Insulin and angiotensin II signaling pathways cross-talk: implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease

Insulin (Ins) and angiotensin II (AII) play pivotal roles in the control of two vital and closely related systems: the metabolic and the circulatory, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases - diabetes mellitus (DM) and hypertension (AH). In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate Ins and AII actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls AII synthesis but also interferes with Ins signaling through the proper regulation of AII and the accumulation of bradykinin. At an early intracellular level, AII, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the Ins-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, AII may impose a late control on the Ins signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between DM and AH.Insulina (Ins) e Angiotensina II (AII) são fundamentais no controle de dois sistemas vitais e inter-relacionados: o metabólico e o cardiocirculatório, respectivamente. A disfunção de qualquer um desses hormônios pode levar ao desenvolvimento de duas doenças de alta prevalência, muitas vezes concomitantes e, talvez, com fisiopatologia integrada - diabetes mellitus (DM) e hipertensão arterial (HA). Vários estudos mostram que os sistemas de sinalização intracelular de Ins e AII estão conectados e influenciam um ao outro. Esta comunicação molecular ocorre em diferentes etapas da sinalização celular e é importante para vários fenômenos fisiológicos, desde o desenvolvimento de hipertrofia cardíaca e aquisição de energia pelo coração, até a ação de drogas anti-hipertensivas. No nível extracelular, a enzima de conversão de angiotensina regula a síntese de AII e o acúmulo de bradicinina, e ambos desempenham papel regulador sobre a sinalização de Ins. No nível intracelular, a interação dos sinais de Ins e AII ocorre em dois momentos distintos. Inicialmente, em etapas mais precoces da sinalização celular, a AII, atuando através da cascata JAK-2/IRS-1/PI3-quinase, JNK e ERK, provoca a fosforilação em serina e a conseqüente inibição de elementos-chave da via de sinalização da Ins. Finalmente, a AII induz a expressão da proteína regulatória SOCS-3, que impõe um controle mais tardio sobre o sinal de Ins. Esta revisão discute os avanços mais recentes neste campo e a importância dessa interação molecular na fisiopatologia e na associação clínica de DM e HA.19520

Physicians’ preference towards the non-evidence based hydroxychloroquine treatment for COVID-19: the pandemic effect

OBJECTIVE: To evaluate whether there is a "pandemic effect" promoting irrational medical reasoning. METHODS: Cross-sectional study. Setting state medical councils were asked to send all registered physicians two sequential email invitations to complete a Google Form questionnaire. Between April 15 and May 3, 2020, 370 doctors answered our questionnaire with questions about the prescription of hydroxychloroquine for COVID-19 and vitamin C for sepsis. The questionnaire had a five-point Likert scale (greater number, greater support) on the degree of propensity to prescribe the medication and a binary question (yes or no) to express the doctor's final decision to prescribe. These two questions, in the same order, were asked for scenarios of mild, moderate and severe cases. RESULTS: The propensity to prescribe hydroxychloroquine for COVID-19 increased with the severity of the clinical presentation: for mild cases, 37% (95% CI 32%-42%) of the physicians chose "yes", increasing to 68% (95% CI 63%-72%) and 89% (95% CI 85%-92%) for moderate or severe cases, respectively (Cochran's Q test: P<0.001). The medians and interquartile ranges of the Likert scales for hydroxychloroquine were 2 (1-4), 4 (2-4), 4 (4-5) in mild, moderate and severe cases of COVID-19 (Friedman test: P<0.001). CONCLUSIONS: The propensity of the Brazilian physician to prescribe hydroxychloroquine for COVID-19 is high and, according to the severity of the disease, ranged from 37 to 89%. On the contrary, the propensity to prescribe vitamin C for sepsis, a non-pandemic situation, was lower and not associated with clinical severity. Our data suggest a "pandemic effect" promoting irrationality in medical reasoning

Trends in left ventricular assist device use and outcomes among Medicare beneficiaries, 2004–2011

Objective: To characterise the trends in the left ventricular assist device (LVAD) implantation rates and outcomes between 2004 and 2011 in the Medicare population. Since the approval of the HeartMate II in 2008, the use of LVADs has steadily climbed. Given the increase in LVAD use, issues around discharge disposition, post-implant hospitalisations and costs require further understanding. Methods: We examined LVAD implantation rates and short-term and long-term outcomes among Medicare fee-for-service beneficiaries hospitalised for LVAD implantation. We also conducted analyses among survivors 1-year post-discharge to examine rehospitalisation rates. Lastly, we reported Centers for Medicare & Medicaid Services (CMS) payments for both index hospitalisation and rehospitalisations 1 year post-discharge. Results: A total of 2152 LVAD implantations were performed with numbers increasing from 107 in 2004 to 612 in 2011. The 30-day mortality rate decreased from 52% to 9%, and 1-year mortality rate decreased from 69% to 31%. We observed no change in overall length of stay, but post-procedure length of stay increased. We also found an increase in home discharge dispositions from 26% to 53%. Between 2004 and 2010, the rehospitalisation rate increased and the number of hospital days decreased. The adjusted CMS payment for the index hospitalisation increased from $188 789 to$225 697 over time but decreased for rehospitalisation from $60 647 to$53 630. Conclusions: LVAD implantations increased over time. We found decreasing 30-day and 1-year mortality rates and increasing home discharge disposition. The proportion of patients rehospitalised among 1-year survivors remained high with increasing index hospitalisation cost, but decreasing post-implantation costs over time