Perit Dial Int, 2003 Jul-Aug, 23(4), 331 - 8 Antibiotic administration in an animal model of chronic peritoneal dialysate exposure; Mortier S et al.; OBJECTIVES: The high incidence of intraperitoneal infection remains an important problem in animal models of chronic dialysate exposure . Prophylactic antibiotic administration can be used to resolve this problem, but the isolated effects of antibiotics on peritoneal membrane function and structure are unknown . The present study examined the effects of prophylactic antibiotics on infection rate and peritoneal membrane function and structure in a rat model of chronic dialysate exposure . DESIGN: A first group of rats (A; n = 12) received 10 mL 3.86% glucose dialysate twice daily through a heparin-coated catheter . In a second group of animals (B; n = 12), oxacillin 2.5 mg/day and gentamicin 0.04 mg/day were added to the dialysate . Group C (n = 12) was injected twice daily with an identical dose of antibiotics dissolved in 1 mL of buffer solution . Group D (n = 12) was left untreated . Dialysate cultures were obtained regularly . After 8 weeks of exposure, peritoneal transport studies were performed and samples for histology were obtained . RESULTS: Technique survival was 92% in group A and 100% in the remaining groups . Five rats in group A but none of the animals in the other groups developed peritonitis . The transport rates of small solutes were elevated and net ultrafiltration was decreased in group A compared to the controls . Fibrosis, as evaluated by quantifying Picro Sirius Red staining with image analysis, was significantly elevated in group A (3.48% +/- 1.06% vs 0.72% +/- 0.51% in group D, p < 0.05) but not in group B (0.29% +/- 0.07%) or in group C (0.52% +/- 0.28%) . Vascular density, measured by counting the number of blood vessels that stained positive for endothelial NO synthase, was increased in both groups that were exposed to dialysate: 153.0 +/- 12.9/microm2 in group A and 131.6 +/- 14.3/microm2 in group B, versus 76.76 +/- 12.37/microm2 in group C and 73.2 +/- 10.4/microm2 in group D (p < 0.01) . CONCLUSIONS: Prophylactic administration of oxacillin and gentamicin adequately prevented intraperitoneal infection in an animal model of chronic dialysate exposure . In addition, fibrosis was absent, suggesting intraperitoneal infection rather than dialysate exposure is a causative factor. J Chromatogr A, 2003 Aug 8, 1008(2), 145 - 55 Trace enrichment of (fluoro)quinolone antibiotics in surface waters by solid-phase extraction and their determination by liquid chromatography-ultraviolet detection; Turiel E et al.; A new and simple analytical methodology for the simultaneous analysis of acidic and zwitterionic (fluoro)quinolones in surface waters at trace concentration level is presented . The method is based on the preconcentration of these analytes by a solid-phase extraction procedure and their subsequent quantification by liquid chromatography using ultraviolet detection . The breakthrough volumes of the selected (fluoro)quinolones in four different sorbents--C18, styrenedivinylbenzene (SDB), C18-cation-exchange and SDB-cation-exchange--have been evaluated and varied between 25 and 150 ml depending on the antibiotic and the sorbent used . An exhaustive study of the influence of sample pH on the preconcentration step has been carried out in order to find a suitable procedure for extraction of acidic and zwitterionic FQs in one single step . Under optimum conditions, it was possible to percolate up to 250 ml of water solution onto both C18 and SDB-cation-exchange cartridges with quantitative recoveries for all the analytes tested . However, matrix components of the surface water samples analysed negatively affected the recoveries of the analytes in the SDB-cation-exchange cartridge and thus, C18 cartridges were finally selected for the analysis of the (fluoro)quinolones in lake and river water . The limits of detection achieved with this procedure varied between 8 and 20 ng l(-1) proving its suitability for the determination of the (fluoro)quinolones in water samples at a realistic environmental concentration level. Farm Hosp, 2003 Jul-Aug, 27(4), 258 - 63 {Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases}; Llinares Tello F et al.; A number of literature references suggest that carbapenem-like antibiotics decrease plasma concentrations of valproic acid in epileptic patients . This interaction may result in a recurrence of epileptic seizures in these patients . To clarify the possible mechanism of such carbapenem-valproic acid interaction several experimental studies have been carried out in animals . However, the mechanism of this drug-drug interaction is as yet uncertain . in this article we report three new cases that were observed in our hospital within three months . One of these patients developed seizures . We also review the different mechanisms proposed, as well as cases published to this day . All these data demonstrate that care should be taken in using these potent antibiotics in patients receiving valproic acid. Spectrochim Acta A Mol Biomol Spectrosc, 2003 Sep, 59(11), 2541 - 6 Flow-injection chemiluminescence study of Ce(IV)-Na2SO3-Tb(III)-fluoquinolone antibiotic system with DNA; Yi L et al.; A novel flow injection chemiluminescence (CL) system is developed to determine DNA . According to the fact that DNA linearly quenches the CL intensity of Ce(IV)-Na(2)SO(3)-Tb(III)-fluoquinolone antibiotic (FLUQ) system, DNA concentration is determined . The calibration graphs are linear in the range of 0.04-10 microg/ml (for both natural and denatured DNA), and the 3sigma limits of detection are 7.8 ng/ml (natural DNA) and 9.5 ng/ml (denatured DNA) . According to fluorescence spectrum and CL spectrum, and through studying the reaction of Ce(IV)-Na(2)SO(3)-Tb(III)-FLUQ with nucleotides and bases, we conclude that DNA counteracts the energy transfer from FLUQ to Tb(III), and this function is related to both bases and phosphate groups in DNA. Eksp Klin Farmakol, 2003 Mar-Apr, 66(2), 42 - 5 {Effects of aminoglycoside antibiotics on various structures of the acoustic analyzer}; Fisenko VP; Aminoglycoside antibiotics decrease the microphone potential amplitude and the auditory nerve potential in response to acoustic stimulation . These drugs suppress the bioelectrical activity of medulla, cerebral cortex, and olivo-cochlear efferent system . The experiments on freely moving cats showed that cortical response to electric stimulation of thalamocortical fibers originating from medial geniculate body are more sensitive to aminoglycoside antibiotics than the microphone potential and the auditory nerve potential. J Leukoc Biol, 2003 Nov, 74(5), 908 - 15 Epub 2003 Aug 01. Antibiotic cyclic AMP signaling by "primed" leukocytes confers anti-inflammatory cytoprotection; Abeyama K et al.; The mechanism underlying anti-inflammatory effects of macrolide antibiotics remains uncertain . In this study, we first show the evidences concerning the possible link between leukocytic cyclic adenosine monophosphate (cAMP) signaling and the mechanism of anti-inflammatory, cytoprotective actions of macrolides . The clinical range of macrolides (i.e., erythromycin, roxithromycin, and clarithromycin) preferentially inhibited nuclear factor-kappaB activation mediated by reactive oxygen intermediates, inducing cAMP-dependent signaling {i.e., cAMP and cAMP-responsive element-binding protein (CREB)} by "primed" but not "resting" leukocytes . In this context, cAMP/CREB inhibition with adenosine 3':5'-cyclic monophosphothioate, rp-isomer (rp-cAMPs) and CREB decoy oligonucleotides reduced the anti-inflammatory actions of macrolides . These results thus indicate that macrolide-induced cAMP/CREB signaling, selectively by primed leukocytes, plays a major role in the mechanism of anti-inflammatory actions of macrolides. Anal Bioanal Chem, 2003 Nov, 377(5), 909 - 21 Epub 2003 Aug 30. Hyphenation of liquid chromatography to ion trap mass spectrometry to identify minor components in polypeptide antibiotics; Govaerts C et al.; The application of liquid chromatography-ion trap mass spectrometry for the characterization of linear and cyclic polypeptide antibiotics was investigated . The aim was on-line identification of impurities in those antibiotic complexes without recourse to time-consuming isolation and purification procedures . Hyphenated techniques, such as liquid chromatography coupled to mass spectrometry, are ideally suited for this purpose . Characterization was performed with an ion trap mass spectrometer offering MS(n) capability; this enables more structural information to be obtained . Liquid chromatography in combination with ion trap mass spectrometry was successfully applied for the characterization of impurities in gramicidin, polymyxin B, polymyxin E, and bacitracin and the study of the degradation products of polymyxins B and E. J Am Chem Soc, 2003 Sep 10, 125(36), 10899 - 905 Synthesis of the antifungal macrolide antibiotic (+)-roxaticin; Evans DA et al.; The total synthesis of the antifungal macrolide antibiotic roxaticin has been accomplished . The synthesis relies principally on aldol and directed reduction steps to construct the extended 1,3-polyol array present in the natural product . Three principal nonpolyene containing fragments were assembled and then coupled using Julia olefination and methyl ketone aldol addition reactions . A series of functionalization reactions incorporated the sensitive polyene and provided the protected roxaticin seco-acid, which was lactonized in good yield . Acidic deprotection completed this convergent synthesis of roxaticin. Immunobiology, 2003, 207(4), 237 - 45 Macrophage L-type Ca2+ channel antagonists alter Chlamydia pneumoniae MOMP and HSP-60 mRNA gene expression, and improve antibiotic susceptibility; Azenabor AA et al.; Recent data have shown a unique relationship between Ca2+ signaling in macrophages through L-type channels and the outcome of C . pneumoniae infection of such cells . The present investigation seeks to provide insights into the manner in which macrophage L-type Ca2+ channel operation affects major outer membrane protein (MOMP) and heat shock protein-60 (HSP-60) mRNA gene expression (factors associated with Chlamydia chronicity), and the possible effect of this on antibiotic susceptibility . Intracellular calcium ({Ca2+}i) chelation using varying doses of 1,2-bis (o-aminophenoxy) ethane-N,N,N'N'--tetra acetic acid (acetoxymethyl) ester (BAPTA-AM) induced an increase in MOMP and a decrease in HSP-60 mRNA gene expression . L-type Ca2+ channel antagonists produced an identical but enhanced effect . Since these findings associate specialized Ca2+ channels to Chlamydia chronicity, it was important to determine Ca2+ channel effect on the usual antibiotic refractory form of C . pneumoniae in macrophages . Inhibition of macrophage L-type Ca2+ channel operation improved C . pneumoniae antibiotic susceptibility assessed by decreased inclusion counts or down-regulated MOMP and HSP-60 mRNA gene expression . These findings provide molecular insights into how specialized Ca2+ channels influence Chlamydia chronic course in macrophages and demonstrates a role for L-type Ca2+ channel inhibitors in enhanced C . pneumoniae susceptibility to antibiotic therapy. J Antimicrob Chemother, 2003 Oct, 52(4), 675 - 8 Epub 2003 Sep 01. Outpatient antibiotic prescriptions from 1992 to 2001 in the Netherlands; Kuyvenhoven MM et al.; OBJECTIVES: Although Dutch outpatient antibiotic prescription rates are low compared with other European countries, continuing to scrutinize trends in outpatient antibiotic use is important in order to identify possible increases in antibiotic use or inappropriate increases in the use of particular classes of antibiotics . METHODS: We assessed the volume of Dutch outpatient antibiotic prescriptions from 1992 to 2001 by calculating the mean number of outpatient antibiotic prescriptions (indicating the number of times physicians decide to prescribe an antibiotic agent) per 1000 patients insured by the Dutch Sickness Fund per year, according to subgroups (narrow-spectrum penicillins, broad-spectrum penicillins, tetracyclines, macrolides, sulphonamides and trimethoprim, and quinolones) . Data were obtained from the Dutch Drug Information Project/Health Care Insurance Board . RESULTS: The total volume of outpatient antibiotic prescriptions in 2001 was 394 prescriptions per 1000 patients insured by the Dutch Sickness Fund . Overall, the rates were stable between 1992 and 2001, with small variations across years, but with marked differences in volumes within antibiotic groups across these years: a decrease in prescribing of narrow-spectrum penicillins (-29%), amoxicillin (-23%), tetracycline (-24%), doxycycline (-19%) and trimethoprim and derivatives (-45%) was accompanied by an increase in prescribing of co-amoxiclav (+85%), macrolides (+110%) and quinolones (+86%) . CONCLUSIONS: The international trend of a decline in the use of narrow-spectrum and older penicillins and prescribing more broad-spectrum and new chemotherapeutics was shown to exist in a low prescribing country, The Netherlands . Therefore, inappropriate antibiotic prescribing should remain prominent on the research agenda in intervention studies in order to improve the appropriate selection of antibiotic class and to reduce the prescription of antibiotics. Eur J Biochem, 2003 Sep, 270(18), 3675 - 83 Kinetics of enzyme acylation and deacylation in the penicillin acylase-catalyzed synthesis of beta-lactam antibiotics; Alkema WB et al.; Penicillin acylase catalyses the hydrolysis and synthesis of semisynthetic beta-lactam antibiotics via formation of a covalent acyl-enzyme intermediate . The kinetic and mechanistic aspects of these reactions were studied . Stopped-flow experiments with the penicillin and ampicillin analogues 2-nitro-5-phenylacetoxy-benzoic acid (NIPAOB) and d-2-nitro-5-{(phenylglycyl)amino}-benzoic acid (NIPGB) showed that the rate-limiting step in the conversion of penicillin G and ampicillin is the formation of the acyl-enzyme . The phenylacetyl- and phenylglycyl-enzymes are hydrolysed with rate constants of at least 1000 s-1 and 75 s-1, respectively . A normal solvent deuterium kinetic isotope effect (KIE) of 2 on the hydrolysis of 2-nitro-5-{(phenylacetyl)amino}-benzoic acid (NIPAB), NIPGB and NIPAOB indicated that the formation of the acyl-enzyme proceeds via a general acid-base mechanism . In agreement with such a mechanism, the proton inventory of the kcat for NIPAB showed that one proton, with a fractionation factor of 0.5, is transferred in the transition state of the rate-limiting step . The overall KIE of 2 for the kcat of NIPAOB resulted from an inverse isotope effect at low concentrations of D2O, which is overridden by a large normal isotope effect at large molar fractions of D2O . Rate measurements in the presence of glycerol indicated that the inverse isotope effect originated from the higher viscosity of D2O compared to H2O . Deacylation of the acyl-enzyme was studied by nucleophile competition and inhibition experiments . The beta-lactam compound 7-aminodesacetoxycephalosporanic acid (7-ADCA) was a better nucleophile than 6-aminopenicillanic acid, caused by a higher affinity of the enzyme for 7-ADCA and complete suppression of hydrolysis of the acyl-enzyme upon binding of 7-ADCA . By combining the results of the steady-state, presteady state and nucleophile binding experiments, values for the relevant kinetic constants for the synthesis and hydrolysis of beta-lactam antibiotics were obtained. Pediatrics, 2003 Sep, 112(3 Pt 1), 527 - 31 Treatment of otitis media with observation and a safety-net antibiotic prescription; Siegel RM et al.; OBJECTIVE: Several studies have demonstrated that acute otitis media (AOM) in children can be managed without antibiotics . Because children with AOM have traditionally been treated with antibiotics in the United States, there are concerns that parents may not be comfortable with their children being treated with pain control alone . Recently, Cates in England showed that antibiotic usage for AOM could be decreased by prescribing a safety-net antibiotic prescription (SNAP) to be filled if symptoms do not resolve with observation after 48 hours . It is not clear whether a SNAP will be acceptable to parents in other settings such as the United States . The objective of our study was to determine whether parents in the United States find a SNAP for AOM acceptable and whether antibiotic usage could be decreased by its use . METHODS: A pediatric practice-based research network in a midwestern community of 1.8 million was the setting for this study . The Cincinnati Pediatric Research Group (CPRG) includes practices in Ohio, Kentucky, and Indiana . Children who were between 1 and 12 years of age and presented to the offices of the CPRG with uncomplicated AOM were eligible for the study . Children were excluded when they had temperature >101.5 degrees F, had an ear infection in the past 3 months, showed signs of another bacterial infection, or were toxic appearing . Families were given acetaminophen, ibuprofen, or topical otic anesthetic drops for pain control . They were also given a prescription for an antibiotic and instructed not to fill it unless symptoms either increased or did not resolve after 48 hours . The data were entered directly by investigators via an Internet site . RESULTS: A total of 194 children were enrolled in 11 offices over 12 months; 175 (90%) completed the follow-up interview . The average child's age was 5.0 years . Only 55 (31%) of the 175 who were contacted for follow-up had filled their antibiotic prescription . Compared with their previous experience, parents were overwhelmingly willing to treat AOM with pain medication alone (chi(2) = 111) . Seventy-eight percent (95% confidence interval: 71%-84%) of parents reported that the pain medication was effective . Sixty-three percent (95% confidence interval: 55%-70%) of parents reported that they would be willing to treat future AOM episodes without antibiotics and with pain medication alone . CONCLUSIONS: A subset of parents find a safety-net prescription and pain control acceptable in the treatment of AOM, and antibiotic usage can be lowered with this strategy. Anal Chem, 2003 Jun 1, 75(11), 2730 - 9 FTMS structure elucidation of natural products: application to muraymycin antibiotics using ESI multi-CHEF SORI-CID FTMS(n), the top-down/bottom-up approach, and HPLC ESI capillary-skimmer CID FTMS; McDonald LA et al.; The molecular formulas for the structures and substructures of muraymycin antibiotics A1 (C52H90N14O19, MW 1214) and B1 (C49H83N11O18, MW 1113) were determined using electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS) . The muraymycin A1 and B1 structures were elucidated by utilizing capillary-skimmer fragmentation with up to five stages of mass spectrometry (MS5) . Multi-CHEF, a multiple ion isolation method, was used at each stage of MS(n) to isolate a parent ion and up to four reference ions, for exact-mass calibration . The parent ions were fragmented by SORI-CID and the product ions internally calibrated with average absolute mass errors less than 1 ppm at each stage in the fragmentation processes . Using the top-down/bottom-up approach, the molecular formulas for the antibiotics were determined by summing the elemental formulas of the neutral losses, obtained by measuring the mass differences (<500 Da) between the genetically related sequential parent ion masses in the MS(n) spectra, with the unique elemental formula of the lowest parent ion mass (<500 Da) . The structures of 12 additional compounds in the muraymycin complex were elucidated using HPLC ESI capillary-skimmer CID FTMS by correlating their fragmentation patterns with those of muraymycins A1 and B1 . Sequential neutral losses of an aminosugar, a valine, a uridine, and an ester fatty acid from the muraymycin parent ions provided diagnostic fragments for characterization. Anal Chem, 2003 Jun 1, 75(11), 2640 - 6 Interference-free analysis using three-way fluorescence data and the parallel factor model . Determination of fluoroquinolone antibiotics in human serum; Munoz de la Pena A et al.; Three-way fluorescence data and multivariate calibration based on parallel factor analysis (PARAFAC) are combined for the simultaneous quantitation of three fluoroquinolone anitibiotics (norfloxacin, enoxacin, and ofloxacin) in human serum samples . The three analytes can be adequately determined with limits of detection of 0.2, 3.0, and 0.5 microg L(-1), respectively, with minimum experimental effort . The selected analytical methodology fully exploits the so-called second-order advantage of the employed three-way data, allowing obtaining individual concentrations of calibrated analytes in the presence of any number of uncalibrated (serum) components . In contrast to PARAFAC, less satisfactory results were obtained with a multidimensional partial least-squares (nPLS) model trained with the same calibration set. Drug Deliv, 2003 Jul-Sep, 10(3), 201 - 7 Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation; Justo OR et al.; Liposomal encapsulation of tuberculostatic drugs can potentially increase their therapeutic index . The incorporation of isoniazid, pyrazinamide, rifampicin, ethionamide, and streptomycin in extruded distearoylphosphatidylcholine/cholesterol liposomes designed for administration through inhalation was evaluated . Ethionamide and rifampicin were incorporated during lipid film formation, whereas solutions of the remaining drugs were used to hydrate preformed lipid bilayers . Final drug to lipid ratios around 0.3 were achieved for isoniazid and pyrazinamide, and mean vesicle diameters varied from 286 to 329 nm . No expressive drug leakage or mean vesicle diameter changes occurred during 3 weeks . No significant incorporation was achieved for streptomycin, ethionamide, and rifampicin. Org Lett, 2003 Sep 4, 5(18), 3233 - 6 Synthesis of proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway; Tao J et al.; {structure: see text} A chemoenzymatic synthesis was described to prepare proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway . The successful synthesis of these fragile molecules relies heavily on mild enzymatic deprotection and efficient enzymatic kinetic resolution to minimize epimerization, decomposition, multiple orthogonal protections, and retro aldol reactions often encountered in their chemical synthesis. Comput Methods Programs Biomed, 2003 Oct, 72(2), 139 - 54 Methods, architecture, evaluation and usability of a case-based antibiotics advisor; Gierl L et al.; In this paper, we discuss the usability of an antibiotics therapy adviser, with a broad, complex spectrum of functions which we have developed within the ICONS project . We present the architecture of the system, case-based reasoning methods used, steps and results of medical evaluations, which are concerning the quality of the recommended therapies, the user friendliness of the system and the interpretation of laboratory results . Furthermore, we discuss problems of transferability of such a system from one site to another as well as problems of local susceptibility patterns and individual dose regimens. Mol Microbiol, 2003 Sep, 49(5), 1179 - 90 Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization; Oliynyk M et al.; The analysis of a candidate biosynthetic gene cluster (97 kbp) for the polyether ionophore monensin from Streptomyces cinnamonensis has revealed a modular polyketide synthase composed of eight separate multienzyme subunits housing a total of 12 extension modules, and flanked by numerous other genes for which a plausible function in monensin biosynthesis can be ascribed . Deletion of essentially all these clustered genes specifically abolished monensin production, while overexpression in S . cinnamonensis of the putative pathway-specific regulatory gene monR led to a fivefold increase in monensin production . Experimental support is presented for a recently-proposed mechanism, for oxidative cyclization of a linear polyketide intermediate, involving four enzymes, the products of monBI, monBII, monCI and monCII . In frame deletion of either of the individual genes monCII (encoding a putative cyclase) or monBII (encoding a putative novel isomerase) specifically abolished monensin production . Also, heterologous expression of monCI, encoding a flavin-linked epoxidase, in S . coelicolor was shown to significantly increase the ability of S . coelicolor to epoxidize linalool, a model substrate for the presumed linear polyketide intermediate in monensin biosynthesis. J Environ Sci Health A Tox Hazard Subst Environ Eng, 2003 Sep, 38(9), 1971 - 9 Treatment of spent broth from an antibiotic manufacturing unit using anaerobic fixed film fixed bed reactor; Satyanarayan S et al.; Studies on bench scale reactor were undertaken to determine its performance at various organic loading rate (OLR) and hydraulic retention time (HRT) . The results indicated BOD and COD removals in the range of 67.2-77.4% and 57.8-69.1% respectively at the OLRs between 0.84 and 2.5 kgCOD/m3 d and HRT of 10 days . Daily gas production was measured by gas flow meter . Daily gas production varied between 0.268 and 0.326 m3/kgCOD added at the different OLRs . Studies were also carried out at lower HRT of 5 days . But BOD/COD removals reduced and correspondingly gas production also reduced . Gas composition remained constant at both the HRT and the Methane content was around 65-68% while the CO2 was around 32-35% . This paper discusses in detail the feasibility of upflow anaerobic fixed film fixed bed (UAFFFB) reactor system in treating the strong spent broth from the antibiotic industry. J Chromatogr A, 2003 Jul 18, 1006(1-2), 121 - 6 Optimization of experimental conditions for the preparative displacement chromatography of antitumor anthracycline antibiotics on carboxylic sorbents; Toshchevikova AY et al.; The physico-chemical conditions and the limits of the rates of mobile phases are determined when effective regimes of preparative chromatography in the conditions of sharpening the boundaries of chromatographic zones of anthracycline antibiotics are realized . The influence of pH on the equilibrium, kinetics and dynamics of sorption of anthracycline antibiotics (rubomycin, doxorubicin and carminomycin) on the carboxylic sorbents has been studied. Guang Pu Xue Yu Guang Pu Fen Xi, 2002 Oct, 22(5), 825 - 7 {Study on two kinds of antibiotics by the fluorescence thin-layer chromatograph}; Huang SP et al.; Carbostyril medicine is a kind of important chemically synthesized antibiotics, used extensively in the clinic . Ofloxacin (OFXL) and ciprofloxacin (CPLX), being similar in structures, were separated by micellar thin layer chromatography . The 0.0015 mol.L-1 Cetyl trimethyl ammonium bromide (CTAB) and 1% sodium dodecyl sulfate (SDS) (1:1) mixture containing ammonia liquor (1%) and polyamide plates were selected, respectively, as mobile and stationary phases . Various factors affecting the Rf values of drugs on the plates such as the concentration of CTAB, SDS and ammonia liquor, were investigated . Under the appropriate condition, the corresponding Rf is 0.87 and 0.76 . The fluorescence determination was carried out at the 280 nm excitation wave-length . Moreover, the stability and the sensibility were measured . The first analytical application of micellar as a mobile phase for the separation of OFLX and CPLX was developed. J Chromatogr Sci, 2003 Jul, 41(6), 311 - 6 A chromatographic approach to analyze dansyl amino acid-HP-beta-CD association using macrocyclic antibiotic as the stationary phase; Andre C et al.; The retention mechanism for a series of D,L-dansyl amino acids in high-performance liquid chromatography is investigated using a teicoplanin stationary phase and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the mobile phase additive (0-16mM) . A theoretical treatment is developed to determine the HP-beta-CD influence on the equilibrium between the teicoplanin phase and the aqueous medium, respectively . From the experimental data, the association constants of the D,L-dansyl amino acids-HP-beta-CD inclusion complexes are determined and discussed in relation to the enantiomer structure . A thermodynamic study confirms that both the retention and complexation mechanisms are independent of the dansyl amino acid molecular structure and its absolute carbon configuration. Kansenshogaku Zasshi, 2003 Jul, 77(7), 499 - 504 {Epidemiological investigation of "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)"}; Hanaki H et al.; Mu3 strain with heterogeneous intermediated-resistance to vancomycin (hetero-VISA) reported in 1997, also have possessed a character of an antagonistic effect of beta-lactam antibiotics and vancomycin . Mu3 is only strain which satisfies the definition of hetero-VISA in Japan . But, MRSA with antagonistic effects of beta-lactam antibiotics and vancomycin, was reported by many institutions . To separate hetero-VISA, we called "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)" . But the detection rate of clinical isolated BIVR in Japan is unknown, we reported on the detection method and the epidemiological investigation for BIVR . Mu 3 agar containing 4 micrograms/mL of vancomycin is used to detect BIVR . Mu3 strains were spread on the agar, BIVR can grow around the paper disc impregnated with ceftizoxime or grow on the whole surface on Mu 3 agar after incubation . The detection rate of BIVR was 45 in 717 (6.3%) clinical isolated strains . In detected strains as BIVR, the number of strains with grown on the whole surface of Mu3 agar showing a high resistance to vancomycin were 10 strains (1.4%) . Besides, from 106 strains of blood isolates MRSA, BIVR were detected 16 strains (15.1%), from 611 strains of non-blood isolates MRSA, BIVR were detected 29 strains (4.7%) (P < 0.0001) . In BIVR strains grown on the whole surface of Mu3 agar, the number of BIVR strains isolated from blood were 8 in 106 (7.5%), from non-blood were 2 in 611 (0.3%) (P < 0.0001) . On one side, hetero-VISA were not detected from all of BIVR growing on the whole surface of Mu3 agar . As a result, detection method and the definition of BIVR were quite different from those of hetero-VISA . An existence of BIVR in Japan was confirmed, we thought that the high detection rate of BIVR isolated from blood compared with that of non-blood showed the pathogenecity of BIVR which contribute to MRSA infections. Nucleic Acids Res, 2003 Sep 1, 31(17), 5074 - 83 Effect of polyamines on the inhibition of peptidyltransferase by antibiotics: revisiting the mechanism of chloramphenicol action; Xaplanteri MA et al.; Chloramphenicol is thought to interfere competitively with the binding of the aminoacyl-tRNA 3'-terminus to ribosomal A-site . However, noncompetitive or mixed-noncompetitive inhibition, often observed to be dependent on chloramphenicol concentration and ionic conditions, leaves some doubt about the precise mode of action . Here, we examine further the inhibition effect of chloramphenicol, using a model system derived from Escherichia coli in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes, under ionic conditions (6 mM Mg2+, 100 mM NH4+, 100 microM spermine) more closely resembling the physiological status . Kinetics reveal that chloramphenicol (I) reacts rapidly with AcPhe-tRNA.poly(U).70S ribosomal complex (C) to form the encounter complex CI which is then isomerized slowly to a more tight complex, C*I . A similar inhibition pattern is observed, if complex C modified by a photoreactive analogue of spermine, reacts in buffer free of spermine . Spermine, either reversibly interacting with or covalently attached to ribosomes, enhances the peptidyltransferase activity and increases the chloramphenicol potency, without affecting the isomerization step . As indicated by photoaffinity labeling, the peptidyltransferase center at which chloramphenicol binds, is one of the preferred cross-linking sites for polyamines . This fact may explain the effect of spermine on chloramphenicol binding to ribosomes. J Food Prot, 2003 Aug, 66(8), 1499 - 502 Comparative study of a semisynthetic derivative of natamycin and the parent antibiotic on the spoilage of shredded cheddar cheese; Suloff EC et al.; A water-soluble N-alkyl semisynthetic derivative of natamycin was synthesized by the Michael addition reaction of the parent with an N-substituted malemide . A comparative study was carried out to investigate the effectiveness of the semisynthetic derivative and the parent antibiotic in suppressing mold growth on shredded Cheddar cheese stored in modified atmosphere packaging (MAP) . The effects of 0-, 10-, and 20-ppm antimycotic treatments were examined . A 20-ppm natamycin treatment effectively suppressed visible mold growth (< 10(4) CFU/g) in MAP samples for up to 30 days after packages were opened . The performance of the 20-ppm semisynthetic derivative was similar to that of the 10-ppm natamycin treatment . For these treatments, visible mold growth did not occur in MAP samples until 20 days after packages were opened . These results indicate that the semisynthetic derivative of natamycin is less effective than the parent compound in suppressing mold growth on shredded Cheddar cheese. Org Biomol Chem, 2003 Jan 7, 1(1), 60 - 6 DNA recognition by the anthracycline antibiotic respinomycin D: NMR structure of the intercalation complex with d(AGACGTCT)2; Searle MS et al.; Respinomycin D is a member of the anthracycline family of antitumour antibiotics that interact with double stranded DNA through intercalation . The clinical agents daunomycin and doxorubicin are the most well-studied of this class but have a relatively simple molecular architecture in which the pendant daunosamine sugar resides in the DNA minor groove . Respinomycin D, which belongs to the nogalamycin group of anthracyclines, possesses additional sugar residues at either end of the aglycone chromophore that modulate the biological activity but whose role in molecular recognition is unknown . We report the NMR structure of the respinomycin D-d(AGACGTCT)2 complex in solution derived from NOE restraints and molecular dynamics simulations . We show that the drug threads through the DNA double helix forming stabilising interactions in both the major and minor groove, the latter through a different binding geometry to that previously reported . The bicycloaminoglucose sugar resides in the major groove and makes specific contacts with guanine at the 5'-CpG intercalation site, however, the disaccharide attached at the C4 position plays little part in drug binding and DNA recognition and is largely solvent exposed. Graefes Arch Clin Exp Ophthalmol, 2003 Sep, 241(9), 730 - 3 Epub 2003 Aug 20. Risk factors for antibiotic-resistant conjunctival bacterial flora in patients undergoing intraocular surgery; Mino de Kaspar H et al.; BACKGROUND: The purpose of this study was to determine if patients with certain risk factors are more likely to harbor conjunctival bacterial flora resistant to multiple antibiotics . METHODS: In this prospective study, detailed medical history and slit-lamp examination were performed on all patients prior to intraocular surgery . Patients with local risk factors were defined as those with chronic blepharitis, conjunctivitis or discharge . Those with systemic risk factors were patients with diabetes, autoimmune, immunodeficient or skin disorders, asthma and those taking immunosuppressant medications . Conjunctival cultures were obtained prior to preoperative antibiotics and povidone-iodine . Bacteria isolated were identified and antibiotic susceptibility was determined . Bacteria resistant to five or more antibiotics were defined as multi-resistant (MR) . RESULTS: Among the 207 patients enrolled in the study, 73 patients had local risk factors . Of these patients, 32 patients (44%) carried MR organisms, compared to 32 of the 134 patients (24%) without local risk factors (P=0.0049) . Thirty-two of 71 patients (45%) with systemic risk factors harbored MR organisms, compared to 32 of 136 patients (24%) without systemic risk factors (P=0.0025) . Seventeen of 93 patients (18%) who had neither local nor systemic risk factors had MR organisms on their conjunctiva . In contrast, 17 of the 30 patients (57%) with both local and systemic risk factors (57%) carried MR bacteria (P=0.0001) . CONCLUSION: Patients with local and/or systemic risk factors are more likely to harbor MR organisms . This may be one mechanism for the reported increased risk of postoperative endophthalmitis in this group of patients. Biopolymers, 2003 Sep, 70(1), 42 - 57 Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures; Vicens Q et al.; The potential of RNA molecules to be used as therapeutic targets by small inhibitors is now well established . In this fascinating wide-open field, aminoglycoside antibiotics constitute the most studied family of RNA binding drugs . Within the last three years, several x-ray crystal structures were solved for aminoglycosides complexed to one of their main natural targets in the bacterial cell, the decoding aminoacyl-tRNA site (A site) . Other crystallographic structures have revealed the binding modes of aminoglycosides to the three existing types of resistance-associated enzymes . The present review summarizes the various aspects of the molecular recognition of aminoglycosides by these natural RNA or protein receptors . The analysis and the comparisons of the detailed interactions offer insights that are helpful in designing new generations of antibiotics . Int J Cancer, 2003 Oct 20, 107(1), 99 - 105 History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL); Kato I et al.; A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL) . Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records . Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview . Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model . There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview . The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively . These associations were primarily due to antibiotic use against respiratory infections and dental conditions . Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma . Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks . Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL . However, a direct role of antibiotics in NHL induction has not been ruled out . Sante, 2003 Jan-Mar, 13(1), 23 - 7 {Systematic preventive antibiotic therapy during hysterosalpingography in an African tropical environment: is this practice justified?}; N'Gbesso RD et al.; To find out whether preventive antibiotic therapy can be justified in the practice of hysterosalpingography in a tropical environment where the infectious risk is notoriatly high, the authors performed a prospective study concerning 49 females patients . The patients in genital activity period, were willing and volunteers and were aged from 20 to 44 years . They were examined by hysterosalpingography during a period of three months . Patients were distributed in two homogenous group, one group of 25 patients who had a preventive antibiotic therapy and the second group with 24 patients with no preventive antibiotic therapy . Hysterosalpingography examinations were performed with sterile and single-use equipment . All patients were clinically examined for medical record purposes: gynaecologic, obstetric, pelvic infection, oral contraception, previous hysterosalpingography . Biologic dosages were realized, including blood count and erythrocyte sedimentation, culture of vaginal sampling, C reactive protein rate . The results obtained showed no significant difference between the two groups . The authors conclude that hysterosalpingography can be also performed in a tropical environment without using systematic preventive antibiotic therapy provided that asepsisrules are strictly observed. J Invest Dermatol, 2003 Sep, 121(3), 596 - 606 Molecular responses to photogenotoxic stress induced by the antibiotic lomefloxacin in human skin cells: from DNA damage to apoptosis; Marrot L et al.; Photo-unstable chemicals sometimes behave as phototoxins in skin, inducing untoward clinical side-effects when exposed to sunlight . Some drugs, such as psoralens or fluoroquinolones, can damage genomic DNA, thus increasing the risk of photocarcinogenesis . Here, lomefloxacin, an antibiotic from the fluoroquinolone family known to be involved in skin tumor development in photoexposed mice, was studied using normal human skin cells in culture: fibroblasts, keratinocytes, and Caucasian melanocytes . When treated cells were exposed to simulated solar ultraviolet A (320-400 nm), lomefloxacin induced damage such as strand breaks and pyrimidine dimers in genomic DNA . Lomefloxacin also triggered various stress responses: heme-oxygenase-1 expression in fibroblasts, changes in p53 status as shown by the accumulation of p53 and p21 proteins or the induction of MDM2 and GADD45 genes, and stimulation of melanogenesis by increasing the tyrosinase activity in melanocytes . Lomefloxacin could also lead to apoptosis in keratinocytes exposed to ultraviolet A: caspase-3 was activated and FAS-L gene was induced . Moreover, keratinocytes were shown to be the most sensitive cell type to lomefloxacin phototoxic effects, in spite of the well-established effectiveness of their antioxidant equipment . These data show that the phototoxicity of a given drug can be driven by different mechanisms and that its biologic impact varies according to cell type. Int Clin Psychopharmacol, 2003 Sep, 18(5), 297 - 8 Increased use of antibiotics in clozapine-treated patients; Landry P et al.; A retrospective chart review of hospitalized patients was completed to verify whether there were differences in the prescription rate of antibiotics to patients treated with clozapine . Subjects were inpatients with a diagnosis of schizophrenia or schizoaffective disorder . Charts of all patients who received clozapine for 24 consecutive months during a period of 48 consecutive months of hospitalization were selected for the study . For each patient, we compared the number of infections treated with an antibiotic during the 24 months pre-clozapine versus the period when they were treated with clozapine . Our study suggests that the number of antibiotic prescriptions is significantly increased in patients treated with clozapine. Boll Chim Farm, 2003 May, 142(4), 151 - 6 Pharmaco-economical analysis of the treatment with antibiotics in a surgery department; Dimitrov D; 6-Oxo-4(2-thienyl)-2-thioxo-1,3-dihydropyrimidine-5-carbonitrile (1) was synthesized and reacted with alkyl halides to give the S-alkyl compounds (2a,b), which reacted with phosphorous oxychloride to yield (3a,b) . Reaction of 3a,b with phenyl-hydrazine, hydrazine hydrate, ammonia, acid hydrazides and thiourea leads to formation of the compounds (4a,b), the dihydrazino compound derivative (5), the amino compounds (7a,b), triazolopyrimidine derivatives (9a-d), and the mercapto compounds (10a,b), respectively . Treatment of (10a) with chloroacetone gave (11a), which condensed with benzaldehyde giving the tricyclic compound (12) . Also (10b) reacted with ethyl chloroacetate followed by hydrolysis and cyclization yielded (14) . Heating of (5) gave (6), which reacted with sodium nitrite and/or carbondisulphide and give (15) and (16), respectively. World J Gastroenterol, 2003 Aug, 9(8), 1832 - 3 Efficacy of saccharomyces boulardii with antibiotics in acute amoebiasis; Mansour-Ghanaei F et al.; AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis . METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites engulfing RBCs found in stool were enrolled in the study . Regimen 1 included metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days . Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1 . Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4 . Student's t-test, chi(2) and McNemar's tests were used for statistical analysis . RESULTS: Three patients refused to participate . The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27 patients) . The two groups were similar regarding their age, sex and clinical manifestations . In Group 1, diarrhea lasted 48.0+/-18.5 hours and in Group 2, 12.0+/-3.7 hours (P<0.0001) . In Group 1, the durations of fever and abdominal pain were 24.0+/-8.8 and 24.0+/-7.3 hours and in Group 2 they were 12.0+/-5.3 and 12.0+/-3.2 hours, respectively (P<0.001) . Duration of headache was similar in both groups . At week 4, amebic cysts were detected in 5 cases (18.5 %) of Group 1 but in none of the Group 2 (P<0.02) . CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage. Org Lett, 2003 Aug 21, 5(17), 3119 - 21 Synthesis of the tetracyclic core of anthracycline antibiotics by an intramolecular dehydro Diels-Alder approach; Rodriguez D et al.; {reaction: see text} A conceptually new approach to the tetracyclic core of the anthracycline antibiotics is reported . With use of this approach, the 7,8,9,10-tetrahydronaphthacene-5,12-dione skeleton has been synthesized in three steps, from commercially available reagents, in yields of up to 85%. Antibiot Khimioter, 2003, 48(3), 34 - 41 {Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections}; Beketov AS et al.; We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection . A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15) . Patients were randomized to be treated with either 500 mg meropemen i.v . every 8 hours or 500 mg imipenem/cilastatine i.v . every 8 hours or 2 g cefepime i.v . every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours . Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group . Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles . For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles . Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam . The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations . Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol. Respirology, 2003 Sep, 8(3), 359 - 64 Antibiotic desensitization in adults with cystic fibrosis; Burrows JA et al.; OBJECTIVE: Allergic reactions to antibiotics occur in up to 30% of patients with cystic fibrosis (CF) . Repeated antibiotic exposure and immune hyper-responsiveness increase the risk of allergic reactions and may limit antibiotic choice . Desensitization may allow the successful administration of an antibiotic despite previous allergy . We aimed to determine the success of antibiotic desensitization in patients with CF in an adult CF unit over a 7-year period . METHODOLOGY: A retrospective medical record review was performed on the 19 patients who had undergone antibiotic desensitization procedures . Data collected included drug allergy and intolerance profiles, nature of allergies, and the outcome of desensitization procedures . Desensitization procedures were performed in a ward setting according to published methods . RESULTS: Nineteen patients (13 females) reported 62 drug allergies with a mean of 3.3 per patient . Of the 71 desensitization procedures undergone by this group, 54 (76%) were successful . Fifteen of the 19 patients were allergic to two or more beta-lactam antibiotics . Over half of the patients were desensitized to more than one antibiotic . Nine different antibiotics were used in 31 different patient/drug combinations . A successful outcome was achieved in 18/31 (58%) combinations, with three requiring treatment for mild allergic reactions . Allergic reactions caused drug cessation in a total of 19 patient/drug combinations (three after initial successful desensitization and full courses of antibiotics) . Over 50% of these reactions occurred on day 1 . Desensitization failures were more common in patients with well-documented allergic reactions to a specific drug . CONCLUSION: This study demonstrates that multiple antibiotic allergies are common in adults with CF . Cross-reactivity between beta-lactam antibiotics may limit antibiotic choice for the treatment of pulmonary exacerbations . Antibiotic desensitization allows safe and successful treatment in the ward setting of many patients with previous allergies to an antibiotic . In many patients symptoms of allergy still occur and result in cessation of the antibiotics . Use of corticosteroids and antihistamines may improve the success rate of desensitization procedures. Stroke, 2003 Sep, 34(9), e163 - 6 Epub 2003 Aug 07. Antibiotics in primary prevention of stroke in the elderly; Brassard P et al.; BACKGROUND AND PURPOSE: An increasing number of reports have linked infections to atherosclerosis and thrombosis . Thus, use of antibiotics may lower the risk of developing cerebrovascular disease . We investigated whether antibiotic use is associated with the risk of stroke in elderly individuals treated for hypertension . METHODS: A cohort of 29 937 elderly subjects initiating antihypertensive therapy between 1982 and 1995 was formed from the Quebec healthcare insurance database . A nested case-control design was used in which each subject hospitalized with a primary discharge diagnosis of stroke between 1987 and 1995 was matched on calendar time to 5 randomly selected controls from the cohort . Conditional logistic regression was used to estimate odds ratios of stroke after adjustment for predisposing factors . RESULTS: We identified 1888 cases and 9440 controls . The overall adjusted odds ratio for current antibiotic use was 0.80 (95% confidence interval, 0.63 to 1.01), and that for recent use was 0.81 (95% confidence interval, 0.70 to 0.94) . Penicillin was the only individual antibiotic class that showed a protective association across different time windows . No significant association was found between stroke risk and the use of fluoroquinolones, macrolides, tetracyclines, or cephalosporins . CONCLUSIONS: Although no clear, consistent associations between overall antibiotic use and cerebrovascular disease could be found, an intriguing association between penicillin use and stroke should be explored further. J Pharm Biomed Anal, 2003 Aug 21, 32(6), 1219 - 25 Fluorimetric determination of some antibiotics in raw material and dosage forms through ternary complex formation with terbium (Tb(3+)); Bebawy LI et al.; A highly sensitive and specific fluorimetric method was developed for the determination of cefazolin sodium I, cefoperazone sodium II, ceftriaxone sodium III, and cefixime IV . The proposed method involves the formation of ternary complex with Tb(3+) in the presence of Tris buffer . The quenching of the terbium fluorescence due to the complex formation was quantitative for the four studied drugs . The effect of pH, concentration of Tris buffer and terbium were studied . The formation of the complex was highly dependent on the pH . The optimum pH was found to be pH 8 for cefazolin sodium I, ceftriaxone sodium III, cefixime IV and pH 10 for cefoperazone sodium II . The optimum concentration for Tb(3+) was found 1 ml of 10(-4) M solution and for Tris buffer 1 ml of the prepared solution . Under the described conditions, the proposed method was applicable over the concentration range 8.79 x 10(-6)-7.91 x 10(-5), 9.7 x 10(-6)-4.49 x 10(-)5, 6.10 x 10(-6)-2.50 x 10(-5), and 4.92 x 10(-6)-2.95 x 10(-5) mol with mean percentage accuracy of 99.79+/-0.24, 98.97+/-1.25, 100.05+/-0.79, and 100.15+/-0.54 for I, II, III, and IV, respectively . The proposed method was applied successfully for the determination of studied drugs in bulk powder and in pharmaceutical formulations . The results obtained by applying the described method were statistically analyzed and compared with those obtained by applying the official method . The proposed method was used as stability indicating method for the determination of the studied drugs in the presence of their degradation products. Prostaglandins Leukot Essent Fatty Acids, 2003 Oct, 69(4), 229 - 35 Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes; Miyazaki M et al.; We investigated the action of macrolide antibiotics, which are considered to have anti-inflammatory activity, on lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 synthesis and the expression of mRNAs for cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 in human leukocytes . The production of LPS-stimulated PGE2 was significantly increased in peripheral polymorphonuclear leukocytes (PMNLs) and in mononuclear leukocytes (MNLs) . Amounts of mRNAs for COX-2 and cPLA2, but not for COX-1, were enhanced by LPS in PMNLs and MNLs . The LPS-enhanced PGE2 synthesis and the expression of cPLA2 and COX-2 mRNAs were inhibited by clarithromycin, azithromycin and dexamethasone in PMNLs and MNLs . The mRNA expression of COX-1 in PMNLs was decreased by clarithromycin and azithromycin . Macrolide antibiotics inhibited PGE2 synthesis in human leukocytes by suppressing cPLA2, COX-1, and COX-2 mRNA expression . These data indicate one mechanism of macrolide anti-inflammatory activity. Microbiology, 2003 Aug, 149(Pt 8), 2173 - 82 Overexpression of the polynucleotide phosphorylase gene (pnp) of Streptomyces antibioticus affects mRNA stability and poly(A) tail length but not ppGpp levels; Bralley P et al.; The pnp gene, encoding the enzyme polynucleotide phosphorylase (PNPase), was overexpressed in the actinomycin producer Streptomyces antibioticus . Integration of pIJ8600, bearing the thiostrepton-inducible tipA promoter, and its derivatives containing pnp into the S . antibioticus chromosome dramatically increased the growth rate of the resulting strains as compared with the parent strain . Thiostrepton induction of a strain containing pJSE340, bearing pnp with a 5'-flanking region containing an endogenous promoter, led to a 2.5-3 fold increase in PNPase activity levels, compared with controls . Induction of a strain containing pJSE343, with only the pnp ORF and some 3'-flanking sequence, led to lower levels of PNPase activity and a different pattern of pnp expression compared with pJSE340 . Induction of pnp from pJSE340 resulted in a decrease in the chemical half-life of bulk mRNA and a decrease in poly(A) tail length as compared to RNAs from controls . Actinomycin production decreased in strains overexpressing pnp as compared with controls but it was not possible to attribute this decrease specifically to the increase in PNPase levels . Overexpression of pnp had no effect on ppGpp levels in the relevant strains . It was observed that the 3'-tails associated with RNAs from S . antibioticus are heteropolymeric . The authors argue that those tails are synthesized by PNPase rather than by a poly(A) polymerase similar to that found in Escherichia coli and that PNPase may be the sole RNA 3'-polynucleotide polymerase in streptomycetes. Zhonghua Jie He He Hu Xi Za Zhi, 2003 Apr, 26(4), 199 - 202 {Study on the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamase-producing clinical isolates}; Lu J et al.; OBJECTIVE: To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates . METHODS: Antibiotics susceptibility was tested by E-test method, and multi-resistance plasmids were screened and isolated by extracting transformant plasmids . Inserted gene Cassettes of class 1 integron were amplified and analyzed by polymerase chain reaction (PCR) and DNA sequencing . RESULTS: Eight of the nine ESBL-producing plasmids were found to comprise class 1 integron sequence, of them 7 harbored 1 or 2 antibiotic resistant gene cassettes which encoding resistance to aminoglycosides (aacA4, aadA2 or aadA5), trimethoprim (dhfrA12 or dfrA17), rifampicin (arr-3) and chloramphenicol (cmlA6) . The function of these gene cassettes corresponded to the resistance profiles of their electro-transformants . CONCLUSION: Multi-resistance gene cassettes located on plasmids and mediated by class 1 integron may play an important role in causing the development and dissemination of multiple-antibiotic resistance in ESBL-producing clinical isolates. J Chromatogr A, 2003 Jun 27, 1003(1-2), 21 - 8 Determination of antibiotics from soil by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry; Schlusener MP et al.; A method for the analysis of several macrolide and ionophore antibiotics, as well as tiamulin, from soil was developed using pressurized liquid extraction (PLE), reversed-phase liquid chromatography and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry (LC-APCI+-MS-MS) . The analytes were extracted from soil by PLE in 30 min and the extracts were cleaned up by solid-phase extraction (SPE) on a diol SPE cartridge . Liquid chromatographic (LC) separation of the antibiotics was achieved in 35 min . Recovery experiments were performed using spiked soil and concentrations varying from 1 to 2000 microg/kg . By using a macrolide internal standard the recovery rates for the macrolides erythromycin and roxithromycin ranged from 43 to 94% (RSD 20-23%), for the ionophore salinomycin the recovery rate was 76% (RSD 29%), while the pleuromutilin tiamulin was completely recovered . The limits of detection ranged from 0.2 to 1.6 microg/kg . In soil samples a maximum concentration of 0.7 microg/kg tiamulin was found. Can J Vet Res, 2003 Jul, 67(3), 239 - 40 Effects of aminoglycoside antibiotics on renal antioxidants, malondialdehyde levels, and some serum biochemical parameters; Yazar E et al.; Effects of amikacin, gentamicin, kanamycin, and streptomycin on renal tissue superoxide dismutase, glutathione peroxidase, glutathione and malondialdehyde, serum creatinine, potassium, sodium, total protein, glucose, uric acid, and total bilirubin levels were investigated . All aminoglycoside antibiotics decreased renal tissue glutathione levels. Nucleic Acids Res, 2003 Aug 1, 31(15), 4410 - 6 Hydropathic analysis of the free energy differences in anthracycline antibiotic binding to DNA; Cashman DJ et al.; Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding . The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values . In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of -3.6 +/- 1.1 kcal x mol(-1) (experimental -2.5 +/- 0.5 kcal x mol(-1)) from the groove binding daunosamine sugar . The net energetic contribution of removing the hydroxyl at position C9 is -0.7 +/- 0.7 kcal x mol(-1) (-1.1 +/- 0.5 kcal x mol(-1)) . The energetic contribution of the 3' amino group in the daunosamine sugar (when replaced with a hydroxyl group) is -3.7 +/- 1.1 kcal x mol(-1) (-0.7 +/- 0.5 kcal x mol(-1)) . We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine . The energetic contribution of the hydroxyl group at C14 is +0.4 +/- 0.6 kcal x mol(-1) (-0.9 +/- 0.5 kcal x mol(-1)), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA . Also, there appears to be considerable conformational uncertainty in this region . This computational procedure calibrates our methodology for future analyses where experimental data are unavailable. Ambul Pediatr, 2003 Jul-Aug, 3(4), 203 - 10 Correlates of parental antibiotic knowledge, demand, and reported use; Kuzujanakis M et al.; BACKGROUND: Clinicians cite parental misconceptions and requests for antibiotics as reasons for inappropriate prescribing . AIMS: To identify misconceptions regarding antibiotics and predictors of parental demand for antibiotics and to determine if parental knowledge and attitudes are associated with use . METHODS: Survey of parents in 16 Massachusetts communities . Domains included antibiotic-related knowledge, attitudes about antibiotics, antibiotic use during a 12-month period, demographics, and access to health information . Bivariate and multivariate analyses evaluated predictors of knowledge and proclivity to demand antibiotics . A multivariate model evaluated the associations of knowledge, demand, and demographic factors with parent-reported antibiotic use . RESULTS: A total of 1106 surveys were returned (response rates: 54% and 32% for commercially-insured and Medicaid-insured families) . Misconceptions were common regarding bronchitis (92%) and green nasal discharge (78%) . Two hundred sixty-five (24%) gave responses suggesting a proclivity to demand antibiotics . Antibiotic knowledge was associated with increased parental age and education, having more than 1 child, white race, and receipt of media information on resistance . Factors associated with a proclivity to demand antibiotics included decreased knowledge, pressure from day-care settings, lack of alternatives offered by clinicians, and lack of access to media information . Among all respondents, reported antibiotic use was associated with younger child age and day-care attendance . Among Medicaid-insured children only, less antibiotic knowledge and tendency to demand antibiotics were associated with higher rates of antibiotic use . CONCLUSIONS: Misconceptions regarding antibiotic use are widespread and potentially modifiable by clinicians and media sources . Particular attention should be paid to Medicaid-insured patients in whom such misconceptions may contribute to inappropriate prescribing. Chem Commun (Camb), 2003 Jul 21, (14), 1692 - 3 Concerted interaction between conjugated double bond CHs and multiple OHs in polyene macrolide antibiotic chainin: weak =C-H...O interactions responsible for intrinsic molecular assembly; In Y et al.; The concerted interactions observed between five conjugated double bond CHs and four hydroxy Os in the crystal of chainin, a polyene macrolide antibiotic, clarified the existence of unprecedented, weak =C-H...O interactions, which is important for forming its intrinsic molecular assembly. Fam Pract, 2003 Aug, 20(4), 417 - 9 Acute otitis media--a brief explanation to parents and antibiotic use; Pshetizky Y et al.; BACKGROUND: Acute otitis media (AOM) is a common self-limiting disease in children . Antibiotic use is controversial . Physicians in the USA and in Israel prescribe antibiotics almost universally, while physicians in other countries report good outcome without any treatment . Parents' expectation is an important factor influencing a physician's decision to prescribe antibiotics . OBJECTIVES: Our aim was to assess whether a brief explanation to parents regarding the self-limited nature of AOM and the controversy regarding antibiotic prescription for the disease will influence the parents' decision regarding antibiotics use . METHODS: Parents of the children participating in the study in two primary care clinics belonging to HMO-Clalit Health Services (CHS) in the southern district of Israel were randomly assigned to an intervention (44) and control (37) group . The intervention group received the brief explanation . The two groups received prescription for antibiotics . The subjects comprised 81 children aged 3 months to 4 years visiting the family practice clinics and diagnosed with AOM . The rate of antibiotics purchase, using the prescription given and the factors influencing the decision were evaluated . RESULTS: Fewer parents administered antibiotics to their children in the intervention group compared with the control group (37% versus 63%, respectively, P < 0.0001) . Mother's education level was the only factor found to be significantly lower in the group that eventually purchased antibiotics (P < 0.05) . CONCLUSIONS: In children with AOM, a brief explanation by the family physician to the child's parents about the disease and the expected spontaneous recovery could decrease antibiotic use by approximately 50%. J Antibiot (Tokyo), 2003 May, 56(5), 454 - 8 Takanawaenes, novel antifungal antibiotics produced by Streptomyces sp . K99-5278 . II . Structure elucidation; Fukuda T et al.; The structures of takanawaenes A, B and C, novel antifungal antibiotics produced by Streptomyces sp . K99-5278, were elucidated by various spectroscopic analyses including UV and NMR, and spectrometric analyses including MS . They have the common skeleton of a 28-membered pentaene macrolide. Salud Publica Mex, 2003 May-Jun, 45(3), 159 - 64 Use of antibiotics in upper respiratory infections on patients under 16 years old in private ambulatory medicine; Pelaez-Ballestas I et al.; OBJECTIVE: To assess antibiotic use for upper respiratory infections (URI) treatment on patients under 16 years-old who are beneficiaries of a pre-paid health care scheme . MATERIAL AND METHODS: A database containing the record of all the medical prescriptions for URI treatment, from May 1997 to April 1998 was analyzed . Patients were under 16 years old and had been diagnosed with common colds, pharyngitis, bronchitis, sinusitis, otitis, and other unspecified upper respiratory tract infections . Three hundred and fifty-one physicians of seven different specialties who attended 25,300 beneficiaries wrote such prescriptions . RESULTS: A total of 30,889 assorted medications were prescribed to 5,533 patients with the above diagnoses . Antibiotics were prescribed for 77.5% of all diagnoses, ranging from 58% for pharyngitis to 91% for laryngitis . The most frequently used antibiotics were: penicillin, cephalosporins, and macrolides . CONCLUSIONS: This study presents the information of antibiotics prescription practices for URI in a pre-paid health plan in Mexico . These findings may be used to support specific campaigns for rational use of antibiotics among children attended at private ambulatory health care practices. Chemistry, 2003 Jul 21, 9(14), 3282 - 91 Multistep solid-phase synthesis of an antibiotic and receptor tyrosine kinase inhibitors using the traceless phenylhydrazide linker; Stieber F et al.; The hydrazide group is an oxidatively cleavable traceless linker for solid-phase chemistry . This linker technology was used to develop a multistep solid-phase synthesis of an antibiotic that is active against Mycobacterium tuberculosis . Furthermore, we describe an efficient method for the traceless synthesis of 2-aminothiazoles that display dual inhibitory activity against the receptor tyrosine kinases VEGFR-2 and Tie-2 . The synthesis method proceeds through 9 steps on the solid phase and should give access to a much larger library of 2-aminothiazoles, from which a new class of anti-angiogenesis drugs may be developed. J Mol Biol, 2003 Jul 25, 330(5), 1061 - 75 Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit; Hansen JL et al.; Structures of anisomycin, chloramphenicol, sparsomycin, blasticidin S, and virginiamycin M bound to the large ribosomal subunit of Haloarcula marismortui have been determined at 3.0A resolution . Most of these antibiotics bind to sites that overlap those of either peptidyl-tRNA or aminoacyl-tRNA, consistent with their functioning as competitive inhibitors of peptide bond formation . Two hydrophobic crevices, one at the peptidyl transferase center and the other at the entrance to the peptide exit tunnel play roles in binding these antibiotics . Midway between these crevices, nucleotide A2103 of H.marismortui (2062 Escherichia coli) varies in its conformation and thereby contacts antibiotics bound at either crevice . The aromatic ring of anisomycin binds to the active-site hydrophobic crevice, as does the aromatic ring of puromycin, while the aromatic ring of chloramphenicol binds to the exit tunnel hydrophobic crevice . Sparsomycin contacts primarily a P-site bound substrate, but also extends into the active-site hydrophobic crevice . Virginiamycin M occupies portions of both the A and P-site, and induces a conformational change in the ribosome . Blasticidin S base-pairs with the P-loop and thereby mimics C74 and C75 of a P-site bound tRNA. J Am Acad Audiol, 2003 Apr, 14(3), 157 - 68; quiz 170-1 Audiologic monitoring for potential ototoxicity in a phase I clinical trial of a new glycopeptide antibiotic; Campbell KC et al.; This study describes audiologic methodology and results for evaluating potential ototoxicity in a phase I clinical trial of a new glycopeptide . This study was conducted under good clinical practices, which are regulated by the US Food and Drug Administration (FDA) (21 Code of Federal Regulations), and input from the FDA was sought prior to study implementation . Healthy, normal volunteers underwent extensive medical and audiologic assessments as part of this phase I dose- escalation study of dalbavancin, a new glycopeptide, to assess potential side effects . Audiologic monitoring included air-conduction thresholds in the conventional (0.25-8 kHz) and high-frequency (10-16 kHz) ranges . At baseline, subjects were also tested using word recognition, bone conduction testing if indicated, and tympanometry . Full testing was to be repeated if any subject met the American Speech-Language-Hearing Association (ASHA) 1994 criteria for ototoxic change . However, no subjects demonstrated ototoxic change after receiving dalbavancin, nor were any false-positive results obtained. Eur J Clin Pharmacol, 2003 Aug, 59(4), 331 - 5 Epub 2003 Jul 15. Utilisation of antibiotics in young children: opposite relationships to adult educational levels in Danish and Swedish counties; Melander E et al.; BACKGROUND: Antibiotic utilisation varies profoundly among and within countries, and the extent of antibiotic utilisation correlates with the frequency of bacterial resistance, particularly among children . Hence, it is important to assess which factors may influence prescribing . In addition to variations in morbidity, health-care organisation, drug regulatory and supply systems, prescriber's attitudes, parents' behaviour, attitudes and socio-economic positions seem important . We compared socio-economic position (educational level of adults) and antibiotic utilisation in children in the municipalities within a Danish and a Swedish county which are geographically close, have similar social and economic development, and similar drug regulatory and supply systems . METHODS: Data on antibiotic utilisation (1998), expressed in defined daily doses per 1000 inhabitants per day (DDD/TID), were obtained from the Copenhagen County Health Insurance register and from the National Corporation of Swedish Pharmacies . Data on municipal educational levels were obtained from Statistics Denmark and Statistics Sweden . RESULTS: The utilisation of antibiotics in 0- to 6-year-old children was higher in the Swedish than in the Danish county but varied between the municipalities within both the Swedish (9.6-17.7 DDD/TID) and the Danish (8.0-12.9 DDD/TID) counties . Most notably, utilisation rates correlated negatively with the education levels in the Danish (r=-0.539, P=0.021) but positively in the Swedish (r=+0.390, P=0.025) municipalities . CONCLUSION: The observed variations in antibiotic prescribing may reflect different parental and/or prescriber attitudes towards use of antibiotics and they emphasise that antibiotic prescribing is influenced by factors other than the prevalence of bacterial infections . Relationships between socio-economic position (educational level) and drug utilisation should not be generalised from one area to another. Bioorg Med Chem Lett, 2003 Aug 4, 13(15), 2607 - 10 Synthesis and activity of novel benzoxazole derivatives of mannopeptimycin glycopeptide antibiotics; Sum PE et al.; A series of benzoxazole derivatives of the mannopeptimycin glycopeptide antibiotics was synthesized via a novel benzoxazole formation reaction by treating aminophenol of mannopeptimycin-beta with an aldehyde and DDQ in DMF . Some of these derivatives (e.g., 5b, 5d, 5m, and 7b) showed good activity against Gram-(+) bacteria when compared to the parent compound mannopeptimycin-beta. J AOAC Int, 2003 May-Jun, 86(3), 494 - 500 Survey of residual tetracycline antibiotics and sulfa drugs in kidneys of diseased animals in the Aichi Prefecture, Japan (1995-1999); Oka H et al.; Animal kidneys were collected in order to survey the incidence of tetracycline (TC) antibiotics and sulfa (SA) drug residues in slaughtered animals that did not pass inspection for human consumption by the Japanese Food Sanitation Law and the Meat Inspection Law at the slaughterhouses in Aichi Prefecture, Japan, from April 1995 to March 2000 . The kidneys were analyzed by AOAC Official Method 995.09 for TCs and our previously reported liquid chromatographic method for SAs . Among 292 animals (94 cattle and 198 pigs), 106 (36.6%) and 41 (14.0%) contained TCs and SAs, respectively, including chlortetracycline, 59 (20.2%); oxytetracycline, 47 (16.1%); sulfamonomethoxine, 35 (12.0%); sulfadimethoxine and sulfamethoxazole, each 2 (0.7%); and sulfamerazine and sulfisoxazole, each 1 (0.3%) . A small number of animals (5 cattle and 9 pigs) contained more than one drug residue . The frequency of residue detections was significantly higher for TCs than SAs in both cattle and pig kidneys (p < 0.001). J AOAC Int, 2003 May-Jun, 86(3), 484 - 9 Kinetic spectrophotometric determination of the macrolide antibiotic josamycin in formulations; Al-Majed AA et al.; A simple kinetic spectrophotometric method was developed for the determination of josamycin in its dosage forms . The method is based on oxidation of the drug with alkaline potassium permanganate at room temperature for a fixed time of 20 min and measuring the produced green color at 611 nm . The absorbance-concentration plot is rectilinear over the range of 2-10 microg/mL (2.4 x 10(6)-1.2 x 10(-5)M) with minimum detectability of 1.0 microg/mL (1.2 x 10(-6)M) . The determination of josamycin by fixed concentration and the rate-constant methods is also feasible with the calibration equations obtained, but the fixed-time method proved to be more applicable . The procedure was applied successfully to commercial tablets, and statistical analysis showed that the results compared favorably with those obtained by reference methods . The effect of sensitizers and surfactants on the performance of the proposed method was also studied . A proposal of the reaction pathway was presented. Ann Transplant, 2003, 8(1), 70 - 8 Cellular viability and ultrastructure of stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was an evaluation of viability and damage of biological cells sterilized with antibiotics and cryopreserved a year after the implantation . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one-year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histologic investigations were based on paraffin sections of formalin-fixed valve cusps, stained with H&E and Masson trichrome . Valve viability was assessed using intravital staining with fluoresceine diacetate, whereas damaged cells were visualized by intravital staining with neutral red . Additionally, the ultrastructural studies were performed . The viability and ultrastructural results were compared with the pathologic process in the valve . Conclusions: 1 . preliminary preparation with antibiotic sterilisation and cryopresrevation induces valve leaflet oedema and degenerative ultrastructural processes, colliquative cell necrosis and apoptotic morphology of a part of valve cells; 2 . cryopreserved and antibiotic sterilised pulmonary valve after one-year implantation behaves lining cells, but ultrastructural changes indicates many degenerative phenomena in smaller degree than after preparation, sterilization and cryopreservation . Histopathologically the degenerative changes were prevalent. Ann Transplant, 2003, 8(1), 55 - 69 Mathematical analysis of calcifications in stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was morphometric and mathematic analysis of calcification profiles present in the leaflets of a cryopreserved and alive heart valve depending on the diagnosed pathologic process . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one-year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histologic investigations were based on paraffin sections of formalin-fixed valve cusps, stained with H&E and Masson trichrome, calcium deposits were stained von Kossa technique . The measured values included: 1 . area and equivalent diameter, 2 . length, 3 . breadth, 4 . perimeter, 5 . elongation, 6 . roundness, 7 . fullness coefficient . Conclusions: 1 . A process of initial processing and cryopreservation of biological valve increases a dimension and disturbs a shape of microcalcifications . 2 . Cryopreserved biological valves explanted after one-year implantation into an animal in a tricuspid position possess microcalcifications and calcification foci . The size of microcalcifications decreases together with an intensification of degenerative processes of the connective tissue, especially in hyalinization . Hyalinization of the biological valve tissue seems to be favorable for a valve durability and as a pathological process decreasing calcification . 3 . Mathematic analysis of morphometric features defining differences in size and shape of each calcification indicate morphologic and morphometric autonomy of calcifications, characteristic for the analyzed group of valve pathologic changes. Ann Transplant, 2003, 8(1), 45 - 54 Integrative measurements of calcifications in stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position; Nozynski JK et al.; The aim of the study was the characterization of calcification in the leaflets of a cryopreserved and alive heart valve depending on the diagnosed pathologic process . Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one year period . After this time the valves removed and studied morphologically . The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures . Histological investigations were based on paraffin sections, calcium deposits were stained von Kossa technique . The measured values included integrative parameters as: 1 . area fraction, 2 . number of calcifications per area, 3 . anisotropy . Conclusions: 1 . A process of initial processing, sterilization and cryopreservation of biological valve increases a number of microcalcifications . 2 . Cryopreserved biological valves explanted after one-year implantation into an animal in a tricuspid position possess fine calcifications and calcification foci . A number and size of fine calcifications decreases together with an intensification of degeneration and regressive processes of the connective tissue, especially in hyalinization . Hyalinization of the biological valve tissue seems to be favorable for a valve durability and as a pathological process decreasing calcification . 3 . Mathematic analysis of morphometric features defining density and structure of calcifications indicate similarities among cryopreservation and initial processing groups, hyalinization, inflammation, whereas in a group of calcification foci, the similarity can be noticed between inflammation and hyalinization group. J Perinatol, 2003 Jul-Aug, 23(5), 372 - 7 Pneumonia in term neonates: laboratory studies and duration of antibiotic therapy; Engle WD et al.; OBJECTIVES: To compare 2 days of antibiotic therapy (AT) to 4 days of AT in neonates with pneumonia and to assess the usefulness of neutrophil values (NV), C-reactive protein (CRP), and procalcitonin (PCT) in this population . DESIGN: The study population consisted of consecutive, eligible term neonates begun on AT for suspected pneumonia . Of 51 neonates, 26 qualified for randomization (14, 2-day group; 12, 4-day group) . NV were obtained with the initial evaluation and 12 and 24 hours later . CRP and PCT were obtained 12 and 48 hours after the initial evaluation . RESULTS: None of the 12 neonates in the 4-day group developed recurrent respiratory symptoms . Three of the 14 neonates randomized to the 2-day group had recurrence of symptoms, resulting in study termination . NV, CRP, and PCT were similar in the 2- and 4-day groups . In the three neonates who developed respiratory symptoms, all absolute total neutrophil values and five out of nine absolute total immature neutrophil values were abnormal . However, all immature:total neutrophil values were normal, and CRP was strikingly elevated in only one neonate; only one of six PCT values was abnormal . In a secondary analysis of all 51 study neonates, CRP and PCT did not provide additional benefit over NV in differentiating neonates with pneumonia . CONCLUSIONS: Four days of AT appears to be adequate for selected term neonates with pneumonia; however, 2 days of AT appears to be inadequate for this population . Relative to NV, CRP and PCT appear to have a limited role. Can J Gastroenterol, 2003 Jun, 17 Suppl B, 49B - 52B Helicobacter pylori resistance to antibiotics: prevalence, mechanism, detection . What's new? Megraud F. Helicobacter pylori resistance to antibiotics is increasingly reported and may limit the efficacy of current treatment regimens . Their resistance mechanism has been found to be point mutations for all antibiotics . Macrolide resistance is the most clinically important, but can be detected efficiently by molecular methods . Metronidazole resistance has limited clinical impact but testing methods are not reliable . Seldomly found cases of resistance, such as to amoxicillin and tetracycline, have had their mechanism recently elucidated . The existence of rapid and practical methods for the detection of macrolide resistance (eg, Fluorescence Resonance Energy Transfer assay) should improve management of H pylori-positive patients in the future, by allowing an adapted first-line therapy. Am J Respir Crit Care Med, 2003 Nov 1, 168(9), 1060 - 7 Epub 2003 Jul 03. Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia; Ost DE et al.; The optimal strategy for ventilator-associated pneumonia remains controversial . To clarify the tradeoffs involved, we performed a decision analysis . Strategies evaluated included antibiotic therapy with and without diagnostic testing . Tests that were explored included endotracheal aspirates, bronchoscopy with protected brush or bronchoalveolar lavage, and nonbronchoscopic mini-bronchoalveolar lavage (mini-BAL) . Outcomes included dollar cost, antibiotic use, survival, cost-effectiveness, antibiotic use per survivor, and the outcome perspective of financial cost-antibiotic use per survivor . Initial coverage with three antibiotics was better than expectant management or one or two antibiotic approaches, leading to both improved survival (54% vs . 66%) and decreased cost (US dollars 55447 vs . US dollars 41483 per survivor) . Testing with mini-BAL did not improve survival but did decrease costs (US dollars 41483 vs . US dollars 39967) and antibiotic use (63 vs . 39 antibiotic days per survivor) . From the perspective of minimizing cost, minimizing antibiotic use, and maximizing survival, the best strategy was three antibiotics with mini-BAL. Manag Care Interface, 2003 Jun, 16(6), 34 - 40, 55 Costs of broad-spectrum antibiotic use for acute sinusitis, chronic bronchitis, and pneumonia in a managed care population; Coughlin CM et al.; Respiratory infections place a heavy burden on patients, providers, employers, and health care systems . The prescribing of antibiotics is common, despite the fact that many respiratory conditions are caused by viruses . The economic effect of treating respiratory tract infections with broad-spectrum antibiotics was retrospectively analyzed by means of health care claims data from six managed care health plans affiliated with a large national insurer . A regression model was used to adjust for factors that can influence treatment costs, such as age, baseline cost, retreatment, and drug cost . The costs of treating chronic bronchitis, pneumonia, and acute sinusitis with moxifloxacin, gatifloxacin and nonfluoroquinolone broad-spectrum agents were significantly lower than the costs associated with levofloxacin treatment. Appl Environ Microbiol, 2003 Jul, 69(7), 4256 - 9 Development of antibiotic-overproducing strains by site-directed mutagenesis of the rpsL gene in Streptomyces lividans; Okamoto-Hosoya Y et al.; Certain rpsL (which encodes the ribosomal protein S12) mutations that confer resistance to streptomycin markedly activate the production of antibiotics in Streptomyces spp . These rpsL mutations are known to be located in the two conserved regions within the S12 protein . To understand the roles of these two regions in the activation of silent genes, we used site-directed mutagenesis to generate eight novel mutations in addition to an already known (K88E) mutation that is capable of activating antibiotic production in Streptomyces lividans . Of these mutants, two (L90K and R94G) activated antibiotic production much more than the K88E mutant . Neither the L90K nor the R94G mutation conferred an increase in the level of resistance to streptomycin and paromomycin . Our results demonstrate the efficacy of the site-directed mutagenesis technique for strain improvement. Br J Cancer, 2003 Jul 7, 89(1), 43 - 9 Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study; Innes HE et al.; Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy . However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate . The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient intravenous antibiotics in patients with low-risk neutropenic fever . In all, 126 episodes of low-risk neutropenic fever occurred in 102 patients . Patients were randomised to receive either: an oral regimen of ciprofloxacin (750 mg 12 hourly) plus amoxicillin-clavulanate (675 mg 8 hourly) for a total of 5 days, or a standard intravenous regimen of gentamicin and tazocin (piperacillin/tazobactam) until hospital discharge . Patients randomised to oral antibiotics were eligible for discharge following 24 h of hospitalisation, if clinically stable and symptomatically improved . The efficacy of the two arms was similar: initial treatment was successful without antibiotic modification in 90% of episodes in the intravenous arm and 84.8% of episodes in the oral arm, P=0.55, absolute difference between the groups 5.2%; 95% confidence interval (CI) for the difference -7 to 17.3% . Only one episode in the oral arm was associated with significant clinical deterioration: this occurred within the initial in-patient assessment period . The median in-patient stay was 4 days in the intravenous arm (range 2-8) and 2 days in the oral arm (range 1-16 days), P&<0.0005 . The reduction in hospital stay led to significant cost-savings in the oral arm . In conclusion, this study suggests that oral antibiotics in conjunction with early hospital discharge for patients who remain stable after a 24 h period of in-patient monitoring offers a feasible and cost-effective alternative to conventional management of low-risk neutropenic fever. J Bacteriol, 2003 Jul, 185(14), 4276 - 9 Structural insight into the antibiotic action of telithromycin against resistant mutants; Berisio R et al.; The crystal structure of the ketolide telithromycin bound to the Deinococcus radiodurans large ribosomal subunit shows that telithromycin blocks the ribosomal exit tunnel and interacts with domains II and V of the 23S RNA . Comparisons to other clinically relevant macrolides provided structural insights into its enhanced activity against macrolide-resistant strains. Chem Biol, 2003 Jun, 10(6), 541 - 9 The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by nonomuraea species; Sosio M et al.; The glycopeptide A40926 is the precursor of dalbavancin, a second-generation glycopeptide currently under clinical development . The dbv gene cluster, devoted to A40926 biosynthesis, was isolated and characterized from the actinomycete Nonomuraea species ATCC39727 . From sequence analysis, 37 open reading frames (ORFs) participate in A40926 biosynthesis, regulation, resistance, and export . Of these, 27 ORFs find a match in at least one of the previously characterized glycopeptide gene clusters, while 10 ORFs are, so far, unique to the dbv cluster . Putative genes could be identified responsible for some of the tailoring steps (attachment of glucosamine, sugar oxidation, and mannosylation) expected during A40926 biosynthesis . After constructing a Nonomuraea mutant by deleting dbv ORFs 8 to 10, the novel compound dechloromannosyl-A40926 aglycone was isolated. J Am Chem Soc, 2003 Jul 9, 125(27), 8238 - 43 Total synthesis of an antitumor antibiotic, Fostriecin (CI-920); Miyashita K et al.; The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described . A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C . The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H . Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction . The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction . The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative . Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one . The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers. J Am Chem Soc, 2003 Jul 9, 125(27), 8218 - 27 Solid-phase synthesis of bleomycin group antibiotics . Construction of a 108-member deglycobleomycin library; Leitheiser CJ et al.; The bleomycins (BLMs) are structurally related glycopeptide antibiotics isolated from Streptomyces verticillus that mediate the sequence-selective oxidative damage of DNA and RNA . Deglycobleomycin, which lacks the carbohydrate moiety, cleaves DNA analogously to bleomycin itself, albeit less potently, and has been used successfully for analyzing the functional domains of bleomycin . Although structural modifications to bleomycin and deglycobleomycin have been reported, no bleomycin or deglycobleomycin analogue having enhanced DNA cleavage activity has yet been described . The successful synthesis of a deglycobleomycin on a solid support has permitted the facile solid-phase synthesis of 108 unique deglycobleomycin analogues through parallel solid-phase synthesis . Each of the deglycobleomycin analogues was synthesized efficiently; the purity of each crude product was greater than 60%, as determined by HPLC integration . The solid-phase synthesis of the deglycobleomycin library provided near-milligram to milligram quantities of each deglycobleomycin, thereby permitting characterization by (1)H NMR and high-resolution mass spectrometry . Each analogue demonstrated supercoiled plasmid DNA relaxation above background cleavage; the library included two analogues that mediated plasmid relaxation to a greater extent than the parent deglycobleomycin molecule. J Biochem Biophys Methods, 2003 Jun 30, 56(1-3), 297 - 309 Size-exclusion high-performance liquid chromatography in the study of the autoassociating antibiotic gramicidin A in micellar milieu; Bano MC et al.; Gramicidin A (gA) is a polypeptide antibiotic which forms dimeric channels specific for monovalent cations in biological membranes . It is a polymorphic molecule that adopts several different conformations, double-stranded (ds) helical dimers (pore conformation) and single-stranded beta-helical dimers (channel conformation) . This study investigated the conformational adaptability of gramicidin A when incorporated into micelles as membrane-mimetic model system . Taking advantage of our reported, versatile, size-exclusion high-performance liquid chromatography (SE-HPLC) strategy that allows the separation of double-stranded dimers and monomers, we have quantitatively characterized the conformational transition undergone by the peptide in the micellar milieu . The importance of both hydrophobic/hydrophilic moieties of the amphipaths in the stabilization of concrete conformational species is demonstrated using detergents with different hydrocarbon chain length and/or polar head . SE-HPLC is a valuable, rapid, accurate technique for the structural characterization of hydrophobic autoassociating peptides that work in lipid environments such as biological membranes. Anal Sci, 2003 Jun, 19(6), 927 - 32 Resonance Rayleigh scattering measurement of aminoglycoside antibiotics with Evans Blue; Liu SP et al.; In a weak acid medium, some aminoglycoside antibiotics, such as kanamycin (KANA), gentamicin (GEN), tobramycin (TOB) and neomycin (NEO), or acid bisazo dye Evans Blue (EB) can only produce very weak resonance Rayleigh scattering (RRS) signals . However, when two agents react with each other to form ion-association complexes, the RRS intensity can be greatly enhanced and a new RRS spectrum with a significant enhancement of the RRS intensity in the wavelength range from 350 nm to 600 nm can be observed . The maximum scattering peak is at 570 nm . There is a linear relationship between the RRS intensity and the antibiotic concentration in the range of 0.01-6.0 microg mL(-1) at 570 nm . This RRS method for the determination of aminoglycoside antibiotics at trace-amount levels has been developed . The detection limits (3sigma) of the four antibiotics, whose order of sensitivity from high to low ranks as KANA > NEO > TOB > GEN, are 5.2-6.9 ng mL(-1) . This method has good selectivity and has been successfully applied to the quick determination of antibiotics not only for injections and ear drops, but for clinic serum samples as well . In addition, the reaction mechanism by using a quantum chemistry method and the influencing factors of the RRS spectra and the enhancement reasons of RRS have been discussed. FEBS Lett, 2003 Jul 10, 546(2-3), 241 - 6 Membrane topology of ABC-type macrolide antibiotic exporter MacB in Escherichia coli; Kobayashi N et al.; MacB is an ABC-type membrane protein that exports only macrolide compounds containing 14- and 15-membered lactones, cooperating with a membrane fusion protein, MacA, and a multifunctional outer membrane channel, TolC . We determined the membrane topology of MacB by means of site-specific competitive chemical modification of single cysteine mutants . As a result, it was revealed that MacB is composed of four transmembrane (TM) segments with a cytoplasmic N-terminal nucleotide binding domain of about 270 amino acid residues and a periplasmic large hydrophilic polypeptide between TM segments 1 and 2 of about 200 amino acid residues. Expert Opin Pharmacother, 2003 Jul, 4(7), 1097 - 103 Acne: comparing hormonal approaches to antibiotics and isotretinoin; Larsen TH et al.; Acne is a common and disfiguring disease affecting a significant proportion of the general population . In milder cases topical therapy is sufficient . However, in more severe cases where papulopustular or nodulocystic acne is present, there is a need of systemic treatment . The latter include antibiotics, anti-androgens and retinoids . A systematic review of the literature was performed of systemic monotherapy using these drugs . Because of the significant methodological variability of the studies examined, it was not possible to make a meta-analysis . Instead the overall effects were assessed by calculating mean weighted effects across different reported effect variables . Isotretinoin scored 85 +/- 10% improvement compared with the baseline, whereas tetracyclines and cyproterone acetate plus ethinyloestradiol were less effective (54 +/- 3% versus 65 +/- 4% improvement compared with baseline, respectively) . Moreover, studies suggested that isotretinoin reduces the risk of acne relapse in the few studies that included a follow-up period . A number of restrictions limit the general use of these drugs as monotherapy, e.g., potential teratogenicity . There is a continued need for effective drugs for the therapy of acne, although judicious combined use of existing topical and systemic therapies offers great relief to many patients . In addition, methodological problems in previous studies prevent adequate synthesis of existing knowledge within the framework of evidence-based medicine . There is therefore a demand for future standardisation of further acne studies to enable direct comparison of different treatment efficacies. J Chromatogr A, 2002 Mar 1, 948(1-2), 193 - 201 Preparation of monodisperse porous polymethacrylate microspheres and their application in the capillary electrochromatography of macrolide antibiotics; Zhang S et al.; Monodisperse poly(glycidyl methacrylate-divinylbenzene) microspheres were prepared by a simple one-step dispersion polymerization process . Examination of the polymeric microspheres showed that they had a mean particle diameter of 3 microm and dual pore size distribution with mean pore diameters of 300 and 800 A . The microspheres were functionalized by introducing quaternary ammonium/octadecyl groups to obtain positively charged beads in a wide pH range . The functionalized beads were packed into fused-silica capillary having 50 microm inner diameter and used to separate erythromycin derivatives by capillary electrochromatography (CEC) . These samples require gradient elution when separated by high-performance liquid chromatography (HPLC) or micro-HPLC, but with the new columns isocratic elution suffices for their separation by CEC . The column efficiency ranged from 40,000 to 50,000 theoretical plates. Am J Respir Crit Care Med, 2003 Sep 1, 168(5), 581 - 7 Epub 2003 Jun 26. In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells; Shimizu T et al.; To examine the in vivo effects of macrolide antibiotics on mucus hypersecretion, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats and by intranasal LPS instillation . Oral administration of clarithromycin (CAM) (5-10 mg/kg) significantly inhibited OVA- and LPS-induced mucus production and neutrophil infiltration, whereas josamycin and ampicillin showed no effect . In vitro effects of macrolide antibiotics on airway epithelial cells were examined using NCI-H292 cells and human nasal epithelial cells cultured in air-liquid interface . Mucus secretion was evaluated by ELISA using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18) . CAM and erythromycin significantly inhibited spontaneous and tumor necrosis factor-alpha (20 ng/ml)-induced mucus secretion from NCI-H292 cells at 10-6 to 10-7 M and from human nasal epithelial cells at 10-4 to 10-5 M . MUC5AC messenger RNA expression was also significantly inhibited . These results indicate that the 14-member macrolide antibiotics, CAM and erythromycin, exert direct inhibitory effects on mucus secretion from airway epithelial cells and that they may be useful for the treatment of mucus hypersecretion caused by allergic inflammation and LPS stimulation. Ann Emerg Med, 2003 Jul, 42(1), 117 - 23 Continuity of antibiotic therapy in patients admitted from the emergency department; Shah MN et al.; STUDY OBJECTIVE: We describe discontinuities in antibiotic therapy in patients with community-acquired pneumonia admitted from the emergency department (ED) to an inpatient unit . METHODS: We performed a retrospective cohort study of patients with community-acquired pneumonia admitted from the ED to the internal medicine service at an academic tertiary care hospital between July 1997 and June 1999 . We characterized the frequency of antibiotic delays after arrival on the inpatient unit in relation to antibiotic dosing intervals . We performed paired analysis on the patients treated both with an antibiotic dosed every 6 hours and an antibiotic dosed every 24 hours . RESULTS: Three hundred seventy-five patients were identified . The mean age was 61 years . Sixty-two percent were female . Five hundred fifty-one antibiotic doses were started in the ED and continued on the inpatient unit, with 177 ordered every 6 hours, and 351 ordered every 24 hours . Seventy-five percent of the antibiotics dosed every 6 hours and 19% of the antibiotics dosed every 24 hours were delayed more than 30 minutes (P <.001) . Analysis of the 146 patients receiving both an antibiotic dosed every 6 and 24 hours showed that the first inpatient dose of antibiotics administered every 6 hours were 10 times more likely to be delayed than antibiotics dosed every 24 hours (95% confidence interval 5.0 to 23) . The median delay for antibiotics dosed every 6 hours was 258 minutes (range 45 to 3,360 minutes), and the median delay for antibiotics dosed every 24 hours was 192 minutes (range 32 to 2,124 minutes) . CONCLUSION: Discontinuous therapy, represented through a delayed first inpatient antibiotic dose, is common in patients with community-acquired pneumonia admitted from the ED . Although the effect on outcome is unknown, theoretical concerns should lead emergency physicians to consider using longer-acting antibiotics to minimize delayed therapy. Am J Obstet Gynecol, 2003 Jun, 188(6), 1413 - 6; discussion 1416-7 Antibiotic