Immunomodulation and protection induced by DNA-hsp65 vaccination in an animal model of arthritis

We described a prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65-kDa heat shock protein (DNA-hsp65) in experimental murine tuberculosis. However, high homology of the vaccine to the corresponding mammalian hsp60, together with the CpG motifs in the plasmidial vector, could trigger or exacerbate an autoimmune disease. In the present study, we evaluate the potential of DNA-hsp65 vaccination to induce or modulate arthritis in mice genetically selected for acute inflammatory reaction (AIR), either maximal (AIRmax) or minimal (AIRmin). Mice immunized with DNA-hsp65 or injected with the corresponding DNA vector (DNAv) developed no arthritis, whereas pristane injection resulted in arthritis in 62% of AIRmax mice and 7.3% of AIRmin mice. Administered after pristane, DNA-hsp65 downregulated arthritis induction in AIRmax animals. Levels of interleukin (IL)-12 were significantly lower in mice receiving pristane plus DNA-hsp65 or DNAv than in mice receiving pristane alone. However, when mice previously injected with pristane were inoculated with DNA-hsp65 or DNAv, the protective effect was significantly correlated with lower IL-6 and IL-12 levels and higher IL-10 levels. Our results strongly suggest that DNA-hsp65 has no arthritogenic potential and is actually protective against experimentally induced arthritis in mice.     

Small animal PET for the evaluation of an animal model of genital infection

Background: [¹⁸F]‐FDG is a widely used tracer for the non‐invasive evaluation of hypermetabolic processes like cancer and inflammation. However, [¹⁸F]‐FDG is considered inaccurate for the diagnosis of urinary tract and genital infections because of its urinary excretion. Since the 1970s, Gallium scintigraphy is a well established test that has been used for the evaluation of inflammation and infection in human patients. Aim: The aim of this study was to assess the feasibility of ⁶⁸Ga‐Chloride small animal PET for the analysis of an animal model of genital infection, induced after the vaginal inoculum of Chlamydia muridarum. Material and methods: Thirty mice were infected by placing 15 μl of sucrose phosphate glutamic acid (SPG) 10⁷ inclusion forming units of C. muridarum into the vaginal vault. As controls of inflammation, three animals were challenged with 15 μl of SPG and one healthy animal was used to assess the tracer biodistribution. Four animals died during the experiment. Eleven animals were evaluated with ⁶⁸Ga‐Chloride small animal PET (GE, eXplore Vista) 3–5, 10–12, 17–19 days after infection, as well as three controls of inflammation and one healthy animal. Infection was monitored by obtaining cervical‐vaginal swabs from all the animals on the day of each PET procedure. Moreover, five groups of three animals each were killed at 6, 13, 20, 27 and 34 days after infection were studied. Results: ⁶⁸Ga‐PET turned out positive in all the infected animals, concordantly to data obtained by the cervical swabs and by the ex vivo analysis. The tumour‐to‐background ratio (TBR) decreased over time as the inflammation tended to naturally extinguish. The controls showed a slightly increased uptake of tracer due to the aseptic inflammation caused by SPG and frequent cervical swabs. The healthy control did not show any pelvic uptake. Conclusion: ⁶⁸Ga‐Chloride is a promising tracer for the assessment of genital infection in a mouse animal model.     

白细胞介素-1β作用下椎间盘退变动物模型的建立

目的:制作白细胞介素-1β(IL-1β)作用下推间盘退变(IVDD)的动物模型.方法:新西兰大白兔32只,随机分为两组.IL-1β组(IL组),椎间盘内(L3～4、L4～5、L5～6)注射20μL(10 ng/mL)IL-1β;力学组(ME组),咬除椎体棘突及一侧上下关节突.IL组动物椎间盘(T12～L1、L1～2、L2～3)作为对照组(SH组).各组分别于术后6周及12周分批处死.HE染色在偏差显微镜下进行椎间盘组织观察;透射电镜观察椎间盘组织超微结构.结果:标本大体形态学变化IL组与ME组在6周及12周时椎间盘髓核组织外观基本一致,呈现退变性改变;SH组6周与12周时椎间盘髓核组织外观基本一致,椎间盘退变不明显.HE染色显微镜下椎间盘细胞病理形态学变化IL组与ME组在6周与12周时髓核组织呈现退变性改变,SH组6周与12周时椎间盘退变不明显.透射电镜下椎间盘细胞病理形态学变化IL组与ME组的变化基本相似,6周时椎间盘细胞呈现退变性改变,12周时加重.SH组椎间盘髓核细胞及纤维环细胞在6周与12周时均无明显退变.结论:IL-1β作用下IVDD动物模型与外力作用下IVDD相似,成功建立了IL-1β作用下的IVDD动物模型.     

压力性尿失禁动物模型的建立及效果评价

背景:目前治疗压力性尿失禁的方法有药物治疗、物理-行为治疗及手术治疗等多种,但仍在探索优化中.目的:探索通过截断双侧阴部神经及支配髂骨尾骨肌、耻骨尾骨肌的盆底神经肌友,建立稳定的压力性尿失禁动物模型的方法.方法:6周龄SD雌性大鼠18只,体质量(199.44±8.41)g.随机分为3组,正常组、模型组和假手术组各6只.对模型组大鼠作双侧阴部神经及盆底神经肌支截断,假手术组分离暴露上述神经但不作截断,正常组大鼠不作特殊处理.术后2周测定3组大鼠的漏尿点压力.压力测定后取正常大鼠及模型大鼠的膀胱颈尿道交界部的横截面作组织学分析.结果与结论:假手术组1只大鼠于术后1周死亡.余大鼠皆存活并顺利测定漏尿点压力.与正常大鼠相比,模型组大鼠平均漏尿点压力下降约33%(P＜0.05),而假手术组大鼠与正常组大鼠平均漏尿点压力差异无显著性意义(P＞0.05).组织学检查显示,与正常大鼠比较,模型组大鼠尿道横纹肌排列疏松,而肌纤维也出现一定的萎缩.提示截断双侧阴部神经及盆底神经肌支可建立较为稳定的压力性尿失禁动物模型.     

Bicarbonate therapy for the cardiovascular toxicity of amitriptyline in an animal model

The beneficial hemodynamic effects of sodium bicarbonate as treatment for tricyclic antidepressant poisoning were investigated in an animal model. Seven adult dogs (17.5 to 20 kg) were poisoned by an intravenous infusion of amitriptyline. Toxicity was defined as a doubling of the initial QRS width. A continuous infusion was used to maintain toxicity for 30 minutes after which 44.5 mEq of sodium bicarbonate was administered intravenously. Five of the animals survived to completion of the experiment. Three of the surviving animals developed dysrhythmias. All dysrhythmias ceased within one minute of administration of sodium bicarbonate. An increase in mean blood pressure (P less than .05) and serum pH (P less than .05) and a decrease in mean QRS width (P less than .05) occurred following administration of sodium bicarbonate. The maintenance of toxicity for 30 minutes suggests that this model can be used for future studies of tricyclic antidepressant poisoning.     

牵张性脊髓损伤动物模型制备及评价

背景：建立牵张性脊髓损伤动物模型,对进一步探讨其病理生理改变及临床意义提供了良好的基础.目的：就牵张性脊髓损伤动物模型的制备及评价方面做一综述.方法：应用计算机检索CNKI和PubMed数据库中关于牵张性脊髓损伤动物模型的文章,在关键词中以＂牵张性;脊髓损伤;动物模型;神经功能;运动功能＂或＂tractive,spinal cord injury,animal model,neural function,motor function＂为检索词进行检索.选择文章内容与牵张性脊髓损伤相关,同一领域文献则选择近期发表或发表在权威杂志文章.初检得到285篇文献,根据纳入标准选择30篇文章进行综述.结果与结论：脊髓损伤模型繁多,包括挫伤模型、压迫损伤模型、牵张性损伤模型、缺血损伤模型、横断损伤和化学损伤等.牵张性脊髓损伤动物模型的建立,对进一步探讨其病理生理改变及临床意义提供了良好的基础.     

牵张性脊髓损伤动物模型制备及评价

背景:建立牵张性脊髓损伤动物模型,对进一步探讨其病理生理改变及临床意义提供了良好的基础。目的:就牵张性脊髓损伤动物模型的制备及评价方面做一综述。方法:应用计算机检索CNKI和PubMed数据库中关于牵张性脊髓损伤动物模型的文章,在关键词中以"牵张性;脊髓损伤;动物模型;神经功能;运动功能"或"tractive,spinal cord injury,animal model,neural function,motor function"为检索词进行检索。选择文章内容与牵张性脊髓损伤相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到285篇文献,根据纳入标准选择30篇文章进行综述。结果与结论:脊髓损伤模型繁多,包括挫伤模型、压迫损伤模型、牵张性损伤模型、缺血损伤模型、横断损伤和化学损伤等。牵张性脊髓损伤动物模型的建立,对进一步探讨其病理生理改变及临床意义提供了良好的基础。     

异氟醚吸入麻醉时药代动力学模型模型的建立及临床测评

目的 确定异氟醚 (Iso)吸入麻醉时浓度 -时间数学模型 ,并评价其可信性。方法 20例ASA1～2级全麻病人 ,气管插管后持续以1L/minO2 载入挥发罐1.5%Iso靶浓度 ,麻醉气体监测仪测定病人呼气末Iso浓度 (FETIso)。其中A组10例以FETIso与时间作图并建立数学模型 ;B组10例根据数学模型计算理论值 ,并与实际值进行执行误差(PE %)分析。 结果 1.本实验条件下数学模型为FETIso(t)/104=43.4136e0.1042t-27.2380e-11.7658t;2.理论值执行误差除1min为 +30.3%外 ,其他各点均在±10 %以内。结论 该数学模型能较为正确地预测FETIso ;而挥发罐所给定的Iso靶浓度在实验观察结束时尚未能达到。     

An animal model for the study of Chamomilla in stress and depression: pilot study

The behavioral and hematological effects of treatment with Chamomilla 6cH in mice subjected to experimental stress are described. Swiss mice were randomly divided into pairs, one animal was inoculated with Ehrlich's tumor, the other was treated daily with Chamomilla 6cH or control or received no treatment. After 7 days, the animals were observed in an open-field arena and blood samples taken. Mice who cohabitated with a sick cage-mate showed a decrease in their general activity, but those treated with Chamomilla 6cH were less severely affected (p=0.0426). No hematological changes were observed. In a second experiment, the forced swimming test was applied to mice pre-treated with Chamomilla 6cH, controls were: water, 10% ethanol or amitriptyline. Only the amitriptyline and ethanol treated groups showed significant excitatory behavior (p=0.0020), Chamomilla 6cH treated animals' scores intermediate between water control and ethanol or amitriptyline. A decrease in the leukocyte count was observed in the amitriptyline and Chamomilla 6cH treated groups (p=0.039). These data suggest that treatment with Chamomilla 6cH is related to the recovery of basal behavioral conditions in mice subjected to stressful conditions.     

α-亚麻酸对实验性糖尿病动物内皮功能保护作用的研究

目的 通过对实验性糖尿病动物模型外周血中内皮细胞功能相关标志物的测定,推测α-亚麻酸在保护血管内皮功能中的作用.方法 制备实验性糖尿病动物模型,分为3组进行喂养：（1）正常对照组（Control组,n=12）;（2）糖尿病对照组（DM组,n=14）;（3）ALA处理组（DM＋ALA组,n=14）.喂养4周后,测定外周血中NO、内皮素（ET）-1、可溶性P选择素（sP-selectin）和可溶性细胞间黏附分子（sICAM）-1的含量,并应用离体灌流法评价ALA对血管舒张功能的影响.结果 （1）DM组血清中NO水平明显低于Control组（P〈0.01）,DM＋ALA组血清中NO水平明显高于DM组（P〈0.01）;（2）DM组血清中ET-1水平明显高于Control组（P〈0.01）,DM＋ALA组血清中ET-1水平明显低于DM组（P〈0.01）;（3）DM组血清中sP-selectin和sICAM-1水平明显高于Control组（P〈0.01）,DM＋ALA组血清中sP-selectin和sICAM-1水平明显低于DM组（P〈0.01）;（4）DM＋ALA组的大鼠降主动脉对ACh的舒张反应较DM组明显增强（P〈0.01）.结论 应用α-亚麻酸干预后,实验性糖尿病动物外周血中内皮损伤标志物的水平下降,而NO的水平升高,说明α-亚麻酸对内皮功能具有一定的保护作用.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Mouse model of cervicovaginal toxicity and inflammation for preclinical evaluation of topical vaginal microbicides

Clinical trials evaluating the efficacy of nonoxynol-9 (N-9) as a topical microbicide concluded that N-9 offers no in vivo protection against human immunodeficiency virus type 1 (HIV-1) infection, despite demonstrated in vitro inactivation of HIV-1 by N-9. These trials emphasize the need for better model systems to determine candidate microbicide effectiveness and safety in a preclinical setting. To that end, time-dependent in vitro cytotoxicity, as well as in vivo toxicity and inflammation, associated with N-9 exposure were characterized with the goal of validating a mouse model of microbicide toxicity. In vitro studies using submerged cell cultures indicated that human cervical epithelial cells were inherently more sensitive to N-9-mediated damage than human vaginal epithelial cells. These results correlated with in vivo findings obtained by using Swiss Webster mice in which intravaginal inoculation of 1% N-9 or Conceptrol gel (containing 4% N-9) resulted in selective and acute disruption of the cervical columnar epithelial cells 2 h postapplication accompanied by intense inflammatory infiltrates within the lamina propria. Although damage to the cervical epithelium was apparent out to 8 h postapplication, these tissues resembled control tissue by 24 h postapplication. In contrast, minimal damage and infiltration were associated with both short- and long-term exposure of the vaginal mucosa to either N-9 or Conceptrol. These analyses were extended to examine the relative toxicity of polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under evaluation as a candidate topical microbicide. In similar studies, in vivo exposure to 1% PEHMB caused minimal damage and inflammation of the genital mucosa, a finding consistent with the demonstration that PEHMB was >350-fold less cytotoxic than N-9 in vitro. Collectively, these studies highlight the murine model of toxicity as a valuable tool for the preclinical assessment of toxicity and inflammation associated with exposure to candidate topical microbicides.     

睾丸损伤的超声分型及临床应用评价

目的　探讨睾丸损伤的超声分型及其临床应用价值。方法　分析 15例阴囊闭合性损伤的高频彩色多普勒超声表现和手术所见。结果　 15例阴囊外伤中 ,睾丸完全破裂 2例 ,部分破裂 4例 ,挫伤 4例 ,单纯血肿 3例 ,正常 2例。睾丸损伤的超声诊断符合率为 93 .3 % (14 /15 )。睾丸损伤的超声表现可分为破碎型、破裂型、钝挫型和包膜下血肿型。结论　超声检查不但能够对睾丸损伤进行分型 ,而且有助于临床治疗方案的选择。     

一种简便的正常大鼠腹膜透析模型建立

目的建立1种简便的正常大鼠腹膜透析动物模型。方法应用SD大鼠,实验分为4组:正常组、假手术组、4.25%腹膜透析组、1.25%腹膜透析组。自制透析管是经腹部植入后从背部引出,腹膜透析大鼠每只每日透析30ml,腹腔保留1h。在腹膜透析的第1周和第四周检测肾功能和白蛋白,同时观察体重、腹膜透析流出液量及并发症。结果两组腹膜透析组间白蛋白及体重测定相比无统计学差异,但两者与正常组相比差异有显著性;在第1周及第4周流出液量相似,无统计学差异,腹膜透析的主要并发症为腹膜炎、大网膜包裹及导管移位等。结论本实验建立的这种正常大鼠腹膜透析动物模型可模拟人类腹膜透析。     

血管性痴呆的动物模型、神经病理及其胆碱能机制

目的建立血管性痴呆(VD)的动物模型,并探讨VD认知障碍的发病机制。方法建立老龄大鼠VD模型,进行数字减影血管造影(DSA)检查、穿梭箱试验、神经病理检查和胆碱乙酰转移酶(ChAT)免疫组化测定。结果慢性脑血流灌注不足2月后出现明显的认知功能障碍,缺血4月后更明显;海马CA1区ChAT免疫反应阳性神经元分布及其数量较对照组显著减少,且与学习记忆障碍呈正相关。结论多发性脑梗死、进行性的皮层和海马神经元退变以及白质损害是VD的病理基础;额叶皮层和海马胆碱能神经元的损伤可能是认知功能受损害的形态学基础。     

改良激素性股骨头坏死动物模型的建立与评价

背景:在股骨头坏死发病机制的研究中,目前仍缺乏有效的动物模型,各种股骨头坏死治疗新方法的发展需要能够模拟人股骨头坏死自然病程动物模型的基础实验.目的:通过联合应用马血清和低剂量甲基强的松龙建立激素性兔股骨头缺血性坏死动物模型.方法:20只健康日本大耳白兔随机分成2组.实验组动物注入马血清,间隔2周后,再次注入马血清,第1次注射马血清后24 h肌肉注射甲基强的松龙,每隔1周注射1次,共8周.对照组动物单纯注射同等量的生理盐水.于第1次注射马血清前、注射甲基强的松龙后2,4,8周行血液学检查.并分别于注射甲基强的松龙后4,8周行MRI检查、苏木精-伊红染色和电镜观察股骨头缺血坏死情况.结果与结论:与对照组比较,2,4,8周实验组三酰甘油、胆固醇均明显上升(P<0.05);激活部分凝血酶时间则明显下降(P<0.05).4周实验组MRI显示部分动物可见局部信号改变,8周时可见皮质下出血;对照组比较,4,8周实验组骨髓周围有坏死的骨髓细胞碎片存在,空骨陷窝率逐渐增加(P< 0.01);4周时实验组个别骨细胞结构模糊不清,或有大空泡;8周时部分骨细胞核破裂、核溶解,凋亡细胞大量出现,骨胶原结构排列紊乱.结果证实联合运用激素和马血清明显提高股骨头缺血性坏死的发生率,能够较好地建立激素性兔股骨头缺血性坏死动物模型.     

Repeated measurements of transfer factor in rabbits: an animal model suitable for evaluation of short-term exposure

Summary. Acute temporary changes in lung function may be of use as a biological exposure indicator. However, studies of humans occupationally exposed to complex airborne irritants are often expensive and time demanding. Therefore, an animal model could be a valuable complement. A rabbit model has been evaluated where transfer factor was measured twice during the same day, and with the rabbit awake and available for exposure, in between. Anaesthesia and intubation in 22 rabbits (2–6 [0–2] kg [Mean (SD)]) were immediately followed by two measurements of transfer factor and alveolar volume. Transfer factor was estimated by the single breath CO-technique used in humans. The samples were analysed for CO and He on a gas chromatograph. After one pair of measurements the rabbit was allowed to wake up and after 5 h the duplicate measurements were repeated. The mean values of transfer factor, alveolar volume and transfer constant were 0–50 (0–09) mmol min^-1 kPa^-1, 127 (8) ml and 3–9 (0–6) mmol min^-1 kPa^-11^-1, respectively. The intraindividual coefficients of variation were 7-3%, 5-3% and 6–7%, respectively. Five hours later when the duplicate measurements were repeated, transfer factor, alveolar volume and transfer constant were unchanged still. The results suggest that relatively small changes in transfer factor may be detected without losing power, and thus that this model could be used as a biological exposure indicator.,