Nonhuman primate

Although nonhuman primates have been useful in studies on the role of nutrition in a number of human diseases with an adult onset, they have been of little value in the case of osteoporosis because of the protracted time over which studies on this disease must be conducted. The cost of providing the numbers of animals necessary for statistical validity with adequate housing and veterinary care and with experimental diets over a period of one to two decades is generally prohibitive. 

Whether true facsimiles of human postmenopausal and senile osteoporosis occur in other primates is unclear. Thinning of cortical bone between the ages of 10 and 20 yr has been observed in a cross-sectional sample of pigtailed macaques (Bowden et ai, 1979). However, thinning apparently occurs in premenopausal females at a rate similar to that seen in postmenopausal women, and the influence of the menopause on bone loss in this species is obscure. 

The pattern of age-related bone loss in dogs has been extensively investigated, notably by Jee and co-workers (1976), and has been found to resemble that in man. The morphology of bone is similar, and about 80% of bone mass is made up of cortical bone in both species. Female dogs also exhibit a faster rate of bone loss than do males. However, dog bone exhibits a much more rapid rate of bone remodelling. An iliac trabecular bone turnover rate of nearly 200%/yr has been reported for 2-year-old beagles (Jee et al. 1978). Also, dogs lose bone four times as fast as humans do (Jee et al., 1976), yet their fracture rate is lower. This difference in susceptibility to fractures has been attributed to a relatively 

In addition to their compositional similarity to human bones, dog bones are accessible to biopsy for longitudinal study of nutritional effects on the skeleton. This property, plus their rapid rate of remodelling, suggests that adult dogs are capable of yielding nutritional information relevant to human osteoporosis within a practicable experimental time frame. 

Osteopenia can be induced in adult cats by immobilization, by feeding a low calcium diet, or by feeding a high phosphorus diet. Indeed, bone disease is a common clinical problem in cats fed all-meat diets unsupplemented with calcium. On the other hand, their carnivorous diet denotes a capacity to buffer the large metabolic acid load generated by a high protein intake without depletion of bone buffers. 

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A synthetic neurotoxin that causes parkinsonism in human and nonhuman primates, mice, gold fish, and dogs. MPTP is inert but metabolized by MAO-B to the neurotoxin MPP+ (1,2-dihydropyridine ion). This neurotoxin causes depletion of dopamine and degeneration of nigrostriatal dopamine neurons similar to what is observed in Parkinson s disease. 

Reich DL, Silvay G Ketamine an update on the first twenty-five years of clinical experience. Can J Anaesth 36 186—197, 1989 Ricaurte GA, Forno LS, Wilson MA, et al (+/-)3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates. JAMA 260 51-55, 1988... 

Positron emission tomography studies using "C-toluene in nonhuman primates and mice showed a rapid uptake of radioactivity into striatal and frontal brain regions (Gerasimov et al. 2002). Maximal uptake of the radiotracer by these structures occurred 1 minutes after intravenous administration. Subsequently, clearance of the radiotracer from the striatal and frontal areas occurred rapidly, with a clearance half-life from peak uptake of 10—20 minutes. Radiotracer clearance from white matter appears to be slower... 

Ricaurte, G.A. Fomo, L.S. Wilson, M.A. DeLanney, L.E. Irwin, L. Molliver, M.E. and Langston, J.W. ( )-3,4-methylenedioxyamphetamine selectively damages central serotonergic neurons in nonhuman primates. 

Kitt, C.A. Walker, L.C. Molliver. M.E. and Price, D.L. Serotoninergic neurites in senile plaques in cingulate cortex of aged nonhuman primate. Synapse 3 12-18, 1989. 

Studies of MDMA-Induced Neurotoxicity in Nonhuman Primates A Basis for Evaluating Long-Term Effects in Humans... 

This chapter will review some recently completed studies on the long-term effects of MDMA in nonhuman primates. The goals of these studies were to (1) determine if the neurotoxic effects of MDMA, which have been well documented in the rodent (see below), generalize to the primate (2) compare the relative sensitivity of primates and rodents to the neurotoxic effects of MDMA (3) ascertain if the toxic effects of MDMA in the monkey are restricted to nerve fibers (as they are in the rat), or if they involve cell bodies as well (4) evaluate how closely toxic doses of MDMA in the monkey approximate those used by humans and (5) examine whether 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) can be used to detect MDMA-induced serotonergic damage in the CNS of primates. Before presenting the results of these studies, previous results in the... 

Palmer 1989 Robinson et al.1983). However, the ratio was almost certainly affected by initial chelation with Ca-DPTA, followed by daily intravenous therapy with the chelating agent, Zn-DPTA, treatments that would have increased the urinary excretion of americium (Breitenstein and Palmer 1989). The above not withstanding, the observations made on this subject demonstrate that fecal excretion was an important pathway of excretion in this subject long after mechanical clearance of americium from the respiratory tract would have been complete. This is consistent with observations made in nonhuman primates that show that americium is excreted into bile (see Section 3.4.4.4). However, the extent to which the biliary excretion pathway in humans might resemble that of nonhuman primates is not known. 

Valente AJ, Graves DT, Vialle-Valentin CE, Delgado R, Schwartz CJ. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry 1988 27(11) 4162 1168. 

The available inhalation data for Durad MP280, Fyrquel 220, Cellulube 220, Skydrol 500B-4, and cyclotriphosphazene (reviewed in the next paragraph) are inadequate to derive intermediate-duration MRLs for these individual fluids, principally because the studies were conducted in species (rats or rabbits) that are generally considered to be insensitive to the delayed neurotoxicity of acute exposure to organophosphate esters. Cats, dogs, or nonhuman primates more accurately model the human expression of OPIDN than rats and rabbits, and studies in these species would provide a better basis for MRL derivation. 

Bergman, J., Madras, B.K., Johnson, S.E., and Spealman, R.D., Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys, J. Pharmacol. Exp. Then, 251, 150, 1989. 

Cosgrove, K., Ellis, S., Al-Tikriti, M. et al. Assessment of the effects of chronic nicotine on P2-nicotinic acetylcholine receptors in nonhuman primate using [I-123]5-IA-85830 and SPECT. Paper presented at the 66th Annual Scientific Meeting of the College on Problems of Drug Dependence, 2004, San Juan, Puerto Rico. 

Evidence from rodent, nonhuman primate, and post-mortem human studies indicates that METH is highly toxic to the CNS. This section briefly reviews neurotoxicity associated with METH abuse with particular attention on monoamines. Excellent and detailed reviews have been published elsewhere.77 237-242... 

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