Relationship of adipokines with insulin sensitivity in African Americans.

INTRODUCTION: Cytokines produced by adipose tissue, including adiponectin, have been associated with metabolic abnormalities. The purpose of this study was to examine the relationship of insulin sensitivity measured by euglycemic hyperinsulinemic insulin clamp with plasma adiponectin and other adipokines in young adult African Americans. METHODS: Participants were healthy African Americans. Anthropometric measures, blood pressure, an oral glucose tolerance test and an euglycemic hyperinsulinemic insulin clamp were performed. Insulin sensitivity measurements were adjusted for percentage of fat mass. Plasma concentrations of adiponectin, plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6) were assayed on plasma from fasting blood samples. Pearson correlation coefficients and multiple regression models were fitted to assess the association between glucose sensitivity and cytokines. RESULTS: In univariate analysis, there were statistically significant correlations of plasma adiponectin level (r = 0.19, P = 0.004), PAI-1 (r = -0.19, P = 0.020) and IL-6 (r = -0.24, P \u3c 0.001) with measures of insulin sensitivity after adjustment for both fat mass and insulin clamp concentration. In multivariate analysis, adiponectin [geometric mean ratios (GMR) 1.15, P = 0.007], PAI-1 (GMR 0.998, P = 0.021) and body mass index (GMR 0.95, P \u3c 0.001) were each independently associated with insulin sensitivity. For IL-6, there was no significant association with insulin sensitivity independent of obesity. CONCLUSION: These data show a significant and independent positive correlation of adiponectin with insulin sensitivity. The relationship of IL-6 with insulin sensitivity seems to be dependent on adiposity

A Meta-Analysis of the Effects of SGLT-2 Inhibitors on Serum Electrolytes

Introduction: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors affect serum electrolytes levels, especially magnesium. This study aims to integrate direct and indirect trial evidence to evaluate the relative effects of all SGLT2 inhibitors against each other on electrolyte levels in patients with type 2 diabetes (T2D). Methods: Electronic databases were systematically searched through December 2018 to identify eligible randomized controlled trials (RCTs) that reported mean changes in serum electrolyte levels, including magnesium, sodium, potassium, phosphate, calcium, and urate in patients with T2D. Random-effects pairwise and network meta-analyses were performed to calculate the weighted mean difference (WMD) before and after SGLT2 treatment. Results: Twenty-four RCTs involving 17,820 patients with five SGLT2 inhibitors were included. Compared with placebo, SGLT2 inhibitors were significantly associated with elevations in serum magnesium by 0.08 mmol/L and serum phosphate by 0.03 mmol/L, and significantly associated with decreases in serum urate by 37.62 umol/L. Our network meta-analysis showed significant increases in serum magnesium among the patients taking canagliflozin (WMD = 0.08 mmol/L), dapagliflozin (WMD = 0.08 mmol/L), empagliflozin (WMD = 0.06 mmol/L), and ertugliflozin (WMD = 0.06 mmol/L) compared to placebo. No statistically detectable differences were evident between any two of SGLT2 inhibitors. Discussion: SGLT2 inhibitors could significantly increase serum magnesium, indicating a potentially similar class-effect. However, more data for long-term efficacy and safety of raising serum magnesium and phosphate in T2D patients with different clinical phenotypes are needed for further investigation

FC-98 Regulates TLR9-Mediated of CXCL-10 Expression in Dendritic Cells via MAPK and STAT1 Signaling Pathway

Dendritic cells (DCs), as the most potent professional antigen presenting cells, play a crucial role in both innate and adaptive immune systems. Genomic bacterial DNA mimicked by unmethylated CpG motifs is discovered to possess immunostimulatory effects. CpG-DNA recognized by Toll-like receptor 9 (TLR9) on DCs arouses many immune diseases (such as cancer, viral infection, and autoimmune disorders). In this study we investigated the effects of FC-98 on CpG-induced bone marrow-derived DCs (BMDCs). The results showed that FC-98 significantly inhibited the CpG-induced BMDCs maturation and function by suppressing the expression of surface markers (CD40, CD80, CD86, and MHCII). Moreover, FC-98 downregulated the expression of C-X-C motif chemokine 10 (CXCL-10) both at the mRNA and protein level after CpG induction. Meanwhile, FC-98 markedly affected the migration of BMDCs to T cells without affecting their endocytosis capacity. Furthermore, FC-98 was confirmed to decrease CXCL-10 expression by inhibiting CpG-induced activation of MAPKs (ERK, JNK, and p38) and STAT1 signaling. Overall, these results suggested that FC-98 was a potential molecule in the treatment of CXCL-10-mediated immune diseases

Admission blood pressure indexes and risk of in-hospital death and dependency among acute hemorrhagic stroke patients, Inner Mongolia, China

Purpose: To study the association between blood pressure (BP) SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) and clinical outcome in acute hemorrhagic stroke patients in the Chinese population. Methods: 1,760 hemorrhagic stroke patients admitted to six hospitals from January 1, 2003 to December 31, 2005 were included in the study. BP and other variables were collected within the first 24-hr of admission. Clinical outcomes at discharge were evaluated by neurologists. Multivariate-adjusted odds ratios associated with increment of 1 standard deviation (SD) mmHg in four BP were determined by multiple logistic regression analysis. Results: The four BP indexes at admission were positively associated with death and SBP, DBP, MAP were associated with dependency. Adjusted odds ratios (95% confident interval) of death associated with increment of 1 SD mmHg were 1.74 (1.44,2.12), 1.39 (1.15,1.69),1.61 (1.32,1.96) and 1.66 (1.39,1.99) for SBP, DBP, MAP and PP, respectively (all P < 0.01), and adjusted odds ratio of dependency associated with increment of 1 SD mmHg was 1.15 (1.03,1.27), 1.21 (1.09,1.34) and 1.19 (1.07,1.32) for SBP, DBP and MAP, respectively (all P < 0.05). Conclusion: Increased SBP, DBP, MAP and PP at admission were all associated with in-hospital mortality, and increased SBP, DBP and MAP were associated with dependency at discharge among hemorrhagic stroke patients

Application of topical gentamicin ointment in the treatment of Nagashima‐type palmoplantar keratosis in children with a nonsense mutation

ABSTRACT Importance Nagashima‐type palmoplantar keratosis (NPPK) is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7. Despite the increasing interest in readthrough gentamicin treatment of NPPK, clinical evidence for this treatment is limited. Objective This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations. Methods We designed a bilaterally controlled study of topical gentamicin ointment. Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study. A 0.1% gentamicin ointment was applied to one hand and an emollient to the other for 3 months. A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed. Results Ten children with NPPK were included in this study. In comparison with the emollient side, the topical gentamicin side showed significant improvements in hyperkeratosis, erythema, maceration, and desquamation after 1 and 3 months of treatment (P < 0.05). However, hyperhidrosis and odor did not improve significantly. No adverse events were observed during the systemic safety monitoring examinations. Interpretation Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations, indicating that it is a promising therapeutic choice in children with NPPK