慢性肾功能衰竭患者血浆同型半胱氨酸水平和血清叶酸、维生素B12的关系

目的:研究慢性肾功能衰竭(CRF)患者血浆总同型半胱氨酸(tHcy)水平及其与血清叶酸、维生素B12(VitB12) 的关系.方法:采用荧光偏振免疫分析法检测45例CRF患者和40例正常对照组血浆tHcy浓度,并同时用离子捕捉免疫分析法检测其血清叶酸和微粒子酶联免疫分析法检测血清VitB12的含量.结果:CRF患者血浆tHcy浓度[(24±12)μmol·L-1]显著高于正常对照组[(8.0±2.9)μmol·L-1](P<0.01);CRF患者血清叶酸水平[(18±6.3)nmol·L-1]显著低于正常对照组[(21±8.3)nmol·L-1](P<0.01),VitB12水平[(423±154)pmol·L-1]显著低于正常对照组[(485±181)pmol·L-1](P<0.01).相关分析显示,两组血浆tHcy浓度与叶酸、VitB12水平均呈负相关性.结论:CRF患者普遍存在高同型半胱氨酸血症,叶酸、VitB12缺乏可能是诱发高同型半胱氨酸血症的重要因素之一.     

叶酸联合维生素B12对血透患者同型半胱氨酸水平的影响

目的探讨大剂量叶酸(FA)联合维生素B12对维持性血液透析(MHD)患者同型半胱氨酸(Hcy)血浆水平的影响.方法 52例MHD患者随机分为四组,每天分别口服0、15、30、60 mg的FA,服FA患者同时每天肌注维生素B12500μg,治疗3个月.用放射免疫法测0、1、2、3个月及停药后3个月FA和维生素B12的血浆水平,用荧光偏振免疫分析法测同时间点总同型半胱氨酸(tHcy)血浆水平.结果 MHD患者tHcy血浆水平[(22.13±8.03)μmol/L]明显高于健康人[(7.23±1.97)μmol/L],大剂量与常规剂量FA均能降低血浆tHcy水平,但不能使tHcy恢复到正常,不同剂量FA合并维生素B12均能明显提高血浆FA和维生素B12水平.结论MHD患者普遍存在高同型半胱氨酸血症(HHcy),常规剂量FA加维生素B12可降低血浆tHcy水平,但不能完全正常化.     

叶酸和甲钴胺对高同型半胱氨酸血症缺血性脑卒中复发的影响

目的 探讨叶酸和甲钴胺(维生素B12)对高同型半胱氨酸血症(Hhcy)患者缺血性脑卒中(ICS)复发的影响.方法 伴有Hhcy的ICS患者195例,分为治疗组112例和对照组83例.两组均给予常规治疗;治疗组加用叶酸片2 mg/d、维生素B6 25mg/d及维生素B12 500μg/d.随访2年,比较治疗前后同型半胱氨酸(Hcy)水平,评价ICS患者的再发性脑血管事件发生率.结果 2年后,对照组血浆Hcy水平与常规治疗前相仿[(16.6±5.2)μmol/L vs.(16.1±4.7)μmol/L](P>0.05),而治疗组血浆Hcy水平明显较治疗前降低[(8.2±4.7)μmol/L vs.(17.6±5.9)μmol/L](P<0.05).治疗组脑血管事件复发率低于对照组(6.3%vs.8.4%)(P<0.05).结论 口服叶酸加维生素B6和维生素B12可降低Hhcy,改善ICS患者的远期预后.     

帕金森病患者血浆同型半胱氨酸水平与其临床特征的关系

目的探讨帕金森病(PD)患者血浆同型半胱氨酸(Hcy)水平与临床特征的关系。方法检测PD患者(PD组,52例)和健康体检者(对照组,62例)血浆Hcy浓度,分析PD患者血浆Hcy水平与性别、年龄的关系。结果 PD组血浆Hcy高于对照组[(16.24±6.70)μmol/L vs.(13.83±5.40)μmol/L](P<0.05)。PD组男性Hcy水平高于女性[(18.34±6.63)μmol/L vs.(14.44±6.32)μmol/L](P<0.05)。结论血浆Hcy升高可能是帕金森病的危险因素之一,其水平与PD患者性别、年龄有关。     

妊娠期高血压疾病患者血浆总同型半胱氨酸浓度监测

目的：探讨妊娠期高血压疾病患者血浆总同型半胱氨酸（tHcy）浓度检测的临床意义。方法：采用荧光偏振免疫分析法检测300例妊娠期高血压疾病患者（其中轻度231例,重度69例）和300例正常同期妊娠妇女血浆tHcy浓度,同步取静脉血采用离子捕捉免疫分析法检测其血清叶酸和微粒子酶联免疫分析法检测其血清维生素B12的浓度。结果：血浆tHcy浓度妊娠期高血压疾病患者[（11.79±3.52）μmol·L^-1]显著高于正常妊娠组[（6.72±2.43）μmol·L^-1]（P〈0.01）,且重度患者[（16.85±5.61）μmol·L^-1]显著高于轻度患者[（11.46±3.22）μmol·L^-1]（P〈0.01）;血清叶酸浓度妊娠期高血压疾病患者[（11.74±3.58）nmol·L^-1]显著低于正常妊娠组[（14.91±4.63）nmol·L^-1]（P〈0.01）,血清维生素B12浓度妊娠期高血压疾病患者[（328.89±90.06）pmol·L^-1]显著低于正常妊娠组[（405.37±94.18）pmol·L^-1]（P〈0.01）。结论：妊娠期高血压疾病患者血浆tHcy浓度显著上升,血清叶酸、VitB12浓度显著下降。随着病情的加重,妊娠期高血压疾病患者血浆tHcy浓度呈逐渐上升趋势,监测血浆tHcy浓度对了解妊娠期高血压疾病病情具有重要意义。     

子痫前期患者血浆总同型半胱氨酸水平及其与叶酸、维生素B12的关系

目的：测定子痫前期患者血浆总同型半胱氨酸（tHcy）、血清叶酸、维生素B12水平,以探讨子痫前期患者血浆tHcy水平及其与叶酸、维生素B12的相互关系。方法：采用荧光偏振免疫分析法测定320例子痫前期患者（其中轻度236例,重度84例）和320例正常同期妊娠妇女血浆tHcy水平,同时用离子捕捉免疫分析法测定其血清叶酸水平,用微粒子酶联免疫分析法测定其血清维生素B12水平。结果：子痫前期组血浆tHcy水平为（11．65±3．54）μmol·L^-1,显著高于正常妊娠组[（6．73±2．58）μmol·L^-1]（P〈0．01）,且重度患者[（16．57±5．21）μmol·L^-1]显著高于轻度患者[（10．48±4．11）μmol·L^-1]（P〈0．01）;血清叶酸水平子痫前期组[（11．82±3．67）nmol·L^-1]显著低于正常妊娠组[（14．71±3．89）nmol·L^-1]（P〈0．01）;血清维生素B12水平子痫前期组[（338±91）pmol·L^-1]显著低于正常妊娠组[（406±88）pmol·L^-1]（P〈0．01）。结论：子痫前期患者血浆tHcy水平明显升高,且随着病情的加重血浆tHcy水平呈逐渐上升趋势,血浆tHcy水平与叶酸、维生素B12水平呈负相关。     

青年高同型半胱氨酸血症患者心脑血管疾病相关危险因素分析

目的探讨青年高同型半胱氨酸患者心脑血管疾病的相关危险因素。方法连续选取2018年1月至2019年1月在解放军总医院第七医学中心急诊科就诊的年龄小于45岁的青年患者260例为研究对象, 将血清同型半胱氨酸水平≥ 15.0 μmol/L的126例患者设为高同型半胱氨酸组, 将血清同型半胱氨酸水平 < 15.0 μmol/L的134例患者设为对照组。分别检测两组患者身高、体质量、体质量指数、血压及血清同型半胱氨酸、空腹血糖、血尿酸、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和N-末端脑钠肽前体等指标的水平, 比较两组患者心脑血管疾病相关危险因素变化情况。结果高同型半胱氨酸组患者体质量指数、血尿酸及冠心病、脑卒中患病率与对照组比较, 差异均有统计学意义[(26.42±3.54)kg/m2比(22.14±3.22)kg/m2, t=10.21, P=0.016;(308.71±78.44)μmol/L比(285.05±92.09)μmol/L, t=2.22, P=0.027;73/126比61/134, χ2=4.00, P=0.045;19/126比6/134, χ2=...     

前庭自旋转试验与血浆同型半胱氨酸水平检测对耳源性眩晕疾病的诊断价值

目的 探讨血浆同型半胱氨酸水平检测与前庭自旋转试验对耳源性眩晕病的诊断价值.方法 纳入确诊为耳源性眩晕疾病患者80例,其中梅尼埃病26例、良性阵发性位置性眩晕34例、前庭神经炎20例,另设健康对照组80例.分别于确诊后检查各组的前庭自旋转试验、血浆同型半胱氨酸水平,分析前庭自旋转试验中水平增益、相移,垂直增益、相移,水平非对称性的异常与耳源性眩晕疾病的相关性,同型半胱氨酸水平与耳源性眩晕疾病的相关性.结果 三组耳源性眩晕疾病患者的同型半胱氨酸水平[(19.64 ±5.34)、17.43 ±4.53)、16.76 ±4.36)μmol· L-1]均明显高于健康对照组(10.78 ±5.43) μmol· L-1,差异有统计学意义(P<0.05);三组同型半胱氨酸血症的发病率61.54%、50.00%、40.00%均明显高于健康对照组5.00%,差异有统计学意义(P<0.05);前庭自旋转试验结果异常48例,非对称性异常8例,均与前庭损伤侧相符合,异常结果中垂直增益异常6例,且均为增益降低;水平增益升高2例、增益降低30例,相位异常40例,水平增益及垂直增益均异常5例,均表现为相位延迟,垂直相位异常6例,水平相位异常26例.结论 前庭自旋转试验与血浆同型半胱氨酸水平检测是定位诊断的一种客观检测手段,是耳源性眩晕疾病中敏感筛查方法,也可为前庭功能检查及指导治疗提供依据.     

舒血宁注射液对脑梗死患者临床疗效及血浆Hcy、UCH-L1及血清fibulin-5水平的影响

目的 探讨舒血宁注射液对脑梗死患者疗效及血浆同型半胱氨酸(Hcy)、泛素羧基末端水解酶-1(UCH-L1)及血清衰老关键蛋白抗原-5(fibulin-5)水平的影响.方法 选取124例脑梗死患者,根据随机数字表法将患者分为治疗组(n=62)及对照组(n=62),两组均接受神经内科常规治疗,同时给予依达拉奉辅助治疗,治疗组在对照组基础上给予舒血宁注射液静脉输注治疗,比较两组治疗效果、神经功能、日常生活恢复情况、血液流变学指标及治疗前后血浆Hcy、UCH-L1及血清fibulin-5水平变化.结果 治疗组总有效率为93.55％,对照组总有效率为77.42％,差异有统计学意义(P<0.05).治疗组治疗后美国国立卫生院神经功能缺损评分(NIHSS)为(5.18±0.86)分低于对照组(9.78±1.18)分(P<0.05),而日常生活功能评分(ADL)为(74.96±5.26)分高于对照组(61.42±4.85)分(P<0.05).治疗组治疗后血浆D-二聚体(D-D)、纤维蛋白原(FIB)、血浆黏度(CP)、红细胞聚集指数(RCAI)水平分别为(125.22±22.45)μg·L-1、(128.96±23.69)g·L-1、(1.52±0.47)mPa·s、(0.82±0.14)％,对照组治疗后D-D、FIB、CP、RCAI水平分别为(215.98±24.98)μg·L-1、(219.33±20.77)g·L-1、(1.78±0.38)mpa·s、(1.10±0.21)％,比较差异有统计学意义(P<0.05).治疗组治疗后血浆Hcy、UCH-L1及血清fibulin-5水平分别为(8.52±1.63)μmol·L-1、(0.25±0.12)μg·L-1、(45.22±2.96)μg·L-1,对照组治疗后血浆Hcy、UCH-L1及血清fibulin-5水平分别为(10.36±2.45)μmol·L-1、(0.40±0.18)μg·L-1、(68.96±4.85)μg·L-1,差异有统计学意义(P<0.05).结论 舒血宁注射液能有效提高脑梗死患者临床治疗效果,改善患者血液黏稠度,降低血浆Hcy、UCH-L1、fibulin-5水平,有利于脑梗死患者预后.     

普拉克索联合恩他卡朋治疗对帕金森病非运动症状的临床疗效及安全性评价北大核心CSCD

目的评价普拉克索联合恩他卡朋对帕金森病非运动症状患者的血清同型半胱氨酸及血尿酸水平影响。方法入选66例帕森金病非运动症患者,分为试验组和对照组,每组33例。对照组口服恩他卡朋,最初剂量为0.1 g,试验组在对照组基础上加用普拉克索,最初剂量为0.375 mg,3周为一个疗程。观察2组患者治疗前和治疗半年后的血清同型半胱氨酸、血尿酸水平及相关情况评分,比较2组患者治疗后的药物疗效及不良反应情况。结果治疗后,试验组总临床疗效(93.94%)显著高于对照组(78.79%)。试验组的血清同型半胱氨酸水平(9.31±0.78)μmol·L-1显著低于对照组(15.46±1.02)μmol·L-1,血尿酸水平(302.45±58.89)μmol·L-1显著高于对照组(269.33±40.59)μmol·L-1。试验组异动时间、开期时间、关期时间显著优于对照组(P<0.05)。试验组相关评分改善效果显著优于对照组(P均<0.05)。结论普拉克索联合恩他卡朋治疗帕森金病非运动症状能明显改善患者的血清同型半胱氨酸及血尿酸水平,不良反应少,疗效良好。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.