Cardiovascular complications, such as myocardial infarction, atherosclerosis, cardiomyopathy and heart failure are amongst the major causes of morbidity and mortality among diabetic patients. Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle mediated by hyperglycemia and oxidative stress. Endothelial progenitor cells (EPCs) have shown promising potential to repair the diabetes induced cardiac damage. EPCs differentiate into functional and mature endothelial cells. However, challenges such as deteriorated functional abilities and survival of EPCs derived from diabetic subjects limit the possible outcome of autologous EPCs based therapies. Diazoxide (DZ), a highly selective mito-KATP channel opener, has been shown to improve the ability of mesenchymal stem cells and skeletal myoblasts for the repair of damage to heart muscles. In the present study, effect of DZ preconditioning was evaluated in determining the ability of diabetes affected bone marrow-derived EPCs to repair streptozotocin (STZ) induced DCM in rats. Diabetic EPCs (DM-EPCs) were characterized by immunocytochemistry, flow cytometry and reverse transcriptase PCR for endothelial markers: vWF, VE Cadherin, VEGFR2, PECAM, CD34 and eNOS. Preconditioning was performed in vitro, by incubation of DM-EPCs in 200 μM DZ for 30 minutes, followed by H2O2 induced oxidative stress and hyperglycemic stress. Oxidative stress to preconditioned and non preconditioned DM-EPCs was induced by exposure to 200 μM H2O2 for 2 hours whereas for hyperglycemic stress induction, the cells were exposed to 30 mM glucose media. Non-preconditioned EPCs with and without exposure to H2O2 were served as controls. IX The treated cells were evaluated for survival (XTT cell viability assay), senescence, paracrine potential (by ELISA for VEGF) and alteration in gene expression (VEGF, SDF-1α, HGF, bFGF, Bcl2 and caspase-3). DZ preconditioning of DM-EPCs significantly increased survival accompanied by enhanced release of VEGF and reduced senescence in DZ DM-EPCs+H2O2 group as compared to DM EPCs+H2O2 group under oxidative and hyperglycemic stress conditions. Furthermore, DZ preconditioned DM-EPCs exhibited upregulated expression of prosurvival genes under oxidative stress (VEGF, SDF-1α, HGF, bFGF and Bcl2) and under hyperglycemic stress (VEGF and Bcl2) while down regulated the expression of Caspase-3 in DZ DM-EPCs+H2O2 group as compared to DM-EPCs+H2O2 group under oxidative and hyperglycemic stress conditions as determined by reverse transcriptase PCR and real time PCR. For in vivo studies, diabetes was induced in Wistar rats by injecting 40 mg/kg streptozotocin. After eight weeks, 2x106/70 μl of serum free medium, each of DZ preconditioned DM-EPCs and non-preconditioned DM-EPCs were transplanted into the left ventricle (LV) of diabetic rats (n꞊6 rats per group). After four weeks, DZ preconditioned DM-EPCs transplanted group showed improved contractility of diabetic heart as compared to untreated DM-EPCs group. There was decrease in collagen content estimated by Masson''s trichrome and Picrosirius red staining in DZ DM-EPCs transplanted group as compared to untreated DM-EPCs transplanted group. Furthermore, reduced cells injury were observed in DZ DM-EPCs group as evidenced by decreased expression of caspase-3 and increased expression of prosurvival genes Bcl2, VEGF and bFGF by semi-quantitative real time PCR. X In conclusion, the present study demonstrated that DZ preconditioning enhanced DM-EPCs survival under oxidative and hyperglycemic stresses and their ability to treat DCM.
حضور بابا پیر سید ولی محمد شاہ سائیں رحمۃ اللہ علیہ (آف پیر شاہ والے ) میری بدل دیویں تقدیر ولی شاہ باباؒ جی توں ایں مولا علی دا وزیر ولی شاہ باباؒ جی آلِ نبی، اولادِ علی ایں، پائی شان نرالی توں جو وی آیا در تیرے تے گھلیا نہ کوئی خالی توں کوہجھیاں نوں گل لا کے سائیاں لگیاں دی لج پالی توں میری معاف کریں تقصیر ولی شاہ باباؒ جی میری بدل دیویں تقدیر ولی شاہ باباؒ جی اہل علاقہ گھر گھر سائیاں تیرے دیوے بلدے شان انہاں دی پچھنی کی جیہڑے تیری سنگت رلدے ناں تیرا ہک وار جے لیّے ساڈڑے دکھڑے ٹلدے شعلہ پیر تیری تصویر ولی شاہ باباؒ جی میری بدل دیویں تقدیر ولی شاہ باباؒ جی ولیاں دا سرتاج سداویں تیرے شان نرالے نیں تیرے منن والے سائیاں ہر جا رہن سوکھالے نیں ایڈ سخاوت ہور نہ کوئی، بن منگیوں بھرے پیالے نیں دیویں درشن کامل پیر ولی شاہ باباؒ جی میری بدل دیویں تقدیر ولی شاہ باباؒ جی
سیاں نے دربار تیرے تے جھرمٹ ویکھو پایا ہجر فراق تیرے وچ سیاں رو رو حال ونجایا جنہاں سک مرشد دی رکھی اوہناں درشن پایا دیویں صدقہ بدر منیر ولی شاہ باباؒ جی میری بدل دیویں تقدیر ولی شاہ باباؒ جی کیتھل پیر دا فیض روحانی شہر قبولے آیا اے مئے نوشاں نوں دستگیرؒ سائیں بھر بھر جام پلایا اے بابے پیر ولی شاہؒ تے تاں ہوکا پیا دیوایا اے تیرے در دا بناں فقیر ولی شاہ باباؒ جی میری بدل دیویں تقدیر ولی شاہ باباؒ جی پیر مبشر پوتا سائیں دا بڑیاں شاناں والا مہر محبت ایڈی اس وچ ہر دا پچھے حالا صورت سیرت دادے والی سب نوں دیوے سنبھالا ہویا قادریؔ زلف اسیر ولی...
Legitimation among scholars, since they fall to category of hadith dho’if (weak). Therefrom, several scholars argued that we might use them for hujjah mutlaq (absolute argumentation), while some others said it might be wiser not to use them at all. Yet there is also another opinion which said it could be used under special conditions. Based on this, this study aims to uncover and shed light the disagreements above scientifically, as well as to find he differences and the influence of the jurisprudence of law-making (fiqh). Then, the researchers sought to raise a strong opinion based on the arguments presented in the thesis, so which the researchers and or anyone who wants to practice the Hadith may find helpful.
Diabetes mellitus is a growing public health concern and a chronic metabolic disease worldwide. It is recognized as a group of metabolic disorder characterized by chronic hyperglycemia and glucose intolerance, due to insulin deficiency, impaired effectiveness of insulin action or both. A number of oral health complications are frequently associated with diabetes mellitus. These include various inflammatory diseases like gingivitis, periodontitis and oral soft tissue pathologies. This study was done to explore an association between oral mucosal lesions and type 2 Diabetes mellitus with reference to clinical periodontal status, self-reported oral symptoms, oral yeast colonization, smoking, as well as tobacco-chewing habits. A total of 800 individuals’ i.e 395 patients with type 2 diabetes mellitus and 405 normal individuals were enrolled in this study. Previously diagnosed type 2 diabetic subjects were recruited from Baqai institute of diabetology and endocrinology and normal individuals from Baqai Medical University (from January 2010 to September 2012). Patients with type 1 diabetes were not included in this study. Four hundred and five systemically healthy subjects without diabetes and other illness with oral diseases were similar in socio-economic level and age recruited as control subjects after checking their fasting blood glucose level. These patients were selected from the department of periodontology and oral medicine, Baqai Medical University at the same time as the type 2 diabetes mellitus group. All clinical examinations were carried out by research scholar with the aid of a plane mouth mirror, gauze and a WHO CPITN probe. Radiography was not applied. Moreover, in cases requiring further confirmation, biopsies were obtained to establish an accurate diagnosis. The oral mucosal alterations were classified in two types’ oral mucosal lesions (OML) and potentially malignant disorders (PMDs), and periodontal disease was classified into Gingivitis and Periodontitis. In this study oral mucosal lesion was highly significant with a p value of < 0.0001 (odd ratio 2.601, CI 1.929-3.509) in type 2 diabetic as compared to non-diabetic. With respect to specific oral mucosal lesions we observed a highly significant association p<0.0001 (Odds ratio4.275, CI 7 2.798-6.534) of coated tongue (26.8%) with type 2 diabetes mellitus patients.Concerning potentially malignant disorder our study did not find any association between diabetes mellitus and potentially malignant disorder. We found a highly significant association of potentially malignant disorder p<0.001(odd ratio15.164, CI 5.119-44.921) and mixed lesions p<0.0001(odd ratio 8.571,CI 2.731-26.896) in individual using smokeless tobacco. In addition another relationship exists between periodontal disease and smokeless tobacco use. It shows that the smokeless tobacco caused a higher prevalence of gingivitis (76.4%) and periodontitis (77.4%) in the study population. Concerning oral hygiene habits, almost 87% of the total sample population surveyed reported daily oral hygiene habits. Brushing was the most frequent technique used (48.1%). Periodontitis was more frequent in diabetics than in non-diabetics. In our study we found a highly significant p<0.0001 association of periodontitis with type 2 diabetes mellitus. This is in agreement with many previous studies which pose diabetes as a risk factor for periodontal disease. With respect to glycemic control this study showed that there was a high percentage of periodontitis in patients with poor glycemic control, however statistical analysis disclosed no association between glycemic control and periodontal disease (odd ratio 1.621, CI 0.768-3.420). The cut-off point for Hemoglobin A1c (7%) used to distinguish those who were poorly controlled from those with better control. This study showed that the prevalence of oral mucosal lesions tends to be higher in diabetic than non-diabetics patients, however no association was observed between potentially malignant disorder and type 2 diabetes mellitus. A highly significant association of periodontitis with type 2 diabetes mellitus has been observed. In addition a highly significant association of potentially malignant disorder and mixed lesions in individual using smokeless tobacco was found. This study provides evidence that diabetes has a strong negative influence on oral health.