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

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 influence of nimodipine on plasma-catecholamines, ADH, ACTH and cortisol during standardized, modified neurolept-anaesthesia was investigated in 20 patients for major abdominal and thoracic surgery. The application of nimodipine led to an intra- and postoperative increase in both adrenaline and noradrenaline. No influence could be demonstrated on ADH, ACTH or cortisol. Group-levels of MAP were lower in the nimodipine-group. No statistical differences became obvious for HR, glucose, lactate and free glycerol. The increases in adrenaline and noradrenaline can be attributed to a cardiocirculatory rebound-phenomenon due to the vasodilative properties of the substance. Under the conditions of adequate fentanylanalgesia, no influence of nimodipine on ADH, ACTH or cortisol was found.
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PMID:[Effect of nimodipine on plasma catecholamines and perioperative endocrine stress parameters]. 284

The influence of laryngoscopy and intubation with or without topical lidocaine anesthesia on the endocrine stress response was investigated in six groups of 40 orthopedic surgery patients differing in premedication and technique of lidocaine application (one- or two-step method). Controls were included without lidocaine application. Plasma levels of catecholamines (by HPLC) were measured before induction and 1, 5, and 10 min after intubation, ADH-levels (by RIA) before induction and 5 and 10 min after intubation. In addition, mean arterial pressure (MAP, MAP), HR, and the incidence of coughing and cardiac arrhythmias were observed. The statistical evaluation (analysis of variance with repeated measures on one factor) considered P values of less than 0.05 significant. There was no influence of laryngoscopy and intubation on plasma catecholamine levels during the observation period. A continuous decrease in both levels of epinephrine and norepinephrine was significant. ADH levels showed no significant changes. Lidocaine had no influence on these endocrine parameters. MAP and HR increased after intubation in all groups studied. The increase in HR was less pronounced after lidocaine treatment. Coughing (4 patients) and ventricular dysrhythmia (2 patients) were observed only in patients without lidocaine treatment. In conclusion, no influence of different modes of treatment on the endocrine stress response during intubation became obvious. There was no indication that the cardiovascular symptoms during laryngoscopy and intubation are caused by systemic stress. An explanation may be a direct neural impulse via sympathetic efferents to the heart. On the other hand, topical application of lidocaine did prevent coughing and cardiac irritation, and the increase in HR was attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The endocrine stress-reaction to orotracheal intubation and topical anesthesia with lidocaine]. 368 17

Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenously applied IFN-alpha, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation. These effects of alcohol occurred independently of i) alcohol metabolism via ADH and CYP2E1, and ii) cytotoxic or cytostatic effects of ethanol. In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication. Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink 12.Recombinant interferon alpha (IFN-alpha) therapy produces sustained responses (ie clearance of viremia) in 8-12% of patients with chronic hepatitis C 3. Significant improvements in response rates can be achieved with IFN plus ribavirin combination 456 and pegylated IFN plus ribavirin 78 therapies. However, over 50% of chronically infected patients still do not clear viremia. Moreover, HCV-infected patients who abuse alcohol have extremely low response rates to IFN therapy 9, but the mechanisms involved have not been clarified.MAPKs play essential roles in regulation of differentiation, cell growth, and responses to cytokines, chemokines and stress. The core element in MAPK signaling consists of a module of 3 kinases, named MKKK, MKK, and MAPK, which sequentially phosphorylate each other 10. Currently, four MAPK modules have been characterized in mammalian cells: Extracellular Regulated Kinases (ERK1 and 2), Stress activated/c-Jun N terminal kinase (SAPK/JNK), p38 MAP kinases, and ERK5 11. Interestingly, ethanol modulates MAPKs 12. However, information on how ethanol affects MAPKs in the context of innate antiviral pathways such as the Jak-Stat pathway in human cells is extremely limited. When IFN-alpha binds its receptor, two receptor associated tyrosine kinases, Tyk2 and Jak1 become activated by phosphorylation, and phosphorylate Stat1 and Stat2 on conserved tyrosine residues 13. Stat1 and Stat2 combine with the IRF-9 protein to form the transcription factor interferon stimulated gene factor 3 (ISGF-3), which binds to the interferon stimulated response element (ISRE), and induces transcription of IFN-alpha-induced genes (ISG). The ISGs mediate the antiviral effects of IFN. The transcriptional activities of Stats 1, 3, 4, 5a, and 5b are also regulated by serine phosphorylation 14. Phosphorylation of Stat1 on a conserved serine amino acid at position 727 (S727), results in maximal transcriptional activity of the ISGF-3 transcription factor complex 15. Although cross-talk between p38 MAPK and the Jak-Stat pathway is essential for IFN-induced ISRE transcription, p38 does not participate in IFN induction of Stat1 serine phosphorylation 1416171819. However, cellular stress responses induced by stimuli such as ultraviolet light do induce p38 MAPK mediated Stat1 S727 phosphorylation 18. In the current report, we postulated that alcohol and HCV proteins modulate MAPK and Jak-Stat pathways in human liver cells. To begin to address these issues, we characterized the interaction of acute ethanol on Jak-Stat and MAPK pathways in Huh7 cells, HCV replicon cells lines, and primary human hepatocytes.
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PMID:Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells. 1632 17

MAP kinases JNK and p38 play an important role in many immune and inflammatory processes, whereas glucocorticoids exert immunosuppressive and anti-inflammatory activities. We found previously that activation of p38 or JNK inhibits glucocorticoid receptor (GR)-mediated transcriptional activation of a mouse mammary tumor virus (MMTV) promoter-driven luciferase construct in HeLa cells. It appears that this effect is DNA regulatory element-specific, since p38 or JNK activation stimulates GR-dependent transcription from TAT3-ADH promoter-luciferase construct in the same cells. The apparent promoter-specificity of this action suggests that not all glucocorticoid-activated genes are negatively regulated by p38 or JNK. Using different MMTV/TAT3 chimeric reporters we demonstrate that the presence of other accessory binding sites of the MMTV construct contributes to the inhibitory effect of activated p38 or JNK on the MMTV-driven transcriptional activity; and diminishes, but does not reverse the stimulation observed using the TAT GREs from the TAT3-ADH promoter-luciferase construct. On the other hand, comparison of the effects of GRE sequences, either in isolation or in the context of the MMTV LTR accessory binding sites, demonstrates that the responsiveness of the GR depends on the GRE sequence; indicating that in addition to transcription factors bound nearby, interaction with the DNA itself modulates GR activity.
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PMID:Promoter-context as a determinant of glucocorticoid receptor-responsiveness to activation of p38 and JNK mitogen-activated protein (MAP) kinases. 2304 44