Neural Biomarkers for Assessing Different Types of Imagery in Pictorial Health Warning Labels for Cigarette Packaging: A Cross-Sectional Study

Objective Countries around the world have increasingly adopted pictorial health warning labels (HWLs) for tobacco packages to warn consumers about smoking-related risks. Research on how pictorial HWLs work has primarily analysed self-reported responses to HWLs; studies at the neural level comparing the brain\u27s response to different types of HWLs may provide an important complement to prior studies, especially if self-reported responses are systematically biased. In this study we characterise the brain\u27s response to three types of pictorial HWLs for which prior self-report studies indicated different levels of efficacy. Methods Current smokers rated pictorial HWLs and then observed the same HWLs during functional MRI (fMRI) scanning. Fifty 18–50-year-old current adult smokers who were free from neurological disorders were recruited from the general population and participated in the study. Demographics, smoking-related behaviours and self-reported ratings of pictorial HWL stimuli were obtained prior to scanning. Brain responses to HWLs were assessed using fMRI, focusing on a priori regions of interest. Results Pictorial HWL stimuli elicited activation in a broad network of brain areas associated with visual processing and emotion. Participants who rated the stimuli as more emotionally arousing also showed greater neural responses at these sites. Conclusions Self-reported ratings of pictorial HWLs are correlated with neural responses in brain areas associated with visual and emotional processing. Study results cross-validate self-reported ratings of pictorial HWLs and provide insights into how pictorial HWLs are processed

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial

<p>Abstract</p> <p>Background</p> <p>Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release.</p> <p>Methods</p> <p>We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period.</p> <p>Results</p> <p>Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications.</p> <p>Conclusion</p> <p>We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism.</p> <p>Trial Registration</p> <p>This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01331486">NCT01331486</a>.</p

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors

The phosphodiesterase type 5 (PDE-5) inhibitors are effective in treating erectile dysfunction (ED). ED and heart failure (HF) share similar risk factors, and commonly present together. This association has led to questions ranging from the safety and efficacy of PDE-5 inhibitors in HF patients to a possible role for this class of medication to treat HF patients with or without ED. In addition to endothelial dysfunction, there are causes of ED specific to patients with HF including low exercise tolerance, depression and HF medications. Before treating HF patients with PDE-5 inhibitors, patients should be assessed for their risk of a cardiac event during sexual activity. PDE-5 inhibitors are safe and effective in treating ED in HF patients. An improvement in erectile function by PDE-5 inhibitors was associated with an improvement in quality of life and reduction in depression. Several studies demonstrated the effect of PDE-5 inhibitors on HF per se. PDE-5 inhibitors improved endothelial dysfunction, increased exercise tolerance, decreased pulmonary vascular resistance and pulmonary artery pressure, and increased cardiac index. Several mechanisms whereby PDE-5 inhibitors improve HF have been proposed. PDE-5 inhibitors already have a role in treating primary pulmonary hypertension; however additional studies are needed to determine if they will become a standard therapy for HF patients

Endurance Training Alters Skeletal Muscle MCT Contents in T2DM Men

Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower K-m) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skeletal muscle MCT contents in T2DM men (n=8, years=56 +/- 9, body mass index (BMI)=32 +/- 4kg/m(2)). Protein content analyses (immunohistochemical stainings) were performed in biopsies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease -41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research