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Biomedical subjects

S K Jain

Publications and source records attributed to S K Jain.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effect of hyperketonemia on blood monocytes in type-I diabetic patients and apoptosis in cultured U937 monocytes.

Recent studies have proposed a role for a reduced number of circulating monocytes in the development of atherosclerosis and circulatory diseases in diabetes. Ketosis is frequently encountered in type-I diabetics. This study was undertaken to test the hypothesis that hyperketonemia can lower blood monocyte count in type-I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood levels of acetoacetate (AA) and triglycerides were significantly higher in diabetics compared with normals. To examine whether hyperketonemia can directly alter the monocyte count in diabetics, we studied the effect of ketone bodies AA and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell line as an in vitro model. The cell culture studies showed a dose-dependent growth inhibition and induction of apoptosis as a result of treatment with AA in U937 cells. Furthermore, there was a significant decrease in GSH and increase in lipid peroxidation products in AA-treated U937 cells. Taken together, this study suggests that elevated levels of ketone body AA can result in oxidative damage, accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn can lower monocyte count in the blood of type-I diabetic patients.

Apoptosis↗
PubMed1999

Visceral leishmaniasis masquerading as tuberculosis in a patient with AIDS.

We report a case of visceral leishmaniasis presenting as significant lymphadenopathy in a patient with acquired immune deficiency syndrome. The lymphadenopathy was initially suspected to be tubercular in nature on pathological examination. This report highlights the increasing incidence of acquired immune deficiency syndrome and Leishmania co-infection in India, and the importance of demonstrating tubercle bacilli on culture before suggesting a diagnosis of tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients.

Recent studies have suggested that elevated cellular lipid peroxidation may play a role in the development of cellular dysfunction and other complications of diabetes. People with type 1 diabetes frequently encounter elevated levels of the ketone bodies acetoacetate (AA), beta-hydroxybutyrate (BHB), and acetone (ACE). This study was undertaken to test the hypothesis that ketosis might increase lipid peroxidation and lower glutathione (GSH) levels of red blood cells (RBCs) in diabetic patients. This study demonstrates that incubation of AA with normal RBCs in phosphate-buffered saline (37 degrees C for 24 h) resulted in marked GSH depletion, oxidized glutathione accumulation, hydroxyl radical generation, and increased membrane lipid peroxidation. Increases in oxygen radicals and lipid peroxidation and depletion of GSH in RBCs were not observed with BHB or ACE treatments. Similarly, there was a significant generation of superoxide ion radicals even in a cell-free buffer solution of AA, but not in that of BHB. The presence of BHB together with AA did not influence the capacity of AA to generate oxygen radicals in a cell-free solution or the increase in lipid peroxidation of RBCs incubated with AA. The antioxidants vitamin E and N-acetylcysteine (NAC) blocked increase in lipid peroxidation in AA-treated RBCs. To examine the effects of ketone bodies in vivo, studies were performed that showed a significant decrease in GSH and an increase in lipid peroxidation levels in RBCs of hyperketonemic diabetic patients, but not in normoketonemic type 1 diabetic patients, when compared with age-matched normal subjects. This study demonstrates that elevated levels of the ketone body AA can increase lipid peroxidation and lower GSH levels of RBCs in people with type 1 diabetes.

3-Hydroxybutyric Acid↗
PubMed1999

Effect of hyperketonemia on plasma lipid peroxidation levels in diabetic patients.

OBJECTIVE: This study was undertaken to examine the effect of ketosis on plasma lipid peroxidation levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma levels of lipid peroxidation products (malondialdehyde) and ketone bodies (acetoacetate and beta-hydroxybutyrate) were determined in diabetic patients (n = 70) and age-matched normal volunteers (n = 25). Diabetic patients with total ketone body levels > 1.0 mmol/l were considered hyperketonemic, and those with levels < or = 1.0 mmol/l were considered normoketonemic. RESULTS: After normalization versus total lipids, levels of lipid peroxidation were significantly higher in the plasma of hyperketonemic diabetic patients (P < 0.05), but not in normoketonemic diabetic patients, compared with age-matched normal volunteers. In addition, low ketonemia was associated with lower lipid peroxidation levels when lipid peroxidation and ketonemia were determined in the same patient (n = 7) at two different clinic visits. CONCLUSIONS: This study demonstrated an association between hyperketonemia and increased lipid peroxidation levels in diabetic patients, which suggests that ketosis is a risk factor in the elevated lipid peroxidation levels associated with diabetes. Further investigation is needed to determine whether antioxidant supplementation can be particularly beneficial in reducing lipid peroxidation and complications in type 1 diabetic patients who frequently encounter ketosis.

3-Hydroxybutyric Acid↗
PubMed1998

Alkaline unfolding and salt-induced folding of bovine liver catalase at high pH.

We have studied the alkaline unfolding of bovine liver catalase and its dependence on ionic strength by enzymic activity measurements and a combination of optical methods like circular dichroism, fluorescence and absorption spectroscopies. Under conditions of high pH (11.5) and low ionic strength, the native tetrameric enzyme dissociates into monomers with complete loss of enzymic activity and a significant loss of alpha-helical content. Increase in ionic strength by addition of salts like potassium chloride and sodium sulphate resulted in folding of alkaline-unfolded enzyme by association of monomers to tetramer but with significantly different structural properties compared to native enzyme. The salt-induced tetrameric intermediate is characterized by a significant exposure of the buried hydrophobic clusters and significantly reduced alpha-helical content compared to the native enzyme. The refolding/reconstitution studies showed that the salt-induced partially folded tetrameric intermediate shows significantly higher efficiency of refolding/reconstitution as compared to alkaline-denatured catalase in the absence of salts. These studies suggest that folding of multimeric enzymes proceeds probably through the hydrophobic collapse of partially folded multimeric intermediate with exposed hydrophobic clusters.

Animals↗
PubMed1998

Hyperketonemia (acetoacetate) increases the oxidizability of LDL + VLDL in Type-I diabetic patients.

The reason for the disproportionately higher level of vascular disease in patients with diabetes is not known. Oxidative modification of low-density lipoproteins has been implicated in impaired cholesterol uptake and its deposition in the arterial wall and atherosclerosis. The present study has examined the effects of hyperketonemia, glycemic control and duration of diabetes on the in vitro oxidative susceptibility to Cu++ of low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) from 34 Type-I diabetic patients without any clinical sign of vascular disease and 22 age-matched normal individuals. LDL + VLDL was isolated from plasma using a micro-affinity column. LDL + VLDL isolated from diabetic patients and age-matched normal individuals was treated with 25 mM CuCl2 for 1.5, 3 and 5 h. The ketone bodies acetoacetate (AA) and beta-hydroxybutyrate (BHB), as well as glycated hemoglobin (HbA1), were measured in the blood by standard methods. There was no difference in the in vitro oxidative susceptibility of LDL + VLDL at all time periods between Type-I diabetics (n = 34) and age-matched normal individuals (n = 22). However, among diabetics, when patients were separated into normoketonemic (NK) and hyperketonemic (HK) groups, in vitro oxidation of LDL + VLDL at 1.5 h from hyperketonemic diabetics was a 69% greater (p < .02) compared with that of normoketonemic diabetics and 80% greater (p < .02) compared with that of normal individuals. There was a significant correlation (r = 0.38, p < .03) between the in vitro oxidation of LDL + VLDL at 1.5 h and AA levels in diabetic patients. The level of in vitro oxidizability of LDL + VLDL did not have any correlation with levels of BHB (r = 0.20, p > .26), HbA1 (r = 0, p > .99), glucose (r = 0.06, p > .75) or duration of diabetes (r = 0.15, p > .40) in diabetic patients. In vitro incubation of normal plasma with AA resulted in an increase in the Cu + induced lipid peroxidation of LDL + VLDL. This study suggests that frequent episodes of ketosis and elevated levels of AA constitute a risk factor for the oxidative modification of low-density lipoproteins and development of vascular disease in diabetic patients.

Acetoacetates↗
PubMed1998

Glutathione and glucose-6-phosphate dehydrogenase deficiency can increase protein glycosylation.

Glycosylation (glycation) of proteins can cause cataractogenesis and cellular damage. Using a human red blood cells (RBC) model and two different methods, this study shows that the glycation of hemoglobin increases significantly in glutathione (GSH) deficient RBC exposed to high glucose levels in vitro. Hemoglobin glycation was assessed using both affinity and ion-exchange chromatography. GSH-deficiency was accomplished artificially by treating RBC with 1-chloro-2,4-dinitrobenzene (CDNB) as well as by using hereditary G6PD-deficient RBC. GSH replenishment by dithioerythritol (DTE) and dithiothreitol (DTT) significantly blocked the glycation of hemoglobin in GSH-deficient cells. There was a significant negative correlation between levels of GSH and glycated hemoglobin following treatment with DTE (r = -0.98, n = 5, p < .001) and DTT (r = -0.94, n = 5, p < .02). This demonstrates that GSH depletion can indeed increase glycation. Thus, GSH and G6PD-deficient cells are at a significantly greater risk for the glycation of proteins, which in turn can cause increased cellular damage.

Blood Glucose↗
PubMed1998

Propylene glycol-mediated cell injury in a primary culture of human proximal tubule cells.

Propylene glycol (propane-1,2-diol; PD) is a widely used solvent for intravenous drugs. Clinical studies have reported serious side effects, including the development of renal insufficiency in patients receiving PD as drug vehicle. Despite such clinical reports, the data on the toxicity of PD in isolated renal cells are limited. Using primary cultured human proximal tubule (HPT) cells as an in vitro model, we have previously shown the acute toxic effects of PD in HPT cells (Morshed et al., Fundam. Appl. Toxicol. 23, 38-43, 1994). Since most cases of clinical toxicity are noted after prolonged administration of PD, the current studies were designed to investigate the toxicity of repeated exposure of PD in HPT cells. The onset of toxicity was determined using 10-50 mM racemic, sinister, and rectus PD (rac-, S-, and R-PD, respectively) for periods up to 6 days. Cytotoxicity was noted by decreases in thymidine incorporation, in mitochondrial metabolic activity, and in lysosomal accumulation of neutral red. Exposure of HPT cells to 50 mM PD produced toxic responses, while at 10 mM, responses were not significantly greater than those of osmotic controls. The toxicity was caused by a PD-specific mechanism and by a secondary mechanism without any enantiomeric specificity. The HPT cell toxicity was associated with a 35% increase in cellular thiobarbituric acid-reactive substances and a 20% decrease in glutathione. These findings suggest the development of a mild, subacute toxicity in normally proliferating HPT cells at concentrations that could be achieved in human plasma when PD is used as a drug vehicle.

Cell Division↗
PubMed1998

Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells.

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.

3-Hydroxybutyric Acid↗
PubMed1998

Postpartum amenorrhoea in rural eastern Uttar Pradesh, India.

This paper calculates the mean duration of the postpartum amenorrhoea (PPA) and examines its demographic, and socioeconomic correlates in rural north India, using data collected through 'retrospective' (last but one child) as well as 'current status' (last child) reporting of the duration of PPA. The mean duration of PPA was higher in the current status than in the retrospective data; the difference being statistically significant. However, for the same mothers who gave PPA information in both the data sets, the difference in mean duration of PPA was not statistically significant. The correlates were identical in both the data sets. The current status data were more complete in terms of the coverage, and perhaps less distorted by reporting errors caused by recall lapse. A positive relationship of the mean duration of PPA was found with longer breast-feeding, higher parity and age of mother at the birth of the child, and the survival status of the child. An inverse relationship was found with higher education of a woman, higher education of her husband and higher socioeconomic status of her household, these variables possibly acting as proxies for women's better nutritional status.

Amenorrhea↗
PubMed1998

Enzymatic synthesis of artemisinin from natural and synthetic precursors.

To investigate the biosynthetic pathway of artemisinin, an assay system for the determination of activity of the enzymes involved in its synthesis has been developed. Results from these experiments have shown that HEPES provides a better buffer system than Tris-HCl. The enzyme(s) requires Mg2+ and/or Mn2+, and the addition of ATP and NADPH+H+ significantly enhances the enzyme activity. A new substrate, dihydroarteannuin B, has been synthesized that can easily be radiolabeled with high specific activity. It is utilized by the enzyme system and is converted to artemisinin with the same efficiency as the natural substrates. This can be conveniently used as a precursor for elucidation of the pathway for artemisinin biosynthesis.

Antimalarials↗
PubMed1998

Tuberculous Addison's disease: lack of normalization of adrenocortical function after anti-tuberculous chemotherapy.

OBJECTIVE: Tuberculosis of the adrenal glands is a common cause of Addison's disease in developing countries. We conducted a study to determine if treatment of such patients with modern anti-tuberculous chemotherapy would lead to an improvement in plasma cortisol and aldosterone levels. DESIGN: Prospective study. PATIENTS: 5 patients with Addison's disease secondary to tuberculosis. MEASUREMENTS: Basal and ACTH stimulated plasma cortisol and aldosterone levels were measured prior to instituting anti-tuberculous chemotherapy, as well as one month after its conclusion. Four patients were again studied over the next 2-5 years. RESULTS: Peak plasma cortisol levels prior to treatment were markedly reduced (range, < 14-110 mumol/l). There was no improvement one month (< 14-143 mumol/l) or 2-5 years (< 14-69 mumol/l) after completing anti-tuberculous chemotherapy. Peak plasma aldosterone at diagnosis was < 56-210 pmol/l; it was undetectable in 4 patients. No improvement was observed one month (< 56-210 pmol/l), or 2-5 years (< 56-389 pmol/l) after stopping anti-tuberculous chemotherapy. Plasma aldosterone levels at both these time points were far lower than those in control subjects (median 736 pmol/l, 560-1512 pmol/l; p < 0.01). One patient had an increase in peak aldosterone from < 56 pmol/l to 389 pmol/l, though peak cortisol actually declined in this subject (from 110 mumol/l to 69 mumol/l). CONCLUSIONS: Treatment of tuberculous Addison's disease with anti-tuberculous chemotherapy does not lead to normalization of ACTH stimulated plasma cortisol or aldosterone levels during the 2-5 year period of study. However, prolonged follow up with regular adrenal function tests is warranted in all such patients.

Addison Disease↗
PubMed1998

Lipid metabolising enzymes in isolated rat testicular germ cells and changes associated with meiosis.

To assess the lipid metabolising potential of testicular germ cells undergoing meiosis, spermatocytes and spermatids were isolated from adult rat testis and purified by centrifugal elutriation followed by density gradient centrifugation. Seven key enzymes of lipid metabolism (namely beta-hydroxybutyrate dehydrogenase, carnitine acetyl transferase, ATP citrate lyase, hydroxyacyl-CoA dehydrogenase, glycerol 3-phosphate dehydrogenase, acetyl-CoA carboxylase and long chain acyl-CoA synthetase) were assayed in cell homogenates. The results indicated that germ cells possess the key enzymes for de novo synthesis and oxidation of fatty acids. The significant increase in activities of anabolic enzymes and decrease in activities of catabolic enzymes in post-meiotic germ cells indicated a shift in lipid metabolism towards fatty acid synthesis during meiosis. Long chain acyl-CoA synthetase activity was not detected in the two cell types. The study indicates a major reorganization of fatty acid turnover during meiosis with equilibrium shifting in favour of synthesis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients.

OBJECTIVE: To study the effect of vitamin E supplementation on platelet hyperaggregability in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Written informed consent according to the Institutional Review Board on Human Experimentation guidelines was obtained from diabetic patients (n = 29) and their age-matched normal siblings (n = 21) to participate in this study. Diabetic patients were supplemented with DL-alpha-tocopherol (vitamin E) capsule (orally, 100 IU/day) or placebo for 3 months in a double-blind clinical trial. Alternate diabetic patients were assigned to vitamin E or placebo during regular visits to the clinic. Fasting blood was collected from each diabetic patient before the start and after the vitamin E or placebo supplementation. Platelet aggregability was assessed by competitive enzyme-linked immunosorbent assay of the blood TxB2 (a stable thromboxane metabolite). Plasma vitamin E and MDA (malondialdehyde, a product of lipid peroxidation) was assessed by high-performance liquid chromatography. Data were analyzed statistically on 12 diabetic patients on vitamin E and 12 on placebo supplementation. RESULTS: Diabetic patients (n = 29) had 62% higher (P < 0.05) levels of TxB2 and 15% higher levels (P < 0.05) of MDA in comparison to normal subjects (n = 21). Plasma TxB2 levels had a significant correlation with MDA levels (r = 0.45, P < 0.02) but not with the HbA1 (r = -0.08), glucose (r = -0.13), duration of diabetes (r = -0.04), or age (r = 0.12) of diabetic patients. Vitamin E supplementation lowered MDA levels by 30% (P < 0.04), TxB2 levels by 51% (P < 0.03), and triglyceride levels by 22% (P < 0.04) in diabetic patients. There were no differences in these parameters before versus after placebo supplementation. CONCLUSIONS: The elevated blood level of TxB2 (hyperaggregability of platelets) is significantly related to the level of lipid peroxidation products (oxidative stress) in type 1 diabetic patients. Supplementation of modest doses of vitamin E (100 IU/day) significantly lowers blood TxB2 and lipid peroxidation products levels in type 1 diabetic patients.

Child↗
PubMed1998

Brain drug delivery system bearing dopamine hydrochloride for effective management of parkinsonism.

Dopamine hydrochloride bearing positively charged small liposomes was prepared by sonicating the multilamellar vesicles. These vesicles were characterized for their physical attributes (shape, size, charge, drug entrapment efficiency, and drug leakage). The drug release kinetics from the liposomes were also studied and found to be Fickian-type diffusion. In vivo performance of the drug-entrapped liposomes was assessed by periodic measurement of drug- (chlorpromazine) induced catatonia in Sprague-Dowley rats. These results were compared with the plain dopamine HCl and levodopa preparations as well with the marketed formulation of levodopa containing carbidopa (Syndopa). These studies revealed that the dopamine can be effectively delivered to the brain by incorporating it into liposomes, and its degradation in circulation can also be protected. The results of liposomal formulation were found to be superior compared to plain levodopa as well as Syndopa.

Animals↗