血脂异常影响因素与药物防治研究

目的探讨高脂血症的预防及药物治疗手段。方法通过对285位居民进行调查分析,结合相关文献,总结高脂血症的发病规律及防治要点。结果与结论高脂血症发病率女性高于男性,60～69岁之间的患者血脂二项升高明显。高脂血症预防重于治疗,食疗重于药疗。饮食、运动疗法是首要的基本治疗措施,药物治疗主要是他汀类、贝特类及中药。     

他汀类药物与贝特类药物联合应用的临床研究

目的探讨他汀类与贝特类药物联合应用治疗混合性高脂血症的临床疗效及安全性。方法选择混合性高脂血症患者68例,采用辛伐他汀和非诺贝特两种药物联用治疗,连续用药两个月。结果经两个月的药物治疗,所有患者的TC、LDL—C、TG水平下降,HDL—C水平提升。2例患者出现恶心、呕吐,1例出现左肩肌肉轻度酸沉,谷丙转氨酶轻度升高。其余患者均无不良反应。结论小剂量他汀类与贝特类药物联合应用治疗混合性高脂血症,有利于改善患者血脂的各项指标,临床疗效显著,安全性高,可值得临床推广应用。     

“拜斯亭”撤市事件对他汀类药物临床应用的启示

血脂异常与冠心病的发生、发展有着非常密切的联系。高脂血症患者,尤其是合并有心血管疾病高危因素的高脂血症患者,其调脂治疗的必要性已成共识。在诸多类的血脂调节药中,他汀类调脂药是具有广泛循证医学证据支持的一类里程碑式的药物。     

抗高脂血症的药物选择

高脂血症是血浆脂蛋白代谢异常的结果 ,可表现为高胆固醇血症、高甘油三脂血症或混合性高脂血症。血脂过高与动脉粥样硬化和冠心病的病死率密切相关 ,危害着人类的健康。目前临床所使用的血脂调节剂主要有五大类 :胆汁螯合剂如考来烯胺 (消胆胺 )等 ;烟酸类如烟酸肌醇酯、阿西莫司 (乐脂平 )等 ;贝特类如吉非贝特 (诺衡 )、非诺贝特 (力平脂 )等 ;他汀类如洛伐他汀、辛伐他汀等 ;鱼油制剂如多烯康。本文综合文献及针对患者血脂成分如总胆固醇 (TC)、甘油三酯 (TG)等的异常情况对上述调脂药物的选择作一简要阐述。1 仅降低血清TC的药物1 1…     

他汀类联合非诺贝特治疗混合型高脂血症和致动脉粥样硬化血脂异常的社区应用

目的:探讨他汀类联合非诺贝特治疗混合型高脂血症和致动脉粥样硬化血脂异常的社区应用.方法:选取2010年1月~2015年10月我社区卫生服务中心管理的270例混合型高脂血症和致动脉粥样硬化血脂异常患者为研究对象,随机数字表法均分为三组各90例,给予阿托伐他汀治疗的记为a组,给予辛伐他汀联合非诺贝特治疗的记为b组,给予阿托伐他汀联合非诺贝特治疗的记为c组,对三组治疗临床疗效、血脂达标率及药物安全性进行观察比较.结果:三组治疗后TG、TC、LDL-C分别均较治疗前显著降低,HDL-C显著升高,治疗后b、c组TG、TC、LDL-C均较a组降低显著,HDL-C升高显著,差异具有统计学意义(P<0.05);b、c组治疗后血脂指标相比无显著差异(P>0.05);治疗后b、c组血脂总达标率分别均较对照组显著升高(P<0.05),b、c组相比无显著差异(P>0.05);治疗后三组药物不良反应总发生率两两比较无显著差异,均无统计学意义(P>0.05).结论:他汀类联合非诺贝特治疗混合型高脂血症和致动脉粥样硬化血脂异常临床疗效显著,可有效调节患者血脂水平,是一种疗效确切、安全、可靠的药物方案,值得社区推广.     

胆固醇吸收抑制剂依泽替米贝的研究进展

高脂血症是引起动脉粥样硬化等心血管疾病发生的重要危险因素,大量的证据表明,降低血浆中总胆固醇水平可以降低心血管疾病的危险性。实际上,不仅低密度脂蛋白-胆固醇（LDLC）水平的升高会增加心血管疾病的发病率和致死率,三酰甘油（TG）水平的增加和高密度脂蛋白-胆固醇（HDL—C）水平的降低也被认为是导致心血管疾病危险的可依赖指标。新型的降脂药物应该是既能降低LDL—C,又不能升高TG水平。目前,临床治疗高脂血症的药物主要包括胆固醇合成抑制剂（如他汀类）、苯氧酸类（如贝特类）、胆汁酸螯合剂（如消胆胺）及其它（如烟酸类似物）。     

治疗高脂血症的新药研究进展

高脂血症是动脉粥样硬化的危险因素,与冠心病、中风及股动脉狭窄等病症息息相关,严重威胁人类健康。他汀类药物因确切的疗效,已成为大多数临床医生的首选。但大剂量服用他汀类药物会产生肌毒和肝转氨酶升高,并不适用于所有的心血管类疾病。此外贝特类和烟酸类药物会产生胃肠道不适和肝肾损伤。因此寻找疗效显著、安全可靠的调血脂药一直是医药工作者长期研究的课题。综述基于Pubmed上关于人高脂血症(胆固醇、三酰甘油、LDL-C、HDL-L)主要治疗药物的相关研究,对近年来调血脂药物研究进展进行综述。     

重性精神病合并高脂血症的危害及他汀类降脂治疗进展

合并心血管疾病是重性精神病患者过早死亡的首要原因,而血脂代谢紊乱是心血管疾病的重要危险因素,但迄今仍未引起足够的重视。目前,血脂异常的防治指南多推荐强化降脂干预治疗,即在治疗性生活方式改变无效的情况下,采用药物调脂治疗。其中他汀类是临床应用最广泛的降脂药,他汀类能有效调整重性精神病合并高脂血症的血脂水平,不良反应仅见于个案报道。     

高血脂患者的药物选用

高脂血症是心血管疾病的主要危险因素之一,高脂血症可表现为高胆固醇血症、高甘油三酯血症或两者兼有,降脂药种类繁多,以胆固醇水平升高为主选用他汀类,以甘油三酯水平升高为主选用贝特类,以高密度脂蛋白降低为主选用烟酸类,顽固性高脂血症者选用抑制胆固醇吸收剂。混合型高脂血症者选用胆酸隔置剂。     

高脂血症的临床用药

心血管疾病是目前威胁我国人民健康的重大疾病之一,而由脂代谢紊乱所致的高脂血症是动脉粥样硬化(AS)及冠心病(CHD)的重要致病因素.因此血脂调节药的研究已渐成为心血管疾病防治工作中的重要课题.根据有关专家对北京、上海、广州等17家"三级甲等"医院1000余例高脂血症患者治疗现状的最新调查,其临床用药位居首位的是他汀类,占调脂处方总数的59.0%,余依次为贝特类(23.7%),中成药(11.4%),多烯脂肪酸类(3.9%)及烟酸类(1.7%)等[1].本文就高脂血症的临床用药作一简述.     

alpha-glucosidase (CHO) (Genzyme)

Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.     

(S)-oxybutynin (Sepracor)

Sepracor is developing (S)-oxybutynin, a single-isomer version of Alza's Ditropan (racemic oxybutynin), a muscarinic acetylcholine receptor antagonist, as a potential treatment for urinary incontinence.     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic

Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.     

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.     

1,2-环己二胺柠檬酸铂(Ⅱ)及异柠檬酸铂(Ⅱ)的合成和抗癌活性

报道了1,2-环己二胺异柠檬酸铂(Ⅱ)及1,2-环己二胺柠檬酸铂(Ⅱ)的合成及鉴定方法。抗癌试验表明前者在40及80mg/kg 剂量下对小鼠 L1210、P388及S180均有明显的抑瘤作用,且有部分动物可治愈;后者对 L1210也有明显的抑瘤作用,但较前者为弱。     

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.     

4（R）—（6—氨基—9H—嘌呤—9—基）—2（R）—（羟甲基）四氢呋喃—3（R）—醇的合成

为寻找抗HIV化合物,我们以D－核糖为原料,经甲基化、硅烷基化、还原裂解反应制得重要中间体1－脱氧核糖（5）,再通过形成环状亚砜化合物,与NaN3发生反应后,经过还原、缩合、环合、氨化、脱保护基反应制得异脱氧腺嘌呤核苷（1）,各步反应收率均超过70％。其抗HIV活性测定尚在进行中。     

Psychopharmacological profile of 1-(m-(trifluoromethyl) phenyl) piperazine (TFMPP)

The effect of TFMPP, an agonist of the 5-HT1b receptors, was studied in mice on several psychopharmacological parameters. In contrast to imipramine-like drugs, TFMPP neither antagonized reserpine-induced hypothermia nor increased yohimbine-induced toxicity. Similarly to imipramine-like drugs, TFMPP antagonized oxotremorine-induced hypothermia and was active in the behavioural despair test. In addition, TFMPP normalized a social behavioural deficit induced by isolation. The effects of TFMPP on oxotremorine-induced hypothermia in the behavioural despair test and in the isolation-induced social behavioural deficit are all antagonized by d-1 propranolol. It is concluded that TFMPP seems to possess psychotropic activity resembling only in part that of imipramine-like drugs and that these actions may be mediated through 5-HT1b receptors.