The effect of dexamethasone on spinal glutamine synthetase and glutamate dehydrogenase expression in morphine-tolerant rats.

BACKGROUND: Excitatory amino acids play an important role in morphine tolerance. Recently, we demonstrated that a single morphine challenge induces an increase in spinal cerebrospinal fluid excitatory amino acid concentrations in morphine-tolerant rats, and that dexamethasone inhibits the development of morphine tolerance. We further examined the effect of intrathecal dexamethasone infusion on the development of morphine tolerance and on expression of the intracellular glutamate metabolizing enzymes, glutamate dehydrogenase and glutamine synthetase, in the spinal cord. METHODS: Male Wistar rats, implanted with an intrathecal catheter, were divided into four groups that were infused for 5 days with intrathecal morphine (15 microg/h), saline (1 microL/h), dexamethasone (2 microg/h), or dexamethasone (2 microg/h) plus morphine (15 microg/h). On Day 5, the spinal cords were removed and prepared for Western blot analysis of glutamate dehydrogenase and glutamate synthetase. RESULTS: Glutamate dehydrogenase and glutamate synthetase concentrations were downregulated in the morphine-tolerant rat spinal cords. Concurrent infusion of dexamethasone attenuated morphine tolerance and the associated glutamate dehydrogenase and glutamate synthetase downregulation. CONCLUSION: Intrathecal dexamethasone attenuates long-term morphine infusion-induced glutamate dehydrogenase and glutamate synthetase downregulation and antinociceptive tolerance.

Levels of glutamic acid decarboxylase (GAD), gamma amino butyric acid transaminase (GABA-T), glutamic acid dehydrogenase (GLDH) and proteins in cerebrospinal fluid of certain neurological disorders.

Important glutamic acid metabolising enzymes in brain namely GAD, GABA-A and GLDH have been studied in the CSF of tuberculous meningitis (TBM), pyogenic meningitis (PM) and brain tumor (BT). The levels of GAD were reported as picomoles of GABA formed/mg of protein/hour. The control levels of the enzymes were GAD = 129 +/- 54, GABA-T = 533 +/- 146 and GLDH...O. 198 +/- 0.097. The levels of GAD were significantly increased (P < 0.001), in both TBM and PM, the values were 302 +/- 81 and, 290 +/- 97 respectively. The GABA-T levels were significantly raised (P < 0.001) only in PM cases 639 +/- 171. The values were reported as nano moles of GABA transformed/mg of protein/hour. The CSF-GLDH levels (unit/litre) showed significant elevation (P +/- 0.001) in TBM in PM, the values were 0.41 +/- 0.1 and 0.41 +/- 0.18 respectively. The CSF proteins were markedly elevated in all the conditions.

[Changes in the biochemical composition of the cerebrospinal fluid in acute carbophos poisoning]. / Izmeneniia biokhimicheskogo sostava tserebrospinal'noi zhidkosti pri ostrom otravlenii karbofosom.

As far as the pathogenesis of poisonings with organophosphorus pesticides is concerned, in addition to irreversible inhibition of acetylcholinesterase (AGE) in tissues, of importance are changes in the other systems which essentially determine the outcome of intoxication. The purpose of the present study was to examine the nature of changes occurring in total protein and protein fractions, free amino acids (aspartic and glutamic acids, glycine, isoleucine, leucine) and in certain enzymes (AST, ALT, CP, GGTP, GDH) in the cerebrospinal fluid (CSF) of patients with acute Malathion insecticide poisoning. 137 patients aged 20 to 50 years were placed under observation. There were 77 men and 60 women. 40 persons had poisoning of medium gravity and 97 were severely poisoned. The intake of the CSF was performed on days 1, 3, 10, 14 and 21 since the disease onset. It has been established that in acute Malathion insecticide poisoning, the CSF content of the stimulating mediator amino acids, aspartic and glutamic, rises within the early periods, whereas the concentration of the inhibitory mediator glycine decreases. The changes in protein fractions of the CSF are characterized by a fall of the content of globulins and a rise of albumins, thus attesting to the predominance of pathological processes in the brain, especially in the initial period of intoxication, and to the impairment of the blood-brain barrier. The development of intoxication is associated with activation in the CSF of LDN, CP, GGTP and GDH as well as by activation of LDH isozymes which is viewed as the result of the membranotoxic effect of a Malathion insecticide.

[Possible pathways of changes in the activity of a number of enzymes in spinal fluid in stroke]. / O vozmozhnykh putiakh izmeneniia aktivnosti riada fermentov v likvore pri mozgovykh insul'takh.

Examination of 234 cases with cerebral stroke showed that the activity of enzymes in the cerebrospinal fluid (CSF) of these patients increased as compared to the control group. In hemorrhagic strokes their activity was considerably higher than in ischemic ones. In 92 cases the results of examination were compared to sectional findings. The activity of enzymes was affected by numerous factors including the speed of stroke development, its nature, the size of the focus, the distance of the latter from the CSF pathways, and the severity of brain oedema.

[Cytochemical determination of the enzyme activity of cerebrospinal fluid lymphocytes in dogs]. / Tsitokhimicheskoe opredelenie aktivnosti nekotorykh fermentov limfotsitov likvora sobak.

Cytochemical methods commonly used in hematology were applied to studying the liquor lymphocytes of dogs. According to our observation of decreasing their activity, the enzymes examined are placed in the following order: alpha-glycerophosphate, glutamate, lactate, and succinate dehydrogenase. High and reliable values of asymmetry and excess coefficients show the absence of the normal distribution of enzymatic activity in the investigated population of lymphocytes.

[Effect of gamma-irradiation on the enzyme activity of cerebrospinal fluid lymphocytes in dogs]. / Vliianie gamma-oblucheniia na fermentativnuiu aktivnost' limfotsitov likvora sobak.

Cytochemical activity of succinate dehydrogenase (SDG), L-glycerophosphate dehydrogenase (L-GPDG), lactate dehydrogenase (LDG), and glutamate dehydrogenase (GDG) increased immediately after total-body irradiation with a dose of 129 mC/kg. After 2 h, LDG activity only returned to the control level. Irradiation of the head with the same dose caused less pronounced changes. Changes caused by lethal irradiation (1290 mC/kg) were different: there was an increase after exposure of the abdomen and a decrease in the activity of SDG and L-GPDG after irradiation of the head.