银杏酮酯预处理对心肌缺血再灌注大鼠心肌的保护作用及可能机制

目的探讨银杏酮酯预处理对心肌缺血再灌注大鼠心肌的保护作用及可能机制。方法以36只雄性Wistar大鼠为研究对象,将实验动物随机分为3组:假手术组、心肌缺血再灌注模型组与银杏酮酯组。采用结扎大鼠冠状动脉左前降支的方法,建立大鼠心肌缺血再灌注损伤模型。假手术组穿线后不结扎,模型组于缺血前30 min腹腔注射生理盐水,银杏酮酯组大鼠于缺血前30 min腹腔注射银杏酮酯(100mg/kg)。造模24h后处死大鼠,HE染色观察心肌组织变化,ELISA法测定血清肌酸激酶-同工酶(CK-MB)和肌钙蛋白(cTnI)水平以及炎性因子白介素1 (IL-1)、白介素6 (IL-6)与肿瘤坏死因子-α(TNF-α)水平,Western blot方法检测心肌组织缝隙连接蛋白(Cx43)蛋白表达。结果假手术组大鼠心肌纤维排列整齐,模型组心肌纤维排列紊乱,心肌间质出现炎性细胞浸润,银杏酮酯组心肌组织较模型组有明显改善。与假手术组相比,模型组大鼠血清CK-MB、cTnI、IL-1、IL-6与TNF-α水平显著上升,心肌组织Cx43蛋白表达显著降低;与模型组相比,银杏酮酯组大鼠血清CK-MB、cTnI、IL-1、IL-6与TNF-α水平显著降低,心肌组织Cx43蛋白表达显著升高。结论银杏酮酯预处理可降低缺血-再灌注大鼠心肌损伤程度及炎性反应。     

Caspase抑制剂对大鼠心肌缺血／再灌注损伤Fas／FasL表达的影响

目的探讨大鼠心肌缺血／再灌注时caspase抑制剂对心肌细胞凋亡及Fas／FasL基因mRNA表达的影响及其机制。方法以穿线结扎或松扎左冠状动脉制备大鼠心肌缺血／再灌注模型。42只大鼠随机分为假手术组、Z-VAD-fmk治疗组和缺血／再灌注对照组,并分设缺血4-5min后再灌注3,6,12h3个时相点。以缺口末端标记法检测心肌细胞凋亡的变化,逆转录聚合酶链反应法检测Fas／FasL基因mRNA的表达改变,并分析心肌组织病理学损伤程度。结果心肌缺血／再灌注后心肌细胞凋亡指数及Fas/FasL基因mRNA表达均增高,caspase抑制剂预处理下调Fas／FasL表达水平,减少心肌细胞凋亡。结论心肌细胞凋亡与Fas／FasL系统参与了心肌缺血／再灌注损伤过程,caspase抑制剂Z-VAD-fmk通过抑制凋亡和下调Fas／FasL表达,减低再灌注损伤。     

心肌缺血再灌注损伤模型大鼠经艾塞那肽预处理后心肌细胞的凋亡

背景：有研究表明艾塞那肽可改善心肌梗死和心力衰竭等过程发挥心血管保护作用,但其对缺血再灌注损伤后心肌细胞凋亡的作用尚未阐明。 目的：艾塞那肽预处理心肌缺血再灌注损伤模型大鼠,观察其对心肌组织细胞凋亡及对凋亡因子Bcl-2、Bax表达的影响。 方法：建立心肌缺血再灌注损伤模型大鼠,用艾塞那肽进行预处理,并设缺血再灌注组和假手术组作对照。 结果与结论：免疫组织化学染色、原位末端标记检测RT-PCR检测显示,与缺血再灌注组比较,艾塞那肽组Bcl-2的mRNA和蛋白表达显著升高(P < 0.05),Bax mRNA和蛋白表达显著降低(P < 0.05),心肌细胞凋亡指数显著降低(P < 0.05)。结果证实,艾塞那肽对大鼠心肌缺血再灌注有保护作用,其机制可能是通过上调Bcl-2的表达,下调Bax的表达,从而抑制心肌细胞凋亡有关。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

心肌再灌注对抑郁大鼠心肌细胞凋亡以及bcl-2、bax和caspase-3表达的影响

目的: 探讨心肌缺血再灌注(I/R)对抑郁大鼠心肌细胞凋亡及凋亡基因bcl-2、bax和 caspase-3 的影响。方法: Wistar大鼠32只,随机分为4组,每组各8只。A组:非抑郁大鼠假手术组;B组:抑郁大鼠假手术组;C组:非抑郁大鼠心肌I/R组;D组:抑郁大鼠心肌I/R组。采用慢性轻度不可预知性应激结合孤养制备抑郁模型,用敞箱实验和液体消耗实验观察大鼠行为改变;运用结扎左冠状动脉前降支的方法复制心肌I/R模型。运用 TUNEL法检测心肌凋亡细胞;运用免疫组化法和逆转录-聚合酶链反应(RT-PCR)方法检测bcl-2、bax和 caspase-3 的表达。结果: (1)与A、B组比较,C、D组心肌细胞凋亡数量显著增加(P<0.01),A、B两组间比较无显著差异;与C组比较,D组心肌细胞凋亡数量显著增加(P<0.05)。(2)与A、B组比较,C、D组Bcl-2、Bax和caspase-3蛋白和mRNA表达显著增加(P<0.01),A、B两组间比较无显著差异; 与C组比较,D组Bcl-2蛋白和mRNA表达显著减少(P<0.05),而Bax和caspase-3蛋白和mRNA表达显著增加(P<0.05)。结论: 心肌缺血再灌注可加重抑郁大鼠缺血心肌细胞凋亡,其机制可能与上调bax和 caspase-3 基因表达、下调 bcl-2 基因表达有关。     

姜黄素预处理对急性心肌缺血大鼠心肌细胞凋亡相关因子表达的影响

 【摘要】 目的 探讨姜黄素预处理对急性心肌缺血大鼠心肌细胞凋亡相关因子表达的影响。方法 30只SD雄性大鼠随机分为姜黄素预处理组、心肌缺血2h组及假手术组,采用冠状动脉结扎的方法建立大鼠心肌缺血模型。用TUNEL法观察各组大鼠的心肌细胞凋亡情况;采用RT-PCR检测各组大鼠心肌细胞bcl-2及caspase-3 mRNA的表达水平,并探讨它们之间的关系。结果 与心肌缺血组相比,姜黄素预处理组bcl-2 mRNA的表达水平明显升高,心肌细胞凋亡数与bcl-2 mRNA表达量之间成明显的负相关(r=-0.93, P<0.05);姜黄素预处理组caspase-3 mRNA的表达水平降低,心肌细胞凋亡数与caspase-3 mRNA表达量值之间成明显的正相关(r=0.89, P<0.05)。结论 姜黄素对心肌缺血大鼠模型心肌梗死有明显保护作用,其作用机制可能与调节心肌细胞凋亡相关因子作用有关。     

阿魏酸川芎嗪对缺血再灌注大鼠心肌细胞凋亡及凋亡相关蛋白表达的影响

 目的：观察阿魏酸川芎嗪对缺血再灌注损伤大鼠心肌细胞凋亡的影响,并探讨其可能机制。方法：将60只雄性SD大鼠随机分成5组：（1）假手术组;（2）缺血再灌注组;（3）川芎嗪(4 mg/kg)组;（4）阿魏酸川芎嗪低剂量(4 mg/kg)组;（5）阿魏酸川芎嗪高剂量(8 mg/kg)组。采用结扎左冠状动脉前降支30 min、再灌注120 min的方法复制大鼠心肌缺血再灌注模型;各组大鼠于再灌注前10 min分别颈静脉注射给药,于再灌注结束后,进行血清生化及心肌组织学检测。结果：阿魏酸川芎嗪能显著降低心肌缺血再灌注损伤大鼠血清中肌酸激酶同功酶、乳酸脱氢酶、心肌钙蛋白I和丙二醛的水平,提高总超氧化物歧化酶活性,增加心肌Bcl-2蛋白的表达,减少心肌Bax蛋白的表达, 提高Bcl-2/Bax 的比值和降低心肌细胞凋亡指数,与缺血再灌注组比较,差异有统计学意义（P＜0.01）。阿魏酸川芎嗪各项指标优于川芎嗪（P＜0.05或P＜0.01）。结论：阿魏酸川芎嗪能减轻大鼠心肌缺血再灌注损伤;其抗缺血再灌注诱导的心肌细胞凋亡的机制可能与其上调Bcl-2蛋白和下调Bax蛋白表达有关。     

姜黄素预处理减轻急性心肌缺血大鼠心肌细胞凋亡

目的探讨姜黄素预处理减轻急性心肌缺血大鼠心肌细胞凋亡的机制。方法大鼠随机分为假手术组、心肌缺血2 h组及姜黄素预处理组,采用冠状动脉结扎的方法建立大鼠心肌缺血模型。用TUNEL法观察各组大鼠的心肌细胞凋亡情况;采用RT-PCR和Western blot检测各组大鼠心肌细胞凋亡相关因子mRNA和蛋白表达水平,并探讨它们之间的关系。结果与心肌缺血组相比,姜黄素预处理组BCL-2/β-actin/mRNA和蛋白表达相对值水平明显升高(P<0.05),心肌细胞凋亡数与BCL-2/β-actin蛋白表达相对值之间成明显的负相关(P<0.05);姜黄素预处理组caspase-3/β-actin mRNA和蛋白的表达相对值降低(P<0.05),心肌细胞凋亡数与caspase-3/β-actin mRNA和蛋白表达相对值之间成明显的正相关(P<0.05)。结论姜黄素对心肌缺血大鼠模型心肌梗死有明显保护作用,其作用机制可能与调节心肌细胞凋亡相关因子作用有关。     

表没食子儿茶素没食子酸酯对缺血再灌注心肌细胞凋亡的作用

目的：观察表没食子儿茶素没食子酸酯（EGCG）对缺血再灌注损伤大鼠心肌细胞凋亡的影响。 方法： 采用结扎大鼠左冠状动脉前降支30 min，然后松开再灌注60 min的方法，复制大鼠心肌缺血再灌注损伤模型。实验分假手术组、缺血再灌注组（IR）、EGCG不同剂量治疗组和丹参（SM）组。用原位缺口末端标记法（TUNEL）检测心肌凋亡细胞，用链酶亲和素-生物素-酶复合物（SABC）免疫组化法检测凋亡相关基因Bcl-2和Bax蛋白表达。 结果： 在假手术组未发现凋亡细胞，IR组细胞凋亡明显，Bcl-2和Bax蛋白表达增加，但以Bax更明显，Bcl-2/Bax值显著低于假手术组（P<0.01）；EGCG组凋亡细胞明显少于IR组，Bcl-2表达显著大于而Bax表达显著少于IR组，Bcl-2/Bax值显著高于IR组（P<0.01）。 结论： EGCG能明显抑制IR引起的心肌细胞凋亡，其作用机制可能与下调Bax和上调Bcl-2蛋白表达，提高Bcl-2/Bax值有一定关系。     

粉防己碱对缺血-再灌注损伤大鼠心肌细胞凋亡及Bcl-2/Bax蛋白表达的影响

目的探讨粉防己碱对缺血-再灌注损伤大鼠心肌细胞凋亡及Bcl-2/Bax蛋白表达的影响。方法结扎大鼠左冠状动脉前降支（LAD）30min后松开,再灌注24h建立心肌缺血-再灌注损伤模型。将48只雄性SD大鼠随机分为：假手术组（Sham组）,缺血-再灌注损伤组（IRI组）,粉防己碱预处理组（Tet组）。再灌注结束后检测血清肌酸激酶同工酶MB（CK-MB）和心肌梗死范围（IS/AAR,%）。应用原位末端标记法（TUNEL法）检测各组凋亡细胞,计算凋亡指数（AI）,应用免疫组化法检测心肌Bcl-2、Bax蛋白表达,计算Bcl-2/Bax值,进行组间比较。结果与IRI组相比,Tet可明显降低CK-MB值（976.57±160.69）vs（1910.38±221.10）U/L,P〈0.01,减小心肌IS/AAR%,（23.28±4.38）%vs（43.76±6.30）%,P〈0.01。与IRI组比较,粉防己碱预处理可显著减少心肌细胞凋亡,AI显著降低（8.62±2.45%vs19.36±5.28%,P〈0.01）。粉防己碱预处理使Bcl-2表达增加,Bax表达下降,Bcl-2/Bax值显著升高（P〈0.01）。结论粉防己碱能明显抑制缺血-再灌注损伤引起的心肌细胞凋亡,其作用机制可能与促进Bcl-2蛋白表达,减少Bax蛋白表达、升高Bcl-2/Bax比值有关。     

TLR3在大鼠心肌缺血再灌注损伤中的表达及其意义

目的观察Toll样受体3(Toll like receptor-3,TLR3)在大鼠心肌缺血再灌注损伤中表达的变化,探讨其在心肌缺血再灌注损伤中可能的作用与意义。方法 72只实验SD大鼠随机分3组(n=24):假手术组、缺血再灌注组、预处理缺血再灌注组。假手术组为冠状动脉左前降支(left anterior descending coronary artery,LAD)放置穿线但不结扎,缺血再灌注组压迫结扎LAD 30 min后再灌注2 h。预处理缺血再灌注组为压迫结扎LAD 5 min松开5 min,共3个循环,再停灌30 min,最后再灌注120 min。模型成功后进行心肌梗死面积(TTC)、RT-PCR、Western blots、ELISA、免疫组化学检测。结果假手术组TLR3 mRNA及蛋白呈微弱表达;缺血再灌注组中缺血区心肌细胞肿胀,周围大量中性粒细胞浸润,血清LDH(lactate dehyhrogenase)、CK(creatine kinase)活性及TNF-α水平升高(P0.01,vs假手术组),缺血区心肌细胞TLR3 mRNA及蛋白呈强烈高表达(P0.01,vs假手术组);与缺血再灌注组相比,预处理缺血再灌注组缺血区心肌细胞TLR3 mRNA及蛋白表达明显减低(P0.01,vs缺血再灌注组),血清LDH、CK活性及TNF-α水平也明显下降(P0.01,vs缺血再灌注组)。免疫组化结果显示,假手术组TLR3呈微弱表达于胞浆,而缺血区TLR3主要强烈表达分布于细胞核与细胞浆。同时免疫荧光结果提示,TNF-α与TLR3部分细胞有共表达。结论心肌缺血再灌注损伤模型中,TLR3的基因和蛋白表达水平明显升高,TLR3表达水平与心肌缺血再灌注损伤的进展有一定相关性。     

Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma

Background: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV₁ after 4 weeks. Results: The change in peak FEV₁ response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV₁ was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV₁ was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV₁ value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)     

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab

Background: The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases.

Aim: We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL).

Methods: Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment.

Results: Seven patients were followed and median age was 56.0?±?5.0?years (range, 41.9–71.6?years). At baseline, the mean level of IgG was 333.7?±?40.8?and IgM 40.9?±?11.3?mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%).

Conclusion: Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.     

Establishing Safety with Patients with Dissociative Identity Disorder

Abstract

The incidence of self-mutilation and suicidality among patients with dissociative disorders is quite high. It is necessary for clinicians working with this population to be adept at dealing with safety problems. This article presents a sequence of basic steps that can be used when helping dissociative patients establish safety, a discussion of the functions of self-destructiveness, and an overview of specific experiences and thinking patterns that contribute to self-destructiveness among dissociative patients.     

Gynecomastia with marked cellular atypia associated with chemotherapy

Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy. The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized.     

Intervention with epinephrine in hypotension associated with mastocytosis

The occurrence of the episodes of vasodilatory hypotension can be a life-threatening manifestation of systemic mastocytosis. This article describes the reversal by epinephrine of episodes of severe hypotension in two hospitalized patients with mastocytosis. Recognition of the efficacy of epinephrine in hypotension associated with mastocytosis can be important when other methods fail to restore hemodynamic stability.     

拉米夫定与泛昔洛韦联合治疗乙型肝炎病毒慢性感染的临床研究

目的 观察拉米夫定与泛昔洛韦联合治疗乙型肝炎病毒(HBV)慢性感染的临床疗效。方法 慢性乙型肝炎患者90例。设联合治疗组28例，单用拉米夫定组30例，单用泛昔洛韦组32例。联合治疗组给予口服拉米夫定0．1g／d(PO)，泛昔洛韦1．5g／d(PO)，24周。拉米夫定、泛昔洛韦单用组剂量及疗程分别同联合治疗组。结果 3组均无明显副反应，丙氨酸转氨酶(ALT)复常率无差异。3组HBV DNA阴转率分别为89．3％、66．7％、40．6％，差异有显著性。乙型肝炎表面抗原(HBeAg)阴转率分别为28．6％、23．3％、21．9％，差异无显著性。结论 拉米夫定与泛昔洛韦联合用药安全、耐受性好，临床显示联合治疗对HBV DNA的抑制作用显著优于单用药。