TRANSPLANTATION OF INSULIN-SECRETING CLUSTERS GENERATED FROM MESENCHYMAL STEM CELLS to CONTROL INDUCED DIABETES IN RATS

Diabetes mellitus [D.M] is a disease with a high and increasing prevalence. Insulin-producing cells [IPCs] generated from mesenchymal stem cells [MSCs] have shown immense potential for therapy. This study aimed to compare the differentiation potential of 2 kinds of MSCs obtained from human bone marrow [BM], and umbilical cord blood [UCB] into IPCs. In addition, their therapeutic efficiency to control streptozotocin [STZ] - induced diabetic rats was investigated. MSCs were isolated from human BM and UCB, expanded and differentiated to IPCs. The Cells were evaluated by flow cytometry analysis for MSCs markers, RT-PCR for insulin gene expression and ELISA detection of C-peptide release. IPCS were transplanted into the liver of diabetic rats and then evaluated by weekly measurement of the fasting blood glucose [FBG] levels, and detection of in vivo release of C-peptide. This study demonstrated that FBG levels were reduced in diabetic rats transplanted with IPCs, but in rats transplanted with UCB-derived cells were significantly lower than in those transplanted with BM-derived cells. The amount of C-peptide released from transplanted IPCs derived from BM-MSCs and UCB-MSCs was non-significantly different. The results indicate that UCB- MSCs and BM-MSCs are promising stem cell sources for IPCs that help in the development of a new strategy for treatment of D.M. However, transplantation of IPCs derived from UCB brings better results than BM-derived cells

Nitric oxide synthase and some biochemical markers in evaluation of liver diseases

A total of 60 subjects were included in this study [48 hepatic patients and 12 healthy controls of matched age and sex]. All individuals were classified into the following groups each comprises 12 individuals: Group I: Hepatic cirrhosis, Group II: Chronic viral hepatitis C, Group III: Hepatic malignancy, Group IV: Bilharzial hepatic fibrosis, Group V: Healthy control. Whole blood and plasma samples from all patients and control groups were taken and assayed for: 1-Nitric oxide metabolites [nitrite and nitrate]. 2-Malondialdehyde [MDA], lipid perioxidation product. 3-iNOS expression [mRNA] using RT-PCR

Results: The serum levels of both NO metabolites and MDA showed significant increase in all patients groups compared with the control group. iNOS expression was increased in all patients groups compared with control group. The products of RT-PCR amplification of iNOS revealed appearance of the desired band of RT-PCR products of iNOS at 259 bp showing apparent different densities of each band which means different intensities of expression between patients groups. Gel image was digitalized using soney digital camera model [digital mavica] and was quantified using Scion image software on Intel Pentium 4

Conclusion: 1- Nitric oxide is increased in all patients groups so, it may plays multiple roles in different liver diseases either, beneficial and protective against fibrosis, portal hypertension in liver cirrhosis, viraemia in hepatitis c infection, and tumerogenesis in hepatocellular carcinoma or the opposite via production of reactive nitrogen species. Further studies using NO donners and iNOS inhibitors should be done to detect NO roles in each group separately hoping to reach to NO therapeutics in different liver diseases. 2Malondialdehyde [lipid peroxidation products] increased significantly in different types of liver diseases so; it may have a role in the pathogenesis of them and its progression to cancer

Relations between endothelial functions, carotid intima media thickness and microalbuminuria in type 2 diabetes mellitus

This study aimed to determine the association between endothelial function biomarkers [von Wille brand Factor [vWF], soluble adhesion molecules [sVCAM-1 and sICAM-1], carotid intima-media thickness [IMT] and microalbuminuria [MAU] in type 2 diabetes mellitus non-insulin dependent diabetes mellitus [NIDDM] patients and their role in development of atherosclerosis. The current study comprised 40 NIDDM patients [18 males and 22 female], classified into the following groups according to presence or absence of MAU: Group I: Comprised 20 NIDDM Patients with microalbuminuria and Group II: Comprised 20 NIDDM Patients without microalbuminuria. [normo-albuminuric]. For comparioon. 20 healthy volunteers of matched age and sex were considered as controls. Lipid profile [Total cholesterol, LDL-C, HDL-C and triglycerides], vWF, sVCAM-1 and sICAM-1 are estimated in the plasma samples of an studied groups. Also, carotid IMT and brachial artery flow-mediated dilatation [FMD] and nitroglycerine-induced dilatation [NID] are measured for all patients and control groups. There was a significant increase in cholesterol and LDL-C and decrease in HDL-C in plasma of both patients groups. Significant increase in carotid NT and significant decrease In FMD% and NID% at brachial artery in both patients groups. Also, there was a significant increase in vWF, sVCAM-1 and slCAM-1 in both patients groups. All studied parameters were highly significant in patients group I [with MAU] when compared with those of patients group H [without MAU]. On the other hand, there was a positive correlation between all studied parameters in the patients group with MAU. So, endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are apparent in NIDDM patients especially with microalbuminuria. Further work is needed to determine whether endothelial function can be used as a therapeutic target to reduce cardiovascular diseases and improve clinical outcome

Expression of inducible nitric oxide synthase in ischemic heart diseases and myocardial infarction

There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiological importance in heart diseases. So, the present study was conducted to evaluate the role of inducible ntric oxide synthase [iNOS] in coronary heart diseases either ischemic heart disease [IHD] or myocardial infarction [MI] and to detect the expression of iNOS gene in these diseases. The current study was con ducted on 50 patients [25 patients With ischemic heart disease and 25 patients with myocardial infarction] with mean age 55.53 +/- 4.18 years and 12 healthy volunteers of matched age and sex were taken as control. The serum levels of nitrite and CGMP were measured by spectrophotometric method and ELISA assay, respectively and also detection of the iNOS gene expression in the total RNA extracted from different studied groups were done. Results of the present study have demonstrated that: a significant increase in nitrite and cGMP levels in myocardial infarction group compared to control group. Anon-significant increase in nitrite and cGMP levels in myocardial infarction group compared to control group. Anon-significant increase in nitrite and CGMP levels in ischemic heart disease group compared to control group. Also, iNOS gene expression was found to be positive in 76% of myocardial infarction group and negative in ischemic heart disease group. Positive correlation between serum nitrite and serum cGMP in all patients groups. Also, positive correlation between serum nitrite, serum cGMP and iNOS gene expression. So, in conclusion, iNOS may have a role in the patho-genesis of coronary heart diseases and the use of iNOS gene transfer or the use of antisense technology aiming at inhibiting the expression of iNOS may be of beneficial therapeutic values in these conditions