Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The indolizidine alkaloid swainsonine, a potent inhibitor of Golgi alpha-mannosidase II, has been shown to reduce tumor cell metastasis, enhance cellular immune responses, and reduce solid tumor growth in mice. In our previous Phase I study, swainsonine administered by 5-day continuous infusion inhibited L-phytohemagglutinin-reactive N-linked oligosaccharide expression on peripheral blood lymphocytes. Significant toxicities included edema and elevated serum aspartate aminotransferase (AST). One patient with head and neck cancer had objective (>50%) tumor remission. Two patients showed symptomatic improvement. The objectives of this Phase IB trial were to examine the pharmacokinetics, toxicities, and biochemical effects of bi-weekly oral swainsonine at escalating dose levels (50-600 microgram/kg) in 16 patients with advanced malignancies and 2 HIV-positive patients unsuitable for conventional therapy. Eastern Cooperative Oncology Group performance status was </=2. The maximum tolerated dose was defined as 300 microgram/kg/day due primarily to serum AST abnormalities and dyspnea. Other adverse events present in >20% of patients included increase in serum AST (all patients), fatigue (n = 9), anorexia (n = 6), dyspnea (n = 6), and abdominal pain (n = 4). Inhibition of Golgi alpha-mannosidase II occurred in a dose-dependent manner. Examination of immunological parameters revealed a transient decrease in CD25(+) peripheral blood lymphocytes and, in seven of eight patients, an increase in CD4(+):CD8(+) ratios at 2 weeks. Serum drug levels peaked 3-4 h following a single oral dose in most patients and were proportional to dose at levels >/=150 microgram/kg. We conclude that oral swainsonine is tolerated by chronic intermittent administration at doses up to 150 microgram/kg/day. Adverse events considered drug related were similar to those observed in the infusional study but with fatigue and neurological effects also noted. Investigations of alternative dosing schedules with low starting doses are suggested for further clinical testing.
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PMID:Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. 981 86

A probable outbreak of oak (Quercus calliprinos) toxicosis in a herd of beef cattle--heifers and first-calving cows--grazing in the Judean foothills of Israel is described. Toxicosis probably occurred because of the consumption of oak leaves and buds during a period of pasture scarcity without any feed supplementation. A progressive syndrome of wasting, dullness, anorexia, polyuria, nephrosis, constipation and recumbency, culminating in death, was seen. A high mortality rate of 83% (38/46 animals) was noted. The clinical-pathological findings revealed increases in blood urea, creatinine, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK), lactate dehydrogenase (LDH) and inorganic phosphorus. Decreases were found in alkaline phosphatase (ALP), total serum protein, albumin (ALB), triglyceride (TG), calcium (Ca), magnesium (Mg), sodium (Na) and chloride (CI). The main pathological findings were severe nephrosis, chronic interstitial nephritis, and occasional intestinal ulceration. On the basis of epidemiology, clinical signs, clinical-pathological and pathological findings and renal histology, a tentative diagnosis of oak toxicosis was made.
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PMID:Probable toxicosis in cattle in Israel caused by the oak Quercus calliprinos. 983 Jun 93

The records of 14 cases of bovine hypokalaemia observed between 1983 and 1996 were reviewed. The most common history included a protracted, often infectious, disease. All age groups were represented. Although previously reported as a risk factor, isoflupredone acetate had not been administered to five of the cases. The following clinical signs were recorded in 10 cases: abnormal position of the head and neck, severe weakness, rumen hypomotility or atony, abnormal faeces, anorexia and tachycardia. Cardiac dysrhythmia was observed in six cases. Acid-base imbalance (alkalosis in 10 cases), hyperglycaemia and increased activities of aspartate aminotransferase and creatine kinase were associated with hypokalaemia ranging from 1.35 to 2.49 mmol/litre. Treatments included symptomatic treatment, supportive care and potassium chloride given intravenously and orally at an average total daily dose of 42 g/100 kg bodyweight (26 g by mouth and 16 g intravenously) for an average of five days. Eleven cases recovered after an average of three days.
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PMID:Description of 14 cases of bovine hypokalaemia syndrome. 983 71

This is the first confirmed report of exertional rhabdomyolysis in a non-human primate. The monkey was singly housed and presented with anorexia and reluctance to move. There was no external evidence of trauma. Clinicopathologic findings included mild azotemia, marked elevation in serum creatine phosphokinase (CPK), alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days post-incident, the peripheral skeletal muscle had marked multifocal myonecrosis and fibrillar disruption without an inflammatory reaction. Treatment included diuresis and pain relief, and urinary output was monitored. The monkey recovered over the next two weeks. The major significance of skeletal muscle damage is the potential of released myoglobin to cause acute renal failure in the presence of other co-factors such as hypovolemia, acidosis, or ischemia. CPK levels can be highly variable and are inconsistent with the degree of muscle damage; however, CPK is thought to be the most sensitive enzyme marker for muscle necrosis. Because of the potential life-threatening sequelae, exertional rhabdomyolysis should be included as a differential diagnosis when similar clinical and pathological signs are observed.
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PMID:Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca mulatta). 1020 11

Absidiosis was produced experimentally in 18 buffalo calves by intravenous inoculation of spores of Absidia corymbifera. Infected animals exhibited dullness, depression, partial anorexia and an initial pyrexia and coughing during the first week and two animals died on each of 9, 13 and 16 days post infection (DPI). The haemoglobin concentration and total erythrocyte count showed no appreciable change from their basal values at any stage of the experiment. However, the erythrocyte sedimentation rate and total leukocyte count increased significantly in the infected animals. The differential leukocyte count revealed a relative neutrophilia from 5 to 20 DPI. There was a significant increase in the serum total proteins, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, serum alkaline phosphatase, total immunoglobulins and circulating immune complexes in the infected animals as compared to the controls. In the sera of the infected animals, specific Absidia corymbifera IgM and IgG antibodies were detected from 3 DPI to 6 DPI respectively by Dot-EIA. Type I and type III skin hypersensitivity were detected from 10 DPI and type IV hypersensitivity from 15 DPI onwards. The gross and microscopic pathological lesions were seen mainly in the lungs, in all except one of the affected animals. This animal died 9 DPI and mycotic granulomas were also seen in its heart and kidneys. The microscopic lesions in the lung took the form of well-developed granulomas.
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PMID:Sequential clinical, haematological, biochemical, immunopathological and histopathological alterations in buffalo calves (Bubalus bubalis) intravenously infected with Absidia corymbifera. 1044 50

Lesions consistent with exertional myopathy (EM) were documented postmortem in four North American river otters (Lutra canadensis) during translocation for a population restoration project. Clinical signs in these otters included depression, anorexia and shock. Gross lesions in one otter included locally extensive linear, pale areas within the subscapularis, rectus abdominis, quadriceps, and dorsal laryngeal muscles. Microscopic lesions were characterized by acute to subacute myofiber necrosis of varying severity, and occurred in a variety of skeletal muscles as well as cardiac muscle in one otter. Based on these observations, we conducted a retrospective review of records of otters which experienced similar capture, transfer, and holding protocols between 1995 and 1997, but with a successful outcome (n = 69). Significant elevations in serum aspartate aminotransferase (AST) and creatine kinase (CK) were observed in 19 (28%) of the otters, but may have been higher due to delayed sample collection from some otters. However, none of the otters with elevated enzymes exhibited clinical signs suggestive of EM. These findings indicate that river otters may develop EM when translocated, but many cases may be mild or clinically inapparent.
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PMID:Exertional myopathy in translocated river otters from New York. 1047 89

Preparturient hypocalcemia was identified in 4 cats in a specific pathogen-free colony between 1995 and 1996. All cats had an acute onset of clinical signs, 3 to 17 days prior to parturition. Signs of depression, weakness, tachypnea, and mild muscle tremors were the most common clinical signs, following by vomiting and anorexia. Additional abnormalities included hypothermia, third eyelid prolapse, dehydration, pallor, lethargy, flaccid paralysis, and hyperexcitability. Hematologic abnormalities included leukocytosis with neutrophilia and lymphopenia. Hypocalcemia was documented in each queen. Common serum biochemical abnormalities included high aspartate aminotransferase and creatine kinase activities. All cats responded to IV or SC administration of 10% calcium gluconate. Queens were then given calcium orally prior to and following parturition. The queens did not have additional complications for the duration of the gestational or lactational periods.
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PMID:Preparturient hypocalcemia in four cats. 1053 Mar 27

Changes in hematological and serum biochemistry parameters in female zinc (Zn)-dosed farm-raised mallards (Anas platyrhynchos) fed four different diets were examined. Sixty ducks received an average dose of 0.97 g of Zn in the form of eight, 3.30-mm diameter shot pellets containing 98% Zn and 2% tin, and another 60 ducks were sham-dosed as controls. Fifteen ducks from each of the two dosing groups were assigned to one of four dietary treatments: corn only, corn with soil, commercial duck ration only, or commercial duck ration with soil. Shot-pellet dissolution rates ranged from 7 mg/Zn/day to 27 mg/Zn/day. Regardless of diet, the Zn dose resulted in mortality; incoordination; paralysis and anorexia; decreased body, liver, pancreas, gonad, and gizzard weight; increased kidney weight; and macroscopic lesions. Zn-dosed ducks had a lower mean erythrocyte packed cell volume (PCV), higher mean reticulocyte count, and a greater number of individuals with immature and/or abnormal erythrocytes, than did control mallards. Mean total leucocyte counts were higher in Zn-dosed ducks than in controls. Zn-dosed ducks that had soil available had higher leucocyte counts than those without soil. Zn-dosed ducks were characterized by a marked heterophilia and relative lymphopenia. In Zn-dosed ducks, the mean lymphocyte count was highest in those provided a commercial duck ration, and lowest in those fed corn. In control ducks, the mean lymphocyte count was highest in ducks fed corn, and lowest in those provided soil along with a commercial duck ration. Zn-dosed mallards had higher serum aspartate aminotransferase and amylase levels, and lower alkaline phosphatase activities than control ducks. Serum phosphorus and uric acid concentrations were higher, and calcium, glucose, and total protein levels lower, in Zn-dosed ducks than in control ducks. Diet did affect serum calcium, phosphorus, total protein, and uric acid concentrations. Differences in erythrocyte and leucocyte parameters, serum enzyme activities, and metabolite concentrations were associated with dose and diet effects. Diets high in protein and other organic matter and calcium and phosphorus did not prevent or substantially alleviate Zn toxicosis in farm-raised mallard ducks.
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PMID:Influence of diet on the hematology and serum biochemistry of zinc-intoxicated mallards. 1068 52

A 13-year-old castrated domestic shorthair cat was examined because of fever, anorexia, and dermatologic lesions. Crusting, erythema, and well-demarcated purple discoloration of the foot pads and the tips of the pinnae, nose, and tail were seen. A white flocculent precipitate was detected in cooled serum. This precipitate dissolved upon rewarming, consistent with a cryoglobulin. Hypercalcemia, high alanine and aspartate aminotransferase activities, thrombocytopenia, and a monoclonal IgG gammopathy were found. Numerous hepatic nodules were detected by means of abdominal ultrasonography. Cytologic evaluation of fine-needle aspirates of the liver and spleen revealed numerous plasma cells, and evaluation of a bone marrow aspirate revealed plasmacytosis. A diagnosis of multiple myeloma and monoclonal IgG cryoglobulinemia was made, and the cat was euthanatized.
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PMID:Monoclonal immunoglobulin G cryoglobulinemia and multiple myeloma in a domestic shorthair cat. 1101 10

Susceptibility of sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture is described in 12 sheep assigned as untreated controls, C. colocynthis-treated at 0.25g/kg/day, N. oleander-treated at 0.25g/kg and plant mixture-treated at 0.25g of C. colocynthis/kg plus 0.25g of N. oleander/kg. The daily use of 0.25g of C. colocynthis/kg for 42 days was not fatal to sheep and caused slight diarrhoea, catarrhal enteritis, centrilobular hepatocellular fatty change and degeneration of the renal tubular cells. Single oral doses of 0.25g of N. oleander/kg were lethal to sheep within 18-24h and caused uneasiness, grinding of the teeth, dyspnoea, anorexia, frequent urination, ruminal bloat, ataxia and recumbency before death. The main lesions were widespread congestion and haemorrhage, pulmonary cyanosis and emphysema and severe hepatonephropathy. Rapid death was also observed in sheep receiving single doses of the mixture of the two plants. Effects were correlated with changes in the activities of serum lactic dehydrogenase (LDH) and aspartate transaminase (AST) and concentrations of cholesterol, bilirubin, total protein, albumin, globulin and urea and haematological parameters.
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PMID:Response of Najdi sheep to oral administration of Citrullus colocynthis fruits, Nerium oleander leaves or their mixture. 1132 8


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