The effect of various types of oxygenators on the pulmonary microvessels and surfactant activity

Experiments were conducted on 28 dogs to study the changes of microvessels and their effect on the functional condition of pulmonary surfactants after 120-minute venoarterial perfusion and extrapulmonary gas exchange with the use of a foamy-film oxygenator and a "Sever" membrane oxygenator. A direct relationship between the condition of the microvessels and changes of pulmonary surfactant activity was revealed: factors (contact type oxygenators) causing an unfavourable effect on the terminal link of pulmonary circulation induced rapid (in 2-3 hours) development of disturbances in the surfactant system. These changes are less marked in membrane oxygenation.     

Therapieergebnisse des Morbus Hodgkin in den Stadien I und II

Zusammenfassung Behandlungsergebnisse des Morbus Hodgkin der Stadien I und II werden durch Vergleich der Überlebensdaten der Literatur nach verschiedenen Strahlentherapieprogrammen und nach zusätzlicher Chemotherapie diskutiert.Im Stadium I A bleiben 90–97% und im Stadium II A 75–80% der Patienten nach ausgedehnter Strahlentherapie rezidivfrei. Für das Stadium IIB werden 0–80% langdauernde Remissionen nach alleiniger Strahlentherapie berichtet.Zusätzliche Chemotherapie verbessert die Rezidiv-, aber nicht die Überlebenszahlen der Stadien I und II. Gruppen mit hohem Rezidivrisiko (große Mediastinaltumoren, E-Befall der Lunge und lymphozytenarme Histologie) werden dargestellt.     

高原肺心病患者血液中HMGB1检测及与痰液中相关因子的关系研究

目的 探讨高原慢性肺心病患者血液中高迁移率族蛋白1(high mobility group box 1,HMGB1)变化及与痰液中相关因子的关系.方法 选择慢性肺心病急性期患者48例,健康查体自愿者18人作为对照组.在肺心病患者急性期及治疗病情缓解后1周,检测外周血HMGB1表达及痰液中HMGB1表达、TNF-α水平、SOD活性、MDA水平变化.结果 肺心病组急性期患者外周血HMGB1阳性率显著高于缓解期,缓解期显著高于对照组,与痰液HMGB1表达正相关.血液HMGB1表达阳性组痰液TNF-α水平及MDA水平显著高于阴性组.结论 HMGB1有助于反映高原慢性肺源性心脏病支气管局部炎症反应.     

C-reactive protein (CRP) increases VEGF-A expression in monocytic cells via a PI3-kinase and ERK 1/2 signaling dependent pathway

C-reactive protein (CRP) is an independent predictor of atherosclerosis and its complications. Monocytes/macrophages are implicated in this complex disease which is, among other mechanisms, characterised by angiogenesis. The aim of this study was to analyse whether CRP plays a role in VEGF-A regulation by monocytic cells. Our findings show that CRP up-regulates VEGF-A mRNA expression and protein excretion in THP-1 cells in a concentration- and time-dependent manner. Furthermore, we studied the signaling pathway underlying this effect. CRP increases VEGF-A expression via a PI3-kinase and an extracellular-signal-regulated kinase (ERK) 1/2 dependent pathway. Our results suggest that CRP could play a role in the angiogenesis process via immune cells such as monocytes.     

Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure

BACKGROUND/AIMS: Recent clinical observations reported the occurrence of amino acid substitutions at position 181 of the HBV polymerase, associated with a viral breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harboring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance. METHODS: We performed a clonal analysis of the HBV polymerase gene amplified by PCR from serum samples during viral breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs. RESULTS: Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, but not with rtM204V/I mutations following lamivudine, adefovir or lamivudine+adefovir breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptibility to lamivudine (<10-fold), adefovir (2- to 8-fold) and tenofovir (2- to 3-fold). Interestingly, the association of rtA181T with rtN236T on one clinical isolate genome increased the resistance to these three drugs. All the tested mutants remained sensitive to entecavir. CONCLUSIONS: Our observations suggest that a single amino acid change at position rt181 may induce cross-resistance to lamivudine and adefovir. These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance.     

Cardiovascular toxicity of minoxidil in the marmoset

The aim of the experiments was to assess the toxicity of minoxidil, a potent vasodilator, in marmosets. The animals were treated either at escalating doses from 2 to 40mg/kg, escalating doses from 40 to 200mg/kg or single doses of 150mg/kg or 200mg/kg. ECG recording and echocardiographic examination were conducted before and 1h after treatment. Necropsy and histopathology were performed 24h after the last dose. The treatment with minoxidil induced myocardial necrosis, coronary arteriopathy and degeneration of renal tubules in animals treated with 150mg/kg or 200mg/kg. Myocardial necrosis associated with fibrosis in some animals was located mainly in the left and right ventricles (including papillary muscles), but also in the right atrium, left atrium and/or interventricular septum. Arteriopathy was observed in small coronary arteries of the right or left atrium. ECG and echocardiographic examinations showed that in animals treated with 150mg/kg or 200mg/kg, there were positive chronotropic and inotropic effects that compensated for the hypotensive effect of the drug and were considered to have played a key role in the pathogenesis of the cardiovascular lesions. The cardiotoxicity of minoxidil in marmosets was similar to that described in dogs, but occurred at much higher doses. In conclusion minoxidil produced cardiovascular toxicity in the marmoset, which was probably due to the marked changes in the cardiac function associated with exaggerated pharmacological effects of the compound. The marmosets were found to be less sensitive than dogs to the cardiotoxicity of minoxidil.     

藏族药五味甘露药浴散加减方对佐剂关节炎大鼠药效及血清NF-κB,TNF-α,IL-1,EGF的影响

目的:观察藏族药五味甘露药浴散加减方对佐剂关节炎大鼠的药效及其对大鼠血清核因子-κB(NF-κB),肿瘤坏死因子-α(TNF-α),白细胞介素-1(IL~(-1)),表皮生长因子(EGF)水平的影响。方法:SD健康大鼠60只,随机选取10只作为正常组,除正常组外,采用弗氏完全佐剂关节炎(AA)大鼠模型,随机分为模型组,地塞米松组(0.150 mg·kg~(-1),ig),五味甘露药浴散加减方高、中、低剂量组(104.00,52.00,26.00 g·L~(-1)),药浴组每天40℃药浴30 min,模型组和正常组每天40℃温水浴30 min,给药4周,用致炎后足跖肿胀度,苏木素-伊红(HE)染色法观察致炎侧足踝关节滑膜病理改变评价藏族药五味甘露药浴散加减方对AA大鼠的治疗效果,测定大鼠胸腺、脾脏脏器系数,酶联免疫吸附测定(ELISA)测定血清NF-κB,TNF-α,IL~(-1),EGF水平。结果:与正常组比较,模型组AA大鼠致炎侧足跖肿胀度明显增大,滑膜细胞增厚、巨噬细胞增生和炎细胞浸润,血清中NF-κB,TNF-α,IL~(-1),EGF水平明显升高,脾脏系数、胸腺系数明显降低(P0.05,P0.01);与模型组比较,地塞米松组和五味甘露药浴散加减方高剂量组能明显减小AA大鼠致炎侧足跖肿胀度,能改善滑膜细胞增厚、巨噬细胞增生和炎细胞浸润,血清中NF-κB,TNF-α,IL~(-1)水平明显降低(P0.05,P0.01),五味甘露药浴散加减方中剂量组NF-κB水平也明显降低(P0.05,P0.01),五味甘露药浴散加减方各剂量组大鼠血清中EGF水平无明显变化,脾脏系数明显增大(P0.05),高、中剂量组胸腺系数明显增大(P0.05)。结论:藏族药五味甘露药浴散加减方能有效的减小佐剂性关节炎大鼠致炎侧足跖肿胀度,改善AA大鼠踝关节滑膜炎病变,高剂量效果最好,其机制可能与降低血清中NF-κB,TNF-α,IL~(-1)的水平、调节脾脏和胸腺的功能有关。