Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia causes secondary brain damage after severe head injury (SHI). Cerebral perfusion is commonly estimated by monitoring CPP, but the adequacy of cerebral oxygenation requires further measurements, such as jugular oxygen saturation or, more recently, PtiO2 monitoring. In 7 patients with severe head injury, ICP, MAP, CPP, SjO2 and PtiO2 were monitored for a mean time of 9.0 +/- 2.2 days. Most of the data were in a "normal" range. Focusing on values under the thresholds of 60 mm Hg for CPP and 20 mm Hg for PtiO2, we found a relationship between CPP and PtiO2. Looking at the PtiO2 time-course, we observed a quite constant increasing trend during the first 48 hours of monitoring, then the values remained relatively constant within a normal range. Our data show that decreases of PtiO2 are not uncommon after severe head injury and therefore it seems that monitoring of PtiO2 in SHI may be useful in order to minimize secondary insults.
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PMID:Effects of cerebral perfusion pressure on brain tissue PO2 in patients with severe head injury. 977 59

The loss of ability to proliferate (terminal differentiation) and reduction in capability to resist ischemia are key phenomena observed during postnatal development of the heart. Mitogen-activated protein kinases (MAPKs) mediate signaling pathways for cell proliferation/differentiation and stress responses such as ischemia. In this study, the expression of these kinases and their associated kinases were investigated in rat heart ventricle. Extracts of 1-, 10-, 20-, 50-, and 365-day-old rat heart ventricles were probed with specific antibodies and their immunoreactivities were quantified by densitometry. Most of the mitogenic protein kinases including Raf1, RafB, Mek1, Erk2, and Rsk1 were significantly down-regulated, whereas the stress signaling kinases, such as Mlk3, Mekkl, Sekl, Mkk3, and Mapkapk2 were up-regulated in expression during postnatal development. Most MAP kinases including Erk1, JNKs, p38 Hog, as well as Rsk2, however, did not exhibit postnatal changes in expression. The proto-oncogene-encoded kinases Mos and Cot/Tpl 2 were up-regulated up to two- and four-fold, respectively, during development. Pakl, which may be involved in the regulation of cytoskeleton as well as in stress signaling, was downregulated with age, but the Pak2 isoform increased only after 50 days. All of these proteins, except RafB, were also detected in the isolated adult ventricular myocytes at comparable levels to those found in adult ventricle. Tissue distribution studies revealed that most of the protein kinases that were up-regulated during heart development tended to be preferentially expressed in heart, whereas the downregulated protein kinases were generally expressed in heart at relatively lesser amounts than in most of other tissues.
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PMID:Expression of mitogen-activated protein kinase pathways during postnatal development of rat heart. 977 26

This review will focus on the free radical signaling mechanism of preconditioning. The results from our laboratory as well as studies from other laboratories suggest that reactive oxygen species function as second messenger during myocardial adaptation to ischemia. This review provides evidence for the first time that tyrosine kinase and MAP kinases are the targets for reactive oxygen species generated in the preconditioned myocardium. The finding that p38 MAP kinase might be upstream of NF kappa B further supports our previous reports that MAPKAP kinase 2 could be the most likely link between the preconditioning and adaptation mediated by gene expression. p38 activation appears to be an important step in the translocation and activation of the nuclear transcription factor NF kappa B, which in turn may be involved in the induction of the expression of a variety of stress-inducible genes.
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PMID:Oxygen free radical signaling in ischemic preconditioning. 1041 20

Previous experimental studies showed that the benefit of ischemic preconditioning (IPC) is abolished by K(ATP) channel blockade with glibenclamide. However, the newly discovered K(ATP) channel blocker HMR 1883 (1-[[5-[2-(5-chloro-o-anisamido)ethyl]-methoxyphenyl]sulfonyl]-3-m ethylthiourea) shows marked antifibrillatory activity in the dose range of 3 mg/kg to 10 mg/kg i.v. in various experimental models without affecting blood glucose levels. In order to investigate in a head to head comparison glibenclamide and HMR 1883 with respect to their influence on IPC, experiments were performed in rabbits with ischemia-reperfusion using myocardial infarct mass as final read out. Male New Zealand White rabbits (2.6-3.0 kg) were subjected to 30-min occlusion of a branch of the left descending coronary artery (LAD) followed by 2-h reperfusion. For IPC experiments the LAD was additionally occluded for two periods of 5 min, each followed by 10-min reperfusion, before the long-term ischemia. Infarct mass was evaluated by TTC staining and expressed as a percentage of area at risk. Rabbits (n=7/group) were randomly selected to receive (i.v.) saline vehicle 5 min prior to the 30-min occlusion period in infarct studies without IPC or to receive glibenclamide (0.3 mg/kg) or HMR 1883 (3 mg/kg) in IPC experiments, these substances being given 5 min prior to the first preconditioning or 5 min prior to the long-term ischemia of 30 min. Myocardial risk mass as a percentage of left ventricular mass did not differ between groups. The same was true for the ratio of left ventricular mass to 100 g body weight. Myocardial infarct mass as a percentage of the area at risk in the saline vehicle group without IPC was 41+/-3%. Whereas glibenclamide significantly increased infarct mass (from 41+/-3% to 55+/-4%), HMR 1883 did not affect it. IPC reduced infarct mass from 41+/-3% to 21+/-4% (P<0.05 vs. control without IPC). Glibenclamide given prior to IPC or prior to the long-term ischemia totally abolished the IPC effect (42+/-2% and 55+/-4%, respectively; P<0.05 vs. control). In contrast, HMR 1883 under the same conditions did not affect infarct size when given prior to IPC or prior to the long-term ischemia (21+/-3% and 26+/-2%, respectively). The monophasic action potential duration (MAP50) was reduced from 103+/-3 ms under normoxic conditions to 82+/-2 ms, 5 min after ischemia in the absence of drugs. This ischemia-induced shortening of the MAP was prevented by both HMR 1883 (MAP50 103+/-3 ms) and glibenclamide (MAP50 106+/-3 ms). In conclusion, although both K(ATP) channel blockers prevented ischemia-induced shortening of MAP, HMR 1883 did not abolish the beneficial effects of IPC on myocardial infarct mass in rabbits, whereas glibenclamide totally reversed this cardioprotective effect of IPC. This suggests that the sarcolemmal ATP-sensitive potassium channels are not involved in the mechanism of IPC.
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PMID:The K(ATP) channel blocker HMR 1883 does not abolish the benefit of ischemic preconditioning on myocardial infarct mass in anesthetized rabbits. 1076 61

We encountered a patient with hypertrophic cardiomyopathy complicated with exercise-induced myocardial ischemia. Exercise-stress 99mTc-tetrofosmin imaging demonstrated reversible ischemia in the lateral wall, whereas resting fatty acid imaging with a new beta-methyl branched fatty acid analogue, I-123-15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (123I-9-MPA), showed impaired uptake and accelerated washout kinetics in the inferoapical and posteroseptal walls but not in the ischemia-related region. These findings suggest that the metabolic derangement is closely related to cardiomyopathy per se rather than exercise-induced myocardial ischemia in this patient with hypertrophic cardiomyopathy and a spastic coronary lesion so that myocardial perfusion and 123I-9-MPA imagings may contribute to clarifying the etiological background of impaired myocardial fatty acid metabolism.
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PMID:Impaired myocardial accumulation of 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid in a patient with hypertrophic cardiomyopathy and exercise-induced ischemia due to vasospasm. 1077 May 82

Between January 1990 and December 1999, 20 patients underwent the valve surgery concomitant with coronary artery bypass grafting. There were 16 males and 4 females, their mean age was 66.5 years. Of the 20 patients, aortic stenosis was noted in 7, aortic regurgitation in 3, mitral stenosis in one, and mitral regurgitation in 9 patients. The cause of mitral regurgitation was considered to be an ischemic change in six patients, including ruptured papillary muscle due to myocardial infarction in two patients. On the contrary, LMT lesion was recognized in 5, LAD lesion in 17, LCX in 16, and RCA in 12 patients. Seven patients had preoperative myocardial infarction, three patients were required preoperative IABP support. AVR was performed in 10, MVR in 5, and MAP in 5 patients. The number of bypass was 1.9 +/- 0.85. Four patients died of LOS and MOF. The remaining 16 patients have been doing well. The significant difference between the survived and the not survived patients was recognized in the factor of emergency, preoperative IABP, papillary muscle rupture due to myocardial infarction, history of PTCA, LAD lesion, and the time of CPB. The factors regarding coronary artery had the influence on the outcome of a patients of valve surgery concomitant with CABG. Therefore, an appropriate myocardial protection and perioperative management for ischemia were mandatory.
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PMID:[Perioperative risk factors in valve surgery concomitant with coronary artery bypass grafting]. 1093 83

Physical activity and functional capacity have not been assessed by questionnaire for criterion validity in women. We wished to evaluate the ability of a physical activity and a functional capacity assessment questionnaire to predict functional capacity measured by treadmill exercise stress testing, as well as correlate with cardiac risk factors and angiographic coronary artery disease (CAD) in women. In a National Heart, Lung and Blood Institute (NHLBI)-sponsored cross-sectional population study involving four academic medical centers, 476 women with cardiac risk factors undergoing coronary angiography for evaluation for suspected myocardial ischemia were enrolled in the Women's Ischemia Syndrome Evaluation (WISE). The main outcome measures were functional capacity measured during symptom-limited exercise treadmill testing, cardiac risk factors, and CAD, using core laboratory-determined measures. Physical activity measured by the Postmenopausal Estrogen and Progesterone Intervention physical activity questionnaire (PEPI-Q) and functional capacity measured by the Duke Activity Status Index (DASI) questionnaire, correlated with functional capacity measured in metabolic equivalents (METS), as estimated during symptom-limited exercise treadmill testing (r = 0.27, p = 0.001 and r = 0.31, p = 0. 0002, respectively). The DASI was a significant independent predictor of functional capacity even after adjustment for cardiac risk factors, and the PEPI-Q was not. The DASI and PEPI-Q scores were inversely associated with higher numbers and levels of cardiac risk factors, as well as angiographic CAD. The DASI questionnaire is a reasonable correlate of functional capacity achieved during symptom-limited treadmill exercise testing in women with suspected myocardial ischemia. Lower functional capacity or physical activity measured by the DASI and PEPI-Q, respectively, is associated with more prevalent cardiac risk factors and angiographic CAD. These findings suggest that the DASI and, to a lesser extent, the PEPI-Q have criterion validity for use in health-related research in women.
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PMID:Physical activity and functional capacity measurement in women: a report from the NHLBI-sponsored WISE study. 1102 69

Our recent results indicate that pancreatic enzymes in the ischemic intestine are involved in the production of in vivo activators, which stimulate cells in the cardiovascular system and initiate multiple organ failure. Since the intestine is a rich source of xanthine oxidase (XO), we investigated whether XO may be involved in the production of circulating activators in shock. The small intestine was perfused with saline (SAL group), a broad acting pancreatic enzyme inhibitor, ANGD (ANGD group), allopurinol (ALLOP group), or a combination of ANGD and allopurinol (ANGD + ALLOP group). 100 min of splanchnic arterial occlusion was followed by 120 min of reperfusion. Leukocytes from asymptomatic volunteers were incubated with plasma from experimental animals, and the fractions of pseudopod positive cells were counted as an indicator for the activator. ANGD served to preserve the arterial blood pressure (MAP) close to its control values (96.6 +/- 6.2 % in ANGD versus 60.9 +/- 6.2 % in SAL, 120 min after reperfusion, P < 0.05). In line with our previous experiments, ANGD decreased the formation of activator (30.5 +/- 4.8% in SAL versus 7.3 +/- 1.6 % in ANGD, 120 min after reperfusion, P< 0.05). Although allopurinol inhibited the XO in the small intestine, no protection from early indicators of multi-organ injury was detected. The recovery of MAP and reduced levels of plasma activator achieved in the ANGD + ANGD group was similar to those in the ALLOP group. These results indicate that XO may not serve as a significant source for plasma derived activators in an acute phase of shock after severe intestinal ischemia.
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PMID:Mechanisms for blockade of in vivo activator production in the ischemic intestine and multi-organ failure. 1109 84

Adenosine (Ado) accumulates in tissues under metabolic stress. On myocardial cells, the nucleoside interacts with various receptor subtypes (A(1), A(3), and probably A(2A) and A(2B)) that are coupled, via G proteins, to multiple effectors, including enzymes, channels, transporters and cytoskeletal components. Studies using Ado receptor agonists and antagonists, as well as animals overexpressing the A(1) receptor indicate that Ado exerts anti-ischemic action. Ado released during preconditioning (PC) by short periods of ischemia followed by reperfusion induces cardioprotection to a subsequent sustained ischemia. This protective action is mediated by A(1) and A(3) receptor subtypes and involves the activation and translocation of PKC to sarcolemmal and to mitochondrial membranes. PKC activation leads to an increased opening of ATP-sensitive K(+) (K(ATP)) channels. Recent studies implicate mitochondrial rather than sarcolemmal K(ATP) channels in the protective action of PC. Other effectors possibly contributing to cardioprotection by Ado or PC, and which seem particularly involved in the delayed (second window of) protection, include MAP kinases, heat shock proteins and iNOS. Because of its anti-ischemic effects, Ado has been tested as a protective agent in clinical interventions such as PTCA, CABG and tissue preservation, and was found in most cases to enhance the post-ischemic recovery of function. The mechanisms underlying the role of Ado and of mitochondrial function in PC are not completely clear, and uncertainties remain concerning the role played by newly identified potential effectors such as free radicals, the sarcoplasmic reticulum, etc. In addition, more studies are needed to clarify the signalling mechanisms by which A(3) receptor activation or overexpression may promote apoptosis and cellular injury, as reported by a few recent studies.
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PMID:Adenosine, adenosine receptors and myocardial protection: an updated overview. 1155 31

Protection against ischemic kidney injury is afforded by 24 h of ureteral obstruction (UO) applied 6 or 8 days prior to the ischemia. Uremia or humoral factors are not responsible for the protection, since unilateral UO confers protection on that kidney but not the contralateral kidney. Prior UO results in reduced postischemic outer medullary congestion and leukocyte infiltration. Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. Very few cells stain positively for proliferating cell nuclear antigen after obstruction, indicating that subsequent protection against ischemia is not related to proliferation with increased numbers of newly formed daughter cells more resistant to injury. UO increases the expression of heat shock protein (HSP)-25 and HSP-72. The increased HSP-25 expression persists for 6 or 8 days, whereas HSP-72 does not. HSP-25 expression is increased in the proximal tubule cells in the outer stripe of the outer medulla postobstruction, prior to, and 24 h after ischemia. In LLC-PK(1) renal epithelial cells, adenovirus-expressed human HSP-27 confers resistance to chemical anoxia and oxidative stress. Increased HSP-27 expression in LLC-PK(1) cells results in reduced H(2)O(2)-induced phosphorylation of JNK1/2 and p38. In conclusion, prior transient UO renders the kidney resistant to ischemia. This resistance to functional consequences of ischemia is associated with reduced postischemic activation of JNK, p38 MAP kinases, and their upstream MAPK kinases. The persistent increase in HSP-25 that occurs as a result of UO may contribute to the reduction in phosphorylation of MAPKs that have been implicated in adhesion molecule up-regulation and cell death.
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PMID:Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. 1169 40


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