1,721,089 research outputs found
Assisted reproductive technologies and stroke: Risk factor, predictor of poor outcome, or both?
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Comment on "Characterization of circulating leukocytes and correlation of leukocyte subsets with metabolic parameters 1 and 5 years after diabetes diagnosis"
No full textThe STOP DIABETES study: when prevention works
No full textAlthough many drugs are now available, a large effort is still needed to prevent diabetes. The STOP DIABETES study evaluated individuals at risk for type 2 diabetes (T2D) by a 2-h 75-g oral glucose tolerance test (OGTT). Based on the three main defective physiological responses, subjects were stratified as at low, intermediate, or high risk, and treated accordingly with lifestyle modifications and drugs. Participants at intermediate and high risk experienced the greatest reduction of T2D conversion. Interestingly, a group of individuals developing T2D presented a normal glucose tolerance at baseline, but a 1-h plasma glucose concentration > 155 mg/dL. These results are critical as prediabetes can increase the incidence of cardiovascular disease. Considering the timeframe between the first defects in glucose metabolism and the manifestation of diabetes complications, the effort to tackle the glycemic impairment as soon as possible represents an outstanding task to reduce the incidence of diabetes. Ideally, the earlier glycemic alterations are recognized, the lesser armamentarium needs to be used, and the lower is the expense in terms of drugs, complications, and related events and costs. Finally, a wealth of studies clearly demonstrated the importance of 1-h plasma glucose concentration, which has been proposed as an adjunctive diagnostic tool to detect prediabetes earlier. In conclusion, by an OGTT, a lot of individuals at risk for T2D may be detected when the central role for the 1-h plasma glucose concentration is also considered. Consequently, these subjects would be treated early and with less drugs and delay T2D complications
NLRP3 inflammasome as a key player in pericarditis: rationale for a targeted therapeutic strategy
No full textObjectives. To (i) determine the formation of the NLRP3 inflammasome in the pathogenesis of pericarditis and (ii) recreate pericardial inflammation in mice with a toll-like-receptor-2/inflammasome inducer and assess the effect of anti-inflammatory drugs on inflammasome-mediated disease.
Background. Acute pericarditis is typically responsive to colchicine, an anti-inflammatory drug blocking the NLRP3 inflammasome.
Methods. Pericardial biopsies from patients with chronic pericarditis were stained for the inflammasome components – NLRP3, caspase-1, and ASC. A murine model of pericarditis was developed through intrapericardial injection of zymosan A. Ibuprofen and different inflammasome pathway blockers (colchicine, NLRP3 inhibitor 16673-34-0 [NLRP3inh], anakinra, and IL-1 trap) were administered, and echocardiography and tissue pathology were performed.
Results. Patients with pericarditis showed increased inflammasome presence compared with controls (NLRP3: 1.9±0.15 vs. 1.21±0.1; Caspase-1: 2.5±0.2 vs 1.4±0.09; ASC: 2.4±0.2 vs. 1.1±0.3). The mouse model showed pericardial effusion (+83%), pericardial thickness (+45%), and an increased staining of inflammasome, IL-1alpha, and IL-1beta compared with sham. Treatment with ibuprofen reduced effusion compared to vehicle (-42%). Colchicine and NLRP3inh significantly reduced effusion (-28% and -46%) and inflammasome activation (-93% and -78%). NLRP3inh reduced pericardial thickness (-32%). Anakinra and IL-1 trap attenuated pericardial effusion (-13% and -43%), pericardial thickness (-20% and -44%), and inflammasome staining compared to vehicle (-75% and -96%).
Conclusions. The NLRP3 activity was assessed in human pericarditis samples. Our new experimental mouse model replicated the key elements of acute pericarditis phenotype and shows the therapeutic efficacy of IL-1 blockers. NLRP3 pathway inhibition of could represent a valid therapeutic approach for the treatment of pericarditis
Sofosbuvir/velpatasvir: A promising combination
No full textHepatitis C virus (HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents (DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural (NS)5B polymerase inhibitor, and velpatasvir, a NS5A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2 (against HCV genotype 2) and the ASTRAL-3 (against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease
Update on strategies limiting iatrogenic hypoglycemia
No full textThe prevalence of type 2 diabetes mellitus (T2DM) is increasing all over the world. Targeting good glycemic control is fundamental to avoid the complications of diabetes linked to hyperglycemia. This narrative review is based on material searched for and obtained via PubMed up to April 2015. The search terms we used were: 'hypoglycemia, diabetes, complications' in combination with 'iatrogenic, treatment, symptoms.' Serious complications might occur from an inappropriate treatment of hyperglycemia. The most frequent complication is iatrogenic hypoglycemia that is often associated with autonomic and neuroglycopenic symptoms. Furthermore, hypoglycemia causes acute cardiovascular effects, which may explain some of the typical symptoms: ischemia, QT prolongation, and arrhythmia. With regards to the latter, the night represents a dangerous period because of the major increase in arrhythmias and the prolonged period of hypoglycemia; indeed, sleep has been shown to blunt the sympatho-adrenal response to hypoglycemia. Two main strategies have been implemented to reduce these effects: monitoring blood glucose values and individualized HbA1c goals. Several drugs for the treatment of T2DM are currently available and different combinations have been recommended to achieve individualized glycemic targets, considering age, comorbidities, disease duration, and life expectancy. In conclusion, according to international guidelines, hypoglycemia-avoiding therapy must reach an individualized glycemic goal, which is the lowest HbA1c not causing severe hypoglycemia and preserving awareness of hypoglycemia
Comment on G. Veronese and colleagues. Costs associated with emergency care and hospitalization for severe hypoglycemia
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