Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid aspiration is a serious complication of anesthesia and other forms of unconsciousness that can result in the adult respiratory distress syndrome (ARDS), which continues to have a very high mortality despite our current therapeutic interventions. This type of injury damages the alveolar epithelium, principally alveolar type I cells, and requires proliferation of alveolar type II cells to restore gas exchange units. Since keratinocyte growth factor (KGF) has been shown to be a potent mitogen for alveolar type II cells, we evaluated whether intrabronchial administration of KGF would minimize lung injury due to the unilateral instillation of 0.1 N hydrochloric acid (HCl). Rats were pretreated or post-treated by intrabronchial instillation of KGF (5 mg/kg) into the left lung before HCl instillation. All rats receiving KGF at 48 or 72 h before HCl instillation survived for the 7-day observation period, whereas the mortality rate for those receiving HCl alone or saline followed by HCl was 31% and 33%, respectively. Pretreatment with KGF at 72 h but not at 24 or 48 h considerably ameliorated morphologic damage produced by HCl. Inflammatory cells in bronchoalveolar lavage were markedly decreased 3 and 7 days after HCl instillation by the 72-h KGF pretreatment. Pretreatment with KGF at 72 h also attenuated the reduction of total lung capacity, decreased the alpha 1(I) procollagen mRNA levels, and diminished hydroxyproline accumulation due to HCl instillation. Saline pretreatment at 72 h had no significant effect on the HCl injury and subsequent physiologic abnormalities. Our attempts to improve outcome with post-treatment instillation of KGF were unsuccessful. We conclude that KGF pretreatment reduces lung injury due to acid instillation and can prevent subsequent pulmonary fibrosis.
Am J Respir Cell Mol Biol 1996 Oct
PMID:Keratinocyte growth factor reduces lung damage due to acid instillation in rats. 887 76

Although thiopental is known to potentiate halothane-epinephrine arrhythmias, the precise mechanism of this potentiation is obscure. The authors investigated the comparative role of alpha 1 and beta adrenergic actions in the thiopental-induced potentiation of halothane-epinephrine arrhythmias in dogs. Adult mongrel dogs were anesthetized with halothane alone (1.3%) or thiopental (20 mg kg-1) plus halothane and monitored continuously for systemic arterial pressures and for premature ventricular contractions. The arrhythmogenic doses of phenylephrine and isoproterenol were determined during the two anesthetic methods and the effect of thiopental on the arrhythmogenic action of alpha 1 and beta agonists was examined. Thiopental failed to exert a significant potentiation of arrhythmogenic effect of phenylephrine or isoproterenol, when these agents were administered separately. On the other hand, the potentiation of arrhythmogenicity by thiopental was remarkable in the case of combined administration of both the agonists, that is, thiopental enhanced the synergistic interaction between phenylephrine and isoproterenol for inducing arrhythmias during halothane anesthesia. In addition, the potentiation was more prominent when a low dose of isoproterenol and a high dose of phenylephrine was combined than that when a high dose of isoproterenol and a low dose of phenylephrine was given in combination. The results indicate that thiopental significantly potentiates the arrhythmogenic interaction of alpha 1 and beta adrenergic agonists administered concurrently, although individual potentiation of these agonists is not significant.
Res Commun Mol Pathol Pharmacol 1996 Aug
PMID:Adrenoceptor mechanism involved in thiopental-induced potentiation of halothane-epinephrine arrhythmias in dogs. 888 93

In the present study, we examined the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA i specific brain regions following experimental lateral fluid percussion traumatic brain injury (TBI) in rats. Adult Sprague-Dawley rats (n = 42) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and subjected to lateral fluid percussion brain injury of moderate severity (2.4 atm.) centered over the left temporoparietal cortex, or 'sham' treatment (anesthesia and surgery without injury). Animals were killed by decapitation at 1, 6 or 24 h post injury, brains removed, and tissue samples of left (injured) parietal cortex (LC), right parietal cortex (RC), left adjacent cortex (LA), right adjacent cortex (RA), left hippocampus (LH) and right hippocampus (RH) were prepared. Total RNA was isolated and Northern blot hybridization was performed. TNF-alpha mRNA is expressed as the percent relative radioactivity of macrophage (positive control) RNA. In sham or naive animals, no consistent changes in expression of TNF-alpha mRNA were observed in any of the six brain areas at any times (less than 5%). A marked increase of TNF-alpha mRNA expression was observed in LH (104 +/- 17, P < 0.05 compared with sham), LC (105 +/- 21, P < 0.05) and LA (69 +/- 8, P < 0.01) in the traumatized hemisphere 1 h following injury. An increased TNF-alpha mRNA expression was also observed in LH (46 +/- 8, P < 0.05), LC(30 +/- 3, P < 0.01) and LA(32 +/- 3, P < 0.01) at 6 h which resolved by 24 h following injury. In the contralateral hemisphere, expression of TNF-alpha mRNA was increased in RH (46 +/- 2, P < 0.01) at 1 h and in RA (26 +/- 6%, P < 0.05) at 6 h. These results indicate that following parasagittal fluid percussion brain injury, the temporal expression of TNF-alpha mRNA is altered in specific brain regions, including those of the non-traumatized hemisphere. Post-traumatic alteration in gene expression of TNF-alpha might play an important role in both the acute and regenerative response to CNS trauma.
Brain Res Mol Brain Res 1996 Mar
PMID:Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS. 896 49

Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To address this issue, we synthesized enantiomers to (+)-3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile and (+)-3alpha-hydroxy-5alpha-pregnan-20-one. In this study, we show that potentiation of GABA-mediated currents and gating of the GABA(A) channel by steroids, as well as steroid-induced anesthesia in tadpoles and mice, is enantioselective, with the (+)-enantiomers exhibiting significantly greater potency in all assays. The correlation between the effects of steroid enantiomers on channel behavior and their effects as anesthetics provides strong evidence that GABA(A) receptors play a predominant role in steroid-induced anesthesia. The enantiomers also provide a tool to probe the relative contributions of direct chloride channel activation versus potentiation of GABA-elicited currents to the induction of anesthesia. Studies examining the effects of combinations of (+)- and (-)-3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile were consistent with the hypothesis that potentiation of GABA-activated currents contributes to steroid-induced anesthesia but indicated that direct steroid activation of GABA(A) receptors is not mechanistically important in producing anesthesia.
Mol Pharmacol 1996 Dec
PMID:Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia. 896 80

The purpose of this study was to develop a primate model for assessing EEG, behavior and histology, and to test the effect of NMDA receptor blockade in transient focal ischemia. Squirrel monkeys (Saimiri sciureus) under halothane anesthesia were subjected to 110 min of transient focal ischemia (n = 15) by temporary clip occlusion of the MCA. An eight-lead EEG was recorded. Neurobehavioral testing was done in a subgroup of animals (n = 6). Brain temperature (37.5 degrees C) was monitored and controlled to avoid hypothermia or intergroup temperature differences, and blood pressure was regulated to 60 mmHg. The entire brain was subserially sectioned, and 52 standardized coronal sections encompassing the infarct were examined histologically 2 wk after the ischemia. Animals were randomized to receive either (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) 1 mg/kg of maleate salt or carrier solution, 20 min and again at 12 h after the onset of ischemia. Cingulate and retrosplenial cortex were examined for NMDA-antagonist-induced neuronal necrosis. No reduction, or trend toward reduction of neurobehavioral deficit was seen with MK-801. MCA occulsion reduced EEG power over the ischemic hemisphere. MK-801 appeared to cause brain activation, and globally increased power at several frequencies. MK-801 did not reduce infarction in either neocortex (p > 0.05) or striatum (p > 0.05). No selective neuronal necrosis was seen in the cingulate or retrosplenial cortex. We conclude that MK-801 given 20 min after the onset of transient ischemia offers no significant neuroprotective effect against either neurobehavioral deficit or ischemic infarction in this model of transient focal ischemia. Further experiments in unanesthetized animals are necessary to determine if MK-801-induced necrosis exists in the gyrencephalic brain, but the enhancement of primate brain electrical activity by MK-801 suggests that brain activation occurs in primates as it does in rodents.
Mol Chem Neuropathol
PMID:Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia. 897 96

Succinic semialdehyde reductase (SSR) that catalyzes the reduction of succinic semialdehyde (SSA) to gamma-hydroxybutyrate (GHB) has been identified as one of the NADPH-dependent aldehyde reductases. Reduction of SSA to GHB strongly supports the proposal that GHB biosynthesis may be an important step in the GABA shunt. It is pharmacologically significant in anesthesia, evoking the state of sleep, and an increase in brain dopamine level. Monoclonal antibodies against bovine brain succinic semialdehyde reductase were produced. Using the anti-succinic semialdehyde reductase antibodies, we investigated the distribution of brain succinic semialdehyde reductase in rat brain. The brain tissues were sectioned with a basis on the rat brain atlas of Paxinos and were stained by the immunoperoxidase staining method using monoclonal antibodies. In the section of the frontal lobe, immunoreactive cells were observed in the lateral septal area, the ventral pallidum, which belongs to the substantia innominata. We could observe immunoreactive cells in the reticular thalamic nucleus, which is closely related with 'sleeping', the basal nuclei of Meynert, which is associated with Alzheimer's disease, and hypothalamic nuclei. Immunoreactive cells were also shown in raphe nuclei or the reticular formation of the midbrain, cerebellum, and inferior olivary nuclei of the medulla oblongata. Succinic semialdehyde reductase-immunoreactive cells were distributed extensively in rat brain, especially immunoreactive cells were strongly observed in the areas associated with the limbic system and reticular formation.
Mol Cells 1997 Feb 28
PMID:Distribution of succinic semialdehyde reductase in rat brain. 908 59

The effects of diazepam, a typical benzodiazepine receptor agonist, on gastric acid secretion were studied in both conscious pylorus-ligated rats and the perfused stomach of rats under urethane anesthesia. Diazepam did not affect acid secretion in conscious pylorus-ligated rats. Under urethane anesthesia, diazepam showed a definite stimulation on gastric acid secretion. However this stimulatory action was caused neither by 4'-chlordiazepam, which is a peripheral benzodiazepine receptor agonist, nor beta-carbline-3-carboxylic acid methyl ester, which is an inverse benzodiazepine receptor agonist. Pretreatment with atropine, hexamethonium or bilateral truncal vagotomy inhibited the diazepam-induced acid secretion. Pretreatment with flumazenil, which is a benzodiazepine receptor antagonist, reduced the acid secretion induced by diazepam, but pretreatment with 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide, which is a peripheral benzodiazepine receptor antagonist, did not reduce the acid secretion induced by diazepam. 3-Mercaptopropionic acid, which is an inhibitor of GABA biosynthesis, picrotoxin and pentylenetetrazol inhibited diazepam-stimulated acid secretion. Gastric acid secretion stimulated by baclofen was not affected by flumazenil, 3-mercaptopropionic acid or picrotoxin. These results suggest that acid secretion is centrally stimulated by diazepam in rats under anesthesia, and the stimulatory action is closely associated with benzodiazepine-GABA complex receptors.
Res Commun Mol Pathol Pharmacol 1997 Feb
PMID:Stimulatory effect of diazepam on gastric acid secretion in the continuously perfused stomach in rats under urethane anesthesia. 909 Jul 52

The contribution of ATP sensitive potassium (K(ATP)) channels to the infarct-size limiting effect of preconditioning is considered to be anaesthetic-dependent in the rabbit heart. It has previously been reported that ischaemic preconditioning prevents ischaemia-induced reductions in activities of sarcolemmal adenylate cyclase (AC) and Na+, K(+)-ATPase. Anaesthetic dependency of the role of K(ATP) channels in the preservation of these enzyme activities, induced by ischaemic preconditioning, as well as that induced by activation of A1-adenosine receptors, was examined in rabbits anaesthetized with either pentobarbital or ketamine-xylazine and subjected to 20 min of regional ischaemia. Adenylate cyclase and Na+, K(+)-ATPase activities were lower in the ischaemic than in the non-ischaemic region of the hearts in control rabbits, but not in animals subjected to ischaemic preconditioning, or those pretreated with the A1-adenosine receptor agonist R(-)-N6-(2-phenylisopropyl) adenosine. The protective effects of both ischaemic preconditioning and A1-adenosine receptor activation were prevented by 6 mg/kg, but not 3 mg/kg, of the K(ATP) channel blocker, glibenclamide, in rabbits anaesthetized with pentobarbital, while these effects were prevented by 3 mg/kg of the blocker in rabbits anaesthetized with ketamine-xylazine. Moreover, K(ATP) channel opener, cromakalim, prevented the ischaemia-induced decreases in enzymatic activities in rabbits subjected to either type of anaesthesia. Thus, although the antagonistic effect of glibenclamide is blunted under pentobarbital, compared to ketamine-xylazine anaesthesia, K(ATP) channels contribute to preservative actions independent of the type of anaesthesia in the rabbit heart.
J Mol Cell Cardiol 1997 Apr
PMID:K(ATP) channels contribute to the cardioprotection of preconditioning independent of anaesthetics in rabbit hearts. 916 Aug 78

Anesthetic agent, arterial pCO2 level, and opioid peptides have all been implicated in the pathophysiology of experimental stroke models. The effects of halothane, alpha-chloralose, and differing concentrations of arterial pCO2 on injury volume and CSF beta-endorphin levels were studied in a feline model of experimental focal cerebral ischemia. The type of anesthetic agent used had no effect on injury volume following 6 h of focal cerebral ischemia. Over a 6-h period, beta-endorphin levels significantly increased from 10.1 +/- 5.0 fmol/mL at zero time to 14.4 +/- 7.2 fmol/mL at 6 h under halothane anesthesia (p < 0.05), whereas they did not significantly change (10.1 +/- 6.7 to 7.8 +/- 4.7 fmol/mL) under alpha-chloralose anesthesia. In contrast, hypercapnia had no effect on beta-endorphin levels, but significantly increased injury volume from 30.6 +/- 5.7% of the ipsilateral hemisphere under normocapnic conditions to 37.1 +/- 5.9% under hypercapnic conditions (p < 0.05). These results suggest that hypercapnia increases injury volume in a feline model of focal cerebral ischemia, and pCO2 should be controlled in experimental focal cerebral ischemia models.
Mol Chem Neuropathol 1997 May
PMID:Effects of halothane, alpha-chloralose, and pCO2 on injury volume and CSF beta-endorphin levels in focal cerebral ischemia. 927 Oct 3

The free radical levels in the cerebrospinal fluid of 8 patients with neurological diseases and 9 undergoing lumbar anesthesia for surgery were measured. The ascorbate free radical level 10 min after lumbar puncture showed a positive correlation with the hydroxyl radical level. In the patient with mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free radicals increased upon discontinuation of treatment and decreased upon its resumption, and the ascorbate free radical levels without therapy fell after lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect the degree of oxidative stress in the central nervous system.
Biochem Mol Biol Int 1997 Aug
PMID:Free radicals in the cerebrospinal fluid are associated with neurological disorders including mitochondrial encephalomyopathy. 928 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>