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[Microbiological development studies in a clinically healthy, closed primate colony (Macaca mulatta, Macaca arctoides) after the establishment of a Salmonella infection].

A case of a Salmonella infantis septicemia in a primate (Macaca mulatta) probably induced by shipment stress gave rise to microbiological examination of fecal samples from all animals of a since 1976 closed colony of Macaca mulatta and Macaca arctoides. During 3 investigations carried out in 3 week intervals salmonella-positive animals were separated immediately from the stock. At the first examination 3 of 52, and at the second 2 of 49 samples were found to be salmonella-positive. At the third series all of the remaining 47 animals proved to be salmonella-negative. All isolates were identified as S. infantis. Feeding of contaminated, dried prawns was suspected as the most probable source of infection. A simultaneous examination of 96 of the stool specimens revealed Y. enterocolitica in 4 samples. Additionally, electron-microscopy of pooled fecal samples (3 to 4 animals each) led to demonstration of corona-, adenovirus and small round virus-like particles in one pool each. Moreover, coronavirus-like particles could be detected in 7 of 13 (1st examination series), 5 of 15 (2nd series) and 1 of 13 pools (3rd series).

Animals↗

Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureus used for research at the Fiocruz primate center.

Physiological parameters of laboratory animals used for biomedical research is crucial for following several experimental procedures. With the intent to establish baseline biologic parameters for non-human primates held in closed colonies, hematological and morphometric data of captive monkeys were determined. Data of clinically healthy rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and squirrel monkeys (Saimiri sciureus) were collected over a period of five years. Animals were separated according to sex and divided into five age groups. Hematological data were compared with those in the literature by Student's t test. Discrepancies with significance levels of 0.1, 1 or 5% were found in the hematological studies. Growth curves showed that the sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier ages, the differences between sexes could not be distinguished (p < 0.05). Sexual dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of about 32 months. Data presented in this paper could be useful for comparative studies using primates under similar conditions.

Age Factors↗

Transmission of Sarcocystis suihominis from humans to swine to nonhuman primates (Pan troglodytes, Macaca mulatta, Macaca irus).

Sporocysts of Sarcocystis suihominis obtained from human feces were used to infect swine. Heart, tongue, and skeletal muscle from experimentally infected and noninfected control swine were fed via stomach tube to nonhuman primates including chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), and cynomolgus monkeys (Macaca irus). All primates fed infected swine tissues shed sporocysts beginning 13 to 15 days postinfection and were still shedding sporocysts at the conclusion of the experiment, 30 days postinfection. Rhesus and cynomolgus monkeys were fed infected swine tissues a second time and shed sporocysts. All primates remained in good health throughout both experiments and exhibited no unusual clinical signs as a result of infection.

Animals↗

Embryotoxicity of sex steroidal hormone combinations in nonhuman primates: I. Norethisterone acetate + ethinylestradiol and progesterone + estradiol benzoate (Macaca mulatta, Macaca fascicularis, and Papio cynocephalus).

Two sex steroid hormone combinations which have been used clinically as tests for detection of early pregnancy were examined for embryotoxic effects in macaques and baboons. Norethisterone acetate and ethinyl estradiol (NEA + EE) were orally administered to rhesus and cynomolgus monkeys and baboons at dosages ranging from one to 1,000 times the human dose equivalent (HDE) during days 20-50 of pregnancy. Progesterone and estradiol benzoate (P + EB) were delivered by two to six intramuscular injections to rhesus and cynomolgus monkeys between gestational days 20 and 35 at 0.1-25 X HDE. Fetuses were examined following cesarean section at 100 +/- 2 days (NEA + EE) or at term (P + EB). The results showed increased embryolethality over controls at 100-1,000 X HDE (NEA + EE) and at 10 and 25 X HDE (P + EB). Besides growth retardation, isolated cases of minor nongenital malformations were observed only in cynomolgus monkeys following treatment with both hormone combinations mainly at embryolethal dose levels and were considered spontaneous in nature. Virilization of female cynomolgus fetuses following NEA + EE treatment was manifested as two cases of clitoral enlargement in the 300 X HDE group and two cases of increased anogenital distance with reduced vaginal opening in the 1,000 X HDE group. The highest dose of NEA + EE was also maternally toxic, as two maternal deaths occurred at the end of the treatment period. One dead female cynomolgus fetus exposed to P + EB (10 X HDE) also exhibited masculinized external genitalia.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

A linkage study of protein-coding loci in Macaca mulatta and Macaca fascicularis.

Genealogical and gene marker data from the closely related species Macaca mulatta and Macaca fascicularis have been used to search for linkage between genes coding for the blood proteins albumin, carbonic anhydrase 1 and 2, diaphorase 1 and 2, group-specific component, glucose phosphate isomerase, hemoglobin alpha chains, isocitrate dehydrogenase, prealbumin, and transferrin. The results are consistent with conservation of the linkage between the loci coding for albumin and group-specific component and loci coding for the two carbonic anhydrase isozymes, as observed in other species. Among the 38 possible pairwise comparisons, no new linkage groups were identified. Tight linkage can be excluded for most pairs of loci.

Animals↗

Expression of peripherin in the brain of macaques (Macaca mulatta and Macaca fascicularis) occurs in astrocytes rather than neurones and is associated with encephalitis.

Peripherin is a member of the type III intermediate filament family, expressed in neurones of the peripheral nervous system of many species and in a discrete subpopulation of neurones of the central nervous system (CNS) during early development in rodents. Previous studies on rats have shown that peripherin immunoreactivity increased significantly in cell bodies of spinal motor neurones following axonal injury. Our study examined the expression of peripherin in the cerebrum of normal macaques (Macaca mulatta and Macaca fascicularis) and those with encephalitis of viral (simian immunodeficiency virus and simian virus 40) or autoimmune (experimental allergic encephalomyelitis) aetiology. Immunohistochemistry, immunoelectronmicroscopy, immunofluorescence and confocal microscopy were performed on tissue sections using antibodies against cell-specific markers and peripherin. Peripherin-positive cells were absent in the cerebrum of normal macaques of all ages examined, whereas animals with encephalitis had peripherin-positive cells associated with inflammatory infiltrates. Further evaluation revealed that these peripherin-positive cells were not neurones, but were predominantly astrocytes expressing glial fibrillary acidic protein. Our study suggests that peripherin is not neurone-specific in the CNS of macaques; peripherin is expressed in astrocytes of animals with encephalitis.

Animals↗

Lymphocyte cultures of Macaca mulatta and Macaca fascicularis.

Lymphocytes of Macaca mulatta and Macaca fascicularis were cultured using a microculture technic. The use of RPMI-1640 with fetal calf serum as a culture medium and an extra dose of phytohemagglutinin produced excellent results. Staining of the chromosomes by the Gemsa banding technic did not reveal any differences between the karyotypes of the Macaca species.

Anemia↗

Placental transfer of phenylalanine in Macaca mulatta and Macaca fascicularis.

We investigated placental transport mechanisms of phenylalanine in Macaca mulatta and Macaca fascicularis. In the beginning of the third trimester we administered i.v. phenylalanine and p-chlorophenylalanine to pregnant animals. Initial higher phenylalanine concentrations were observed followed by a rapid decrease in both rhesus mothers and fetuses when compared with phenylalanine levels in fascicularis mothers and fetuses. In general, however, placental transfer mechanisms of phenylalanine did not differ significantly between the two species.

Animals↗

Comparative blood values of Macaca mulatta and Macaca fascicularis.

Hematological and clinical biochemistry values of two species of monkeys (Macaca mulatta and Macaca fascicularis) were measured by using auto-analyzers. WBC and RBC counts of M. fascicularis were high and Hb, MCV, MCH and MCHC values of M. fascicularis were low in comparison with those of M. mulatta. Albumin and creatinine levels of M. fascicularis were lower than those of M. mulatta. Total protein and A1P values of female M. fascicularis were higher than those of female M. mulatta. Differences between the sexes were observed in MCV, inorganic phosphorus, total protein, albumin and creatinine in M. mulatta, whereas in M. fascicularis, such differences were demonostrated as to creatinine, phospholipids and triglycerides.

Animals↗

Comparative study of lung cytologic features in normal rhesus (Macaca mulatta), cynomolgus (Macaca fasicularis), and African green (Chlorocebus aethiops) nonhuman primates by use of bronchoscopy.

Invasive bronchoscopy and bronchoaveolar lavage (BAL) fluid collection represents an important tool in studies of the respiratory system of nonhuman primates. Bronchoscopy and BAL fluid collection was performed on groups of rhesus (Macaca mulatta) and cynomolgus (Macaca fasicularis) macaques and African green monkeys (Chlorocebus aethiops), and the resulting comparative lavage cytologic features are described. Analysis of the BAL fluid did not reveal significant differences among species with respect to total cells recovered or differential cellular composition. This description of the method used to lavage the nonhuman primates and the resulting lung cytologic findings provide important comparative data for three species commonly used in biomedical research.

Animals↗

Effect of different promoters on immune responses elicited by HIV-1 gag/env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina.

pCMV-NL(Deltapol) and pAKV-NL(Deltapol) expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter/enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV-NL(Deltapol) and pAKV-NL(Deltapol) in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Macaca mulatta, pCMV-NL(Deltapol) generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NL(Deltapol). Similarly, in Macaca nemestrina pCMV-NL(Deltapol) elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NL(Deltapol), in general, failed to produce antibody levels comparable to pCMV-NL(Deltapol). However, injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation.

3T3 Cells↗

Characterization of the insulin-like growth factor (IGF) axis in the serum of maternal and fetal macaques (Macaca mulatta and Macaca fascicularis).

The insulin-like growth factors (IGFs) are key effectors of fetal growth and development which are modulated by serum carrier proteins (IGF binding proteins [IGFBPs]). Studies were performed to evaluate the developmental profile of IGFs and IGFBPs in the macaque, an important nonhuman primate model for human development and disease. IGF-I, IGF-II, and IGFBP-3 were studied in the rhesus (Macaca mulatta) and long-tailed (Macaca fascicularis) monkey fetus and dam during the second and third trimesters of pregnancy. Serial fetal blood samples were collected by cardiocentesis every 10 days from gestational day (GD) 90-160, and at 1 month postnatal age; maternal blood samples were collected at similar timepoints. Results indicated that maternal sera IGF-I and IGF-II did not change significantly whereas fetal concentrations of serum IGF-I and IGF-II increased approximately two-fold during the second to the third trimesters. No significant differences were detected between the two species. Western-ligand blot analysis revealed predominant IGFBPs of 45-40 (IGFBP-3) and 28 kDa (IGFBP-1) in both the maternal and fetal compartments, and Western-immunoblot analysis using a specific antisera against IGFBP-3 indicated 45-40 and 28 kDa immunoreactive forms. Thus, although IGF-I, IGF-II, and IGFBP-3 remained relatively unaffected in maternal sera during this period of gestation, fetal concentrations of IGF-I, IGF-II, and IGFBP-3 increased in a developmental profile similar to the human fetus.

Animals↗

[Dopamine of the caudate nucleus in Perodictious potto, Macaca mulatta and Macaca fascicularis].

The dopamine, dopac and tyrosinehydroxylase contents of the caudate nucleus in the prosimian Perodicticus potto and in the simii Macaca mulatta and M. fascicularis have been estimated. The results do not support the hypothesis according to which the sluggishness of the potto is somehow related to a low dopamine content of part of the extrapyramidal system as found in the Parkinson-syndrome.

Animals↗

[Experimental research on the preparation of dentin-pulp tissue of teeth exposed to CO2 laser beams in dogs and macaques (Macaca mulatta and Macaca fascicularis].

Traumatic inflammation due to application of CO2 laser radiation (lambda = 10.6 microns) on the dentin and on pulp of 342 teeth of 8 dogs (Beagle) and of 6 monkeys (Macaca sp. mulatta et fascicularis) stimulate in dentino-pulpal tissue morphological phenomenon, studied after 5 days, 1 and 3 months by microscopy and microradiography. The dentin exposed to a density of energy of: 2 X 10(3) J/cm2 shows a burn, a rarefaction and a cellular degeneration, followed by a neoformation of calcified dentin, of about 300 microns thick in 3 months, due to the excitation of odontoblasts or produced by pulpal cells functioning before. A density of energy of 10(3) J/cm2 order applied to the pulp beads to its partial necrosis, to various inflammatory aspects (vascular, cellular, tissular) and to a quasi-constant regeneration of by a neo-dentin bridge of 200 micron at 1 month. This method seems able to allow the analysis of cell activity (start, activation, blocking).

Animals↗