豨莶脂溶性成分的研究

从豨莶(Siegesbeckia orientalis L.)的地上部分,分离出八个化合物,其中I和I根据理化性质和光谱数据确定其结构为ent-17-acetoxy-18-isobutyryloxy-16(α)-kauran-19-oicacid(I)和ent-17-ethoxy-16(α)-kauran-19-oicacid(II),均为新化合物,分别被命为豨莶酯酸(siegesesteric acid,I)和豨莶醚酸(siegesetheric acid,I)。其余化合物分别鉴定为腺梗豨莶萜醇酸(ent-16β,17-dihydroxy-kauran-19-oicacid,II),奇任醇(kirenol,IV,β-谷甾醇葡萄糖甙(β-sitosterolglucoside,V),二十一醇(heneicosanol,VI),花生酸甲酯(methyl arachidate,VII)和β-谷甾醇(β-sitosterol,VII)。除奇任醇和β-谷甾醇外,均为首次从该植物中分得。     

十名志愿者口服维拉帕米缓释片药代动力学和心电图研究

对10名男性受试者单剂量po240mgVer缓释片药代动力学及心电图变化进行研究。血药浓度—时间数据用零级吸收过程的一室模型拟合,其药代动力学参数:T_max5.9±1.6h;C_max118.9±37.2μg·L^-1;T₁ 5.4±1.5h;k₀30.5±17.5μg·L^-1·h^-1;T_1/210.8±4.9h。PR间期延长有显著意义,血药浓度与PR间期变化满足S 型模型,其药效学参数:EC₅₀ 64.6±16.9μg·L^-1; E_max54±11ms;s 1.68±0.66。     

Predicting abdominal adipose tissue in overweight Latino youth.

OBJECTIVES: 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. STUDY DESIGN: Cross-sectional. PARTICIPANTS: 196 overweight 8-13-year-old Latino youth. Two-thirds (n = 131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n = 65) was used as a cross-validation group. METHODS AND PROCEDURES: Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). RESULTS: The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p < 0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p < 0.001). Regression analyses showed approximately 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. CONCLUSIONS: Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level.     

Impaired glucose tolerance and reduced beta-cell function in overweight Latino children with a positive family history for type 2 diabetes

The objective of this study was to examine relationships between impaired glucose tolerance (IGT) and body composition and insulin-related phenotypes in 150 overweight Latino children with a family history of type 2 diabetes. Glucose tolerance was assessed by an oral glucose challenge. Body composition was assessed by dual energy x-ray absorptiometry and magnetic resonance imaging. Insulin sensitivity, the acute insulin response, and the disposition index (DI), as an index of beta-cell function, were determined by an iv glucose tolerance test and compared between normal glucose-tolerant and IGT children. IGT was present in 28% of children, and was similar across obesity groups, but higher in children exposed to gestational diabetes mellitus (41% IGT). There were no significant differences in body composition, fat distribution, insulin sensitivity, or acute insulin response, but DI was significantly lower in IGT children by 16% (P < 0.02), and DI was inversely related to age. In conclusion, IGT is present in 28% of overweight Latino children with a family history of type 2 diabetes, is not influenced by obesity, is more prevalent in children exposed to gestational diabetes mellitus, and is related to poor beta-cell function, which shows signs of deterioration with age in this population.     

Dietary fat intake and insulin resistance in black and white children

OBJECTIVE: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. RESEARCH METHODS AND PROCEDURES: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24-hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above-AMDR/within-AMDR guidelines), and differences were analyzed by 2 x 2 analysis of covariance, adjusting for covariates. RESULTS: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above-AMDR compared with within-AMDR blacks) and was not seen in whites. DISCUSSION: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

The relation of sugar intake to beta cell function in overweight Latino children

BACKGROUND: Few studies have investigated the association between sugar intake and insulin dynamics in children, and none have examined this association in overweight Latino youth. OBJECTIVE: We aimed to examine the relation between dietary components, especially sugar intake, and insulin dynamics in overweight Latino youth. DESIGN: We examined 63 overweight Latino children aged 9-13 y. Dietary intake was determined by 3-d records, and body composition was measured with dual-energy X-ray absorptiometry. Insulin sensitivity (S(I)), acute insulin response (AIR), and disposition index (an index of beta cell function) were measured by using a frequently sampled intravenous-glucose-tolerance test and minimal modeling. Hierarchical regression analysis ascertained the potential independent relation between insulin dynamics and dietary components. RESULTS: The relation between macronutrient intake and any variable related to insulin dynamics was not significant. However, higher total sugar intake, although not related to S(I), was significantly associated with lower AIR (beta = -0.296, P = 0.045) and lower beta cell function (beta = -0.421, P = 0.043), independent of the covariates age, sex, body composition, Tanner stage, and energy intake. Sugar-sweetened beverage intakes trended toward inverse association with lower AIR (beta = -0.219, P = 0.072) and beta cell function (beta = -0.298, P = 0.077). CONCLUSIONS: In overweight Latino children, higher intakes of sugar and sugar-sweetened beverages were associated with lower AIR and disposition index, which suggested that these children already have early signs of poor beta cell function. These results emphasize the need for early nutritional interventions to reduce daily sugar intake in overweight Latino children and potentially reduce their risk for type 2 diabetes.     

Insulin sensitivity, insulin secretion and beta-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

OBJECTIVE: To examine cross-sectional differences in insulin sensitivity, insulin secretion and beta-cell function during puberty in overweight Hispanic boys and girls with a family history of type 2 diabetes. STUDY DESIGN AND PARTICIPANTS: This cross-sectional, observational study included 214 8-13-y-old Hispanic children with a BMI percentile > or = 85th percentile and family history of type 2 diabetes. METHODS AND ANALYSES: Participants underwent a physical examination, body composition measures, oral glucose tolerance test (OGTT), and frequently-sampled intravenous glucose tolerance test. Unadjusted and adjusted general linear models (GLM) tested whether insulin/glucose dynamics differed by Tanner stage and gender. RESULTS: Unadjusted group comparisons showed that fasting insulin increased whereas insulin sensitivity (SI) and the disposition index (DI) (a measure of pancreatic beta-cell function) decreased across Tanner stage groups (all P < 0.05). No differences in the acute insulin response to glucose (AIRg), fasting glucose or 2-h glucose were found. After adjusting for covariates, there was no independent effect of Tanner stage on SI (P = 0.9) or AIRg (P = 0.2), but DI was slightly lower in later Tanner stages suggesting decreased beta-cell function in the more mature groups (P = 0.10). CONCLUSIONS: Overweight Hispanic children with a family history of type 2 diabetes may represent a unique population given that pubertal insulin resistance was not evident once analyses controlled for body composition. Longitudinal analyses are required to determine whether the slightly diminished beta-cell function in later Tanner stages plays a role in the development of type 2 diabetes.     

Insulin sensitivity, cardiorespiratory fitness, and physical activity in overweight Hispanic youth

OBJECTIVE: To determine whether cardiorespiratory fitness and/or physical activity (PA) were related to measures of insulin sensitivity and secretion independent of body composition in overweight Hispanic children. RESEARCH METHODS AND PROCEDURES: Ninety-five Hispanic children (n = 55 boys; n = 40 girls; 8 to 13 years old) participated in this investigation. The frequently sampled intravenous glucose tolerance test was used to determine the insulin sensitivity index (SI), the acute insulin response, and the disposition index. Cardiorespiratory fitness [maximal oxygen uptake (VO(2max))] was evaluated using a treadmill protocol, and PA was determined by an interviewer-administered questionnaire. Body composition was measured using DXA. RESULTS: Unadjusted correlations indicated that VO(2max) (milliliters of O(2) per minute) was negatively related to SI (r = -0.46, p < 0.05) and disposition index (r = -0.31, p < 0.05) and positively associated with fasting insulin (r = 0.29, p < 0.05), but these relationships were no longer significant once gender, Tanner stage, fat mass, and soft lean tissue mass were included as covariates (all p > 0.05). Multivariate linear regression analysis showed that body fat mass explained 53% of the variance in SI and that VO(2max) (milliliters of O(2) per minute) was not independently related to SI. Cardiorespiratory fitness was positively related to both fat mass (r = 0.43, p < 0.001) and soft lean tissue mass (r = 0.89, p < 0.001). PA was not related to any measure of insulin sensitivity and secretion. DISCUSSION: Cardiorespiratory fitness, as determined by VO(2max) (milliliters of O(2) per minute), was not independently related to insulin sensitivity or secretion, suggesting that VO(2max) influences insulin dynamics indirectly through fat mass.     

转染癌基因的骨髓基质干细胞体外分化特征

目的:观察转染癌基因的骨髓基质干细胞在体外分化情况,为肝细胞癌的细胞源研究提供实验依据。方法:实验于2003-05/2004-06在南方医科大学药理教研室实验室完成。①两步法获取大鼠肝细胞,梯度离心法分离大鼠骨髓基质干细胞。②单基因转染是单独将c-myc或K-ras癌基因瞬时转染大鼠骨髓基质干细胞,6孔培养板中培养,24h后荧光显微镜下观察骨髓基质干细胞转染结果。双基因转染步骤相同,只是将c-myc和K-ras癌基因同时转染大鼠骨髓基质干细胞。③c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组常规培养,加入含体积分数为0.1胎牛血清的DMEM培养基,于37℃、体积分数为0.05的CO2孵箱培养,每24h半量更换培养液。④c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组将已转染癌基因的骨髓基质干细胞,置于叠加的培养板半透膜的上方(细胞密度均为1×105个/cm2),再将肝细胞置于半透膜的下方(每孔细胞密度为3×105/cm2)进行共培养,其余步骤同常规培养。⑤通过反转录聚合酶式反应和细胞免疫组化检测骨髓基质干细胞分化情况。结果:①癌基因转染24h骨髓基质干细胞检测结果:单独转染c-myc或K-ras癌基因的细胞,其绿色荧光蛋白呈均匀一致分布;双基因转染的细胞,绿色荧光蛋白呈点片状分布。②各组骨髓基质干细胞向肿瘤细胞分化检测结果:c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组的骨髓基质干细胞,均未向肿瘤细胞分化;c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组的骨髓基质干细胞,均向肝细胞癌发展;空白对照组骨髓基质干细胞细胞均为阴性。此外,双癌基因转染 肝细胞组的骨髓基质干细胞分化增殖迅速,反转录聚合酶式反应和免疫组化检测发现,培养第7天出现甲胎蛋白表达,并迅速增加,而第7天出现的白蛋白和细胞角蛋白18表达迅速减弱,第14天消失。结论:转染癌基因的骨髓基质干细胞,在向肝细胞诱导的条件下,部分癌基因可以使干细胞分化为肝癌细胞;多癌基因转染时,更易于使干细胞分化为肝癌细胞。     

Decreased beta-cell function in overweight Latino children with impaired fasting glucose

OBJECTIVE: To determine whether overweight Latino children with impaired fasting glucose (IFG) (> or = 100 mg/dl) have increased insulin resistance or decreased beta-cell function compared with those with normal fasting glucose (NFG). RESEARCH DESIGN AND METHODS: We studied 207 healthy overweight Latino children, aged 8-13 years, with a family history of type 2 diabetes. Fasting and 2-h glucose and insulin were assessed by oral glucose tolerance test. Insulin sensitivity (S(i)), the acute insulin response to glucose (AIRg), and the disposition index (DI; an index of beta-cell function) were determined using the insulin-modified intravenous glucose tolerance test and minimal modeling. Body composition was determined by dual-energy X-ray absorptiometry. RESULTS: There were no differences in body composition between NFG (n = 182) and IFG (n = 25) children. Compared with children with NFG, children with IFG had higher fasting and 2-h glucose values and higher fasting insulin. After adjusting for covariates, children with IFG had no difference in S(i) but 15% lower DI than NFG children (2,224 +/- 210 vs. 2,613 +/- 76, P < 0.05). Multivariate linear regression showed that AIRg and DI, but not S(i), were significant predictors of fasting blood glucose. CONCLUSIONS: In overweight Latino adolescents with a family history of type 2 diabetes, IFG is associated with impaired beta-cell function and therefore may identify children likely to be at risk for progression to type 2 diabetes. The actual risk of progression of IFG to type 2 diabetes remains to be determined by prospective longitudinal studies.