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Biomedical subjects

K Patil

Publications and source records attributed to K Patil.

At least 37 records · Page 2Linked to original sources

Comparative studies on the effects of semipurified and commercial diet on longevity and spontaneous and induced lesions in the Syrian golden hamster.

Syrian golden hamsters were fed a semipurified or commercial diet from weaning throughout life. Bis(2-oxopropyl)nitrosamine (BOP) was administered at 8 weeks of age (10 mg/kg body wt, sc). Longevity was improved by 26% and 36% increases in the mean life-spans of male and female hamsters, respectively, fed the semipurified diets. Carcinogen treatment did not alter survival. The age-adjusted occurrence rates of pancreatic ductular proliferation, carcinomas, adenomas, and common duct polyps were higher in hamsters fed commercial diet; this indicates an earlier onset of these BOP-induced lesions in hamsters fed this diet. However, their overall incidences were generally similar when the two diet groups were compared. Acinar cell nodules were observed only in hamsters fed semipurified diets and were elevated in BOP-treated females. The onset of pancreatic ductular proliferation and adenomas, bile duct proliferation, parathyroid hyperplasia, and common duct papillary hyperplasia was earlier in females than in male hamsters, especially in groups fed commercial ration. Generalized vascular calcification was observed at an elevated rate and reached a higher overall incidence in hamsters fed commercial ration. The age-adjusted rate of amyloidosis was high in female hamsters and elevated in groups that consumed the commercial ration. In addition, colitis and islet cell hyperplasia occurred more often and earlier in hamsters fed commercial ration, but gallbladder stones occurred most in animals fed semipurified diet. This paper discusses the possible association between these and other observed lesions and survival.

Adenoma↗

The importance of reverse triiodothyronine in hypothyroid children on replacement treatment.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) values were measured by radioimmunoassay in 40 children with congenital hypothyroidism who were being given levothyroxine (0.05-0.35 mg/day) and in 14 normal controls. In 15 of the children with hypothyroidism the treatment, judged by serum T4 and TSH values and thyrotrophin releasing hormone (TRH) test, seemed to be adequate and their mean rT3 value and rT3:T4 ratio were comparable with the controls. The remaining 25 children had a raised serum T4 and a low TSH value. Only 4 (16%) of these children had an abnormally high T3 concentration but the rT3 value was raised in 23 (92%) and their mean rT3 value and rT3:T4 ratio were significantly higher than in the control children. Less than 20% of this 'overtreated' group, however, had clinical hyperthyroidism. We suggest that in patients on T4 replacement treatment the peripheral thyroid homeostatic mechanisms produce larger amounts of rT3, thereby preventing high T3 values where serum T4 values are raised. This may explain why the 'overtreated' children showed no clinical evidence of hyperthyroidism. These findings emphasise the protective and selective role of peripheral monodeiodination.

Adolescent↗

Syncarcinogenic effect of the environmental pollutants cyclopenteno[cd]pyrene and benzo[a]pyrene in mouse skin.

Benzo[a]pyrene (BP) and cyclopenteno[cd]pyrene (CPEP) are widespread environmental pollutants. CPEP is a relatively potent carcinogen in mouse skin with an activity second only to BP among environmental aromatic hydrocarbons. We have studied the combined application of BP and CPEP on mouse skin to determine their possible synergistic carcinogenic effect. Nine-week-old female Swiss mice in groups of 30 were treated on the back with high (H), medium (M) and low (L) doses, respectively, of 20 (H), 6.6 (M) or 2.2 (L) nmol BP or 200 (H), 66.6 (M) or 22.2 (L) nmol CPEP in 50 microliters acetone twice weekly for 48 weeks. Other groups received BP-H + CPEP-H, BP-M + CPEP-M, BP-L + CPEP-L, BP-H + CPEP-L, BP-M + CPEP-L, BP-L + CPEP-H, or BP-L + CPEP-M. A significant, 3- to 7-fold syncarcinogenic effect occurred when BP-M + CPEP-M were administered together. A smaller, but significant, synergistic effect (1.2- to 3.8-fold) was also observed when BP-M + CPEP-L or BP-L + CPEP-M was applied. Because of the syncarcinogenic effect of BP and CPEP, their abundance in engine emissions and ambient air samples may present a major source of carcinogenic risk.

Animals↗

Modification of pancreatic carcinogenesis in the hamster model. X. Effect of streptozotocin.

An experiment was conducted to examine the possibility that the carcinogenic effect on the pancreas of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP) is based on similar mechanisms; groups of outbred Syrian golden hamsters were treated with SZ (single iv injection, 30 mg/kg body wt) alone, BOP alone (single sc injection, 10 mg/kg body wt), and SZ and BOP simultaneously. The experiment was terminated 52 weeks after treatment began. Of the hamsters treated with SZ alone, 44% developed islet cell tumors, most of which were of pleomorphic cell types. In addition, 40% of the hamsters developed pseudoductules and 12% developed ductular adenomas. The carcinogenicity of SZ for the exocrine pancreas was further indicated by induction of ductular carcinomas by SZ plus BOP, the incidence of which was significantly higher (P less than .0001) than that induced by BOP alone.

Adenoma, Islet Cell↗

Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride.

The effect of the antioxidant vitamin E on the tumor-inducing ability of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was investigated in randomly bred Swiss mice. Three groups of mice that were 6 weeks of age at the beginning of the experiment received the following treatments: a) vitamin E acetate [DL-alpha-tocopheryl acetate (TA)] at a 4% dose level in a powdered diet for life; b) 1,2-DMH, 10 weekly sc injections at 20 micrograms/g body weight; c) combination of a and b treatments. The administration of TA enhanced the tumorigenicity of 1,2-DMH, as evidenced by statistically significant incidences of tumors in the duodenum, cecum, colon, rectum, and anus. The present finding apparently is in contrast with the reported inhibitory effect of TA on colon carcinogenesis by 1,2-DMH.

1,2-Dimethylhydrazine↗

Liver and forestomach tumors and other forestomach lesions in rats treated with morpholine and sodium nitrite, with and without sodium ascorbate.

Administration to rats of ascorbate with morpholine and nitrite was previously shown to inhibit the liver tumor production and to enhance the induction of forestomach tumors, as compared to treatment with morpholine and nitrite. In a repetition of this experiment, 10 g morpholine/kg in the diet and 2 g sodium nitrite/liter in the drinking water were administered for life to male MRC-Wistar rats without (group 1) or with (group 2) 22.7 g sodium ascorbate/kg in the diet. Group 3 was untreated. Group 2 showed a lower liver tumor incidence with a longer latency than group 1, indicating a 78% inhibition by ascorbate of in vivo N-nitrosomorpholine (NMOR) formation. The incidence of forestomach papillomas was 3% in group 1, 38% in group 2, and 8% in group 3. The difference between groups 1 and 2 was not significant due to the shorter life-span of group 1. Group 1 and especially group 2 had more forestomach hyperplasia and hyperkeratosis than group 3. Ascorbate might have enhanced induction of these lesions because of an action synergistic with that of NMOR. However, it is most likely that the lowered NMOR dose and concomitantly increased survival produced by the ascorbate were solely responsible for the increased incidence of forestomach papillomas and other lesions in group 2.

Animals↗

Tumorigenic action of repeated subcutaneous administration of N-methyl-N-formylhydrazine in mice.

N-Methyl-N-formylhydrazine (MFH), an ingredient of the edible false morel mushroom, was administered to Swiss mice as 40 weekly subcutaneous injections at 20 micrograms/g body weight for females and 10 micrograms/g body weight for males. The treatments gave rise to statistically significant incidences of lung tumors: 56% in females and 40% in males. The administration of the chemical resulted in no detectable carcinogenic effect in other organs. The findings are discussed in light of the results from earlier studies with this compound.

Animals↗

Tumorigenicity of minute dose levels of N-methyl-N-formylhydrazine of Gyromitra esculenta.

Separate administrations of 0.0005 to 0.00025% N-methyl-N-formylhydrazine in drinking water to 6-week-old randomly bred Swiss mice for the remainder of their lifetime induced lung neoplasms. At the high dose level, 64% of the females and 48% of the males developed lung tumors, while the corresponding tumor incidences at the lower dose level were 62% in the females and 54% in the males. In untreated controls, the lung tumor incidences were 29% in the females and 19% in the males. Histopathologically, the lesions were classified as adenomas and adenocarcinomas of the lungs. N-methyl-N-formylhydrazine is a stable constituent of the edible false morel mushroom Gyromitra esculenta. The environmental significance is discussed, in view of the carcinogenicity of minute doses of this chemical.

Adenocarcinoma↗

The establishment of normal limits for serum proteins measured by the rate nephelometer. Concepts of normality revisited.

A study of the distribution of nephelometrically determined data for IgG, IgM, IgA, C3, C4, and haptoglobin was made in two geographically separate, healthy populations. Evaluation of these data by several tests of statistical normality revealed that the tests vary considerably in power; i.e., data that one rejects as gaussian may be accepted by the other. No rules exist to enable one to decide which is the best test to apply in a given situation. This study indicates that the uncritical application of X +/- 2 S.D. for the reference range of clinical laboratory tests may be fraught with error, which may not be obvious and may not provide clinically useful information in many cases. A large scale clinical investigation designed to empirically obtain limits of different laboratory tests with desired levels of specificity and sensitivity for different disease states may prove rewarding and yield knowledge more useful for clinical purposes. Until such an investigation is carried out, however, we recommend determination of reference ranges by a nonparametric percentile estimate (2.5 to 97.5 per cent), which makes no a priori assumptions about the distribution of the data in the population.

Adolescent↗

Carcinogenic effects of 1,1-di-n-butylhydrazine in mice.

Lifetime administration of 0.03125% 1,1-di-n-butylhydrazine in drinking water to Swiss mice, from 6 weeks of age, induced tumors of the lungs, forestomach and liver. The tumor incidences in these tissues in untreated controls were 25, 2 and 0.5%, whereas in the treated groups the corresponding tumor incidences increased to 68, 39 and 5%, respectively. Histopathologically these lesions were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas of the forestomach, and benign hepatomas and liver cell carcinomas. The work is part of a structure activity inquiry and its specific aim is to disclose whether the dialkyl derivatives of hydrazine are more active carcinogens than the monoalkyl analogues.

Animals↗

Carcinogenesis of 4-(hydroxymethyl)benzenediazonium ion (tetrafluoroborate) of Agaricus bisporus.

4-(Hydroxymethyl)benzenediazonium tetrafluoroborate was administered as 26 weekly s.c. injections of 50 microgram/g body weight to randomly bred Swiss mice. In addition, as a solvent control, sodium tetrafluoroborate was given as 26 weekly s.c. injections at 25 microgram/g body weight in 0.9% NaCl solution to another group of mice. The 4-(hydroxymethyl)benzenediazonium tetrofluoroborate treatment induced tumors in the subcutis and skin in incidence of 20 and 12%, respectively; while in the solvent sodium tetrafluoroborate-injected mice, the corresponding tumor incidence were 6 and 0%, respectively. Histopathologically, the tumors were classified as a fibroma, fibrosarcomas, rhabdomyosarcomas, and an angiosarcoma in the subcutis and also as squamous cell papillomas and carcinomas of the skin. 4-(Hydroxymethyl)benzenediazonium ion is an ingredient of the cultivated mushroom of commerce Agaricus bisporus.

Animals↗

Gyromitrin as a tumor inducer.

Acetaldehyde methylformylhydrazone (gyromitrin) was administered in propylene glycol as 12 weekly subcutaneous injections of 50 micrograms/g weight to randomly bred Swiss mice. The treatment induced lung and preputial gland tumors in incidences of 51 and 0% in females and 46 and 28% in males, respectively. In the propylene glycol injected control groups, the corresponding tumor incidences were 28 and 0% in females and 32 and 0% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and squamous cell papillomas and carcinomas and adenocarcinomas of preputial glands. Gyromitrin is an ingredient of the wild edible false morel mushroom Gyromitrin esculenta. The environmental significance of the findings is discussed.

Acetaldehyde↗

Lifespan carcinogenicity tests with native carrageenan in rats and hamsters.

Native carrageenan (Gelcarin), a widely used food additive, was tested for carcinogenicity in MRC rats and Syrian golden hamsters through lifespan studies. Three groups of 30 males and 30 females from these species received carrageenan at dose levels of either 5%, 2.5% or 0.5% in the diet daily for the animal's lifespan. A trend toward an increased incidence of benign mammary tumors in females and testicular neoplasms in males occurred at the median dose level (2.5%); however, the incidence of these tumors was not statistically significant. Hamsters did not develop neoplasms in response to treatment at any dose levels. From the results of this experiment, carrageenan demonstrated no carcinogenic effects in either species.

Adenofibroma↗

Tumorigenesis by N-n-propyl-N-formylhydrazine in mice.

Continuous administration of 0.04% N-n-propyl-N-formylhydrazine (PFH) for life in drinking water to 6-week-old randomly bred Swiss mice induced tumours of the lungs, preputial glands, liver and gallbladder. The tumour incidences in these 4 tissues were 91, 22, 8 and 6%, whereas in the untreated controls they were 25, 0, 0.5 and 0.5%, respectively. The higher dose of 0.08% PFH, given under identical conditions, induced only tumours of the lungs, liver and gall bladder in low incidences, since the compound was too toxic for the mice. Histopathologically, the tumours were classified as adenomas and adenocarcinomas of the lungs, squamous-cell papillomas, and carcinomas and fibrosarcoma of preputial glands, benign hepatomas and liver-cell carcinoma, as well as adenomas and adenocarcinoma of the gall bladder. The investigation is part of our structure/activity relationship inquiry aimed at revealing the mechanism of action of the N-alkyl-N-formylhydrazine series of chemicals.

Animals↗

Carcinogenesis by a single dose of N-methyl-N-formylhydrazine.

Single sc injections of N-methyl-N-formylhydrazine were given to randomly bred Swiss mice. The females received 180 micrograms per gram of body weight, while two groups of males were treated with either 120 or 100 micrograms per gram of body weight. The treatment resulted in induction of tumors of lungs with an incidence of 40% in the females. In males treated with the higher and lower doses, the incidences of preputial gland tumors were 12 and 12%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs, squamous cell papillomas, and carcinomas of preputial glands. N-Methyl-N-formylhydrazine is a constituent of the edible wild false morel mushroom Gyromitra esculenta, to which the human population is exposed in measurable quantities, sometimes at a single meal.

Adenocarcinoma↗