bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole administered by oral and topical routes
Authors: Martin PJ , Chambers M , Hennessy DR 
Published: April 2009

Objective  To determine the efficacy of triclabendazole (TCBZ) against 28‐day‐old, early immature liver fluke in cattle and its pharmacokinetics following administration by the oral or topical (pour‐on) route.Procedures  Cattle (n = 18) were infected with 500 TCBZ‐susceptible liver fluke metacercariae and randomly allocated to three groups. At 28 days after infection, the groups were: (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination with oxfendazole and selenium (TOS); (3) treated with pour‐on TCBZ at 30 mg/kg in combination with abamectin (TA). Blood samples were taken immediately prior to treatment and serially after treatment to assess the plasma profile of TCBZ metabolites. Ten weeks after treatment all animals were slaughtered and total liver fluke counts, fluke egg counts and liver pathology were assessed.Results  Both the TOS and TA treatments resulted in significant reductions of 28‐day‐old liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and the reductions following TOS treatment were significantly greater than those following TA treatment. The blood profile of TCBZ metabolites in TOS‐treated animals showed a significantly greater area under the plasma concentration time curve and a higher maximum observed concentration than those treated with TA. There was significantly less liver pathology in TOS‐treated animals than in the TA‐treated animals.Conclusion  TCBZ administered orally at 12 mg/kg resulted in greater efficacy against 28‐day‐old, early immature liver fluke than was achieved by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and liver pathology was less in TOS‐treated animals than in TA‐treated animals.
The Effects of Ambient Solar UV Radiation on Alkaloid Production by Erythroxylum novogranatense var. novogranatense†
Authors: Lydon John , Casale John F. , Kong Hyesuk , Sullivan Joseph H. , Daughtry Craig S. T. , Bailey Bryan 
Published: April 2009

AbstractTruxillines are alkaloids produced by Erythroxylum species and are thought to be derived from the UV‐driven dimerization of cinnamoylcocaines. This study was conducted to determine the effects of ambient UV radiation on the production of truxillines in Erythroxylum novogranatense var. novogranatense. Field plants were grown under shelters covered with plastic filters that were transparent to UV radiation, filtered UV‐B, or both filtered UV‐B and UV‐A radiation. The treatments had no significant effect on plant biomass or specific leaf weight. Absorption values in the UV‐C and UV‐A region of acidified‐methanol leaf extracts were higher for plants exposed to UV radiation compared to the no UV radiation treatment. There was a trend in decreasing levels of trans‐cinnamoylcocaine and a statistically significant decrease in levels of cis‐cinnamoylcocaine in the leaves of plants exposed to UV radiation compared to the no UV radiation treatment. Truxilline levels increased in leaves from plants exposed to UV radiation compared to the no UV radiation treatment. Most significantly, the ratio of truxillines to total cinnamoylcocaines in the leaves was affected by UV, increasing with increased UV exposure. The results support the hypothesis that UV radiation is involved in the formation of truxillines from cinnamoylcocaines.
Analysis of whole genomic expression profiles ofHelicobacter pylorirelated chronic atrophic gastritis with IL‐1B‐31CC/‐511TT genotypes
Authors: WANG Shao Ying , SHEN Xiao Ying , WU Cai Yun , PAN Feng , SHEN Yuan Yuan , SHENG Hai Hui , CHEN Xi Mei , GAO Heng Jun 
Published: April 2009

OBJECTIVE:   Many studies have linked cytokine interleukin‐1B gene polymorphisms toH. pylori‐related gastric cancer development. The current study evaluated the characterization of whole genomic expression profiles of the premalignant condition:H. pylori‐related chronic atrophic gastritis (CAG) with IL‐1B‐31CC/‐511TT genotypes.METHODS:  IL‐1B‐31/‐511 gene polymorphisms were determined by DNA sequences. RNA was extracted and expression profiles were performed using Agilent human whole genomic oligonucleotide microarrays (G4112F). The expression of three samples withH. pyloriinfection was compared to that of three samples withoutH. pyloriinfection from samples of six CAG patients, all with IL‐1B‐31CC/‐511TT genotypes. Differentially expressed genes related toH. pylori‐induced CAG with IL‐1B‐31CC/‐511TT genotypes were screened and analyzed further by Gene Ontology (GO) and pathway. Validation of the microarray data was performed using qRT‐PCR.RESULTS:  A total of 124 differentially expressed genes and 32 GO term annotations were identified betweenH. pyloripositive and negative groups in the six CAG samples with IL‐1B‐31CC/‐511TT genotypes. The signaling pathways identified were oxidative phosphorylation and epithelial cell signaling inH. pyloriinfection. Five overlapping genes were contained in identified GO terms and pathways: ATP6V0B, NDUFS5, NDUFV2, ATP6V1F and ATP6V1G1. Comparisons of qRT‐PCR data and the previously reported data with the results of gene chips support the validity of our microarray data.CONCLUSION:  TheH. pylori‐related CAG with IL‐1B‐31CC/‐511TT genotypes has shown to be the more malignant phenotype thanH. pylorinegative CAG with IL‐1B‐31CC/‐511TT genotypes. Mitochondrial energy metabolism probably plays a crucial role as it is the molecular mechanism of host–bacterial interactions.
Polymorphism of thymidylate synthase gene and chemosensitivity of 5‐fluorouracil regimen in metastatic gastrointestinal cancer
Authors: CUI Yue Hong , LIU Tian Shu , ZHUANG Rong Yuan , GAO Hen Jun , LI Hong 
Published: April 2009

OBJECTIVE:  To explore the polymorphism of thymidylate synthase (TS) gene and chemosensitivity of a 5‐fluorouracil (5‐FU)‐containing regimen in metastatic colorectal and gastric cancer.METHODS:  Sixty‐eight patients with metastatic gastric or colorectal cancer were included in this study. Doublets or triplets of 28 base pairs (bp) in the 5‐untranslated region (UTR) of TS gene promoter were detected by polymerase chain reaction (PCR) analysis. Fragments of polymorphic products, 2R/2R, 2R/3R and 3R/3R were detected by the Agilent BioAnalyzer chip‐lab system. All patients were followed up until the censoring date. A χ2 test was used to analyze the polymorphism. A Kaplan–Meier curve and a log‐rank test were used to determine disease progression and overall survival.RESULTS:  Among 68 patients, polymorphism expressions were 4.4% in 2R/2R, 29.4% in 2R/3R and 66.2% in 3R/3R, and clinical responses were 33.3%, 73.3% and 47.6%, respectively (2R/3R versus 3R/3R, P= 0.058). In the 64 evaluable cases, the median time to progression (TTP) was 4 months and the TTP were 3 months in 2R/2R, 6 months in 2R/3R and 4 months in 3R/3R, separately (log‐rank test, P= 0.0316). Response rates to the 5‐FU regimen were also better in the 2R/3R group than in the 3R/3R group both in metastatic colorectal cancer and advanced gastric cancer.CONCLUSION:  Our study suggested that polymorphism of 3R/3R was more common in Chinese gastrointestinal cancer patients. Patients with a TS polymorphism expressed as 2R/3R might be more sensitive to 5‐FU regimen than those with a polymorphism expressed as 3R/3R.
Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease
Authors: CHUA Kek Heng , HILMI Ida , NG Ching Ching , ENG Tzy Lui , PALANIAPPAN Shanthi , LEE Way Seah , GOH Khean‐Lee 
Published: April 2009

OBJECTIVE:  The NOD2/CARD15 gene has been identified as an important susceptibility gene for Crohn's disease (CD) but the three common disease predisposing mutations (DPM) found in developed countries have not been identified in Asian populations. The aim of our study was to look for the DPM in our multiracial population and to discover whether there were any differences in the three major ethnic groups; Malay, Chinese and Indian.METHODS:  Blood samples from consecutive CD patients and healthy controls were obtained and analyzed for the three common mutations (R702W, G908R, 1007fs) but in addition to this, we also looked for the SNP5 and JW1 variants which are associated with CD in Ashkenazi Jews. A polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) technique was used to identify the mutations, which was confirmed by sequencing. The baseline socio‐demography and clinical characteristics of the CD patients were recorded.RESULTS:  Overall 45 patients (three Malays, 15 Chinese, 26 Indians and one other) with confirmed CD and 300 controls were recruited. The three common DPM were not observed in either the CD patients or the controls. Neither the SNP5 nor the JW1 mutation was found in any of the controls. However, the SNP5 mutation was identified in six (13.3%) Indian CD patients and the JW1 mutation in eight CD patients who are different from those carrying the SNP5 mutation: one Malay (33.3%), two Chinese (13.3%), one other (Portuguese) and four Indians (15.4%). The presence of SNP5 was strongly associated with CD in the Indian population and that of JW1 was strongly associated with CD overall and in each of the major ethnic groups. There was a trend towards a younger age of onset and stricturing disease in patients carrying the JW1 mutation.CONCLUSION:  These findings suggest the presence of novel DPM in the NOD2/CARD15 gene in Asian patients with CD.
A 7‐year study of lamivudine therapy for hepatitis B virus e antigen‐positive chronic hepatitis B patients in China
Authors: YAO Guang Bi , ZHU Mei , CUI Zhen Yu , WANG Bao En , YAO Ji Lu , ZENG Ming De 
Published: April 2009

OBJECTIVE:  To evaluate the long‐term efficacy and safety of lamivudine treatment for chronic hepatitis B and the impact of emergence of YMDD mutation of hepatitis B virus (HBV).METHODS:  A total of 429 patients with serum HBsAg, HBeAg and HBV DNA positive were randomized to receive either lamivudine 100 mg daily or a placebo in a 3:1 ratio for the first 12 weeks. Thereafter, all patients were administered with lamivudine 100 mg/d for 5 years and followed up for 2 years.RESULTS:  After 12 weeks of the lamivudine treatment, serum HBV DNA levels decreased rapidly and HBV DNA negativity (<1.6 pg/mL) was 92.2%, whereas it was only 14.1% (P < 0.01) in the placebo group. At the end of 5 years, serum HBV DNA continued to be substantially suppressed. The loss of HBeAg and seroconversion were significantly correlated with baseline alanine aminotransferase (ALT) levels, in patients with baseline ALT > 2 × upper limits of normal, the loss of HBeAg was 54% and seroconversion rate was 50%, respectively. YMDD mutation developed in 70.8% of the patients at years 5. In YMDD mutant patients, HBV DNA levels were increased moderately and with mild to moderate elevations of ALT. ALT flares (ALT > 5ULN) occurred in 22 patients, 16 with YMDD variants and six with non‐variants. One year durability of seroconversion after stopping lamivudine was 80%.CONCLUSION:  Lamivudine is effective and tolerable for chronic hepatitis B.
Parentage in natural populations: novel methods to detect parent‐offspring pairs in large data sets
Authors: CHRISTIE MARK R. 
Published: April 2009

AbstractParentage analysis in natural populations presents a valuable yet unique challenge because of large numbers of pairwise comparisons, marker set limitations and few sampled true parent–offspring pairs. These limitations can result in the incorrect assignment of false parent–offspring pairs that share alleles across multi‐locus genotypes by chance alone. I first define a probability, Pr(δ), to estimate the expected number of false parent–offspring pairs within a data set. This probability can be used to determine whether one can accept all putative parent–offspring pairs with strict exclusion. I next define the probability Pr(φ|λ), which employs Bayes’ theorem to determine the probability of a putative parent–offspring pair being false given the frequencies of shared alleles. This probability can be used to separate true parent–offspring pairs from false pairs that occur by chance when a data set lacks sufficient numbers of loci to accept all putative parent–offspring pairs. Finally, I propose a method to quantitatively determine how many loci to let mismatch for study‐specific error rates and demonstrate that few data sets should need to allow more than two loci to mismatch. I test all theoretical predictions with simulated data and find that, first, Pr(δ) and Pr(φ|λ) have very low bias, and second, that power increases with lower sample sizes, uniform allele frequency distributions, and higher numbers of loci and alleles per locus. Comparisons of Pr(φ|λ) to strict exclusion and CERVUS demonstrate that this method may be most appropriate for large natural populations when supplemental data (e.g. genealogies, candidate parents) are absent.
Ten novel microsatellite loci characterized for a remarkably widespread fish: Galaxias maculatus (Galaxiidae)
Authors: CARREA CECILIA , PATERSON IAN G. , CUSSAC VICTOR E. , RUZZANTE DANIEL E. 
Published: April 2009

AbstractTen polymorphic microsatellite markers (five tetra‐, one compound tetra‐, one octa‐ and three dinucleotides) were isolated and characterized for Galaxias maculatus, a fish species widely distributed in the Southern Hemisphere. Markers were tested in 89 individual samples from a single location and the number of alleles ranged between 2 and 28. Observed and expected heterozygosities ranged from 0.103 to 0.910 and 0.098 to 0.935 respectively. No evidence was detected for either linkage disequilibrium (P‐values > 0.05 for each locus pair) or deviations from HWE (P‐values > 0.05 for every loci).
Effects of Prednisone Alone or Prednisone with Ultralow‐Dose Aspirin on the Gastroduodenal Mucosa of Healthy Dogs
Authors: Heather Graham A. , Leib Michael S. 
Published: April 2009

Background:The coadministration of prednisone and ultralow‐dose aspirin has been recommended for the management of various diseases, but the safety of this combination in dogs has not been studied.Hypotheses:The gastroduodenal lesions associated with prednisone and ultralow‐dose aspirin administration will be similar to those caused by prednisone alone, but both treatments will result in more severe lesions than placebo.Animals:Eighteen healthy adult purpose‐bred dogs.Methods:Randomized, blinded, placebo‐controlled study of 3 treatment groups for 27 days: placebo, prednisone, and prednisone and aspirin. Gastroduodenoscopy was performed before and on days 5, 14, and 27 of treatment and mucosal lesions scores were assigned. Mucosal lesion scores were compared by a Kruskal‐Wallis test. Clinical signs were compared by the Friedman's chi‐square test (significance atP< .05).Results:There were no significant differences in the gastroduodenal lesion scores among groups, or within groups at any time during the study. Significantly more dog‐days of diarrhea occurred in the prednisone and aspirin group during treatment, compared with baseline. No significant differences in clinical signs were found among any of the groups.Conclusion:The concurrent use of prednisone and ultralow‐dose aspirin did not increase the severity of gastroduodenal lesions compared with prednisone or placebo. Coadministration of prednisone and ultralow‐dose aspirin increases the frequency of mild, self‐limiting diarrhea in some dogs.
Piperaquine Pharmacodynamics and Parasite Viability in a Murine Malaria Model
Authors: Moore Brioni R. , Ilett Kenneth F. , Page-Sharp Madhu , Jago Jeffrey D. , Batty Kevin T. 
Published: April 2009

ABSTRACT

Piperaquine (PQ) is an important partner drug in antimalarial combination treatments, but the long half-life of PQ raises concerns about drug resistance. Our aim was to investigate the extended antimalarial effect of PQ in a study of drug efficacy, reinoculation outcomes, and parasite viability after the administration of a single dose of PQ in the murine malaria model. Initially, male Swiss mice were inoculated with
Plasmodium berghei
and at 64 h after parasite inoculation were given PQ phosphate at 90 mg/kg of body weight intraperitoneally. Parasite viability, drug efficacy, reinoculation responses, and parasite resistance were determined at 25, 40, 60, 90, and 130 days after drug administration. At each time point, six mice were reinoculated with 10
7
P. berghei
parasites and blood was harvested from another four mice for viability passage into naïve mice (
n
= 5 for each blood sample) and from another two mice for determination of the plasma PQ concentration. The efficacy study demonstrated that the residual PQ concentrations did not suppress the infection after 25 days. Viable parasites were present up to 90 days after PQ dosing, although only 50% and 25% of the passaged parasites remained viable at 60 and 90 days postdosing, respectively. Viable parasites passaged into the naïve hosts were generally resistant to PQ when they were exposed to the drug for a second time. PQ was found to have a substantial antimalarial effect in this model, and the effect appears to be sufficient for a host immunological response to be established, resulting in the long-term survival of
P. berghei
-infected mice.
In Vitro Activities of Echinocandins againstCandida kruseiDetermined by Three Methods: MIC and Minimal Fungicidal Concentration Measurements and Time-Kill Studies
Authors: Cantón Emilia , Pemán Javier , Valentín Amparo , Espinel-Ingroff Ana , Gobernado Miguel 
Published: April 2009

ABSTRACTWe evaluated the in vitro activities of anidulafungin, micafungin, and caspofungin againstCandida kruseiby determining MIC and minimum fungicidal concentration (MFC) measurements and by the time-kill method. The geometric mean (GM)-MIC/GM-MFC values were 0.1/0.34, 0.25/0.44, and 1/2.29, respectively. The mean times to reach 99.9% growth reduction were 19.1 ± 18.2 h (mean ± standard deviation) for 2 mg/liter anidulafungin, 37.4 ± 8.8 h for 2 mg/liter caspofungin, and 30.7 ± 12.2 h for 1 mg/liter micafungin. Anidulafungin exhibited the highest time-kill rate, followed by micafungin. The three echinocandins showed fungicidal activity at concentrations reached in serum.
Simultaneous Determination of Voriconazole and Posaconazole Concentrations in Human Plasma by High-Performance Liquid Chromatography
Authors: Kahle Kathrin , Langmann Peter , Schirmer Diana , Lenker Ulrike , Keller Daniela , Helle Annegret , Klinker Hartwig , Heinz Werner J. 
Published: April 2009

ABSTRACT
A simple, sensitive, and selective high-performance liquid chromatographic method for the simultaneous determination of voriconazole and posaconazole concentrations in human plasma was developed and validated. Quantitative recovery following liquid-liquid extraction with diethyl ether was achieved. Linearity ranged from 0.10 to 20.0 μg/ml for voriconazole and from 0.05 to 10.0 μg/ml for posaconazole. The intra- and interday coefficients of variation were less than 8.5%, and the lower limits of quantitation were <0.05 μg/ml.
Genetic and Biochemical Characterization of the First Extended-Spectrum CARB-Type ß-Lactamase, RTG-4, from
Acinetobacter baumannii
Authors: Potron Anaïs , Poirel Laurent , Croizé Jacques , Chanteperdrix Vanessa , Nordmann Patrice 
Published: April 2009

ABSTRACT

Acinetobacter baumannii
isolate KAR was uncommonly more resistant to cefepime and cefpirome than to ceftazidime and cefotaxime. Cloning and expression of the β-lactamase gene content of this isolate into
Escherichia coli
TOP10 identified ß-lactamase RTG-4 (or CARB-10), which corresponds to the first reported extended-spectrum CARB-type enzyme. RTG-4 is a plasmid-encoded Ambler class A β-lactamase whose sequence differs by 4 amino acid substitutions from the narrow-spectrum β-lactamase RTG-3. RTG-4 hydrolyzes cefepime and cefpirome and weakly hydrolyzes ceftazidime due to the single Ser-to-Thr substitution at Ambler position 69. RTG-4 is less susceptible to inhibition by tazobactam and sulbactam than RTG-3. Expression of β-lactamase RTG-4 in a wild-type
A. baumannii
reference strain showed that it conferred resistance to cefepime and cefpirome. The genetic environment of the
bla
RTG-4
gene was made of a peculiar transposon located on a ca. 50-kb plasmid. IS
Aba9
, located upstream of
bla
RTG-4
, may be responsible for its acquisition by recognizing a secondary right inverted repeat sequence, thus acting by a one-ended transposition process.
Population Modeling and Monte Carlo Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Rifampin in Lungs
Authors: Goutelle Sylvain , Bourguignon Laurent , Maire Pascal H. , Van Guilder Michael , Conte John E. , Jelliffe Roger W. 
Published: April 2009

ABSTRACT

Little information exists on the pulmonary pharmacology of antituberculosis drugs. We used population pharmacokinetic modeling and Monte Carlo simulation to describe and explore the pulmonary pharmacokinetics and pharmacodynamics of rifampin (RIF; rifampicin). A population pharmacokinetic model that adequately described the plasma, epithelial lining fluid (ELF), and alveolar cell (AC) concentrations of RIF in a population of 34 human volunteers was made by use of the nonparametric adaptive grid (NPAG) algorithm. The estimated concentrations correlated well with the measured concentrations, and there was little bias and good precision. The results obtained with the NPAG algorithm were then imported into Matlab software to perform a 10,000-subject Monte Carlo simulation. The ability of RIF to suppress the development of drug resistance and to induce a sufficient bactericidal effect against
Mycobacterium tuberculosis
was evaluated by calculating the proportion of subjects achieving specific target values for the maximum concentration of drug (
C
max
)/MIC ratio and the area under the concentration-time curve from time zero to 24 h (AUC
0-24
)/MIC ratio, respectively. At the lowest MIC (0.01 mg/liter), after the administration of one 600-mg oral dose, the rates of target attainment for
C
max
/MIC (≥175) were 95% in ACs, 48.8% in plasma, and 35.9% in ELF. Under the same conditions, the target attainment results for the killing effect were 100% in plasma (AUC
0-24
/MIC ≥ 271) but only 54.5% in ELF (AUC
0-24
/MIC ≥ 665). The use of a 1,200-mg RIF dose was associated with better results for target attainment. The overall results suggest that the pulmonary concentrations obtained with the standard RIF dose are too low in most subjects. This work supports the need to evaluate higher doses of RIF for the treatment of patients with tuberculosis.