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