(S)-[5-Methyl-3-(3-methyl­thio­phen-2-yl)-4,5-dihydro­isoxazol-5-yl]methanol

In the title compound, C10H13NO2S, the thio­phene and isoxazoline rings are almost coplanar, the dihedral angle between their least-squares planes being 2.08 (1)°. The O—H atoms of the methyl hy­droxy group and the N atom of the isoxazole ring are orientated in the same direction to allow for the formation of inter­molecular O—H⋯N hydrogen bonds that lead to a supra­molecular chain along the a axis

Toxicity Studies on Secretio Bufonis: A Traditional Supplement in Asia

AbstractObjectivesThis study was performed to investigate the toxicity of Secretio Bufonis (SB) on male mice and assess its no-observed-adverse-effect-level (NOAEL).Materials and MethodsAfter feeding an aqueous solution of SB extracts to mice for either 1 or 8 weeks, their blood and urine were assayed and their liver and kidney morphology examined. The numerical data was analyzed by the Mann-Whitney U-test and analysis of variance test.ResultsMice administered SB in 50 mg/kg/day for 1 week had higher heart weights and higher aspartate transaminase activities; those administered SB in 0.01 and 0.05 mg/kg/day for 8 weeks had lower creatinine concentrations; and those administered SB in 0.5 mg/kg/day for 8 weeks had higher brain weights and higher blood urea nitrogen.ConclusionsThe extracts of SB had cardiac toxicity in the short term and hepatotoxicity in the long term. The NOAEL of the extract was under 5 mg/kg/day for 1 week and under 0.25 mg/kg/day for 8 weeks

A Toxicological Study of HangAmDan-B in Mice

AbstractThe aim of the study was to define the toxicity of HangAmDan-B (HAD-B) in mice over the short and long term. HAD-B was studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. Doses used in 1 week single oral dose toxicity tests were 0, 0.2, 1, 5, and 25 g/kg/day and those of repeated toxicity test were 0, 0.04, 0.2, 1, and 2 g/kg/day. Blood and urine samples were assayed and their morphology observed. Numerical data were compared using Mann-Whitney U test and analysis of variance. Significantly decreased red blood cell levels in mice from S2-HAD-B, S3-HAD-B, S4-HAD-B, and S5-HAD-B groups were observed in single oral dose toxicity tests. Hemoglobin, hematocrit, and mean cell hemoglobin values in mice from the S4-HAD-B and S5-HAD-B groups were also significantly decreased. No mortalities or significant differences in all factors were observed during the dosing period of the repeated dose toxicity test. Administering 2 g/kg/day of HAD-B in mice over a 5-week period showed no significant hematological changes. However, risk of anemia with more than 5 g/kg/ day administration of HAD-B was found. In general, HAD-B appears to be safe and nontoxic, and a no observed adverse effect level in mice was established at 2 g/kg/ day. This data serves as satisfactory preclinical evidence for the safety of HAD-B should a future clinical trial for HAD-B be launched. Further studies are required to confirm these safety results and to carry out a safety trial in humans

Incidence and Risk Factors of Insulin Resistance Syndrome in 20-59 Year-Old Korean Male Workers

We investigated the incidence of insulin resistance syndrome (IRS) according to the criteria of diagnoses suggested by the American College of Endocrinology/American Association of Clinical Endocrinologists and the risk factors associated with the development of IRS. Among 2,048 subjects without a history of/or drug treatment for hypertension, diabetes, dyslipidemia with normal findings at baseline, 1,578 subjects aged 20-59 yr were followed prospectively for 2 yr. The incidence of IRS was 6.9 per 100 persons/year. The relative risk (RR) due to age was 1.03 (95% CI: 1.00-1.05) with every one-year increase in age. The RR associated with an abnormal waist-hip ratio group (≥0.9) was increased by 1.74 (95% CI:1.17-2.58) compared to the normal group (<0.9); RR associated with abnormal alanine transferase was increased (≥35 IU/L) by 1.70 (95% CI: 1.20-2.41) compared to the normal group (<35 IU/L); and the RR associated with abnormal low-density lipoprotein (LDL) cholesterol was increased (≥160 mg/L) by 1.70 (95% CI: 1.19-2.44) compared to the normal LDL cholesterol (<160 mg/L). Lastly, the RR of current smokers was increased by 1.63 (95% CI: 1.09-2.42) compared to that of non-smokers. It is necessary to develop methods of prevention and therapeutic approach to manage the integrated risk factors as opposed to individual factors

Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial

Background. Anorexia occurs in about half of cancer patients and is associated with high mortality rate. However, safe and long-term use of anorexia treatment is still an unmet need. Objective. The purpose of the present study was to examine the feasibility of Sipjeondaebo-tang (Juzen-taiho-to, Shi-Quan-Da-Bu-Tang) for cancer-related anorexia. Methods. A total of 32 participants with cancer anorexia were randomized to either Sipjeondaebo-tang group or placebo group. Participants were given 3 g of Sipjeondaebo-tang or placebo 3 times a day for 4 weeks. The primary outcome was a change in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes included Visual Analogue Scale (VAS) of anorexia, FAACT scale, and laboratory tests. Results. Anorexia and quality of life measured by FAACT and VAS were improved after 4 weeks of Sipjeondaebo-tang treatment. However, there was no significant difference between changes of Sipjeondaebo-tang group and placebo group. Conclusions. Sipjeondaebo-tang appears to have potential benefit for anorexia management in patients with cancer. Further large-scale studies are needed to ensure the efficacy. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02468141

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

(a) Immunoblotting analysis of IRβ in the hippocampus and frontal cortex of 18-month old wildtype and APN-KO mice. (b) Densitometric analysis of the ratio of IRβ. Mean ± S.E.M.; ***p < 0.001, n.s. statistically not significant; Scale bar: 100 μm. (JPG 30 kb

Elevated red cell distribution width is associated with advanced fibrosis in NAFLD

Background/AimsThe red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores.MethodsThis study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively.ResultsAfter adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and ≥2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of ≥1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score.ConclusionsElevated RDW is independently associated with advanced fibrosis in NAFLD

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities. © 2013 Stuckenholz et al