Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities

BACKGROUND: Hypopituitarism in adults is associated with increased vascular mortality, which has been attributed to GH deficiency. OBJECTIVE: To compare the lipid profile and coronary risk predicted by the Framingham Heart Study equation in GH-deficient hypopituitary patients and healthy age and gender-matched controls. DESIGN: A cross-sectional observational study. METHODS: We studied 50 adult-onset growth hormone deficient hypopituitary patients (23F, 27M), on appropriate conventional hormone replacement and 45 controls (22F, 23M) matched for age, gender and smoking habit. The subjects (age range 30-75 years) were free from diabetes, hypertension, ischaemic heart disease (IHD) and peripheral vascular disease. All hypogonadal male patients were on testosterone replacement therapy. A similar proportion of female patients (8/23) and controls (7/22) were on HRT. Body mass index (BMI), waist-hip ratio (WHR) and blood pressure were recorded. After an overnight fast blood glucose, total-cholesterol, triglycerides, HDL-cholesterol, apolipoproteins A-I, B and Lp (a) were measured. Coronary risk was calculated for each individual from age, gender, systolic blood pressure, total and HDL cholesterol, smoking habit and presence of diabetes and left ventricular hypertrophy using the Framingham equation. RESULTS: BMI and WHR were significantly increased in GHD hypopituitary adults of both sexes, but to a greater extent in females. Triglycerides were elevated in both sexes. Total and LDL-cholesterol were increased in both sexes (significantly only in males), and HDL cholesterol and apo A-I were lower (significantly only in females). The reduction in HDL cholesterol was correlated negatively with adiposity (BMI), particularly when centrally distributed (WHR) in patients and controls. LDL cholesterol did not correlate to adiposity but higher levels were present in GH-deficient subjects. The total to HDL cholesterol ratio was significantly increased in patients of both genders (P = 0.002). There were no differences in the apolipoproteins B and Lp(a) between patients and controls. Absolute risk (mean +/- SEM) of a fatal or non-fatal coronary event during the next 5 years was significantly greater in GHD hypopituitary patients than control subjects (4.82 +/- 0.73% vs. 2.94 +/- 0.53, P = 0.04). Cardiovascular risk relative to the local population (RR) was significantly higher in GHD hypopituitary adults (RR = 1.43 CL 1.06-1.80, P = 0.011) but not in the control group (1.08 CL 0.59-1.6). When divided by gender, RR for male patients was not increased (1.14 CL 0.83-1.45, P = 0.096). However, female patients had significantly higher RR (1.7 CL 1.05-2.5, P = 0.048). The RR for male and female controls was not different from the local population. CONCLUSION: Changes in lipid levels help to explain the results from risk factor modelling which show increased coronary risk in growth hormone deficient hypopituitary patients, particularly females. The abnormal lipid profile is characterized in both genders by an increase in the total to HDL ratio [corrected], an important parameter in the Framingham equation. The lipid abnormalities conferring increased risk is related to growth hormone deficiency either directly (LDL) or indirectly through increased central obesity (HDL) [corrected]. Adverse calculated coronary risk might provide a new objective indication for consideration of GH replacement therapy in adults.     

棉花花总黄酮片中黄酮类化合物的测定

目的 建立棉花花总黄酮片中总黄酮、金丝桃苷、异槲皮素的测定方法。方法 利用紫外分光光度计，以芦丁为对照品测定总黄酮，HPLC同时测定黄酮类化合物金丝桃苷和异槲皮素。结果 3批棉花花总黄酮片中总黄酮分别为71.6、73.5、75.2 mg/片，金丝桃苷分别为4.28、4.35、4.23 mg/片，异槲皮素分别为18.55、18.73、18.31 mg/片。结论 该方法专属性强，灵敏度高、重现性好，可用于棉花花总黄酮片中黄酮类化合物的测定。     

Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1

Protein aggregation can induce explicit neurotoxic events that trigger a number of presently untreatable neurodegenerative disorders. Chaperones, on the other hand, play a neuroprotective role because of their ability to unfold and refold abnormal proteins. The progressive nature of neurotoxic events makes it important to discover endogenous factors that affect pathologic and molecular phenotypes of neurodegeneration in animal models. Here, we identified microtubule-associated protein tau, and chaperones Hsp70 (heat shock protein 70) and DNAJA1 (DJ2) as endogenous substrates of cereblon (CRBN), a substrate-recruiting subunit of cullin4-RING-E3-ligase. This recruitment results in ubiquitin-mediated degradation of tau, Hsp70, and DJ2. Knocking out CRBN enhances the chaperone activity of DJ2, resulting in decreased phosphorylation and aggregation of tau, improved association of tau with microtubules, and reduced accumulation of pathologic tau across brain. Functionally abundant DJ2 could prevent tau aggregation induced by various factors like okadaic acid and heparin. Depletion of CRBN also decreases the activity of tau-kinases including GSK3α/β, ERK, and p38. Intriguingly, we found a high expression of CRBN and low levels of DJ2 in neuronal tissues of 5XFAD and APP knock-in male mouse models of Alzheimer’s disease. This implies that CRBN-mediated DJ2/Hsp70 pathway may be compromised in neurodegeneration. Being one of the primary pathogenic events, elevated CRBN can be a contributing factor for tauopathies. Our data provide a functional link between CRBN and DJ2/Hsp70 chaperone machinery in abolishing the cytotoxicity of aggregation-prone tau and suggest that Crbn^−/− mice serve as an animal model of resistance against tauopathies for further exploration of the molecular mechanisms of neurodegeneration.     

骆驼刺中黄酮类化合物的提取工艺研究

目的 筛选出提取骆驼刺中黄酮类化合物的最佳工艺.方法 采用正交实验,考察乙醇浓度(A)、料液比(B)、提取时间(C)、提取次数(D)4个因素对骆驼刺(Alhagi sparsifolia shap.)中总黄酮提取率的影响,用紫外分光光度计法进行检测.结果 最佳提取工艺为:溶剂为40%乙醇,料液比1:20,提取时间1.5h,提取3次.结论 该工艺条件提取率高且稳定.     

A noninvasive assessment of pharmacological interaction of amines in the lung

Lung endothelial binding sites of N-isopropyl-123I-p-iodoamphetamine (123I-IMP) were assessed employing the principle of competitive binding assay adapted for in vivo measurement using a computer-scintillation camera technique. A noninvasive modification of the Chinard-Crone technique was applied to the study of pulmonary extraction. 123I-IMP, the test cellular tracer and 99Tcm-dextran the vascular reference tracer were used in dogs to determine the first pass pulmonary extraction of 123I-IMP. The lung extraction of 123I-IMP decreases progressively from 90 to 62% as the amount of propranolol (administered 10 min prior to the injection of 99Tcm-dextran) gradually increased from 0 to 20 mg. The dissociation constant of 123I-IMP lung binding sites reaction in the presence of propranolol was calculated by Scatchard plot and found to be 10 mg. The in vivo procedure described in this paper will enable us to develop a model for the assay of the binding sites in the lungs for amine and its influence in both health and disease.     

新疆4种绢蒿属植物及近缘种银蒿的ITS/ITS2条形码鉴定研究

目的：评价ITS/ITS2热点条形码序列对新疆4种绢蒿属植物及其近缘种银蒿的鉴别能力,为绢蒿属植物分类鉴定提供分子参考依据。方法：对15份绢蒿属及银蒿植物样本进行DNA提取、PCR扩增、双向测序,采用CodonCode Aligner软件对序列峰图进行校对拼接,MEGA6.0分析序列碱基组成及变异,计算K2P遗传距离并构建聚类邻接树,预测ITS2序列二级结构,评估鉴别能力。结果：西北绢蒿、针裂叶绢蒿种内变异位点及信息位点数均小于银蒿。ITS序列种间、种内遗传变异均大于ITS2序列。ITS/ITS2 序列邻接（NJ）树均聚为3支,绢蒿属、银蒿1、银蒿2。绢蒿属ITS2序列二级结构与银蒿有差异。结论：通过ITS/ITS2序列的种间K2P遗传距离、邻接树、ITS2序列二级结构分析,ITS、ITS2序列具很好的属鉴定效果,不同产地的针裂叶绢蒿被区分开。     

Effects of Gossypium herbaceam extract administration on the learning and memory function in the naturally aged rats: neuronal niche improvement

Aging-associated cognitive impairment is an important health care issue since individuals with mild cognitive impairment are more likely to develop Alzheimer's disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment associated with aging were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70, and 140 mg/kg exerted an improved effect on the learning and memory impairment in aged rats. Subsequently, GHE afforded a beneficial action on eradication of free radicals without influence on the activity of glutathione peroxidase and superoxide dismutase. GHE treatment enhanced the expression levels of nerve growth factor. Meanwhile, proliferation of neural progenitor cells was elevated in hippocampus after treatment with GHE. Taken together, neurogenic niche improvement could be involved in the mechanism underlying neuroprotection of GHE against aging-associated cognitive impairment. These findings suggested that GHE might be a potential agent as cognitive-enhancing drugs that delay or halt mild cognitive impairment progression to Alzheimer's disease or treatment of aging-associated cognitive impairment.     

甘草次酸/11-脱氧甘草次酸甲酯的合成

以甘草次酸为原料,采用经典的克莱门森还原制备了11-脱氧甘草次酸,接着在不同的催化体系中(浓硫酸、浓盐酸、干盐酸气)研究了合成了甘草次酸甲酯的最佳条件,结果表明以干盐酸气催化可获得较高的产率。并在该条件下合成了11-脱氧甘草次酸甲酯。合成的化合物经过IR,1HNMR,13CNMR等进行了表征。     

榅桲子总黄酮提取工艺研究

目的 优选榅桲子中总黄酮的最佳提取工艺条件.方法 以芦丁为对照品,用分光光度法在506 nm波长处测定榅桲子总黄酮含量,优选总黄酮的提取工艺.结果 测得样品中总黄酮含量为13.60 mg•g-1,最佳提取工艺：乙醇浓度为75%,料液比1：10(倍)、回流时间 2.5 h,回流温度60 ℃,提取3次.结论 选用芦丁为对照品,用紫外分光光度法测定榅桲子总黄酮含量准确度较高,方法 简便,切实可行.