Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis)

BACKGROUND: It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. METHODS: Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. RESULTS AND CONCLUSIONS: Body temperature measurements from NIFT were statistically different (P < 0.0001) from rectal thermometry. In addition, there was greater between- and within-subject variability in values using NIFT. There was no correlation between any sites of the NIFT and rectal thermometry. It was concluded that NIFT was not a valid alternative to rectal thermometry in cynomolgus macaques.     

Cutaneous melanoma with metastasis in a cynomolgus monkey (Macaca fascicularis)

Background  A 3.3-year-old-male cynomolgus macaque ( Macaca fascicularis ) showed a focally extensive soft, dark, discoid dermal mass, 0.5 cm in diameter, on the dorsal surface of the right hind foot, over the fourth and fifth metatarsal bones.
Methods and results  Microscopic examination revealed a cutaneous melanoma with local lymphatic invasion, characterized by neoplastic melanocytes within the subcapsular sinus of popliteal and inguinal lymph nodes. The diagnosis was confirmed by immunohistochemistry and transmission electron microscopy.
Conclusions  To our knowledge, this is the first documented case of melanoma in a cynomolgus monkey.     

Multi-tiered treatment of pressure sores in two cynomologous macaques (Macaca fascicularis)

Successful treatment of one Grade IlI and two Grade IV pressure sores on two female Macaca fascicularis, subsequent to a T11 hemilaminectomy and left spinal cord hemisection, was achieved through a combined strategy of wound care, diet, and husbandry. Wound care consisted of early and thorough debridement of all necrotic tissue, initial twice daily cleaning with an iodine scrub and application of a multi-ingredient ointment. Tissue hydrolyzer, a drying agent, vitamin E, ground selenium, and topical antibiotics were applied to the wound during the respective 45- and 46-day courses of treatment. Oral antibiotics were administered; vitamins C and E, and selenium were increased in the diet. No infection occurred and both animals recovered fully to complete the study. Importantly, pressure sores in subsequent study animals were prevented by post-operative padding of the perch with towel-covered foam and placement of a wheelchair cushion on the floor of the cage.     

High Definition Oscillometry: a novel technique for non-invasive blood pressure monitoring in the cynomolgus monkey (Macaca fascicularis)

Background  Current approaches for accurate blood pressure determination rely predominantly on invasive techniques. High Definition Oscillometry (HDO) was evaluated as a potential non-invasive approach for accurate blood pressure recordings in cynomolgus monkeys.
Methods  In conscious animals, systolic, diastolic, mean arterial blood pressure (MAP) and pulse/minute were determined 15 times within approx. 9 minutes per individual. This session was performed during 3 consecutive days. Anaesthesia induced hypotension was controlled simultaneously with HDO and telemetry as reference.
Results  Repeated measurements were highly reproducible. After procedural habituation, mean MAP was 96.2 ± 13.7 mmHg in males and 86.9 ± 4.3 mmHg in females. Mean intraindividual coefficients of variation ranged between 10.8% and 2.4% depending on the session and parameter. Values determined by HDO corresponded to those reported for invasive techniques.
Conclusion  Our results demonstrate, using telemetry as reference, the accuracy of HDO-based non-invasive blood pressure measurements in macaques to detect drug-related cardiovascular changes.     

Endometrial and cervical polyps in 22 baboons (Papio sp.), 5 cynomolgus macaques (Macaca fascicularis) and one marmoset (Callithrix jacchus)

Background  Endometrial and cervical polyps are masses of endometrium or cervical epithelium that bulge into the uterine or cervical lumen. The physiopathology and contributing factors of endometrial polyps development are still unknown.
Methods  Clinical and pathology records of 28 non-human primates with histologically confirmed endometrial and cervical polyps were reviewed. Twenty-one baboons with endometrial polyps were evaluated for age at diagnosis, body weight, menstrual cycle length, presence of endometriosis and adenomyosis and number of offspring, cesarean sections, and stillbirths.
Results  Endometrial polyps in baboons were associated with increased age, decreased menstrual cycle lengths, endometriosis, and decreased parity. No differences were found for weight, adenomyosis, or number of cesarean sections or stillbirths.
Conclusions  Baboons are a promising model for the study of endometrial polyps because of their similarity to humans in both the development of endometrial polyps and association of many of the same risk factors.     

Regional histomorphology of cancellous bone in Macaca fascicularis

The structural and dynamic characteristics of cancellous bone from biopsy sites representing different degrees of weight bearing were quantified following double fluorochrome labeling of adult male Macaca fascicularis. A strong correlation of bone formation rate was found between the humerus, tibia, and iliac crest within the same individual. There was no significant correlation between differing biopsy sites for the structural measures of bone. The coefficient of variation for bone formation rate at different sites from the same animal was comparable to the coefficient of variation for different animals measured at the same biopsy site. The present study suggests that any accessible site of cancellous bone will yield a representative measure of bone formation rate, but that structural measures are not generalizable between different sites. © 1996 Wiley-Liss, Inc.     

Familial early onset macular degeneration in cynomolgus monkeys (Macaca fascicularis)

The mode of inheritance of macular degeneration was determined with 45 cynomolgus monkeys (18 females and 27 males) who were the offspring of one breeding male with typical macular degeneration. In the first generation, 27 offspring (10 females and 17 males) were born from mating between the macular degeneration-affected founder male and 5 normal female breeders. Among them, 18 monkeys (9 females and 9 males) were judged as having macular degeneration (affected). Next, the distribution of affected offspring was examined with 18 offspring who were born from 3 different mating pairs, normal vs normal, affected vs normal and affected vs affected, when they became 2 years old. All of the 9 monkeys (4 females and 5 males) obtained from the 2 pairs of normal vs normal were normal. On the other hand, 6 affected monkeys (3 females and 3 males) were detected in 8 offspring from the mating pair of affected vs normal, and the single offspring produced by the mating pair of affected vs affected was affected. These results showed that this degeneration must be early onset familial macular degeneration controlled by autosomal dominant gene(s).     

Congenital bronchiolo-alveolar airway malformation in a cynomolgus macaque (Macaca fascicularis)

Pulmonary congenital anomalies in animals are rare. Previously reported malformations include accessory lung formation, pulmonary hypoplasia, pulmonary agenesis, and various forms of hamartoma. Congenital bronchiolo-alveolar airway malformation, a new entity, is described in a 1-day-old male cynomolgus macaque. This neonate experienced breathing difficulties shortly after birth and died while therapy was being administered. Grossly, the right lung was markedly increased in size, firm, and pink. Histopathologically, sections of right lung showed irregular bronchiole-like and alveolus-like structures. There was marked widening of alveolar septae by loosely arranged mesenchymal cells and many centrally located capillaries. Alveoli were lined by cuboidal epithelial cells. There were scattered islands of immature cartilage. A grossly enlarged lung containing bronchiole-like and alveolus-like structures, immature cartilage islands, and many capillaries within alveolar septae on histopathologic examination, is inconsistent with previously described congenital pulmonary anomalies in animals and humans.     

Pregnancy-induced sclerosis in the myometrial vessels of cynomolgus monkeys (Macaca fascicularis)

Sclerotic changes were found histologically in the myometrial vessels of 27 out of 33 cynomolgus monkeys (Macaca fascicularis). The sclerosis was composed of fibrous proliferations and intimal thickening. These changes were not observed in nulliparous cases, but were found only in multiparous ones. The findings suggest that the sclerotic changes in the myometrial vessels of cynomolgus monkeys are a pregnancy-induced phenomenon.     

Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report

BACKGROUND: Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans. It has also been reported to progress to irreversible airway obstruction. This disease has been reported in dogs and horses, but not in non-human primates. METHODS: Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist. RESULTS: Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways. There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening. CONCLUSIONS: This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic bronchitis-like features in a M. mulatta.     

Objective measures of health and well-being in laboratory rhesus monkeys (Macaca mulatta)

BACKGROUND: Non-human primates are an invaluable part of biomedical research. Strict regulations insure animals have a maximum likelihood of well-being and optimum health during the course of experimental procedures. Objective assessment of well-being is a critical component of these assurances. METHODS: Here we describe an objective and quantitative system we used to identify two well-being concerns in laboratory rhesus monkeys (Macaca mulatta). We provide a series of indicators for use by laboratory personnel to promote laboratory primate well-being. The indicators measure (1) potentially life threatening clinical concerns, (2) developing clinical issues, (3) atypical behaviors, and (4) laboratory performance. We include specific criteria to facilitate veterinary intervention. RESULTS: The assessment, applied to two case studies reported here, enabled swift veterinary intervention returning the animals to a healthy state. CONCLUSIONS: The measures described here provide a battery of observable and objective measures across multiple dimensions that can further ensure both excellent science and veterinary care.     

Ependymal cyst in a cynomolgus macaque (Macaca fascicularis)

Background A focal hypointense intracranial lesion was detected by magnetic resonance imaging in the right caudal occipital lobe of the cerebrum in an asymptomatic cynomolgus macaque (Macaca fascicularis). Results Following euthanasia, gross evaluation of the lesion revealed a 1 cm diameter, wedge‐shaped intracranial cavitation without apparent communication with the ventricles. Histologically, the lesion was lined by ciliated cuboidal to low columnar epithelium that showed immunopositivity for cytokeratin, S‐100, and GFAP. Conclusion Based upon the gross, histologic, and immunohistochemical findings, this lesion was classified as an ependymal cyst. In the human patients, ependymal cysts are benign, non‐infectious, non‐inflammatory lesions of the central nervous system that are believed to originate from aberrant migration of ependymal cells during development. To our knowledge, this is the first report of an ependymal cyst in a non‐rodent veterinary species and the first report of a benign intracranial cyst of any classification in a non‐human primate.     

Novel hyperprolactinemia and hyperprolactinemic anovulation model using the cynomolgus monkey (Macaca fascicularis)

We investigated the relationship between the menstrual cycle and hormone levels in cynomolgus monkeys, and developed a sulpiride-induced hyperprolactinemic anovulation model. On this study, we demonstrated the usefulness of the commercial human prolactin immunoradiometric assay kit for the measurement of cynomolgus monkey serum samples. In the normal menstrual cycle of the cynomolgus monkey, serum prolactin concentrations were not significantly different between luteal and follicular phases. However, the serum prolactin concentration tended to elevate at the ovulation stage. And serum progesterone began to increase after an estradiol surge, and then declined before the ensuing preovulatory rise in estradiol. During the luteal phase, the serum concentration of progesterone was elevated. Moreover, we aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in the cynomolgus monkey. The serum prolactin level gradually increased during the twice-daily administration of sulpiride, and the drug produced as big a response at 5 mg/kg. In this study, the length of the menstrual cycle was approximately 29 days in normal cynomolgus monkeys. When treatment with sulpiride had been continued for more than one month, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle, and the absence of ovulation was recognized by laparoscopy. Moreover, in this period we found that amenorrhea or anovulatory menstruation in the experimental animals. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. Our findings suggest that the cynomolgus monkey is useful as a endocrinological model that uses prolactin as a parameter and as an anovulatory model; thus, it could be a useful model for the hyperprolactinemic amenorrhea and/or anovulation seen in humans.     

The cynomolgus monkey (Macaca fascicularis) is the best animal model for the study of steroid glucuronidation

Intense research efforts performed during the past decade clearly established the major role of glucuronidation and uridine-diphospho-glucuronosyltransferase (UGT) enzymes for steroid metabolism in humans. However, a clear understanding of the physiological importance of this metabolic process requires in vivo studies. Numerous evidences ascertain that simians are the most appropriate animal models for such studies. Indeed human and monkey have a similar pattern of steroidogenesis, unlike common laboratory mammals such as rat or mouse. Furthermore, human and monkey are unique in having high levels of circulating androsterone glucuronide and androstane-3-diol glucuronide (3-Diol-G). In addition, characterization of eight monkey UGT proteins demonstrated the similarity of their conjugation activity toward steroid hormones. Like human ones, monkey enzymes are expressed in steroid target tissues, where they preferentially glucuronidate androgen and estrogen metabolites. In monkey tissues, immunohistochemical studies demonstrated that UGT2B proteins are expressed in a cell-type specific manner in ovary and kidney, where they control androgens and aldosterone inactivation. These results identify the cynomolgus monkey as an appropriate animal model for the determination of cellular localization of UGT enzymes in steroid target tissues and for the identification of endogenous or exogenous stimuli affecting steroid glucuronidation.     

Alteration of the menstrual cycle in baboons placed on tethering devices and moved to individual housing--a stress model for a follicular phase defect

BACKGROUND: During an attempt to identify endocrine characteristics in the baboon that would more precisely predict ovulatory status for assisted reproductive techniques, we observed severe alterations in the menstrual cycle length upon introducing an environmental stress. This environmental stress involved moving animals from their baseline gang cage environment to individual indoor caging and placing them on a tethering apparatus. METHODS: Five adult female baboons were followed for changes in sex skin indicative of menstrual cycle timing and move from outdoor gang gages to individual indoor cages during the early follicular phase of their cycle. A tether device including a surgically implanted cannula was then installed to facilitate daily blood draws without sedation. Radioimmuonoassays were performed to monitor serum estradiol levels and lapraroscopic surveillance was used to confirm time of ovulation. RESULTS: Complete data sets were collected from four of the female baboons. In each case, a prolongation of the menstrual cycle was noted either during the cycle during which the females were moved to indoor caging or during the cycle immediately following the move. This prolongation was isolated to the follicular phase of the affected cycle. CONCLUSIONS: We conclude that otherwise normal handling procedures, including movement to new caging, and/or installation of a tether device, can impart a stress effect on reproductively cycling adult female baboons, such that folliculogenesis is delayed.     

A gonadotropin-releasing hormone agonist and an activator of protein kinase C improve in vitro oocyte maturation in Macaca fascicularis

Cynomolgus monkey oocytes were recovered from follicles > 1,000 μm in diameter at day 8 in gonadotropin-stimulated cycles and cultured in vitro for 2 days. Germinal vesicle breakdown (GVBD) occurred in 30.3% of control oocytes (n = 76) compared with 54.0% and 55.0% of oocytes cultured in presence of a gonadotropin-releasing hormone agonist (GnRHa), Buserelin (n = 50), or a protein kinase C activator, 1-oleoyl-2-acetyl-rac-glycerol (OAG, n = 40), respective (P < .01). As similar results were obtained using OAG or Buserelin, we hypothesize that the action of Buserelin upon the primate oocyte is protein-kinase-C dependent. The possible effects of Buserelin on in vivo oocyte maturation have to be detemined.