不同年龄实验恒河猴自然死亡的肝脏病变谱分析

目的观察人工饲养条件下实验恒河猴肝脏病理改变,探讨肝脏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)的肝脏进行病理检查,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88例检出肝脏病变,有肝细胞变性、肝细胞坏死、炎细胞浸润、吞噬细胞增生、肝淤血、纤维组织增生、肝脓肿、寄生虫共八种主要病变,出现率最高的为肝细胞水样变性(34.19%)。除肝脓肿外,幼年组、成年组、老年组八种病变均有检出。卡方检验显示:肝细胞水样变性成年组病变率明显高于幼年组;肝细胞脂肪变性老年组明显高于成年组和幼年组;轻度炎细胞浸润病变老年组明显高于成年组;纤维组织增生老年组明显高于幼年组(P<0.05)。结论人工饲养条件下死亡实验猴肝脏病变检出率较高,实验猴肝脏病理改变随年龄增长而病变加重,提示在进行实验猴肝脏研究时,应注意对自发性病变的判别,药物安全性评价实验应避免选择老年猴做为研究对象。死亡实验猴肝脏病变谱研究,对实验猴的质量控制和相关动物实验有重要指导价值。     

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。     

人工饲养条件下恒河猴血液学、血液生化正常参考值测定及分析

目的测定人工饲养条件下104只健康恒河猴的血液学、血液生化正常参考值,并分析不同性别、不同年龄阶段(青幼年组∶3～4岁,成年组∶5～10岁,老年组∶11～25岁)恒河猴的血液学、血液生化值的差异及相互关系.方法应用全自动血液细胞分析仪和全自动血液生化分析仪,测定及分析非麻醉状态下健康恒河猴血液学和血液生化正常值.结果血液学值中较明显低 (P<0.05) 的项目为MED.血液生化值中♀猴比♂猴明显低 (P<0.01)的项目有ALT、ALP、GGT、CHOL、APOA、HDL、LDL、P3+、BUN,较明显低 (P<0.05) 的项目为ALB.较明显高 (P<0.05) 的项目为UA.各年龄组之间的分析如下:血液学值中RDW值为青幼年组比成年组及老年组均明显低(P<0.01),MEDIAN值为成年组比青幼年组较明显高 (P<0.05),血液生化值中青幼年组比成年组及老年组均明显高 (P<0.01)的项目有ALT、ALP、GGT、P3+,青幼年组比成年组明显高(P<0.01)的项目为BUN、ALP、AST、,青幼年组比老年组明显高(P<0.01)的项目为CK、TF;成年组比老年组明显低(P<0.01)的项目为CREAT,较明显低 (P<0.05) 的为TRIG.结论本文建立了人工饲养条件下健康恒河猴血液学和血液生化值的正常指标,并讨论了年龄、性别对其正常指标的影响,可供参考.     

恒河猴血清孕酮含量测定方法

目的建立恒河猴血清中孕酮含量测定方法。方法本文采用放射免疫测定技术。结果孕酮的回收率为94％,批内CV为5．1％～8．3％,批间CV为4．5％～7．7％,灵敏度为5～10Pg。说明该方法具有较高的灵敏度、特异性、准确性。分别测定了幼年组、成年组和老年组的雌性恒河猴的血清中的孕酮含量分别为：（0．20±0．04）ng／mL、（6．26±0．17）ng,mL和（0．35±0．06）ng/mL;成年雌性恒河猴月经周期孕酮的变化范围为：滤泡期为（1．10±0．12）ng／mL,排卵期（2．36±0．18）ng/mL,黄体期（6．17±0．15）ng/mL,妊娠期随着妊娠月份的增加,孕酮浓度也增加,最高可达50ng／mL。结论经实验验证,该方法灵敏、可靠、适用,可作为恒河猴血清中孕酮含量测定的一种方法。     

人工饲养恒河猴、食蟹猴的繁殖性能初报

目的探索北京地区人工饲养恒河猴与食蟹猴的繁殖性能,为温带地区猕猴的人工饲养和繁殖方式提供借鉴。方法对军事医学科学院实验动物中心饲养的317只恒河猴繁殖群（30只雄猴,287只雌猴）和78只食蟹猴繁殖群（8只雄猴,70只雌猴）近两年的繁殖性状进行观察和统计分析。结果恒河猴母猴妊娠率、繁殖率和成活率分别为60.73%、54.45%和96.89%。食蟹猴母猴妊娠率、繁殖率和成活率分别为79.86%、56.12%和75.00%。结论食蟹猴和恒河猴可以成功的在温带地区饲养和繁殖,但人工饲养食蟹猴的妊娠率与产仔率较恒河猴高,而仔猴成活率则低于恒河猴。     

人工繁育恒河猴婴猴生长发育指标的测定分析

目的建立人工繁殖恒河猴婴猴生长发育指标的标准数据库。方法随机对90只人工饲养繁殖的恒河猴（从100d至1周岁）进行体重、身长、尾长、前肢长、后肢长发育指标测定。结果测定后的数据,经统计学分析和绘制生长曲线图,发现人工饲养条件下的恒河猴（1周岁前）,其生长发育指标基本均匀一致,只有个别出现发育迟缓或发育不良现象。随时间推移,雄性生长速度要快于雌性。结论所建立的恒河猴婴猴正常生长发育生理指标,为提高人工饲养繁育恒河猴技术和不断改善恒河猴营养与发育健康提供了科学数据。     

不同年龄大鼠血清抗中肾旁管激素水平与卵巢储备功能的关系

目的探讨不同年龄组雌性大鼠血清抗中肾旁管激素（AMH）变化的规律和原因,探讨AMH在预测卵巢储备功能方面的作用。方法SD雌性大鼠分为幼年组、成年组和老年组。运用ELISA和免疫荧光化学方法,检测血清和卵巢中AMH的表达。结果血清AMH水平,幼年组5.26±0.13 ng/mL,成年组2.34±0.11 ng/mL,老年组0.69±0.04 ng/mL,随年龄增长显著降低（P〈0.001）。卵巢中AMH阳性卵泡的数量,幼年组19.5±1.3,成年组10.8±1.5,老年组3.8±0.6,随年龄增长显著降低（P〈0.001）。结论随着大鼠年龄增长,卵巢中分泌AMH的生长卵泡数量减少,使血清AMH水平下降,提示卵巢储备功能下降。AMH是一个较好的检测卵巢储备功能的指标。     

蜂桶寨自然保护区中华姬鼠及社鼠肥满度的年龄和季节变化

肥满度被广泛用于动物生长状况与环境、生存、繁殖等方面的研究。为揭示横断山脉森林环境中中华姬鼠（Apodemus draco）和社鼠（Niviventer confucianus）肥满度的变化规律及影响原因,我们于2008年4~11月对四川省蜂桶寨国家级自然保护区内中华姬鼠和社鼠肥满度在各年龄组及不同季节中的变化进行了研究。结果显示,中华姬鼠肥满度在各年龄组间的差异显著,其变化趋势为老年组>成年组>亚成年组>幼年组;亚成年组及老年组肥满度在各季节间无显著差异,而在成年组则差异明显,以春季中最高。社鼠肥满度在各年龄组间无显著性差异;亚成年组肥满度在各季节间差异显著,在夏秋季中最低,同时成年组及老年组肥满度在季节间无显著差异。中华姬鼠和社鼠亚成年组、成年组及老年组肥满度与海拔无显著的线性关系。分析认为,中华姬鼠老年组个体可能在应对外界环境方面要强于幼年个体而具有最高的肥满度,成年个体肥满度的季节变化可能受食物资源季节差异和繁殖能量需求的影响;社鼠成年及老年个体能通过相应的季节性调节维持肥满度的稳定,而亚成年个体在调节方面较弱,故其肥满度在夏秋季最低。     

臭鼠的种群年龄结构研究

１９８６年１月至１９９３年１２月,作者在浙江萧山围垦农区采用体重法将臭　种群分为５个年龄组。雄体：Ⅰ．幼年组（体重≤３０８）、Ⅱ．亚成年组（体重＞３０９,≤４０ｇ）、Ⅲ．成年１组（体重＞４０ｇ,≤５２ｇ）、Ⅳ．成年ＩＩ组（体重＞５２８,≤６４８）、Ⅴ．老年组（体重＞６４ｇ）;雌体：幼年组（体重≤２４ｇ）,Ⅱ．亚成年组（体重＞２４ｇ;≤３６ｇ）．Ⅲ．成年Ⅰ组（体重＞３６９,≤４６ｇ）,Ⅳ．成年Ⅱ组（体重＞４６８,≤５４ｇ）,Ⅴ．老年组（体重＞５４ｇ）。各年龄组的繁殖特性存在差异。种群以成年Ⅰ组为主,但其种群的年龄结构存在有性别差异,雄性种群以成年Ⅰ组、成年Ⅱ组和老年组为主,雌性种群以亚成年组和成年Ⅰ组为主。种群的年龄结构存在季节性变化。在室内,雄性在春季和冬季以成年Ⅱ组为主,夏季和秋季以老年组为主;在室外春季、秋季和冬季均以成年Ⅰ组为主,夏季则以成年Ⅱ组为主。室内雌性在各季节均以成年Ⅰ组为主,而在室外春季和冬季以亚成年组为主,夏季和秋季以成年Ⅰ组为主。其种群年龄结构存在有年变化。     

雄性猕猴血清中促黄体素的分泌水平

本文采用促黄体素（ＬＨ）体外生物测定法，对不同年龄组雄性猴血清中促黄体素分泌水平进行了分析。结果表明：幼年组为５．４±１．７ｎｇ／ｍｌ，成年组为４５．６±１２．８ｎｇ／ｍｌ，老年组为６９．２±２１．５ｎｇ／ｍｌ。提示雄性猕猴ＬＨ分泌模式与人很相似。     

Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta)

Identifying changes with age in physiological variables of captive nonhuman primates will aid in the proper treatment and clinical diagnosis of these animals, as well as enhance our understanding of nonhuman primate models for human aging. Information for 33 physiological variables was obtained from the Primate Aging Database, a multi-centered database being developed for clinical and research use. Using multiple regression analyses, we investigated the relationship of age to hematological variables, blood chemistry and body weight in 345 captive rhesus monkeys (age range 7-30 years) from three different primate research facilities. The analyses revealed that 15 of these variables show a significant relationship with chronological age and are altered in older as compared with adult animals. Here we present the first phase of a project that will: a) identify changes with age in physiological variables among adult captive rhesus macaques; and b) characterize normative values for the aging rhesus population.     

Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureus used for research at the Fiocruz primate center

Physiological parameters of laboratory animals used for biomedical research is crucial for following several experimental procedures. With the intent to establish baseline biologic parameters for non-human primates held in closed colonies, hematological and morphometric data of captive monkeys were determined. Data of clinically healthy rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and squirrel monkeys (Saimiri sciureus) were collected over a period of five years. Animals were separated according to sex and divided into five age groups. Hematological data were compared with those in the literature by Student's t test. Discrepancies with significance levels of 0.1, 1 or 5% were found in the hematological studies. Growth curves showed that the sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier ages, the differences between sexes could not be distinguished (p < 0.05). Sexual dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of about 32 months. Data presented in this paper could be useful for comparative studies using primates under similar conditions.     

A test of the randomness of paternity of members of maternal sibships in six captive groups of rhesus monkeys (Macaca mulatta)

Results of previous studies have shown that in captive groups of rhesus monkeys (Macaca mulatto)fathers associate more frequently with their own offspring than with those of other males and that mothers are most permissive of physical contact between their own infant and a juvenile when that juvenile shares the same father with her infant. These two observations suggest that the identity of offspring born in captive groups of rhesus monkeys is recognized by at least some adult members of the group. Consistent patterns of mating among mating seasons might explain this apparent recognition of offsprings’ paternity. Fathers, for example, might regularly associate with young who maintain a close relationship with females with whom they have previously mated, and mothers might selectively permit juveniles who maintain a close relationship with males with whom they have previously mated to associate with their infants. This hypothesis is tested in this paper by comparing the observed distribution of 70 maternal sibships, members of which were fathered by the same or by different adult males over a 4-year period in six captive groups of rhesus monkeys, with that distribution expected based on random mating from season to season. Seasonal mating patterns were found to be random. Preparations are now underway to test this hypothesis in several free-ranging groups.     

A comparison of the demographic structure and growth of free-ranging and captive groups of rhesus monkeys (Macaca mulatta)

Vital statistics are employed to estimate rates of mortality, fetility and growth for a group of about 450 captive rhesus monkeys housed in six separate enclosures at the California Primate Research Center (CPRC). These rates were compared with those previously reported for a free-ranging group of rhesus monkeys. Relative to the free-ranging group, the CPRC monkeys experienced higher fertility below age 5 and lower mortality beyond age 3. These rates are associated with a potential intrinsic rate of increase of about 10%, a rate which is about 50% higher than that for the free-ranging group. Reasons for this marked difference in reproductive success of the two groups are discussed.     

Differential MicroRNAs Expression in Serum of Patients with Lung Cancer, Pulmonary Tuberculosis, and Pneumonia

MicroRNAs (miRNAs) play critical regulatory roles in the physiological and pathological processes. The high stability of miRNAs in human serum represents attractive novel diagnostic biomarkers of clinical conditions. Several studies have shown that aberrant expression of miRNAs in human cancer including lung cancer, but little is known about their effects on some infectious lung diseases such as pulmonary tuberculosis (TB) and pneumonia. In this study, we investigated miRNA expression pattern in serum of Egyptian patients with lung cancer, TB, and pneumonia compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of a series of circulating miRNAs (miR-21, miR-155, miR-182, and miR-197) in serum from patients with lung cancer (n = 65), pulmonary tuberculosis (n = 29), pneumonia (n = 29), and transudate (n = 16) compared with matched healthy controls (n = 37). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-21, miR-155, and miR-197 were significantly elevated in the patients with lung cancer and pneumonia whereas miR-182 and miR-197 levels were increased only in patients with lung cancer and TB, respectively, compared with controls. Receiver operating characteristic analysis revealed that miR-182, miR-155, and miR-197 have superior diagnostic potential in discriminating patients with lung cancer, pneumonia, and TB, respectively, from controls. Our results conclude that the differential expression of the four studied miRNAs can be potential non-invasive biomarkers for patients with lung cancer, TB and pneumonia.     

Characterization of dermatologic changes in geriatric rhesus macaques

Abstract: Nonhuman primates are frequently used for aging studies. We observed a high prevalence of skin disease among a group of geriatric rhesus monkeys (mean age ? 25 years; n ? 9) used in aging behavioral studies. Gross and histopathologic changes in the skin of these geriatric rhesus were compared with skin from control adult monkeys (mean age ? 10; n ? 4) and sun-exposed monkeys (mean age ? 11; n = 4) to characterize age-related skin changes. Biopsy specimens were taken from four specified skin locations (lateral to bridge of nose, ventral midline, dorsal midline, perineal area) and from additional areas where skin lesions were present. Samples were routinely processed and evaluated by light microscopy. Blood samples were collected and tested for estrogen, thyroid-stimulating hormone, triiodothyronine, thyroxine, and Cortisol levels. The axilla was swabbed and samples were obtained for bacterial culturing. All nine of the geriatric monkeys had notable dermal lesions, while one of the control monkeys and one of the sun-exposed monkeys had abnormal findings. Major gross findings included increased areas of erythematous skin, wrinkling, focal skin scaling, thinning of hair, foot calluses, and exudative lesions. Histologic skin changes included subacute dermatitis, acanthotic dermatitis, and a lesion resembling an early solar lentigo in the sun-exposed animal. These changes were not associated with hormonal abnormalities or bacterial pathogens. Histologic changes are compatible with nonspecific skin changes observed in elderly humans. This study establishes a baseline of dermatologic changes of the aging rhesus macaque.     

Prompted progression order in a troop of captive rhesus monkeys

It is a routine practice to subject captive groups of primates to single-file movement; yet no records on the sequences of such progressions have been published. The present study analyzes the progression sequence during prompted single-file movement for the purpose of routine weighing in a captive troop of rhesus monkeys (Macaca mulatta). The animals had to overcome fear before leaving their home pen; nonetheless, they left in a well-defined, stable sequence. An individual's position in this progression order as well as the consistency with which it retained its place were dependent on its age but not on its dominance status. It was suggested that the monkeys gradually learned with age to master their fear with the prospect of quickly returning to their home pen.     

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

Background

Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation.

Methods

Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m³ for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m³ for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m³ and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett''s multiple comparison. Histopathological findings were evaluated using a Pearson''s Chi-Square test.

Results

Animals exposed to manganese sulfate at ≥0.3 mg Mn/m³ for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m³ for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure.

Conclusion

High-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m³) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.