酚妥拉明对野百合碱引起的大鼠肺动脉高压的影响

本文研究结果表明:野百合碱是一个有效的引起Wistar大鼠肺动脉高压模型的药物;酚妥拉明(0.2mg·kg~(-1)0.4mg·kg~(-1))im.每天2次.连续用药21d后.可降低野百合碱引起的肺动脉高压.但对股动脉血压无明显影响。酚妥拉明(0·52mg·kg~(_1))iv一次即可明显降低野百合碱引起的大鼠肺动脉高压和股动脉压。     

莨菪类药物对大鼠脑,心肌血流量和心指数的影响

采用放射性生物微球法观察了莨菪类药物(HD)对大鼠脑血流量(CBF)、心肌血流量(MBF)和心指数(C1)的影响.结果表明HD明显增加CBF和MBF。减小CI.本文三种药物增加大脑半球 CBF作用随剂量增加而增强,Ani10～40 mg·kg~(-1)iv增加26～73％;东莨菪碱(Sco)1.25～5mg·kg~(-1)iv增加17～38％;阿托品(Atr)2.5～10mg·kg~(-1)iv增加17～64％,HD增加MBF作用远较增加CBF作用强.Ani 10～20 mg·kg~(-1)iv增加128～198％;但40 mg·kg~(-1)iv作用明显减弱;Sco 1.25～5mg·kg~(-1)iv增加5l～116％;Atr 5～10 mg·kg~(-1)iv增加113～137％,三药均可明显减小CI。     

磷酸喹哌抗实验性心律失常作用

磷酸喹哌(PQP)9mg·kg~(-1)iv明显降低小鼠室颤的死亡率;PQP 18mg·kg~(-1)ip对氯仿诱发小鼠室颤具有保护作用;PQP 6.3mg·kg~(-1)ip显著增加恒速(10mg·L~(-1)·min~(-1)滴注乌头碱引起麻醉大鼠室性早搏(VE)、室性心动过速(VT)、室性纤颤(VF)所需的乌头碱用量;PQP5.4 mg·kg~(-1)iv显著增加恒速(50mg·L~(-1)·min~(-1))滴注哇巴因引起麻醉豚鼠VE、VT和VF所需哇巴因用量;PQP3.36mg·kg~(-1)iv明显缩短肾上腺素诱发家兔室性心律失常的持续时间.结果表明PQP具有抗心律失常作用。小鼠PQPLD_(50)iv为93.33 mg·kg~(-1)。     

山莨菪碱对脑缺血局部血流量的影响

用放射性生物微球法,观察了山莨菪碱对双侧颈总动脉结扎(BCAL)后大鼠脑局部血流量的影响.BCAL使大鼠大脑半球血流量显著减少,以中部最明显。山莨菪减10mg·kg~(-1)iv明显增加缺血最严重的大脑中部血流量,20mg·kg~(-1)iv明显增加整个大脑半球血流量,40mg·kg~(-1)iv则作用减弱。BCAL后心肌血流量明显增加,山莨菪碱20mg·kg~(-1)iv使其进一步增加,但40mg·kg_(-1)iv则使其显著减少。10～20·mg·kg~(-1)iv对BCA L后的心指数无明显影响,40mg·kg~(-1)iV则使其明显增大。     

槲皮素在兔体内的药代动力学

槲皮素为黄酮类化合物。兔iv槲皮素10m g·kg~(-1)后.血药浓度—时间曲线符合二室模型。T_(1/2)(α)为2.91 ±1.36min,T_(1/2)(β)183.78±82.67min,V_B为0.624±0.225 L·kg~(-1),CL为3.15±2.11 ml·kg~(-1)·min~(-1).槲皮素10mg·kg~(-1)ig后,生物利用度为42.7％,药峰浓度(C_(Dk))为10.9mg·L~(-1),药峰时间(t_(pk))为60min。iv槲皮素后.药物以原型和代谢产物两种形式经尿、胆汁排泄,消除较迅速。     

芍药甙在兔和大鼠体内的药动学研究

兔iv25mg·kg~(-1)芍药甙后,血药浓度—时间曲线符合二室模型。药动学参数为T_(1/2α)=5.93min,T_(1/2β)66.02min,V(?)=516.8ml·kg~(-1),CL=6.11ml·kg~(-1)·min~(-1)。兔ig250mg·kg~(-1)芍药甙,生物利用度为F=7.24％±4.15％,T_(max)=77.4min,C_(max)=21.57mg·L~(-1)大鼠ig550mg·kg~(-1)芍药甙,24h内粪、尿排泄量及iv55mg·kg~(-1)7h内胆汁排泄量分别占给药量的10.61％、1.08％、864％。离体肝脏灌流结果提示:芍药甙在肝内代谢少.     

2-巯基苯并咪唑SD大鼠灌胃给药的毒性研究

目的:研究2-巯基苯并咪唑(MBI)对 SD 大鼠所产生的毒性反应的性质和程度、剂量和毒性效应的关系、无毒反应剂量以及毒性的主要靶器官。方法:采用 SD 大鼠,灌胃给予 MBI,分为溶媒对照组和3个给药组(MBI 2 mg·kg~(-1),MBI 10 mg·kg~(-1),MBI 50 mg·kg~(-1)),连续给药28 d,期间对体重、摄食量进行监测。给药结束次日解剖取材,测定血液学及血清生化学指标,并对大鼠主要脏器进行大体观察和组织病理学检查。结果:50 mg·kg~(-1)MBI 使大鼠的体重增长及摄食量的增加受到明显抑制;10 mg·kg~(-1)和*或50 mg·kg~(-1)MBI 导致雌雄大鼠甲状腺、脑、肝脏重量明显升高,胸腺、脾脏重量显著下降;使雄性大鼠垂体、肺、睾丸重量明显升高,雌性肾上腺、颚下腺重量显著下降,肾脏重量显著升高;50 mg·kg~(-1)剂量引起大鼠 AST、LDH、CRE、BUN、CHO 等血清生化水平的显著变化;组织病理学检查发现,10 mg·kg~(-1)以上剂量的 MBI 可引起雄性和雌性动物甲状腺增生性病变、垂体前叶β细胞肿胀以及雄性动物胸腺萎缩;50 mg·kg~(-1)MBI 可引起雄性和雌性动物肝损伤,肾上腺皮质细胞的脂肪变性,以及雌性动物肾盂扩张。结论:MBI 毒性作用的主要靶器官为甲状腺;MBI 在 SD 大鼠的最大无毒反应剂量为2 mg·kg~(-1)。     

丙泊酚静脉注射对大鼠心室功能及心肌β肾上腺素受体的影响

目的研究丙泊酚静脉注射对大鼠心室功能及心肌β肾上腺素受体密度及亲和力的影响。方法24只清洁级雄性Wistar大鼠随机分为3组,每组8只:对照组、丙泊酚5 mg·kg~(-1)组及丙泊酚10 mg·kg~(-1)组。记录丙泊酚给药前及给药后30 min内所有动物的心率(HR)、左室收缩压(LVSP)及左室内压力变化最大速率(+dp/dt_(max)、-dp/dt_(max)),并采用放免法测定给药后30 min时心肌β肾上腺素受体密度(B_(max))及亲和力(K_d)。结果(1)HR、LVSP、+dp/df_(max)及-dP/dt_(max)分别在丙泊酚5 mg·kg~(-1)静脉给药后9、5、30及9 min内明显低于给药前值;并在给药后9、7、7及9 min内分别明显低于对照组(P<0.05或0.01)。HR、LVSP、+dp/dt_(max)及-dp/df_(max)分别在丙泊酚10 mg·kg~(-1)静脉给药后25、5、30及8 min内明显低于给药前值;并在给药后8、7、7及8 min内分别明显低于对照组(P<0.05或0.01)。丙泊酚2组间比较无明显差异(P>0.05)。(2)丙泊酚5 mg·kg~(-1)组及10 mg·kg~(-1)组B_(max)明显高于对照组(P<0.01);丙泊酚10 mg·kg~(-1)组K_d值明显高于对照组及丙泊酚5 mg·kg~(-1)组(P<0.05);其余各组间比较无明显差异(P>0.05)。结论丙泊酚可引起给药后30 min内心室功能抑制,5 mg·kg~(-1)及10 mg·kg~(-1)上调给药后30 min心肌β肾上腺素受体密度。     

CPU86017及其旋光异构体对抗异丙肾上腺素对小鼠心肌的损害作用*

目的:比较口服给CPU86017(对氯卞基四氢小檗碱)及其C-13a旋光异构体(SR和SS)对抗异丙肾上腺亲(ISO)所致小鼠心肌损害作用。方法:连续皮下注射ISO(1 mg·kg~(-1))10 d建立心肌肥厚模型,在d5～d10各治疗组分别灌胃给予普萘洛尔(5 mg·kg~(-1))、CPU 86017(40 mg·kg~(-1)),SR+SS(40 mg·kg~(-1))和SS(40 mg·kg~(-1))。末次给药24 h后取血处死小鼠。测定心重指数(全心重量/体重)和左心室重量指数(左心室重量/体重);左心室匀浆中丙二醛(MDA)和超氧化物歧化酶(SOD)活力;血清中谷草转氨酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)活力。结果:CPU86017及SR,SS异构体均可显著逆转ISO模型组升高的心重指数,心肌中过度增加的MDA水平及降低的SOD活力,并显著降低血清中升高的AST,CK和LDH水平,其治疗效果与普奈洛尔相当。结论: CPU86017及其旋光异构体均明显对抗ISO所致的心肌肥大性损害作用。     

促甲状腺激素释放激素对大鼠内毒素性休克的影响

研究了不同剂量TRH(促甲状腺激素释放激素)对大鼠大肠杆菌内毒素性休克的影响,并与纳洛酮进行比较.发现低(0.22mg·kg~(-1),iv)、中(0.67mg·kg~(-1),iv)、高(2mg·kg~(-1),iv)剂量的TRH均能迅速纠正内毒素性低血压,且明显提高大鼠24h存活率.2mg·kg~(-1)纳洛酮的升压效应与低剂量TRH相当,但前者在较低血压水平上提高大鼠存活率的作用更强,此点与TRH不同.     

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.

     

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.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.