Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.
Introduction: Insulin-like growth factor-1 (IGF-1) is a potent mitogen for glomerular mesangial cells which can stimulate cell migration and the production of fibronectin, proteoglycan, and type IV collagen, thereby promoting the development of the chronic kidney disease (CKD) in patients with diabetes. Objectives: The aim of the study was to assess the associations between serum levels of IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) and CKD in diabetic patients. Patients and Methods: We investigated 102 Belarusian men and women with diabetes type 2 aged 56.67±0.81 years. Control group included 68 healthy people the same age. We estimated GFR with the use of the CKD-EPI creatinine-cystatin C equation to determine eGFRcr_cys. Serum total IGF-1 and IGFBP-3 levels were measured using immunoradiometric assay (IRMA) (Beckman Coulter, Czech Republic s.r.o.). Results: Patients with diabetes had significantly lower level of IGF-1 than controls. However, IGFBP-3 levels were similar in the two groups. Diabetic patients with CKD had significantly higher levels of IGF-1 and IGFBP-3 than diabetic patients without CKD (P=0.0031). However, according to multivariate analysis, only IGF-1 and cystatin C were associated with renal impairment. In detail, the odds of having eGFR<60 mL/min/1.73 m2 increased with rising IGF-1 levels (OR: 1.025, [CI 1.002-1.048]). Conclusion: Our study revealed that higher serum IGF-1 levels were positively associated with CKD in patients with diabetes. We suggest that IGF-1 might be a predictor of CKD in patients with diabetes. Further research is necessary to confirm the observed this association and to detect the causal relations.
Investigating the adipose tissue surrounding the heart and large vessels, the so-called pericardial fat, is of great interest for researchers. Pericardial fat is currently being considered a new cardiovascular risk factor, which forces us to reconsider the pathogenesis of various cardiovascular disorders. The article describes the concept of pericardial fat, including its heterogeneous structure and origin determining its functional role. In addition, the specific characteristics of pericardial fat in patients from various clinical groups are described. The main attention is paid to the significance of the metabolic activity of pericardial adipose tissue and its effect on nearby structures, such as the heart and coronary arteries. Based on modern scientific concepts, we have identified the main components of pathogenesis of coronary atherosclerosis, myocardial fibrosis and atrial fibrillation and the role of pericardial adipose tissue. The relationship between adipose tissue characteristics and risk factors for heart disease development remains questionable and requires further investigation. The article summarizes the importance of future studies of the parameters and properties of adipose tissue in individuals with identified cardiovascular pathology.
Objective. To evaluate the role of the T(-344)C polymorphism of CYP11B2 gene in the development of cardiorenal syndrome (CRS) in diabetes mellitus (DM).Materials and methods. 270 patients with type 1 and type 2 diabetes aged over 25 years were examined. All patients underwent molecular genetic analysis using deoxyribonucleic acid isolated from whole venous blood.Results. The TT genotype was associated with the risk of developing CRS manifestations such as left ventricular hypertrophy (odds ratio (OR) 2.64; 95% CI (0.93–4.19), chronic heart failure (OR 4.26; 95% CI (2.26 - 8.06), subclinical atherosclerosis (OR 4.04; 95% CI (1.89 - 8.58), chronic kidney disease (CKD) (OR 10.77; 95% CI (3.56 - 32.61), and the CT genotype (OR 3.28; 95% CI (1.02 – 10.59) with CKD risk..Conclusion. There are pathogenetic associations between renin-angiotensin-aldosterone system, cardiovascular complications and a decrease of renal function. Further research is needed for a deep understanding of the complex pathogenetic mechanisms of the development and progression of cardiovascular and renal pathology.
Spina bifida is a developmental defect of the spinal cord and / or spine that results from abnormal closure of the embryonic neural tube. Many factors have been described to determine the risks of developing this pathology, but the incidence of the defect is still high. 61 % of patients with Spina bifida have neurogenic bladder dysfunction based on intravesical hypertension, which contributes to reverse urethral flow and bladder-uretero-renal reflux associated with chronic inflammatory and obstructive urinary tract disease. In 25-50 % of patients with Spina bifida, urological pathology is complicated by the development of chronic kidney disease, which significantly reduces the quality of life of these patients. In some types of Spina bifida, urological symptoms may be prominent or even isolated and may indicate the presence of the malformation. Therefore, early diagnosis of Spina bifida and timely prophylactic and therapeutic measures are of particular importance.
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