Possible Beneficial Effect of Exercise, by Reducing Oxidative Stress, on the Incidence of Preeclampsia

We hypothesize that regular exercise enhances antioxidative enzymes in pregnant women, which reduce oxidative stress and, thus, the incidence of preeclampsia. Oxidative stress with enhanced lipid peroxide formation could lead to endothelial dysfunction in preeclampsia. Other conditions, such as increased transferrin saturation and decreased iron-binding capacity, directly and indirectly promote the process of oxidative stress and subsequent endothelial dysfunction. Exercise increases oxidative metabolism and produces a prooxidant environment. This acidic environment during exercise (at or beyond anaerobic threshold) promotes oxygen release from hemoglobin and increases in PO2 in tissues, as well as releases iron from transferrin. When exercise is repeated regularly, the body promptly adjusts so that oxidative stress is eliminated or reduced. The body's adaptations to a regular exercise habit seem to have an antioxidant effect. In humans, training effects have been identified with an enhanced activity of antioxidative enzymes. Another concerted adaptation that regular exercise brings to women's bodies is resistance against production of prooxidants by increasing the number of mitochondria. Equally important is a training effect that decreases susceptibility to lipid peroxidation. Evidence suggests that physically active women are less likely to develop preeclampsia. In theory, intracellular and extracellular conditions resulting from regular exercise should counteract the enhancement of oxidative stress, thus interfering with the process leading to endothelial dysfunction. This position paper describes a hypothesis and includes a brief review of exercise physiology and biochemical research in preeclampsia. Unlike other preventive treatments, such as aspirin or calcium supplements, a regular exercise habit leads to a positive and healthy lifestyle without concern of side effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63167/1/152460901317193558.pd

Estudo biológico e comportamental de lagartas de Spodoptera frugiperda visando à produção de Baculovírus spodoptera

A utilização de bioinseticida a base de Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) possui potencial para o controle de Spodoptera frugiperda (Lepidoptera: Noctuidae), porém sua obtenção em larga escala depende da maximização da produção in vivo. Assim, alguns fatores biológicos e comportamentais devem ser estudados para aperfeiçoar a produção de SfMNPV com intuito de disponibilizar um bioinseticida eficiente, economicamente viável e que possa ser usado no manejo de S. frugiperda nos mais diversos sistemas agrícolas. Entre os fatores relacionados ao hospedeiro, a temperatura e a idade para inoculação do vírus são de extrema importância, pois interferem diretamente no ciclo de vida e na replicação viral. O comportamento também deve ser avaliado, para evitar condições de criação do hospedeiro que favoreçam o canibalismo e causa prejuízo na multiplicação in vivo do SfMNPV. Assim, objetivou-se determinar a melhor condição térmica para criar as lagartas e a idade ideal, para inocular e multiplicar o vírus no hospedeiro, bem como, verificar a ocorrência do comportamento canibal em lagartas de S. frugiperda. Os experimentos foram conduzidos no Laboratório de Controle Microbiano de Insetos do Núcleo de Desenvolvimento Científico e Tecnológico em Manejo Fitossanitário de Pragas e Doenças (NUDEMAFI), localizado no Centro de Ciências Agrárias da UFES, em Alegre, Espírito Santo, Brasil. A pesquisa foi desenvolvida em duas etapas, a primeira para determinar a condição térmica e a idade ideais para criar e inocular, respectivamente, o hospedeiro com o vírus, para multiplicação in vivo de SfMNPV. A segunda etapa foi para avaliar o comportamento canibal de lagartas da espécie S. frugiperda criadas a 22, 25 e 31°C, inoculadas com SfMNPV quando com idades de 10, 8 e 4 dias, respectivamente, e mantidas em diferentes densidades populacionais (5, 10, 25 e 50 lagartas por recipiente). A mortalidade diminuiu com o aumento da temperatura e da idade do hospedeiro nas temperaturas de 25, 28 e 31 °C. O aumento na taxa de canibalismo foi 12 diretamente proporcional à densidade populacional quando as lagartas foram criadas a 22 °C, inoculadas aos 10 dias de idade e 25 ºC, inoculadas aos 8 dias e atingiram 63,5 e 62,5%, respectivamente na densidade populacional de 50 lagartas. Mas, quando as lagartas foram criadas a 31ºC e inoculadas com idade de 4 dias, a densidade populacional não afetou o comportamento canibal, taxa média de 24%, inferior aos outros tratamentos com 50 lagartas por recipiente. Demonstrando que é viável para a multiplicação viral, criar lagartas a 31 °C e aos 4 dias de idade inocular o vírus, podendo a partir de então colocar até 50 lagartas por recipiente, o que reduz a mão-de-obra necessária para individualizar as lagartas e otimiza o espaço físico em uma biofábrica. Portanto, se para otimizar o processo produção viral e o serviço em uma biofábrica, é preciso maximizar a produção viral, reduzir o tempo de multiplicação do vírus e o canibalismo entre as lagartas, com ausência de contaminação da criação, a temperatura e idade ideais para criação massal de S. frugiperda e inoculação do vírus nas lagartas, respectivamente, visando produção de baculovírus em larga escala são de 31 ºC e 4 dias

Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

<p>Abstract</p> <p>Background</p> <p>Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction.</p> <p>Methods</p> <p>Diabetes (DM) was induced in rats by streptozotocin (STZ). Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII) were examined by hydroethidine and immunofluorescence, respectively.</p> <p>Results</p> <p>The dilatory response to acetylcholine (ACh) significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP) was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively) of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O₂^●-) production. O₂^●-production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished.</p> <p>Conclusion</p> <p>Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.</p

Translating the oxidative stress hypothesis into the clinic: NOX versus NOS

Cardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeutic approaches are symptom-orientated. Knowing the molecular mechanism of disease would enable more targeted therapies. One postulated underlying mechanism of cardiovascular diseases is oxidative stress, i.e. the increased occurrence of reactive oxygen species such as superoxide. Oxidative stress leads to a dysfunction of vascular endothelium-dependent protective mechanisms. There is growing evidence that this scenario also involves impaired nitric oxide (NO)-cyclic GMP signalling. Out of a number of enzyme families that can produce reactive oxygen species, NADPH oxidases stand out, as they are the only enzymes whose sole purpose is to produce reactive oxygen species. This review focuses on the clinically validated targets of oxidative stress, NO synthase (NOS) and the NO receptor, soluble guanylate cyclase as well as the source of ROS, e.g. NADPH oxidases. We place recent knowledge in the function and regulation of these enzyme families into clinical perspective. For a comprehensive overview of the biology and pharmacology of oxidative stress and possible other sources and targets, we refer to other literature overviews

Tyrosine Nitration of PA700 Links Proteasome Activation to Endothelial Dysfunction in Mouse Models with Cardiovascular Risk Factors

Oxidative stress is believed to cause endothelial dysfunction, an early event and a hallmark in cardiovascular diseases (CVD) including hypertension, diabetes, and dyslipidemia. However, the targets for oxidative stress-mediated endothelial dysfunction in CVD have not been completely elucidated. Here we report that 26S proteasome activation by peroxynitrite (ONOO−) is a common pathway for endothelial dysfunction in mouse models of diabetes, hypertension, and dyslipidemia. Endothelial function, assayed by acetylcholine-induced vasorelaxation, was impaired in parallel with significantly increased 26S proteasome activity in aortic homogenates from streptozotocin (STZ)-induced type I diabetic mice, angiotensin-infused hypertensive mice, and high fat-diets -fed LDL receptor knockout (LDLr−/−) mice. The elevated 26S proteasome activities were accompanied by ONOO−-mediated PA700/S10B nitration and increased 26S proteasome assembly and caused accelerated degradation of molecules (such as GTPCH I and thioredoxin) essential to endothelial homeostasis. Pharmacological (administration of MG132) or genetic inhibition (siRNA knockdown of PA700/S10B) of the 26S proteasome blocked the degradation of the vascular protective molecules and ablated endothelial dysfunction induced by diabetes, hypertension, and western diet feeding. Taken together, these results suggest that 26S proteasome activation by ONOO−-induced PA700/S10B tyrosine nitration is a common route for endothelial dysfunction seen in mouse models of hypertension, diabetes, and dyslipidemia

Neonatal cerebrovascular autoregulation.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes

Endothelium-dependent responses in cerebral blood vessels

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Superoxide anion is an endothelium-derived contracting factor

The calcium ionophore A23187 causes endothelium-dependent contractions in canine basilar arteries. Removal of the endothelium, or treatment with indomethacin or superoxide dismutase (SOD), prevented the endothelium-dependent excitatory effect of the calcium ionophore. Catalase and deferoxamine were without effect. Superoxide anion generated by xanthine plus xanthine oxidase in the presence of catalase caused contractions of the vascular smooth muscle, which were abolished by SOD or heat inactivation of xanthine oxidase. The A23187-induced production of prostaglandins F(2α) and E2 and thromboxane B2 was abolished by the removal of endothelium and by treatment with indomethacin but was not affected by the presence of SOD plus catalase. These observations are consistent with the hypothesis that superoxide anion, rather than prostaglandins generated by hydroperoxidase activity of cyclooxygenase, is an endothelium-derived contracting factor in canine cerebral arteries.link_to_subscribed_fulltex

Effects of SIN-1 on isolated canine basilar arteries

The effects of 3-morpholinosydnonimine (SIN-1) were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended in Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2. Changes in isometric force were recorded. SIN-1, nitric oxide, and sodium nitroprusside caused concentration-dependent relaxations of control preparation contracted by uridine-5'-triphosphate. The removal of endothelium augmented the relaxation to the nitrovasodilators. Increasing concentrations of SIN-1 reduced endothelium-dependent contractions to the calcium ionophore A23127 and arachidonic acid. The results of the present study suggest that SIN-1 causes relaxation and prevents endothelium-dependent contractions in cerebral arteries. The inhibitory effect of SIN-1 is reduced by the presence of endothelium possibly by interaction with endothelium-derived relaxing factors and/or superoxide anions produced in endothelial cells. The inhibition of endothelium-dependent contractions could be due in part to chemical interactions between endothelium-derived contracting factor (superoxide anion) and the nitric oxide liberated by SIN-1.link_to_subscribed_fulltex