抑郁症患者急性时相反应蛋白水平检测及其临床意义

目的探讨血清高敏C反应蛋白(hs-CRP)、白蛋白(Alb)、前白蛋白(PA)、转铁蛋白(TF)含量在抑郁症患者诊疗中的临床意义。方法采用溴甲酚绿法测定60例抑郁症患者和40名健康人血清Alb水平,采用免疫比浊法测定其血清hs-CRP、PA、TF水平。结果抑郁症患者血清hs-CRP水平为(5.12±2.07)mg/L,明显高于对照组[(1.88±1.29)mg/L,P<0.01];Alb、PA、TF水平分别为(42.6±4.2)g/L、(244±48)mg/L、(1.98±0.42)g/L,均明显低于对照组[(46.1±4.6)g/L、(293±52)mg/L、(2.46±0.39)g/L,P<0.01]。Pearson相关分析显示汉密顿抑郁量表(HAMD)总分与hs-CRP呈明显正相关(r=0.592,P<0.01),与Alb、PA、TF呈负相关(r分别为-0.463、-0.525、-0.491,P均<0.01)。结论抑郁症患者体内急性时相反应蛋白(APP)水平存在异常,hs-CRP、Alb、PA、TF水平测定在抑郁症临床治疗中有着重要意义。     

慢性肾功能衰竭患者超敏C反应蛋白水平的临床观察

目的探讨慢性肾功能衰竭(CRF)患者超敏C反应蛋白(hs-CRP)水平与肾功能、透析方式、营养状况及脂代谢之间的关系。方法收集新华医院住院患者280例,测定血尿素氮(BUN)、血肌酐(Scr)、前白蛋白(PA)、总蛋白(TP)、白蛋白(alb)、hs-CRP、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)、脂蛋白(a)[Lp(a)]、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)、体质量(kg)和患者入院当天的24小时尿蛋白定量;根据肾小球滤过率(GFR)将上述患者分为对照组(GFR≥90 ml/min)34例、肾功能不全组(GFR 30~89 ml/min)59例和肾功能衰竭组(GFR≤30 ml/min)187例;同时根据透析方式将肾功能衰竭患者分为非透析组78例,血透组88例和腹透组21例;比较各组间各项指标的相互关系。结果hs-CRP与肾功能呈显著负相关(r=-0.44,P<0.01),与Lp(a)呈正相关(r=0.35,P<0.01)。腹透组的hs-CRP水平显著升高。在肾功能衰竭组中,hs-CRP与PA、alb呈负相关(分别为r=-0.34,P<0.01;r=-0.37,P<0.01),而对TG、HDL-C、LDL-C、ApoA和ApoB的影响不明显。结论CRF患者中存在hs-CRP水平升高的炎症反应;而炎症反应与CRF患者的腹膜透析方式、营养不良和高Lp(a)血症密切相关。     

肝硬化患者血清前白蛋白、腺苷脱氨酶测定及临床应用评价

目的探讨肝硬化患者血清前白蛋白、腺苷脱氨酶测定及其临床意义。方法151例肝硬化患者和50例健康体检者,应用日立7600型全自动生化分析仪检测其血清前白蛋白(PA)和腺苷脱氨酶(ADA)的活力含量,并对其结果进行回顾性分析。结果151例肝硬化患者及50例对照组血清PA和ADA含量显示,代偿期为(228.5±74.1)mg/L和(11.2±4.8)IU/L,显著高于对照组(P<0.05),失代偿期为(159.5±109.8)mg/L和(16.8±6.8)IU/L,显著高于对照组(P<0.01)。结论PA和ADA测定可分别从肝脏的蛋白质、酶及胶原代谢三个方面辅助诊断肝硬化,同时由于PA和ADA的检测具有快速、价廉的特点,可作为肝硬化患者病情监测的有效指标。     

血清前白蛋白测定在不同肝病中的临床意义

目的探讨血清前白蛋白（PA）在不同肝病中的水平变化及其临床意义。方法选择261例肝病患者[其中慢性乙型病毒性肝炎112例（轻度25例,中度54例,重度33例）,急性黄疸型肝炎65例,肝炎肝硬化52例（代偿期12例,失代偿期40例）,原发性肝癌32例]和100例健康体检者（对照组）。采用免疫比浊法﹑溴甲酚绿比色法分别检测所有受试者血清PA及血清白蛋白（ALB）,比较不同肝病之间及同一种肝病不同阶段的血清PA、ALB水平的变化及关系。结果慢性乙型病毒性肝炎患者中,随肝炎程度的加重,其血清PA及ALB值均逐渐降低,中度、重度患者的血清PA值与轻度比较差异均具有统计学意义（P〈0.05）,重度与中度比较差异亦具有统计学意义（P〈0.05）。肝炎肝硬化患者中,与代偿期患者比较,失代偿期患者的血清PA值明显降低（P〈0.05）。与对照组比较,除了轻、中度慢性乙肝血清ALB之外,不同类型肝病的血清PA及ALB值均有不同程度的差异（P〈0.05或P〈0.01）。急性黄疸型肝炎及原发性肝癌与对照组比较,血清PA及ALB均显著降低（P〈0.05）,但PA下降更加显著（P〈0.05）。结论肝病患者血清PA水平比血清ALB水平更灵敏地反映肝功能损害情况。     

慢性肝病中血清前白蛋白检测的临床意义探讨

目的探讨慢性肝病中血清前白蛋白检测的临床意义。方法研究组82例,均为慢性肝病患者,对照组80例为我院体验健康者;对两组研究对象进行空腹静脉抽血,并分别检测血清前白蛋白(PA)、血清白蛋白(ALB)、凝血酶原时间(PT)值,对比分析。结果研究组患者的PA值明显低于对照组,ALB值低于对照组,PT值高于对照组,经统计学比较均有显著差异(P<0.05);慢性乙肝患者随着病情的加重,其PA值明显降低,中度、重度患者的PA值与轻度比较有显著差异,重度与中度比较也具有显著差异(P<0.05);肝硬化患者中,失代偿期患者的PA值明显低于代偿期,经统计学分析具有显著差异(P<0.05)。ALB、PT仅重度慢性乙肝、肝硬化失代偿期、原发性肝癌与对照组比较差异具有显著性(P<0.05)。结论 PA对检测慢性肝病患者的肝脏损伤程度具有极强的敏感性,患者肝脏受损程度越重,其PA检测值越低。     

血清白细胞介素-18在慢性肾功能衰竭患者中的表达及其意义

目的 观察慢性肾功能衰竭(CRF)患者血清白细胞介素(IL)-18水平的变化及与相关指标的关系,探讨其临床意义.方法 入选的CRF患者60例,分为肾功能衰竭非透析组(肾衰组)18例、血透组22例、腹透组20例.另设正常对照组20例.用EusA方法 检测血清IL-18、肿瘤坏死因子(TNF)-α和超敏C-反应蛋白(hs-CRP)水平,常规实验室方法 检测血清白蛋白(ALB)、TC、TG和血肌酐(SCr),根据简化的肾病饮食改良(MDRD)公式计算肾小球滤过率(GFR).比较各组间的差别.结果 CRF患者的血清IL-18水平在肾衰组[(497.7±120.7)ns/L]、血透组[(538,1 ±113.2)ns/L]、腹透组[(565.7±122.1)ng/L]均较正常对照组[(163.9±42.2)ng/L]显著升高(均P<0.01),而腹透组明显高于肾衰组(P<0.05),血透组和肾衰组之间的差异无统计学意义(P>0.05).患者的血清IL-18水平与TNF-α、hs.CRP、SCr呈显著正相关(r值分别为0.636、0.436、0.367,均P<0.01),与GFR呈显著负相关(r=-0.515,P<0.05).结论 CRF患者无论透析还是非透析,其血清IL-18水平均显著升高,并与TNF-α、CRP、GFR等因素有关.因此IL-18可能是CRF患者亚临床炎症的一种标志物.     

肝硬化患者超敏-C反应蛋白、腺苷脱氨酶检测结果分析

目的探讨肝硬化患者血清超敏-C反应蛋白(hs-CRP)、腺苷脱氨酶(ADA)检测的临床意义。方法采用OLYM-PUSAU 5400全自动生化分析仪对155例肝硬化患者和45例健康对照者分别进行血清hs-CRP和ADA检测。结果 155例患者血清ADA和hs-CRP水平分别为:肝硬化代偿期组(47.3±14.6)U/L和(5.8±2.6)mg/L,失代偿期组(56.2±29.7)U/L和(12.5±7.2)mg/L;两组均明显高于健康对照组[(15.5±4.3)U/L和(2.3±0.6)mg/L],3组之间结果比较,差异有统计学意义(P<0.01)。结论肝硬化患者血清ADA和hs-CRP水平均升高,且失代偿期组明显高于代偿期组,ADA和hs-CRP水平检测可作为肝硬化患者病情监测的有效指标,对临床有一定的指导意义。     

慢性心力衰竭患者心型脂肪酸结合蛋白与超敏C-反应蛋白的变化及其相关性

目的 观察慢性心力衰竭(CHF)患者血清心型脂肪酸结合蛋白(H-FABP)和超敏C-反应蛋白(hs-CRP)的浓度变化,并探讨其相关性及临床意义.方法 选择不同心功能级别的CHF患者60例及同期健康体检者30例,测定其血清H-FABP及hs-CRP的浓度,同时用彩色多普勒超声测定左心室射血分数(LVEF).结果 CHF组H-FABP[(6.11±1.49)μg/L]及ks-CRP[(12.77±3.65)mg/L]的浓度均较对照组[分别为(4.24±1.40)μg/L和(4.85±1.35)mg/L]升高(t值分别为5.746和7.543,P均<0.01),而LVEF明显降低[(42.13±6.55)%比(61.50±3.89)%],差异有统计学意义(t=-14.902,P<0.01).在CHF各亚组,H-FABP及hs-CRP的浓度均随着心功能级别的增加而升高(F值分别为26.288和351.784,P均<0.01),而LVEF降低(F=252.834,P<0.01).线性相关分析H-FABP的浓度与hs-CRP的浓度呈正相关(r=0.801,P<0.01),与LVEF呈负相关(r=-0.718,P<0.01);ks-CRP的浓度与LVEF呈负相关(r=-0.881,P<0.01).结论 血清H-FABP和hs-CRP的浓度随着CHF患者的病情加重而升高,两者的浓度变化呈正相关,与LVEF呈负相关;定量测定血清H-FABP和hs-CRP有助于CHF患者的危险分层.     

血清胰岛素样生长因子1和炎症状态与2型糖尿病肾病营养不良

目的探讨2型糖尿病肾病肾衰竭患者营养不良的原因.方法测定2型糖尿病肾病肾功能衰竭组患者与慢性肾小球肾炎肾功能衰竭组患者清晨空腹血清胰岛素样生长因子1(IGF-1),血清C反应蛋白,血清白蛋白的水平,同期检测3个月的时间内下肢小腿肌肉最粗处周径的变化量与上肢中臂肌肉周径的变化量.结果 2型糖尿病肾病肾功能衰竭组的血清IGF-1(69.07±18.46) μg/L与白蛋白(35.07±2.74) g/L明显低于慢性肾小球肾炎肾功能衰竭组(86.37±15.06) μg/L vs 37.37±2.68) g/L,P<0.01,0.05,2型糖尿病肾病肾功能衰竭组患者组的血清C反应蛋白明显升高(32.00±24.56) g/L vs (13.95±10.11) g/L,P<0.01.两组血清IGF-1与C反应蛋白皆呈显著负相关,r=-0.50～-0.56,P=0.046,0.014.两组血清IGF-1与下肢小腿肌肉最粗处周径变化量皆呈显著正相关,r=0.59,0.48,P=0.016,0.03.结论 2型糖尿病肾病肾功能衰竭组患者营养状况差于慢性肾小球肾炎肾功能衰竭组患者,与其体内持续较低的血清IGF-1水平与较高的C反应蛋白水平有关,二者相互作用是导致2型糖尿病肾病肾功能衰竭患者蛋白质-热卡营养不良的重要原因.     

C-反应蛋白对慢性肾功能衰竭患者预后的影响

目的探讨C-反应蛋白（CRP）对慢性肾功能衰竭患者预后的影响。方法筛选安阳市人民医院肾内科2006年1月至2006年12月间住院慢性肾功能衰竭期、尿毒症期患者,入院后给予慢性肾功能衰竭标准治疗及对症治疗,第2天测定血浆高敏C-反应蛋白（hs-CRP）浓度。将入选者分为hs-CRP≤3 mg/L与hs-CRP〉3 mg/L两组,分析两组3年再住院率及病死率。调整临床危险因素后,使用卡方检验评价CRP对慢性肾功能衰竭患者预后的影响。结果 112例入选者中67%hs-CRP〉3 mg/L,其3年病死率高于hs-CRP≤3 mg/L组患者（P=0.03）,3年再住院率两组间比较差异无统计学意义（P=0.24）。结论 CRP与慢性肾功能衰竭患者不良预后相关。     

Plasma protein turnover and tissue exchange; influence of dietary protein and protein depletion

The rate of plasma protein turnover is more rapid in dogs receiving adequate dietary protein than when a diet devoid of protein is fed. Both albumin and combined globulins are involved in this change. The difference in turnover is reflected in a total protein half-life of 4.8 days with protein feeding versus 7.8 days without protein in the diet and in the metabolism of 1.0 and 0.65 gm. per kilogram of body weight per day on the respective diets. Additions of dietary protein from 10 to 30 per cent caused no further increase in the rate of plasma protein turnover. With protein depletion due to plasmapheresis and a very low protein diet there is evidence of reduced protein metabolism as indicated by nitrogen retention as well as a reduction in total plasma protein breakdown and interchange of isotope between plasma and tissue proteins. Following introduction of labeled plasma protein into the circulation the net amount of isotope transferred to tissues has been computed from the difference between total plasma protein breakdown and combined C¹⁴ excretion in urine and expired air. In animals receiving adequate dietary protein, tissue transfer amounts to 70 per cent of the total lost from the plasma proteins each day while the percentage rises to 85 in depleted dogs deprived of protein. In dogs with both plasma and tissue proteins labeled it can be estimated that, under conditions of protein feeding, an amount of C¹⁴ approximately equal to that lost from the plasma must recycle to account for the observed decrease in Apparent plasma protein turnover rate, (t½ of 15 versus 5 days). Without protein in the diet the isotope contribution of the tissues to the maintenance of plasma protein levels must be as great as or greater than that transferred in the opposite direction.     

腺苷酸活化蛋白激酶与骨骼肌蛋白质降解

背景:机体运动时骨骼肌收缩,ATP被大量消耗,产生大量腺苷一磷酸,导致腺苷酸活化蛋白激酶的激活。目的:综述不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶对骨骼肌蛋白质降解的研究成果。方法:检索中国期刊网、维普期刊数据库、www.ncbi.nlm.nih.gov/pubmed和http://highwire.stanford.edu/网站与腺苷酸活化蛋白激酶、运动、蛋白质降解研究相关的文章。并对腺苷酸活化蛋白激酶的结构与作用,不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶升高对骨骼肌蛋白质降解的内容进行分析综述。结果与结论:共纳入相关文献35篇。本文综述了腺苷酸活化蛋白激酶的结构、作用的研究进展;在抗阻运动和中到大强度的周期运动中,腺苷酸活化蛋白激酶活性都可能升高,而在小强度周期运动过程中腺苷酸活化蛋白激酶活性可能不升高;腺苷酸活化蛋白激酶的活化可能对骨骼肌蛋白质的降解有促进作用。     

腺苷酸活化蛋白激酶与骨骼肌蛋白质降解

背景：机体运动时骨骼肌收缩,ATP被大量消耗,产生大量腺苷一磷酸,导致腺苷酸活化蛋白激酶的激活。目的：综述不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶对骨骼肌蛋白质降解的研究成果。方法：检索中国期刊网、维普期刊数据库、www.ncbi.nlm.nih.gov/pubmed和http：//highwire.stanford.edu/网站与腺苷酸活化蛋白激酶、运动、蛋白质降解研究相关的文章。并对腺苷酸活化蛋白激酶的结构与作用,不同运动过程中腺苷酸活化蛋白激酶活性的变化,以及腺苷酸活化蛋白激酶升高对骨骼肌蛋白质降解的内容进行分析综述。结果与结论：共纳入相关文献35篇。本文综述了腺苷酸活化蛋白激酶的结构、作用的研究进展;在抗阻运动和中到大强度的周期运动中,腺苷酸活化蛋白激酶活性都可能升高,而在小强度周期运动过程中腺苷酸活化蛋白激酶活性可能不升高;腺苷酸活化蛋白激酶的活化可能对骨骼肌蛋白质的降解有促进作用。     

Specificity of protein C and protein S assays

Summary Specific tests for the measurement of protein C antigen and activity and protein S antigen are used in the clinical laboratory for the routine diagnosis of hereditary protein C and protein S deficiency. The performance of these tests is reviewed and discussed. Special attention is paid to the application of these tests for the analysis of patients on oral anticoagulant therapy. Presented at the ‘2nd International Symposium on Standardization and Quality Control of Coagulation Tests: Implications for the Clinical Laboratory’, Rome, September 28–29, 1989.     

Acquisition of inhibitor-sensitive protein kinases through protein design.

Protein phosphorylation is the major post-translational modification used by eukaryotic cells to control cellular signaling. Protein kinases have emerged as attractive drug targets because heightened protein kinase activity has been associated with several proliferative diseases, most notably cancer and restenosis. Until now, it has been very difficult to confirm the utility of protein kinases as inhibitor targets because very few small molecules that selectively inhibit one particular kinase are known. Discovery of highly specific kinase inhibitors has been slow because the protein family contains approximately 2000 members, all of which share a conserved active site fold. Recent work in several laboratories has sought to circumvent the problem of kinase structural degeneracy by engineering drug sensitivity into Src family tyrosine kinases and mitogen-activated protein kinases through site-directed mutagenesis. By introducing a unique non-naturally occurring amino acid into a conserved region of the enzyme's binding site, a target protein kinase can be rapidly sensitized to a small molecule. Introduction of the engineered kinase into a cell line or animal model should greatly expedite the investigation of protein kinase inhibition as a viable drug treatment. The purpose of this review is to summarize these recent advances in protein kinase drug sensitization.     

Modulation of protein kinase signaling by protein phosphatases and inhibitors

Protein tyrosine phosphatases (PTPs) form a large family of enzymes that serve as key regulatory components in signal transduction pathways. Defective or inappropriate regulation of PTP activity leads to aberrant tyrosine phosphorylation, which contributes to the development of many human diseases. In addition to controlling the phosphorylation states of protein kinase substrates, PTPs can also directly modulate protein kinase activity. Evidence suggests that PTPs can exert both positive and negative effects on a signaling pathway. Thus, further understanding of the fundamental role of protein tyrosine phosphorylation in complex and critical signal transduction pathways requires detailed studies of both the kinases and the phosphatases. In this review, we first summarize our current understanding of PTP structure and function. We then discuss the molecular basis of PTP substrate specificity, focusing primarily on mitogen-activated protein (MAP) kinase phosphatase 3. We demonstrate that the MAP kinase phosphatases display exquisite substrate specificity requiring extensive protein-protein interactions for precise down-regulation of MAP kinase activity. We also highlight our recent progress in developing small molecule PTP1B inhibitors. Using a novel combinatorial approach that is designed to target both the active site and a unique peripheral site in PTP1B, we have obtained a PTP1B inhibitor with 2.4 nM affinity and orders of magnitude selectivity against a panel of PTPs. Currently, some of the compounds are being evaluated in both cell and animal models to further define the role of PTP1B in insulin signaling.     

Activated protein C

Summary.  Protein C is a vitamin K-dependent plasma protein zymogen whose genetic mild or severe deficiencies are linked with risk for venous thrombosis or neonatal purpura fulminans, respectively. Studies over past decades showed that activated protein C (APC) inactivates factors (F) Va and VIIIa to down-regulate thrombin generation. More recent basic and preclinical research on APC has characterized the direct cytoprotective effects of APC that involve gene expression profile alterations, anti-inflammatory and anti-apoptotic activities and endothelial barrier stabilization. These actions generally require endothelial cell protein C receptor (EPCR) and protease activated receptor-1. Because of these direct cytoprotective actions, APC reduces mortality in murine endotoxemia and severe sepsis models and provides neuroprotective benefits in murine ischemic stroke models. Furthermore, APC reduces mortality in patients with severe sepsis (PROWESS clinical trial). Although much remains to be clarified about mechanisms for APC's direct effects on various cell types, it is clear that APC's molecular features that determine its antithrombotic action are partially distinct from those providing cytoprotective actions because we have engineered recombinant APC variants with selective reduction or retention of either anticoagulant or cytoprotective activities. Such APC variants can provide relatively enhanced levels of either cytoprotective or anticoagulant activities for various therapeutic applications. We speculate that APC variants with reduced anticoagulant action but normal cytoprotective actions hold the promise of reducing bleeding risk because of attenuated anticoagulant activity while reducing mortality based on direct cytoprotective effects on cells.