bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Orally Administered T-705 on Lethal Avian Influenza A (H5N1) Virus Infections in Mice
Authors: Sidwell Robert W. , Barnard Dale L. , Day Craig W. , Smee Donald F. , Bailey Kevin W. , Wong Min-Hui , Morrey John D. , Furuta Yousuke 
Published: December 2006

ABSTRACTT-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) was inhibitory to four strains of avian H5N1 influenza virus in MDCK cells, with the 90% effective concentrations ranging from 1.3 to 7.7 μM, as determined by a virus yield reduction assay. The efficacy was less than that exerted by oseltamivir carboxylate or zanamivir but was greater than that exerted by ribavirin. Experiments with mice lethally infected with influenza A/Duck/MN/1525/81 (H5N1) virus showed that T-705 administered per os once, twice, or four times daily for 5 days beginning 1 h after virus exposure was highly inhibitory to the infection. Dosages from 30 to 300 mg/kg of body weight/day were well tolerated; each prevented death, lessened the decline of arterial oxygen saturation (SaO2), and inhibited lung consolidation and lung virus titers. Dosages from 30 to 300 mg/kg/day administered once or twice daily also significantly prevented the death of the mice. Oseltamivir (20 mg/kg/day), administered per os twice daily for 5 days, was tested in parallel in two experiments; it was only weakly effective against the infection. The four-times-daily T-705 treatments at 300 mg/kg/day could be delayed until 96 h after virus exposure and still significantly inhibit the infection. Single T-705 treatments administered up to 60 h after virus exposure also prevented death and the decline of SaO2. Characterization of the pathogenesis of the duck influenza H5N1 virus used in these studies was undertaken; although the virus was highly pathogenic to mice, it was less neurotropic than has been described for clinical isolates of the H5N1 virus. These data indicate that T-705 may be useful for the treatment of avian influenza virus infections.
Oral versus Intravenous Flucytosine in Patients with Human Immunodeficiency Virus-Associated Cryptococcal Meningitis
Authors: Brouwer Annemarie E. , van Kan Hendrikus J. M. , Johnson Elizabeth , Rajanuwong Adul , Teparrukkul Prapit , Wuthiekanun Vannaporn , Chierakul Wirongrong , Day Nick , Harrison Thomas S. 
Published: December 2006

ABSTRACT
In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.
Reversible Inhibition of Mitochondrial Protein Synthesis during Linezolid-Related Hyperlactatemia
Authors: Garrabou Glòria , Soriano Alejandro , López Sònia , Guallar Jordi P. , Giralt Marta , Villarroya Francesc , Martínez Jose A. , Casademont Jordi , Cardellach Francesc , Mensa Josep , Miró Òscar 
Published: December 2006

ABSTRACTThe objective of the present study was to determine the mitochondrial toxicity mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term schedule of linezolid treatment were studied during the acute phase of hyperlactatemia and after clinical recovery and lactate normalization following linezolid withdrawal. Mitochondrial studies were performed with peripheral blood mononuclear cells and consisted of measurement of mitochondrial mass, mitochondrial protein synthesis homeostasis (cytochromecoxidase [COX] activity, COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA] content), and overall mitochondrial function (mitochondrial membrane potential and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we found extremely reduced protein expression (16% of the remaining content compared to control values [100%],P< 0.001) for the mitochondrially coded, transcribed, and translated COX-II subunit. Accordingly, COX activity was also found to be decreased (51% of the remaining activity,P< 0.05). These reductions were observed despite the numbers of COX-II mitochondrial RNA transcripts being abnormally increased (297%,P= 0.10 [not significant]) and the mitochondrial DNA content remaining stable. These abnormalities persisted even after the correction for mitochondrial mass, which was mildly decreased during the hyperlactatemic phase. Most of the mitochondrial abnormalities returned to control ranges after linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid inhibits mitochondrial protein synthesis, leading to decreased mitochondrial enzymatic activity, which causes linezolid-related hyperlactatemia, which resolves upon discontinuation of linezolid treatment.
Can Alcohol-Based Hand-Rub Solutions Cause You To Lose Your Driver's License? Comparative Cutaneous Absorption of Various Alcohols
Authors: Brown T. L. , Gamon S. , Tester P. , Martin R. , Hosking K. , Bowkett G. C. , Gerostamoulos D. , Grayson M. L. 
Published: December 2006

ABSTRACT
We assessed cutaneous ethanol (ETOH) and isopropanol (ISOP) absorption after intensive (30 times per h) use of alcohol-based hand-rub solutions by healthcare workers (HCWs). ETOH was detectable in the breath of 6/20 HCWs (0.001 to 0.0025%) at 1 to 2 min postexposure and in the serum of 2/20 HCWs at 5 to 7 min postexposure. Serum ISOP levels were unrecordable at all time points.
Once-Weekly Micafungin Therapy Is as Effective as Daily Therapy for Disseminated Candidiasis in Mice with Persistent Neutropenia
Authors: Gumbo Tawanda , Drusano George L. , Liu Weiguo , Kulawy Robert W. , Fregeau Christine , Hsu Vasha , Louie Arnold 
Published: December 2006

ABSTRACT

The effect of micafungin dose scheduling on the treatment of candidemia is unknown. Neutropenic mice with disseminated
Candida glabrata
infection were treated with single intraperitoneal micafungin doses of 0 to 100 mg/kg of body weight and sacrificed 7 days later. The maximal decline in kidney fungal burden was 5.8 log
10
CFU/g. A 1-week pharmacokinetic-pharmacodynamic study revealed a micafungin serum half-life of 6.13 h. In mice treated with ≥50 mg/kg, there was maximal fungal decline without regrowth during the 1-week dosing interval. Next, doses associated with 34% (34% effective dose [ED
34
]) and 50% (ED
50
) of maximal kill were administered at one of three dose schedules: a single dose at
t
= 0, two equal doses at
t
= 0 and
t
= 3.5 days, and 7 equal doses daily. Some mice received a single dose of 100 mg/kg. Fungal burden was examined on days 1, 5, and 7. In mice treated with the ED
34
, microbial kill with the daily therapy initially lagged behind the intermittent doses but exceeded it by day 7. In mice treated with the ED
50
, daily and intermittent doses had equivalent day 7 effects. In mice treated with 100 mg/kg, there was no regrowth. The relative likelihoods that the area under the concentration-time curve/MIC ratio was linked to microbial kill versus peak concentration/MIC ratio or time above the MIC was 10.3 and 10,161.2, respectively. In all the experiments, no paradoxical increase in fungal burden was observed with high micafungin doses. However, only a single
Candida
isolate was tested. Regimens that simulated micafungin concentration-time profiles in patients treated with a single micafungin dose of 1,400 mg once a week demonstrated maximal fungal decline. Once-weekly micafungin therapy is as efficacious as daily therapy in a murine model of disseminated candidiasis.
Evaluation of the In Vivo Activity of Tribendimidine against
Schistosoma mansoni
,
Fasciola hepatica
,
Clonorchis sinensis
, and
Opisthorchis viverrini
Authors: Keiser Jennifer , Shu-Hua Xiao , Chollet Jacques , Tanner Marcel , Utzinger Jürg 
Published: December 2006

ABSTRACT

We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of
Clonorchis sinensis
in rats. A 400-mg/kg dose of tribendimidine reduced
Opisthorchis viverrini
in hamsters by 95.7%. High doses of tribendimidine showed no activity against
Schistosoma mansoni
and
Fasciola hepatica
.
In Vitro Activities of Amphotericin B, Caspofungin, Itraconazole, Posaconazole, and Voriconazole against 45 Clinical Isolates of Zygomycetes: Comparison of CLSI M38-A, Sensititre YeastOne, and the Etest
Authors: Torres-Narbona Marta , Guinea Jesús , Martínez-Alarcón José , Peláez Teresa , Bouza Emilio 
Published: December 2006

ABSTRACT
We evaluated the activities of amphotericin B, itraconazole, voriconazole, caspofungin, and posaconazole against zygomycetes by CLSI M38-A, Etest and Sensititre. The most active drug was posaconazole, followed by amphotericin B and itraconazole. The correlation of the Etest and Sensititre with CLSI M38-A was moderate for posaconazole but poor for the others.
Impact of Antimicrobial Usage on Antimicrobial Resistance in Commensal
Escherichia coli
Strains Colonizing Broiler Chickens
Authors: Smith J. L. , Drum D. J. V. , Dai Y. , Kim J. M. , Sanchez S. , Maurer J. J. , Hofacre C. L. , Lee M. D. 
Published: December 2006

ABSTRACT

Escherichia coli
strains isolated from commercial broilers and an experimental flock of chickens were screened to determine phenotypic expression of antimicrobial resistance and carriage of drug resistance determinants. The goal of this study was to investigate the influence of oxytetracycline, sarafloxacin, and enrofloxacin administration on the distribution of resistance determinants and strain types among intestinal commensal
E. coli
strains isolated from broiler chickens. We detected a high prevalence of resistance to drugs such as tetracycline (36 to 97%), sulfonamides (50 to 100%), and streptomycin (53 to 100%) in
E. coli
isolates from treated and untreated flocks. These isolates also had a high prevalence of class 1 integron carriage, and most of them possessed the streptomycin resistance cassette,
aadA1
. In order to investigate the contribution of
E. coli
strain distribution to the prevalence of antimicrobial resistance and the resistance determinants, isolates from each flock were DNA fingerprinted by enterobacterial repetitive intergenic consensus sequence (ERIC) PCR. Although very diverse
E. coli
strain types were detected, four ERIC strain types were present on all of the commercial broiler farms, and two of the strains were also found in the experimental flocks. Each
E. coli
strain consisted of both susceptible and antimicrobial agent-resistant isolates. In some instances, isolates of the same
E. coli
strain expressed the same drug resistance patterns although they harbored different
tet
determinants or streptomycin resistance genes. Therefore, drug resistance patterns could not be explained solely by strain prevalence, indicating that mobile elements contributed significantly to the prevalence of resistance.
Characterization of Environmental Sources of the Human and Animal Pathogen
Cryptococcus gattii
in British Columbia, Canada, and the Pacific Northwest of the United States
Authors: Kidd Sarah E. , Chow Yat , Mak Sunny , Bach Paxton J. , Chen Huiming , Hingston Adrian O. , Kronstad James W. , Bartlett Karen H. 
Published: December 2006

ABSTRACT

Cryptococcus gattii
has recently emerged as a primary pathogen of humans and wild and domesticated animals in British Columbia, particularly on Vancouver Island.
C. gattii
infections are typically infections of the pulmonary and/or the central nervous system, and the incidence of infection in British Columbia is currently the highest reported globally. Prior to this emergence, the environmental distribution of and the extent of colonization by
C. gattii
in British Columbia were unknown. We characterized the environmental sources and potential determinants of colonization in British Columbia.
C. gattii
was isolated from tree surfaces, soil, air, freshwater, and seawater, and no seasonal prevalence was observed. The
C. gattii
concentrations in air samples were significantly higher during the warm, dry summer months, although potentially infectious propagules (<3.3 μm in diameter) were present throughout the year. Positive samples were obtained from many different areas of British Columbia, and some locations were colonization “hot spots.”
C. gattii
was generally isolated from acidic soil, and geographic differences in soil pH may influence the extent of colonization.
C. gattii
soil colonization also was associated with low moisture and low organic carbon contents. Most of the
C. gattii
isolates recovered belonged to the VGIIa genetic subtype; however, sympatric colonization by the VGIIb strain was observed at most locations. At one sampling site, VGIIa, VGIIb, VGI, and the
Cryptococcus neoformans
serotype AD hybrid all were coisolated. Our findings indicate extensive colonization by
C. gattii
within British Columbia and highlight an expansion of the ecological niche of this pathogen.
Persistence, Transmission, and Virulence Characteristics ofAeromonasStrains in a Duckweed Aquaculture-Based Hospital Sewage Water Recycling Plant in Bangladesh
Authors: Rahman Mokhlasur , Huys Geert , Rahman Motiur , Albert M. John , Kühn Inger , Möllby Roland 
Published: December 2006

ABSTRACTThe persistence and transmission ofAeromonasin a duckweed aquaculture-based hospital sewage water treatment plant in Bangladesh was studied. A total of 670 samples from different sites of the hospital sewage water treatment plant, from feces of hospitalized children suffering from diarrhea, from environmental control ponds, and from feces of healthy humans were collected over a period of three years. In total, 1,315 presumptiveAeromonasisolates were biochemically typed by the PhenePlate rapid screening system (PhP-AE). A selection of 90 representative isolates was further analyzed with PhenePlate (PhP) extended typing (PhP-48), fatty acid methyl ester analysis, and amplified fragment length polymorphism (AFLP) fingerprinting. In addition, the prevalence of the putative virulence factors hemolysin and cytotoxin and the presence of the cytolytic enterotoxin gene (AHCYTOEN) were analyzed.Aeromonaswas found at all sites of the treatment plant, in 40% of the samples from environmental control ponds, in 8.5% of the samples from hospitalized children suffering from diarrhea, and in 3.5% of samples from healthy humans. A significantly high number ofAeromonasbacteria was found in duckweed, which indicates that duckweed may serve as a reservoir for these bacteria. PhP-AE typing allowed identification of more than 192 distinct PhP types, of which 18 major PhP types (MTs) were found in multiple sites and during several occasions. AFLP fingerprinting revealed the prevalence of genotypically indistinguishableAeromonasisolates among certain PhP MTs recovered from different sampling occasions and/or at multiple sites. Hemolytic and cytotoxic activities were observed in 43% of the tested strains, whereas 29% possessed the cytolytic enterotoxin gene AHCYTOEN. Collectively, two specific MTs associated with diarrhea were shown to exhibit high cytotoxicity. Furthermore, all tested isolates of these major types were positive for the cytolytic enterotoxin gene. In conclusion, our data indicate that certain phenotypically and genotypically stable clonal lineages ofAeromonashave persisted in the treatment system for a prolonged period and might spread from the hospitalized children suffering from diarrhea to fish produced for human consumption through the sewage water treatment system.
PCR-Based Detection ofAngiostrongylus cantonensisin Tissue and Mucus Secretions from Molluscan Hosts
Authors: Qvarnstrom Yvonne , Sullivan James J. , Bishop Henry S. , Hollingsworth Robert , da Silva Alexandre J. 
Published: December 2006

ABSTRACTAngiostrongylus cantonensisis a common cause of human eosinophilic meningitis. Recent outbreaks of this infection have shown that there is a need to determine the distribution of this nematode in the environment in order to control transmission.A. cantonensisis generally identified morphologically in the molluscan intermediate host by microscopic examination, which can be labor-intensive. The aim of this study was to develop a PCR-based method to detectA. cantonensisdirectly from molluscan tissue. A total of 34Parmarioncf.martensi(Simroth) semislugs, 25 of which were naturally infected withA. cantonensis, were used to develop this assay. Tissue pieces (approximately 25 mg) were digested with pepsin-HCl to recover third-stage larvae for morphological identification or were used for DNA extraction. PCR primers were designed to amplify 1,134 bp from theAngiostrongylus18S rRNA gene, and the amplicons produced were sequenced for identification at the species level. Both microscopy and the PCR-DNA sequencing analysis indicated that the same 25 semislugs were positive forA. cantonensis, showing that the two methods were equally sensitive and specific for this application. However, morphological detection requires access to living mollusks, whereas molecular analysis can also be performed with frozen tissue. The PCR-DNA sequencing method was further evaluated using tissue fromVeronicella cubensis(Pfeiffer) slugs and mucus secretions from infectedP. martensi. To our knowledge, this is the first use of a PCR-based method to confirm the presence ofA. cantonensisin mollusks collected in the environment.
Circumventing the Effect of Product Toxicity: Development of a Novel Two-Stage Production Process for the Lantibiotic Gallidermin
Authors: Valsesia G. , Medaglia G. , Held M. , Minas W. , Panke S. 
Published: December 2006

ABSTRACT

Lantibiotics such as gallidermin are lanthionine-containing polypeptide antibiotics produced by gram-positive bacteria that might become relevant for the treatment of various infectious diseases. So far, self-toxicity has prevented the isolation of efficient overproducing strains, thus hampering their thorough investigation and preventing their exploitation in fields other than the food area. We wanted to investigate the effect of lantibiotic precursor peptides on the producing strains in order to evaluate novel strategies for the overproduction of these promising peptides. In this study, gallidermin was chosen as a representative example of the type A lantibiotics. A
Staphylococcus gallinarum
Tü3928 mutant, whose gene for the extracellular pregallidermin protease GdmP was replaced by a kanamycin-resistance gene, was constructed. Mass spectrometry (MS) analysis indicated that this mutant produced fully posttranslationally modified gallidermin precursors with truncated versions of the leader peptide, but not the entire leader as predicted from the
gdmA
sequence. In filter-on-plate assays, these truncated pregallidermins showed no toxicity against
Staphylococcus gallinarum
Tü3928 up to a concentration of 8 g/liter (corresponding to approximately 2.35 mM), while gallidermin produced clear inhibitory zones at concentrations as low as 0.25 g/liter (0.12 mM). We showed that the lack of toxicity is due entirely to the presence of the truncated leader, since MS as well as bioassay analysis showed that the peptides resulting from tryptic cleavage of pregallidermins and gallidermin produced by
S. gallinarum
Tü3928 had identical masses and approximately the same specific activity. This demonstrates that even a shortened leader sequence is sufficient to prevent the toxicity of mature gallidermin. In nonoptimized fermentations, the
gdmP
mutant produced pregallidermin to a 50%-higher molar titer, suggesting that the absence of self-toxicity has a beneficial effect on gallidermin production and giving a first confirmation of the suitability of the overproduction strategy.
Metabolic Engineering of Carotenoid Biosynthesis in
Escherichia coli
by Ordered Gene Assembly in
Bacillus subtilis
Authors: Nishizaki Tomoko , Tsuge Kenji , Itaya Mitsuhiro , Doi Nobuhide , Yanagawa Hiroshi 
Published: December 2006

ABSTRACT

We attempted to optimize the production of zeaxanthin in
Escherichia coli
by reordering five biosynthetic genes in the natural carotenoid cluster of
Pantoea ananatis
. Newly designed operons for zeaxanthin production were constructed by the ordered gene assembly in
Bacillus subtilis
(OGAB) method, which can assemble multiple genes in one step using an intrinsic
B. subtilis
plasmid transformation system. The highest level of production of zeaxanthin in
E. coli
(820 μg/g [dry weight]) was observed in the transformant with a plasmid in which the gene order corresponds to the order of the zeaxanthin metabolic pathway (
crtE-crtB-crtI-crtY-crtZ
), among a series of plasmids with circularly permuted gene orders. Although two of five operons using intrinsic zeaxanthin promoters failed to assemble in
B. subtilis
, the full set of operons was obtained by repressing operon expression during OGAB assembly with a
p
R
promoter-
c
I repressor system. This result suggests that repressing the expression of foreign genes in
B. subtilis
is important for their assembly by the OGAB method. For all tested operons, the abundance of mRNA decreased monotonically with the increasing distance of the gene from the promoter in
E. coli
, and this may influence the yield of zeaxanthin. Our results suggest that rearrangement of biosynthetic genes in the order of the metabolic pathway by the OGAB method could be a useful approach for metabolic engineering.
Integrated Real-Time PCR for Detection and Monitoring of
Legionella pneumophila
in Water Systems
Authors: Yaradou Diaraf Farba , Hallier-Soulier Sylvie , Moreau Sophie , Poty Florence , Hillion Yves , Reyrolle Monique , André Janine , Festoc Gabriel , Delabre Karine , Vandenesch François , Etienne Jerome , Jarraud Sophie 
Published: December 2006

ABSTRACT

We evaluated a ready-to-use real-time quantitative
Legionella pneumophila
PCR assay system by testing 136 hot-water-system samples collected from 55 sites as well as 49 cooling tower samples collected from 20 different sites, in parallel with the standard culture method. The PCR assay was reproducible and suitable for routine quantification of
L. pneumophila
. An acceptable correlation between PCR and culture results was obtained for sanitary hot-water samples but not for cooling tower samples. We also monitored the same
L. pneumophila
-contaminated cooling tower for 13 months by analyzing 104 serial samples. The culture and PCR results were extremely variable over time, but the curves were similar. The differences between the PCR and culture results did not change over time and were not affected by regular biocide treatment. This ready-to-use PCR assay for
L. pneumophila
quantification could permit more timely disinfection of cooling towers.