经静脉二次谐波超声造影对正常兔肝造影分期的声学定量分析

目的　利用声学定量技术对正常兔肝的超声造影分期进行探讨。方法　对 10只健康大白兔进行二次谐波超声造影 ,观察经耳缘静脉注射造影剂时 ,门静脉主干血流阻断前后 ,肝组织声学定量 (AD)曲线形态及测值变化 ;及经耳缘静脉和经肠系膜静脉注射造影剂时 ,肝组织AD曲线形态及测值变化。结果　经耳缘静脉注射造影剂 ,正常兔肝组织AD曲线形态呈单峰形 ,近似直角三角形 ,可分为上升段、高峰段和下降段 ,峰值密度(PI)值为 (18.4± 1.7)dB。上升段为肝动脉期 ,高峰段和下降段均为门静脉期 ;门静脉主干血流阻断后 ,肝组织AD曲线形态与阻断前基本相似 ,但峰值略减低 ,其PI值平均减低 2dB。经耳缘静脉注射造影剂后 10～ 15s再经肠系膜静脉注射造影剂 ,肝组织AD曲线呈“驼峰征” ,第二个峰高于第一个峰。结论　正常兔肝声学造影肝动脉期短暂 ,门静脉期长。肝组织回声增强主要由于肝动脉来源造影剂所致 ,门静脉来源造影剂增强幅度低 ,仅起次要作用     

家兔房室交界区的形态学观察及其意义

目的:观察家兔心房室结周围的纤维联系,探讨结间传导及折返机制。方法:选20只家兔心脏做房室交界区水平面及矢状面连续切片,HE染色光学显微镜下观察并拍照。结果:房间隔主要观察到3种形态的细胞,P细胞、T细胞和普通心房肌细胞。房室结由致密结和后延伸两部分组成。致密结分浅、深两层。房室结周围有3条纤维与之相连。后方为两束过渡纤维,分别源于冠状窦口及其下方,上方通过普通房肌与下房间隔相连。各肌纤维之间形成回路。结论:结间传导存在着形态学证据,肌纤维形成的回路很可能成为兴奋发生转折的部位。     

Animal models in neonatal resuscitation research: What can they teach us?

Animal models have made and continue to make important contributions to neonatal medicine. For example, studies in fetal sheep have taught us much about the physiology of the fetal-to-neonatal transition. However, whereas animal models allow multiple factors to be investigated in a logical and systematic manner, no animal model is perfect for humans and so we need to understand the fundamental differences in physiology between the species in question and humans. Although most physiological systems are well conserved between species, some small differences exist and so wherever possible the knowledge generated from preclinical studies in animals should be tested in clinical trials. However, with the rise of evidence-based medicine the distinction between scientific knowledge generation and evidence gathering has been confused and the two have been lumped together. This misunderstands the contribution that scientific knowledge can provide. Science should be used to guide the gathering of evidence by informing the design of clinical trials, thereby increasing their likelihood of success. While scientific knowledge is not evidence, in the absence of evidence it is likely to be the best option for guiding clinical practice.     

Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits

Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA) produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation     

Potentiation of Reduced Uteroplacental Perfusion Pressure Hypertension in Pregnant Rabbits

Objective: We tested whether indomethacin (IND) potentiates the elevation of blood pressure induced by the reduction of the uteroplacental perfusion pressure (RUPP).

Methods: In pregnant rabbits on the 21st day of the 30-day gestation, the uteroplacental perfusion pressure was reduced by 68 ± 5% using a clip placed on the abdominal aorta below the renal arteries. IND suppositories (15 mg/kg each) were administered 1 and 2 days following surgery.

Results: After the second dose, MAP of IND-treated RUPP rabbits was higher (92 ± 9 mm Hg, n = 10) than in those receiving placebo (78 ± 12, n = 9, P <. 01). MAP of sham-operated pregnant rabbits with or without IND was 61 ± 9 and 58 ± 8 mm Hg, respectively (NS). Placebo-treated RUPP animals evidenced an enhanced urinary sodium excretion as compared to nor-motensive control rabbits receiving placebo (3.27 ± 0.69 mmol/kg/day vs. 1.49 ± 0.74, P <. 001). Enhanced urinary sodium excretion was blunted by IND in RUPP rabbits (1.25 ± 0.37, P <. 001).

Conclusion: (1) IND potentiates the hypertensive response induced by RUPP. (2) the reduction of urinary sodium excretion may be one of the several pharmacological effects of IND aggravating hypertension in this state.     

A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B cell lines (60–90% at the highest concentration tested). These findings suggest that KSHV-LPs may be an ideal platform for developing a safe and effective prophylactic KSHV vaccine. We envision performing future studies in animal models that are susceptible to KSHV infection, to determine correlates of immune protection in vivo.     

Embryo–fetal exposure and developmental outcome of thalidomide following oral and intravaginal administration to pregnant rabbits

Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo–fetal development study using oral and intravaginal thalidomide administration at 2 mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo–fetal developmental toxicity risks with thalidomide exposure via the vaginal route.     

The pharmacokinetics and hypoglycaemic effect of sunitinib in the diabetic rabbits

BackgroundDiabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated.MethodsThe research was carried out on a control group (n = 6) and a group of rabbits with diabetes (n = 6). The rabbits were treated with sunitinib in the oral dose of 25 mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with validated HPLC method with UV detection.ResultsThe comparison of the sunitinib C_max and AUC_0–∞ in the diabetic group with the control group gave the ratios of 1.63 [90% confidence interval (CI) [1.59; 1.66] and 2.03 [1.97; 2.09], respectively. Statistically significant differences between the analyzed groups were revealed for C_max (p = 0.006), AUC_0–∞ (p = 0.0088), and AUC_kel (p = 0.009). The maximum glycaemia drop of 14.4–69.6% and 15.4–33.5% was observed in the diabetic animals and in the control group, respectively. The glycaemia values returned to the initial values in 24 h after the administration of the drug.ConclusionsThe research proved the significant influence of diabetes on the pharmacokinetics of sunitinib and it confirmed the hypoglycaemic effect of the TKI in diabetic rabbits and in normoglycaemia.     

氧疗对高原失血性休克家兔心功能作用的研究

目的　探讨氧疗对高原失血性休克兔心功能的影响。方法　 15只家兔随机分为实验组和对照组。模拟高原环境 ,低压舱减压至海拔 4 0 0 0m ,将动物股动脉放血使其平均动脉压 (MAP)降至 4 0mmHg ,实验组动物给予 80 %O2 吸入和抗休克治疗 ;对照组只给予抗休克治疗 ,动态观察两组血流动力学变化。结果　与对照组相比 ,实验组动物的MAP、左室收缩压 (LVSP)、左室舒张末压 (LVEDP)和左室压力上升及下降的最大速率 (±dp/dtmax)于治疗后 4h均显著增高 (P <0 0 5 ) ,而实验组动物的平均肺动脉压 (mPAP)则在治疗后 1h即显著低于对照组 (P <0 0 5 ) ;实验组动物的治疗后 8h存活率明显高于对照组 (P <0 0 5 )。结论　氧疗在高原失血性休克的救治过程中对心功能具有明显的改善作用。     

HIFU非热效应诱导兔肝VX2肿瘤损伤

目的 探讨高强度聚焦超声(HIFU)非热效应机制诱导兔肝VX2肿瘤损伤的效果及其特点。方法 将22只兔肝VX2肿瘤模型随机分为热效应组(n=11)和非热效应组(n=11),在实时测温下行不同参数HIFU辐照,分别诱导热效应和非热效应损伤,结合病理学检查和辐照剂量对肿瘤的损伤情况对比分析。结果 热效应组和非热效应组的时间-温度曲线分别表现为"快速升高、缓慢下降"和"缓慢升高、缓慢下降",损伤体积分别为(1.10±0.22)cm³和(1.21±0.24)cm³(P＞0.05)。辐照区域伴有不同程度的并发症,两组比较差异无统计学意义(P＞0.05);热效应组和非热效应组残瘤率分别为72.73%和18.18%(P＜0.05);破坏最大血管管径分别为(135.27±22.09)μm和(877.64±253.68)μm(P＜0.001)。与热效应组比较,非热效应组的辐照点数明显降低、辐照时间缩短、总时间延长(P均＜0.001),两组间损伤效率差异无统计学意义(P＞0.05)。结论 HIFU非热效应可有效损伤兔肝VX2肿瘤及其滋养血管。