Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effects of two stabilised analogues of TRH, RX 77368 and CG 3509, in a rat cerebral ischaemia model produced by unilateral occlusion of the middle cerebral artery. The analogues were given intraventricularly after artery occlusion. The extent of the cortical ischaemia was evaluated after 10 days by somatosensory evoked potential (SEP) recording, followed by tetrazolium staining of brain slices for NADH-diaphorase activity. RX 77368 (2 X 10 micrograms; 15 min, 24 h) significantly improved the survival rate, protected the SEP and reduced the area of infarct. In contrast, neither a smaller dose of RX 77368 (2 X 3 micrograms) nor a 4 h delay in the treatment had any significant beneficial effects. Although CG 3509 (2 X 10 micrograms) resulted in an apparent improvement in survival, its overall effects were not statistically significant. The findings indicate that stabilised TRH analogues may have beneficial effects when given to animals with focal cerebral ischaemia.
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PMID:The effects of TRH analogues on cerebral ischaemia produced by middle cerebral artery occlusion in the rat. 313 37

To elucidate the mechanism by which TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro], act on the maturation of homoiothermy, the chronic effects of intrathecal administration of the peptides on body temperature, serum thyroid hormone levels, and mitochondrial energy-producing enzyme activities were examined in neonatal rats. The two peptides or an equimolar mixture of both were injected intrathecally at a dose of 3, 6 and 9 nmol for 7 consecutive days during the 1st, 2nd or 3rd week of life, respectively. Control rats were treated with saline and they were sacrificed at 6 weeks of age. Although food and water intake were not decreased, body weight gain was slightly reduced in the rats treated with TRH or cyclo(His-Pro) during the 1st and 2nd week of life, whereas the mixture-treated rats showed normal weight gain. Body temperature at 25 degrees C was not different in the TRH- and cyclo(His-Pro)-treated groups, whereas after cold exposure (5 degrees C for 3 h), the groups treated with TRH during the 1st and 2nd week of life had an impaired thermoregulation at 5 weeks of age. Serum T4 and T3 concentrations were similar in all groups, except in the rats treated with TRH during the 2nd week of life; their thyroid hormone levels were slightly reduced. The TRH treatment suppressed mitochondrial cytochrome c reductase and glucose-6-phosphatase activities, whereas cyclo(His-Pro) reduced cytochrome c reductase and malic enzyme activities. In contrast, alpha-glycerophosphate dehydrogenase was enhanced by both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of thyrotropin-releasing hormone and histidyl-proline diketopiperazine on the maturation of homeothermia and mitochondrial enzyme activities in neonatal rats. 314 9

The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
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PMID:Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment. 781 45