Resveratrol and cognitive decline : a clinician perspective

Resveratrol (3,5,4'-trihydroxystilbene) belongs to a family of polyphenolic compounds known as stilbenes, particularly concentrated in grape and red wine. The aim of our review was to critically review the available evidence of resveratrol effects on brain function and its potential impact on therapy. In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes. Resveratrol also inhibits pro-inflammatory enzyme expression, reduces nuclear factor-\u3baB activation and cytokine release. Treatment with resveratrol can affect multiple signaling pathway effectors involved in cell survival, programmed cell death and synaptic plasticity. Direct and/or indirect activation of the deacetylase sirtuins by resveratrol has also been suggested. In humans, clinical evidence derived from randomized clinical trials suggests that resveratrol is able to improve cerebral blood flow, cerebral vasodilator responsiveness to hypercapnia, some cognitive tests, perceived performances, and the A\u3b240 plasma and cerebrospinal fluid level

Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management

Omega-3 polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with omega-6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasocostrincting rather than vasodilating and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme (ACE) activity, angiotensin II formation, TGF-beta expression, enhance eNO generation and activate the parasympathetic nervous system. The final result is improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving dyslipidemic patients, diabetics and elderly subjects, as well as normotensive and hypertensive subjects confirm this working hypothesis. Future research will clarify if PUFA supplementation could improve the antihypertensive action of specific blood pressure lowering drug classes and of statins

Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Lo studio ACCORD: contestualizzazione ed intepretazione clinica.

Analisi critica dello Studio ACCOR

Antidiabetic properties of berberine: from cellular pharmacology to clinical effects.

Berberine is an alkaloid highly concentrated in the roots, rhizomes and stem bark of various plants. It affects glucose metabolism increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon like peptide-1 (GLP-1) levels. Upon GLP-1 receptors activation, adenylyl cyclase is activated and cyclic adenosine monophosphate (cAMP) generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarisation, and calcium influx through the voltage dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose consuming tissues, such as adipose, liver or muscle cells, berberine affects both GLUT-4 and retinol binding protein-4 (RBP-4) in favour of glucose uptake into cells, stimulates glycolysis by AMPK activation and has effects on the peroxisome proliferator-activated receptor \uf067 (PPAR\uf067) molecular targets and on the phosphorylation of insulin receptor substrate 1 (IRS-1), finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing with the use of high dosages

Dislipidemia e coronaropatia.

Epidemiologia della malattia coronarica e possibilit\ue0 di intervento terapeutico

New Management Strategies for the Hypertensive Patient \u2013 from the Disease to the Patient:

It is well known that hypertension is a strong independent risk factor for coronary and cerebrovascular diseases, as well as for heart failure, atrial fibrillation and chronic renal failure, in both industrialised and developing countries,1 thus substantially contributing to the global burden of disease. Moreover, it is well known that reducing blood pressure (BP) in hypertensive patients is associated with a significant reduction in the rate of cardiovascular complications and decline in renal function.2,3 The association between blood pressure and cardiovascular risk is continuous, without apparent lower threshold, up to the value of 70mmHg, which epidemiologically supports the assumption that the lower the blood pressure, the better the cardiovascular prognosis.2 Today, a remarkable number of antihypertensive drug classes with robust scientific evidence of long-term efficacy and safety are available on the market. The therapeutic arsenal includes many different compounds, such as diuretics, beta-adrenergic receptor blockers, alpha-adrenergic receptor blockers, angiotensinogen-converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists.2,4 Other dru

Nutraceuticals for blood pressure control

Significant effects on blood pressure (BP) have been reported from large nutritional interventions, particularly the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet. In more recent years, numerous studies have investigated the possible BP-lowering effect of different nutraceuticals; these range from specific foods to minerals, lipids, whole proteins, peptides, amino acids, probiotics, and vitamins. While a very large body of evidence supports the use of potassium, L-arginine, vitamins C and D, cocoa flavonoids, beetroot juice, some probiotics, coenzyme Q10, controlled-release melatonin, aged garlic extract, and coffee, the use of other nutraceuticals, such as green tea, flaxseed, and resveratrol, has not as yet been supported by adequate evidence. In some cases, e.g. proteins/peptides, the responsible component needs also to be fully uncovered. Finally, while for most of the products only short-term studies are available, with no specific end-points, an ongoing very large prospective study on chocolate flavanols will answer the question whether this may reduce cardiovascular risk. Thus, in addition to data on long-term safety, further clinical research is advisable in order to identify, among active nutraceuticals, those with the best cost-effectiveness and risk-benefit ratio for a wide use in the general population with a raised cardiovascular risk consequent to uncomplicated hypertension