Physical activity and risk factors for hip fractures in Thai men

To test the hypothesis that hip fracture is associated with physical activity in Thai elderly men, a case-control study was conducted in Bangkok, Thailand. A total of 187 men aged 51 years over, resident in Bangkok, admitted consecutively with a radiologically confirmed first hip fracture were studied. 177 age-matched community controls were randomly recruited from the same neighborhood of the cases. Physical activity was independently associated with reduced risk of hip fracture after controlling for confounding factors. Very active and active past physical activity markedly reduced risk of hip fracture in comparison to subjects with inactive past physical activity. Recent active physical activity was also protective against hip fracture. This prompts a need to identify strategy to promote physical activity among the elderly and at an early age.     

槟榔灭钉螺增效成分的研究

对从槟榔(Areca catechu L.的干燥成熟种子)核中分离出的组分进行灭钉螺增效实验,研究表明,最有效成分为槟榔碱(Arecoline,Are.)。它与植物灭钉螺药商陆皂甙或化学灭钉螺药五氨酸钠等联合使用,可显著降低二者的投药量。     

Engineered NS1 for Sensitive,Specific Zika Virus Diagnosis from Patient Serology

Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.     

Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer

Cancer Chemotherapy and Pharmacology - CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize...     

Long-term effectiveness against cholera of oral killed whole-cell vaccine produced in Vietnam

We assessed the long-term protection afforded by a killed whole-cell oral cholera vaccine produced in Vietnam. A mass immunization of children and adults with the killed whole-cell oral cholera vaccine was undertaken in half of the communes of Hue, Vietnam, in 1998; the remaining communes were immunized in 2000. No cholera was observed in Hue until 2003, when an outbreak of El Tor cholera made it possible to conduct a case-control study. The overall vaccine effectiveness 3-5 years after vaccination was 50% (9-63%). This low-cost, easily administered vaccine should be considered as a tool for the control of cholera.     

IMP-4 and OXA beta-lactamases in Acinetobacter baumannii from Singapore

OBJECTIVE: To compare the incidence of carbapenemase genes in Acinetobacter baumannii between two time periods. METHODS: We studied 114 isolates of imipenem-resistant A. baumannii collected over two 5 month periods (in 1996 and 2001). Isolates showing carbapenemase activity by plate bioassay were screened for carbapenemase genes using PCR. Chromosomal DNA from strains carrying carbapenemase genes was subjected to PFGE after digestion with ApaI. RESULTS: The incidence of imipenem-resistant A. baumannii in our hospital rose from 1.1 per 1000 admissions in 1996 to 2.3 per 1000 admissions in 2001. However, the number of carbapenemase-producing A. baumannii rose only slightly in 2001 (0.8 per 1000 admissions) compared to 1996 (0.5 per 1000 admissions). Of 44 isolates with carbapenemase activity, 4 isolates carried bla(IMP-4), 5 carried bla(OXA-58), and 40 carried bla(OXA-23). In addition, most isolates carried a bla(OXA-51)-type beta-lactamase gene. All strains with bla(IMP-4), also carried bla(OXA-58) and bla(PSE-1), but not bla(OXA-51)-type beta-lactamase genes. PCR analysis repeated on seven recent isolates of susceptible A. baumannii showed only the presence of bla(OXA-51)-type beta-lactamase genes. A total of five novel bla(OXA-51)-type beta-lactamase genes (bla(OXA-88),-91,-93,-94, and -95) and one new bla(OXA-58)-type beta-lactamase gene (bla(OXA-96)) were found. CONCLUSIONS: The incidence of carbapenemase genes did not vary significantly between the two study periods. There is a wide diversity of OXA genes in A. baumannii in Singapore. The most common carbapenemase gene found in our study was bla(OXA-23).     

A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects

AIM

Aflibercept (VEGF-Trap), a novel anti-angiogenic agent that binds to VEGF, has been investigated for the treatment of cancer. The aim of this study was to develop a mechanism-based pharmacokinetic (PK) model for aflibercept to characterize its binding to VEGF and its PK properties in healthy subjects.

METHODS

Data from two phase I clinical studies with aflibercept administered as a single intravenous infusion were included in the analysis. Free and bound aflibercept concentration−time data were analysed using a nonlinear mixed-effects modelling approach with MONOLIX 3.1.

RESULTS

The best structural model involved two compartments for free aflibercept and one for bound aflibercept, with a Michaelis–Menten type binding of free aflibercept to VEGF from the peripheral compartment. The typical estimated clearances for free and bound aflibercept were 0.88 l day⁻¹ and 0.14 l day⁻¹, respectively. The central volume of distribution of free aflibercept was 4.94 l. The maximum binding capacity was 0.99 mg day⁻¹ and the concentration of aflibercept corresponding to half of maximum binding capacity was 2.91 µg ml⁻¹. Interindividual variability of model parameters was moderate, ranging from 13.6% (V_max) to 49.8% (Q).

CONCLUSION

The present PK model for aflibercept adequately characterizes the underlying mechanism of disposition of aflibercept and its nonlinear binding to VEGF.