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

Basic neuroscience research findings during the past five years have established a clear relationship between the excitatory amino acid (EAA) neurotransmitters (glutamic and aspartic acid) and various pathological states. A major mechanism of neural tissue degeneration following cerebral ischemia, and perhaps other neurodegenerative diseases, seems to involve overactivity of the EAA system in brain. This process is called delayed excitotoxicity and it has become a focal point for the design of new drugs that inhibit its course (EAA receptor blockers). Very recently it has been shown that it is possible to block delayed excitotoxicity using adenosine A1 receptor agonists which inhibit EAA release pre-synaptically. This approach is very effective in reducing post-stroke neurological damage in a number of animal models and has certain advantages when compared to the EAA receptor blocker strategy. Adenosine agonists not only inhibit excitotoxicity but they also block granulocyte activation and the capillary no-reflow phenomenon which results. An additional adenosinergic approach involves brain permeable adenosine uptake blockers which would serve to increase adenosine levels somewhat selectively at ischemic foci thereby inhibiting EAA release. The adenosinergic approach to stroke therapeutics may be a potentially effective strategy for new drug development in neurology, and may have general applicability to other neurodegenerative disease states where excitotoxicity is being implicated.
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PMID:Adenosinergic approaches to stroke therapeutics. 197 12

Within 5 hours of the onset of ischaemic stroke the filterability patterns and the counts of the granulocyte, monocyte and lymphocyte subfractions were monitored. The results were compared to those of a healthy matched control group and to those of a matched group with cardiovascular risk factors. The granulocyte filterability rate was significantly impaired in the group at risk and even more so in the stroke group suggesting alterations in it may be a sign of latent ischaemia.
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PMID:Leucocyte rheology in the early stages of ischaemic stroke. 277 Jan 90

Six anesthetized dogs treated with indomethacin, prostacyclin (PGI2), and heparin were compared with 7 anesthetized controls (ischemia without treatment) to determine whether cyclooxygenase inhibition would lead to enhanced granulocyte accumulation because of preferential formation of lipoxygenase products. Cortical somatosensory evoked response, [14C]iodoantipyrine autoradiographic blood flow, and 111In-labelled granulocyte accumulation were compared 4 hours after a 60-minute exposure to multifocal brain ischemia. Treatment with indomethacin, PGI2, and heparin eliminated neuron-disabling brain blood flows without altering early postischemic granulocyte accumulation. Granulocyte accumulation after 4 hours of reperfusion was not significantly different in control and treated dogs. The final amplitude of the cortical somatosensory evoked response in the treated group averaged 38.0 +/- 13.6% (mean +/- SEM) of the corresponding baseline value compared with 21.0 +/- 4.6% in the control group, but this difference was not significant.
Stroke
PMID:Indomethacin, prostacyclin, and heparin improve postischemic cerebral blood flow without affecting early postischemic granulocyte accumulation. 329 33

In an anesthetized canine model in which ischemia was induced by incremental air embolism, 16 animals were exposed to 1 hr of ischemia and monitored for 10 min (n = 4), 60 min (n = 6), or 240 min (n = 6). Fourteen animals were observed for corresponding periods without being subjected to ischemia 70 min (n = 4), 120 min (n = 4), or 300 min (n = 6). Autologous granulocytes were labeled with 111In and reinfused just before ischemia. At the conclusion of each experiment, a 14C-iodoantipyrine autoradiographic blood flow study was performed. Granulocyte accumulation measured by gamma scintigraphy (cpm/gm) occurred in the injured hemisphere of ischemic animals at 60 min in anterior brain segments and at 240 min in anterior, middle, and posterior segments. By means of a double-label autoradiography technique, clustering of punctate granulocyte images was detected in regions of low flow or heterogeneous flow in half of the animals at both 60 min and 240 min postischemia. Granulocyte clustering did not occur in the autoradiograms of nonischemic animals. The results implicate granulocyte participation in the acute phase of ischemic brain injury and signal a convergence of hemostatic and inflammatory processes during the immediate postischemic period.
Stroke
PMID:Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. 396 35

Separated lymphoid cells from patients suffering from multiple sclerosis (MS) were co-cultivated with various cell lines. Over 80% of such co-cultivations showed destruction of the tissue-culture monolayers, whereas less than 5% of "normal" blood co-cultivation behaved in the same manner. Because of the possible involvement of virus in the aetiology of MS, many positive co-cultivations were 1) examined electron-microscopically, but no virus particles were seen; and 2) tested for measles and herpes viruses using immunofluorescent techniques, but these also proved negative. Leukocytes from stroke patients showed monolayer destruction in about 50% of cases. Granulocyte contamination was high in the stroke blood samples. Reduction of granulocyte numbers to "normal" levels completely abrogated the effect in the stroke samples, but had no effect on the MS co-cultivations. Monolayer destruction by MS leukocytes also appeared not to be due to lymphotoxin.
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PMID:Monolayer destruction by leukocytes from patients with multiple sclerosis. 699 97

We have previously demonstrated an association between development of the cotton lung disease byssinosis and endotoxin concentrations in the work environment. Endotoxin has been shown to exert its effects through granulocyte activation and hence release of elastase and other proteases at the bronchoalveolar surface. alpha 1-Antitrypsin is a protease inhibitor, and hence, alpha 1-Antitrypsin concentrations in the blood and then on the alveolar surface might be important for the protection against endotoxin effects. Airborne endotoxin concentrations in the work place and S-alpha 1-Antitrypsin (a1A) was measured in 226 workers in cotton mills in Vejle and of these 206 were further phenotyped. The following models were considered: Model 1. The S-a1A concentration is determining the risk for development of byssinosis. The lower the concentration, the higher the risk. Model 2. The degree of exposure to endotoxin is determining. The higher the airborne concentration and the longer time working in that, the higher is the risk. Model 3. The phenotype of a1-A is determining. Only MS and/or MZ phenotypes represent a risk disposition. The goals for analytical quality for a1-A measurements were estimated in the two relevant models. The specifications are: Regarding model 1: analytical coefficient of variation CVA < 3% and analytical bias--1 mumol/L < BA < +1 mumol/L. Model 2: a1-A is not of significant importance and specifications cannot be evaluated. Regarding model 3: There is a direct relationship between cut-off point and analytical performance, e.g. an imprecision of SA 3 mumol/L and cut-off of 38 mumol/L will allow for a BA of -1 mumol/L.
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PMID:Is a low serum concentration of alpha 1-antitrypsin associated with an increased susceptibility for byssinosis in cotton mill workers? Considerations regarding analytical quality requirements and economical consequences. 797 59

We evaluated clinical effects and toxicities of a combination of fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) for treatment of infections complicated with hematological disorders in 61 patients. Fifty-eight patients were evaluable, including 40 with acute leukemia, 13 with malignant lymphoma and 5 with other hematological disorders. Clinical efficacies were excellent in 21 cases, good in 13 cases, fair in 2 cases and poor in 22 cases. The efficacy rate was 58.6% (34 cases/58 cases). This treatment was also effective in 12 of 20 cases in which granulocyte counts were less than 500/microliters through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 1 case. Mild elevations of GOT and GPT were observed. Thus, the combination of FOM and CVA/TIPC is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.
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PMID:[Clinical effects of a combination treatment with fosfomycin and clavulanic acid/ticarcillin for infections in patients complicated with hematological disorders]. 805 94

Although the microvascular compartment contributes significantly to intravascular volume, its importance to disease is often underestimated. Events surrounding cerebral ischemia and recent interest in strategies which may lead to cerebral artery reperfusion in thrombotic or embolic stroke have raised enquiries about the role(s) the microvasculature may play during ischemia and reperfusion. Except in a few instances, little is known about the organization of the microvasculature in cerebral tissue. However, it is apparent that ischemia, inflammatory insults, and infectious processes affect the cerebral microvascular endothelia, cellular elements of the circulating blood compartment, and hemostasis. The precise mechanisms are under study. Observations in isolated microvascular systems from brain tissue, direct visualization of the pial cortical vasculature, and in situ preparations which allow study of the subcortical microvasculature have added to our understanding of these processes. During focal cerebral ischemia and reperfusion alterations of endothelial cell reactivity, coagulation system activation, and granulocyte-endothelial cell interactions are a few of the events affecting microvascular integrity which have been documented. Oxygen free radical generation, selectin and integrin expression and intercellular adhesion, vasomotor responses, endothelial permeability changes, and coagulation system and platelet activation are some of the microvascular processes currently under study which appear to be triggered during ischemia and reperfusion. In view of these events the responses of the cerebral microvasculature to ischemic injury remain relatively unexplored.
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PMID:Microvascular changes during cerebral ischemia and reperfusion. 818 69

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.
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PMID:Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion. 823 Dec 1

The 21-aminosteroid tirilazad mesylate (U74006F) is a lipophilic antioxidant and free radical scavenger that has been reported to attenuate brain or spinal cord injury caused by trauma, stroke, ischemia and reperfusion injury. In this study, we have examined the effect of U74006F in reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. Rats received either 1) TNBS and U74006F 2) TNBS and vehicle or 3) saline and vehicle. Rats were sacrificed 1, 2 and 3 weeks after IBD induction. Colon to body weight ratio (an index of tissue edema) was markedly increased in the vehicle-treated IBD rats after 1 week of administration of TNBS. The ratio was significantly lower after U74006F treatment and the trend remained even after 3 weeks of chronic inflammation. Myeloperoxidase (MPO) activity in vehicle-treated IBD rats was substantially increased compared with controls during the entire 3 weeks of the experiment. U74006F-treated animals had significantly reduced MPO activity (60% lower) when compared with vehicle-treated animals at the end of the second and third weeks. These observations were confirmed by histopathology studies showing reduced granulocyte infiltration after drug treatment. U74006F treatment decreased basal (by 70%) and fMLP stimulated (by 75%) superoxide generation from colonic tissue from IBD rats compared with vehicle treatment after 2 weeks, but there was no apparent difference in superoxide generation among all three groups after 3 weeks. The results of this study suggested that administration of U74006F effectively reduces the inflammatory parameters in this chronic rat model of IBD. As such, U74006F may be therapeutically beneficial for the treatment of IBD in humans.
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PMID:The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats. 855 41


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