Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Investigations into the development of new therapeutic agents for lung inflammatory disorders have led to the discovery of plant-based alternatives. The rhizomes of Anemarrhena asphodeloides have a long history of use against lung inflammatory disorders in traditional herbal medicine. However, the therapeutic potential of this plant material in animal models of lung inflammation has yet to be evaluated. In the present study, we prepared the alcoholic extract and derived the saponin-enriched fraction from the rhizomes of A. asphodeloides and isolated timosaponin A-III, a major constituent. Lung inflammation was induced by intranasal administration of lipopolysaccharide (LPS) to mice, representing an animal model of acute lung injury (ALI). The alcoholic extract (50–200 mg/kg) inhibited the development of ALI. Especially, the oral administration of the saponin-enriched fraction (10–50 mg/kg) potently inhibited the lung inflammatory index. It reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Histological changes in alveolar wall thickness and the number of infiltrated cells of the lung tissue also indicated that the saponin-enriched fraction strongly inhibited lung inflammation. Most importantly, the oral administration of timosaponin A-III at 25–50 mg/kg significantly inhibited the inflammatory markers observed in LPS-induced ALI mice. All these findings, for the first time, provide evidence supporting the effectiveness of A. asphodeloides and its major constituent, timosaponin A-III, in alleviating lung inflammation.
Acute Lung Injury ; Administration, Intranasal ; Administration, Oral ; Alcoholics ; Anemarrhena* ; Animals* ; Bronchoalveolar Lavage Fluid ; Herbal Medicine ; Humans ; Lung* ; Mice ; Models, Animal* ; Plants ; Pneumonia* ; Rhizome*

PURPOSE: Parathyroid hormone (PTH) therapy has drawn attention, as an alternative to anti-resorptive drugs since PTH accelerates bone density by anabolic action. The purpose of this study was to identify the effect of intermittent PTH administration on jaw bones of rat undergone bilateral ovariectomy. MATERIALS AND METHODS: Nine female Sprague-Dawley rats were divided into three groups. PTH group was ovariectomized (OVX) to induce osteoporosis and PTH 30 microg/kg was administered 1 week after the surgery. In OVX group, ovariectomy was performed and only vehicle was administered by subcutaneous injection 3 times per week. Control group was subjected to sham surgery. The animals were sacrificed 8 weeks after the surgery and specimens were obtained from ilium and upper and lower jaw bones. Histological investigation was carried out by using an optical microscope and micro-computed tomography was taken to examine structural property changes in each bone sample. RESULT: In the ilium, the bone volume ratio (bone volume/total volume, BV/TV) of PTH, OVX and control groups was 53.75%+/-7.57%, 50.61%+/-12.89%, 76.20%+/-5.92% (P=0.061) and bone mineral density (BMD) was 1.12+/-0.09, 0.88+/-0.48, 1.38+/-0.07 g/cm3 (P=0.061). In the mandible, BV/TV of PTH, OVX and control groups was 64.60%+/-12.17%, 58.26%+/-9.63%, 67.54%+/-14.74% (P=0.670) and BMD was 1.21+/-0.17, 1.19+/-0.13, 1.27+/-0.18 g/cm3 (P=0.587). In the maxilla, BV/TV of PTH, OVX and control groups was 61.19%+/-8.92%, 52.50%+/-11.22%, 64.60%+/-12.17% (P=0.430) and BMD was 1.20+/-0.11, 1.11+/-0.16, 1.21+/-0.17 g/cm3 (P=0.561). No statistically significant difference was found in any variables in all groups. Histological observation revealed that the ilium in OVX group demonstrated sparsely formed trabecular bones compared with other groups. However, upper and lower trabecular bones did not present significant differences. CONCLUSION: Intermittent administration of PTH appears to affect the microstructure of rat jaw bones, but statistical significance was not found. However, the measurements in this study partly implicated the possible anabolic effect of PTH in vivo.
Anabolic Agents ; Animals ; Bone Density ; Female ; Humans ; Ilium ; Injections, Subcutaneous ; Jaw* ; Mandible ; Maxilla ; Osteoporosis ; Ovariectomy ; Parathyroid Hormone* ; Rats* ; Rats, Sprague-Dawley

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C (50 mug/ml) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolic-related enzymes, and as a result, could improve overall epidermal barrier function.
Ascorbic Acid* ; Calcium ; Epidermis ; Humans ; Hydrolysis ; Keratinocytes ; Serine C-Palmitoyltransferase ; Sphingomyelin Phosphodiesterase ; Vitamins*

BACKGROUND: Because there is no specific treatment for the common cold, many previous studies have focused on prevention of the common cold. There were some studies reporting that regular, moderate-intensity exercise increases immunity and prevents the common cold. We conducted a meta-analysis to determine the effects of exercise on prevention of the common cold. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL for studies released through June 2013. We manually searched the references. Two authors independently extracted the data. To assess the risk of bias of included literature, Cochrane Collaboration's tool for assessing risk of bias was used. Review Manager ver. 5.2 (RevMan, Cochrane Collaboration) was used for statistical analysis. RESULTS: Four randomized controlled trials were identified. A total of 281 participants, 134 in the exercise group and 147 in the control group, were included. The effect of exercise on the prevention of the common cold had a relative risk (RR) of 0.73 (95% confidence interval [CI], 0.56 to 0.95; I2 = 7%). The mean difference of mean illness days between exercise group and control group was -3.50 (95% CI, -6.06 to -0.94; I2 = 93%). In the subgroup analysis, the RR of under 16 weeks exercise was 0.79 (95% CI, 0.58 to 1.08). CONCLUSION: In this meta-analysis, regular, moderate-intensity exercise may have an effect on the prevention of the common cold. But numbers of included studies and participants were too small and quality of included studies was relatively poor. Subsequent well-designed studies with larger sample size are needed to clarify the association.
Bias (Epidemiology) ; Common Cold* ; Sample Size ; Sick Leave

Red ginseng and its extracts have been used as traditional medicines and functional foods in countries worldwide. The aim of this study was to examine the bioavailability of pectin lyase-modified red ginseng extracts (GS-E3D), and the effects of GS-E3D on adipogenesis of 3T3-L1 adipocytes, as well as on metabolic disorders such as hyperglycemia, dyslipidemia, and fatty liver in high-fat diet fed obese C57BL/6 mice. Mice were divided into 5 groups: normal diet group, high fat diet-vehicle group, high fat diet + 0.1 g/kg GS-E3D (0.1-GS-E3D), high fat diet + 0.3 g/kg (0.3-GS-E3D), high fat diet + 1.0 g/kg (1.0-GS-E3D). Treatment of GS-E3D reduced differentiation of 3T3-L1 adipocytes with low cytotoxicity. In the animal model, compared to the high fat diet control, serum glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TG, and leptin level were reduced in treatment animals in a dose-dependent manner. In addition, we found that GS-E3D could decrease total hepatic lipid droplets. These results suggest that GS-E3D, as a dietary supplement, has beneficial effects on obesity and may have useful effects in health-care products.
Adipocytes ; Adipogenesis ; Animals ; Biological Availability ; Blood Glucose ; Cholesterol ; Diet ; Diet, High-Fat ; Dietary Supplements ; Dyslipidemias ; Fatty Liver ; Functional Food ; Hyperglycemia ; Leptin ; Mice ; Mice, Obese* ; Models, Animal ; Obesity ; Panax*

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders in Chinese medicine, especially respiratory inflammation. Previously, a new phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity against several animal models of inflammation, especially against an animal model of acute bronchitis. In the present investigation, the effects of BL on animal models of septic inflammation and chronic bronchitis are examined. Against lipopolysaccharide (LPS)-induced septic inflammation in mice, BL (200-400 mg/kg) reduced the induction of some important proinflammatory cytokines. At 1 h after LPS treatment, BL was found to considerably inhibit TNF-alpha production when measured by cytokine array. At 3 h after LPS treatment, BL inhibited the induction of several proinflammatory cytokines, including IFN-gamma and IL-1beta, although dexamethasone, which was used as a reference, showed a higher inhibitory action on these biomarkers. Against chronic bronchitis induced by LPS/elastase instillation in rats for 4 weeks, BL (200-400 mg/kg/day) significantly inhibited cell recruitment in bronchoalveolar lavage fluid. Furthermore, BL considerably reduced lung injury, as revealed by histological observation. Taken together, these results indicate that BL may have a potential to treat systemic septic inflammation as well as chronic bronchitis.
Animals ; Asian Continental Ancestry Group ; Biomarkers ; Bronchitis ; Bronchitis, Chronic* ; Bronchoalveolar Lavage Fluid ; Broussonetia* ; Cytokines ; Dexamethasone ; Humans ; Inflammation* ; Lonicera* ; Lung Injury ; Mice ; Models, Animal ; Rats ; Tumor Necrosis Factor-alpha

A 17-year-old man was diagnosed as Peutz-Jeghers syndrome (PJS) because of pigmented lip and multiple gastrointestinal polyps. He had anemia and underwent polypectomy on the duodenum and colon. His maternal family members were patients with PJS. His mother used to be screened with endoscopy to remove large polyps. One and half years later, he underwent jejunal segmental resection due to intussusceptions. He underwent endoscopic polypectomy every 2 to 3 years. When he was 23 years old, high-grade dysplasia was found in colonic polyp and his mother underwent partial pancreatectomy due to intraductal papillary mucinous carcinoma. When he was 27 years old, diffuse gastric polyps on the greater curvature of corpus expanded and grew. Therefore, wide endoscopic polypectomy was done. Histological examination revealed focal intramucosal carcinoma and low-grade dysplasia in hamartomatous polyps. We report cases of cancers occurred in first-degree relatives with PJS.
Adenocarcinoma, Mucinous ; Adolescent ; Anemia ; Colon ; Colonic Polyps ; Duodenum ; Endoscopy ; Gastrointestinal Neoplasms ; Humans ; Intussusception ; Lip ; Mothers ; Pancreatectomy ; Pancreatic Neoplasms ; Peutz-Jeghers Syndrome ; Polyps ; Stomach Neoplasms

Perineuriomas are composed of differentiated perineurial cells. Perineuriomas have been recently recognized by the immunoreactivity for epithelial membrane antigen (EMA). Microscopically, perineuriomas show proliferation of spindle cells with wavy nuclei and delicate elongated bipolar cytoplasmic processes. The tumor cells are usually negative for the S-100 protein. Ultrastructurally, perineurial cells reveal slender, nontapered processes containing pinocytic vesicles and discontinuous basal lamina. Interestingly, hybrid tumors of benign peripheral nerve sheath tumor (PNST) have been recently reported by using immunohistochemical and ultrastructural investigations. Herein, we report a case of soft tissue perineurioma arising in the skin of a 56-year-old female; another case of a hybrid tumor of perineurioma and schwannoma in the posterior mediastinum occurred in a 53-year-old male, which is the first case of the hybrid PNST tumor reported in Korea.
Basement Membrane ; Chimera ; Cytoplasm ; Humans ; Korea ; Male ; Mediastinum ; Middle Aged ; Mucin-1 ; Nerve Sheath Neoplasms ; Neurilemmoma ; Peripheral Nerves ; S100 Proteins ; Skin

BACKGROUND: Pathologic examination is a very important diagnostic procedure. It is the most important method to decide the therapeutic plan and to predict the prognosis of cancer patients. The Resource-Based Relative Value Scale (RBRVS) is a schema used to determine how much money medical providers should be paid. In Korea, a modified RBRVS has been used since the year 2000. METHODS: We researched the July 2010 RBRVS for Korea and the US medicare. The individual Relative Evaluation Index (REI) is defined as the ratio of an individual RBRVS to the mean RBRVS. The REIs of pathologic examination in Korea and America were compared. RESULTS: For an endoscopic biopsy specimen, the pathologic examination REI in Korea was 55.4% of the American REI. The Korean REI of a prostate biopsy (8 sites) was only 5.7% of the American REI. The Korean REI was 28.1% of the American REI for the hysterectomy for uterine myoma, and the Korean REI was 67.6% of the American REI for resection of stomach or colon cancer. CONCLUSIONS: The RBRVS of pathologic examination in Korea remains undervalued. Considering the importance of pathologic examination in medicine, the RBRVS in Korea should be increased.
Americas ; Biopsy ; Colon ; Diagnostic Techniques and Procedures ; Humans ; Hysterectomy ; Korea ; Medicare ; Myoma ; Pathology, Surgical ; Prognosis ; Prostate ; Relative Value Scales ; Stomach ; United States