Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood alpha-fetoprotein, carcinoembyronic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, hemoglobin and red cell sedimentation rate were measured in patients with stages III and IV gastric carcinoma and patients with benign diseases of the stomach. Alanine aminotransferase, sorbitol dehydrogenase and glutamate dehydrogenase were found diagnostically not informative in gastric carcinoma stages III and IV. A complex of measurements of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyl transpeptidase and aspartate aminotransferase detected gastric carcinoma metastases to the liver in 84.6% of cases as against 61.5% detected by measurements of alpha-fetoprotein alone. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase helped differentiate between gastric carcinoma stages III and IV. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, hemoglobin, and red cell sedimentation rate improved the diagnostic sensitivity in detection of gastric carcinoma stages III and IV to 70.8 and 100%, respectively.
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PMID:[Laboratory tests in the diagnosis of stomach cancer]. 800 Jul 94

The relative sensitivities of eight commonly used clinical chemistry end points and histopathology to detect potential toxic effects in liver and kidney were evaluated for a series of 61 13-week rat toxicity studies conducted for the National Toxicology Program. The data consisted of 1-,2- to 3-, and 13 week clinical chemistry measurements and 13-week histopathological assessments of liver and kidney. Except for serum alkaline phosphatase, treatment-related alterations of individual clinical chemistry variables occurred in 20-48% of the studies, depending on the analyte, sampling time, and sex. Liver and kidney lesions were reported for 31% and 41% of the studies respectively. There was an association between treatment-related increases in alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and histopathological changes in the liver. SDH activity had greater positive and negative predictive values than similar changes in ALT; by week 1 in females and weeks 2-3 in both sexes. SDH predicted morphological hepatic change at study termination with 75% or better accuracy. If increases in activities of both enzymes occurred simultaneously, however, terminal histopathological changes could be predicted, in both sexes, with 75% accuracy by week 1, increasing to 100% by weeks 2-3. There also was an association between treatment-related increases in urea nitrogen (UN) and creatinine (Cre) concentrations and morphological kidney change. Cre concentration had greater positive predictive values than similar changes in UN; by weeks 2-3 in males and week 13 in both sexes. Cre predicted morphological renal change at study termination with 56% or better accuracy. UN concentration was associated and predictive of morphological kidney change only in females at week 13. Depending on time point and sex, serum alkaline phosphatase activity increased in 5-22% of the studies. Increases in total bile acid concentration occurred in 33-48% of the studies. Because both tests are used as markers of cholestasis, this marked discrepancy was unexpected. Treatment-related decreases in alkaline phosphatase activity occurred, however, in 39-56% of the studies; serum alkaline phosphatase may be more useful as an indicator of decreased food intake (decreased activity) than of cholestasis (increased activity). In summary, treatment-related alterations of clinical chemistry and histopathology occurred frequently in this series of toxicity studies in rats. Changes in the chemistry end points also occurred frequently at interim time points, indicating that clinical chemistry evaluations can be useful for detecting potential treatment effects throughout a study. This observation is important, since histopathological evaluations are limited to animal termination and not useful for detecting transient responses or the onset of treatment-related effects.
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PMID:Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats. 859 28

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.
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PMID:Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing. 874 16

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.
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PMID:Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats. 882 36

Cisplatin [cis-dichlorodiammineplatinum (II)] is a widely used chemotherapeutic drug that is toxic to the kidney. Concurrent administration of cysteine together with vitamin E, Crocus sativus and Nigella sativa reduced the toxicity of cisplatin in rats. When administered i.p. for 5 alternate days with 3 mg/kg cisplatin, cysteine (20 mg/kg) together with vitamin E (2 mg/rat) an extract of Crocus sativus stigmas (50 mg/kg) and Nigella sativa seed (50 mg/kg) significantly reduced blood urea nitrogen (BUN) and serum creatinine levels as well as cisplatin-induced serum total lipids increases. In contrast, the protective agents given together with cisplatin led to an even greater decrease in blood glucose than that seen with cisplatin alone. The serum activities of alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine aminotransferase of cisplatin-treated rats were significantly decreased, whereas the activities of glutathione reductase and isocitrate dehydrogenase were significantly increased. Addition of cysteine and vitamin E, Crocus sativus and Nigella sativa in combination with cisplatin partially prevented many changes in the activities of serum enzymes. In cisplatin-treated rats, the liver activities of isocitrate dehydrogenase and aspartate aminotransferase were significantly increased, whereas much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of alkaline phosphatase, isocitrate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase and gamma-glutamyl transferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Also, administration of cysteine and vitamin E, Crocus sativus and Nigella sativa together with cisplatin partially reversed many of the kidney enzymes changes induced by cisplatin. Cysteine together with vitamin E, Crocus sativus and Nigella sativa tended to protect from cisplatin-induced falls in leucocyte counts, haemoglobin levels and mean osmotic fragility of erythrocytes and also prevented the increase in haematocrit. The results of this study indicate a basis for the toxic effects of cisplatin, and suggest a possible way of counteracting the toxicity by introducing protective agents such sulphydryl compounds, other antioxidants and extracts of natural products. It also appears that cells adapt to the effects of cisplatin through the induction of systems that produce NADPH, which in turn compensates the decrease of free sulphydryl groups. We conclude that cysteine and vitamin E, Crocus sativus and Nigella Sativa may be a promising compound for reducing cisplatin-toxic side effects including nephrotoxicity.
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PMID:Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. 960 69

The purpose of this study was to relate dose-dependent hepatotoxicity stemming from prolonged exposure to sublethal concentrations of the cyclic heptapeptide microcystin-LR (Mcyst) to hepatic Mcyst concentrations and protein phosphatase activity. Mcyst is a potent inhibitor of protein phosphatase types 1 and 2A (PP1 and PP2A). Twenty male Sprague-Dawley rats were infused continuously with 0, 3, 6, or 9 micrograms Mcyst/day for 28 days using intraperitoneal mini-osmotic pumps containing highly purified toxin or saline. At the end of 28 days, dose-dependent increases in several serum biochemical tests including sorbitol dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bile acids had occurred. Serum albumin decreased in a dose-dependent fashion. Liver activity of both PP1 and PP2A decreased in a dose-dependent manner, but with a relatively greater effect on PP2A than PP1. Liver cytosol Mcyst concentrations, measured by direct competitive ELISA, also increased in a dose-dependent manner, although at a higher rate than would be predicted from the incremental increase in dose given. This disproportional increase is suggestive of the bioaccumulation of Mcyst with increasing dose. Histopathological abnormalities included hepatocellular apoptosis and cytosolic vacuolation of principally zone 3 hepatocytes. Immunohistochemical stains revealed Mcyst predominantly within pericanalicular regions of zone 3 hepatocytes. It was concluded that prolonged exposure to sublethal concentrations of Mcyst results in multiple dose-dependent hepatotoxic effects that correspond to decreased hepatic serine/threonine protein phosphatase activity and increasing cytosolic Mcyst concentrations. The disproportional increase of hepatic Mcyst concentrations observed may suggest the bioaccumulation of toxin and an increasing relative risk of hepatotoxicity with increasing dose.
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PMID:Prolonged sublethal exposure to the protein phosphatase inhibitor microcystin-LR results in multiple dose-dependent hepatotoxic effects. 972 Jan 45

Clinical, clinico-pathological and serological studies were performed in sheep experimentally infected with Babesia ovis. Acute babesiosis occurred in all the lambs infested with adult Rhipicephalus bursa ticks and in one lamb infested with the larvae. The rate of parasitaemia and the degree of anaemia were not correlated. Decrease in the packed-cell volume ranged from 30 to 40%. Parasitized erythrocytes were not observed to block capillaries in the brain, which explained the absence of nervous symptoms in acute babesiosis. The kidneys were the most severely affected organs, exhibiting acute glomerulonephritis. The lesions observed were suggestive of vascular alteration and vascular stasis, leading to anoxia of the tissues. A disseminated intravascular coagulation (DIC) syndrome was recorded in sheep infected with babesiosis. A marked increase in the enzymes of the transaminase groups, mainly aspartate aminotransferase (AST), was observed. Enzymatic changes (increases in AST, alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) and decreases in sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP) and malic enzyme (MEZ)), decreases in total proteins and albumin, and increases in urea and creatinine might reflect the degree of severity of the damage to the liver and kidney tissues. Most of the lambs (85%) that were infested with larvae, and all lambs infested with adult R. bursa ticks, reacted serologically to B. ovis antigen. The serological reactions following infestation with the larvae occurred much later than those following infestation with the adult stage. The lambs which were infested with larvae showed mild clinical reactions when challenged by infected R. bursa adults, as compared with the reactions to the challenge in naive control animals. The serological findings, in addition to the fact that one splenectomized lamb reacted to larval infestation with acute ovine babesiosis, show that the preimaginal stages of R. bursa can transmit B. ovis, usually causing a sub-clinical disease. It is suggested that infections derived from preimaginal ticks in the winter can preimmunize sheep for the subsequent more severe infections derived from adult ticks in the summer. Furthermore, in the absence of a reliable vaccine against B. ovis, grazing flocks in the enzootic regions should be exposed to the preimaginal stages during their activity period (October-February) before exposure to the adult ticks in spring and summer (April-July).
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PMID:Clinical, clinico-pathological and serological studies of Babesia ovis in experimentally infected sheep. 978 Aug 25

Parotid and mandibular saliva was obtained from red kangaroos by concurrent acetylcholine isoprenaline stimulation. Salivary proteins were separated by horizontal electrophoresis on either cellulose acetate or starch gels and assessed by specific staining techniques for 23 enzymes commonly found in mammalian tissues and body fluids. Parotid saliva was positive for acid phosphatase, alpha-amylase, carbonic anhydrase, glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase and superoxide dismutase activities. Mandibular saliva was positive for alcohol dehydrogenase in addition to the above six enzymes. The kangaroo salivas lacked activity for alkaline phosphatase, beta-galactosidase and non-specific esterase which occur in saliva from some mammalian species.
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PMID:Enzyme activity in parotid and mandibular saliva from red kangaroos, Macropus rufus. 978 23

The effect of prolonged chronic cyanide exposure on liver and kidney integrity, as well as some associated enzyme and metabolite changes, were investigated in New Zealand white rabbits (initial mean weight 1.52 kg) using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological procedures. Two groups of rabbits were fed for 40 weeks on either pure growers' mash or growers' mash containing 702 ppm inorganic cyanide. Results obtained indicate that the cyanide-fed rabbits had significantly decreased liver activities of alkaline phosphatase, glutamate pyruvate transaminase and sorbitol dehydrogenase relative to controls (P<0.05). On the other hand, there were significant increases (P<0.05) in the serum activities of these enzymes in the cyanide-treated group. Kidney alkaline phosphatase activity was significantly decreased (P<0.05), while serum urea and creatinine were significantly higher (P<0.05) in the cyanide group relative to controls. The cyanide treatment led to significant increases in both tissue and serum activities of lactate dehydrogenase. In addition, liver and kidney rhodanese activities were significantly raised in the cyanide-fed group. There were marked degenerative changes in the liver and kidney sections from the cyanide-treated rabbits. These results suggest that chronic cyanide exposure may be deleterious to liver and kidney functions.
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PMID:Liver and kidney lesions and associated enzyme changes induced in rabbits by chronic cyanide exposure. 1049 76

Toxic effects of exposure to 1,2,3-trimethylbenzene (hemimellitene) in the condition of subchronic inhalation experiment were examined. Rats were exposed to vapours of hemimellitene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After termination of a 3-month inhalation, animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examinations. Subchronic inhalation exposure to hemimellitene resulted in an overall, low systemic toxicity. There were no changes in body weight gain and food consumption. At a concentration of 1230 mg/m3, the increase in relative liver weight was observed in male rats. It was accompanied by slight increase in sorbitol dehydrogenase activity. The increase in alkaline phosphatase activity was found in females only. Some disturbances in haematological parameters, characterised by the decrease in red blood cells and slight increase in white blood cells, segmented neutrophils and lymphocytes were observed in rats at high exposure concentration of 1230 mg/m3. The pulmonary lesions as well as the increased number of goblet cells and interstitial lung parenchyma infiltration were noted in male and female rats from the highest exposure groups.
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PMID:Subchronic inhalation toxicity of 1,2,3-trimethylbenzene (hemimellitene) in rats. 1110 46


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