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This study analyzes the time course of the changes induced by subarachnoid hemorrhage (SAH) in the sensitivity of cat cerebral arteries to noradrenaline and serotonin. Cerebral arteries to noradrenaline and serotonin. Cerebral arteries displayed a supersensitivity to these amines, which was most marked 3 days after the experiment and then gradually disappeared. The supersensitivity to serotonin was greater and longer than the response to noradrenaline. The increase in the vascular contractile response induced by SAH was similar to that seen after superior cervical ganglionectomy or intracisternal injections of 6-hydroxydopamine. It is suggested that supersensitivity to noradrenaline and serotonin induced by SAH may be involved in the production of chronic cerebral vasospasm.

Introduction and PurposeLaparoscopic sleeve gastrectomy (LSG) in patients with a BMI between 30 and 35 kg/m2 plus comorbidities has shown to be safe and effective. The purpose of this study is to describe our outcomes in this group of patients after 3 years of follow-up.Materials and MethodsRetrospective descriptive analysis of patients with initial BMI between 30 and 35 kg/m2 plus comorbidities were submitted to LSG between 2006 and 2013. We analyzed gender, age, comorbidities, BMI, total weight loss (%TWL), excess weight loss (%EWL), comorbidity resolution, morbidity, and mortality. Postoperative success was defined as %TWL over 20% and EWL% over 50% maintained for at least 1 year and comorbidity remission with no need of medication.ResultsOf the patients, 477 underwent a LSG in the above period and 252 met inclusion criteria; 188 (75%) were female and 64 (25%) were male. Median age was 39 years (15–70). Three-year follow-up was 43.9% (111 patients). Median preoperative BMI was 32.3 kg/m2 (30–34.3). Median postoperative %TWL was 12.9, 23.2, 28.2, 24.3, and 22.1% at 1, 6, 12, 24, and 36 months, respectively. %EWL was 42.88, 77.44, 98.42, 83.2, and 75.8%. Median surgical time was 86.9 min (40–120). There was comorbidity remission at 36 months. Insulin resistance was remitted in 89.4%, dyslipidemia 52%, non-alcoholic fatty liver disease 84.6%, hypertension 75%, and GERD 65%. T2DM had 60% of complete remission and 40% improvement. There were morbidity in six patients (2.4%), two reoperations, no leaks, and no mortality.ConclusionsPerforming LSG in patients with grade I obesity is safe and effective. BMI should not be the only indicator to consider bariatric and metabolic surgery. We still require further studies and longer follow-up.

The effect of subarachnoid hemorrhage (SAH) on the adrenergic innervation of cat cerebral arteries was analyzed. Intracisternal injections of autologous blood reduced the noradrenaline content from the perivascular nerves. Dopamine beta-hydroxylase and the uptake of 3H-noradrenaline were also decreased. These changes returned to normal in a period of 2 to 3 weeks after the SAH. Superior cervical ganglionectomy and intracisternal injections of 6-hydroxydopamine also reduced these three parameters. It is suggested that SAH induces a transient adrenergic denervation of the cerebral arteries that might be involved in the production of the chronic cerebral vasospasm.

The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1β in the NLRP3 inflammasome via NF-κB could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo . Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1β, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro , which is paralleled by vascular dysfunction in vivo . Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo . Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1β positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effects.