Smoking load reduction is insufficient to downregulate miR-301b, a lung cancer promoter.

Several circulating miRNAs identified in the plasma of smokers have been implicated as promoters of nasopharyngeal and lung carcinoma. To investigate the plasma profile of miRNAs in subjects who reduces the number of smoked cigarettes and who quit after six months. We accompanied 28 individuals enrolled in a Smoking Cessation Program over 6 months. At Baseline, clinical characteristics, co-morbidities, and smoking history were similar among subjects. After 6 months, two groups were defined: who successfully quitted smoking (named "quitters", n = 18, mean age 57 years, 11 male) and who reduced the number of cigarettes smoked (20-90%) but failed to quit smoking (named "smokers", n = 10, mean age 52 years, 3 male). No significant clinical changes were observed between groups at baseline and after a 6-month period, however, quitters showed significant downregulations in seven miRNAs at baseline: miR-17 (- 2.90-fold, p = 0.029), miR-20a (- 3.80-fold, p = 0.021); miR-20b (- 4.71-fold, p = 0.027); miR-30a (- 3.95-fold, p = 0.024); miR-93 (- 3.63-fold, p = 0.022); miR-125a (- 1.70-fold, p = 0.038); and miR-195 (- 5.37-fold, p = 0.002), and after a 6-month period in 6 miRNAs: miR-17 (- 5.30-fold, p = 0.012), miR-20a (- 2.04-fold, p = 0.017), miR-20b (- 5.44-fold, p = 0.017), miR-93 (- 4.00-fold, p = 0.041), miR-101 (- 4.82-fold, p = 0.047) and miR-125b (- 3.65-fold, p = 0.025). Using time comparisons, only quitters had significant downregulation in miR-301b (- 2.29-fold, p = 0.038) after 6-month. Reductions in the number of smoked cigarettes was insufficient to change the plasma profile of miRNA after 6 months. Only quitting smoking (100% reduction) significantly downregulated miR-301b related to hypoxic conditions, promotion of cell proliferation, decreases in apoptosis, cancer development, and progression as increases in radiotherapy and chemotherapy resistance.

Effects of gastric bypass surgery in patients with hypertension: rationale and design for a randomised controlled trial (GATEWAY study).

INTRODUCTION: Obesity and overweight are becoming progressively more prevalent worldwide and are independently associated with a significant increase in the risk of cardiovascular diseases. Systemic arterial hypertension is frequently found in association with obesity and contributes significantly to increased cardiovascular risk. We hypothesise that Roux-en-Y gastric bypass (RYGB) surgery, a procedure that effectively reduces body weight, can also positively impact blood pressure control in obese and hypertensive individuals. METHODS AND ANALYSIS: A unicentric, randomised, controlled, unblinded clinical trial. Sixty obese (body mass index between 30 and 39.9) and moderately well controlled hypertensive patients, in use of at least two antihypertensive medications at maximum doses or more than two in moderate doses, will be randomly allocated, using an online, electronic and concealed method, to receive either RYGB plus optimised clinical treatment (OCT) or OCT alone. The primary end point is the reduction of antihypertensive medication at 1 and 2 years of follow-up. Data analysis will primarily be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: The study was approved by the local institutional review board that works in total compliance with the latest version of the Helsinki Declaration, the Good Clinical Practices (GCP), the 'America's Document' and the national regulatory laws. Before the beginning of any study-related activities, each study participant is asked to provide a signed informed consent. TRIAL REGISTRATION NUMBER: NCT01784848.

Tabagismo e Hipertensão arterial: como o tabaco eleva a pressão / Smoking and High Blood Pressure: how the tobacco raises the pressure

A doença cardiovascular causa 29% das mortes por doenças tabaco-relacionadas. A relação entre o tabagismo e a hipertensão arterial provém de uma complexa interação entre fatores hemodinâmicos, sistema nervoso autonômico e múltiplos mediadores vasoativos (disfunção endotelial). De forma aguda, a nicotina gera ativação do sistema nervoso simpático e provoca aumento da frequência cardíaca, pressão arterial e contratilidade miocárdica com redução da oferta de oxigênio aos vasos e miocárdio. Os efeitos em longo prazo do tabagismo na pressão arterial são complexos e os achados contraditórios. Hipertensos fumantes possuem pior prognóstico cardiovascular mesmo quando tratados para hipertensão por um provável efeito farmacológico deletério aos compostos do cigarro. Esse pior prognóstico com essa associação torna fundamental reconhecer o tabagismo como doença, entender a abordagem aos fumantes e oferecer tratamento adequado para esta difícil dependência, notadamente negligenciada por clínicos e cardiologistas

The relationship between smoking and high blood pressure comes from a complex interaction between hemodynamic factors, autonomic nervous system and multiple vasoactive mediators (endothelial dysfunction). Acutely, nicotine generates activation of the sympathetic nervous system and causes increased heart rate, blood pressure and myocardial contractility with reduced oxygen supply to the vessels and myocardium. The long-term effects of smoking on pressure blood are complex and have contradictory findings. Hypertensive smokers have worse cardiovascular prognosis even when treated for hypertension by a possible pharmacological deleterious effect to the cigarette compounds. This worse prognosis is fundamental to recognize smoking as a disease, understand the approach to smokers and offer appropriate treatment for this difficult addiction, notably neglected by clinicians and cardiologists.

Ascorbic acid improves impaired venous and arterial endothelium-dependent dilation in smokers.

AIM: To compare the acute effects of ascorbic acid on vasodilation of veins and arteries in vivo. METHODS: Twenty-six healthy non-smokers and 23 healthy moderate smokers were recruited in this study. The dorsal hand vein compliance technique and flow-mediated dilation were used. Dose-response curves to bradykinin and sodium nitroprusside were constructed to test the endothelium-dependent and -independent relaxation before and after acute infusion of ascorbic acid. RESULTS: Smokers had an impaired venodilation with bradykinin compared with non-smokers (68.3%+/-13.2% vs 93.7%+/-20.1%, respectively; P<0.05). Ascorbic acid administration in the dorsal hand vein significantly increased the venodilation with bradykinin in smokers (68.3%+/-13.2% vs 89.5%+/-6.3% before and after infusion, respectively; P<0.05) but not in non-smokers (93.7%+/-20.1% vs 86.4%+/-12.4% before and after infusion, respectively). Similarly, the arterial response in smokers had an impaired endothelium-dependent dilation compared with that in non-smokers (8.8%+/-2.7% vs 15.2%+/-2.3%, respectively; P<0.05) and ascorbic acid restored this response in smokers (8.8%+/-2.7% vs 18.7%+/-6.5% before and after infusion, respectively; P<0.05), but no difference was seen in non-smokers (15.2%+/-2.3% vs 14.0%+/-4.4% before and after infusion, respectively). The endothelium-independent dilation did not differ in both the groups studied. No important hemodynamic change was detected using the Portapress device. CONCLUSION: Smokers had impaired endothelium-dependent vasodilation responsiveness in both arterial and venous systems. Ascorbic acid restores this responsiveness in smokers.