Angiotensin converting enzyme [ACE] l/D gene polymorphism in children with idiopathic nephrotic syndrome

Various genetic markers have been studied to predict susceptibility and course of nephrotic syndrome. The Angiotensin-converting enzyme [ACE] gene carries insertion [I] and deletion [D]polymorphism within its intron 16. The presence of D-allele in the ACE gene has been reported as a probable genetic risk factor for idiopathic nephrotic syndrome [INS] and may be also related to poor responsiveness to steroids which is the single most important clinical parameter in determining the course of the disease. The aim is to determine the distribution of the ACE gene insertion/deletion [l/D] polymorphism, and its effect on clinical, laboratory, histological findings and therapeutic response in childhood INS. Fifty one nephrotic syndrome patients [35 males and 16 females] were enrolled in the study. All patients received oral steroids as in initial therapy for their nephrotic syndrome. The pattern of response to steroid therapy was determined and patients divided into 2 groups: steroid sensitive [SS] and non-steroid sensitive [non-SS]. The non-SS group was further divided into steroid dependent [SD] and steroid resistant [SR] patients. Clinical, laboratory and histological features were determined. Fifty unrelated healthy adults were recruited as controls. The genotypes for ACE l/D polymorphism were analyzed by using a PCR based method. Twenty patients were SS and 31 were non-SS, of the non-SS group, 18 were SD and 13 were SR. The presence of hypertension at presentation was significantly related to steroid unresponsiveness. Among the SS group the frequencies of the Ii, ID, and DD genotypes of the ACE gene were 20%[n=4], 65%[n=13] and 15%[n=3], respectively, while the frequencies among the Non-SS group were 19.4%[n=6], 74.2%[n=23] and 6.5%[n=2], respectively. The differences between the two groups were statistically insignificant [Chi square=0.59]. The corresponding incidence for control was 12%, 68% and 10% respectively. The differences between controls versus the entire patient group, the SS group and the non-SS group were not statistically significant [p value>0.05 in all]. The frequency of D+genotype was 80%[n=16] in the SS group compared to 80.6%[n=25] in the Non-SS group, the difference between the two groups was statistically insignificant [Fisher's exact=1]. The pattern of the ACE gene polymorphism showed insignificant correlation with age of onset of the disease, hypertension at presentation, stability of renal functions and renal biopsy results. The current study on Egyptian children with INS reveals no association between ACE gene l/D polymorphism and clinical, histological findings, steroid responsiveness, or progression of the disease These results are at variance with reports from other parts of the world suggesting that the impact of ACE gene polymorphism on pediatric INS is likely to be influenced by the ethnic origin. Results of this study revealed an association between hypertension at presentation and non-responsiveness to steroid. Patients with steroid non responsiveness were more liable to develop impaired renal function

Biological significance of stem cells [CD34 +] and vascular endothelial growth factor [VEGF] in the peripheral blood of patients with acute myocardial infarction

Reports on stem cell transplantation-an innovative approach to repair damaged myocardium following acute myocardial infarction [AMI]-have raised the question of a possible spontaneous mobilization of corresponding stem cells from the bone marrow of ischemic patients. Exposed to vascular endothelial-derived growth factor [VEGF], such cells would differentiate into myocardial cells within the infarcting myocardium, thus hopefully initiating the reparative process. The present work assessed the prevalence of marrow derived stem cells expressed in term of percent of CD34 + cells in the peripheral blood of patients sustaining AMI, as well as the serum level of VEGF needed for their differentiation into cardiac myocytes. We studied 21 male patients with AMI [mean age 52.5 +/- 8.9 years]. Myocardial infarction was anterior in 10 and inferior in 11 patients. Eleven healthy males [mean age 53.9 +/- 9.4 years] served as controls. Following admission, all patients and controls were subjected to clinical examination including 12-lead ECG with routine laboratory evaluation comprising total and differential CBC, hepatic and renal functions, as well as relevant cardiac serum enzymes with the latter repeatedly measured every 8 hours to detect the highest peak of CK. Specific laboratory measurements included flowcytometric analysis of peripheral blood mononuclear cells to detect CD34 + population and serum VEGF level by ETA on admission, 3 day, and prior to discharge. Comparing the mean percent values of CD34 + cells on admission [7.02 +/- 3.08], ischemic patients exhibited insignificantly higher levels of CD34 on the 3rd day [8.57 +/- 3.5] as well as on discharge [8.45 +/- 3.5]. The above mentioned values were also insignificantly different from samples withdrawn from control subjects [8.84 +/- 3.4]. However, CD34 cell population was positively correlated with the extent of myocardial damage expressed in terms of peak CK. Thus with an arbitrary limit of >/= 30% rise in CD34, two patients subgroups could be stratified, with 12 patients having >/= 30% rise in CD 34, exhibiting a peak CK of 2498.6 IU/L, and 9 patients showing < 30% rise in CD34 presenting a peak CK of 1312.9 IU/L. However this relationship was not of statistical significance. Serum VEGF surprisingly showed a trend towards decrease rather than increase when compared to control subjects [1.23 +/- 0.99 versus 2.79 +/- 1.67 respectively, p = 0.001], with the decline maintained over the 3rd day and prior to discharge in most patients, raising the issue of increased consumption during the process of stem cell differentiation. Acute myocardial infarction apparently initiated a series of molecular and biological events whereby continued mobilization of bone marrow stem cells [expressed by continuing rise of CD34 marker] was triggered. Subsequent homing into myocardium lead to continuous consumption of VEGF needed for their differentiation into cardiac myocytes. This phenomenon could be part of a spontaneous reparative process potentially raising hopes of therapeutic applications