Sunggyu Kim

Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes

Aim:  The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy.

A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a common and serious regimen-related toxicity after hematopoietic stem cell transplantation (HSCT). There is no safe and proven therapy for established VOD, and focus has been on its prevention. Previous studies have shown that a continuous infusion of unfractionated heparin or ursodiol may reduce the incidence of VOD. In order to compare the efficacy of heparin plus ursodiol with that of heparin alone, we conducted a prospective, randomized study involving 165 consecutive patients who underwent HSCT for a variety of disorders. Eighty-two patients were assigned to receive heparin plus ursodiol, and 83 were assigned to receive heparin alone. Thirteen and 16 patients were diagnosed as having VOD in the heparin plus ursodiol group and the heparin alone group, respectively (15.9% vs 19.3%; P = 0.348). Eighty-nine percent of the heparin plus ursodiol group and 89.2% of the heparin alone group were surviving at day 100 post-HSCT (P = 0.298). The only independent variable associated with an increased risk of VOD was an allogeneic type of HSCT (P = 0.018). In conclusion, this study shows that there is no difference in efficacy between heparin plus ursodiol and heparin alone for the prevention of hepatic VOD.Bone Marrow Transplantation (2002) 29, 137–143. doi:10.1038/sj.bmt.1703342

Relationship between body composition and bone mineral density (BMD) in perimenopausal Korean women

Objectives  Osteoporosis is a disease that increases the fracture rates and it is the major cause of increased mortality and morbidity in the elderly people. To determine which component of body composition is most important to bone health, we analysed the relationship between elements of the body composition and bone mineral density (BMD) in Korean women.

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Summary:Cytokines including IL-6 and TNF-α play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-α levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-α levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD ⩾grade II had higher lumbar bone loss than patients with GVHD <grade I. In conclusion, immunosuppressants, GVHD occurrence and increase in bone-resorbing cytokines in the early post-BMT period were associated with later bone loss after BMT. Further studies are needed to elucidate the precise mechanism.

A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes

Aim: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase‐4 (DPP‐IV) inhibitor, LC15‐0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise.

Efficacy and safety of the dipeptidyl peptidase‐4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone

This study was designed to assess the efficacy and safety of a dipeptidyl peptidase‐4 inhibitor, gemigliptin versus sitagliptin added to metformin in patients with type 2 diabetes.

Serum 1,5-anhydroglucitol is associated with diabetic retinopathy in Type 2 diabetes

Diabet. Med. 29, 1184‐1190 (2012)

The role of serum adipocyte fatty acid-binding protein on the development of metabolic syndrome is independent of pro-inflammatory cytokines

BACKGROUND AND AIM Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults. METHODS AND RESULTS A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P<0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P<0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P<0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P<0.001) CONCLUSION Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation.

Summary:The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T3 decreased to a nadir 3 weeks post-BMT and serum T4 was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-α increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T3 and T4 levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T4 at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-α were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

Src/Syk/IRAK1-targeted anti-inflammatory action of Torreya nucifera butanol fraction in lipopolysaccharide-activated RAW264.7 cells

ETHNOPHARMACOLOGICAL RELEVANCE Seed of Torreya nucifera (L.) Siebold & Zucc is used to treat several diseases in Asia. Reports document that T. nucifera has anti-cancer, anti-inflammatory, anti-oxidative activities. In spite of numerous findings on its pharmacological effects, the understanding of the molecular inhibitory mechanisms of the plant remains to be studied. Therefore, we aimed to explore in vitro anti-inflammatory mechanisms of ethyl acetate fraction (Tn-EE-BF) prepared from the seed of T. nucifera in LPS-stimulated macrophage inflammatory responses. MATERIALS AND METHODS For this purpose, we measured nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated macrophages. Additionally, using RT-PCR, luciferase reporter gene assay, immunoblotting analysis, and kinase assay, the levels of inflammatory genes, transcription factors, and inflammatory signal-regulatory proteins were investigated. Finally, the constituent of Tn-EE-BF was identified using HPLC. RESULTS Tn-EE-BF inhibits NO and PGE2 production and also blocks mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in a dose dependent manner. Tn-EE-BF reduces nuclear levels of the transcriptional factors NF-κB (p65) and AP-1 (c-Jun and FRA-1). Surprisingly, we found that Tn-EE-BF inhibits phosphorylation levels of Src and Syk in the NF-κB pathway, as well as, IRAK1 at the protein level, part of the AP-1 pathway. By kinase assay, we confirmed that Src, Syk, and IRAK1 are suppressed directly. HPLC analysis indicates that arctigenin, amentoflavone, and quercetin may be active components with anti-inflammatory activities. CONCLUSION Tn-EE-BF exhibits anti-inflammatory activities by direct inhibition of Src/Syk/NF-κB and IRAK1/AP-1.