Long-term tobacco exposure and immunosenescence: paradoxical effects on T-cells telomere length and telomerase activity

Immunosenescence are alterations on immune system that occurs throughout an individual life. The main characteristic of this process is replicative senescence, evaluated by telomere shortening. Several factors implicate on telomere shortening, such as smoking. In this study, we evaluated the influence of smoking and Chronic Obstructive Pulmonary Disease (COPD) on cytokines, telomere length and telomerase activity. Blood samples were collected from subjects aged over 60 years old: Healthy (never smokers), Smokers (smoking for over 30 years) and COPDs (ex-smokers for ≥15 years). A young group was included as control. PBMCs were cultured for assessment of telomerase activity using RT-PCR, and cytokines secretion flow cytometry. CD4+ and CD8+ purified lymphocytes were used to assess telomere length using FlowFISH. We observed that COPD patients have accelerated telomere shortening. Paradoxically, smokers without lung damage showed preserved telomere length, suggesting that tobacco smoking may affect regulatory mechanisms, such as telomerase. Telomerase activity showed diminished activity in COPDs, while Smokers showed increased activity compared to COPDs and Healthy groups. Extracellular environment reflected this unbalance, indicated by an anti-inflammatory profile in Smokers, while COPDs showed an inflammatory prone profile. Further studies focusing on telomeric maintenance may unveil mechanisms that are associated with cancer under long-term smoking

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus

Background: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction ( 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.This article publication was funded by Sociedade Brasileira de Diabetes (SBD)

Tendência dos acidentes de trânsito em Campinas, São Paulo, Brasil: importância crescente dos motociclistas Trends in traffic accidents in Campinas, São Paulo State, Brazil: the increasing involvement of motorcyclists

Com o objetivo de descrever a tendência de ocorrência de acidentes de trânsito, sua mortalidade, tipo de veículo envolvido, tamanho da frota e perfil das vítimas em Campinas, São Paulo, Brasil, entre 1995 e 2008, foram estimadas taxas de motorização e ocorrência de acidentes, letalidade, mortalidade proporcional, taxas de mortalidade e razões entre taxas. A frota de motocicletas cresceu 241%. Apesar da queda da letalidade dos acidentes de ocupantes de motos entre 2000 e 2008, esta categoria representou 49,3% do total de acidentes fatais em vias públicas em 2008. As motos foram responsáveis pelas maiores taxas de atropelamento (66,7 atropelados/mil acidentes) e de atropelamentos seguidos de morte (4 óbitos/mil acidentes). Os homens mantiveram risco de morrer no trânsito muito superior ao das mulheres. Nos atropelamentos, predominaram elevadas taxas de mortalidade em idosos; entre os ocupantes de veículos, os mais atingidos foram os de 15 a 29 anos. Na faixa de 15 a 39 anos, entre 2006 e 2008, quase 80% eram ocupantes de moto. Ações pluri-institucionais devem priorizar a prevenção de acidentes entre motociclistas.<br>In order to describe trends in traffic accidents, mortality, vehicle types, fleet sizes, and victims' characteristics in Campinas, São Paulo State, Brazil, from 1995 to 2008, this study analyzed vehicle rates, traffic accident rates per inhabitant and per vehicle, case-fatality rates, proportional mortality, mortality rates, and rates ratios. The motorcycle fleet increased 241%. Although the case-fatality rate of motorcycle users from 2000 to 2008 decreased, in 2008 they accounted for 49.3% of fatal accidents on public byways in Campinas. Motorcycles were responsible for the highest run-over rate (66.7 pedestrians/1,000 accidents) and highest pedestrian fatality rate (4 deaths/1,000 accidents). Men showed much higher mortality rates than women. Pedestrian victims were mainly elderly; most vehicle occupants in traffic accidents were in the 15 to 29-year age bracket. From 2006 to 2008, nearly 80% of vehicle users 15 to 39 years of age were motorcyclists. Motorcycle accident prevention should be a priority, using multi-institutional measures