Associations between obesity, weight change and decreased renal function in Korean type 2 diabetic patients: a longitudinal follow-up study.

BACKGROUND: We aimed to examine the associations between the risk of decreased renal function, obesity, and weight changes in Korean type 2 diabetic patients with normal renal function. METHODS: Type 2 diabetic patients (n = 1060) who visited the diabetic clinic at Soonchunhyang University Bucheon Hospital between 2001 and 2007 with follow up surveys completed in 2016 to 2017 were recruited into the study. Decreased renal function was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2. Weight change was calculated between baseline and each follow-up survey. Multivariate analysis was used to evaluate the longitudinal association of baseline obesity and weight changes with the risk of decreased renal function. RESULTS: This study revealed that baseline obesity was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients (odds ratio [OR] 1.40; 95% confidence intervals [CI] 1.08-2.04; p = 0.025). Follow-up (mean = 12 years) revealed that weight gain > 10% was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients with normal renal function at baseline (OR 1.43; CI 1.11-2.00; p = 0.016). Weight loss was not associated with the risk of decreased renal function in type 2 diabetic patients with normal renal function at baseline. CONCLUSIONS: Baseline obesity was associated with the increased risk of decreased renal function in Korean type 2 diabetic patients with normal renal function. Weight gain > 10% independently predicted the risk of decreased renal function. Large prospective studies are needed to clarify causal associations between obesity, weight change, and decreased renal function in patients with type 2 diabetes.

Association between alcohol consumption status and obesity-related comorbidities in men: data from the 2016 Korean community health survey.

BACKGROUND: This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men. METHODS: A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week. RESULTS: Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P < 0.0001), hypertension (OR, 1.76; 95% CI, 1.636 to 1.894; P < 0.0001), and dyslipidemia (OR, 1.356; 95% CI, 1.247 to 1.474; P < 0.0001). In contrast, mild to moderate alcohol consumption was associated with a lower risk of diabetes (OR, 0.799; 95% CI, 0.726 to 0.88; P = 0.0015) and high alcohol consumption was not associated with a higher risk of diabetes (OR, 0.945; 95% CI, 0.86 to 1.039; P = 0.0662). Among drinkers, except for social drinkers, binge drinking was significantly associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia. CONCLUSIONS: High alcohol consumption was associated with higher risks of obesity, hypertension, and dyslipidemia in Korean men. In contrast, high consumption was not associated with a higher risk of diabetes. In particular, binge drinkers were associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia compared to non-binge drinkers.

Anti-inflammatory and Antioxidant Effects of Selenium on Orbital Fibroblasts of Patients With Graves Ophthalmopathy.

PURPOSE: In the present study, the authors investigated the effects of selenium on inflammation, hyaluronan production, and oxidative stress in primary cultured orbital fibroblasts of patients with Graves ophthalmopathy (GO). METHODS: Orbital adipose/connective tissue specimens were obtained during the course of orbital surgery for patients with GO (n = 7) and other noninflammatory problems (n = 5). After incubation with various concentrations of sodium selenite for 48 hours, supernatants from primary cultures were collected. Hyaluronan and cytokine levels were measured using commercially available enzyme-linked immunosorbent assay kits. To determine the effect of selenium on reactive oxygen species (ROS) production stimulated by H2O2 (100 µM) for 30 minutes, the cells were pretreated with various concentrations of sodium selenite for 60 minutes. RESULTS: Interleukin (IL)-6 and tumor necrosis factor-alpha levels were significantly higher in orbital fibroblasts of patients with GO than in orbital fibroblasts of control patients. Hyaluronan production was suppressed by selenium in cultured orbital fibroblasts of patients with GO. Inflammatory cytokines such as IL-1α, IL-8, and tumor necrosis factor-alpha were suppressed by selenium in cultured orbital fibroblasts of patients with GO. IL-1ß and IL-6 were not suppressed by selenium in cultured orbital fibroblasts of patients with GO. Selenium pretreatment reduced intracellular ROS generation stimulated by H2O2 in cultured orbital fibroblasts of patients with GO. CONCLUSIONS: In conclusion, hyaluronan production, inflammatory cytokines, and intracellular ROS generation were suppressed by selenium in cultured orbital fibroblasts of patients with GO. Several inflammatory cytokines may be suppressed by selenium in cultured orbital fibroblasts of patients with GO. This study provide the basis for use of selenium in the treatment of GO.

Inter- and Intra-Molecular Organocatalysis of SN2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis.

We present the intra- and inter-molecular organocatalysis of SN2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular SN2 fluorination of the veratrole substrates are measured to be very small (<1% in 12 h) in the absence of crown ether promoters, whereas the SN2 fluorination of the substrate possessing a crown ether unit proceeds to near completion (~99%) in 12 h. We also studied the efficacy of intermolecular rate acceleration by an independent promoter 18-crown-6 for comparison. We find that the fluorinating yield of a veratrole substrate (leaving group = -OMs) in the presence of 18-crown-6 follows the almost identical kinetic course as that of intramolecular SN2 fluorination, indicating the mechanistic similarity of intra- and inter-molecular organocatalysis of the crown ether for SN2 fluorination. The calculated relative Gibbs free energies of activation for these reactions, in which the crown ether units act as Lewis base promoters for SN2 fluorination, are in excellent agreement with the experimentally measured yields of fluorination. The role of the metal salt CsF is briefly discussed in terms of whether it reacts as a contact ion pair or as a "free" nucleophile F-.

Stimuli-Responsive Conformational Transformation of Peptides for Tunable Cytotoxicity.

The stimuli-responsive conformational transformation of peptides possessing a constrained form triggered by specific biological microenvironment would provide an effective strategy for the development of highly specific peptide therapeutics. Here, we developed a peptide containing a cytotoxic helical KLA sequence with therapeutic specificity through the use of stimuli-responsive conformational transformation. The KLA peptide is modified to form a cyclic structure to allow for constrained helicity that confers low cytotoxicity. The modified KLA peptide is electrostatically complexed to hyaluronic acid to facilitate enhanced endocytosis into the cancer cells. After endocytosis, the peptide is released from the complex into the cellular cytoplasm by hyaluronidases on the surface of the cellular membrane. Specific intracellular stimuli then trigger the release of the strain that suppresses peptide helicity, and the inherent helical conformation of the KLA peptide is restored. Therefore, the stimuli-responsive conformational transformation of a peptide from low to high helicity selectively induces cell death by disruption of the plasma and mitochondrial membrane.

Prognostic value of acoustic structure quantification in patients with Hashimoto's thyroiditis.

OBJECTIVES: Assessment of thyroid parenchymal echogenicity on ultrasonography is a predictor of future thyroid dysfunction. Our objective was to determine the prognostic value of acoustic structure quantification (ASQ) to predict the outcome of patients with Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: We prospectively evaluated 90 patients with HT using ASQ from May to December 2013. Surveillance for the development of overt hypothyroidism was conducted over a median period of 40 months (3-55). ASQ were dichotomized based on optimal cutoff values obtained from ROC curve analysis. The probability of developing overt hypothyroidism was compared between the dichotomized subgroups using Kaplan-Meier analysis and log-rank tests. Multivariate Cox regression analysis was performed to determine significant prognostic factors. RESULTS: The cumulative rate of overt hypothyroidism was 67.7%. The median interval to overt hypothyroidism was 27.9 months (95% confidence interval, 12.0-38.0 months). There was no significant difference in the risk of overt hypothyroidism using qualitative echogenicity between groups (p = 0.669) according to Kaplan-Meier analysis. However, the ASQ average (p < 0.001), standard deviation (p = 0.015), and focal disturbance ratio (p < 0.001) were significantly associated with an increased risk of overt hypothyroidism. Multivariate Cox regression analysis revealed that a higher ASQ average (hazard ratio, 1.03; p = 0.03) and higher thyroid-stimulating hormone level (hazard ratio, 1.02; p = 0.02) were independent predictors of overt hypothyroidism. CONCLUSIONS: ASQ has potential as a prognostic biomarker for predicting the risk of overt hypothyroidism in patients with HT. KEY POINTS: • ASQ provides quantitative prognostic information of thyroid parenchymal echogenicity. • ASQ parameters improved the stratification of patients who are prone to develop overt hypothyroidism in HT. • ASQ can serve as prognostic biomarker in HT.

Mesoporous Silica Nanocarriers with Cyclic Peptide Gatekeeper: Specific Targeting of Aminopeptidase†N and Triggered Drug Release by Stimuli-Responsive Conformational Transformation.

Utilizing stimuli-responsive conformational transformation of a cyclic peptide as a gatekeeper for mesoporous nanocarriers has several advantages such as facile introduction of targeting capabilities, low enzymatic degradation during blood circulation and enhanced specific binding to selected cells. In this report, a Asn-Gly-Arg (NGR)-containing dual-functional cyclic peptide gatekeeper on the surface of mesoporous nanocarrier is prepared not only for active targeting of the aminopeptidase N (APN) expressed on cancer cells but also stimuli-responsive intracellular drug release triggered by a glutathione (GSH)-induced conformational transformation of the peptide gatekeeper. The peptide gatekeeper on the surface of nanocarriers exhibits on-off gatekeeping by conformational transformation triggered by intracellular glutathione of the cancer cells. H1299 cells (high APN expression) showed greater uptake of the nanocarrier by endocytosis and higher apoptosis than A549 cells (low APN expression).

Nanotubular self-organization of amide dendrons with focal ß-sheet forming peptide units.

To develop rational design principles for a self-organized structure using dendron-peptide conjugates, a ß-sheet forming short peptide (VVLL) was introduced to the focal point of a second-generation amide dendron (2G-VVLL) and its self-organization characteristics were investigated. 2G-VVLL self-organized into a nanotubular structure in the aqueous phase. The twisted ß-sheet structure of the focal peptide unit was essential for the construction of the nanotubular structure. The design principle could be applied to another dendron-peptide conjugate (2G-AAVV). These findings are expected to assist in the construction of novel precisely controlled nanoarchitectures using amide dendrons with focal peptide units.

Investigation of Acoustic Structure Quantification in the Diagnosis of Thyroiditis.

OBJECTIVE: The objective of this study was to evaluate the ability of acoustic structure quantification (ASQ) to diagnose thyroiditis. MATERIALS AND METHODS: The echogenicity of 439 thyroid lobes, as determined using ASQ, was quantified and analyzed retrospectively. Thyroiditis was categorized into five subgroups. The results were presented in a modified chi-square histogram as the mode, average, ratio, blue mode, and blue average. We determined the cutoff values of ASQ from ROC analysis to detect and differentiate thyroiditis from a normal thyroid gland. We obtained data on the sensitivity and specificity of the cutoff values to distinguish between euthyroid patients with thyroiditis and patients with a normal thyroid gland. RESULTS: The mean ASQ values for patients with thyroiditis were statistically significantly greater than those for patients with a normal thyroid gland (p < 0.001). The AUCs were as follows: 0.93 for the ratio, 0.91 for the average, 0.90 for the blue average, 0.87 for the mode, and 0.87 for the blue mode. For the diagnosis of thyroiditis, the cutoff values were greater than 0.27 for the ratio, greater than 116.7 for the mean, and greater than 130.7 for the blue average. The sensitivities and specificities were as follows: 84.0% and 96.6% for the ratio, 85.3% and 83.0%, for the average, and 79.1% and 93.2% for the blue average, respectively. The ASQ parameters were successful in distinguishing patients with thyroiditis from patients with a normal thyroid gland, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average. With the use of the aforementioned cutoff values, the sensitivities and specificities for distinguishing between patients with thyroiditis and euthyroid patients without thyroiditis were 77.05% and 94.92% for the ratio, 85.25% and 82.20% for the average, and 77.05% and 92.37% for the blue average, respectively. CONCLUSION: ASQ can provide objective and quantitative analysis of thyroid echogenicity. ASQ parameters were successful in distinguishing between patients with thyroiditis and individuals without thyroiditis, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average.

The relationship between serum adipocytokines and Graves' ophthalmopathy: A hospital-based study.

Adipocytokines are thought to be associated with inflammatory disorders and autoimmune diseases. However, limited information is available on the relationship between serum adipocytokine levels, Graves' disease (GD), and Graves' ophthalmopathy (GO). The present study examined the relationship between serum adipocytokine levels and GD and GO. A total of 80 patients with GD participated in this study. The medical records of patients were reviewed retrospectively. GO activity was assessed using the clinical activity score (CAS). GO severity was assessed by the modified NOSPECS classification and included soft tissue involvement, proptosis, and extraocular muscle involvement. Serum adiponectin, leptin, resistin, and retinol-binding protein 4 (RBP-4) levels were measured using commercially available enzyme-linked immunosorbent assays. The prevalence of GO was 36.3%. Serum adiponectin, leptin, and resistin levels were significantly higher in patients with GO than in those without GO. The CAS was positively correlated with serum adiponectin and leptin levels. The total eye score was positively correlated with serum adiponectin, leptin, resistin, and RBP-4 levels. A multivariate analysis revealed that serum leptin and resistin levels were associated with the presence of GO after adjusting for clinical factors. Free thyroxine was negatively correlated with serum leptin level. These results suggest that adipocytokines, such as leptin and resistin, may play a role in inflammatory and autoimmune processes of GD and GO. Future studies with larger numbers of patients are required to establish relationships between serum adipocytokines levels and GO and ascertain the role of adipocytokines in GD and GO.