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)

Polyamino acids including polyaspartic acid (PAA) have been reported to provide protection against the development of aminoglycoside-induced nephrotoxicity in the rat as assessed by histopathology scoring. We sought to confirm and extend these observations by determining whether PAA also prevented functional and biochemical lesions of gentamicin-nephrotoxicity in an animal model studied extensively in our laboratory. Rats were given injections of: 1) 0.9% NaCl at 2.5 ml/kg b.wt. per day; 2) PAA (mol.wt. 15,000) at 500 mg/kg per day; 3) gentamicin at 100 mg/kg per day or 4) gentamicin at 100 mg/kg per day and PAA at 500 mg/kg per day for 6 days. Rats injected with gentamicin exhibited: 1) increased urinary excretion of the brush border membrane enzyme alanine aminopeptidase and the lysosomal enzyme N-acetyl-beta-d-glucosaminidase after the first injection; 2) increased total phospholipid and malondialdehyde but decreased catalase activity in the renal cortex; 3) elevation of serum creatinine and depression of creatinine clearance and 4) extensive proximal tubular cell necrosis all determined 24 hr after the last injection of gentamicin. Rats injected with gentamicin plus PAA also exhibited increased urinary excretion of alanine aminopeptidase not different in magnitude from that of rats injected with gentamicin alone, whereas N-acetyl-beta-d-glucosaminidase rose more slowly and returned to base line by day 4. Total renal cortical phospholipid was elevated to the same extent in the two groups. Malondialdehyde was not different from control and catalase activity was significantly less depressed in rats injected with gentamicin plus PAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyaspartic acid protects against gentamicin nephrotoxicity in the rat. 274 94

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.
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PMID:Diltiazem enhances gentamicin nephrotoxicity in rats. 275 19

To investigate the potential myocardial ischemic effects of ritodrine, we studied 36 singleton and four twin preterm pregnancies during ritodrine therapy. We serially determined serum creatinine phosphokinase (CPK-MB fraction) and lactic dehydrogenase isoenzymes and performed electrocardiography before and during ritodrine infusion and again within the first 24 hours of oral drug therapy. We observed that serum CPK-MB and lactic dehydrogenase isoenzymes remained within the normal range during therapy periods. The incidence of sinus tachycardia and non-specific T wave changes were 100% and 25%, respectively. In three of four twin pregnancies, ST-T segment depression in leads I, V4, V5, and V6 of the electrocardiogram was noted. Our study suggests that (1) the recommended ritodrine regimen does not produce direct myocardial damage, and (2) ritodrine may cause cardiac ischemia as determined by electrocardiography, which theoretically would progress to myocardial damage if not treated properly.
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PMID:Cardiac isoenzymes and electrocardiographic changes during ritodrine tocolysis. 224 70

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.
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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.
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PMID:Urinary bladder rupture in a two-year-old horse: sequel to a surgically repaired neonatal injury. 288 12

The progression of effects induced by administration of ochratoxin A were characterized in young male broiler chickens (Hubbard x Hubbard). The experimental design consisted of four dietary treatments of ochratoxin A (0, 1.0, 2.0, and 4.0 micrograms ochratoxin A/g feed) and 11 replicates of 10 broilers/replicate. Broilers were housed in electrically heated batteries with feed and water available ad libitum. Broilers were weighed, bled, killed by cervical dislocation, and necropsied at 3, 6, 9, 12, 15, 18, and 21 days of age. Toxicity of ochratoxin A to broilers was evident as early as 6 days of age, when significant (P less than .05) growth depression occurred at 4.0 micrograms dietary ochratoxin A/g feed. Dietary ochratoxin A significantly increased the relative weights of the liver, kidney, spleen, pancreas, and gizzard. Anemia, characterized by a significant decrease in packed-cell volume and hemoglobin levels, was present during ochratoxicosis. Hepatotoxicity of dietary ochratoxin A was evident through an observed significant reduction in serum levels of total protein, albumin, globulin, cholesterol, triglyceride, and blood urea nitrogen, and a significant increase in the serum activities of gamma glutamyl transferase and cholinesterase. A significant increase in serum uric acid and creatinine levels was indicative of nephrotoxicity. These data provide a description of the progression of ochratoxicosis in broilers that should be useful in diagnosis and in improved understanding of ochratoxicosis.
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PMID:Progression of ochratoxicosis in broiler chickens. 290 99

We have assessed the effects of acute and chronic administration of etodolac, ketoprofen, and indomethacin on renal function in patients with mild to moderate chronic renal insufficiency (CRI). We studied 18 normal volunteers and 24 patients with CRI due to hypertension and/or diabetes mellitus with creatinine clearances between 19 and 83 mL/min/1.73 m2. Clearance studies were performed with the first dose of nonsteroidal antiinflammatory drug (NSAID) to compare acute effects of the agent with a no-drug control. Subjects then received the NSAID for three to five days and, on the last day of study, underwent another clearance study to assess the effects of a single dose of NSAID superimposed on chronic dosing. With each dose of each NSAID, inulin and paraaminohippurate (PAH) clearances and fractional excretion of NA+ decreased. However, the baseline control collections after chronic dosing did not differ from the no-drug control periods. Hence, the decline in renal function with each dose is transient, and no overall adverse effect on renal function occurred with chronic dosing. In five patients with cirrhosis, we assessed the renal sparing effects of sulindac. After equilibration on a fixed sodium intake, they received a 200-mg dose of sulindac. In one patient, no adverse effect occurred; the remaining patients suffered declines in creatinine clearance of 29%, 87%, 37%, and 37%, respectively. This effect was transient and returned to control values six to eight hours after sulindac administration. At the time of maximal depression of renal function, serum concentrations of sulindac sulfide were comparable to those in subjects with normal hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nonsteroidal antiinflammatory drugs on renal function in patients with renal insufficiency and in cirrhotics. 294 56

We have evaluated the effects of dextrofenfluramine treatment on body weight control during a 90 day period, in obese patients on a calorie-restricted diet. The weight loss in dextrofenfluramine-treated patients was significantly higher than in placebo group. The rate of weight loss was linear up to the end of the trial in d-fenfluramine patients. Neural disturbances (vertigo, headache, depression) were the most frequent side effects observed in both the d-fenfluramine and in the placebo-treated groups, without significant differences between the groups. A total number of 23 patients in the dextrofenfluramine group and 20 patients in the placebo group complained side effects. Six patients (five in the d-fenfluramine group and one in the placebo group) discontinued the treatment, due to the side effects. No modifications of the biochemical parameters considered (fasting blood glucose, bilirubin, alkaline phosphatase, creatinine, blood cell counts, asparate-amino transferase (AST), alanine-amino transferase (ALT), total plasma and HDL cholesterol, and triglycerides) were observed at the end of the trial. A significant reduction of total serum cholesterol was observed in both groups at the end of the period of treatment. In conclusion, dextrafenfluramine was proved to be in short term trials an effective and safe tool in overweight control in obese patients.
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PMID:Efficacy and safety of dexfenfluramine in obese patients: a multicenter study. 305 15

A 28-year-old woman, had, every month, a premenstrual manic-depressive cycle beginning with a hypomanic episode followed by a depression which improved with menstruation. The lithium serum level oscillated in a regular and inverse relationship to the mood changes, although the patient received a constant dosage of lithium: 16.2 mmol/l per day. The lithium level reached its highest value at the time of the greatest intensity of depression (1.10 mmol/l), and its lowest value during the time of hypomania (0.30 mmol/l), whereas it showed only small oscillations around 0.5 mmol/l when the patient's mood was normal. RBC lithium concentration and lithium excretion in the urine followed the same pattern. The daily creatinine excretion was usually within normal limits. It must be hypothesized that there are compartments or stores, to and from which lithium is transported, by mechanisms related to the biological basis of mood changes.
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PMID:The influence of mania and depression on the pharmacokinetics of lithium. A longitudinal single-case study. 315 25

Thirty-eight children received 41 living-donor kidney transplants in an 11-year period; 73% of the grafts are functioning well. The parents of the recipients were the usual donors (60% of the donors were mothers and 25% of the donors were fathers); however, there were five donations from siblings and one donation from a donor who was related emotionally to the recipient. The most frequent perioperative complications were respiratory but these were not serious and did not cause any long-term sequelae. The principal long-term complications that related to--or were perceived by the donor as being related to--the procedure were incisional pain (20% of donors) and depression (25% of donors). These were not related to the success or otherwise of the transplantation. At follow-up, five (12%) donors had diastolic blood pressure levels of greater than 90 mmHg or were receiving antihypertensive therapy; this prevalence is similar to that which is found in the community. Two donors had urinary protein excretion rates of greater than 200 mg/24 h (210 mg/24 h and 350 mg/24 h, respectively). Creatinine clearance rates fell by 15% in women and by 5% in men. Serum creatinine levels had risen by 40% in men and by 35% in women after the nephrectomy; these levels had changed little at follow-up. All donors said that they would have proceeded with the donation even with fore-knowledge of what they would experience during and after the donation. Living-donor renal transplantation is a procedure with very low but definite operative risks which nevertheless provides a means for the early effective replacement of renal function in children with growth potential. The donors are enabled to make a major contribution to the life and well-being of the child, and they regard the perioperative complications as minimal. There do not appear to be any serious long-term complications of renal donation.
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PMID:The living, related kidney donor: a follow-up study. 328 5


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