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)

Hemodynamic effects of DBcAMP given at 0.05 to 0.3 mg/kg/min for 30 minutes to patients with low cardiac output less than 2.21/min/m2, to patients on IABP and on dopamine or dobutamine were investigated after open-heart surgery. Hemodynamic improvements were observed in cardiac index from 1.81 +/- 0.3 (mean +/- SD) to 2.56 +/- 0.401/min/m2 (p less than 0.001), stroke index from 20.5 +/- 5.2 to 26.4 +/- 5.2 ml/best/m2 (p less than 0.001). TRP decreased from 1963.8 +/- 682.8 to 1153.9 +/- 449.0 (p less than 0.001). These changes were similar to those of Groups II (3.0 greater than or equal to C1 greater than or equal to 2.21/min/m2) and of Group III (C1 greater than 3.01/min/m2). Increases were also observed in CI from 2.28 +/- 0.67 to 2.96 +/- 0.671/min/m2 (p less than 0.001) and in stroke index from 24.4 +/- 7.2 to 29.5 +/- 6.4 ml/best/m2 (p less than 0.001) and significant decreases were observed in TPR and PVR in patients receiving dopamine or dobutamine. These results strongly suggest the inotropic action of DBcAMP was independent on the beta receptor activity and could be a powerful adjunct in the treatment of low cardiac output patients on whom the dopamine or dobutamine was ineffective.
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PMID:[Hemodynamic effects of DBcAMP in patients with low cardiac output syndrome following open-heart surgery]. 608 11

In a previous study, we showed that centrally mediated hypotensive responses are enhanced in aortic barodenervated (ABD) rats as compared with sham-operated (SO) rats. In the present study, we tested the hypothesis that the high basal total peripheral resistance (TPR) of ABD rats accounts for enhanced hypotensive responses to clonidine in this rat model. Aortic barodenervation resulted in acute increases in blood pressure (BP) and heart rate (HR) in anesthetized rats, associated with significant increases in plasma norepinephrine (NE) levels and TPR; cardiac index (CI) and stroke volume (SV) were not affected. After recovery from anesthesia, conscious ABD rats had significantly increased BP at 3 h after barodenervation; BP returned to SO levels by 48 h even though plasma NE levels and TPR remained significantly increased. On the other hand, CI and SV showed significant reductions, beginning at 3 h, and remained low throughout the postdenervation period (48 h); the reduction in CI offset the increase in TRP and may therefore account for the restoration of BP of ABD rats to normal levels. Beginning at similar baseline BP values, cumulative intracisternal (i.c.) doses of clonidine (0.02-2.5 micrograms) elicited greater decreases in BP and plasma NE levels in conscious ABD as compared with SO rats. These responses were centrally mediated because systemic administration of 0.12 micrograms clonidine, a dose that elicited near maximal hypotensive response after i.c. administration, affected neither BP nor plasma NE levels. Contrary to the hypothesis, the hypotensive effect of clonidine in ABD rats resulted exclusively from a reduction in CO (owing to reductions in both HR and SV) because TPR was not affected. These findings suggest that (a) in ABD rats, a reduction in CO offsets a sustained sympathetically mediated elevation in TPR and restores BP to normal levels; and (b) an enhanced hypotensive response to clonidine in ABD as compared with SO rats cannot be accounted for by a higher basal TRP but rather by elicitation of greater reductions in CO through a centrally mediated sympathoinhibitory action.
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PMID:Centrally mediated reduction in cardiac output elicits the enhanced hypotensive effect of clonidine in conscious aortic barodenervated rats. 752 49

1. The effect of the selective histamine H3 receptor agonist, R-alpha-methylhistamine given intravenously (10-100 micrograms kg-1) was examined on baseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea-pigs. 2. R-alpha-methylhistamine produced a dose-dependent hypotension and fall in TPR at 30 and 100 micrograms kg-1. A decrease in heart rate (HR) was observed at a dose of 100 micrograms kg-1. R-alpha-methylhistamine (10-100 micrograms kg-1) also produced a dose-dependent fall in rate pressure product (RPP). There was no effect on cardiac output (CO) or stroke volume (SV) at these doses. 3. Histamine H1 and H2 blockade in animals pretreated with a combination of chlorpheniramine (0.3 mg kg-1) and cimetidine (3.0 mg kg-1) did not alter the haemodynamic actions of R-alpha-methyl-histamine (100 micrograms kg-1, i.v.). Pretreatment with the selective H3 antagonist, thioperamide (1 mg kg-1), completely blocked the action of R-alpha-methylhistamine on haemodynamic parameters. 4. To study the mechanism of action of R-alpha-methylhistamine, the vasodilator hydralazine (1 mg kg-1, i.v.) was used. Hydralazine lowered BP, TRP and RPP in guinea-pigs pretreated with ipratropium (50 micrograms kg-1, i.v.). Hydralazine had no effect on HR, SV or CO. 5. R-alpha-methylhistamine (100 micrograms kg-1) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 micrograms kg-1). On the other hand, the vasodilator hydralazine (1 mg kg-1, i.v.) inhibited the effects of adrenaline (3 micrograms kg-1) on TPR and RPP. The effect of both doses of adrenaline on BP were attenuated by hydralazine. Therefore, the inhibitory effects of R-alpha-methylhistamine are not mediated through a direct action on vascular smooth muscle.6. In adrenalectomized guinea-pigs, R-alpha-methylhistamine (100 microg kg-1) produced a drop in BP and HR.There was no difference between the effects of R-alpha-methylhistamine on blood pressure and heart rate in adrenalectomized and non-adrenalectomized guinea-pigs.7. These results show that activation of peripheral H3 receptors lowers basal BP, HR and TPR, most likely by a peripheral prejunctional mechanism. The fall in BP and TPR is probably due to a decrease in noradrenaline release from sympathetic effector nerves innervating the resistance blood vessels.
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PMID:Production by R-alpha-methylhistamine of a histamine H3 receptor-mediated decrease in basal vascular resistance in guinea-pigs. 790 73

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

Serum and peripheral blood leukocytes from the chimpanzees (Pan troglodytes) of the colony of the Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, were tested for the presence of STLV-I-specific antibodies and proviral DNA. Antibodies were determined by gelatin particle agglutination and Western blot (WB) assays utilizing HTLV-I antigens. Proviral DNA was detected by four PCR assays targeting three different regions of STLV-I genome: the fragments of the env and pol genes and LTR. Twenty of twenty-two DNA samples from WB-positive animals were PCR positive. None of the DNA samples from WB-negative (n = 5) and WB-indeterminate (n = 4) animals was PCR positive. The results of the nested and double nested env PCR tests were fully concordant; the seminested LTR PCR test was much less sensitive. The DNA sequences from the env (483 bp) and the pol (200 bp) genes and LTR (705 bp) were determined for six, two, and two chimpanzee STLV-I isolates, respectively. Phylogenetic analysis revealed that chimpanzee STLV-I isolates can be attributed to three clades. The first of these clades (SS-PTR1/CSA) included STLV-I isolates from the chimpanzees and West African subspecies of African green monkeys (Cercopithecus a. sabaeus). The other clades (S-PTR2 and S-PTR3) included STLV-I isolates only from chimpanzees. However, both S-PTR2 and S-PTR3 clustered together with Central African HTLV-I comprising the human/simian clade (HS-HSA/PTR). This pattern of phylogenetic clustering suggests that interspecies transmission of STLV-I occurred between chimpanzees and African green monkey subspecies as well between chimpanzees and human populations in Central Africa.
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PMID:Phylogenetic analysis of simian T-lymphotropic virus Type I (STLV-I) in common chimpanzees (Pan troglodytes): evidence for interspecies transmission of the virus between chimpanzees and humans in Central Africa. 940 May 94

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

Manipulation of the kynurenine pathway of tryptophan metabolism has yielded a plethora of agents that are now being developed as neuroprotectants and anticonvulsants. This pathway is involved in the production of the excitotoxin quinolinic acid and the neuroprotectant kynurenic acid. Approaches used in the development of therapeutic agents include production of analogues or pro-drugs of kynurenic acid and inhibitors of the enzyme responsible for the synthesis of quinolinic acid. Indeed, analogues of the amino acid receptor antagonist kynurenic acid are now in, or are about to enter, clinical trials for stroke and related disorders. This review summarizes the mechanism of action of these various agents, the development of glutamate receptor antagonists from kynurenic acid and the range of their potential uses in neurology and psychiatry.
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PMID:Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection. 1074 Feb 91

Strokes (intracranial thomboses or haemorrhaging) cause death and disability, but effective treatments are lacking. The metabolism of tryptophan leads to the generation of quinolinic acid, an agonist potentially neurotoxic at glutamate receptors, and kynurenic acid, an antagonist at the same population of receptors. The commercial development of the kynurenine pathway has included the use of analogues of kynurenic acid as antagonists at glutamate receptors. A second has been to use prodrugs of kynurenic acid or its analogues. Alternatively, it is proving possible to interfere directly with the kynurenine pathway to block the synthesis of quinolinic acid and promote the formation of kynurenic acid. This change yields neuroprotectant and anticonvulsant compounds.
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PMID:Inhibitors of the kynurenine pathway. 1075 80

In most tissues, including brain, a major proportion of the tryptophan which is not used for protein synthesis is metabolised along the kynurenine pathway. Long regarded as the route by which many mammals generate adequate amounts of the essential co-factor nicotinamide adenine dinucleotide, two components of the pathway are now known to have marked effects on neurones. Quinolinic acid is an agonist at the N-methyl-D-aspartate sensitive subtype of glutamate receptors in the brain, while kynurenic acid is an antagonist and, thus, a potential neuroprotectant. A third kynurenine, 3-hydroxykynurenine, is involved in the generation of free radicals which can also damage neurones. Quinolinic acid is increasingly implicated in neurodegenerative disorders, most especially the AIDS-dementia complex and Huntington's disease, while kynurenic acid has become a standard for the identification of glutamate-releasing synapses, and has been used as the parent for several groups of compounds now being developed as drugs for the treatment of epilepsy and stroke.
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PMID:Endogenous neurotoxins from tryptophan. 1093 23


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