Peripheral inflammatory and fibrinolytic markers in adolescents with growth hormone deficiency: relation to postprandial dyslipidemia

OBJECTIVE: To determine whether peripheral inflammatory and fibrinolytic markers are elevated in growth hormone-deficient (GHD) adolescents and associated with increased postprandial lipoproteins. STUDY DESIGN: Fifteen GHD children on GH treatment with a chronologic age of 12.7 +/- 2.5 years and 10 untreated GHD adolescents with a chronologic age of 13.0 +/- 2.6 years were studied. Triglycerides (TG), C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured in the fasting state and 4 hours after ingesting a high-fat meal; 15 healthy adolescents served as controls. RESULTS: Fasting and postprandial TG of untreated GHD children were higher than those in treated subjects and healthy controls. Fasting TNF-alpha, CRP, and fibrinogen concentrations of untreated GHD adolescents were higher than those in healthy controls, but similar to those of GH-treated GHD adolescents. Although fibrinogen levels increased after a high-fat meal in GHD adolescents, CRP, TNF-alpha, and IL-6 concentrations did not increase further. Fasting and postprandial TG of untreated GHD adolescents were positively associated with fasting and postprandial CRP, and with postprandial TNF-alpha and IL-6 concentrations. Fasting TG also correlated positively with fasting fibrinogen concentrations in untreated and treated GHD adolescents. CONCLUSIONS: The pronounced inflammatory response seen in GHD adolescents seems to be associated with the presence of elevated levels of fasting and postprandial TG, which may result in an increased susceptibility for premature atherosclerosis.     

Dual effect of hydrogen peroxide on store-mediated calcium entry in human platelets

Redox regulation is important for the modulation of cytosolic Ca(2+) concentration. Hence, we have investigated the effect of H(2)O(2) on store-mediated Ca(2+) entry (SMCE). In fura-2-loaded human platelets treatment with H(2)O(2) resulted in a concentration-dependent increase in Ca(2+) release from intracellular stores, while the effect on Ca(2+) entry was biphasic. In addition, 1mM H(2)O(2) reduced SMCE induced by agonists. The inhibitory effect of 1mM H(2)O(2) was prevented by inhibition of actin polymerization with cytochalasin D. Consistent with this, we found that 10microM H(2)O(2) and store depletion by treatment with thapsigargin plus ionomycin induced a similar temporal sequence of actin reorganization, while exposure to 1mM H(2)O(2) shifted the dynamics between polymerization and depolymerization in favor of the former. One millimolar H(2)O(2)-induced polymerization was reduced by treatment with methyl 2,5-dihydroxycinnamate and farnesylthioacetic acid, inhibitors of tyrosine kinases and Ras superfamily proteins, respectively. Finally, exposure to 1mM H(2)O(2) significantly increased store depletion-induced p60(src) activation. We conclude that H(2)O(2) exerted a biphasic effect on SMCE. The inhibitory role of high H(2)O(2) concentrations is mediated by an abnormal actin reorganization pattern involving both Ras- and tyrosine kinases-dependent pathways.     

A prospective study of the incidence of childhood celiac disease

OBJECTIVES: To estimate the frequency of celiac disease (CD) in children in the general population of Denver, Colorado. STUDY DESIGN: From 22,346 newborns characterized as expressing 0, 1, or 2 HLA-DR3(DQB1*0201) alleles, 987 were selected for a prospective stratified cohort study. Participants were followed for as long as 7 years with serial testing for serum IgA anti-transglutaminase antibodies and for evidence of CD (intestinal mucosal changes or persistent seropositivity). RESULTS: Of 40 children with at least one positive serologic test, 19 had evidence of CD (10 by biopsy, 9 by persistent seropositivity). Those expressing 0, 1, or 2 HLA-DR3 alleles had, respectively, 0.3% (95% CI, 0.0-2.7), 3.4% (3.0-11.7), and 3.2% (1.0-11.0) risk for evidence of CD by age 5 years. The adjusted risk estimate for evidence of CD by age 5 years for the Denver general population was 0.9% (0.4-2.0), or 1 in 104 (1:49-221). After adjusting for number of HLA-DR3 alleles expressed, risk was higher in females: RR=3.34 (1.00-10.9, P=.048). Evidence of CD was not observed before age 2.6 years. CONCLUSIONS: Celiac disease may affect 0.9% of Denver children by 5 years of age. Children positive for the HLA-DR3 allele and females appear to be at increased risk.     

Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model

Rodents treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) are a model of two hepatic toxic manifestations: porphyria and the appearance of hepatic cytoplasmic protein aggregates (Mallory-Denk Bodies, MDBs). MDBs are induced after long-term DDC feeding, consist primarily of keratins 8 and 18, and contain glutamine-lysine cross-links generated by transglutaminases (TGs). TGs are Ca²⁺-dependent enzymes which catalyze the formation of covalent bonds between proteins and between proteins and polyamines. The aim of the current study was to investigate the time-course of TG hepatic activity in CF1 male mice either acutely or chronically treated with DDC and to correlate this activity with polyamine and porphyrin levels. On day 3 of the treatment, statistically significant increases in TG activity (75%), porphyrin content (6740%) and spermidine levels (73%) were observed. Although not statistically significant, at this time point putrescine levels showed an increase of 52%. The highest TG activity was observed on day 30 (522%), while porphyrin levels were still gradually increasing by day 45 (37,000%). From day 7 of the treatment and until the end of the experiment, putrescine levels remained increased (781%). Spermine levels were not affected by the treatment. The DDC-induced increases in putrescine and spermidine levels herein reported seem to be an early event contributing to the stimulation of liver TG activity, and thus to the promotion of cross-linking reactions between keratin proteins. This in turn would contribute to the formation of protein aggregates, which would lead to the appearance of MDBs. Due to the pro-oxidant and antioxidant properties of polyamines, it is possible to speculate that putrescine and spermidine may also participate at several levels in the oxidative stress processes associated with MDB formation.     

Hydrangea dulcis folium preserves β-cell mass in diabetic db/db mice

The anti-diabetic efficacy of Hydrangea dulcis folium (HDF) was studied in db/db mice and their littermates (db/-). Supplementation of HDF (1% and 3%) decreased glucose level significantly by 2- and 4-fold and increased significantly insulin level by 3- and 4.5-fold compared to db/db mice (P < 0.05). Administration of HDF (1% and 3%) ameliorates hyperglycemia and improves glucose homeostasis in db/db mice in a dose-dependent manner by preventing loss of β-cell mass resulting in increase of insulin secretion. In addition, 3% HDF treatment significantly reduced the food intake, weight gain, and blood lipids in db/db mice.     

The benchmark dose approach in food risk assessment: Is it applicable and worthwhile?

The benchmark dose (BMD) approach is being increasingly used in the area of food risk assessment because it offers several advantages compared to the conventional no-observed-adverse-effect-level approach. The aim of this work was to check the applicability of the BMD approach on toxicity data available from pesticides, mycotoxins and natural toxins.     

泰安市健康人CH、TG参考值调查

对250例泰安市健康成人的血清CH、TG浓度进行了测定,参考值为:CH:3.52～6.84mmol/L;TG:0.82~1.98mmol/L。均高出传统的参考范围,表明随着人们饮食水平不断提高,CH、TG参考值有上升趋势,建议各实验室重新确立本地区的CH、TG参考值。     

社区人群甘油三脂异常分析与对策

目的：对我市某社区人群中甘油三脂异常进行统计分析并提出改善意见，降低社区人群甘油三脂水平。方法：根据社区人群的体检报告，筛选出甘油三脂异常标本作为分析对象。结果：确定甘油三脂异常标本1314个，约占体检人数的30．6％。结论：该社区人群的甘油三脂异常率偏高，与人群生活方式与饮食习惯有关，社区活动和户外活动少也是原因之一，特别是60岁以上老年人群。     

非酒精性脂肪性肝病发生中Perilipin和ADRP表达变化实验研究

目的：探讨高脂饮食诱导大鼠非酒精性脂肪性肝病（NAFLD）形成过程中，肝组织Perilipin（脂滴包被蛋白）和ADRP（脂肪分化相关蛋白）的表达变化及意义。方法：建立大鼠高脂饮食NAFLD模型并设正常对照组，观察时间点为建模后4w、8w和12w，观察大鼠肝组织病理变化，检测血浆游离脂肪酸及甘油三酯水平，免疫组织化学染色法检测肝组织中Perilipin和ADRP蛋白水平。结果：成功制作大鼠NAFLD实验模型，与正常组相比，NAFLD组大鼠血浆FFA水平和TG水平从第4w起显著升高（P〈0．01），NAFLD组大鼠肝组织Perilipin蛋白表达水平显著低于正常组（P〈0．01），ADRP蛋白表达水平显著高于同期正常组（P〈0．01）。Perilipin及ADRP表达与FFA及TG具有显著相关性。结论：高脂饮食可制作NAFLD大鼠模型，Perilipin和ADRP与NAFLD的形成有关。