Osteopenia and osteoporosis in adult baboons (Papio hamadryas)

BACKGROUND: Little is known about the degree to which baboons, an important animal model in skeletal research, spontaneously experience age-related osteopenia and osteoporosis. METHODS: We measured bone mineral density (BMD) in 667 baboons, assigned T-scores to older animals based on sex-specific young adult reference groups, and compared reproductive history in older females with low BMD to those with normal BMD. RESULTS: Approximately 25% of older baboon females were osteopenic. No females or males were osteoporotic. Neither parity nor interbirth interval spine clearly distinguished low vs. normal BMD groups. Intersite correspondence in low BMD was highest between sites in the same region rather than sites of the same bone type. CONCLUSION: As with humans, osteopenia is common among older females. The absence of osteoporotic animals may be due to colony maintenance resulting in truncation of the aged population and selection for healthier animals in the oldest ranges.     

Hematology and blood biochemistry in infant baboons (Papio hamadryas)

Although published normative reference standards for hematologic and clinical chemistry measures are available for adult baboons, their applicability to infants has not been addressed. We analyzed these measures in 110 infant baboons (55 females and 55 males) from a large breeding colony at the Southwest Regional Primate Research Center in San Antonio, Texas. The sample consists of olive baboons and olive/yellow baboon hybrids, 1 week to 12 months of age. We produced cross-sectional reference values and examined the effects of age, sex, and subspecies on these variables. Hematology reference ranges for infant baboons are similar to, but wider than, those for adults. Reference ranges for blood biochemistry measures are generally more dissimilar to adults, indicating that for many variables, reference ranges for adult baboons are not adequate for infants. Although sex and subspecies differences are rare, age accounts for more than 10% of the variance in many of the variables.     

Effects of age,sex, and heredity on measures of bone mass in baboons (Papio hamadryas)

Abstract: Bone mass and bone density were estimated in 219 pedigreed baboons (Papio hamadryas) by radiographic morphometry of the left second metacarpal. Compact bone width (total bone width – medullary canal diameter) and bone ratio (compact bone width/total bone width) decreased with increasing age squared in both sexes. The heritability of medullary canal diameter was 0.64±0.11, of compact bone width was 0.40±0.15 and of bone ratio was 0.67±0.13. The results indicate baboons are a useful model for studies of age, sex and genetic effects on bone mass.     

Gingival histoplasmosis: An atypical presentation of African histoplasmosis in three baboons (Papio spp)

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown and may complicate colony management decisions.     

Reversal of Ketamine/Xylazine combination anesthesia by Atipamezole in olive baboons (Papio anubis)

Background  The potential of Atipamezole (ATI) to reverse Ketamine/Xylazine (KET/XYL) anesthesia in the Olive baboon ( Papio anubis ) was studied.
Methods  Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO₂) were monitored. Baboons were treated with: KET/XYL only, KET/XYL followed by 100 μg/kg ATI or by 200 μg/kg ATI administered 25 minutes after KET/XYL.
Results  Atipamezole rapidly reversed depressed HR and SAP (10 ± 5.2 minutes), RR (5 ± 2 minutes) and SpO₂ (3 ± 6 minutes) and significantly decreased MAT (13 ± 2.2 minutes) vs. KET/XYL alone (35 ± 5 minutes). Emesis was absent and salivation was observed after administration of 200 μg/kg ATI only.
Conclusions  Atipamezole at 100 μg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects.     

Early sexual maturity in male hamadryas baboons (Papio hamadryas hamadryas) and its reproductive implications

We present data on sexual maturity in young hamadryas baboon males (Papio hamadryas hamadryas) and its reproductive consequences in a large captive baboon colony. Hamadryas baboons live in a multilevel social system, with one-male units (OMUs) as the smallest social entity. Male leaders of OMUs are believed to monopolize matings within their OMUs; hence mating is believed to be polygynous and monandrous. In a captive colony of hamadryas baboons, we found evidence that young males less than 4 years old fathered at least 2.5% of 121 offspring born subsequent to vasectomy of all adult males, and males aged 4-5 years fathered at least 16.5% of the offspring. Additional evidence that these young males are able to sire offspring came from a morphological comparison of sperm from hamadryas males of different ages. The sperm of a 48-month-old hamadryas baboon were morphologically indistinguishable from viable sperm from adult males, whereas sperm from a 45-month-old male showed some aberrations. If successful copulations by adolescent males constitute a regular pattern even in free-ranging hamadryas baboons, a hamadryas male's chances to reproduce would not be limited to his role as an OMU leader as previously assumed, and a male's reproductive career would consist of two phases: the adolescent phase, and the OMU leader male phase.     

Reproductive and neonatal outcomes in captive bred baboons (Papio hamadryas)

Abstract: Baboons are widely used in biomedical research. Although it is widely held that Papio hamadryas breed well in captivity, each established colony has a different reproductive success often hypothesised to be due to husbandry practices. The National Baboon Colony in Australia is a unique colony that houses Papio hamadryas to mimic that structure seen in the wild. In this article; we have analysed their reproductive parameters and neonatal outcomes. The success of the colony husbandry practices was demonstrated by lack of maternal mortality, low foetal morbidity, and known maternal and paternal linage.     

Behavioral variation and reproductive success of male baboons (Papio anubis x Papio hamadryas) in a hybrid social group

We take advantage of an array of hybrid baboons (Papio anubis x Papio hamadryas) living in the same social group to explore the causes and consequences of different male mating strategies. Male hamadryas hold one-male units and exhibit a sustained, intense interest in adult females, regardless of the latter's reproductive state. Anubis baboons, by contrast, live in multi-male, multi-female groups where males compete for females only when the latter are estrous. These two taxa interbreed to form a hybrid zone in the Awash National Park, Ethiopia, where previous work has suggested that hybrid males have intermediate and ineffective behavior. Here, we first examine male mating strategies with respect to morphological and genetic measures of ancestry. We found significant relationships between behavioral measures and morphology; males with more hamadryas-like morphology had more hamadryas-like behavior. However, genetic ancestry was not related to behavior, and in both cases intermediates displayed a previously unreported level of behavioral variation. Furthermore, male behavior was unrelated to natal group. Second, we evaluated reproductive success by microsatellite-based paternity testing. The highest reproductive success was found for individuals exhibiting intermediate behaviors. Moreover, over nine years, some genetically and morphologically intermediate males had high reproductive success. We conclude that the behavior of hybrid males is therefore unlikely to be an absolute barrier to admixture in the region.     

Endometrial and cervical polyps in 22 baboons (Papio sp.), 5 cynomolgus macaques (Macaca fascicularis) and one marmoset (Callithrix jacchus)

Background  Endometrial and cervical polyps are masses of endometrium or cervical epithelium that bulge into the uterine or cervical lumen. The physiopathology and contributing factors of endometrial polyps development are still unknown.
Methods  Clinical and pathology records of 28 non-human primates with histologically confirmed endometrial and cervical polyps were reviewed. Twenty-one baboons with endometrial polyps were evaluated for age at diagnosis, body weight, menstrual cycle length, presence of endometriosis and adenomyosis and number of offspring, cesarean sections, and stillbirths.
Results  Endometrial polyps in baboons were associated with increased age, decreased menstrual cycle lengths, endometriosis, and decreased parity. No differences were found for weight, adenomyosis, or number of cesarean sections or stillbirths.
Conclusions  Baboons are a promising model for the study of endometrial polyps because of their similarity to humans in both the development of endometrial polyps and association of many of the same risk factors.     

Genetics of adult body mass and maintenance of adult body mass in captive baboons (Papio hamadryas subspecies)

Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons. Am. J. Primatol. 42:281–288, 1997. © 1997 Wiley-Liss, Inc.     

Effects of ketamine sedation on glucose clearance,insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas)

Since the effects of ketamine sedation seem to differ between subspecies of baboons, we assessed the endocrine response to an intravenous glucose tolerance test (IVGTT) in 12 hamadryas baboons. The first phase insulin secretion, basal insulin, and glucose levels, as well as the glucose clearance, were significantly lower in sedated baboons as compared to fully awake animals. Glucagon and Cortisol were significantly higher, while growth hormone was lower during ketamine sedation. Papio hamadryas appears to be a promising pre-clinical model for the study of endocrine replacement therapy in insulin-dependent diabetes. However, the data obtained must be interpreted with the knowledge that the anesthetic employed to allow for testing of the animals does have an effect on the parameters described in this report.     

Kinetics of stable isotope and body composition in olive baboons (Papio anubis) estimated by deuterium dilution space: a pilot study

Morphometrics and isotope-labelled water were used to determine body composition [total body water, total body fat and fat-free mass (FFM)] of three captive female olive baboons (Papio anubis). Mean mass was 16.5 kg, comparable with other captive settings but heavier than wild olive baboons. Average water content was 66%; FFM averaged 90.5%. Baboon females have less body fat than human counterparts. Compared with captive or wild baboons, these females were adequately nourished for their energy expenditure. A positive association between total mass and FFM existed, but due to the small sample no general relationship was observed for body fat or FFM and condition or size measures. The kinetics of deuterium equilibration in body fluids for baboons was determined as 3-4 hours after injection, similar to that for humans. Deuterium dilution technique appears to be an appropriate method for studying body composition in baboons, although a larger sample is needed for relationships between morphometric indices and body composition.     

Disproportionate participation by age/sex classes in aggressive interactions between long-tailed macaques (Macaca fascicularis) and human tourists at Padangtegal monkey forest, Bali, Indonesia

We observed 420 aggressive interactions between tourists and Macaca fascicularis at the Padangtegal Wanara Wana Temple forest site in Bali, Indonesia, during the months of June and July 2001. The data collected included patterns of aggression, presence or absence of food, and demographic information on resident macaques and human visitors. Analyses of the interactions suggest that macaques respond differentially to humans according to the age/sex classes involved. Additionally, adult and subadult male macaques participated in more aggressive behaviors than expected, while adult female macaques and immatures participated in such behaviors less than expected. These variations in interaction patterns between macaques and tourists may have substantial implications for management issues and the potential for pathogen transmission.     

Lipopolysaccharide (LPS) Stimulates the Production of Tumor Necrosis Factor (TNF)-α and Expression of Inducible Nitric Oxide Synthase (iNOS) by Osteoclasts (OCL) in Murine Bone Marrow Cell Culture

Osteoclasts (OCL) resorb bone. They are essential for the development of normal bones and the repair of impaired bones. The function of OCL is presumed to be supported by cytokines and other biological mediators, including tumor necrosis factor (TNF)-α and nitric oxide (NO). Bacterial lipopolysaccharide (LPS) is a potent inducer of TNF-α and inducible nitric oxide synthase (iNOS), which is the specific enzyme for synthesizing NO from L-arginine. To obtain direct evidence on LPS-induced TNF-α production and iNOS expression by OCL, OCL-enriched cultures were prepared by 7-day cocultures of bone marrow cells of adult BALB/c mice and osteoblastic cells (OBs) derived from calvaria of newborn BALB/c mice, and the generation of TNF-α and iNOS in OCL stimulated with LPS was examined immunocytochemically. When the cultured cells were stimulated with 100 ng/ml of LPS, OCL clearly showed TNF-α and iNOS expression. Without LPS-stimulation, no expression was observed. TNF activity in the culture supernatants of the OCL-enriched cultures in the presence of LPS was also detected by cytotoxic assay that used TNF-sensitive L929 cells. The dentin resorption activity of OCL was estimated by area and number of pits formed on dentin slices, which were covered by the OCL fraction and cultured in the presence or absence of LPS, sodium nitroprusside (SNP; a NO generating compound), N^G-monomethyl L-arginine acetate (L-NMMA; a competitive inhibitor of NO synthase (NOS)), or LPS plus L-NMMA. Pit formation was obviously inhibited in the presence of SNP and slightly inhibited in the presence of L-NMMA, but it was not affected in the presence of LPS or LPS plus L-NMMA. These findings indicate that OCL produces TNF and expresses iNOS in response to LPS, but the LPS-activation of OCL scarcely affects pit formation by them.     

Augmented oxygen-mediated transcriptional activation of cytochrome P450 (CYP)1A expression and increased susceptibilities to hyperoxic lung injury in transgenic mice carrying the human CYP1A1 or mouse 1A2 promoter in vivo

Background/aims

TEC, a member of the TEC family of non-receptor type protein tyrosine kinases, has recently been suggested to play a role in hepatocyte proliferation and liver regeneration. This study aims to investigate the putative mechanisms of TEC kinase regulation of hepatocyte differentiation, i.e. to explore which signaling pathway TEC is involved in, and how TEC is activated in hepatocyte after hepatectomy and hepatocyte growth factor (HGF) stimulation.

Methods

We performed immunoprecipitation (IP) and immunoblotting (IB) to examine TEC tyrosine phosphorylation after partial hepatectomy in mice and HGF stimulation in WB F-344 hepatic cells. The TEC kinase activity was determined by in vitro kinase assay. Reporter gene assay, antisense oligonucleotide and TEC dominant negative mutant (TEC^KM) were used to examine the possible signaling pathways in which TEC is involved. The cell proliferation rate was evaluated by ³H-TdR incorporation.

Results

TEC phosphorylation and kinase activity were increased in 1 h after hepatectomy or HGF treatment. TEC enhanced the activity of Elk and serum response element (SRE). Inhibition of MEK1 suppressed TEC phosphorylation. Blocking TEC activity dramatically decreased the activation of Erk. Reduced TEC kinase activity also suppressed the proliferation of WB F-344 cells. These results suggest TEC is involved in the Ras-MAPK pathway and acts between MEK1 and Erk.

Conclusions

TEC promotes hepatocyte proliferation and regeneration and is involved in HGF-induced Erk signaling pathway.     

Atlantic salmon (Salmo salar) muscle precursor cells differentiate into osteoblasts in vitro: Polyunsaturated fatty acids and hyperthermia influence gene expression and differentiation

The formation and mineralisation of bone are two critical processes in fast-growing Atlantic salmon (Salmo salar). The mechanisms of these processes, however, have not been described in detail. Thus, in vitro systems that allow the study of factors that influence bone formation in farmed Atlantic salmon are highly warranted. We describe here a method by which unspecialised primary cells from salmon white muscle can differentiate to osteoblasts in vitro. We have subsequently used the differentiated cells as a model system to study the effects of two factors that influence bone formation in Atlantic salmon under commercial farming conditions, namely polyunsaturated fatty acids, PUFAs, and temperature. Muscle precursor cells changed their morphology from triangular or spindle-shaped cells to polygonal or cubical cells after 3 weeks in osteogenic medium. In addition, gene expression studies showed that marker genes for osteoblastogenesis; alp, col1a1, osteocalcin, bmp2 and bmp4 increased after 3 weeks of incubation in osteogenic media showing that these cells have differentiated to osteoblasts at this stage. Adding CLA or DHA to the osteoblast media resulted in a reduced PGE₂ production and increased expression of osteocalcin. Further, temperature studies showed that differentiating osteoblasts are highly sensitive to increased incubation temperature at early stages of differentiation. Our studies show that unspecialised precursor cells isolated from salmon muscle tissue can be caused to differentiate to osteoblasts in vitro. Furthermore, this model system appears to be suitable for the study of osteoblast biology in vitro.