Estradiol and dehydroepiandrosterone potentiate levodopa-induced locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys

Six monkeys were rendered hemiparkinsonian with a unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These monkeys displayed ipsilateral circling under basal conditions, and after dopaminergic stimulation with levodopa they decreased their ipsilateral circling and started turning to the contralateral side of their lesion. The effect of 17β-estradiol and dehydroepiandrosterone (DHEA) was investigated in these animals. 17β-Estradiol (0.1 mg/kg) added to a threshold dose of levodopa significantly potentiated contralateral circling (mean/30 min) compared to saline or threshold levodopa treatment whereas the duration of circling remained unchanged. DHEA (1–15 mg/kg) alone induced contralateral circling, compared to saline treatment, for 90 min. In addition, DHEA (1–15 mg/kg) potentiated the contralateral circling (mean/30 min) induced by a threshold dose of levodopa and did not change the duration of levodopa circling. A maximal response was observed with 1 or 5 mg/kg of DHEA combined with levodopa depending on the monkey. No correlation was found between the dose for the maximal DHEA response and baseline circling or threshold dose of levodopa. These results suggest that 17β-estradiol or DHEA is able to potentiate locomotor activity of hemiparkinsonian monkeys. The DHEA doses investigated are similar to those presently used in humans. DHEA may be an alternative to 17β-estradiol to modulate dopaminergic activity.     

Relationship of skeletal muscle glucose 6-phosphate to glucose disposal rate and glycogen synthase activity in insulin-resistant and non-insulin-dependent diabetic rhesus monkeys

Summary Reduced insulin action on skeletal muscle glycogen synthase activity and reduced whole-body insulin-mediated glucose disposal rates in insulin-resistant subjects may be associated with an alteration in muscle glucose transport (or phosphorylation) or with a defect distal to glucose 6-phosphate. To examine this issue we determined the glucose 6-phosphate concentration and glycogen synthase activity in muscle samples obtained under basal and euglycaemic hyperinsulinaemic clamp conditions in 27 rhesus monkeys (Macaca mulatta). They ranged from metabolically normal (n =11) to insulin-resistant (n =8) to overtly diabetic (non-insulin-dependent) (n =8). The glucose 6-phosphate measured under insulin-stimulated conditions was inversely correlated to insulin-stimulated glycogen synthase independent activity (r = –0.54, p<0.005), the change in glycogen synthase independent activity (insulin-stimulated minus basal) (r = –0.58, p<0.002) and to whole-body insulin-mediated glucose disposal rate (r = –0.60, p<0.002). The insulin-resistant and diabetic monkeys had significantly higher insulin-stimulated glucose 6-phosphate concentrations (0.57±0.11 and 0.62±0.11 nmol/mg dry weight, respectively) compared to the normal monkeys (0.29±0.05 nmol/mg dry weight) (p's <0.05). We conclude that under euglycaemic/hyperinsulinaemic conditions, a defect distal to glucose 6-phosphate is a major contributor to reduced whole-body insulin-mediated glucose disposal rates and to reduced insulin action on glycogen synthase in insulin-resistant and diabetic monkeys. [Diabetologia (1994) 37: 127–133] Received: 28 May 1993 and in revised form: 13 August 1993     

Failure to infect rhesus monkeys with hepatitis C virus strains of genotypes 1a, 2a or 3a

The chimpanzee is the only recognized animal model for the study of hepatitis C virus (HCV). However, recently it was reported that rhesus monkeys were susceptible to HCV and developed hepatitis during infection. In the present study, we inoculated two rhesus monkeys each with HCV strain H77 (genotype 1a), strain HC-J6 (genotype 2a) or strain S52 (genotype 3a). Weekly serum samples were tested for liver enzyme values, HCV antibodies and HCV RNA. We did not find evidence of HCV infection in any of the monkeys during 24 weeks of follow-up. Our study demonstrates that rhesus monkeys are not readily infected with HCV and apparently do not represent a useful animal model for the study of HCV.     

人工饲养条件下死亡实验恒河猴肠道病理改变特点分析

目的 观察人工饲养条件下实验恒河猴肠道病理改变,探讨实验猴肠道疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料.方法 对1998 ～2008年云南地区饲养的自然死亡的155只恒河猴(年龄2～20岁)的肠道进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析.结果 155例恒河猴中58例检出肠道病变,有慢性肠炎、急性肠炎、黏膜充血水肿、出血、糜烂、溃疡、穿孔、寄生虫共8种主要病变,出现率最高的为急性肠炎(20.00％).实验猴不同年龄组肠道病变类型分布基本相同,肠道病变率随年龄增长而增高,不同年龄组间统计学分析差异无显著性.结论 人工饲养条件下死亡实验猴肠道病变检出率较高,急性肠炎是实验猴的主要致死原因之一,实验猴肠道病理改变随年龄增长而病变加重.对实验猴饲养和研究时,应重视肠道病变因素,尤其是急性肠炎.死亡实验猴肠道病变研究对实验猴的质量控制和相关动物实验有重要指导价值.     

实验猴身份自动识别、自动捕捉、电子芯片数据信息管理系统的研制

目的通过电子芯片植入与识别技术和计算机管理系统对接,建立每只实验猴的数据档案,其中包括遗传谱系、生理数据、实验记录。方法通过建立实验猴的电子通道,以非接触方式通过计算机管理,应用射频识别信号系统,实现实验猴身份快速自动识别、自动捕捉、数据读写、电子档案信息管理、数据远程传输的目的,减少人为因素对实验猴的干扰和引起的应激反应。结果该系统的建立极大的减少了实验和饲养实验猴过程中捕捉猴的困难,身份识别困难,减少了对工作人员和实验猴的伤害,减轻了工作量,减低了人为因素对实验结果的干扰和动物应激反应对实验数据的影响。电子档案具有终身有效,随猴携带,全球唯一序列号,不可复制,不可仿制,标签唯一性。结论实验猴身份自动识别、自动捕捉、电子芯片数据信息管理系统的研制成功,为实验动物个体电子档案建立和群体数据库的管理提供了一种高速、有效、科学、可靠的计算机管理手段,改变通道模式即可应用于大型凶猛动物或不适合人接触捕捉动物的识别和管理,具有广泛的应用前景,目前在国内外尚无同类系统。     

3～4岁猕猴生理指标的测定

目的 建立3～4岁猕猴生理指标基础数据.方法 对100只3～4岁猕猴(♂ 50只,♀50只)进行了较全面的血液学和心肺功能等生理指标的测定,包括血常规30项、血液生化22项、凝血功能2项以及血压、心电图、呼吸次数.结果 血常规中,雌性猕猴的平均红细胞血红蛋白浓度(MCHC)极显著低于雄性猕猴(P＜0.01);雌性猕猴极显著高于雄性的项目有血小板计数(PLT)、血小板压积(PCT)、嗜酸性粒细胞计数(EO#)、嗜碱性粒细胞计数(BASO#)、嗜酸性粒细胞百分比(EO％)与嗜碱性粒细胞百分比(BASO％)(P＜0.01);显著高的项目有白细胞计数(WBC)和淋巴细胞计数(LYMPH)(P＜0.05).血液生化指标中,雌性猕猴极显著低于雄性的项目为尿素氮(BUN)、总胆红素(TBIL)、γ-谷氨酰转肽酶(GGT)与无机磷(IP)(P＜0.01);显著低的项目为天冬氨酸转氨酶(AST)、白蛋白(ALB)和直接胆红素(DBIL)(P＜0.05);雌性猕猴显著高于雄性的项目为血糖(GLU),血钙(Ca)和甘油三酯(TG)(P＜0.05).血凝与血压、心电图的各参数中,雌、雄性别的猕猴之间无显著性差异.呼吸次数的监测结果显示雌性猕猴的呼吸次数较雄性猕猴极显著减少(P＜0.01).结论 建立了3～4岁实验用猕猴的生理指标的正常值,为猕猴实验和疾病诊断中相关生理指标的分析提供了基础参考值.     

Internal pallidum and substantia nigra control different parts of the mesopontine reticular formation in primate

The locomotor area has recently emerged as a target for deep brain stimulation to lessen gait disturbances in advanced parkinsonian patients. An important step in choosing this target is to define anatomical limits of its 2 components, the pedunculopontine nucleus and the cuneiform nucleus, their connections with the basal ganglia, and their output descending pathway. Based on the hypothesis that pedunculopontine nucleus controls locomotion whereas cuneiform nucleus controls axial posture, we analyzed whether both nuclei receive inputs from the internal pallidum and substantia nigra using anterograde and retrograde tract tracing in monkeys. We also examined whether these nuclei convey descending projections to the reticulospinal pathway. Pallidal terminals were densely distributed and restricted to the pedunculopontine nucleus, whereas nigral terminals were diffusely observed in the whole extent of both the pedunculopontine nucleus and the cuneiform nucleus. Moreover, nigral terminals formed symmetric synapses with pedunculopontine nucleus and cuneiform nucleus dendrites. Retrograde tracing experiments confirmed these results because labeled cell bodies were observed in both the internal pallidum and substantia nigra after pedunculopontine nucleus injection, but only in the substantia nigra after cuneiform nucleus injection. Furthermore, anterograde tracing experiments revealed that the pedunculopontine nucleus and cuneiform nucleus project to large portions of the pontomedullary reticular formation. This is the first anatomical evidence that the internal pallidum and the substantia nigra control different parts of the brain stem and can modulate the descending reticulospinal pathway in primates. These findings support the functional hypothesis that the nigro‐cuneiform nucleus pathway could control axial posture whereas the pallido‐pedunculopontine nucleus pathway could modulate locomotion. © 2011 Movement Disorder Society     

微波辐射对猕猴重要脏器生理功能的影响研究

目的探讨微波辐射对猕猴重要脏器电生理功能的影响。方法雄性猕猴15只,根据平均功率密度的不同,随机分为假辐射组,2、5、7和11 mW/cm2微波辐射组,采用Biopac公司生产的MP-150多导生理记录及分析系统,分别于辐射前及辐射后即刻、1 d、3 d、7 d、14 d和30 d,对猕猴心电图（ECG）、脑电图（EEG）、肌电图（EMG）及体温等指标进行检测。结果 7和11 mW/cm2组EEG见δ频段相对功率谱分别于辐射后7 d和14 d内显著升高,而β频段相对功率谱均于辐射后3 d内明显下降,14 d见升高,30 d见部分恢复。2 mW/cm2和5 mW/cm2组δ频段与β频段相对功率谱辐射后未见明显变化。11 mW/cm2组心率于辐射后即刻明显减慢、心电图R波和T波波幅均于辐射后1 d内显著降低,且心律不齐,30 d时基本恢复。辐射后即刻至30 d,各实验组猕猴的体温及肌电均无明显改变。结论 7和11 mW/cm2微波辐射可引起猕猴脑电生理功能损伤,且与辐射剂量呈正相关;11 mW/cm2微波辐射可引起猕猴心脏电生理功能损伤;2~11 mW/cm2微波辐射对猕猴体温及肌电均无明显影响。     

人重组粒细胞巨噬细胞集落刺激因子和白介素3融合蛋白对猕猴重度急性骨髓型放射病的实验治疗研究

目的　探讨人重组粒细胞巨噬细胞集落刺激因子和白介素３ 融合蛋白（Ｇ３） 对猕猴重度急性骨髓型放射病时,促进白细胞（ ＷＢＣ） 、血小板（ＰＬＴ） 的恢复功能。方法　猕猴２０ 只,６０Ｃｏ γ射线全身均匀照射,吸收剂量４ Ｇｙ,照后立即分别按４０ μｇ·ｋｇ－１ｄ－１ 和２０ μｇ·ｋｇ－１·ｄ－ １ 经皮下注射Ｇ３ ,连续注射２０ 天,照后隔日连续观察外周血象变化,临床表现,观察３５ 天,实验结束进行骨髓象和病理学检查。结果　外周血白细胞总数和中性粒细胞、血小板的最低值、早期恢复峰值,Ｇ３ 组均高于对照组;照后血象低谷期（１３ ～２１ 天）的平均值,Ｇ３ 组也都高于对照组,Ｇ３ 可缩短ＷＢＣ、中性粒细胞计数（ＡＮＣ） 和ＰＬＴ 减少期的时间。结论　Ｇ３ 对猕猴重度急性骨髓型放射病,可明显促进ＷＢＣ、ＡＮＣ和ＰＬＴ的恢复,减少出血感染,延长存活期。     

Effects of Weightlessness and Movement Restriction on the Structure and Metabolism of the Soleus Muscle in Monkeys after Space Flight

After humans and animals have been in conditions of real and modeled weightlessness, the most marked changes are seen in the slow tonic muscles, particularly soleus. Studies of the effects of weightlessness and movement restriction on the soleus muscle in monkeys demonstrated significant reductions in the sizes of slow and rapid fibers due mainly to the actions of real weightlessness (rather than movement restriction in the space capsule). Protein loss in soleus muscle fibers in monkeys following space flight was more marked than loss of other components, including water. The level of atrophy of soleus muscle fibers in these conditions was greater than the decrease in the number of capillaries. Succinate dehydrogenase activity in soleus muscle fibers decreased proportionally to the reduction in fiber size.