肿瘤坏死因子-α、白细胞介素-6和脂联素与2型糖尿病胰岛素抵抗的关系

目的 研究2型糖尿病（T2DM）患者肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和脂联素与胰岛素抵抗的关系.方法 选择80例T2DM患者（T2DM组）和40例健康体检者（对照组）,测定各组空腹血清TNF-α,IL-6和脂联素水平,同时分别测定各组患者体质量指数（BMI）、空腹血糖、血清胰岛素水平,计算胰岛素抵抗指数（HOMA-IR）.结果 T2DM组TNF-α、IL-6水平均明显高于对照组,脂联素水平明显低于对照组（均P＜0.05）.在T2DM组中,TNF-α和IL-6均与HOMA-IR呈正相关（P＜0.01,P＜0.05）,脂联素与HOMA-IR呈负相关（P＜0.01）.结论 IL-6、TNF-α及脂联素参与了2型糖尿病的发病过程,与胰岛素抵抗密切相关.     

血清网膜素、脂联素在丙型肝炎肝硬化患者的临床意义

目的 测定丙型肝炎肝硬化患者血清网膜素、脂联素水平,探讨其与胰岛素、Child-Pugh分级及肝脏生化指标及血脂间的关系.方法 测定56例丙型肝炎肝硬化(A级17例,B级20例,C级19例)患者和32例健康对照的血清网膜素、脂联素及相关的临床生化参数.结果 肝硬化患者血清网膜素、脂联素水平明显高于正常对照组(P<0唵.05),肝硬化组内A、B、C三级间网膜素、脂联素水平差异无统计学意义(P>0.05),肝硬化组患者血清网膜素、脂联素水平与HOMA-IR、胰岛素水平无明显相关性(r值分别为-0.07、-0.14、-0.10、-0.04,P>0.05),网膜素水平与脂联素呈正相关(r=0.37,P<0.01).结论 丙型肝炎肝硬化时网膜素、脂联素升高,可作为预测丙型肝炎肝硬化的指标,但不能作为肝功能严重程度的指标.     

糖尿病脂肪肝患者网膜素-1与脂联素、炎症因子关系研究

【摘要】目的研究2型糖尿病（T2DM）合并非酒精性脂肪性肝病（NAFLD）患者血浆网膜素-1与脂联素和肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、高敏C反应蛋白（hs-CRP）等炎症因子的关系。方法采用酶联免疫吸附法（ELISA）检测T2DM合并NAFLD组（A组,63例）、T2DM不合并NAFLD组（B组,63例）和正常对照组（C组,70例）的血浆网膜素-1和脂联素水平,同时测定上述3组生化指标及炎症指标（hs-CRP、TNF-α和IL-6）,应用相关分析和多元回归分析方法分析血浆网膜素-1与脂联素及炎症指标的关系,应用Logistic回归分析T2DM合并NAFLD的影响因素。结果A组血浆网膜素-1（27.02±2.82）μg/L、脂联素水平（11.98±3.63）mg/L低于B组[分别为（31.52±2.81）μg/L（15.85±3.28）mg/L]和C组[分别为（35.92±2.80）μg/L、（ 19.88±3.44）mg/L],且B组低于C组（P＜0.01）,A组血浆网膜素-1水平与脂联素、高密度脂蛋白胆固醇（HDL-C）正相关,与TNF-α、IL-6、空腹血（FBG）、胰岛素抵抗指数（HOMAIR）、内脏脂肪面积、腰围、腰臀比（WHR）、游离脂肪酸（FFA）负相关（P＜0.05或P＜0.01）;多元逐步线性回归分析表明脂联素、TNF-α、IL-6是血浆网膜素-1水平的影响因素。Logistic回归分析显示网膜素-1、hs-CRP、内脏脂肪面积及游离脂肪酸（FFA）是T2DM合并NAFLD的独立影响因素（P＜0.01）。结论 T2DM患者合并NAFLD与网膜素-1降低相关,网膜素-1表达可能会受到脂联素及炎症因子的影响。     

2型糖尿病患者颈动脉粥样硬化与血清网膜素-1的相关研究

目的探讨血清网膜素-1与2型糖尿病(T2DM)患者颈动脉粥样硬化(CAS)的关系。方法选取30例新诊断T2DM不伴CAS患者及30例T2DM伴CAS患者作为研究组,30名正常糖耐量(NGT)者作为对照组。酶联免疫吸附试验(ELISA)法测定血清网膜素-1水平,并测定空腹血糖(FPG)、糖化血红蛋白(Hb A1c)、空腹胰岛素(FINS)、血脂等指标;CAS检测采用彩色多普勒超声仪。结果 1血清网膜素-1水平在T2DM伴CAS组、新诊断T2DM不伴CAS组均明显低于NGT组[(45±12)和(73±12)和(86±27)ng/L(P<0.05或P<0.01)];在CAS组较非CAS组显著降低(P<0.01)。2血清网膜素-1与体质量指数(BMI)、FPG、Hb A1c、FINS、胰岛素抵抗指数(HOMA-IR)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)呈负相关(P<0.05或P<0.01),与高密度脂蛋白胆固醇(HDL-C)呈正相关(P<0.01)。3网膜素-1是CAS的独立保护因素,HOMA-IR是CAS的独立危险因素。结论血清网膜素-1水平随着糖尿病病情发展逐渐降低,可能参与了T2DM患者CAS的发生。     

冠心病合并2型糖尿病相关生化指标的检测及临床意义

目的探讨冠心病合并2型糖尿病患者血清生化指标特点并研究其危险因素。方法分别检测正常人、冠心病、2型糖尿病和冠心病合并2型糖尿病患者BMI指数、PP、FBG、TC、TG、LDL、HDL、LP(a)、hs-CRP、HbA1c、UA和脂联素,比较四组研究对象之间的差异。结果 CHD组、T2DM组和CHD+T2DM组患者BMI指数、FBG、TC、TG、LDL、LP(a)、UA和脂联素与正常组相比的差异具有统计学意义(P<0.05);CHD组和CHD+T2DM组的PP和hs-CRP与正常组的差异有统计学意义(P<0.05),而在T2DM组中则无统计学意义(P>0.05);T2DM组和CHD+T2DM组的FBG和HbA1c显著高于正常组(P<0.05),而在CHD组中无明显差异(P>0.05)。BMI指数、FBG、TC、TG、LDL、LP(a)、HbA1c和脂联素是糖尿病和冠心病的危险因素(P<0.05),PP、UA和hs-CRP则为冠心病的危险因素(P<0.05),HbA1c为糖尿病的危险因素(P<0.05),HDL为冠心病和糖尿病的保护因素(P<0.05)。结论冠心病合并2型糖尿病患者脂代谢指标显著高于正常人,血尿酸和脂联素增高为危险因素,HDL为保护因素。     

2型糖尿病患者血清脂联素水平变化及其与胰岛素抵抗关系的探讨

目的观察2型糖尿病、冠心病患者血清脂联素水平的变化,分析2型糖尿病患者血清脂联素与甘油三酯、体重指数及胰岛素抵抗的关系。方法选取单纯糖尿病患者34例,冠心病患者35例,糖尿病合并冠心病患者30例,健康对照30名作为研究对象,应用放射免疫分析方法测定所有受试者血清脂联素水平,同时测定糖尿病患者及糖尿病合并冠心病患者血清甘油三酯、空腹胰岛素、空腹血糖、体重指数,计算自身稳定型评价胰岛素抵抗(homeostaticmodelassessment-insulinresistance,HOMA-IR)指数。所有计量资料数值以x±s表示,均数之间的差异选用方差分析;各变量之间的关系用直线相关和多元线性回归分析。结果2型糖尿病组[(20±11)滋g/ml]、冠心病组[(18±15)滋g/ml]血清脂联素水平明显低于健康对照组[(37±20)滋g/ml],P值均<0.01;2型糖尿病合并冠心病组血清脂联素水平低于单纯2型糖尿病组[(11±3)滋g/mlvs(29±10)滋g/ml,P<0.01];HOMA-IR指数低于单纯2型糖尿病组[(1.0±0.5)vs(1.3±0.7),P<0.05];2型糖尿病组患者血清脂联素水平与体重指数呈负相关(r=-0.291,P<0.05)、与HOMA-IR指数呈显著负相关(r=-0.473,P<0.01);经多元线性回归分析显示,体内血清脂联素水平只与HOMA-IR指数呈负相关(回归系数=-0.571,P=0.000)。结论2型糖尿病患者、?     

血清脂联素水平与2型糖尿病患者动脉粥样硬化的相关性

目的探讨脂联素(APN)与2型糖尿病(T2DM)动脉粥样硬化的相关性。方法采用ELISA法检测T2DM动脉粥样硬化病变组(AS组,60例)、T2DM非动脉粥样硬化病变组(NAS组,96例)和正常对照组(NC组,68例)血清APN水平。同时检测糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),并计算体重指数(BMI)和胰岛素抵抗指数(HOMA-IR)。结果 APN在NC组、NAS组、AS组依次减低(P<0.05);AS组和NAS组APN水平与BMI、HOMA-IR、HbAl呈负相关(r值分别为-0.467、-0.444、-0.168)(P<0.05),与HDL-C正相关(r值为0.176)(P<0.05);APN、HOMA-IR与HbAlc是DM患者动脉粥样硬化发生的独立危险因素。结论 APN是DM患者动脉粥样硬化发生的独立危险因素,有可能是治疗T2DM大血管并发症的新靶点。     

罗格列酮对2型糖尿病患者血清脂联素、内脂素水平的影响

目的 探讨罗格列酮对2型糖尿病（T2DM）患者血清脂联素、内脂素水平的影响.方法 我院初次诊断的T2DM患者共95例,按照随机数字表法随机分为对照组（40例）和治疗组（55例）.对照组接受糖尿病知识教育,进行饮食干预和运动疗法,早晚口服二甲双胍缓释片500 mg,治疗过程中不用影响血糖的其他药物.治疗组在对照组的基础之上,加用罗格列酮4 mg/d.两组疗程均为16周.治疗前、后分别测定患者空腹血糖（FBG）、餐后2h血糖（PBG）、糖化血红蛋白（HbA1C）、空腹胰岛素（FINS）、血清脂联素和内脂素,并计算胰岛素抵抗指数（HOMA-IR）.结果 T2DM患者血清脂联素水平明显降低[（7.8±3.2） mg/L vs.（3.2±1.3）mg/L],内脂素水平明显升高[（85.6±18.5）μg/Lvs.（127.8±20.1）μg/L]（P＜0.01）.罗格列酮能明显降低T2DM患者FBG、PBG、HbA1C、FINS水平,改善HOMA-IR （P＜0.001）;与对照组相比,治疗组血清脂联素水平明显增高[（3.2±0.9）mg/L vs.（7.7±2.1）mg/L],内脂素水平明显降低[（125.3±18.8）μg/L vs.（79.3±16.4）μg/L （P＜0.01）].T2DM患者血清脂联素与BMI、FPG、HOMA-IR和内脂素呈负相关（P＜0.01）;内脂素水平与BMI、FPG和HOMA-IR呈正相关（P＜0.01）.结论 罗格列酮可通过调控脂联素和内脂素水平,改善胰岛素的敏感性,降低胰岛素的抵抗性,达到纠正高胰岛素血症、降低血糖水平的目的,值得临床推广应用.     

血浆网膜素水平与代谢综合征的关系研究

目的:探讨2型糖尿病(T2DM)合并代谢综合征(MS)患者血浆网膜素水平的变化.方法:收集T2DM患者95例和正常对照(NC)组36例,将T2DM患者分为T2DM不合并MS组(A组)46例,T2DM合并MS组(B组)49例.采用ELISA检测3组空腹血浆网膜素水平,检测各组血糖、血脂、空腹胰岛素(Fins)、收缩压(SBP)、舒张压(DBP),计算腰臀比(WHR)、体质量指数(BMI),胰岛索抵抗指数(HOMA-IR),并分析各指标与网膜素的关系.结果:血浆网膜素水平NC组最高,A组其次,B组水平最低;其与腰围(WC)、臀围(HC)、BMI、三酰甘油(TG)、空腹血糖(FBG)、75 g葡萄糖负荷后2 h血糖(2hPG)、Fins、HOMA-IR、SBP、DBP呈负相关(r分别为-0.465、-0.473、-0.814、-0.696、-0.380、0.635、-0.691、-0.684、-0.663、-0.522,P＜0.01),与高密度脂蛋白胆固醇(HDL-C)呈正相关(r=0.279,P＜0.01).BMI、2hPG和WC是空腹血浆网膜素的影响因素.结论:MS患者血浆网膜素水平与胰岛素抵抗和肥胖密切相关,可能在MS的发病过程中起到重要作用.     

脂联素及TNF-α与2型糖尿病视网膜病变的关系

目的探讨脂联素(adiponectin)及肿瘤坏死因子α(TNF-α)在2型糖尿病(DM)视网膜病变(DR)发病中的作用。方法应用酶联免疫吸附方法(ELISA)对90例2型糖尿病患者(再分为无DR组、背景组DR组和增殖期DR组)及40名健康人血清中的脂联素及TNF-α进行测定。结果①DM组血清脂联素及TNF-α的含量低于对照组(P<0.05);②BDR组的脂联素及TNF-α含量低于NDR组(P<0.05);③PDR组的脂联素及TNF-α含量低于NDR组(P<0.01);④PDR组的脂联素含量及TNF-α低于BDR组(P<0.05);⑤DR的严重程度与脂联素水平呈负相关(r=-0.428,P<0.01)。结论脂联素及TNF-α的降低在DM的发病机制中起重要作用,而2型糖尿病合并视网膜病变时,血中脂联素及TNF-α水平更低,脂联素及TNF-α可能参与了DR的发生和发展。     

Alcohol,Age, and Piloting: Judgment,Mood, and Actual Performance

We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching. 04 g/dL (.04%) BAL, after. 10% BAL, and then 2,4, 8,24, and 48 h after. 10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve.     

Smooth-pursuit eye movements,and diazepam,CPZ, and secobarbital

This study examined the effects on smooth-pursuit eye tracking of single doses of CPZ (0.667 and 1.334 mg/kg), diazepam (0.071, 0.142, and 0.284 mg/kg), and secobarbital (100 mg). Only the barbiturate significantly affected the ability to follow a moving target with smooth-pursuit eye movements. In repeated testing of a single subject, 130 mg of secobarbital disrupted smooth-pursuit movements at least until 24 hrs after ingestion.This study was supported in part by grant MH-19477, USPHS, and USFDA contract No. 72-42. Dr. Holzman is the recipient of Research Scientist Award No. K5-MH-70900, USPHS. We express our thanks to Dr. Alfred Heller for helpful comment.     

Temperature,pH, salinity,hardness, and particulates mediate nickel toxicity to eubacteria,an actinomycete,and yeasts in lake,simulated estuarine,and sea waters

The survival of some eubacteria, an actinomycete, and yeasts after acute and chronic exposures to nickel (Ni) in lake, simulated estuarine, and sea waters and the influence of environmental factors on Ni toxicity were determined. Nickel toxicity to microbes in marine systems was reduced by increasing the salinity, by decreasing the temperature, and by the incorporation of simulated sediment. The toxicity of Ni to microbes in fresh water was reduced by increasing the pH, by increasing the hardness, and by the incorporation of suspended particulates. Chronic toxicity studies indicated that fresh waters are more sensitive than marine waters to Ni pollution, as microbial survival was greater in marine than in fresh waters stressed with equivalent concentrations of Ni.     

Opiates,catecholamines, behavior,and mood

Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.     

Gradualism, identity, reinforcements, and change

This paper reflects the ongoing development of gradualism, a drug treatment perspective that seeks to make use of the full array of effective, creative, and innovative harm reduction and abstinence-oriented treatments available to help addicted individuals move along a continuum from active/chaotic use to abstinence or moderation, as appropriate. The essence of gradualism is an emphasis on positive change and transformation as therapeutic goals. The paper first looks at manifestations of gradualism in harm reduction treatment facilities. Following this is a discussion of the role of identity transformation in the change process. The final section explores how contingency management or motivational incentive interventions could be used in harm reduction settings to facilitate this kind of therapeutic movement.     

Chemistry,Manufacturing, and Controls Information in NDAs and ANDAs,Supplements, Annual Reports,and Other Regulatory Filings

Advice to the pharmaceutical industry regarding the chemistry, manufacturing, and controls and microbiology (sterility assurance) information to be included in regulatory submissions to the Center for Drug Evaluation and Research (CDER) can be found in the pertinent statutes, regulations, and guidances. The primary statute is the Federal Food, Drug and Cosmetic Act (the Act); applicable regulations appear in 21 CFR 312 and 314. Neither the Act nor the regulations provide sufficient detail on the information that should be included in these submissions. Over the past 14 years CDER has issued a series of guidelines and guidances that provide specific detail related to the recommended filing mechanisms and information that CDER expects applicants to provide. Some of these guidances are applicable to original submissions and some are applicable to post-approval changes. This article will provide an overview of The Act, the pertinent regulations, and the pre- and post-approval guidances.     

Fibroblasts, myofibroblasts, and fibrosis: fact, fiction, and the future

Fibroblasts and their activated phenotype known as myofibroblasts are nonexcitable cells found in all organs of the body. In the heart, fibroblasts, along with the endothelial and smooth muscle cells of the blood vessels, make up approximately 30% of tissue mass. In vitro, myofibroblasts cocultured with cardiac myocytes can propagate electrical signals down cellular strands indicating that under these conditions myofibroblasts are capable of depolarizing enough to maintain electrical propagation. This has obvious implications for cardiac biology if heterocellular coupling between fibroblasts and myocytes were to occur in the intact heart either under normal conditions or during cellular stress. The purpose of this review series is to highlight the newest information on cardiac fibroblasts and myofibroblasts and to review the data on their interactions with cardiac myocytes.     

Polymorphism, pseudopolymorphism, and amorphism of peracetylated alpha-, beta-, and gamma-cyclodextrins

Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-alpha-cyclodextrin (TAalphaCyD), heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TAbetaCyD), and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TAgammaCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAalphaCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAbetaCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAgammaCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAalphaCyD.2H2O and TAbetaCyD.CH3OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.     

Propylthiouracil,and methimazole,and carbimazole-related hepatotoxicity

Introduction: Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.

Areas covered: This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.

Expert opinion: PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.