Effects of different environmental enrichment devices on cage stereotypies and autoaggression in captive cynomolgus monkeys

Autoaggression and stereotypies in individually housed cynomolgus monkeys were compared in a standard primate cage and an enriched playpen environment. Stereotypy and autoaggression were markedly reduced in the playpen, but reappeared on return to the home cage. Some of the various activities available in the playpen but not others engaged the animals' attention.     

Effects of fasting on hematologic and clinical chemical values in cynomolgus monkeys (Macaca fascicularis)

Background Fasting is an important pre‐analytical factor that may affect clinical pathology parameters in toxicological and pharmacological studies. Little information is available on how fasting affects clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis).The aim of this study was to evaluate the influence of fasting on clinical pathology parameters in healthy adult cynomolgus monkeys. Methods Five female and six male cynomolgus monkeys were fasted for 0, 8, 16, and 24 hours. Changes in body weight (BW), core hematologic, and serum clinical chemical parameters were evaluated. Results The BW significantly decreased after 24 hours of fasting. Significant decreases in red blood cell count, hemoglobin, hematocrit, and mean corpuscular volume and increases in mean cell hemoglobin and mean cell hemoglobin concentration were observed at 16 hours in males. In females, increasing the duration of fasting caused a significant time‐dependent increase in platelets. Blood urea nitrogen showed significant decreases in female and male monkeys after fasting. Alkaline phosphatase increased in females after fasting. Aspartate transaminase significantly increased both in females and males at 8 hours. In females, alanine transaminase and lactate dehydrogenase significantly increased at 8 hours. Albumin significantly decreased in males 24 hours, but increased in females 16 hours after fasting. Serum glucose and triglyceride were not affected by fasting. Serum calcium decreased and inorganic phosphorus increased in males after fasting. Conclusion These results suggested that clinical pathology data would vary after fasting. The decision to feed or fast before blood collection for clinical pathology tests should be made based on careful consideration.     

Characterization of a PRISTANE‐induced lupus‐associated model in the non‐human primate cynomolgus monkey

Background

Lupus is an autoimmune disease with complex syndrome. Rodent models have limitations for recapitulating the spectrum of the disease. A more powerful translational model is desirable.

Method

Lupus‐associated model in cynomolgus monkeys was induced by two intraperitoneal injections of 2, 6, 10, 14‐tetramethylpentadecane (PRISTANE). Lupus‐specific biomarkers and manifestations over a 246‐day period were observed at multilevel. To visualize and quantify kidney function in real time, contrast‐enhanced ultrasound was used.

Results

The indicative biomarkers and manifestations fulfilled major diagnosis criteria according to the “Criteria of Lupus” of the American College of Rheumatology. Significant changes in time‐intensity curve parameters were observed, indicating impaired renal function and the method as a feasible, non‐invasive diagnostic method in primate model.

Conclusions

We successfully induced lupus‐associated model with systemic lupus syndrome. This primate model can be a valuable translational model for further pathogenesis and symptomology studies and for exploring therapeutic candidates.     

Influence of improved FcRn binding on the subcutaneous bioavailability of monoclonal antibodies in cynomolgus monkeys

Engineering monoclonal antibodies (mAbs) with improved binding to the neonatal Fc receptor (FcRn) is a strategy that can extend their in vivo half-life and slow their systemic clearance. Published reports have predominantly characterized the pharmacokinetics of mAbs after intravenous administration. Recently, studies in mice suggest FcRn may also play a role in affecting the subcutaneous bioavailability of mAbs. Herein, we examined whether five mAbs engineered with the T250Q/M428L Fc mutations that improved their FcRn interactions, and subsequently their in vivo pharmacokinetics after intravenous administration, had improved subcutaneous bioavailability compared with their wild-type counterparts in cynomolgus monkeys. Similar to the intravenous administration findings, the pharmacokinetic profiles of our variant mAbs after subcutaneous injection showed improved half-life or clearance. In contrast, a clear effect was not observed on the subcutaneous bioavailability. We expect that while FcRn may play a role in determining mAb subcutaneous bioavailability, multiple biopharmaceutical and physiological factors are likely to influence the success of engineering strategies aimed at targeting this pathway for improving bioavailability.     

Comparative effects of interferon alpha‐2b and pegylated interferon alpha‐2b on menstrual cycles and ovarian hormones in cynomolgus monkeys

BACKGROUND : The covalent modification of interferon (IFN) α2b with monomethyoxy polyethylene glycol (PEG) reduces its clearance rate and increases its half‐life. High doses of interferon (IFN) α2b have previously been shown to affect maintenance of pregnancy in rhesus monkeys. Given the role of ovarian hormones in reproductive function and pregnancy, this study was conducted to assess the effects of PEG‐IFNα2b or IFNα2b (comparative control) on ovarian hormones and menstrual cyclicity in cynomolgus monkeys. In addition, the potential for reversibility of PEG‐IFNα2b or IFNα2b‐related observations was assessed. METHODS : Monkeys were administered 3,105 µg/m² human recombinant (hr) IFNα2b or 52, 262, or 4,239 µg/m² PEG‐hr‐IFNα2b every other day for one menstrual cycle, followed by a post‐dose period of up to two menstrual cycles. RESULTS : Monkeys administered 3,105 µg/m² hr‐IFNα2b or 52, 262, or 4,239 µg/m² PEG‐hr‐IFNα2b exhibited transient decreases in food consumption, leukocyte and erythrocyte parameters. Monkeys administered 3,105 µg/m² hr‐IFNα2b exhibited lengthened menstrual cycles that were associated with a delay in reaching peak ovarian hormone levels and lower respective peak concentrations. Similarly, monkeys administered 4,239 µg/m² PEG‐hr‐IFNα2b exhibited lengthened menstrual cycles and a delay in reaching peak ovarian hormone levels and slightly lower respective peak concentrations. Post‐dosing menstrual cycle length, estradiol and progesterone profiles exhibited evidence of recovery in both the hr‐IFNα2b and the high‐dose PEG‐hr‐IFNα2b groups. CONCLUSIONS : Administration of hr‐IFNα2b or PEG‐hr‐IFNα2b at high doses to cynomolgus monkeys resulted in similar effects on menstrual cycles, estradiol and progesterone profiles, and exhibited evidence of reversibility upon cessation of dosing. These results suggest that the previously observed high‐dose IFNα‐related effects on the maintenance of pregnancy in monkeys are likely the result of altered ovarian function. Birth Defects Res (Part B) 86:29‐39, 2009. © 2009 Wiley‐Liss, Inc.     

Five months of daily standardized exercise for sedentary monkeys

A system to physically exercise rhesus monkeys is described, based on their natural capacity to climb. It is composed of an enclosure where a motor-driven rope is continually going down. The two stage training to this task is easily performed. The total work of each run, evaluated with the weight of the animal and the distance climbed, may be very stable. It was used to provide five sedentary monkeys with daily physical training for five months.     

Optimal conditions for blastogenic response of peripheral blood lymphocytes to T and B cell mitogens in cynomolgus monkeys

Optimal conditions for the mitogen-induced proliferation of T and B lymphocytes of cynomolgus monkeys were determined. The T cell mitogens concanavalin A and phytohemagglutinin, at concentrations of 1.25–10 μg/ml and 1.25–10 μg/ml, respectively, and the T and B cell mitogen pokeweed mitogen, at concentrations of 0.2–10 μg/ml, induced high lymphoproliferative responses, the average stimulation index (SI) being 34–93. Since suitable mitogens have not been reported for monkey B cells, we tested three types of lipopolysaccharide (LPS): two derived from Escherichia coli—one extracted with phenol and one extracted with trichloroacetic acid (TCA); and one derived from Salmonella typhimurium, extracted with phenol. All three LPS had a high mitogenic effect for monkey lymphocytes, with SI of 2.3–6.4. The highest response was observed for 25 μg/ml of Salmonella LPS, and the addition of trypsin to the culture augmented the proliferative response of low or non-responder lymphocytes. © 1994 Wiley-Liss, Inc.     

Effect of testosterone on epididymal proteins in castrated rhesus monkeys

The effect of testosterone on regulation of epididymal protein synthesis has been investigated in castrated rhesus monkeys (Macaca mulatta). The proteins in the treated monkeys were characterized using polyacrylamide gel electrophoresis (under nondenaturing and denaturing conditions) and electrofocusing. At least four distinct proteins have been shown to be synthesized by the monkey epididymis under testosterone influence. Two of these proteins were detected following two days of testosterone treatment while the other two proteins were detected after a six-day treatment period. None of these proteins was detectable in monkeys treated with estradiol for six days. Electrofocusing of epididymal cytosol proteins from untreated and testosterone-treated and castrated monkeys also confirmed the presence of four androgen-dependent proteins in this species. The isoelectric points of these proteins were shown to range between 5.8 and 6.4. The molecular weights of these proteins were found to vary between 47,500 and 66,000. The in vitro incorporation of ³H-labeled amino acids was markedly greater in the androgen-primed epididymis as compared with the control tissue.     

Noninvasive technique for the repeated sampling of salivary free cortisol in awake,unrestrained squirrel monkeys

The use of noninvasive measures of hypothalamic-pituitary-adrenal (HPA) axis function is of growing interest among preclinical and clinical investigators. This report describes a method for the repeated assessment of salivary free cortisol in awake, unrestrained squirrel monkeys (Saimiri sciureus) based on a saliva sampling technique previously developed for rhesus monkeys. Individually housed adult male squirrel monkeys were trained to chew on dental rope attached to a pole, from which saliva was extracted by centrifugation and analyzed for cortisol by radioimmunoassay (RIA). Eight of nine monkeys readily acquired the task, reliably providing adequate saliva samples for the assay. Salivary free cortisol levels were examined in these subjects under basal conditions and in response to two types of neuroendocrine challenge. Levels of salivary free cortisol showed relatively low intra- and interindividual variability, with mean individual morning levels ranging between 17.1 and 37.9 microg/dl. Squirrel monkeys demonstrated a consistent daily rhythm in salivary free cortisol ranging from a high of 27.4 +/- 5.2 microg/dl (mean +/- SEM) at 12 P.M. to a low of 7.5 +/- 1.6 microg/dl at 6 P.M. Intravenous (IV) challenges with 1 microg/kg ACTH, or 10 and 50 microg/kg CRF resulted in significant increases in salivary free cortisol. The described sampling technique provides a reliable and sensitive means for repeated measurement of HPA activity in unrestrained, awake squirrel monkeys. In addition, our findings illustrate several features of HPA system rhythmicity and reactivity using salivary cortisol instead of blood plasma or serum.     

人工辅助投食对滇金丝猴肠道微生物群落的影响

【背景】肠道菌群与宿主的消化吸收、免疫抵抗和行为等息息相关,并受宿主的饮食、生活环境等因素影响。【目的】人工辅助投食能增加野生动物的营养摄入,但对其肠道菌群影响的研究较少。【方法】以云南白马雪山国家级自然保护区内的野生和人工辅助投食滇金丝猴群的新鲜粪便为材料,通过高通量测序探究人工辅助投食对猴群肠道菌群的影响。【结果】人工辅助投食的猴群肠道菌群丰富度、均匀度及谱系多样性更高,并且个体间群落组成差异更小。通过多级物种差异判别分析(linear discriminant analysis effect size, LEfSe)分析发现,人工辅助投食对20种不同分类水平的细菌相对丰度有影响,包括提升了厚壁菌门(Firmicutes)等8种类群的相对丰度,降低了变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)等12种类群的相对丰度。通过构建微生物相关网络发现,野生猴群肠道菌群网络结构更加复杂,鲁棒性更高。京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)功能预测结果表明,人工辅助投食降低了猴群肠...     

Visitor reaction to pacing behavior: influence on the perception of animal care and interest in supporting zoological institutions

Many publications within the field of zoo animal welfare have stated the importance of decreasing stereotypic behavior (e.g., pacing) to help ensure a positive visitor experience. The idea behind these statements is that visitors want to see animals engaged in natural behavior. Additionally, it is thought that watching an animal exhibit species-appropriate behavior could help increase a visitor's connection to wildlife and ultimately their interest in conservation. However, until recently, no information was available to validate such statements. The purpose of this research was to examine people's reaction to viewing an animal engaged in pacing behavior. Participants were randomly selected to fill out a survey after watching a short video of either a tiger pacing or resting (control). Results indicate that having viewed a tiger pacing significantly decreases people's perception of the level of care animals receive at that facility. In addition, people's interest in supporting zoos decreased as a result of viewing this behavior. Results are discussed from an animal welfare, business, and conservation perspective.     

A new approach for categorizing pig lying behaviour based on a Delaunay triangulation method

Machine vision-based monitoring of pig lying behaviour is a fast and non-intrusive approach that could be used to improve animal health and welfare. Four pens with 22 pigs in each were selected at a commercial pig farm and monitored for 15 days using top view cameras. Three thermal categories were selected relative to room setpoint temperature. An image processing technique based on Delaunay triangulation (DT) was utilized. Different lying patterns (close, normal and far) were defined regarding the perimeter of each DT triangle and the percentages of each lying pattern were obtained in each thermal category. A method using a multilayer perceptron (MLP) neural network, to automatically classify group lying behaviour of pigs into three thermal categories, was developed and tested for its feasibility. The DT features (mean value of perimeters, maximum and minimum length of sides of triangles) were calculated as inputs for the MLP classifier. The network was trained, validated and tested and the results revealed that MLP could classify lying features into the three thermal categories with high overall accuracy (95.6%). The technique indicates that a combination of image processing, MLP classification and mathematical modelling can be used as a precise method for quantifying pig lying behaviour in welfare investigations.     

Two new species of night monkeys,genus Aotus (Cebidae,platyrrhini): A preliminary report on Aotus taxonomy

The nine allopatric species of Aotus recognized represent two natural groups distinguished by karyotype, color, and pelage patterns. Correlated with these group characters are reported differences in serum proteins and degrees of susceptibility or immunity to experimental infection with malarial parasites. The primitive gray-neck species group of Aotus contains A. brumbacki (new species), A. lemurinus (with subspecies lemurinus and griseimembra), A. trivirgatus, and A. vociferans. The derived red-neck group contains A. nancymai (new species), A. miconax. A. infulatus, and A. azarae (with subspecies azarae and boliviensis). Only the two new species are described but a key to the species and subspecies gives the diagnostic characters of each. The gray-neck group occurs almost entirely north of the Amazon, the red-neck group almost entirely south. The distributional exceptions are enclave populations resulting from river bend cutoffs. Formation of an enclave population of A. nancymai is discussed and available information on the biology of this species is reported.     

Influence of breeding site availability on the oviposition behaviour of Aedes aegypti

Despite the importance of the mosquito Aedes aegypti in thetransmission of arboviruses, such as yellow fever, Chikungunya fever and denguefever, some aspects of their behaviour remain unknown. In the present study, theoviposition behaviour of Ae. aegypti females that were exposed todifferent densities of breeding sites (2, 4, 8 and 16) was evaluated in laboratoryand semi-field conditions. The number of breeding sites that were used wasproportional to the number available, but tended towards stabilisation. Females usedfour-six breeding sites on average, with a maximum of 11. A high percentage of eggswas observed in the water, along with the presence of a breeding site termed“favourite”, which received at least 40% of the eggs. The results are discussed inecological, evolutionary and epidemiological approaches.