Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans

BACKGROUND:Consumption of flavonoid-rich beverages, including tea and red wine, has been associated with a reduction in coronary events, but the physiological mechanism remains obscure. Cocoa can contain extraordinary concentrations of flavanols, a flavonoid subclass shown to activate nitric oxide synthase in vitro. OBJECTIVE: To test the hypothesis that flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in humans. DESIGN: The study prospectively assessed the effects of Flavanol-rich cocoa, using both time and beverage controls. Participants were blinded to intervention; the endpoint was objective and blinded. METHODS: Pulse wave amplitude was measured on the finger in 27 healthy people with a volume-sensitive validated calibrated plethysmograph, before and after 5 days of consumption of Flavanol-rich cocoa [821 mg of flavanols/day, quantitated as (-)-epicatechin, (+)-catechin, and related procyanidin oligomers]. The specific nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) was infused intravenously on day 1, before cocoa, and on day 5, after an acute ingestion of cocoa. RESULTS: Four days of flavanol-rich cocoa induced consistent and striking peripheral vasodilation (P = 0.009). On day 5, pulse wave amplitude exhibited a large additional acute response to cocoa (P = 0.01). L-NAME completely reversed this vasodilation (P = 0.004). In addition, intake of flavanol-rich cocoa augmented the vasodilator response to ischemia. Flavanol-poor cocoa induced much smaller responses (P = 0.005), and none was induced in the time-control study. Flavanol-rich cocoa also amplified the systemic pressor effects of L-NAME (P = 0.005). CONCLUSION: In healthy humans, flavanol-rich cocoa induced vasodilation via activation of the nitric oxide system, providing a plausible mechanism for the protection that flavanol-rich foods induce against coronary events.     

Mediators in HIV-associated cardiovascular disease: a focus on cytokines and genes

As longevity increases in HIV-infected individuals, late effects such as cardiovascular disease and, more specifically, symptomatic heart failure are emerging as leading health issues. In the present review, we discuss possible cytokine and gene-mediated effects on HIV-associated cardiovascular illness that may play a role in diagnosis, management, and therapy of HIV-associated heart failure.     

Mouse models as a tool for understanding neurodegenerative diseases

PURPOSE OF REVIEW: The purpose of this review is to present recent advances in the both the creation and the use of mouse models of human neurodegenerative disease. We briefly touch on the technologies used to make these models, and then focus on recent results from new models. We discuss why such models are useful when they do - and do not - mimic the human disorder. RECENT FINDINGS: The numbers of mouse models are increasing dramatically and are starting to yield important results for human disease. We present a selection of new and important models and the results of recent investigations of these animals. SUMMARY: An accepted protocol when studying any form of human neurodegenerative disease is to investigate the genetics, pathology, neurophysiology, response to therapeutics, etc., of the disorder in the mouse. This approach is clearly bearing fruit for our understanding and treatment of human neurodegeneration.     

Muscarinic receptor subtype determines vulnerability to amyloid beta toxicity in transfected cos-7 cells

Research has suggested that there are age-related increases in neuronal sensitivity to insult from oxidative stress (OS) and that the CNS alterations seen in Alzheimer disease (AD) and vascular dementia (VaD) are superimposed upon declining nervous and vascular systems. Since muscarinic receptors (mAChR) may be important in regional sensitivity, regulation of micro- circulation, and in various aspects of both neuronal (AbetaPP processing) and vascular functioning, we postulated that the various mAChR subtypes may show differential sensitivity to OS. Indeed, recent findings indicated that M1, M2, or M4 AChR-transfected COS-7 cells showed greater OS sensitivity [as reflected in Ca2+ buffering (i.e., the ability to extrude or sequester Ca2+ following oxotremorine-induced depolarization)] than those transfected with M3 or M5 AChR when exposed to dopamine. Interestingly, the results from the present study indicate that similar findings were also observed when the cells were exposed to Abeta 25-35 and Abeta 1-40 showed similar effects on M1 and M3 AChR. No effects were seen with Abeta 35-25 or Abeta 40-1. Thus, cells transfected with M1, M2 or M4 AChR showed greater disruptions in calcium regulation (as assessed via fluorescent imaging analysis prior to and following 750 microm oxotremorine) than those transfected with M3 or M5 AChR. We also examined the effects of calcium channel antagonists (e.g., Nifedipine) or antioxidants (vitamin E) in protecting against the deleterious effects of Abeta. Results are discussed in terms of differences in MAChR structure that could lead to selective Abeta effects and the possible implications on memory and AbetaPP processing.     

Utility of the trail making test in the assessment of malingering in a sample of mild traumatic brain injury litigants

The Trail Making Test (TMT) is one of the most commonly administered tests in neuropsychological assessments. It has been shown to be a valid indicator of brain damage due to traumatic brain injury (TBI), as well as a number of other neuropathological conditions. TMT error and ratio scores have been suggested as possible markers of malingering. The present study examined the utility of various TMT scores as malingering measures in 94 TBI litigants. Litigants were divided into those suspected of (n = 27) and those not suspected of malingering (n = 67) based on scores obtained on the Test of Memory Malingering and/or the Rey 15-Item Test. TMT errors did not discriminate between suspected and nonsuspected malingerers; however, the overall level of performance on the TMT was suppressed in suspected malingerers. The TMT ratio score was significantly lower in litigants suspected of malingering, although the clinical utility of this ratio is minimal. Results of the present study suggest using caution when interpreting TMT scores as markers of malingering in TBI litigants.     

Increasing physical activity in people with type 2 diabetes

OBJECTIVE: To evaluate effect of exercise consultation on physical activity and resultant physiological and biochemical variables at 6 months in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 70 inactive people with type 2 diabetes were given standard exercise information and were randomized to receive an exercise consultation (n = 35) or not (n = 35). Exercise consultation, based on the transtheoretical model, combines motivational theory and cognitive behavioral strategies into an individualized intervention to promote physical activity. Changes from baseline to 6 months were assessed in 1) physical activity (7-day recall, accelerometer, cardiorespiratory fitness, stage, and processes of change), 2) physiological variables (blood pressure and BMI), and 3) biochemical variables (HbA(1c), lipid profile, and fibrinogen). RESULTS: Between-group differences were recorded for the change in minutes of moderate activity (P < 0.001) and activity counts (P < 0.001) per week. Experimental participants recorded an increase in activity counts per week and minutes of moderate activity per week (P < 0.001). The control group recorded no significant changes. More experimental participants increased stage of change (chi(2) = 22.6, P < 0.001). Between-group differences were recorded for the change in total exercise duration and peak gradient (P < 0.005), HbA(1c) (P = 0.02), systolic BP (P = 0.02), and fibrinogen (P = 0.03). CONCLUSIONS: Exercise consultation increased physical activity and improved glycemic control and cardiovascular risk factors in people with type 2 diabetes.