非人灵长类动物急性肝功能衰竭模型的建立

目的:构建一种稳定的非人灵长类大动物急性肝衰竭模型.方法:将15只食蟹猴随机分成3组,经颈外静脉分别注射0.45、0.3和0.15 g/kg D-氨基半乳糖胺,构建食蟹猴肝衰竭动物模型.动态检测给药前(0 h)、给药后12、24、36、48、60、72、96 h生命体征、颅内压(ICP)及血清丙氨酸转氨酶(ALT)、凝血酶原时间(PT)、总胆红素(TBIL)、血氨(NH3)的变化.观察动物临床表现及病程进展情况,记录动物生存时间,动物死亡后行组织病理学检查.结果:0.45 g/Kg和0.3 g/Kg组动物全部死亡,生存时间分别为56.1 h±8.1 h和109.8 h±11.2 h,0.15 g/Kg实验猴除1只98 h死亡外其余全部存活.0.45 g/Kg和0.3 g/Kg组动物各时点的ALT、TBIL、PT、NH3及ICP均明显高于基线值(0h),差异有统计学意义(P＜0.05),0.15 g/Kg实验猴各指标在60 h后渐恢复正常.死亡动物组织病理检查见肝细胞坏死,肝内炎性细胞浸润.结论:以0.3 g/Kg的D-氨基半乳糖胺诱发食蟹猴急性肝功能衰竭动物模型,符合急性肝功能衰竭的临床表现、病理变化,可用于急性肝功能衰竭的动物实验研究.     

CORRECTION

Background  Connective tissue growth factor (CTGF) is a secreted protein containing several domains that mediate interactions with growth factors, integrins and extracellular matrix components. CTGF plays an important role in extracellular matrix production by its ability to mediate collagen deposition during wound healing. CTGF also induces neovascularization in vitro, suggesting a role in angiogenesis in vivo. We herein evaluated whether CTGF was required for extracellular matrix synthesis of meniscal fibrochondrocytes and/or angiogenesis during the repair of meniscal tears.

Methods  Meniscal fibrochondrocytes were isolated from the inner-1/2 of rabbit meniscus by trypsin collagenase treatment and further treated with 100 ng/ml CTGF in vitro. Characterization of fibrochondrocytes was identified by flow cytometry analyzing CD31, CD44, CD45 and CD105, and was further tested by type II collagen immunocytochemistry. Changes in gene expression of meniscal fibrochondrocytes were monitored by quantitative real-time polymerase chain reaction. Histological sections prepared from a 3-mm portion of a longitudinal tearing defect in the middle of the rabbit meniscus were subjected to fluorescence-immunohistochemistry analysis at 1, 4 and 10 weeks following surgical treatment with 1.5 μg of CTGF/fibrin-glue composites.

Results  Quantitative RT-PCR assay showed that types I and II collagen and vascular endothelial growth factor mRNA expression in the 100 ng/ml CTGF group were remarkably enhanced as compared to levels in the no-dose group at 14 days ((2.38±0.63) fold, (2.96±0.87) fold, (2.14±0.56) fold, respectively). Likewise, fluorescence-immunohistochemical analysis revealed that in the group implanted with CTGF-fibrin glue, types I and II collagen, as well as the capillaries, completely filled the defect by 10 weeks, postoperatively. In contrast, only soft tissue repair occurred when PBS-fibrin glue was implanted.

Conclusions  These findings suggest that CTGF can significantly promote extracellular matrix deposition (types I and II collagen) within the meniscal avascular zone; CTGF can greatly heighten the expression of vascular endothelial growth factor activity simultaneously in vivo, further enhancing the repair of meniscal tears in the avascular zone.

     

Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure

AIM: To evaluate a hybrid bioartificial liver support system (HBALSS) in cynomolgus monkeys with acute liver failure.METHODS: To establish a model of acute liver failure, 0.3 g/kg of D-galactosamine was injected intravenously into cynomolgus monkeys. Chinese human liver cells were introduced into a perfusion bioreactor to carry out hybrid bioartificial liver support treatment. Forty-eight hours after the injection, one group of cynomolgus monkeys received HBALSS care, and a second experimental group received no treatment. Clinical manifestations of all animals, survival time, liver and kidney functions and serum biochemistry changes were recorded. Simultaneous detection of the number, viability and function of hepatocytes in the hybrid bioartificial liver were also performed.RESULTS: Forty-eight hours after the injection of D-galactosamine, serum biochemistry levels were significantly increased, whereas albumin levels and the Fischer index were significantly reduced compared to baseline (all Ps < 0.05). Of the ten monkeys in the HBALSS treatment group, five survived, with an average duration of survival of 128 ± 3 h. All cynomolgus monkeys in the control group died, with a duration of survival of 112 ± 2 h. Survival time was significantly longer with HBALSS treatment (P < 0.05). Moreover, the number, viability and function of hepatocytes were maintained at a high level with HBALSS.CONCLUSION: The novel hybrid bioartificial liver plays a significant role in liver support by significantly reducing serum biochemistry levels and extending animal survival time.     

三种不同术式治疗复发性翼状胬肉的疗效观察

目的:评价羊膜移植、自体角膜缘干细胞移植、羊膜移植联合自体角膜缘干细胞移植3种不同术式治疗复发性翼状胬肉的效果。方法:将127例127眼复发性翼状胬肉患者随机分为A,B,C三组,采用不同手术方式。其中A组45例45眼行羊膜移植术;B组40例40眼行自体角膜缘干细胞移植术;C组42例42眼行羊膜移植联合自体角膜缘干细胞移植术。术后随访12～24mo,分析对比3种不同术式的手术复发率。结果:A组10眼复发,复发率为22.2%;B组9眼复发,复发率为22.5%;C组3眼复发,复发率为7.1%。A组与B组比较差异无统计学意义,C组与A,B组比较有显著性差异(P<0.05)。结论:羊膜移植联合自体角膜缘干细胞移植术治疗复发性翼状胬肉术后复发率最低,是治疗复发性翼状胬肉较为理想的手术方式,值得临床推广应用。     

在体兔脑组织电阻抗频率特性测量及电阻抗断层成像

背景电阻抗断层成像技术是对人体表施加无害电信号,体表测量其响应,用重构算法得到人体内部的电阻抗或其变化的分布图像.与现有的CT,MRI等技术相比,电阻抗断层成像技术具有实时性强、费用低廉、便于连续监测和功能成像等优势.目的在体测量兔脑组织在缺血前后的电阻抗频率特性,并对缺血脑组织进行电阻抗断层成像技术,验证电阻抗断层成像技术对脑功能变化成像的可能性.设计单一样本实验.单位解放军第四军医大生物医学工程系医学电子工程教研室.材料实验于2001-08/09在解放军第四军医大学生物医学工程系医学电子工程教研室电阻抗断层成像实验室完成.选择成年健康家兔10只用于实验.方法采用颈总动脉结扎法制造脑缺血动物模型,对缺血前后的脑组织电阻抗特性进行在体测量.利用电阻抗断层成像系统对单侧脑组织供血变化进行成像.主要观察指标①缺血前后的脑组织在0.1 Hz～1 MHz频率范围内电阻抗频率特性曲线.②单侧脑组织供血变化电阻抗断层成像结果.结果1只家兔钻透硬脑膜,9只家兔结果进入分析.①在缺血脑损伤发生后,脑阻抗明显增大,在10 Hz以下脑阻抗变化率可达75%,在1 kHz～1 MHz频率范围脑阻抗变化率约为15%且比较稳定.②初步的动态成像结果显示,脑组织供血变化一侧与其电阻率变化位置相一致.结论缺血前后脑组织阻抗变化率满足成像要求,可以将其作为一个成像变量.     

IFNγ对培养大鼠肝细胞DNA和胶原的影响

目的观察ＩＦＮγ对培养大鼠肝细胞ＤＮＡ和胶原的影响．方法应用３Ｈ胸腺嘧啶核苷和３Ｈ脯氨酸掺入量及掺入抑制率测定的方法．结果在５ｋＵ／Ｌ～１００ｋＵ／Ｌ浓度范围内的ＩＦＮγ能明显抑制培养大鼠肝细胞ＤＮＡ（１００ｋＵ／Ｌ为６４６％）和胶原（１００ｋＵ／Ｌ为６７４％）合成，抑制程度与浓度和时间呈正相关（Ｐ＜００１）．结论ＩＦＮγ抗肝纤维化作用的机制之一是能抑制肝细胞增殖及胶原合成     

Memory and executive function impairment predict dementia in Parkinson's disease.

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty-five out of 164 patients (27%) became demented during a mean follow-up of 3.7 +/- 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87-0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59-0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77-0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73-0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD.     

用连续量输入的人工神经网络评定心脏收缩功能

作者应用人工神经网络技术，实现心脏收缩功能的计算机自动评定，以探讨人工神经网络技术在生物医学评定、分类和诊断等问题中的应用方法，该研究采用心脏收缩时间间期的７项指标，应用反向传播神经网络，以连续量作为网络输入，对２０２位受试者的心脏收缩功能进行评定，人工神经网络的评定结果与专家评定结果相比较，符合率可达９５．５４％．结果表明，连续量输入方式在逼近实际分类边界，减小网络规模，加快网络学习方面优于数字量输入方式．     

Adenosine Triphosphate Liposomes: Encapsulation and Distribution Studies

Four methods for encapsulating adenosine triphosphate (ATP) in liposomes were evaluated. Optimum entrapment required emulsifying ATP with the lipids used to form the liposome membrane in a high-speed homogenizer followed by evaporating the organic solvent with vigorous stirring. Under these optimum conditions ATP entrapment was 38.9%; i.e., the dosage form contained 38.9 g of ATP per 100 g of lipid. The distribution of positively charged liposomes loaded with ATP was studied in dogs with experimentally induced myocardial infarction. Intravenous injection of positively charged ATP liposomes caused accumulation of ATP in myocardial infarct tissue. Myocardial infarct tissue has reduced blood flow; since positively charged liposomes accumulated in infarct tissue, liposomes may be a drug delivery system for this disease state.