Voluntary consumption of substances of unknown palatability by vervet monkeys: a refinement.

BACKGROUND: Pure compounds and herbal medicines, had to be administered orally to vervet monkeys for testing. A reliable method was sought to avoid daily gavaging. METHODS: Substances were incorporated into the maize meal based diet of this facility for voluntary consumption. Food intake was monitored. RESULTS: In all but one case, consumption of the treated food was in excess of 90%. In all cases, the purpose of the study was achieved. Habituation was usually only required to the vehicle, and was accomplished by incremental increases to the desired concentration. Aversion was overcome by the addition of a small amount of honey. Plasma concentrations of a compound metabolite could be measured in one case after gavage and food consumption, and were similar for both methods. CONCLUSION: The method enables reliable voluntary consumption of diverse substances. Since stressful gavaging is avoided, it is a valuable contribution to the 3Rs.

Risks associated with environmental enrichment: intestinal obstruction caused by foraging substrate.

Questions are occasionally asked about the safety of enrichment techniques, considering that many novel ways are frequently employed to ensure environmental complexity. A juvenile male vervet monkey was found with a phytobezoar of straw obstructing the sigmoid colon. The straw was foraging substrate, which is used in communal cages. Due to the extent of the resulting necrosis in the sigmoid and descending colon, the monkey had to be killed. This is the only individual to have suffered a harmful effect from the foraging substrate from amongst 120 vervet monkeys, which have been permanently housed on straw for over 5 years.

Endometrial function in vervet monkeys (Cercopithecus aethiops): morphology, beta3 integrin and insulin-like growth factor binding protein-1 expression during the menstrual cycle and pregnancy in the normal and disrupted endometrium.

The expression of endometrial beta3 integrin and insulin-like growth factor binding protein-1 (IGFBP-1) was studied in cycling and pregnant vervet monkeys. There were clear changes of beta3 integrin expression during the menstrual cycle, with the strongest immunostaining observed on day 26. Moderate to strong expression was observed during pregnancy. The expression of IGFBP-1 during the menstrual cycle was weak but upregulated during pregnancy with moderate to strong staining. The administration of a single dose of onapristone at 10 mg/kg on days 17, 21 and 22 of the menstrual cycle, followed by a biopsy on days 22, 22 and 26, respectively, and during pregnancy (34-44 days menstrual age) 24 h before the biopsy, disrupted and desynchronized the endometrium. However, no effect on beta3 integrin expression could be observed and staining reflected the untreated patterns. The same applied to IGFBP-1 except that during pregnancy the expression of this protein was reduced or abolished. The results suggest that beta3 integrin is associated with endometrial receptivity in vervet monkeys and that IGFBP-1 plays an important role during pregnancy in this species. The administration of onapristone appeared to only influence IGFBP-1 expression. To our knowledge, this is the first time that these endometrial proteins have been investigated in vervet monkeys. This study should therefore contribute to improving our understanding of the reproductive function of this species.

Probable genetic origin for a large number of cataracts among captive-bred vervet monkeys (Chlorocebus aethiops).

During a period of 6 years, uni- or bilateral cataracts occurred in 55 captive-bred vervet monkeys, representing 27.6% of all offspring produced in that time. Fifty-eight percent of all cases were detectable only by ophthalmoscopy. A total of 30% of cases were offspring of wild-caught parents, 40% from first-generation captive-bred parents, 4% from second-generation captive-bred parents, and 26% from parents of which one was wild caught. Cataracts that could be observed macroscopically appeared at about 6-8 mo of age. A sample of juvenile vervet monkeys with cataracts and their parents had no antibodies against rubella virus, herpes simplex virus, or toxoplasma gondi, and all except two wild-caught breeding females had no antibodies against cytomegalovirus. Plasma vitamin D3 (25 [OH] D), calcium, phosphorus, and glucose concentrations of six cataract cases were comparable to a control group of healthy individuals. The exclusion of these extraneous factors, as well as the fact that the majority of all cases were related, was considered evidence of hereditary etiology. Males and females that had either produced offspring with cataracts or were related to individuals with cataracts were replaced. To date, 35 babies have been born, and no new cases have since occurred.

Toxicity of culture material of Fusarium verticillioides strain MRC 826 to nonhuman primates.

We conducted a chronic feeding study in vervet monkeys (Cercopithecus aethiops) over 13.5 years. The experimental design consisted of two dietary treatment groups, each including males and females, fed varying levels of culture material of Fusarium verticillioides (Sacc.) Nirenberg (= F. moniliforme Sheldon) strain MRC 826 mixed into their daily food ration. Two females were included as treatment controls. We conducted blood chemical analyses bimonthly and recorded all clinical signs during the course of the experiment. We took liver biopsies at various stages during the initial phase of the experiment. Several monkeys were terminated in extremis during the experiment. Detailed feed intake profiles were determined 5 years after the experiment began, and the fumonisin B (FB) mycotoxin content of the feed was determined during the final stages of the experiment. The apparent FB consumption patterns were related to changes observed in the biochemical parameters in the blood and urine, including the liver function enzymes and creatinine clearance as well as differential blood counts and sphingolipid levels in the serum and urine. An apparent no-effect threshold for kidney and liver damage is estimated to be between 0.11 and 0.18 mg FB/kg body weight (bw)/day, which corresponds to a feed contamination level of between 8.21 and 13.25 mg FB/kg bw diet. Apart from the effects on the liver and kidney, a wide variety of parameters, including cholesterol and creatine kinase, were also adversely affected. Several blood parameters, including white and red blood cells, also significantly decreased in the treated animals. The serum sphinganine level and the sphingosine/sphinganine ratio, monitored toward the end of the experiment, significantly increased in both the low-dose and high-dose animals. The present study provides important information about the diversity of lesions induced by culture material of F. verticillioides in vervet monkeys and the dosage levels of fumonisins to be used in long-term studies in nonhuman primates.

The detection and monitoring of early pregnancy in the vervet monkey (Cercopithecus aethiops) with the use of ultrasound and correlation with reproductive steroid hormones.

Twenty early pregnancies were diagnosed and monitored in vervet monkeys by ultrasonography. Non-gravid uteri became increasingly echogenic from cycle days 7 to 26. The first definite sign of pregnancy was a gestational cavity of 2 mm (+/- 0.80) at 33.0 (+/- 1.48) days menstrual age, which was also used to date all subsequent features. Earlier signs, such as an endometrial line swelling or endometrial 'pregnancy' ring, as reported for other non-human primate species, could not be reliably and consistently used to diagnose pregnancy in vervet monkeys. A rapid increase of the gestational cavity size from days 37 to 49 corresponded closely to a rapid increase in plasma progesterone concentration from day 39 to 49. The first yolk sac was recognizable at 38.0 days (+/- 3.10) and measured 3.3 mm (+/- 0.40) in diameter. A heart beat could be detected at 45.5 (+/- 1.73) days and the size of the first measurable embryo at 35 days was 2 mm. The dating of most features was within the range reported for other non-human primate species.

The maturation of sperm motility in the epididymis and vas deferens of the vervet monkey, Cercopithecus aethiops.

Among the diverse facets of sperm maturation, changes in motility are conspicuous and hence studies of sperm kinematics might provide good indices for sperm maturation. Accordingly, the maturation of sperm motility in the epididymis and vas deferens of the vervet monkey, Cercopithecus aethiops, was assessed using a computer-aided sperm motility analysis system. The results revealed clear trends in the development of both sperm motility per se and in the movement characteristics of motile spermatozoa from different regions of the epididymis, the vas deferens and the ejaculate, reflecting maturational changes associated with the attainment of functional motility and fertility. Motion of spermatozoa from the caput epididymis was sluggish and irregular. As the spermatozoa moved through the corpus epididymis, motility increased sharply, and continued to improve through the cauda epididymis and vas deferens. Despite the high proportion of motile cells, full maturation of motion capabilities was not completed in spermatozoa from the corpus epididymis. Only once spermatozoa had reached the cauda epididymis and vas deferens did they attain their full vigour, and swam rapidly (greater VCL, VSL and VAP) with straightline trajectories (greater LIN, WOB and STR; lower ALH, MAD and CURV). After acquiring their maximal percentage motility and progressive velocity in the cauda epididymis and vas deferens, a slight decline in motility and vigour occurred in ejaculated spermatozoa, and was possibly associated with the ageing of stored spermatozoa. The results from this investigation have revealed clear trends in the maturation of the motility of vervet monkey spermatozoa during their transit through the epididymis and vas deferens and final emergence in the ejaculate, and have provided crucial baseline information on the reproductive physiology of this potentially valuable biomedical model to serve as a reference for future studies in reproductive toxicology.

Abnormal morphology of vervet monkey sperm.

Ejaculates of 14 colony-bred and 14 wild-caught vervet monkeys were examined for morphologically abnormal sperm. Sperm head abnormalities were rare in both groups, occurring at rates of 0.01-0.29%. Tail abnormalities predominated, particularly bent midpieces and coiled and folded tails, which all occurred at rates of 3.79-17.18%. Except for the nipple acrosome, there was no difference in the rate at which sperm abnormalities were found in both groups. Three abnormalities were found only in colony-bred and three only in wild-caught individuals. Some common abnormalities, all affecting the tail, were highly variable in consecutive ejaculates from the same individuals.

A mobile cage facilitates periodic social contact and exercise for singly caged adult Vervet monkeys.

A mobile exercise cage that expands the quantity and improves the quality of the space available to singly caged adult Vervet monkey males is described. It was easily fitted into an existing caging system and the addition of a resident consort female made it possible for the males to mate and have regular social contact.

Pleural Mesocestoides and cardiac shock in an obese vervet monkey (Cercopithecus aethiops).

Only one case of infection by tetrathyridia larvae of the tapeworm genus Mesocestoides was detected in 416 necropsies of captive vervet monkeys (Cercopithecus aethiops). Two hundred nine larvae were distributed between both pleural cavities. Mass and size ranges of larvae were determined. A plasma cell reaction indicated a humoral immune response to parasite antigens, which may have contributed to acute, lethal cardiac shock. Coagulative myocytolysis was confirmed. The history of this case and associated circumstantial evidence and reports in the literature suggest that infection of primates by tetrathyridia probably occurs after capture rather than before.

Assessment of acrosomal integrity of vervet monkey spermatozoa after cryopreservation.

Cryopreservation of Vervet monkey semen caused a highly significant reduction in the percentage of normal acrosomes and a highly significant increase in the percentage of mildly damaged, severely damaged, and lost acrosomes. This was demonstrated by staining ten post-thaw semen samples, which enabled a visualization of the acrosomal damage. The incidence of post-thaw intact acrosomes in this cryopreservation method was found to be similar to that reported for man and cynomolgus monkey semen.

Cryopreservation of vervet monkey semen and recovery of progressively motile spermatozoa.

A method to cryopreserve semen from the Vervet monkey (Cercopithecus aethiops) has been developed, yielding a mean post thaw recovery of 63.60% of pre-freeze progressive motility. The extender contained a TES-TRIS buffer, egg yolk, dextrose, streptomycin, penicillin, and glycerol as cryoprotectant. The pH ranged from 7.10-7.18 and the osmolality was 330-345 mOsmol/L.

Parathyroid hormone, ionised calcium, and potentially interacting variables in plasma of an Old World primate.

Bone turnover and calcium homeostasis in man can only be modelled validly in Old World nonhuman primates. In order to interpret the models it is necessary to establish endocrine and biochemical parameters of bone mineral metabolism. This report is probably the first description of acute phase parathyroid responses to manipulations of blood ionised calcium, and of reference values for potentially interacting variables, in vervet monkeys. Plasma parathyroid hormone concentrations were measured in vervets under defined conditions, and ranges reported as normal for other nonhuman primates and man are summarised.

Folic acid and vitamin B12 status of vervet monkeys used for nutritional research.

Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys (Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12.8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90.7, 132.3 and 152.8 ng/ml, respectively. A megadose of 25.6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml.

Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet.

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.

Torsion of the colon in vervet monkeys: association with an atherogenic Western-type of diet.

The risk of torsion of the colon in adult male vervet monkeys (Cercopithecus aethipos) increased when they were fed with an atherogenic Western-type of diet. No cases occurred in females and rapid diagnosis is necessary to prevent lethal consequences.

Mycotoxic peripheral myelinopathy, myopathy, and hepatitis caused by Diplodia maydis in vervet monkeys.

During recent historical times many Africans changed their diet to one based on maize. The grain is regularly contaminated by fungi which are toxigenic to domestic animals and birds. After one of the fungi, Diplodia maydis, in pure culture on maize, was added to the food of omnivorous primates there was demyelination of nerves, atrophy, degeneration and necrosis of muscle, and hepatitis. These preliminary results are applicable to veterinary and laboratory animal sciences. They may also be medically significant since neuromuscular syndromes of unknown cause are prevalent among Africans. Nerve conduction velocities and organ weights are defined for vervet monkeys.

Hormonal vaginal cytology of vervet monkeys.

The cellular proliferation and maturation of the vaginal epithelium of adult female Vervet monkeys was examined during their menstrual cycles. At the same time the serum contents of estrogen and progesterone were analysed. Gradual but distinct patterns demarcated the phases of the menstrual cycle cytologically. The karyopyknotic index paralleled the estrogen concentration. Mid-cycle peak maturation produced many anucleate squames, which exfoliated, forming a diagnostic vaginal discharge.