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Banerjee D.,University of Calcutta | Banerjee D.,Sinha Institute of Medical Science and Technology | Mazumder S.,University of Calcutta | Sinha A.K.,Sinha Institute of Medical Science and Technology
Blood Coagulation and Fibrinolysis | Year: 2014

The aggregation of platelets by ADP is reported to be mediated through prostaglandin synthesis. In contrast, nitric oxide is known to inhibit platelet aggregation through the synthesis of cyclic AMP and cyclic GMP. Studies were conducted to determine the role of ADP, if any, on the synthesis of nitric oxide in platelets. Both normal male and female volunteers between the ages of 30 and 45 years participated in the study. Thromboxane A2 (TXA2) was measured as thromboxane B2 by ELISA. Nitric oxide was measured by methhaemoglobin method. It was found that the treatment of platelet-rich plasma (PRP) with different concentrations of ADP (0-8.0μmol/l) resulted in increased platelet aggregation, and at 8.0μmol/l ADP, the basal nitric oxide level was found to be maximally decreased from 0.3±0.10 nmol/10 platelets to 0 nmol/10 platelets in PRP (P<0.0001; n=10). Line-weaver-Burk plot of nitric oxide synthase (NOS) activity in the presence of 2.0μmol/l ADP reduced the Vmax from 6.662 to 2.22 nmol nitric oxide/h per mg protein compared with control. Inhibition of nitric oxide synthesis by N-methyl-L-arginine acetate ester (L-NAME), an inhibitor of NOS, was found to aggregate platelets due to the reduction of platelet nitric oxide level (Pearson's coefficient of correlation, r=-0.986, P<0.001, n=10). The treatment of PRP to L-NAME was found to increase TXA2 synthesis to 1.679±0.05 from 0 pmol/10 platelets. These results suggested that inhibition of NOS in platelets resulted in platelet aggregation through TXA2 synthesis in PRP through a novel pathway. Copyright © Lippincott Williams & Wilkins. Source


Ghosh R.,Sinha Institute of Medical Science and Technology | Karmohapatra S.K.,Sinha Institute of Medical Science and Technology | Bhattacharya G.,Calcutta National Medical College and Hospital | Kumar Sinha A.,Sinha Institute of Medical Science and Technology
Endocrine | Year: 2010

Pancreatic β cells, stimulated by glucose, are known to synthesize and secrete insulin. As liver diseases are reported to cause diabetes mellitus, studies were conducted to determine the possibility of glucose-induced insulin synthesis in the liver cells. The glucose-induced insulin synthesis was determined by in vitro translation of mRNA from the hepatocytes. The cDNA from mRNA was prepared and sequence analysis was performed. Incubation of hepatocytes from the liver of adult mice (n = 10) with glucose (0.02 M) resulted in the insulin synthesis [0.03 (mean) ± 0.006 (S.D.) μunits/mg/h] compared to the pancreatic β cells [0.04 ± 0.004 μunits/mg/h]. Immunohistochemical study also demonstrated the glucose-induced synthesis of insulin in liver cells. Incubation of the mice hepatocytes with glucose resulted in the synthesis of insulin mRNA. The purified mRNA which was used to prepare cDNA resulted in the formation of proinsulin I and proinsulin II genes corresponding to 182 and 188 base pairs, respectively. Sequence analysis of the cDNA indicated that proinsulin I as well as proinsulin II gene could be involved in the synthesis of insulin by hepatocytes. These results suggested that insulin synthesis in both hepatic and pancreatic cells could be involved in the control of diabetes mellitus. © 2010 Springer Science+Business Media, LLC. Source


Ghosh R.,Sinha Institute of Medical Science and Technology | Bhattacharya R.,Sinha Institute of Medical Science and Technology | Bhattacharya G.,Calcutta National Medical College and Hospital | Sinha A.K.,Sinha Institute of Medical Science and Technology
International Journal of Biomedical Science | Year: 2012

The role of stress induced development of Type-1 diabetes mellitus (T1DM) as opposed to autoimmunity remains obscure. It has been reported that a stress induced protein, identified to be dermcidin isoform 2 (dermcidin) inhibited insulin synthesis in both the pancreatic β cells and the hepatic cells. As dermcidin effect could be neutralized by the increased production of systemic nitric oxide (NO), investigations were carried out to determine the feasibility of controlling stress induced T1DM through the neutralization of dermcidin by systemic increase of NO. To determine the role of plasma dermcidin level in T1DM subjects (n=45), if any, when the plasma dermcidin level were determined, it was found that the protein level was increased in 65% of the participating volunteers. Efforts were made to normalize the plasma glucose level (median=175 mg/dL) in these T1DM subjects by systemic increase of NO by applying a cotton pad contain-ing 0.28mmol sodium nitroprusside on the abdominal skin. It was found that the systemic increase of NO level decreased the blood glucose level of 275 mg/dL (median) to 115 mg/dL (median) in these volunteers within 24 h with concomitant increase of plasma insulin level from 7.5 μunits/dL to 101 μunits/dL at the same time. The increase of plasma insulin level was accompanied by the decrease of dermcidin level of 124.5 nM to 18 nM with increase of NO from 0.43 ± 0.19 nM to 4.1 ± 1.56 nM. The results suggested that the stress induced T1DM by dermcidin could be controlled by the systemic increase of NO which in consequence led to increased synthesis of insulin. © 2012 Raieshwary Ghosh et al. Source


Ghosh R.,Sinha Institute of Medical Science and Technology | Ray U.,University of Tasmania | Jana P.,Sinha Institute of Medical Science and Technology | Bhattacharya R.,Kalyani Gandhi Memorial Hospital | And 2 more authors.
PLoS ONE | Year: 2014

Introduction: Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI). Nitric oxide (NO) has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 μM (median) compared to 4.0 μM (median) in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. Methods and Results: The restoration of plasma NO level was achieved by a sticking small cotton pad (10 x 25 mm) containing 0.28 mmol sodium nitroprusside (SNP) in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283) were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 mM) the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. Conclusion: Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. Trial Registration: www.ctri.nic.in CTRI/2013/12/004236 © 2014 Ghosh et al. Source


Jana P.,Sinha Institute of Medical Science and Technology | Maiti S.,Vidyasagar University | Ghosh R.,Sinha Institute of Medical Science and Technology | Ghosh T.K.,Post Graduate Institute of Medical Education and Research | Sinha A.K.,Sinha Institute of Medical Science and Technology
Cardiovascular Endocrinology | Year: 2013

Women, before menopause, are known to be resistant to the development of acute ischemic heart disease (AIHD). As the inhibition of platelet aggregation is reported to prevent incidences of AIHD, the effects of estradiol and estriol on ADP-induced platelet aggregation in platelet-rich plasma were determined. It was found that it was not estradiol, the most potent estrogenic hormone, but estriol, less potent than estradiol, that had a minimum inhibitory concentration (MIC) of 0.6 nmol/l for 100% inhibition of ADP-induced platelet aggregation. In contrast, the MIC of estradiol was 2.0 nmol/l (P < 0.005, n= 40). The stimulation of nitric oxide (NO) by 0.6 nmol/l estriol in platelet-rich plasma was 0.55 nmol/108 cells/h and the stimulation by the 2.0 nmol/l estradiol was 0.179 nmol/108 cells/h. Treatment of intact platelets with 0.05% Triton X-100 released a membrane NO synthase in the supernatant that had basal Km of 5.28 mmol/l with Vmax of 0.029 nmol NO/mg/h. The treatment of the supernatant with 0.6 nmol/l estriol decreased the Km to 3.42 mmol/l with increased Vmax to 0.337 nmol NO/mg/h. These results showed that estriol was one of the most potent inhibitors of platelet aggregation with MIC that was in subnanomolar ranges, which is lower than any other inhibitors currently known and suggested that estriol might prevent AIHD in women before menopause. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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