Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions.

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.

Relationship between angiogenesis biomarker endocan and apolipoproteins in patients with acute myocardial infarction.

Aim: In the current study, serum levels of endocan in patients attended with ST-elevation myocardial infarction, as well as the possible correlation with apolipoprotein-A1 (APO-A1) and APO-B were investigated.Materials & methods: In 80 men, endocan, cTnI, APO-A1, and APO-B levels were measured. Finally, the correlation of endocan with APO-A1, APO-B, and APO-B/ APO-A1 ratio was assessed.Results: Significant changes in APO-A1, APO-B, endocan levels, and APO-B/APO-A1 ratio were found in acute myocardial infarction cases compared with the control arm (p < 0.05). In addition, our finding showed a significant correlation between APO-B and endocan levels, but not APO-A.Conclusion: High endocan level is an independent indicator of endothelial dysfunction and ischemic cardiovascular conditions, which could be related to APO-B.

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Evaluation of BAX and BCL-2 Gene Expression and Apoptosis Induction in Acute Lymphoblastic Leukemia Cell Line CCRFCEM after High- Dose Prednisolone Treatment

Objective: Glucocorticoids are one of the most important drugs in the treatment of acute lymphoblastic leukemia for children. It is very important to response to glucocorticoid in the prognosis of these patients. Therefore, resistance to treatment is a major problem in lymphoid leukemia cases. In, this study, CCRF-CEM cell line was selected as a chemotherapy-resistant model. The aim of this study was to evaluate the effect of high dose prednisolone on induction of apoptosis and changes in BAX and BCL-2 gene expression at different times. Methods: CCRF-CEM cell lines were grown in standard conditions. Based on previous studies, a dose of 700 µM as subtoxic dose was selected. Changes in gene expression of BAX and BCL-2 were evaluated by using real time PCR techniques. Also stained with annexin V and the induction of apoptosis was assessed by FACS machine. Results: In this study it was found that prednisolone in high doses at different times significantly increased the gene expression of BAX and on the other hand the amount of BCL-2 expression was reduced. Cells that treated for 48 hours had more significant changes in gene expression. Based on flowcytometry data, prednisolone can induce apoptosis in a time dependent manner on this cancerous resistant cell line. Conclusions: Apoptosis induced by high-dose prednisolone in the CCRF-CEM cells, which is almost resistant, and possibly mediated by reducing the expression of BCL-2 and BAX up-regulation.

Correlation Between Circulating Visfatin and Nitric Oxide Metabolites Levels in Patients With Diabetic Nephropathy.

INTRODUCTION: Diabetic nephropathy is one of the serious complications of diabetes mellitus. Visfatin is an intracellular enzyme with insulin-mimicking effects. It enhances the expression of endothelial nitric oxide (NO) synthase in renal cells. This study aimed to investigate serum levels of visfatin and NO metabolites in patients with diabetic nephropathy. MATERIALS AND METHODS: A total of 80 diabetic patients were enrolled and classified into nephropathic and non-nephropathic patients. Serum visfatin and insulin levels were estimated using an enzyme-linked immunosorbent assay, and NO metabolites were estimated using a colorimetric assay. RESULTS: Serum visfatin and NO metabolites levels were significantly elevated in the patients with diabetic nephropathy. Serum visfatin levels and NO metabolites were significantly higher in the nephropathic patients (P = .003; 95% confidence interval, 2.29 to 10.81; P < .001; 95% confidence interval, 3.14 to 9.46, respectively) as compared to the control group, whereas homeostatic model assessment-insulin resistance was significantly lower (P = .02; 95% confidence interval, -1.51 to -1.01).There was no correlation between body mass index, blood pressure, lipid profile, insulin, and glucose levels and serum visfatin and NO metabolites levels. CONCLUSIONS: The results of this study demonstrated that there were high levels of visfatin and NO metabolites in patients with diabetic nephropathy. In addition, there was a positive correlation between visfatin and NO metabolites levels in nephropathic and non-nephropathic diabetic patients.

The role of cholesterol-enriched diet and paraoxonase 1 inhibition in atherosclerosis progression.

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor (P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower (P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions.

Influence of a high cholesterol regime on epicardial and subcutaneous adipose tissue fatty acids profile in rabbits.

BACKGROUND: We have shown that the fatty acid profile of epicardial adipose tissue (EAT) in patients with obstructed coronary vessels is different from that of the subcutaneous adipose tissue (SAT). The diversity and amount of fatty acids in the adipose tissue can be affected by the component of the lipids in diet. As a result, this study investigated the influence of a high cholesterol regime on EAT and subcutaneous adipose tissue fatty acids profile in rabbits. METHODS: Sixteen New Zealand white rabbits were randomly divided into two equal groups. The control group received a normal standard diet, whereas the test group was fed with the high cholesterol regime for 2 months. At the end of this period, the rabbits were anesthetized, 1-5 mg of EAT and SAT were removed, and their fatty acids content was determined. RESULTS: The high cholesterol regime caused a significant increase in low-density lipoprotein (LDL) and triglycerides levels and a marked decrease in high-density lipoprotein (HDL) concentration. After 2 months, in the EAT, fatty acids 16:0 and 18:1t and saturated fatty acid (SFA) showed a significant increase (P<0.05), whereas, fatty acids 12:0, 18:1, 18:2, and 18:3, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), ω3, and ω6 had a significant decrease (P<0.05). In SAT, fatty acids 18:3, 20:4, 22:6, MUFA, and ω3 decreased and PUFA, SFA, and ω6 significantly increased (P<0.05). CONCLUSION: Consumption of a high cholesterol regime for 2 months resulted in a significant increase in atherogenic fatty acids and a decrease in antiatherogenic ones in the EAT. EAT is very sensitive to lipid changes of the regime comparing to SAT.