Toxicological studies on (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic. Its subacute toxicity and recovery study in beagle dogs.
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Biomedical subjects
Publications and source records attributed to C Gopinath.
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A rare type of mixed mammary tumour, described in a CD female rat, represents the first record of a mixed mammary tumour in a rat with both epithelial and chondroid components.
The prolonged effects of overdosage with lentinan in the rhesus monkey are associated with foam cell reactions in lung, liver, kidney, spleen, lymph nodes and bone marrow and with varying degrees of vasculitis and associated reactions. A dose level of 0.5 mg/kg/day was without adverse effect.
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The usefulness of measuring serum bile acid concentrations by RIA in a number of acute experimental liver injuries of rats was assessed by comparing the concentrations with the results of some of the routinely employed methods of examining hepatotoxic changes. Centrilobular liver cell injury produced by CCl4 revealed leakage of GPT and GDH and to a lesser extent AP; along with minimal increase in serum bile acid levels. Serum bilirubin concentration remained unchanged. Surgical bile duct ligation resulted in marked rises in AP, GPT and GDH and total bilirubin levels and levels of serum bile acids. Intravenous injection of MnSO4 induced focal necrosis of liver and bile canalivular dilation associated with elevated GDH and GPT concentrations. AP and bilirubin levels were unchanged. Bile acid levels were raised among female rats. 2,4-Xylidine induced hepatotoxicity revealed bile duct hyperplasia, liver cell enlargement, liver cell necrosis, biliary canalicular dilation and proliferation of endoplasmic reticulum. GDH and GPT levels were raised along with bile acid concentrations. This study suggested that assay of bile acid concentration is a sensitive indicator of several acute hepatic injuries.
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Adrenal calcification occurred in 52.6% of rhesus monkeys, 4.7% of cynomolgus monkeys and 2.4% of baboons examined. In contrast, ovarian calcification was observed in 62.3% of baboons, 38% of cynomolgus and 22.3% of rhesus monkeys examined.
11 cases of spontaneous pituitary neoplasms in rats, which showed infiltration into brain tissue, are reported. This represents an incidence of about 0.42%.
Ethinyl estradiol treatment to female rats resulted in increased levels of serum alkaline phosphatase, but was not associated with any other manifestation of toxicity such as increased serum transaminases or toxic lesions. Elevated serum alkaline phosphatase seen in rats treated with chloroform was associated with frank hepatotoxicity. Induction of hepatic drug metabolising enzymes in rats by phenobarbitone treatment did not result in raised serum alkaline phosphatase levels. Estradiol benzoate treatment to rats also did not increase serum alkaline phosphatase levels. Ethinyl estradiol also resulted in increased alkaline phosphatase content in the liver, intestine and bone. The raised intestinal alkaline phosphatase content of rats treated with phenobarbitone or estradiol benzoate was not associated with an increase in the serum levels. There was histochemical evidence of induction of canalicular alkaline phosphatase in the liver in Ethinyl Estradiol treatment. The study of the electrophoretic separation of serum alkaline phosphatase of ethinyl estradiol treated rats revealed the presence of a new fast moving fraction, similar to those seen in bile duct ligated rats. It is concluded that the serum alkaline phosphatase increase during ethinyl estradiol treatment at least in part is from the liver, due to new synthesis.
Subcutaneous injections of isoprenaline sulphate in dogs (1-3 mg/kg) resulted in myocardial injury. Good correlation was observed between abnormal ECG recordings, serum enzyme concentrations and myocardial lesions in the acute phase of injury. However, in cases where less extensive myocardial injury was produced due to lower doses of isoprenaline or in cases of the reparative phase of the isoprenaline-induced myocardial injury, serum enzymes were not useful indicators of the change. Similary, ECG recordings taken peripherally also did not show alteration in the reparative phase of the injury in spite of extensive myocardial lesions.
1. Twenty-five 1-week-old male chicks were fed for 6 weeks on a standard diet incorporating 7% dried and ground ragwort (Senecio jacobea). The chicks received the standard diet for a further 6 weeks whilst a control group of 25 similar birds received the standard diet throughout. 2. Two birds from each group were killed at intervals of about 1 week and their livers were examined histologically and histochemically. 3. Ragwort feeding caused megalocytosis, focal necrosis, focal hyperplasia and portal fibrosis. There were no veno-occlusive changes. 4. As the lesion progressed there was an overall loss of enzyme activity especially in the areas of necrosis. The groups of small hyperplastic cells showed normal or increased activity and there was increased enzyme activity in the megalocytes. 5. The development of groups of proliferating cells may be a prelude to the neoplastic changes described in earlier reports of longer term studies of the effects of pyrolizidine alkaloids on the liver of chicks.
Four Clun Forest, Suffolk cross sheep were given daily intravenous injections of copper sulphate. Three similar sheep acted as controls. The copper dosed sheep developed haemolysis and showed liver, kidney and brain damage similar to that seen in chronic copper poisoning. All animals survived for 30 days and two would have lived longer. Reticulocytes were produced after four days and continued to be produced, sometimes in high number throughout the course of the experiment.
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Under general anaesthesia the common bile duct was ligated in two sheep and two calves. Occlusion of the duct was permanent and was followed by portal fibrosis, proliferation of bile ducts and intrahepatic bile stasis. Mild hepatic cell damage was accompanied by the release of glutamate dehydrogenase, sorbitol dehydrogenase and arginase into serum. The release of gamma-glutamyl transpeptidase was slower but more continuous. One sheep and one calf developed peritonitis associated with the leakage of bile from a biopsy wound in the live. One of these animals and the other two on which biopsy was not performed became photosensitised on exposure to sunlight. The concentration of phylloerythrin was high in serum and urine. All animals became jaundiced and the increased concentration of bilirubin in serum and urine was mainly direct reacting, ie, conjugated with glucuronic acid.