J Enzyme Inhib Med Chem, 2002 Dec, 17(6), 425 - 9 In vitro activity of a new antifungal azolyl-substituted indole against Aspergillus fumigatus; Pagniez F et al.; A new 2-(alpha-azolylbenzyl)indole derivative exhibited high in vitro activity against 10 strains of Aspergillus fumigatus . This active compound, MT18n, had MIC of 2 microg/mL and is slightly less active than itraconazole and amphotericin B . The mechanism of action of this compound was evaluated through scanning electron microscopy, ergosterol biosynthesis inhibition and phospholipase A2-like activity inhibition studies . Scanning electron microscopy allowed observation of the membrane perturbations caused by MT18n and inference of a critical role of MT18n in membrane synthesis inhibition . Like other azole derivatives MT18n inhibits ergosterol biosynthesis, with a minimal inhibitory concentration of 6 microM . On the other hand, MT18n (10 microM) decreased the secreted phospholipase A2-like activity of Aspergillus fumigatus, an enzyme involved in the invasion process of the host . These results show the high in vitro activity of MT18n against Aspergillus fumigatus and suggest that this compound disturbs the membrane structure via ergosterol biosynthesis inhibition and exhibits phospholipase activity inhibition. Structure (Camb), 2003 Apr, 11(4), 411 - 22 Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands; McFarland BJ et al.; Engagement of diverse protein ligands (MIC-A/B, ULBP, Rae-1, or H60) by NKG2D immunoreceptors mediates elimination of tumorigenic or virally infected cells by natural killer and T cells . Three previous NKG2D-ligand complex structures show the homodimeric receptor interacting with the monomeric ligands in similar 2:1 complexes, with an equivalent surface on each NKG2D monomer binding intimately to a total of six distinct ligand surfaces . Here, the crystal structure of free human NKG2D and in silico and in vitro alanine-scanning mutagenesis analyses of the complex interfaces indicate that NKG2D recognition degeneracy is not explained by a classical induced-fit mechanism . Rather, the divergent ligands appear to utilize different strategies to interact with structurally conserved elements of the consensus NKG2D binding site. Minerva Anestesiol, 2003 Jan-Feb, 69(1-2), 35 - 56, 56-65 Critical points for sepsis management at the patient bedside; Tulli G; Following an interpretative philosophy, dyna-mic and faithful to the complexity theory, a clinical pathway is outlined close to the reality, at the patient bedside, that is comprehensive of the diagnostic process in its temporal dynamism, of the therapeutic process in its specificity (antibiotic therapy, surgical souce control), in the use of organs supportive therapy (haemodynamic, respiratory, renal, etc.) and in the use of adjunctive and immunomodulatory therapies (APC, AT, etc.) . The importance of the contextual activation of microbiological, immunological and coagulative monitorings is underlined . Through a critical review of the more recent literature, a strict relationship, in sepsis and septic shock, between inflammation and coagulation is described, that allowed the activated protein C (drotrecogin alpha activated) success, in terms of reduction of the absolute and relative mortality . This therapeutic success is contextualized into two other important therapeutic successes, recently obtained in severe sepsis and septic shock, based on the medical evidence, one using low doses of corticosteroids and the other using the early (6 h) goal directed haemodynamic therapy to restore a balance between oxygen delivery and oxygen demand . Once systemic inflammation is complicated by organ failure, there are few options . Treatment with activated protein C lowers the risk of death but is associated with an increased risk of bleeding and is likely to be expensive . The strategies described by the groups of Rivers and Annane offer the opportunity for good therapeutic results, by preventing the progression or even the development of sepsis and its complications: septic shock and multiple organ dysfunction. Prog Drug Res, 2003, Spec No, 191 - 241 Susceptibility testing of fungi--current status and open questions; Seibold M et al.; The increase of fungal infections and the improvement of therapeutical options demand reliable antifungal susceptibility testing . In vitro susceptibility testing of fungi--in contrast to bacteria--is not yet established as a routine method . The NCCIS (National Committee for Clinical Laboratory Standards) guidelines for susceptibility testing of yeasts (and proposed for hyphomycetes) are most important for standardization . Meanwhile, essential parts of this test procedure are accepted, but it should still be improved . The concept of using only one test medium for all drugs and test organisms is not realized so far . There are also some test situations that prevent the NCCLS standard from being applied . Based on our experience, this article describes the NCCLS methods and their modifications . It places emphasis on lipophilic drugs showing controversies despite standardization . Furthermore, the prediction of MICs on the clinical outcome is discussed . Since there are some pitfalls in testing antifungals, this should be done in experienced laboratories only . The MIC has to be regarded as only one, but an important, factor in the management of fungal diseases . Host-, drug-, and pathogen-specific data should be considered simultaneously. Int J Antimicrob Agents, 2003 Apr, 21(4), 364 - 91 Comité de l'Antibiogramme de la Société Française de Microbiologie report 2003; Members of the SFM Antibiogram Committee; Following the recommendations of the WHO Expert Committee for Biological Standardization (Technical reports No . 610, 1977), the French Society for Microbiology created an Antibiogram Committee (CA-SFM), with the aim of proposing the standards which define the clinical categories of antibiotic susceptibility (formerly therapeutic categories) . The MIC and zone diameter interpretive standards, as well as the specific recommendations for certain species or certain antibiotic groups, are published in a yearly report. Immunogenetics, 2003 Mar, 54(12), 850 - 5 Epub 2003 Mar 06. MICB typing by PCR amplification with sequence specific primers; Gonzalez S et al.; MICB is a member of the MIC (MHC class I chain-related gene) family . Sixteen MICB alleles have been described; however, the functional relevance and population distribution of MICB alleles or their potential association to disease has not yet been evaluated . In this study, we have developed a PCR system using sequence-specific primers (PCR-SSP) that allows unambiguous amplification of all MICB alleles . This approach has been applied to type 100 healthy unrelated individuals from the Spanish population . The extent of polymorphism in this population is lower than that initially expected, and only nine alleles were detected . The alleles MICB01021 (46%), MICB0103101 (13.5%), MICB0104 (13.5%) and MICB0106 (12.5%) were found to be the most frequent alleles . HLA-B and MICA transmembrane polymorphism typing were also performed in this population . Our data showed that MICB is in linkage disequilibrium with MICA and even with HLA-B . Thus, the linkage disequilibrium with MICA and HLA-B suggests that MICB is a potential candidate for those diseases classically associated with HLA class I alleles. Br J Cancer, 2003 Apr 7, 88(7), 1101 - 4 Quantitative analysis of macrophage inhibitory cytokine-1 (MIC-1) gene expression in human prostatic tissues; Nakamura T et al.; Macrophage inhibitory cytokine-1 (MIC-1) gene is a member of transforming growth factor-beta superfamily and was reported to be highly overexpressed in human prostate cancer using microarray technology . The aim of this study was to evaluate the quantitative expression of MIC-1 in malignant and benign prostate tissues and to associate expression levels with clinicopathological parameters of prostate cancer . Matched (paired) prostatic tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 66 patients who underwent radical prostatectomy . Quantitative RT-PCR was performed using SYBR Green I on the Roche LightCycler system . Macrophage inhibitory cytokine-1 gene overexpression in cancerous tissues was observed in 88% of cases, compared to noncancerous tissues (P<0.001) . The expression level of MIC-1 in cancerous tissues was significantly higher than in noncancerous tissue (P<0.001) . Higher expression of MIC-1 gene was significantly associated with higher Gleason score (P=0.004) . The expression of the MIC-1 gene in prostate cancer is significantly higher than in noncancerous tissues, especially in more aggressive forms of the disease (Gleason score>5) . This is in contrast to prostate-specific antigen that is downregulated in higher-grade tumours . The upregulation of MIC-1 in prostate cancer and in advanced and more aggressive prostatic tumours suggests that MIC-1 protein should be evaluated as a potential diagnostic and prognostic biomarker. Acta Pol Pharm, 2002 Nov-Dec, 59(6), 439 - 42 Antimycobacterial activity of some pyrido-1,2-thiazine derivatives; Malinka W et al.; The 3-benzoylpyrido-1,2-thiazine-1,1-dioxides 1 and the related pyrazolopyrido-1,2-thiazine-5,5-dioxides 2 with a 4-arylpiperazin-1-ylpropyl side chained by the nitrogen atom of the thiazine ring were evaluated in vitro against Myobacterium tuberculosis H37Rv . Some of the tested compounds proved to be potent antimycobacterial agents and for the most active of them (1a,b) minimum inhibitory concentrations (MIC = 3.13 and 6.25 microg/ml, respectively) were determined . The correlation between mycobacterium growth inhibition and the lipophilicity (logPcalc.) within the series of derivatives 1 and 2 was studied. Biophys J, 2003 Apr, 84(4), 2293 - 305 Polyvalent cations as permeant probes of MIC and TRPM7 pores; Kerschbaum HH et al.; Recent studies in Jurkat T cells and in rat basophilic leukemia cells revealed an Mg(2+)-inhibited cation (MIC) channel that has electrophysiological properties similar to TRPM7 Eyring rate model expressed exogenously in mammalian cells . Here we compare the characteristics of several polyvalent cations and Mg(2+) to block monovalent MIC current from the outside . Putrescine, spermidine, spermine, PhTX-343 (a derivative of the naturally occurring polyamine toxin philanthotoxin), and Mg(2+) each blocked in a dose- and voltage-dependent manner, indicating a blocking site within the electric field of the ion channel . Spermine and the relatively bulky PhTX-343 exhibited voltage dependence steeper than that expected for the number of charges on the molecule . Polyamines and Mg(2+) are permeant blockers, as judged by relief of block at strongly negative membrane potentials . Intracellular dialysis with spermine (300 microM) had no effect, indicating an asymmetrical pore . At the single-channel level, spermine and Mg(2+) induced flickery block of 40-pS single channels . I/V characteristics and polyamine block are similar in expressed TRPM7 and in native MIC currents, consistent with the conclusion that native MIC channels are composed of TRPM7 subunits . An Eyring rate model is developed to account for I/V characteristics and block of MIC channels by polyvalent cations from the outside. Bioorg Med Chem Lett, 2003 Apr 17, 13(8), 1419 - 23 Identification of a broad-spectrum azasordarin with improved pharmacokinetic properties; Serrano-Wu MH et al.; The synthesis and antifungal activity of 5'- and 5'-6'-substituted azasordarin derivatives are described . Modification of the 5'-position led to the discovery of the spirocyclopentyl analogue 7g, which is the first azasordarin to register single-digit MIC values versus Aspergillus spp . Further investigation identified the 5'-i-Pr derivative 7b, which displays superior pharmacokinetic properties compared to other azasordarins. Diagn Microbiol Infect Dis, 2003 Mar, 45(3), 203 - 6 Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species; Canton E et al.; Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104 Candida parapsilosis, 14 C.glabrata, 13 C.tropicalis, 15 C.krusei, and 19 C.albicans) and 36 C.dubliniensis from oropharyngeal infections . Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method . MFCs (> or =99.9% killing) were obtained following MIC determination (inoculum size, 10(4) CFU/ml) by seeding the entire volume of all clear wells . The best fungicidal activity was for C . albicans, (MFC90 1 microg/ml) and the lowest for C.parapsilosis, C.tropicalis and C.glabrata (MFC90 16 microg/ml) . Although MFCs were > or =16x MIC for some isolates, including C . glabrata, the overall MFCs were > or =2x MICs . However, major differences between MICs and MFCs were observed for C.parapsilosis and C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC > or =32MIC) . MFCs for C.tropicalis and C . glabrata were > or =2 microg/ml . By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for Candida spp. J Cataract Refract Surg, 2003 Mar, 29(3), 487 - 91 Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous; Yalvac IS et al.; PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections . SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey . METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium . The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery . Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose . Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence . RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC . The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL . Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous . The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL . Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous . Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353) . Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001) . CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes . Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber . The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy. Vet Dermatol, 2003 Apr, 14(2), 99 - 102 Synergistic inhibition of the growth in vitro of Microsporum canis by miconazole and chlorhexidine; Perrins N et al.; An agar dilution technique was used to assess the minimum inhibitory concentrations (MIC) of miconazole, chlorhexidine and a 1:1 combination of both agents for 10 isolates of Microsporum canis . For nine of 10 of the isolates, a combination of miconazole and chlorhexidine was more effective than either agent alone; fractional inhibitory concentration indices indicated a synergistic effect for five isolates and an additive effect for four . These results illustrate the potent antimycotic effect of miconazole and chlorhexidine against M . canis and are in accordance with previous clinical studies that showed the value of using miconazole and chlorhexidine shampoo in association with oral griseofulvin in the treatment of feline dermatophytosis caused by M . canis. Kansenshogaku Zasshi, 2003 Feb, 77(2), 83 - 8 {Fundamental studies on legionellosis--the growth with in Acanthamoeba sp . and antibiotics susceptibility of Legionella spp . isolated from soil samples in Japan}; Furuhata K et al.; As part of an epidemiological study of legionellosis, we investigated the growth within Acanthamoeba sp . and antibiotic susceptibility of 62 strains of Legionella spp . isolated from surface soils nationwide in 2001 . 1) All strains tested grew in Acanthamoeba sp., suggesting that the strains were pathogenic . The minimum bacterial number required for the growth in the amoeba was 10(3)-10(8) CFU/ml and there were differences between the strains . 2) Susceptibility to 10 drugs was investigated using the Etest . The MIC90 values of imipenem, as a beta-lactam, and rifampicin, as an antitubercular agent, were 0.047 microgram/ml and 0.064 microgram/ml, respectively, showing high sensitivity . In contrast, sensitivity to minocycline, as a tetracycline, and piperacillin, as a beta-lactam, was low and the MIC90 values were 12 micrograms/ml and 16 micrograms/ml, respectively . Sensitivity to minocycline was particularly low, with a MIC value of 32 micrograms/ml, in two strains . The above findings suggested that all soil-derived strains were pathogenic, and susceptibility of the strains tended to be slightly lower than that of clinical isolates. Bioorg Med Chem, 2003 Apr 17, 11(8), 1653 - 62 Hydrophobic derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate: a new type of D-glucosamine-6-phosphate synthase inhibitors with antifungal action; Janiak AM et al.; Several N-acyl and ester derivatives of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) have been synthesised and tested as inhibitors of fungal enzymes involved in early steps of chitin biosynthesis and for antifungal activity . All the tested derivatives were found to be much poorer inhibitors of the enzyme, D-glucosamine-6-phosphate (GlcN-6-P) synthase, than the parent compound but some of them exhibited much better antifungal activity . MIC values for the investigated compounds ranged between 10 mg mL(-1), found for ADGP and 0.3 mg mL(-1) for the most active derivative, namely ADGP dimethyl ester . Increased affinity of ADGP derivatives to the artificial immobilised cell membrane was correlated with their enhanced ability to be taken up by fungal cells by free diffusion . It was found that some of the examined derivatives behaved as 'pro-drugs' and after internalisation were converted into ADGP in the cell-free extract . This conversion was relatively rapid for ADGP esters but very slow for N-acyl derivatives . Results of our studies demonstrate a possibility of design and preparation of GlcN-6-P synthase inhibitors exhibiting antifungal activity. Am J Health Syst Pharm, 2003 Mar 15, 60(6), 565 - 8 Economic benefit of a meropenem dosage strategy based on pharmacodynamic concepts; Kuti JL et al.; The economic benefit of a meropenem dosage strategy based on pharmacodynamic concepts is described . The pharmacodynamics of novel meropenem dosing regimens were compared with FDA-approved regimens by using Monte Carlo simulation with 5000 subjects . Using the meropenem NCCLS-susceptibility breakpoint of 4 micrograms/mL, the percentage of the dosing interval that drug concentration remained above the minimum inhibitory concentration (%t > MIC) was calculated for each regimen . Probability distributions for half-life and volume of distribution using previously published pharmacokinetic data from healthy volunteers were developed . Cost-minimization analysis was performed from the institution's perspective using both drug acquisition and supply costs . Daily costs for the lower dosage regimens were calculated using 2001 average wholesale prices . The mean %t > MIC for meropenem 500 mg administered every six hours (43.91% {95% confidence interval (CI), 36.77-51.46%}) was similar to that of 1000 mg every eight hours (45.77% {95% CI, 40.06-50.69%}) . The mean %t > MIC for meropenem 1000 mg administered every six hours (61.02% {95% CI, 54.71-67.43%}) was similar to the regimen of 2000 mg every eight hours (57.77% {95% CI, 51.84-63.76%}) . The 500-mg regimen reduced drug costs by $38.64 per day compared with the standard regimen of 1000 mg administered every eight hours . A pharmacodynamically influenced dosage strategy for meropenem resulted in %t > MIC exposure similar to standard regimens and required a lesser amount of the drug, thereby reducing costs without compromising efficacy. Compr Psychiatry, 2003 Mar-Apr, 44(2), 154 - 61 The Spanish-Language Version of the Diagnostic Interview for DSM-IV personality disorders: development and initial psychometric evaluation of diagnoses and criteria; Grilo CM et al.; We describe the development of the Spanish-Language Version of the Diagnostic Interview for DSM-IV Personality Disorders (S-DIPD-IV) . Initial descriptive (frequency and gender distribution of personality disorders {PDs}) and psychometric findings (inter-rater reliability of diagnoses, internal consistency, and criteria inter-relatedness) are reported based on administration of the S-DIPD-IV to 95 adult monolingual Hispanic patients . The S-DIPD-IV had adequate inter-rater reliability for most PD (mean kappa =.83) . Except for the significantly greater proportion of males diagnosed with antisocial PD, no significant gender differences in the distribution of PD were observed . Within-category inter-relatedness of PD criteria was evaluated by coefficient alpha and mean intercriterion correlations (MIC) . Between-category criteria overlap was evaluated by intercategory mean intercriterion correlations between all pairs of PD (ICMIC) . For PD criteria, alpha ranged .36 to .99 (mean =.75, median =.81), MIC ranged .07 to .95 (mean = .36), and ICMIC ranged.09 to.45 (mean = .24) . Six PD (borderline, antisocial, narcissistic, avoidant, obsessive-compulsive, and depressive) had no instances in which their criteria sets correlated higher with those of other PD than their own . Two PD (histrionic and dependent PD) had some instances of overlap, and four PD (paranoid, schizotypal, schizoid, and passive-aggressive) had pervasive overlap with other PD criteria sets . These findings suggest the utility of the S-DIPD-IV for assessing PD in Spanish-speaking Hispanic outpatients . Our initial findings for this patient group suggest that, except for antisocial PD in males, specific PD diagnoses are not differentially distributed by gender . Moreover, except for cluster A PD, the criteria for specific PD tend to be more highly correlated within than across PD . The S-DIPD-IV appears to have utility to facilitate PD research with Hispanic groups . Parasitol Res, 2003 Apr, 89(6), 467 - 72 Epub 2003 Jan 10. The toxicity of praziquantel against Mesocestoides vogae (syn . corti) tetrathyridia can be assessed using a novel in vitro system; Saldana J et al.; We recently standardised Mesocestoides vogae (syn . corti) tetrathyridia cultures in the presence of sodium taurocholate . Parasite clustering and segmentation were observed as taurocholate-dependent effects in biphasic and monophasic media, respectively, and both were inhibited by a specific minimum inhibitory concentration (m.i.c.) of the cestocidal drugs albendazol and praziquantel . In the present study, we analysed the relationship between clustering inhibition and drug toxicity using praziquantel and a mouse experimental infection . In an "in vitro-in vivo" trial, a significant (ANOVA, P<0.05) reduction was observed in the infectivity of tetrathyridia previously cultured with praziquantel m.i.c . (0.06 micro g/ml) for 10 days . In an "in vivo-in vitro" trial, the clustering of tetrathyridia recovered from mice treated with praziquantel was found to be markedly reduced: 22%, compared with 83% cluster-containing wells of parasites from control mice . These results show that the outcome of infection and the suppression of taurocholate-induced clustering provide consistent indications of praziquantel toxicity against M . vogae, an observation confirmed by histological studies . The easily recorded clustering inhibition of M . vogae tetrathyridia in biphasic medium is a potentially useful system for the assessment of drug toxicity against cestode larvae. Bioorg Med Chem Lett, 2003 Apr 7, 13(7), 1253 - 5 Antimycobacterial pimarane diterpenes from the Fungus Diaporthe sp; Dettrakul S et al.; Two new pimarane diterpenes, diaportheins A (1) and B (2), were isolated from a culture broth of the fungus Diaporthe sp . BCC 6140 . Diaporthein B (2) strongly inhibited the growth of Mycobacterium tuberculosis with the MIC value of 3.1 microg/mL, while diaporthein A (1) showed only mild activity (MIC value of 200 microg/mL). Cell Mol Biol Lett, 2003, 8(1), 105 - 10 pH-dependent influence of a quaternary ammonium salt and an aminoester on the yeast Saccharomyces cerevisiae ultrastructure; Oblak E et al.; Quaternary ammonium salts inhibited the growth of yeast especially at pH higher (pH 8) than optimal . It was postulated that compounds integrate with the cell membrane and interfere with its functions . The yeast cell ultrastructure investigated under an electron microscope confirms this hypothesis . A relatively high percentage of cells treated at pH 6 with the quaternary ammonium salt of alanine derivative (DMALM-12) at the minimal inhibitory concentration showed an irregularity in the cell shape . No such irregularity was observed in the control . Besides, in the cells treated with the drug, practically no lipid droplets were seen at all . Inside the control cells, electron-dense round bodies were clearly seen and interpreted as vacuoles . These bodies were absent in the cells treated with DMALM-12 . Although the yeast cells growing at pH 8 showed a more or less normal shape, they seemed to have difficulty in budding - no fully developed buds were found in the preparations . Only some convexities of the cell wall were seen that could be the beginning of budding which stopped early after the start . Some changes in the round bodies interpreted as vacuoles were visible: they were less dense and full of granules. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1447 - 8 In vitro activity of a new antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae; Roblin PM et al.; The in vitro activity of NVP-PDF386 (VRC4887), a novel new peptide deformylase inhibitor, and those of levofloxacin and clarithromycin were tested against 21 isolates of Chlamydia pneumoniae . The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by NVP-PDF386 for all isolates of C . pneumoniae were 0.008 micro g/ml (range, 0.008 to 0.015 micro g/ml) compared to 0.25 and 0.06 micro g/ml for levofloxacin and clarithromycin, respectively. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1439 - 42 Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers; Laethem T et al.; The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated . Ten forearm blisters were formed (n = 12) 12 h prior to the last dose . Concentrations of ertapenem in blister fluid exceeded 4 micro g/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval . The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1416 - 8 In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points; Shalit I et al.; Caspofungin and itraconazole were studied alone and in combination against 31 clinical isolates of Aspergillus spp . according to NCCLS M38-P guidelines . MICs and microscopic minimal effective concentrations (MECs) were recorded, and synergy was calculated by using both end points . Synergy or synergy to additivity was found in 30 of 31 isolates by using MIC end points . With MEC end points no synergy was found and indifference was detected in 26 of 31 strains. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1275 - 84 Flucytosine-fluconazole cross-resistance in purine-cytosine permease-deficient Candida lusitaniae clinical isolates: indirect evidence of a fluconazole uptake transporter; Noel T et al.; An unusual interaction between flucytosine and fluconazole was observed when a collection of 60 Candida lusitaniae clinical isolates was screened for cross-resistance . Among eight isolates resistant to flucytosine (MIC >/= 128 micro g/ml) and susceptible to fluconazole (0.5 < MIC < 2 micro g/ml), four became flucytosine-fluconazole cross resistant when both antifungals were used simultaneously . Fluconazole resistance occurred only in the presence of high flucytosine concentrations, and the higher the fluconazole concentration used, the greater the flucytosine concentration necessary to trigger the cross-resistance . When the flucytosine- and fluconazole-resistant cells were grown in the presence of fluconazole alone, the cells reversed to fluconazole susceptibility . Genetic analyses of the progeny from crosses between resistant and sensitive isolates showed that resistance to flucytosine was derived from a recessive mutation in a single gene, whereas cross-resistance to fluconazole seemed to vary like a quantitative trait . We further demonstrated that the four clinical isolates were susceptible to 5-fluorouracil and that cytosine deaminase activity was unaffected . Kinetic transport studies with {(14)C}flucytosine showed that flucytosine resistance was due to a defect in the purine-cytosine permease . Our hypothesis was that extracellular flucytosine would subsequently behave as a competitive inhibitor of fluconazole uptake transport . Finally, in vitro selection of spontaneous and induced mutants indicated that such a cross-resistance mechanism could also affect other Candida species, including C . albicans, C . tropicalis, and C . glabrata . This is the first report of a putative fluconazole uptake transporter in Candida species and of a possible resistance mechanism associated with a deficiency in the uptake of this drug. Drug Dev Ind Pharm, 2003 Feb, 29(2), 215 - 21 Ophthalmic delivery of ciprofloxacin hydrochloride from different polymer formulations: in vitro and in vivo studies; Charoo NA et al.; Reservoir-type ocular inserts were fabricated using sodium alginate containing ciprofloxacin hydrochloride as the core (drug reservoir) that was sandwiched between the Eudragit and/or polyvinylacetate films . Ocular inserts were packaged in aluminium foil and sterilized by gamma radiation . These were tested for sterility as per British Pharmacopoeia (BP) . Ocular inserts were evaluated for in vitro release rate studies, microbial efficacy, in vivo release studies, efficacy against induced bacterial conjunctivitis in rabbit's eyes, concentration in the aqueous humor, and stability studies as per the International Conference on Harmonization (ICH) guidelines . Ocular inserts passed the test for sterility . They showed zero-order release of the drug in the in vitro and in vivo release studies over a period of 120 hr . The drug was found to be active against selected microorganisms as was proved by microbial efficacy studies . A high correlation coefficient was found between in vitro and in vivo release rate studies . Better improvement was observed in artificially induced bacterial conjunctivitis in rabbit's eyes, compared with marketed eye drops and placebo . Drug concentration in the aqueous humor was found above Minimum Inhibitory Concentration (MIC-90) against selected microorganisms . Shelf-life of the product was found to be more than 2 years. Ir J Med Sci, 2002 Oct-Dec, 171(4), 193 - 6 Combination chemotherapy in the treatment of inoperable non-small cell lung cancer; Rutherford RM et al.; BACKGROUND: Chemotherapy is an established intervention in inoperable non-small cell lung cancer (NSCLC), yet few Irish patients receive this treatment . AIM: To determine survival, toxicity and radiological response following chemotherapy for NSCLC at our institution . METHODS: Retrospective audit of all patients receiving chemotherapy for histologically proven, inoperable NSCLC from January 1997 to December 2000 . RESULTS: There were 80 treatment episodes in 77 patients, mean age 62 years . Forty-eight (60%) patients had locally advanced and 32 (40%) metastatic disease . Mitomycin, Ifosfamide, Carboplatin (MIC) and Paclitaxel/Carboplatin (PC) were the most commonly administered regimens . Median survival for locally advanced and metastatic disease was 13.9 months and 7.1 months respectively . Severe neutropenia and thrombocytopenia were each witnessed after less than 9% of cycles . Eleven (16.7%) patients had radiological response including 4 (6.1%) complete responses . CONCLUSION: Survival for inoperable NSCLC treated with chemotherapy was encouraging and achieved at low toxicity. AAPS PharmSci . 2002;4(4):E20. Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: preliminary trial in humans; Schwach-Abdellaoui K et al.; The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37 degrees C, for up to 14 days . Total polymer degradation concomitant with drug release was obtained . Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis . In the first trial including 6 patients, single-rooted teeth and molar teeth with furcations were treated immediately after scaling and root planing . Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period . However, retention of the formulation was minimal in this first study . An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets . For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens. Bioorg Med Chem Lett, 2003 Mar 24, 13(6), 1051 - 4 Substituted 4-methylquinolines as a new class of anti-tuberculosis agents; Jain R et al.; We report synthesis and anti-tuberculosis activities of a series of novel ring-substituted quinolines . The most effective compound of the series 3d (MIC=6.25 microg/mL, Mycobacterium tuberculosis H37Rv strain) was synthesized in one step; thus is an attractive lead molecule for anti-tuberculosis drug development . The results of this study represent the discovery of ring-substituted 4-methylquinolines as new class of potential anti-tuberculosis agents. Arzneimittelforschung, 2003, 53(2), 126 - 32 Suitability of cefotiam and cefuroxime axetil for the perioperative short-term prophylaxis in tonsillectomy patients; Muller R et al.; The efficacy of the perioperative short-term prophylaxis with cefotiam (CAS 66309-69-1) and cefuroxime axetil (CAS 64544-07-6) was analysed by the assessment of the pharmacological kinetics in the serum and the tonsil tissue in 50 patients with recurrent tonsillitis . Twenty-four patients received 1 g cefotiam by the intravenous route 30 min to 4 h before the tonsillectomy, and 26 patients received 250 mg cefuroxime axetil orally 1 to 6 h before the tonsillectomy . Bactericidal serum levels were reached for cefotiam up to 4 h after intravenous application and for cefuroxime axetil up to 3 h after oral application . In the tissue of the tonsil there were proved levels which were definitely above the MIC 90 (MIC = minimum inhibitory concentration) known for the clinically relevant germs for cefotiam after 30 min up to 2 h, for cefuroxime axetil after only 2 h . Considering the distribution areas, the capacity of the protein binding and the microbiological measuring methods, one can expect an efficient antibiotic coverage after an intravenous one-shot bolus injection of 1 g cefotiam from 30 min to 4 h and after oral application of 250 mg cefuroxime axetil on an empty stomach from 1 to 6 h . Because of the short duration of a tonsillectomy and the serum and tonsil tissue kinetics cefotiam and cefuroxime axetil are suitable for the perioperative antibiotic prophylaxis of high-risk patients. Water Sci Technol, 2003, 47(3), 249 - 53 Antibiotic selective pressure for the maintenance of antibiotic resistant genes in coliform bacteria isolated from the aquatic environment; Park JC et al.; Coliform bacteria isolated from the aquatic environment were investigated for antibiotic susceptibility and detailed structures of class 1 integrons . A high proportion of isolates were found to be resistant to sulfamethoxazole, aminoglycosides, and beta-lactams . The 750 (53.6%) isolates were resistant to one or more of the antibiotics tested out of 1,400 coliform bacteria . Based on the MIC of antibiotics and antibiogram, 150 isolates were selected and further studied for class 1 integrons . The intI1 gene was found in 36 (24.0%) of the 150 isolates . Twelve isolates carried the gene cassettes responsible for antibiotic resistance, while no gene cassettes were found in 24 isolates . Seven different genes, dfrA5, dfrA7, dfrA12, dfrA17, aaA2, aaA5, and aad(3'), were detected in gene cassettes . The dfrA and aad genes located on class 1 integrons were responsible for resistance to trimethoprim and aminoglycosides . The remaining 24 coliform bacteria had the incomplete or non-functional class 1 integrons . These results indicated that antibiotic selective pressures may play an important role to maintain gene cassettes of class 1 integrons and in the absence of sustained antibiotic pressures, such as the aquatic environment, coliform bacteria may carry empty or non-functional class 1 integrons. Folia Microbiol (Praha), 2002, 47(6), 742 - 6 Fatty acid analysis of Stenotrophomonas maltophilia clinical strains showing different susceptibility to antibiotics at 30 and 37 degrees C; Hejnar P et al.; Isolates of Stenotrophomonas maltophilia species display the feature "temperature-dependent susceptibility" (TDS) to antibiotics . Both 30TDS strains (at least 4 times lower value of minimum inhibitory concentration (MIC) of an antibiotic at 30 than at 37 degrees C) and 37TDS strains (at least 4 times lower value of MIC at 37 than at 30 degrees C) were described . Changes in the distribution of saturated and unsaturated fatty acids (FA) at 30 and 37 degrees C were considered as one of possible causes of the TDS phenomenon . Gas chromatography was used to determine the distribution of individual FA in five 37TDS strains of S . maltophilia (Group I); in five strains with MIC values unaffected by the cultivation temperature (Group II) and in six 30TDS (four strains) or 30/37TDS (two strains) isolates (Group III) . At identical temperatures, no statistically significant differences in the distribution of major FA (iso-15:0, anteiso-15:0, 16:0 and 16:1) were registered between individual groups . Statistically significant (p < 0.05) differences between groups were found in minor FA only (iso-16:0, iso-17:0 and iso-17:1) . Distribution changes of cellular FA at 30 and 37 degrees C can be considered to play only a minor role in the formation of the TDS phenomenon. J Comb Chem, 2003 Mar-Apr, 5(2), 172 - 87 Combinatorial lead optimization of {1,2}-diamines based on ethambutol as potential antituberculosis preclinical candidates; Lee RE et al.; Despite relatively modest potency, ethambutol (EMB, (S,S)-{N,N-di-2-amino-1-butanol}ethylenediamine) is a mainstay of contemporary chemotherapy for the treatment of tuberculosis . We have developed a solid-phase synthesis of 1,2-diamine analogues of EMB using a novel acylation-reduction sequence that is compatible with high-throughput 96-well format chemistry . Using this procedure, we have synthesized 63 238 diamine analogues in pools of 10 that are suitable for testing . MIC and a target-based reporter assay were used to direct deconvolution of 2796 individual compounds from these mixtures, and the 69 most potent molecules were resynthesized in milligram quantities for hit confirmation . Purification of these individual active diamine analogues allowed the identification of 26 compounds with activity equal to or greater than EMB . Amines which occurred most frequently in active compounds included many with large hydrophobic moieties, suggesting that optimization was perhaps selecting for the isoprenoid binding site of the arabinosyltransferase target of EMB . N-Geranyl-N'-(2-adamantyl)ethane-1,2-diamine (109), the most active of these diamines, displayed a 14-35-fold improvement in activity in vitro against Mycobacterium tuberculosis, as compared to EMB. Planta Med, 2003 Feb, 69(2), 155 - 7 Coumarins and carbazoles from Clausena excavata exhibited antimycobacterial and antifungal activities; Sunthitikawinsakul A et al.; Four known coumarins, dentatin (1), nor-dentatin (2), clausenidin (3) and xanthoxyletin (5), and six known carbazole derivatives, 3-formylcarbazole (6), mukonal (7), 3-methoxycarbonylcarbazole (8), murrayanine (9), 2-hydroxy-3-formyl-7-methoxycarbazole (10) and clauszoline J (11) were isolated from Clausena excavata . Compounds 1 and 6 were first isolated from the crude chloroform extract of the rhizomes . Compounds 1, 2, 3, 6, 7, 8, 10 and 11 showed antimycobacterial activity at a minimum inhibitory concentration (MIC) of 50, 100, 200, 100, 200, 50, 100 and 100 microg/mL, respectively . O-Methylated clausenidin ( 4), prepared from 3, exhibited antimycobacterial activity at MIC 50 microg/mL . Compounds 6, 7, 8 and 10 showed antifungal activity with IC 50 values of 13.6, 29.3, 9.5 and 2.8 microg/mL, respectively . All compounds demonstrated no cytotoxicity against KB and BC-1 cell lines. J Clin Microbiol, 2003 Mar, 41(3), 1143 - 6 Proficiency testing program for clinical laboratories performing antifungal susceptibility testing of pathogenic yeast species; Ramani R et al.; Antifungal susceptibility testing is expected to facilitate the selection of adequate therapy for fungal infections . The general availability of antifungal susceptibility testing in clinical laboratories is low, even though a number of standard methods are now available . The objective of the present study was to develop and evaluate a proficiency testing program (PTP) for the antifungal susceptibility testing of pathogenic yeasts in laboratories licensed by the New York State Department of Health . A number of quality control standards, and methods for documenting laboratory performance, were developed in consultation with the laboratory directors . The participating laboratories were provided with five American Type Culture Collection strains of pathogenic yeasts for which the minimum inhibitory concentrations (MICs) of amphotericin B and fluconazole were well defined . A majority of laboratories (14 of 17) used broth microdilution, and these were evenly split between the NCCLS M-27A protocol and the Sensititre YeastOne method . The other three laboratories performed susceptibility testing with Etest . Overall, the levels of agreement between MIC reference ranges and the reported MICs were 85 and 74% for amphotericin B and for fluconazole, respectively . All laboratories except one successfully detected fluconazole resistance in a Candida krusei strain . However, amphotericin B resistance in a Candida lusitaniae strain was not detected by any of the participating labs . It is concluded that a suitably designed PTP could adequately monitor the competence of clinical laboratories performing antifungal susceptibility testing. J Med Microbiol, 2003 Mar, 52(Pt 3), 239 - 45 Characterization of rifampicin-resistant Mycobacterium tuberculosis in Taiwan; Hwang HY et al.; Sixty-three rifampicin-resistant (Rif(r)) isolates of Mycobacterium tuberculosis from Kaohsiung, Taiwan, were analysed for mutations in the core region (69 bp, codons 511-533) of the rpoB gene . Some 84.1 % (53/63) of the resistant isolates showed mutations in this region, especially in codons 531 (41.5 %), 526 (18.9 %), 516 (15.1 %) and 533 (7.5 %) . Five novel alleles of a total of 16 different types of mutations were identified in Rif(r) isolates . Ten Rif(r) isolates (15.9 %) exhibited no mutations in the core region of rpoB . Also, they did not show mutations in another 365 bp fragment (codons 99-220) of rpoB . The agar proportion method was used to determine the relationship between the degree of rifampicin resistance and alterations in the core region of rpoB . The results revealed that the mean MIC was 92.38 micro g ml(-1) for the 53 isolates with a mutation in the core region, whereas the mean MIC of the other 10 isolates without mutations was only 24.8 micro g ml(-1) . This indicates that the isolates with mutations in the core region had higher levels of resistance than those without mutations in this region . IS6110 restriction fragment length polymorphism (RFLP) was used for typing of 55 Rif(r) M . tuberculosis isolates . Isolates contained two to 19 copies of IS6110, with sizes ranging from 600 to 16 000 bp . The majority (85 %) contained six to 16 copies . No strains lacking IS6110 were found . A total of 54 of 55 RFLP types were defined at the 90 % similarity level . The observation of varied IS6110-associated banding patterns indicates that an outbreak of drug-resistant tuberculosis did not occur in this area. J Environ Monit, 2003 Feb, 5(1), 100 - 5 Diffusive sampling of methyl isocyanate using 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ) as derivatizing agent; Henneken H et al.; A diffusive sampling method for the determination of methyl isocyanate (MIC) in air is introduced . MIC is collected using a glass fiber filter impregnated with 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ) . The urea derivative formed is desorbed from the filter with acetonitrile and analyzed by means of high-performance liquid chromatography (HPLC) using fluorescence detection (FLD) with lambdaex = 471 nm and lambdaex = 540 nm . Additionally, a method was developed using tandem mass spectrometric (MS-MS) detection, which was performed as selected reaction monitoring (SRM) on the transition {MIC-NBDPZ + H}+ (m/z 307) to {NBDPZ + H}+ (m/z 250) . The diffusive sampler was tested with MIC concentrations between 1 and 35 microg m(-3) . The sampling periods varied from 15 min to 8 h, and the relative humidity (RH) was set from 20% up to 80% . The sampling rate for all 15 min experiments was determined to be 15.0 mL min(-1) (using HPLC-FLD) with a relative standard deviation of 9.9% for 56 experiments . At 80% RH, only 15 min sampling gave acceptable results . Further experiments revealed that humidity did not affect the MIC derivative but the reagent on the filter prior to and during sampling . The sampling rate for all experiments (including long term sampling) performed at 20% RH was found to be 15.0 mL min(-1) with a relative standard deviation of 6.3% (N = 42) . The limit of quantification was 3 microg m(-3) (LC-MS-MS: 1.3 microg m(-3)) for 15 min sampling periods and 0.2 microg m(-3) (LC-MS-MS: 0.15 microg m(-3)) for 8 h sampling runs applying fluorescence detection. Diagn Microbiol Infect Dis, 2003 Feb, 45(2), 131 - 5 In vitro activity of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B against aspergillus spp; Serrano Mdel C et al.; Voriconazole, anidulafungin (VER002, LY303366) and caspofungin are promising antifungal agents which provide a good protection against a variety of fungi, including yeasts and filamentous fungi . In this study, we tested the in vitro efficacy of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B, against different species of Aspergillus spp . isolated from clinical specimens, using a microdilution broth method and following the NCCLS guidelines (document M38-P) . We also evaluated the effect that time readings have on MIC results . For caspofungin, we determined the minimun effective concentration (MEC), defined like the lowest concentration of caspofungin causing abnormal hyphal growth . Anidulafungin (VER002, LY303366) was the most active antifungal agent tested with MIC(90) of < or =0,03 mg/L . The activity of voriconazole, and itraconazole very similar with MIC(90) of 0,12 mg/L, 0,12 mg/L respectively . For caspofungin the MEC(90) was of 0,25 mg/L . Amphotericin B was the lest active antifungal agent studied with MIC(90) of 1 mg/L . There were no differences between MIC values at 48 and 72 h . These data demonstrate promising activity of voriconazole, anidulafungin (VER002, LY303366) and caspofungin against Apergillus spp. Pharm Res, 2003 Jan, 20(1), 117 - 25 Direct formation of nanospheres from amphiphilic beta-cyclodextrin inclusion complexes; Memisoglu E et al.; PURPOSE: The aim of this work was to develop and characterize a highly loaded nanoparticulate system based on amphiphilic beta-cyclodextrins (CDs) to facilitate the parenteral administration of poorly soluble antifungal model drugs bifonazole and clotrimazole . METHODS: Inclusion complexes were characterized with spectroscopic techniques . Particle size distribution of nanospheres were determined by photon correlation spectroscopy (PCS) . Nanospheres were assessed for hemolytic activity . Entrapped and released drug quantities were determined and minimum inhibitory concentration (MIC) values of drugs, amphiphilic beta-CDs, and drug loaded nanospheres were evaluated . RESULTS: 1:1 inclusion complexes of model drugs with amphiphilic beta-CDs gave nanospheres <300 nm (polydispersity index < 0.15) by nanoprecipitation technique without using surfactants . By direct preparation from preformed inclusion complexes, loading was increased 2- to 8-fold depending on CD type and loading technique . Conventionally loaded CD nanospheres displayed immediate release whereas preloaded and highly loaded nanospheres liberated model drugs over a period of 1 h reducing the initial burst effect . MIC values of bifonazole and clotrimazole were lowered significantly when associated to amphiphilic beta-CD nanospheres . CONCLUSION: Amphiphilic beta-CDs form nonsurfactant, highly loaded nanospheres with lower hemolytic activity than that of natural CDs directly from inclusion complexes . They enhanced solubility and subsequently therapeutic efficacy of the model drugs. Antimicrob Agents Chemother, 2003 Mar, 47(3), 1081 - 7 Use of the microbial growth curve in postantibiotic effect studies of Legionella pneumophila; Smith RP et al.; Using the standard Craig and Gudmundsson method (W . A . Craig and S . Gudmundsson, p . 296-329, in V . Lorian, ed., Antibiotics in Laboratory Medicine, 1996) as a guideline for determination of postantibiotic effects (PAE), we studied a large series of growth curves for two strains of Legionella pneumophila . We found that the intensity of the PAE was best determined by using a statistically fitted line over hours 3 to 9 following antibiotic removal . We further determined the PAE duration by using a series of observations of the assay interval from hours 3 to 24 . We determined that inoculum reduction was not necessarily the only predictor of the PAE but that the PAE was subject to the type and dose of the drug used in the study . In addition, there was a variation between strains . Only levofloxacin at five and ten times the minimum inhibitory concentration (MIC) resulted in a PAE duration of 4 to 10 h for both strains of L . pneumophila tested . Ciprofloxacin at five and ten times the MIC and azithromycin at ten times the MIC caused a PAE for one strain only . No PAE could be demonstrated for either strain with erythromycin or doxycycline . Using the presently described method of measuring PAE for L . pneumophila, we were able to detect differences in PAE which were dependent upon the L . pneumophila strain, the antibiotic tested, and the antibiotic concentration . We suggest the use of mathematically fitted curves for comparison of bacterial growth in order to measure PAE for L . pneumophila. Antimicrob Agents Chemother, 2003 Mar, 47(3), 997 - 1001 Comparing pharmacokinetics of amoxicillin given twice or three times per day to children older than 3 months with pneumonia; Fonseca W et al.; For children with ambulatory pneumonia, the World Health Organization (WHO) recommends oral amoxicillin (15 mg/kg of body weight/dose) thrice daily (t.i.d.) or oral cotrimoxazole (4 mg of trimethoprim/kg/dose) twice daily (b.i.d.) . The more frequent amoxicillin dosing may lead to compliance problems . To compare the pharmacokinetics and levels of amoxicillin in plasma in the current WHO acute respiratory infection recommendations with the 25-mg/kg/dose b.i.d . regimen, we performed a two-group parallel study of 66 children ages 3 to 59 months with pneumonia . Amoxicillin was given orally at 25 mg/kg/dose b.i.d . or 15 mg/kg/dose t.i.d . Amoxicillin concentrations were determined by high-performance liquid chromatography after the first dose on days 1 and 3 . After the first dose on day 1, the mean area under the concentration-time curve (AUC) for amoxicillin after the 25-mg/kg dose was 54.7 versus 24.9 micro g . h/ml after the 15-mg/kg dose . After the first dose on day 3, the mean AUC was 44.1 versus 28.5 micro g . h/ml . All but two children had plasma amoxicillin concentrations above 0.5 micro g/ml for >50% of the dose interval on both days . Six children on day 1 and five children on day 3 had concentrations above 1.0 micro g/ml for <50% of the dose interval . On day 1, 16 of 27 children in the b.i.d . group and 11 of 26 children in the t.i.d . group had concentrations that were above 2.0 micro g/ml for <50% of the dose interval, and on day 3, 18 of 31 children in the b.i.d . group and 8 of 31 children in the t.i.d . group had concentrations that were above 2.0 micro g/ml for <50% of the dose interval . Amoxicillin b.i.d . is a feasible alternative for t.i.d . dosing . To lengthen the time above the MIC at higher concentration levels, a 30- to 40-mg/kg/dose b.i.d . should be considered instead of the 25 mg/kg/dose used in this study. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2002 Feb, 22(2), 122 - 5 {Effect of Erigeron breviscapus injection on ventricular and vascular remodeling in spontaneous hypertension rats}; Zhou JZ et al.; OBJECTIVE: To observe the ventricular and vascular remodeling reversal effect of Erigeron breviscapus injection (EBI), a protein kinase C inhibitor, in spontaneous hypertension rats (SHR) . METHODS: Twenty-four SHR were divided into 4 groups, they were treated respectively with EBI, Fosinopril, Enalapril and normal saline 10 mg/kg per day by intraperitoneal injection for 8 weeks . Systolic blood pressure (SBP), ventricular weight index (VWI) and protein kinase C (PKC) activity in myocardial cells were determined, ultrastructural changes of heart and vessel were observed by polaroscope and transmission electron microscope, and the area and content of myocardial interstitial collagen (MIC) were determined by image analyzer system . RESULTS: The left ventricular hypertrophy was regressed to certain degree after EBI, Fosinopril and Enalapril treatment, but no significant change in heart rate and right VWI was found . Fosinopril and Enalapril were superior to EBI in lowering SBP and left VWI, and EBI was more obvious in improving myocardial ultrastructure such as hypertrophy and degeneration . All the 3 drugs could improve the MIC and vascular remodeling, the MIC area, content and collagen volume fraction in the EBI group were lowered after treatment, as compared with those in the control group, but comparison between the three groups showed no significant difference . The 3 drugs could reduce the PKC activity in myocardial cell membrane, and EBI showed the effect more significant than that of the other two (P < 0.05) . CONCLUSION: EBI could reverse the myocardial, interstitial and vascular remodeling, improve the rigidness of cardiac muscle, thus, has protective effect on heart. Vet Ther, 2002 Winter, 3(4), 409 - 19 Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin in dogs following single oral administration of enrofloxacin at 7.5, 10, or 20 mg/kg; Boothe DM et al.; Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin were monitored following oral administration of enrofloxacin at 7.5, 10, and 20 mg/kg to six healthy female bloodhounds using a randomized crossover design . Plasma samples were collected at various times over 24 hours following drug administration . Both the parent drug and its metabolite were detected by high-performance liquid chromatography, and plasma drug concentration-versus-time curves were subjected to noncompartmental pharmacokinetic analysis . Descriptive statistics were determined for each dosage, and comparisons were made among dosage groups for selected pharmacokinetic parameters . Increasing dosages of enrofloxacin resulted in increased plasma concentrations of both enrofloxacin and ciprofloxacin . Maximum concentration (Cmax) was 2.12 +/- 0.59, 2.1 +/- 0.34, and 4.74 +/- 1.05 mcg/ml for enrofloxacin and 1.30 +/- 0.31, 1.30 +/- 0.32, and 1.86 +/- 0.35 mcg/ml for ciprofloxacin when enrofloxacin was given at dosages of 7.5, 10, and 20 mg/kg, respectively . Cmax and area under the curve (AUC) for both enrofloxacin and ciprofloxacin were significantly greater at 20 mg/kg than at 7.5 and 10 mg/kg . Disappearance half-life was similar for all dosages, ranging from 4.6 to 5.2 hours for enrofloxacin and 8.8 to 10.7 hours for ciprofloxacin . Ciprofloxacin contributed up to 42% of the Cmax and up to 55% of the AUC of the total (enrofloxacin plus ciprofloxacin) . For organisms with a minimum inhibitory concentration (MIC) of 0.5 mcg enrofloxacin/ml, an inhibitory quotient (IQ; Cmax:MIC) of 8 or more was achieved in plasma only at 20 mg/kg. Rev Esp Quimioter, 2002 Sep, 15(3), 268 - 71 {Study of the susceptibility of black yeasts of the Exophiala genus to antifungals using the Sensititre System}; Puerto JL et al.; Black yeasts belong to a group of dematiaceous fungi which are difficult to classify and identify . One of the genera that cause human infection, mainly phaeohyphomycosis, is Exophiala, which includes the species E . berger, E . castellanii, E . dermatitidis, E . jeanselmei, E . lecanii-corni, E . moniliae, E . pisciphila, E . salmonis and E . spinifera . We carried out a susceptibility study of five of these species (E . castellanii, E.dermatitidis, E, jeanselmei, E . lecanii-corni and E . moniliae), isolated from cutaneous exudates, to the usual antimycotic agents . Strains were cultured on Sabouraud agar and potato-dextrose agar . Species identification was made by conidiogenous microscopic observation and the following characteristics: maximum growth temperature, tolerance to cicloheximide and carbohydrate assimilation . Susceptibility to antimycotic agents (amphotericin B, fluconazole, itraconazole, ketoconazole and 5-fluorocytosine) was determined by the Sensititre YeastOne (Aamar Blue) commercial method . Amphotericin B activity was good for the five tested species, although the MIC for E . jeanselmei was high (1 mg/l . MICs for fluconazole were high for all the species, but only E . moniliae and E . lecanii-corni c be considered resistant . Activity of itraconazole, ketoconazole and 5-fluorocytosine was good. Boll Chim Farm, 2002 Nov-Dec, 141(6), 423 - 7 Formulation studies on modified releasing amoxicillin trihydrate microcapsules; Canefe K et al.; In vitro researches and in vivo animal experiments show that, generally the antibiotic concentration should be above minimum inhibitory concentration for optimal efficiency . There is also direct and indirect evidence from human trials to support this claim . Consequently, a modified-release dosage form of the beta-lactam antibiotics might be therapeutically more efficient than the existing conventional products, which are rapidly absorbed to produce transient peaks in serum drug levels . In our study, Amoxicillin was chosen as the model drug, because it is currently one of the most widely prescribed oral semisynthetic penicillins . By using various types of polymers and different formulations of them, we tried to improve a microparticular system . We succeeded in obtaining optimal production of particulars in the prepared microcapsule form with the solvent evaporation technique . By applying suitable pharmaceutical technological production parameters, the production of the dosage form which releases modified-release form of the model antibiotic is provided . Production processes and availability for the aim is controlled by using the pharmaceutical technological tests, mainly with the methods according to USP XXIV . Consequently compared to the classical Amoxicillin trihydrate dosage forms used in treatment, we managed to form the microcapsule structure containing modified release. Hua Xi Yi Ke Da Xue Xue Bao, 2002 Apr, 33(2), 253 - 5 {The in vitro study of the effects of 11 kinds of traditional Chinese medicine on the growth and acid production of Actinomyces viscosus}; Xiao Y et al.; OBJECTIVE: To assess the effects of different natural medicines on the growth and acid production of Actinomyces viscosus, thus making preparations for screening an effective agent to mediate the balance of oral microflora . METHODS: Actinomyces viscosus ATCC 19246 was chosen as the experimental bacteria . 11 kinds of traditional Chinese medicine, such as Rhizoma Ligustici Chuanxiong, Sargentodoxa Cuneata and Galla Chinensis were extracted by means of maceration, percolation and reflux extraction . First, the values of MIC of various extracts were measured . Second, the experimental medium containing various extracts was prepared . The concentration of the extracts was lower than the MIC of the medicine, and the initial pH of the medium was 7.4 . Then Actinomyces viscosus was cultured in the medium for 48 h, and finally the rest pH was measured . RESULTS: When the concentration of the medicines was lower than or equal to 8.000 mg/ml, it was found that all kinds of medicine except Radix Notoginseng can inhibit the growth of Actinomyces viscosus effectively, especially Polistes mandarinus and Semen Arecae . Tea polyphenols, Radix Notoginseng, Radix et Rhizoma Rhei, Polistes mandarinus and Sargentodoxa cuneata can inhibit the acid production of Actinomyces viscosus effectively, but Radix Scutellariae, Rhizoma Ligustici Chuanxiong, Semen Arecae, Radix Angelicae Dahuricae, Galla Chinensis and Catechu have no preliminary effect on it . CONCLUSION: Tea polyphenols, Radix et Rhizoma Rhei, Polistes mandarinus and Sargentodoxa cuneata can inhibit the growth and the acid production of Actinomyces viscosus effectively. Zhong Yao Cai, 1999 Jun, 22(6), 295 - 8 {Chemical constituents of the essential oil from the fruits of Lindera glauca and its antifungal activities}; Yang D et al.; The chemical constituents of the two essential oils extracted from the fruits of Lindera glauca by hydrodistillation and petroleum ether have been studied by means of GC-MS . Among which, 32 kinds of constituents were identified in distilling oil and 22 kinds in solvent oil . The main components in distilling oil were n-carpric acid (25.39%), germacrene A (10.71%), n-dodecanole acid (10.08%), epishyobunol acetate (7.29%) and caryophyllene oxide (5.44%), and in solvent oil were camphene (17.55%), 3,6,6-trimethyl-2-norpinene (16.85%), capric acid, ethyl ester (13.61%), eucalyptol (8.10%), and alpha-cis-ocimene (7.38%), In vitro the distilling oil exhibited more manifest antifungal properties than the solvent oil with MIC between 0.03-0.5 ml/L for pathogenic fungi species and 1.0-1.5 ml/L for moulds . Almost having not contained the sesquiterpenoids and their derivatives in the solvent oil maybe were a reason of poor inhibitory. Vet J, 2003 Mar, 165(2), 143 - 8 Strategic administration of enrofloxacin in poultry to achieve higher maximal serum concentrations; Sumano LH et al.; To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions . A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration . A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs . concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2) . Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered . The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2) . Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration . Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment. Arch Biochem Biophys, 2003 Feb 15, 410(2), 222 - 9 Isolation, purification, and physicochemical characterization of a D-galactose-binding lectin from seeds of Erythrina speciosa; Konozy EH et al.; A lectin was isolated from the saline extract of Erythrina speciosa seeds by affinity chromatography on lactose-Sepharose . The lectin content was about 265 mg/100g dry flour . E . speciosa seed lectin (EspecL) agglutinated all human RBC types, showing no human blood group specificity; however a slight preference toward the O blood group was evident . The lectin also agglutinated rabbit, sheep, and mouse blood cells and showed no effect on horse erythrocytes . Lactose was the most potent inhibitor of EspecL hemagglutinating activity (minimal inhibitory concentration (MIC)=0.25 mM) followed by N-acetyllactosamine, MIC=0.5mM, and then p-nitrophenyl alpha-galactopyranoside, MIC=2 mM . The lectin was a glycoprotein with a neutral carbohydrate content of 5.5% and had two pI values of 5.8 and 6.1 and E(1%)(1 cm) of 14.5 . The native molecular mass of the lectin detected by hydrodynamic light scattering was 58 kDa and when examined by mass spectroscopy and SDS-PAGE it was found to be composed of two identical subunits of molecular mass of 27.6 kDa . The amino acid composition of the lectin revealed that it was rich in acidic and hydroxyl amino acids, contained a lesser amount of methionine, and totally lacked cysteine . The N-terminal of the lectin shared major similarities with other reported Erythrina lectins . The lectin was a metaloprotein that needed both Ca(2+) and Mn(2+) ions for its activity . Removal of these metals by EDTA rendered the lectin inactive whereas their addition restored the activity . EspecL was acidic pH sensitive and totally lost its activity when incubated with all pH values between pH 3 and pH 6 . Above pH 6 and to pH 9.6 there was no effect on the lectin activity . At 65 degrees C for more than 90 min the lectin was fairly stable; however, when heated at 70 degrees C for 10 min it lost more than 80% of its original activity and was totally inactivated at 80 degrees C for less than 10 min . Fluorescence studies of EspecL indicated that tryptophan residues were present in a highly hydrophobic environment, and binding of lactose to EspecL neither quenched tryptophan fluorescence nor altered lambda(max) position . Treating purified EspecL with NBS an affinity-modifying reagent specific for tryptophan totally inactivated the lectin with total modification of three tryptophan residues . Of these residues only the third modified residue seemed to play a crucial role in the lectin activity . Addition of lactose to the assay medium did not provide protection against NBS modification which indicated that tryptophan might not be directly involved in the binding of haptenic sugar D-galactose . Modification of tyrosine with N-acetylimidazole led to a 50% drop in EspecL activity with concomitant acetylation of six tyrosine residues . The secondary structure of EspecL as studied by circular dichroism was found to be a typical beta-pleated-sheet structure which is comparable to the CD structure of Erythrina corallodendron lectin . Binding of lactose did not alter the EspecL secondary structure as revealed by CD examination. Zhong Yao Cai, 1999 Aug, 22(8), 414 - 5 {Study on activities of eight kinds of traditional Chinese medicine against urogential Chlamydia trachomatis}; Li J et al.; In order to screen the susceptibilities of urogenital chlamydia trachomatis (CT) to 8 kinds of traditional Chinese medicine by microculture technigue of McCoy cell in Vitro . The results showed that 8 kinds of Chinese medicines all had activities against urogenital CT . Their minimal inhibitory concentrations (MIC) were from 0.49 mg/ml to 15.63 mg/ml . The number and the volume of inclusions were reducing gradually, disappeared finally . These traditional Chinese medicines hadn't any action of cytotoxicity to McCoy cell . The result of this study will be useful for the further study. Zhong Yao Cai, 1999 Aug, 22(8), 400 - 2 {Chemical composition of essential oil from leaves of litsea cubeba and its antifungal activities}; Wang F et al.; The 24 chemical constituents of the essential oil extracted from the leaves of Litsea cubeba have been identified by means of GC-MS technique . Among which, alpha-cis-ocimene(25.11%), 3,7-dimethyl-1,6-octadien-3-ol(16.85%) and n-transnerolidol (13.89%) were the principal components . In vitro this oil had a manifest antifungal activities with MIC between 0.03-0.4 microliter/ml for utilized pathogenic fungi and 1.0-2.0 microliters/ml for moulds. J Antimicrob Chemother, 2003 Feb, 51(2), 435 - 8 Antimycobacterial activity of diospyrin derivatives and a structural analogue of diospyrin against Mycobacterium tuberculosis in vitro; Lall N et al.; Three derivatives and one structural analogue of diospyrin were synthesized and investigated for their inhibitory activity against Mycobacterium tuberculosis employing the rapid radiometric method in vitro . A novel aminoacetate derivative was found to be more active than the parent compound, the MICs being 50 and 100 mg/L, respectively, for a drug-susceptible strain, H37Rv, of M . tuberculosis . This derivative also exhibited an MIC of 50 mg/L for a few multidrug-resistant strains of M . tuberculosis . The other two derivatives and the analogue did not show any significant antimycobacterial activity at the highest concentration (100 mg/L) tested. Environ Toxicol Chem, 2003 Feb, 22(2), 252 - 60 Toxicity of lead in aqueous medium to desulfovibrio desulfuricans G20; Sani RK et al.; The toxicity of Pb(II) to sulfate-reducing bacteria (SRB) was studied using Desulfovibrio desulfuricans G20 in a medium specifically designed to assess metal toxicity . The effects of Pb(II) toxicity were observed in terms of longer lag times, lower specific growth rates, and in some cases no measurable growth . With an increase in medium pH from 6 to 8, Pb(II) toxicity decreased . At all pH values, in the presence of Pb(II) concentrations ranging from 3 to 15 microM, specific growth rates decreased and lag times increased . The minimum inhibiting concentration (MIC) of Pb(II) causing a complete inhibition in growth at pH 6 was 10 microM, as compared to 15 microM at pH 7.2 and 8 . These MIC values are 40 times lower than previously reported for SRB . Results also show that with increases in initial cell protein concentration (inoculum size), soluble Pb(II) removal rates increased and the degree to which Pb(II) caused increased lag times was reduced . In the presence of Pb(II), in all cases in which D . desulfuricans grew (even after a 312-h lag time), the final cell protein concentration was equivalent to that of the Pb-free control . Live/dead staining, based on membrane integrity, indicated that while Pb(II) inhibited growth, Pb(II) did not cause a loss of D . desulfuricans membrane integrity. Invest Ophthalmol Vis Sci, 2003 Feb, 44(2), 505 - 9 Intraocular ciprofloxacin levels after oral administration in silicone oil-filled eyes; Talwar D et al.; PURPOSE: To evaluate penetration of oral ciprofloxacin in the retro-silicone oil space fluid (RSOF) in silicone oil (SO)-filled eyes . METHODS: One dose of 750 mg ciprofloxacin was given to two groups of five patients with vitrectomized eyes with SO endotamponade, 4 hours (group I) and 8 hours (group II) before SO removal . In 10 vitrectomized eyes with SO endotamponade (group III) and another 10 patients scheduled for vitrectomy for the first time (group IV), two 750-mg doses every 12 hours, with the last dose 12 hours before surgery, were given . Blood samples were taken at the time of collection of RSOF samples in groups I, II, and III and of the vitreous in group IV . All samples were assayed for ciprofloxacin by high-performance liquid chromatography . RESULTS: The mean drug concentration in the RSOF was 0.34 +/- 0.09, 0.37 +/- 0.04, 0.84 +/- 0.29, and 0.44 +/- 0.11 micro g/mL in groups I, II, III, and IV respectively . The mean serum concentration was 1.29 +/- 0.63, 1.08 +/- 0.14, 1.93 +/- 0.84, and 1.34 +/- 0.55 micro g/mL in groups I, II, III, and IV respectively with no statistically significant difference between groups III and IV (P = 0.081) . CONCLUSIONS: Antibiotic levels in the RSOF in SO-filled eyes after oral administration of ciprofloxacin in two 750-mg doses exceeded the minimal inhibitory concentration for 90% of isolates (MIC(90)) for most bacterial species and was higher than levels reached in the vitreous in nonvitrectomized eyes (P = 0.001). Anticancer Res, 2002 Nov-Dec, 22(6C), 4179 - 81 Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen; Mahady GB et al.; BACKGROUND: Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa), has been shown to prevent gastric and colon cancers in rodents . Many mechanisms have been proposed for the chemopreventative effects, although the effect of curcumin on the growth of Helicobacter pylori has not been reported . H . pylori is a Group 1 carcinogen and is associated with the development of gastric and colon cancer . MATERIALS AND METHODS: A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H . pylori, including 5 cagA+ strains . RESULTS: Both the methanol extract and curcumin inhibited the growth of all strains of H . pylori in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml . CONCLUSION: These data demonstrate that curcumin inhibits the growth of H . pylori cagA+ strains in vitro, and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects. Wei Sheng Wu Xue Bao, 2001 Dec, 41(6), 723 - 30 {Preliminary study on citral impaires the Aspergillus flavus membrane}; Luo M et al.; Compared with the normally growing A . flauas, the content as below was determined: the utilization ratio to protein and reducing sugar of hyphostroma poisened by citral, the activity of {Na+, K+}-ATPase capable of decomposition ATP, and the seepagevity ratio of electrolyte . In addition, the shape change in spore was observed via the scanning electron microscope (SEM) and the fast multi-channel micro-spectrophotomer (FMCM) . The result above all suggested facts as following after it's poised by the citral in MIC . The surface of hyphostroma and spore turned into be porous and rough . The pass trace on spore shriveled and closed . The rate of conduct electricity increased by 52.8% . The utilization ratio to protein and reducing sugar respectively decreased 61.5% and 44.3% . The rate of spore's sprout dropped to 61.4% . The molecular structure of membrane was so distinctly changed that it lost the selective permeability . There was inhibition on hyphostroma growth and spore sprout. Biophys J, 2003 Feb, 84(2 Pt 1), 922 - 7 MIC channels are inhibited by internal divalent cations but not ATP; Kozak JA et al.; TRPM7 channels are nonselective cation channels that possess a functional alpha-kinase domain . It has been proposed that heterologously expressed TRPM7 channels are activated (Runnels et al., 2001) or inhibited (Nadler et al., 2001) by dialyzing the cell with millimolar levels of ATP . The endogenous correlate of TRPM7 has been identified in T-lymphocytes and RBL (rat basophilic leukemia) cells and named MagNuM (for Mg(2+)-nucleotide-inhibited metal) or MIC (for Mg(2+)-inhibited cation) . Here, we report that internal Mg(2+) rather than MgATP inhibits this current . Cytoplasmic MgATP, supplied by dialysis at millimolar concentrations, effectively inhibits only when a weak Mg(2+) chelator is present in the pipette solution . Thus, MgATP acts as a source of Mg(2+) rather than a source of ATP . Using an externally accessible site within the pore of the MIC channel itself as a bioassay, we show that equimolar MgCl(2) and MgATP solutions contain similar amounts of free Mg(2+), explaining the fact that numeric values of Mg(2+) and MgATP concentrations necessary for complete inhibition are the same . Furthermore, we demonstrate that Mg(2+) is not unique in its inhibitory action, as Ba(2+), Sr(2+), Zn(2+), and Mn(2+) can substitute for Mg(2+), causing complete inhibition . We conclude that MIC current inhibition occurs simply by divalent cations. Trends Immunol, 2003 Feb, 24(2), 82 - 7 HLA-G and MIC expression in tumors and their role in anti-tumor immunity; Seliger B et al.; Non-classical MHC class Ib molecules have attracted growing interest in recent years, especially because they interact with non-T-cell inhibitory or triggering receptors expressed on natural killer (NK) and T cells, suggesting that they have a role in immune recognition . Abnormalities in MHC class Ib expression are frequently found in human tumors of various histologies and might be associated with poor clinical outcome despite the local accumulation of immune competent cells . Available data suggest that the balance between activating and suppressing signals significantly influences the efficacy of the immune response and consequently of tumor progression. Cancer Genet Cytogenet, 2002 Nov, 139(1), 67 - 70 Malignant peripheral primitive neuroectodermal tumor of the kidney; Vicha A et al.; Ewing family of tumors is a group of highly aggressive neoplasias that occur most commonly in the first two decades of life . These tumors are most frequently localized in bones, less frequently in soft tissues . They usually appear as undifferentiated small round-cell tumors . With current treatment regiments, 5-year disease-free survival rates exceed 60% in patients with a localized disease . Patients with metastatic disease at the time of their first presentation have a poor prognosis . We describe a rare case of visceral primitive neuroectodermal tumor with the involvement of the kidney in a 9-year-old girl . The tumor was studied with immunohistochemistry, cytogenetics, and molecular biology methods . Strong expression of protein MIC(2) by immunochemistry (antibody HBA 71) with subsequent demonstration of a translocation consistent with t(11;22)(q24;q12) using cytogenetic and reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the histopathological diagnosis of peripheral primitive neuroectodermal tumor . We detected minimal residual disease in bone marrow using RT-PCR. Antimicrob Agents Chemother, 2003 Feb, 47(2), 588 - 93 The antifungal protein from Aspergillus giganteus causes membrane permeabilization; Theis T et al.; We investigated the inhibitory effects of the antifungal protein (AFP) from Aspergillus giganteus on the growth of several filamentous fungi . For this purpose, the MICs of AFP were determined and ranged from 0.1 micro g/ml for Fusarium oxysporum to 200 micro g/ml for Aspergillus nidulans . The antifungal activity of AFP was diminished in the presence of cations . We were able to show that incubation of AFP-sensitive fungi with the protein resulted in membrane permeabilization using an assay based on the uptake of the fluorescent dye SYTOX Green . No permeabilization by AFP could be detected at concentrations below the species-specific MIC . Furthermore, AFP-induced permeabilization could readily be detected after 5 min of incubation . Localization experiments with fluorescein isothiocyanate-labeled AFP and immunofluorescence staining with an AFP-specific antibody supported the observation that the protein interacts with membranes . After treatment of AFP-sensitive fungi with AFP, the protein was localized at the plasma membrane, whereas it was mainly detected inside the cells of AFP-resistant fungi . We conclude from these data that the growth-inhibitory effect of AFP is caused by permeabilization of the fungal membranes. Antimicrob Agents Chemother, 2003 Feb, 47(2), 524 - 8 Activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis; Goswick SM et al.; Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis . Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived . We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis . Azithromycin has shown in vitro activity against Acanthamoeba spp . and in vivo activity against experimental toxoplasmosis . In our study, the MIC of azithromycin against N . fowleri was 13.4 micro M (10 micro g/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 micro M (0.1 micro g/ml) . Azithromycin protected 100% of mice infected with N . fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period . We conclude that azithromycin has both in vitro and in vivo activity versus N . fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis. Diagn Microbiol Infect Dis, 2002 Dec, 44(4), 359 - 61 In vitro susceptibility of Mycoplasma hominis clinical isolates to tetracyclines, quinolones and macrolides; Samra Z et al.; We tested the in vitro activity of levofloxacin, ciprofloxacin, doxycycline, tetracycline, erythromycin, roxithromycin, clarithromycin and azithromycin against 110 clinical isolates of Mycoplasma hominis . The minimal inhibitory concentrations (MICs) were determined with the Etest . The minimal concentrations at which 90% of the isolates were inhibited (MIC(90)) were 0.064 microg/ml doxycycline and 0.19 microg/ml tetracycline . In 9 isolates (8.1%), the MIC for doxycycline was 4-12 microg/ml . These isolates were also resistant to tetracycline with a MIC of 32-128 microg/ml . No significant difference was found between doxycycline and tetracycline (p = 0.076) . Comparison of the two quinolones revealed that the MIC(90) for levofloxacin was 0.19 microg/ml and for ciprofloxacin, 0.5 microg/ml . A significant difference was found between doxycycline/tetracycline and levofloxacin or ciprofloxacin (p = 0.0001), and between levofloxacin and ciprofloxacin (p = 0.001) . All the isolates were highly resistant to the macrolides with MIC > or = 256 microg/ml . This finding has important implications for cases in which Mycoplasma infection is suspected and culture and/or in vitro susceptibility tests are not available. Diagn Microbiol Infect Dis, 2002 Dec, 44(4), 347 - 52 Evaluation of BACTEC MGIT 960 PZA medium for susceptibility testing of Mycobacterium tuberculosis to pyrazinamide (PZA): compared with the results of pyrazinamidase assay and Kyokuto PZA test; Aono A et al.; The fully automated BACTEC MGIT 960 PZA medium for susceptibility testing of Mycobacterium tuberculosis to pyrazinamide (PZA) was evaluated using 101 Mycobacterium tuberculosis clinical isolates . The results obtained with the system were compared with those of the pyrazinamidase (PZase) assay and the Kyokuto PZA test based on a broth culture, which is commercially available in Japan . The overall concordance rate was 90.1% (91/101) among the three methods in the initial test . The concordance rates between the BACTEC MGIT 960 PZA medium vs the PZase assay, the BACTEC MGIT 960 PZA medium vs the Kyokuto PZA test, and the PZase assay vs the Kyokuto PZA test were 93.1, 91.1, and 96.0%, respectively . On the repeat test of the 10 strains with discrepant results among the three methods, the concordance rates reached over 97% between each of the two systems . The results of the repeat test were confirmed by MIC testing and sequencing analysis of the pncA gene encoding PZase of M . tuberculosis . The mean turnaround times from incubation for PZA susceptibility testing were almost similar for the two methods based on liquid media, the BACTEC MGIT 960 PZA medium and the Kyokuto PZA test (7.7 and 7.4 days, respectively) . These results indicate that both methods based on liquid media, the fully automated BACTEC MGIT 960 PZA medium and the Kyokuto PZA test for susceptibility testing to PZA, are useful for rapid diagnosis of PZA resistant tuberculosis. Tissue Antigens, 2002 Dec, 60(6), 526 - 8 A new allele within the transmembrane region of the human MICA gene with seven GCT repeats; Rueda B et al.; Major histocompatibility complex class I chain-related genes (MIC) belong to a multicopy gene family located within the HLA class I region of chromosome 6 . They encode for proteins that have a completely different organization, expression, and products from classical HLA class I gene products . One member of this family is the MICA gene, which is characterized by its high degree of polymorphism, with over 50 MICA alleles described . Moreover, MICA exon 5 presents a microsatellite polymorphism consisting of a variable number of GCT repeats that encode for 4, 5, 6, 9, or 10 alanine residues, and a variant (MICA A5.1) that includes a nucleotide insertion (GCT-->GGCT) . In this study, we report a novel allele in the transmembrane region of the MICA gene consisting of seven GCT repeats found in a family based study of MICA polymorphism in celiac disease. J Endod, 2003 Jan, 29(1), 44 - 7 Antibiotic susceptibility of bacteria associated with endodontic abscesses; Baumgartner JC et al.; Antibiotics to treat endodontic infections are routinely prescribed based on previously published susceptibility tests . There is increased concern that bacteria have increased resistance to the currently recommended antibiotics . The purpose of this investigation was to perform antibiotic susceptibility tests on a panel of bacteria recently isolated from endodontic infections . The bacteria in this study were aseptically aspirated with a needle from endodontic abscesses, cultivated, and identified at the species level . Each of the 98 species of bacteria was tested for antibiotic susceptibility to a panel of six antibiotics using the Etest . The antibiotics were penicillin V, amoxicillin, amoxicillin + clavulanic acid, clindamycin, metronidazole, and clarithromycin . The percentages of susceptibility for the 98 species were penicillin V: 83/98 (85%), amoxicillin: 89/98 (91%), amoxicillin + clavulanic acid: 98/98 (100%), clindamycin: 94/98 (96%), and metronidazole: 44/98 (45%) . Metronidazole had the greatest amount of bacterial resistance; however, if it is used in combination with penicillin V or amoxicillin, susceptibility of the combination with penicillin V or amoxicillin increased to 93% and 99%, respectively . Clarithromycin seems to have efficacy, but it is still considered an antibiotic under investigation because the minimum inhibitory concentration has not been established. Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Jun, 18(3), 143 - 6 {Properties and infiltration arts of machinable infiltration ceramic(MIC)}; Yang H et al.; OBJECTIVE: The purpose of this study is to explore the infiltration arts of MIC and study the effects of different packing density of Al2O3 matrix on the properties of MIC . METHODS: alpha-Al2O3 specimens were fabricated by pouring alpha-Al2O3 slip with different powder/liquid ratios(P/L = 3.5, 7.5, 10.5) into a mold, and subsequently pre-fired at 1160 degrees C for 6 hours to form Al2O3 matrix . The packing density of the matrices were measured . Infiltration concepts were introduced into this study by infiltrating molten mica micro-crystalline glass into the porous Al2O3 matrix at 1160 degrees C for 6 hours to form a continuous interpenetrating composite . The composite then underwent micro-crystallization by nucleating at 550 degrees C for 1 hour and crystallizing at 900 degrees C for 1 hour, which resulted in the MIC . Mechanical properties including three point flexural strength, elastic modulus, Vicker's hardness, indentation fracture toughness and Weibull's modulus of flexural strength were determined . Parameters of machinability(H/KIC)2 of MIC were calculated . XRD and SEM were employed to study its microstructure . RESULTS: The resulted matrices reached packing densities of 63%, 76%, 78% with P/L of 3.5, 7.5 and 10.5 . The MIC attained high strength and good machinability after infiltration . Three-point flexural strength and indentation fracture toughness were 342, 431, 374 MPa and 4.05, 4.14, 5.02 MPa m1/2 for MIC with packing density of 63%, 76%, 78% separately . And parameters of machinability were 5.41, 6.84 and 7.39 respectively . Packing density of Al2O3 matrix significantly influenced the mechanical properties . Maximum properties were obtained with a matrix packing density of 75%(P/L = 7.5), with a Weibull's modulus of flexural strength of 6.8 . Machinability decreased with the increase of P/L ratio . Micro-crystallizing treatment resulted in the formation of evenly distributed mica crystalline in the composite, which contributed to the high strength of this composite material . CONCLUSION: MIC is a new infiltrated ceramic with favorable strength and machinability which can satisfy the prosthodontic requirements as all ceramic crown and bridge materials, it also shows promising outlook for future developments and clinical usage. Hua Xi Kou Qiang Yi Xue Za Zhi, 1999 Nov, 17(4), 325 - 8 {Investigation of aluminum oxide matrix of the machinable infiltrated ceramic(MIC)}; Yang H et al.; OBJECTIVE: To explore the effects of different powder/liquid ratio during the procedure of aluminum oxide slip preparation on the properties and microstructure of the machinable infiltrated ceramic(MIC) aluminum matrice . METHODS: PI alpha-Al2O3 powder was employed in this study . Aluminum slip with different powder/liquid ratios of 3.5, 4.5, 5.5, 6.5, 7.5, 8.5, 9.5 and 10.5 was prepared separately . Specimens were slip-casted and pre-fired, and whose physical properties were determined and morphology of specimens was examined under scanning electromicroscope . RESULTS: The packing density increased while the linear shrinkage decreased, when the powder/liquid ratio increased . Elevated pre-firing temperature resulted in higher flexural strength of the matrice . The matrice demonstrated porous morphology under electromicroscope, and neck-fusion between Al2O3 particles was observed and increased with elevated prefiring temperature . CONCLUSION: MIC is a kind of easy-manipulated material with high packing density, optimum porosity and lower linear shrinkage, so it may be an ideal aluminum matrix for infiltrated ceramic. Transpl Infect Dis, 2002 Dec, 4(4), 212 - 7 Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation . Scedosporiasis and recent advances in antifungal therapy; Safdar A et al.; Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation . We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease . This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis . Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue . A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk. J Pharm Sci, 2003 Feb, 92(2), 407 - 13 Preparation of in situ-forming ophthalmic gels of ciprofloxacin hydrochloride for the treatment of bacterial conjunctivitis: in vitro and in vivo studies; Charoo NA et al.; Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC) and carbopol 934 . The sol-to-gel systems were sterilized by gamma radiation and/or filtration . The sol-to-gel systems were evaluated for rheological characteristics, in vitro release behavior, microbial efficacy, in vivo release behavior, and efficacy against induced bacterial conjunctivitis in rabbits' eyes . Concentration in aqueous humor was determined and stability studies were carried out as per the ICH guidelines . The system passed the test for sterility . The sol-to-gel system exhibited a zero-order drug release pattern over 24 h in in vitro release studies . The drug was active against selected microorganisms in microbial efficacy studies . Better improvement in artificially induced bacterial conjunctivitis in rabbits' eyes was observed in animals treated with the sol-to-gel system compared with marketed eye drops . Drug concentration in aqueous humor was greater than the minimum inhibitory concentration (MIC 90) against selected microorganisms . The shelf-life of the product was >2 years . Mikrobiologiia, 2002 Nov-Dec, 71(6), 778 - 85 {The production of phenazine antibiotics by the Pseudomonas aureofaciens strain with plasmid-controlled resistance to cobalt and nickel}; Siunova TV et al.; Plasmid pBS501 responsible for the resistance of the wild-type Pseudomonas sp . BS501 (pBS501) to cobalt and nickel ions was conjugatively transferred to the rhizosphere Pseudomonas aureofaciens strain BS1393, which is able to synthesize phenazine antibiotics and to suppress a wide range of phytopathogenic microorganisms . The transconjugant P . aureofaciens BS1393 (pBS501) turned out to be resistant to cobalt and nickel with an MIC of 8 mM . When grown in a synthetic medium with 0.25 mM cobalt, the transconjugant accumulated 6 times more cobalt than the wild-type strain BS501 (pBS501) (1.2 and 0.2 microgram Co/mg protein) . Electron microscopic studies showed that cobalt accumulates on the surface of transconjugant cells in the form of electron-opaque granules . In a culture medium with 2 mM cobalt or nickel, strain BS1393 produced phenazine-1-carboxylic acid in trace amounts . The transconjugant P . aureofaciens BS1393 (pBS501) produced this antibiotic in still smaller amounts . Unlike the parent strain BS1393, the transconjugant P . aureofaciens BS1393 (pBS501) was able to suppress in vitro the growth of the phytopathogenic fungus Gaeumannomyces graminis var . tritici 1818 in a medium containing 0.5 mM cobalt or nickel. J Infect Chemother, 2002 Dec, 8(4), 374 - 7 Usefulness of a colorimetric method for testing antifungal drug susceptibilities of Aspergillus species to voriconazole; Yamaguchi H et al.; The usefulness of a colorimetric method using Alamar Blue (Alamar Blue method) for susceptibility testing of Aspergillus species to voriconazole and three existing antifungal agents, itraconazole (ITCZ), flucytosine (5-FC), and amphotericin B (AMPH-B), was studied using four ATCC strains of three species, including two strains of A . fumigatus and one each of A . flavus and A . niger . For comparison, the broth microdilution method for antifungal susceptibility testing of filamentous fungi proposed by the National Committee for Clinical Laboratory Standards (NCCLS method M38-P) was also used . Minimum inhibitory concentration (MIC) endpoints were read spectrophotometrically for the Alamar Blue method and visually for the NCCLS method after 46-50 h . Like the NCCLS method, Alamar Blue produced highly reproducible results for all the drugs and strains tested; most MIC values obtained by nine tests were within the range of 2 twofold dilutions for each strain . Voriconazole and ITCZ susceptibility testing with the Alamar Blue method and the NCCLS method yielded comparable results in 94% of the tests, meaning that the endpoints obtained were identical or differed by no more than 2 twofold dilutions . On the other hand, susceptibility testing for 5-FC and AMPH-B yielded scores of 25% and 64%, respectively . Our study suggests the potential value of the Alamar Blue method as a convenient alternative to the NCCLS M38-P method for routine testing of Aspergillus species susceptibility to at least voriconazole and ITCZ. J Antibiot (Tokyo), 2002 Oct, 55(10), 873 - 80 TPU-0037-A, B, C and D, novel lydicamycin congeners with anti-MRSA activity from Streptomyces platensis TP-A0598; Furumai T et al.; In screening for anti-MRSA antibiotics, novel lydicamycin congeners, TPU-0037-A, B, C and D, were isolated from a culture broth of an actinomycete strain . The producing strain, TP-A0598, was isolated from a seawater sample collected in Toyama Bay, Japan, and identified as Streptomyces platensis based on taxonomic characteristics . TPU-0037-A, B, C and D were purified by HP-20 resin, ODS column chromatographies and preparative HPLC, consecutively, and their structures were determined to be 30-demethyllydicamycin, 14,15-dehydro-8-deoxylydicamycin, 30-demethyl-8-deoxylydicamycin and 8-deoxylydicamycin, respectively, by NMR and MS analyses . The new congeners showed antibiotic activity against gram-positive bacteria including MRSA with the MIC of 1.56 to approximately 12.5 microg/ml. Microb Drug Resist, 2002 Winter, 8(4), 311 - 9 Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole; Hsueh PR et al.; The incidence of nosocomial Candida fungemia increased 36-fold from 1981 (0.8/10,000 discharges) to 2000 (28.8/10,000 discharges) at the National Taiwan University Hospital, a 2000-bed teaching hospital in northern Taiwan . To understand the current status of resistance to available antifungal agents among Candida species causing invasive infections, the in vitro susceptibilities of 222 isolates (collected from July, 1999-June, 2001) were determined . Among all of the Candida species tested, 6% and 7% were resistant to fluconazole and itraconazole, respectively . The MIC90 values of voriconazole and amphotericin B were 0.5 and 1 microg/ml, respectively, although some isolates of C . krusei (amphotericin B and voriconazole MIC, >64 microg/ml) and C . tropicalis and C . glabrata (voriconazole MICs, >64 microg/ml) were less susceptible to voriconazole or amphotericin B . About one-half of the C . glabrata isolates belonged to susceptible dose-dependent (SDD, 36%) or resistant (12%) categories for fluconazole and 96% belonged to SDD (56%) or resistant (40%) category for itraconazole . When compared with fluconazole susceptibility data of blood Candida isolates recovered from patients treated at the same hospital (NTUH) from two different time periods (January, 1994, to June, 1995, and January, 1997, to June, 1999 described in previous reports), the incidence of increased susceptibility of non-krusei Candida isolates to fluconazole was evident . This trend of increasing susceptibility for fluconazole did not correlate to the increasing use of this agent in the hospital . None of the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR using four random oligonucleotide primers for 14 isolates, which exhibited fluconazole MICs of > or = 16 microg/ml, were identical, indicating an absence of clonal dissemination among these isolates in the hospital. J Clin Microbiol, 2003 Jan, 41(1), 403 - 9 Evaluation of broth microdilution testing parameters and agar diffusion Etest procedure for testing susceptibilities of Aspergillus spp . to caspofungin acetate (MK-0991); Espinel-Ingroff A; The NCCLS M38-A document does not describe guidelines for testing caspofungin acetate (MK-0991) and other echinocandins against molds . This study evaluated the susceptibilities of 200 isolates of Aspergillus fumigatus, A . flavus, A . nidulans, A . niger, and A . terreus to caspofungin (MICs and minimum effective concentrations {MECs}) by using standard RPMI 1640 (RPMI) and antibiotic medium 3 (M3), two inoculum sizes (10(3) and 10(4) CFU/ml), and two MIC determination criteria (complete {MICs-0} and prominent growth inhibition {MICs-2}) at 24 and 48 h . Etest MICs were also determined . In general, caspofungin MIC-2 and MEC pairs were comparable with both media and inocula (geometric mean ranges of MECs and MICs, respectively, with larger inoculum: 0.12 to 0.64 microg/ml and 0.12 to 0.44 microg/ml with RPMI versus 0.04 to 0.51 microg/ml and 0.03 to 0.21 microg/ml with M3); however, MEC results were less influenced by testing conditions than MICs, especially with the larger inoculum . Overall, the agreement between caspofungin Etest MICs and broth dilution values was higher with MECs obtained with M3 (>90%) and the large inoculum than under the other testing conditions . Because RPMI is a more stable and chemically defined medium than M3, the determination at 24 h of the easier visual MECs with RPMI and the inoculum recommended in the M38-A document appears to be a suitable procedure at present for in vitro testing of caspofungin against Aspergillus spp . Future in vitro correlations with in vivo outcome of both microdilution and Etest procedures may detect more-relevant testing conditions. J Clin Microbiol, 2003 Jan, 41(1), 78 - 83 In vitro activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida species infrequently isolated from blood; Pfaller MA et al.; We determined the in vitro susceptibilities of 314 strains of Candida spp., representing 13 species rarely isolated from blood, to posaconazole and voriconazole as well as four licensed systemic antifungal agents (amphotericin B, flucytosine, fluconazole, and itraconazole) . The organisms included 153 isolates of C . krusei, 67 isolates of C . lusitaniae, 48 isolates of C . guilliermondii, 10 isolates of C . famata, 10 isolates of C . kefyr, 6 isolates of C . pelliculosa, 5 isolates of C . rugosa, 4 isolates of C . lipolytica, 3 isolates of C . dubliniensis, 3 isolates of C . inconspicua, 2 isolates of C . sake, and 1 isolate each of C . lambica, C . norvegensis, and C . zeylanoides . MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B) . Resistance to both amphotericin B and fluconazole was observed in strains of C . krusei, C . lusitaniae, C . guilliermondii, C . inconspicua, and C . sake . Resistance to amphotericin B, but not to fluconazole, was also observed among isolates of C . kefyr and C . rugosa . Posaconazole and voriconazole were active (MIC, < or = 1 micro g/ml) against 94 to 100% of these isolates . In contrast to the more common species of Candida causing bloodstream infection, these rare species appear to be less susceptible to the currently licensed systemic antifungal agents, with the exception of voriconazole . Continued surveillance will be necessary to detect the emergence of these species as more prevalent, resistant pathogens . The new triazoles appear to offer acceptable coverage of uncommon Candida sp . bloodstream infections. Zhongguo Zhong Yao Za Zhi, 2000 May, 25(5), 306 - 8 {Observation of cell ultrastructuse in suppurative otitis media treated with bosneol and application}; Chang SP et al.; OBJECTIVE: To explore the pharmacological action and optimal concentration of borneol in treating suppurative otitis media . METHOD: Aspergillus niger separated from the secretion in external auditory canal of the patient and the fungus strains kept in the laboratory were used to determine the minimum fungus inhibiting concentration (MIC) and minimum fungus killing concentration (MFC) of borne . The change of cell ultrastructure after borneol taking effect was observed under electron microscope . RESULT: Borneol MIC and MFC turned out to be 5% and 10% respectively . The cell wall of Aspergillus niger became thicker and blurred with vacuoles . In the cytoplasm various materials were found deep dyed and agglutinated with many fat drops . The electron density increased and the ridge arrangement was in disorder . Some organelles were destroyed, and many areas of electron blank appeared . Some cells became warped and deformed and lost their original structure . CONCLUSION: Borneol can destroy the structure of fungus cells, make fungus dissolve and dieout and thus features a fungus inhibiting and killing function . The optimal inhibiting concentration is 5% and killing concentration 10%. Cell Mol Biol Lett, 2002, 7(4), 1121 - 9 Lysosomotropic N,N- dimethyl alpha-aminoacid N-alkyl esters and their quaternary ammonium salts as plasma membrane and mitochondrial ATPases inhibitors; Oblak E et al.; A set of n-alkyl esters of N,N-dimethylglycine (DMG-n) and their methobromides (DMGM-n) was synthesized, and their activities on yeast Saccharomyces cerevisiae were compared . The compounds differ in the number of carbon atoms in the aliphatic chain . Aminoesters with 12 carbon atoms appeared to be most active . Unlike quaternary ammonium salts previously tested, the activities of the compounds were not pH-dependent; the minimal inhibitory concentrations (MIC) were identical at pH 8 and at pH 6 . In contrast to quaternary ammonium salts, aminoesters showed similar effects on respiratory sufficient (rho+) and respiratory deficient (rho0) mutants . When tested on glucose stimulated proton extrusion, aminoesters applied at MIC increased external pH . Aminoesters inhibited the plasma membrane H+-ATPase, whereas they were less inhibitory on the mitochondrial ATPase . In order to further compare the aminoesters and their corresponding quaternary ammonium salts, derivatives of N,N-dimethylalanine (DMAL-n and DMALM-n, respectively) were synthesized . The quaternary ammonium salts appeared to have a higher inhibitory potency than aminoesters, especially at pH 8, and alanine derivatives inhibited growth at a lower concentration than glycine derivatives . Both alanine derivatives of the aminoester and the quaternary ammonium salt inhibited the plasma membrane H+- ATPase at lower concentrations than glycine derivatives, but the alanine aminoester was without a detectable effect on the mitochondrial ATPase. Int J Antimicrob Agents, 2003 Jan, 21(1), 39 - 48 Parasitological cure of acute and chronic experimental Chagas disease using the long-acting experimental triazole TAK-187 . Activity against drug-resistant Trypanosoma cruzi strains; Urbina JA et al.; We investigated the activity of TAK-187, an experimental antifungal triazole with a long terminal half-life in several experimental animals, against Trypanosoma cruzi . In vitro studies showed that the minimal inhibitory concentration (MIC) against the (extracellular) epimastigote form was 0.3-1 microM, while the corresponding concentration against clinically relevant intracellular amastigotes was 1 nM . At the MIC the endogenous epimastigote C4,14-desmethyl sterols were replaced by di- and tri-methylated sterols, supporting the notion that the primary target of TAK-187 is the parasite's sterol C14alpha demethylase . We investigated the in vivo activity of the compound in a murine model of acute Chagas disease, using T . cruzi strains with different susceptibilities to the drugs currently used clinically (nitrofurans and nitroimidazoles) . It was found that TAK-187 given orally at 20 mg/kg induced complete protection against death and high levels (60-100%) of parasitological cures, independently of the infecting strain and even when administered every other day (e.o.d.), consistent with its long terminal half-life in mice . Other experiments, using longer treatment periods were carried out in both acute and chronic models of the disease and showed that TAK-187 given at 10-20 mg/kg e.o.d . induced 80-100% survival with 80-100% of parasitological cures of survivors in both models . No toxic side effects were observed in any of the experimental protocols . TAK-187 is a potent anti-T . cruzi compound with trypanocidal activity in vivo and should be considered for further studies as a potential specific treatment of human Chagas disease. Int J Antimicrob Agents, 2003 Jan, 21(1), 27 - 38 In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease; Urbina JA et al.; Ravuconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in humans . In this work, we investigated the in vitro and in vivo activities of this compound against Trypanosoma cruzi . Ravuconazole showed very potent in vitro anti-T . cruzi activity with minimal inhibitory concentrations (MIC) of 300 and 1 nM against the extracellular epimastigote and intracellular amastigote forms, respectively . As with other azole derivatives, ravuconazole at the MIC led to an essentially complete depletion of the epimastigotes' endogenous C4,14-desmethyl sterols and their replacement by di- and tri-methylated sterols . In murine acute models of acute Chagas disease, it was found that ravuconazole treatment led to high levels of parasitological cures, but only when given twice a day (b.i.d.), consistent with its short terminal half-life in mice (4 h) . Furthermore, it was found that this curative activity was restricted towards nitrofuran/nitroimidazole-susceptible (CL) and partially drug-resistant (Y) strains of T . cruzi, with no curative activity