Junctional membrane inositol 1,4,5-trisphosphate receptor complex coordinates sensitization of the silent EGF-induced Ca2+ signaling

Ca2+ is a highly versatile intracellular signal that regulates many different cellular processes, and cells have developed mechanisms to have exquisite control over Ca2+ signaling. Epidermal growth factor (EGF), which fails to mobilize intracellular Ca2+ when administrated alone, becomes capable of evoking [Ca2+]i increase and exocytosis after bradykinin (BK) stimulation in chromaffin cells. Here, we provide evidence that this sensitization process is coordinated by a macromolecular signaling complex comprised of inositol 1,4,5-trisphosphate receptor type I (IP3R1), cAMP-dependent protein kinase (PKA), EGF receptor (EGFR), and an A-kinase anchoring protein, yotiao. The IP3R complex functions as a focal point to promote Ca2+ release in two ways: (1) it facilitates PKA-dependent phosphorylation of IP3R1 in response to BK-induced elevation of cAMP, and (2) it couples the plasmalemmal EGFR with IP3R1 at the Ca2+ store located juxtaposed to the plasma membrane. Our study illustrates how the junctional membrane IP3R complex connects different signaling pathways to define the fidelity and specificity of Ca2+ signaling

Efficacy and safety of ginsam, a vinegar extract from Panax ginseng, in type 2 diabetic patients: Results of a double‐blind, placebo‐controlled study

Abstract Aims/Introduction: The efficacy, dose–response relationship and safety of ginsam, a vinegar extract from Panax ginseng, were evaluated in an 8‐week, double‐blind, randomized, placebo‐controlled study in drug‐naïve patients with type 2 diabetes. Materials and Methods: A total of 72 diabetic patients were randomized to receive 1500, 2000 or 3000 mg of ginsam, or placebo daily for 8 weeks (n = 18 in each group). The primary end‐point was the changes from the baseline HbA1c level. The secondary end‐points were the changes of fasting and postprandial 2‐h glucose concentration, and the proportion of patients achieving a reduction in HbA1c >0.5%. Results: In the intention‐to‐treat analysis, ginsam treatment reduced HbA1c level significantly: −0.56 ± 0.25% in the 1500 mg group, −0.31 ± 0.12% in the 2000 mg group, and −0.29 ± 0.11% in the 3000 mg group (all P 0.5% differed significantly between the placebo group (11.1%) and the 1500 mg (27.8%) and 2000 mg (27.8%) groups. No severe adverse events were observed in any group. Conclusions: An 8‐week treatment with ginsam, a vinegar extract from P. ginseng, moderately improved HbA1c level and was well tolerated in type 2 diabetic patients with inadequate glycemic control. This trial was registered with ClinicalTrial.Gov (no. NCT01008163). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00185.x, 2011

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

BACKGROUND: Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. METHODS AND FINDINGS: As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. CONCLUSIONS: Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution

Efficacy of selenium supplementation for mild-to-moderate Graves ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial

Background The therapeutic effect of selenium has been demonstrated in mild Graves ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea. Methods The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3months, clinical activity of GO at 3 and 6months, thyroid autoantibody titers at 3 and 6months, and the response rate at 3 and 6months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6. Discussion The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO.

Recommendation for the use of newly introduced Tdap vaccine in Korea

Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL™ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX® (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society