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

We describe a series of experiments in which a subhuman primate model was used to create temporary and permanent cerebral ischemia by three separate mechanisms. In the first group of five baboons, a hemodynamic model was produced by creating unilateral and bilateral carotid stenotic lesions of varying degrees with and without associated reduction in systemic perfusion pressure. Only global ischemic changes and no focal changes resulted. In the second group of three baboons, a macroembolic model was produced by introducing solid particulate material into the extracranial circulation. No reversible contralateral focal neurologic changes resulted. In the third group of 11 baboons, cerebral ischemia was produced by introducing agents known to cause platelet aggregation (arachidonic acid, adenosine diphosphate, and collagen) into the extracranial arterial circulation. Arachidonic acid caused seizures, adenosine diphosphate caused severe postural hypotension, and only collagen fibrils produced a picture resembling a transient ischemic attack. We propose a theory that intravascular activation of the prostaglandin cascade by chemical initiation may result in the pathophysiologic changes of transient cerebral ischemia.
Stroke 1989 Mar
PMID:Pathogenesis of transient ischemic attacks and stroke in baboons. 292 78

In this review we have attempted a synthesis of ideas from cross-bridge theories of muscle contraction with biochemical mechanisms of the actomyosin ATPase. This synthesis of ideas has been based on experimental approaches that permit mechanical and biochemical investigations on the same system. We have formulated an example of how biochemical processes may be influenced by strain in the cross-bridge and have highlighted how much has yet to be learned about the biochemistry (and protein structure) of the working stroke of the cross-bridge. Processes that do not appear to be related to the working stroke such as ATP-induced dissociation of actomyosin or protein-bound ATP hydrolysis appear to be similar kinetically in fibers and isolated actomyosin. But, as might be expected, this is not the case in those processes that involve force production and the performance of mechanical work. There appears to be a sound base from which the mechanochemistry of individual processes within the cross-bridge cycle can be analyzed in detail. There is a need for the development of spectroscopic techniques, particularly those that might detect the rate of Pi and ADP dissociation from cross-bridges into the medium. The combination of pulse photolysis of caged ATP and time-resolved structure analysis by use of synchrotron radiation (53) should lead to better understanding of the structure of cross-bridge states in relation to the chemistry and mechanics of transient intermediates.
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PMID:Relationships between chemical and mechanical events during muscular contraction. 294 Oct 26

We studied the effect of acetylsalicylic acid (ASA) versus placebo on B-thromboglobulin (B-TG) and platelet factor 4 (PF4) plasma levels and ADP-induced platelet aggregation in 25 male patients with transient ischaemic attacks (TIA). The patients were allocated randomly to two groups: 14 patients received oral treatment with ASA 500 mg b.i.d. for 14 days, 11 patients placebo b.i.d. for the same period. B-TG and PF4 plasma levels and ADP-induced platelet aggregation were determined in basal conditions, and two hours, and seven and fourteen days after starting with ASA or placebo. In addition, the same parameters were studied in a group of 20 healthy males of matched age. Basal levels of plasma B-TG and PF4 and the maximal amplitude of ADP-induced platelet aggregation were abnormally high in TIA patients. ASA caused a significant reduction of B-TG plasma levels in TIA patients 2 hours after the first administration, but no effect was observed at the 7th and 14th day of treatment. PF4 plasma levels were unaffected by ASA treatment. It is concluded that ASA, at the dose conventionally used in clinical trials, does not affect the release of two alpha-granule proteins.
Stroke
PMID:No effect of acetylsalicylic acid on B-thromboglobulin and platelet factor 4 plasma levels in patients with transient ischaemic attacks. 294 96

Many characteristics expected from the cyclic ATPase mechanism of Scheme 1 are apparent in reactions measured directly in muscle fibers. ATP detaches rigor cross-bridges rapidly. Reattachment and force generation are also rapid compared to the overall cycling rate, but reversibility of many of the reactions allows significant population of detached states during contraction. ATP hydrolysis shows rapid, "burst" kinetics and is also readily reversible. Pi is released before ADP in the cycle. Pi release is slow in relaxed fibers but is promoted by the interaction between myosin and actin during contraction. Actomyosin kinetics differ in fibers from the ATPase reaction in solution in that Pi binds more readily to AM' X ADP in fibers, and complex, Ca2+-dependent kinetics are evident for ADP release. These properties suggest that the mechanical driving stroke of the cross-bridge cycle and events during physiological relaxation are closely linked to the product release steps. All of the reactions, except step 7a, in the main pathway for ATP hydrolysis, indicated in Scheme 1 by heavy arrows, are fast compared to the overall cycling rate in isometric contractions. Based on this finding, we expect step 7a (or isomerizations of the flanking states) to be relatively slow (approximately 3 s-1). But neither the rate-limiting reaction, nor the expected major dependence on mechanical load or shortening that would explain the Fenn effect, have actually been detected. Use of the pulse photolysis and oxygen exchange methods with structural and spectroscopic techniques and with perturbations of mechanical strain promise to reveal these aspects of the mechanism.
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PMID:Kinetics of the actomyosin ATPase in muscle fibers. 295 53

In the present study the hypothesis is tested that hypoxia causes morphological damage to the inner mitochondrial membrane and that this damage can be reversed by modification of the reoxygenated perfusate. Using the working rat heart model, hearts in group I (n = 40) were subjected to a 30 min normothermic, normoxic phase and a 90 min hypoxic phase, followed by 60 min reoxygenation. Hearts in group II (n = 32) were also subjected to a 30 min normoxic and a 90 min hypoxic phase. However, after 30 min of reoxygenation 1.5 mmol/l 2-mercaptopropionylglycine (MPG) was injected in the reoxygenated solution in order to test its ability to improve mitochondrial function. Mitochondrial function was assessed by measuring oxygen uptake (ST3), ST4, respiratory control index (RCI), ADP/O and oxidative phosphorylation rate (OPR). In addition mechanical function (heart rate, aortic and coronary flow, cardiac output, stroke volume) was monitored along with ultrastructural parameters. 90 min of hypoxia caused a deterioration of all parameters with persistent impairment in hemodynamic, morphologic and biochemical functions after 60 min of reoxygenation (group I). The role of the ATP-synthetases in the pathogenesis of oxygen-paradox is discussed. In contrast, the MPG-enriched reoxygenated solution (group II) improved hemodynamics, ultrastructure and mitochondrial function significantly (alpha = 0.05). It is concluded from these data that the ATP-synthetases are damaged during oxygen-deficiency and that MPG may be a useful drug for protecting the inner mitochondrial membranes during reoxygenation.
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PMID:Improvement of myocardial function after global hypoxia by protection of the inner mitochondrial membrane. 295 43

Glucagon has been shown to increase further the enhanced tolerance for hypoxia of mice with elevated blood ketones and to stimulate ketone utilization by rat brain slices, suggesting that glucagon may affect brain metabolism. In addition to stimulating gluconeogenesis, glucagon alters the metabolism of mitochondria isolated from liver and heart. This study was designed to test whether glucagon can act directly and selectively on brain mitochondrial substrate oxidation. Mitochondria were isolated from normal murine brains using differential centrifugation through Ficoll gradients. Glucagon (3.6 microM) stimulated respiration in the presence of glutamate, and glutamate plus beta-hydroxybutyrate, but not in the presence of glutamate plus malate, succinate or beta-hydroxybutyrate alone. With glutamate as the substrate the hormone significantly increased State 3 oxygen consumption rates from control values of 91 mol O2/mol of cytochrome aa3/min to 117 mols O2/mol/aa2/min (p less than 0.0001), and also increased State 4 rates slightly but significantly. Glucagon did not change mitochondrial respiratory control ratios, but increased estimated rates of ATP synthesis from 434 (control) to 597 mols ADP consumed/mol aa3/min (p less than 0.0001). The data indicate that in vitro glucagon has a direct and substrate-specific stimulatory effect on isolated brain mitochondria. These substrate-specific effects were not altered when respiration was studied in the presence of postmitochondrial supernatant or exogenous 3',5'-cyclic AMP, indicating that glucagon, in addition to an in vivo action via activation of membrane-bound adenylate cyclase, can act, at least in vitro, directly and selectively on brain mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke
PMID:Substrate-specific stimulation by glucagon of isolated murine brain mitochondrial oxidative phosphorylation. 300 83

We studied energy metabolism after experimental subarachnoid hemorrhage in rats. Four different cerebral areas were tested: frontal cortex, occipital cortex, hippocampus, and brainstem. Vmax of the following enzymatic activities was evaluated: in the homogenate: hexokinase, phosphofructokinase, and lactate dehydrogenase for the glycolytic pathway, and glucose-6-phosphate dehydrogenase for the hexose monophosphate shunt; in the purified nonsynaptic mitochondria: NAD+-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase for the Krebs cycle, and cytochrome oxidase for the electron transfer chain. We also evaluated some parameters related to the respiration of nonsynaptic mitochondria (State 3, State 4, uncoupled state, respiratory control ratio, and ADP:O ratio). Subarachnoid hemorrhage did not significantly affect Vmax of the enzymatic activities related to anaerobic and aerobic metabolism; however, mitochondrial respiration was affected, particularly in the presence of NADH-producing substrates (glutamate + malate).
Stroke 1988 Mar
PMID:Bioenergetics of different brain areas after experimental subarachnoid hemorrhage in rats. 335 25

The purpose of our study was to investigate the effects of different doses of acetylsalicylic acid on platelet aggregation. Among inpatients of the National Taiwan University Hospital, 236 cases of completed stroke and seven cases of reversible ischemic neurologic deficit that were diagnosed by computed tomography of the brain and that had not ingested acetylsalicylic acid or acetylsalicylic acidlike drugs for greater than 2 weeks before admission were selected for this study. Thromboxane B2 and 6-keto-PGF1 alpha were measured by radioimmunoassay, threshold concentration of adenosine diphosphate was measured by Born's method, and circulating platelet aggregates were measured by the method of Wu and Hoak. Various single doses of acetylsalicylic acid (75, 300, or 600 mg) or 300 mg acetylsalicylic acid every 6 hours for four doses or one dose of 300 mg acetylsalicylic acid with 75 mg dipyridamole significantly suppressed the mean plasma thromboxane B2 concentrations and elevated the mean adenosine diphosphate threshold concentrations. Abnormal plasma thromboxane B2 concentrations, adenosine diphosphate threshold concentrations, or circulating platelet aggregate ratios were significantly normalized after administration of these regimens. The effects were not significantly different among treatment groups. Forty milligrams of acetylsalicylic acid seemed to have less platelet-inhibitory effect. A single dose of 75 mg acetylsalicylic acid significantly inhibited platelet hyperfunction and effectively corrected the abnormal plasma thromboxane B2 concentrations, adenosine diphosphate threshold concentrations, and circulating platelet aggregate ratios. Higher doses did not enhance the inhibitory effect. In addition, this single dose of acetylsalicylic acid did not significantly suppress plasma 6-keto-PGF1 alpha. We conclude that 75 mg acetylsalicylic acid per day is adequate to inhibit platelet hyperfunction.
Stroke 1988 May
PMID:Inhibitory effect of acetylsalicylic acid on platelet function in patients with completed stroke or reversible ischemic neurologic deficit. 336 89

Platelet-activating factor (PAF) is metabolized by a specific enzyme, PAF acetylhydrolase, which may play an important role in the manifestation of the biological activities of PAF in vivo. The activity of PAF acetylhydrolase in plasma of patients with ischemic stroke was higher than that in healthy controls. The incidence of irreversible platelet aggregation in response to PAF, as well as to ADP, was found to be higher in patients than in controls. The patients whose platelets responded with irreversible aggregation to PAF displayed a higher activity of plasma PAF acetylhydrolase than those with only reversible aggregation. In controls, PAF acetylhydrolase activity correlated positively, although weakly, with LDL-cholesterol, which may reflect the major role of LDL in carrying this enzyme. However, since there was no significant difference in plasma levels of lipids and apoproteins between patients and controls (except for apo B) and there was no significant relationship between the enzyme activity and the levels of other lipids and apoproteins, it is unlikely that increased plasma level of PAF acetylhydrolase activity in stroke patients is accounted for by an abnormality of lipoprotein metabolism. Platelet hyperfunction may be associated with augmented generation of PAF, which, in turn, may bring about the induction of the inactivating enzyme, PAF acetylhydrolase.
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PMID:Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from patients with ischemic cerebrovascular disease. 339 78

148 patients with various forms of cerebrovascular disease (CVD) were studied by means of a multiparametric analysis of in vitro platelet aggregation, based on the following six parameters: ADP and epinephrine primary and secondary aggregation thresholds and percent maximum aggregation induced by optimal concentrations of ADP and epinephrine. These patients were assigned to four study groups, according to clinical diagnosis supported by CT scan, of transient ischemic attack and reversible neurological deficit (TIA-RIND), or completed stroke, in the presence or absence respectively of antiplatelet medical treatment at the time of the study. A statistically significant increase of the in vitro platelet aggregation was found in 44.4% of the untreated TIA-RIND patients and in 33.9% of the untreated stroke patients. However this last group showed a higher percentage of very marked hyperaggregation. Differences between the two treated study groups and controls were not significant. No difference was found in collagen- and ristocetin-induced aggregation between the patient groups and the controls.
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PMID:A multiparametric index of platelet in vitro aggregation in cerebrovascular disease. 342 15


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