bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Navicular Region of Newborn Foals and Adult Horses by Magnetic Resonance Imaging
Authors: Hevesi A. , Stanek Ch. , Garamvolgyi R. , Petrasi Zs. , Bogner P. , Repa I. 
Published: June 2004

SummaryMagnetic resonance imaging (MRI) was tested for evaluation of the soft tissue structures of the equine digit in 16 limbs, derived from three adult warmblood horses and two newborn warmblood foals. The following measuring sequences were used in sagittal, transversal and coronal planes: spin echo, gradient echo, inversion recovery. The images were made with a 1.5 Tesla Siemens scanner in a CP‐Helmholtz circular coil. To compare the visualization of the same tissue structures in adult and in newborn cases the limbs were imaged with the routinly used MRI sequences that are used for mature tissues. In newborn foals the bursa podotrochlearis could not be determined with the used sequences. For both the adult and newborn limbs the most visualization of the same tissue structures including the fluid spaces and growth plates were taken by the inversion recovery sequence. T2 sequence was very informative in adult cases but moderately in newborn foals.
Pulmonary metastatectomy in the management of four dogs with hypertrophic osteopathy
Authors: Liptak J. M. , Monnet E. , Dernell W. S. , Withrow S. J. 
Published: June 2004

AbstractThe efficacy and outcome of pulmonary metastatectomy in the management of hypertrophic osteopathy (HO) secondary to metastatic osteosarcoma was retrospectively evaluated in four dogs. Metastatectomy was performed by subpleural enucleation, partial lung lobectomy or complete lung lobectomy through either a median sternotomy or thoracoscopically. Perioperative morbidity was minimal. Clinical signs associated with HO resolved within 24 h of pulmonary metastatectomy in all dogs. Durable remission of symptomatic HO was achieved in all dogs (range, 50–294 days), although recurrence of HO was noted in one dog, 246 days postmetastatectomy due to metastasis to the lungs and chest wall. Pulmonary metastatectomy resulted in a rapid and prolonged resolution of HO, and the clinical benefits of metastatectomy potentially exceed the morbidity associated with the surgical procedure.
Defined Anaerobic Growth Medium for Studying
Candida albicans
Basic Biology and Resistance to Eight Antifungal Drugs
Authors: Dumitru Raluca , Hornby Jacob M. , Nickerson Kenneth W. 
Published: June 2004

ABSTRACT

The polymorphic fungus
Candida albicans
is one of the most versatile opportunistic pathogens in humans. Many organs of the human body are potential targets for infection by this pathogen, but infection is commonly localized in the gastrointestinal tract, an environment providing anaerobic growth conditions. We describe a chemically defined anaerobic growth medium for four strains of
Candida albicans
(A72, SC5314, MEN, and 10261). It is a defined liquid glucose-phosphate-proline growth medium supplemented with oleic acid, nicotinic acid, and ammonium chloride. The cells did not require or respond to added ergosterol. Oleic acid and nicotinic acid are growth factors which are required only for the anaerobic growth of
C. albicans
. An important technical feature of this study was the use of anaerobically grown inocula to study anaerobic growth. Anaerobically, the cells grew exclusively as mycelia at 25, 30, and 37°C. The doubling time at 30°C was ca. 20 h. The cells did not produce farnesol and did not respond to exogenous farnesol, and they were resistant to the highest tested levels of amphotericin B and four of the azole antifungals. We suggest that the anaerobic growth of
C. albicans
may contribute to the trailing end point phenomenon and the resistance of
C. albicans
biofilms to antifungal drugs.
Factors Associated with Relative Rates of Antibiotic Resistance in
Pseudomonas aeruginosa
Isolates Tested in Clinical Laboratories in the United States from 1999 to 2002
Authors: Flamm Robert K. , Weaver Mellany K. , Thornsberry Clyde , Jones Mark E. , Karlowsky James A. , Sahm Daniel F. 
Published: June 2004

ABSTRACT

For the period from 1999 to 2002 in the United States, the in vitro susceptibilities of 52,637
Pseudomonas aeruginosa
isolates to 10 antimicrobial agents were evaluated. The isolates were from 29 laboratories, 11 of which participated in The Surveillance Network for four consecutive years. Isolates were collected from adult patients (≥18 years of age) in intensive care units (ICU), non-ICU inpatients, nursing home patients, and outpatients; data were analyzed to evaluate factors, such as year of isolation, patient age group, isolate specimen source, and patient type (hospitalized patients [ICU, non-ICU, or nursing home] or outpatients). Rates of resistance for the 4-year period were highest for isolates from patients in ICU and 18- to 39-year-old patients and for isolates from the lower respiratory tract. Resistance decreased with age. Resistance was lowest in isolates from outpatients, in isolates from ≥70-year-old patients, and from specimens from the upper respiratory tract. Multidrug resistance (MDR) (resistance to three or more antimicrobial agents) accounted for 24.9% of all isolates. The MDR rate was highest in isolates from patients in nursing homes (29.9%) and ICU (29.5%).
Optimizing Pharmacodynamic Target Attainment Using the MYSTIC Antibiogram: Data Collected in North America in 2002
Authors: Kuti Joseph L. , Nightingale Charles H. , Nicolau David P. 
Published: June 2004

ABSTRACT

The OPTAMA Program is intended to examine typical antimicrobial regimens used in the treatment of common nosocomial pathogens and the likelihood of these regimens attaining appropriate pharmacodynamic exposure in different parts of the world. A 5,000-subject Monte Carlo simulation was used to estimate pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin-tazobactam, and ciprofloxacin against
Escherichia coli
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
, and
Pseudomonas aeruginosa
. Standard dosing regimens from North America were used. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and MIC data came from the 2002 MYSTIC Program. Ciprofloxacin displayed the lowest target attainment against all bacterial species (41 to 46% for
A. baumannii
, 53 to 59% for
P. aeruginosa
, and 80 to 85% for the
Enterobacteriaceae
). Increasing the dose to 400 mg every 8 h did not significantly increase target attainment against nonfermenters. Piperacillin-tazobactam target attainments were similar to that of ceftazidime against all pathogens. Higher doses of both compounds were needed to achieve better target attainments against
P. aeruginosa
. Overall, meropenem, imipenem, and cefepime attained the highest probabilities of attainment against the
Enterobacteriaceae
(99 to 100%). The carbapenems appear to be the most useful agents against
A. baumannii
(88 to 92%), and these agents, along with higher doses of any of the β-lactams, would be the most appropriate choices for empirical therapy for
P. aeruginosa
infection. Given the lack of agreement between percent susceptibility and probability of target attainment for certain antimicrobial regimens, a methodology employing stochastic pharmacodynamic analyses may be a more useful tool for differentiating the most-optimal compounds and dosing regimens in the clinical setting of initial empirical therapy.
Patterns of Amphotericin B Killing Kinetics against Seven
Candida
Species
Authors: Cantón Emilia , Pemán Javier , Gobernado Miguel , Viudes Angel , Espinel-Ingroff Ana 
Published: June 2004

ABSTRACT

In a previous study tolerance to amphotericin B (AMB) was found among
Candida parapsilosis
and
C. dubliniensis
strains by seeding the whole volumes of wells used for MIC determinations, and minimum fungicidal concentrations (MFC) for non-
C. albicans Candida
strains were demonstrated to be above the levels safely achievable in serum. As an extension of that study, we performed time-kill assays with 26 blood culture isolates (6
C. albicans
, 5
C. parapsilosis
, 5
C. krusei
, 4 C.
glabrata
, 3
C. lusitaniae
, and 3
C. tropicalis
isolates), 3 oropharyngeal
C. dubliniensis
isolates, 3 AMB-susceptible isolates (ATCC 90028, ATCC 22019, ATCC 6254), and 6 AMB-resistant isolates (ATCC 200955, ATCC 200956, ATCC 200950, ATCC 200951, ATCC 200952, ATCC 200953) using RPMI 1640 medium and 0.12 to 32 μg of AMB per ml and determined the numbers of CFU per milliliter at 0, 2, 4, 8, 12, 24, and 48 h. MFCs and time-kill patterns were species specific (MFCs, ≤1 μg/ml for all
C. dubliniensis
and
C. albicans
isolates except AMB-resistant strain ATCC 200955; MFCs, 2 to >16 μg/ml for the other isolates). The times required to reach the fungicidal endpoint (99.9% killing) at four times the MIC were 2 h for
C. albicans
and
C. dubliniensis
, 16 h for
C. glabrata
, 24 h for
C. parapsilosis
and
C. lusitaniae
, and ≥40 h for
C. tropicalis
and
C. krusei
. The killing rate increased as the AMB concentration was increased up to 2 μg/ml. The highest killing rates were achieved for
C. albicans
,
C. dubliniensis
, and
C. lusitaniae
, while viable
C. tropicalis, C. krusei
, and
C. parapsilosis
cells were present after 48 h (MICs, ≤2 μg/ml) when AMB was used at 2 μg/ml. Time-kill curves and MFCs can detect viable cells after 48 h when AMB is used at ≥2 μg/ml. The failure of AMB treatment could be due to its poor killing activity against some species at the concentrations reached in patients' serum.
Terpenes Arrest Parasite Development and Inhibit Biosynthesis of Isoprenoids inPlasmodium falciparum
Authors: Rodrigues Goulart Herbert , Kimura Emília A. , Peres Valnice J. , Couto Alicia S. , Aquino Duarte Fulgencio A. , Katzin Alejandro M. 
Published: June 2004

ABSTRACTDevelopment of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids inPlasmodium falciparumwas recently described. Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized inP. falciparum. These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure to the intermediates of the isoprenoids pathway, as potential antimalarial drugs. Different terpenes andS-farnesylthiosalicylic acid were tested on cultures of the intraerythrocytic stages ofP. falciparum, and the 50% inhibitory concentrations for each one were found: farnesol, 64 μM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; andS-farnesylthiosalicylic acid, 14 μM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(n)-3H]farnesyl pyrophosphate triammonium salt ([3H]FPP) was used as precursor. Farnesol, nerolidol, and linalool showed stronger inhibitory activity on the biosynthesis of the isoprenic side chain of the benzoquinone ring of ubiquinones in the schizont stage. Treatment of schizont stages withS-farnesylthiosalicylic acid led to a decrease in intensity of the band corresponding a p21rasprotein. The inhibitory effect of terpenes andS-farnesylthiosalicylic acid on the biosynthesis of both dolichol and the isoprenic side chain of ubiquinones and the isoprenylation of proteins in the intraerythrocytic stages ofP. falciparumappears to be specific, because overall protein biosynthesis was not affected. Combinations of some terpenes orS-farnesylthiosalicylic acid tested in this work with other antimalarial drugs, like fosmidomycin, could be a new strategy for the treatment of malaria.
Saccharomyces cerevisiae
Multidrug Transporter Qdr2p (Yil121wp): Localization and Function as a Quinidine Resistance Determinant
Authors: Vargas Rita C. , Tenreiro Sandra , Teixeira Miguel C. , Fernandes Alexandra R. , Sá-Correia Isabel 
Published: June 2004

ABSTRACT

This work reports the functional analysis of
Saccharomyces cerevisiae
open reading frame
YIL121w
, encoding a member of a family of drug:H
+
antiporters with 12 predicted membrane-spanning segments (DHA12 family). Like its close homologue Qdr1p, Yil121wp was localized at the plasma membrane, and its increased expression also led to increased tolerance to the antiarrhythmia and antimalarial drug quinidine. The quinidine resistance phenotype was confirmed for different yeast strains and growth media, including a prototrophic strain, and
YIL121w
was named the
QDR2
gene. Both
QDR1
and
QDR2
were also implicated in yeast resistance to the herbicide barban (4-chloro-2-butynyl [3-chlorophenyl] carbamate), and the genes are functionally interchangeable with respect to both resistance phenotypes. The average intracellular pH of a yeast population challenged with quinidine added to the acidic growth medium was significantly below the intracellular pH of the unstressed population, suggesting plasma membrane permeabilization by quinidine with consequent increase of the H
+
influx rate. For the same extracellular quinidine concentration, internal acidification was more intense for the Δ
qdr2
deletant compared with the parental strain. Although
QDR2
transcription was not enhanced in response to quinidine, the results confirmed that Qdr2p is involved in the active export of quinidine out of the cell, thus conferring resistance to the drug.
Multiple-Dose Pharmacokinetics and Safety of a Novel Broad-Spectrum Cephalosporin (BAL5788) in Healthy Volunteers
Authors: Schmitt-Hoffmann Anne , Nyman Lars , Roos Brigitte , Schleimer Michael , Sauer Jill , Nashed Norman , Brown Thomas , Man Anthony , Weidekamm Erhard 
Published: June 2004

ABSTRACT

BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activity against methicillin-resistant
Staphylococcus aureus
(MRSA) and penicillin-resistant
Streptococcus pneumoniae
. Safety and pharmacokinetic data from a multiple-dose study with 16 healthy male volunteers are reported. Subjects were randomized to receive BAL5788 at 500 or 750 mg (as BAL9141 equivalents;
n
= 6 subjects per dose) or placebo (
n
= 2 subjects per dose). The doses were given as 200-ml infusions over 30 min once daily on days 1 and 8 and twice daily on days 2 to 7. BAL5788 was well tolerated, with no severe or serious adverse events (AEs) or dosing-related changes in laboratory parameters, electrocardiographic findings, or vital signs. Drug accumulation in plasma was negligible during the dosing period. The results of pharmacokinetic analyses agreed well with data reported from a previous single-ascending-dose study. The elimination half-life of BAL9141 was about 3 h. The volume of distribution at steady state was equal to the volume of the adult extracellular water compartment. BAL9141 was predominantly eliminated in urine, and renal clearance of the free drug corresponded to the normal glomerular filtration rate in adults. After multiple infusions of 750 mg, the mean concentrations of BAL9141 in plasma exceeded the MIC at which 100% of MRSA isolates are inhibited (4 μg/ml) for approximately 7 to 9 h, corresponding to 58 to 75% of a 12-h dosing interval.
Absorption of Ester Prodrugs in Caco-2 and Rat Intestine Models
Authors: He Xin , Sugawara Mitsuru , Takekuma Yoh , Miyazaki Katsumi 
Published: June 2004

ABSTRACT

The aim of this study was to elucidate the absorption mechanism in Caco-2 and rat intestine models in order to improve the accuracy of prediction of oral absorption of ester prodrugs. Pivampicillin and cefcapene pivoxil hydrochloride (CFPN-PI), ester-type oral antibiotics, were chosen as model ester prodrugs. The level of esterase activity in Caco-2 cells was lower than that measured in the rat jejunum when
p
-nitrophenyl acetate was used as a substrate. Almost complete ester hydrolysis occurred before the ester prodrugs reached the basolateral side of the monolayer, and the disappearance of prodrugs was thought to be due to metabolism or transport after addition to the apical side of the monolayer. When pivampicillin and CFPN-PI were used, the amounts of ampicillin and cefcapene (CFPN) produced by hydrolysis of prodrugs were increased because intracellular degradation of prodrugs resulted in intracellular accumulation. On the other hand, when ampicillin or CFPN was used, only a small amount of the drug reached the basolateral side of the monolayers and no intracellular accumulation was observed. The permeability of CFPN-PI, the solubility of which is dependent on the acidity of gastric juice, across a Caco-2 monolayer or rat intestine, was also investigated by using an in vitro system that mimics the physiological state of the human gastrointestinal tract. The oral absorption of CFPN-PI in humans is predicted to be good either in the Caco-2 model or in the rat intestine model. It is concluded that our system may be a valuable tool for evaluation of oral absorption of ester prodrugs metabolized during permeation through the intestinal epithelium. Broader evaluation of such a system is warranted.
Pneumocystis jiroveci
Dihydropteroate Synthase Polymorphisms Confer Resistance to Sulfadoxine and Sulfanilamide in
Saccharomyces cerevisiae
Authors: Meneau I. , Sanglard D. , Bille J. , Hauser P. M. 
Published: June 2004

ABSTRACT

Failure of anti-
Pneumocystis jiroveci
prophylaxis with sulfa drugs is associated with mutations within the putative active site of the fungal dihydropteroate synthase (DHPS), an enzyme encoded by the multidomain
FAS
gene. This enzyme is involved in the essential biosynthesis of folic acid. The most frequent polymorphisms are two mutations leading to two amino acid changes (
55
Trp-Arg-
57
Pro to
55
Ala-Arg-
57
Ser), observed as a single or double mutation in the same
P. jiroveci
isolate. In the absence of a culture method for
P. jiroveci
, we studied potential resistance to sulfa drugs conferred by these polymorphisms by using
Saccharomyces cerevisiae
as a model. Single or double mutations identical to those observed in the DHPS domain of the
P. jiroveci FAS
gene were introduced by in vitro site-directed mutagenesis into alleles of the
S. cerevisiae FOL1
gene, which is the orthologue of the
P. jiroveci FAS
gene. The mutated alleles were integrated at the genomic locus in
S. cerevisiae
and expressed by functional complementation in a strain with a disrupted
FOL1
allele. The single mutation
55
Trp to
55
Ala conferred resistance to sulfanilamide, whereas the single mutation
57
Pro to
57
Ser conferred resistance to both sulfanilamide and sulfadoxine. Both single mutations also separately conferred hypersensitivity to sulfamethoxazole and dapsone. The resistance to sulfadoxine is consistent with epidemiological data on
P. jiroveci
. The double mutation
55
Trp-Arg-
57
Pro to
55
Ala-Arg-
57
Ser conferred on
S. cerevisiae
a requirement for
p
-aminobenzoate, suggesting reduced affinity of DHPS for this substrate. This characteristic is commonly observed in mutated DHPS enzymes conferring sulfa drug resistance from other organisms. However, the double mutation conferred hypersensitivity to sulfamethoxazole, which is not in agreement with epidemiological data on
P. jiroveci
. Taken together, our results suggest that the DHPS polymorphisms observed in
P. jiroveci
confer sulfa drug resistance on this pathogen.
Dihydropteroate Synthase Mutations in
Pneumocystis jiroveci
Can Affect Sulfamethoxazole Resistance in a
Saccharomyces cerevisiae
Model
Authors: Iliades Peter , Meshnick Steven R. , Macreadie Ian G. 
Published: June 2004

ABSTRACT

Dihydropteroate synthase (DHPS) mutations in
Pneumocystis jiroveci
have been associated epidemiologically with resistance to sulfamethoxazole (SMX). Since
P. jiroveci
cannot be cultured, inherent drug resistance cannot be measured. This study explores the effects of these mutations in a tractable model organism,
Saccharomyces cerevisiae
. Based on the sequence conservation between the DHPS enzymes of
P. jiroveci
and
S. cerevisiae
, together with the structural conservation of the three known DHPS structures, DHPS substitutions commonly observed in
P. jiroveci
were reverse engineered into the
S. cerevisiae
DHPS. Those mutations, T
597
A and P
599
S, can occur singly but are most commonly found together and are associated with SMX treatment failure. Mutations encoding the corresponding changes in the
S. cerevisiae dhps
were made in a yeast centromere vector, p414FYC, which encodes the native yeast DHPS as part of a trifunctional protein that also includes the two enzymes upstream of DHPS in the folic acid synthesis pathway, dihydroneopterin aldolase and 2-amino-4-hydroxymethyl dihydropteridine pyrophosphokinase. A yeast strain with
dhps
deleted was employed as the host strain, and transformants having DHPS activity were recovered. Mutants having both T
597
and P
599
substitutions had a requirement for
p
-aminobenzoic acid (PABA), consistent with resistance being associated with altered substrate binding. These mutants could be adapted for growth in the absence of PABA, which coincided with increased sulfa drug resistance. Upregulated PABA synthesis was thus implicated as a mechanism for sulfa drug resistance for mutants having two DHPS substitutions.
Novel Type V Staphylococcal Cassette Chromosome
mec
Driven by a Novel Cassette Chromosome Recombinase,
ccrC
Authors: Ito Teruyo , Ma Xiao Xue , Takeuchi Fumihiko , Okuma Keiko , Yuzawa Harumi , Hiramatsu Keiichi 
Published: June 2004

ABSTRACT

Staphylococcal cassette chromosome
mec
(SCC
mec
) is a mobile genetic element composed of the
mec
gene complex, which encodes methicillin resistance, and the
ccr
gene complex, which encodes the recombinases responsible for its mobility. The
mec
gene complex has been classified into four classes, and the
ccr
gene complex has been classified into three allotypes. Different combinations of
mec
gene complex classes and
ccr
gene complex types have so far defined four types of SCC
mec
elements. Now we introduce the fifth allotype of SCC
mec
, which was found on the chromosome of a community-acquired methicillin-resistant
Staphylococcus aureus
strain (strain WIS [WBG8318]) isolated in Australia. The element shared the same chromosomal integration site with the four extant types of SCC
mec
and the characteristic nucleotide sequences at the chromosome-SCC
mec
junction regions. The novel SCC
mec
carried
mecA
bracketed by IS
431
(IS
431
-
mecA
-Δ
mecR1-
IS
431
), which is designated the class C2
mec
gene complex; and instead of
ccrA
and
ccrB
genes, it carried a single copy of a gene homologue that encoded cassette chromosome recombinase. Since the open reading frame (ORF) was found to encode an enzyme which catalyzes the precise excision as well as site- and orientation-specific integration of the element, we designated the ORF cassette chromosome recombinase C (
ccrC
), and we designated the element type V SCC
mec
. Type V SCC
mec
is a small SCC
mec
element (28 kb) and does not carry any antibiotic resistance genes besides
mecA
. Unlike the extant SCC
mec
types, it carries a set of foreign genes encoding a restriction-modification system that might play a role in the stabilization of the element on the chromosome.