Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen male Suffolk lambs fed a 8 ppm Cu basal diet were randomly assigned to 2 groups: 12 copper-loaded (CL) and 4 controls (C). The CL sheep were drenched initially with 3 mg Cu/kg bw daily for a week. Every week an additional dose of 3 mg Cu/kg bw was included in the drench until signs of copper poisoning appeared; the control sheep were drenched with saline solution. The onset of copper poisoning occurred between 42 and 55 d. Food intake and body weight were recorded daily. Blood samples were collected weekly to measure the activity of the liver enzymes gamma-glutamyltransferase (gammaGT), aspartate aminotransferase (AST), sorbitoll dehydrogenase (SDH) and acid phosphatase (AF). The following changes were significantly recorded in the CL sheep in the weeks or days previous to the hemolytic crisis: higher levels of gammaGT were found on the -28th d increasing slowly but continuously until the hemolytic crisis; SDH fluctuated during the period presenting higher levels on the -28th, -14th and -7th d; AST and AF activities increased from the -14th and -7th d respectively; sharp decreases in the activities of SDH and AF at the hemolytic crisis; lower feed intake and body weight gain from the -7th d; and sheep ceased eating concentrates from the -9th d and became anoretic the day before the hemolytic crisis. Plasma copper concentration increased only the day before the hemolytic crisis. There were no changes in respiratory and heart rates, rectal temperature or rumen movements throughout the pre-hemolytic phase. The higher the amount of cumulative copper drenched, the higher was the gammaGT and AST activities. It was concluded that gammaGT followed by AST are the best enzymes to assess copper-load in sheep during the pre-hemolytic phase. Sheep fed copper-rich diets with high plasma activity of these enzymes, decreased feed consumption and subtle loss of body weight are most likely to present with a hemolytic crisis in a few days.
 ...
PMID:Assessment of some clinical and laboratory variables for early diagnosis of cumulative copper poisoning in sheep. 1464 Apr 76

The 44-year old female patient was admitted with acute hepatic failure and extensive haemolysis under the preliminary diagnosis of Wilson's disease. General characteristic criteria of Wilson's disease as Kayser-Fleischer ring, low serum copper and low ceruloplasmin levels were not observed. The preliminary diagnosis of acute Wilson's disease was established on the basis of the characteristic laboratory values with an AP/bilirubin ratio <2, an AST/ALT ratio >4, accompanying hemolysis and a highly elevated cupruresis. The definitive diagnosis of Wilson's disease was verified after orthotopic liver transplantation by quantitative copper evaluation in the explanted liver. The case represents the yet oldest patient reported with an acute manifestation of Wilson's disease.
 ...
PMID:[44-year-old patient with fulminant liver failure]. 1468 90

The first generation of 3 morphologically different forms of B. glabrata collected from Giza were compared for LC50 values susceptibility to bayluscide and copper sulphate (chemical molluscicides) and Anagallis arvensis and Calendula micrantha (plant molluscicides) and to Schistosoma mansoni infection. Form (2) as juvenile and adult were less sensitive to C. micrantha and A. arvensis. Form (3) as juvenile and form (1) as adult were least sensitive to CuSO4. Approximately the same susceptibility to bayluscide was observed in the 3 forms either as juvenile or adult. The sublethal concentrations of the molluscicides on B. glabrata 3 forms showed no significant difference in the growth or survival rate in between. Form (2) was significantly higher in the egg lying capacity. The total protein concentration was not affected except in certain cases where the increase was primarily due to the increase in the globulin concentrations which indicate with the marked increase observed in the urea concentration and marked increase or inhibition in the activity of either AST or ALT that the digestive gland of the 3 forms of snails is seriously affected by molluscicides. The 3 forms of B. glabrata showed low susceptibility to infection with the local strain of S. mansoni.
 ...
PMID:Difference in the susceptibility to certain molluscicides and Schistosoma mansoni infection of three forms Egyptian Biomphalaria glabrata. 1470 51

Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a total dose of approximately 200 mg kg(-1). The high tumour boron concentration decreased slowly while concentrations in blood decreased rapidly. Boron concentrations in brain and skin were consistently lower than in tumour by a factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.
 ...
PMID:Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice. 1523 4

IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague-Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1+/-14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9+/-17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8+/-122.3 compared with 5436.3+/-984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8+/-76.9 compared with 3166.3+/-379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.
 ...
PMID:Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis. 1534 10

An outbreak of footrot occurred in a flock of Corriedale sheep; 27 animals were treated with antibiotic and footbathed in a 5% copper sulfate solution. Being deprived of water for > 17 h, many sheep drank the footbath solution. After 6 h 16 sheep became ill with acute copper poisoning, 10 animals died within 10 h; 6 were severely ill and were sent to Veterinary Hospital, and 4 had mild signs and recovered without treatment. The sick sheep had anorexia, dullness, grinding teeth, moaning, rumen atony, dehydration, dark blue-green diarrheic feces and congested membranes. They were treated with 3.4 mg tetrathiomolybdate/kg body weight and lactated Ringer's solution iv, oral molybdate, sulfate, kaolin and pectin, and drenched with antacids. Two of the 6 sheep died during hospitalization. The ingestion of copper solution caused an intense gastrointestinal injury that resulted in ulcers, petechial and echymotic hemorrhages in the mucosa, mild hemolysis detected by microscopic hemoglobinuria and a lowered packed cell volume, severe hepatic injury that raised the AST and gammaGT blood values, and moderate kidney lesions with increasing serum blood urea and nitrogen creatinine levels.
 ...
PMID:Acute sheep poisoning from a copper sulfate footbath. 1558 48

Wilson's disease (WD) is a rare liver-based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long-term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring > or = 7, the cutoff value for death without transplantation, survived, whereas 4 scoring < or = 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients.
 ...
PMID:Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. 1577 53

Wilson's disease (WD) is an inherited disorder of copper metabolism characterized by a failure of the liver to excrete copper, leading to its accumulation in the liver, brain, cornea, and kidney, with resulting chronic degenerative changes. It is generally accepted that "presymptomatic" patients--in whom WD is diagnosed in childhood and who are defined as those who, although still asymptomatic, do have liver disease, as indicated by increased serum concentrations of transaminases--should be treated prophylactically. Here we report our results in 22 children treated with continuous oral zinc therapy for 10 years. Zinc sulfate was administered at a dosage of 25 mg elemental zinc twice a day until the age of 6 years, 25 mg three times a day between the ages of 7 and 16 years or until the child attained a body weight of 125 lb, and 50 mg three times a day thereafter. Five years after the start of zinc treatment, we noted highly significant decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urinary copper excretion, but white blood cell counts did not vary significantly. Six of 22 patients continued to demonstrate greater-than-normal ALT concentrations and only 1 patient demonstrated an ALT concentration more than 1.5 times the upper normal limit. Further decreases in ALT, AST, and urinary copper excretion were observed at the end of the 10-year follow-up, but these decreases were not statistically significant. Only 1 patient continued to demonstrate abnormal ALT levels. Again, white blood cells showed no significant variations. All histologic scores (steatosis, inflammation, and fibrosis) were significantly decreased after treatment. Hepatic copper content was also significantly decreased, although it remained higher than normal in all patients. The removal of toxic copper was confirmed by disappearance of Kayser-Fleischer rings in 3 patients. Zinc did not have adverse effects on growth. The efficacy of zinc in WD in presymptomatic pediatric patients has been established in previous studies, and our study adds considerably to the earlier findings because it includes a large number of very young children, as many as 11 younger than 6 years and 20 younger than 10. The excellent clinical results in all patients, coupled with the improvement in hepatic histologic findings in the vast majority, indicate convincingly that zinc treatment can control the disease effectively and safely, preventing its progression over the course of 10 years. Histologic findings reportedly improved in 3 patients treated in an earlier study, but our data are numerically much more relevant. Notably, histologic study of the liver revealed that copper concentration was reduced by treatment, suggesting that oral zinc was able not only to prevent further accumulation of copper but also to promote, at least in part, the depletion of its stores. The lack of adverse effects of zinc on growth suggests that our patients received enough anticopper therapy to prevent damage resulting from copper toxicity but an adequate amount of copper for proper growth and development. In conclusion, our findings indicate that zinc is the treatment of choice in presymptomatic pediatric patients with WD.
 ...
PMID:Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: a single-hospital, 10-year follow-up study. 1587 5

The objective of the experiment was to determine the effectiveness of copper oxide wire particles (COWP) in pregnant ewes and safety to lambs. COWP have been used recently as an anthelmintic in small ruminants to overcome problems associated with nematode resistance to chemical dewormers. Doses of COWP (<or=4 g) have been used in lambs without clinical signs of copper toxicity. Use in pregnant ewes has not been examined. Mature Katahdin ewes were administered 0 (n=14), 2 (n=15), or 4 (n=15)g of COWP 33+/-1.6 days before lambing in late March 2004. Fecal egg counts (FEC) and blood packed cell volume (PCV) were determined between Days 0 (day of COWP administration) and 35. Lambs were weighed within 24h after birth, at 30 and 60 days of age, and in mid-September ( approximately 120 days of age). Blood was collected from lambs within 24h after birth and at 30 days of age for determination of the activity of the liver enzyme, aspartate aminotransferase (AST) in plasma. Within 7 days after COWP administration, FEC decreased by 1308 and 511 eggs/g (epg) in the 2 and 4 g groups, respectively, compared with an increase of 996 epg in the control group (P<0.02). PCV was similar among groups between Days 0 and 35. Lamb plasma AST activity at birth increased with increasing dose of COWP in dams (P<0.001). Plasma AST activity at 30 days of age was similar for lambs from ewes treated with 0 and 2g COWP, but was slightly greater in lambs from ewes treated with 4 g COWP (P<0.02). Birth weights decreased with increasing COWP (P<0.003). By 30 (COWPxbirth type, P<0.02) and 60 (COWPxbirth type, P<0.02) days of age, weight of multiple-born lambs decreased with increasing COWP, while weight of single-born lambs was similar among treatments. In mid-September ( approximately 120 days of age) weights of multiple-born lambs from ewes treated with 4 g COWP tended to be lightest compared with lambs from ewes treated with 0 or 2g COWP or single-born lambs (P<0.09). Lamb survival to 30, 60, or 120 days of age was not affected by COWP treatment to ewes. Administration of 4 g COWP to late pregnant ewes may negatively impact multiple-born offspring, but the 2g appears to be safe for production.
 ...
PMID:The effectiveness of copper oxide wire particles as an anthelmintic in pregnant ewes and safety to offspring. 1597 Mar 88

Metallothionein (MT) is a small sulfydryl-rich protein that binds to and is inducible by heavy metals such as mercury, cadmium, zinc, and copper. However, little is known about the induction of MT by trivalent metals except for bismuth. In this study, we examined the induction of MT synthesis by cerium, a trivalent lanthanoid metal. Administration of cerium chloride (CeCl3) to mice resulted in accumulation of cerium and induction of MT in the liver in a dose-dependent manner. Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium. Administration of CeCl3 caused increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of serum amyloid A (SAA), an acute phase protein. Among inflammatory cytokines examined, interleukin 6 (IL-6) exhibited a marked increase in the serum at 3 h after the CeCl3 administration. In order to evaluate the involvement of IL-6 in the induction of MT by cerium, we examined MT induction by CeCl3 in IL-6 null mice. Both the induction of hepatic MT and the increases in SAA levels were markedly suppressed in IL-6 null mice. These results suggest that IL-6 plays an important role in the induction of hepatic MT by cerium.
 ...
PMID:Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6. 1620 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>