Preserved pharmacological activity of hepatocytes-treated extracts of valerian and St. John's wort

The two herbal extracts valerian (Valeriana officinalis L.) and St. John's wort (Hypericum perforatum L.) were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Quantitative HPLC analysis of valerian extracts revealed considerable metabolic activities with regard to sesquiterpenes and iridoids. The amount of acetoxyvalerenic acid decreased 9-fold, while that of hydroxyvalerenic acid correspondingly increased 9-fold due to O-deacetylation. The valepotriates didrovaltrate, isovaltrate and valtrate decreased 2-, 18- and 16-fold, respectively. However, the binding affinities of the incubated extracts to the benzodiazepine and picrotoxin binding site of the GABA (A) receptor were quite similar to those of the non-incubated extracts. Neither valerenic acids nor valepotriates exhibited any significant effect on the two binding sites when tested as single compounds. Therefore, either other constituents represent the active ones or multiple compounds are necessary for the observed inhibitory and allosteric effects at the GABA (A) receptor. Extracts of St. John's wort were less potently metabolised than valerian. The amount of pseudohypericin and the main flavonoids (hyperoside, rutin, isoquercitrin, quercitrin, quercetin and I3,II8-biapigenin) slightly decreased during the 4-h incubation period. Both the antagonist effect at the corticotropin-releasing factor (CRF) type 1 receptor and the binding inhibition at the 5-HT transporter were attenuated during the metabolic treatment. The reduced antagonist effect correlates with the decreasing amount of pseudohypericin known to be a CRF (1) receptor antagonist. In conclusion, the incubation of plant extracts with freshly prepared rat hepatocytes represents a useful approach to study the pharmacological action of metabolised plant extracts. The consistent pharmacological activity of both valerian and St. John's wort is concordant with the known clinical efficacy of pharmacological activities.     

The Multiple Tasks Test as a predictor of falls in older adults

PURPOSE: Falls are among the most common and serious problems facing the elderly. The Berg Balance Scale (BBS) is the gold standard in measuring falls risk. With higher functioning elders, a ceiling effect is often evidenced using the BBS. The purpose of this study was to determine if the Multiple Tasks Test (MTT) when used in high functioning community dwelling elderly correlated with the BBS. Secondly, this study assessed the unidimensionality of the MTT. If a relationship existed between the performance of multiple tasks and the potential loss of balance resulting in falls, then the MTT would be more appropriate than the BBS at predicting falls in higher functioning individuals. METHODS: Twenty-two independent community dwelling older adults were tested using both the MTT and the BBS on the same day at a senior center. DATA ANALYSIS: Correlations between the BBS and the MTT ranged between -0.765 and -0.79. The results of the Guttman's scalability analysis were a plus percentage ratio of 0.75 and an index of reproducibility of 0.93. Scales with these values are regarded as having evidence of unidimensionality. SUMMARY: All of the MTT tests correlated with the BBS. In addition, the MTT was found to be unidimensional. CONCLUSION: Although the MTT correlated with the BBS and was found to be a good cumulative measure, it would benefit from continued study to examine quantifiability, validity and reliability. With further refinement and study, the MTT may be useful at discriminating fallers from non-fallers in high functioning older adults.     

Redox activity of airborne particulate matter at different sites in the Los Angeles Basin

Epidemiologic studies have shown associations between ambient particulate matter (PM) and adverse health outcomes including increased mortality, emergency room visits, and time lost from school and work. The mechanisms of PM-related health effects are still incompletely understood, but a hypothesis under investigation is that many of the adverse health effects may derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. While the adverse effects from PM have historically been associated with the airborne concentration of PM and more recently fine-particle PM, we considered it relevant to develop an assay to quantitatively measure the ability of PM to catalyze ROS generation as the initial step in the induction of oxidative stress. This ability of PM could then be related to different sources, chemical composition, and physical and spatial/temporal characteristics in the ambient environment. The measurement of ROS-forming ability in relation to sources and other factors will have potential relevance to control of redox-active PM. If oxidative stress represents a relevant mechanism of toxicity from PM, the measurement of redox activity represents a first step in the elucidation of the subsequent downstream processes. We have developed an assay for PM redox activity, utilizing the reduction of oxygen by dithiothreitol which serves as an electron source. We have found that PM will catalyze the reduction of oxygen and have examined the distribution and chemical characteristics of the redox activity of PM fractions collected in different sites in the Los Angeles Basin. Samples of concentrated coarse, fine, and ultrafine PM, obtained with aerosol concentrators, were studied with regard to their chemical properties and redox activity. Redox activity was highest in the ultrafine fraction, in agreement with results indicating ultrafines were the most potent toward inducing that heme oxygenase expression and depleting intracellular glutathione, which has relevance to induction of oxidative stress. Comparison of the redox activity with chemical composition showed a reasonable correlation of redox activity with elemental carbon (r(2)=0.79), organic carbon (r(2)=0.53), and with benzo[ghi]perylene (r(2)=0.82), consistent with species typically found in mobile emission sources.     

ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes

Genetic susceptibility modulates the impact of obesity on risk for type 2 diabetes. The present study evaluates the role of ENPP1 K121Q polymorphism in prediction of type 2 diabetes in three populations that differ in susceptibility to diabetes and environmental exposure. The three cohorts included 679 nonmigrant South Asians living in Chennai, India (223 with type 2 diabetes); 1,083 migrant South Asians living in Dallas, Texas (121 with type 2 diabetes); and 858 nonmigrant Caucasians living in Dallas, Texas (141 with type 2 diabetes). Patients with type 2 diabetes were included in these cohorts if they had diabetes onset before the age of 60 years. The prevalence of subjects carrying the polymorphic ENPP1 121Q allele was 25% in the nondiabetic group and 34% in the diabetic group of South Asians living in Chennai (P = 0.01). The prevalence in the nondiabetic and diabetic groups were 33 and 45% (P = 0.01) for the South Asians living in Dallas and 26 and 39% (P = 0.003) for the Caucasians. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians.     

Neurocognitive functioning in pediatric human immunodeficiency virus infection: effects of combined therapy

OBJECTIVES: To assess the impact of combination antiretroviral therapy on neurocognitive outcomes in perinatally human immunodeficiency virus (HIV)-infected patients and to determine if CD4 percentage and plasma HIV-1 RNA level (viral load) are predictive of future neurocognitive function. DESIGN: Retrospective cohort study. SETTING: An HIV-dedicated urban care center. PARTICIPANTS: One hundred forty-six perinatally HIV-infected children born between June 1990 and May 2003 with at least 1 neurocognitive evaluation. MAIN OUTCOME MEASURES: Neurocognitive standard testing scores as well as diagnosis of progressive encephalopathy, probable progressive encephalopathy, or static encephalopathy. RESULTS: The prevalence of progressive encephalopathy has decreased in children born prior to 1996 (period 1) compared with those born after 1996 (period 2) from 29.6% to 12.1% (P = .049). The prevalence of all progressive encephalopathy and static encephalopathy decreased from 40.7% to 18.2% in period 1 vs 2 (P = .02). For those diagnosed as neurocognitively healthy, neurocognitive scores remained stable over time with a mean (SD) standard score of 89.6 (11.8) at first evaluation compared with 91.9 (11.93) at most recent evaluation. The most recent mean (SD) standard score increased from 82.3 (18) to 87.2 (10.49) in period 1 vs period 2 (P = .001). A weak association was found between both the mean viral load (P = .06) and CD4 percentage (P<.001) and neurocognitive testing score 6 months later. CONCLUSIONS: Since 1996, fewer children have been diagnosed with progressive encephalopathy, and neurocognitive functioning is preserved over time in those deemed neurocognitively healthy at entry. Viral load and CD4 percentage are marginally predictive of future changes in neurocognitive standard scores. These data support the observation that combination antiretroviral therapy is associated with improved neurocognitive outcomes in children with perinatally acquired HIV infection.     

Transpulmonary CT-Guided Radiofrequency Ablation of Liver Metastasis

The percutaneous approach for RF ablation of liver lesions high up in the dome is always difficult. The authors describe a transpulmonary approach that may be simpler and safer to use.     

An observational study of Yasmin in the management of women with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is the commonest endocrine disturbance affecting women in the reproductive age group and encompasses signs of hyperandrogenism, menstrual cycle disturbances and obesity. Some of the symptoms of PCOS may be ameliorated by the combined oral contraceptive pill (COCP). METHODS: A pilot observational study was carried out in a university teaching hospital setting to determine whether the clinical and biochemical features of PCOS are ameliorated by a new COCP, Yasmin, which contains a new progestogen, drosperinone. Treatment with Yasmin was given for 6 months to 17 patients. RESULTS: Thirteen patients (76%) completed 6 months of therapy. Good cycle control was achieved in all patients. Percentage body fat increased, with no overall change in body mass index. Fasting insulin and triglyceride concentrations rose significantly. Serum total testosterone concentrations fell with a concomitant rise in sex hormone binding globulin levels. Hirsutism scores did not change significantly in the 12 women who were clinically hirsute. There was, however, a significant improvement in the acne scores. Four of the 17 patients dropped out of the trial between Cycles 3 and 5 due to side effects. CONCLUSIONS: Yasmin provides good cycle control for women with PCOS, with an improvement in acne over 6 months but not in other symptoms of the syndrome.     

Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations

Three new spectrophotometric methods for the determination of amlodipine besylate have been proposed. The first two methods, i.e. A and B, are based on the oxidation of the drug with Fe(III) and the estimation of Fe(II) produced after chelation with either 1,10-phenanthroline or 2,2'-bipyridyl at 500 and 515 nm, respectively. The Beer's law was obeyed in the concentration ranges of 2-10 and 4-14 microg ml(-1) with molar absorptivity of 2.9 x 10(4) and 2.7 x 10(4) l mol(-1) cm(-1) for methods A and B, respectively. The third procedure depends on the interaction of amlodipine besylate with ammonium heptamolybdate tetrahydrate, which resulted in the formation of molybdenum blue (lambda(max) 825 nm). The linear dynamic range and the molar absorptivity values were found to be 15-59 microg ml(-1) and 1.8 x 10(4) l mol(-1) cm(-1), respectively. The results of the proposed procedures were validated statistically and compared with those obtained by the reference method. The proposed methods were applied successfully to the determination of amlodipine besylate in commercial tablets.