Antioxidant status in acute stroke patients and patients at stroke risk

Background and Purpose: Antioxidant enzymes like copper/ zinc superoxide dismutase (SOD), catalase and gluthatione peroxidase (GSHPx) are part of intracellular protection mechanisms to overcome oxidative stress and are known to be activated in vascular diseases and acute stroke. We investigated the differences of antioxidant capacity in acute stroke and stroke risk patients to elucidate whether the differences are a result of chronic low availability in arteriosclerosis and stroke risk or due to changes during acute infarction. Methods: Antioxidant enzymes were examined in 11 patients within the first hours and days after acute ischemic stroke and compared to risk- and age-matched patients with a history of stroke in the past 12 months ( n = 17). Antioxidant profile was determined by measurement of glutathione (GSH), malondialdehyde (MDA), SOD, GSHPx and minerals known to be involved in antioxidant enzyme activation like selenium, iron, copper and zinc. Results: In comparison to stroke risk patients, patients with acute ischemic stroke had significant changes of the GSH system during the first hours and days after the event: GSH was significantly elevated in the first hours (p < 0.01) and GSHPx was elevated 1 day after the acute stroke (p < 0.05). Selenium, a cofactor of GSHPx, was decreased (p < 0.01). GSHPx levels were negatively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on admission (r = - 0.84, p < 0.001) and NIHSS scores after 7 days ( r = - 0.63, p < 0.05). MDA levels showed a trend for elevation in the first 6 h after the acute stroke ( p = 0.07). No significant differences of SOD, iron, copper nor zinc levels could be identified. Conclusions: Differences of antioxidant capacity were found for the GSH system with elevation of GSH and GSHPx after acute stroke, but not for other markers. The findings support the hypothesis that changes of antioxidant capacity are part of acute adaptive mechanisms during acute stroke. Copyright (C) 2004 S. Karger AG, Basel

Bad Faith Claims Practices in Texas: Do They Exist: Extending a Bad Faith Cause of Action of Texas Workers\u27 Compensation Insurance Claimants.

Abstract Forthcoming

Columbia River Rhyolites: Age-Distribution Patterns and Their Implications for Arrival, Location, and Dispersion of Continental Flood Basalt Magmas in the Crust

Columbia River province magmatism is now known to include abundant and widespread rhyolite centers even though the view that the earliest rhyolites erupted from the McDermitt Caldera and other nearby volcanic fields along the Oregon–Nevada state border has persisted. Our study covers little-studied or unknown rhyolite occurrences in eastern Oregon that show a much wider distribution of older centers. With our new data on distribution of rhyolite centers and ages along with literature data, we consider rhyolites spanning from 17.5 to 14.5 Ma of eastern Oregon, northern Nevada, and western Idaho to be a direct response to flood basalts of the Columbia River Basalt Group (CRBG) and collectively categorize them as Columbia River Rhyolites. The age distribution patterns of Columbia River Rhyolites have implications for the arrival, location, and dispersion of flood basalt magmas in the crust. We consider the period from 17.5 to 16.4 Ma to be the waxing phase of rhyolite activity and the period from 15.3 to 14.5 Ma to be the waning phase. The largest number of centers was active between 16.3–15.4 Ma. The existence of crustal CRBG magma reservoirs beneath rhyolites seems inevitable, and hence, rhyolites suggest the following. The locations of centers of the waxing phase imply the arrival of CRBG magmas across the distribution area of rhyolites and are thought to correspond to the thermal pulses of arriving Picture Gorge Basalt and Picture-Gorge-Basalt-like magmas of the Imnaha Basalt in the north and to those of Steens Basalt magmas in the south. The earlier main rhyolite activity phase corresponds with Grande Ronde Basalt and evolved Picture Gorge Basalt and Steens Basalt. The later main phase rhyolite activity slightly postdated these basalts but is contemporaneous with icelanditic magmas that evolved from flood basalts. Similarly, centers of the waning phase span the area distribution of earlier phases and are similarly contemporaneous with icelanditic magmas and with other local basalts. These data have a number of implications for long-held notions about flood basalt migration through time and the age-progressive Snake River Plain Yellowstone rhyolite trend. There is no age progression in rhyolite activity from south-to-north, and this places doubt on the postulated south-to-north progression in basalt activity, at least for main-phase CRBG lavas. Furthermore, we suggest that age-progressive rhyolite activity of the Snake River Plain–Yellowstone trend starts at ~12 Ma with activity at the Bruneau Jarbidge center, and early centers along the Oregon–Nevada border, such as McDermitt, belong to the early to main phase rhyolites identified here

Temporal and crustal effects on differentiation of tholeiite to calcalkaline and ferro-trachytic suites, High Lava Plains, Oregon, USA

Strongly bimodal, basalt-rhyolite volcanism of the High Lava Plains Province of Oregon followed the Middle Miocene flood basalts of the Pacific Northwest and extends to recent time. During the 8 m.y. of volcanism recorded in the central High Lava Plains, in western Harney Basin, three distinct mafic magmatic trends originate from primitive high-alumina olivine tholeiites (HAOT); they are tholeiitic, calcalkaline and ferro-trachytic. Tholeiitic basalts occur throughout the history and their compositions are derived by crystal fractionation while traversing the crust and mixing with evolved mafic magmas. Scavenging of apatite from crustal rocks and minor contamination with felsic melts accounts for P, incompatible element enrichments and increasing tilts of incompatible element patterns with differentiation. The calcalkaline mafic suite occurs in temporal association with abundant silicic volcanism and is the only suite with Fe decreasing with Mg. Calcalkaline compositions are derived from evolved tholeiitic basalt by crystal fractionation coupled with assimilation of felsic crust or crustal melts. The ferro-trachytic suite occurs mainly late, is highly enriched in incompatible element with patterns parallel to tholeiites from which it is derived by protracted fractionation and recharge. The three suites primarily reflect changes in magma flux and crustal interactions in time. High magma flux promotes crustal melting and contamination of tholeiite to make the calcalkaline suite. On the other hand, ferrotrachytic magmas erupted mainly late in the sequence, during magmatic waning and after significant basaltification of the crust.Keywords: basalt differentiation, calcalkaline trend, phosphorus enrichment, HAOT, trachyandesite, high lava plain

Mitochondrial Protective Effects Caused by the Administration of Mefenamic Acid in Sepsis

The pathophysiology of sepsis may involve the activation of the NOD-type receptor containing the pyrin-3 domain (NLPR-3), mitochondrial and oxidative damages. One of the primary essential oxidation products is 8-oxoguanine (8-oxoG), and its accumulation in mitochondrial DNA (mtDNA) induces cell dysfunction and death, leading to the hypothesis that mtDNA integrity is crucial for maintaining neuronal function during sepsis. In sepsis, the modulation of NLRP-3 activation is critical, and mefenamic acid (MFA) is a potent drug that can reduce inflammasome activity, attenuating the acute cerebral inflammatory process. Thus, this study aimed to evaluate the administration of MFA and its implications for the reduction of inflammatory parameters and mitochondrial damage in animals submitted to polymicrobial sepsis. To test our hypothesis, adult male Wistar rats were submitted to the cecal ligation and perforation (CLP) model for sepsis induction and after receiving an injection of MFA (doses of 10, 30, and 50 mg/kg) or sterile saline (1 mL/kg). At 24 h after sepsis induction, the frontal cortex and hippocampus were dissected to analyze the levels of TNF-α, IL-1β, and IL-18; oxidative damage (thiobarbituric acid reactive substances (TBARS), carbonyl, and DCF-DA (oxidative parameters); protein expression (mitochondrial transcription factor A (TFAM), NLRP-3, 8-oxoG; Bax, Bcl-2 and (ionized calcium-binding adaptor molecule 1 (IBA-1)); and the activity of mitochondrial respiratory chain complexes. It was observed that the septic group in both structures studied showed an increase in proinflammatory cytokines mediated by increased activity in NLRP-3, with more significant oxidative damage and higher production of reactive oxygen species (ROS) by mitochondria. Damage to mtDNA it was also observed with an increase in 8-oxoG levels and lower levels of TFAM and NGF-1. In addition, this group had an increase in pro-apoptotic proteins and IBA-1 positive cells. However, MFA at doses of 30 and 50 mg/kg decreased inflammasome activity, reduced levels of cytokines and oxidative damage, increased bioenergetic efficacy and reduced production of ROS and 8-oxoG, and increased levels of TFAM, NGF-1, Bcl-2, reducing microglial activation. As a result, it is suggested that MFA induces protection in the central nervous system early after the onset of sepsis

Impairment of energy metabolism in hippocampus of rats subjected to chemically-induced hyperhomocysteinemia

AbstractHomocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine (Hcy). Mental retardation, ischemia and other neurological features, whose mechanisms are still obscure are common symptoms in homocystinuric patients. In this work, we investigated the effect of Hcy administration in Wistar rats on some parameters of energy metabolism in the hippocampus, a cerebral structure directly involved with cognition. The parameters utilized were 14CO2 production, glucose uptake, lactate release and the activities of succinate dehydrogenase and cytochrome c oxidase (COX). Chronic hyperhomocysteinemia was induced by subcutaneous administration of Hcy twice a day from the 6th to the 28th day of life in doses previously determined in our laboratory. Control rats received saline in the same volumes. Rats were killed 12 h after the last injection. Results showed that Hcy administration significantly diminished 14CO2 production and glucose uptake, as well as succinate dehydrogenase and COX activities. It is suggested that impairment of brain energy metabolism may be related to the neurological symptoms present in homocystinuric patients