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

Dopamine (DA), serotonin (5-HT), tryptophan (TRP), 5-hydroxyindole acetic acid (5-HIAA), and GABA were assayed spectrofluorometrically in various regions of 16 human post-mortem brains with acute and old cerebral infarction. In both recent and older strokes a total depletion of DA and 5-HT in the necrotic tissue was associated with mild reduction of these compounds in remote non-ischemic areas of the injured, and less of the contralateral cerebral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed considerable accumulation of both 5-HT and 5-HIAA. Marked elevation of the 5-HT precursor TRP and of GABA was present in both the necrotic center and perifocal edema of acute infarcts, which also showed a mild reduction of total proteins. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA with normal TRP levels, indicating normalization of the previously increased 5-HT metabolism and turnover after decrease of acute cerebral edema. These data which confirm previous studies in experimental cerebral ischemia and stroke indicate that disorders in the metabolism of brain monoamines and other putative neurotransmitters contribute to the development of postischemic brain damage and the complicating cerebral edema. They are also in keeping with the concept that unilateral focal ischemia produces bilateral effects on brain monoamines.
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PMID:Changes of some putative neurotransmitters in human cerebral infarction. 3 76

The effects of gamma-hydroxybutyrate (GHB) on 1) monoamine metabolism, and 2) protein synthesis were examined in a gerbil stroke model. The monoamine metabolism was studied by occluding bilateral common carotid arteries for 15 minutes followed by GHB administered intravenously 3 hours later. Tissue monoamine concentration was examined up to 8 hours after recirculation. Three hours after GHB administration, dopamine (DA) had increased to almost twice that of the non-treated group, whereas homovanillic acid, a metabolite of DA, did not show any significant difference. These results may mean that GHB will facilitate DA synthesis but that it has no influence on its release. Therefore, a DA-mediated increase in cerebral blood flow in the cerebral cortex cannot be expected. Tryptophan, a precursor of 5-hydroxytryptamine (5HT), started to increase just after recirculation reaching a level of over four times that of the control value at 2 to 3 hours, and then starting to decrease in the non-treated group. This decline in tryptophan was markedly facilitated by GHB administration within 1 hour. On the other hand, 5HT administration within 1 hour. On the other hand, 5HT increased only very slightly in the cerebral cortex 1 hour after GHB administration, the change ratio being 1/30 of tryptophan. It can therefore be speculated, that the decrease in tryptophan brought about by GHB administration is due to the improvement in disturbed protein synthesis rather than to stimulation of 5HT synthesis. Protein synthesis was studied by administering GHB 2 minutes prior to a 5-minute temporal common carotid artery occlusion. Ninety minutes after recirculation animals were given a single dose of 14C-leucine and further 60 minutes were allowed to pass before sacrifice. Autoradiographs of the GHB-treated group were compared with those of the non-treated group. With GHB pretreatment, autoradiographs showed an increased uptake of 14C-leucine in at least the hippocampus, thalamus, and hypothalamus, and in two out of three animals, there was diffusely increased uptake. Thus, it is speculated that GHB is effective in improving the protein synthesis in the postischemic period. The favorable function of GHB during cerebral ischemia is regarded by many to be prevention of energy failure by reducing cerebral metabolism. On the other hand, the results derived from the present study suggest that GHB may improve protein synthesis in the postischemic period. Thus, we suggest that GHB is useful if given at the acute stage of cerebral ischemia such as during internal carotid artery or middle cerebral artery occlusion.
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PMID:[Effects of gamma-hydroxybutyrate on monoamine metabolism and protein synthesis after transient global cerebral ischemia]. 140 58

Agitation is a difficult problem to manage when patients suffer from cognitive impairment of varied etiology. In this article, the author proposes a combination of trazodone and tryptophan as a therapeutic possibility. The author presents an illustrative case. The patient was a 67 year old woman with a left cerebrovascular accident and a global aphasia who presented behaviour problems: she was restless, agitated, noisy, aggressive, screaming, howling and crying. In spite of treatment with neuroleptic, anxiolytic and antidepressive medication, behaviour did not improve. The use of a combination of trazodone and tryptophan was successful.
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PMID:[Pharmacotherapy to control agitation in patients with cognitive deficits]. 186 30

Excitatory amino acid (EAA)-mediated synaptic transmission is the most prevalent excitatory system within the mammalian brain. Activation of EAA receptors has been postulated to contribute to neuronal cell death in stroke, epilepsy, hypoglycemia, and Huntington's disease. Kynurenic acid is an endogenous substance that inhibits EAA receptors and may therefore influence important physiologic and pathologic processes. The release of intracerebrally synthesized kynurenic acid into the extracellular fluid (ECF), where it may act at EAA receptors, has not been established in vivo. We studied the synthesis and release of kynurenic acid in the rat striatum using intracerebral microdialysis coupled with high performance liquid chromatography and fluorescence detection. The basal ECF concentration of kynurenic acid in the rat corpus striatum was 17.1 +/- 1.1 nM. Peripheral administration of the immediate biosynthetic precursor of kynurenic acid, L-kynurenine, resulted in marked dose-dependent increases in striatal ECF concentrations of kynurenic acid, peaking at 2-2.5 hr. The highest dose of L-kynurenine (100 mg/kg), administered peripherally, resulted in a 108-fold increase in plasma kynurenic acid levels and a 37-fold increase in cerebral ECF levels. Peripheral administration of kynurenic acid, at a dose that caused plasma levels to increase 430-fold, resulted in only 4-fold increases in striatal ECF concentrations. The precursor responsiveness of striatal ECF kynurenic acid to peripherally infused L-kynurenine was blocked by the central application (via the dialysis probe) of aminooxyacetic acid, an inhibitor of the immediate synthetic enzyme for kynurenic acid, kynurenine aminotransferase. Administration of L-tryptophan was less effective than L-kynurenine in increasing ECF kynurenic acid concentrations and did so at a considerably later time interval (6 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors. 216 40

Palatal myoclonus is a movement disorder consisting of rhythmic myoclonus of the soft palate, pharynx, larynx, and other muscles derived from the embryonal branchial arches. These movements are continuous and involuntary, and the patients are, in general, unaware of them. In the majority of patients, palatal myoclonus persists for life. In oculopalatal myoclonus, the eyes can be involved in the form of a nystagmus. Often a clicking noise in one or both ears is the initial symptom which can be heard by the examiner. A variety of etiologies have been linked to palatal myoclonus. The most common defined cause is a stroke. The variable delay between the proposed cause and the appearance of the disorder causes difficulties in determining the exact etiology. Pathologic findings show a transsynaptic hypertrophic degeneration of the inferior olivary nucleus which is due to a lesion of a specific, inhibitory, anatomic pathway. This somatotopic pathway leaves the contralateral dentate nucleus, passes through the superior cerebellar peduncle, and crosses the posterior commissure before joining the central tegmental tract and descending to the ipsilateral inferior olive. Treatment of palatal myoclonus is only occasionally effective. Some patients have responded to tryptophan, carbamazepine, and trihexyphenidyl. Surgical attempts have not been successful. - In the present paper the authors report on a case of an oculopalatal myoclonus following Leber's optic atrophy which involved the brain stem.
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PMID:[Etiology and clinical aspects of palatal myoclonus]. 224 51

The number of platelets and their content in serotonin (5-HT) were determined in 12-week-old spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and in normotensive Wistar-Kyoto rats (WKY). Spontaneously hypertensive rats had 49% more platelets and a 65% higher platelet 5-HT circulating pool than SHRSP and WKY. An increased synthesis of 5-HT by enterochromaffin cells in SHR is suggested by the lower level of plasma total and albumin-bound tryptophan and by the higher free/bound tryptophan ratio found in those rats, as compared with WKY. In SHRSP, a decrease of platelet survival time was reported, associated to an increased platelet production. This would explain the absence of variation of platelet number and 5-HT content.
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PMID:Platelet serotonin and blood tryptophan in spontaneously hypertensive and normotensive Wistar-Kyoto rats. 241 39

Five consecutively admitted patients with aneurysmal subarachnoid hemorrhage were treated with an indwelling lumbar spinal catheter. Daily samples of cerebrospinal fluid were analyzed for erythrocyte, protein, glucose, dopamine, epinephrine, serotonin, 5-hydroxyindoleacetic acid, tryptophan, histamine, thromboxane, 6-ketoprostaglandin F1 alpha, prostaglandin E, and prostaglandin F2 alpha concentrations. The patients' neurologic grade on admission, hospital course, presence of vasospasm, level of consciousness, computed tomographic and angiographic findings, and outcome were compared with the concentrations of the above substances in the cerebrospinal fluid. All patients had elevated concentrations of serotonin, with the highest levels found early in the hospital course of the patients who developed vasospasm. Tryptophan content increased markedly in association with clinical and angiographic vasospasm. Concentrations of prostaglandin F2 alpha correlated highly with development of and fluctuations in clinical vasospasm, with angiographic findings, with neurologic grade on admission, and with outcome. Our results suggest that prostaglandin F2 alpha may be involved in delayed clinical vasospasm in patients with subarachnoid hemorrhage.
Stroke 1989 Feb
PMID:Prostaglandins and vasoactive amines in cerebral vasospasm after aneurysmal subarachnoid hemorrhage. 246 85

Apolipophorin III (apoLp-III) from the migratory locust, Locusta migratoria, represents the only full-length apolipoprotein whose three-dimensional structure has been solved. In the present study, spectroscopic methods have been employed to investigate the effects of deglycosylation (via endoglycosidase F treatment) and complexation with lipid on the stability and conformation of this protein. Addition of isolated lipid-free apoLp-III to sonicated vesicles of dimyristoylphosphatidylcholine (DMPC) resulted in the formation of relatively uniform disklike complexes with an average Strokes diameter of 13.5 nm. Flotation equilibrium experiments conducted in the analytical ultracentrifuge revealed a particle molecular mass of 588 500 Da. Chemical cross-linking and compositional analysis of apoLp-III.DMPC complexes indicated five apoLp-III molecules per disk and an overall DMPC:apoLp-III molar ratio of 122:1. Circular dichroism (CD) spectra of apoLp-III samples suggested a loss of alpha-helical structure upon deglycosylation, while complexation with DMPC did not significantly alter the helix content (estimated to be > 75%). Fluorescence spectroscopy revealed that the apoLp-III tryptophan fluorescence emission maximum was blue-shifted from 347 to 332 and 321 nm upon deglycosylation and complexation with DMPC, respectively. In quenching experiments with native apoLp-III, tryptophan residues were shielded from the positively charged quencher, CsCl. Increased exposure to KI, CsCl, and acrylamide was observed upon deglycosylation, whereas complexation with DMPC yielded lower Ksv values for KI and acrylamide and an increased value for CsCl versus native lipid-free apoLp-III. In guanidine hydrochloride denaturation studies monitored by CD or fluorescence, native, lipid-free apoLp-III displayed a denaturation midpoint of 0.60 M, and delta GDH2O = 5.37 kcal/mol was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors affecting the stability and conformation of Locusta migratoria apolipophorin III. 814 60

I have discussed 10 "new" diseases. Some produce heart disease, some produce strokes, and some may produce both heart disease and stroke. It is of great interest to me that some of them are due not to nature's ravages but to the ingestion of agents such as toxic oil, L-tryptophan, ergot, adriamycin, and psychotropic drugs. I classify these man-made diseases as "environmental" diseases. Use of some of the offending agents cannot be justified; for example, toxic oil and L-tryptophan are not needed. On the other hand, drugs such as ergot preparations are extremely useful when used properly.
Heart Dis Stroke
PMID:"New" causes of heart disease and stroke. 814 82

The conformation of myosin subfragment 1 (S1) in the vicinity of the ATP sensitive tryptophan (Trp510) and the highly reactive thiol (SH1), both residing in the "probe-binding" cleft at the junction of the catalytic and lever arm domains, was studied to ascertain its role in the mechanism of energy transduction and force generation. In glycerinated muscle fibers in rigor, a fluorescent probe linked to SH1 detects a strained probe-binding cleft conformation following a length transient by altering emission intensity without detectably rotating. In myosin S1 in solution, the optical activity of Trp510 senses conformation change in the probe-binding cleft caused by substrate analog trapping of S1 in various structures attainable transiently during normal energy transduction. Also in S1 in solution, the induced optical activity of a fluorescein probe linked to SH1 shows sensitivity to changing probe-binding cleft conformation caused by nucleotide binding to the S1 active site. The changes in the optical activity of Trp510 and SH1 bound fluorescein in response to nucleotide or nucleotide analog binding are interpreted structurally using the S1 crystallographic coordinates and aided by a model of energy transduction that pivots at Gly699 to change probe-binding cleft conformation and to displace the S1 lever arm as during force generation. The crystallographic structure of the probe-binding cleft in S1 resembles most the nucleotide bound conformation in the native protein. A different structure, generated by pivoting at Gly699, better resembles the native rigor conformation of the probe-binding cleft. Pivoting at Gly699 rotates probes at SH1 suggesting that length transients on fibers in rigor do not cause pivoting at Gly699 or reverse the power stroke.
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PMID:Tertiary structural changes in the cleft containing the ATP sensitive tryptophan and reactive thiol are consistent with pivoting of the myosin heavy chain at Gly699. 960 97


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