氰化钠加重缺氧诱导的小鼠脑神经损伤及机制

目的 研究氰化钠(Na CN)急性染毒对密闭缺氧致小鼠脑神经损伤的作用及机制。方法 (1)将小鼠随机分为缺氧+Na CN[0(缺氧对照组),2.56,3.8和5.1 mg·kg^-1]组,ip给予不同浓度Na CN染毒后立即放入密闭缺氧罐,观察小鼠缺氧存活时间。(2)将小鼠分为正常对照组、Na CN 3.8 mg·kg^-1组、缺氧30和60 min组及Na CN(3.8 mg·kg^-1)+缺氧(30和60 min)组,按分组处理后,用动脉血气分析仪检测小鼠动脉血气指标酸碱度(p H)、氧饱和度(s O₂)、氧分压(p O₂)和二氧化碳分压(p CO₂);用激光散斑成像仪检测小鼠大脑皮质脑血流;分别称量脑组织干、湿重,计算脑组织含水率;试剂盒检测海马总超氧化物歧化酶(T-SOD)活性和丙二醛(MDA)含量;TUNEL染色检测小鼠海马细胞凋亡率;HE染色检测海马组织病理变化。结果 (1)与缺氧对照组比较,缺氧+Na CN各剂量组小鼠缺氧存活时间均显著延长(P&l...     

无创呼吸机治疗慢性阻塞性肺疾病合并呼吸衰竭患者的效果

目的 探讨无创呼吸机治疗慢性阻塞性肺疾病合并呼吸衰竭患者的效果。方法 选取我院慢性阻塞性肺疾病合并呼吸衰竭患者,随机分为常规组、呼吸机组,采用对照试验方法探讨分别应用常规治疗、无创呼吸机支持治疗的治疗效果。结果 呼吸机组显效32例,占比64.00%,有效16例,占比32.00%,无效2例,占比4.00%,总有效率96.00%;常规组显效22例,占比44.00%,有效15例,占比30.00%,无效13,占比26.00%,总有效率74.00%。呼吸机组的总有效率高于常规组(χ²=10.25,P <0.05);呼吸机组的肺通气功能指标显著优于常规组,P <0.05;治疗后,常规组的Pa O2为(72.70±4.80)mm Hg,Pa CO₂为(71.90±5.40)mm Hg,呼吸机组Pa O₂为(85.10±5.70)mm Hg,Pa CO₂为(54.80±5.10)mm Hg,呼吸机组的Pa O₂、Pa CO₂优于常规组(t=5.69、6.29,...     

CYP2C9抑制剂对艾瑞昔布大鼠体内药动学的影响

目的：考察CYP2C9抑制剂胺碘酮对艾瑞昔布在大鼠体内药动学的影响。方法： 40只健康雄性SD大鼠随机分为2组（n=20）,实验组连续7 d灌胃胺碘酮灌胃液（40 mg·kg^-1,qd）,对照组灌胃等量空白灌胃液。2组均于第8天单次灌胃艾瑞昔布灌胃液20 mg·kg^-1,按确定时间点取血,LC-MS/MS法测定艾瑞昔布血药浓度,DAS 2.1.1软件拟合药时曲线并计算药动学参数,SPSS 13.0软件进行统计学分析。结果：实验组和对照组的主要药动学参数如下：AUC_{0-24 h}分别为（1 814.8±693.4） ng·h·mL^-1和（1 125.1±457.6） ng·h·mL^-1;AUC_0-∞分别为（2 091.6±887.1） ng·h·mL^-1和（1 331.3±592.6） ng·h·mL^-1;t_1/2分别为（7.8±4.5） h和（7.4±3.8） h;t_max分别为（1.7±0.6） h和（1.46±0.60） h;CL分别为（0.01±0.01） L·h^-1·kg^-1和（0.02±0.01） L·h^-1·kg^-1;V分别为（0.11±0.05） L·kg^-1和（0.17±0.07） L·kg^-1;C_max分别为（268.2±115.7） ng·mL^-1和（162.2±53.0） ng·mL^-1。与对照组相比,实验组大鼠的AUC_{0-24 h}、AUC_0-∞、C_max显著增大（P<0.05）,V、CL显著减小（P<0.05）,其他参数差异无统计学意义（P>0.05）。结论： CYP2C9抑制剂（胺碘酮）对艾瑞昔布在大鼠体内的药动学产生影响。     

成人重度烧伤并发脓毒症的相关因素分析

目的：探讨分析成人重度烧伤并发脓毒症的相关因素,以减低感染率,提高烧伤的防治水平。方法选取重度烧伤的青壮年患者126例,其中重度烧伤患者并发脓毒症60例作为脓毒症组,其余未并发脓毒症的66例患者作为非脓毒症组。将性别、烧伤原因、有无吸入性损伤和首次手术时间和烧伤面积等5个可能诱发脓毒症发生相关因素进行分析,并比较不同烧伤面积,其脓毒症的患病率。结果患者合并吸入性损伤的脓毒症的发生率明显大于无吸入性损伤患者差异有统计学意义（ P<0.05）;在首次手术时间方面,2组间首次手术时间≤3d 、>3d和未进行手术患者的脓毒症发生率差异均有统计学意义（ P<0.05）;而在性别和烧伤原因方面比较,差异无统计学意义（ P>0.05）。不同程度烧伤面积的患者,其脓毒症的患病率差异均有统计学意义（ P<0.05）。当患者的烧伤面积在81%以上时,其脓毒症的患病率明显增高。结论烧伤总面积、患者首次手术时间和吸入性损伤与烧伤后脓毒症的发病相关。     

舒芬太尼联合瑞芬太尼静脉麻醉对兔内毒素性急性肺损伤时促炎因子的影响

目的：探讨舒芬太尼联合瑞芬太尼静脉麻醉与二者单独使用对兔内毒素性急性肺损伤（ALI）时促炎因子的影响。方法：健康成年雄性新西兰大白兔60只，体质量2.2~2.8 kg，随机分为5组（n=12）：对照组（C组）、急性肺损伤组（ALI组）、瑞芬太尼组（RF组）、舒芬太尼组（SF组）、瑞芬太尼+舒芬太尼组（M组）。C组，30 min静脉泵注生理盐水10 mL；ALl组，30 min静脉泵注大肠杆菌脂多糖（LPS）0.7 mg·kg^-1；RF组与SF组先静脉泵注LPS（方法同ALI组）再分别静脉泵注瑞芬太尼0.8 μg·kg^-1·min^-1，舒芬太尼0.02 μg·kg^-1·min^-1；M组先静脉泵注LPS（方法同ALI）后静脉缓慢推注舒芬太尼1.0 μg·kg^-1，3 min后静脉泵注瑞芬太尼0.8 μg·kg^-1·min^-1。各组分别于泵注LPS前（T₀）、泵注结束即刻（T₁）、泵注结束1（T₂）、3（T₃）、6（T₄）h时记录平均动脉血压（MAP）、心率（HR），测定动脉血氧分压（PaO₂）、肿瘤坏死因子（TNF）-α及白介素（IL）-1、IL-6、IL-8的浓度；称量肺组织湿重（W）和干重（D），计算W/D比；观察肺组织病理学结构变化。结果：在T₀~T₁时段，各组各项检测结果均无显著性差异（P>0.05）。在T₂~T₄时段：与C组比较，ALI组、RF组、SF组和M组的MAP、HR、PaO₂均降低（P<0.05），W/D比值、和血浆TNF-α、IL-1、IL-6、IL-8的浓度均升高（P<0.05）；与ALI组比较，RF组、SF组和M组PaO₂、MAP、HR均升高（P<0.05），肺组织W/D比和血浆TNF-α、IL-1、IL-6、IL-8的浓度降低（P<0.05）；M组、RF组和SF组相比较，PaO₂、MAP、HR变化以及肺组织W/D比和血浆TNF-α、IL-1、IL-6、IL-8的浓度变化均无显著性差异（P>0.05）。整个实验过程中各组生命体征的稳定性：C组 > M组 > SF组 > RF组 > ALI组。肺组织病理学损伤结果表明，RF组、SF组和M组均较ALI组减轻。结论：瑞芬太尼、舒太尼静脉麻醉可使内毒素性急性肺损伤兔血液中TNF-α、IL-1、IL-6、IL-8的浓度降低，从而减轻其肺损伤的程度。二者联合使用与单独使用对炎症因子的影响无显著性差异。     

昏迷患者颈静脉及股静脉血气、血气梯度值和氧利用率分析

观察了 19例各种严重颅脑病症及各种原因所致昏迷患者颈静脉及股静脉血气、氧利用率 (O2 UC)以及动 -静脉血气梯度值的变化 ,探讨了昏迷时脑及躯体氧代谢动力学的变化以及临床意义。结果显示 ,对照组颈静脉 p H下降的幅度和 O2 UC均显著降低 (P<0 .0 1,0 .0 0 1) ,同时股静脉 p H下降幅度增大 ,O2 UC较明显增高 ,将以上这种逆向性变化以颈静脉 -股静脉梯度加以分析 ,各指标均出现显著性变化 (P<0 .0 0 1)。     

反式白藜芦醇葡萄糖苷在犬体内的药动学研究

目的：建立Beagle犬血浆中反式白藜芦醇葡萄糖苷（TRG）的测定方法并进行药动学研究。方法：Beagle犬分别灌胃和静脉给予TRG后测定不同时间的血药浓度,运用Topfit 2.0药动学软件计算非房室模型药动学参数。结果：Beagle犬以25,50,100 mg·kg^-13个剂量灌胃给予TRG,TRG血浆峰浓度（C_max）分别为（0.92±0.44）,（1.93±0.46）,（4.02±1.22）mg·L^-1;达峰时间（t_max）分别为（0.83±0.18）,（1.19±0.36）,（0.78±0.17）h;半衰期（t_1/2）分别为（0.93±0.16）,（1.18±0.19）,（1.18±0.29）h;药-时曲线下面积（AUC_0-t）分别为（1.73±0.77）,（4.14±0.52）,（8.67±2.95）mg·h·L^-1。Beagle犬静脉注射TRG 25 mg·kg^-1后,TRG的t_1/2为（1.72±0.41）h,AUC_0-t为（48.9±6.41）mg·h·L^-1,TRG的绝对生物利用度为3.53%。结论：TRG在25~100 mg·kg^-1剂量范围内C_max和AUC_0-t呈线性动力学特征,TRG在Beagle犬体内的绝对生物利用度较低。     

抑制细菌碳酸酐酶作为应对细菌耐药性的新策略

细菌对抗生素的多重耐药和交叉耐药亟需联合其他有效的靶向替代策略进行控制。碳酸酐酶(carbonic anhydrases,CAs)是催化CO₂水合生成HCO₃^-和H⁺的可逆反应的一组金属酶超家族,其活性影响细菌的增殖、生物合成及其在宿主体内的持续感染。靶向抑制CAs活性可降低细菌的生存和适应性,并且不会产生与传统抗生素相同的耐药性。细菌CAs有望成为开发尚无临床耐药性的新型抗菌药物靶标。本文对细菌CAs的分类和结构、生理功能以及细菌现有的CA抑制剂(CA inhibitors,CAIs)的研究进展进行了综述,可为新型抗菌药物研发、解决临床耐药问题提供参考。     

右美托咪定用于颅内动脉瘤介入治疗术对脑部氧代谢水平的影响

目的 探讨右美托咪定用于颅内动脉瘤介入治疗术对于脑部氧代谢水平的影响。方法 选取2021年1月至12月上饶市人民医院收治的80例择期实施颅内动脉瘤介入术的患者为研究对象,按照随机数字表法分为观察组和对照组两组,每组各40例。手术过程中,两组患者采用不同方式进行麻醉维持,对照组给予2%～3%七氟烷吸入,瑞芬太尼0.1～0.2μg/(kg·min)持续输注,观察组给予2%～3%七氟烷吸入,右美托咪定负荷量0.5μg/(kg·min)输注完毕,之后0.4μg/(kg·h)持续输注。比较两组患者麻醉诱导前、手术开始30 min、手术结术后1、6、12、24 h(T0～T5)的脑部氧代谢指标水平[动脉血氧含量(Ca O₂)、颈内静脉血氧含量(Cjv O₂)、动脉-颈内静脉血氧含量差(Da-jv O₂)、脑氧摄取率(CERO₂)]、脑损伤血清指标水平[中枢神经特异性蛋白(S100-β)、神经烯醇化酶(NSE)]。结果 两组T0时的Ca O₂、Cjv O₂、Da-jv ...     

酮洛芬择时释药片Beagle犬体内的生物等效性

目的：研究酮洛芬择时释药片（受试制剂）和酮洛芬胶囊（参比制剂）在Beagle犬体内的药动学特征和生物等效性。方法：采用双周期双交叉试验，每只Beagle犬口服受试制剂和参比制剂，于相应时间点取静脉血检测酮洛芬血药浓度。采用DAS 2.1.1软件分别计算2种制剂的药动学参数，并计算受试制剂的相对生物利用度。通过统计学分析比较2种制剂的生物等效性。结果：受试制剂和参比制剂的主要药动学参数分别为t_1/2（4.28±1.59）h和（5.90±2.33）h，C_max（61.36±2.37）μg·mL^-1和（67.59±10.72）μg·mL^-1，t_max（5.83±0.61）h和（2.04±0.19）h，t_lag（3.46±0.25）h和（0.46±0.22）h，AUC_0-t（341.16±19.09）μg·h·mL^-1和（355.93±51.82）μg·h·mL^-1，AUC_0-∞（354.29±19.91）μg·h·mL^-1和（416.77±42.49）μg·h·mL^-1，受试制剂的相对生物利用度为85.01%。结论：受试制剂和参比制剂的AUC_0-t、C_max是生物等效性的，但在t_max、t_lag生物不等效。受试制剂在一定的时滞（约3.458h）后释药，符合择时释药制剂的释药要求。     

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.

---

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.     

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.