Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

It has now been demonstrated that the μ, δ(1), δ(2), and κ(1) opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias

Female Chimpanzees Use Copulation Calls Flexibly to Prevent Social Competition

The adaptive function of copulation calls in female primates has been debated for years. One influential idea is that copulation calls are a sexually selected trait, which enables females to advertise their receptive state to males. Male-male competition ensues and females benefit by getting better mating partners and higher quality offspring. We analysed the copulation calling behaviour of wild female chimpanzees (Pan troglodytes schweinfurthii) at Budongo Forest, Uganda, but found no support for the male-male competition hypothesis. Hormone analysis showed that the calling behaviour of copulating females was unrelated to their fertile period and likelihood of conception. Instead, females called significantly more while with high-ranking males, but suppressed their calls if high-ranking females were nearby. Copulation calling may therefore be one potential strategy employed by female chimpanzees to advertise receptivity to high-ranked males, confuse paternity and secure future support from these socially important individuals. Competition between females can be dangerously high in wild chimpanzees, and our results indicate that females use their copulation calls strategically to minimise the risks associated with such competition

Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells

Apoptosis in HIV-1-infected CD4+ primary T cells is triggered by the alteration of the PI3K and p53 pathways, which converge on the FOXO3a transcriptional activator. Tat alone can cause activation of FOXO3a and of its proapoptotic target genes. To understand how Tat affects this pathway, we carried out ChIP-Chip experiments with Tat. Tat associates with the promoters of PTEN and two PP2A subunit genes, but not with the FOXO3a promoter. PTEN and PP2A encode phosphatases, whose levels and activity are increased when Tat is expressed. They counteract phosphorylation of Akt1 and FOXO3a, and so activate transcriptional activity of FOXO3a. FOXO3a promotes increased transcription of Egr-1, which can further stimulate the transcription of PTEN, thereby reinforcing the pathway that leads to FOXO3a transcriptional activation. RNAi experiments support the role of PTEN and PP2A in the initiation of the Tat-mediated cascade, which is critical to apoptosis. The increased accumulation of PTEN and PP2A subunit mRNAs during Tat expression is more likely to be the result of increased transcription initiation and not relief of promoter-proximal pausing of RNAPII. The Tat-PTEN and -PP2A promoter interactions provide a mechanistic explanation of Tat-mediated apoptosis in CD4+ T cells

First M87 Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole

When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 ± 3 μas, which is circular and encompasses a central depression in brightness with a flux ratio 10:1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 ± 0.7) × 109 Me. Our radiowave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible

First M87 Event Horizon Telescope Results. II. Array and Instrumentation

The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ~1.3 mm, EHT angular resolution (λ/D) is ~25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s−1, exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87

Lesão iatrogênica de via biliar pós-colecistectomia

OBJETIVO: Descrever os aspectos epidemiológicos, clínicos e cirúrgicos dos pacientes com lesão iatrogênica das vias biliares (LIVB) atendidos no Hospital Geral de Fortaleza (HGF) durante o período de 2005 a 2009. MÉTODOS: Realizou-se estudo retrospectivo dos prontuários dos pacientes internados no HGF diagnóstico de LIVB, obtendo-se as seguintes variáveis: sexo, idade, procedência, condições da colecistectomia, tipo de operação, sintomatologia, exames realizados, achados cirúrgicos, classificação da lesão, tratamento, complicações, tempo total de internamento e condições de alta. RESULTADOS: Foram confirmados 27 casos de LIVB. Duas lesões ocorreram durante a colecistectomia videolaparoscópica. Apenas um paciente foi diagnosticado no intra-operatório.. O sinal mais freqüente foi a icterícia pós-colecistectomia. A hepático-jejunostomia em "Y" de Roux foi a técnica cirúrgica mais empregada (85,2%). A maioria dos pacientes recebeu alta hospitalar em boas condições clínicas (88,8%); no entanto, constatou-se, a elevada morbidade desta patologia, exemplificada pelos múltiplos internamentos e longa permanência hospitalar (média de 31 dias). CONCLUSÃO: A maioria das lesões ocorreu durante a colecistectomia por laparotomia, a icterícia foi o sinal mais freqüente quando da internação Verificou-se uma elevada permanência hospitalar .causada pelas complicações pós-operatórias o que poderia ser explicado pelo diagnóstico tardio ocasionando um grande retardo no tratamento neste pacientes

Paradoxical sleep deprivation increases plasma endothelin levels

The endothelins (ET-1, 2 and 3) constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA). OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group), were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-1/2 was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-1/2 release (6.58 fmol/ml) compared to control (5.07 fmol/ml). These data show that sleep deprivation altered plasma ET-1/2 concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation

Complicações da cirurgia videolaparoscópica no tratamento de doenças da vesícula e vias biliares Videolaparoscopy complications in the management of biliary diseases

RACIONAL: O tratamento de escolha para as doenças da vesícula biliar é a colecistectomia, cujo objetivo é o alívio de sintomas e o tratamento e/ou prevenção das complicações. OBJETIVO: Identificar as principais complicações da cirurgia videolaparoscópica no tratamento das doenças da vesícula biliar e vias biliares. MÉTODO: Realizou-se busca eletrônica na base de dados LILACS e Medline desde o ano de 1981 a agosto de 2007; foram encontrados 57 artigos, sendo utilizados para o estudo 31 e três capítulos de livros. RESULTADOS: A produção científica submetida à análise de conteúdo evidenciou os seguintes núcleos temáticos: variações anatômicas (3 artigos), iatrogenias (5 artigos), síndrome pós-colecistectomia (1 artigo), complicações raras (3 artigos), síndrome de Mirizzi (1 artigo), complicações pulmonares (2 artigos) e tratamento (1 capítulo de livro e três artigos). CONCLUSÕES: As complicações que podem ocorrer na cirurgia videolaparoscópica da vesícula biliar e das vias biliares têm basicamente duas vertentes: uma é a inexperiência dos cirurgiões com o método laparoscópico (curva de aprendizado) e outra, as variações anatômicas com as quais os cirurgiões, mesmo os mais experientes, podem se deparar.<br>BACKGROUND: The treatment of choice for diseases affecting the gallbladder is the cholecystectomy, whose aim is improvement of symptoms, treatment and/or prevention of complications. AIM: Identify the main complications with laparoscopic surgery used to treat diseases affecting the gallbladder and the bile ducts. METHODS: An internet search in the LILACS and Medline database covering the period from 1981 up to August 2007 was carried out and 57 studies were found relevant. The present work draws on 31 of these studies and one textbook chapter. RESULTS: The analysis of the content of the studies selected yielded the following thematic issues: anatomic variations (3 studies), iatrogenies (5 studies), post-cholecystectomy syndrome (1 study), rare complications (3 studies), Mirizzi's syndrome (1 study), pulmonary complications (5 studies) and treatment (1 chapter of a medicine textbook and 3 studies). CONCLUSIONS: The complications arising from the videolaparoscopic surgery of the gallbladder and bile ducts are fundamentally due to two factors: the surgeon's lack of training in the laparoscopic technique (learning curve), and the unexpected anatomic variations, which even experienced surgeons may face