血清中胺碘酮浓度的测定

目的 :建立测定血清中胺碘酮浓度的HPLC法。方法 :色谱柱为Diamonsil(TM)C18(2 0 0mm× 4 6mm ,5 μm) ;流动相 :甲醇∶水∶10 %冰乙酸∶10 %正丁胺 (92∶8∶0 19∶0 2 3,V/V/V/V) ;流速 1mL·min-1;检测波长 2 4 1nm ;内标物为普罗布考。结果 :胺碘酮线性范围为 0 2 0 38～ 2 0 376mg·L-1,r=0 9989,平均回收率为 92 2 % ,平均日内RSD为 2 4 7% ,日间RSD为 4 37%。结论 :本法操作简便、快速、准确 ,可用于胺碘酮血药浓度的临床监测     

HPLC法测定小剂量胺碘酮及去乙基胺碘酮血药浓度

目的:建立RP-HPLC法测定小剂量胺碘酮及去乙基胺碘酮的血药浓度.方法:色谱柱:Nova-PakC18柱(3.9 mm×150 mm, 4 μm);流动相:甲醇-醋酸盐缓冲液(pH 4.5)-三乙胺(80∶20∶0.5), 在使用前超声脱气15 min;检测波长:242 nm;以丹参酮IIA为内标.结果:胺碘酮及去乙基胺碘酮在0.4～8.0 μg·mL-1范围内线性关系良好,相关系数分别为0.9987与0.9982,日内、日间RSD均小于10%(n=5).结论:此方法快速、准确、灵敏、简便,适用于小剂量胺碘酮及去乙基胺碘酮血药浓度测定.     

高效液相色谱法测定血清中胺碘酮浓度

目的 　建立反相高效液相色谱法测定人血清中胺碘酮的浓度。方法 　采用液 -液提取 ,流动相为甲醇∶水∶三乙胺 (2 0 0∶ 3 6∶ 0 .1) ,醋酸调 p H值至 7.15 ,检测波长 2 40 nm。结果 　线性范围为 0 .4～ 4μg· m L- 1 平均回收率 10 1.6% ,日内 RSD小于 6% ,日间 RSD小于 9%。结论 　本方法操作简便、快速、准确 ,适用于生物样品中胺碘酮的血药浓度监测。     

静脉注射胺碘酮对阵发性房颤复律的疗效

目的 :观察静注胺碘酮对阵发性房颤 (AF)复律的临床疗效。方法 :将 5 1例阵发性AF患者分为胺碘酮组 (n =2 6 )和普罗帕酮组 (n =2 5 )。胺碘酮组先给予胺碘酮 15 0mg ,iv ,0 5h后再给予胺碘酮 15 0mg ,iv ,继之以 1mg·min-1,ivgtt,6h ,随后以 0 5mg·min-1,ivgtt,2 4h。普罗帕酮组给予普罗帕酮 70mg ,iv ,继之以 0 5mg·min-1,ivgtt,总量至 2 80mg。结果 :胺碘酮组4h内转复 8例 (30 8% ) ,4～ 8h内转复 8例 (30 8% ) ,8～ 12h内转复 2例 (7 7% ) ,12～ 2 4h内转复 2例 (7 7% ) ,未转复 6例 ,总显效率为 76 9%。普罗帕酮组 4h内转复 7例 (2 8% ) ,4～ 8h内转复 6例 (2 4 % ) ,8～ 12h内转复 3例 (12 % ) ,12～ 2 4h内转复1例 (4% ) ,未转复 8例 ,总显效率为 6 8%。结论 :静注胺碘酮和普罗帕酮对阵发性AF复律疗效相当     

胺碘酮治疗无症状心肌缺血伴室性早搏的临床疗效

目的 :观察胺碘酮治疗冠心病无症状心肌缺血 (SMI)伴室性早搏 (VPB)的疗效和安全性。方法 :将 92例患者分成胺碘酮组、硝酸异山梨酯组和普罗帕酮组。疗程 38d ,用DCG观察SMI和VPB改善情况。结果 :与治疗前比较 ,胺碘酮组SMI发作次数明显降低 [(2 3± 1 0 )vs (7 7± 4 3) ,P <0 0 1],持续时间明显缩短 [(3 7± 1 8)minvs (19 4± 12 4 )min ,P <0 0 1],胺碘酮组疗效较硝酸异山梨酯组显著提高 (P <0 0 5 ) ;胺碘酮组治疗VPB有效率 90 6 %,较普罗帕酮疗效好 (P <0 0 5 )。未见严重不良反应。结论 :胺碘酮治疗SMI伴VPB有确切疗效和安全性。     

高效液相色谱法测定人血清中胺碘酮浓度

目的建立以高效液相色谱法测定人血清中胺碘酮浓度的方法。方法色谱柱为ShimadzuShim-packVP-ODS,流动相为甲醇∶乙腈∶醋酸-醋酸钠缓冲液(80∶10∶10),流速为0.8mL.min-1,紫外检测波长为241nm,内标为枸橼酸他莫昔芬。结果胺碘酮检测浓度在0.4～3.2mg·L-1范围内线性关系良好(r=0.9997),方法回收率为101.4%～109.0%,绝对回收率为79.5%～87.0%,日内和日间RSD<10%。结论本方法快速、专一,可用于人血清中胺碘酮浓度的测定。     

离子对RP-HPLC测定盐酸丁螺环酮缓释片中主药的含量

目的　测定盐酸丁螺环酮缓释片中盐酸丁螺环酮的含量。方法　采用离子对反相高效液相色谱法。Nova PakC18色谱柱 ,流动相为甲醇 -乙腈 -离子溶液 (十二烷基硫酸钠 2 5g ,二乙胺 1ml,加水至 10 0 0ml,冰醋酸调pH 3 0 ) (10∶5 0∶4 0 ) ,检测波长为 2 6 5nm。结果　盐酸丁螺环酮的含量在 0 32～ 1 6 μg·ml-1浓度范围内线性关系良好 (r =0 9999)。平均回收率 97 5 6 %(n =5 )RSD =1.13%。结论　所用方法简便、快速、准确。     

高效液相色谱法测定血清中吗氯贝胺浓度

目的 :建立测定血清中吗氯贝胺的HPLC法 ,观察 6条犬单次口服吗氯贝胺胶囊后血药浓度经时变化。方法 :选用SSEXsilODS色谱柱 (15 0mm× 4 6mm ,5 μm) ,以氯霉素作内标 ,在碱性条件下用乙酸乙酯萃取。流动相为乙腈∶水∶三乙胺 =30∶6 9 5∶0 5 ,用冰乙酸调pH值到 5 5 ,在紫外 2 4 0nm波长处测定。结果 :吗氯贝胺标准曲线在0 0 5 - 2 0 μg·ml- 1 内r=0 9998,最低检出浓度为 5 0ng·ml- 1 。平均回收率为 96 88% ,日内RSD为 1 72 % - 8 2 2 % ,日间RSD为 4 5 1% - 5 0 5 %。结论 :本法灵敏、准确、重复性好 ,可以满足吗氯贝胺药代动力学的试验要求     

胺碘酮长疗程个体化治疗老年心律失常54例观察

目的 :探讨胺碘酮长疗程个体化治疗老年心律失常的临床疗效和安全性。方法 :选择 5 4例 6 0岁以上心律失常患者给予胺碘酮个体化治疗 ,疗程 1年以上 ,观察治疗前后和治疗 1年后患者心律失常的有效控制率、Q -T间期变化以及不良反应。结果 :5 4例患者的维持量为 14 5± 6 5mgd- 1,比推荐用量小 ,而胺碘酮治疗心律失常的有效率仍高达 88 9% ;Q -T间期轻度延长 (386± 5 5ms比 4 34± 5 2ms,P <0 0 5 )。不良反应少 ,未出现扭转室速和室颤发作 ;无肝肾损害等副作用。不良反应也较文献报道的非个体化治疗方案少 (3 7%比 5 %～ 15 % )。结论 :胺碘酮长疗程个体化治疗老年心律失常临床疗效确切 ,维持量较小 ,不良反应少     

RP-HPLC法测定盐酸胺碘酮包衣脉冲片中盐酸胺碘酮的含量

目的:建立测定盐酸胺碘酮包衣脉冲片中盐酸胺碘酮含量的方法。方法:采用反相高效液相色谱法。色谱柱为Agilent2C518℃柱。,流结动果相:盐为酸2%胺三碘乙酮胺检(测用浓磷度酸在调0p.H02至0～4.08).2-5乙0腈m(g·4m0L∶6-01)范,检围测内波与长峰为面积24积0n分m值,流线速性为关1系.0良mL好·(mri=n-01.,9进99样9)量,平为均20加μL样,回柱收温率为分别为99.28%、99.53%、99.85%,RSD=0.59%。结论:该方法简便、快速、准确、灵敏度高、重复性好,可用于盐酸胺碘酮包衣脉冲片的质量控制。     

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.