Biomedical subjects

P Hu

Publications and source records attributed to P Hu.

219 records · Page 13Linked to original sources

PubMedDate not supplied

Cross-sectional association between markers of inflammation and serum sex steroid levels in the postmenopausal estrogen/progestin interventions trial.

BACKGROUND: Standard risk factors do not adequately capture cardiovascular risk in postmenopausal women. We sought to determine the associations between levels of sex steroids and levels of inflammatory markers in postmenopausal women. METHODS: We analyzed baseline data from a subset of postmenopausal women aged 45-64 years who had stored samples during a randomized controlled trial. We measured levels of C-reactive protein (CRP), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble intercellular adhesion molecule (sICAM), and circulating sex steroids. Multiple linear regression models were created with each of the following hormone levels as the primary exposure variable: estrone, total estradiol, bioavailable estradiol, total testosterone, bioavailable testosterone, progesterone, and sex hormone-binding globulin (SHBG). Sociodemographic and lifestyle covariates were derived from standardized self-report questionnaires and direct measurement (weight, height). RESULTS: Mean age of the 623 women was 56 years. After adjustment for age, body mass index (BMI), physical activity, alcohol consumption, and smoking, the bioavailable testosterone level (p = 0.03) was positively and the SHBG level (p < 0.001) was negatively associated with the logCRP level. The increment in CRP level between the highest and lowest quartile of bioavailable testosterone was 1.28 microg/mL. The increment in CRP level between the lowest and highest quartile of SHBG was 2.62 microg/mL. Compared with SHBG or bioavailable testosterone as predictors of logCRP in separate regression models, when both SHBG and bioavailable testosterone were included in the same multivariate linear regression model, only SHBG remained a statistically significant predictor of logCRP. Progesterone level was positively associated with the logMMP-9 level (p < 0.001); no other sex steroid level was associated with the logMMP-9 level. In multiply adjusted models, no association was found between levels of any sex steroid and IL-6 or sICAM level.

Alcohol Drinking↗

PubMedDate not supplied

A molecular genetic approach to amyotrophic lateral sclerosis.

Disorders of the motor neurons may affect both the upper and lower neurons, primarily the lower motor neurons as in the spinal muscular atrophies are primarily the upper motor neurons as in the familial spastic paraplegias. Amyotrophic lateral sclerosis is a degenerative disorder of the motor neuron that results in paralysis and wasting of voluntary muscles. Large motor neurons in the cerebral cortex, brain stem and spinal cord degenerate or are lost. Hyaline inclusions may be seen in the cytoplasm of surviving motor neurons. Acute axonal degeneration of peripheral motor fibers occurs at all levels, including the distal axon. Subclinical involvement of the spinecerebellar tracts, posterior column and Clarke's column as well as loss of large neurons in the dorsal root ganglia and neurons of oculomotor nuclei has been reported. The average duration of life onset of symptoms of amyotrophic lateral sclerosis is three years and ninety per cent of patients died within 5 years. The basic mechanism of disease in amyotrophic lateral sclerosis remains unknown. There is no known treatment that will prevent, reverse or otherwise alter the course of the disease. Autosomal dominant and autosomal recessive forms of amyotrophic lateral sclerosis are genetic models of amyotrophic lateral sclerosis which may provide insight into the disease mechanism of sporadic amyotrophic lateral sclerosis, five to ten percent of adult cases of amyotrophic lateral sclerosis with early onset of symptoms and a more benign course. It is conceivable that both genetic and sporadic forms of amyotrophic lateral sclerosis result from failure of the same or similar neuronal mechanism triggered by defective genes and by an environment agent in sporadic amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗

PubMedDate not supplied

Stereochemical studies on the beta-oxidation of valproic acid in isolated rat hepatocytes.

Stereochemical aspects of the biotransformation of valproic acid (VPA) to four compounds believed to represent products of mitochondrial beta-oxidation, viz. delta 2(E)-VPA, delta 3-VPA, 3-hydroxy-VPA, and 3-oxo-VPA, were examined in freshly isolated rat hepatocytes. Following incubation of the individual enantiomers of [5-13C]VPA and analysis of products by GC/MS techniques, it was possible to determine for each metabolite the relative populations of molecules that had been formed by oxidation on the pro-R vs. the pro-S propyl group of the drug. Metabolism was found to exhibit a slight preference (approximately 1.3:1) for attack on the pro-S side-chain for all four compounds, consistent with the hypothesis that this group shares a common metabolic origin. In contrast, the hepatotoxic terminal olefin, delta 4-VPA, was formed with marked enantiotopic differentiation (approximately 3.8:1) favoring the pro-R side-chain. The reason for the surprisingly low stereo-selectivity displayed by the products of beta-oxidation was investigated with the aid of [3-2H] delta 2(E)-VPA as metabolic substrate. Following incubation with rat hepatocytes, 35% of the substrate remaining after 2 hr was found to have been isomerized to [3'-2H] delta 2(E)-VPA. Because delta 2(E)-VPA is known to be formed from VPA-CoA through the action of 2-methyl-branched-chain acyl-CoA dehydrogenase, it is proposed that the three-carbon side-chains of both parent drug and delta 2(E)-VPA are interconverted as a consequence of reversibility in the second half-reaction of this enzymatic process.

Animals↗