Home About us Contact
|
Home About us Contact | ||
|
|
||
Delayed Activation (delayed + activation)
Selected AbstractsActivation of mitogen activated protein kinase (MAPK) pathways after soman poisoning in rat cerebellar granule neuronsJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008J. Pejchal Abstract The expression of activated p38 mitogen-activated protein kinase (MAPK) and activated MAPK transcription factors c-jun, c-myc and elk-1 were examined in rat cerebellum after soman poisoning to determine the pathogenetic mechanism of the non-specific long-term effects of nerve agents. Male Wistar rats were poisoned by intramuscular administration of soman at a dose 60 µg kg,1 (70% LD50) and samples were taken 1, 7 and 14 days after poisoning, immunohistochemically stained and p-p38MAPK, p-c-jun, p-c-myc and p-elk-1 expressions were measured using image analysis. Control groups were administered with saline instead of soman. The expression of activated p38MAPK and c-myc increased 14 days after soman poisoning while c-jun and elk-1 expressions remained unchanged 1, 7 and 14 days after soman poisoning. Delayed activation of p38 MAPK and its targets might be involved in the pathogenetic mechanism of the long-term neurophysiological toxic effects of nerve agents. Copyright © 2007 John Wiley & Sons, Ltd. [source] Ventricular Fibrillation Induced by Stretch Pulse: Implications for Sudden Death Due to Commotio CordisJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2006FRANK BODE M.D. Introduction: Nonpenetrating chest wall impact (commotio cordis) may lead to sudden cardiac death due to the acute initiation of ventricular fibrillation (VF). VF may result from sudden stretch during a vulnerable window, which is determined by repolarization inhomogeneity. Methods: We examined action potential morphologies and VF inducibility in response to sudden myocardial stretch in the left ventricle (LV). In six Langendorff perfused rabbit hearts, the LV was instrumented with a fluid-filled balloon. Increasing volume and pressure pulses were applied at different times of the cardiac cycle. Monophasic action potentials (MAPs) were recorded simultaneously from five LV epicardial sites. Inter-site dispersion of repolarization was calculated in the time and voltage domains. Results: Sudden balloon inflation induced VF when pressure pulses of 208,289 mmHg were applied within a window of 35,88 msec after MAP upstroke, a period of intrinsic increase in repolarization dispersion. During the pressure pulse, MAPs revealed an additional increase in repolarization dispersion (time domain) by 9 ± 6 msec (P < 0.01). The maximal difference in repolarization levels (voltage domain) between sites increased from 19 ± 3% to 26 ± 3% (P < 0.05). Earliest stretch-induced activation was observed near a site with early repolarization, while sites with late repolarization showed delayed activation. Conclusions: Sudden myocardial stretch can elicit VF when it occurs during a vulnerable window that is based on repolarization inhomogeneity. Stretch pulses applied during this vulnerable window can lead to nonuniform activation. Repolarization dispersion might play a crucial role in the occurrence of fatal tachyarrhythmias during commotio cordis. [source] CREB-dependent cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression is mediated by protein kinase C and calciumJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Hung Pham Abstract Cellular production of prostaglandins (PGs) is controlled by the concerted actions of cyclooxygenases (COX) and terminal PG synthases on arachidonic acid in response to agonist stimulation. Recently, we showed in an ileal epithelial cell line (IEC-18), angiotensin II-induced COX-2-dependent PGI2 production through p38MAPK, and calcium mobilization (J. Biol. Chem. 280: 1582,1593, 2005). Agonist binding to the AT1 receptor results in activation of PKC activity and Ca2+ signaling but it is unclear how each pathway contributes to PG production. IEC-18 cells were stimulated with either phorbol-12,13-dibutyrate (PDB), thapsigargin (TG), or in combination. The PG production and COX-2 and PG synthase expression were measured. Surprisingly, PDB and TG produced PGE2 but not PGI2. This corresponded to induction of COX-2 and mPGES-1 mRNA and protein. PGIS mRNA and protein levels did not change. Activation of PKC by PDB resulted in the activation of ERK1/2, JNK, and CREB whereas activation of Ca2+ signaling by TG resulted in the delayed activation of ERK1/2. The combined effect of PKC and Ca2+ signaling were prolonged COX-2 and mPGES-1 mRNA and protein expression. Inhibition of PKC activity, MEK activity, or Ca2+ signaling blocked agonist induction of COX-2 and mPGES-1. Expression of a dominant negative CREB (S133A) blocked PDB/TG-dependent induction of both COX-2 and mPGES-1 promoters. Decreased CREB expression by siRNA blocked PDB/TG-dependent expression of COX-2 and mPGES-1 mRNA. These findings demonstrate a coordinated induction of COX-2 and mPGES-1 by PDB/TG that proceeds through PKC/ERK and Ca2+ signaling cascades, resulting in increased PGE2 production. J. Cell. Biochem. © 2006 Wiley-Liss, Inc. [source] The neuro-cardio-endocrine response to acute subarachnoid haemorrhageCLINICAL ENDOCRINOLOGY, Issue 5 2002Eric A. Espiner Summary objective Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH. design, patients, measurements Eighteen patients with verified SAH of variable severity were studied in a single unit for a 14-day period post ictus under controlled conditions of sodium and fluid intake. All received a standardized protocol of daily dexamethasone and nimodipine throughout the study. Severity was graded using criteria of Hess and Hunt at admission. Stress hormones (AVP, catecholamines and admission plasma cortisol), markers of cardiac injury (ECG and daily plasma troponin T) and cardiac hormones (ANP and BNP) were measured daily and related to severity, plasma sodium and renin,aldosterone activity. Hormone levels (ANP, BNP and endothelin) in cerebrospinal fluid (CSF) were also measured in nine patients. results Intense neurohormonal activation (AVP, cortisol and catecholamines) at admission was associated with increased levels of both plasma ANP and BNP whereas levels in CSF were unaffected. In individual patients plasma levels of ANP and BNP were strongly correlated (P < 0·001). Cardiac events (abnormal ECG and/or elevated troponin) occurred in six of seven patients graded severe but neither stress hormones nor cardiac peptides differed significantly in patients with mild (n = 11) vs. severe (n = 7) SAH. During the course of a progressive fall in plasma sodium concentration (P = 0·001), there was a delayed activation of renin,aldosterone which was inversely correlated with declining levels of plasma ANP/BNP (P < 0·002). conclusions Excessive secretion of both ANP and BNP occurs in all patients after acute subarachnoid haemorrhage and is unrelated to severity, stress hormone activation or markers of cardiac injury. Inhibition of renin,aldosterone by cardiac hormones may impair renal sodium conservation and contribute to developing hyponatraemia. In the absence of evidence for activation of natriuretic peptides within the brain, the prompt and consistent increase in both ANP and BNP strongly supports the view that the heart is the source of increased natriuretic peptide secretion after acute subarachnoid haemorrhage. [source] | ||||||||||