Patas Research Articles

Phenycyclidine in combination with d-amphetamine: Differential effects on acquisition and performance of response chains in monkeys

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When phencyclidine was administered alone, overall response rate decreased and percent errors increased in both components with increasing doses. d-Amphetamine alone generally decreased rate and increased errors in learning, but increased rate and had no effect on accuracy in performance. When phenycyclidine was administered in combination with d-amphetamine, the phenycyclidine dose-effect curves tended to shift to the left as the dose of d-amphetamine was increased. The extent to which the curves shifted, however, dependent on both the schedule component and the behavioral measure. For example, with accuracy, the shift was more evident in learning than in performance. Combinations of phencyclidine with a high dose of d-amphetamine generally produced supra-additive effects; i.e., the effects on rate and accuracy were greater than expected from simple addition of the effects of each drug given alone.

Embryonic development in Erythrocebus patas.

The developmental stages of 12 Erythrocebus patas embryos, ranging in gestational age from 30 to 50 days, is described. The pattern of embryogenesis in E. patas closely parallels the anatomic characteristics of human and other nonhuman primate embryos between stages 12 and 23. However, there is a delay in development in E. patas similar to that observed in human embryos which differs from the macaques and baboons. This temporal difference in the embryonic period is an important factor in the design and analysis of early pregnancy studies in this species.

Development of a Nonhuman Primate Model for Fetoscopy

Twenty-four fetoscopy procedures were performed on 22 monkeys (19 Macaca mulatta, one M. fascicularis, two Erythrocebus patas) with gestational ages ranging from 66 to 145 days. Insertion of the fetoscope without ultrasound guidance was easy in 14 and difficult in ten procedures. Amniotic fluid exchange with normal saline, to improve visualization, was successful in eight of 13 procedures. Fetal blood sampling was successful in four of nine attempts. Nine monkeys aborted within 17 days of the fetoscopy, the remaining 13 went to term or were used in other research protocols. Major complications included maternal hemorrhage into the amniotic fluid, inability to enter the amniotic cavity, and abortion. Maternal serum alpha-fetoprotein following fetoscopy was not a useful indicator of subsequent abortion.

Thermoregulation in Erythrocebus patas: a thermal balance study.

A thermal balance study over an ambient temperature (Ta) range of 15-40 degrees C was performed on six nonacclimated patas monkeys (Erythrocebus patas) weighing between 3.9 and 6.0 kg. O2 consumption, CO2 production, mean weighted skin temperature (Tsk), rectal temperature (Tre), respiratory evaporative water loss (Eresp), and total evaporative water loss (Etot) were measured continuously after equilibration at each Ta. Tsk increased as Ta increased, whereas Tre was maintained between 37.6 and 38.4 degrees C at Ta from 15 to 40 degrees C. Total evaporative heat losses increased with increasing Ta to a mean value of 76 W/m2 at 40 degrees C. Eresp was relatively constant and increased from 1.0 to 8.0 W/m2 at 15 and 40 degrees C, respectively. Whole-body conductance was similar to that previously reported for Macaca mulatta except at the highest Ta (40 degrees C), where the values for the patas monkey were significantly lower than those reported for the rhesus monkey (rhesus = 72 W/m2; patas = 33 W/m2). The data demonstrate that the patas monkey can maintain its core temperature within a narrow range over a wide range of Ta values. Additionally, Etot in the patas monkey is significantly higher than what has been reported in other nonhuman primates and approaches that reported in humans.

Serological investigation of an outbreak of simian varicella in Erythrocebus patas monkeys.

An epizootic of simian varicella occurring in a colony of Erythrocebus patas monkeys was studied serologically by using radioimmunoassay and neutralization tests against (i) a virus strain isolated from an animal that died during the epizootic, (ii) a simian varicella virus strain from an earlier outbreak of simian varicella-like disease at another facility, and (iii) human varicella-zoster virus. Serological tests detected more cases of infection among the animals exposed to virus during the epizootic than were evidenced by clinical findings; only 6 of the 26 animals with seroconversion developed a rash. Good correlation was seen between antibody responses demonstrated by radioimmunoassay and by the neutralization tests. Specificity of the radioimmunoassay was evidenced by the complete agreement with neutralization results for 17 animals which failed to show an antibody response over the course of the outbreak and were assumed not to have been infected. Thus radioimmunoassay is a reliable, rapid, and relatively economical method which could be used for serological screening of primates entering experimental colonies to identify those which might be potential sources of outbreaks through activation of latent simian varicella virus infection. Close correlation was seen between antibody responses to the virus strain from the current outbreak and the one from another epizootic, indicating that the two outbreaks were caused by antigenically similar viruses. Animals showing neutralizing antibody responses to the simian varicella viruses also showed responses to human varicella-zoster virus, which further substantiates the close antigenic relationship between human and simian varicella viruses.

Blood Values of Free‐Ranging Patas Monkeys (Erythrocebus patas)

Free-ranging patas monkeys (Erythrocebus patas) from El Guayacán island, Puerto Rico, were surveyed to establish values for the hemogram, serum biochemicals, calcium, and phosphorus. Results were tabulated for males and nonpregnant/nonlactating, pregnant, and lactating females. A summary of blood values from previous studies on captive patas monkeys was also tabulated for comparison.

Cryopreservation of third-stage larvae of Brugia malayi and Dipetalonema viteae.

Methods are described for the cryopreservation of third-stage larvae of Brugia malayi. Optimum conditions utilized larvae free from the mosquito host frozen at the rate of -1 degree or -0.8 degrees C per min in medium containing 9% dimethyl sulfoxide and 0.004 M polyvinylpyrrolidone. Nonfrozen or thawed larvae were inoculated intraperitoneally into jirds (Meriones unguiculatus), the thawed larvae after cryogenic storage for 5-378 days. In general, the percentage of adult worms recovered at necropsy was comparable between the two groups and ranged from a mean of 6-9% of the larval inoculum. In addition, three of four patas monkeys (Erythrocebus patas) inoculated with thawed B. malayi larvae developed patent infections. The cryopreservation of third-stage larvae of Dipetalonema viteae also is discussed.

Influence of age, sex, and caging on joint mobility in the patas monkey (Erythrocebus patas).

Normal range of joint mobility in the extremities of the patas monkey, Erythrocebus patas, was established for a free-ranging colony of 64 animals at La Parguera, Puerto Rico (Caribbean Primate Research Center). Eighty-five animals that had been caged (30" X 30" cages) for up to 5 years were used for comparison. Passive joint mobility of anesthetized animals was measured with a goniometer. Nine parameters (five on the forelimb and four on the hindlimb) were measured on each animal. The data were sorted into subsets according to the animal's age, sex, place of birth, and type of confinement, if any. The number of animals in each subset was recorded and the mean (in degrees) and standard deviation for each parameter were calculated. A P less than or equal to 0.05 on two-tailed Student's t-tests was considered significant. Comparisons between free-ranging males and females showed significant differences in one or two parameters for all age groups. A cross-sectional sample of free-ranging animals of both sexes showed that significant changes in joint mobility occurred only in the first 18 months of life. Joint mobility of all caged animals, however, was highly variable, and even between the more mature animals there were significant differences in several parameters. Almost all comparisons of subsets of the same age and sex showed significant differences between caged and free-ranging animals in at least one parameter. When the caged animals were laboratory-born, however, these differences were significant in five out of nine parameters. The results suggest that, although caging itself affects joint mobility, the age of first confinement may have an even greater effect than the length of the confinement.

Diurnal births and perinatal behavior among wild patas monkeys: Evidence of an adaptive pattern

Data from a 2-year field study of patas monkeys (Erythrocebus patas) in Kenya support our earlier suggestion that diurnal births are a species-typical pattern of patas. In this respect patas are very unusual, as all existing information shows that nocturnal births are typical of both captive and freeranging monkeys. Patas do not give birth at night because to do so would render ineffective their night-resting strategy which reduces vulnerability to predation at night. Giving birth during the day, however, does not eliminate the risk of being preyed on; nor are all times of day equally favorable for giving birth. Our field data suggest that a patas female gives birth at those times of day when she is least likely to lose contact with her group or to encounter predators.

Fluorescence of experimental atheromatous plaques with hematoporphyrin derivative.

Fluorescence of hematoporphyrin derivative (HPD) has been used clinically to localize malignant neoplasms because of its selective accumulation in these tissues. We tested the hypothesis that HPD may also be selectively concentrated within atheromatous plaques. 48 h after HPD injection in a variety of species, selective fluorescence of atheromatous plaques of the aorta was seen in each animal (rabbits and Patas monkey) exhibiting such lesions. No fluorescence could be demonstrated in aortic segments free of atheromatous involvement. Since the efficacy of photodynamic destruction of malignant tumors with HPD has been demonstrated in clinical studies, the observations of the present study may have therapeutic implications in atheromatosis.

Studies on the metabolism of the new anti-hypertensive agent, indoramin, in man.

The absorption, metabolism and excretion of the new antihypertensive agent indoramin (Baratol) have been studied in male volunteers following oral administration of the drug labelled either with 14C or with tritium. Absorption of the drug proceeded at moderate rate, peak plasma radioactivity levels being seen by 3 h after dosing. Metabolism was extensive as shown by very little unchanged compound appearing in urine. Two major urinary metabolites accounting for some 35-40% of the renally excreted material were identified as acid labile conjugates of indoramin itself and indole 6-hydroxylated indoramin. The pattern of biotransformation appeared to be similar to that in the patas monkey, the species used in the long term safety evaluation of the drug. Excretion of the drug and metabolites occurred primarily via the faeces which accounted for 49.7 +/- 4.9% of the dose. A further 31.7 +/- 2.4% was recovered in the urine. Renal elimination of total radioactivity occurred in an apparently monoexponential manner with a half-life of 11.9 +/- 1.2 h.

Reproductive performance of a laboratory breeding colony of patas monkeys (Erythrocebus patas).

Reproductive statistics were gathered over a 5½-year period on a colony of Erythrocebus patas. Pregnancies occurred throughout the year under laboratory conditions with a suggestion of a mating peak in the late fall and early winter. Menstrual cycles were monitored and found to average 30.6 days in length. Maximal vaginal cornification occured on day 15 of the cycle suggesting a midcycle ovulation. However, production of timed-mated pregnancies indicated ovulation occurred earlier and that breeding on days 10, 11, and 12 after menstruation was more likely to result in pregnancy. The gestation length was found to average 167.2 days in 142 harem-bred females and 167.5 days in 11 timed-mated pregnancies. Sixty-two percent of all pregnancies resulted in live births; 28% of the conceptions terminated with in-utero death of the fetus. Stillborn infants were delivered in 9% of the pregnancies. Infant mortality during the first 6 months of life was 10.2%. Females raised in the colony conceived their first offspring at approximately 3 years of age and males were able to sire infants at 3 years and 8 months.

Interferon prophylaxis against simian varicella in Erythrocebus patas monkeys.

Erythrocebus patas monkeys were given placebo or human leukocyte interferon (5 x 10(5) units/kg of body weight per day im) for five days during an epizootic of simian varicella. During the 14 days beginning with the first day of treatment, the attack rate for simian varicella was 14.3% (two of 14) among interferon recipients compared to 70% (nine of 13) among placebo recipients (P less than 0.025). Excluding animals with antibody to simian varicella when the study began, 18% (two) of 11 interferon recipients had symptoms of infection compared to 80% (nine) of 11 placebo recipients (P less than 0.025). The epizootic began in a room housing male animals. The incidence of infection in male placebo recipients was 100% (seven of seven) compared to 14% (one of seven) in male interferon recipients (P less than 0.01). The efficacy of interferon prophylaxis in the simian varicella model supports its continued evaluation for the management of human varicella in high-risk patients.

Alternative Mechanisms of Social Organization in Monkeys

AbstractObservations on a captive group of patas monkeys were supplemented with field observations to analyse the process by which a gregarious animal keeps track of the position and activity of other group members and regulates the distance between them and itself. This process can take place without the exchange of specialised signals (displays) and is described as a mechanism of group organisation alternative to a mechanism based on the exchange of displays. Displays and formalised interaction patterns can provide additional, complementary information, especially about transient features of social organisation.

Mansonella ozzardi: A Redescription with Comments on Its Taxonomic Relationships *

Mansonella ozzardi is redescribed from adult worms collected from the subcutaneous tissues of patas monkeys (Erythrocebus patas) infected with a Haitian strain of the filaria. The worms are small and very slender; females measure about 49 mm in length by 0.15 mm in diameter and males, 26 by 0.07 mm. Haitian (Caribbean) and Colombian (Amazon) forms of the filaria are morphologically identical, as are their microfilariae. Mansonella is most closely related to Tetrapetalonema. Based on taxonomic priority the latter becomes a synonym of Mansonella. As a consequence, T. perstans and T. streptocerca of man in Africa are designated as M. perstans (Manson, 1891) n. comb. and M. streptocerca (Macfie and Corson, 1922) n. comb. Further, M. ozzardi is most closely related to the species M. llewellyni (Price, 1962) n. comb., a parasite of the raccoon, and M. interstitium (Price, 1962) n. comb. found in squirrels, both in North America.

Phencyclidine in combination with pentobarbital: Supra-additive effects on complex operant behavior in pigeons

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under afixed ration schedule. Errors produced a brief timeout but did not reset the chain. When phencyclidine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. Similar effects were found with a high dose of pentobarbital alone. When phencyclidine was administered in combination with pentobarbital dose-effect curves for rate and accuracy shifted to the left as the dose of pentrobarbital was increased. Cobinations of phencyclidine with a high dose of pentobarbital produced supra-additive effects;i.e., the effects on rate and accuracy were greater than expected from simple addition of the effects of each drug given alone. These results extend the generality of previous findings in patas monkeys in a similar repeated-acquisition task.

The disposition of a novel tetrahydroquinoline, tiquinamide, in rats and patas monkeys.

The absorption of tiquinamide occurred rapidly and extensively in both rats and patas monkeys. The major site of localization of radioactivity was in the stomach in both species. Tiquinamide was 50-60% bound to rat plasma and 50-75% to monkey plasma. The elimination of unchanged drug from plasma took place rapidly, with half lives of 1.6 h in rats and 0.7 h in monkeys. Elimination of total radioactivity in the rat was very slow and monoexponential, with a half-life of 90 h. However, in the monkey it took place in a biphasic manner and most radioactivity was eliminated in the first phase with a half-life of 0.75 h. Possible reasons for the species difference in elimination are discussed. The principle route of excretion in both species was via the urine. Excretion was slower in the rat than in the monkey. In the former species, only 50% of the administered dose was excreted in the first 24 h after dosing, and a further 12% was recovered from the carcasses after 7 days. In the monkey, however, excretion was virtually complete in the first 6 h.

Ultrastructure of experimental coronary artery atherosclerosis in cynomolgus macaques: A comparison with the lesions of other primates

We studied the ultrastructure of the left anterior descending coronary artery in 6 female cynomolgus macaques fed atherogenic food containing 0.5% cholesterol for 6 months, and in 2 female cynomolgus macaques that had received food low in cholesterol. Animals given the atherogenic food had coronary artery lesions of a characteristic two-level architecture consisting of a lipid-poor upper cap, and of a lipid-rich lower core. The cap consisted of layers of smooth muscle cells that were rich in rough endoplasmic reticulum and contained few myofilaments and relatively few lipid droplet inclusions. The core consisted mainly of macrophages overloaded with droplet inclusions (macrophage foam cells), droplet-laden smooth muscle cells, and extracellular lipid and cell debris. Some macrophage foam cells were in mitosis. The largest lipid cores contained multinucleate giant cells with large intracellular crystal clefts. Dead macrophage foam cells were the source of the extracellular lipid and debris particles. Intimal cores often extended into the adjacent media. The adventitia was involved in the intima-media lesions in 3 of the animals. Compared with the coronary artery lesions of rhesus macaques and patas monkeys given similar atherogenic diets, cynomolgus monkey lesions were morphologically closer to human atherosclerotic plaques with respect to their stratification into a cap and a core.

Phencyclidine in combination with pentobarbital: Supra-additive effects on complex operant behavior in patas monkeys

In one component of a multiple schedule, patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When administered alone, phencyclidine and pentobarbital, at the higher doses, generally decreased the overall response rate and increased the percent errors in both components. The performance component tended to be less sensitive than the learning component to the drug effects. When phencyclidine was administered in combination with pentobarbital, the phencyclidine dose-effect curves for both rate and accuracy generally shifted progressively to the left as the dose of pentobarbital was increased. In two of three monkeys, combinations of phencyclidine with a high dose of pentobarbital consistently produced greater rate-decreasing and error-increasing effects than expected from simple addition of the effects of each drug given alone. In other words, the phencyclidine-pentobarbital combinations produced supra-additive effects on responding under the multiple schedule.

Disseminated strongyloidiasis in Erythrocebus patas.

Five fatal cases of disseminated strongyloidiasis were identified in Erythrocebus patas caged singly or in groups of two to four in an indoor research facility. This is the first report of fatal hyperinfective strongyloides infection in a species other than great apes and man. Severe pulmonary hemorrhage, duodenitis, and proximal colitis with microscopically demonstrable larvae in affected tissues were the key necropsy findings. E. patas is an available, suitable model for the study of disseminated strongyloidiasis.