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Biomedical subjects

D K Sinha

Publications and source records attributed to D K Sinha.

At least 19 recordsLinked to original sources

Acute renal failure in pregnancy in a developing country: twenty years of experience.

UNLABELLED: Acute renal failure (ARF) has become a rare complication of pregnancy in developed countries. The aim of this study was to describe changing trends in pregnancy-related acute renal failure (PR-ARF) in two successive periods; 1982-1991 and 1992-2002. From July 1982 to December 2002, 190 cases of PR-ARF were observed in Eastern India (11.6% of total number of ARF needing dialysis). Obstetrical complications were causative factors for ARF in 15% (65/426) and 10% (125/1201) of patients in the two periods, respectively. The incidence of PR-ARF fell from 15% in 1982-1991 to 10% in 1992-2002, with respect to the total number of acute renal failure cases. Post-abortal ARF showed a declining trend, 9% in the 1980s to 7% in the 2000s, of the total number of ARF cases. Preeclampsia-eclampsia was the cause of obstetrical ARF in 23% (1982-1991) and 14.4% (1992-2002) of cases in these two periods. The percentage of total ARF due to eclampsia declined from 3.5% during the period 1982-1991 to 1.4% in 1992-2002. Puerperal sepsis contributed to 0.8% of total ARF in recent years, compared to 2.4% in the earlier period. The incidence of cortical necrosis decreased significantly (p < 0.001) from 17% in 1982-1991 to 2.4% in the 2000s. The maternal mortality reduced to 6.4% in 1992-2002 from initial high mortality of 20% in the period of 1982-1991. CONCLUSION: PR-ARF which remained high in the initial period has decreased in recent years. This is associated with a declining trend in

Abortion, Induced↗

Spectrum of renal disease in malaria.

Between January 2000 and December 2001, renal involvement in 81 cases of malaria was studied. Their age ranged between 05 and 66 (mean 35.5) years. Distribution of malarial parasite was P falciparum (75), mixed infection (4) and P vivax (2). The evidence of clinical renal disease in the form of acute renal failure, electrolyte abnormality, abnormal urinary sediment and increased urinary protein excretion (>500 mg/24 hours) was found in 100%, 91.3%, 46.9% and 18.5% respectively. Probable aetiopathogenesis of acute renal failure (ARF) was multifactorial. Volume depletion (72.8%) was the dominant cause of ARF in these patients. In addition, hyperbilirubinaemia, intravascular haemolysis and sepsis were responsible for ARF in 64.2%, 70.3% and 25.9% cases respectively. All the patients were managed with anti-malarial drugs and dialysis support was needed in 35 patients (43.2%). Prognosis of malarial acute renal failure is favourable with mortality rate of 18.5%. Multi-organ failure was the commonest cause (33.3%) of death.

Acute Kidney Injury↗

Pregnancy induced mammary tumor specific effector cells are present long after parturition in a breast cancer model in rats.

Pregnancy is known to provide protection against 7,12 dimethylbenz[a]anthracene-(DMBA) induced mammary carcinogenesis in rats. We observed in earlier studies that splenocytes of parous rats have significant cytotoxicity against mammary tumor cells both in vitro and in vivo. However, it remains to be established how long these cytolytic cells persist after parturition in parous host. The present study was designed using parous rats, 36 or more days after parturition. We observed that fresh splenocytes from these rats had low cytolytic activity against mammary tumor cells. However, when these cells were re-stimulated with irradiated mammary tumor cells in vitro, they had significantly higher cytotoxicity against mammary tumor cells. These studies show for the first time that pregnancy induced cytotoxic splenocytes are present long after parturition and they can be restimulated in vitro to enhance the cytotoxic effect.

9,10-Dimethyl-1,2-benzanthracene↗

Tumorigenesis of rat mammary epithelial cells by N-nitroso-N-methylurea in an in vitro system: characterization of the microtumors.

Chemical carcinogenesis is a lengthy process that involves the rather loosely defined stages of initiation, promotion, and progression. Several model systems of mammary carcinogenesis have been designed to elucidate the mechanisms of chemical carcinogenesis. Most of these systems have included animal models. While organ specific chemical carcinogenesis can be initiated in these systems, the subsequent stages of promotion and progression are difficult to study in detail. Investigations on in vitro carcinogenesis have shown transformation of mammalian cells in culture; the transformational event, however, is difficult to discern within the monolayer culture. We have recently reported the development of an in vitro carcinogenesis system that allows both the initiation as well as the progression of mammary cells in a collagen gel matrix culture system. The cells transformed by a chemical carcinogen develop into discernible microtumors within the three dimensions of a collagen gel culture. Isolation of these microtumors from the collagen gel and subsequent culture in monolayer has produced cells capable of colony formation in soft agar. The present study further characterizes these microtumors originated in vitro by analysis of cell growth kinetics versus parallel control cells. In addition, flow cytometric and cytogenetic studies have been performed to investigate the chromosomal stability of these cells. It was also observed that the microtumors, produced in vitro from mammary epithelial cells of an inbred strain of rats, show the ability to form tumors upon transplantation into the fat pad of syngeneic hosts.

Animals↗

Effect of low dose recombinant human omega erythropoietin (rHuEPO) on anaemia in patients on hemodialysis.

The effect of low dose rHuEPO therapy in ESRD patients on regular dialysis therapy was assessed in a prospective study in 22 patients. Routine hematological and biochemical tests, bone marrow aspiration, serum iron and ferritin studies were performed. The quality of life was also assessed. rHuEPO was administered in a dose of 25 units/kg i.v. post dialysis 3 times a week for 8 weeks, followed by 36 units/kg for further 4 weeks. Significant rise (p = 0.0001) in Hb & PCV with rise in reticulocyte count (0.016) was noted. Serum ferritin was a better index of iron status of the body. Significantly improved anemia and quality of life of ESRD patients on hemodialysis was seen in 95% of the patients.

Adult↗

The energy cost of metalliferous mining operations in relation to the aerobic capacity of Indian miners.

Mining in India is still relatively unmechanized, and in the hot, humid, and noisy environment with uncomfortable postures, many work operations impose a considerable physiological strain. The physical characteristics, including aerobic capacities, of 54 workers in an Indian metalliferous mine have been studied, and their energy expenditures measured during long periods of work in different tasks. The mean VO2max was 2.32 +/- 0.6 l/min and the mean body mass was 60 +/- 4 kg. Averaged energy expenditures for different tasks ranged between 9.4 and 22.8 kJ/min and were usually more than 33% of the workers' maximal work capacity. Recommendations about reducing the stress of mining work are made.

Anthropometry↗

In vitro carcinogenesis of mammary epithelial cells by N-nitroso-N-methylurea using a collagen gel matrix culture.

Carcinogenesis is a lengthy process which eventually culminates in the transformed phenotype, cancer. However, much remains to be defined about the process of transformation. In vivo models for the study of the carcinogenic process present limitations because it is not possible to detect the premalignant stages in the animals. An in vitro model, on the other hand, facilitates the study of the carcinogenic process because it enables one to dissect out the crucial events required for carcinogenesis to occur. As carcinogenesis is believed to be a multistep process; initiation, promotion, and progression, a multistep, in vitro system has been devised in our laboratory to mimic each of these stages. We have previously shown the formation of "microtumors" in collagen gels, induced by 7,12-dimethylbenz(a) anthracene. In the present study the direct acting water soluble, mammary carcinogen, N-nitroso-N-methylurea (NMU) was used for tumorigenesis of mammary epithelial cells in culture. Mammary epithelial cells from virgin Sprague-Dawley rats were propagated and exposed to single or multiple doses of NMU while growing as a monolayer in glass petri dishes (initiation). Initiation cells were then plated into a collagen gel matrix culture. Prolonged growth in the collagen gels afforded for the progression of the transformed cells into discernable microtumors in the three-dimensional matrix of the collagen. The morphology of these "tumors" was determined by histologic sections of the gels. Fewer, if any, such structures existed in the untreated gels.

Animals↗

Pregnancy-induced antitumor cytotoxicity of T cell-rich fraction against mammary adenocarcinoma cells in rats.

Our earlier observations indicated that splenocytes from parous rats have high cytotoxic activity against mammary tumor cells in vitro. It has also been observed that this cytotoxic activity of splenocytes from parous rats can be adoptively transferred to virgin rats of same age. The present investigation is an attempt to determine the cell type in spleens of parous rats that cause the cytotoxicity against mammary tumors. The spleens from both virgin and parous rats were removed aseptically and T and B cell-rich fractions were separated. 7,12-Dimethylbenz[a]anthracene-induced rat mammary tumor epithelial cells were used as targets and the T and B cell-rich fractions from either virgin or parous rats were used as effectors. The parous rats were divided into two groups according to the time period after parturition. Group I contained rats that were 5-13 days after delivery, while the rats in group II were 14 or more days post parturition. In vitro cytotoxicity was determined by incubating the tumor cells with spleen cells in the target/effector ratio of 1:3, 1:10 and 1:30 and using the standard 51Cr release assay. In all ratio groups of T cell-rich fractions particularly in group II, there was significantly higher cytotoxicity against mammary tumor cells. None of the B cell-rich fractions from parous rats were significantly more cytotoxic than those from virgin controls.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibition of mammary tumorigenesis in virgin rats by adoptive transfer of splenocytes from parous donors.

Splenocytes from parous rats have been previously found to have cytotoxic activity against mammary tumor cells in vitro. Experiments were carried out to determine if this pregnancy-induced cytotoxic nature of the splenocytes is inherent and transferable. Splenocytes from parous rats wer adoptively transferred to a group of virgin rats. Another group of age-matched, virgin rats received splenocytes from virgin donors in a similar way. After a period of rest, at the age of 55 days, the rats belonging to both of the groups, received 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. A third group of untreated virgin rats were also given the chemical carcinogen the same way as above and were considered as intact controls. The rats were monitored for development and growth of mammary tumor from 60 days of DMBA administration. After 4 months of DMBA administration the rats were sacrificed and mammary glands were examined for tumors. Mammary glands with no visible tumors were taken for whole mount preparation, to be examined for microscopic lesions. The results showed that 33 of 41 intact control rats, developed tumor and 27 of the 34 rats that received spleen cells from virgin rats developed tumors. Of the rats that received spleen cells from parous rats, only 18 out of 37 rats developed tumors, indicating an inhibition of tumor induction in these rats. Growth rate of the tumors in this group was also slower than in the control groups.

Animals↗

Pregnancy-induced cytotoxicity of splenocytes against mammary tumor cells in rats.

Our earlier observations indicate the possibility of involvement of a 'host factor' in pregnancy-induced protection against mammary carcinogenesis. The present investigation is an attempt to determine if this "host factor" is of immunological nature. Rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene were used as target, and splenocytes from parous rats of the same strain were used as effector cells. The parous rats were divided into two groups according to the time period after parturition. Group 1 contained rats which were 5-13 days after delivery, group 2 had rats 14 or more days after parturition. In vitro cytotoxicity was determined by incubating the tumor cells with spleen cells in the target:effector ratios of 1:3, 1:10 and 1:30. Both groups 1 and 2 showed significant lysis of mammary tumor cells. These results were confirmed by the trypan blue exclusion test. The results showed a significantly higher cytotoxic capability of the spleen cells from parous rats against mammary tumor cells as compared to spleen cells from age-matched nulliparous rats.

Animals↗

Inhibition of mammary carcinogenesis in rats by dietary restriction.

Mammary tumors were induced by 7,12-dimethylbenz[a]anthracene (DMBA) in Sprague-Dawley female rats kept under different dietary restrictions. Starting at 40 days of age, 4 groups of rats were either full-fed or fed 25%, 50% or 80% of their daily ration. At 55 days of age DMBA was given by intravenous injection. Rats were continued on the restricted diet until 150 days after carcinogen treatment. Rats on 25% diet lost weight rapidly and the experiment had to be terminated. Rats on the 50% diet maintained a lower body weight throughout the experiment; only 12% developed tumors. Rats on the 80% diet lost weight initially, but at the termination of the experiment, there was no significant difference in body weight between this group and the full-fed controls. Of the rats on 80% diet, 34% developed tumors, compared to 92% tumor incidence in the full-fed controls. Vaginal smears were normal in the animals fed the 80% diet, while some irregularity was observed in the 50% group. Breeding capability in rats on the 80% diet was not affected, since there was no observable difference in the pregnancy rate between these animals and their controls. There was also no difference in plasma level of estrogen between the 80% diet group and the full-fed controls at the time of carcinogen treatment. [3H]Thymidine labelling index was significantly affected by 50% restriction of diet while there was no significant change in the 80% group.

9,10-Dimethyl-1,2-benzanthracene↗

Collagen gel culture of rat mammary tumor cells as an assay system for determination of therapeutic efficacy of chemotherapeutic agents.

Collagen gel culture of rat mammary epithelial cells was used as an in vitro assay system for determination of the therapeutic efficacy of three cytotoxic agents commonly used in the treatment of human breast cancer, namely 5-fluorouracil (5-FU), methotrexate, and Adriamyin (ADR). The same three drugs were also evaluated in vivo, and a good correlation was obtained between the results in these two systems. A 9-d culture was shown to be more reliable than a 12-d culture, because nondrug-related cell mortality became a confounding factor after 12 d. Although further experiments are necessary, it is suggested that collagen gel culture may well prove to be a useful assay system for determination of sensitivity of tumor cells to cytotoxic drugs with possible clinical applications in the choice of treatment modality administered to cancer patients.

Animals↗

Prevention of mammary carcinogenesis in rats by pregnancy: effect of full-term and interrupted pregnancy.

In this study, the role of parity in conferring protection of the mammary gland against chemical carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) was investigated. Experiments were also carried out to determine if an 'interrupted' pregnancy was capable of reducing the incidence of mammary tumour induction. Since it has been suggested that morphological development or the proliferative pattern of the mammary gland at the time of carcinogen administration may be involved in reducing the susceptibility of the mammary gland to chemical carcinogenesis, experiments were designed to elucidate the possible influence of these two factors. Sprague-Dawley female rats were mated and were either allowed to complete pregnancy and parturition or were subjected to Caesarian section on day 5, 10 or 15 of the pregnancy. When DMBA was administered i.v. to animals which had been allowed to complete a full-term pregnancy, only 14% developed tumours, compared to 70% in age-matched nulliparous controls. Termination of the pregnancy on days 5, 10 or 15 was as effective in reducing tumour incidence as full-term gestation and parturition, but still resulted in partial and statistically significant inhibition, compared to age-matched nulliparous controls. There was no significant difference in 3H-thymidine labelling index (LI) at the time of DMBA treatment in the parous rats compared to age-matched nulliparous controls. We also observed no significant differences in the morphological development of the mammary gland in parous and nulliparous rats of the same age. These results indicate that the protective mechanism may not lie in the mammary gland per se, but may indeed be a host factor, such as hormonal or immunological changes occurring in the host as a result of the pregnancy.

9,10-Dimethyl-1,2-benzanthracene↗

Role of serum and hormones during the growth and development of rat mammary tumor epithelial cells in collagen gel culture.

The characteristics of hormone-dependent rat mammary tumors in response to serum and hormones were determined in collagen gel matrix culture. Epithelial cells from 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas were embedded in collagen gel and the effect of estrogen, progesterone, prolactin, insulin, and serum was tested. The total cell number and [3H]thymidine incorporation were used to determine the growth pattern of the cells in culture. It was found that in medium containing 20% porcine serum and supplemented with insulin, estrogen, progesterone and prolactin, both the cell number and [3H]thymidine labeling index increased with time, after an initial lag. Serum seemed to be essential to maintain growth of the tumor cells, because hormones alone, in the absence of serum, were unable to sustain growth of the cells. When estrogen, progesterone, prolactin, and insulin were tested individually in the presence of 20% porcine serum, only estrogen demonstrated a significant stimulatory effect.

Animals↗

Antiestrogenic properties of substituted benz[a]anthracene-3,9-diols.

The antiestrogenic potency of benz[a]anthracene-3,9-diol, as well as its 7- and 12-methyl derivatives, was evaluated by measuring he inhibition in the onset of estrus brought about by this compound in ovariectomized rats treated with 17beta-estradiol. At a dose of 0.5 mg and 7,12-dimethyl derivative caused a decrease in the percentage of rats in estrus from 78 to 44%. This decrease is identical with that caused by 0.05 mg of nafoxidine.

Animals↗