环孢素A对肾移植术后患者血总胆固醇水平的影响

目的研究接受肾移植手术后常规服用环孢素A(CsA)的患者其全血谷浓度C0及服药后2 h的血药浓度C2对其总胆固醇水平是否有影响.方法选择我院接受肾移植术病人28例,采用荧光偏振免疫分析法(FPIA)测定C0、C2,按C0分为Ⅰ组:150～250 ng/ml,Ⅱ组:250～400 ng/ml;按C2进行分组,Ⅰ组:<1000 ng/ml,Ⅱ组:1000～1300 ng/ml,Ⅲ组:>1300 ng/ml.检测其术前及术后的血总胆固醇水平.结果按C0,Ⅰ组C0=(215.20±23.12) ng/ml,总胆固醇升高(2.134±1.00) mmol/L,Ⅱ组C0＝(302.36±54.08) ng/ml,总胆固醇升高(2.19±1.1) mmol/L,两组手术前后血总胆固醇水平均显著升高,P<0.01.C0与血总胆固醇水平相关性分析,r=0.200,P>0.05;按C2,Ⅰ组C2=(748.53±155.63) ng/ml,总胆固醇升高(2.33±1.01) mmol/L,Ⅱ组C2=(1131.63±71.27) ng/ml,总胆固醇升高(1.99±1.16) mmol/L,Ⅲ组C2=(1578.18±376.01) ng/ml,总胆固醇升高(2.33±0.48) mmol/L,3组手术前后血总胆固醇水平均显著改变,P<0.01.C2与血总胆固醇水平相关性分析,r=0.237,P>0.05 .结论术后一个月,各组患者的总胆固醇均有明显增加(P<0.01),但与C0和C2无明显相关性.     

环孢素A对肾移植术后患者血总胆固醇水平的影响

目的研究接受肾移植手术后常规服用环孢素A(CsA)的患者其全血谷浓度C0及服药后2 h的血药浓度C2对其总胆固醇水平是否有影响。方法选择我院接受肾移植术病人28例,采用荧光偏振免疫分析法(FPIA)测定C0、C2,按C0分为Ⅰ组:150~250 ng/m l,Ⅱ组:250~400 ng/m l;按C2进行分组,Ⅰ组:<1000 ng/m l,Ⅱ组:1000~1300 ng/m l,Ⅲ组:>1300 ng/m l。检测其术前及术后的血总胆固醇水平。结果按C0,Ⅰ组C0=(215.20±23.12)ng/m l,总胆固醇升高(2.134±1.00)mmol/L,Ⅱ组C0=(302.36±54.08)ng/m l,总胆固醇升高(2.19±1.1)mmol/L,两组手术前后血总胆固醇水平均显著升高,P<0.01。C0与血总胆固醇水平相关性分析,r=0.200,P>0.05;按C2,Ⅰ组C2=(748.53±155.63)ng/m l,总胆固醇升高(2.33±1.01)mmol/L,Ⅱ组C2=(1131.63±71.27)ng/m l,总胆固醇升高(1.99±1.16)mmol/L,Ⅲ组C2=(1578.18±376.01)ng/m l,总胆固醇升高(2.33±0.48)mmol/L,3组手术前后血总胆固醇水平均显著改变,P<0.01。C2与血总胆固醇水平相关性分析,r=0.237,P>0.05。结论术后一个月,各组患者的总胆固醇均有明显增加(P<0.01),但与C0和C2无明显相关性。     

曲美他嗪联合卡维地洛对高血压心脏病慢性心力衰竭患者心功能及N末端脑钠肽前体、肌钙蛋白Ⅰ的影响

目的 探讨曲美他嗪联合卡维地洛对高血压心脏病慢性心力衰竭(CHF)患者心功能及N末端脑钠肽前体(NT-proB-NP)、肌钙蛋白Ⅰ(cTnⅠ)的影响.方法 选取高血压心脏病CHF患者70例,采用随机数字表法分为观察组和对照组,各35例.两组均进行常规治疗,对照组加用卡维地洛,起始剂量为6.25 mg· d-1,以后根据个人情况调整剂量,最大可加至25~50 mg· d-1,观察组在对照组基础上加用曲美他嗪20毫克/次,3次/天,两组均治疗6个月后进行评价.两组治疗前后采用Lee氏评分进行心力衰竭症状评分,彩色多普勒超声测定LVEF,记录6 min步行距离(6 MWD);采集两组治疗前后清晨空腹静脉血,采用放射免疫法测定血浆NT-proBNP、cTnⅠ,ELISA法测定脂联素(APN),Clauss法测定纤维蛋白原(FG);采用全自动生化分析仪测定三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平.结果 观察组治疗后Lee氏评分为(2.03 ±0.35)分,对照组为(2.91 ±0.79)分,观察组治疗后Lee氏评分低于对照组(t=6.025,P<0.001);观察组治疗后LVEF、6 MWD分别为(54.27 ±6.55)%、(283.59 ±23.79)m,对照组分别为(44.17 ±7.43)%、(219.74 ±25.68)m,观察组治疗后LVEF、6 MWD高于对照组(t=6.034,P<0.001;t=10.791,P<0.001);观察组治疗后TC、LDL-C水平分别为(4.24 ±0.62)mmol· L-1、(1.87 ±0.71)mmol· L-1,对照组分别为(5.07 ±0.85)mmol· L-1、(2.65 ±0.72) mmol· L-1,观察组治疗后TC、LDL-C水平低于对照组(t=4.667,P<0.001;t=4.564,P<0.001),观察组治疗后HDL-C水平为(1.67 ±0.28)mmol· L-1,对照组为(1.32 ±0.26)mmol· L-1,观察组治疗后HDL-C 水平高于对照组(t=,5.419,P<0.001);观察组治疗后NT-proBNP、cTnⅠ、APN、FG水平分别为(1.54 ±0.27)μg· L-1、(0.68 ±0.21)μg· L-1、(7.38 ±2.24) mg· L-1、(2.98 ±0.64)g· L-1,对照组分别为(2.56 ±0.38)μg· L-1、(1.25 ±0.14)μg· L-1、(11.76 ±3.19)mg· L-1、(3.75 ±0.51)g· L-1观察组治疗后NT-proBNP、cTnⅠ、APN、FG水平低于对照组(t=12.945,P<0.001;t=13.361,P<0.001;t=6.648,P<0.001;t=5.567,P<0.001).结论 曲美他嗪联合卡维地洛可有效调节高血压心脏病CHF患者血脂水平,降低NT-proBNP、cTnⅠ、APN、FG水平,从而有效改善心功能.     

盐酸沙格雷酯对大鼠体内细胞色素P4502D1/2的影响

目的观察盐酸沙格雷酯对大鼠细胞色素P4502D1/2(CYP2D1/2)的底物右美沙芬药动学的影响。方法♂SD大鼠,随机分成2组,对照组按右美沙芬组10 mg·kg-1灌胃给药,盐酸沙格雷酯组按右美沙芬和盐酸沙格雷酯均10 mg·kg-1同时灌胃给药,按不同时间从大鼠眼底静脉丛取血,血样处理后,用LC-MS/MS法测定大鼠血浆中右美沙芬的浓度,用DAS 2.0软件进行分析,求出其主要药代动力学参数。结果盐酸沙格雷酯组与对照组比较,右美沙芬的T12明显延长(2.49 h±0.93 h vs 1.47 h±0.20 h,P<0.05),Cmax明显升高(325.7μg·L-1±133.2μg·L-1vs 104.5μg·L-1±52.4μg·L-1,P<0.05),AUC0-t(785.5μg·L-1·h±451.9μg·L-1·h vs 244.8μg·L-1·h±168.3μg·L-1·h,P<0.05)和AUC0-∞(804.7μg·L-1·h±445.6μg·L-1·h vs 251.4μg·L-1·h±173.4μg·L-1·h,P<0.05)明显增大。结论盐酸沙格雷酯在大鼠体内对右美沙芬的代谢有抑制作用,能降低其消除过程。     

丹红注射液联合瑞舒伐他汀对冠心病合并高脂血症患者MFG-E8、Klotho蛋白表达及血脂水平的影响

目的 探究丹红注射液联合瑞舒伐他汀对老年冠心病合并高脂血症患者血清乳脂肪球表皮生长因子-8(MFG-E8)、Klotho蛋白表达及血脂水平的影响.方法 选取冠心病合并高脂血症老年患者86例,根据就诊顺序编号,以随机数字表法分为观察组与对照组,各43例.对照组予以瑞舒伐他汀治疗,观察组予以瑞舒伐他汀+丹红注射液治疗,两组均连续治疗4周.观察统计两组治疗效果、不良反应情况,并比较治疗前后两组血清MFG-E8、Klotho蛋白表达、炎性因子[超敏C反应蛋白(Hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]及血脂[低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)]水平.结果 (1)两组治疗后血脂相关指标水平均较治疗前改善,且观察组LDL-C(3.25±0.70)mmol·L-1、TG(1.70±0.99)mmol·L-1、TC(4.85±0.98)mmol·L-1均低于对照组(3.89±0.92)mmol·L-1、(2.45±1.05)mmol·L-1、(5.56±1.19)mmol·L-1,差异有统计学意义(P<0.05);(2)两组治疗后炎性因子水平均较治疗前改善,且观察组Hs-CRP(4.12±0.94)mg·L-1、TNF-α(0.39±0.25)μg·L-1、IL-6(9.15±2.48)ng·L-1均低于对照组(8.52±2.31)mg·L-1、(0.68±0.34)μg·L-1、(14.32±2.95)ng·L-1,差异有统计学意义(P<0.05);(3)两组治疗后Klotho、MFG-E8蛋白表达水平均较治疗前升高,且观察组Klotho蛋白表达水平(43.25±1.74)ng·L-1、MFG-E8蛋白表达水平(512.38±19.58)mg·L-1均高于对照组(34.85±1.87)ng·L-1、(325.47±12.94)mg·L-1,差异有统计学意义(P<.05);(4)观察组治疗总有效率95.35％(41/43)高于对照组74.42％(32/43),差异有统计学意义(P<0.05);观察组不良反应率20.93％(9/43)与对照组16.28％(7/43)相比,差异无统计学意义(P>0.05).结论 对冠心病合并高脂血症老年患者予以瑞舒伐他汀联合丹红注射液治疗,可有效降低血清Klotho、MFG-E8蛋白表达、血清炎性因子及调节血脂水平,疗效较为显著,且安全性较高.     

炔雌醇/环丙孕酮联合二甲双胍对多囊卵巢综合征患者单核细胞趋化蛋白-1及血脂的影响

目的探讨炔雌醇/环丙孕酮联合二甲双胍对多囊卵巢综合征(PCOS)患者单核细胞趋化蛋白-1(MCP-1)及血脂的影响,并观察其临床疗效。方法 60例PCOS患者随机分为治疗组和对照组各30例。对照组仅给予二甲双胍0.25 g,po,tid;治疗组在对照组基础上加用炔雌醇/环丙孕酮(每片含环丙孕酮2 mg和炔雌醇35μg)1片,qd,po。观察和比较两组患者治疗前后MCP-1、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)水平的变化,并观察各组临床疗效及不良反应。结果治疗组患者血清MCP-1、TC、TG水平分别为(89.22±21.56)μg.L-1,(4.34±0.41)mmol.L-1,(1.21±0.24)mmol.L-1,均较治疗前明显下降(P<0.05),而HDL-C为(1.91±0.21)mmol.L-1,较治疗前明显升高(P<0.05);对照组MCP-1、TC、TG、HDL-C分别为(120.24±29.15)μg.L-1,(4.74±0.66)mmol.L-1,(1.47±0.57)mmol.L-1,(1.51±0.32)mmol.L-1,治疗组改善程度较对照组更明显(P<0.05);治疗组月经稀少、痤疮、多毛及卵巢体积增大、多囊性改变等临床表现较治疗前明显缓解,且改善程度较对照组更明显(P<0.05)。结论炔雌醇/环丙孕酮联合二甲双胍是治疗PCOS安全有效的方法,通过抑制MCP-1的分泌,降低血脂而取得良好的临床疗效。     

肝炎肝硬化患者肝功能生化检验的临床研究

目的探究分析肝炎肝硬化患者实施肝功能生化检验的效用以及价值。方法选取50例肝炎肝硬化患者作为试验组,另选取同期接受正常体检的健康人群50例作为对照组,两组研究对象均行肝功能生化检验。比较两组的肝功能指标(总胆汁酸、血清白蛋白、血清胆碱酯酶、血清总胆固醇)水平,并比较不同肝功能分级患者的肝功能指标水平。结果试验组总胆汁酸水平为(52.36±22.17)μmol/L,显著高于对照组的(6.19±1.84)μmol/L,差异具有统计学意义(P<0.05)。试验组血清白蛋白、血清胆碱酯酶以及血清总胆固醇水平分别为(27.23±6.34)g/L、(2451.67±315.39)U/L、(3.04±0.86)mmol/L,对照组血清白蛋白、血清胆碱酯酶以及血清总胆固醇水平分别为(67.84±7.58)g/L、(7492.84±968.82)U/L、(4.25±1.43)mmol/L;试验组的血清白蛋白、血清胆碱酯酶以及血清总胆固醇水平均显著低于对照组,差异均具有统计学意义(P<0.05)。肝功能A级患者共15例,其总胆汁酸、白蛋白、血胆碱酯酶以及血胆固醇水平分别为(19.08±4.45)μmol/L、(39.05±7.19)g/L、(3145.67±341.39)U/L、(3.68±1.13)mmol/L;肝功能B级患者共20例,其总胆汁酸、白蛋白、血胆碱酯酶以及血胆固醇水平分别为(45.28±20.34)μmol/L、(26.17±5.38)g/L、(2208.49±295.12)U/L、(3.05±0.72)mmol/L;肝功能C级患者共15例,其总胆汁酸、白蛋白、血胆碱酯酶以及血胆固醇水平分别为(93.42±42.14)μmol/L、(20.86±4.35)g/L、(1505.83±203.15)U/L、(2.16±0.51)mmol/L。不同肝硬化级别患者的总胆汁酸、血清白蛋白、血清胆碱酯酶以及血清总胆固醇水平比较差异均具有统计学意义(P<0.05)。随着肝功能分级的升高,患者的血清白蛋白、血清胆碱酯酶以及血清总胆固醇随之不断降低,而总胆汁酸水平则随之升高。结论对肝炎肝硬化患者实施肝功能生化检验,能够有效反映患者肝脏受损情况。     

鞘内注射吗啡对切口痛大鼠脊髓兴奋性氨基酸含量的影响

目的　研究在大鼠切口疼痛模型上鞘内注射吗啡对脊髓 (L4～ 5)兴奋性氨基酸 (天门冬氨酸和谷氨酸 )含量的影响。方法　雄性SD大鼠 32只 ,随机分为 4组 ,每组 8只。组Ⅰ为假手术组 ;组Ⅱ术前 30min鞘内注射人工脑脊液 (ACSF) 2 0 μl;组Ⅲ和组Ⅳ分别在术后 30min和术前 30min鞘内注射吗啡 10 μg。按Brennan法制成大鼠足底切口疼痛模型 ,以累计疼痛评分确定疼痛行为。应用邻苯二甲醛柱前衍生高效液相色谱法测定脊髓兴奋性氨基酸含量。结果　组Ⅱ累计疼痛评分 (17± 3)明显高于组Ⅰ (P <0 0 1) ,与组Ⅱ比较 ,组Ⅲ和组Ⅳ累计疼痛评分 (组Ⅲ :3± 2 ,组Ⅳ :2 5± 2 )明显降低 (P <0 0 1)。与组Ⅰ (天门冬氨酸 :1 90±0 2 8μmol/g ,谷氨酸 :3 9± 0 5 1μmol/g)比较 ,组Ⅱ的脊髓天门冬氨酸 (2 36± 0 39μmol/g)和谷氨酸 (4 8±0 89μmol/g)的含量明显升高 ;组Ⅲ和组Ⅳ的脊髓天门冬氨酸含量分别为 2 0 0± 0 34μmol/g和 2 0 2± 0 2 9μmol/g ,均明显低于组Ⅱ (P <0 0 5 ) ;组Ⅲ和组Ⅳ的脊髓谷氨酸含量分别为 3 9± 0 5 9μmol/g和 4 0± 0 5 6μmol/g ,也明显低于组Ⅱ (P <0 0 5 )。而两用药组上述指标比较以及用药组与组Ⅰ比较均无显著差异 (P >0 0 5 )。结论　在大鼠切口疼痛模型中     

芍药苷对胶原诱导型关节炎大鼠下丘脑-垂体-肾上腺轴的影响

目的探讨芍药苷治疗胶原诱导型关节炎(CIA)是否与调节下丘脑-垂体-肾上腺(HPA)轴有关。方法 Wistar大鼠右足趾皮内注射牛Ⅱ型胶原(CⅡ)和弗氏完全佐剂制备CIA大鼠模型,7 d后大鼠背部和尾根部皮下注射CⅡ加强免疫1次。初次免疫后第14天ig给予地塞米松2 mg.kg-1或芍药苷25,50和100 mg.kg-1,每天1次,连续28 d。初次免疫后第14,21,28,35和42天观察CIA大鼠的足爪肿胀度和关节炎指数的变化。给药结束后第2天大鼠摘眼球取血,放射免疫法检测血浆促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质酮(CS)含量;制备血清,用ELISA法检测白细胞介素4(IL-4)、干扰素γ(IFN-γ)、IL-1β、肿瘤坏死因子α(TNF-α)和抗CⅡ抗体含量。结果与正常对照组相比,模型对照组大鼠关节红肿,关节炎指数升高(P<0.01),血中CRH、CS、抗CⅡ抗体、IFN-γ、IL-1β和TNF-α水平明显升高(P<0.01),IL-4水平下降(P<0.01),ACTH无明显改变。ig给予芍药苷50和100 mg.kg-1可抑制CIA大鼠关节肿胀,降低关节炎指数(P<0.05),在第42天关节炎指数由模型对照组的6.4±0.7降至5.6±0.5和5.4±0.7(P<0.05);使模型对照组血清IFN-γ由(21.3±2.5)ng.L-1降至16.6±1.3和(16.1±1.9)ng.L-1(P<0.01),IL-1β由(37.3±4.2)ng.L-1降至32.1±2.9和(31.2±4.1)ng.L-1(P<0.01),TNF-α由(53.9±7.9)ng.L-1降至39.4±6.8和(31.3±6.1)ng.L-1(P<0.01),抗CⅡ抗体由(2.13±0.32)ng.L-1降至1.35±0.58和(1.10±0.42)ng.L-1(P<0.01),IL-4由(26.6±3.0)ng.L-1升至41.9±3.1和(49.1±4.2)ng.L-1(P<0.01);能使血浆CRH的水平由模型对照组的(2.3±0.5)μg.L-1升高至4.9±1.0和(5.3±1.1)μg.L-1(P<0.01),CS由(33±10)μg.L-1升高至47±9和(51±13)μg.L-1(P<0.01),ACTH水平亦有明显升高(P<0.01)。结论芍药苷治疗CIA可能与调节PHA轴有关。     

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.     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.