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The molecular mechanisms underlying HIV-induced inflammation, which persists even during effective long-term treatment, remain incompletely defined. Here, we studied pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections in macaques and African green monkeys, respectively. We longitudinally analyzed genome-wide DNA methylation changes in CD4 + T cells from lymph node and blood, using arrays. DNA methylation changes after SIV infection were more pronounced in lymph nodes than blood and already detected in primary infection. Differentially methylated genes in pathogenic SIV infection were enriched for Th1-signaling (e.g., RUNX3, STAT4, NFKB1) and metabolic pathways (e.g., PRKCZ). In contrast, nonpathogenic SIVagm infection induced DNA methylation in genes coding for regulatory proteins such as LAG-3, arginase-2, interleukin-21 and interleukin-31. Between 15 and 18% of genes with DNA methylation changes were differentially expressed in CD4 + T cells in vivo. Selected identified sites were validated using bisulfite pyrosequencing in an independent cohort of uninfected, viremic and SIV controller macaques. Altered DNA methylation was confirmed in blood and lymph node CD4 + T cells in viremic macaques but was notably absent from SIV controller macaques. Our study identified key genes differentially methylated already in primary infection and in tissues that could contribute to the persisting metabolic disorders and inflammation in HIV-infected individuals despite effective treatment.

Background: Non-human primates (NHPs) are important models of medical research on obesity and cardiovascular diseases. As two of the most commonly used NHPs, cynomolgus macaque (CM) and African green monkey (AGM) own different capacities in lipid metabolism of which the mechanism is unknown. This study investigated the expression profiles of lipid metabolism-related microRNAs (miRNAs) in CM and AGM and their possible roles in controlling lipid metabolism-related gene expression., Methods: By small RNA deep sequencing, the plasma miRNA expression patterns of CM and AGM were compared. The lipid metabolism-related miRNAs were validated through quantitative reverse-transcription (RT) polymerase chain reaction (PCR). Related-target genes were predicted by TargetScan and validated in Vero cells., Results: Compared to CM, 85 miRNAs were upregulated with over 1.5-fold change in AGM of which 12 miRNAs were related to lipid metabolism. miR-122, miR-9, miR-185, miR-182 exhibited the greatest fold changes(fold changes are 51.2, 3.8, 3.7, 3.3 respectively; all P < 0.01). And 77 miRNAs were downregulated with over 1.5-fold change in AGM of which 3, miR-370, miR-26, miR-128 (fold changes are 9.3, 1.8, 1.7 respectively; all P < 0.05) were related to lipid metabolism. The lipid metabolism-related gene targets were predicted by TargetScan and confirmed in the Vero cells., Conclusion: We report for the first time a circulating lipid metabolism-related miRNA profile for CM and AGM, which may add to knowledge of differences between these two non-human primate species and miRNAs' roles in lipid metabolism.

Background: Management of diabetes remains a major health and economic challenge, demanding test systems in which to develop new therapies. These studies assessed different methodologies for determining glucose tolerance in green monkeys., Methods: Twenty-eight African green monkeys between 4 and 24 years old underwent single or repeat intravenous glucose tolerance testing (IVGTT), oral glucose tolerance testing (OGTT), and/or graded glucose infusion testing., Results: Geriatric monkeys exhibited glucose intolerance with impaired glucose-stimulated insulin secretion following IVGTT. Repeat IVGTT and OGTT assessments were inconsistent. Monkeys with low glucose-stimulated insulin secretion after graded glucose infusion exhibited elevated blood glucose levels., Conclusion: IVGTT and graded glucose infusion protocols revealed differences in glucose tolerance among green monkeys at single time points, including age-dependent differences suggestive of shifts in pancreatic beta-cell functional capacity, but care should be applied to study design and the interpretation of data in the setting of longitudinal studies., (© 2018 The Authors. Journal of Medical Primatology published by John Wiley & Sons Ltd.)

Vervet monkeys are among the most widely distributed nonhuman primates, show considerable phenotypic diversity, and have long been an important biomedical model for a variety of human diseases and in vaccine research. Using whole-genome sequencing data from 163 vervets sampled from across Africa and the Caribbean, we find high diversity within and between taxa and clear evidence that taxonomic divergence was reticulate rather than following a simple branching pattern. A scan for diversifying selection across taxa identifies strong and highly polygenic selection signals affecting viral processes. Furthermore, selection scores are elevated in genes whose human orthologs interact with HIV and in genes that show a response to experimental simian immunodeficiency virus (SIV) infection in vervet monkeys but not in rhesus macaques, suggesting that part of the signal reflects taxon-specific adaptation to SIV.

Chikungunya virus (CHIKV) is a globally emerging pathogen causing debilitating arthralgia and fever in humans. First identified in Tanzania (1953), this mosquito-borne alphavirus received little further attention until a 2004 re-emergence in Kenya from an unknown source. This outbreak subsequently spread to the Indian Ocean, with adaptation for transmission by a new urban vector. Under the hypothesis that sylvatic progenitor cycles of CHIKV exist in Kenya (as reported in West Africa, between non-human primates (NHPs) and arboreal Aedes spp. mosquitoes), we pursued evidence of enzootic transmission and human spillover events. We initially screened 252 archived NHP sera from Kenya using plaque reduction neutralization tests. Given an overall CHIKV seroprevalence of 13.1% (marginally higher in western Kenya), we sought more recent NHP samples during 2014 from sites in Kakamega County, sampling wild blue monkeys, olive baboons, and red-tailed monkeys ( N = 33). We also sampled 34 yellow baboons near Kwale, coastal Kenya. Overall, CHIKV seropositivity in 2014 was 13.4% (9/67). Antibodies reactive against closely related o'nyong-nyong virus (ONNV) occurred; however, neutralization titers were too low to conclude ONNV exposure. Seroprevalence for the flavivirus dengue was also detected (28%), mostly near Kwale, suggesting possible spillback from humans to baboons. CHIKV antibodies in some juvenile and subadult NHPs suggested recent circulation. We conclude that CHIKV is circulating in western Kenya, despite the 2004 human outbreaks only being reported coastally. Further work to understand the enzootic ecology of CHIKV in east Africa is needed to identify sites of human spillover contact where urban transmission may be initiated.

Background: Established RIs for geriatric African Green monkeys (Chlorocebus aethiops sabaeus) are critical for clinical differentiation of normal aging from disease-related changes in this population., Objective: The aim of this study was to establish hematologic and serum biochemical RIs for a Caribbean captive population of geriatric (≥ 15 years of age) African Green monkeys, or Vervets., Methods: Inclusion and exclusion criteria were defined for a cohort of 109 healthy, aged (15- to 30-year-old, median 19-year-old) Vervets. Both male (34) and female (75) monkeys were included in RI generation. Complete manual and analyzer-generated blood counts and serum biochemistry profiles were performed at Ross University School of Veterinary Medicine, West Farm, St. Kitts, West Indies. All results were evaluated using Reference Value Advisor. Isolated outliers were identified using Dixon's outlier range statistic and not included in determination of RIs for individual analytes. Reference intervals were determined using parametric and nonparametric methods depending on the distribution. Data, including mean, median, maximum, and minimum values, were tabulated., Results: Of the 109 animals, 12 monkeys were excluded due to abnormal physical examination results (2 monkeys), and ≥ 2 confirmed outliers (9 monkeys), or evidence of disease based on laboratory data (one monkey)., Conclusions: This study provides useful RIs for assessment of hematology and serum biochemical variables in a geriatric population of African Green monkeys in the Caribbean., (© 2017 American Society for Veterinary Clinical Pathology.)

Background: The objective was to evaluate the procollagen type I N-propeptide (PINP), osteocalcin (OC), β-crosslaps (β-CTX), and parathyroid hormone (PTH) in relation to age and sex of Chlorocebus aethiops in captivity., Methods: Seventy-three monkeys were divided into four age groups: AG1 (juvenile); AG2 (young adult); AG3 (adult); and AG4 (senile). An electrochemiluminescence immunoassay with an Elecsys 2010 analyzer was used to determine the serum markers of bone., Results and Conclusions: Sex did not influence the results of the markers. However, the variables PINP, OC, and β-CTX were negatively correlated with age (r = -0.643; r = -0.711; r = -0.488; P < 0.001, respectively), and PTH was correlated positively with age (r = 0.418, P < 0.001). The data obtained can be used as biomarkers of bone metabolism reference intervals in healthy C. aethiops in captivity., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Some factors such as sex, age, and captivity conditions have a direct influence on the normal hematological and serum biochemical parameters of African green monkeys. On the other hand, reliability in reported values is in many cases limited by studied animal number (<200) and there is not report on the correlation of these parameters with the age in each sex animal group. Thus, this study sought determining normal hematological (11) and serum biochemical parameters (9) of 400 captive housed African green monkeys and also correlate them with the age of the animals., Methods: A total of 200 females and 200 males were grouped by the sex and age groups (1-2, 3-4, 5-6, and 7-8 years old) for measuring normal values of hematological and serum biochemical parameters and to study the correlation of these parameters with the age of the animals., Results: As key outcome, the main hematological and serum biochemical reference values of African green monkeys were determined. Significant differences (P < 0.05) were found among 95% of studied parameters between males and females. About 75% and 95% of the parameters were influenced by the age in the female and male groups, respectively. About 35% of hematological and serum biochemical parameters correlated positively (R(2) > 0.5) with the age in the female monkeys. On the contrary in the male monkeys, only 45% of parameters correlated positively with the age (R(2) > 0.5)., Conclusions: Thus, authors believe that results of this study are important for assisting researchers in the assessment of health status of captive housed African green monkeys for preclinical studies., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clinical decisions and experimental analyses often involve the assessment of hematology and clinical chemistry. Using clinical pathology to assess the health status of NHP in breeding colonies or data from studies than involve pregnancy can often be complicated by pregnancy status. This study had 2 objectives regarding the hematology and clinical chemistry of African green monkeys (AGM, Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum animals with nonpregnant, nonlactating animals and 2) to create age- and sex-specific reference intervals. Subjects in this study were 491 AGM from the Vervet Research Colony of the Wake Forest University Primate Center. Results indicated that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus, sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC, neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and the postpartum period. Age- and sex-specific reference intervals consistent with guidelines from the American Society for Veterinary Clinical Pathology were established and further expand the understanding of how to define health in AGM on the basis of clinical pathology. The combination of understanding the changes that occur in pregnancy and postpartum and expansive reference intervals will help guide clinical and experimental decisions.

Epigenetic mechanisms are associated with the development of many chronic diseases and due to their reversible nature offer a unique window of opportunity to reverse the disease phenotype. This study investigated whether global DNA methylation correlates with dysglycemia in the vervet monkey (Chlorocebus aethiops). Diet-induced changes in DNA methylation were observed where global DNA methylation was twofold lower in monkeys fed a high fat diet (n = 10) compared to monkeys fed a standard diet (n = 15). An inverse correlation was observed between DNA methylation, blood glucose concentrations, bodyweight, and age, although the association was not statistically significant. Consumption of a high fat diet is associated with the development of metabolic disease; thus, these results suggest the use of global DNA methylation as a biomarker to assess the risk for metabolic disease. Moreover, this study provides further support for the use of the vervet monkey as a model system to study metabolic diseases such as type 2 diabetes. Integration of altered DNA methylation profiles into predictive models could facilitate risk stratification and enable intervention strategies to inhibit disease progression. Such interventions could include lifestyle modifications, for example, the increased consumption of functional foods with the capacity to modulate DNA methylation, thus potentially reversing the disease phenotype and preventing disease.

Female vervet monkeys (Chlorocebus aethiops sabaeus) are used as an experimental model for chronic diseases relevant to women's health. However, reproductive senescence (menopause) has not yet been characterized for vervet monkeys. Here we describe the histologic, hormonal, and menstrual markers of reproductive senescence in vervet monkeys from the Wake Forest Vervet Research Colony. Ovaries from monkeys (age, 0 to 27 y) were serially sectioned (5 μm), stained, and photographed. In every 100th section, the numbers of primordial, primary, and secondary follicles were determined, and triplicate measurements were used to calculate mean numbers of follicles per ovary. Antimüllerian hormone (AMH), follicle stimulating hormone, and menstrual cycle length were measured in additional monkeys. Primordial follicles and AMH decreased significantly with age, and significant correlations between numbers of primordial and primary follicles and between numbers of primary and secondary follicles were noted. Histologic evaluation revealed that ovaries from 4 aged monkeys (older than 23 y) were senescent. One aged monkey transitioned to menopause, experiencing cycle irregularity over 4 y, eventual cessation of menses, and plasma AMH below the level of detection. Finally, with increasing age, the percentage of female vervets with offspring declined significantly. The present study provides insight into ovarian aging and reproductive senescence in vervet monkeys. Results highlight the importance of considering this nonhuman primate as a model to investigate the relationships between ovarian aging and chronic disease risk.

Specific alterations in the pulsatility of luteinizing hormone (LH) are linked to obesity-related subfertility in ovulatory women. Vervet monkeys (Chlorocebus aethiops sabaeus) are an Old World nonhuman primate that develops obesity and has a menstrual cycle similar to humans. We evaluated follicular-phase LH pulses in 12 adult normal-weight female vervets. Serum was collected every 10 min for 4 h by using a tether device in conscious, freely moving monkeys on menstrual cycle days 2 through 5. Serum estradiol was collected daily during the follicular phase to identify the luteal-follicular transition. For comparison, we used data from 12 ovulatory normal-weight women who had undergone frequent blood sampling of early-follicular LH. LH pulse frequency was similar, with 2.8 ± 0.7 LH pulses during 4 h in vervets compared with 2.3 ± 0.7 LH pulses during 4 h in women. The LH pulse mass (percentage change in the pulse peak over the preceding nadir) was 123.2% ± 27.4% in vervets and 60.9% ± 14.9% in humans. The first day of low serum estradiol after the follicular-phase peak was denoted as the day of the luteal-follicular transition. Luteectomy was performed on luteal days 7 through 9, and corpora lutea were confirmed by histology. We demonstrate that follicular LH patterns in vervets are similar to those in humans and that the luteal phase is easily identified by monitoring daily serum estradiol. These findings demonstrate that vervet monkeys are a suitable animal model for evaluating LH pulse dynamics longitudinally in studies of diet-induced obesity.

Mutant forms of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis. In addition, wild-type TTR causes senile systemic amyloidosis, a sporadic disease seen in the elderly. Although spontaneous development of TTR amyloidosis had not been reported in animals other than humans, we recently determined that two aged vervet monkeys (Chlorocebus pygerythrus) spontaneously developed systemic TTR amyloidosis. In this study here, we first determined that aged vervet monkeys developed TTR amyloidosis and showed cardiac dysfunction but other primates did not. We also found that vervet monkeys had the TTR Ile122 allele, which is well known as a frequent mutation-causing human TTR amyloidosis. Furthermore, we generated recombinant monkey TTRs and determined that the vervet monkey TTR had lower tetrameric stability and formed more amyloid fibrils than did cynomolgus monkey TTR, which had the Val122 allele. We thus propose that the Ile122 allele has an important role in TTR amyloidosis in the aged vervet monkey and that this monkey can serve as a valid pathological model of the human disease. Finally, from the viewpoint of molecular evolution of TTR in primates, we determined that human TTR mutations causing the leptomeningeal phenotype of TTR amyloidosis tended to occur in amino acid residues that showed no diversity throughout primate evolution. Those findings may be valuable for understanding the genotype-phenotype correlation in this inherited human disease.

Singlet oxygen ((1)O(2)) produced during inflammatory reactions and during photodynamic therapy deactivates by producing in tissues secondary reactive oxygen species and peroxides (SOS) as well as other degradation products. We investigated the influence of animal species on SOS production secondary to standardized (1)O(2) production by performing in vitro experiments with rose bengal as the (1)O(2) producer, human serum (HS) as a control, sera derived from various animal species, and dichloro-dihydro-fluorescein as a nonspecific marker that becomes fluorescent when oxidized. The overall SOS production in HS from a presumed healthy cohort of 53 donors (31 males and 22 females) gave a mean "normal" value of 0.91 compared with a previous pool of 75 male sera samples. SOS production after a photo-reaction was two or four times lower in HS than in fetal calf serum or mice sera, respectively. In mice, the "nude" characteristic increased even more than in the SOS production. In the Aves order, this production appeared to be distributed randomly according to the number of branches after the appearance of Amniotas. For primates, SOS production appeared to decrease linearly with the number of branches (R(2) = 0.98). Adding hemolysates from complete bloods to the corresponding sera induced an increase in SOS production in all species, proportional to the production in sera. These findings should be kept in mind when interpreting results from studies of secondary reactive oxygen species-induced pathways following (1)O(2) production, regardless of its origin.

Cardiovascular disease remains the leading cause of mortality in westernized countries, despite optimum medical therapy to reduce the levels of low-density lipoprotein (LDL)-associated cholesterol. The pursuit of novel therapies to target the residual risk has focused on raising the levels of high-density lipoprotein (HDL)-associated cholesterol in order to exploit its atheroprotective effects. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of lipid metabolism and are thus a new class of target for therapeutic intervention. MicroRNA-33a and microRNA-33b (miR-33a/b) are intronic miRNAs whose encoding regions are embedded in the sterol-response-element-binding protein genes SREBF2 and SREBF1 (refs 3-5), respectively. These miRNAs repress expression of the cholesterol transporter ABCA1, which is a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL levels and providing protection against atherosclerosis; however, extrapolating these findings to humans is complicated by the fact that mice lack miR-33b, which is present only in the SREBF1 gene of medium and large mammals. Here we show in African green monkeys that systemic delivery of an anti-miRNA oligonucleotide that targets both miR-33a and miR-33b increased hepatic expression of ABCA1 and induced a sustained increase in plasma HDL levels over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in fatty acid oxidation (CROT, CPT1A, HADHB and PRKAA1) and reduced the expression of genes involved in fatty acid synthesis (SREBF1, FASN, ACLY and ACACA), resulting in a marked suppression of the plasma levels of very-low-density lipoprotein (VLDL)-associated triglycerides, a finding that has not previously been observed in mice. These data establish, in a model that is highly relevant to humans, that pharmacological inhibition of miR-33a and miR-33b is a promising therapeutic strategy to raise plasma HDL and lower VLDL triglyceride levels for the treatment of dyslipidaemias that increase cardiovascular disease risk.

The aim of this study was to characterise the sequential haematological changes in vervet monkeys infected with Trypanosoma brucei rhodesiense and subsequently treated with sub-curative diminazene aceturate (DA) and curative melarsoprol (MelB) trypanocidal drugs. Fourteen vervet monkeys, on a serial timed-kill pathogenesis study, were infected intravenously with 10(4) trypanosomes of a stabilate T. b. rhodesiense KETRI 2537. They were treated with DA at 28 days post infection (dpi) and with MelB following relapse of infection at 140 dpi. Blood samples were obtained from the monkeys weekly, and haematology conducted using a haematological analyser. All the monkeys developed a disease associated with macrocytic hypochromic anaemia characterised by a reduction in erythrocytes (RBC), haemoglobin (HB), haematocrit (HCT), mean cell volume (MCV), platelet count (PLT), and an increase in the red cell distribution width (RDW) and mean platelet volume (MPV). The clinical disease was characteristic of human African trypanosomiasis (HAT) with a pre-patent period of 3 days. Treatment with DA cleared trypanosomes from both the blood and cerebrospinal fluid (CSF). The parasites relapsed first in the CSF and later in the blood. This treatment normalised the RBC, HCT, HB, PLT, MCV, and MPV achieving the pre-infection values within two weeks while RDW took up to 6 weeks to attain pre-infection levels after treatment. Most of the parameters were later characterised by fluctuations, and declined at one to two weeks before relapse of trypanosomes in the haemolymphatic circulation. Following MelB treatment at 140 dpi, most values recovered within two weeks and stabilised at pre-infection levels, during the 223 days post treatment monitoring period. It is concluded that DA and MelB treatments cause similar normalising changes in the haematological profiles of monkeys infected with T. b. rhodesiense, indicating the efficacy of the drugs. The infection related changes in haematology parameters, further characterise the vervet monkey as an optimal induced animal model of HAT. Serial monitoring of these parameters can be used as an adjunct in the diagnosis and prognosis of the disease outcome in the vervet monkey model., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Hematology and clinical chemistry (HCC) reference values are critical in veterinary practice and in vivo pre-clinical research, enabling detection of health abnormalities, response to therapeutic intervention or adverse toxicological effects, as well as monitoring of clinical management., Methods: In this report, reference ranges for 46 HCC parameters were characterized in 331 wild-caught and colony-bred African green monkeys. Effects of sex, weight and duration of captivity were determined by one-way analysis of variance., Results: Significant sex differences were observed for several HCC parameters. Significant differences were also observed for select HCC variables between newly caught animals and those held in captivity for 1-12 months or longer., Conclusions: Comparison of this data with other non-human primate species and humans highlights similarities and disparities between species. Potential causes of interpopulation variability and relevance to the use of the African green monkey as a non-human primate model are discussed., (© 2010 John Wiley & Sons A/S.)

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.

Leptin was originally thought to be an antiobesity hormone, but increasing evidence suggests that its ancestral role was to mobilize neuroendocrine responses to starvation. Research on wild primates is critical for interpreting the high leptin values seen in Western human populations and captive animals. This study examined natural variation in serum leptin in wild vervet monkeys (Chlorocebus aethiops), testing the hypothesis that serum leptin in vervets varies with sex, adiposity, ecology, and reproductive state. Analyses made use of a unique dataset comprised of serum and morphometric measurements obtained from vervet monkeys in four Kenyan sites differing in altitude, temperature, rainfall, and access to human foods. Leptin and gonadal steroid concentrations were analyzed in serum samples from 116 adults. Low leptin levels in males and acyclic females support the contention that levels seen in captivity are not typical for wild primates. Measures of adiposity were not correlated with serum leptin, reflecting the extremely low fat storage in wild cercopithecine primates. Associations with habitat and season, however, indicate that leptin does register ecological variation in energy balance. Leptin levels were higher in sites and seasons with higher rainfall. Moreover, leptin varied significantly with reproductive state, with higher levels in pregnant than in acyclic females. Changes in leptin with gestation stage and duration of lactation suggest that transitory and reversible elevations were an important part of its ancestral role. These data show that in this wild primate population leptin is a sensitive index of natural variation in habitat and seasonally fluctuating reproductive state., ((c) 2008 Wiley-Liss, Inc.)

Background: Thirty-four wild Chlorocebus aethiops monkeys were trapped for research purposes., Methods: During routine quarantine check-up, cerebrospinal fluid (CSF) and blood were microscopically examined for parasites. Estimations of CSF protein levels were made by the biuret method and the white cell counts by the hemocytometer., Results: Seven monkeys demonstrated microfilariae in blood and CSF. This was accompanied by a two- and ninefold increase in CSF total protein and white cell counts, respectively. Necropsy of one of the blood and CSF microfilariae-positive animals revealed the presence of adult worms in the brain meninges. The parasites were identified as the zoonotic filaroid nematode Meningonema peruzii., Conclusions: Wild C. aethiops monkeys developed CSF changes resulting, most probably, from infection with M. peruzii. Moreover, the monkeys could be acting as an important reservoir. The study highlights the need for epidemiological and pathogenological studies of this parasite, which is of public health significance. Moreover, C. aethiops proved to be a useful primate model for the study of this zoonotic infection.

This study investigated fluctuations in hematological values of 50 wild-caught vervet monkeys (African green monkeys, grivets, Chlorocebus aethiops) during habituation to captivity. The monkeys were categorized into four groups according to age and sex viz adult males, adult females, juvenile males, and juvenile females. The erythrocyte values were significantly higher (P<0.05) in the adult males than in the other animals. There was an increase in most of the erythrocyte parameters studied during the monitoring period with the most significant being hemoglobin, hematocrit, and mean corpuscular volume. However, the red cell distribution widths, which were higher in adult females, declined. The total white blood cell (WBC) counts, which were higher in adult females than in the other animals, were closely correlated with granulocytes counts. The WBC levels decreased in all the animals throughout the 8 months study, indicating gradually decreasing stress, but they were relatively stable in males. The platelet counts declined significantly (P<0.05) and at 8 months post capture the counts were higher in females than in males. The juvenile female platelet counts were relatively stable during the monitoring period. The maintenance of the monkeys on an improved stable diet and in environment-controlled housing combined with progressing psycho-physiological adaptation may be important factors for the gradual improvements of the hematological values recorded. There were wide variations in these between individual animals emphasizing the need for long adaptation combined with establishment of individual baseline values before experimental studies., ((c) 2007 Wiley-Liss, Inc.)

Normal hematologic values for African green monkeys have been reported, but these results are confounded by the effect of chemical restraint (for example, ketamine), physical restraint, and capture stress. The dual-lumen central venous catheter, jacket, and tether combination we describe here allows intravenous fluid administration and repeated blood sampling without the use of anesthesia or inducing capture-related stress. The use of a low-concentration heparin solution for catheter maintenance significantly increased the mean patency time, compared with a saline-only catheter flush solution. Adding a low-concentration heparin solution creates a suitable system for serial blood collection in the African green monkey for as long as 25 d.

Myeloid dendritic cells probably play an important role in the immune response against HIV and SIV, and in the enhancement of CD4+ T cell infection. Here, we have investigated phenotypic and functional features of myeloid monocyte-derived DC (MDDC) from African green monkeys (AGMs). AGMs are natural hosts of SIV and exhibit no signs of abnormal T cell activation despite high SIV plasma viremia. We identified mAbs that cross-react specifically with homologous molecules expressed on AGM DC. We adapted a protocol to derive AGM MDDC by culture in the presence of GM-CSF and IL-4. The differentiated cells possessed a typical dendritic morphology and the majority were CD11c+ DC-SIGN+. AGM MDDC displayed a high expression of typical maturation markers, such as CD83, CD86 and DC-LAMP, and moderate immunostimulatory capacity, suggesting that the cells were in a semi-mature state. Stimulation resulted in further maturation, as shown by up-regulation of CD80 and decrease of endocytosis ability. However, neither increase of HLA-DR or CD40 expression nor enhanced immunostimulatory capacity was observed. The latter was associated with a low pro-inflammatory cytokine production during mixed lymphocyte reactions and a cytokine balance in favour of IL-10 in contrast to human MDDC. This is the first characterization of AGM MDDC. The tools described here are a crucial step for future studies in vivo or in vitro on the function of myeloid DC using the AGM animal model.

Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the adult human population due to high seroprevalence, an effect that would reduce vector immunogenicity. To address this issue, we evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is serotypically distinct from common human pathogens, as a vaccine vector. Two strains were evaluated: the attenuated vaccine strain LaSota (NDV-LS) that replicates mostly in the chicken respiratory tract and the Beaudette C (NDV-BC) strain of intermediate virulence that produces mild systemic infection in chickens. A recombinant version of each virus was modified by the insertion, between the P and M genes, of a gene cassette encoding the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) protein, a test antigen with considerable historic data. The recombinant viruses were administered to African green monkeys (NDV-BC and NDV-LS) and rhesus monkeys (NDV-BC only) by combined intranasal and intratracheal routes at a dose of 10(6.5) PFU per site, with a second equivalent dose administered 28 days later. Little or no virus shedding was detected in nose-throat swabs or tracheal lavages following immunization with either strain. In a separate experiment, direct examination of lung tissue confirmed a highly attenuated, restricted pattern of replication by parental NDV-BC. The serum antibody response to the foreign HN protein induced by the first immunization with either NDV vector was somewhat less than that observed following a wild-type HPIV3 infection; however, the titer following the second dose exceeded that observed with HPIV3 infection, even though HPIV3 replicates much more efficiently than NDV in these animals. NDV appears to be a promising vector for the development of vaccines for humans; one application would be in controlling localized outbreaks of emerging pathogens.

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.

Hematologic and serum biochemical values are of great importance in assessing animal health. Normal reference ranges for vervet monkeys (Chlorocebus aethiops sabaeus) have seldom been reported, making it difficult for clinicians to interpret blood values. The purpose of this study was to determine what effects age and sex have on hematologic and serum biochemical values of vervet monkeys and to establish clinically relevant reference ranges for all life stages of each gender. Blood samples were collected from 140 healthy vervet monkeys of Caribbean origin consisting of 60 females and 80 males. Male and female data were displayed separately within six life-stage categories (yearlings, juveniles, adolescents, young adults, adults, and aged). The effects of sex and age on these values were examined statistically. Significant age-related factors included red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, alkaline phosphatase, albumin, total protein, globulin, direct bilirubin, blood urea nitrogen, creatinine, glucose, calcium, phosphorus, potassium, albumin/globulin ratio, blood urea nitrogen/creatinine ratio, and sodium/potassium ratio values. Significant sex-related values included red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophil count, total bilirubin, direct bilirubin, creatinine, glucose, calcium, phosphorus, total carbon dioxide, chloride, potassium, and sodium/potassium ratio values.

Amyloid beta (Abeta) protein immunotherapy lowers cerebral Abeta and improves cognition in mouse models of Alzheimer's disease (AD). Here we show that Caribbean vervet monkeys (Chlorocebus aethiops, SK) develop cerebral Abeta plaques with aging and that these deposits are associated with gliosis and neuritic dystrophy. Five aged vervets were immunized with Abeta peptide over 10 months. Plasma and cerebral spinal fluid (CSF) samples were collected periodically from the immunized vervets and five aged controls; one monkey per group expired during the study. By Day 42, immunized animals generated plasma Abeta antibodies that labeled Abeta plaques in human, AD transgenic mouse and vervet brains; bound Abeta1-7; and recognized monomeric and oligomeric Abeta but not full-length amyloid precursor protein nor its C-terminal fragments. Low anti-Abeta titers were detected in CSF. Abetax-40 levels were elevated approximately 2- to 5-fold in plasma and decreased up to 64% in CSF in immunized vervets. Insoluble Abetax-42 was decreased by 66% in brain homogenates of the four immunized animals compared to archival tissues from 13 age-matched control vervets. Abeta42-immunoreactive plaques were detected in frontal cortex in 11 of the 13 control animals, but not in six brain regions examined in each of the four immunized vervets. No T cell response or inflammation was observed. Our study is the first to demonstrate age-related Abeta deposition in the vervet monkey as well as the lowering of cerebral Abeta by Abeta vaccination in a non-human primate. The findings further support Abeta immunotherapy as a potential prevention and treatment of AD.

Adrenal gland weights, stomach mucosal lesions, and morning serum cortisol and prolactin levels were measured in 15 juvenile and adult male African green monkeys (Cercopithecus aethiops) that were shot by a hunter, euthanized after 24 hr of captivity, or euthanized after 45 days of captivity and intermittent blood sampling. Hormone levels were measured in seven additional males that had been in captivity for 7 mo. Mean serum cortisol concentrations were significantly lower in free-ranging wild monkeys at the time they were shot than in the monkeys after 1 day in captivity. Cortisol concentrations were significantly higher in wild-caught monkeys on the day after capture than they were in the same animals after 18 and 26 days of captivity. Cortisol concentrations were also significantly higher in the wild-caught monkeys 18 days after capture than in the laboratory-habituated monkeys in captivity for 7 mo. Mean prolactin concentration was significantly lower in the wild-caught monkeys on day 2 after capture, and the levels increased gradually to 45 days in captivity and was highest in monkeys that had been captive for 7 mo.

The disruption in sphinganine (Sa) and sphingosine (So) concentrations in plasma and urine of vervet monkeys (Cercopithecus aethiops) was measured following a single gavage dose of either 1 (low dose) or 10 mg (high dose) fumonisin B(2) (FB(2))/kg body weight. Blood and urine were collected over a 51-day period. In the low-dose monkeys, none of the parameters measured increased significantly above the control values. In the high-dose monkeys the plasma Sa/So ratios were significantly increased (P< 0.05) above the corresponding control ratios after 3 days and continued to be significantly raised for another 27 days, whereafter the ratios declined to control values after 51 days. The plasma aspartate transaminase (AST) activities increased significantly above their control values from day 5 to day 23 and the gamma-glutamyl transferase (GGT) activities from day 7 until the end of the study period. The plasma cholesterol concentration and alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities increased transiently, but not significantly, and returned to control values within the study period. The urinary Sa/So ratio, plasma creatinine and urea values in both groups of monkeys did not increase above the control values. This study demonstrated that a single large dose of FB(2) can cause transient disruption of sphingoid metabolism in vervet monkeys.

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.

A clinical biochemistry analyser designed specifically for veterinary use was used to analyse plasma samples from 24 vervet monkeys (Cercopithecus aethiops). Two millilitres of heparinised blood was collected from each of the 24 monkeys on four occasions at intervals of one week. Plasma was separated and analysed for the concentrations of triglycerides, cholesterol, total proteins, albumin, globulins, creatinine and blood urea nitrogen (BUN) and the activities of alkaline phosphatase (AP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK). The tests were easy to perform, used small volumes of plasma, and yielded consistent results for most of the analytes. The activities of CK and AP, but not AST, appeared to be influenced by haemolysis, and there were significant individual variations in the activity of LDH.

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.

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.

Many investigations in humans indicate that epinephrine, norepinephrine and their ratio may correlate with such traits as social competence, academic achievement, and aggression. However, the socioeconomic, dietary, and environmental confounds accompanying most human studies complicate their interpretation. Social status, aggression, and other social behaviors can be reliably assessed in nonhuman primates under conditions controlling for crucial environmental factors. If interpretation of human studies is correct, dominant and subordinate male vervet monkeys should exhibit distinctive patterns of catecholamine secretion. To test this possibility, seventeen adult male monkeys living in six stable social groups were observed for 6 months. Based on their success in agonistic events, subjects were categorized as dominant or subordinate. Alpha scores were calculated from empirically derived factors to provide a noncategorical measure of dominant behavioral style. Plasma epinephrine and norepinephrine samples obtained from anesthetized subjects did not differ between dominant and subordinate males. Alpha scores, however, distinguished high from low norepinephrine/epinephrine ratio groups. These findings are consistent with studies in humans linking high epinephrine, low norepinephrine, and social competence.

Colonies of nonhuman primates at the Bowman Gray School of Medicine (BGSM) were tested for antibodies to two retroviruses associated with immunodeficiency by indirect immunofluorescence (IFA) and western blot. A total of 471 cynomolgus macaques (Macaca fascicularis), 144 rhesus monkeys (M. mulatta) and 67 stumptail monkey M. arctoides) were tested for SRV-1, and 152 African green monkeys (Cercopithecus aethiops) were tested for SIV. Of the macaques tested, 170 (36%) cynomolgus, 5 (3%) rhesus and 8 (12%) stumptails were positive for SRV-1 antibodies by IFA. Of the African green monkeys, 54 (36%) were IFA positive for SIV antibodies. A total of 143 African green monkeys tested by IFA also were tested by western blot. In the African green monkeys, the IFA had a positive predictive value of 98% and a negative predictive value of 96%. Of 176 IFA positive macaque sera tested by western blot, 49 (28%) were positive, 55 (31%) were considered equivocal (only one band, usually to p27 core protein), and 72 (41%) were negative.

Whole blood serotonin levels in adult male vervet monkeys living in social groups are sensitive to the animals' social environment. The mechanisms that translate different behavioral and environmental cues into altered whole blood serotonin levels are unknown. In this study, we have measured platelet number, size, serotonin content, and serotonin uptake, as well as the serum concentrations of tryptophan, Mg+2 and Ca+2. Results showed that whole blood serotonin levels, platelet serotonin content, and the serotonin uptake parameter Vmax were stable within animals on repeated sampling. The whole blood serotonin level was highly positively associated with platelet serotonin content, and the platelet serotonin content was highly positively associated with Vmax. These findings suggested that whole blood serotonin levels were a function of the number of platelet uptake sites.

A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for nonhuman primate serum apolipoprotein A-I (apoA-I) is described. The assay is a noncompetitive, sandwich ELISA in which polystyrene microtiter plates were used with purified, monospecific goat anti-monkey apoA-I antibodies adsorbed on the wells. The serum samples were added to the coated wells, incubated, and after washing, antibodies conjugated to horseradish peroxidase were added. After further washing, the bound label was assayed. A heat treatment step, 52 degrees C for 3 hr, was used to maximize the apoA-I immunoreactive sites in diluted serum. Serum samples extracted with chloroform-methanol, delipidated with tetramethylurea, or denatured by heating gave essentially equivalent results. The working range of the apoA-I standards was 0.5 to 5 ng and parallel responses were observed for apoA-I in serum, in isolated HDL, and in buffer as a purified apoprotein. Recovery of apoA-I added to serum was quantitative (106 +/- 3%). The intra- and interassay coefficients of variation were 6.2 and 6.9%, respectively. The enzyme immunoassay yielded values that compared favorably with those obtained by radial immunodiffusion (r = 0.84). ApoA-I concentration in African green monkey serum was highly correlated with the HDL cholesterol concentration (r = 0.86). It is concluded that this ELISA is an accurate and precise method for determination of apoA-I concentrations in primate serum.

Aflatoxin B1 significantly depressed serum lipid levels in specimens of Cercopithecus aethiops, Cercopithecus mona, Erythrocebus patas and Papio anubis. Serum cholesterol, total phospholipids and total lipids were not affected to the same extent.

Six male cynomolgus monkeys and five male African green monkeys were fed dietary cholesterol to induce hypercholesterolemia. The two groups studied had equivalent total plasma cholesterol concentrations. Low density lipoproteins (LDL) were isolated from whole plasma by ultracentrifugation and separated from other lipoprotein classes by agarose column chromatography. LDL were further subfractionated by density gradient ultracentrifugation in a VTi-50 vertical rotor. The material within five density regions was pooled from each sample and molecular weight, electrophoretic mobility, apoprotein heterogeneity, and percentage composition were determined for each subfraction. In general, cynomolgus monkey LDL were larger and more polydisperse than African green monkey LDL, and the LDL subfractions of cynomolgus monkeys were generally of lower densities although molecular weights at any density were in the same range for both species. ApoB-100 was the major apoprotein in each subfraction. ApoE was frequently present in the less dense subfractions while apoA-I was often seen in the more dense subfractions. Cynomolgus monkey LDL appeared to contain more apoE than African green monkey LDL. Over the entire spectrum of LDL, the percentage composition of the particles at any given density was indistinguishable between the species. In general, the average cynomolgus monkey LDL was larger, more polydisperse, less dense, and appeared to contain more apoE than the average African green monkey LDL. One or all of these differences might help explain the increased susceptibility to diet-induced atherosclerosis seen in cynomolgus monkeys.

Human type A-B-O blood group antigens were tested in a local population of Ethiopian vervet monkeys (Cercopithecus aethiops). One animal was of group AB, the others were A. This represents a lower rate of polymorphism at this locus than has been observed among South African populations of the same species.

Soluble blood group substances, isolated from the red blood cells of humans, baboons, and vervet monkeys by ethanol extraction, possessed serologically active specificities for the following antigens: A, B, H, Lea, LebL, P, P19 Pk and I. Human red blood cells lacking any of these specificities by the direct hemagglutination test also lacked the related antigens in their soluble extract. The only exception was in "Bombay" Oh cells, from which soluble H substance could be readily isolated. Soluble substances obtained from baboon and vervet monkey red blood cells, which lack the human variety of A, B, and H antigens on their red blood cells, inhibited both human and lectin anti-H reagents. The detection of "hidden" H activity in Oh cells will pose some important questions regarding membrane characteristics and the role of immune surveilance.

Dominant male adult vervet monkeys have whole-blood serotonin concentrations approximately twice those of subordinate adult males. We examined the effects of spontaneous and induced changes in social status, temporary isolation from the social group, and membership in single male groups on whole-blood serotonin concentrations. We found that in male vervet monkeys, elevated blood serotonin concentration is a state-dependent consequence of active occupation of the dominant male social position, and we believe that a reinterpretation of the significance of hyperserotonemia in humans may be warranted.

In the process of biological control of uninfected green monkey kidney (GMK) cell cultures a thermostable hemagglutinating agent designated No. 5056 was isolated alongside with adenovirus-SV. By its antigenic properties the 5056 strain was identified as adeno-associated virus type 4 (AAV-4). In control of 574 specimens of GMK culture batches, 40 AAV-4 strains were isolated in the presence of a helper adenovirus. Some biological properties of the isolates and their resistance to certain physical and chemical treatments were studied. Two isolates of the satellite virus were examined in the electron microscope. A correlation between the rate of AAV-4 isolation from GMK cultures and the presence of complement-fixing antibody to AAV-4 in monkey sera was observed.

Haematology values are presented for the vervet monkey (Cercopithecus aethiops), and the relative effects of high dose ketamine anaesthesia, stress of capture and repeated bleedings assessed. Anaesthesia resulted in decreased WBC and RBC values, attributed to depression of cardiovascular function. These effects were the reverse of those of alarm and strenuous exercise (leukocytosis and polycythaemia) during capture. Stress resulted in relatively high white and low red blood cell counts. Opposing effects of stress and anaesthesia led to comparable haematological values for trained, non-anaesthetized vervets and stressed, anaesthetized vervets. Effects of repeated bleedings were opposite in anaesthetized and non-anaesthetized animals. These effects, however, along with those of ketamine anaesthesia and stress, were relatively insignificant compared with the wide variation in haematological values found among individuals. The biological importance of these effects thus appeared to be slight. The concept of 'normal values' is discussed.

Seven small groups of vervet monkeys (Cercopithecus aethiops aethiops), totaling 124 individuals, from Awash National Park, Ethiopia, were trapped and blood samples were obtained. Twenty-three loci were examined by starch gel electrophoresis and four loci, Tf, E, ADA, and PMG2 were found to be polymorphic. The average heterozygosity (H) of the population was calculated to be 5.6%. No significant deviations from Hardy-Weinberg equilibrium proportions occurred and a chi-square test for group homogeneity was also not significant. Average Fst for all polymorphic loci was calculated to be 0.062. This suggests that the entire group functions as a single Mendelian population.

Significant differences between species in the mean level of enzyme activity, ranging from 50 to 400%, were detected during a study of 10 enzymes from erythrocytes of humans and five non-human primates. The activity differences were consistent with variation, between species, at the structural loci for specific enzymes rather than differences in mean cell age, hemoglobin content or other pleiotropic effects. For seven of the eight loci at which direct comparisons among the six species could be made, the number of species-specific activity differences was greater than the number of variants observed by electrophoresis. Thus not only do activity measurements detect previously "hidden" variation among species but they also provide information regarding genetic differences which may be of potential physiological and/or selective relevance.

Twenty-nine African green monkeys were fed diets for 22 months containing 0.79 mg cholesterol/kcal and 40% of calories as either safflower oil or butter with or without the addition of an estrogen- and progestin-containing oral contraceptive. Plasma cholesterol concentrations ranged from 199 to 250 mg/dl. Animals consuming the safflower oil diet had plasma cholesterol concentrations that averaged 61 mg/dl lower than those consuming butter. At least 72% of this lowering was due to a reduction in low density lipoproteins. Triglyceride concentrations were also slightly lower in animals consuming the safflower oil diet. The oral contraceptive lowered total plasma cholesterol concentrations in both diet groups by an average of 41 mg/dl with 54% of this lowering (22 mg/dl) due to a reduction in high density lipoprotein cholesterol. This effect occurred only during the 3 weeks while the contraceptive was being administered and was not apparent 1 week after stopping the drug. Animals consuming safflower oil had bile that was more lithogenic and had more gallstones than did those consuming butter. Addition of the oral contraceptive caused a slight increase in bile lithogenicity, but this increase was not statistically significant. There was no significant interaction between the oral contraceptive and either of the diets to exacerbate cholelithiasis. At the plasma cholesterol concentrations achieved only minimal amounts of atherosclerosis developed and there were no indications of differences due to diet or oral contraceptive in the extent of atherosclerosis.

In an attempt to establish relationships between the endocrine and lipid metabolism during pregnancy, the changes in total plasma cholesterol (TPC) and lipoprotein cholesterol that occur during pregnancy in the African green monkey were investigated longitudinally in ten females in relation to the changes in progesterone, estradiol, and fasting insulin concentrations. Respective means for TPC, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) plus very low-density lipoprotein (VLDL) cholesterol were 343 +/- 35, 108 +/- 9, and 235 +/- 36 mg/dL prior to the estimated date of conception in ten females fed a high-fat, high-cholesterol diet. The concentration of these lipids fell to 225 +/- 31, 54 +/- 4, and 168 +/- 29 mg/dL for TPC (P less than 0.001), HDL cholesterol (P less than 0.001), and LDL + VLDL cholesterol (P less than 0.001), respectively, by midpregnancy (84 days). Progesterone concentrations increased during the first 60 days of pregnancy and were negatively correlated with HDL cholesterol concentrations (r = -0.57, P less than 0.02). After reaching their highest mean value, progesterone concentrations then plateaued at lower concentrations until parturition. The decrease in progesterone concentrations was associated with an initial rise in estradiol concentrations, which reached their highest concentrations in late pregnancy and were inversely correlated with HDL-cholesterol concentrations (r = -.32, P less than 0.01). Although glucose concentrations remained steady during gestation, insulin concentrations were elevated compared to postpartum concentrations (P less than 0.05) suggesting that insulin resistance occurred during the pregnancy in this nonhuman primate.(ABSTRACT TRUNCATED AT 250 WORDS)

Two distinctive aminopeptidase isozymes have been identified in the serum of the vervet monkey. The L-methionine-sensitive cytosol aminopeptidase (AP; E.C. 3.4.11.1) is present in all samples, while the cystyl aminopeptidase (CAP; E.C. 3.4.11.3) isozyme, which is resistant to inhibition by 0.1 M L-methionine, is found only in the serum of pregnant females. The pregnancy-specific CAP isozyme appears in the serum between the fifth and the eleventh weeks of a nearly 22-week pregnancy. The overall aminopeptidase activity and the activity of the L-methionine-insensitive isozymes alone are both significantly greater in the serum of pregnant females than in nonpregnant females. Consequently, the presence of the cystyl aminopeptidase isozyme in the serum is a useful diagnostic indicator of pregnancy in the vervet monkey.

The timing of a single daily meal of monkey chow in African green vervets exerts a synchronizing influence on plasma cortisol concentrations with an initial increase after feeding followed by a decrease to minimal levels five hours after feeding.