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Dietary fat and hypercholesteremia in the Cebus monkey. II. Esterification and disappearance of cholesterol-4-C14.

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C(14). The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-(14)-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection. After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard. Monkeys were fasted before and after intragastric administration of cholesterol-4-C(14) in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption.

Animals↗

Experimental atherosclerosis in Cebus monkeys.

Atherosclerosis has been produced in Cebus monkeys by dietary means. This disease has been produced by feeding diets high in cholesterol and low in sulfur amino acids over periods of 18 to 30 weeks. Within 2 to 8 weeks this regimen caused the concentration of cholesterol in the serum to rise to 300 to 800 mg. per cent. The hypercholesterolemia could be largely prevented by feeding 1 gm. per day of dl-methionine or l-cystine as supplements to the diet. After the serum concentration had become elevated, it could be restored to normal by feeding 1 gm. of dl-methionine but only partially restored by 0.5 gm. of l-cystine daily. The vascular lesions were in the ascending aorta but extended from the valves of the left ventricle to the proximal portions of the carotid and femoral arteries. Minimal lesions have been observed in the coronary arteries. The aortic lesions were chiefly characterized by the presence of lipid-laden phagocytes and increase in collagen and elastic fibers. The lipids were in part cholesterol derivatives. Visceral cholesterolosis was not associated with this disease.

Animals↗

Comparative assessment of soy and milk protein quality in infant cebus monkeys.

Protein qualities of lactalbumin (L), casein (C), soy concentrate (SC), soy isolate (SI), and soy isolate plus 15.3 mg methionine/g protein (SIM) were investigated in a slope-ratio assay using 32, 8-wk old cebus monkeys. Growth (28 days) and nitrogen balance (NB) (days 19-28) data were evaluated in a multiple-regression format with nitrogen intake and body weight as the independent variables. Based upon growth, potencies compared to L were: C, 72.1; SC, 52.5; SI, 40.6; and SIM, 72.2. Based upon NB, comparable potencies were: C, 62.2; SC, 69.0; SI, 46.8; and SIM, 90.7. NB data showed that the potency of SC was significantly greater than SI and that methionine supplementation of SI improved it to a potency not distinguishable from the standard. The marked improvement from SI to SIM emphasizes the beneficial effect of sulfur amino acid supplementation of soy protein for an infant primate species.

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Area V4 in Cebus monkey: extent and visuotopic organization.

We used electrophysiological mapping and myeloarchitectural criteria in order to define the location, extent and visual topography of the fourth visual area (V4) in anesthetized and paralyzed Cebus monkey. Based on these criteria, the borders of V4 with surrounding areas were defined both on the dorsal and ventral cortical surfaces. In addition, to better visualize the visuotopic organization and to evaluate its regularity, we constructed bidimensional maps and projected the recording sites onto them. Area V4 has an almost complete representation of the binocular visual field with the lower visual field represented dorsally (V4d) and the upper field ventrally (V4v). We found this representation to be more extensive than those previously described. The representation of the central portion of the visual field is largely expanded in comparison with that of the periphery. This emphasis in central vision could be related with the involvement of V4 in the ventral stream of visual information processing. Receptive field size increases with increasing eccentricity, while cortical magnification factor decreases. The cortical magnification factor measured along isopolar lines is, on average, 1.5-2.0 times greater than that measured along the isoeccentric lines, suggesting the existence of a small anisotropy in central and peripheral V4.

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Sperm migration through the female genital tract of the New World monkey Cebus apella.

This study was designed to characterize sperm migration in the female genital tract of Cebus apella. Forty-eight cycles of eighteen females mated during the periovulatory period were studied. Eggs were searched for and spermatozoa were counted in segmental flushings of the genital tract performed in situ 1-7 h, 19-31 h, or 45-56 h after coitus. Of 14 eggs recovered, 8 were fertilized, thus assuring a reasonable normality of prefertilization phenomena in both males and females. A downward gradient of several orders of magnitude in sperm numbers was recognized from cervix to ampulla, particularly over the first interval. The population in the cervix and uterus decreased progressively between the first and last interval. Spermatozoa were recovered from the ampulla as early as 1 h after mating. Different trends were observed in the isthmus and ampulla. From the first to the last interval, sperm numbers decreased in the ampulla, but not in the isthmus. The number of spermatozoa recovered from the ampulla of the ovulatory side 1-31 h postcoitum was higher in postovulatory than in preovulatory monkeys, while in the nonovulatory side, recovery was similar in the two conditions. This findings suggests that the passage of spermatozoa up to the site of fertilization is under local control and is synchronized with ovulation. The pattern of sperm migration that emerges from these data bears similarities to the pattern in nonprimate species as well as distinctive features. A unique feature in common with the pattern in human is the early establishment of a fairly abundant and persistent sperm population in the ampulla.

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Muc1 and glycan expression in the oviduct and endometrium of a New World monkey, Cebus apella.

Cebus apella is a New World monkey that has a menstrual cycle of 18-23 days with implantation at approximately luteal Day 5. The aim of this study was to characterize by lectin- and antibody-labeling the distribution of Muc1 and associated glycans on the endometrial and oviductal epithelium during the luteal phase of the cycle. Endometrial histology showed a thin endometrium, with glands extending deeply into the myometrium. No obvious evidence of secretory differentiation in cells of either the superficial or the basal segments of glands could be obtained using a panel of antibodies and lectins that marked epithelial glycoprotein, and glycosylation changes observed in some other primate endometrial cycles were not observed in this study. Antibodies to human MUC1 were shown to cross-react with C. apella, and Muc1 was localized to the apical epithelial surfaces of both the endometrial and the tubal epithelium, with stronger expression in the latter. Again, no cyclic changes were noted. Antibodies specific to the isoform Muc1/Sec showed strong staining at the apical tubal epithelium, but no reactivity was detectable in the luminal epithelium of the uterus. This observation suggests differences between the two glycocalyces and could help to explain why C. apella embryos do not implant in this location.

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GABAergic retinocollicular projection in the New World monkey Cebus apella.

GABA immunoreactivity was examined in the retina of the New World monkey Cebus apella. Labeled cell bodies were identified as horizontal, bipolar, interplexiform, amacrine and a population of putative ganglion cells. To determine whether ganglion cells were immunoreactive to GABA, double-labeling experiments were performed using Fast Blue as retrograde neuronal tracer injected into the superior colliculus. Retinas containing FB-labeled ganglion cells were subsequently incubated with antiserum against GABA. Although retinocollicular ganglion cells were found in three different layers (ganglion cell layer, inner nuclear layer and inner plexiform layer), our experiments revealed GABA-positive ganglion cells only in the outer half of the ganglion cell layer.

Amidines↗

Effects of serotonergic and anticholinergic drugs in haloperidol-induced dystonia in Cebus monkeys.

In rodents, serotonin (5-HT) antagonists counteract behavioral and biochemical effects of neuroleptic drugs. Therefore, we have studied the effect of different 5-HT drugs and one anticholinergic drug in acute dystonia in five cebus monkeys chronically treated with haloperidol. Acute dystonia induced by subcutaneous injections of haloperidol was slightly reduced by the 5-HT antagonist methysergide (4.0 mg/kg), while mianserin, ketanserin, and ritanserin (R 55 667; a new selective and potent 5-HT receptor blocker) had no effect. This was contrasted by the marked antidystonic effect of the anticholinergic drug biperiden (0.05-1.0 mg/kg). The 5-HT agonist citalopram, a specific 5-HT uptake inhibitor, had no significant effect. It is concluded that 5-HT antagonists have no useful effect in neuroleptic-induced dystonia.

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Effects of benztropine on ketamine-induced behaviors in Cebus monkeys.

Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, causes a schizophrenic-like psychosis in normal volunteers and exacerbates psychotic symptoms in patients with schizophrenia. Recent work has shown that ketamine and other NMDA antagonists affect a range of behaviors in nonhuman primates, particularly those associated with motor and mental function such as attention and perception. Several lines of study also suggest that NMDA antagonists interact with cholinergic mechanisms. The effects of benztropine, an anticholinergic agent, on ketamine-induced behaviors were evaluated in a double-blind randomized test design in 20 Cebus monkeys. Benztropine (0.05, 0.1 and 0.25 mg/kg, i.m.) was injected 1 hour before ketamine (2.5 and 5.0 mg/kg, i.m.) administration. Behaviors scored for 90 minutes after ketamine administration included salivation, dystonia and reactivity to external stimuli. Benztropine almost completely blocked ketamine-induced hypersalivation, and partially ameliorated the dystonia syndrome by 50%, but did not affect ketamine-induced decreased reactivity to external stimuli. These results suggest that cholinergic mechanisms only moderately influence ketamine-induced central nervous system effects of motor dysfunction, and may not play a substantive role in the ketamine-induced deficit of reactivity to external stimuli, which involves a complex interaction of mental functions such as attention and perception, as well as motor behavior.

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Cytoarchitecture and musculotopic organization of the facial motor nucleus in Cebus apella monkey.

The architecture and musculotopic organization of the facial motor nucleus in the Cebus apella monkey (a New World primate) were investigated using histological techniques and a multiple labelling strategy, in which horseradish peroxidase-conjugated neuroanatomical tracers (CTB-HRP and WGA-HRP) and fluorescent tracers were injected into individual facial muscles. The facial motor nucleus was formed by multipolar motoneurons and had an ovoid shape, with its rostrocaudal axis measuring on average 1875 micro m. We divided the nucleus into four different subnuclei: medial, intermediate, dorsal and lateral. Retrograde labelling patterns revealed that individual muscles were innervated by longitudinal functional columns of motoneurons. The columns of the orbicularis oculi, zygomaticus, orbicularis oris, auricularis superior, buccinator and platysma muscles were located in the dorsal, intermediate, lateral, medial, lateral and intermediate subnuclei, respectively. However, the motoneuron columns of the levator labii superioris alaeque nasi muscle and frontalis muscle could not be associated with a specific subnucleus. The present results confirm previous studies regarding the musculotopic organization of the facial motor nucleus. However, we observed some particularities in terms of the relative size of each column in C. apella, which might be related to the functional and behavioral importance of each muscle in the particular context of this primate.

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Effects of inactivation of the lateral pulvinar on response properties of second visual area cells in Cebus monkeys.

1. In the present study, we investigated the influence of the pulvinar nucleus upon response properties of single cells in the second visual area (V2) of Cebus monkeys. The method used consisted of the inactivation of a portion of the lateral pulvinar by GABA injections while studying the response properties of cells in V2 at the same visuotopic location as that of the inactivation. 2. After GABA injection in the pulvinar, most cells in V2 (67%) showed changes in spontaneous and/or stimulus-driven activities. Contrary to the effect found with inactivation of the striate cortex, which promotes a reduction in the response of V2 neurons, we found that the main effect of pulvinar inactivation was an increment in stimulus-driven responses of V2 cells (39% of units studied). A reduction of responses was observed in 27% of units. 3. A change in orientation and/or direction selectivity was found in 91% of cells after inactivation of the pulvinar. Most commonly, the orientation selectivity of a neuron was decreased during pulvinar inactivation. 4. The inactivation results indicate that the pulvinar projections have a modulatory effect on the activity of V2 cells.

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Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

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Aortic aneurysm in a Cebus apella monkey with experimentally induced atherosclerosis.

The sudden death of a Cebus apella female (> 19 years old) on an experimental hyperlipidic diet during three years is described. The gross lesions were hemothorax, atherosclerotic plaques in the aortic curve, and an aneurysm in the ascending aorta. Histologically, an enlargement of the intima in the ascending aorta with hyalinization and a thrombus were observed. The media was thinned and showed sclerosis and hemorrhage extending to the tunica adventicia.

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Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound.

Capuchin monkey (Cebus apella) is a new world primate that in recent years has become important in biomedical research. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter (BPD), thorax height (TH), and femur length (FL) were performed. Identification of the GS was possible on day 23+/-2.8 (X +/- SE). The embryo and its heartbeat was detected on day 32.7+/-2.8, the GL being measurable thereafter. By day 45.4+/-1.4 BPD and TH were measurable. FL could only be measured from day 70.6+/-2.1. Predictive regression equations of gestational age (GA) were modeled with data obtained. In addition, preliminary data of fetal heart rate showed a decrease in frequency with advancing gestation.

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Selective D1 and D2 receptor manipulation in Cebus monkeys: relevance for dystonia and dyskinesia in humans.

Selective D1 and D2 dopamine (DA) antagonists and agonists were given to 4 Cebus monkeys who had previously received haloperidol treatment for 4 years. SCH 23390 (a selective D1 antagonist) and raclopride (a selective D2 antagonist) induced identical syndromes consisting of dystonia and oral dyskinesia. Biperiden (an anticholinergic drug) and LY 171555 (a selective D2 agonist) completely antagonized the dystonia and dyskinesia induced by SCH 23390 as well as raclopride. The combined treatment with LY 171555 and SCH 23390 (but not LY 171555 and raclopride) caused pronounced sedation. LY 171555 induced repetitive movements of head, legs and trunk, but no oral dyskinesia. SKF 38393 (a partial D1 agonist) caused slight sedation, minimal oral dyskinesia and a significant reduction in D2 agonist-induced repetitive movements.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Continuous compensatory tracking by a cebus monkey.

A cebus monkey was trained to hold a continuously moving voltmeter needle on-target for 60 seconds to obtain a food-pellet reinforcement. The task confronting the animal was relatively complex in that the high-frequency error voltage fed to the voltmeter needle was nulled by the animal by means of a joystick physically separated from the stimulus display.

Animals↗

Slow and saccadic eye movements evoked by microstimulation in the supplementary eye field of the cebus monkey.

1. Intracortical microstimulation was used to map the supplementary eye field (SEF) in eight hemispheres of five Cebus apella monkeys. Monkeys were immobilized during experiments with Telazol (tiletamine HCl and zolazepam HCl), a dissociative anesthetic agent that was demonstrated to have no significant effect on microstimulation-induced eye movement parameters compared with similar experiments in alert, behaviorally trained monkeys. The functional subregions were defined with the use of low-threshold current (< or = 50 microA). Electrically elicited eye movements were videotaped and quantified. Both slow and saccadic eye movements were reliably evoked at low threshold by microstimulation in each of eight hemispheres studied. The two types of eye movements were clearly distinguished by their significantly different duration and velocity (P < 0.0001) and their different responses to long stimulus trains. The results strongly support the proposal that the SEF produces not only saccadic eye movements as previously reported but also slow (pursuit) eye movements.

Anesthetics↗

Seasonal variation in the testicular volume of capuchin monkeys (Cebus apella) in captivity.

The study of the reproductive strategy developed by different species in order to adapt to their environmental conditions and their meaning in an evolutionary perspective is essential for understanding the mechanisms involved in the process of reproduction. Non-human primates are very interesting models for this purpose. Some species show a typical seasonal reproductive pattern, such as rhesus macaques (Macaca mulatta) [Sade, 1964; Conaway and Sade, 1965] and ring-tailed lemurs (Lemur catta) [Zuckerman, 1953], while others, such as gorillas (Gorilla gorilla) and chimpanzees (Pan troglodytes) [Puschmann, 1975], show relative independence of the environment. Neotropical primates display many different breeding strategies. Female capuchin monkeys (Cebus apella), for instance, having reached puberty, have fertile cycles year-round [Hamlett, 1939; Nagle and Denari, 1983]. Interestingly, there are reports of a clear peak of births in free-living [Hamlett, 1939] and captive colonies [Welker et al., 1983] in the dry season, i.e. May-June in the southern hemisphere. Some authors suggest that a seasonal variation in spermatogenesis could explain the birth peak [Freese and Oppenheimer, 1981]. The aim of this study was to investigate this theory, measuring seasonal variation in total testicular volume in a captive group of male capuchin monkeys and assessing its temporal correlation with the birth season as an indirect indication of variation in male fertility.

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