Are nontreponemal tests suitable for monitoring syphilis treatment efficacy? Evidence from rabbit infection models

ObjectivesWe aimed to characterize kinetics of non-treponamal antibody titres during the natural course of syphilis and explore their roles in monitoring syphilis treatment efficacy.MethodsSixty New Zealand white male rabbits were challenged with Nichols or Amoy Treponema pallidum strains, and the rapid plasma reagin (RPR) test was performed to quantify non-treponemal antibody titres during the infection course. Viable T. pallidum in the challenged rabbits was assessed with rabbit infectivity tests.ResultsThe RPR titres of the Nichols or Amoy strain between no benzathine penicillin G (BPG) and BPG treatment subgroups displayed a similar trend: first ascending and then descending. Compared with baseline, the proportions of fourfold decline in RPR titres in the Nichols or Amoy group presented a similar result on days 30, 60 and 180 between the no BPG and BPG treatment subgroups (0%, 0/5; 80%, 4/5; 100%, 5/5; vs. 0%, 0/5; 80%, 4/5; 100%, 5/5; p 0.999; 0%, 0/5; 80%, 4/5; 80%, 4/5; vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.098, respectively). Compared with the maximum baseline titre, the proportion of fourfold decline in PRR titre also showed a similar result in the two groups on days 30, 60 and 180 between the no BPG and the BPG treatment subgroups (0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 40%, 2/5; 100%, 5/5; 100%, 5/5; p 0.129; 0%, 0/5; 100%, 5/5; 100%, 5/5, vs. 80%, 4/5; 100%, 5/5; 100%, 5/5; p 0.091, respectively. Moreover, regardless of whether the RPR titres presented a fourfold decline, viable T. pallidum could be detected in untreated rabbits' lymph nodes at 30, 60 and 180 days post infection, while viable T. pallidum was not detected in any of the treated rabbits' lymph nodes.ConclusionsThe RPR titre increased and then decreased (even became negative) during the natural course of syphilis, similar to that seen after BPG treatment. The RPR tetre is thus a questionable indicator of syphilis treatment efficacy.     

PRP及前列地尔对兔缺血皮瓣的影响

【摘要】 目的 探讨富血小板血浆（PRP）、前列地尔注射液及其联合应用对兔缺血皮瓣的影响。 方法 选择 40 只健康新西兰兔随机分为20组，每组2 只，每只兔背部设计两块以中线对称的 10cm×2.5cm 大小超长宽比例任意皮瓣，形成每组 4 个兔背缺血皮瓣模型。每组随机分为对照瓣及实验瓣1、试验瓣2、试验瓣3。对照瓣：采用局部及静脉均注射生理盐水；实验瓣1：局部注射 PRP，静脉注射生理盐水；试验瓣2：局部注射生理盐水，静脉注射前列地尔注射液（0.8mL/kg)；试验瓣3：局部注射 PRP，静脉注射前列地尔注射液。术后 7d 在统一标准下拍照并取材。测量各瓣存活面积，计算皮瓣存活率；HE 染色后镜下观察各瓣组织结构层次、炎性细胞浸润情况及微血管口径变化；免疫组化检测 CD34 表达、测量微血管密度；酶联免疫吸附法（ELISA）检测血管内皮生长因子（VEGF）含量。结果 术后 7d，各瓣远端均发生不同程度坏死，经测量计算后得出：各瓣平均存活面积、存活率、微血管密度、VEGF 含量由大到小依次为：实验瓣3＞实验瓣1＞实验瓣2＞对照瓣，组间比较差异有统计学意义（均P＜0.05)。HE 染色后镜下观察可见：所有实验瓣较对照瓣组织水肿轻，新生毛细血管增多；实验瓣3较对照瓣及实验瓣1、实验瓣2结构、层次更清晰分明，新生毛细血管最多，大部分管腔扩大，炎性细胞浸润较少，组织水肿轻；实验瓣1较实验瓣2组织结构分明，新生毛细血管较多，炎性细胞浸润较少，但实验瓣2血管管腔直径更大。结论 富血小板血浆、前列地尔注射液单独应用时均能不同程度改善兔缺血皮瓣缺血坏死，提高皮瓣存活率，并且二者联合应用效果优于单独使用。     

TGF和BMP在兔上颌缝牵张成骨中的表达

目的:观察兔上颌缝牵张成骨时TGF-β和BMP在前颌缝中的表达,探讨上颌骨改建的机制及意义。方法:年轻家兔12只,随机分为7d组6只,14d组6只,戴自制前牵引装置,均持续前牵上颌骨,分别在牵引后7、14d处死动物,切取一侧前颌缝组织块,制作标本,免疫组织化学方法对TGF-β、BMP进行染色,光镜观察、灰度值分析,并进行统计分析。结果:14d较7d2因子高表达(TGF-β、BMP均P<0.05);骨缝外侧带较中央带高表达;成骨活跃者成纤维细胞增多,血管分布增多;骨缝缘无典型的活跃成骨细胞排列。结论:牵张成骨过程中TGF-β和BMP表达升高。     

Mastication-induced modulation of orofacial sensory inputs as seen in the jaw reflex and single neuronal activities in the face primary somatosensory cortex of the rabbit

The aim of the present study was to compare the effect of mastication on non-nociceptive orofacial sensory transmission of the somatosensory pathways and that on the jaw reflex arc. To achieve this, single-unit activities of the face primary somatosensory cortex (face-SI) neurons responding to low-intensity electrical stimulation of the inferior alveolar nerve (IAN) and the jaw-opening reflex (JOR) were recorded during mastication in awake rabbits. The entire masticatory sequence was divided into the preparatory period (PP), the rhythmic-chewing period (RC) and the preswallow period (PS). A total of 112 face-SI neurons were tested for the effects of mastication. The responsiveness of most neurons and the JOR were modulated during different periods of mastication. The IAN-evoked activity was attenuated in a majority of the neurons during at least one of the masticatory periods. The JOR was suppressed during the RC and PS, while the modulatory effect was variable during the PP. Regression analysis showed that the modulatory effect of mastication on the IAN-evoked neuronal activity and that on the JOR was not well correlated. It was notable that a considerable number of face-SI neurons showed mastication-related activity although their responsiveness to IAN stimulation was strongly suppressed (i.e. almost "gated out") during mastication. The findings indicate that (1) sensory transmissions of the somatosensory and reflex pathways may be modulated in a different manner during mastication, and that (2) activity of face-SI neurons during mastication may not necessarily be a simple reflection of movement-induced stimulation of orofacial mechanoreceptors.     

兔双侧下颌骨牵张成骨实验动物模型的建立

目的:建立兔双侧下颌骨牵张成骨实验动物模型。方法:选用16只成年雄性新西兰大白兔,随机分为4组,每组4只。在双侧下颌骨第一前磨牙前方无牙区行骨切开术,用自制牵张器固定。经过7d潜伏期,以每次0.5mm的速度牵张,每天2次,连续7d。分别在潜伏期末、牵张结束、固定期第14天、第28天处死动物,切取标本行X线和组织学观察。结果:全部动物的下颌骨被成功延长,牵张间隙逐渐被新生骨组织充填。结论:该方法建立的动物模型具有可行性和可重复性。     

家兔创伤性面神经损伤的组织病理学研究

为了建立各种面神经损伤的实验动物模型，对６８只家兔１３６侧面神经颊面干分别造成暴露、牵拉、挤压、压榨及切断后吻合与不吻合６种损伤，于伤后不同时间取材，切片行Ｂｏｄｉａｎ及Ｗｅｉｌ染色，光镜下观察神经轴突、髓鞘、Ｓｃｈｗａｎｎ细胞及神经纤维周围结缔组织的变化。结果表明，暴露可造成神经Ⅰ度损伤；挤压、牵拉、压榨可造成Ⅱ～Ⅲ度损伤；神经断裂后不吻合者预后明显较吻合者差。神经受损后的病理改变，在中、重度损伤与神经电图变化相一致，而轻度损伤及严重损伤后期两者可能不一致。伤后１５天为临床评价面神经功能恢复的最佳时间。神经受损面积对髓鞘病变影响明显，而损伤性质及程度对轴突病变影响明显。该动物模型的建立为深入进行面神经损伤及修复的研究提供了条件。     

Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits

Background

Sunitinib (Sutent) is a Food and Drug Administration–approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits.

Materials and methods

Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated.

Results

All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal.

Conclusions

These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal.     

缬沙坦对炎性动脉粥样硬化的影响

目的:探讨缬沙坦对动脉粥样硬化(AS)的影响及可能的机制。方法:26只雄性日本大耳白兔随机分3组,正常对照组、AS模型组和缬沙坦组,观察各组实验前后血脂和C反应蛋白(CRP)水平,并进行主动脉血管内皮病理形态学观察和血管细胞黏附因子(VCAM-1)的免疫组化分析。结果:与AS模型组比较,缬沙坦组血脂水平差异无显著性(P>0.05);CRP水平降低(P<0.01);主动脉血管内膜斑块减少,内膜/中膜厚度比明显降低(P<0.01);血管内皮VCAM-1表达减少(P<0.05)。结论:缬沙坦对动脉粥样硬化有抑制作用,该作用可能与脂质代谢无关,而与抑制炎症有关。     

椎间盘内注射医用臭氧对椎间盘退变模型自身免疫反应的影响

目的:观察椎间盘内注射医用臭氧对椎间盘退变(intervertebral disc degeneration,IDD)动物模型自身免疫反应的影响,探讨其作用机理.方法:50只新西兰兔随机分为A、B、C、D、E共5组,其中A组为正常组,不作处理;B组为假手术组,仅暴露纤维环而不穿刺;C、D、E组采用后外侧纤维环穿刺的方法建立腰椎间盘退变模型(L6/7),在造模后14dD组模拟临床手术椎间盘内注射臭氧干预,E组椎间盘内注射医用纯氧,于造模后14d、21d对5组动物进行自由行走疼痛行为学评分,并于21d获取各组动物外周血,L6、L7神经根及L6/7髓核,运用透射比浊法测定各组动物血清中免疫球蛋白IgG和IgM水平,ELISA法测定血清中TNF-α、IL-1、IL-6的含量;免疫组化染色观察髓核中抗原抗体复合物沉积情况,应用图像分析系统记录染色阳性细胞的累积光密度值(integrated optical density,IOD);BCA蛋白定量法检测腰神经根中PLA2的活性.结果:造模后1周左右(平均7.4d)C、D、E组动物手术侧后肢活动减少,并在爬行前进时明显偏离手术侧,行走疼痛学评分分别为2.81±0.13分、2.69±0.11分、2.64±0.31分,组间比较差异无统计学意义(P＞0.05);D组注射臭氧后上述异常行为逐渐减轻,处死前行走疼痛学评分为0.54±0.12分,低于C组(2.75±0.17分)及E组(2.52±0.96分)(P＜0.05);D组动物血清中IgG、IgM水平(6.05±0.49g/L,1.98±0.28g/L)低于C组(8.98±0.77g/L,2.40±0.25g/L)及E组(8.52±0.63g/L,2.91±0.3 1g/L) (P＜0.05),与A组(5.43±0.29g/L,1.72±0.15g/L)及B组(4.97±0.35g/L,1.66±0.27g/L)比较差异无统计学意义(P＞0.05);D组炎性细胞因子TNF-α、IL-1、IL-6的含量(98±11pg/ml,247±21pg/ml,149±23.4pg/ml)亦低于C组(256±39pg/ml,404±19pg/ml,231±41.3pg/ml)及E组(244±45pg/ml,410±15pg/ml,249±21.7pg/ml) (P＜0.05),与A组(70±6pg/ml,223±17pg/ml,141±12.6pg/ml)及B组(79±1 1pg/ml,238±32pg/ml,138±17.4pg/ml)比较差异无统计学意义(P＞0.05);D组髓核中抗原抗体复合物阳性沉积光密度值(7.40±3.56)小于C组(27.49±12.84)及E组(29.55±10.38)(P＜0.05),其相应节段腰神经根PLA2活性(0.0189±0.0072μmol/min·L)较C组(0.1685±0.0103μmol/min·L)及E组(0.1994 ±0.080μmol/min·L)明显下降(P＜0.01),与A组(0.0036±0.0081μmol/min·L和B组(0.0098±0.0043 μmoL/min·L)比较差异无统计学意义(P＞0.05).结论:医用臭氧能够在一定程度上抑制腰椎间盘退变模型中异常的自身免疫反应,这可能是臭氧治疗椎问盘退变引起的腰痛的作用机制之一.