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Biomedical subjects

R K Seth

Publications and source records attributed to R K Seth.

At least 19 recordsLinked to original sources

Effects of larval exposure to sublethal concentrations of the ecdysteroid agonists RH-5849 and tebufenozide (RH-5992) on male reproductive physiology in Spodoptera litura.

Sublethal concentrations of the bisacylhydrazine moulting hormone agonists, RH-5849, and tebufenozide (RH-5992) were fed to sixth (final) instar larvae of Spodoptera litura. Both RH-5849 and tebufenozide adversely affected the mating success of S. litura when the surviving treated males were crossed with normal females. The ecdysone agonists decreased the longevity of treated males and of untreated females when crossed with treated males. The number of eggs laid by untreated females mated to treated males was decreased, and the fertility (percentage of hatching success) of the resulting eggs was reduced. These effects on male reproductive success were at least in part explained by a reduction in the number of sperm transferred during mating. The adverse effects of tebufenozide on male reproductive function were qualitatively the same as those of RH-5849, but tebufenozide was active at lower concentrations. To understand the reason for these adverse effects on male reproduction, we investigated the effects of the insecticides on male reproductive physiology. Male reproductive tract development and testicular volume of resulting adult moths were adversely affected by sublethal larval exposure to the ecdysone agonists. Dose-dependent reductions occurred in the production of eupyrene and apyrene spermatozoa in the adult testes, and in the number of spermatozoa released from the testes into the male reproductive tract. The descent into the male tract of both eupyrene and apyrene sperm was found to start at the normal stage of development in both normal and treated insects, but the daily rhythm of sperm descent was subsequently disturbed in the insecticide-treated moths. This affected the numbers of sperm in the upper vas deferens (UVD), seminal vesicle (SV), and duplex (duplex). Injections of RH-5849 given to pharate adult or newly emerged adult S. litura also caused drastic reduction in the number of sperm in the upper regions of the male tract, when measured 24 h after injection. The possible importance of pest population reduction through the sublethal anti-reproductive effects of insecticides is discussed.

Animals↗

Radiation responses of Sf9, a highly radioresistant lepidopteran insect cell line.

PURPOSE: Lepidopteran insect cells are known to exhibit very high radioresistance. Although very effective DNA excision-repair has been proposed as a contributing factor, a detailed understanding of insect cell radiation responses has not yet been obtained. Therefore, the study was carried out to understand the in vitro radiation responses of Sf9 lepidopteran cells. MATERIALS AND METHODS: Exponentially growing asynchronous Sf9 cells (derived from ovaries of Spodoptera frugiperda) were exposed to gamma-radiation doses of 2-200 Gy. Cell survival, growth inhibition, cell cycle progression delay, alterations in cell morphology as well as induction of DNA damage, micronuclei and apoptosis were studied at various post-irradiation time intervals. RESULTS: Biphasic survival response curves were obtained with D0 rising from 20 Gy (at doses < or = 60 Gy) to 85 Gy (between 60 and 200 Gy), corroborating earlier reports on lepidopteran cells. An additional downward deviation at 2 Gy indicated a hypersensitive response. Dose-dependent growth inhibition with a transient G2 delay starting 12 h and extending up to 48-96 h was observed at doses of 10-200 Gy, while a brief G1/S transition delay was observed only at higher doses (> or = 100 Gy). Significant DNA damage was detected only at 20 Gy and higher doses, in contrast with human cells that showed similar damage at 2 Gy. Interestingly, micronuclei were not induced at any of the doses tested, although spontaneous micronucleation was evident in <1% of cells. Lack of micronucleus induction even at doses that induced significant DNA damage and a transient G2 block (20-50 Gy) strongly indicated a role of holocentric lepidopteran chromosomes. Apoptosis was detected only in a small proportion of cells (3%) exposed to 200 Gy, and cell/nucleus size and granularity increased by 72-96 h post-irradiation in a dose-dependent manner. Sf9 nucleoids extracted at 2 M NaCl showed higher compactness than the nucleoids prepared from human cells. CONCLUSIONS: It is clearly shown that lepidopteran cells are highly resistant to the induction of DNA damage and micronuclei, and display very low induction of apoptosis at doses up to 200 Gy. While the lack of micronucleus induction seems to be primarily due to the holocentric nature of their chromosomes, certain unique signalling pathways might be responsible for the low induction of apoptosis. Factors causing protection of Sf9 cellular DNA from radiation-induced damage are presently being investigated.

Animals↗

Regulation of c-fos induction in lens epithelial cells by 12(S)HETE-dependent activation of PKC.

PURPOSE: 12(S)-Hydroxyeicosatetraenoic acid (12(S)HETE), a 12-lipoxygenase metabolite of arachidonic acid, is required for epidermal growth factor (EGF)-dependent DNA synthesis and c-fos induction in lens epithelial cells. The present study was undertaken to identify signal transduction events upstream of c-fos induction that may be regulated by 12(S)HETE. METHODS: The rabbit lens epithelial cell line, N/N1003A, was cultured in serum-free medium, with or without EGF. Activation of PKC and other selected enzymes was examined in the presence of the lipoxygenase inhibitor baicalein and/or exogenous 12(S)HETE. Relative abundance of PKC isoforms in subcellular fractions was determined by immunoblot analysis with isoform-specific antibodies. PKC activity in subcellular fractions was measured by peptide substrate phosphorylation, with and without pseudosubstrate peptide inhibitor. Phosphorylated enzymes were detected by immunoblot analysis. Relative levels of c-fos mRNA were determined by RT/PCR with internal standard. RESULTS: Baicalein blocked EGF-dependent translocation and activation of PKC, without affecting phosphorylation of Erk1/2. Of several PKC isoforms investigated (alpha, betaI, betaII, and gamma), only PKCalpha and betaII were significantly activated by EGF and inhibited by baicalein. 12(S)HETE, in combination with EGF, countered the effect of lipoxygenase inhibitors on PKC activation, and 12(S)HETE in the absence of EGF stimulated PKC translocation. Also of note, 12(S)HETE alone activated PKCgamma, an isoform that was not significantly activated by EGF. Inhibiting PKC activation with GF109203X blocked induction of c-fos by EGF but did not affect EGF-stimulated phosphorylation of Erk1/2, indicating that the effect of PKC on c-fos induction is independent of the Erk1/2 pathway. CONCLUSIONS: In lens epithelial cells, 12(S)HETE-dependent activation of PKCalpha and betaII acts in concert with other EGF-dependent signals to induce c-fos mRNA.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Protective function of alpha-tocopherol against the process of cataractogenesis in humans.

In a random trial 50 patients with unilateral/ bilateral idiopathic immature senile cataract (cortical n = 25, nuclear n = 25) requiring surgery at least in one eye were included in the present study. Reduced glutathione (GSH), vitamin E, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were studied in these patients receiving either vitamin E (n = 12 in each subgroup) or placebo (n = 13 in each group) for 30 days. A comparable increase of vitamin E in both types of lens homogenates of cataractous patients was observed in the study group. The level of GSH in cortical cataractous lenses in the study group was significantly raised (p < 0.001) whereas it was not increased significantly in nuclear cataractous lenses (p > 0.05) as compared to the placebo group. The percentage decrease in MDA levels was greater in cortical cataracts (38.07%) than in the nuclear type (27.94%). The activity of GSH-Px in cortical lenses was higher than that in the nuclear cataractous lens. The change in the size of lens opacity in cortical cataractous patients receiving vitamin E therapy was significantly decreased as compared to the placebo group. There may be a direct modulating effect of vitamin E on some GSH-related enzymes and the cortex of the lens might be protected more than the nucleus.

Antioxidants↗

Comparison of sodium nitroprusside added peritoneal dialysis and standard haemodialysis.

Thirty patients of acute or acute on chronic renal failure (ACRF) were randomly divided into two group of 15 cases each. Group A patients received 36 cycles of intermittent peritoneal dialysis (PD) with an exchange volume of one litre and duration of one hour per cycle. The 36 cycles of PD were divided into 12 clearance periods of 3 cycles each. Sodium Nitroprusside (SNP) was added in a dose of 4 mg/litre of dialysate in alternate clearance periods. Group B patients were given 4 hours of haemodialysis (HD) to compare the efficacy of two modes of dialysis. Symptomatic relief was observed in various uraemic signs and symptoms like vomiting, level of consciousness, fluid overload, hiccough and asterexis in most of the patients in both the groups. The percentage fall in blood urea and serum creatinine was 57.02 Vs 58.04 mg% and 46.9 Vs 47.8 mg% in group A and B respectively (P 70.5 each). Total dialysate urea removal following PD and HD was 118.8 +/- 57.3 gm and 98.5 +/- 37.0 gm respectively and also there was no significant difference in total creatinine removal. No untoward effects were observed with PD. However, following HD, 5 patients developed hypotension, supraventricular tachycardia was observed in one and disequilibrium syndrome in 8 of them. Therefore, it can be concluded that SNP added PD is comparable to 4 hours of haemodialysis both clinically as well as biochemically and in situations where facilities for HD do not exist or it is contraindicated, PD may be preferred mode of therapy.

Adult↗

Serum lipid peroxide and other enzyme levels of patients suffering from thermal injury.

The levels of the lipid peroxidation product malondialdehyde (MDA) and the activity of transaminases and alkaline phosphatases were estimated in the sera of 25 thermally injured patients at various time intervals after injury. The level of MDA was increased during the early postburn period, whereas the activities of transaminases and alkaline phosphatase became elevated later after injury. It is concluded that an increased concentration of lipid peroxidation product (MDA) in the early postburn period may affect the spleen, liver and kidney, resulting in the release of enzymes into blood stream. Such damage may be checked by the antioxidants superoxide dismutase or allopurinol.

Adult↗

Effect of atenolol and labetalol on serum lipids.

Adverse alterations in lipid profile suggesting higher atherogenicity were observed following 12 weeks treatment with atenolol in patients of hypertension. No significant alterations in lipid profile were observed with labetalol therapy.

Atenolol↗

Effect of vasodilator and surface active drugs on the efficacy of peritoneal dialysis.

The effect of sodium nitroprusside (SNP), a vasodilator drug, and chlorpromazine (CPZ), a surface active drug, on the efficacy of peritoneal dialysis was studied in 25 patients with acute or acute on chronic renal failure in a double blind fashion. Each drug was added to the dialysate during different sets of cycles. In each patient, six clearance periods of 3 cycles each were studied and peritoneal clearances of creatinine and urea and ultrafiltration rates were measured during each clearance period. SNP increased the peritoneal clearance of creatinine and urea by 28.8 percent each (p < 0.001) while CPZ increased the peritoneal creatinine and urea clearance by 17.7 and 26.0 percent respectively (p < 0.001 each). Both drugs significantly increased the ultrafiltration rates (p < 0.001). SNP was found to be superior to CPZ and had prolonged effect even after cessation of administration.

Acute Kidney Injury↗

Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis.

Adenosine deaminase activity was measured in cerebrospinal fluid of patients with confirmed tuberculous and bacterial meningitis. The values were compared with those of control subjects without meningitis. A statistically significant increase in the level of this enzyme was noted in the two types of meningitis, but no definite demarcation in the levels was observed between the two types. Therefore increases in adenosine deaminase activity may not be of such diagnostic significance as reported elsewhere.

Adenosine Deaminase↗

Lipid profile in enteric fever.

Lipid profile is known to alter in patients with severe sepsis, but few studies regarding the status of lipid levels in enteric fever are available. Twenty patients with enteric fever, belonging to different age groups and both sexes, along with an equal number of matched patients with fever due to non-enteric causes, were studied with regard to alterations in lipid profile. We observed a severe and protracted hypertriglyceridaemia, decrease in HDL-cholesterol levels and increase in LDL-cholesterol levels in patients with enteric fever at the peak of fever. The values returned to normal on recovery and convalescence. This study serves to highlight the complexity of lipid variation during Salmonella typhi infection.

Adolescent↗

Plasmodium berghei: oxidant defense system.

Glutathione oxidant defense system protects the erythrocyte from oxidative damage. This defense system was studied in mouse erythrocytes infected with Plasmodium berghei and in isolated parasites. The efficiency of this system was found to be increased in parasitized erythrocytes compared to the normal erythrocytes. The increase in the components of the oxidant defense system in the parasitized cells could result from parasitic addition to these components. This defense system present in the parasite may protect the parasite from oxidative damage and help the parasite in its growth and development.

Animals↗

Glutathione peroxidase activity and reduced glutathione content in erythrocytes of patients with chronic renal failure.

Erythrocytes from 18 patients with chronic renal failure (CRF) and 10 healthy subjects were examined with respect to glutathione peroxidase (GSH-Px) activity and reduced glutathione (GSH) contents. The activity of GSH-Px and GSH content were found to be lower in RBC from CRF patients as compared with normal RBC. These reduced levels of GSH and GSH-Px in the red cells of uraemic patients may predispose the cells to oxidative damage.

Adult↗