Cercopithecus Aethiops Sabaeus Research Articles

The Third Branch of the Main Trunk of the Left Coronary Artery in Cercopithecus aethiops sabaeus. Is the Nonhuman Primate Model Appropriate?

The aim of this study was to investigate the morphometry of branching patterns of the main trunk of the left coronary artery (MT of LCA) in nonhuman primates, and comment on the current nomenclature. The biometric study was performed using stereomicroscopic dissection of hearts of healthy and fertile nonhuman primates (Cercopithecus aethiops sabaeus) of both sexes. Our results reveal that the MT of LCA terminates in a bifurcation into the anterior interventricular branch (AIB) and the circumflex branch (CB) (74.6%), trifurcation into the AIB, CB, and diagonal branch (DB) (23.6%), or occasionally quadrifurcation into the AIB, CB, and two DBs (1.8%). This is similar to the case in humans. Furthermore, two morphological aspects of the DB spatial distribution, in addition to its branching pattern, resemble the DB in humans. Myocardial bridges observed over the DB in the Cercopithecus aethiops heart further contribute to the similarity with humans. The resemblance of the DB and its branches to their human counterparts make them a suitable model for experimental study on coronary circulation.

Hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in African green monkeys (Cercopithecus aethiops sabaeus). Its use in non‐clinical toxicological studies

The purpose of this study is to better characterize the hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in young adult Cercopithecus aethiops sabaeus of both sexes. The rhesus and cynomolgus monkeys are widely used as experimental primate models. However, only few articles have been published testing toxicological effects of pharmaceuticals on African green monkey. The present study was carried out with the recompilation of all parameters recorded before the first drug administration in five sub-chronic or chronic toxicological studies performed on 66 Cercopithecus aethiops sabaeus, born in Cuba. This study provides hematological, biochemical, respiratory, cardiovascular and electroneurophysiological data for both choosing animals to be included into experiments and monitoring these parameters during the study. We conclude that this study provides valuable integrated data for determining the health status, including electroneurophysiological parameters, data not previously reported for this species, of the African green monkey.

The effect of c-Kit inhibition on mast cells in skin, colon, and lung (39.46)

Abstract Stem Cell Factor (SCF) signaling via its receptor tyrosine kinase, c-Kit, is vital for mast cell development, function and survival. The effect of inhibition of c-Kit function using subcutaneous administration of a specific blocking monoclonal antibody weekly for up to 28 days was examined in African Green monkeys (Cercopithecus aethiops sabaeus). Treatment-related effects on mast cell populations were evaluated in tissue samples collected from wounded skin and colon biopsies on days 0, 7, 14, 21, and 28 (colon only) and skin, lung, and gastrointestinal tract collected at necropsy on day 28. Mast cells were visualized by Astra blue staining and immunohistochemistry for CD117, tryptase, and/or chymase. Specific c-Kit inhibition resulted in depletion of mast cells in unchallenged skin, colon, and lung after 28 days. Additionally, c-Kit antibody treatment inhibited the injury-induced expansion of dermal mast cells adjacent to wounded skin. Mast cells have been implicated as important mediators in a wide range of inflammatory diseases including asthma, rheumatoid arthritis, inflammatory bowel disease, and fibrosis. This is the first report of use of an antibody to deplete tissue mast cells in relevant organs in non-human primates.

Systemic and skin toxicity in cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti-epidermal growth factor receptor monoclonal antibody nimotuzumab

Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody (mAb) registered for treating head and neck tumours. The present study was designed to evaluate the systemic and skin toxicity of chronic intravenous administration of the h-R3 in a relevant species demonstrated by comparing the h-R3 binding affinity constants (Kd) in microsomal placental fractions from Homo sapiens and Cercopithecus aethiops monkeys using an EGF-Receptor radioligand competition assay. The Kd obtained for Nimotuzumab were 9.1x10-8 M for monkeys and 4.5x10-8 M for humans. Monkeys (n=18) were distributed into 3 groups with 3 animals of each sex in each group. Group I received saline; group II received 2.85 mg/kg of h-R3; and group III received 28.57 mg/kg of the h-R3, which represent 1 and 10 times the human dose, and they were weekly intravenously treated during 26 weeks. During the study there were no deaths. Electroneurophysiological, sanguine chemistry and haematological results did not evidence alterations. Areas of haematomas, probably related with the administration procedure, were observed at the administration zones of all animals. The electrocardiography study showed at the end of the study a slight increase in the cardiac frequency of 4 treated animals without others signs. Unexpectedly, skin biopsies and a detailed clinical inspection of the animals did not detect the presence of cutaneous rash or any other skin toxicity sign reported for the majority of the anti-EGF-R monoclonal antibodies. It is concluded that doses up to 28.5 mg/kg of h-R3, intravenously administered during 26 weeks to Cercopithecus aethiops monkeys, do not produce considerable toxic effects.

PrimaTB STAT-PAK assay, a novel, rapid lateral-flow test for tuberculosis in nonhuman primates.

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP.

Secondary sexual coloration and CSF 5‐HIAA are correlated in vervet monkeys (Cercopithecus aethiops sabaeus)

Identifying indirect markers of the physiology or neuroendocrinology of a primate can provide a powerful tool to scientists. Anecdotal descriptions and recent experimental evidence suggests that the colorful sexual skin in adult male vervet monkeys (Cercopithecus aethiops sabaeus) might be sensitive to social changes, including dominance relationships, which could be related to serotonergic activity. The present study examined whether individual differences in scrotal coloration were related to cisternal cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid (CSF 5-HIAA) in a captive population of vervet monkeys. Darkly colored males had relatively higher CSF 5-HIAA concentrations than paler males, and scrotal color hue was also related CSF 5-HIAA concentrations. These preliminary data are compatible with the hypothesis that scrotal coloration serves as an indirect marker of serotonergic activity. These findings suggest that color assessments might be useful to consider for study design, as well as for animal welfare and captive management.

Artificial colour treatment mediates aggression among unfamiliar vervet monkeys (Cercopithecus aethiops): a model for introducing primates with colourful sexual skin

AbstractAggression and agonism typically accompany the initial interactions exchanged between unfamiliar primates. As a part of a larger study examining the social function of scrotal colour in vervet monkeys (Cercopithecus aethiops sabaeus), this paper offers experimental data to show how scrotal colour can influence aggression, and how artificial colour treatment can be used as an effective tool for managing aggression. Study animals were 81 vervet monkey pairs composed of 162 similarly-sized, unfamiliar adult males originating from non-adjacent parishes in Barbados. Non-contact and contact aggression were recorded on a continuous basis during 90 minute introductions. The main effects of the Test male scrotal colour, Stimulus male colour, and the interaction of the Test male and Stimulus male colours were not significant predictors of non-contact aggression. The effects of scrotal colouration of the Test male and Stimulus male were not significant predictors of contact aggression either, but there was a significant interaction effect; pairs of males with similar scrotal colour engaged in contact aggression more often than pairs of males differing in colour. Painting the scrotum dark led to more aggression when these males were paired with dark coloured males and less aggression when these males were paired with pale coloured males. These findings suggest a practical and inexpensive means of reducing the likelihood of aggression when introducing new animals. These results may also be applicable for other taxa that have colourful sexual skin, such as mandrills, drills, talapoins, patas monkeys, and many guenon species.

Plasma cytokine levels: Relationship to early maternal interactions in socially reared vervet monkeys ( Cercopithecus aethiops sabaeus)

Plasma cytokine levels: Relationship to early maternal interactions in socially reared vervet monkeys ( Cercopithecus aethiops sabaeus)

Multiple dose toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 intravenously administered to Cercopithecus aethiops sabaeus monkeys.

The h-R3 is a humanized growth factor receptor monoclonal antibody (mAb) in development for the treatment of head and neck tumours in which malignant cells overexpress the Epidermal Growth Factor receptor. The present study was designed to evaluate the toxicity of repeated intravenous doses of the h-R3 mAb in a relevant species demonstrated by the avidin-biotin-peroxidase immunohistochemical (IHC) technique in skin biopsy samples from three Cercopithecus aethiops sabaeus monkeys (green monkeys). Additionally, 18 green monkeys were daily intravenously treated during 14 consecutive days. Monkeys were distributed into three experimental groups with three animals of each sex in each group. Group I received saline solution and served as control group; group II received 2.85 mg/kg of h-R3 mAb; and group III received 11.4 mg/kg of the h-R3 mAb. During the study there were no deaths, neither pathological clinical signs, or variations in the corporal weight curve. The electroneurophysiological and sanguine chemistry results did not evidence alterations related to the assay substance. Areas of haematomas, haemorrhages and inflammation, probably related with the administration procedure, were observed at the administration zones of all animals; this fact could also explain the increase in the neutrophil count of all animals at the end of the study. The electrocardiography study showed that in the 14 days of the study one female monkey, from the higher dose group, shifted its cardiac axis from +60 degrees to + 120 degrees; this finding could be interpreted as a right ventricular elongation due to the relative high daily administered volume. It is concluded that doses up to 11.4 mg/kg of h-R3, intravenously administered during 14 consecutive days to Cercopithecus aethiops sabaeus monkeys do not produce considerable toxic effects in the studied system.

289 In vitro effects of preserved or unpreserved antiglaucoma drugs on apoptotic marker expression by human trabecular cells

This study compares the effects of orbitofrontal and temporal neocortical lesions on the integration and expression of grooming, huddling, and spatial relationships in vervet monkeys (Cercopithecus aethiops sabaeus). Two groups of socially living vervet monkeys were observed in a large outdoor enclosure. Nine members (four male and five female) of one group received orbitofrontal lesions and seven members of the other group (four male and three female) were subjected to temporal neocortical lesions. Unoperated control subjects, matched for age, gender, and rank, received sham operations. Animals with orbitofrontal lesions groomed less, huddled less, and were less likely to be within 1 m of their nearest neighbor. Animals with temporal neocortical lesions also groomed less, but their huddling behavior and spatial relationships were not altered. These data suggest that when a single species of Old World monkey is observed in a similar setting using comparable behavioral units, the effects of orbitofrontal and temporal neocortical lesions on affiliative behaviors can be dissociated.

291 Dose repeated toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 (Theracim) by endovenous route in cercopithecus aethiops sabaeus monkeys

291 Dose repeated toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 (Theracim) by endovenous route in cercopithecus aethiops sabaeus monkeys

Sex differences in response to children's toys in nonhuman primates ( Cercopithecus aethiops sabaeus)

Sex differences in children's toy preferences are thought by many to arise from gender socialization. However, evidence from patients with endocrine disorders suggests that biological factors during early development (e.g., levels of androgens) are influential. In this study, we found that vervet monkeys ( Cercopithecus aethiops sabaeus) show sex differences in toy preferences similar to those documented previously in children. The percent of contact time with toys typically preferred by boys (a car and a ball) was greater in male vervets ( n=33) than in female vervets ( n=30) ( P<.05), whereas the percent of contact time with toys typically preferred by girls (a doll and a pot) was greater in female vervets than in male vervets ( P<.01). In contrast, contact time with toys preferred equally by boys and girls (a picture book and a stuffed dog) was comparable in male and female vervets. The results suggest that sexually differentiated object preferences arose early in human evolution, prior to the emergence of a distinct hominid lineage. This implies that sexually dimorphic preferences for features (e.g., color, shape, movement) may have evolved from differential selection pressures based on the different behavioral roles of males and females, and that evolved object feature preferences may contribute to present day sexually dimorphic toy preferences in children.

The finding of an inverse relationship between social dominance and feeding priority among pairs of unfamiliar adult male vervet monkeys (Cercopithecus aethiops sabaeus).

Dominance is often presumed to confer priority of access to resources. This study evaluated the relationship between two assessments of dominance: (1) social dominance, based on agonistic interactions and (2) feeding priority among pairs of unfamiliar adult vervet monkeys (Cercopithecus aethiops sabaeus) differing in scrotal colour, but matched for height, weight and testicular volume, during paired introduction experiments. Results of this investigation showed that neither size differences nor scrotal colour were predictive of feeding priority, and social dominance was inversely related to feeding priority. This finding demonstrates that different assessments of dominance can yield different outcomes even within the same primate taxon. I propose that male dominance rank may best predict access to resources when there is direct contest competition over a resource, which is not immediately exhaustible, whereas highly impulsive low ranking males may gain a competitive edge in scramble competitions for ephemeral and small resources.

Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates.

It is well established that gonadal hormonal manipulation results in morphologic changes in the rat hippocampus. The great similarities in the hippocampal formation between nonhuman primates and humans, as well as the differences in this structure between humans and rats, led to this investigation of whether hormonal manipulation in female subhuman primates influences pyramidal cell spine density in the CA1 hippocampal subfield, as it does in rats. African green monkeys (Cercopithecus aethiops sabaeus) were ovariectomized, and half of the animals received estrogen replacement therapy. One month later, the monkeys were killed. In the first group of experiments, pyramidal cell spines were analyzed on Golgi-impregnated material taken from the CA1 hippocampal subfield. In the second experiment, unbiased electron microscopic stereologic calculations were performed to estimate the volumetric density of spine synapses in the same hippocampal subfield. Analysis of the Golgi-impregnated material showed that the spine density of CA1 pyramidal cells is much lower in the ovariectomized animals than in ovariectomized and estrogen-replaced monkeys. The unbiased, electron microscopic, stereologic calculation confirmed the light microscopic observation. The volumetric density (number of spine synapses/microm(3)) of spine synapses was significantly lower (43.33%) in the ovariectomized animals than in ovariectomized and estrogen-replaced monkeys. Because the hippocampus is involved in specific mnemonic functions, this observation highlights the importance of hormone replacement therapy in postmenopausal conditions.

Social Impulsivity Inversely Associated with CSF 5-HIAA and Fluoxetine Exposure in Vervet Monkeys

Animal and human research suggests that the central serotonin system is involved in the inhibition of impulsive behavior. Two studies were designed to assess this relationship in male vervet monkeys (Cercopithecus aethiops sabaeus) using a standardized test of impulsivity in a social context: the Intruder Challenge. In the first study, an index of impulsivity in response to an unfamiliar adult male intruder (including latency to approach and aggressive and assertive interactions) was inversely correlated with levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (r = −0.33, p < .01, n = 138). The approach, but not aggressive, component of the Impulsivity Index was the primary contributor to this relationship (partial r = −0.27, p < .01). The second experiment compared responses to the Intruder Challenge after 9 weeks of daily treatment with fluoxetine (2 mg/kg, i.m.) or vehicle. Fluoxetine-treated subjects (n = 6) had significantly lower Impulsivity Index scores than controls (n = 12). The results from these two investigations provide evidence for serotonergic influences on social impulsivity.

Individual differences in response to a stranger: social impulsivity as a dimension of temperament in vervet monkeys (Cercopithecus aethiops sabaeus).

Social impulsivity in response to a stranger was assessed in male vervet monkeys (Cercopithecus aethiops sabaeus) using the Intruder Challenge Test. Vervets (N = 128, ages 3-18 years) were presented with an unfamiliar adult male at the periphery of the home enclosure. An index of impulsivity reflecting variation in the tendency to rapidly approach, engage, and challenge the intruder was derived from factor analysis of behavioral responses. Scale reliability (alpha = .84) and test-retest consistency (intraclass correlation = .83) were high, indicating that this index reliably and efficiently measures a stable aspect of temperament from impulsive to inhibited. Impulsivity scores peaked at age 4, when vervet males typically emigrate from the natal group. The highest ranking males in each group were more likely to score in the moderate range, whereas lower ranking males were more likely to score in the highest (impulsive) or lowest (inhibited) quartiles.

Individual differences in response to a stranger: Social impulsivity as a dimension of temperament in vervet monkeys (Cercopithecus aethiops sabaeus).

Individual differences in response to a stranger: Social impulsivity as a dimension of temperament in vervet monkeys (Cercopithecus aethiops sabaeus).

The transentorhinal cortex of the African green monkey: a combined light- and electron-microscopic study of calcium-binding protein containing neurons.

The transentorhinal cortex (TEC) is a primate-specific transition zone between the entorhinal allocortex and the temporal isocortex. Neurons in the lamina pre-alpha of TEC are known to be the first to develop intraneuronal changes in the course of Alzheimer's disease. In order to shed light on this important feature, we studied as yet unknown morphological and neurochemical characteristics of the TEC of the African green monkey (Cercopithecus aethiops sabaeus). Using light- and electron-microscopic immunocytochemistry, the distribution and morphology of neurons containing calcium-binding proteins were described and compared with those in the adjacent cortices. Light-microscopic analysis revealed that parvalbumin-containing neurons were distributed in all cortical layers. Calbindin-containing cells were fewer but also present in each layer. Calretinin-containing neurons were largely confined to the upper layers of the TEC. All three types of neuron showed pyramidal-like, multipolar and bipolar shapes; their dendrites were smooth or beaded. Ultrastructural studies revealed immunopositive somata with infolded nuclei and large amounts of cytoplasm. The somata were only sparsely innervated by symmetric synapses. Immunopositive dendrites were almost exclusively covered with immunonegative axon terminals establishing symmetric and asymmetric synapses. Immunopositive terminals established symmetric contacts with immunonegative dendrites and somata. Only occasionally, could synaptic contacts between immunopositive pre- and postsynaptic structures be observed. The comparison of neurons in the TEC and adjacent cortices revealed no striking differences. In summary, the morphological and neurochemical characteristics of TEC neurons as analyzed in our study do not provide an explanation for the early onset of neurodegenerative changes in the TEC.

Dynamic changes in cerebral glucose metabolism in conscious infant monkeys during the first year of life as measured by positron emission tomography

Recently, advances in spatial resolution have provided the opportunity to utilize positron emission tomography (PET) to examine local cerebral metabolic rates for glucose (lCMR glc) in large animals noninvasively, thereby allowing repeated lCMR glc measurements in the same animal. Previous studies have attempted to describe the ontogeny of cerebral glucose metabolism in anesthetized nonhuman primates using [ 18 F ]fluorodeoxyglucose (FDG) and PET. However, the use of sedation during the tracer uptake period may influence lCMR glc. This study was conducted to describe lCMR glc in conscious infant vervet monkeys ( Cercopithecus aethiops sabaeus) during the first year of life utilizing FDG–PET. Cross-sectional studies ( n=23) displayed lowest and highest lCMR glc in all structures at the 2–3 and 8–9 month age groups, respectively. The metabolic pattern suggested an increase in lCMR glc values between 2 and 8 months of age with decreased metabolism observed at 10–12 months of age in all regions. Peak lCMR glc values at 8 months were an average of 84±24% higher than values seen at the youngest age examined quantitatively (2–3 months). The regions of greatest and smallest increases in lCMR glc at 8 months were the cerebellar hemispheres (90%) and the thalamus (39%), respectively. Longitudinal analysis in 4 animals supported this developmental pattern, demonstrating the ability to detect changes in cerebral glucose metabolism within animals and the potential for FDG–PET in nonhuman primate models of brain maturation. By determining the normative profile of lCMR glc during development in monkeys, future application of FDG–PET will provide the opportunity to longitudinally assess the effects of environmental or pharmacological intervention on the immature brain.

18F]fluoro-β-fluoromethylene- m-tyrosine derivatives show stereo, geometrical, and regio specificities as in vivo central dopaminergic probes in monkeys

Stereo ( d and l), geometrical ( E and Z), and regiospecific (2-, 4-, and 6-[ 18F]fluoro) analogs of β-fluoromethylene- m-tyrosine (FMMT) have been investigated in adult vervet monkeys ( Cercopithecus aethiops sabaeus, n=12) in vivo with positron emission tomography (PET). Brain transport through the blood–brain barrier and central aromatic amino acid decarboxylase (AAAD)-mediated decarboxylation rates were established. Results show strict structural dependency of the kinetic behavior of radiofluorinated FMMT analogs, with the E-isomer exhibiting a higher specificity over the ( Z) geometrical counterpart for central dopaminergic structures. The 6-[ 18F]fluoro substituted l-( E)-FMMT was also favored over the 2- and 4-[ 18F]fluorosubstituted isomers in terms of their ability to localize in the same brain areas. The role of PET in drug development is also exemplified in this work.