Role of adiponectin in patients with non-insulin dependent diabetes mellitus

Adiponectin is a collagen-like protein that is solely secreted by adipocytes. Different studies showed that it plays an important role in the pathophysiology of insulin resistance, diabetes and dyslipidemia and thus affects risk for cardiovascular disease and obesity. In the present study the role of adiponectin in pathogenesis of type 2 diabetes mellitus was evaluated. The current study was carried on 51 diabetic patients with documented NIDDM and 22 age and sex matched healthy controls. Diabetic patients were subdivided into 2 subgroups according to BMI where 40 were obese and 11 were non obese and according to the presence of cardiovascular disease with obesity where 16 were obese with CVD and 24 were obese with no CVD. Controls were subdivided according to BMI where 7 were non obese and 15 were obese. The levels of plasma adiponectin, insulin, c-peptide, fasting blood glucose, glycated hemoglobin, lipid profile, NO and lipid peroxides. The results of the present study showed that adiponectin was significantly lower in all groups with variations compared to controls, in obese patients with CVD than those without CVD. NO and MDA levels were higher in diabetic patients than in controls and the highest levels of MDA were observed in patients with cardiovascular disease. Lipid profile was altered in diabetic patients showing higher levels than in controls. In the diabetic patients, adiponectin was significantly positively correlated with NO and HDL, while it was significantly negatively correlated with glucose, HbA1C, Cholesterol, LDL, insulin and c-peptide. The ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future

Tissue levels of platelet-derived endothelial cell growth factor[thymidine phosphorylase], vascular endothelial growth factor and cathepsin-D in patients with bronchogenic carcinoma

1] To acquire more information about the important role of platelet derived-endothelial cell growth factor thymidine phosphorylase [PD-ECGF/TP], vascular endothelial growth factor [VEGF] and cathepsin-D [Cath-D] as angiogenic factors in the pathogenesis, progression and prognosis of lung cancer. 2] To investigate the correlation between these biochemical indices and the clinico- pathologic status of the patients. Patients: The study included histopathologically confirmed lung biopsies of 37 patients with bronchogenic carcinoma, 12 patients with benign chest diseases and 12 non inflammatory non malignant biopsies as a control group. Bronchogenic carcinoma cases were classified histopathologically into squamous cell carcinoma [14 cases], adenocarcinoma [10 cases], large cell carcinoma [6 cases] and small cell lung carcinoma [7 cases]. Design: A randomized, group comparative, single center study. Setting: Assiut University Hospital. The present study showed a significant increase in the tissue levels of PD-ECGF/TP, VEGF and Cath-D in patients with lung cancer in comparison to patients with benign chest diseases and controls. Significant higher tissue levels of the studied bioindices were observed in patients with inoperable cancer, advanced stages, bulky tumors and with lymph node metastasis. Significant higher tissue levels of VEGF and Cath-D were also demonstrated in lung adenocarcinoma compared to other pathologic types of lung cancer. Significant positive correlations were found between the studied bioindices in the lung cancer patients. The present study indicates the importance of PD-ECGF/TP, VEGF and Cath-D as angiogenic factors in the malignant progression and prognosis of lung cancer. Therefore the development of new therapeutic agents with an anti angiogenic action like PD-ECGF/TP and VEGF inhibitors may be of great importance in the management of patients with lung cancer

Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandine E-[2] in the venous and cavernous blood of patients with erectile dysfunction

To investigate the balance between the release of the smooth muscle vasoconstrictors [endothelin-l [ET-1] and angiotensin II [Ang II]] and relaxants [nitric oxide [NO] and prostaglandin E-[2] [PGE-[2]]] by determining the alterations in plasma levels of ET-l, Ang II, NO and PGE2 in the venous and cavernosal blood of patients with organic and psychogenic erectile dysfunction [ED]. Patients: The study included 32 patients complaining of ED for more than one year [mean age +/- SEM 43.7 +/- 2.07]. The patients were subdivided into two groups: 16 organic ED patients [mean age +/- SEM 48.13 +/- 2.77 years] and 16 psychogenic ED patients [mean age +/- SEM 43.0 +/- 3.03 years]. Fifteen healthy potent age matched [mean +/- SEM 44.86 +/- 2.9 years] male volunteers were enrolled as a control group. For each patient venous and cavernous blood were obtained, while only venous blood were obtained from controls. Design: A randomized, group comparative, single-center study. Setting: Assiut University Hospital. Intervention: Plasma levels of ET- 1, Ang II, NO and PGE-[2] in the venous and cavernous blood of ED patients and in the venous blood of controls were estimated. Main outcome measures: ET-1, Ang II, NO and PGE-[2]. The present study showed significant increase in the plasma levels of ET-1 and Ang II, in addition to significant decrease in the plasma levels of NO and PGE[2] in the venous blood of ED patients in comparison to the controls. Patients with organic ED showed significant higher levels of ET- 1 and significant lower levels of NO in both venous and cavernous blood in comparison to those with psychogenic ED. Significant higher levels of cavernous Ang H were found in the two groups of ED patients in relation to venous blood. However, there were also no significant differences in PGE[2] levels in venous and cavernous blood of both groups of patients. There were significant positive correlations in both venous and cavernous blood between ET-l and Ang II and between NO and PGE[2] in total ED patients and the two subgroups. In addition significant negative correlations were found between venous and cavernous ET- 1 and NO; ET-1 and PGE[2] Ang II and NO and between Ang II and PGE[2] The imbalance between vasoconstrictors and vasodilators may play an important role in the pathogenesis of erectile dysfunction. ET- 1 may be a clinical marker of diffuse endothelial disease manifested by ED. Since ACE activity controls Ang II there might be a rationale for the use of ACE inhibitors to prevent or treat ED. NO and PGE2 may provide new strategies for pharmacologic treatment of ED

Renal tublar dysfunction in patients with type 2 diabetes mellitus

1] To determine the activity of urinary enzymes [N-acetyl-beta-D-glucosaminidase [NAG], a lysosomal enzyme, gamma-glutamyltranspeptidase [GGT], alkaline phosphatase [ALP], brush border enzymes and beta2 microglobulin [beta2-MG] as one of the tubular proteins] as markers of tubular damage which may reflect early stage of diabetic nephropathy. 2] To clarify the importance of estimation of these enzymes as noninvasive cheap tools in monitoring the course of diabetic nephropathy [DN]. 3] To evaluate serum levels of angiotensin converting enzyme [ACE] as a marker of endothelial cell disorder in diabetic patients. Patients: The study included 75 subjects, 60 were non-smokers type 2 diabetic patients and 15 healthy, nonsmoker, age and sex matched controls. The patients were classified into 3 groups, the 1st group was 20 normoalbuminuric diabetic patients, the 2nd group was 20 patients with microalbuminuria [urinary albumin is >30 mg - <300 mg/day], and the 3rd group was 20 patients with macroalbuminuria [>300 mg/day]. Setting: Departments of Biochemistry and Internal Medicine, Faculty of Medicine, Assiut University, EGYPT. There were significant increased levels of the urinary NAG, ALP and beta2-MG, serum ACE and glycated haemoglobin [HbA1c], in addition to significant decreased levels of GGT, in the three diabetic groups compared to the corresponding levels of controls. These changes were encountered in the microalbuminuric group compared to the normoalbumjnuric group and in the macroalbuminuric group compared to both the normoalbuminuric and microalbuminuric groups. Patients with either nephropathy alone or multi-diabetic complications showed that serum ACE, and urinary NAG, ALP and beta2-MG were significantly higher, while, urinary GGT was significantly lower than those without complications and in those with multi-diabetic complications than those with DN alone. In the normoalbuminuric group, microalbuminuria [MA] showed significant positive correlations with the urinary beta2-MG and serum ACE and a significant negative correlation with the urinary GGT. Serum ACE showed also significant negative correlation with the urinary GGT and a significant positive correlation with the urinary beta2-MG. In the microalbuminuric group, MA showed significant positive correlations with urinary beta2 MG, serum ACE and HbA1c and a significant negative correlation with urinary GGT. Serum ACE showed a significant negative correlation with urinary GGT and significant positive correlations with urinary beta2-MG and HbA1c For early detection of diabetic nephropathy, it would now seem recommended to include markers of tubular dysfunction such as urinary NAG, serum ACE and urinary ALP in addition to measuring albumin excretion

Levels of sFas/Apo-1, Caspase-3 and tumor necrosis factor alpha in patients with acut ischemic cerebral stroke

[1] To investigate the levels of some proteins regulating apoptosis namely soluble Fas/Apo-l [sFas], caspase-3 and tumor necrosis factor alpha [TNF-alpha] in acute ischemic cerebral stroke. [2] To evaluate the potential relationship between the levels of these parameters and brain damage. Patients: The study included thirty patients [16 males and 14 females] with acute ischemic stroke selected from the Internal Medicine Department of Assiut University Hospital over a period of 12 months. A control group of 20 non smoker healthy volunteers [11 males and 9 females] with matched ages were included in the study. Design: A randomized, group comparative, single-center study. Setting: Biochemistry and Internal Medicine Departments at Assiut University Hospital, Egypt. Significant elevated levels of sFas/Apo-1, caspase-3 and TNF-alpha were observed in patients in comparison to those of the controls. These elevations were more pronounced among smokers and those with myocardial disease. Significant positive correlations were found between sFas/Apo-1 and each of caspase-3 and TNF-alpha, and between the size of infarction and the three studied apoptotic parameters. The results demonstrated a significant increase in the levels of the apoptotic markers in acute ischemic stroke patients especially among smokers and those with myocardial disease. The extent of apoptosis detected in this study seems to play a role in the outcome of acute ischemic cerebral stroke. Therefore, the present study recommended the use of neuroprotective therapies [e.g. caspase-3 inhibitors] aiming at minimizing the activation of toxic pathways and at enhancing the activity of endogenous neuroprotective mechanisms in cerebral ischemic patients

Renal tubular dysfunction in patients with type 2 diabetes mellitus

It is well established that the detection of microalbuminuria in patients with diabetes mellitus indicates the presence of glomerular involvement in early renal damage. Recent studies have demonstrated that there iso also a tubular component of renal complications in diabetes, as shown by the detection of renal tubular proteins and enzymes in urine. So, the objective of this study was to determine the activity of urinary enzymes [N-aceiyl-beta-D-glucosaminidase [NAG], a lysosomal enzyme, gamma-glutamyltranspeptidase [GGT], alkaline phosphalase [ALP], brush border enzymes and /32 microglobulin [beta 2MG,] as one of the tubular proteins] as markers of tubular damage which may reflect early stage of diabetic nephropathy [DN] and to clarify the importance of estimation of these enzymes as noninvasive cheap tools in monitoring the course of DN [degree of proteinuria]. Also we studied the serum level of angiolensine converting enzyme [ACE] to evaluate the endothelial disorder in diabetic patients. Patients and Methods: 3 groups of non smoker type 2 diabetic patients were studied, 1[st] group was 20 normo-albuminuric diabetic patients, 2[nd] group was 20 patients with microalbuminurea [urinary albumin is >30 mg - <300 mg/day], and the 3[rd] group was 20 patie!ts with macroalbuminuria [: 300 mg/day]. Another 15 healthy age and sex matched subjects were recruited as a control group. For each patient and control subject the followings were estimated: [1] urinary glucose, 2 hours postprandial blood glucose, and glycated haemoglohin as parameters of gl, vcaemic control [2] blood urea, serum creatinine, 24-hour urinary protein and microalbuminuria to detect DN, ['3,] Serum ACE, urinary NAG. ALP, GGT and beta 2 microglobulin. The serum urinary NAG, ALP, beta 2MG, HbA[1c] and 2-hour postprandial blood glucose were significantly higher in the diabetic groups compared to controls. While GGT was significantly lower in the diabetic groups compared to controls. Also the increase in serum ACE, urinary NAG, ALP and beta 2MG positively correlated with the degree of albuminuria, HbA[1c] and 2-hour postprandial blood glucose while urinary GGT negatively correlated with the previous parameters. The significant progressive increase in ACE activity in the studied groups supports the hypothesis of ACE activity being an essential partner in the development of DN The elevation of the levels of NAG, ALP and beta 2 microglobulin, and the decrease in the level of GGT in the first group and the progressive change in their levels with the pathological increase in the level of urinary albumin, suggest that these changes are useful in the diagnosis of early stage of DN before the development of microalbuminuria. GGT and NAG appear more simple and readily available compared with others