AVALIAÇÃO DO RISCO CARDÍACO, CONFORME ESCORES DE RISCO DE FRAMINGHAM, EM PACIEN- TESAMBULATORIAIS DE SALVADOR DO SUL, SÃO PEDRO DA SERRA E BARÃO - RS

As doenças cardiovasculares constituem a principal causa de mortalidade no mundo e o seu crescimento significativo nos países emdesenvolvimento alerta para um grande impacto nas classes menos favorecidas. O presente trabalho realizado no Laboratório Chiesa,Hospital São Salvador, Salvador do Sul – RS, tem como objetivo, avaliar o percentual de risco para evento coronariano utilizando oEscore de Risco de Framingham (ERF) em parte da população dos municípios de Salvador do Sul, São Pedro da Serra e Barão, nosmeses de setembro, outubro e novembro de 2004. O total de pacientes avaliados no período foi de 354, homens e mulheres, sendo que242 (68%) apresentaram baixo risco, 62 (18%) apresentaram médio risco e 50 (14%) apresentaram alto risco de desenvolver eventocoronariano em 10 anos. Mais de 2/3 dos indivíduos apresentam algum tipo de dislipidemia, sendo que no grupo de alto risco chega à82%. É baixo o percentual de fumantes e neste grupo as dislipidemias não são freqüentes. Diabéticos no grupo de alto risco chegam apraticamente metade dos pacientes. A hipertensão arterial sistêmica atinge cerca de 40% dos pacientes e no grupo de alto risco atinge90%. Estes resultados confirmam a importância e a necessidade de se verificar o perfil lipídico, bem como realizar a estratificação derisco e estabelecer metas lipídicas de tratamento para a aterosclerose nesta comunidade

Animal models of metabolic disorders in the study of neurodegenerative diseases : an overview

The incidence of metabolic disorders, as well as of neurodegenerative diseases—mainly the sporadic forms of Alzheimer’s and Parkinson’s disease—are increasing worldwide. Notably, obesity, diabetes, and hypercholesterolemia have been indicated as early risk factors for sporadic forms of Alzheimer’s and Parkinson’s disease. These conditions share a range of molecular and cellular features, including protein aggregation, oxidative stress, neuroinflammation, and blood-brain barrier dysfunction, all of which contribute to neuronal death and cognitive impairment. Rodent models of obesity, diabetes, and hypercholesterolemia exhibit all the hallmarks of these degenerative diseases, and represent an interesting approach to the study of the phenotypic features and pathogenic mechanisms of neurodegenerative disorders. We review the main pathological aspects of Alzheimer’s and Parkinson’s disease as summarized in rodent models of obesity, diabetes, and hypercholesterolemia

Diphenyl diselenide, a simple glutathione peroxidase mimetic, inhibits human LDL oxidation in vitro

Oxidative modification of low-density lipoprotein (LDL) represents an important factor in atherogenesis. In the present study, we have investigated the antioxidant capability of diphenyl diselenide (PhSe)2, a simple organoseleno compound, against copper (Cu2+) and peroxyl radical-induced human LDL oxidation in vitro. In initial studies using human serum, (PhSe)2 caused a dose-dependent inhibition of Cu2+-induced lipid peroxidation, which was correlated to thiol consumption. (PhSe)2 increased lipid peroxidation lag phase and decreased lipid peroxidation rate in isolated human LDL, evaluated by measuring both conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) levels. Consistent with these observations, (PhSe)2 showed a marked inhibitory effect on 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH)-induced oxidation of LDL or parinaric acid (PnA) incorporated into LDL. (PhSe)2 also displayed a dose-dependent protective effect against Cu2+-induced lipid peroxidation in rat aortic slices. Interestingly, besides the antioxidant effects of (PhSe)2 toward the lipid moieties of LDL, which was related to its thiol-peroxidase activity, protein moieties from human isolated LDL were also protected against Cu2+-induced oxidation. The results presented herein are the first to show that (i) (PhSe)2 inhibits lipid peroxidation in human isolated LDL in vitro, (ii) this phenomenon is related to its thiol-peroxidase activity, and (iii) this chalcogen also prevents the oxidation of protein moieties of human LDL. Taken together, such data render (PhSe)2 a promising molecule for pharmacological studies with respect to the atherogenic process.http://www.sciencedirect.com/science/article/B6T12-4S21TS2-1/1/38250cf8bae4a4195ccd8905cf5c2a8

Diphenyl diselenide protects neuronal cells against oxidative stress and mitochondrial dysfunction : involvement of the glutathione-dependent antioxidant system

Oxidative stress and mitochondrial dysfunction are critical events in neurodegenerative diseases; therefore, molecules that increase cellular antioxidant defenses represent a future pharmacologic strategy to counteract such conditions. The aim of this study was to investigate the potential protective effect of (PhSe)2 on mouse hippocampal cell line (HT22) exposed to tert-BuOOH (in vitro model of oxidative stress), as well as to elucidate potential mechanisms underlying this protection. Our results showed that tert-BuOOH caused time- and concentration- dependent cytotoxicity, which was preceded by increased oxidants production and mitochondrial dysfunction. (PhSe)2 pre-incubation significantly prevented these cytotoxic events and the observed protective effects were paralleled by the upregulation of the cellular glutathione-dependent antioxidant system: (PhSe)2 increased GSH levels (> 60%), GPx activity (6.9-fold) and the mRNA expression of antioxidant enzymes Gpx1 (3.9-fold) and Gclc (2.3-fold). Of note, the cytoprotective effect of (PhSe)2 was significantly decreased when cells were treated with mercaptosuccinic acid, an inhibitor of GPx, indicating the involvement of GPx modulation in the observed protective effect. In summary, the present findings bring out a new action mechanism concerning the antioxidant properties of (PhSe)2. The observed upregulation of the glutathione-dependent antioxidant system represents a future pharmacologic possibility that goes beyond the well-known thiol-peroxidase activity of this compound

High cholesterol diet exacerbates blood-brain barrier disruption in LDLr–/– mice : impact on cognitive function

Background: Evidence has revealed an association between familial hypercholesterolemia and cognitive impairment. In this regard, a connection between cognitive deficits and hippocampal blood-brain barrier (BBB) breakdown was found in low-density lipoprotein receptor knockout mice (LDLr–/–), a mouse model of familial hypercholesterolemia. Objective: Herein we investigated the impact of a hypercholesterolemic diet on cognition and BBB function in C57BL/6 wild-type and LDLr–/– mice. Methods: Animals were fed with normal or high cholesterol diets for 30 days. Thus, wild-type and LDLr–/– mice were submitted to memory paradigms. Additionally, BBB integrity was evaluated in the mice’s prefrontal cortices and hippocampi. Results: A tenfold elevation in plasma cholesterol levels of LDLr–/– mice was observed after a hypercholesterolemic diet, while in wild-type mice, the hypercholesterolemic diet exposure increased plasma cholesterol levels only moderately and did not induce cognitive impairment. LDLr–/– mice presented memory impairment regardless of the diet. We observed BBB disruption as an increased permeability to sodium fluorescein in the prefrontal cortices and hippocampi and a decrease on hippocampal claudin-5 and occludin mRNA levels in both wild-type and LDLr–/– mice treated with a hypercholesterolemic diet. The LDLr–/– mice fed with a regular diet already presented BBB dysfunction. The BBB-increased leakage in the hippocampi of LDLr–/– mice was related to high microvessel content and intense astrogliosis, which did not occur in the control mice. Conclusion: Therefore, LDLr–/– mice seem to be more susceptible to cognitive impairments and BBB damage induced by exposure to a high cholesterol diet. Finally, BBB disruption appears to be a relevant event in hypercholesterolemia-induced brain alterations

Impact of Open Access Policy on Brazilian Science and Global Trends

Abstract Open access (OA) publishing provides free online access to research articles without subscription fees. In Brazil, absence of financial support from academic institutions and limited government policies pose challenges to OA publication. Here, we used data from the Web of Science and Scopus to compare with global trends in journal accessibility and scientific quality metrics. Brazilian authors publish more OA articles, particularly in Global South journals. While OA correlates with quality for global authors, it had no impact on Brazilian science. To maximize impact, Brazilian authors should prioritize Q1 journals regardless of OA status. High-impact or Global North journal publication seems more relevant for Brazilian science than OA. Our findings indicate that the present open access policy has been ineffective to improve the impact of Brazilian science, providing insights to guide the formulation of scientific public policies

Potential neuroprotective and antiinfammatory efects provided by omega-3 (DHA) against Zika virus infection in human SH-SY5Y cells

Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Once neuronal cells are infected, the virus is capable of modulating cell metabolism, leading to neurotoxicity and cellular death. The negative efect of ZIKV in neuron cells has been characterized. However, the description of molecules capable of reversing these cytotoxic efects is still under investigation. In this context, it has been largely demonstrated that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is highly neuroprotective. Here, we hypothesized that DHA’s neuroprotective proprieties could have an infuence on ZIKV-induced neurotoxicity in SHSY5Y cells. Our data showed that pre-treatment of SH-SY5Y cells with DHA increased the cell viability and proliferation in ZIKV-infected cells. Moreover, DHA triggered an anti-infammatory response in those infected cells. Besides, DHA was capable of restoring mitochondria function and number in ZIKVinfected SH-SY5Y cells. In addition, cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at diferent times of infection. Taking together, these results demonstrated that DHA has a potential anti-infammatory and neuroprotective efect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Avaliação da expressão do citocromo P4501A1 hepático e das defesas antioxidantes em ratos tratados com benzonidazol

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da SaúdeO benzonidazol (BZN) é um derivado nitroimidazol dotado de uma notável atividade tripanocídica e vem sendo utilizado no Brasil como o único fármaco empregado no tratamento da doença de Chagas. Possivelmente, o mecanismo de ação do BZN seja via produção de espécies reativas de oxigênio (ERO) geradas através do processo de biotransformação, induzindo uma condição de estresse oxidativo no T. cruzi, o qual é deficiente em defesas antioxidantes. Com o intuito de estudar a toxicidade do BZN via geração de ERO, foram avaliadas as defesas antioxidantes, bem como o dano celular e a indução/expressão do CYP4501A1 no hospedeiro, em ratos machos tratados durante diferentes períodos de tempo (2, 4, 6, 10 e 30 dias) com 40mg/Kg de peso de BZN. Após o tratamento, foram examinados os biomarcadores do estresse oxidativo como as atividades da catalase (CAT), superóxido dismutase (SOD), glutationa redutase (GR), glutationa peroxidase (GPx), dano celular (TBARS), os níveis de tióis não proteicos (GT, GSH e GSSG), bem como a atividade e a expressão do sistema da fase I de biotransformação, CYP4501A1 e a atividade da GST, nos hepatócitos destes animais. Nossos resultados revelaram que o BZN causou uma condição de estresse oxidativo nos hepatócitos do hospedeiro, caracterizado pelo aumento dos níveis de TBARS bem como a indução de algumas e inibição de outras defesas antioxidantes, além da indução do CYP1A1, observada através da medida da atividade EROD e por Western blotting, de uma maneira tempo-dependente. A atividade da GST foi inibida durante o tratamento com BZN. O dano tecidual, observado através da medida de TBARS, mostrou um aumento exponencial até 10 dias de tratamento, mantendo-se igualmente aumentado em 30 dias. Por outro lado, as atividades da CAT e da GR aumentaram no início, sendo que a atividade da GR permaneceu diminuída até o final do tratamento, enquanto que a CAT, após 30 dias, teve sua atividade aumentada em relação aos controles. A atividade da GPx esteve diminuída em 2 e 30 dias de tratamento, enquanto a atividade da SOD permaneceu inalterada durante todo o período experimental. Os níveis de GT e GSH apresentaram um comportamento similar, estando diminuídos no início do tratamento; todavia, as concentrações hepáticas aumentaram no final do período experimental; a GSSG mostrou-se elevada durante todo o tratamento. Sumarizando, estes resultados indicam que, mesmo em doses terapêuticas, o tratamento com BZN proporciona uma condição de estresse oxidativo nos hepatócitos dos ratos tratados com BZN, caracterizando uma toxicidade relacionada com a geração de ERO no hospedeiro, via indução do CYP1A1, além de sua conhecida toxicidade no parasita