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PubMedDate not supplied

[General intubation anesthesia in primates for experimental otoneurologic surgery].

INTRODUCTION: We report our experience in anaesthetic and surgical management of primates (M. fascicularis) in an experimental otoneurosurgical procedure. MATERIAL & METHODS: The VIII cranial nerve was bilaterally sectioned in a translabyrinthine approach in 21 adult primates. In 14 animals subsequently, a prototype of auditory brainstem implant was placed unilateraly within the brain stem for surface stimulation of cochlear nuclei. Premedication consisted in an intramuscular mixture of ketamine, midazolam and atropine. Surgical procedure was performed under intubated general anaesthesia, after propofol (1.5 mg/kg) administration and maintained with nitrous oxide and halotane. RESULTS: The mixture of ketamine, midazolam and atropine produced a deep anaesthesia in 4 +/- 1.7 minutes, permitting safe animal handling. Atraumatic nasotracheal intubation without muscle relaxing agents was easily achieved in all animals. Anaesthesia was adequately maintained with nitrous oxide and halotane. Animals did not present any relevant incidents during surgery, and were extubated 10 +/- 2.5 minutes after cessation of gas administration. Post-operatively, no relevant surgical complications occurred. CONCLUSIONS: We report an anaesthetic technique that provides an optimal restrain and anaesthesia for experimental otoneurosurgical procedures with primates. This technique offers a quick recovery and avoids the use of muscular relaxing agents for intubation, and thus could be safely used in other kind of surgical procedures.

Anesthesia, General↗
PubMed2001

[Effect of antiorthostatic hypokinesia and its combination with +Gz runs on the otolith regulation of cardiac rhythm in primates].

Amplitude of cardiac rhythm response to the otolith stimulus (AR-R), i.e. rapid reduction of the EKG R-R interval was determined in 24 Macacas mulatta before and after 28-d head-down (-6 degrees) immobilization (HDI). In two experimental series the animals were divided into 2 groups (control and CF) with 6 primates in each. In the HDI series-1, the CF animals were rotated on a centrifuge with a 3.62-m arm at 1.2 up to 1.6 +Gz for 30-40 minutes 4-5 times a week. In HDI series-2, the CF animals were rotated 30 min at 1.2 +Gz 2-3 times a week. In a day after HDI, AR-R was significantly reduced in both CF groups, which, when compared with EKG R-R intervals, suggests attenuation of equally parasympathetic and sympathetic influences on the heart. In 7 days since HDI, AR-R was close to baseline values in control primates on both series and CF primates in series-2, whereas in the CF group in series-2 AR-R exceeded baseline values. Significant differences in mean AR-R values in the control and CF groups in series-1 following 7 days after HDI point to the prophylactic effect of small but regular g-loads manifested in more rapid recovery of initial level of the cardiac rhythm regulation.

Animals↗
PubMed2001

The role of the primate amygdala in conditioned reinforcement.

Conditioned reinforcement refers to the capacity of a conditioned stimulus to support instrumental behavior by acquiring affective properties of the primary reinforcer with which it is associated. Conditioned reinforcers maintain behavior over protracted periods of time in the absence of, and potentially in conflict with, primary reinforcers and as such may play a fundamental role in complex social behavior. A relatively large body of evidence supports the view that the amygdala (and in particular the basolateral area) contributes to conditioned reinforcement by maintaining a representation of the affective value of conditioned stimuli. However, a recent study in primates (Malkova et al., 1997), using a second-order visual discrimination task, suggests that the amygdala is not critical for the conditioned reinforcement process. In the present study, excitotoxic lesions of the amygdala in a new world primate, the common marmoset, resulted in a progressive impairment in responding under a second-order schedule of food reinforcement. In addition, the responding of amygdala-lesioned animals was insensitive to the omission of the conditioned reinforcer, unlike that of control animals, for which responding was markedly reduced. In contrast, lesioned animals were unimpaired when responding on a progression of fixed-ratio schedules of primary reinforcement. These data confirm that the amygdala is critical for the conditioned reinforcement process in primates, and taken together with other recent work in monkeys, these results suggest that the contribution of the amygdala is to provide the affective value of specific reinforcers as accessed by associated conditioned stimuli.

Acoustic Stimulation↗
PubMed2001

Early development of neuronal activity in the primate hippocampus in utero.

Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.

Animals↗
PubMed2001

Pathogenesis of replication competent retroviruses derived from mouse cells in immunosuppressed primates: implications for use of neoplastic cells as vaccine substrates.

T-cell lymphomas developed in three of 10 immunosuppressed rhesus macaques during early experiments using retroviral vectors to transfer marker genes into CD34+ bone marrow cells for subsequent transplantation in the animals. Direct PCR analyses of RNA obtained from tumour tissues from these macaques revealed the presence of several different recombinant murine leukaemia viruses (MuLV). Most prominent was a recombinant designated Mo(LTR)Ampho(env) in which the amphotropic env of the helper packaging virus was joined to a modified form of long terminal repeat (LTR) of the Moloney MuLV-derived vector that contained an additional copy of the core enhancer. This new LTR afforded enhanced replication upon the Mo(LTR)Ampho(env) MuLV in several different rhesus cell types compared with the prototype amphotropic MuLV4070A. Unexpectedly, at least two types of a mink cell focus-forming (MCF) MuLV element, arising from endogenous retroviral sequences expressed in the murine packaging cell line, were also transmitted and highly expressed in one of the macaques. Furthermore, murine virus-like VL-30 sequences were detected in the rhesus lymphomas, but these were not transcribed into RNA. The unanticipated presence of this array of MuLV-related structures in a primate gene transfer recipient highlighted the generation of recombinant retroviruses when the vector producer line produced replication competent viruses. These recombinants had an enhanced tropism and pathogenicity in the primate gene transfer recipients and frequently caused lymphomas. This primate experiment highlights the potential risk from contamination of a vaccine cell substrate with a replicating retrovirus.

Animals↗
PubMed1998

[Experimental study on regenerative capacity and form of corneal endothelial cells in the primate].

OBJECTIVE: To investigate the regenerative capacity and form of the corneal endothelial cells of the primate. METHODS: Chromosome, HE stainings and autoradiography were made for the cornea of human and monkey. RESULTS: After trauma, corneal endothelial cells of the adult monkey in vivo showed regenerative power. The regenerative form of corneal endothelial cells of the adult, infant and fetal primate was amitosis under both physiologic and pathologic conditions. CONCLUSION: The corneal endothelial cells of the primate have regenerative power, and the form is amitosis.

Adult↗
PubMed2002

Air trapping and arboreal locomotor adaptation in primates: a review of experiments on humans.

A review was made of experiments on humans in which air trapping by glottis closure during three-dimensional movements were examined in four subjects including former Olympic gymnasts. In brachiation and horizontal bar exercises, the behaviour of the larynx was monitored with a fiberoptic endoscope, and EMG-data were recorded from shoulder muscles. The results revealed that immobilization of the polyaxial connection between the shoulder girdle and the thorax by air trapping occurs in phases of extreme loading of the upper limbs. The closure of the airway by the larynx in humans serves three functions: first, the prevention of errors in deglutition; second, the production of vocal sounds; third, the retention of air inside the thoracic cavity. The latter function, air trapping, allows the immobilization of the rib cage for the muscular fixation of the shoulder blade on the trunk in movements that imply unusually high external forces acting on the upper limbs. This morphological-functional innovation probably has been made when early mammals invaded the three dimensional arboreal habitat, because it gave the tree-dwelling early primates the device to anchor themselves by the arms alone and to avoid falling out of trees. The specific functional characteristic of primates is the hermetic closure of the vocal and vestibular folds by rapidly contracting muscles in the folds. So the closure of the glottis, which in humans seems primarily an adaptation to the production of vocal tones, seems to go back to the adaptation of Tertiary arboreal primates to movements in a three-dimensional environment. Our conclusions are in agreement with the results of other contributions to this volume.

Adaptation, Physiological↗
PubMed2002

Shoulder movements during quadrupedal locomotion in arboreal primates.

The kinematics of scapula and shoulder joint movements were analyzed in three species of arboreal quadrupedal primates using cineradiography. Our findings indicate that scapular movement is highly important for forelimb movement in primates with this ancestral mode of locomotion. Retroversion of the scapula (syn. caudal rotation or extension) during the stance phase contributes more than 40% to the stride length of the forelimb. Lateral forelimb excursions, a general feature for arboreal primates, are based on complex three-dimensional scapular movements guided by the clavicle. Humeral abduction is achieved by scapular abduction and transversal rotation of the scapula about its longitudinal axis, and is therefore strikingly different from humeral abduction in humans. At the same time, the movements of the shoulder joint are limited to flexion and extension only.

Animals↗
PubMed2002

Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration.

The primate striatum contains tyrosine hydroxylase (TH)-immunoreactive (ir) neurons, the numbers of which are augmented after dopamine depletion. Glial cell line-derived neurotrophic factor (GDNF) strongly modulates the viability and phenotypic expression of dopamine ventral mesencephalic neurons. The effect of GDNF on TH-ir neurons intrinsic to the striatum has yet to be investigated. In the present study, stereological counts of TH-ir striatal neurons in aged and parkinsonian nonhuman primates revealed that GDNF delivered via a lentiviral vector (lenti-) further increased the number of these cells. Aged monkeys treated with lenti-GDNF displayed an eightfold increase in TH-ir neurons relative to lenti-beta-galactosidase-treated monkeys. Unilateral 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine treatment alone in young monkeys resulted in a bilateral eightfold increase in TH-ir striatal cells. This effect was further magnified sevenfold on the side of lenti-GDNF treatment. These cells colocalized with the neuronal marker neuronal-specific nuclear protein. Some of these cells colocalized with GDNF-ir, indicating that an alteration in phenotype may occur by the direct actions of this trophic factor. Thus, GDNF may mediate plasticity in the dopamine-depleted primate brain, which may serve to compensate for cell loss by converting striatal neurons to a dopaminergic phenotype.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Prevalence of rotavirus antibodies in a non-human primate colony.

A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy.

Journal Article↗
PubMed2003

Antigen recognition by serum antibodies in non-human primates experimentally infected with Mycobacterium tuberculosis.

Tuberculosis is a significant threat to non-human primates and their caretakers. The diagnosis of tuberculosis in living non-human primates is currently based on the tuberculin skin test, which is cumbersome and sometimes inaccurate. Development of an accurate serodiagnostic test requires identification of the key antigens of Mycobacterium tuberculosis involved in antibody production. When sequential serum samples obtained from 17 cynomolgus, rhesus, and African green monkeys up to seven months since experimental infection with M. tuberculosis Erdman were screened for antibody against purified proteins of M. tuberculosis, three highly seroreactive antigens were identified. One protein, ESAT-6, reacted with sera from all infected animals. Two additional proteins, alpha-crystallin and MTSA-10, were recognized by sera from approximately 90% of infected animals. Time course analysis of antibody production indicated that the earliest response was usually to ESAT-6 alone or to ESAT-6 and other antigen(s). These results provide experimental evidence of the potential value of ESAT-6 as an antigen for use in serodiagnosis of tuberculosis in non-human primates.

Animals↗
PubMed1992

Lasting effects of (+-)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in nonhuman primates: neurochemical observations.

The purpose of this study was to assess the duration of (+-)-3,4-methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5-hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

[Psychosomatic evaluation of primates with the use of a psychomotor testing system].

The higher nervous system reactions of rhesus monkeys to the head-down tilt (HDT, 28 d, -5 degrees) and preventive centrifugation were evaluated with the use of a computerized psychological testing system (PTS). Prior to HDT, the primates elaborated conditioned instrumental food-obtaining reflexes by playing computer games. Drilled to perform PTS tests to the best of their ability, the animals were to fulfill two PTS tests of increasing complexity in HDT. Test results were used to determine the dynamics of primates' cognitive function and the psychological state. The investigation consisted of two series with two groups of monkeys in each series. Twelve animals of each group (10 had skill in performing the PTS tests) were distributed into 2 subgroups. Every other day one of the subgroups was exposed to centrifugation at 1 to 2.5 g. In the first series, 10 monkeys worked on the simplest test, i.e. spotting a static object. All animals showed interest in the computer game, and played a lot and successfully during HDT. In the second series, the animals were challenged with a more difficult test of following a moving object with the cursor. Based on the analysis of experimental data, a significant variability in achievement and emotional behavior of the primates should be attributed to different types of the nervous system.

Affect↗
PubMed2004

Endogenous morphine and codeine in the brain of non human primate.

BACKGROUND: Morphine is the most used compound among narcotic analgesics. Apart from its presence in the poppy plant, morphine has been shown to be endogenously present in different tissues of mammals and lower animals. MATERIAL/METHODS: The presence of endogenous morphine and codeine was investigated by Gas Chromatography/ Mass Spectrometry (GC/MS) in the brain of non human primate. The release of endogenous morphine from monkey brain slices was studied in vitro in the presence of high potassium concentrations with and without calcium in the medium. RESULTS: Endogenous morphine, and its direct precursor codeine, was for the first time detected by GC/MS in the brain of non human primate. High potassium concentrations depolarized neurons releasing endogenous morphine twofold above basal line levels in a calcium dependent mechanism. CONCLUSIONS: This finding confirms the presence of the endogenous alkaloid throughout the phylogenesis of the nerve system of mammals and lower animals and indicates that endogenous morphine might function as a neuromodulator/neurotransmitter agent in the central nervous system (CNS) of non human primates.

Animals↗
PubMed2004

The reorganization of the motor system in primates after the loss of a limb.

As a result of an extensive search, we were able to obtain a limited number of macaque monkeys, New World squirrel monkeys, and prosimian galagos years after they had received a therapeutic amputation of a forelimb or hindlimb as a treatment for injury. Forelimb or hindlimb regions of primary motor cortex, M1, were stimulated in these primates with microelectrodes using amounts of current just sufficient to evoke a movement. Results were compared to those obtained from normal primates or from M1 contralateral to the intact limb in the same primates. In all cases, more sites in M1 contralateral to the amputated limb evoked movements of the limb stump and muscle in the adjoining shoulder or hip. In two of the macaque monkeys, injections in M1 reveal more widespread intrinsic connections than in normal M1, and in several monkeys and galagos, injections of tracers in muscles of the stump, shoulder, or hip labeled spinal cord motor neurons that normally project to the distal limb. These anatomical results suggest that the functional changes in M1 following amputation are mediated in part by the formation of new connections.

Amputation, Traumatic↗
PubMedDate not supplied

Comparative morphology of the pars ventralis nucelus of lateral geniculate complex in some prosimian and simian primates.

The progressive elaboration of the sense of vision, which is reflected not only in the perfection of the structural mechanisms of the eye itself, but also in the divergent modifications of the pre-existing neural components and circuits of the visual system in the brain. This concept gave the much needed impetus to study the morphology of the pars ventralis nucleus of lateral geniculate complex in graded series of primates. The three species of prosimian primates and four species of simian primates were used in this investigation, to make a comparative survey of the external morphology of the pars ventralis nucleus using 2-dimensional and 3-dimensional reconstruction techniques. Observations were made with reference to general configuration, size, positional relationship, migration and extent of the nucleus in various planes. All the investigations done on pars ventralis were also performed on pars dorsalis nucleus of each species, as the phylogeny of these two nuclei of lateral geniculate complex goes hand in hand. The study shows that the pars ventralis is the more primitive element and as a dependency of the subthalamus with tectal connections, it becomes progressively superseeded by the dominance of the pars dorsalis with its cortical connections. Thus this most important diencephalic centre of vision is destined to be reduced in higher mammals. Whereas the fate of pars dorsalis in the higher mammalian series, is a history of progressive elaboration which proceeds simultaneously with the development of the visual cortex of the cerebrum.

Animals↗
PubMed2004

Physiological reactions of primates to 9-D immersion and head-down tilt.

Purpose of the investigation was to compare physiological reactions of primates (Macaca mulatta) to microgravity simulated by immersion and head-down tilt (HDT). In immersion experiments, primates in waterproof suits were put into motion-restraining chairs and immersed into water (t=35.4 degrees C) breast-deep for 9 days. In 9-d HDT experiments, prone primates were motor restrained in dedicated tilt beds at -5 degrees. It was found that the CNS functioning was significantly affected, the plasma volume reduced and the marrow erythropoietic function declined. Atrophy developed in leg muscles on a backdrop of iliopectineal spongy osteopenia. Loss in hydration, inhibition of erythropoietic hemopoiesis and iliopectineal spongy osteopenia were more pronounced following immersion than HDT.

Adaptation, Physiological↗
PubMed2005

[Immune and interferon status of primates].

The authors of the article have first determined standards of interferon (IFN) status of healthy primates (M. mullatta) belonging to different age groups, such as serum IFN, spontaneous IFN production, IFN-a and IFN-y production. They showed that old healthy primates have low ability of IFN-a and IFN-y production and high serum IFN level. The parameters of IFN status were compared to the number of B- and T-lymphocytes and their subpopulations; qualitative evaluation of protective properties of young and old healthy primates' immunity was carried out.

Adult↗