High Branched-Chain Amino Acid Concentrations Are Found in Preterm Baboons Receiving Intravenous Amino Acid Solutions and Mimic Alterations Found in Preterm Infants.

BACKGROUND: Parenteral amino acid (AA) nutrition administration after premature birth is necessary to ensure adequate growth and neurodevelopment. However, optimizing safety and efficacy remains a major challenge. This study investigated the effects of intravenous AA administration on plasma AA profiles in premature baboons and infants. METHODS: Premature baboons were delivered by cesarean section at 125 days (67% gestation) and chronically ventilated. At 24 hours of life, a parenteral AA protocol comparable to the early and high AA regimens used in premature infants was initiated. Serial plasma AA concentrations were obtained on days of life (DOLs) 1, 3, and 7 and compared with concentrations at similar DOLs from preterm infants. Fetal baboon (165 ± 2 days; 89% gestation) and term baboon plasma AA concentrations were obtained for comparison. RESULTS: Premature baboons receiving early and high parenteral AA supplementation exhibited significant differences in plasma AA concentrations compared with fetuses. In particular, concentrations of leucine, isoleucine, valine, and ornithine were elevated (fold increase: 2.14, 2.03, 1.95, and 16.5, respectively; P < 0.001) on DOL 3 vs fetuses. These alterations mimicked those found in preterm infants. CONCLUSION: Early and high AA supplementation in extremely premature baboons significantly disrupted plasma AA concentrations. Elevated concentrations of branched-chain AAs and ornithine raise concerns for adverse neurodevelopmental outcomes. These results are consistent with those found in premature human infants and emphasize the need to optimize parenteral AA solutions for the unique metabolic requirements of premature infants. Improved technologies for rapid monitoring of AA concentrations during treatment are essential.

Comparison of vitamin D metabolites in wild and captive baboons.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D3 synthesis, captive primates are supplemented with vitamin D3 (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D2&3 (25(OH)D2&3 ), and 24,25 dihydroxyvitamin D2&3 (24,25(OH)2 D2&3 ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D3 while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D3 . Further metabolic conversion of 25(OH)D3 to 24,25(OH)2 D3 indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.

Blood meal identification in the cryptic species Anopheles gambiae and Anopheles coluzzii using MALDI-TOF MS.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has recently emerged in entomology as a technique to identify arthropods and their blood meal source. In this study, female Anopheles gambiae were fed on five host blood sources: ocelot (Leopardus pardalis), binturong (Arctictis binturong), springbok (Antidorcas marsupialis), jaguar (Panthera onca) and Hamadryas baboon (Papio hamadryas), while Anopheles coluzzii were fed on three hosts: dromedary (Camelus dromedarius), Barbary sheep (Ammotragus lervia) and pig (Sus scrofa). We obtained the MS spectra from 240 engorged mosquito abdomens and selected high quality ones from 72 mosquito abdomens to upgrade our home-made database. We excluded from the analysis any spectra of low quality (n = 80), and the remaining 88 specimens were subjected to a blind test analysis against the home-made database. We obtained 100% correct identification of the blood meal source for the specimens collected, 1, 12 and 24 h post-feeding, whereas for the specimens collected 36 h post-feeding, the correct identification rate decreased dramatically. We confirm here that MALDI-TOF MS can be used to identify the blood meal origin of freshly engorged mosquitoes, which opens new perspectives for further studies, including the impact of the mosquito species on blood meal identification.

TITLE: Identification du repas sanguin des espèces cryptiques Anopheles gambiae et Anopheles coluzzii par l'utilisation de MALDI-TOF MS. ABSTRACT: L'identification par spectrométrie de masse à temps de vol par désorption/ionisation assistée par matrice (MALDI-TOF MS) a récemment émergé en entomologie pour l'identification des arthropodes et de leur source de sang. Des femelles d'Anopheles gambiae ont été nourries de sang de cinq hôtes, ocelot (Leopardus pardalis), binturong (Arctictis binturong), springbok (Antidorcas marsupialis), jaguar (Panthera onca) et babouin Hamadryas (Papio hamadryas), et des femelles d'Anopheles coluzzii ont été nourries sur trois hôtes, dromadaire (Camelus dromedarius), mouflon à manchettes (Ammotragus lervia) et porc (Sus scrofa). Nous avons obtenu les spectres MS à partir de 240 abdomens de moustiques engorgés et avons sélectionné ceux de 72 abdomens de moustiques de haute qualité pour améliorer notre base de données maison. Nous avons exclu de l'analyse les spectres de faible qualité (n = 80) et les 88 échantillons restants ont été soumis à une analyse de test en aveugle contre la base de données maison. Nous avons obtenu 100 % d'identification correcte de la source de sang pour les échantillons collectés, 1, 12 et 24 heures après l'alimentation, mais le taux d'identification correct a diminué de façon spectaculaire pour les échantillons collectés 36 heures après l'alimentation. Nous confirmons ici que la MALDI-TOF MS peut être utilisée pour identifier l'origine des repas sanguins des moustiques fraîchement engorgés et ouvre de nouvelles perspectives pour d'autres études, y compris l'impact des espèces de moustiques sur l'identification des repas sanguins.

High-resolution gas chromatography/mass spectrometry metabolomics of non-human primate serum.

RATIONALE: Metabolomics analyses using gas chromatography/mass spectrometry (GC/MS)-based metabolomics are heavily impeded by the lack of high-resolution mass spectrometers and limited spectral libraries to complement the excellent chromatography that GC platforms offer, a challenge that is being addressed with the implementation of high-resolution (HR) platforms such as 1D-GC/Orbitrap-MS. METHODS: We used serum samples from a non-human primate (NHP), a baboon (Papio hamadryas), with suitable quality controls to quantify the chemical space using an advanced HRMS platform for confident metabolite identification and robust quantification to assess the suitability of the platform for routine clinical metabolomics research. In a complementary approach, we also analyzed the same serum samples using two-dimensional gas chromatography/time-of-flight mass spectrometry (2D-GC/TOF-MS) for metabolite identification and quantification following established standard protocols. RESULTS: Overall, the 2D-GC/TOF-MS (~5000 peaks per sample) and 1D-GC/Orbitrap-MS (~500 peaks per sample) analyses enabled identification and quantification of a total of 555 annotated metabolites from the NHP serum with a spectral similarity score Rsim  ≥ 900 and signal-to-noise (S/N) ratio of >25. A common set of 30 metabolites with HMDB and KEGG IDs was quantified in the serum samples by both platforms where 2D-GC/TOF-MS enabled quantification of a total 384 metabolites (118 HMDB IDs) and 1D-GC/Orbitrap-MS analysis quantification of a total 200 metabolites (47 HMDB IDs). Thus, roughly 30-70% of the peaks remain unidentified or un-annotated across both platforms. CONCLUSIONS: Our study provides insights into the benefits and limitations of the use of a higher mass resolution and mass accuracy instrument for untargeted GC/MS-based metabolomics with multi-dimensional chromatography in future studies addressing clinical conditions or exposome studies.

Loa loa and Onchocerca ochengi miRNAs detected in host circulation.

A combination of deep-sequencing and bioinformatics analysis enabled identification of twenty-two microRNA candidates of potential nematode origin in plasma from Loa loa-infected baboons and a further ten from the plasma of an Onchocerca ochengi-infected cow. The obtained data were compared to results from previous work on miRNA candidates from Dirofilaria immitis and O. volvulus found in host circulating blood, to examine the species specificity of the released miRNA. None of the miRNA candidates was found to be present in all four host-parasite scenarios and most of them were specific to only one of them. Eight candidate miRNAs were found to be identical in the full sequence in at least two different infections, while nine candidate miRNAs were found to be similar but not identical in at least four filarial species.

Quantitative determination of telavancin in pregnant baboon plasma by solid-phase extraction and LC-ESI-MS.

The increasing incidence and severity of methicillin- and vancomycin-resistant infections during pregnancy prompted further development of telavancin. The understanding of the pharmacokinetics of telavancin during pregnancy is critical to optimize dosing. Due to ethical and safety concerns the study is conducted on the pregnant baboons. A method using solid-phase extraction coupled with liquid chromatography-single quadrupole mass spectrometry for the quantitative determination of telavancin in baboon plasma samples was developed and validated. Teicoplanin was used as an internal standard. Telavancin was extracted from baboon plasma samples by using Waters Oasis(®) MAX 96-Well SPE plate and achieved extraction recovery was >66% with variation <12%. Telavancin was separated on Waters Symmetry C18 column with gradient elution. Two SIM channels were monitored at m/z 823 and m/z 586 to achieve quantification with simultaneous confirmation of telavancin identification in baboon plasma samples. The linearity was assessed in the range of 0.188µg/mL to75.0µg/mL, with a correlation coefficient of 0.998. The relative standard deviation of this method was <11% for within- and between-run assays, and the accuracy ranged between 96% and 114%.

Effect of 30% nutrient restriction in the first half of gestation on maternal and fetal baboon serum amino acid concentrations.

Mechanisms linking maternal nutrient restriction (MNR) to intra-uterine growth restriction (IUGR) and programming of adult disease remain to be established. The impact of controlled MNR on maternal and fetal amino acid metabolism has not been studied in non-human primates. We hypothesised that MNR in pregnant baboons decreases fetal amino acid availability by mid-gestation. We determined maternal and fetal circulating amino acid concentrations at 90 d gestation (90dG, term 184dG) in control baboons fed ad libitum (C, n 8) or 70% of C (MNR, n 6). Before pregnancy, C and MNR body weights and circulating amino acids were similar. At 90dG, MNR mothers had lower body weight than C mothers (P< 0·05). Fetal and placental weights were similar between the groups. MNR reduced maternal blood urea N (BUN), fetal BUN and fetal BUN:creatinine. Except for histidine and lysine in the C and MNR groups and glutamine in the MNR group, circulating concentrations of all amino acids were lower at 90dG compared with pre-pregnancy. Maternal circulating amino acids at 90dG were similar in the MNR and C groups. In contrast, MNR fetal ß-alanine, glycine and taurine all increased. In conclusion, maternal circulating amino acids were maintained at normal levels and fetal amino acid availability was not impaired in response to 30% global MNR in pregnant baboons. However, MNR weight gain was reduced, suggesting adaptation in maternal-fetal resource allocation in an attempt to maintain normal fetal growth. We speculate that these adaptive mechanisms may fail later in gestation when fetal nutrient demands increase rapidly, resulting in IUGR.

Investigation of potential carbohydrate antigen targets for human and baboon antibodies.

BACKGROUND: The continued presence of a primate antibody-mediated response to cells and organs from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs indicates that there may be antigens other than Gal alpha 1,3Gal (alpha Gal) against which primates have xenoreactive antibodies. Human and baboon sera were tested for reactivity against a panel of saccharides that might be potential antigen targets for natural anti-non-alpha Gal antibodies. METHODS: Human sera (n = 16) and baboon sera (n = 15) of all ABO blood types were tested using an enzyme-linked immunoadsorbent assay for binding of IgM and IgG to a panel of synthetic polyacrylamide-linked saccharides (n = 15). Human sera were also tested after adsorption on alpha Gal immunoaffinity beads. Sera from healthy wild-type (WT, n = 6) and GTKO (n = 6) pigs and from baboons (n = 4) sensitized to GTKO pig organ or artery transplants (of blood type O) were also tested. Forssman antigen expression on baboon and pig tissues was investigated by immunohistochemistry. RESULTS: Both human and baboon sera showed high IgM and IgG binding to alpha Gal saccharides, alpha-lactosamine, and Forssman disaccharide. Human sera also demonstrated modest binding to N-glycolylneuraminic acid (Neu5Gc). When human sera were adsorbed on alpha Gal oligosaccharides, there was a reduction in binding to alpha Gal and alpha-lactosamine, but not to Forssman. WT and GTKO pig sera showed high binding to Forssman, and GTKO pig sera showed high binding to alpha Gal saccharides. Baboon sera sensitized to GTKO pigs showed no significant increased binding to any specific saccharide. Staining for Forssman was negative on baboon and pig tissues. CONCLUSIONS: We were unable to identify definitively any saccharides from the selected panel that may be targets for primate anti-non-alpha Gal antibodies. The high level of anti-Forssman antibodies in humans, baboons, and pigs, and the absence of Forssman expression on pig tissues, suggest that the Forssman antigen does not play a role in the primate immune response to pigs.

Human immune reactivity against liver sinusoidal endothelial cells from GalTα(1,3)GalT-deficient pigs.

Elimination of galactose-α(1,3)galactose (Gal) expression in pig organs has been previously shown to prevent hyperacute xenograft rejection. However, naturally present antibodies to non-Gal epitopes activate endothelial cells, leading to acute humoral xenograft rejection. Still, it is unknown whether xenogeneic pig liver sinusoidal endothelial cells (LSECs) from α(1,3)galactosyltransferase (GalT)-deficient pigs are damaged by antibody and complement-mediated mechanisms. The present study examined the xeno-antibody response of LSECs from GalT-deficient and wild pigs. Isolated LSEC from wild-type and GalT pigs were expose to human and baboon sera; IgM and IgG binding was analyzed by flow cytometry. Complement activation (C3a and CH50) was quantified in vitro from serum-exposed LSEC cultures using Enzyme-Linked ImmunoSorbent assay (ELISA). Levels of complement-activated cytotoxicity (CAC) were also determined by a fluorescent Live-Dead Assay and by the quantification of LDH release. IgM binding to GalT knockout (KO) LSECs was significantly lower (80% human and 87% baboon) compare to wild-type pig LSEC. IgG binding was low in all groups. Moreover, complement activation (C3a and CH50) levels released following exposure to human or baboon sera were importantly reduced (42% human and 52% baboon), CAC in GalT KO LSECs was reduced by 60% in human serum and by 72% in baboon serum when compared to wild-type LSECs, and LDH release levels were reduced by 37% and 57%, respectively. LSECs from GalT KO pigs exhibit a significant protection to humoral-induced cell damage compared to LSECs from wild pigs when exposed to human serum. Although insufficient to inhibit xenogeneic reactivity completely, transgenic GalT KO expression on pig livers might contribute to a successful application of clinical xenotransplantation in combination with other protective strategies.

Parameters of the cytokine system functioning in laboratory primates.

The cytokine status (IFN, IL, etc.) of different monkey species (M. mulatta, P. hamadryas, C. aethiops) was studied. The interferon status is determined by the following parameters: IFN content in circulating blood and production of IFN-alpha and IFN-gamma by lymphocytes after appropriate in vitro induction. The interferon status of monkeys is similar to that of humans. The capacity to produce IFN reduces with age. It was found that genes of virtually all studied cytokines are expressed in blood cells and hence, in immune system cells.

Fetal blood sampling in baboons (Papio spp.): important procedural aspects and literature review.

BACKGROUND: The baboons (Papio cynocephalus) have similarities with human placentation and fetal development. Fetal blood sampling allows investigators to assess fetal condition at a specific point in gestation as well as transplacental transfer of medications. Unfortunately, assessing fetal status during gestation has been difficult and fetal instrumentation associated with high rate of pregnancy loss. Our objectives are to describe the technique of ultrasound guided cordocentesis (UGC) in baboons, report post-procedural outcomes, and review existing publications. METHODS: This is a procedural paper describing the technique of UGC in baboons. After confirming pregnancy and gestational age via ultrasound, animals participating in approved research protocols that required fetal assessment underwent UGC. RESULTS: We successfully performed UGC in four animals (five samples) using this technique. Animals were sampled in the second and third trimesters with fetal blood sampling achieved by sampling a free cord loop, placental cord insertion site or the intrahepatic umbilical vein. All procedures were without complication and these animals delivered at term. CONCLUSIONS: Ultrasound guided fetal umbilical cord venipuncture is a useful and safe technique to sample the fetal circulation with minimal risk to the fetus or mother. We believe this technique could be used for repeated fetal venous blood sampling in the baboons.

Gene expression profile of Th1 and Th2 cytokines and their receptors in human and nonhuman primates.

BACKGROUND: To date comparative knowledge concerning gene expression profiles of T-helper 1(Th1)/Th2 cytokines and their receptors between human and non-human primates is scarce. METHODS: We assessed the gene expression level of both Th1 [interleukin-4(IL-4)] and Th2 [IL-12, interferon-gamma(IFN-gamma)] cytokines and the receptors (IL-4Ralpha, IFN-gammaR1, IFN-gammaR2) in peripheral blood mononuclear cells (PBMC) from humans, chimpanzee, baboon, and macaque by a quantitative real-time reverse transcriptase-polymerase chain reaction(RT-PCR). RESULTS: The expression level of the IFN-gamma gene was markedly lower in humans than that in non-human primates. The IL-4 gene expression was significantly higher, whereas that of IL-12 was distinctly lower, in human/chimpanzee than in baboon/macaque. The IFN-gammaR2 gene expression was especially higher in the macaque than in the other three primates. CONCLUSIONS: These results indicate distinct gene expression of Th1/Th2 cytokines and their receptors in primates. These also suggest characteristic differences in Th1/Th2 immune responses affecting host defense and/or disease susceptibility among these primates.

Enzootic simian piroplasm (Entopolypoides macaci ) in wild-caught Kenyan non-human primates.

BACKGROUND: Three species of non-human primates comprising African green monkeys (AGMs), (Cercopithecus aethiops, n = 89), Syke's monkeys (Cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci. METHODS: Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke's monkeys and 33.3% in baboons. RESULTS: Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer. CONCLUSION: This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non-human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.

Biochemical and white blood cell profiles of baboon neonates consuming formulas with moderate and high dietary long-chain polyunsaturated fatty acids.

BACKGROUND: Clinical chemistry and complete blood count (CBC) values were determined in 14 term baboons (Papio species) consuming formula with moderate or high levels of dietary long-chain polyunsaturated fatty acids (LCPUFA) from 2-12 weeks of age. METHOD: Neonates were randomized to three groups: C: Control, no LCPUFA; L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); L3:1.00% DHA/0.67% ARA (w/w). Blood chemistries were assessed at 6 and 12 weeks and CBC parameters were measured at 2, 4, 8, 10, 12 weeks of age. RESULTS: Dietary LCPUFA had significant effects on serum triglyceride (C > L,L3) and calcium (L > C,L3). No other significant effects of diet were detected; pooled values are presented for all other parameters. CONCLUSION: These data provide longitudinal biochemical and white cell/platelet/immunological data on LCPUFA-fed baboons over the first 12 weeks of life. Data ranges are similar to reference data in cases for which values exist and hematological changes reflect trends observed during human neonatal development.

Hormonal correlates of ontogeny in baboons (Papio hamadryas anubis) and mangabeys (Cercocebus atys).

This study investigates the relationship between serum hormone levels and morphometrics during ontogeny in olive baboons (Papio hamadryas anubis) and sooty mangabeys (Cercocebus atys), to test hypotheses about the endocrine regulation of species size differences. First, we expect that levels of hormones and binding proteins predict size change during ontogeny in both species. Second, a high level of integration among the hormones and binding proteins analyzed is expected, with the implication that they act in combination to influence the development of body size and shape. Utilizing a mixed longitudinal sample, we compare change in 18 different measurements, which reflect overall size growth as well as growth in length and circumference, with levels of six growth-related hormones and binding proteins. We examine the relationship between hormone and binding protein levels and morphometrics, using multivariate analyses and "arithmetically-estimated" velocity curves of hormones, binding proteins, to characterize how the endocrine factors analyzed relate to growth. Results suggest that levels of these endocrine factors can be used to predict local and overall growth during ontogeny and that integration between multiple hormone axes is indicated. While important for growth in both species, ontogenetic changes in hormone and binding protein levels are more tightly correlated with changes in morphometric measurements in baboons than mangabeys. These results have important implications for understanding why some smaller-bodied species have higher absolute growth-related hormone levels than larger-bodied species.

The survival and function of baboon red blood cells, platelets, and plasma proteins: a review of the experience from 1972 to 2002 at the Naval Blood Research Laboratory, Boston, Massachusetts.

The studies reported in this monograph were performed between 1972 and 2002 when it was possible to study healthy male and female baboons. A colony of baboons was maintained for 30 years without any adverse events observed in these baboons in the numerous studies that were performed. These protocols were reviewed and approved by the institutional animal care and use committees (IACUC) at the sites where the studies were performed and by the veterinarian services of the U.S. Navy's Bureau of Medicine and Surgery, the Office of Naval Research, and the Department of Defense. The physiology of red blood cells (RBCs), platelets (PLTs), and plasma proteins in the baboon was investigated together with the viability and function of preserved RBCs, PLTs, and plasma proteins. These studies in the baboon could not have been performed in normal volunteers and patients. The data obtained have provided critical information to explain the clinical observations reported in normal volunteers and patients after transfusion of fresh and preserved blood products. These studies were supported by the U.S. Navy's Bureau of Medicine and Surgery and the Office of Naval Research. In addition, the support of the late Congressman J. Joseph Moakley from Massachusetts is acknowledged because without his support many of these studies could not have been performed. The authors acknowledge the contributions of the numerous research collaborators identified in the 52 peer-reviewed publications that cite other funding agencies that supported the research that is reported, the editorial assistance of Ms Cynthia Ann Valeri, and the assistance of Ms Deborah Tattersall who prepared the figures and tables reported in this publication.

Serological detection of adenoviruses in non-human primates maintained in a colony in Kenya.

BACKGROUND: Adenoviruses are known to cause several human diseases including acute febrile respiratory syndromes, epidemic conjunctivitis and gastroenteritis. These diseases associated with adenovirus infection affect adults and are usually more severe in infants and children. Forty-seven human adenoviruses serotypes have so far been identified adenovirus. The diversity of these viruses has delayed progress on vaccine development due to difficulties in identifying appropriate vaccine targets. To date, limited studies have been done to determine the prevalence of adenovirus infection in non-human primates with the goal of developing a non-human primate model that can be used to study the mechanisms of infection. OBJECTIVE: To determine the prevalence of enteric adenovirus infection in Kenyan non-human primates. DESIGN: A prospective study to investigate the prevalence of enteric andenovirus infection in captive non-human primates maintained in a colony. SETTING: Faecal samples were collected from monkeys trapped from different geographical areas of Kenya and also from the ones maintained in a colony at the Institute of Primate Research (IPR), Kenya. SUBJECTS: Ninety four faecal samples were collected from three species of non-human primates consisting of various ages and sex. Samples were collected from monkeys trapped from different geographical areas of Kenya and also from the ones maintained in a colony at the Institute of Primate Research (IPR), Kenya. All the faecal samples were screened for presence of adenoviruses using a commercial antigen-capture enzyme immunoassay (EIA) kit, this is an enzyme-linked immunosorbent assay (ELISA) kit designed for diagnosis of human enteric adenoviruses in stool samples. RESULTS: The highest prevalence of adenoviruses, detected by EIA kit, was in olive baboons (Papio anubis, 52.9%), followed by vervet monkeys (Cercopithecus aethiops, 48.9%) and the yellow baboons (Papio cynocephalus, 18.8%). Sub-grouping within each species (based on age and sex) indicated no significant differences (p > 0.05) in adenovirus infection signifying equal susceptibility. The prevalence of adenoviruses in vervet monkeys that were also Simian Immunodeficiency virus (SIV) seropositive was determined and shown to be 63.2%. CONCLUSION: The results of this study indicate that adenovirus infection is prevalent among non-human primates in Kenya. These findings suggest that cross species transmission in Kenyan non-human primates may be a common occurrence and there is a possibility of zoonotic transmission of adenoviruses. Furthermore, our results highlight the potential of using these non-human primates as models for testing safety and efficacy of candidate adenovirus vaccines prior to clinical trials in humans.

Ontogeny of hematological cell and biochemical profiles in maternal and fetal baboons (Papio species).

The normal ranges of hematological cell profiles and biochemistry are documented in adult non-pregnant, pregnant, juvenile, and neonatal baboons. Despite the extensive use of the baboon as a model for the study of various aspects of pregnancy, there is no data from paired mothers and their fetuses at different stages of gestation. Hematologic and biochemical profile data were obtained from eight non-pregnant female baboons, 37 mothers and 38 fetal baboons at 30 +/- 2, 90 +/- 2, 125 +/- 2, and 175 +/- 2 days of gestation (mean +/- range; dGA; term, 180 dGA). Changes observed in fetal and maternal blood during normal baboon pregnancy were similar to those reported in human pregnancy. The level of alkaline phosphatase was two times higher in fetal blood circulation than that reported in human pregnancy.

Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons with high and low lipemic responses to dietary lipids.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) 1 and ACAT2 play an important role in cellular cholesterol esterification and thus modulate intestinal cholesterol absorption and hepatic lipoprotein secretion. The relative expression levels of ACAT1 and ACAT2 in human tissues differ from those in other animals, including nonhuman primates. The present study compared the relative expression levels of ACAT1 and ACAT2 in baboons with high and low lipemic responses to dietary lipids. We isolated RNA and prepared cDNA from frozen liver and small intestine from high- and low-responding pedigreed baboons necropsied after consuming a high-cholesterol and high-fat diet for 18 months. The expression of ACAT1 and ACAT2 was measured by TaqMan real-time quantitative PCR normalized to 18s ribosomal RNA. The expression of ACAT1 was higher than that of ACAT2 in the liver, whereas the expression of ACAT2 was higher than that of ACAT1 in the duodenum and jejunum. There was no difference in the expression of ACAT1 or ACAT2 in the liver and intestine between high- and low-responding baboons except that the expression of ACAT1 was higher in the duodenum of high responders than in that of low responders. Western blot analysis also showed a higher level of ACAT1 protein in the duodenum of high responders than in that of low responders. There was a significant correlation between duodenal ACAT expression levels and total plasma cholesterol concentration in baboons. These results suggest that differences in ACAT1 expression may affect plasma cholesterol concentration and partly affect diet-induced hyperlipidemia.

Serum leptin in nonpregnant and pregnant women and in old and new world nonhuman primates.

Leptin is a hormone that is produced during mammalian pregnancy in the placental trophoblast and other tissues, including! fetal and maternal adipocytes. Synthesis of the polypeptide and the presence of its specific receptors throughout the human maternal fetoplacental unit suggest direct effects on conceptus growth and development. However, both the physiologic roles of leptin and the mechanisms regulating leptin synthesis in human pregnancy differ from those in laboratory and domestic species, necessitating the development of non-human primate research models. Therefore, we compared serum leptin concentrations in nonpregnant and pregnant women with those in both old world nonhuman primates (i.e., baboon, rhesus monkey, cynomolgus monkey) and new world nonhuman primates (i.e., squirrel monkey, titi monkey). As expected, maternal leptin levels were elevated in human and baboon pregnancies (P < 0.05 and P < 0.001, respectively). Levels in both species of old world monkeys were also greatly enhanced (P < 0.001). Although maternal serum concentrations were slightly elevated compared to nonpregnant levels in both species of new world monkeys, overall concentrations were dramatically lower than for either old world primates or humans. Results provide comparisons of serum leptin concentrations in pregnant and nonpregnant humans and baboons with those in both old and new world monkeys and further characterize these nonhuman primates as models for the investigation of leptin dynamics in pregnancy.