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Background: Statin-associated muscle symptoms are one of the side effects that physicians should consider when prescribing statins. In this study, creatine kinase (CK) levels were measured following statin prescription, and various factors affecting the CK levels were determined using machine learning.Methods: Changes in the CK were observed every 3 months for a 12-month period in patients who received statins for the first time at Seoul St. Mary's Hospital. For each visit, we developed four basic models based on changes in the CK levels. Extreme gradient boosting, a scalable end-to-end tree boosting algorithm, which employs a decision-tree-based ensemble machine learning algorithm, was used for the prediction of changes in the CK.Results: A total of 23,860 patients were included. Among them, 19 patients (0.08%) had increased CK levels of 2,000 IU·L−1 or more 3 months after statin prescription, and 65 patients (0.27%) exhibited CK levels of over 2,000 IU·L−1 at least once during the 12-month study period. The area under the receiver operator characteristic of each model for each visit was 0.709–0.769, and the accuracy was 0.700–0.803. In each of the models, the variables that had the strongest influence on changes in the CK were sex and previous CK value.Conclusions: Through machine learning, factors influencing changes in the CK were identified. These results will provide the basis for future research, through which the optimal parameters of the CK prediction model can be found and the model can be used in clinical applications.

Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

Background: While randomized controlled trials provide useful information about drug safety and efficacy, they do not always reflect the observed results in the real world. The prospective, observational, non-comparative trial in South Korea was designed to evaluate the efficacy and safety of pitavastatin in clinical practice in 28,343 patients.Methods: This study was conducted in 893 facilities in Korea from April 2, 2012 to April 1, 2017. This study was designed to administer 1, 2, or 4 mg pitavastatin to patients with hyperlipidemia at the age of 20 or older for at least 8 weeks.Results: For 126 days of mean duration of administration of pitavastatin, the % change of low density lipoprotein cholesterol indicated a dose dependent reduction: –23.4%, –29.1%, and –35.2% in the 1, 2, and 4 mg groups, respectively in patients who have not been treated with lipid lowering medications prior to study. Only 1.74% (492/28,343) of pitavastatin-treated patients experienced adverse events, of which 0.43% (123/28,343) were adverse drug reactions. Less than 1% of patients experienced the grade 2 or more toxicity (Common Terminology Criteria for Adverse Events v4.03) in alanine aminotransferase, aspartate aminotransferase, serum creatinine, and serum creatine phosphokinase. Although there were no rhabdomyolysis in 28,343 patients, 0.04% of patients had been reported pitavastatin-related musculoskeletal disorders.Conclusion: Overall, this observational study showed that pitavastatin was well tolerated and effectively modified the lipid profile, reducing cardiovascular and cerebrovascular risk in Korean patients with hypercholesterolemia in the real world.

Background: Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea. METHODS: Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities. RESULTS: Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.

The objective of this study was to evaluate the efficacy and safety of gemigliptin added to a stable dose of insulin alone or of insulin in combination with metformin in patients with type 2 diabetes mellitus. After a two-week run-in period, patients were randomized 2:1 to receive gemigliptin 50 mg or placebo once daily as add-on to background therapy with insulin or insulin plus metformin for 24 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline at Week 24. Baseline characteristics were similar between the gemigliptin (n = 188) and placebo (n = 95) groups in terms of HbA1c (8.1%). At Week 24, the gemigliptin group showed a statistically significant reduction in mean HbA1c from baseline as compared with placebo (between-group mean difference, -0.7% [95% CI, -0.9% to -0.4%]; P-value < 0.0001). The incidence of overall adverse events and the number of hypoglycaemic adverse events were similar between the study groups. Gemigliptin added to insulin alone or to insulin in combination with metformin resulted in superior glycaemic control compared to that in the placebo group and was well tolerated for 24 weeks in patients with type 2 diabetes mellitus, without causing weight gain or increasing the incidence of hypoglycaemia.

Background: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and

Many Brassica species require vernalization (long-term winter-like cooling) for transition to the reproductive stage. In the past several decades, scientific efforts have been made to discern the molecular mechanisms underlying vernalization in many species. Thus, to identify the key regulators required for vernalization in Brassica rapa L., we constructed a linkage map composed of 7,833 single nucleotide polymorphism (SNP) markers using the late-flowering Chinese cabbage (B. rapa L. ssp. pekinensis) inbred line ‘Chiifu’ and the early-flowering yellow sarson (B. rapa L. ssp. trilocularis (Roxb.)) line ‘LP08’ and identified a single major QTL on the upper-arm of the chromosome A02. In addition, we compared the transcriptomes of the lines ‘Chiifu’ and ‘LP08’ at five vernalization time points, including both non-vernalized and post-vernalization conditions. We observed that BrFLC2 was significantly downregulated in the early flowering ‘LP08’ and had two deletion sites around the BrFLC2 genomic region compared with the BrFLC2 genomic region in ‘Chiifu.’ In the present study, we also demonstrate that early flowering in ‘LP08’ line is attributed to the low expression of BrFLC2, which is caused by nonsense-mediated mRNA decay (NMD). Therefore, this study provides a better understanding of the molecular mechanisms underlying floral transition in B. rapa.One sentence summaryNMD-mediated degradation of BrFLC2 mRNA transcripts is the main cause of rapid flowering of oilseed-type B. rapa ‘LP08’ plants.

Ethnopharmacological relevance Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. Aim of the study In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). Materials and methods A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. Results The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. Conclusion AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.

Background This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of

Objectives: To determine the prevalence and clinical characteristics of diabetic peripheral neuropathy in patients with type 2 diabetes in Korea. Methods: From the National Health Information database maintained by the Korean National Health Insurance Service (NHIS) a representative sample cohort of 1,201,208 participants was randomly selected, comprising 2.2% of the total eligible Korean population in 2006, and followed until 2015. Data source: NHIS-NSC: National Health Insurance Service-National Sample Cohort. Results: The annual prevalence of DPN increased from 24.5% in 2006 to 26.3% in 2007 and thereafter it tended to gradually decrease to 21.2% in 2015. DPN medication was administered in 68% to 69% of DPN patients. Drug therapy was prescribed for up to 90% mono therapy, dual combination treatment for up to 10%, and triple combination treatment for up to 1%. Prescribed medications for DPN from 2006 to 2015 were α-lipoic acid (54.7% to 43.2%), anticonvulsant drugs (21.7% to 36.8%), tricyclic antidepressants (21.3% to 12.6%), serotonin-norepinephrine reuptake inhibitors (0.3% to 5.5%), γ-linoleic acid (2.3% to 1.9%). Persistency for pharmacological treatment of DPN was 30.0%- 48.5%, and the rate of persistency was increasing over time. The incidence of lower-extremity amputation was greater in patients with DPN compared with those without and the incidence has been gradually increasing through the follow-up period. Conclusion: The prevalence of DPN patients is about a quarter of those with diabetes, and medication is about 70 percent, and most medications are administered with mono therapy. Disclosure C. Kim: None. T. Park: None. S. Moon: None. S. Kim: None. K. Lee: None.

Amyloid plaque is a product of aggregation of β-amyloid peptide (Aβ) and is an important factor in the pathogenesis of Alzheimer’s Disease (AD). Aβ is a major component of amyloid plaque and vascular deposits in the AD brain. The enzyme β- secretase is required for the production of Aβ; thus, prevention of the formation of Aβ through the inhibition of β-secretase is a major focus in the study of the treatment of AD. In this study, we investigated β-secretase inhibitory activity of an Arctoscopus japonicus peptide. An Alcalase hydrolysate had the highest β-secretase inhibitory activity. A β-secretase inhibitory activity peptide was separated using ion exchange column chromatography (carboxy-methyl: CM, quaternary methyl ammonium: QMA) and reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column. The IC50 value of the purified peptide was 248.2±1.73 μg/mL. The β-secretase inhibitory peptide was identified as a six amino acid residue of Gly-Pro-Val-Gly-Ala- Pro (MW: 497.27 Da). In cell viability experiments, the final purified fraction, the carboxy-methyl ion exchange column fraction (CM-F1) showed no significant cytotoxic effect in SH-SY5Y cells at concentrations below 100 μg/mL in 24 h. The results of this study suggest that peptides separated from Arctoscopus japonicus may be beneficial as β-secretase inhibitor compounds in functional foods.

Background: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naive newly-diagnosed type 2 diabetes mellitus. Methods: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was mea sured at week 24. Results: The reduction in the levels of HbA1c was -1.62%±0.07% in the vogmet group and -1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of

Aims To evaluate the association between impaired heart rate variability (HRV) and cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). Methods A total of 655 patients with T2DM who underwent cardiovascular autonomic function testing were consecutively recruited and followed up prospectively. Time- and frequency-domain HRV were assessed for 5 min by beat-to-beat heart rate recording. We estimated the development of CVD events during a follow-up period. Results During a median follow-up of 7.8 years, 9.6% (n = 49) of patients developed CVD (10.6 per 1000 patient-years). The mean age and diabetes duration were 54.9 ± 8.6 years and 9.4 ± 7.3 years, respectively. Patients who had cardiovascular autonomic neuropathy (CAN) had decreased HRV compared with those with normal autonomic function. Multivariable cox hazard regression analysis revealed the lowest 10th percentile of the SD of the normal-to-normal interval (HR 2.62; 95% CI 1.30–5.31), total power (HR 2.81; 95% CI 1.37–5.79), low-frequency power (HR 2.68; 95% CI 1.28–5.59), and high-frequency power (HR 2.24; 95% CI 1.09–4.59) were significant predictors for developing CVD in patients with T2DM. Conclusions Time- and frequency-domain measures of HRV independently predicted cardiovascular outcome in patients with T2DM.

Background Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle. Methods Male 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls. Results At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5′-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats. Conclusions ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance.

Objective Poly(lactide-co-glycolide) (PLGA) nanoparticles are promising materials for the development of new drug-releasing systems. The purpose of this study was to evaluate the in vivo retention time of materials loaded in nanoparticles as compared with that of the material alone by in vivo imaging in nude mice. Materials and Methods Mice (n = 20) were injected with 0.1 mL fluorescent material 1,1'-dioctadecyl-3,3,3',3' tetramethylindotricarbocyanine iodide (DiR)-loaded PLGA nanoparticles (200 nm) into the right paraspinal muscle, and the same volume of pure DiR solution was injected into the left paraspinal muscle. Fluorescence images were obtained using an in vivo optical imaging system. Fluorescent images were taken 1 day after the injection, and seven more images were taken at 1-week intervals. Image analysis was done with ImageJ program, and one region of interest was chosen manually, which corresponded to the highest signal-intensity area of fluorescence signal intensity. Results After 7 weeks, 12 mice showed a right-sided dominant signal, representing the DiR loaded PLGA nanoparticles; 5 mice showed a left-side dominant signal, representing the free DiR solution; and 3 mice showed no signal at all beginning 1 day after the injection. During the 7-week period, the mean signal intensities of the free DiR solution and DiR-loaded PLGA nanoparticles diverged gradually. On day 1, the mean signal intensity of free DiR solution was significantly higher than that of DiR-loaded PLGA (p < 0.001). Finally, by week 7, DiR-loaded PLGA express significantly high signal intensity compared with free DiR solution (p = 0.031). Conclusion The results of the current study suggested that therapeutic agents bound to PLGA nanoparticles may exhibit prolonged retention times.

Background This report presents the recent prevalence and comorbidities related to diabetes in Korea by analyzing the nationally representative data. Methods Using data from the Korea National Health and Nutrition Examination Survey for 2013 to 2014, the percentages and the total number of subjects over the age of 30 years with diabetes and prediabetes were estimated and applied to the National Population Census in 2014. Diagnosis of diabetes was based on fasting plasma glucose (≥126 mg/dL), current taking of antidiabetic medication, history of previous diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. Impaired fasting glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125 mg/dL among those without diabetes. Results About 4.8 million (13.7%) Korean adults (≥30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults had IFG. However, 29.3% of the subjects with diabetes are not aware of their condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most subjects with diabetes (89.1%) were under medical treatment, and mostly being treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated. With respect to overall glycemic control, 43.5% reached the target of HbA1c

Background: We evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data. Methods: We collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hos pitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic mod el assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels

Intra-articular (IA) administration of therapeutic agents has been employed to selectively deliver active compounds at their site of action for the treatment of chronic joint diseases such as osteoarthritis, rheumatoid arthritis, and joint pain. Direct IA delivery of active compounds to local tissues occasionally provides improved therapeutic outcomes with reduced dose, while minimizing systemic exposure and undesirable adverse effects. However, many small drugs (

To develop a single-shot vaccine containing diphtheria toxoid (DT) with a sufficient immune response, poly(lactide-co-glycolide) (PLGA) microspheres were prepared by water-in-oil-in-water double emulsification and solvent extraction techniques using low or high-molecular-weight PLGA (LMW-MS or HMW-MS). Stearic acid (SA) was introduced to HMW-MS (HMW/SA-MS) as a release modulator. Mean particle sizes (dvs, μm) varied between the prepared microspheres, with LMW-MS, HMW-MS, and HMW/SA-MS having the sizes of 29.83, 110.59, and 69.5 μm, respectively; however, the protein entrapment and loading efficiency did not vary, with values of 15.2-16.8 μg/mg and 61-75%, respectively. LMW-MS showed slower initial release (~ 2 weeks) but faster and higher release of antigen during weeks 3~7 than did HMW-MS. HMW/SA-MS showed rapid initial release followed by a continuous release over an extended period of time (~ 12 weeks). Mixed PLGA microspheres (MIX-MS), a combination of HMW/SA-MS and LMW-MS (1:1), demonstrated a sufficient initial antigen release and a subsequent boost release in a pulsatile manner. Serum antibody levels were measured by ELISA after DT immunization of Balb/c mice, and showed a greater response to MIX-MS than to alum-adsorbed DT (control). A lethal toxin challenge test with MIX-MS (a DT dose of 18 Lf) using Balb/c mice revealed complete protection, indicating a good candidate delivery system for a single-shot immunization.

// Dong Woo Yeom 1, * , Bo Ram Chae 1, 2, * , Jin Han Kim 1 , Jun Soo Chae 1 , Dong Jun Shin 1 , Chang Hyun Kim 1 , Sung Rae Kim 1 , Ji Ho Choi 1 , Seh Hyon Song 2 , Dongho Oh 2 , Se Il Sohn 2 and Young Wook Choi 1 1 College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea 2 Daewon Pharm. Co., Ltd, Seoul 04994, Republic of Korea * These authors have contributed equally to this work Correspondence to: Young Wook Choi, email: ywchoi@cau.ac.kr Keywords: valsartan; SMEDDS; solid carrier; tablet; optimization Received: June 27, 2017 Accepted: September 20, 2017 Published: October 09, 2017 ABSTRACT In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul ® MCM (13.2 mg), Tween ® 80 (59.2 mg), Transcutol ® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite ® PS-10 (119.1 mg) and Vivapur ® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of

Background and aims To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. Materials and methods In this randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase III study, 160 patients with T2D were assigned to either an evogliptin 5 mg or placebo group for 24 weeks. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) from baseline to week 24. Results The mean baseline HbA1c levels were similar between the evogliptin and the placebo groups (7.20 ± 0.56 vs. 7.20 ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared to placebo (−0.23 vs. 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c < 6.5% was significantly higher in the evogliptin group than that in the placebo group (33.3 vs. 15.2%, respectively, P = .008). The overall incidence of adverse events, including hypoglycemia, was similar between the two groups. Conclusions In this 24-week study, once daily evogliptin monotherapy significantly improved glycemic control and was well tolerated in patients with T2D.

We studied the ultrasonic effect on the leaching of copper from poorly soluble chalcopyrite (CuFeS2) mineral in aqueous FeCl3 solution. The leaching experiment employed two methods, basic leaching and ultrasonic-assisted leaching, and was conducted under the optimized experimental conditions: a slurry density of 20 g/L in 0.1M FeCl3 reactant in a solution of 0.1M HCl, with an agitation speed of 500 rpm and in the temperature range of 50 to 99 °C. The maximum yield obtained from the optimized basic leaching was 77%, and ultrasonic-assisted leaching increased the maximum copper recovery to 87% under the same conditions of basic leaching. In terms of the leaching mechanism, the overall reaction rate of basic leaching is determined by the diffusion of both the product and ash layers based on a shrinking core model with a constant spherical particle; however, in the case of ultrasonic-assisted leaching, the leaching rate is determined by diffusion of the ash layer only by the removal of sulfur adsorbed on the surface of chalcopyrite mineral.

The aim of this study was to determine an appropriate index for age-related sarcopenia and sarcopenic obesity (SO) and investigate relationships among sarcopenia, insulin resistance and risk of type 2 diabetes. Our analyses included 1285 men and 1724 women who had complete data available for body composition analysis and the 75 g oral glucose tolerance test. A whole-body DXA scan was performed for each patient to measure the total and regional lean mass (kg), the total body fat (kg), and the total body fat percentage (%). The appendicular skeletal muscle mass ASM (kg) was defined as the sum of the lean mass of the arms and legs. Sarcopenia was assessed by the ASM/height2, or the ASM/weight (%). Obesity was identified based on the total body fat percentage or the BMI. The mean ages of men and women were 62.8 ± 8.4 years and 63.3 ± 8.6 years, respectively. As measured using the ASM/Ht2, the cut-off values for sarcopenia were 6.61 kg/m2 in men and 4.25 kg/m2 in women. For the ASM/Wt %, the cut-offs were 30.1% in men and 23.4% in women. ASM/weight, but not ASM/height2, was inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR). The prevalence of sarcopenia and SO, defined as ASM/weight less than the one standard deviation below the sex-specific normal mean of a younger reference group and a BMI of over 25 kg/m2, tended to be higher with increased HOMA-IR tertile. Compared to either sarcopenia or obesity alone, SO was associated with a higher risk of developing type 2 diabetes (P < 0.001, OR = 4.23, 95% CI = 2.08-8.99) in those 60 years or older after adjusting for confounding factors. Subjects with sarcopenia were at especially high risk of newly diagnosed diabetes in older age groups (P < 0.001, OR = 2.92, 95% CI = 1.21-7.02). Sarcopenia and SO, assessed by the ASM/weight and BMI, were strongly associated with the degree of insulin resistance and the risk of developing type 2 diabetes in older adults.