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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative merits of a comprehensive series of contemporary methods for detection of acute nephrotoxicity were evaluated. Male Sprague-Dawley rats were given 0, 0.25, 0.5, 1.0, or 3.0 mg mercuric chloride (HgCl2)/kg body weight by ip injection. Indices of nephrotoxicity were examined 8, 24, 48, 72, and 96 h later. Alterations in urine osmolality, volume, and protein levels were seen within 24 h in response to 1 mg/kg or more of HgCl2. Administration of 0.5-3.0 mg/kg produced dose-dependent increases in urinary excretion of maltase activity and glucose by 24 h, the period of peak effect. There was no increase in maltase or alkaline phosphatase (AP) activity in the serum of these animals. Enzymuria was not apparent in rats that had marked elevations in serum AP, argininosuccinate lyase, and ornithine carbamyl transferase activities as a result of physical (i.e., dichlorodifluoromethane-frozen) or chemical (carbon tetrachloride-induced) damage of the liver. Morphological alterations, in the proximal tubular epithelium of perfusion-fixed kidneys from HgCl2-dosed rats, paralleled the changes in enzyme excretion with respect to time of onset and dose-effect. There was a dose-dependent inhibition of tetraethylammonium (TEA) and p-aminohippurate (PAH) uptake by renal cortical slices at 24 h. Interestingly, increases in uptake of TEA and PAH were seen 8 h after a 1-mg/kg dose. Clearance of inulin and PAH in vivo were altered at 8 h by 0.5 and 1 mg/kg. Marked depression of these functional indices was seen at 24 h, by which time blood urea nitrogen (BUN) levels were increased. The 0.5- and 1.0-mg/kg doses also produced time- and dose-dependent increases in intracellular Na+ content which were maximal at 24 h. These results illustrate the importance of using a combination of biochemical and functional tests to elucidate the sequence of events in the kidney following toxic insult. Nevertheless, some of the simpler, traditional techniques (e.g., histopathology, urinalyses, BUN) were sensitive and organ-specific, and should continue to be very useful in nephrotoxicity testing/screening.
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PMID:Assessment of functional, morphological, and enzymatic tests for acute nephrotoxicity induced by mercuric chloride. 622 7

Sodium diethyldithiocarbamate (DDTC) administered following cis-diamminedichloroplatinum(II) (DDP) has been reported to attenuate structural renal damage and elevation of blood urea nitrogen in rats. Since DDP damages primarily proximal tubular epithelium in this species, we compared proximal tubular function, glomerular function, and histology in male Sprague-Dawley rats treated with DDP followed by either DDTC or 0.9% NaCl solution (NS) rescue. Male Sprague-Dawley rats received a single i.p. injection of DDP (7.5 mg/kg)-mannitol (75 mg/kg)-NaCl (67.5 mg/kg). Forty-five min later, rats were given i.p. injections of either DDTC (750 mg/kg) dissolved in 0.5 ml of NS (DDP + DDTC group; ten rats) or 0.5 ml NS (DDP + NS group; nine rats); additional rats received either DDTC only (DDTC group; six rats) or no treatment (untreated control group; six rats). All groups were sacrificed 5 days later by ether anesthesia and exsanguination. Compared to the untreated control group, the DDTC group had slightly lower mean blood urea nitrogen at sacrifice [12.5 +/- 0.5 (S.E.) versus 15.4 +/- 0.8 mg/dl; p less than 0.025 by unpaired Student's t test]; there was no difference in serum creatinine. The DDP + DDTC group had no diarrhea and no presacrifice deaths in contrast to diarrhea and three presacrifice deaths in the DDP + NS group. Blood urea nitrogen was also lower in the DDP + DDTC group at sacrifice (187 +/- 30 versus 383 +/- 39 mg/dl; p less than 0.005). However, weight loss and serum creatinine were not different. Structural acute tubular necrosis was marked in both DDP groups but was less severe in the DDP + DDTC group than in the DDP + NS group. Proximal tubular function was indexed by the uptake of the organic base N-[14C]methyl nicotinamide (NMN) and the organic acid p-aminohippurate in renal cortical slices incubated 90 min in Cross and Taggart medium. NMN uptake (expressed as slice to medium ratio) was slightly lower in the DDTC group than in untreated controls (4.1 +/- 0.2 versus 5.0 +/- 0.2; p less than 0.025). Marked depression of p-aminohippurate and NMN uptake occurred in both DDP + DDTC and DDP + NS groups. There was no difference in NMN uptake, but depression of p-aminohippurate uptake was slightly less severe in the DDP + DDTC group (5.3 +/- 0.7 versus 3.1 +/- 0.3; p less than 0.005). We conclude that DDTC rescue attenuates structural DDP injury in this animal model. DDP-mediated proximal tubular dysfunction was only marginally attenuated by DDTC; glomerular filtration rate, as indexed by serum creatinine, was not protected. DDTC attenuation of DDP toxicity may be mediated in part via reducing volume depletion due to DDP-associated diarrhea.
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PMID:cis-diamminedichloroplatinum(II) nephrotoxicity: tubular function after rescue with sodium diethyldithiocarbamate in rats. 630 93

Experiments were designed to test the hypothesis that growth depression and azotemia in chronic renal failure can be minimized by providing a nutritional formula that is adequate is essential nutrients but minimizes urinary excretion of all solutes. Unrestrained rats were fed exclusively by continuous intragastric infusion with a mixture containing sucrose, essential amino acids, N-free analogues thereof, minerals, corn oil, and vitamins, designed to minimize urinary solute excretion while permitting growth. After 5 days, renal excretory function was reduced to 1/10 by reinfusing 90% of each day's urinary output intragastrically for the next 3 wk. Weight gain (3.6 +/- 0.1 g/day), linear growth and carcass N accretion were the same as in nonreinfused rats receiving substantially the same formula by intragastric catheter. Except for sight acidosis (CO2 18.5 mM) accumulation of electrolytes did not occur. Average final serum urea N was only 42.5 +/- 7.1 mg/dl. The results are considered as supporting the hypothesis.
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PMID:Growth of rats with severe renal insufficiency fed a formula designed to minimize urinary solutes. 640 12

Fifteen gravid, crossbred gilts were utilized in an experiment to measure the effect of five isonitrogenous dietary treatments (12% crude protein, sorghum-soybean meal; sorghum; sorghum + lysine; sorghum + threonine; sorghum + lysine + threonine) on N balance, colostrum composition and plasma constituents (protein, urea N and IgG). All gilts were fed a standard corn-soybean meal diet from breeding until switched to the sorghum basal diet, on d 60 of gestation. Treatment diets were imposed at d 70. Nitrogen retention, measured between d 103 and 113 of gestation, was improved (P less than .002) by lysine addition. Nitrogen retention was similar (P greater than .10) for gilts fed either the 12% crude protein, sorghum-soybean meal diet or the lysine + threonine-supplemented diet. Plasma protein levels at farrowing were depressed (P less than .06) in those gilts fed sorghum diets without supplemental lysine and plasma urea N was elevated (P less than .10). Plasma protein and plasma urea N were not affected by threonine supplementation (P greater than .10). In contrast, the depression of plasma IgG was ameliorated (P less than .03) by threonine and unaffected by lysine supplementation. These results confirm the hypothesis that lysine is the first limiting amino acid in sorghum protein for gravid gilts as determined by N retention but indicate that threonine is likely the first limiting amino acid for the production of the specific protein, IgG.
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PMID:Effect of lysine and threonine supplementation of sorghum gestation diets on nitrogen balance and plasma constituents in first-litter gilts. 642 57

The oral administration of a suspension of N-phenylanthranilic acid (N-PAA), over the range of 0.5 to 2 mmol/kg for 14 consecutive days, caused a dose-related renal papillary necrosis (RPN), which involved no more than 30% of the medullary apex. This area of necrosis was no greater following daily doses of 3 and 5 mmol/kg of N-PAA for 14 days, but cortical degenerative changes were induced. The area of the necrotic lesion was greater in the left kidneys of individual rats than in the right kidneys. The apex-limited histopathological changes associated with the administration of low doses of N-PAA were not reflected by altered electrolyte or water homeostasis and only high doses of N-PAA caused significant changes. Urinary volume was significantly increased (in animals treated with 5 mmol/kg), whereas urinary osmolality (greater than 2 mmol/kg N-PAA), and Na+ (5 mmol/kg), K+ (5 mmol/kg), and Cl- (5 mmol/kg) excretion was decreased compared to controls. Blood urea nitrogen was increased at doses greater than 3 mmol/kg in association with cortical degenerative changes. When untreated rats were dosed orally with NH4Cl (400 mg/kg) there was a lag period between 0 and 2 hr (when no changes in H+ excretion occurred), but the urinary pH was depressed in the 2- to 4-hr collection period. Only those rats treated with the highest dose of N-PAA (5 mmol/kg) showed a significantly impaired urinary acidification after NH4Cl loading. There was, however, a statistically significant dose-related decrease in the excretion of Cl- following NH4Cl dosing, provided urine was sampled between 0 and 2 hr. These data highlight the failure of the commonly used renal function tests (such as urinary volume, osmolality, and electrolyte excretion) to reflect apex-limited RPN, unless cortical degenerative changes were also present. The dose-related depression of Cl- excretion in the 0- to 2-hr period following oral NH4Cl loading, suggests that appropriately timed sampling of this urinary anion could offer an improved criterion for the diagnosis of RPN.
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PMID:The effect of N-phenylanthranilic acid-induced renal papillary necrosis on urinary acidification and renal electrolyte handling. 647 61

The effects of N-nitrosothiazolidine (NNT) and N-nitrosomorpholine (NNM) on different biological parameters were investigated and compared. The oral LD50 value of NNT (1950 +/- 85 mg/kg) showed that it was about 6 times less toxic than NNM (LD50 = 320 mg/kg, po; Druckrey et al., 1967). Lethal and near-lethal doses (greater than or equal to 1500 mg/kg, po) of NNT caused central nervous system depression (reduced spontaneous motor activity, loss of righting and pain reflexes, without loss of consciousness), stereotypical behavior such as, purposeless chewing jaw movements lasting more than one hour, muscular rigidity, and in some rats, rare and brief clonic convulsions, 3 to 24 h after dosing. These neurotoxic signs, as a whole, were reminiscent of opioid intoxication. Rats that died after NNT-treatment had kidney necrosis in the distal tubules, but all survivors had normal kidneys. NNT (500 and 1000 mg/kg, sc) had no effect on the relative liver weights, but it inhibited liver mitosis at 24, 48, and 72 h after treatment. NNM (100 mg/kg, sc) decreased the relative liver weights on 3 posttreatment days; it inhibited liver mitosis after 24 h and enhanced it after 48 h in male rats. Both NNT and NNM increased the relative adrenal weights, but only NNM enhanced adrenocortical mitosis. In general, NNT had no effect on serum enzymes (SGOT, SGPT, LDH, HBDH), but it increased blood urea nitrogen (BUN) and serum creatinine 24 h after administration. Pretreatment of rats with 3 doses of NNT (150 mg/kg X d, po) increased the pentobarbital-induced sleep (PST) by 26% (not significant), while 3 doses of NNM (50 mg/kg X d, po) increased PST by 188%. In addition, NNM caused a severe centrilobular liver necrosis and glycogen depletion, associated with a marked rise in serum enzymes (SGOT, SGPT, LDH, HBDH) and fall in serum glucose. Compared with NNM, NNT, which was found in fried bacon (Kimoto et al., 1982; Gray et al., 1982), seemed to be a relatively nontoxic nitrosamine.
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PMID:Comparison of the acute toxicities of N-nitrosothiazolidine and N-nitrosomorpholine. 649 89

A reproducible experimental disease model in horses using Streptococcus zooepidemicus was developed. An intravenous challenge dose of 1 X 10(10) colony-forming units (CFU), followed 24 h later with another challenge of 1 X 10(8) CFU of Strep. zooepidemicus produced the desired disease model. The disease was characterized by depression, pyrexia, anorexia, abnormal lung sounds, inflammation of joints, moderate to severe lameness, gradual loss of condition and emaciation. The effects of the disease on hematology, serum chemical profile and different protein fractions were studied. The disease state had no effect on serum glucose, sodium, potassium, chloride, urea nitrogen, creatinine, uric acid, calcium, phosphorus and enzymes SGOT or SGPT. However, the alkaline phosphatase showed a gradual decline. The serum iron levels dropped markedly and remained low to the last day of observations (post-infection day, PID 13). On serum protein electrophoresis, the albumin showed a gradual decrease; whereas, alpha II, beta and gamma globulin levels rose suggesting an immune response. The elevation of rectal temperatures and white blood cell counts related well with clinical observations. The serum iron levels proved very helpful in predicting the severity of clinical signs and often dropped before the onset of clinical signs and pyrexia.
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PMID:Standardization of an experimental disease model of Streptococcus zooepidemicus in the equine. 649 45

Strychnine toxicosis is characterized by inducible tetanic seizures and metaldehyde poisoning by fine fasciculations progressing to generalized tremors and seizures. Intoxication with 1080 causes seizures, random running movements, vomiting, defecation, urination, acidosis and hyperglycemia. Intoxication with rodenticides causing coagulopathy is characterized by hemorrhage into body cavities but not necessarily external hemorrhage. Anticholinesterase insecticides cause salivation, urination and defecation, while chlorinated hydrocarbon insecticides cause CNS disturbances. Ethylene glycol intoxication results in ataxia, depression, coma, vomiting and tachypnea, followed by acute renal failure. Urea poisoning causes bloat and CNS signs in cattle. Monensin intoxication in horses lasts several days and causes stiffness, colic, uneasiness and recumbency. Salt poisoning results in depression, seizures and hypernatremia. Lead poisoning is associated with central and peripheral nervous system signs, as well as increased numbers of nucleated RBC and basophilic stippling of RBC. Arsenic poisoning results in GI pain, diarrhea, weakness and death. Copper toxicosis in sheep is manifested by hemolytic anemia, hemoglobinemia and hemoglobinuria. Plants that may intoxicate domestic animals include sorghum, greasewood, halogeton, water hemlock, Japanese yew, larkspur, lupine, milk-weed, philodendron, oleander, castor bean and precatory bean.
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PMID:Practical toxicologic diagnosis. 649 3

Effect of sodium selenite on renal toxicity and antitumor activity of cis-diamminedichloroplatinum (Cisplatin; CDDP) repeatedly administered to mice inoculated with Ehrlich ascites tumor cells were examined. Simultaneous repeated administration of selenite with CDDP markedly improved the growth depression, the renal toxicity indicated by blood urea nitrogen value and the diarrhea caused by CDDP, and inhibited the growth of Ehrlich ascites tumor cells cooperatively with CDDP. This results suggest that selenium compounds are useful for prevention of the toxic side effects of CDDP.
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PMID:Effect of selenite on renal toxicity and antitumor activity of cis-diamminedichloroplatinum in mice inoculated with Ehrlich ascites tumor cell. 654 Mar 2

The effect of glucose on alanine-stimulated urea synthesis was studied in six healthy volunteers during 6 h of constant alanine infusion, 2.8 mmol h-1 kg-1 b. wht., and during 12 h of constant glucose infusion, 4.0 mmol h-1 kg-1 b. wht., with superimposed alanine infusion. The urea nitrogen synthesis rate (UNSR) was determined at intervals of 2 h as urinary excretion rate corrected for accumulation and intestinal hydrolysis. UNSR depended on the blood alanine and glucagon concentration, but was not correlated with glucose, lactate, or insulin concentrations. The slope of the linear relation between UNSR and alanine concentration (the 'Functional Hepatic Nitrogen Clearance') was on the average 24.4 1 h-1 and decreased to 12.8 1 h-1 by glucose (mean difference +/- SE of the difference 10.6 +/- 7.3, P less than 0.01). The relation between glucagon and alanine concentration was linear, and the slope was decreased to 40 per cent by glucose (P less than 0.05). The slope of the linear relation between UNSR and glucagon was not changed by glucose. Thus the catabolism of alanine nitrogen is decreased by glucose because of a reduction of the urea synthesis. Data suggest that this may be due to a depression of the glucagon response to alanine.
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PMID:Effects of glucose on alanine-derived urea synthesis. 654 35


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