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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has recently been shown that transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Experimental data and theoretical considerations indicate that transition metal cations may destabilize the ionic form of histidine residues within proteins, thereby decreasing their pK(a) values. Because the release of transition metal cations and acidification of the local environment represent important events associated with brain injury, the ability of Zn2+ and Cu2+ to bind to neurotrophins in acidic conditions may alter neuronal death following stroke or as a result of traumatic injury. To test the hypothesis that metal ion binding to neurotrophins is influenced by pH, the effects of Zn2+ and Cu2+ on NGF conformation, receptor binding and NGF tyrosine kinase (trkA) receptor signal transduction were examined under conditions mimicking cerebral acidosis (pH range 5.5-7.4). The inhibitory effect of Zn2+ on biological activities of NGF is lost under acidic conditions. Conversely, the binding of Cu2+ to NGF is relatively independent of pH changes within the studied range. These data demonstrate that Cu2+ has greater binding affinity to NGF than Zn2+ at reduced pH, consistent with the higher affinity of Cu2+ for histidine residues. These findings suggest that cerebral acidosis associated with stroke or traumatic brain injury could neutralize the Zn2+-mediated inactivation of NGF, whereas corresponding pH changes would have little or no influence on the inhibitory effects of Cu2+. The importance of His84 of NGF for transition metal cation binding is demonstrated, confirming the involvement of this residue in metal ion coordination.
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PMID:The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis. 1148 54

Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% ( P < 0.0001) and 73% ( P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after 1 hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.
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PMID:Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. 1174 Feb

A German couple was struck by lightning. Both patients survived this event. Whereas the husband was unconscious for only a few minutes, his wife fell into coma for 24 h. The lightning stroke entered the body of the woman behind the left ear and left it at the left shoe. The stroke caused a partial evaporation of a gold ornamental chain on the neck, resulting in a tattoo of the neck skin. A biopsy of the skin 6 months after the event showed the accumulation of gold particles of different size in the dermis down to the subcutaneous fatty tissue. In semithin sections, histiocytes, multinucleated foreign giant cells, and fibroblasts were visible with uptaken metallic particles. In transmission electron microscopy, gold globules of up to 30 microm in diameter were visible outside the cells in the collageneous matrix of the connective tissue besides smaller metallic particles up to 5 nm inside lysosomes and residual bodies of phagocytic cells. Four different kinds of gold particles could be differentiated: globules, granular irregular particles, tubules, and tanglelike tracks. In scanning electron microscopy, gold particles were demonstrated by backscatter detection in the connective tissue of subcutis, where the EDX elemental analysis showed strong signals of aurum (Au), copper (Cu), and argentum (Ag). The detected metals were quantified by AAS as 70% gold, 21% silver, and 9% copper, which demonstrates the composition of gold alloy of the neck chain of the patient. Tanglelike tracks and elongated gold deposits represent crystals of gold salts, as detected by electron diffraction and polarization microscopy. Attempts to remove the gold particles from the skin to remove the tattoo should not be undertaken because the gold is deep and widespread.
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PMID:Detection of gold particles in the neck skin after lightning stroke with evaporation of an ornamental chain. 1218 73

Oral contraceptives (OCs) and IUDs are still the most popular contraceptive methods; their small potential risk for users has been well advertized in recent years. Copper IUDs are more effective than inert IUDs; it seems that the T-Cu 380, the T-Cu220 C, and the T-Nova have low failure rates. Excessive menstrual bleeding still remains the main side effect, and pelvic infection the main complication. Risk of cerebrovascular accident is the main side effect of OCs; the risk increases greatly in smokers and in hypertensive women. After termination of OCs return to fertility is quick and easy; OCs can prevent pelvic infection and, possibly, ovarian cancer. New methods of fertility control, now still under experimentation, include subdermal implants of a silastic capsule containing a steroid which is released continuously. According to recent studies the failure rate of this method is only 0.4%, and acceptability is very high. Silastic vaginal rings releasing levonorgestrel-estradiol have also been tested with excellent results, and with a very low pregnancy rate; the only side effect seems to be leukorrhea. Failure rate for progesterone-releasing IUDs is only 1.9%, termination rate for bleeding and pain is 6.1%, and continuation rate is 82.8%. This new method has the advantage of decreasing the amount of menstrual bleeding. Intracervical devices releasing levonorgestrel are not more effective than regular IUDs; their insertion is much easier and can be done by paramedical personnel. LRH analog administration by nasal spray has also proven to inhibit ovulation.
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PMID:[Current trends in female contraception (author's transl)]. 1226 57

Family planning practitioners tend to be unaware of the reproductive health needs of disabled people. In many developing countries, disabled women are not taken for routine gynecologic examinations because it is assumed they will not have children. Even in developed countries, women with paralysis, impaired motor function, and other obvious physical disabilities are rarely offered counseling on sexuality or contraception. With proper education and counseling, disabled men and women may finally be in a position to make a truly informed decision about their reproductive lives. The selection of a contraceptive method for a disabled woman depends on consideration of factors such as the quality of circulation, abnormal clotting, the degree of physical sensation, manual dexterity, possible interactions with other medications, the effect of contraceptives on the disease process, problems with menstrual hygiene, and depression. For example, oral contraceptives are contraindicated in women with impaired circulation, a history of cerebrovascular accident, and immobility of the extremities. Methods than increase menstrual bleeding (e.g., copper IUDs) can cause hygiene problems for women with compromised manual dexterity. Although use of a barrier method may be difficult for women with poor coordination or upper-extremity disabilities, sexually transmitted disease (STD) prevention is especially important for women with pelvic sensory impairments that could allow STD symptoms to go unrecognized. Also in need of assessment in patients with physical disabilities are the impact of the disability on sexual expression and the possibility that sexual abuse is occurring.
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PMID:Disabled have many needs for contraception. 1229 57

Intracerebral infusion of lysed erythrocytes causes brain edema without inducing ischemic cerebral blood flow. Reports have indicated that oxidative damage contributes to secondary brain injury in stroke. In the present study, we investigated whether erythrocyte lysis after intracerebral hemorrhage (ICH) might result in oxidative brain damage. This study had four parts. Male Sprague-Dawley rats received an infusion of autologous lysed erythrocytes into the right striatum. Control rats only had a needle insertion. Neurological deficits, brain water and ion contents were determined in the first part. In the second part, hemoxygenase-1 (HO-1), manganese superoxide dismutase (Mn-SOD), copper/zinc SOD (CuZn-SOD) and protein carbonyl levels were determined by Western blot analysis. In the third part, immunohistochemistry was performed for HO-1. DNA damage was examined using DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) in the fourth part. Infusion of lysed RBCs induced marked edema in the ipsilateral striatum and profound neurological deficits. Western blot analysis and immunohistochemistry indicated that HO-1 was upregulated 24 h after infusion of lysed red blood cells. Both Mn-SOD and CuZn-SOD contents decreased, protein carbonyl levels increased in the ipsilateral striatum, and there was the appearance of PANT- and TUNEL-positive cells suggesting oxidative mechanisms in the erythrocyte-induced brain injury. In conclusion, oxidative stress caused by components of the lysed erythrocytes contributes to the brain injury after ICH.
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PMID:Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. 1238 37

Compared with other regions in the United States, the southern region has had the highest stroke mortality rate and a more prevalent and resistant hypertension. We designed this analysis of the data obtained from the National Health and Nutritional Examination Survey III (NHANES-III), which is a community-based cross-sectional survey, to describe regional variations in blood pressure and the reported consumption of nutrients, focusing on those linked to blood pressure, in the United States. We selected the following variables from the NHANES-III data for this analysis: systolic and diastolic blood pressures, protein, carbohydrates, total fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, fiber, sodium, potassium, calcium, magnesium, zinc, copper, iron, riboflavin, niacin, thiamin, alcohol and vitamins C, E, B-6 and B-12. Of the 17,752 participants in the survey who were 18 y of age or older, the south had the highest systolic and diastolic blood pressures (P < 0.005 for each) and reported the highest consumption of monounsaturated fatty acids, polyunsaturated fatty acids and cholesterol (P < 0.05 for all) and the least amount of fiber in the multivariate analysis (P < 0.005). The highest reported sodium consumption was in the south region (3.4 +/- 0.02 g), and the lowest was in the west (3.2 +/- 0.03 g; P < 0.05). The south also consumed the least potassium, calcium, phosphorous, magnesium, copper, riboflavin, niacin, iron and vitamins A, C and B-6 (P < 0.005). There was no difference among the four regions in frequency of "adding salt on the table." The region of the United States that includes the "stroke belt" has dietary patterns that may contribute to the high prevalence of hypertension and cardiovascular disease.
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PMID:Regional variations of blood pressure in the United States are associated with regional variations in dietary intakes: the NHANES-III data. 1251 92

We report 2 cases of patients with hemosiderosis of the central nervous system. The diagnosis was made in 1999 in a stroke unit. The patients had both deafness, but their clinical presentation was different, due to heterogeneous features of this pathology. Hemosiderosis of the central nervous system is due to chronic subarachnoidal hemorrhage. Magnetic resonance imaging is extremely sensitive to the presence of hemosiderin and is the investigation of choice enabling diagnosis and sometimes bleeding source (50 p. cent). The interest of our observations concerned the source of bleeding. In the first patient, diagnostic work-up was negative. For the second one, the deposition of hemosiderin was explained by 3 possible sources. If a bleeding source can be identified, surgery is the optimal treatment. Copper chelation, like Trientine can be used, but there is no evidence-based for using this treatment.
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PMID:[Peripheral haemosiderosis of the central nervous system]. 1291 74

Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is a potent cholesterol-lowering drug that reduces the risk of myocardial infarction and stoke. In this study, we examined its neuroprotective effects against hippocampal CA1 neuronal damage following transient cerebral ischemia in gerbils. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries for 5 min. Pitavastatin, at a dose of 3, 10 or 30 mg/kg, was administered orally twice a day for 5 consecutive days and transient cerebral ischemia was induced in mice 1 h after the last treatment with pitavastatin. Histopathological observations showed that neuronal damage to the hippocampal CA1 neurons, which was observed 5 days after ischemia in animals, was prevented by pitavastatin treatment. Immunohistochemical staining for copper/zinc superoxide dismutase (SOD) and manganese SOD decreased in the hippocampal CA1 sector of gerbils 2 days after ischemia when histological neuronal destruction was not yet found, but was clearly observed in pitavastatin-treated animals. These results indicate that pitavastatin can protect dose-dependently against ischemia-induced neuronal damage and that the mechanism of the neuroprotection may be related to the preservation of SODs, especially copper/zinc-SOD. This in part explains how pitavastatin therapy, which targets free radicals, has beneficial effects against disorders including ischemic stroke.
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PMID:Pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, reduces hippocampal damage after transient cerebral ischemia in gerbils. 1533 28

Edaravone, a newly synthesized synthetic radical scavenger, has been identified and adopted as an anti-stroke agent. However, its mechanism and the effect of edaravone on lipoprotein oxidation are not fully understood. Therefore, whether edaravone could suppress oxidation of low-density lipoprotein (LDL) and be involved in the expression of endothelial nitric oxide synthase (eNOS) in relation to anti-atherogenesis by improving and conserving vascular circulation was investigated. We investigated the in vitro effects of edaravone on copper- and endothelial cell-mediated LDL oxidation, and the expression of eNOS in human umbilical vein endothelial cells (HUVEC) modulated by oxidized LDL. The in vivo effect of edaravone on antioxidative effect was also studied in male rats intravenously administered with edaravone. Edaravone apparently inhibited copper- and HUVEC-mediated LDL oxidation at the concentration equivalent to serum concentrations in clinical use. The intravenous administration of edaravone also enhanced serum radical-scavenging property in rats. We tested the effect of edaravone on protein and mRNA expression of eNOS in HUVEC. Edaravone enhanced eNOS expression in HUVEC, presumably because of increased stability of eNOS mRNA, and reversed eNOS expression reduced by oxidized LDL nearly to the control levels. The present study demonstrates for the first time that edaravone increases eNOS expression with the inhibition of LDL oxidation, and that edaravone can reverse oxidized LDL-mediated reduction in eNOS expression in endothelial cells. The preventive action of edaravone from ischemic disease consequence may be attributed to these eNOS up-regulation with decreased oxidation.
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PMID:Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase. 1572 Oct 14


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