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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although radiotherapy is a front line treatment for brain tumors, little is known about the in vivo molecular responses of brain to irradiation. In this study, expression of c-fos, c-jun and junB immediate-early genes were followed in mouse brain after irradiation. C-fos and junB, but not c-jun, mRNA was induced within 15 min in unanesthetized irradiated mice. Induction was transient and lasted < 4 h. The response was dose-dependent with increases in c-fos and junB mRNA levels after dose of > or = 2 and 7 Gy, respectively. Anesthesia of mice with pentobarbitol delayed the increases in mRNA expression and the response was attenuated. Pre-treatment of mice with dexamethasone, in a schedule which suppressed acute-phase gene expression after brain irradiation, did not significantly change c-fos and junB induction. Our results show that c-fos and junB responses occur in the brain in response to irradiation and that they can be modified by pentobarbital treatment but suggest that there is no direct correlation between the level of mRNA expression and later expression of cytokines or other acute-phase response genes.
Brain Res Mol Brain Res 1997 Sep
PMID:Induction of c-fos and junB mRNA following in vivo brain irradiation. 933 19

Nitric oxide (NO) is an important biological messenger involved in the regulation of blood vessel tone, neurotransmission, inflammatory responses, and host defenses. Inhalational anesthetics have been shown to inhibit the function of the NO signaling pathway in a variety of tissues. In addition, acute inhibition of the NO signaling pathway significantly reduced the required alveolar concentration of halothane or isoflurane for anesthesia, which suggests a role for the NO signaling pathway in mechanisms of anesthesia and consciousness. We now report that inhalational anesthetics affect gene expression of nitric oxide synthases (NOS) (EC 1.14.13.39), the enzymes that synthesize NO from L-arginine. Both halothane and isoflurane, at clinically relevant concentrations, significantly up-regulate the mRNA, protein, and activity level of NOS in lipopolysaccharide-treated macrophages (inducible NOS; type II NOS), and bovine pulmonary endothelial cells (endothelial constitutive NOS; type III NOS). This is a novel interaction between inhalational anesthetics and the NO signaling pathway and has wide-ranging implications for both clinical medicine and experimental biology.
Mol Pharmacol 1997 Oct
PMID:Inhalational anesthetics up-regulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity. 938 23

The increasing popularity of genetically engineered mice in cardiovascular research has made it important to evaluate cardiac function in small animals. We have developed a system to enable simultaneous pressure-dimension analysis of the mouse left ventricle. The chest was opened under anesthesia, and a 1.4 F micromanometer catheter was inserted into the left ventricle through the apex. A pair of sonomicrometry crystals were attached to the anterior and posterior walls using tissue adhesive. Pressure and dimension were recorded simultaneously at baseline and after isoproterenol injection (1 micro g, intraperitoneally). The ascending aorta was occluded transiently to estimate the end-systolic pressure-dimension relationship (ESPDR), which was parameterized subsequently by the quadratic equation: Pes=C2 X (Des-D0)2+E0 X (Des-D0), where Pes is end-systolic pressure, Des is end-systolic dimension, D0 is the dimension axis intercept, E0 is the local slope at D0, and C2 is the curvilinearity coefficient. The maximum and minimum external dimensions at baseline were 5.82+/-0.50 (s.d.) mm and 5.49+/-0.46 mm with fractional shortening of 0.057+/-0.014 (n=12). The ESPDR was significantly curvilinear and increased convexity after isoproterenol injection (C2, -444+/-281 to -1113+/-780 mmHg/mm2, P<0. 05; E0, 536+/-175 to 889+/-276 mmHg/mm, P<0.001), while the dimension axis intercept remained relatively constant (D0, 5.39+/-0. 46 to 5.37+/-0.52 mm). In conclusion, the combination of miniature piezo-electric crystals and a micromanometer enables continuous measurement of pressure and dimension of in situ mouse left ventricle. This technology may be useful in evaluating the cardiac phenotype of genetically engineered mice.
J Mol Cell Cardiol 1998 Feb
PMID:End-systolic pressure-dimension relationship of in situ mouse left ventricle. 951 12

Our previous findings in female rats suggest that the potent effects of sex steroids on mood and mental state may be mediated, in part, by the effect of estrogen on the 5-hydroxytryptamine2A receptor (5-HT2AR) in brain. The aim of the present study was to determine the effect of acute (approximately 32h) sex steroid manipulation on central 5-HT2AR in the adult male Wistar rat. Castration (under halothane anesthesia) decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the 5-HT2AR mRNA content in dorsal raphe nucleus and the density of 5-HT2AR binding sites in frontal, cingulate and primary olfactory cortex and nucleus accumbens. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT2AR binding sites in the caudate-putamen, a brain region where aromatase is scarce. These findings are discussed in relation to the possible role of the 5-HT2AR in depression, schizophrenia and Alzheimer's Disease.
Brain Res Mol Brain Res 1998 Aug 31
PMID:Testosterone as well as estrogen increases serotonin2A receptor mRNA and binding site densities in the male rat brain. 972 88

It has been reported that antiarrhythmic drugs possessing the property of potassium channel blockade were most effective in preventing halothane-epinephrine induced arrhythmias. Recent attention has focused on ATP-sensitive potassium (K(ATP)) channels because of their contribution to the cardiovascular actions of volatile anesthetics. The present study was designed to evaluate whether K(ATP) channels or transient outward potassium channels (Ito) were involved in the mechanism of halothane-epinephrine arrhythmias in rat. Rats were anesthetized with halothane (1.5%), and the lungs were mechanically ventilated. The arrhythmogenic thresholds of epinephrine during halothane anesthesia were determined in 74 rats receiving saline or one of tested agents. The arrhythmogenic dose of epinephrine (ADE) was significantly increased by a K(ATP) channel opener, JTV506 (P < 0.01), and had a tendency to be increased by other K(ATP) channel openers, cromakalim, nicorandil, KRN2391 and Y 26763, but were not affected by a K(ATP) channel blocker, glibenclamide. The Ito blocker, 4-aminopyridine, also significantly increased the ADE. Epinephrine produced second-degree or complete atrioventricular block in 4 out of 7 rats receiving glibenclamide. These results suggest that Ito but not K(ATP) channels might be involved in the mechanism in producing halothane-epinephrine arrhythmias.
Res Commun Mol Pathol Pharmacol 1998 Jun
PMID:Role of potassium channels in halothane-epinephrine arrhythmias. 973 12

The specific lesion(s) and potential compensatory alterations of excitation-contraction coupling in heart failure are not clear in detail. We therefore subjected five dogs to 2-5 weeks of rapid ventricular pacing until heart failure developed. Data obtained from these five dogs with pacing-induced heart failure were compared to data from six healthy controls. Under anesthesia, in situ steady state responses of regional contractile function to intracoronary calcium infusion were established. Maximal calcium-activated regional contractile function in dogs with heart failure was 46% less than in controls; calcium sensitivity was unchanged [pCa50 2.55+/-0.31 v 2.82+/-0.17 (+/-s.d.)]. Our data point to a decrease in maximal calcium-activated force and an unchanged calcium sensitivity if an unchanged calcium transient is assumed, or a compensatory increase in calcium sensitivity of failing myocardium if a decreased calcium transient is assumed.
J Mol Cell Cardiol 1998 Aug
PMID:Calcium responsiveness in canine pacing-induced heart failure. 973 46

The effects of nembutal and ketamine anesthesia on motor evoked potentials (MEPs) and spinal segment reflex (H-response, F and M waves) were investigated in rats by magnetic stimulation. These potentials were generated by magnetic stimulation of the motor cortex and the spinal cord (L4-L5). After application of nembutal, MEP and H-response decreased in amplitude, eventually disappearing. The amplitudes of F and M waves increased and persisted at the increased levels during anesthesia. The latencies of F and M waves were constant before and after anesthesia. Following ketamine administration, the threshold, latency and amplitude of the magnetically induced MEPs, and M, F and H responses were not influenced systematically. The results suggested that MEPs and H-response depression and/or disappearance due to synaptic site suppression after nembutal anesthesia, and the increase and persistence of increased F and M waves amplitudes were all due to the increasing motoneuron excitability, whereas ketamine did not affect synaptic sites subjected to magnetic stimulation.
Res Commun Mol Pathol Pharmacol 1998 Jul
PMID:Magnetically induced motor evoked potentials and H-reflex during nembutal and ketamine anesthesia administration in rats. 975 43

Estrogen increases serotonin transporter (SERT) mRNA and binding sites in female rat brain. In order to determine whether changes in SERT are gender- and steroid-specific we have now carried out studies on adult male Wistar rats which were either intact or castrated (under halothane anesthesia) and injected with arachis oil, estradiol benzoate (EB), testosterone propionate (TP) or the non-aromatizable androgen, 5alpha-dihydrotestosterone (5alpha-DHT). The number of SERT mRNA-expressing cells in the dorsal raphe (DR) nucleus was decreased by castration and increased by treatment (for approximately 32 h) with EB or TP, but not 5alpha-DHT. Sex steroids had no effect on the number of SERT mRNA-expressing cells in the median raphe nucleus. The density of SERT sites, assessed by autoradiography of [3H]paroxetine binding, was significantly reduced in arcuate nucleus and median raphe after castration, and increased in arcuate, basolateral amygdala and ventromedial hypothalamic nucleus by treatment with EB or TP, but not 5alpha-DHT. Estradiol, but not testosterone or 5alpha-DHT reduced the density of SERT sites in midbrain central grey. These data show that testosterone as well as estrogen affects SERT expression in male brain, and that the action of testosterone probably depends upon its enzymatic conversion, by aromatase, to estradiol. Our findings may have implications for sex steroid control of mood and behavior, and the action of neurotoxic derivatives of amphetamine, such as 3, 4-methylenedioxymethamphetamine, in the human.
Brain Res Mol Brain Res 1999 Jan 08
PMID:Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids. 987 62

Succinylcholine is the most important rapid-acting depolarizing muscle relaxant during anesthesia. Its desirable short duration of action is controlled by butyrylcholinesterase, the detoxifying enzyme. There are two reported cases of prolonged paralysis from succinylcholine in patients poisoned with the organophosphorus insecticides parathion and chlorpyrifos. The present study examines the possibility that other organophosphorus and methylcarbamate pesticides might also prolong succinylcholine action by inhibiting butyrylcholinesterase using mice treated intraperitoneally as a model and relating inhibition of blood serum hydrolysis of butyrylthiocholine to potentiated toxicity (mouse mortality). The organophosphorus plant defoliant tribufos (4 h pretreatment, 160 mg/kg) and organophosphorus plant growth regulator ethephon (1 h pretreatment, 200 mg/kg) potentiate the toxicity of succinylcholine by seven- and fourfold, respectively. Some other pesticides or analogs are more potent sensitizers for succinylcholine toxicity with threshold levels of 0.5, 1.0, 1.7, 8, 10, and 67 mg/kg for phenyl saligenin cyclic phosphonate, profenofos, methamidophos, tribufos, chlorpyrifos, and ethephon, respectively. Enhanced mortality from succinylcholine is generally observed when serum butyrylcholinesterase is inhibited 55-94%. Mivacurium, a related nondepolarizing muscle relaxant also detoxified by butyrylcholinesterase, is likewise potentiated by at least threefold on 4 hour pretreatment with tribufos (25 mg/kg) or profenofos (10 mg/kg).
J Biochem Mol Toxicol 1999
PMID:Organophosphorus pesticide-induced butyrylcholinesterase inhibition and potentiation of succinylcholine toxicity in mice. 989 Jan 96

The transgenic mice overexpressing heat shock protein 72 (HSP72) or antioxidants have been reported to be more resistant to myocardial ischemia/reperfusion injury. However, it remains unknown whether whole body heat stress (HS) which may induce HSP72 or endogenous antioxidants affords similar protection in the mouse heart. Adult male mice were treated with either HS (42 degrees C for 15 min) or anesthesia only (SC) against a group of non-stressed controls (NC). At 6 or 24 h later, the hearts were excised and perfused at a constant pressure of 55 mmHg in Langendorff mode. Following 30 min equilibration, hearts were subjected to 20 min of global ischemia and 30 min reperfusion (37 degrees C). Ventricular force was measured by a force-displacement transducer attached to the apex. Leakage of intracellular enzymes (CK, LDH) was measured in coronary efflux. Infarct size was determined by tetrazolium staining. The results showed that no significant differences between HS, SC, and NC groups in ventricular contractile function, CK and LDH release, or infarct size were observed at either time window. HS enhanced the expression of HSP72 in mouse hearts by two- to three-fold, whereas antioxidant enzyme activities (catalase and MnSOD) did not change significantly. We conclude that HS does not precondition the isolated perfused mice hearts against ischemia/reperfusion injury, despite induction of HSP72.
J Mol Cell Cardiol 1998 Nov
PMID:Whole body heat shock fails to protect mouse heart against ischemia/reperfusion injury: role of 72 kDa heat shock protein and antioxidant enzymes. 992 59


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