Effects of a contractile prostaglandin antagonist (L-640, 035) upon allergen-induced bronchoconstriction in hyperreactive rats and conscious squirrel monkeys

The effects of an antagonist of contractile prostanoids, L-640,035 (3-hydroxymethyl-dibenzo[b,f]thiepen-5-dioxide) upon antigen-induced bronchoconstriction have been studied in inbred rats with non-specific bronchial hyperreactivity and in conscious squirrel monkeys. L-640,035 was a potent inhibitor of antigen-induced dyspnea (ED₅₀ 3.1 mg/kg p.o.) in inbred rats pretreated with methysergide (3 μg/kg i.v.) but produced no significant inhibition in untreated rats. Administration of L-640,035 (10 mg/kg p.o.) to conscious squirrel monkeys exposed to aerosols of ascaris antigen markedly inhibited changes in pulmonary resistance (R_L) and dynamic compliance (C_DYN). At a lower dose (1 mg/kg p.o.) the inhibition of changes in C_DYN were similar but the effects on R_L were reduced. It was concluded first that contractile prostanoids may be important mediators of antige-induced bronchoconstriction and secondly that L-640,035 may be effective in human allergic asthma.     

Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction

In this study we investigated the effect of the selective and potent thromboxane A2 (TxA2) receptor antagonist GR32191 on smooth muscle contraction induced by the TxA2 analogue U46619, prostaglandin (PG) D2, PGF2 alpha, and methacholine (MCh) in guinea pig airways in vitro and the airways response provoked by inhaled PGD2 and MCh in asthmatic subjects in vivo. GR32191 antagonized competitively the contractile responses of all three prostanoids to a similar degree but had no effect on MCh-induced contractions. In asthmatic subjects GR32191, in a single oral dose of 80 mg, did not affect base-line airway caliber or MCh-induced broncho-constriction but caused significant inhibition of PGD2-induced bronchoconstriction, displacing the concentration-response curves to the right by greater than 10-fold. The effect of the same oral dose of GR32191 on allergen-induced immediate bronchoconstriction was subsequently investigated in allergic asthmatic subjects. In individual subjects, GR32191 inhibited to varying degrees the overall bronchoconstrictor response, with the maximum effect occurring between 10 and 30 min after allergen challenge. These studies suggest that prostanoids contribute to the immediate bronchoconstriction induced by inhaled allergen in allergic asthmatics, and that this effect is mediated by stimulation of a thromboxane receptor.     

Reproductive synchronization in squirrel monkeys (Saimiri)

Groups of squirrel monkeys (Saimiri) that are exposed to certain seasonal environmental stimuli experience a yearly reproductive cycle with discrete mating and birth seasons. Seasonal rainfall or some rainfall induced seasonal changes (such as changes in vegetation or insect fauna) appear to be responsible for timing theSaimiri reproductive cycle. Animals of both sexes show significant physiological and behavioral changes during the yearly cycle. Whether the environmental timing factors affect both the males and the females equally, or affect only one sex directly and the other sex indirectly through social communication is not clear. Three mechanisms by which the reproductive activity of both males and females could be synchronized are presented, and data from a laboratory study and a field study relevant to each mechanism are presented. Several social interaction patterns frequently observed in the field study suggest that (1) male sexual activity may excite female sexual activity through male penile display and/or other stereotyped interactions and/or (2) female sexual activity may excite male sexual activity through pheromone and/or other communication channels.     

Effects of reproductive state on vocalizations in squirrel monkeys (Saimiri sciureus)

Vocalizations and behavior of a group of 6 squirrel monkeys, 2 males and 4 females, were recorded during the nonbreeding and breeding seasons. Behavioral and physical criteria were used to determine the presence of estrus. During the breeding season the types of vocalizations uttered by estrous females changed, and the adult male increased his rate of vocalizing. Err vocalizations by estrous females were associated with increased following and initiation of affiliative behavior with the adult male, and may have functioned to facilitate these interactions. Errs appeared to be related to changes in female reproductive state rather than to the behavior of others. The adult male increased vocalizations associated with sexual and aggressive behavior (squeals and cackles), primarily in response to the estrous females' persistent initiation of interactions with him. We concluded that certain vocalizations in Saimiri reflected changes in the reproductive state of males and females, and functioned to mediate changes in social bonding during the breeding season.     

Stomatocytosis in a colony of captive squirrel monkeys (Saimiri sciureus)

Chronic stomatocytosis, which increased in severity as a function of the time that animals were held in captivity, was observed in a small colony of squirrel monkeys. The stomatocytosis was associated with increasing hematocrits possibly due to a change in packing characteristics of the erythrocytes rather than any overt changes in the erythrocyte mass. Reticulocytes remained at control levels throughout development of the stomatocytosis. The most probable cause of this alteration in erythrocyte shape distribution was dietary, but the exact etiology was not determined.     

Aneurysms in a large colony of squirrel monkeys (Saimiri sciureus)

This communication reports the findings of a retrospective study of extracranial aneurysms found at necropsy in a large colony of squirrel monkeys (Saimiri sciureus). Eleven (1.5%) of 730 cases had dissecting, saccular, or fusiform aneurysms of the carotid arteries or aorta. Saccular and fusiform aneurysms were found only in animals that had been fed atherogenic diets, whereas dissecting aneurysms occurred in both normo- and hypercholesterolemic monkeys. Neither the type or location of aneurysms, however, could be predicted by the length of time an animal consumed an atherogenic diet, nor by the total mean serum cholesterol concentration. The anatomical characteristics, location, and incidence of aneurysms found in squirrel monkeys resembled closely those observed in human autopsy cases.     

Chemotherapy of haemobartonellosis in squirrel monkeys (Saimiri sciureus)

Splenectomised Saimiri sciureus squirrel monkeys are being used increasingly as an experimental host for human malarial studies, notably for the assessment of candidate vaccines against Plasmodium falciparum blood-stage infection. Recently, we have reported that colony-reared S. sciureus monkeys are asymptomatic carriers of Haemobartonella sp. and that patent Haemobartonella infection, activated following splenectomy, may interfere with the course of P. falciparum parasitaemia in these animals. For several years, splenectomised S. sciureus monkeys were routinely submitted to oxytetracycline therapy before their use in malarial studies in order to prevent a possible spontaneous Heamobartonella infection. However, we report here that such antibiotic therapy is often ineffective and that neoarsphenamine chemotherapy may be considered as an alternative to cure both latent and patent haemobartonellosis in S. sciureus monkeys.     

Play vocalizations of squirrel monkeys (Saimiri sciureus)

Vocalizations occurring during play bouts were studied in 2 pairs of young male squirrel monkeys. Two main call types, one having four variants, are described. Vocalization rate varied with the type of ongoing behavior and with play bout duration, an association considered to be indicative of motivation to play. Structural differences also varied with bout duration and longer bouts had longer and more complex calls. In addition to providing direct information about motivation, vocalizations may have a metacommunicative function in alerting adult group members (not play partners) to the presence of playful activity.     

Microsatellite polymorphisms in Bolivian squirrel monkeys (Saimiri boliviensis)

Two different approaches were used to identify new microsatellite polymorphisms among captive Bolivian squirrel monkeys (Saimiri boliviensis). In the first case, PCR primers for published human microsatellite loci were screened using genomic DNA from squirrel monkeys. Six polymorphic loci were identified using DNA samples from 19 unrelated individuals. The average heterozygosity among these six loci is 0.73. In the second set of experiments, a DNA library was created from Saimiri genomic DNA, and clones were selected from that library by screening with probes containing di-, tri-, and tetranucleotide repeats. Six novel microsatellites were identified this way, with an average heterozygosity of 0.59. Primer pairs for these six cloned microsatellites were also screened using a series of DNA samples from ten other platyrrhine species to assess the potential utility of these loci in other taxa. This study provides 12 new DNA polymorphisms that will be useful for various studies of this genus and demonstrates that both approaches can be used to develop new DNA polymorphisms in platyrrhine species.     

Seasonality of reproduction in captive squirrel monkeys (Saimiri Sciureus)

Seasonality of reproduction is believed to be influenced by environmental factors such as humidity, temperature, and photoperiod. In primates, there has been much speculation about which environmental factors have the greatest influence on reproductive seasonality. To determine whether environmental factors affect seasonality of reproduction of squirrel monkeys in captivity, I used path analysis to compare number of births and matings per month with monkeys kept in indoor enclosures (maintained at optimal temperatures) and those kept in outdoor enclosures (exposed to the elements). Since a different pattern of seasonality was found to occur, I was able to test whether temperature, rainfall, or photoperiod could explain the temporal variation in reproduction. Squirrel monkeys raised in captivity displayed different patterns of seasonality of reproduction, depending on the conditions in which they are housed ( chi(2)3 25.12, P<0.001; G = 28.10, P<0.001). Temperature seemed to have a large impact on number of births and matings per month (matings: path coefficient = 0.799; births: path coefficient = -1.315). Understanding what factors regulate reproduction for animals and how these factors affect reproduction differently in wild versus captive populations are important to conservation and management of species.     

Characterization of Gilbert-like syndrome in squirrel monkeys (Saimiri sciureus)

Bolivian squirrel monkeys, unlike those of Brazilian origin, exhibit a marked fasting hyperbilirubinemia (FH) similar to that observed in Gilbert's syndrome in man. Since no delays in the hepatic clearance of sulfobromophthalein or indocyanine green are present, the Bolivian monkey appears to be similar to Gilbert's type I syndrome. FH can be significantly decreased by either phenobarbital or tin-protoporphyrin pretreatment. Nicotinic acid-induced hyperbilirubinemia and delayed tolbutamide clearance were not observed as in the human syndrome.     

Breeding and rearing squirrel monkeys (Saimiri sciureus) in captivity.

A breeding colony of squirrel monkeys (Saimiri sciureus) was established to provide animals for behavioral research concerned with early development. The origin of the initial breeders was Peru, Colombia, and Bolivia. During the past 10 years, the colony has grown to 125 adult females, 20 adult males, and 120 immature animals of various ages. The annual conception rate for the last 5 years averaged 68%. This resulted in 84% viable births of which 82% survived past 6 months of age. The majority of the births (65%) occurred during June-August, and 87% during May-September. The most efficient and successful breeding strategy was to form mixed-sexed groups of 10--15 females and 2--3 males before the mating season began and to maintain the integrity of these groups with minimal interference. Progeny were reared apart from their natural mother without difficulty, and their growth and development were found to be similar to those of mother-reared monkeys.     

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist

L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.     

Mycobacterium kansasii infection in squirrel monkeys (Saimiri sciureus sciureus)

Abstract: This report documents asymptomatic infections of Mycobacterium kansasii in four of five tuberculin positive squirrel monkeys (Saimiri sciureus sciureus). The mycobacterial DNA amplified by polymerase chain reaction (PCR) from a bronchial lymph node had no affinity for the species specific probes of M. tuberculosis, M. avium, and M. intracellular, thus allowing the presumptive diagnosis of an atypical mycobacterial infection. Infection by Mycobacterium kansasii was confirmed by culture of bronchial lymph nodes from three monkeys. The source of the infection was never identified.     

Haptic discrimination of size and texture in squirrel monkeys ( Saimiri sciureus )

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm).The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.     

Haptic discrimination of size and texture in squirrel monkeys (Saimiri sciureus)

The present study analyzed haptic abilities of four squirrel monkeys. Using a two-alternative forced-choice procedure, stimuli were presented in a visually opaque box, allowing unrestrained test subjects to grab through a small opening and touch the discriminanda. Difference thresholds were determined by a modified method of limits. In the first experiment we determined size difference thresholds for the discrimination of circular cylinders using standard stimuli differing in diameter from 10 mm to 35 mm. In the second experiment a texture difference threshold was obtained for the discrimination of grooved surfaces (groove width 2-7 mm). The squirrel monkeys achieved a mean size difference threshold of 8% stimulus difference. The linear increase of absolute thresholds as a function of the starting stimulus size showed that haptic size discriminations in squirrel monkeys correspond to Weber's law. Three of the animals achieved a texture difference of 10% stimulus difference, while one monkey showed a distinctively lower haptic acuity. An analysis of the exploratory behavior points to a subject-related difference in the significance of cutaneous and kinesthetic information during size discriminations. Whereas differences in the animals' exploratory behavior did not correlate with the size difference threshold a subject achieved, different thresholds for texture discrimination can be explained by the different exploratory procedures the monkeys used to touch grooved surfaces. The low difference thresholds determined for the squirrel monkeys in the present study point to the significance of unrestrained test conditions for the assessment of the haptic capacity of a species.