缺血性卒中急性期他汀类药物治疗对血清超敏C-反应蛋白影响及预后评价

对他汀类药物治疗组(他汀治疗组)或非他汀类药物治疗组(对照组)患者入院时和发病30 d时临床资料进行分析,并比较两组血清超敏C-反应蛋白水平的变化。结果显示,他汀治疗组患者发病30 d时血清超敏C-反应蛋白低于对照组(t=9.925,P=0.015),发病后3个月预后优于对照组(χ2=4.762,P=0.029);经逐步Logistic回归分析,入院时美国国立卫生研究院卒中量表评分(OR=1.383,95%CI:1.062~1.800;P=0.028)和发病48 h血清超敏C-反应蛋白水平(OR=1.472,95%CI:0.500~4.370;P=0.001)对患者发病3个月时的预后具有独立预测作用。提示他汀类药物可以降低急性缺血性卒中患者血清超敏C-反应蛋白水平,对发病3个月时的预后具有预测作用。     

阿托伐他汀对脑梗死患者C-反应蛋白及血脂的影响

目的研究阿托伐他汀对脑梗死患者C-反应蛋白及血脂的影响。方法60例脑梗死患者给予阿托伐他汀10mg,口服,1次/d,疗程4周。观察治疗前后血清C-反应蛋白及血脂浓度的变化。结果使用阿托伐他汀治疗后患者血清C-反应蛋白、胆固醇、甘油三脂、低密度脂蛋白显著降低,高密度脂蛋白上升。结论阿托伐他汀能够降低脑梗死患者的血脂及C-反应蛋白,从而降低脑血管病的发生。     

急性缺血性卒中血清超敏C-反应蛋白与改良TOAST分型和OCSP分型关系的研究

探讨急性缺血性卒中患者血清超敏C-反应蛋白(hs-CRP)表达变化与改良TOAST分型和OCSP分型之间的关系。实验室检测显示,缺血性卒中组患者血清hs-CRP表达水平高于正常对照组[(13.68±6.92)mg/L对(3.98±0.76)mg/L;t=6.922,P=0.002]。TOAST分型中以心源性栓塞型患者血清hs-CRP水平[(16.82±6.16)mg/L]最高,然后依次为动脉粥样硬化血栓形成型[(15.71±5.68)mg/L]、不明病因型[(10.06±3.89)mg/L]和小动脉型[(9.86±3.75)mg/L,P=0.027];OCSP分型由高至低分别为完全前循环梗死型[(17.02±6.98)mg/L]、后循环梗死型[(15.91±7.12)mg/L]、部分前循环梗死型[(12.83±4.95)mg/L]和腔隙性梗死型[(10.61±5.73)mg/L,P=0.005]。提示急性缺血性卒中患者血清hs-CRP表达水平在改良TOAST分型和OCSP分型各亚型中存在差异,可以此指导临床治疗和判断预后。     

阿托伐他汀对脑梗死患者C-反应蛋白及血脂的影响

目的研究阿托伐他汀对脑梗死患者D反应蛋白及血脂的影响。方法60例脑梗死患者给予阿托伐他汀10mg，口服，1次／d，疗程4周。观察治疗前后血清C-反应蛋白及血脂浓度的变化。结果使用阿托伐他汀治疗后患者血清C-反应蛋白、胆固醇、甘油三脂、低密度脂蛋白显著降低，高密度脂蛋白上升。结论阿托伐他汀能够降低脑梗死患者的血脂及C-反应蛋白，从而降低脑血管病的发生。     

阿托伐他汀对急性脑梗死患者血清超敏C反应蛋白及一氧化氮水平的影响

目的研究阿托伐他汀对急性脑梗死(ACI)患者血清超敏C反应蛋白(hs-CRP)及一氧化氮(NO)水平的影响。方法将60例ACI患者随机分为阿托伐他汀组(30例)和常规治疗组(30例)。阿托伐他汀组在常规治疗基础上加用阿托伐他汀20mg,每日1次,连续服用14d。在治疗前后检测血清hs-CRP和NO含量,并进行神经功能缺损程度评分(NDS)评定。结果治疗14d时两组血清hs-CRP水平均较治疗前明显下降(均P<0.01),且阿托伐他汀组较常规治疗组下降明显(P<0.01);两组血清NO水平较治疗前明显升高(均P<0.01),且阿托伐他汀组较常规治疗组升高明显(P<0.05);两组NDS评分较治疗前明显下降(均P<0.01),且阿托伐他汀组较常规治疗组下降明显(P<0.05)。结论阿托伐他汀能明显降低ACI患者血清hs-CRP水平,升高NO水平;有助于ACI患者的神经功能恢复。     

进展性与非进展性脑卒中患者阿托伐他汀治疗前后血清超敏C反应蛋白和基质金属蛋白酶-9的变化

目的观察进展性和非进展性急性期脑卒中患者阿托伐他汀治疗前后血清超敏C反应蛋白(hs-CRP)和基质金属蛋白酶-9(MMP-9)的变化,探讨阿托伐他汀治疗进展性脑卒中患者的可能机制。方法选择137例急性脑卒中患者,分为进展组45例和非进展组92例,应用免疫比浊法和酶联免疫吸附试验方法检测两组患者阿托伐他汀治疗前后hs-CRP和MMP-9的表达水平,评价患者阿托伐他汀治疗前后神经功能缺损程度并评估治疗效果。结果进展组卒中患者阿托伐他汀治疗前后比较hs-CRP和MMP-9的表达水平显著降低;非进展组治疗前后比较hs-CRP的表达水平显著降低,而MMP-9变化不明显;进展组和非进展组脑卒中患者阿托伐他汀治疗有效率分别为85.34%和84.37%,两组间相比差异无统计学意义。结论阿托伐他汀治疗进展性和非进展性卒中均有效,两组比较差异无统计学意义,但是阿托伐他汀治疗前后两种类型卒中患者hs-CRP和MMP-9发生了不同程度好转的改变。     

瑞舒伐他汀与阿托伐他汀对急性脑梗死患者血脂、血清超敏C反应蛋白及颈动脉粥样硬化斑块作用的比较

目的比较瑞舒伐他汀与阿托伐他汀对急性脑梗死患者血脂、超敏C反应蛋白(hs-CRP)及颈动脉粥样硬化斑块的影响。方法在标准缺血性脑卒中治疗的基础上,瑞舒伐他汀组加用瑞舒伐他汀10mg/d,阿托伐他汀组加用阿托伐他汀片20 mg/d,治疗6个月。于治疗前及治疗后6个月,检测患者血脂、hsCRP水平,颈动脉超声检查颈动脉粥样硬化斑块情况。结果与治疗前比较,瑞舒伐他汀组与阿托伐他汀组6个月时总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和hs-CRP水平均显著降低(均P0.05)。6个月时,瑞舒伐他汀组TC、TG、LDL-C及hs-CRP水平显著低于阿托伐他汀组及对照组(均P0.05)。3组间治疗前内-中膜厚度(IMT)差异无统计学意义;与治疗前及对照组比较,瑞舒伐他汀组与阿托伐他汀组6个月时IMT及低回声斑块比率显著降低,高回声斑块率显著增高(均P0.05)。瑞舒伐他汀组、阿托伐他汀组及对照组患者第6个月的NIHSS评分及mRS评分均显著低于治疗前(均P0.05)。治疗前及治疗后6个月时,3组间NIHSS评分及mRS评分差异无统计学意义。结论瑞舒伐他汀与阿托伐他汀能显著降低急性脑梗死患者血脂及血清hs-CRP水平,抑制动脉粥样硬化斑块的形成。瑞舒伐他汀的降脂及抗炎作用比阿托伐他汀更强。     

阿托伐他汀调脂治疗对急性脑梗死患者血清超敏C反应蛋白白细胞介素-17及基质金属蛋白酶-8的影响

目的观察阿托伐他汀对急性脑梗死患者血清超敏C反应蛋白(hs-CRP)、白细胞介素-17(IL-17)、基质金属蛋白酶-8(MMP-8)及血脂的影响。方法将76例急性脑梗死患者随机分为对照组和观察组,对照组只给予常规治疗;观察组给予常规治疗及口服阿托伐他汀片20mg,晚上口服,1次/d,疗程2周。分别在确诊24h内和治疗后观察2组患者血清超敏C反应蛋白、白细胞介素-17、基质金属蛋白酶-8及血脂的变化情况,并就阿托伐他汀对急性脑梗死患者的临床疗效进行评价。结果治疗2周后,观察组患者与对照组相比血清超敏C反应蛋白、白细胞介素-17、基质金属蛋白酶-8、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)显著降低,高密度脂蛋白(HDL-C)显著升高,差异有统计学意义(P0.05)。结论阿托伐他汀能够降低急性脑梗死患者血清超敏C反应蛋白、白细胞介素-17、基质金属蛋白酶-8的水平,并对急性脑梗死患者具有良好的调脂作用,显著降低患者血脂水平从而减轻患者脑缺血性损害。     

不同剂量阿托伐他汀对缺血性脑血管病患者临床生化指标的影响

目的探讨不同剂量阿托伐他汀对缺血性脑血管病患者临床生化指标的影响。方法采用随机双盲对照方法,收集我院100例缺血性脑血管患者,随机分成2组,实验组(50例)在常规治疗缺血性脑血管病基础上给予阿托伐他汀40mg/d治疗,对照组(50例)在常规治疗缺血性脑血管病基础上给予阿托伐他汀20mg/d治疗,疗程均为3个月。检测并对比2组治疗前后临床生化指标。结果 2组三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、同型半胱氨酸(Hcy)、C反应蛋白(CRP)水平与治疗前比较均显著下降(P0.05);同时,2组高密度脂蛋白胆固醇(HDL-C)与治疗前比较明显升高(P0.05)。实验组空腹血糖(FBS)、糖化血红蛋白(HbA1c)水平与治疗前比较明显升高(P0.05),对照组无明显变化(P0.05)。结论不同剂量的阿托伐他汀治疗3个月后均能有效改善血脂水平,而高剂量(40mg/d)阿托伐他汀可能导致血糖异常,低剂量(20mg/d)阿托伐他汀对患者血糖升高无影响,对于缺血性脑血管病患者采用低剂量阿托伐他汀治疗更安全有效。     

缺血性卒中急性期他汀类药物治疗对血清超敏C反应蛋白的影响及预后评价

目的探索缺血性卒中急性期他汀类药物治疗对血清超敏C反应蛋白影响及预后评价。方法选取2010-07—2012-09于我院神经内科治疗的急性缺血性卒中患者120例,收集基线资料,根据是否接受他汀类药物治疗分为他汀治疗组和对照组,于入院时及发病后3个月时行神经功能缺损程度及日常生活活动能力进行评价,同时对影响预后因素进行多因素Logistic回归分析。结果 2组一般资料、NIHSS评分、BI及mRS评分比较差异均无统计学意义(P0.05);实验室指标测定发现,2组除总胆固醇、低密度脂蛋白胆固醇含量有显著差异外,其余各类指标差异均无统计学意义(P0.05);采用他汀类药物治疗后,他汀治疗组患者发病30d时血清hs-CRP水平显著降低(P0.01);预后良好组患者接受他汀类药物治疗例数、NIHSS评分均显著升高,而合并冠心病例数及发病后48h血清hs-CRP水平显著降低(P均0.05),NIHSS评分及发病后48h血清hs-CRP水平可作为急性缺血性卒中患者发病3个月时预后的指标(P0.05)。结论缺血性卒中患者急性期血清超敏C反应蛋白水平可用于患者发病后3个月预后的预测,行他汀类药物治疗可通过降低血清超敏C反应蛋白水平对预后产生影响。     

A novel protein interacts with a clock-related protein, rPer1

Cocaine administration evokes cardiovascular responses that are variable in rats such that the pressor response is attributable to either a large increase in systemic vascular resistance and a decrease in cardiac output (vascular responders) or a smaller increase in systemic vascular resistance and no change or an increase in cardiac output (mixed responders). This study was designed to determine the role of central corticotropin releasing factor (CRF) and adrenergic receptors in mediating specific hemodynamic response patterns. Rats were instrumented for ascending aortic blood flow determination (cardiac output) using a pulsed Doppler system, arterial pressure measurement and for intravenous and intracerebroventricular (icv) administration of drugs. After characterizing the hemodynamic response pattern in individual rats to cocaine (5 mg/kg, i.v., 4-6 trials), selective receptor antagonists were administered icv 10 min before cocaine (5 mg/kg, i.v.). Pretreatment with the CRF antagonist alpha-helical CRF(9-41) (10 microg/5 microl, icv) prevented the decrease in cardiac output in vascular responders without altering hemodynamic responses to cocaine in mixed responders. Astressin (5 microg/5 microl, icv) exerted a similar effect in vascular responders. The alpha(2) receptor antagonist, yohimbine (3 microg/microl, icv) also prevented the decrease in cardiac output in vascular responders. Lower doses of alpha-helical CRF(9-41) (1 and 3 microg) were ineffective whereas higher doses of either CRF antagonist were lethal within 24 h. In contrast, propranolol (3 or 30 microg, icv) pretreatment enhanced the cocaine-induced decrease in cardiac output and increase in systemic vascular resistance noted in vascular responders and resulted in a decrease in cardiac output in mixed responders. We conclude that CRF and adrenoceptors in the CNS play an important role in determining the hemodynamic response pattern to cocaine. Furthermore, central beta-adrenoceptors may be responsible for the reported effects of intravenous propranolol on cocaine-induced responses.     

Recombinant human protein C: comparative functional studies with human plasma protein C

Protein C (PC) is the central protein in a major antithrombotic regulatory mechanism. Hereditary deficiencies of PC are associated with thrombosis. Therapeutic PC replacement may be an important treatment if pure functional human protein C is available in sufficient quantity. Human PC has been produced on a commercial scale using recombinant techniques. To study the functional properties of recombinant protein C (r-PC), we undertook a comparative investigation of the basic properties of r-PC and plasma protein C (n-PC). Both were isolated by immunopurification methods. Protac C activation proceeded at the same rate and kinetics for both forms. With thrombin-thrombomodulin (T-TM) activation, r-PC is significantly better than the activation of n-PC (for r-PC: Kcat/Km = 378 vs. n-PC: Kcat/Km = 35). No difference in the anticoagulant (aPTT prolongation) or profibrinolytic activities (inactivation of PAI-1 and PAI-3) were observed between activated r-PC and n-PC. Based on these functional studies, recombinant protein C has similar properties to the plasma form of protein C. However, T-TM activation of r-PC occurs faster than the n-PC. The mechanism is unknown, but may be due to the presence of larger amounts of single chain protein C which exists in a conformation more rapidly activated by the T-TM complex.     

Association of protein S p.Pro667Pro dimorphism with plasma protein S levels in normal individuals and patients with inherited protein S deficiency

A dimorphism in PROS1 gene (c.A2,001G, p.Pro667Pro) has been associated with significantly reduced levels of both free and total protein S in carriers of the GG genotype. It is not known how the GG genotype could influence PS levels in normals, whether it could influence the levels of protein S in carriers of mutations in PROS1 gene and whether this genotype acts as an isolated or additive risk factor for venous thrombosis. With this as background, we evaluated the association of p.Pro667Pro dimorphism with free and total protein S centrally measured in a panel of 119 normal controls, 222 individuals with low protein S and 137 individuals with normal PS levels belonging to 76 families with protein S deficiency enrolled in the ProSIT study. Transient expression of recombinant wild type protein S and p.Pro667Pro protein S was performed to evaluate the role of the A to G transition at position 2001 in vitro. The p.Pro667Pro polymorphism was also expressed together with a p.Glu67Ala variant to assess a possible influence on protein S levels in protein S deficient subjects. Free and total protein S levels were significantly lower in normal women. In normal women only was the GG genotype associated with significantly lower free protein S levels in comparison to AA and AG genotypes (P=0.032). No significant influence of GG genotype was observed in patients, either with known mutations or with low protein S levels. These data were confirmed by in vitro transient expression, showing no difference in secretion levels of the p.Pro667Pro variant (even in association with the p.Glu67Ala mutation), compared to the wild type protein S. The genotype in itself was neither a significant risk factor for venous thrombosis nor a risk modifier in patients with known mutations.     

Amyloid precursor protein interacts with notch receptors

The amyloid precursor protein (APP) must fulfill important roles based on its sequence conservation from fly to human. Although multiple functions for APP have been proposed, the best-known role for this protein is as the precursor of Abeta peptide, a neurotoxic 39-43-amino acid peptide crucial to the pathogenesis of Alzheimer's disease. To investigate additional roles for APP with an eye toward understanding the molecular basis of the pleiotropic effects ascribed to APP, we isolated proteins that interacted with the plasma membrane isoform of APP. We employed a membrane-impermeable crosslinker to immobilize proteins binding to transmembrane APP in human embryonic kidney (HEK)293 cells expressing APP751 (HEK275) or rat embryonic day 18 primary neurons infected with a virus expressing APP. Notch2 was identified as a potential APP binding partner based on mass spectrometry analysis of APP complexes immunopurified from neurons. To confirm the interaction between Notch2 and APP, we carried out immunoprecipitation studies in HEK275 cells transiently expressing full-length Notch2 using Notch2 antibodies. The results indicated that APP and Notch2 interact in mammalian cells, and confirmed our initial findings. Interestingly, Notch1 also coimmunoprecipitated with APP, suggesting that APP and Notch family members may engage in intermolecular cross talk to modulate cell function. Finally, cotransfection of APP/CFP and Notch2/YFP into COS cells revealed that these two proteins colocalize on the plasma membrane. Intracellularly, however, although some APP and Notch molecules colocalize, others reside in distinct locations. The discovery of proteins that interact with APP may aid in the identification of new functions for APP.     

Thalamic degeneration with negative prion protein immunostaining

A 34-year-old woman presented with an insidious 5-year history of cognitive decline and apathy, associated with hypersomnia, ataxia, and dysarthria. Magnetic resonance imaging of the brain showed cortical and subcortical atrophy. At autopsy we found abnormalities in the subcortical grey matter and brainstem, with a relatively preserved cerebral cortex. The thalami showed symmetrical neuronal loss and astrocytosis, particularly severe in the dorsal medial nucleus, followed by the lateral nuclei group. Prion protein immuno-staining was negative, and there was no spongiform change. No mutations were detected in the prion protein gene. Received: 23 April 1999/Received in revised form: 16 August 1999/Accepted: 8 October 1999     

Prion protein fragment interacts with PrP-deficient cells

A fragment of the prion protein (PrP106-126) induces cell death in cultures of wild-type embryonic day (E)16 mouse cortical neurons but not cells derived from mice devoid of cellular PrP(PrP^o/o). Two common binding partners for PrP106-126 expressed in both wild-type and PrP^o/o mouse brain were isolated and their sequences determined. The two proteins were found to be α and β tubulin. Further evidence that tubulin binds PrP106-126 within cells comes from cell culture experiments. Colchicine toxicity on PrP^o/o mouse cortical cells is enhanced by PrP106-126 and taxol enhances toxicity of PrP106-126 on wild-type mouse cortical cells. Our evidence shows that a fragment of PrP can bind a cellular protein and in so doing, alters the metabolism of cells even when they do not express native PrP. This indicates that PrP106-126 is nontoxic to PrP^o/o cells, not because of an inability to interact with these cells but because of the loss of some aspect of a PrP expression-dependent phenotype. J. Neurosci. Res. 52:260–267, 1998. © 1998 Wiley-Liss, Inc.