Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

BACKGROUND AND PURPOSE--Endothelin-1, in concentrations similar to that present in cerebrospinal fluid after fluid percussion brain injury (FPI), increases superoxide anion (O2-) production. Endothelin-1 also contributes to altered cerebral hemodynamics after FPI through impairment of ATP-sensitive K+ (KATP) channel function through protein kinase C (PKC) activation. Generation of O2- additionally occurs after FPI. Nitric oxide and cGMP elicit pial artery dilation through KATP channel activation. The present study was designed to determine whether PKC activation generates O2-, which, in turn, could link such activation to impaired KATP channel function after FPI. METHODS--Injury of moderate severity (1.9 to 2.1 atm) was produced by the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O2- generation. RESULTS--Phorbol 12, 13-dibutyrate (10(-6) mol/L), a PKC activator, increased superoxide dismutase-inhibitable NBT reduction from 1+/-1 to 37+/-5 pmol/mm2. Staurosporine (10(-7) mol/L), a PKC antagonist, blocked the NBT reduction after phorbol 12,13-dibutyrate and blunted the NBT reduction observed after FPI (1+/-1 to 15+/-2 versus 1+/-1 to 5+/-1 pmol/mm2 after FPI in the absence versus presence of staurosporine). Exposure of the cerebral cortex to a xanthine oxidase O2--generating system increased NBT reduction in a manner similar to FPI and blunted pial artery dilation to the KATP channel agonists cromakalim and calcitonin gene-related peptide, the nitric oxide releasers sodium nitroprusside and S-nitroso-N-acetylpenicillamine, and the cGMP analogue 8-bromo-cGMP (10+/-1% and 21+/-1% versus 4+/-1% and 9+/-1% for 10(-8) and 10(-6) mol/L cromakalim before and after activated oxygen-generating system exposure). CONCLUSIONS--These data show that PKC activation increases O2- production and contributes to such production observed after FPI. These data also show that an activated system that generates an amount of O2- similar to that observed with FPI blunted pial artery dilation to KATP channel agonists and nitric oxide/cGMP. These data suggest, therefore, that O2- generation links PKC activation to impaired KATP channel function after FPI.
Stroke 1999 Jan
PMID:Superoxide generation links protein kinase C activation to impaired ATP-sensitive K+ channel function after brain injury. 988 Apr 4

A case of shoulder-hand syndrome (algodystrophy, reflex sympathetic dystrophy) in a stroke patient is presented. Six weeks after stroke the condition started with pain, swelling and considerable reduction of movements of the hand and wrist followed by involvement of shoulder joint a few days later. Initially, the complaints were attributed to excessive rehabilitation, however, when cessation of exercises and anti-inflammatory treatment failed to improve, the diagnosis of shoulder-hand syndrome was suspected. Three phase bone scintigraphy performed 2 weeks after the onset of symptoms revealed features of possible algodystrophy. X-ray revealed no significant changes. The patient satisfactory responded to nasal salmon calcitonin treatment 300 units daily during 4 weeks. The reassessment performed 3 months after the onset of disease showed regression of most signs and symptoms as well as satisfactory range of motion of the hand and shoulder. Bone scintigraphy revealed typical algodystrophy pattern (diffusely increased periarticular uptake). The cause of such evolution of scintigraphic changes as well as some implications of nasal calcitonin administration were discussed.
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PMID:[Shoulder-hand syndrome after stroke: a case report]. 1039 36

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent dilators of human brain arteries, and they have been implicated in the neurogenic inflammation underlying migraine headache and in the evolution of stroke, respectively. However, little is known about the presynaptic and postsynaptic distribution of their respective receptors in the human cerebrovascular bed and trigeminovascular system. In the current study, the expression of mRNA for ADM and the two cloned human CGRP1 receptors (identified here as A-CGRP1 receptors [Aiyar et al., 1996] and K-CGRP1 receptors) [Kapas and Clark, 1995] were evaluated in human brain vessels and trigeminal ganglia. Further, the ability of CGRP and ADM to activate adenylate cyclase in cerebromicrovascular and astroglial cell cultures was determined, and the receptors involved were characterized pharmacologically. Isolated human pial vessels, intracortical microvessels, and capillaries, as well as cultures of brain endothelial (EC), smooth muscle (SMC), and astroglial (AST) cells, all expressed mRNA for the two cloned CGRP1 receptors; however, message for the K-CGRP1 receptor was barely detectable in microvascular tissues and cells. In contrast, only isolated capillaries and cultured AST exhibited message for the ADM receptor. In human trigeminal ganglia, mRNA for ADM and the two CGRP1 receptors was systematically present. The CGRP dose-dependently increased (up to 50-fold) cAMP formation in cell cultures, an effect significantly blocked by 0.1 to 10 micromol/L of the CGRP1 receptor antagonist CGRP8-37. The ADM receptor agonist, ADM13-52 (1 micromol/L), similarly increased cAMP production in all cell types, and this response was virtually abolished by 1 micromol/L CGRP8-37. Low concentrations (1 to 10 micromol/L) of the ADM receptor antagonist ADM22-52 blocked the ADM13-52-induced cAMP formation in AST (26% at 10 micromol/L, P < 0.05), whereas they potentiated this response in brain EC and SMC (40% and 100%, P < 0.001, respectively). Even at a higher dose (50 micromol/L), ADM22-52 inhibited the ADM13-52 effect in vascular cells (45%) much less effectively than in AST (95%). These results indicate that both CGRP and ADM can affect human brain vessels through a CGRP1 receptor, and they further suggest the presence of functional ADM receptors in human astroglial cells.
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PMID:Functional calcitonin gene-related peptide type 1 and adrenomedullin receptors in human trigeminal ganglia, brain vessels, and cerebromicrovascular or astroglial cells in culture. 1056 74

The reactivity of intrarenal arteries to vasoconstrictor and vasodilator polypeptides was examined in adult stroke-prone spontaneously hypertensive rats (SHRSP). The contraction response to endothelin-1 (ET-1) was greater in SHRSP than in age-matched Wistar-Kyoto rats (WKY), and so was the pD2 estimate (8.05+/-0.03 in SHRSP, and 7.73+/-0.06 in WKY; n=5, P < 0.05). The contraction response to, and the pD2 estimate of, vasopressin were comparable in SHRSP and WKY. Neuropeptide Y did not contract the intrarenal arteries. In norepinephrine-precontracted arteries with intact endothelium, substance P and neurokinin A did not relax the arteries of either SHRSP or WKY, while calcitonin gene-related peptide (CGRP) induced a profound relaxation response. Relaxation response to CGRP was significantly greater in SHRSP than in WKY. Atrial, brain, and C-type natriuretic peptides (ANP, BNP, CNP), vasoactive intestinal polypeptide (VIP), and peptide histidine isoleucine (PHI) all caused relaxation responses, with a greater extent of relaxation to ANP, BNP, and VIP and a less extent to CNP and PHI. However, there were no significant differences in these relaxation responses between SHRSP and WKY. The current results revealed the character of heterogeneity of rat intrarenal arteries in response to vasoconstrictor and vasodilator peptides, and showed an enhanced reactivity to ET-1 and to CGRP in SHRSP.
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PMID:Reactivity of intrarenal arteries to vasoconstrictor and vasorelaxant polypeptides in adult stroke-prone spontaneously hypertensive rats. 1064 9

Studies on the aetiology and treatment of post-stroke hand oedema and shoulder-hand syndrome (SHS) published from January 1973 until August 1998 were identified. Eleven studies were included with at least some control for confounding. These were evaluated on 11 methodological criteria and by standardized effect sizes. There were five aetiological studies: four cohort studies and one study consisting of two case series using a within-subjects design. The matters investigated included lymph scintigraphy in hand oedema, bone scintigraphy, putative risk factors and the existence of autonomic dysregulation and peripheral nerve lesions in SHS. There were six therapeutic studies: one randomized controlled trial, one non-randomized controlled trial, one cohort study and three case series, of which two studies used a within-subjects design. These studies investigated continuous passive motion and neuromuscular stimulation in hand oedema as well as oral corticosteroids, intramuscular calcitonin and trauma prevention in SHS. A great diversity of pathophysiological and therapeutic insight was found. Based on systematic analysis of the literature, the following conclusions seem justified: (i) the shoulder is involved in only half of the cases with painful swelling of wrist and hand, suggesting a "wrist-hand syndrome" between simple hand oedema and SHS; (ii) hand oedema is not lymphoedema; (iii) SHS usually coincides with increased arterial blood flow; (iv) trauma causes aseptic joint inflammations in SHS; (v) no specific treatment has yet proven its advantage over other physical methods for reducing hand oedema; and (vi) oral corticosteroids are the most effective treatment for SHS.
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PMID:Systematic review of aetiology and treatment of post-stroke hand oedema and shoulder-hand syndrome. 1078 34

Adrenomedullin is a potent endogenous vasodilating and natriuretic peptide that is similar in structure to calcitonin gene-related peptide (CGRP). The gene involved in the synthesis of adrenomedullin has been localized to a single locus on chromosome 11, with specific sites on the genome to regulate transcription. Adrenomedullin is normally found in human plasma and in other organs. It is thought that one of the clearance sites for this peptide is in the pulmonary circulation. Endothelial cells are assumed to be one of the major sources of plasma adrenomedullin. Adrenomedullin is an important factor in regulating local and systemic vascular tone, by its activity as an autocrine/paracrine and circulating hormone. Depending on the site of action, adrenomedullin seems to bind to a CGRP receptor and send signals by either cyclic adenosine monophosphate or nitric oxide. From the results of experiments in animals, it has become clear that adrenomedullin's effects are species-specific. However, what is commonly seen with adrenomedullin is peripheral vasodilatation, a positive inotropic action, increased cardiac output, and increased stroke volume. In addition, adrenomedullin has actions in the brain, lungs, and kidneys to regulate regional hemodynamics. With these activities defined, recent studies have suggested a potential therapeutic role for adrenomedullin.
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PMID:Adrenomedullin: a vasoactive and natriuretic peptide with therapeutic potential. 1172 67

It is estimated that 28,000,000 women in the United States have low bone mass (osteopenia) or osteoporosis. More than 1.5 million osteoporotic fractures occur annually. Because osteoporosis is asymptomatic until fracture occurs, early diagnosis requires both an awareness of risk and specific testing. The National Osteoporosis Foundation (NOF) has published guidelines for diagnosis and treatment, but these have important limitations. Bone mineral density (BMD) testing is the method of choice for diagnosis, and is more predictive of fracture risk than hypertension is of stroke or hypercholesterolemia is of myocardial infarction. Although the diagnosis of osteoporosis, as defined by the World Health Organization, is a T-score of < or =-2.5, the association between BMD and fracture risk is a continuous rather than threshold effect, and NOF guidelines suggest treating at higher T-scores, depending on risk factors. Important risk factors include age, current smoking, low body weight (<127 lbs.), maternal history of fracture, and personal history of fracture. Data from the National Osteoporosis Risk Assessment (NORA) study are presented, demonstrating the usefulness of peripheral BMD measurements in identifying postmenopausal women at risk of fracture. Several therapeutic options, including hormone replacement therapy, raloxifene, calcitonin, alendronate, and risendronate, are now available to the clinician. It can be argued that we currently have all necessary tools to eliminate osteoporosis and osteoporotic fracture.
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PMID:The role of the primary care physician in diagnosis and management of osteoporosis. 1208 Dec 56

The expression pattern of proinflammatory cytokines, neuronal nitric oxide synthase (nNOS), substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord and the bladder in response to permanent middle cerebral artery occlusion (MCAO) was investigated. In this connection, the gene expression of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 in the lumbosacral spinal cord and the bladder as determined by real-time polymerase chain reaction was upregulated. In the spinal cord, the immunoreactivity of TNF-alpha and IL-1beta was mainly localized in the ventral horn motoneurons contralateral to MCAO. In the bladder, TNF-alpha was mainly expressed in the inflammatory cells. The expression of nNOS immunoreactivity as well as nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining in the spinal cord and bladder was also markedly increased in response to MCAO. Furthermore, the temporal and spatial expression of nNOS paralleled that of TNF-alpha and IL-1beta in the spinal cord. On the other hand, there was no noticeable change in gene expression and immunoreactivity of SP and CGRP. The present results have shown that cytokines and nNOS expression are elevated in areas far removed from the primary site of ischemic infarct, namely, the lumbosacral spinal cord and bladder. This together with some neuronal deaths maybe linked to the dysfunction of the latter in a clinical stroke. On the other hand, the apparent lack of SP and CGRP changes following MCAO suggests that the two neurotransmitters are not directly involved.
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PMID:Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. 1512 Aug 43

Adrenocorticotroph cell pituitary adenomas immunoreactive for adrenocorticotropic hormone (ACTH) but unassociated with preoperative signs of hypercortisolism constitute between 6% and 43% of all ACTH adenomas. Few large series have been published. At our referral center for pituitary diseases, we have encountered 12 patients with silent ACTH adenomas, none of whom exhibited definite clinical features of hypercortisolism preoperatively. Two patients presented with apoplexy, and in 2 patients preoperative neuroimaging studies mimicked craniopharyngioma. Pathological examination revealed 8 adenomas with variably basophilic cytoplasm (type I, including 1 each with coarse basophilic granules and Crooke's hyaline change) and 4 with predominantly chromophobic cytoplasm (type II). Diffuse versus patchy (30% to 50% of cells) immunostaining best distinguished these 2 types; calcitonin staining was focal or negative in both. Two patients had unexpected postoperative courses consistent with acute cortisol insufficiency; 1 patient suffered from a severe flu-like illness, and the other had dizziness and was found to have a serum cortisol level of < 1.0 microg/dL. Both patients improved after cortisol replacement followed by a slow taper. Another patient developed 2 separate pituitary adenomas, a silent ACTH adenoma followed by a pure prolactinoma resected months later. Clonality studies demonstrated that the 2 tumors had arisen from different clonal populations. These cases offer additional insights into clinical, neuroimaging, histological, and biological features of silent ACTH adenomas. Because 2 of these patients seemed to require postoperative cortisol supplementation that otherwise would not have been given, clinicians should be notified about ACTH immunostaining in adenomas from patients without preoperative diagnoses of Cushing's disease, to optimize postoperative care.
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PMID:Silent corticotroph adenomas: further clinical and pathological observations. 1534 17

The aim of the present study was to compare in man the innervation pattern and the functional responses to neuronal messengers in medium sized lenticulostriate and branches of the posterior cerebral arteries (PCA). The majority of the nerve fibers found were sympathetic and displayed specific immunoreactivity for tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Only few nerve fibers displayed vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity. In both arteries, the contractions induced by noradrenaline (NA), NPY and 5-hydroxytryptamine (5-HT) and the relaxant responses induced by acetylcholine (ACh), VIP and pituitary adenylate cyclase activating peptide-27 (PACAP) as well as CGRP and SP were compared in vitro. In conclusion, there was no major difference in innervation pattern or vasomotor sensitivity (pEC50 and pIC50 values) between the two vessels. However, the general pattern indicates stronger vasomotor responses (Emax and Imax) in the PCA branches as compared to the lenticulostriate arteries which may lend support for the clinical observation of a difference in stroke expression between the two vascular areas.
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PMID:Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries. 1557 98


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