Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic ammonia toxicity in experimental mice was induced by exposing them for 2 and 5 days to 5 % (v/v) ammonia solution. The enzymes concerned with glutamate metabolism (aspartate-, alanine- and tyrosine aminotransferases, glutamate dehydrogenase and glutamine synthetase) and (Na+ + K+)-ATPase were estimated in the three regions of brain (cerebellum, cerebral cortex and brain stem) and in liver. Glutamate, aspartate, alanine, glutamine and GABA, RNA and protein were also estimated in the three regions of brain and liver. A significant rise in the activity of (Na+ + K+)-ATPase in all the three regions of brain along with a fall in the activity of alanine aminotransferase was noticed. Changes in the activities of other enzymes were also observed. A significant increase in alanine and a decrease in glutamic acid was observed while no change was observed in the content of other amino acids belonging to the glutamate family. As a result of this, changes in the ratios of glutamate/glutamine and glutamate + aspartate/GABA was observed. The results indicated that the brain was in a state of more depression and less of excitation. Under these conditions the liver tissue was showing a profound rise in the activity of the enzymes of glutamate metabolism. The results are further discussed.
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PMID:Chronic metabolic effects of ammonia in mouse brain. 9 19

Ribavirin administered orally at 75 mg/kg/day in 3 divided doses for 10 days, beginning either 1 or 4 days, after aerosol exposure of cats to calicivirus strain 255, failed to have any beneficial effect on the clinical course of the disease or to reduce viral excretion. Indeed, there was enhanced severity of the clinicopathologic findings in the treated exposed group, due largely to hemorrhage resulting from profound thrombocytopenia. Other toxic effects included depression of red and white blood cells, increased alanine aminotransferase activity, icterus, and body weight loss. Toxic effects were largely reversed within 1 week of cessation of treatment.
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PMID:Effect of orally administered ribavirin on experimental feline calicivirus infection in cats. 69 43

Urethral obstruction induced in adult male cats caused clinical signs identical with those observed in naturally occurring disease. Central nervous system depression, anorexia, dehydration, vomiting, muscle weakness, and hypothermia occurred. Weight loss (due to water loss and catabolism), metabolic acidosis, mild hyponatremia, hyperkalemia, hypermagnesemia, hypocalcemia, hyperphosphatemia, hyperglycemia, azotemia, and hyperproteinemia were also observed. Serum amylase, alkaline phosphatase, and alanine aminotransferase activities were normal. Ten of 13 cats (group 1), with 72 hours' induced obstruction but not treated with parenteral fluids, died either before the obstruction was relieved or within 8 days afterward. Eight cats (group 2) with induced obstruction for 49 to 98 hours developed severe clinical and biochemical alterations. Treatment with a multiple-electrolyte solution, in addition to relief of urethral obstruction, resulted in favorable clinical and biochemical responses. These cats survived and were clinically healthy at 9 to 10 days after relief of obstruction. It was concluded that use of a multiple-electrolyte solution to correct acidosis, restore circulatory volume, and enhance renal excretion of potassium was effective supportive therapy after urethral obstruction was removed.
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PMID:Characterization and treatment of water, electrolyte, and acid-base imbalances of induced urethral obstruction in the cat. 87 80

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.
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PMID:Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. 133 43

N-Acetylcysteine (NAC) is protective against acetaminophen-induced hepatotoxicity primarily by providing precursor for the glutathione synthetase pathway, while cysteamine has been demonstrated to alter the cytochrome P-450 dependent formation of toxic acetaminophen metabolite. Mice administered acetaminophen (500 mg/kg) had elevations of serum alanine aminotransferase (ALT) to 273.0 +/- 37.5 and 555.8 +/- 193.4 U/mL at 12 and 24 h, respectively, after injection. Administration of cysteamine (100 mg/kg) or NAC (500 mg/kg) significantly reduced serum ALT activity (p less than 0.001). Reducing the dose of NAC or cysteamine by 50% greatly reduced their hepatoprotective effect while the co-administration of the reduced doses of NAC (250 mg/kg) and cysteamine (50 mg/kg) following acetaminophen overdose prevented elevation of serum ALT activity (39.2 +/- 1.17 and 32.5 +/- 5.63 U/mL at 12 and 24 h post-injection, p less than 0.001) and preserved normal mouse hepatic histology. Neither NAC (500 mg/kg), cysteamine (100 mg/kg), or the lower doses in combination of both agents were found to alter the half-life or peak levels of acetaminophen. Liver microsomal aryl hydrocarbon hydroxylase activity measured 24 h after drug administration was not significantly different between treatment groups and controls receiving only saline. These results indicate a possible role for the concomitant use of NAC and cysteamine in the prevention of hepatic necrosis following toxic doses of acetaminophen. Neither decrease in plasma acetaminophen levels nor depression of cytochrome P-450 enzyme activity appears to be the mechanism of protection when these doses of NAC, cysteamine, or both drugs together are administered with a toxic dose of acetaminophen in mice.
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PMID:Cysteamine in combination with N-acetylcysteine prevents acetaminophen-induced hepatotoxicity. 158 51

The ability of morphine and other opioid analgesic drugs to diminish hepatocellular glutathione (GSH) concentrations was examined in ICR mice. When administered intraperitoneally, morphine, hydromorphone, ethylmorphine, l-alpha-acetylmethadol (LAAM), and meperidine all caused a significant decrease in hepatic GSH concentrations in male mice while codeine, methadone, butorphanol, nalbuphine, and pentazocine were without effect even at doses up to those approaching acute lethality. Depression of hepatic GSH equivalent to that observed after ip administration could be elicited by icv administration of small doses of morphine, ethylmorphine, and hydromorphone. LAAM and meperidine were ineffective following icv administration in these experiments. The discrepancy between results following ip versus icv administration of LAAM and meperidine suggests that hepatic metabolism of some opioids may be important for their activity in the CNS, as both norLAAM and normeperidine diminished hepatic GSH when administered by the icv route. The opioid-induced lowering of hepatic GSH does not appear to be sex-dependent since morphine and LAAM produced qualitatively and quantitatively similar effects on hepatic GSH in female mice. Morphine administered icv produced a substantial increase in the hepatotoxicity of two compounds dependent upon GSH for detoxification, acetaminophen and cocaine, as measured by serum alanine aminotransferase activities. These observations indicate that a number of opioid analgesic drugs have the potential to diminish hepatic GSH. Further, these results support earlier studies which indicate that central opioid effects on hepatic GSH are mediated through mu-opioid receptor stimulation. Last, these studies suggest that a centrally initiated opioid action on hepatic GSH may significantly influence the susceptibility of the liver to the effects of some hepatotoxic agents.
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PMID:Depression of hepatic glutathione by opioid analgesic drugs in mice. 247 Dec 91

Risperidone (R 64766) was administered during 4 weeks in increasing doses to 17 psychotic patients, to evaluate the hematological and cardiovascular safety, the therapeutic effect, side effects, effects upon endocrinological parameters and the pharmacokinetic profile. Following a placebo wash-out period of 1 week, the initial dose was 10 mg daily, increasing with 5 mg per week until the maximal dose of 25 mg daily was reached during the 4th week of treatment. Doses up to 20 mg daily resulted in a significant improvement of the total BPRS score and of the different BPRS factor scores; with higher doses, no further clinical benefit was achieved except for the hostility and anxiety-depression factor, while sedation became more prominent. No increase of extrapyramidal symptoms was noticed. Except for the sedation observed with higher doses, risperidone was well tolerated. No clinically relevant effects on cardiovascular and ECG parameters were noticed, and except for a slight increase of aspartate aminotransferase and alanine aminotransferase in one patient, no laboratory abnormalities were observed. Prolactin showed an expected increase, while the other endocrinological parameters revealed no changes. Risperidone had a linear pharmacokinetic profile.
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PMID:Therapeutic effect and safety of increasing doses of risperidone (R 64766) in psychotic patients. 248 Jun 16

In vivo studies were performed in the dog to verify if sodium lactate had an important effect on the metabolism of glutamine by the kidney. The animals were infused with 0.6 M sodium lactate to induce acute metabolic alkalosis with plasma bicarbonate of 29.7 mM. During these experiments, it was demonstrated that the renal uptake of glutamine increased by 46%, while the renal production of ammonia was unchanged. The renal production of alanine rose from 6.0 to 16.8 mumol/min. Plasma concentration of lactate increased from 1.3 to 19.2 mM, while that of pyruvate increased from 0.075 to 0.454 mM. In the renal tissue, alpha-ketoglutarate, malate, oxaloacetate, lactate, pyruvate, citrate, and alanine increased significantly. Similar changes were found in the liver and skeletal muscle. The observed changes are best described by transamination of pyruvate and glutamate under the influence of alanine aminotransferase (GPT). It can be calculated that this reaction was responsible for 76% of the production of ammonia from glutamine, the latter being necessary to provide glutamate for the synthesis of alanine. Dogs infused with 0.3 M sodium bicarbonate instead of sodium lactate with the same degree of acute metabolic alkalosis, showed a depression of 40% in the renal uptake of glutamine with a 38% decrease in renal ammoniagenesis and a 20% fall in the production of alanine. The present studies demonstrate that the production of ammonia from glutamine is not necessarily related to changes in acid-base balance, but may be associated with biochemical alterations related to the synthesis of alanine by the kidney.
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PMID:The metabolic response of the kidney to acute sodium lactate alkalosis. 286 25

The ability of the alpha adrenoreceptor antagonists phentolamine and yohimbine to antagonize cocaine-induced hepatotoxicity was determined in phenobarbital-induced B6C3/F1 mice. Hepatotoxicity was assessed by the histologic extent of necrosis, incidence of latent lethality and increases in serum alanine aminotransferase activity. The depression of hepatic glutathione levels also were measured. The administration of a single 5-mg/kg dose of phentolamine antagonized the decrease in glutathione levels and the elevation of aminotransferase activity caused by a 60-mg/kg dose of cocaine. Similar results were obtained in mice pretreated with the alpha-2 antagonist yohimbine. Whereas the duration of antagonism could be extended by administering a 30-mg/kg dose of yohimbine, the magnitude of the antagonism was not increased. In contrast to the experiments with the larger dose, multiple hourly doses of 2.5 mg/kg of yohimbine increased both the duration of antagonism and the magnitude of protection against the hepatotoxicity produced by cocaine. Yohimbine pretreatment reduced cocaine-induced latent lethality by 50%, but did not alter the time to lethality. The results of these experiments indicate that the alpha adrenoreceptor antagonist reduces the toxicity of cocaine rather than merely delaying its time of onset. This effect does not appear to result from an inhibition of the toxic metabolite(s) of cocaine, as a 10-fold molar excess of yohimbine failed to antagonize lipid peroxidation caused by in vitro incubation of cocaine with hepatic microsomes. Additional experiments in mice whose liver metabolism had not been induced by prior pretreatment with phenobarbital revealed that 60 mg/kg of cocaine lowered glutathione but was not hepatotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of cocaine-induced hepatotoxicity by the alpha adrenergic antagonists phentolamine and yohimbine. 288 51

The coadministration of phentolamine, an alpha-adrenoreceptor antagonist, was found to be effective in antagonizing the hepatotoxicity produced by bromobenzene in B6C3F1 mice. Multiple doses of phentolamine, administered in dosages of 10 mg/kg, attenuated almost completely the acute lethality resulting from a 0.5 ml/kg dosage of bromobenzene. Consistent with this decline in lethality, the coadministration of phentolamine significantly altered the magnitude of hepatocellular necrosis, the elevation of serum alanine aminotransferase activity, and the glutathione depression normally produced by this dose of bromobenzene. These protective effects were not limited to phentolamine. Idazoxan, an adrenergic antagonist more specific for alpha 2-receptors, was equally effective in antagonizing the bromobenzene-induced hepatotoxicity. Measurements of serum catecholamine levels revealed that the administration of hepatotoxic doses of bromobenzene elevates serum epinephrine levels. Furthermore, the phentolamine antagonism of the bromobenzene hepatotoxicity could be correlated to elevated serum epinephrine levels in both a temporal and dose-dependent manner. Although the mechanism of the phentolamine antagonism remains to be established, one promising hypothesis involves its prevention of an epinephrine-mediated compromise in the glutathione-dependent detoxification of bromobenzene.
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PMID:Antagonism of bromobenzene-induced hepatotoxicity by the alpha-adrenergic blocking agents, phentolamine and idazoxan. 290 Nov 48


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