Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to compare the influence of different regimens for induced hypotension down to Power a limit of 80 mmHg (systolic) on sympatho-adrenergic responses in 10 volunteers. Volunteers were investigated in five batteries of tests using glyceryl trinitrate (10 micrograms/kg BW/min), sodium nitroprusside (10 micrograms/kg BW/min maximal dosage), nifedipine (0.35 micrograms/kg BW/min) and urapidil (bolus injections of 25, 25 and 50 mg, followed by an infusion of 180 ml/h) and placebo. Catecholamines in plasma were detected by HPLC/ECD within a period of 1 h of hypotension and 1 h of recovery at 11 measuring points. Using sodium nitroprusside and glyceryl trinitrate, a significant hypotension was achieved. Urapidil was less potent. No hypotension was observed during or after treatment with nifedipine. Heart rate increased during treatment with sodium nitroprusside and glyceryl trinitrate. Sodium nitroprusside, glyceryl trinitrate and urapidil caused significant rises in noradrenaline levels. With nifedipine, noradrenaline increased within the normal range. Adrenaline left the normal range only during urapidil treatment. MAP, HR, and levels of noradrenaline and adrenaline returned to the initial values 5 min after discontinuation of the sodium nitroprusside infusion. After treatment with glyceryl trinitrate and urapidil, MAP was still low even 60 min after discontinuation of treatment. Urapidil caused marked increases in noradrenaline and adrenaline, which persisted even into the recovery phase. With regard to clinical management and sympatho-adrenergic responses, sodium nitroprusside is the most useful of these compounds for the reduction of hypotension. Having similar potency and active metabolites, glyceryl trinitrate has a longer duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sympatho-adrenergic reactions during drug-induced hypotension. A comparative study on probands]. 210 51

To investigate the influence of acute normovolemic hemodilution (ANH) on endocrine parameters in orthopedic surgery patients, 20 patients scheduled for total prosthetic replacement of the hip under epidural anesthesia with bupivacaine 0.5% were randomly allocated to the following groups: ANH group, (about 7.5 ml/kg body weight within 30 min) during substitution with 6% HES 200/0.5; Control group (without hemodilution). During a period before the onset of anesthesia and on the 1st day after the operation, MAP, HR, plasma concentrations of adrenaline and noradrenaline (by HPLC/ECD), and of ADH, ACTH and cortisol (by RIA) were determined at 8 points, as were glucose, lactate and free glycerol. Biometric data were comparable between the groups. MAP was significantly higher in the ANH group, and the intraoperative decrease was less pronounced. Adrenaline, ACTH, and cortisol revealed no specific influence of ANH and remained within the normal range in both groups. Noradrenaline was above the normal range in both groups and increased slightly (about 20%) during ANH. ADH was significantly higher in the control group. No specific influence of ANH was found with respect to glucose, lactate and free glycerol. In conclusion, ANH had no negative effects on the endocrine stress response during orthopedic surgery under epidural anesthesia. Sympatho-adrenergic reactions were only moderate and tolerable, even for patients with compensated cardiovascular disorders. Slight increases in endocrine parameters in the perioperative period documented adequate stress protection with epidural anesthesia.
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PMID:[Endocrine reactions during acute normovolemic hemodilution]. 216 33

The mechanism of action of theophylline is still the subject of controversy. Possible mechanisms that have been suggested are inhibition of phosphodiesterase, release of catecholamines, effects on intracellular calcium, and adenosine antagonism. With regard to these aspects, it was the aim of this study to compare sympatho-adrenal responses after theophylline application during different anesthetic techniques. A total of 60 patients scheduled for orthopedic surgery were investigated: they were divided into three groups of 20 patients who received either halothane anesthesia with thiopentone induction, modified neurolept anesthesia with fentanyl and midazolam, or spinal anesthesia with bupivacaine and mepivacaine. Within these three groups, the patients were randomly allocated to a theophylline collective receiving an injection of theophylline, 4 mg/kg body weight and to the control group. Plasma levels of epinephrine and norepinephrine (by HPLC/ECD), glucose, lactate and free glycerol and MAP and HR were determined over a period of 120 min. In all groups, epinephrine levels increased immediately after injection of theophylline; group levels of epinephrine were higher in the theophylline-groups than in controls (P less than 0.0001). A remarkable increase was observed within 60 min. Peak epinephrine concentrations were comparable after single injections of 100 micrograms or infusions of 5 micrograms/min. The norepinephrine increase after theophylline injection was brief and less pronounced. MAP, HR, glucose, lactate and free glycerol were not influenced by theophylline. A comparison of the theophylline patients showed no statistical differences attributable to the different anesthetic techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sympatho-adrenergic reactions following theophylline administration with the use of various anesthesia technics]. 276 71

Overexpression of the HER2 (neu/c-erbB-2) oncogene frequently coincides with an aggressive clinical course of certain human adenocarcinomas. Expression and secretion of aberrant HER2 splice variants has been reported in various cell lines and tissues and can interfere with the oncogenic HER2 activity. Here we demonstrate, using two different approaches, that expression of a truncated 100 kDa HER2 variant which encodes the extracellular domain of HER2 (HER-ECD) inhibits growth factor-mediated tumour cell proliferation. A HER2-ECD cDNA encoding the truncated variant was overexpressed in MCF7 breast cancer cells. HER2-ECD overexpression decreased spontaneous proliferation of MCF7 cells as well as heregulin-mediated soft agar colony formation. Concomitantly, heregulin-induced phosphorylation of HER4 as well as downstream activation of p44/p42 MAP-kinases was decreased. To confirm these data, ribozymes were targeted to the 3'-untranslated region of the 2.3 kb HER2-ECD mRNA which is spontaneously expressed in MKN7 gastric cancer cells. HER2-ECD-targeted ribozymes downregulated HER2-ECD expression and enhanced EGF-mediated soft agar colony formation of MKN7 cells. In parallel, EGF-induced activation of p44/p42 MAP-kinases and activation of c-Fos expression were increased in ribozyme-transfected MKN7 cells. Finally, in RT-PCR we found a trend towards a progressive loss of 2.3 kb HER2-ECD mRNA expression in more advanced gastric tumours. These data show that the HER2-ECD variant inhibits growth factor-mediated tumour cell proliferation suggesting an important role during the progression of human cancer.
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PMID:Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumour cell proliferation. 1136 Jan 94

We have investigated the localization and regulation of growth hormone (GH) receptor-related proteins in the ovine mammary gland. Using a new rabbit polyclonal antibody (7122A) directed against the recombinant extracellular domain of GH receptor (GHR-ECD) for western blot assays, we found two bands with apparent molecular weights of 70,000 and 50-60,000 Da in ovine mammary gland solubilized proteins. The 70,000-protein was consistent with a membrane GH receptor form deprived of post-translational modifications such as phosphorylation, glycosylation or ubiquitin binding. The 50-60,000 Da was consistent with soluble GH binding protein, generated by the cleavage of membrane GH receptor. The intensity of related GHR proteins increased slightly throughout mammary gland development and was correlated with the amount of GHR immunoreactivity observed in the mammary gland sections. Moreover, a temporal and spatial regulation of GHR immunoreactivity was found in alveolar epithelial cells. Clearly, marked GHR immunoreactivity was associated with the apical membranes of alveolar epithelial cells at lactation. The up-regulation of related GHR proteins during the differentiation of mammary tissue supports the hypothesis that GH may act specifically via its own receptors. In ovine mammary cells, GH was able to promote a time-dependent activation of MAP kinases such as prolactin (Prl) and placental lactogen (PL). GH was also able to promote slight and transient Stat5 DNA-binding activity. Differences in the time dependence of Stat5 DNA-binding activation by the three different ligands, GH, Prl and PL, were found. All these results emphasize the direct action of GH on ovine mammary cells and highlight the specificity of action of this ligand.
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PMID:Transduction pathways of GH in ovine mammary acini involving regulated and functional growth hormone receptors. 1601 27