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)

NH4Cl was infused into the left renal artery of anesthetized dogs at 50-125 mum/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 mum/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO3 during arterial infusion of NH4Cl prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 mum/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.
 ...
PMID:Some effects of ammonium salts on renal histology and function in the dog. 0 Jun 32

The separate administration of mercuric chloride (HgCl2) and sodium selenate (Na2SeO4) to male rats in drinking water or a combined administration of both (50 ppm Hg, 15 ppm Se) caused different signs of toxicity over a 22 week period. The HgCl2 group showed histopathological and ultrastructural lesions as evidenced by periportal fatty degeneration and cell necrosis in the liver and tubular necrosis with proteinaceous casts in the kidney. The Na2SeO4 group showed the most severe depression of growth and food and water consumption, but no pathological changes were seen in the liver or kidney. Simultaneous administration of both toxicants produced a protective effect on weight loss and histopathology. These effects were associated with the formation of electron dense nuclear inclusions in kidney proximal tubule cells and similar electron dense formations in the reticuloendothelial cell cytoplasm and in the extracellular space of Disse in the liver. These formations were shown to contain both Se and Hg by energy dispersive X-ray microanalysis. The basis of the protective interaction of these two elements appears to result from an alteration of the chemical form or association of the mercury and selenium.
 ...
PMID:Effects of separate and combined chronic mercuric chloride and sodium selenate administration in rats: histological, ultrastructural, and x-ray microanalytical studies of liver and kidney. 54 21

The main adverse reaction to the immunosuppressive drug cyclosporine is dose-dependent renal dysfunction. Although renal vasoconstriction without major tubular dysfunction is usually noted, recent studies have demonstrated an inhibition of renal cortical microsomal protein synthesis. Sprague-Dawley rats and appropriate pair-fed controls were given cyclosporine orally in doses of 5, 10, 25, and 50 mg/kg/day for periods up to 10 days. A dose-dependent decline in glomerular filtration rate and effective renal plasma flow was maximal by day 3 and did not worsen despite continued dosing. Microsomal protein synthesis as measured by [3H]leucine incorporation was also depressed in a dose-dependent fashion; however, inhibition did not reach the nadir until day 4, 1 day after renal dysfunction was established. When cyclosporine was discontinued, microsomal protein synthesis was normalized by 4 days after drug withdrawal; in contrast, the return of glomerular filtration rate and effective renal plasma flow to normal required 8 days after drug discontinuation. Tubular function as measured by fractional excretion of lithium, enzymuria, and urinary osmolality was well maintained despite the depression of renal hemodynamics. There was no evidence of tubular necrosis by light or electron microscopy. Although cyclosporine produces reductions in renal microsomal protein synthesis, measured by "run-off" translation assays, these effects appear unlikely to be the direct cause of acute renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cyclosporine-induced renal dysfunction: correlations between cellular events and whole kidney function. 193 33

A 38-year-old male developed acute oliguric renal failure following repeated glue sniffing for about 8 hours. In addition, he had severe liver cell injury, mild myonecrosis and bone marrow depression indicating generalized tissue toxicity. The high urinary spot sodium during the oliguric phase and the total renal functional recovery after a period of oliguria followed by polyuria favoured a diagnosis of acute toxic tubular necrosis causing acute renal failure. Toluene which is used as the solvent is presumably the toxic agent involved in glue sniffing. It is advised that toluene inhalation be considered in the differential diagnosis of acute renal failure especially in the young. Literature on the renal toxicity of toluene is briefly reviewed.
 ...
PMID:Oliguric acute renal failure due to glue-sniffing. Case report. 194 58

Studies on the mechanism of immunosuppression shown by adenine comprised two areas: (1) Toxicity studies on hepatic, muscle and renal tissues were undertaken to ascertain if immunosuppression was a result of a non specific toxicity. (2) Studies to determine whether immunosuppression is a function of the inhibitory effect on de novo and salvage pathways of purine nucleotide metabolism. Toxicity studies in mice indicated that adenine caused an acute, reversible renal tubular necrosis and that allopurinol, when combined with adenine, could abrogate both the renal toxicity and immunosuppressive activity of the purine base. This result indicated that the toxic and/or immunosuppressive compound may be a xanthine oxidase catalysed product of adenine. Further studies indicated that it was unlikely that a major part of the immunosuppressive activity of adenine was due to the renal toxicity exerted by this compound. Splenic PRPP levels were found to peak on day 4 after antigen administration (day 0) and this corresponded with the peak in antibody plaque response which occurred at day 4 to 5. Adenine given at an immunosuppressive dose of 25 mumoles/mouse on day 0, 1 resulted in a significant inhibition of splenic PRPP levels on day 2 of the response. This effect on splenic PRPP levels on day 2 was also found with hypoxanthine given at an immune enhancing dose and therefore would indicate that depression of splenic PRPP per se is not responsible for the immunosuppression. Adenosine given at immunosuppressive doses was found not to affect PRPP levels in the spleen and hepatic PRPP levels were unaffected by adenine, adenosine and hypoxanthine. The in vivo effects of adenine on hypoxanthine-guanine phosphoribosyltransferase showed that adenine could inhibit significantly this salvage pathway in spleen and liver and that this inhibition could be overcome with concomitant administration of allopurinol. A metabolite of adenine which could contribute to its immunosuppressive activity may be 2-hydroxyadenine since it is derived from the xanthine oxidase catalysed oxidation of adenine inhibited hypoxanthine-guanine phosphoribosyltransferase gave similar renal toxicity to adenine and was immunosuppressive.
 ...
PMID:Studies on the mechanism of immunosuppression with adenine. 241 71

Intravenous doses of buthionine sulfoximine (BSO, NSC 326231), an inhibitor of glutathione synthesis, were eliminated rapidly from mouse plasma in a biexponential manner. The initial phase of the plasma concentration versus time curve had a half-life of 4.9 min and accounted for 94% of the total area under the curve. The half-life of the terminal phase of the curve was 36.7 min and the area accounted for only 6% of the total area under the curve. Plasma clearance of BSO was 28.1 ml/min/kg and the steady state volume of distribution was 280 ml/kg. The oral bioavailability of BSO, based on plasma BSO levels, was extremely low. However, comparable glutathione depletion was apparent after i.v. and p.o. doses of BSO, suggesting a rapid tissue uptake and/or metabolism of BSO. Therefore, due to the rapid elimination of BSO from mouse plasma, plasma drug levels do not directly correlate with BSO-induced tissue glutathione depletion. Administration of multiple i.v. doses of BSO to male and female mice resulted in a marked 88% depletion of liver glutathione at doses of 400-1600 mg/kg/dose. Toxicity of i.v. administered BSO was limited to a transient depression of peripheral WBC levels in female mice given six doses of 1600 mg/kg. Multiple i.v. doses of BSO of up to 800 mg/kg/dose (every 4 h for a total of six doses) did not alter the toxicity of i.v. administered melphalan. However, multiple doses of 1600 mg/kg/dose of BSO did potentiate histopathological evidence of melphalan-induced bone marrow toxicity in 30% of the mice and, additionally, the combination of BSO and melphalan produced renal tubular necrosis in 80% of the male mice. The potentiation of melphalan induced toxicity did not appear to be related to GSH depletion, since: quantitatively similar amount of GSH depletion occurred at lower dose of BSO without any increase in melphalan toxicity.
 ...
PMID:Pharmacokinetics of buthionine sulfoximine (NSC 326231) and its effect on melphalan-induced toxicity in mice. 276 4

Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.
 ...
PMID:Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks. 291 49

Potassium and magnesium deficiency have been reported as risk factors for experimental gentamicin nephrotoxicity. Amiloride, a potassium-sparing diuretic, also leads to increased renal magnesium reabsorption. Amiloride, 2 mg/kg/day, was given to groups of 8-12 Fischer 344 rats receiving gentamicin, 20 mg/kg b.i.d., for 3, 7, 10 and 14 days. Control animals received the vehicle for gentamicin, amiloride alone or gentamicin alone. The degree of renal failure and weight loss were similar in gentamicin and gentamicin + amiloride groups at all time points despite increases in serum potassium and magnesium in the amiloride-treated animals. Tubular dysfunction as assessed by depression of renal cortical slice uptake of p-aminohippurate and N-methylnicotinamide was not improved by the addition of amiloride. In addition, a comparable degree of tubular necrosis and regeneration was observed in all gentamicin-treated groups. Maximum gentamicin concentrations in the renal cortex did not differ. Thus, despite reduction of urinary losses of potassium and magnesium with resultant increased serum values, amiloride did not protect against experimental gentamicin nephrotoxicity. The tubular electrolyte wasting noted clinically is likely to be a result, rather than a cause of proximal tubular cell damage.
 ...
PMID:Effect of amiloride on experimental gentamicin nephrotoxicity. 400 Mar 46

Salt poisoning developed in captive sandhill cranes (Grus canadensis) when sea salt was added to normal drinking water to produce a sodium chloride concentration of 1%. Two of 18 cranes died and 2 were euthanatized when moribund. Muscle weakness, paresis, dyspnea, and depression were observed. Brain and serum sodium, serum uric acid, and plasma osmolality values were abnormally high. Lesions were those of visceral gout, renal tubular necrosis, nephrosis, and skeletal muscle necrosis.
 ...
PMID:Iatrogenic salt poisoning in captive sandhill cranes. 732 5

Two major episodes of acute hemolytic disease in lambs were associated with high mortality. Clinical signs were severe depression, dyspnea, and tachycardia. Gross postmortem findings included hemoglobinuria and icterus. Histologic examination revealed tubular necrosis and periacinar hepatocellular necrosis. Leptospira interrogans serotype pomona was proposed as the causative agent because high serum antibody titers for this bacterium were found in lambs and ewes in the affected flocks.
 ...
PMID:Leptospirosis in lambs. 735 86


1 2 3 Next >>