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Biomedical subjects

C Gopinath

Publications and source records attributed to C Gopinath.

At least 19 recordsLinked to original sources

Age-related changes in thyroid structure and function in Sprague-Dawley rats.

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.

Aging

Morphological assessment of visual dysfunction.

The eye is an isolated unit but with a potentially high degree of sensitivity to toxic substances. The multiplicity of types of reaction to injury reflects the unique anatomical, physiological and biochemical features of the eye. The following are examples of such: The albino rat is not a good model for retinal toxicity because of problems of phototoxic retinopathy, the absence of pigment within the pigment epithelial layer and the high incidence of spontaneous retinal pathologies; The ocular toxicity of a compound cannot be anticipated from its chemical structure; Pharmacological side effects are similar between species, and are predictive for man; Mechanisms of ocular toxicity are poorly understood.

Animals

Harderian gland tumours in mice.

A survey of the occurrence of harderian gland tumours in Charles River CD-1 mice (Caesarian derived) showed a relatively higher incidence of harderian gland adenomas in males (5%) in comparison with females (2%) among 3302 untreated control mice from two-year carcinogenicity studies. This sex difference did not apply to the incidence of harderian gland carcinomas. Porphyrin pigment was observed in some of the tumours. Metastasis of the harderian gland carcinoma was seen in lymph node and lung, and in one case the thymus and liver was also affected. Vacuolation, due to fat was seen as helpful diagnostic feature.

Adenoma

Giant-cell tumour of soft tissue in two Sprague-Dawley rats.

Two cases of soft tissue giant-cell tumours are reported in Sprague-Dawley rats. The lesions had the characteristic appearance of multinucleate tumour giant cells and were unassociated with bone. A search of the literature failed to reveal any previous report of this lesion in the rat.

Animals

Central-peripheral delayed neuropathy caused by diisopropyl phosphorofluoridate (DFP): segregation of peripheral nerve and spinal cord effects using biochemical, clinical, and morphological criteria.

Systemic injection of diisopropyl phosphorofluoridate (DFP; 1 mg/kg, sc) causes delayed neuropathy in hens. This effect is associated with a high level of organophosphorylation of neuropathy target esterase (NTE) followed by an intramolecular rearrangement called "aging." Phenylmethanesulfonyl fluoride (PMSF) also attacks the active center of NTE but "aging" cannot occur. This compound does not cause neuropathy and protects against a subsequent challenge systemic dose of DFP. Intraarterial injection of DFP (0.185 mg/kg) into only one leg of hens caused a high NTE inhibition (greater than 80%) in the sciatic nerve of the injected leg, but not in other parts of the nervous system (37% average). A unilateral neuropathy with typical histopathological lesions developed in the injected leg. PMSF (0.55 mg/kg) injected into each sciatic artery caused 47% inhibition of sciatic nerve NTE but only 17-22% inhibition of NTE elsewhere; it did not produce clinical or histopathological lesions. When these hens were challenged with DFP (1 mg/kg, sc), high inhibition of residual-free NTE (greater than 85%) occurred throughout the nervous system and clinical signs of a syndrome different from the classical delayed neuropathy developed: this spinal cord type of ataxia was associated with histopathological lesions in the spinal cord but not in peripheral nerve. PMSF (1 mg/kg) injected into only one sciatic artery caused selective protective inhibition of sciatic nerve NTE of that leg. After systemic challenge by DFP, clinical effects expressed were a combination of spinal cord ataxia plus unilateral peripheral neuropathy. The challenge dose of DFP (1 mg/kg, sc) was insufficient to produce clear histopathological lesions in unprotected peripheral nerves although spinal lesions were found in these hens. Thus clinical evaluation of the peripheral nervous system by means of walking tests and a simple test of "leg retraction" reflexes was more sensitive and specific in diagnosis of peripheral neuropathy than was the histopathology.

Animals

A report on drug-induced kerato-conjunctivitis sicca in dogs.

Kerato-conjunctivitis sicca is reported in beagle dogs treated with an antispasmodic compound for 26 weeks during a routine toxicity study. There was a deficiency of lachrymal secretion associated with keratitis and corneal vascularization. Histopathologically, the changes were characterized by vascularization, fibroblast proliferation and infiltration of inflammatory cells in the substantia propria. In some cases, the inflammation also occurred in corneal epithelium, ocular conjunctiva and corneal limbi.

Animals

Mesovarian leiomyomas in the rat.

Prolonged treatment with two chemically distinct beta-stimulants, Salbutamol and Terbutaline, resulted in mesovarian leiomyomas in Sprague-Dawley rats. Development of these tumors induced by Salbutamol was prevented by concurrent administration of the beta-blocker Propranolol. Mesovarian leiomyomas induced by Salbutomol did not show any regression or progression during a 44-week postdosing recovery period. This report also gives the first recorded incidence of spontaneous mesovarian leiomyomas in the rat.

Albuterol

The toxicity of gossypol to the male rat.

When (+/-) gossypol acetic acid was administered to male Sprague-Dawley rats for 26 weeks, the most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Minor biochemical changes were noted at this dosage level. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a "no effect" level.

Animals

Serum alkaline phosphatase elevation in female rats treated with ethinyl estradiol.

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.

Alkaline Phosphatase

Isoprenaline-induced myocardial necrosis in dogs.

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.

Animals

The effect of ragwort (Senecio jacobea) on the liver of the domestic fowl (Gallus domesticus) : a histopathological and enzyme histochemical study.

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.

Adenosine Triphosphatases

Copper toxicity in sheep: the effects of repeated intravenous injections of copper sulphate.

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.

Animals