肝素及小肝素分子对培养平滑肌细胞的双重调节作用

为研究肝素及小肝素分子对培养的平滑肌细胞生长的作用,以探讨其是否可以作为一种抗血管平滑肌细胞增殖的药物,采用＾３Ｈ－胸腺嘧啶脱氧核苷掺入法观察肝素及小肝素分子对培养的人主动脉平滑机细胞合成ＤＮＡ的影响。肝素及小肝素分子的量以糖醛酸表示,以其浓度计算（１８、３５一７０ｍｇ／Ｌ）。结果发现,肝素及小肝素分子对生长良好的平滑肌细胞有抑制作用,不同浓度肝素的抑制率分别为６６％、６９％和６９％,而不同浓度小     

The Influence of Heparin on the Wound Healing Response to Collagen Implants in vivo

The biologic response to fibrillar collagen (collagen) and fibrillar collagen plus heparin(collagen/heparin) implants have been compared in the rat subcutaneous and guinea pig dermal wound models. The reconstituted bovine dermal collagen implants were injected subcutaneously in rats at concentrations ranging from 18 to 30 mg/ml and in volumes ranging from 0.5 to 1.0 ml. The biologic response to the collagen implants alone was characterized by a transient invasion of a modest number of inflammatory cells within the first three days of implantation that was followed by limited fibroblast invasion into the peripheral 1/3 of the implant during the course of the next three to four weeks. Occasionally, blood vessels were observed to invade the peripheral regions of the implant. The degree (number) and extent (depth) of cell invasion were inversely related to initial collagen implant concentration. Addition of heparin (0.3-20 μg/mg collagen) to these implants resulted in a significant dose-dependent increase in the degree and extent of fibroblast invasion. Radiolabeling studies showed that the collagen and collagen/heparin implants were cleared from the subcutis at identical rates. Implantation of these formulations in a guinea pig dermal wound model was also performed, using a semi-occlusive wound dressing (Opsite) to maintain the implant in the wound site. The fibrillar collagen implant alone was pushed upward by developing granulation tissue at the base of the wound and served as a support for epidermal cell migration, proliferation, and differentiation as wound closure proceeded. The implant was slowly invaded and turned over as granulation tissue developed from the base and margins of the wound bed. The inclusion of heparin in these implants resulted in a significantly different pattern of wound healing. The collagen/heparin implants histologically presented a more broken-up or porous appearance following implantation, which was associated with a greater degree of penetration of developing granulation tissue into the implant itself as compared to the collagen implants. Radiolabeling studies revealed that clearance rates of implants with and without heparin from wound sites were similar, as noted in the rat subcutis. Laser doppler flowmetry studies suggested that the heparin-containing implants were more vascular than control wound sites or sites treated with collagen alone.     

不同途径应用低分子肝素对血小板活性的影响及阿司匹林的干预作用

目的:探讨不同途径应用低分子肝素(LMWH)对血小板活性的影响,并观察联用常规剂量100 ms/d的阿司匹林对该影响的干预作用.方法:107例患者依据用药途径不同分为静脉达肝素钠组(n=29)、皮下达肝素钠组(n=27)、静脉达肝素钠加阿司匹林组(n=25)和皮下达肝素钠加阿司匹林组(n=26).分别采用酶联免疫双抗体夹心法(ELISA)和流式细胞技术检测静脉及皮下应用低分子肝素后血小板活化指标:血小板α颗粒膜糖蛋白-140(GMP-140)、血管性假血友病因子相关抗原(vWF:Ag)及血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)受体复合物的变化,并观察联用常规剂量阿司匹林干预后上述指标的变化.结果:不同途径应用低分子肝素对血小板激活的影响:血小板膜糖蛋白Ⅱb/Ⅲa水平:静脉达肝素钠组注射0.5 h后和皮下达肝素钠组注射2天后均较其注射前升高,差异均有统计学意义(P<0.05).血小板α颗粒膜糖蛋白-140水平:静脉达肝素钠组注射0.5 h后较其注射前升高,差异有统计学意义(P<0.05).阿司匹林对不同途径应用低分子肝素激活血小板的干预作用:静脉达肝素钠加阿司匹林组和皮下达肝素钠加阿司匹林组,血小板膜糖蛋白Ⅱb/Ⅲa水平、血小板α颗粒膜糖蛋白-140水平,2组各时间点较注射前差异无统计学意义(P>0.05);而血管性假血友病因子相关抗原水平,静脉达肝素钠加阿司匹林组注射0.5 h后较其注射前下降,差异有统计学意义(P<0.05).结论:静脉或皮下应用低分子肝素均可以激活血小板,且联用常规剂量100 mg/d的阿司匹林能够有效抑制由低分子肝素引起的血小板活性增高.     

饲料中蛋白质水平对Wistar大鼠体重影响观察

为观察饲料中蛋白质水平对Wistar大鼠生长的影响,分别饲喂含蛋白质31．2％、23．8％和16．1％的饲料,观察大鼠体重的变化,三组Wistar大鼠体重增长有差异（P＜0．05）。雌雄间体重有极显差异（P＜0．01）。     

The Effect of Bolus Viscosity on Laryngeal Closure in Swallowing: Kinematic Analysis Using 320-Row Area Detector CT

The present study examined the effect of bolus viscosity on the onset of laryngeal closure (relative to hyoid elevation), the duration of laryngeal closure, and other key events of swallowing in ten healthy volunteers. All volunteers underwent 320-row area detector computed tomography swallow studies while swallowing 10 ml of honey-thick barium (5 % v/w) and thin barium (5 % v/w) in a 45° reclining position. Three-dimensional images of both consistencies were created in 29 phases at an interval of 0.10 s (100 ms) over a 2.90-s duration. The timing of the motions of the hyoid bone, soft palate, and epiglottis; the opening and closing of the laryngeal vestibule, true vocal cords (TVC), and pharyngoesophageal segment; and the bolus movement were measured and compared between the two consistencies. The result showed differing patterns of bolus movement for thin and thick liquids. With thin liquids, the bolus reached the hypopharynx earlier and stayed in the hypopharynx longer than with thick liquids. Among events of laryngeal closure, only the timing of TVC closure differed significantly between the two consistencies. With thin liquids, TVC closure started earlier and lasted longer than with thick liquids. This TVC movement could reflect a response to the faster flow of thin liquids. The results suggest that bolus viscosity alters the temporal characteristics of swallowing, especially closure of the TVC.     

低分子肝素治疗短暂性脑缺血发作疗效观察

目的观察低分子肝素治疗短暂性脑缺血发作(TIA)的疗效。方法治疗组加用低分子肝素5000IU腹壁皮下注射,2次/d,连用5~7d,其余治疗同对照组。观察两组患者的临床疗效,治疗前及治疗3~7d的凝血酶原时间、活化部分凝血酶原时间。结果两组患者疗效间差别有显著性意义(P<0·05);两组患者治疗前后凝血酶原时间、活化部分凝血酶原时间差别均无显著性意义(P>0·05)。结论低分子肝素治疗短暂性脑缺血发作疗效显著、安全可靠,临床应用方便,对血液生化指标无明显影响,且出血的发生率低。     

依达拉奉联合低分子肝素钙及肠溶阿司匹林治疗急性进展性脑梗死临床疗效观察

目的观察依达拉奉联合低分子肝素钙及肠溶阿司匹林治疗急性进展性脑梗死的临床疗效。方法选择我院2009年9月—2012年12月收治的急性进展性脑梗死患者150例,将其随机分为治疗组、抗凝组及对照组,各50例。对照组应用肠溶阿司匹林及常规治疗,在此基础上抗凝组联合应用低分子肝素钙,治疗组联合应用依达拉奉及低分子肝素钙,均连续治疗14 d为1个疗程。评定3组患者治疗前及治疗14 d后临床神经功能缺损评分及临床疗效。结果治疗14 d后,治疗组神经功能缺损评分低于其他两组,抗凝组神经功能缺损评分低于对照组(P0.05)。对照组总有效率为76%(38/50),抗凝组总有效率为82%(41/50),治疗组总有效率为90%(45/50),治疗组总有效率高于其他两组,抗凝组总有效率高于对照组(P0.05);3组均无明显不良反应。结论依达拉奉联合低分子肝素钙及肠溶阿司匹林治疗急性进展性脑梗死疗效显著,能明显改善患者神经功能缺损程度,且安全。     

非诺贝特和吡格列酮对代谢综合征大鼠血压及体重的影响

目的:探讨非诺贝特和吡格列酮对高果糖诱导的代谢综合征(MS)大鼠血压及体重的影响.方法:用高果糖饮食饲养SD大鼠构建Ms大鼠模型,将存活的大鼠随机分为空白对照组(n=8),代谢综合征模型组(n=39).又将代谢综合征模型组分为4个亚组:模型对照亚组(n=10),非诺贝特亚组(n=8),毗格列酮亚组(n=11),非诺贝特+吡格列酮哑组(n=10)分别单用非诺贝特和吡格列酮及二者合用干预.分析比较两种药物单用及合用,对MS大鼠收缩压、体重等的影响.结果:吡格列酮亚组干预后与干预前比收缩压降低(P<0.01),胰岛素敏感指数(ISI)升高(P<0.01).非诺贝特亚组干预后与干预前比收缩压、ISI变化均不明显(P>0.05).非诺贝特+吡格列酮亚组干预后与干预前比收缩压降低,ISI升高(P均<0.01),差异有统计学意义.干预后,各药物干预亚组与模型对照亚组问体重差异无统计学意义(P>0.05).结论:单用吡格列酮或合用非诺贝特干预明显改善MS大鼠胰岛素抵抗、降低收缩压,可更好地控制其心血管病的危险因素.     

Effect of Body Weight and Lifestyle Changes on Long-Term Course of Nonalcoholic Fatty Liver Disease in Koreans

BackgroundAlthough the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing, there have been few studies of long-term changes in NAFLD in large numbers of subjects. This study was performed to assess the long-term changes in severity of fatty liver and to analyze the association with changes in body weight and lifestyle factors.MethodsWe analyzed lifestyle factors, biochemical data, and abdominal ultrasonography in subjects who underwent voluntary medical checkups at a 5-year interval. Fatty liver on ultrasonography was graded as normal, mild, moderate, or severe by the degree of echogenicity.ResultsThe analyzed population consisted of 2895 subjects of age 47 ± 8.7 years (range, 20-79 years). Among the 1938 subjects who had normal livers at baseline, 374 subjects (19%) developed fatty liver 5 years later. Those who developed fatty liver showed more weight gain, increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GT), and glucose levels during the 5-year period. Among the 930 subjects who had fatty liver at baseline, 263 (28%) subjects showed a decrease in grade and 209 (22%) progressed to a higher grade of fatty liver after 5 years. The group with a lower grade lost ?2.2 ± 4.3 kg of body weight from baseline, and reduction in hepatic steatosis grade was associated with decreased serum AST, ALT, triglycerides, γ-GT, and fasting glucose levels.ConclusionsEven a small weight reduction was associated with improvements in NAFLD and related metabolic abnormalities such as dyslipidemia and hyperglycemia. Subjects with fatty liver should be advised to lose weight through lifestyle modifications.     

Comparative Effects of Unfractionated Heparin and Low Molecular Weight Heparin on Vascular Endothelial Cell Tissue Factor Pathway Inhibitor Release: A Model for Assessing Intrinsic Thromboresistance

Objectives: The purpose of our study was to characterize tissue factor pathway inhibitor (TFPI) release from human vascular endothelial cells following daily exposure to varying concentrations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Background: A rebound increase in ischemic/thrombotic events, including myocardial infarction and cardiovascular death, has been observed after the abrupt cessation of UFH. In a single center pilot study of patients with acute coronary syndromes (ACS) we reported that thrombin generation was evident within one (1) hour of UFH cessation, increased progressively over the subsequent 24 hours, correlated directly with factor VII activity and inversely with TFPI (concentration and activity). Methods: Human umbilical vein endothelial cells were grown to confluence and incubated with varying concentrations of UFH or dalteparin, a low molecular weight haparin, for up to 144 hours. Daily samples of the cells supernatant were obtained and assayed for TFPI. Cellular reserve and responsiveness to recombinant endothelial cell growth factor (rEGF) stimulation were determined at 168 hours. Results: In low concentrations (0.5 U/mL) UFH caused a progressive rise in TFPI concentration with a peak level of 6.36 ± 0.5 ng/10⁵ cells at 24 hours. By 72 hours of daily exposure, the levels declined to below control values and TFPI release following rEGF stimulation was reduced by approximately 60% compared to control (1.93 ± 0.42 vs 4.3 ± 0.78 ng/10⁵ cells; p = 0.001). Initial endothelial cell release and rate of decline were more robust with high concentrations of UFH (5.0 U/ml). TFPI levels were above control values at each sampling time point up to 120 hours and cellular responsiveness to stimulation was preserved with dalteparin (compared to UFH) (p < 0.001). Conclusions: Thrombin generation and clinical events that occur during treatment with UFH and following its abrupt cessation may represent an acquired state of transiently impaired thromboresistance to the tissue factor-VIIa complex. The differing effects of UFH and LMWH on vascular endothelial cell TFPI synthesis, release and reserve with prolonged administration require further investigation.     

盐酸决奈达隆对家兔体重和甲状腺功能及肝功能的影响

目的研究决奈达隆不同剂量对家兔体重、甲状腺功能及肝功能的影响,探讨其安全性。方法选择新西兰兔27只,随机分为对照组（n=7）,决奈达隆低剂量组[n=9,50mg/（kg^-1·d^-1）,LDR],决奈达隆高剂量组[n=11,100mg/（kg^-1·d^-1）,HDR],专业灌胃器灌胃每日一次,对照组给予等量生理盐水,4周后,观察家兔一般状况、体重,耳缘静脉取血测总T4,总T3,丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（γ-GGT）、碱性磷酸酶（ALP）。结果 LDR组及HDR组各出现2例体重负增长,但三组之间体重增长无差异,三组ALT水平分别为：（20.43±4.23）IU/L,（21.67±5.07）IU/L和（36.82±18.00）IU/L,HDR与对照组之间存在统计学意义（P〈0.05）,与LDR以及LDR与对照组之间无统计学意义;三组ALP水平分别为（143.14±50.9）IU/L,（109.22±38.6）IU/L和（153.82±40.55）IU/L,HDR与LDR之间存在统计学意义（P〈0.01）,三组间T3,T4,T4/T3,AST,γ-GGT水平均无统计学意义,剂量水平和T3、T4、ALT水平无相关性。结论在家兔模型中决奈达隆高剂量组可导致轻度ALT水平异常,可能抑制体重增长,但对甲状腺功能无明显影响。