Adiponectin is Associated with Impaired Fasting Glucose in the Non-Diabetic Population

OBJECTIVES: Adiponectin is strongly associated with diabetes in the Western population. However, whether adiponectin is independently associated with impaired fasting glucose (IFG) in the non-obese population is unknown. METHODS: The serum adiponectin, insulin resistance (IR), and waist circumference (WC) of 27,549 healthy Koreans were measured. Individuals were then classified into tertile groups by gender. IFG was defined as a fasting serum glucose of 100-125 mg/dL without diabetes. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The association of adiponectin and IFG was determined using logistic regression analysis. RESULTS: WC and adiponectin were associated with IFG in both men and women. However, the association of WC with IFG was attenuated in both men and women after adjustment for the HOMA-IR. Adiponectin was still associated with IFG after adjustment for and stratification by HOMA-IR in men and women. Strong combined associations of IR and adiponectin with IFG were observed in men and women. Multivariate adjusted odds ratios (ORs) (95% confidence interval [CI]) among those in the highest tertile of IR and the lowest tertile of adiponectin were 9.8 (7.96 to 12.07) for men and 24.1 (13.86 to 41.94) for women. CONCLUSION: These results suggest that adiponectin is strongly associated with IFG, and point to adiponectin as an additional diagnostic biomarker of IFG in the non-diabetic population.ope

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation

Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day

In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

<p>Abstract</p> <p>Background</p> <p><it>Alpinia katsumadai </it>(AK) extracts and fractions were tested for <it>in vitro </it>antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1) and avian A/Chicken/Korea/MS96/96 (H9N2), by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment.</p> <p>Results</p> <p>In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). The 50% effective inhibitory concentrations (EC₅₀) of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 <it>μ</it>g/mL against A/PR/8/34 (H1N1). The two AK extracts and three AK fractions had EC₅₀values ranging from <0.39 ± 0.4 to 2.3 ± 3.6 <it>μ</it>g/mL against A/Chicken/Korea/MS96/96 (H9N2). By the hemagglutination inhibition (HI) assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 <it>μ</it>g/mL against both A/PR/8/34 (H1N1) and A/Chicken/Korea/MS96/96 (H9N2). Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR.</p> <p>Conclusions</p> <p>These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis.</p

Comparative effectiveness and safety of concomitant treatment with Chuna Manual Therapy and usual care for whiplash injuries: a multicenter randomized controlled trial

Objectives: We aimed to compare the effectiveness and safety of Chuna manual therapy combined with usual care to those of usual care alone for treating whiplash injuries. Design: A two-arm, parallel, assessor-blinded, multicenter pragmatic randomized clinical trial. Setting: Three hospitals in Korea. Participants: Overall, 132 participants between 19 and 70 years of age, involved in traffic accidents and treated at three hospitals in Korea, >2 but <13 weeks prior to enrollment, with neck pain consistent with whiplash-associated disorder grades I and II and a numeric rating scale score ≥5 were included. Interventions: Participants were equally and randomly allocated to the Chuna manual therapy and usual care (n = 66) or usual care (n = 66) groups and underwent corresponding treatment for three weeks. Primary and secondary outcome measures: The primary outcome was the number of days to achieve a 50% pain reduction. Secondary outcomes included areas under the 50% numeric rating scale reduction curve: pain, disability, quality of life, and safety. Results: The Chuna manual therapy + usual care group (23.31 ± 21.36 days; p = 0.01) required significantly fewer days to achieve 50% pain reduction compared to the usual care group (50.41 ± 48.32 days; p = 0.01). Regarding pain severity, functional index, and quality of life index, Chuna manual therapy and usual care were more effective than usual care alone. Safety was acceptable in both groups. Conclusions: In patients with subacute whiplash injury, Chuna manual therapy showed a rapid rate of recovery, high effectiveness, and safety

Herb Mixture Inhibits Proinflammatory Mediators Through the Suppression of JNK and P38 Activation in LPS-Stimulated Raw 264.7 Macrophages

ABSTRACT Inflammation has been implicated as a pathophysiological feature underlying many chronic diseases. In the present study, we investigated the anti-inflammatory effect of new formulation of herb medicine, DG1102, composed by five different herbal ingredients such as Taraxaci Herba, Rhei Rhizoma, Houttuynia cordata Thunb. Houttuyniae Herba, Eriobotryae Folium which has been used for inflammatory diseases, in LPS-stimulated Raw 264.7 macrophages. DG1102 suppressed nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-6, IL-10 and macrophage inflammatory protein production in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, as well as inducible nitric oxide synthase and cyclooxygenase 2 expression. Furthermore, DG1102 suppressed the activation of p38 and c-Jun N-terminal kinase (JNK). Our results suggest that DG1102 has an immune-modulatory activity suppressing production of pro-inflammatory cytokines and chemokine via the suppression of JNK and p38 MAPK activation in LPS-stimulated RAW 264.7 macrophages. The present study provides the biological evidence of the efficacy of medicinal plants in the treatment of inflammatory diseases

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease

Background Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. Methods We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. Results In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. Conclusion ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD

Is a Metallic Microcoil Really a Permanent Embolic Agent for the Management of Distal Guidewire-Induced Coronary Artery Perforation?

Coronary artery perforation (CAP) after percutaneous coronary intervention is a rare, but serious complication. It can cause cardiac tamponade, acute myocardial infarction or death. The treatments of CAP involve prolonged balloon inflation, emergent surgery, coil embolization, and implantation of covered stent. We have successfully performed the emergent microcoil embolization in a patient with uncontrolled Ellis grade 3 guidewire-induced CAP resulting in delayed cardiac tamponade. Contrasting our usual expectation, the 1-year follow-up angiography showed a patent flow at the embolized site