The role of catechol-O-methyltransferase (COMT) and the effects of COMT inhibition in brain and in cardiovascular and renal pathophysiology

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine (DA), noradrenaline (NA) and adrenaline, which are vital neurotransmitters and hormones that play important roles in the regulation of physiological processes. COMT enzyme has a functional Val158Met polymorphism in humans, which affects the subjects COMT activity. Increasing evidence suggests that this functional polymorphism may play a role in the etiology of various diseases from schizophrenia to cancers. The aim of this project was to provide novel biochemical information on the physiological and especially pathophysiological roles of COMT enzyme as well as the effects of COMT inhibition in the brain and in the cardiovascular and renal system. To assess the roles of COMT and COMT inhibition in pathophysiology, we used four different study designs. The possible beneficial effects of COMT inhibition were studied in double-transgenic rats (dTGRs) harbouring human angiotensinogen and renin genes. Due to angiotensin II (Ang II) overexpression, these animals exhibit severe hypetension, cardiovascular and renal end-organ damage and mortality of approximately 25-40% at the age of 7-weeks. The dTGRs and their Sprague-Dawley controls tissue samples were assessed with light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and high-pressure liquid chromatography (HPLC) to evaluate the tissue damages and the possible protective effects pharmacological intervention with COMT inhibitors. In a second study, the consequence of genetic and pharmacological COMT blockade in blood pressure regulation during normal and high-sodium was elucidated using COMT-deficient mice. The blood pressure and the heart rate were measured using direct radiotelemetric blood pressure surveillance. In a third study, the effects of acute and subchronic COMT inhibition during combined levodopa (L-DOPA) + dopa decarboxylase inhibitor treatment in homocysteine formation was evaluated. Finally, we assessed the COMT enzyme expression, activity and cellular localization in the CNS during inflammation-induced neurodegeneration using Western blotting, HPLC and various enzymatic assays. The effects of pharmacological COMT inhibition on neurodegeneration were also studied. The COMT inhibitor entacapone protected against the Ang II-induced perivascular inflammation, renal damage and cardiovascular mortality in dTGRs. COMT inhibitors reduced the albuminuria by 85% and prevented the cardiovascular mortality completely. Entacapone treatment was shown to ameliorate oxidative stress and inflammation. Furthermore, we established that the genetic and pharmacological COMT enzyme blockade protects against the blood pressure-elevating effects of high sodium intake in mice. These effects were mediated via enhanced renal dopaminergic tone and suggest an important role of COMT enzyme, especially in salt-sensitive hypertension. Entacapone also ameliorated the L-DOPA-induced hyperhomocysteinemia in rats. This is important, since decreased homocysteine levels may decrease the risk of cardiovascular diseases in Parkinson´s disease (PD) patients using L-DOPA. The Lipopolysaccharide (LPS)-induced inflammation and subsequent delayed dopaminergic neurodegeneration were accompanied by up-regulation of COMT expression and activity in microglial cells as well as in perivascular cells. Interestingly, similar perivascular up-regulation of COMT expression in inflamed renal tissue was previously noted in dTGRs. These results suggest that inflammation reactions may up-regulate COMT expression. Furthermore, this increased glial and perivascular COMT activity in the central nervous system (CNS) may decrease the bioavailability of L-DOPA and be related to the motor fluctuation noted during L-DOPA therapy in PD patients.

Recolonização de uma área restaurada por morcegos da família Phyllostomidae: padrões de diversidade e uso do espaço

Pós-graduação em Ciências Biológicas (Zoologia) - IBRC

Impacto de interações antrópicas sobre o comportamento de peixes-boi marinhos (Trichechus manatus manatus) reintroduzidos no litoral norte de Alagoas

Atualmente o encalhe de filhotes órfãos representa uma das principais ameaças à conservação do peixe-boi marinho (Trichechus manatus manatus) no litoral nordeste do Brasil. O Projeto Peixe-boi resgata os filhotes encalhados, reabilita em cativeiro e reintroduz estes animais em áreas de ocorrência histórica e em locais onde a população está em declínio. Estudos sobre comportamento animal fornecem uma importante ferramenta para avaliação dos Programas de Reintrodução. Os trabalhos existentes sobre comportamento de peixes-boi marinhos em vida livre sujeitos a interações antrópicas restringem-se a animais nativos na Flórida. No Brasil, há estudos etológicos apenas com espécimes em cativeiro ou recinto em ambiente natural. O objetivo do trabalho foi verificar possíveis alterações comportamentais de peixes-boi reintroduzidos, ou seja, que passaram parte da vida em cativeiro e foram soltos em ambiente natural, em função de interações antrópicas. No período de Fevereiro a Julho de 2010, com o auxílio da radio-telemetria, uma fêmea e dois machos (8 anos de idade) foram observados diariamente, em períodos alternados, com a metodologia do “animal focal”. Para o monitoramento, utilizou-se bicicleta, caiaque e, em locais de difícil acesso, o mesmo foi feito a pé. Totalizou-se 114 horas de observação para Arani e 167 horas para Potiguar. As observações da fêmea Aira ficaram comprometidas em função da perda do equipamento de radio-telemetria. A análise dos dados mostrou uma alta freqüência de comportamentos de interação (mais de 50%) em relação aos demais comportamentos de função vital para os dois machos. Dessas interações, as com animais de mesma espécie e objeto atingiram elevadas freqüências. Verificou-se ainda que a categoria afiliativa foi predominante nas interações entre peixes-bois... (Resumo completo, clicar acesso eletrônico abaixo)

Padrões de movimentação de sabiás (Turdus ssp. Turdidae) em paisagens fragmentadas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento de um sistema de aquisição de dados georreferenciados e de telemetria para monitoramento de parâmetros físicos em sistemas de irrigação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de um sistema de telemetria para monitoramento térmico em casas de vegetação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Airwaves: 100 years of radio

Music composition using prominent broadcast speeches across the whole twentieth century in commemoration of the centenary of Marconi's first transatlantic radio transmission. The work is based on creating music from the found objects of melody derived from spoken intonation. Recordings of the speeches are accompanied throughout by live instrumental music.

Radio and affective rhythm in the everyday

This article explores the role of radio sound in establishing what I term ‘affective rhythms’ in everyday life. Through exploring the affective qualities of radio sound and its capacity for mood generation in the home, this article explores personal affective states and personal organisation. The term affective rhythm relates both to mood, and to routine. It is the combination of both that allows the possibility of thinking about sound and affect, and how they relate to, and integrate with, routine everyday life. The notion of ‘affective rhythm’ forces us to consider the idea of mood in the light of the routine nature of everyday domestic life.

Further results with localization and mapping using range from radio

In this paper, we present recent results with using range from radio for mobile robot localization. In previous work we have shown how range readings from radio tags placed in the environment can be used to localize a robot. We have extended previous work to consider robustness. Specifically, we are interested in the case where range readings are very noisy and available intermittently. Also, we consider the case where the location of the radio tags is not known at all ahead of time and must be solved for simultaneously along with the position of the moving robot. We present results from a mobile robot that is equipped with GPS for ground truth, operating over several km.

The National Aboriginal and Torres Strait Islander Women's Health Strategy on Talkin with Tiga Bayles, 98.9 AM National Indigenous Radio Service (NIRS), Wednesday 21 July 2010. (9.00 - 10.00am).

Radio Program. Talkin with Tiga Bayles, 98.9 AM National Indigenous Radio Service (NIRS), 9.00-10.00am, Wednesday 21 July 2010. (1 hour program).----- Bronwyn Fredericks discssed the National Aboriginal and Torres Strait Islander Women’s Health Strategy was launched at the Australian Women’s Health Network (AWHN) National Conference in Hobart on the 19 May 2010. Within this radio interview the background of the Strategy is discussed, funding, who did the consultations and the writing. In the interview Bronwyn Fredericks outlines the process of the Strategy’s development and its uses for the future.----- It is important to note that this Strategy does not replace other national or State and Territory documents which identify priorities and needs. The aim is to supplement existing work.

Adaptive GPS duty cycling and radio ranging for energy-efficient localization

This paper addresses the tradeoff between energy consumption and localization performance in a mobile sensor network application. The focus is on augmenting GPS location with more energy-efficient location sensors to bound position estimate uncertainty in order to prolong node lifetime. We use empirical GPS and radio contact data from a largescale animal tracking deployment to model node mobility, GPS and radio performance. These models are used to explore duty cycling strategies for maintaining position uncertainty within specified bounds. We then explore the benefits of using short-range radio contact logging alongside GPS as an energy-inexpensive means of lowering uncertainty while the GPS is off, and we propose a versatile contact logging strategy that relies on RSSI ranging and GPS lock back-offs for reducing the node energy consumption relative to GPS duty cycling. Results show that our strategy can cut the node energy consumption by half while meeting application specific positioning criteria.