Study the Association of Tumor Necrosis Factor Promoter Polymorphism with Type 2 Diabetic Nephropathy.

Type 2 Diabetes Mellitus (T2DM) is well known to include an inflammatory component that has been considered to be related to diabetic complications. Diabetic nephropathy (DN) is one of the significant complications as it constitutes the most frequent cause of end-stage renal disease. Tumor Necrosis Factor-α (TNF-α) is known as a multifunctional proinflammatory cytokine which is associated with some pathological processes such as immunoregulation, proliferation, inflammation, and apoptosis. The aim was to explore the association between the TNF-α promoter -1031T/C single nucleotide polymorphism (SNP) and the serum TNF-α level in addition to nephropathy among type 2 diabetic patients. The study included 38 T2DM subjects without nephropathy (DM group), 40 subjects with DN, and 20 controls. Identification of TNF-α promoter gene polymorphism -1031T/C was done by PCR-RFLP, and genotyping was confirmed by direct sequencing. The serum TNF-α level was assessed by ELISA. Correlations were tested by Pearson's correlation analysis. Logistic regression was used to detect the most independent factor for development of DN. The serum level of TNF-α in the DM group was significantly higher than controls (p < 0.001); also, the DN group was considerably higher than controls and DM without nephropathy (p < 0.001). Also, there was a significant positive correlation between serum levels of TNF-α with FBG (fasting blood glucose), creatinine, total cholesterol, LDL-C, HbA1c, and microalbumin/creatinine ratio (ACR) among the DN group (p = 0.042, <0.001, <0.001, <0.001, 0.027, and 0.043, respectively). Mutant homozygous CC and heterozygous TC genotypes were higher in DN than in DM and controls. C allele was more represented in DN than in DM and controls (p = 0.003) while T allele was higher in controls than in DM and DN patients. The levels of TNF-α were higher in subjects who had mutant CC than the wild TT genotype among DN (p < 0.001). C allele was more risky for DN than T allele between DN and controls by 5.4-fold (CI: 1.75-16.68) as well as between DN and DM by 2.25-fold (CI: 1.1-4.59). Conclusion. Serum levels of TNF-α were higher in individuals with mutant CC genotype of -1031T/C TNF-α gene, and C allele could be associated with increased risk for nephropathy among patients with T2DM.

Relationship Between sCD163 and mCD163 and Their Implication in the Detection and Typing of Leprosy.

BACKGROUND: Leprosy is a chronic contagious disease caused by Mycobacterium lepraea. CD163 is a monocyte trans-membrane glycoprotein receptor (mCD163) that sheds from the cell surface and circulates as a soluble (serum) form (sCD163). Changes in the mCD163 and sCD163 levels could mirror the categorization of inflammatory procedure, demonstrating a possible use of CD163 as a diagnostic indicator of inflammation. OBJECTIVE: To investigate the possible role of CD163 (sCD163 and mCD163) in leprosy pathogenesis and to assess whether CD163 is a helpful inflammatory marker of leprosy development and typing. PATIENTS AND METHODS: This case control study included 70 leprosy patients and 30 healthy controls. Leprosy patients were classified according to the Madrid criteria (1953) into: tuberculoid leprosy (TT), border-line leprosy (BL), and lepromatous leprosy (LL). For all participants, complete blood count (CBC), serum CD163 using ELISA and monocytes positive for CD163 using flow cytometry were done. RESULTS: Leprosy patients had significantly low WBCs and platelet counts (p<0.001) and had significantly higher sCD163 (p=0.025) and mCD163 (p=0.042) that were highest in LL followed by BL, then TT patients (p<0.001). There was a significant positive correlation between mCD163 and sCD163 levels in leprosy patients (r=0.896, p<0.001). ROC analysis revealed a significant role of serum sCD163 and of mCD163 positive monocytes in the detection (p<0.001) and typing of leprosy (p=0.002 and p<0.001, respectively). CONCLUSION: Both sCD163 and mCD163 positive monocytes may have an active role in leprosy pathogenesis. They could be potential biomarkers for leprosy detection and typing.

The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload.

BACKGROUND: Cardiac iron toxicity is the leading cause of death among ß-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. OBJECTIVES: To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). METHODS: Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 ß-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. RESULTS: TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E' (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E' ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio < 8 without a difference in Hb levels. CONCLUSION: Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP.