Sarbashri Bank

Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction

The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 μM dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 μM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 μM aspirin, the aggregation of platelets was completely inhibited by NO synthesis.

The control of hyperglycemia by a novel trypsin resistant oral insulin preparation in alloxan induced type I diabetic mice.

A trypsin resistant oral insulin preparation was made by incubating insulin for 2 h at 23 °C with previously boiled cow milk at 100 °C that was coagulated with 0.6 M acetic acid. The precipitate was resuspended in the same volume of milk. The immunoblot analysis of the suspended proteins treated with 200 ng of trypsin/ml for 3 h demonstrated that the 80.1% of the insulin in the suspension survived the proteolytic degradation compared to 0% of the hormone survived in the control. The feeding of 0.4 ml (0.08 unit of insulin) of the resuspended proteins followed by 0.2 ml of the same protein to alloxan induced diabetic mice maximally decreased the blood glucose level from 508 ± 10 mg/dl to 130 ± 10 mg/dl in 7 h with simultaneous increase of the basal plasma concentration of insulin from 3 ± 1.1 μunits/ml to 18 ± 1.5 μunits/ml. In control experiment the absence of insulin in the identical milk suspension produced no hypoglycemic effect suggesting milk was not responsible for the hypoglycemic effect of milk-insulin complex. Coming out of insulin-casein complex from the intestinal gut to the circulation was spontaneous and facilitated diffusion transportation which was found from Gibbs free energy reaction.

LBPS 01-10 THE IMPACT OF A STRESS INDUCED PROTEIN DERMCIDIN ISOFORM-2 ON THE GENESIS OF DIABETES AND HYPERTENSION

Objective: The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause acute ischemic heart diseases (AIHD i.e. ACS, AMI, etc). Strokes are reported to occur due to thrombosis on the arteries of the brain. Dermcidin isoform 2 (dermcidin), an environmentally induced stress protein, was found to high in above mentioned diseases. The effect of this protein was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The mechanism of dermcidin isoform-2 was investigated in the disease progression and its regulation. Design and Method: Platelets aggregation was measured by aggregometer. Dermcidin protein was isolated by SDS-PAGE. Nitric Oxide (NO) was measured by methemoglobin method. Binding of stress protein was analyzed by Scatchard plot. Glucose Activated Nitric Oxide Synthase (GANOS) in liver cells and (r)-cortexin synthesis in the kidney cortex cells was determined by in-vitro translation of mRNA. Dermcidin in the Plasma of Hypertensive Patients was analyzed by immunoblot. Synthesis of (r)-cortexin was determined in the goat kidney cortex cells in the presence of low dose of aspirin. Results: The level of dermcidin was found to five folds higher in AMI than ACS and forty folds higher than normal. The protein was also found in stroke patients. Dermcidin protein possessed a high affinity binding sites in AMI platelets. The NO and insulin level was found to very low in strokes. A specific and unique dose of aspirin and insulin was able to neutralize the effect of dermcidin in AMI and stroke. The plasma dermcidin and cortexin was found to higher and lower respectively in hypertensive patients. It was also found that aspirin could be able to increase the expression of (r)-cortexin. Conclusions: Dabetes and hypertension might be inhibited by the regulation of dermcidin and (r)-cortexin and as a result heart disease and stroke could be restricted. Figure. No caption available.

Extra pancreatic synthesis of insulin

It is currently believed that insulin, an essential hormone for carbohydrate metabolism, is produced only in the pancreas. Many investigators on the other hand had reported that various cells in different organs of the body beside pancreas are also capable of synthesizing insulin. This hormone not only has a critical role in the carbohydrate metabolism, but the protein is also reported to prevent the atherosclerosis and hypertension. The multifunctional synthesis of the protein in different cells in various organs is presented in the review. Insulin was reported to be synthesized in the liver, brain, thymus, adipocytes, gastrointestinal tract, bone marrow and in the leukocytes. Insulin synthesis was confirmed by cDNA analysis, amino acid sequence and by bioassay of the hormone. Liver was found to synthesize insulin, and glucose was found to stimulate NO synthesis in the liver and NO thus produced stimulated insulin and Glut-4 synthesis in the liver. Insulin synthesis occurs not only in human but also all animals. The lymphocytes and the leucocytes in the circulation were found to synthesize insulin. It is possible that synthesis of insulin in leucocytes could be involved for the ready supply of insulin in the prevention of thrombosis in platelets which did not produce any insulin. The synthesis of insulin in different organs in many different animals has also been reported. It was concluded that the synthesis of insulin in different cells was essential to maintain the cellular integrity from carbohydrate derived energy for all living organisms.