Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection.

Vitamin D has been recognised as a potent immunomodulator and its deficiency is common in different population groups including patients with diabetic foot infection. Diabetic foot infection reflects the altered immune status of the host. As cytokine regulation plays a significant role in infection and wound-healing processes, the present study aimed to evaluate the association between vitamin D status and inflammatory cytokine profiles in patients with diabetic foot infection. The serum concentrations of vitamin D (25-hydroxyvitamin D), IL-1ß, IL-6, TNF-α and interferon-γ (IFN-γ) were measured in 112 diabetic foot infection cases and 109 diabetic controls. Severe vitamin D deficiency (25-hydroxyvitamin D concentration < 25 nmol/l) was more common in cases than in controls (48.2 v. 20.5%). Although age, duration of diabetes, HbA1C (glycosylated Hb) concentration and BMI were similar, cases had significantly higher concentrations of IL-6 (P≤ 0.001), IL-1ß (P≤ 0.02) and TNF-α (P≤ 0.006) than controls. A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1ß (r -0.323; P≤ 0.001) as well as IL-6 (r -0.154; P≤ 0.04), but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations. Furthermore, a significant difference in IL-1ß (P≤ 0.007) and IL-6 (P≤ 0.02) concentrations was observed in patients with severe 25-hydroxyvitamin D deficiency compared with patients with 25-hydroxyvitamin D concentration ≥ 25 nmol/l, and this difference was remarkable for TNF-α. In conclusion, severe vitamin D deficiency is associated with elevated inflammatory cytokine concentrations in diabetic patients, particularly in those with foot infection. A 25-hydroxyvitamin D concentration value < 25 nmol/l is suggested as the 'cut-off' for such immunological alterations in patients with diabetes mellitus.

Waist circumference cutoff and its importance for diagnosis of metabolic syndrome in Asian Indians: A preliminary study.

BACKGROUND: There is inconsistency in accepting waist circumference (WC) as mandatory and also regarding its significance for diagnosis of metabolic syndrome (MetS) for different populations. AIM: To study the association of individual parameters of MetS with WC cutoffs suitable for South Asian Indians. MATERIALS AND METHODS: From an ongoing hospital-based study on MetS as per the criteria of diagnosis of modified NCEP ATP III, 713 subjects having a minimum three of the four parameters, i.e., dyslipidemia [low high density lipoprotein (HDL), high triglycerides], dysglycemia and hypertension, without regard to cutoffs of WC, were included in the present study. RESULTS: Receiver operator characteristic curve analysis of WC cut-off points for males was 90 cm with a sensitivity and specificity of 71% and 96%, respectively, and for females was 85 cm with a sensitivity and specificity of 86% and 93%, respectively, associated with the risk factors of MetS. Multiple logistic regression analysis for low density lipoprotein (LDL) cholesterol concentration of ≥3.38 mmol/l showed an odds ratio of 5.03 (95% CI = 1.29-19.5) in males and 3.17 (95% CI = 1.14-8.76) in females which was statistically significant (P < 0.02); in addition to higher WC, higher level of triglyceride (P ≤ 0.0001) and lower level of high density lipoprotein cholesterol (P ≤ 0.02) were observed. CONCLUSION: This study suggests that WC of 90 cm in males and 85 cm in females should be a mandatory criterion of MetS in our subset of population. LDL may be considered one of the components of MetS along with the currently defined WC cutoffs.

Protein-protein docking on molecular models of Aspergillus niger RNase and human actin: novel target for anticancer therapeutics.

The 3D models of human actin protein and A.niger RNase were designed using the templates ACTBIND (PDB ID: 3D3Z) and crystalline profilin-beta-actin (PDB ID: 2BTF), respectively in Modeller9v5. These models are testified using several validation methods including PROCHECK, ERRAT, WHAT-IF, PROSA2003 and VERIFY-3D. The stereo-chemical quality of the models was judged by Ramachandran plot with PROCHECK. The total quality G-factor -0.2, shows a good quality model. The ERRAT score for the human actin and A.niger RNase models are 86.104 and 84.615, respectively, fit well within the range of a high quality model. The ERRAT score for the templates 2BTF and 3D3Z are 91.111 and 97.391, respectively. The WHAT-IF evaluation justifies a reasonable homology model structure as none of the scores for each residue in the homology model is lower than -5.0. The energy-minimized model of human actin with PROSA reveals the Z-score value -10.52 between native conformations of the crystal structures. The VERIFY 3D average score is 0.36. All evidence suggests that the geometric quality of the backbone conformation, the residue interaction, the residue contact and the energy profile of the structures were well within the limits of reliable structures. The interaction energy of docking was calculated using the HEX server. The Etotal, lowest docked energy, and calculated RMSD values were -1.608 kcal mol(-1), -8.369 kcal mol(-1) and 0.617 Å, respectively. The study presented in the current project may be useful to design molecules that may have anticancer activity.