 3-styryl-1,5-diphenyl and 5-styryl-1,3-diphenyl 2-pyrazolines of different substitutions has been synthesized by condensation of substituted alpha,beta-unsaturated ketones with phenylhydrazine hydrochloride in presence of catalytic amount of concentrated HCl . Compounds in the 3-styryl series had OMe, NMe2, NO2, OH and isopropyl substituents and those in the 5-styryl series had OMe, NMe2 and NOs . The 3-styryl-1,5-diphenyl compounds showed little variation in antibacterial activity towards gram-positive and gram-negative bacteria in terms of geometric mean minimum inhibitory concentrations (MIC) . The 4',4"-NMe2, 4',4"-NO2 and 4',4"-OMe compounds were found to possess the highest activity in the series . The 5-styryl-1,3-diphenyl series showed lower activities than the 3-styryl series . The in vitro antimycotic activity of the 4',4"-OH and 2',2"-OH substituted compounds showed good activity than the other molecules in the two series. Arch Microbiol, 1998 Oct, 170(4), 209 - 18 Methylglyoxal production in bacteria: suicide or survival? Ferguson GP, Totemeyer S, MacLean MJ, Booth IR. Methylglyoxal is a toxic electrophile . In Escherichia coli cells, the principal route of methylglyoxal production is from dihydroxyacetone phosphate by the action of methylglyoxal synthase . The toxicity of methylglyoxal is believed to be due to its ability to interact with the nucleophilic centres of macromolecules such as DNA . Bacteria possess an array of detoxification pathways for methylglyoxal . In E . coli, glutathione-based detoxification is central to survival of exposure to methylglyoxal . The glutathione-dependent glyoxalase I-II pathway is the primary route of methylglyoxal detoxification, and the glutathione conjugates formed can activate the KefB and KefC potassium channels . The activation of these channels leads to a lowering of the intracellular pH of the bacterial cell, which protects against the toxic effects of electrophiles . In addition to the KefB and KefC systems, E . coli cells are equipped with a number of independent protective mechanisms whose purpose appears to be directed at ensuring the integrity of the DNA . A model of how these protective mechanisms function will be presented . The production of methylglyoxal by cells is a paradox that can be resolved by assigning an important role in adaptation to conditions of nutrient imbalance . Analysis of a methylglyoxal synthase-deficient mutant provides evidence that methylglyoxal production is required to allow growth under certain environmental conditions . The production of methylglyoxal may represent a high-risk strategy that facilitates adaptation, but which on failure leads to cell death . New strategies for antibacterial therapy may be based on undermining the detoxification and defence mechanisms coupled with deregulation of methylglyoxal synthesis. Arch Oral Biol, 1998 Jul, 43(7), 559 - 65 An approach to differentiate between antibacterial and antiadh