bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Inhibition of Bovine Viral Diarrhea Virus by Aromatic Cationic Molecules
Authors: Givens M. Daniel , Dykstra Christine C. , Brock Kenny V. , Stringfellow David A. , Kumar Arvind , Stephens Chad E. , Goker Hakan , Boykin David W.
Published: June 2003

Bovine viral diarrhea virus (BVDV) is an economically significant pathogen of cattle and a problematic contaminant in the laboratory. BVDV is often used as an in vitro model for hepatitis C virus during drug discovery efforts. Aromatic dicationic molecules have exhibited inhibitory activity against several RNA viruses. Thus, the purpose of this research was to develop and apply a method for screening the aromatic cationic compounds for in vitro cytotoxicity and activity against a noncytopathic strain of BVDV. The screening method evaluated the concentration of BVDV in medium and cell lysates after 72 h of cell culture in the presence of either a 25 or 5 μM concentration of the test compound. Five of 93 screened compounds were selected for further determination of inhibitory (90 and 50%) and cytotoxic (50 and 10%) concentration endpoints. The screening method identified compounds that exhibited inhibition of BVDV at nanomolar concentrations while exhibiting no cytotoxicity at 25 μM concentrations. The leading compounds require further investigation to determine their mechanism of action, in vivo activity, and specific activity against hepatitis C virus.
Allele-Specific
rpoB
PCR Assays for Detection of Rifampin-Resistant
Mycobacterium tuberculosis
in Sputum Smears
Authors: Mokrousov Igor , Otten Tatiana , Vyshnevskiy Boris , Narvskaya Olga
Published: June 2003

We describe an allele-specific PCR assay to detect mutations in three codons of the
rpoB
gene (516, 526, and 531) in
Mycobacterium tuberculosis
strains; mutations in these codons are reported to account for majority of
M. tuberculosis
clinical isolates resistant to rifampin (RIF), a marker of multidrug-resistant tuberculosis (MDR-TB). Three different allele-specific PCRs are carried out either directly with purified DNA (single-step multiplex allele-specific PCR), or with preamplified
rpoB
fragment (nested allele-specific PCR [NAS-PCR]). The method was optimized and validated following analysis of 36 strains with known
rpoB
sequence. A retrospective analysis of the 287 DNA preparations from epidemiologically unlinked RIF-resistant clinical strains from Russia, collected from 1996 to 2002, revealed that 247 (86.1%) of them harbored a mutation in one of the targeted
rpoB
codons. A prospective study of microscopy-positive consecutive sputum samples from new and chronic TB patients validated the method for direct analysis of DNA extracted from sputum smears. The potential of the NAS-PCR to control for false-negative results due to lack of amplification was proven especially useful in the study of these samples. The developed
rpoB
-PCR assay can be used in clinical laboratories to detect RIF-resistant and hence MDR
M. tuberculosis
in the regions with high burdens of the MDR-TB.
Phenotypic and Molecular Characterization of Tetracycline- and Erythromycin-Resistant Strains of
Streptococcus pneumoniae
Authors: Montanari Maria P. , Cochetti Ileana , Mingoia Marina , Varaldo Pietro E.
Published: June 2003

Sixty-five clinical isolates of
Streptococcus pneumoniae
, all collected in Italy between 1999 and 2002 and resistant to both tetracycline (MIC, ≥8 μg/ml) and erythromycin (MIC, ≥1 μg/ml), were investigated. Of these strains, 11% were penicillin resistant and 23% were penicillin intermediate. With the use of the erythromycin-clindamycin-rokitamycin triple-disk test, 14 strains were assigned to the constitutive (cMLS) phenotype of macrolide resistance, 44 were assigned to the partially inducible (iMcLS) phenotype, 1 was assigned to the inducible (iMLS) phenotype, and 6 were assigned to the efflux-mediated (M) phenotype. In PCR assays, 64 of the 65 strains were positive for the tetracycline resistance gene
tet
(M), the exception being the one M isolate susceptible to kanamycin, whereas
tet
(K),
tet
(L), and
tet
(O) were never found. All cMLS, iMcLS, and iMLS isolates had the erythromycin resistance gene
erm
(B), and all M phenotype isolates had the
mef
(A) or
mef
(E) gene. No isolate had the
erm
(A) gene. The
int-Tn
gene, encoding the integrase of the Tn
916
-Tn
1545
family of conjugative transposons, was detected in 62 of the 65 test strains. Typing assays showed the strains to be to a great extent unrelated. Of 16 different serotypes detected, the most numerous were 23F (
n
= 13), 19A (
n
= 10), 19F (
n
= 9), 6B (
n
= 8), and 14 (
n
= 6). Of 49 different pulsed-field gel electrophoresis types identified, the majority (
n
= 39) were represented by a single isolate, while the most numerous type included five isolates. By high-resolution restriction analysis of PCR amplicons with four endonucleases, the
tet
(M) loci from the 64
tet
(M)-positive pneumococci were classified into seven distinct restriction types. Overall, a Tn
1545
-like transposon could reasonably account for tetracycline and erythromycin resistance in the vast majority of the pneumococci of cMLS, iMcLS, and iMLS phenotypes, whereas a Tn
916
-like transposon could account for tetracycline resistance in most M phenotype strains.
Gastric Transitional Zones, Areas whereHelicobacterTreatment Fails: Results of a Treatment Trial Using the Sydney Strain Mouse Model
Authors: van Zanten Sander J. O. Veldhuyzen , Kolesnikow Tassia , Leung Vincent , O'Rourke Jani L. , Lee Adrian
Published: June 2003

Current combination therapies cureHelicobacter pyloriinfection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using theH. pyloriSydney strain (SS1) mouse model. Mice infected withH. pylori(SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.
Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects
Authors: Gajjar D. A. , Bello A. , Ge Z. , Christopher L. , Grasela D. M.
Published: June 2003

Garenoxacin (T-3811ME, BMS-284756) is a novel des-F(6) quinolone that has been shown to be effective in vitro against a wide range of clinically important pathogens, including gram-positive and gram-negative aerobes and anaerobes. This study was conducted to evaluate the safety and tolerability of multiple oral doses (100 to 1,200 mg/day) of garenoxacin in healthy subjects and to determine its multiple-dose pharmacokinetics. Forty healthy male and female subjects (18 to 45 years of age) were enrolled in this randomized, double-blind, placebo-controlled, sequential, multiple- and ascending-dose study. Each subject received a once-daily oral dose of garenoxacin (100, 200, 400, 800, or 1,200 mg) or a placebo for 14 days. Blood and urine samples were collected for measurements of garenoxacin by validated liquid chromatography with dual mass spectrometry, and plasma garenoxacin concentration-time data were analyzed by noncompartmental methods. The effects of garenoxacin on
Helicobacter pylori
, psychometric test performance, and electrocardiograms were assessed, as was drug safety. Over the 14 days of dosing, geometric mean peak concentrations of garenoxacin in plasma (
C
max
) at the 100- and 1,200-mg doses were within the ranges of 1.2 to 1.6 and 16.3 to 24 μg/ml, respectively. The corresponding values for the geometric mean area under the concentration-time curve over the dosing interval (AUC

τ

) for garenoxacin in plasma at the 100- and 1,200-mg doses were within the ranges of 11.5 to 15.7 and 180 to 307 μg · h/ml, respectively. Increases in systemic exposure to garenoxacin in terms of AUC and
C
max
were approximately dose proportional over the 100- to 400-mg dose range but demonstrated increases that were somewhat greater than the dose increments at the 800- and 1,200-mg doses. Median values for the time to achieve
C
max
were in the range of 1.13 to 2.50 h for all doses. The mean elimination half-life for garenoxacin in plasma appeared to be independent of dose and ranged from 13.3 to 17.8 h (day 14). Approximately 30 to 50% of an administered garenoxacin dose was excreted unchanged in the urine. At doses of 100 to 400 mg, steady-state concentrations of garenoxacin in plasma appeared to be attained by the fourth dose. Multiple oral doses of garenoxacin were well tolerated and did not demonstrate clinically significant effects on QT
c
or psychometric test results. Garenoxacin administered alone for 14 days at doses of ≥400 mg demonstrated activity against
H. pylori.
These results suggest that multiple once-daily oral doses of garenoxacin of up to 1,200 mg are safe and well tolerated and that the pharmacokinetics of garenoxacin support once-daily administration.
Neuraminidase Sequence Analysis and Susceptibilities of Influenza Virus Clinical Isolates to Zanamivir and Oseltamivir
Authors: McKimm-Breschkin J. , Trivedi T. , Hampson A. , Hay A. , Klimov A. , Tashiro M. , Hayden F. , Zambon M.
Published: June 2003

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1,000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC
50
s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC
50
s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC
50
s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC
50
s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC
50
s were above the 95% confidence limits and several control isolates for which the IC
50
s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.
Molecular Basis for Fungal Selectivity of Novel Antimitotic Compounds
Authors: Lila Thomas , Renau Thomas E. , Wilson Lori , Philips Jay , Natsoulis Georges , Cope M. Jamie , Watkins William J. , Buysse Jerry
Published: June 2003

Compounds that selectively disrupt fungal mitosis have proven to be effective in controlling agricultural pests, but no specific mitotic inhibitor is available for the treatment of systemic mycoses in mammalian hosts. In an effort to identify novel mitotic inhibitors, we used a cell-based screening strategy that exploited the hypersensitivity of a yeast α-tubulin mutant strain to growth inhibition by antimitotic agents. The compounds identified inhibited yeast nuclear division and included one structural class of compounds shown to be fungus specific. MC-305,904 and structural analogs inhibited fungal cell mitosis and inhibited the in vitro polymerization of fungal tubulin but did not block mammalian cell microtubule function or mammalian tubulin polymerization. Extensive analysis of yeast mutations that specifically alter sensitivity to MC-305,904 structural analogs suggested that compounds in the series bind to a site on fungal β-tubulin near amino acid 198. Features of the proposed binding site explain the observed fungal tubulin specificity of the series and are consistent with structure-activity relationships among a library of related compounds.
Quantitative Analysis of Gentamicin, Azithromycin, Telithromycin, Ciprofloxacin, Moxifloxacin, and Oritavancin (LY333328) Activities against Intracellular
Staphylococcus aureus
in Mouse J774 Macrophages
Authors: Seral Cristina , Van Bambeke Françoise , Tulkens Paul M.
Published: June 2003

Using J774 macrophages, the intracellular activities of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) against
Staphylococcus aureus
(strain ATCC 25923) have been quantitatively assessed in a 24-h model.
S. aureus
was positively localized in phagolysosomes by confocal and electron microscopy, and extracellular growth was prevented with 0.5 mg of gentamicin/liter (1× MIC) in controls. When tested at extracellular concentrations equivalent to their maximum concentrations in human serum, all antibiotics except azithromycin caused a significant reduction of the postphagocytosis inoculum within 24 h, albeit to markedly different extents (telithromycin [2 mg/liter], 0.60 log; ciprofloxacin [4.3 mg/liter], 0.81 log; gentamicin [18 mg/liter], 1.21 log; moxifloxacin [4 mg/liter], 1.51 log; oritavancin [25 mg/liter], 3.49 log). Intracellular activities were not systematically related to drug accumulation (apparent cellular-to-extracellular concentration ratios in infected cells: ciprofloxacin, 3.2; gentamicin, 6.8; telithromycin, 8.7; moxifloxacin, 13.4; azithromycin, 50; oritavancin, 348). Intracellular activity was not directly correlated to extracellular activity as measured in broth. Conditions of pH 5 (i.e., mimicking that of phagolysosomes) markedly reduced the activity of gentamicin, azithromycin, and telithromycin (≥32×) and fairly extensively reduced that of ciprofloxacin and moxifloxacin (≥4×) but did not affect oritavancin activity. We conclude that the cellular accumulation of antibiotics is not the only parameter to take into account for intracellular activity but that local environmental conditions (such as pH) and other factors can also prove critical.
Synergistic In Vitro Interactions between Alpha Interferon and Ribavirin against Bovine Viral Diarrhea Virus and Yellow Fever Virus as Surrogate Models of Hepatitis C Virus Replication
Authors: Buckwold Victor E. , Wei Jiayi , Wenzel-Mathers Michelle , Russell Julie
Published: June 2003

Monotherapy of hepatitis C virus infection with either alpha interferon or ribavirin alone is rather ineffective, while the use of the two antivirals together is much more efficacious. In vitro drug-drug combination analysis utilizing related members of the family
Flaviviridae
, bovine viral diarrhea virus and yellow fever virus, revealed significant direct synergistic interactions between these drugs' antiviral activities that might explain this clinical observation.
Inhibitory Effect of NO-Releasing Ciprofloxacin (NCX 976) on
Mycobacterium tuberculosis
Survival
Authors: Ciccone R. , Mariani F. , Cavone A. , Persichini T. , Venturini G. , Ongini E. , Colizzi V. , Colasanti M.
Published: June 2003

Here, we report the antimycobacterial activity of NCX 976, a new molecule obtained adding a NO moiety to the fluoroquinolone ciprofloxacin, on
Mycobacterium tuberculosis
H37Rv strain, both in a cell-free model and in infected human macrophages. Unlike unaltered ciprofloxacin, NCX976 displayed a marked activity also at low-nanomolar concentrations.
Intracellular Release of Nitric Oxide by NCX 972, an NO-Releasing Metronidazole, Enhances In Vitro Killing ofEntamoeba histolytica
Authors: Sannella Anna , Gradoni Luigi , Persichini Tiziana , Ongini Ennio , Venturini Giorgio , Colasanti Marco
Published: June 2003

The activity of NCX 972, a new molecule obtained by adding a nitric oxide (NO) moiety to metronidazole, was tested against six isolates ofEntamoeba histolyticain xenic cultures. NCX 972 released NO into trophozoite cells and enhanced killing of amoebas in a dose- and time-dependent manner compared to metronidazole.
Nonsense Mutations in the
lsa
-Like Gene in
Enterococcus faecalis
Isolates Susceptible to Lincosamides and Streptogramins A
Authors: Dina Julia , Malbruny Brigitte , Leclercq Roland
Published: June 2003

The
lsa
gene confers intrinsic resistance to lincosamides and streptogramins A in
Enterococcus faecalis
, probably by active efflux. The
lsa
-like genes of two clinical isolates of
E. faecalis
susceptible to lincosamides and dalfopristin contained mutations that produced premature termination codons. Revertant mutants were obtained by selection on agar plates containing clindamycin.
Presence of the Tet M Determinant in a Clinical Isolate of
Acinetobacter baumannii
Authors: Ribera Anna , Ruiz Joaquim , Vila Jordi
Published: June 2003

The
tet
(M) gene encodes a protein which is related to tetracycline ribosomal protection, one of the mechanisms of tetracycline resistance. A
tet
(M) gene that is 100% homologous to the
tet
(M) gene of
Staphylococcus aureus
has been found in a clinical isolate of
Acinetobacter baumannii
, which also carries the
tet
(A) gene encoding a tetracycline efflux pump.
Zinc Eluted from Siliconized Latex Urinary Catheters Decreases OprD Expression, Causing Carbapenem Resistance in
Pseudomonas aeruginosa
Authors: Conejo M. Carmen , García Isabel , Martínez-Martínez Luis , Picabea Leandro , Pascual Álvaro
Published: June 2003

The activities of carbapenems against
Pseudomonas aeruginosa
decreased in the presence of siliconized latex urinary catheters (SLUCs). This effect was associated with the loss of OprD. The zinc that eluted from SLUCs is responsible for this phenomenon. We have found that zinc exerts a negative effect on the expression of OprD, the porin responsible for carbapenem entry into
P. aeruginosa
.
Detection of Nucleotide Variability in
rpoB
in both Rifampin-Sensitive and Rifampin-Resistant Strains of
Chlamydia trachomatis
Authors: Dreses-Werringloer Ute , Padubrin Ingrid , Köhler Lars , Hudson Alan P.
Published: June 2003

A 656-bp PCR fragment from
rpoB
was sequenced from five rifampin-resistant
Chlamydia trachomatis
variants selected in vitro from a wild-type parent with a surprising level of genetic variability in this region. Three variants (MIC, 4 μg/ml) showed Ala522→Val in cluster I (codons 507 to 533), which harbors mutations in most rifampin-resistant bacteria. Two high-level resistance variants (MICs, 64 and 256 μg/ml) showed His526→Tyr in cluster I with additional genetic variation, some of which resulted in amino acid substitutions. None of the latter was situated in clusters related to rifampin resistance in other bacteria.
Ribosomal Mutations Conferring Resistance to Macrolides in
Streptococcus pneumoniae
Clinical Strains Isolated in Germany
Authors: Reinert Ralf René , Wild Angela , Appelbaum Peter , Lütticken Rudolf , Cil Murat Yücel , Al-Lahham Adnan
Published: June 2003

Among a collection of 4,281 pneumococcal isolates, 7 strains isolated in Germany had an unusual macrolide resistance phenotype. The isolates were found to have multiple mutations in the 23S rRNA and alterations in the L4 ribosomal protein. One strain had an amino acid alteration in the L22 ribosomal protein.
Decolorization of Malachite Green and Crystal Violet by Waterborne Pathogenic Mycobacteria
Authors: Jones Jefferson J. , Falkinham Joseph O.
Published: June 2003

Mycobacterium avium,Mycobacterium intracellulare,Mycobacterium scrofulaceum,Mycobacterium marinum, andMycobacterium chelonaetolerate high concentrations of the dyes malachite green and crystal violet. Cells of strains of those species decolorized (reduced) both malachite green and crystal violet. Because decolorized malachite green lacked antimicrobial activity, the resistance of these mycobacteria could be due, in part, to their ability to decolorize the dyes. Small amounts of malachite green and its reduced, decolorized product were detected in the lipid fraction ofM. aviumstrain A5 cells grown in the presence of malachite green, suggesting that a minor component of resistance could be due to sequestering the dyes in the extensive mycobacterial cell surface lipid. The membrane fraction ofM. aviumstrain A5 had at least a fivefold-higher specific decolorization rate than did the crude extract, suggesting that the decolorization activity is membrane associated. The malachite green-decolorizing activity of the membrane fraction ofM. aviumstrain A5 was abolished by either boiling or proteinase exposure, suggesting that the decolorizing activity was due to a protein. Decolorization activity of membrane fractions was stimulated by ferrous ion and inhibited by dinitrophenol and metyrapone.
Inhibitory Activities of Quinolones against DNA Gyrase of
Chlamydia pneumoniae
Authors: Ameyama Satoshi , Shinmura Yuko , Takahata Masahiro
Published: June 2003

The
gyrA
and
gyrB
genes of
Chlamydia pneumoniae
TW-183 were cloned, and their proteins were purified by use of a fusion system with a maltose-binding protein. The 50% inhibitory concentrations of garenoxacin, sparfloxacin, moxifloxacin, gatifloxacin, and levofloxacin were 10.1, 47.5, 39.6, 64.2, and 156.9 μg/ml, respectively, and the MICs against
C. pneumoniae
TW-183 were 0.008, 0.016, 0.063, 0.125, and 0.25 μg/ml, respectively.
Sfh-I, a Subclass B2 Metallo-β-Lactamase from a
Serratia fonticola
Environmental Isolate
Authors: Saavedra Maria José , Peixe Luísa , Sousa João Carlos , Henriques Isabel , Alves Artur , Correia António
Published: June 2003

An environmental isolate of
Serratia fonticola
resistant to carbapenems was shown to contain a genetic determinant encoding a metallo-β-lactamase of the subclass B2. The Sfh-I enzyme exhibits some divergence from the previously characterized enzymes of this subclass. This is the first example of a naturally occurring metallo-β-lactamase in
Enterobacteriaceae
.
In Vitro Activities of Ramoplanin, Teicoplanin, Vancomycin, Linezolid, Bacitracin, and Four Other Antimicrobials against Intestinal Anaerobic Bacteria
Authors: Citron D. M. , Merriam C. V. , Tyrrell K. L. , Warren Y. A. , Fernandez H. , Goldstein E. J. C.
Published: June 2003

By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at ≤2 μg/ml against 287 of 300 (95.7%) gram-positive organisms, including 18 strains of
Clostridium difficile
for which MICs of ramoplanin were 0.25 to 0.5 μg/ml; for 3 of these, linezolid MICs were 8 to 16 μg/ml. Nineteen
Clostridium innocuum
strains for which the vancomycin MIC at which 90% of strains were inhibited was 16 μg/ml were susceptible to ramoplanin at 0.06 to 0.25 μg/ml and to teicoplanin at 0.125 to 1.0 μg/ml. All strains of
Eubacterium
,
Actinomyces
,
Propionibacterium
, and
Peptostreptococcus
spp. were inhibited by ≤0.25 μg of ramoplanin per ml and ≤1 μg of vancomycin per ml. Ramoplanin was also active at ≤4 μg/ml against 15 of 22 of the
Prevotella
and
Porphyromonas
strains tested, but ramoplanin MICs for all 31 strains of the
Bacteroides fragilis
group, the
Fusobacterium mortiferum-Fusobacterium varium
group, and
Veillonella
spp. were ≥256 μg/ml. Ramoplanin displays excellent activity against
C. difficile
and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.
Scopulariopsis brevicaulis, a Fungal Pathogen Resistant to Broad-Spectrum Antifungal Agents
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Mellado Emilia , Buitrago Maria J. , Monzón Araceli , Rodriguez-Tudela Juan L.
Published: June 2003

The antifungal susceptibility results for 32 clinical isolates ofScopulariopsis brevicaulisare presented. Flucytosine and itraconazole were inactive in vitro, and MICs of amphotericin B, voriconazole, and terbinafine for all isolates were high, with geometric means of 13, 25.8, and 14.4 μg/ml, respectively.
In Vitro Susceptibilities ofMalasseziaSpecies to a New Triazole, Albaconazole (UR-9825), and Other Antifungal Compounds
Authors: Garau Margarita , Pereiro Manolo , del Palacio Amalia
Published: June 2003

The in vitro activity of the new triazole albaconazole (UR-9825) in comparison with those of flucytosine, fluconazole, ketoconazole, itraconazole, and voriconazole against 70 strains ofMalasseziaspp. was determined by a microdilution method using a colorimetric indicator for metabolic activity. Albaconazole showed an in vitro profile similar to those of the different antifungals tested (MIC ≤ 0.06 μg/ml for all the strains).
Activity of Telithromycin against Penicillin-Resistant
Streptococcus pneumoniae
Isolates Recovered from French Children with Invasive and Noninvasive Infections
Authors: Bingen Edouard , Doit Catherine , Loukil Chawki , Brahimi Naima , Bidet Philippe , Deforche Dominique , Geslin Pierre
Published: June 2003

We compared the activities of telithromycin, erythromycin, azithromycin, josamycin, penicillin G, amoxicillin, cefpodoxime, and ceftriaxone against invasive and noninvasive non-penicillin-susceptible
Streptococcus pneumoniae
isolates recovered from children. Of the 186 isolates tested, 89% were positive for
erm
(B) by PCR. Telithromycin had the lowest MICs, with MICs at which 90% of the isolates tested are inhibited of 0.032 and 0.25 μg/ml for erythromycin-sensitive and -resistant isolates, respectively.
Development and Validation of a High-Performance Liquid Chromatography Assay for Voriconazole
Authors: Pennick Gennethel J. , Clark Martin , Sutton Deanna A. , Rinaldi Michael G.
Published: June 2003

An analytical method for the determination of voriconazole (UK-109,496; Pfizer) in plasma was developed and validated. The method utilizes solid-phase extraction technology and high-performance liquid chromatography. The lower limit of quantitation is 0.2 μg/ml, and the range of linearity tested was 0.2 to 10 μg/ml.
Intra- and Interindividual Variabilities of Valacyclovir Oral Bioavailability and Effect of Coadministration of an hPEPT1 Inhibitor
Authors: Phan Dana D. , Chin-Hong Peter , Lin Emil T. , Anderle Pascale , Sadee Wolfgang , Guglielmo B. Joseph
Published: June 2003

Variability in valacyclovir bioavailability and the potential for cephalexin-valacyclovir interaction were evaluated. The intraindividual acyclovir area under the concentration-time curve (AUC) varied minimally, whereas interindividual differences were substantial. Coadministration of the human peptide transporter 1 (hPEPT1) substrates valacyclovir and cephalexin minimally reduced the acyclovir AUC. These results suggest a stable valacyclovir absorption phenotype, significant interindividual variability, and minimal interaction between these hPEPT1 substrates.
In Vitro Antimicrobial Susceptibility of
Brachyspira pilosicoli
Isolates from Humans
Authors: Brooke C. J. , Hampson D. J. , Riley T. V.
Published: June 2003

The in vitro antimicrobial susceptibility of the anaerobic intestinal spirochete
Brachyspira pilosicoli
was investigated by an agar dilution method. Human (
n
= 123) and porcine (
n
= 16) isolates were susceptible to metronidazole, ceftriaxone, meropenem, tetracycline, moxifloxacin, and chloramphenicol; erythromycin and ciprofloxacin were not active. Resistance to amoxicillin and clindamycin varied. Amoxicillin susceptibility was restored by clavulanic acid.
Susceptibilities of
Campylobacter jejuni
Isolates from Germany to Ciprofloxacin, Moxifloxacin, Erythromycin, Clindamycin, and Tetracycline
Authors: Wagner Jutta , Jabbusch Miriam , Eisenblätter Martin , Hahn Helmut , Wendt Constanze , Ignatius Ralf
Published: June 2003

To elucidate
Campylobacter jejuni
resistance to antibiotics in Germany, MICs of ciprofloxacin, moxifloxacin, erythromycin, clindamycin, and tetracycline were determined (using agar dilution) for 144 clinical isolates. The data indicate a considerable ciprofloxacin resistance (45.1%) without a clonal relationship of the strains and a greater in vitro activity of moxifloxacin, erythromycin, and clindamycin.
In Vitro Selection and Characterization of
Bacillus anthracis
Mutants with High-Level Resistance to Ciprofloxacin
Authors: Price Lance B. , Vogler Amy , Pearson Talima , Busch Joseph D. , Schupp James M. , Keim Paul
Published: June 2003

Mutants of attenuated
Bacillus anthracis
with high-level ciprofloxacin resistance were isolated using a three-step in vitro selection. Ciprofloxacin MICs were 0.5 μg/ml for first-step mutants, which had one of two
gyrA
quinolone resistance-determining region (QRDR) mutations. Ciprofloxacin MICs were 8 and 16 μg/ml for second-step mutants, which had one of three
parC
QRDR mutations. Ciprofloxacin MICs for third-step mutants were 32 and 64 μg/ml. Mutants for which MICs were 64 μg/ml had one of two additional mutations within the
gyrA
QRDR or one of two mutations within the
gyrB
QRDR. Mutants for which MICs were 32 μg/ml had no additional target modifications but showed evidence of enhanced ciprofloxacin efflux.
Farnesol Biosynthesis in
Candida albicans
: Cellular Response to Sterol Inhibition by Zaragozic Acid B
Authors: Hornby Jacob M. , Kebaara Bessie W. , Nickerson Kenneth W.
Published: June 2003

The dimorphic fungus
Candida albicans
produces farnesol as a quorum-sensing molecule that regulates cellular morphology. The biosynthetic origin of farnesol has been resolved by treating these cells with zaragozic acid B, a potent inhibitor of squalene synthase in the sterol biosynthetic pathway. Treatment with zaragozic acid B leads to an eightfold increase in the amount of farnesol produced by
C. albicans
. Furthermore,
C. albicans
cell extracts contain enzymatic activity to convert [
3
H]farnesyl pyrophosphate to [
3
H]farnesol. Many common antifungal antibiotics (e.g., zaragozic acids, azoles, and allylamines) target steps in sterol biosynthesis. We suggest that the fungicidal activity of zaragozic acid derives in large part from the accumulation of farnesol that accompanies the inhibition of sterol biosynthesis.
Emergence of Macrolide Resistance in Throat Culture Isolates of Group A Streptococci in Ontario, Canada, in 2001
Authors: Katz Kevin C. , McGeer Allison J. , Duncan Carla L. , Ashi-Sulaiman Aisha , Willey Barbara M. , Sarabia Alicia , McCann Jacquie , Pong-Porter Sylvia , Rzayev Yana , de Azavedo Joyce S. , Low Donald E.
Published: June 2003

Of 500 group A streptococci isolated from pharyngeal swabs, 72 (14.4%) were macrolide resistant, compared to 2.1% in 1997. Of these, 66 (92%) were of the M phenotype and 6 (8.3%) were of the MLS phenotype. Pulsed-field gel electrophoresis found that two clones, with patterns identical to those of serotypes M1 and M4, accounted for 19.4 and 68.1% of the macrolide-resistant isolates, respectively.
Addition of Caspofungin to Fluconazole Does Not Improve Outcome in Murine Candidiasis
Authors: Graybill John R. , Bocanegra Rosie , Najvar Laura K. , Hernandez Steve , Larsen Robert A.
Published: June 2003

Caspofungin is a potent antifungal inhibiting glucan synthesis in
Candida
species. However, caspofungin is not 100% curative in candidiasis. Therefore, we evaluated combinations of fluconazole with caspofungin for murine candidemia. We could not show any benefit of combined therapy over individual antifungal drugs.
The M184V Substitution in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Delays the Development of Resistance to Amprenavir and Efavirenz in Subtype B and C Clinical Isolates
Authors: Diallo Karidia , Brenner Bluma , Oliveira Maureen , Moisi Daniela , Detorio Mervi , Götte Matthias , Wainberg Mark A.
Published: June 2003

The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), encoding high-level resistance to lamivudine (3TC), results in decreased HIV-1 replicative capacity, diminished RT processivity, and increased RT fidelity in biochemical assays. We assessed the effect of M184V on the development of resistance to the nonnucleoside RT inhibitors efavirenz (EFV) and nevirapine, and to the protease inhibitor amprenavir (APV) in tissue culture. Genotypic analysis revealed differences in EFV resistance-conferring mutations in subtype B (K103N) versus subtype C (V106 M), and the appearance of both was significantly delayed in the M184V-containing variants compared with the wild type (WT). Similarly, there was a marked delay in the emergence of mutations associated with APV resistance (I54 M/L/V) in subtype B viruses harboring M184V compared with paired WT viral isolates.
Pup development and timing of pupping in harbour seals (Phoca vitulina) in the St. Lawrence River estuary, Canada
Authors: Dubé Y , Hammill M O , Barrette C
Published: June 2003

Surveys to estimate the daily growth rate of harbour seal (Phoca vitulina) pups from birth to weaning and to determine the distribution of births were carried out from early May to late August 1998, 1999, and 2000 at two haulout areas in the St. Lawrence River estuary, Canada. Pups gained mass at a rate of 0.544 kg/day (standard error (SE) = 0.141, range 0.1180.875 kg/day, N = 110). Births began between 12 and 17 May. The median dates of birth were 28 May (95% confidence interval (CI), 2730 May) in 1998, 25 May (95% CI, 2428 May) in 1999, and 26 May (95% CI, 2427 May) in 2000. Births followed a normal distribution in 2000, but late pupping led to an extended tail in both 1998 and 1999. Pupping occurred at the same time in the St. Lawrence River estuary as at Sable Island, a colony located 600 km to the south, but occurred earlier than predicted by the relationship of Temte et al. (1991). The estimated median dates of weaning were 1 July (95% CI, 20 June to 12 July) in 1998, 30 June (95% CI, 19 June to 11 July) in 1999, and 26 June (95% CI, 20 June to 2 July) in 2000. Pooling years resulted in an average lactation duration of 34 days (SE = 1.8).
Eremidrilusn. gen. (Annelida, Clitellata, Lumbriculidae) and new species from California, U.S.A.
Authors: Fend Steven V , Rodriguez Pilar
Published: June 2003

A new Nearctic lumbriculid genus, Eremidrilus, includes four new California species (E. elegans, E. coyote, E. ritocsi, and E. felini) plus the new combination of Trichodrilus allegheniensis Cook, 1971 from the eastern U.S.A. Eremidrilus has the Trichodrilus arrangement of reproductive organs, but is distinguished by a filiform proboscis and male pores on folded porophores. A combination of other characters distinguishes most Eremidrilus species from most Trichodrilus species: (i) elongate-tubular thin-walled atria, (ii) posterior vasa deferentia forming a loop in XI, (iii) no posterior blood vessels, (iv) nephridia not present in VII. Spermathecae restricted to the first postatrial segment and laterally displaced spermathecal pores differentiate the western Eremidrilus species from the single eastern species.
Morphometrics and estimates of force generation by the chelae of a North American population of the invasive green crab,Carcinus maenas(L.)
Authors: Mitchell S C , Kennedy S M , Williams P J , DeMont M E
Published: June 2003

The European green crab, Carcinus maenas, is an invasive species in eastern North America and has the potential to significantly impact wild and aquaculture shellfish in the southern Gulf of St. Lawrence, Canada. To examine potential predation effects on local shellfish and assess the appropriateness of extrapolating results from studies conducted elsewhere, the morphometry of chelae from a recently established population of C. maenas in Nova Scotia was examined for comparison with the presumed founding (European) population, and forces generated by the chelae over a range of crab sizes were estimated. The Nova Scotia population was found to be morphologically very similar to European populations with respect to chela structure. Force generation by the chelae was found to scale with isometry in the female crab and with positive allometry in the male. Estimated forces compare well with previously reported forces, and force generation is calculated to increase in a nonlinear manner proceeding from the chela tips proximally toward the fulcrum. The calculated forces generated by the chelae are clearly sufficient for outright crushing of some shells (e.g., Mya arenaria), even for small crabs, but appear to be too low for crushing those of other molluscs. There is a complex interplay between gape and maximum force along the length of the dactyl that allows great variability in force application, and thus also in the size of prey consumed and prey-handling behaviour. We suggest that for such a lever system, the gape angle of the chelae, which does not change with crab size, is optimal with respect to the resultant force generated.
Is dispersal distance of birds proportional to territory size?
Authors: Bowman Jeff
Published: June 2003

Recent research has demonstrated that dispersal distance and the square root of home-range size covary proportionately across mammal species. I tested whether these findings could be generalized to another taxon. Breeding territories of some bird species are analogous to mammalian home ranges, so I tested whether dispersal distance and territory size in these birds covaried and were proportional. Variables were log10-transformed before analysis. When considered independently of body mass, median natal dispersal distance and breeding territory size were positively related (F[1,29] = 8.91, R2 = 0.23, P = 0.005). Median dispersal distance was proportionally related to the square root of territory size by a multiple of 12. This relationship was especially strong for non-migrants (F[1,15] = 49.84, R2 = 0.77, P = 3.87 × 106). Maximum natal dispersal distance and breeding territory size also covaried when body size effects were removed, but this relationship was only significant when migrants were removed from the sample (F[1,24] = 5.66, R2 = 0.19, P = 0.025). Maximum dispersal distance did not have a proportional relationship with territory size. This could result from sampling error or from real processes (e.g., relatively shorter dispersals by birds with large territories). The proportional relationship between median dispersal distance and territory size can be used as a cross-species scaling rule.
Seasonal change in egg-volume variation within a clutch in the Bull-headed Shrike, Lanius bucephalus
Authors: Takagi Masaoki
Published: June 2003

I studied the seasonal change in egg volume in Bull-headed Shrikes, Lanius bucephalus, to explore the importance of egg-volume variation within a clutch. The mean egg volume did not change over a season; however, the coefficient of variation in egg volume in six-egg clutches significantly increased in 1994 and 1995 but did not change in 1996. Peaks in arthropod biomass occurred early in the breeding seasons in 1994 and 1995, but late in the season in 1996. Higher food availability was related to a reduction in variation in egg volume within a clutch. A significant difference in egg volume was found within six-egg clutches, and the first egg was the smallest. Nestlings that hatched from small eggs early in the hatching order suffered lower mortality rates than nestlings that hatched from large eggs laid late in the hatching order. The duration of time between settlement of a female in a male territory and clutch initiation decreased with date. Intraclutch variation in egg volume may be caused by a trade-off between the time to develop an egg and the volume of the first egg within a clutch. Because eggs that hatch first do not need to be large for the hatchling to survive, the Bull-headed Shrikes may advance the clutch-initiation date at the cost of reducing the volume of the first egg.
Habitat selection and demography of a nonmigratory woodland caribou population in Newfoundland
Authors: Mahoney Shane P , Virgl John A
Published: June 2003

Several studies have shown that habitat selection and population limitation of woodland caribou (Rangifer tarandus caribou) is typically associated with the interaction among human-induced habitat alteration, wolf predation (Canis lupus), and the availability of alternative prey such as moose (Alces alces) and white-tailed deer (Odocoileus virginianus). Although woodland caribou inhabiting Newfoundland have been exposed to moderate levels of timber harvesting, black bears (Ursus americanus), not wolves, are the principal large predator in this system, and moose represent the alternative large prey species. During a 4-year period of timber harvesting, we monitored the location and status of 24 adults and 46 calves to determine coarse-scale habitat selection and survival rates of a nonmigratory and demographically isolated woodland caribou herd in Newfoundland. We also estimated pregnancy and recruitment rates and determined potential causes of mortality. Habitat selection significantly varied among seasons but was consistent with the hypothesis that caribou avoid habitats where the likelihood of contact with a predator or alternative prey was high. Population growth rate (rs= 0.01 ± 0.06 (mean ± 1SD)), calf recruitment (percentage of 10-month old calves = 13%), and adult survival rate (0.87) indicated that the population was stable. Mean pregnancy rate (96%), parturition date, and the lack of evidence for malnutrition in 22 carcasses suggested that the availability of quality forage is not a key factor limiting population growth. Although predation could not be linked to the death of adult caribou, black bears were responsible for 5 of 15 calf fatalities. This study suggests that black bears need to be considered more seriously as a factor influencing coarse-scale habitat selection and demography in woodland caribou herds.
Ideal free distributions in fleet dynamics: a behavioral perspective on vessel movement in fisheries analysis
Authors: Gillis Darren M
Published: June 2003

Since fleet dynamics was defined in the 1980s there has been increasing interest in the role played by vessel behavior in the exploitation of aquatic resources. The ideal free distribution (IFD), from behavioral ecology, has proved useful for examining the relationship between vessel and resource distributions in commercial fisheries. When making inferences based upon the IFD it is critical to examine its underlying assumptions, particularly the form of competition between fishing vessels. When present, an IFD can decouple the relationship between local catch rates and abundance, obscuring declines in smaller or weaker fish stocks. As an alternative, probabilistic methods have also been successfully applied to the study of vessel behavior. However, parsimonious behavioral models like the IFD will often be preferable because (i) they can be examined using the data typically available from commercial fisheries, (ii) they require fewer data than probabilistic models, and (iii) they are easily incorporated into more complex management models as the fishing component. Where deviations from the IFD occur they can provide insights into the relationship between regulations, environment, and vessel activities that will improve our interpretation of the data generated by commercial fisheries.
Quantifying the effect of predators on endangered species using a bioenergetics approach: Caspian terns and juvenile salmonids in the Columbia River estuary
Authors: Roby Daniel D , Lyons Donald E , Craig David P , Collis Ken , Visser G Henk
Published: June 2003

We estimated the consumption of juvenile salmonids (Oncorhynchus spp.) and other forage fishes by Caspian terns (Sterna caspia) nesting on Rice Island in the Columbia River estuary in 1997 and 1998 using a bioenergetics modeling approach. The study was prompted by concern that Caspian tern predation might be a substantial source of mortality to out-migrating juvenile salmonids from throughout the Columbia River basin, many populations of which are listed as threatened or endangered under the U.S. Endangered Species Act. The bioenergetics model used estimates of the energy requirements of the tern population and the proportion of tern energy requirements met by various prey types. The resulting estimate of the number of juvenile salmonids consumed by Rice Island Caspian terns was 8.1 million (5.910.4 million) in 1997 and 12.4 million (9.115.7 million) in 1998. Tern predation rates on juvenile salmonids were substantial, representing up to 15% of the juveniles to reach the estuary from some listed populations. Nevertheless, based on simple age-structured models of salmonid populations, it appears unlikely that management of Caspian tern predation alone would reverse salmonid declines. Management to reduce tern predation could, however, contribute to a comprehensive strategy to recover imperiled salmonid populations in the Columbia River basin.
Do snakes exhibit shifts in feeding ecology associated with the presence or absence of potential competitors? A case study from tropical Africa
Authors: Luiselli Luca
Published: June 2003

Two species of rain-forest snakes, the colubrids Natriciteres fuliginoides and Natriciteres variegata, are potential competitors, because they attain, on average, the same body size (2030 cm long), have similar habits and ecological requirements (they are both diurnal and nocturnal, often semi-aquatic), and have similar dietary spectra ( including both small vertebrates and invertebrates). I studied prey type and predator size  prey size relationships of these snakes in four swamp-forest areas of southeastern Nigeria (West Africa): only N. fuliginoides was found in two of these areas, whereas both species were common in the other two areas. The feeding ecology of N. fuliginoides shifted greatly in the presence of its potential competitor, N. variegata, in terms of prey-type preferences and predatory behaviour as well as in terms of predator size  prey size relationships. In particular, the effects of the potential competitor on the feeding ecology of N. fuliginoides were (i) a shift toward eating many invertebrates from a diet based on many small vertebrates, (ii) a shift toward eating many terrestrial organisms from a diet based on many aquatic organisms, and (iii) a shift in mean prey size for females toward relatively larger prey from a diet based on smaller prey. The resulting effect was a clear partitioning of food resources between the two predator species in both the areas where they are sympatric, whereas N. fuliginoides had a wider dietary spectrum (covering that of the two species together) in the areas where its competitor is not found. The role of intraspecific competition seems less strong, as no apparent resource partitioning in prey type or prey size was observed between males and females of either species or in any study area. However, mean prey size was significantly greater for females than for males of both species and in all study areas, but depended on the significant reverse sexual size dimorphism observed in both species.