Diosgenin, the main aglycon of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice

Trigonella foenum-graecum (fenugreek) can ameliorate dyslipidemia, but the detailed mechanism is unclear. In this study, we examined the effects of fenugreek on hepatic lipid metabolism, particularly lipogenesis, which is enhanced in obesity and diabetes, in diabetic obese KK-Ay mice. KK-Ay mice were fed a control high-fat diet (HFD; 60% of energy as fat) (C group) or an HFD containing 0.5% or 2% fenugreek (0.5F and 2.0F groups, respectively) for 4 wk. Hepatic and plasma TG and mRNA expression levels of lipogenic genes were lower in the 2.0F group at 4 wk (P < 0.05), but not in the 0.5F group, than in the C group. The hydrolyzed saponin fraction, but not the saponin fraction per se, in fenugreek inhibited the accumulation of TG in HepG2 cells. We fractionated the hydrolyzed saponin into 15 fractions by HPLC and examined the effect of these fractions on TG accumulation in HepG2 cells. Fraction 11 inhibited TG accumulation in HepG2 cells and we determined by liquid chromatography tandem MS that the active substance contained in fraction 11 is diosgenin. Diosgenin (5 and 10 μmol/L) inhibited the accumulation of TG and the expression of lipogenic genes in HepG2 cells. Moreover, diosgenin inhibited the transactivation of liver-X-receptor-α, as measured using a luciferase assay system and by gel mobility shift assay. These findings suggest that fenugreek ameliorates dyslipidemia by decreasing the hepatic lipid content in diabetic mice and that its effect is mediated by diosgenin. Fenugreek, which contains diosgenin, may be useful for the management of diabetes-related hepatic dyslipidemias.     

Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice

Objective

The effects of fish oil including ω-3 polyunsaturated fatty acids on aging and lifespan are not well understood. In this study, the influence of long-term ingestion of fish oil on lifespan was examined in senescence-accelerated (SAMP8) mice.

Methods

We investigated the effects of dietary fish oil on lifespan and on lipid composition and oxidative stress in plasma and liver in SAMP8 mice. Male mice were fed a fish oil diet (5% fish oil and 5% safflower oil) or a safflower oil diet (10% safflower oil) from 12 wk of age.

Results

The SAMP8 mice fed fish oil did not have a longer maximum lifespan and had a shorter average lifespan than mice fed safflower oil. To examine the mechanism underlying these results, the effects on oxidative stress of long-term ingestion of fish oil were also examined. SAMP8 mice fed fish oil for 28 wk showed strong oxidative stress that caused hyperoxidation of membrane phospholipids and a diminished antioxidant defense system due to a decrease in tocopherol compared with mice fed safflower oil.

Conclusion

These findings suggest that intake of fish oil increases oxidative stress, decreases cellular function, and causes organ dysfunction in SAMP8 mice, thereby promoting aging and shortening the lifespan of the mice.     

Development of skill scale for communication skill measurement of pharmacist

To purpose of this study was to develop a pharmacist communication skill scale. A 38 items scale was made and 283 pharmacists responded. The original questionnaire consisted of 38 items, with 1-5 graded Likert scale. Completed responses of 228 pharmacists data were used for testing the reliability and the validity of this scale. The first group of items from the original questionnaire were 38, and finally 38 original items were chosen for investigation of content validity, correlation coefficient and commonality. From factor analysis, four factors were chosen among the 31 items as follows: patient respect reception skill, problem discovery and solution skill, positive approach skill, feelings processing skill. The correlation coefficient between this original scale and the KiSS-18 (Social Skill) received high score (r=0.694). The reliability of this scale showed high internal consistency (Cronbach α coefficient=0.951), so the result of test for the validity of this scale supports high content validity. Thus we propose adoption of pharmacist communication skill scale to carry a brief eponymous name as TePSS-31. The above findings indicate that this developed scale possess adequate validity and reliability for practical use.     

Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later‐onset GLA mutation c.936+919G>A (IVS4+919G>A)

Fabry disease (α‐galactosidase A (α‐Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Because optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) α‐Gal A activities and β‐galactosidase/α‐Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS α‐Gal A activity <30% of normal mean and/or activity ratios >10. A second DBS assay reduced these to 91 (0.1%). Of these, 11 (including twins) had <5% (Group‐A), 64 had 5–30% (Group‐B), and 11 had >30% (Group‐C) of mean normal leukocyte α‐Gal A activity. All 11 Group‐A, 61 Group‐B, and 1 Group‐C males had GLA gene mutations. Surprisingly, 86% had the later‐onset cryptic splice mutation c.936+919G>A (also called IVS4+919G>A). In contrast, screening 81,689 females detected two heterozygotes. The novel mutations were expressed in vitro, predicting their classical or later‐onset phenotypes. Newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (∼1 in 1,250), 86% having the IVS4+919G>A mutation previously found in later‐onset cardiac phenotype patients. Further studies of the IVS4 later‐onset phenotype will determine its natural history and optimal timing for therapeutic intervention. Hum Mutat 30:1–9, 2009. © 2009 Wiley‐Liss, Inc.     

Chemosensitivity test for 5-fluorouracil and 5-chloro-2, 4-dihydroxypyridine predicts outcome of gastric cancer patients receiving S-1 postoperatively

Background  

Chemosensitivity tests have long been discussed but remain a topic of research. In this study, we investigated the correlation between the results of a chemosensitivity test for 5-fluorouracil and 5-chloro-2, 4-dihydroxypyridine and the clinical outcomes of gastric cancer patients treated with S-1, an oral fluoropyrimidine, as adjuvant chemotherapy.     

Recurrent severe mitral regurgitation due to left ventricular apical wall motion abnormality caused by coronary vasospastic angina: a case report

A 76-year-old man developed congestive heart failure due to severe mitral regurgitation after episodes of vasospastic angina. Echocardiography demonstrated left ventricular apical akinesis with ballooning and deformity of the anterior mitral leaflet becoming concave toward the left atrium. The acetylcholine provocation test induced diffuse coronary vasospasm in the distal segments of both right and left coronary arteries and reproduced severe mitral regurgitation. Follow-up echocardiography demonstrated decreased mitral regurgitation with ameliorated apical wall motion. Coronary vasospasm remained refractory to antivasospastic medications and severe mitral regurgitation relapsed 1 month after discharge. Mitral valve annuloplasty with a Carpentier-Edwards physio ring was performed, and no recurrence of mitral regurgitation was observed despite some episodes of vasospastic angina. We speculate that vasospastic angina and the resultant apical wall motion abnormality caused tethering of the mitral subvalvular apparatus, leading to inappropriate mitral coaptation and severe regurgitation.     

Transient leukocytopenia associated with a steep surge of pro-inflammatory cytokines in a patient with severe cardiogenic pulmonary edema

Leukocytopenia can be caused by depressed production, increased peripheral destruction, or excessive peripheral pooling. Leukocyte margination is one of the mechanisms responsible for excessive peripheral pooling. A reversible leukocyte margination is caused by an increase in pro-inflammatory cytokines. However, there are limited data for this phenomenon in clinical conditions. We describe a case of unexpected transient leukocytopenia after exchanging an extracorporeal membrane oxygenation (ECMO) system used to treat severe cardiogenic pulmonary edema. To assess the cause of the leukocytopenia, the serum concentrations of pro-inflammatory cytokines and selectins were measured. The concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were markedly, but transiently, elevated in relation to the leukocytopenia. The transient leukocytopenia with pulmonary margination appeared to be caused by a steep surge of pro-inflammatory cytokines stimulated by hypoxia/reoxygenation during the exchange of the ECMO system. This case may suggest the mechanisms responsible for leukocytopenia in the clinical entity referred to as "systemic inflammatory response syndrome"