Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all.
Stroke
PMID:Intravenous glycerol in cerebral infarction: a controlled 4-month trial. 36 Apr 95

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.
 ...
PMID:Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. 109 Mar 93

Glycerol 50 g infused i.v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191-923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7-110.8 mg/l was attained 0-1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29-0.56 h compared to 1.03-3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09-0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
 ...
PMID:Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol. 161 50

The effect of glycerol on local cerebral blood flow was examined in patients with chronic ischemic cerebrovascular diseases (CVD). Twelve patients with minor completed stroke (10 cases) or transient ischemic attacks (2 cases) were subjected to the study (8 males, 4 females, the age ranging 27 to 70 with average of 56 +/- 15 years). Cerebral blood flow (CBF) was measured with stable xenon computerized tomography (Xe-CT). Each patient had 3 sequential Xe-CTs; resting, with intravenous administration of 200 ml of glycerol (group A) or lactated Ringer's solution (group B), and with intravenous administration of 1 g of acetazolamide. The resting CBF, CBF with glycerol, and CBF with acetazolamide were 30.4 +/- 1.6 ml/100 g/min (ml), 35.1 +/- 2.6 ml, 44.2 +/- 2.2 ml in group A, and 29.9 +/- 2.0 ml, 28.5 +/- 1.9 ml, 45.0 +/- 3.2 ml in group B, respectively. Glycerol increased CBF significantly in patients with chronic CVD, and seemed to be effective in ameliorating chronic low perfusion state in these patients.
 ...
PMID:[The effect of glycerol on local cerebral blood flow in patients with chronic ischemic cerebrovascular lesions]. 179 9

1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.
 ...
PMID:Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol. 231 Jun 58

The state of water in cerebral ischemia was studied by using the proton nuclear magnetic resonance (1H-NMR) method. Cerebral ischemia was induced experimentally in Mongolian gerbils by unilateral ligation of the common carotid artery. Longitudinal (T1) and transverse (T2) relaxation times of the ischemic brain were measured with a pulse FT-NMR spectrometer and the water content was determined by the wet/dry method. Quantitative analysis of the relaxation times was performed sequentially during the initial 7 hours following ligation and the data were compared with those of brain edema previously reported by S. Naruse in the rat. Characteristic findings in brain ischemia include prolongation of the slow component of T2 and increase in the water content. A quantitative comparison of relaxation rate and water content demonstrates that ischemic brain edema in Mongolian gerbils is different from cytotoxic and vasogenic types of brain edema. When R2 (1/T2) was plotted against the water content, the slope value of ischemia in the gerbil was between the slope values of the TET intoxication and cold injury induced edemas reported previously. From these results, it might be said that ischemic brain edema includes both the cytotoxic and vasogenic types of brain edema. Glycerol was demonstrated to affect brain ischemia by decreasing the water content and by shortening the slow component of T2. By analysis of the relaxation times and water content, we examined the pathophysiological characteristics of water molecules in ischemic brain tissue.
Stroke
PMID:Proton NMR relaxation times in ischemic brain edema. 381 Jul 13

Glycerol is a potent osmotic dehydrating agent with additional effects on brain metabolism. In doses of 0.25-2.0 g/kg glycerol decreases intracranial pressure in numerous disease states, including Reye's syndrome, stroke, encephalitis, meningitis, pseudotumor cerebri, central nervous system tumor, and space occupying lesions. It is also effective in lowering intraocular pressure in glaucoma and shrinking the brain during neurosurgical procedures. Hyperosmolality with rebound cerebral overhydration is of concern, especially in patients with altered blood brain barriers. They may be avoided if glycerol is administered on an intermittent rather than a continuous basis. Intravascular hemolysis does not occur with oral use. When administered intravenously, hemolysis can be minimized by using glycerol 10% in dextrose 5% with normal saline at rates of 6 mg/kg/min or less. However, intravenous doses of 1-2 g/kg every 2 hr can be administered safely in severe cases of elevated ICP. In such patients, glycerol serum concentration, serum osmolality and ICP monitoring are required to optimize glycerol therapy.
 ...
PMID:Glycerol: a review of its pharmacology, pharmacokinetics, adverse reactions, and clinical use. 692 4

Ischemic brain edema promotes focal cerebral ischemia by increasing intracranial pressure and thereby reducing perfusion pressure, obstructing capillaries and prolonging transport routes within ischemic tissue. There is clinical and experimental evidence that osmotic agents counteract these mechanisms. Moreover, glycerol may act as a free radical scavenger, antioxidant, and activator of plasma prostaglandin (PGI2), resulting in vasodilation. Improvements in ischemic brain energy metabolism after glycerol administration has also been postulated. Results of clinical trials on glycerol treatment of acute ischemic stroke were not conclusive: some demonstrated improved survival in the acute stage, in others survivors benefited in terms of neurological status and/or daily living activities. Other trials did not reveal any superiority of glycerol treatment over placebo. Glycerol is given intravenously as a 10% solution or orally. By the oral route higher intravascular glycerol concentration can be achieved with smaller quantities of fluid. Possible side effects include elevation of blood glucose level with subsequent lactate acidosis in the ischemic brain, serum hyperosmolarity after long-term glycerol administration and--when given intravenously--volume overload in patients with congestive heart failure and hemolysis that may cause renal failure.
 ...
PMID:[Treatment of ischemic cerebral infarct with glycerine]. 756 70

Glycerol is a naturally occurring 3-carbon alcohol in the human body. It is the structural backbone of triacylglycerol molecules, and can also be converted to a glycolytic substrate for subsequent metabolism. Serum glycerol concentrations approximate 0.05 mmol/L at rest, and can increase to 0.30 mmol/L during increased lipolysis associated with prolonged exercise or caloric restriction. When glycerol is ingested or infused at doses greater than 1.0 g/kg bodyweight, serum concentrations can increase to approximately 20 mmol/L, resulting in more than a 10 mOsmol/kg increase in serum osmolality. Glycerol infusion and ingestion have been used in research settings for almost 60 years, with widespread clinical use between 1961 and 1980 in the treatment of cerebral oedema resulting from acute ischaemic stroke, intraocular hypertension (glaucoma), intracranial hypertension, postural syncope and improved rehydration during acute gastrointestinal disease. Since 1987, glycerol ingestion with added fluid has been used to increase total body water (glycerol hyperhydration) by up to 700 ml, thereby providing benefits of improved thermoregulation and endurance during exercise or exposure to hot environments. Despite the small number of studies on glycerol hyperhydration and exercise, it appears to be an effective method of improving tolerance to exercise and other heat-related stressors.
 ...
PMID:Glycerol. Biochemistry, pharmacokinetics and clinical and practical applications. 980 72

Brain oedema is a major cause of early death after stroke. Glycerol is a hyperosmolar agent that is claimed to reduce brain oedema. We sought to determine whether I. V. glycerol treatment in acute stroke, either ischaemic or haemorrhagic, influences death rates and functional outcome in the short or long term and whether the treatment is safe. The Cochrane Stroke Group Trials Register was searched, conference proceedings were screened and some trialists were personally contacted. We considered all completed, controlled, published and unpublished comparisons, evaluating clinical outcome, in which intravenous glycerol treatment was initiated within the first days after stroke onset. Death from all causes, functional outcome and adverse effects were analysed. Analysis of short term death for acute ischaemic and/or haemorrhagic stroke was possible in ten trials where 482 glycerol treated patients were compared with 463 control patients. Glycerol was associated with a non-significant reduction in the odds of death within the scheduled treatment period (OR 0.78, 95 % Confidence Intervals 0.58-1.06). Among patients with definite or probable ischaemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (odds ratio 0.65, 95 % CI 0.44-0.97). However, at the end of the scheduled follow up period there was no significant difference in the odds of death (odds ratio 0.98, 95 % CI 0.73-1.31). Functional outcome was reported in only two studies and there was a non-significant positive effect on outcome at the end of scheduled follow up (odds ratio 0.73, 95 % CI 0.37-1.42). Haemolysis seems to be the only relevant adverse effect of glycerol treatment. This systematic review suggests a favourable effect of glycerol treatment on short term survival in probable or definite ischaemic stroke, but the magnitude of the treatment effect may be minimal (as low as a 3 % reduction in odds). Because of the relatively small number of patients and because the trials have been performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.
 ...
PMID:Glycerol for acute stroke: a Cochrane systematic review. 1196 51


1 2 Next >>