Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sublethal doses of vincristine (VNC) and bacterial lipopolysaccharide (LPS) administered simultaneously to adult male mice resulted in markedly enhanced mortality. All of 10 strains of Pseudomonas aeruginosa tested, 4 of 7 strains of Bacteroides, and 6 of 10 strains of Listeria monocytogenes were able to substitute for purified LPS in enhancing mortality in VNC-treated mice. Inoculation of mice with each of 10 strains of Pseudomonas, each of 7 strains of Bacteroides, and about half of the 10 strains of Listeria tested elicited increased resistance to the lethal action of purified LPS. The patterns of responses of mice receiving a lethal combination of 2 mg of LPS/kg and 1 mg of VNC/kg resembled those of mice receiving a lethal dose of 10 mg of VNC/kg alone or 15 mg of LPS/kg alone with respect to (i) serum glutamic pyruvate transaminase activity, (ii) hematocrit values, and (iii) thrombocytopenia. The patterns of responses of mice receiving a lethal combination of LPS and VNC resembled those of mice receiving a lethal dose of LPS alone with respect to (i) hypothermia, (ii) retention of sulfobromophthalein, (iii) fibrinogen level, (iv) prothrombin activity, (v) blood urea nitrogen levels, and (vi) time of death. These data are consistent with the proposition that the combination of VNC and LPS produces a fatal renal failure. Histological studies confirmed that there was extensive renal damage in mice treated with lethal doses of LPS alone or a lethal combination of LPS and VNC.
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PMID:Enhanced toxicity for mice of combinations of bacterial lipopolysaccharide and vincristine. 94 80

Liver involvement with a variety of viral diseases is a frequent finding in chronic renal failure patients on regular hemodialysis treatment. We evaluated the prevalence of IgG anti-hepatitis C virus antibodies (HVC) in our dialysis unit, looking for risk factors associated with seropositivity and we assessed the type and degree of liver involvement by means of a liver biopsy in those patients with biochemical abnormalities of liver function test. We studied 50 patients aged 13 to 77 years, and performed serial determinations of serum ALT (UI/L). IgG anti HVC was determined by a second generation ELISA Kit (Abbot). We retrieved information from chart review and patient interview, regarding: time on hemodialysis, number of blood transfusions and intravenous IV drug use off dialysis. Liver biopsy specimens were stained with H.E. and Masson and findings were classified as chronic persistent, chronic active hepatitis or cirrhosis, according to Schewer. We compared the findings with those of other patients with liver dysfunction and positive IgG anti HVC who did not have renal failure. Anti-HVC prevalence in our hemodialysis patients was 44%. Anti-HVC seropositive hemodialysed (HD) patients were not different from seronegative HD patients, with regard to age, sex, i.v. drugs usage and peak ALT values. Twelve of 22 HVC positive patients had peak ALT values higher than 40 UI/L (Table 2). Time in HD (75.5 +/- 42.8 m) and number of blood transfusions received (35.3 +/- 28) were clearly different in HVC positive patients, compared to HVC negatives. Histologically, 11 seropositive patients showed chronic persistent hepatitis as the most frequent finding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The prevalence of anti-hepatitis virus C antibodies in chronic hemodialysis patients]. 134 Aug 99

Sixteen beagles were allocated into 4 groups, each group consisting of 2 males and 2 females, which were injected sc with 1,3,5 or 7 mg paraquat/kg. The beagles were observed for 2 w after the administration. At the end of the observation period all the dying and surviving dogs were studied pathologically. The LD50 was calculated as 1.8 (1.0-6.1) in males and 3.5 (2.4-10.1) mg/kg in females. Clinical laboratory tests showed increases in segmented neutrophils and monocytes, decreases in lymphocytes, slight decreases in chloride, moderate increases in BUN, GOT, GPT and phospholipids, slight increases in uric acid, total protein, creatine, total cholesterol and total bilirubin, and prolonged prothrombin times. Marked edema, congestion and hemorrhage of lungs, as well as slight congestion in various organs, were observed grossly. In histopathological examination, marked pulmonary hemorrhage and congestion, fibroblast-like cells in alveolar septa, breakdown of alveolar walls, thickening of alveolar walls and pleura, mild congestion and degeneration of the liver, and mild degeneration of renal tubules were observed. The cause of death was respiratory distress and renal failure. The surviving animals had mild atelectasis of the lungs. Electromicroscopic examination on the surviving animals revealed the appearance of spindle-shaped cells, proliferation of type II alveolar cells and fibroblasts, mitosis of fibroblasts, and abundant collagen fiber in the lung, calcium deposition, stratification and thickening of basement membranes, and localized necrotic epithelial cells in the proximal tubules of kidneys, and stratification of intramitochondrial cristae of the liver. Pulmonary fibrosis in the switchover stage was present with participation from type II alveolar cells, fibroblasts and myofibroblasts.
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PMID:Acute toxicological studies on paraquat: pathological findings in beagle dogs following single subcutaneous injections. 150 67

The concentrations of human plasma albumin (HPA) and alpha-1-acid glycoprotein (AAG) were measured in the serum obtained from 84 healthy subjects, 56 umbilical cords, 41 patients with renal failure, 65 patients maintained on chronic hemodialysis and 46 patients with liver cirrhosis. Severity of liver dysfunction was assessed with the use of Pugh et al. [1973] classification. Of the cirrhotic patients, 12, 22 and 12 patients were classified as mild, moderate and severe liver dysfunction, respectively. The coefficient of variation of AAG was greater than HPA in all groups of subjects, and the variability of HPA and AAG is increased in patients compared to healthy subjects. As the liver dysfunction progresses, HPA concentration decreases whereas, the average AAG concentration is not changed in mild, moderate and severe liver dysfunction. The coefficients of variation for HPA and AAG in moderate and severe liver disease is over twice those for healthy subjects. The concentration of HPA is normally distributed in all groups of subjects, with the exception of the cord serum. The frequency distribution of AAG was normal in healthy subjects whereas, it was asymmetric, being positively skewed, in newborn, in renal and liver patients. The wide interindividual variability and the not-normal frequency distribution of AAG in liver or renal patients make its mean of little value in defining a group. Neither HPA nor AAG correlated with the clearance of creatinine in renal patients. In liver disease, HPA and AAG did not correlate with GPT and GOT activities, prothrombinic activity and bilirubin concentration. HPA did not correlate with AAG in any group.
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PMID:Interindividual variability in the concentrations of albumin and alpha-1-acid glycoprotein in patients with renal or liver disease, newborns and healthy subjects: implications for binding of drugs. 157 57

Besides hepatotoxicity, paracetamol may exert nephrotoxic effects in experimental animals and man. The present study in rats shows that cholestyramine given 4 and 24 h after paracetamol provided protection against both hepato- and nephrotoxicity; this was evidenced by reduced increments in plasma enzyme activities (SDH, GPT), indicating liver damage, and diminished retention of plasma and creatinine, indicating renal failure. The recovery of paracetamol and its conjugates in urine was markedly reduced by cholestyramine at 24-48 h after treatment. The protective effects of cholestyramine are explained by adsorption of paracetamol and conjugates in the intestine undergoing biliary excretion and enterohepatic circulation.
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PMID:Cholestyramine as an antidote against paracetamol-induced hepato- and nephrotoxicity in the rat. 274 Nov 80

An in vivo model of liver hyperplastic noduligenesis was induced in rats by long-term administration of thioacetamide (TAM) (50 mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Plasma and urine were obtained from either TAM or Rh(III) complex or TAM plus Rh(III) complex treated rats to determine the interactions of both substances with the biochemical parameters related to liver function. The rise in alkaline phosphatase (ALP), leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT) and the unchanged activities in the aspartate and alanine aminotransferases (AST, ALT) in plasma of TAM-treated rats indicated that the disease induced by this substance can be considered as a chronic obstructive biliary disease with indices of cell proliferation and tumors. The increased concentration of bilirubin both in the plasma and urine of TAM-treated rats suggested liver cholestasis and hepatobiliary obstruction. The very low values of creatinine clearance indicated that there was some degree of kidney failure due to the effect of TAM. The increased concentration of ammonia both in plasma and urine were probably a consequence of the decreased flux in the urea cycle in the liver. The Rh(III) complex alone did not produce significant changes in the plasma enzyme activities. The only significant changes were found in the concentrations of uric acid and ammonia in the urine. When the Rh(III) complex was administered to TAM-treated rats, significant restoration of the following parameters were observed: plasma enzymatic activities, blood bilirubin and ammonia, uric acid and creatinine in the urine and the creatinine clearance. These results suggest that the altered liver function induced by TAM can be restored by Rh(III) complex. The mechanisms by which this complex acts to counteract the TAM-induced changes are not yet established.
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PMID:Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats. 288 38

In 75 clinically normal unspayed female control dogs between two and eleven years old the average plasma level of aspartate aminotransferase (AST) was 21.6 +/- 5.7 (+/- SD) IU/l, of alanine aminotransferase (ALT) 40.4 +/- 13.0 IU/l and of the AST/ALT ratio 0.6 +/- 0.2. These values showed only minor changes over years. In 96 bitches with the cystic hyperplasia-pyometra complex there was a very significant increase of the AST, decrease of the ALT and increase of the AST/ALT ratio. The changes were more pronounced in 62 clinically ill bitches with typical endometritis post oestrum, in 18 dogs with gram negative organisms in the uterus and in 53 bitches with white blood cell (WBC) levels higher than 40 X 10(9)/1. Renal failure had no influence on the specific changed values. The changed values returned either temporarily to normal after prostaglandin (PGF2 alpha)-treatment or definitely after ovariohysterectomy.
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PMID:The characteristic pattern of aspartate aminotransferase and alanine aminotransferase in the bitch with the cystic hyperplasia-pyometra complex: effect of medical or surgical treatment. 347 12

Serum creatine kinase (CK), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lactic dehydrogenase (LDH) levels were studied at initial peritoneal dialysis in two groups of patients with renal failure. In Group I the patients underwent no intracorporeal interventions other than the implantation of a permanent catheter for peritoneal dialysis. In Group II the patients received injections or infusions in addition to the insertion of the catheter. CK was found to be significantly raised in Group II as a result of the injections or infusions. ASAT and ALAT were within normal range for both groups. LDH was significantly raised in Group II, probably to be explained by the degree of severity of the renal disease. It is concluded that the implantation of a permanent catheter for peritoneal dialysis and the institution of peritoneal dialysis do not per se lead to a rise in the serum concentrations of the enzymes CK, ASAT, ALAT, and LDH.
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PMID:Serum enzyme levels during initial peritoneal dialysis. 705 67

The prevalence of antibodies to the hepatitis C virus (HCV) was determined in 333 peritoneal dialysis (PD) patients from 10 German dialysis units, using an enzyme-linked immunosorbent assay of the second generation (ELISA 2nd gen) which detects antibodies to a structural (C22) and to non-structural (C33c, C100, 5-1-1) recombinant antigens of HCV. Sera from 18/333 (5.4%) patients were anti-HCV positive versus 11/295 (3.7%) when the sera were tested by an ELISA of the first generation (ELISA 1st gen) containing only a nonstructural antigen (C100). In the 18 sera positive by ELISA 2nd gen, antibodies against at least one viral protein were found by recombinant immunoblot assay (RIBA) in 15/333 (4.5%) patients. In the sera of 11/15 (73.3%) patients HCV RNA was detected by nested PCR. Epidemiological evaluation of the patients revealed that the prevalence of anti-HCV was correlated to the female sex (p = 0.005), presence of anti-HBc (p = 0.006), duration of total dialysis (hemodialysis HD and PD) (p = 0.012), duration of HD alone (p = 0.025) and previous renal transplantation (p < 0.001). Only a weak correlation was found to blood transfusions (p = 0.041) and elevation of serum ALT concentration (p = 0.055). But no correlation was found to diagnoses of renal failure (p = 0.129), duration of PD (p = 0.963) and past surgical procedures (p = 1.0). Four of nine peritoneal dialysates of anti-HCV positive patients were found positive for HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of antibodies to hepatitis C virus in patients on peritoneal dialysis--a multicenter study. 751 74

Renal dysfunction can have substantial effects on the pharmacokinetics and pharmacodynamics of drugs. A wide variety of animal models have been developed in an attempt to mimic conditions seen in human renal failure. In reality, no single animal model would be completely satisfactory because the etiology and development of renal failure are diverse. During recent years injection of uranyl nitrate has been found to be the most effective and easiest method to produce renal dysfunction in laboratory animals. Changes over the last 10 years in government regulations on the production and use of radioactive substances make the compound less available. There is, therefore, a need for a more accessible compound comparable to uranyl nitrate as an inducer of renal failure. The present study compares the effects of another known nephrotoxin, cisplatin, with uranyl nitrate in the rat. Cisplatin was chosen because of its ability to produce kidney damage and its identical site and mechanism of action on the kidneys as uranyl nitrate. In the present study, rats were given different i.v. doses of uranyl nitrate or cisplatin dissolved in 0.9% of saline solution. The effects of nephrotoxins were evaluated on the basis of changes in body weight, creatinine and blood urea nitrogen (BUN) concentrations. It was found that the degree of renal damage produced by uranyl nitrate and cisplatin is a function of the administered dose. With increasing dose there is evidence of more severe kidney damage, as measured by substantially increased plasma concentrations of creatinine and BUN. The time required to return to normal creatinine and BUN concentrations was also a function of dose. Furthermore, plasma alanine aminotransferase (ALT) activity was measured as an index of hepatocellular damage. The ALT test showed that a single dose does not affect the liver function. From dose-response curves a dose of 4 mg/kg body weight of uranyl nitrate or cisplatin was chosen to produce acute renal failure in animals for pharmacokinetic study of barbital. Barbital (100 mg/kg) was administered on the fifth day (the day of maximum renal dysfunction) to uranyl nitrate, cisplatin-treated and control rats. The elimination rate constant (k), elimination half life (t1/2), volume of distribution at steady state (Vss), total (CLt) and renal clearance (CLr) were significantly different in treated groups of rats from control, however no such difference was detected between uranyl nitrate and cisplatin-treated group of rats. In short, cisplatin is comparable to uranyl nitrate in producing renal failure in the rat and can be considered a suitable alternative.
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PMID:A comparative study of uranyl nitrate and cisplatin-induced renal failure in rat. 773 34


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