Animal Research Pathology: Regulatory and Safety Considerations.

Animal research pathology encompasses a wide array of procedures and may involve work with a variety of animal species and hazards. To protect laboratory personnel and ensure data integrity, pathologists must be familiar with the activities performed in their laboratories and the applicable regulatory and safety requirements. Failure to address issues proactively may result in exposure of personnel to hazardous materials and/or collection of data in a manner that does not conform to animal welfare or quality control standards. This manuscript provides a brief introduction to important animal research pathology regulatory and safety considerations. The importance of close communication between the principal investigator, pathologist, laboratory personnel, Institutional Animal Care and Use Committee, and institutional safety office/experts is emphasized and a mechanism for improving communication is discussed.

Epigenetics and developmental programming of welfare and production traits in farm animals.

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

Indices of adiposity as predictors of cardiometabolic risk and inflammation in young adults.

BACKGROUND: Studies investigating obesity and cardiometabolic risk have focused on 'at-risk' populations and methodological inconsistencies have produced equivocal findings. The present cross-sectional study investigated indices of body composition as predictors of cardiometabolic risk and their relationship with inflammation in apparently healthy young adults. METHODS: A fasting blood sample was taken from consenting adults (160 males, 32 females, aged 18-40 years) for assessment of cardiometabolic risk markers (blood pressure, lipid profiles and insulin resistance) and inflammatory markers (C-reactive protein, tumour necrosis factor-α, interleukin-6, interleukin-10 and adiponectin). Together with anthropometry, fat mass (FM) and fat-free mass (FFM) were determined by dual-energy X-ray absorptiometry. FM was expressed in absolute terms (kg), as well as relative to total body weight (%), height [FM index (FMI, kg m(-2) )] and FFM (FM : FFM,%). RESULTS: Although anthropometric indices were associated with most cardiometabolic risk markers, the strongest relationship was observed with FMI. Relative to having a low cardiometabolic risk (≤2 markers above clinically relevant cut-offs), each kg m(-2) increase in FMI, increased the likelihood of having an increased cardiometabolic risk by 29% (odds ratio = 1.29; 95% confidence interval = 1.12-1.49). Inflammatory markers were not associated with body composition or cardiometabolic risk. CONCLUSIONS: FMI was the strongest predictor of overall cardiometabolic risk but not inflammation per se. However, anthropometric indices, such as body mass index and waist-to-height ratio, remain valuable surrogate measures of adiposity in this group, particularly when risk markers are considered independently.

Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb.

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼ 50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (MF (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=-0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002-0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation.

Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity.

Vitamin D deficiency is associated with inflammation in older Irish adults.

CONTEXT: Inadequate vitamin D status is common within elderly populations and may be implicated in the etiology of autoimmune disease and inflammation. Few studies have investigated the relationship between vitamin D status and age-related immune dysfunction in humans. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and immune markers of inflammation in a large sample of older adults. DESIGN, SETTING, AND PARTICIPANTS: An observational investigation of 957 Irish adults (>60 years of age) recruited in Northern Ireland (55°N latitude) as part of the Trinity Ulster Department of Agriculture aging cohort study. MAIN OUTCOME MEASURE: We measured serum 25-hydroxyvitamin D (25(OH)D) by liquid chromatography tandem mass spectrometry and serum cytokines IL-6, TNF-α, IL-10, and C-reactive protein (CRP) by ELISA. RESULTS: Concentrations of IL-6, CRP, and the ratios of IL-6 to IL-10 and CRP to IL-10 were significantly higher in individuals with deficient (<25 nmol/L) serum 25(OH)D compared with those with sufficient (>75 nmol/L) status after adjustment for age, sex, and body mass index (P < .05). Vitamin D status was a significant predictor of the IL-6 to IL-10 cytokine ratio, and those participants defined as deficient were significantly more likely to have an IL-6 to IL-10 ratio >2:1 compared with those defined as sufficient. CONCLUSIONS: This study demonstrated significant associations between low vitamin D status and markers of inflammation (including the ratio of IL-6 to IL-10) within elderly adults. These findings suggest that an adequate vitamin D status may be required for optimal immune function, particularly within the older adult population.

Perceived 'healthiness' of foods can influence consumers' estimations of energy density and appropriate portion size.

OBJECTIVE: To compare portion size (PS) estimates, perceived energy density (ED) and anticipated consumption guilt (ACG) for healthier vs standard foods. METHODS: Three pairs of isoenergy dense (kJ per 100 g) foods-healthier vs standard cereals, drinks and coleslaws-were selected. For each food, subjects served an appropriate PS for themselves and estimated its ED. Subjects also rated their ACG about eating the food on a scale of 1 (not at all guilty) to 5 (very guilty). RESULTS: Subjects (n=186) estimated larger portions of the healthier coleslaw than that of the standard version, and perceived all healthier foods to be lower in ED than their standard alternatives, despite being isoenergy dense. Higher ACG was associated with the standard foods. Portion estimates were generally larger than recommendations and the ED of the foods was underestimated. CONCLUSIONS: The larger portions selected for the 'reduced fat' food in association with lower perceived ED and ACG suggests that such nutrition claims could be promoting inappropriate PS selection and consumption behaviour. Consumer education on appropriate portions is warranted to correct such misconceptions.

Impact of birth weight and gender on early postnatal hypothalamic energy balance regulatory gene expression in the young lamb.

Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia.

A case of successful pregnancy in a ewe with uterus didelphys.

Uterus didelphys is a rare congenital abnormality of the reproductive tract. Although it occurs in various species, there are no published reports describing pregnancy outcome in association with this abnormality. Herein we describe a case of successful unilateral singleton pregnancy in a ewe incidentally found to have uterus didelphys during the course of a biomedical research study. The pregnancy was established using assisted reproductive techniques and interrupted in late gestation, at which point the abnormality was identified. Serial ultrasound assessment of foetal biometry revealed a normal foetal growth trajectory. Despite a 45% reduction in placentome number, total placentome weight was near normal secondary to compensatory placentome growth and development. To our knowledge, this is the first detailed report of normal foetal growth in an animal with uterus didelphys and illustrates the ability of the ovine placenta to adapt to a reduced number of placentomes and maintain foetal nutrient supply.

Gestational age, gender and parity specific centile charts for placental weight for singleton deliveries in Aberdeen, UK.

INTRODUCTION: The weight of the placenta is a crude but useful proxy for its function in vivo. Accordingly extremes of placental weight are associated with adverse pregnancy outcomes while even normal variations in placental size may impact lifelong health. Centile charts of placental weight for gestational age and gender are used to identify placental weight extremes but none report the effect of parity. Thus the objective was to produce gender and gestational age specific centile charts for placental weight in nulliparous and multiparous women. METHODS: Data was extracted from the Aberdeen Maternity and Neonatal Databank for all women delivering singleton babies in Aberdeen city and district after 24 weeks gestation. Gestational age specific centile charts for placental weight by gender and parity grouping (n = 88,649 deliveries over a 30 year period) were constructed using the LMS method after exclusion of outliers (0.63% of deliveries meeting study inclusion criteria). RESULTS: Tables and figures are presented for placental weight centiles according to gestational age, gender and parity grouping. Tables are additionally presented for the birth weight to placental weight ratio by gender. Placental weight and the fetal:placental weight ratio were higher in male versus female deliveries. Placental weight was greater in multiparous compared with nulliparous women. DISCUSSION: We present strong evidence that both gender and parity grouping influence placental weight centiles. The differences at any given gestational age are small and the effects of parity are greater overall than those of gender. In contrast the birth weight to placental weight ratio differs by gender only. CONCLUSION: These UK population specific centile charts may be useful in studies investigating the role of the placenta in mediating pregnancy outcome and lifelong health.

Family eating out-of-home: a review of nutrition and health policies.

Childhood obesity is a growing problem worldwide. In recent years, out-of-home (OH) eating has been highlighted as one of the many factors contributing to the obesogenic environment. This review seeks to identify a range of existing guidelines for the provision of healthy food options for families who eat OH frequently. Nationally available nutrition policies were identified using targeted and untargeted searches of the internet to identify established strategies for providing food for children in the family eating out sector in America (US), Australia, Canada and the WHO's European Region (EUR). These were categorised on the basis of eleven pre-defined criteria including: family eating out sector included as stakeholder; inclusion of children's food OH; cost strategies for healthier food choices; provision of nutrition information for customers; nutrition training of catering staff; and monitoring and evaluation structures. Fifty-five policies were reviewed, of which 71% addressed children's food served OH, but principally only for food available in schools. Two voluntary programmes, from Colorado and Slovenia, were identified as possible best practice models as they met a majority of the evaluation criteria. The most frequently used strategy by policies to promote healthier eating OH was the provision of nutrition information on menus, while monitoring and evaluation plans were poorly incorporated into any OH strategies, thus raising issues about their effectiveness. This review has identified a range of initiatives that could be employed to make healthier eating OH more accessible for families. However, to establish best practice guidelines for healthier OH food choices further investigations are required.

Serving size guidance for consumers: is it effective?

Larger portion sizes (PS) may be inciting over-eating and contributing to obesity rates. Currently, there is a paucity of data on the effectiveness of serving size (SS) guidance. The aims of the present review are to evaluate SS guidance; the understanding, usability and acceptability of such guidance, its impact on consumers and potential barriers to its uptake. A sample of worldwide SS guidance schemes (n 87) were identified using targeted and untargeted searches, overall these were found to communicate various inconsistent and often conflicting messages about PS selection. The available data suggest that consumers have difficulty in understanding terms such as 'portion size' and 'serving size', as these tend to be used interchangeably. In addition, discrepancies between recommended SS and those present on food labels add to the confusion. Consumers generally understand and visualise SS best when expressed in terms of household measures rather than actual weights. Only a limited number of studies have examined the direct impact of SS guidance on consumer behaviour with equivocal results. Although consumers recognise that guidance on selecting SS would be helpful, they are often unwilling to act on such guidance. The challenge of achieving consumer adherence to SS guidance is formidable due to several barriers including chronic exposure to larger PS, distorted consumption norms and perceptions, the habit of 'cleaning one's plate' and language barriers for ethnic minorities. In conclusion, the impact of SS guidance on consumers merits further investigation to ensure that future guidance resonates with consumers by being more understandable, usable and acceptable.

Placental weight and efficiency in relation to maternal body mass index and the risk of pregnancy complications in women delivering singleton babies.

Herein we report placental weight and efficiency in relation to maternal BMI and the risk of pregnancy complications in 55,105 pregnancies. Adjusted placental weight increased with increasing BMI through underweight, normal, overweight, obese and morbidly obese categories and accordingly underweight women were more likely to experience placental growth restriction [OR 1.69 (95% CI 1.46-1.95)], while placental hypertrophy was more common in overweight, obese and morbidly obese groups [OR 1.59 (95% CI 1.50-1.69), OR 1.97 (95% CI 1.81-2.15) and OR 2.34 (95% CI 2.08-2.63), respectively]. In contrast the ratio of fetal to placental weight (a proxy for placental efficiency) was lower (P < 0.001) in overweight, obese and morbidly obese than in both normal and underweight women which were equivalent. Relative to the middle tertile reference group (mean 622 g), placental weight in the lower tertile (mean 484 g) was associated with a higher risk of pre-eclampsia, induced labour, spontaneous preterm delivery, stillbirth and low birth weight (P < 0.001). Conversely placental weight in the upper tertile (mean 788 g) was associated with a higher risk of caesarean section, post-term delivery and high birth weight (P < 0.001). With respect to assumed placental efficiency a ratio in the lower tertile was associated with an increased risk of pre-eclampsia, induced labour, caesarean section and spontaneous preterm delivery (P < 0.001) and a ratio in both the lower and higher tertiles was associated with an increased risk of low birth weight (P < 0.001). Placental efficiency was not related to the risk of stillbirth or high birth weight. No interactions between maternal BMI and placental weight tertile were detected suggesting that both abnormal BMI and placental growth are independent risk factors for a range of pregnancy complications.

Decreasing maternal nutrient intake during the final third of pregnancy in previously overnourished adolescent sheep: effects on maternal nutrient partitioning and feto-placental development.

When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and ∼20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation.

Endothelial dysfunction associated with obesity and the effect of weight loss interventions.

Endothelial damage is central to the initiation and progression of atherosclerosis, while in addition vascular endothelial cells secrete several anti-atherogenic substances including the potent vasodilator nitric oxide. Increased adhesion molecule expression, in response to pathophysiological stimuli is perhaps the earliest indicator of compromised endothelial integrity. Obesity and adiposity are associated with an increased risk of CVD, influencing disease progression via a number of mechanisms, including enhanced endothelial activation. This review discusses possible mechanisms linking adiposity and more specifically regional fat depots with endothelial function and evaluates studies investigating the effect of weight loss on endothelial function, assessed by biochemical and physiological measurements. Overall, the research to date suggests that visceral adiposity is a stronger predictor of endothelial activation than overall adiposity, possibly mediated via the action of NEFA in circulation. While in general there is a suggestion that weight loss is associated with significant improvements in endothelial function, this is not apparent in all interventions and published literature to date provides less than convincing evidence for the effects of weight loss on endothelial activation.

Effects of altered glucose supply and adiposity on expression of hypothalamic energy balance regulatory genes in late gestation growth restricted ovine fetuses.

Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.

Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers.

Red meat from grass-fed animals, compared with concentrate-fed animals, contains increased concentrations of long-chain (LC) n-3 PUFA. However, the effects of red meat consumption from grass-fed animals on consumer blood concentrations of LC n-3 PUFA are unknown. The aim of the present study was to compare the effects on plasma and platelet LC n-3 PUFA status of consuming red meat produced from either grass-fed animals or concentrate-fed animals. A randomised, double-blinded, dietary intervention study was carried out for 4 weeks on healthy subjects who replaced their habitual red meat intake with three portions per week of red meat (beef and lamb) from animals offered a finishing diet of either grass or concentrate (n 20 consumers). Plasma and platelet fatty acid composition, dietary intake, blood pressure, and serum lipids and lipoproteins were analysed at baseline and post-intervention. Dietary intakes of total n-3 PUFA, as well as plasma and platelet concentrations of LC n-3 PUFA, were significantly higher in those subjects who consumed red meat from grass-fed animals compared with those who consumed red meat from concentrate-fed animals (P < 0·05). No significant differences in concentrations of serum cholesterol, TAG or blood pressure were observed between groups. Consuming red meat from grass-fed animals compared with concentrate-fed animals as part of the habitual diet can significantly increase consumer plasma and platelet LC n-3 PUFA status. As a result, red meat from grass-fed animals may contribute to dietary intakes of LC n-3 PUFA in populations where red meat is habitually consumed.

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project.

UNLABELLED: In girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60 nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60 nmol/l appears to have implications for bone health outcomes in both girls and boys. INTRODUCTION: Our objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents. METHODS: We conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15 years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH. RESULTS: In girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60 nmol/l (PTH = 47.146 + 370.314 x exp((-0.092 x 25(OH)D))) while no plateau in PTH was observed in boys (PTH = 42.144 + 56.366 x exp((-0.022 x 25(OH)D))). Subjects with 25(OH)D levels <60 nmol/l had significantly higher osteocalcin concentrations (P < 0.05) compared with those who had >or=60 nmol/l, while no significant (P > 0.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (P = 0.046) in those with 25(OH)D concentrations >or= 60 nmol/l. CONCLUSIONS: Serum 25(OH)D levels above 60 nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60 nmol/l in both girls and boys may lead to improved bone health outcomes.

The relationship between gender and age with monocyte tissue factor expression.

BACKGROUND: In normal healthy individuals, the level of tissue factor (TF) expression on monocytes is low. However, studies have shown that patients with cardiovascular disease (CVD) have elevated levels of TF. As the risk of CVD increases with age and is more prominent in the male population, it is postulated that TF expression may be positively correlated with these factors. However, very few studies have examined the relationship between age and gender on TF expression. METHODS: This study evaluated the influence of age and gender on TF expression using data obtained from female (n = 44) and male (n = 27) subjects. We also examined the influence of BMI and total fat intake on TF expression in the same subjects. RESULTS: The results of our study found no significant difference in TF expression between the male and female subgroups. No correlation was found between TF and age, BMI or total fat intake in the male or female groupings. CONCLUSION: It may be postulated that the risk of CVD development in such populations may not be due to increases in TF expression with increasing age or gender differences.

Effects of maternal nutrition and stage of gestation on body weight, visceral organ mass, and indices of jejunal cellularity, proliferation, and vascularity in pregnant ewe lambs.

Peripubertal ewe lambs (44.3 +/- 1.1 kg of initial BW) were used in a 2 x 3 factorial design to test the effects of plane of nutrition (diet) and stage of gestation on maternal visceral tissue mass, intestinal cellularity, crypt cell proliferation, and jejunal mucosal vascularity. Singleton pregnancies to a single sire were established by embryo transfer, and thereafter ewes were offered a control (Control) or high (High) amount of a complete diet (2.84 Mcal/kg and 15.9% CP; DM basis) to promote slow or rapid maternal growth rates. After d 90 of gestation, feed intake of the Control group was adjusted weekly to maintain BCS and meet the increasing nutrient demands of the gravid uterus. Ewes were slaughtered at 50 d (n = 6 Control; n = 5 High), 90 d (n = 8 Control; n = 6 High), or 130 d (n = 8 Control; n = 6 High) of gestation. Ewes were eviscerated and masses of individual organs were recorded. The jejunum was sampled and processed for subsequent analyses. Final ewe BW for Control-fed ewes was similar at d 50 and 90 and increased (P = 0.10) from d 90 to 130 (46.0, 48.9, and 58.2 +/- 1.6 kg, respectively), whereas final BW increased (P