The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

Multivariate analysis of hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis) aged less than a year

Hematological and serum biochemical data obtained from 91 laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged 11 to 362 days were analyzed by the discriminant analysis. All animals used had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. The examination items were as follows: red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), white blood cell count (WBC), glutamic oxaloacetic transaminase activity (GOT), glutamic pyruvic transaminase activity (GPT), total protein concentration (TP), albumin concentration (ALB), albumin-globulin ratio (A/G), blood urea nitrogen (BUN), glucose concentration (GLU), total cholesterol concentration (TCHO), free cholesterol concentration (FCHO), triglyceride concentration (TG), alkaline phosphatase activity (ALP) and calcium concentration (Ca). The animals were divided into four groups (A: Suckling infants, less than 176 days old. B, C, D: Weanlings and juveniles, 121 to 220 days old, 221 to 280 days old, and 281 to 362 days old, respectively). Discrimination was possible among these four groups on the basis of the Mahalanobis' generalized distance. Regarding the canonical discriminant analysis (discriminant analysis with reduction of dimensionality), discrimination was possible. The suckling infant group could be discriminated from the juvenile groups by the first canonical variate. Concerning the juvenile groups, age was highly correlated to the value of the second canonical variate.2+ Judging from an approximate relative eigenvector value for the second canonical variate, the effective discriminant variables were WBC, TP, ALB, A/G, FCHO, TG, and ALP. It can be concluded that these eight parameters are important and useful for monitoring the physiologicals conditions of growing juvenile monkeys.     

Reference values of hematological, serum biochemical and hormonal examinations in female cynomolgus monkeys (Macaca fascicularis) of feral origin

Blood samples were collected from clinically healthy female cynomolgus monkeys imported from Indonesia, the Philippines and Malaysia. These animals were maintained under uniform environmental conditions for four to five years. The blood samples were examined for their hematological, serum biochemical and hormonal values. The ranges of the values as well as their arithmetic means and standard deviations have been tabulated with respect to each examination item.     

Discriminant analyses for pregnancy-related changes in hematological and serum biochemical values in cynomolgus monkeys (Macaca fascicularis)

Hematological and serum biochemical data obtained from 45 non-pregnant and 142 pregnant cynomolgus monkeys (Macaca fascicularis) were analyzed by discriminant analyses. All animals used had been reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. The examination items were as follows: red blood cell count(RBC), hematocrit value(Ht), hemoglobin concentration(Hb), mean corpuscular volume(MCV), white blood cell count(WBC), total protein (TP), albumin (ALB), glucose (GLU), total cholesterol (TCHO), free cholesterol (FCHO), triglyceride (TG), and albumin-globulin ratio (A/G). The pregnant animals were divided into four groups according to their gestation ages (Group I: 1-40 days; II: 41-80 days; III: 81-120 days; and IV: more than 121 days). During pregnancy period (Groups II, III and IV), significant decrease of TP, ALB, TCHO, FCHO and TG was observed. RBC, Ht and Hb decreased in the last of the four periods of pregnancy (Group IV). Discrimination was possible between each of these four pregnant groups and the non-pregnant group on the basis of the Mahalanobis' generalized distance. To clarify the relationship among groups, canonical discriminant analysis (discriminant analysis with reduction of dimensionality) was carried out. As a result, the non-pregnant group and the pregnant I group could be clearly discriminated from the other pregnant groups (II, III, and IV) by the first canonical variate. Judging from the relative eigenvector value of each variable for the first canonical variate, the effective discriminant variables were RBC, Ht, Hb, MCV, TP and A/G.(ABSTRACT TRUNCATED AT 250 WORDS)     

Normal serum biochemical and hematological parameters in Macaca fascicularis.

The effects of age, sex, pregnancy, were analyzed and data from fasted and fed animals were compared in a population of cynomolgus macaques. No significant sex effects were observed for biochemical values and no changes were found in male hematological parameters in relation to age. Most values of females during pregnancy were within normal ranges. Comparison between fed and fasted animals showed that several biochemical parameters (e.g., ALT, glucose, CPK, LDH) and several hematological parameters (e.g., monocytes, eosinophils, basophils, hemoglobin, MCV, MCHC, and MCH) were affected by food intake.     

Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis)

Depressive disorders are prevalent, costly, and poorly understood. Male rodents in stress paradigms are most commonly used as animal models, despite the two-fold increased prevalence of depression in women and sex differences in response to stress. Although these models have provided valuable insights, new models are needed to move the field forward. Social stress-associated behavioral depression in adult female cynomolgus macaques closely resembles human depression in physiological, neurobiological, and behavioral characteristics, including reduced body mass, hypothalamic-pituitary-adrenal axis perturbations, autonomic dysfunction, increased cardiovascular disease risk, reduced hippocampal volume, altered serotonergic function, decreased activity levels, and increased mortality. In addition, behaviorally depressed monkeys also have low ovarian steroid concentrations, even though they continue to have menstrual cycles. Although this type of ovarian dysfunction has not been reported in depressed women and is difficult to identify, it may be the key to understanding the high prevalence of depression in women. Depressive behavior in female cynomolgus monkeys is naturally occurring and not induced by experimental manipulation. Different social environmental challenges, including isolation vs. subordination, may elicit the depression-like response in some animals and not others. Similarly, social subordination is stressful and depressive behavior is more common in socially subordinate monkeys. Yet, not all subordinates exhibit behavioral depression, suggesting individual differences in sensitivity to specific environmental stressors and enhanced risk of behavioral depression in some individuals. The behavior and neurobiology of subordinates is distinctly different than that of behaviorally depressed monkeys, which affords the opportunity to differentiate between stressed and depressed states. Thus, behaviorally depressed monkeys exhibit numerous physiological, neurobiological, and behavioral characteristics same as those of depressed human beings. The nonhuman primate model represents a new animal model of depression with great promise for furthering our understanding of this prevalent and debilitating disease and identifying novel therapeutic targets.     

Effects of primaquine on serum biochemical and hematological parameters in anesthetized Macaca fascicularis

Primaquine phosphate treatment (0.5 mg/kg/day, per os [p.o.], 14 days) significantly increased values for serum sodium, potassium, and uric acid, while calcium levels were decreased in male Macaca fascicularis. Serum values returned to baseline (pretreatment) levels by 30 days following primaquine treatment.     

Age-related changes in hematological and serum biochemical values in cynomolgus monkeys (Macaca fascicularis) bred and reared using the indoor individually-caged system

Blood samples were collected from 1000 or more apparently healthy cynomolgus monkeys of different ages. All the monkeys had been bred and reared under uniform environmental conditions at the Tsukuba Primate Center for Medical Science, NIH, Japan. Biochemical and hematological data were determined with these samples. The calculated arithmetic means and standard deviations were listed for each item of measurement performed (Tables 3, 4 and 5). The correlation between the obtained value and the age was analyzed using a statistical significance level of 0.1% (Table 6). It was revealed that hemoglobin concentration, mean corpuscular volume, alubuminglobulin ratio and triglyceride concentration increased with age, whereas red blood cell count and serum alkaline phosphatase activity decreased with age in both sexes.     

Hematological and serum biochemical effects of nursing on the mother in cynomolgus monkeys (Macaca fascicularis)]

The effects of nursing on maternal hematological and serum biochemical values were analyzed in cynomolgus monkeys reared in indoor cages at Tsukuba Primate Center. In our breeding system, infants are usually separated from their mothers at the age of 121 to 180 days. Mother monkeys of such infants were studied hematologically and biochemically (Group B), as were mother monkeys who happened to have nursed their infants past 181 days after parturition (Group A). During the period with their infants, mother monkeys in the latter group showed lower white blood cell counts (WBC) and higher red blood cell counts (RBC), hematocrit values (Ht) and blood urea nitrogen concentrations (BUN) than the mother monkeys who had been separated from their infants. Also, serum calcium concentrations (Ca) were decreased with prolonged nursing periods, indicating that lactation by the mother monkey probably continues even for a period from 181 days to about one year after parturition if she nurses her infant. Lactation during this period may accelerate hematogenesis and protein metabolism in the mother monkey.     

Weight and size of the placenta in cynomolgus monkeys (Macaca fascicularis).

A gross anatomical survey of the placental development was carried out in 24 cynomolgus monkeys (Macaca fascicularis) of 4, 5, 6, 7, 8, 9, 10, 15 and 20 weeks of gestational age. Eight of the 24 placentas examined were found to be single discoidal and the remaining 16 bidiscoidal. The weight and size of placentas of each animal were measured. The average weight of the 20th week placentas was about 94 times heavier than that of the 4th week ones; the average diameter of the former was about 5 times larger than that of the latter.     

Normal serum biochemical, hematological, and EKG parameters in anesthetized adult male Macaca fascicularis and Macaca arctoides

Selected serum enzymes, cholesterol, triglycerides, glucose, uric acid, protein, albumin, bilirubin, BUN, hematology, and electrocardiograms (EKG) were obtained from adult male cynomolgus (Macaca fascicularis) and adult male stumptailed (Macaca arctoides) macaques. Serum alkaline phosphatase, uric acid, albumin, bilirubin, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and monocytes were significantly lower in the cynomogus monkeys. This relationship was reversed for serum levels of triglycerides, phosphorus, red blood cell counts and lymphocytes. EKG analysis revealed significantly increased PR interval and QRS wave duration in the cynomolgus species. However, there were no differences in heart rate. Right axis deviation was common in both species.     

Presence of antibody to Cyno-EBV in domestically bred cynomolgus monkeys (Macaca fascicularis).

The presence of an antibody to the Cyno-EBV was studied with Cyno-EBV bearing cell line (Ts-B-9) as antigen in 186 domestically bred cynomolgus monkeys (Macaca fascicularis) ranging in age from birth to 18 yr as well as in 20 adult (older than 10 yr) cynomolgus monkeys of wild origin. The maternal antibody to Cyno-EBV persisted for less than four mo after birth in infant monkeys. After one yr of age, all the domestically bred monkeys were consistently positive for Cyno-EBV. In the monkeys of wild origin also, the anti-Cyno-EBV antibody was detected without exception. Antibody titers in adult monkeys varied from 1:80 to 1:640.     

Relationship between fetal position and stillbirth in the cynomolgus monkeys (Macaca fascicularis): retrospective analysis

Retrospective analyses were made on the relationship between fetal position and stillbirth, using 703 pregnant cynomolgus monkeys. Incidence of the breech position was 59.1% to 12 weeks of gestation. The rate decreased stepwise to 10.4% on the day before delivery. Twenty-one (65.6%) of 32 monkeys who were in the breech position on the day before delivery had stillbirths, whereas only one stillbirth occurred among 275 monkeys whose fetuses were in the cephalic position.     

Spontaneous diabetes mellitus in cynomolgus monkeys (Macaca fascicularis)

Glucose tolerance tests were performed with fourteen cynomolgus monkeys. They were divided into two groups with regard to the serum glucose level at the time of routine health-examination. Nine of them had normal glucose level (below 123 mg/dl, the normal group) and the other five monkeys exhibited hyperglycemia (the abnormal group). Fifty per cent glucose solution was administered into the saphenous vein at a dose of 4 ml/head. Blood samples were taken just before and 5, 10, 20, 30, 60 and 120 minutes after the glucose administration. K-value (K = 0.693/t 1/2 X 100) as the decreasing rate of serum glucose during from 5 to 60 minutes after the administration was calculated. Average K-value for eight monkeys of the normal group was 3.12 +/- 0.48. Both immunoreactive insulin level (IRI) and C-peptide immunoreactivity (CPR) increased just after the glucose administration and began to decrease 5 to 30 minutes after the administration in all the eight animals. Remaining one animal (No. 009) of the normal group showed 1.03 in K-value. For the abnormal group, K-value averaged 0.75 +/- 0.25. IRI was slightly higher in this group than in the 8 monkeys of the normal group. Furthermore, the abnormal group did not show any definite change of a certain trend in IRI and CPR. In conclusion, the former 8 monkeys were judged to be normal in the function of pancreatic beta-cells, and the latter 5 monkeys and No. 009 monkey were judged to be suffering from type II (noninsulin dependent) diabetes mellitus at different stages of the disease.     

The cerebral artery in cynomolgus monkeys (Macaca fascicularis)

Cerebral artery structure has not been extensively studied in primates. The aim of this study was to examine the cerebrovascular anatomy of cynomolgus monkeys (Macaca fascicularis), which are one of the most commonly used primates in medical research on human diseases, such as cerebral infarction and subarachnoid hemorrhage. In this study, we investigated the anatomy and diameter of cerebral arteries from 48 cynomolgus monkey brain specimens. We found three anatomical differences in the vascular structure of this species compared to that in humans. First, the distal anterior cerebral artery is single. Second, the pattern in which both the anterior inferior cerebellar artery and posterior inferior cerebellar artery branch from the basilar artery is the most common. Third, the basilar artery has the largest diameter among the major arteries. We expect that this anatomical information will aid in furthering research on cerebrovascular disease using cynomolgus monkeys.     

CD3 polymorphism in cynomolgus monkeys (Macaca fascicularis)

Cynomolgus monkeys were divided into two groups in terms of the reactivity of their lymphocytes with the FN18 monoclonal antibody, which is directed to the CD3 of rhesus monkeys. It was shown that 24 (12.2%) out of 196 monkeys did not have lymphocytes that reacted with the FN18, although T cells from those animals responded well to mitogenic stimulation. We have determined the nucleotide sequences of the CD3delta, CD3gamma, and CD3epsilon chains and found that two amino acids of the CD3epsilon chain of the FN18 non-reactive monkeys were different when compared with the FN18 reactive monkeys. Our results indicated that the CD3epsilon molecule of cynomolgus monkeys is polymorphic at the epitope level, which is recognized by the FN18 monoclonal antibody.     

Medroxyprogesterone acetate, aggression, and sexual behavior in male cynomolgus monkeys (Macaca fascicularis).

Medroxyprogesterone acetate (MPA) is used clinically to treat male sex offenders, but there are conflicting reports about its effects on aggression. To investigate these matters in a nonhuman primate, four intact male cynomolgus monkeys were studied in a testing paradigm that involved the presence of a caged, aggression-arousing stimulus male either immediately before or during a pair-test with an ovariectomized, untreated female partner. After two 4-week periods of pretreatment baseline, males received weekly injections of 40 mg MPA either alone (two 4-week treatment periods) or in combination with testosterone replacement with sc implants (one period) and additional daily injections of 2 mg testosterone propionate (two periods). MPA was then withdrawn while testosterone replacement continued (three periods). The testing paradigm was effective in maintaining aggression, especially male-male aggression, for many months. Male-male aggression increased with MPA treatment, and increased further with testosterone replacement, whereas male-female aggression tended to change in the opposite direction. As in earlier studies, MPA decreased both plasma testosterone and male sexual activity, but restoring plasma testosterone levels in treated males failed to restore their sexual activity. MPA therefore has behavioral effects that are not mediated primarily by its suppression of circulating androgens.     

Cryopreservation of spermatozoa from cynomolgus monkeys (Macaca fascicularis)

Three egg-yolk diluents, which have been used successfully in cryopreservation of human spermatozoa, were compared for their ability to protect macaque semen against cryodamage. TEST (Tes + Tris + egg yolk), TEST with 20% skim milk (TSM), and egg yolk-citrate (EYC), each with 3 or 5% glycerol were compared using 12 ejaculates from 6 male cynomolgus macaques. Computer-aided analysis of sperm motion was used to determine the percentage motility (%M), curvilinear velocity (VCL), and linearity (LIN) of spermatozoa after thawing. The supravital stain Hoechst 33258 and a fluoresceinated pea lectin were used to determine the % of viable spermatozoa with intact acrosomes. TSM and TEST were superior to EYC in terms of % M and of % viable, acrosome-intact spermatozoa. TSM and TEST produced equivalent VCL and LIN values, while EYC had clearly reduced VCL and LIN. There were no interactions between diluent and glycerol level. The 3% glycerol level gave superior results to 5% glycerol for %M. EYC, which is widely used for cryopreservation of human spermatozoa, was not suitable for cynomolgus monkey semen. Artificial insemination with semen cryopreserved in TSM resulted in a healthy, full-term infant.     

Hematology and serum chemistry parameters in juvenile cynomolgus monkeys (Macaca fascicularis) of Mauritius origin: comparison between purpose-bred and captured animals

Background  The vast majority of non-human primates used for experimental activities are purpose-bred. However, in case of particular procedures or specific projects, it may still be necessary to use animals captured in the wild.
Methods  Sixty cynomolgus monkeys were randomly selected on the basis of breeding origin, and assigned to two groups, each of fifteen males and fifteen females. Analyses included the most frequently investigated parameters for hematology, coagulation, and biochemistry.
Results  Differences were observed in some parameters, particularly in eosinophils, basophils and monocytes, and in fibrinogen, total protein, globulins, alanine amino-transferase, creatinine, aspartate amino-transferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, iron, potassium, and phosphorus.
Conclusions  Some values in the cynomolgus monkey may show significant differences according to the breeding background of the animals. Only data obtained from animals of similar origin have to be compared, to avoid misinterpretation during the evaluation of the experimental results.     

Persistent cloaca in a cynomolgus monkey (Macaca fascicularis).

A persistent cloaca was found to occur in a 15-year-old female cynomolgus monkey. This is the first case reported in a nonhuman primate. The embryological basis of this anomaly is discussed, and pertinent anatomical findings in this animal are reported which demonstrate the embryologic defect.