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

Hibernation was induced in hamsters by placing them in a cold room for an extended period of time, after which the hibernating state was confirmed by marked reductions in heart rate, body temperature, and the respiratory rate. The animals were either frozen intact in liquid nitrogen, or aroused and then frozen when body temperature reached 8, 12, 16, 20, 24 or 32 degrees C. A metabolite profile, including glucose-related metabolites, high-energy phosphates, gamma-aminobutyric acid (GABA) and cyclic nucleotides, was determined for both the cerebral cortex and cerebellum. In general, the metabolite changes in the two regions elicited by hypothermia were alike, although some differences were evident. The brains of hibernators were biochemically characterized by (1) a high concentration of energy reserves including glycogen, glucose, adenosine triphosphate, and P-creatine, (2) significantly elevated levels of lactate and GABA, and (3) near depletion of cyclic guanosine monophosphate with only a moderate depression of cyclic adenosine monophosphate. During arousal, the metabolites were restored to near normal values and there was little or no indication that the brain energy metabolism was compromised by the arousal process. The study provides certain insights into the metabolic adaptation of the brain to prolonged periods of profound hypothermia in a hibernating species.
 ...
PMID:Metabolism in the hamster brain during hibernation and arousal. 274 44

The effect of the calcium antagonist, diltiazem, was examined in gentamicin-induced nephrotoxicity states in rats. Animals were injected for 5 days with diltiazem intraperitoneally (40 mg/kg/day), or gentamicin subcutaneously (100 mg/kg/day) or simultaneously with both preparations using the same doses. At the time of sacrifice, the urea and creatinine clearances, as well as urine osmolality were determined and the renal tissues were processed for examination by light microscopy. Gentamicin-injected rats demonstrated the typical pattern of aminoglycoside nephrotoxicity characterized by poliuric renal failure and necrosis of the proximal tubular epithelium. Rats injected with diltiazem revealed only mild depression of urine osmolality. There was no elevation of blood urea nitrogen and serum creatinine or depression of urea and creatinine clearances, and no focal tubular cell necrosis was detected. However, concomitant administration of both compounds considerably increased nephrotoxicity by according both histological indications and renal function measurements. Thus, we conclude that the combination of diltiazem and gentamicin must be used carefully in human clinical practice.
 ...
PMID:Diltiazem enhances gentamicin nephrotoxicity in rats. 275 19

It has been proposed that administration of non-nitrogenous precursors to glycine is necessary to realize the full potential of benzoate metabolism as a pathway for disposal of waste nitrogen during ammonia intoxication (Coude et al., Clin Chim Acta 136: 211-217, 1984). However, when glyoxylate, a keto acid precursor to glycine, was administered with benzoate 1 hr prior to a challenge of ammonia, protection against ammonia toxicity was less successful than with benzoate alone. At the cellular and subcellular levels, glyoxylate and benzoate each inhibited the urea cycle in isolated hepatocytes and pyruvate carboxylase in isolated mitochondria. The action of each drug was associated with depletion of aspartate content in isolated hepatocytes and reduction of pyruvate-dependent incorporation of CO2 into aspartate in assays with isolated mitochondria. Depression of aspartate regeneration by inhibition of pyruvate carboxylase is a likely mechanism for impairment of urea cycle activity by both drugs. In whole animals, inhibition of pyruvate carboxylase may contribute to benzoate toxicity and the adverse influence of glyoxylate on benzoate therapy.
 ...
PMID:Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle. 277 12

Spreading depression refers to a slowly propagating depression of the ordinary electrical activity of the nervous tissue. It can be elicited by different types of physical or chemical non-specific stimuli. Various evidences suggest that transient alterations of cell membranes are involved. For this reason, and considering the action of free radicals on cell membranes, the elicitation of the reaction by dye photoactivation has been investigated. Isolated chick retina superfused in the dark with Ringer solution was able to regularly exhibit spreading depression when submitted to 1 microM rose bengal pulse of 5 min in duration, followed by 2.1 x 10(4) to 4.2 x 10(4) Jm-2 light pulse. The phenomenon was monitored either by visual inspection of the light-scattering milky wave that accompanies the reaction or by recording its characteristic slow voltage variation. The reaction was not triggered if the retina, superfused with the dye, was (a) maintained in the dark; (b) illuminated with red light (3.75 x 10(2) to 2.25 x 10(4) Jm-2), or (c) stimulated by white light but superfused with nitrogen-saturated solutions. It is concluded that, under the present conditions, the elicitation of spreading depression is contingent on the photoactivation of rose bengal in the presence of oxygen.
 ...
PMID:Elicitation of spreading depression by rose bengal photodynamic action. 278 Aug 18

Despite evidence from animal experiments to the contrary, nitrous oxide (N2O) reportedly does not induce myocardial ischemia when used as an adjunct to fentanyl anesthesia in patients with coronary artery disease who have well-preserved left ventricular (LV) function. However, the incidence of ischemia with N2O administration in similar patients with poor LV function may be different. The effects of N2O on segmental LV function, as determined by two-dimensional transesophageal echocardiography, changes in the ST-segment of the electrocardiogram were compared with the effects of an equal concentration of nitrogen (N2) (crossover design) in 70 patients who required elective coronary artery bypass grafting. Of these patients, 24% had left ventricular ejection fraction (LVEF) less than or equal to 40%. Myocardial ischemia was diagnosed in 14 patients during the study: four while awake, seven during induction of anesthesia and tracheal intubation, and four during the remainder of the study (one during N2O and three during 100% oxygen; one patient had two distinct periods of ischemia). No value for LVEF could be found that would distinguish between patients who did or did not have ischemia during the study. Patients treated with beta-adrenergic blocking drugs preoperatively were less likely to develop ischemia (P less than 0.05). Preoperative calcium channel blockers made no such differences. Onset of ischemia was not closely associated with hemodynamic changes. Thus, N2O does not induce clinically detectable myocardial ischemia in patients who have coronary artery disease, and poor LV function in situations in which the effects of deepening anesthetic depth and mild depression of global myocardial function are deemed desirable or harmless.
 ...
PMID:Nitrous oxide does not induce myocardial ischemia in patients with ischemic heart disease and poor ventricular function. 280 10

Cysteine is required for the synthesis of cosubstrates for two pathways of acetaminophen metabolism: 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for sulfation and glutathione (GSH) for detoxification of the reactive metabolite (N-acetyl-p-benzoquinoneimine, NAPQI). Dietary deficiency of cysteine may reduce hepatic production of PAPS and GSH and thereby reduce metabolism of the drug (by sulfation and detoxification of NAPQI) and hence lead to potentiation of acetaminophen liver injury. Conversely, limitation of sulfur-containing amino acids could result in depression of protein synthesis and hepatic cytochrome P450 levels, and hence in decreased reactive metabolite formation and decreased liver injury. To determine whether the potentiating effects exceed the protective effects, rats were fed isocaloric AIN-76 liquid diets containing various levels of methionine as the sole source of sulfur in the diet for 3 weeks prior to administration of acetaminophen. Sulfur deficiency was assessed by measuring urinary inorganic sulfate levels. Sulfur-deficient diets retarded growth but did not affect nitrogen balance. Sulfur-deficient animals had lower basal levels of hepatic GSH. Pharmacokinetic studies revealed that at low doses of acetaminophen (20 mg/kg), animals fed sulfur-deficient diets metabolized the drug more slowly due to a markedly reduced sulfation capacity, whereas at the high dose of acetaminophen (400 mg/kg), rats that were fed sulfur-deficient diets had a higher clearance of the drug than rats that were fed the complete diet. The increase in clearance was due largely to an enhanced glucuronidation capacity and an enhanced P450-dependent oxidation as indicated by mercapturate formation. Histologic studies revealed that rats fed sulfur-deficient diets showed increases in both incidence and severity of acetaminophen hepatic necrosis. Thus, the potentiating effects exceeded the protective effects. These observations raise the possibility that nutritional inadequacy of sulfur-containing amino acids which could occur during protein malnutrition may similarly enhance susceptibility to acetaminophen liver injury in humans.
 ...
PMID:Effects of sulfur-amino acid-deficient diets on acetaminophen metabolism and hepatotoxicity in rats. 281 88

Studies were conducted on the effects of feeding D-amino acids on growth rate and D-amino acid oxidase (DAAO) in chick kidney. The crystalline amino acid (AA) diet provided seven amino acids either in the L-form or the DL-form at two concentrations (DL- or .5 DL-AA diets) with all diets containing equal amounts of L-amino acids. Weight gains of chicks fed the DL-AA diet were consistently lower than those fed the L- or .5 DL-AA diet. Kidney DAAO activity was significantly higher in chicks fed either the DL-AA or .5 DL-AA diet as compared with the L-AA diet. Kidney DAAO activity was essentially the same in chicks fed the DL- and .5 DL-AA diets. Increasing the nonspecific nitrogen in the diet had no effect in alleviating growth depression of the DL-AA.
 ...
PMID:Effects of D-amino acids on growth rate and kidney D-amino acid oxidase in chicks. 288 43

Methylenedioxymethamphetamine (MDMA) was administered to dogs and rats orally once a day for a 28-day period to evaluate the morphological and neuropathological effects. Major clinical signs associated with the administration of MDMA in the dog included circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation. Major clinical signs in the rat included hyperactivity, excitability, piloerection, exophthalmos, and salivation. Gross observations at necropsy in the dog possibly related to administration of the test article included reduced testicular size (one high and one medium dose) and prostatic enlargement in two high-dose animals. No gross lesions were seen in the rats at necropsy. The medium- and the high-dose groups in both sexes in both the rats and the dogs gained significantly less weight than the control and low-dose groups. Food consumption decreased the first week for the high- and medium-dose groups, but a significant reversal toward more normal consumption was noted in the following weeks in both the rats and the dogs. Hematologic, clinical chemistry, and urinalysis values did not appear to be affected by the administration of the test article in the dog. In the rat clinical pathology variables showing a trend to decrease with dose included urinary pH, blood urea nitrogen, glucose, creatinine (females), lactate dehydrogenase (LDH) (females), and chloride. Clinical pathology variables showing a trend to increase with dose included total white blood cell count and phosphorus. Microscopically, testicular atrophy was present in one medium-dose and two high-dose male dogs. Prostatic hyperplasia was present in two high-dose male dogs. No test article-related lesions were seen in the brains of either species.
 ...
PMID:Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat. 288 76

After routine cryptorchid castration, a 2-year-old Thoroughbred colt was admitted 72 hours later because of depression, abdominal distention, and pollakiuria, with production of small quantities of urine. A diagnosis of a ruptured bladder was made on the basis of a large volume of abdominal fluid and a disparity between the urea nitrogen and creatinine concentrations in the serum (70 mg/dl and 8.4 mg/dl, respectively) and in the abdominal fluid (154 mg/dl and 43 mg/dl, respectively). The colt had undergone surgical correction of a ruptured urinary bladder at 4 days of age, and a 5-cm tear through one of the previous scars was identified and repaired during exploratory celiotomy. The previous injury to the bladder was extensive and may have left an inherent weakness in the bladder wall. Evidence of adhesion formation or urethral obstruction was not found. The combination of a full bladder and the trauma associated with induction of anesthesia may have contributed to the recurrence of bladder rupture.
 ...
PMID:Urinary bladder rupture in a two-year-old horse: sequel to a surgically repaired neonatal injury. 288 12

Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations.
 ...
PMID:Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat. 289 15


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