Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular-Coerulear Excitatory Interactions.

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α1-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α1-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α1-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α1-adrenoceptor density in whole hypothalamus and the expression levels of α1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α1-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular-coerulear excitatory interactions in prenatally undernourished young-adult rats.

Design of a trial to evaluate the impact of clinical pharmacists and community health promoters working with African-Americans and Latinos with diabetes.

BACKGROUND: Given the increasing prevalence of diabetes and the lack of patients reaching recommended therapeutic goals, novel models of team-based care are emerging. These teams typically include a combination of physicians, nurses, case managers, pharmacists, and community-based peer health promoters (HPs). Recent evidence supports the role of pharmacists in diabetes management to improve glycemic control, as they offer expertise in medication management with the ability to collaboratively intensify therapy. However, few studies of pharmacy-based models of care have focused on low income, minority populations that are most in need of intervention. Alternatively, HP interventions have focused largely upon low income minority groups, addressing their unique psychosocial and environmental challenges in diabetes self-care. This study will evaluate the impact of HPs as a complement to pharmacist management in a randomized controlled trial. METHODS/DESIGN: The primary aim of this randomized trial is to evaluate the effectiveness of clinical pharmacists and HPs on diabetes behaviors (including healthy eating, physical activity, and medication adherence), hemoglobin A1c, blood pressure, and LDL-cholesterol levels. A total of 300 minority patients with uncontrolled diabetes from the University of Illinois Medical Center ambulatory network in Chicago will be randomized to either pharmacist management alone, or pharmacist management plus HP support. After one year, the pharmacist-only group will be intensified by the addition of HP support and maintenance will be assessed by phasing out HP support from the pharmacist plus HP group (crossover design). Outcomes will be evaluated at baseline, 6, 12, and 24 months. In addition, program and healthcare utilization data will be incorporated into cost and cost-effectiveness evaluations of pharmacist management with and without HP support. DISCUSSION: The study will evaluate an innovative, integrated approach to chronic disease management in minorities with poorly controlled diabetes. The approach is comprised of clinic-based pharmacists and community-based health promoters collaborating together. They will target patient-level factors (e.g., lack of adherence to lifestyle modification and medications) and provider-level factors (e.g., clinical inertia) that contribute to poor clinical outcomes in diabetes. Importantly, the study design and analytic approach will help determine the differential and combined impact of adherence to lifestyle changes, medication, and intensification on clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01498159.

Parkinson's disease and tea: a quantitative review.

PURPOSE: To evaluate the risk of PD associated with tea consumption. MATERIAL AND METHODS: We reviewed all observational studies that evaluated the association between PD risk and tea consumption. Only, 12 studies were identified: 11 case-control and 1 cohort. These studies were carried out between 1981 and 2003. The studies represented different populations from 3 continents; North America, Europe and Asia. The 3 studies from Asia were case-control studies of Chinese populations. RESULTS: There was a clear protective effect of tea consumption in the pooled risk estimate [OR: 0.83 (95% confidence interval 0.74 to 0.92)] with 2215 cases and 145578 controls. However, the homogeneity test was significant (p value of 0.008), denoting heterogeneity across the pooled studies. Pooled analysis applying the random effect model was OR: 0.81 with 95% confidence interval nearly overlapping unity (95% confidence interval 0.67 to 0.98). Tea consumers versus non-consumers in Chinese populations had pooled OR of 0.73 with 95% confidence interval 0.60 to 0.90 (470 cases and 623 controls). The p value of homogeneity test was 0.96, denoting homogeneity across the pooled 3 studies. CONCLUSION: Tea consumption can protect against PD and this protective effect is clearer in Chinese populations. The low rate of tea consumption among persons with PD should provide us many valuable insights into the nature of the illness.

Alzheimer's disease and coffee: a quantitative review.

PURPOSE: To estimate the pooled risk of coffee consumption for Alzheimer's disease (AD). MATERIAL AND METHODS: We have reviewed all observational studies that evaluated the association between AD risk and coffee consumption. Four studies were identified: two case-control studies and two cohorts. These studies were carried out between 1990 and 2002. RESULTS: There was an obvious protective effect of coffee consumption in the pooled estimate [risk estimate: 0.73 (95% confidence interval: 0.58-0.92)]. However, the homogeneity test was highly significant (p<0.01), indicating heterogeneity across the pooled studies. Pooled analysis applying the random effect model was 0.79 with 95% confidence interval overlapping unity (95% confidence interval: 0.46-1.36). Three studies assessed coffee consumption by interview questionnaire. The risk of AD in coffee consumers versus non-consumers in studies that used interview questionnaire had a pooled risk estimate of 0.70 with 95% confidence interval 0.55-0.90. CONCLUSION: Although our pooled estimates show that coffee consumption is inversely associated with the risk of AD, the four studies had heterogeneous methodologies and results. Further prospective studies evaluating the association between coffee consumption and AD are strongly needed.

Urinary bladder cancer and the petroleum industry: a quantitative review.

PURPOSE: To estimate the pooled risk of petroleum industry for urinary bladder cancer. MATERIAL AND METHODS: All observational studies that evaluated the association between urinary bladder risk and the petroleum industry were reviewed. We have only identified eight case-control studies. These studies were carried out between 1989 and 1995. RESULTS: Of the eight localized studies six were exclusively for males. The other two studies included both males and females, but none reported separately the risk among men and women. There was an obvious risk of petroleum industry in the pooled risk (odds ratio 1.4, 95% confidence interval (CI) 1.27-1.54). Also, Q test was not significant (P>0.1), denoting homogeneity across the pooled studies. Pooled analysis applying the random effect model was 1.50 (95% CI 1.29-1.75). CONCLUSION: Although our pooled estimate shows that the petroleum industry is associated with the risk of urinary bladder cancer, the eight studies were based on retrospective data from case-control studies. Further prospective studies evaluating the association between petroleum industry and urinary bladder cancer risk are strongly needed.

Minor alkaloids from Guatteria dumetorum with antileishmanial activity.

Nine known alkaloids [(+)-isodomesticine (1), (+)-norisodomesticine (2), (+)-nantenine ( 3), (+)-neolitsine (4), (+)-lirioferine (5), (+)-N-methyllaurotetanine (6), (+)-norlirioferine (7), (+)-isoboldine (8) and (+)-reticuline (9)] were isolated from young leaves of Guatteria dumetorum. Their structures were confirmed by NMR, mass and UV spectral analysis and by comparison to literature data. The growth inhibitory activity of each alkaloid was determined against the parasite Leishmania mexicana. Compounds 1-4 all showed significant activity whereby potency increased when a methylenedioxy functionality was present, especially at the 1,2-positions.