Circadian and circannual changes in the testicular function of adult rhesus monkeys

The endocrine and gametogenic status of the testes were studied in 9 healthy adult rhesus monkeys of proven fertility throughout a one-year period. Testosterone levels were estimated by radioimmunoassay in blood samples collected at 4 h intervals over a 24 h period once a month. Semen samples and testicular biopsies were also examined once a month. A well-defined circandian rhythm was evident in serum levels of testosterone. The rhythmicity was less pronounced in February and September. The 24 h mean levels of serum testosterone were high between the months of August to March and low in the months of May to July. All animals did not uniformly respond to electro-ejaculation in April and May. Semen volume and total number of spermatozoa were maximal between September and March and least from April to August. Testicular biopsies indicated that all stages of spermatogenesis were evident between September and March and the spermatogenic activity was less evident between April and August. The contents of Sertoli cells showed a seasonal cyclicity; they were laden with lipid droplets during April to August when spermatogenesis was quiescent and vacuolated during September to March when spermatogenesis was active. These studies indicate that the testing of contraceptive drugs needs to be restricted to months of September to March in male rhesus monkeys otherwise, it is possible that the naturally occurring reproductive quiscence may be attributed to the effect of the drug being tested. The data accrued from the present studies also provide quantitative information on circulating levels of testosterone which could be used as a reference background while evaluating the contraceptive drug-effects in male rhesus monkeys.     

Assessment of motor function of the hand in aged rhesus monkeys

In the elderly, intact motor functions of the upper extremity are critical for the completion of activities of daily living. Many studies have provided insight into age-related changes in motor function. However, the precise nature and extent of motor impairments of the upper extremity remains unclear. In the current study we have modified two tasks to assess hand/digit function in both young and aged rhesus monkeys. We tested monkeys from 9 to 26 years of age on these tasks to determine the level of fine motor performance across the adult age range. Compared to young monkeys (9–12 years of age), aged monkeys (15–26 years of age) were mildly impaired on fine motor control of the digits. These findings are consistent with previous studies that have found age-related impairment in fine motor function. However, the magnitude and extent of impairment in the current study does differ from previous findings and is likely due to methodological differences in the degree of task complexity.     

Noninvasive monitoring of follicle development,ovulation, and corpus luteum formation in the marmoset monkey (Callithrix jacchus) by ultrasonography

This is the first paper to describe ovarian changes associated with follicular growth, ovulation, and corpus luteum (CL) formation as monitored by ultrasonography in a multiovular primate, the marmoset monkey (Callithrix jacchus). Examinations were carried out transabdominally on unsedated females using a 10 MHz probe. Cycles were monitored by plasma progesterone and controlled by administration of prostaglandin F2α (PGF). The reliability of ultrasound was validated by comparing findings with direct observation of the ovaries at laparotomy. In eight females, 25 follicles were counted, of which 92% were depicted correctly by ultrasound. Of 14 CLs in five females, number and position were confirmed at laparotomy for 78%. Ultrasound examinations of ovaries throughout the follicular and luteal phase were performed in eight cycles and related to plasma profiles of luteinizing hormone (LH) and progesterone. One of these cycles was anovulatory. In the remaining seven cycles, 19 follicles were considered ovulatory follicles since they were seen on consecutive days and found again as CLs. Growth of individual follicles was monitored by measurements of follicle diameter from day 7 onward. Disappearance of follicles or changes in echogenicity were noted between days 9 and 11, preventing further measurements. Mean follicle size increased from 2.1 mm (range 1.6 mm–2.7 mm) on day 7 to 3.2 mm (range 2.7 mm–4.0 mm) on the day last seen. With one exception, the day follicles were last seen by ultrasound was consistent with the day of the preovulatory LH surge (day 9–11). The postovulatory rise in progesterone occurred 1–2 days later (day 11–13). These findings suggest that the day of ovulation as observed by ultrasound was characterized by either disappearance of follicles or increased follicular echogenicity. In conclusion, ultrasonography provides a reliable, noninvasive method for examinations of the ovarian cycle in the marmoset monkey. © 1996 Wiley-Liss, Inc.     

Purification and characterization of metallothionein from liver of cadmium exposed Rhesus monkeys (Macaca mulatta)

Metallothionein (MT) a low molecular weight, Cd-binding, cysteine rich, cytosolic protein has been isolated, purified and characterized from cadmium exposed Rhesus monkeys maintained on protein calorie malnourished (PCM) diet. Metallothionein was resolved into three isoforms i.e. MT_a, MT_b and MTV_c. The ratio of Cd, Zn and Cu varied in these isometallothioneins. MT_c was the major isometallothionein. UV Spectra of MT_c revealed the presence of mercaptide bonds and absence of aromatic amino acids. These observations were further confirmed by amino acid analysis of MT_c which demonstrated high cysteine content (22.6) followed by serine, glycine and lysine. The molecular weight of MT_c as determined by gel filtration and amino acid analysis was 13000 and 6398 daltons respectively. This demonstrates that MT_c is a non-globular ellipsoid polypeptide. MT_c showed a unique property of binding selenium. Monkey liver metallothionein was immunologically identical with human metallothionein. All the characteristics of MT_c obtained in the present study reveal a similarity between monkey and human metallothionein probably due to closer phylogenetic relationship between the two species.     

Dynamic changes in ovarian follicles measured by ultrasonography during gonadotropin stimulation in rhesus monkeys

The objective was to study dynamic changes of ovaries in rhesus macaques stimulated by gonadotropins to identify an indicator for predicting ovarian response to stimulation. Twenty-one cycling monkeys were given 36 IU/d recombinant human follicle-stimulating hormone (rhFSH) for 8 d. Animals (n = 17) with ≥5 follicles (≥3 mm) in their ovaries on Day 9 of ovarian stimulation were deemed good responders, whereas those with a lesser response were poor responders (n = 4). For these two groups, the mean (±SD) numbers of oocytes retrieved were 44.3 ± 21.4 and 11.0 ± 4.6, respectively. In retrospect, the mean diameters of the ovaries and of the largest follicles, the total number of detectable follicles (diameter >0.5 mm), and serum estradiol concentrations gradually increased during the stimulation period in the good responders but did not increase in the poor responders. Comparing good and poor responders, the number of ovarian follicles >0.5 mm already exhibited a difference (12.9 ± 6.5 vs. 2.9 ± 1.3, respectively, P < 0.05) on Day 1 of stimulation. However, for other end points, differences were not significant until at least Day 5. Moreover, good responders yielded a fivefold higher blastocyst development rate than that of poor responders (P < 0.01). In conclusion, the number of ovarian follicles detected with ultrasonography could be useful to predict the response to FSH stimulation in non-human primates.     

Determination of fetal age by ultrasonography in St. Kitts green monkeys

Ultrasound assessments of fetal growth have been used in other species of primates to estimate fetal age, but there are no published morphometrics for the St. Kitts green monkey (Chlorocebus sabaeus), a species that has been important for studies of transplantation of fetal tissue into the brain as potential treatment for degenerative disease. Previous studies with other primate species have used relatively small numbers of pregnancies, measured repeatedly, to derive regressions for predicting fetal age from ultrasound studies. The present study derives data from 967 pregnancies, collected over a 9-year period, for predicting fetal age from ultrasound measurements of crown rump length, biparietal diameter, head circumference, abdominal circumference, and femur length in the St. Kitts green monkey. Linear and polynomial regressions were determined from pregnancies dated from a 3- to 4-day breeding period and confirmed in a second, independent group of pregnant monkeys with more extended breeding times to determine their accuracy for predicting fetal age. Although similar to morphometrics reported in other monkey species, there were some significant differences. These data will improve the estimates of fetal ages in previously published studies of St. Kitts green monkeys and provide more precise estimates of fetal age in studies of fetal development, genomics, and reproductive toxicology.     

Lethal intragroup aggression by adult male spider monkeys (Ateles geoffroyi)

I report three cases of coalitionary aggression by adult male black-handed spider monkeys (Ateles geoffroyi) against subadult males within their community on Barro Colorado Island (BCI), Panama. Two of these cases were followed by the disappearance and presumed death of the victim. Similar behavior was recently reported by Valero et al. [in press], who suggested that this behavior may be the result of intense male reproductive competition. Like the single instance they reported, the cases I report all occurred when the operational sex ratio was approximately 1:1, which suggests that intense competition among males for access to reproductively viable females may be a contributing factor. Additionally the very low density of spider monkeys on BCI may play a significant role in the occurrence of this lethal aggression. Large numbers of adult males are not necessary to protect a territorial boundary against neighboring groups, and additional males may act merely as mating competition.     

The genetic structure of a primate species: Rhesus macaques and other Cercopithecine monkeys

Among rhesus macaques (Macaca mulatta)and other cercopithecine monkeys, social groups occupying adjacent home ranges (i.e., members of the same local population) exchange individuals and genes and thus exhibit marked genetic similarities. To assess the degree to which this pattern extends beyond the local population, the genetic structure of M. mulattaand six other primate species was determined using Nei’s (1973) gene-diversity analysis. The genetic similarities seen among social groups in the Dunga Gali population of M. mulatta (Melnick et al.,1984a) can be seen over the entire species range. Comparison of these results with the structures of other similarly organized primate species indicates that (1) the average social group contains most of its local population’s genetic diversity, (2) the average local population contains the majority of the genetic diversity found in the region to which it belongs, and (3) the proportion of species gene diversity found in the average regional population varies substantially between species. Genetic homogeneity within local and regional populations is probably the product of gene flow. The application of a number of analytical models of selection and gene flow strongly suggests that gene flow, genetic drift, and zoogeography offer a more parsimonious and plausible explanation for interspecific variation in regional differentiation than does stabilizing selection.     

STZ诱导恒河猴糖尿病动物模型的建立

目的复制稳定的链脲佐菌素诱导糖尿病恒河猴动物模型。方法健康恒河猴5只,小剂量（30mg/kg）多次静脉注射链脲佐菌素,分别在注射后2、3个月进行葡萄糖耐量实验并连续观察血糖、胰岛素、C肽的变化。连续观察12个月。结果随着时间推移,动物出现典型的糖尿病症状。3只动物的血糖静脉注射1次后持续10周稳定,另外2只分别进行了第2、3次注射。动物血糖在12个月内平稳上升、胰岛素、C肽分泌持续下降。2个月时葡萄糖耐量减低明显（P〈0.01）。结论小剂量多次注射STZ后恒河猴可出现持续、稳定的糖尿病表现,可作为相关研究的动物模型。     

Analysis of the shoulder in brachiating spider monkeys.

Adult spider monkeys (Ateles geoffroyi and A. paniscus) were conditioned to brachiate on a rope mill (an arboreal analogue of a treadmill). The postures and excursions of the shoulder girdle were studied by cineradiography. These data, together with conventional cinematographic and anatomical studies, permit reassessment of some characteristic structural and functional features of the shoulder in brachiators. During the propulsive phase, the shoulder joint moves caudad from fifth cervical to seventh cervical levels; at the same time, the joint moves dorsad (from a frontal plane midway between the first thoracic vertebra and the manubrium, to a frontal plane through the spinous processes) and slightly mediad. Spider monkeys position the scapula principally on the dorsum of the thorax, in contrast to quadrupedal primates which maintain a more lateral position (even in suspended postures). During brachiation, the scapula rotates a total of 35°; most of this rotation (20°) occurs in the non-propulsive phase when the free arm is being elevated to secure a new handhold. The sigmoidal shape, twisting of proximal relative to distal ends, and elongation of the clavicle in spider monkeys and other brachiators appear to be related to the specialized positioning of the shoulder girdle on the dorsum of the thorax. Shoulder and elbow movements contribute to the efficiency of the swing in terms of the dynamics of a pendulum.     

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。     

Relationship between physiological tremor and cognitive function in physically active older women

[Purpose]This study aimed to compare the physiological tremor, grip strength, and cognitive function of sedentary and physically active older adults.[Methods]Twenty-four older adults aged ≥65 years participated in this study and were divided into the sedentary (76.5±4.4 years, n=12) and physically active (73.5±3.3 years, n=12) groups. Each group completed the Mini-Mental State Examination (MMSE) for cognitive function assessment. Physiological tremor was measured using an accelerometer for both hands at rest and the left/right hand with a 1,000 g dumbbell on the palm in neutral positions and the elbow flexed at 90°. Physical fitness was measured by grip strength and completion of the Short Physical Performance Battery (SPPB) and the 6-min walk test.[Results]The physically active group showed a significantly lower level of physiological tremor in both hands at rest and the left/right hand with a 1,000 g dumbbell on the palm (P<0.05) than that in the sedentary group. For cognitive function, the physically active group showed significantly higher scores than those in the sedentary group (P<0.001). No significant correlation was found between cognitive function and left/right grip strength (left: r = 0.117, P = 0.585; right: r = 0.230, P = 0.279), physiological tremor in both hands at rest (left: r = -0.524, P < 0.001; right: r = -0.508, P < 0.05), and the left/right hand with a 1,000 g dumbbell on the palm (left: r = -0.505, P < 0.05; right: r = -0.458, P < 0.05).[Conclusion]Physiological tremor of the hands has the potential to be a useful predictor of cognitive function in older adults.     

Insights into circular RNAs: Biogenesis,function and their regulatory roles in cardiovascular disease

As a distinctive member of the noncoding RNA family, circular RNAs (circRNAs) are generated from single-stranded, covalently closed structures and are ubiquitous in mammalian cells and tissues. Due to its atypical circular architecture, it was conventionally deemed insignificant dark matter for a prolonged duration. Nevertheless, studies conducted over the last decade have demonstrated that this abundant, structurally stable and tissue-specific RNA has been increasingly relevant in diverse diseases, including cancer, neurological disorders, diabetes mellitus and cardiovascular diseases (CVDs). Therefore, regulatory pathways controlled by circRNAs are widely involved in the occurrence and pathological processes of CVDs through their function as miRNA sponges, protein sponges and protein scaffolds. To better understand the role of circRNAs and their complex regulatory networks in CVDs, we summarize current knowledge of their biogenesis and function and the latest research on circRNAs in CVDs, with the hope of paving the way for the identification of promising biomarkers and therapeutic strategies for CVDs.     

Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP) is a well-validated target for migraine therapy and a known potent systemic vasodilator. LBR-101 is a monoclonal antibody against CGRP in clinical development for the preventive treatment of episodic and chronic migraine. Understanding the hemodynamic and cardiovascular consequences of chronic CGRP inhibition is therefore warranted. Given the conservation in CGRP sequence between monkeys and humans, addressing this question in monkeys is ideal as it allows dosing at super-therapeutic levels. To this end, two independent studies were conducted in monkeys: a single dedicated cardiovascular safety study and a repeat-dose, chronic study, both with electrocardiogram and hemodynamic assessments. LBR-101 was very well tolerated in both studies, with no clinically significant changes noted in any hemodynamic parameter, nor any relevant changes noted in any ECG parameter. In cynomolgus monkeys, cardiovascular and hemodynamic parameters do not appear to be affected by long-term inhibition of CGRP with LBR-101.     

Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP) is a well-validated target for migraine therapy and a known potent systemic vasodilator. LBR-101 is a monoclonal antibody against CGRP in clinical development for the preventive treatment of episodic and chronic migraine. Understanding the hemodynamic and cardiovascular consequences of chronic CGRP inhibition is therefore warranted. Given the conservation in CGRP sequence between monkeys and humans, addressing this question in monkeys is ideal as it allows dosing at super-therapeutic levels. To this end, two independent studies were conducted in monkeys: a single dedicated cardiovascular safety study and a repeat-dose, chronic study, both with electrocardiogram and hemodynamic assessments. LBR-101 was very well tolerated in both studies, with no clinically significant changes noted in any hemodynamic parameter, nor any relevant changes noted in any ECG parameter. In cynomolgus monkeys, cardiovascular and hemodynamic parameters do not appear to be affected by long-term inhibition of CGRP with LBR-101.     

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。