Effects of acid-base imbalance on vascular reactivity

Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo) and those occurring within the intracellular space (pHi), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI2/cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.FAPESPFAEP

Morfologia da deposição de trombos murais: trajeto da luz residual em aneurismas de aorta abdominal infra-renal

PURPOSE: To assess the most frequent deposition site of mural thrombi in infrarenal abdominal aorta aneurisms, as well as the route of the residual lumen. METHODS: Assessment of CT scan images from 100 patients presenting asymptomatic abdominal aorta aneurism, and followed at HC-FMRP-USP. RESULTS: In 53% of the cases the mural thrombus was deposited on the anterior wall; from these, in 22%, the residual lumen described a predominantly right sided route; in 22%, a left sided route; on the mid line in 5%; and crossing over the mid line in 1%. In 23%, the deposition of thrombi was concentric. In 11% it occured on the posterior wall; from these, in 5%, the route of the residual anterior lumen was predominantly right sided; in 5%, left sided; and crossed over the mid line in 1%. In 13% complex morfological deposition patterns were found. CONCLUSION: Mural thrombi formation was predominantly found on the anterior wall of the aneurismatic mass, with the route of the residual lumen projecting towards the posterior wall.OBJETIVOS: Avaliar o local mais freqüente de deposição do trombo mural em aneurismas de aorta abdominal infrarenal, bem como o trajeto da luz residual. MÉTODOS: Avaliação de tomografias de 100 pacientes do HC-FMRP-USP apresentando aneurisma de aorta abdominal assintomático. RESULTADOS: O trombo mural se deposita na parede anterior em 53% dos casos, sendo que a luz residual posterior descreveu um trajeto predominantemente à direita em 22% dos casos, à esquerda em 22%, na linha mediana em 5% e cruzando da direita para a esquerda em 4%. 23% dos casos apresentaram deposição concêntrica do trombo e 11% apresentaram deposição na parede posterior, sendo o trajeto da luz residual anterior predominante a direita em 5% dos casos, a esquerda em 5% e cruzando a linha mediana em 1%. Padrões morfológicos complexos de deposição do trombo foram encontrados em 13% dos casos. CONCLUSÃO: A formação do trombo mural predominou na parede anterior da massa aneurismática, com o trajeto da luz residual se projetando para a parede posterior.FAEP

Expressão da apoptose em enxertos de veias safenas humana para restauração do fluxo sanguíneo coronariano por derivação

OBJECTIVE: To investigate the possible role of apoptosis on brief distensions of human saphenous veins at different pressures. METHODS: Fresh isolated grafts of human saphenous vein were assigned as control or distended (D) for fifteen seconds at 100, 200 and 300 mmHg. The degree of apoptotic caspases 3, 8, 9 and anti-apoptotic protein Bcl-2 expression were assessed by immunohistochemistry. RESULTS: Fresh isolated segments of distended human saphenous veins presented similar apoptotic protein expression when compared with control veins. However, the Bcl-2 expression was significantly higher in the 300 mmHg distended segments compared with the control vein. CONCLUSION: These findings show that intact segments of human saphenous veins submitted to distensions at different pressures have similar apoptotic proteins expression when compared with non-distended control veins. Therefore, brief distensions commonly performed during surgical harvesting do not trigger apoptosis, and probably are not involved on the physiopathological mechanisms that lead to graft failureOBJETIVO: Investigar o possível papel da apoptose em distensões breves de veias safenas humanas em diferentes pressões. MÉTODOS: Segmentos frescos isolados de veia safena humana foram distribuídos em 4 grupos: controle ou distendidos (D) por quinze segundos a 100, 200 e 300 mmHg. O grau de apoptose das caspases 3, 8, 9 e expressão da proteína anti-apoptótica Bcl-2 foram avaliados por imuno-histoquímica. RESULTADOS: Segmentos frescos distendidos isolados de veias safenas humanas apresentaram expressão protéica para apoptose similar às veias controle. No entanto, a expressão de Bcl-2 foi significativamente maior nos segmentos distendidos a 300 mmHg, quando comparados à veia controle. CONCLUSÃO: Estes achados demonstram que segmentos intactos de veias safenas humanas submetidos a distensões em diferentes pressões têm expressão de proteínas apoptóticas similares quando comparados com veias controle nãodistendidas. Por conseguinte, breves distensões comumente realizadas durante a coleta cirúrgica não ativam o processo de apoptose e, provavelmente, não estão envolvidas em mecanismos fisiopatológicos que levam à falência do enxertoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)(FAEPA) Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP) - Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínica

The role of Tyr(605) and Ala(607) of thimet oligopeptidase and Tyr(606) and Gly(608) of neurolysin in substrate hydrolysis and inhibitor binding

The physicochemical properties of TOP (thimet oligopeptidase) and NEL (neurolysin) and their hydrolytic activities towards the FRET (fluorescence resonance energy transfer) peptide series AbzGFSXFRQ-EDDnp [where Abz is o-aminobenzoyl; X = Ala, Ile, Leu, Phe, Tyr, Trp, Ser, Gln, Glu, His, Arg or Pro; and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine] were compared with those of site-mutated analogues. Mutations at Tyr(605) and Ala(607) in TOP and at Tyr(606) and Gly(608) in NEL did not affect the overall folding of the two peptidases, as indicated by their thermal stability, CD analysis and the pH-dependence of the intrinsic fluorescence of the protein. the kinetic parameters for the hydrolysis of substrates with systematic variations at position P-1 showed that Tyr(605) and Tyr(606) of TOP and NEL respectively, played a role in subsite S-1. Ala(607) of TOP and Gly(608) of NEL contributed to the flexibility of the loops formed by residues 600-612 (GHLAGGYDGQYYG; one-letter amino acid codes used) in NEL and 599-611 (GHLAGGYDAQYYG; one-letter amino acid codes used) in TOP contributing to the distinct substrate specificities, particularly with an isoleucine residue at P-1. TOP Y605A was inhibited less efficiently by JA-2 {N-[1-(R,S)-carboxy-3-phenylpropyl]Ala-Aib-Tyr-p-aminobenzoate}, which suggested that the aromatic ring of Ty,105 was an important anchor for its interaction with wild-type TOP. the hydroxy groups of Tyr 605 and Tyr.. did not contribute to the pH-activity profiles, since the pKs obtained in the assays of mutants TOP Y605F and NEL Y606F were similar to those of wild-type peptidases. However, the pH-k(cat)/K-m dependence curve of TOP Y605A differed from that of wild-type TOP and from TOP Y606F. These results provide insights into the residues involved in the substrate specificities of TOP and NEL and how they select cytosolic peptides for hydrolysis.Universidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilInst Butantan, Lab Especial Toxinol Aplicada, CAT, CEPID, BR-05467010 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Programa Biol Celular, BR-05508900 São Paulo, BrazilUniv São Paulo, Lab Neurociencias, BR-03071000 São Paulo, BrazilUniv Mogi das Cruzes, CIIB, BR-08780911 Mogi Das Cruzes, SP, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Scienc

Trend following, risk parity and momentum in commodity futures

We show that combining momentum and trend following strategies for individual commodity futures can lead to portfolios which offer attractive risk adjusted returns which are superior to simple momentum strategies; when we expose these returns to a wide array of sources of systematic risk we find that robust alpha survives. Experimenting with risk parity portfolio weightings has limited impact on our results though in particular is beneficial to long–short strategies; the marginal impact of applying trend following methods far outweighs momentum and risk parity adjustments in terms of risk-adjusted returns and limiting downside risk. Overall this leads to an attractive strategy for investing in commodity futures and emphasises the importance of trend following as an investment strategy in the commodity futures context

A crise financeira mundial e as empresas seguradoras norte-americanas: o caso da American Internation Group (AIG)

Compreender os objetivos das políticas financeiras contra a crise e seu desempenho para se evitar o risco sistêmico que a cerca.Compreender os objetivos das políticas financeiras contra a crise e seu desempenho para se evitar o risco sistêmico que a cerca

Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain

Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, alpha-neoendorphin, beta-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. in the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. the increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects. (C) 2012 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Associacao de Fundo e Incentivo a Pesquisa (AFIP)Universidade Federal de São Paulo UNIFESP, Dept Biofis, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Biociencias, BR-04039032 São Paulo, BrazilUniv Cidade São Paulo UNICID, Lab Neurociencias, São Paulo, BrazilUniv São Paulo, Dept Biol Celular & Desenvolvimento, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Biofis, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Biociencias, BR-04039032 São Paulo, BrazilFAPESP: 98/14303-3CNPq: 553645/2009-9CNPq: 558924/2008-5CNPq: 481104/2004-6CNPq: 306587/2010-6Web of Scienc

The Effect of Diphenylethane Side-chain Substituents on Dibenzocyclohexadiene Formation and their Inhibition of α-Synuclein Aggregation in vitro

NSERCPeer ReviewedThe naturally-occurring di-catechol lignan nordihydroguaiaretic acid (NDGA) and an analog without methyl groups on the butyl linker both undergo intramolecular cyclization at pH 7.4 to form dibenzocyclooctadienes. Both NDGA and these dibenzocyclooctadienes have been shown to prevent in vitro aggregation of α-synuclein, an intrinsically disordered protein associated with Parkinson's disease. NDGA possesses two vicinal methyl groups on the butyl linker and the presence of these methyl groups attenuates the rate of intramolecular cyclization versus the unsubstituted analog, in opposition to the anticipated Thorpe-Ingold effect, likely due to steric repulsions during cyclization. Numerous 1,2-bis-ethane di-catechols are known to inhibit α-synuclein aggregation in vitro and we hypothesize that these compounds undergo a similar intramolecular cyclization and the cyclized products may be responsible for the activity. To test this hypothesis we prepared a series of 1,2-bis-ethane di-catechols with 0, 2 and 4 methyl substituents on the linker. We have confirmed that these compounds undergo intramolecular cyclization to form dibenzocyclohexadienes and that steric interactions between the methyl substituents leads to an increase in the rate of intramolecular cyclization, which is in contrast to what was observed for lignan di-catechols. The rate of cyclization to form six-membered rings is 10-30 times more rapid than formation of eight membered rings and the dibenzocyclohexadienes also prevent in vitro aggregation of α-synuclein

O Lugar da Democracia na Atual Configuração Internacional

The role of democracy in the international system has stimulated the recentdebate on world order. Underlying the theme is the discussion on globalization and itsconsequences for the nation state. There is no intention of a literature review, but only a fewcritical notes on certain aspects, principles and concepts suggested for the debate. In handlingthese issues, are given positions which have been characterized by the adoption of theoreticalperspectives and interpretations divergent. The text, however, focuses mainly on analyses ofDavid Held, while other views are raised to the extent that their arguments are contradicted,particularly that proceeding from (neo) realist theory.O papel da democracia no sistema internacional tem acalentado o debate recentesobre ordem mundial. Subjacente ao tema encontra-se a discussão sobre a globalização esuas consequências para o Estado-nação. Não se pretende uma revisão bibliográfica, masapenas alguns apontamentos críticos sobre certos aspectos, princípios e conceitos peloassunto aventados. No tratamento dessas questões, são apresentadas posições as quais setêm caracterizado pela adoção de perspectivas teóricas e de interpretações prático-políticasdivergentes. O texto, no entanto, está centrado principalmente nas análises de David Held,ao passo que outras visões são evocadas à medida que se contraponham às suas argumentações,particularmente aquelas provenientes da teoria (neo) realista