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Abstract: IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 −/− mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 −/− and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 −/− and control mice at 4weeks post MI. We found that LI-IGF-1 −/− mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 −/− mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. [Copyright &y& Elsevier]

Abstract: Context: Angiotensin converting enzyme (ACE) activity may influence the production of adrenal androgen precursors and testosterone. Use of ACE inhibitors may therefore have an influence on serum sex hormone concentrations in older men. Design and Methods: 1486 out of 2,000 community-dwelling Chinese men aged 65years who participated in a cohort study were randomly selected to have archived fasting morning serum analyzed for androgen precursors and sex hormones. DNA was extracted from whole blood and analyzed for ACE gene I/D polymorphism. Results: Subjects with the ACE gene D allele (higher ACE activity) had higher serum dehydroepiandrosterone (DHEA) sulphate and DHEA than those with I/I genotype (P=0.014 and 0.018 respectively, Mann Whitney test). These differences were not significant after Bonferroni correction. Among those with history of hypertension, but without diabetes mellitus or cardiac failure, users of ACE inhibitors had significantly lower serum DHEA (median 1.78 versus 1.49ng/ml in non-users, P=0.0074, Mann Whitney test) and also tended to have lower serum androstenedione and androst-5-ene-3β,17β-diol (0.68 versus 0.72ng/ml in non-users; 552.4 versus 624.1pg/ml respectively, both P values <0.05). Serum testosterone and estradiol were not significantly changed. Conclusions: ACE inhibitor use was associated with lower serum DHEA in older men. [Copyright &y& Elsevier]

The purpose of this validation study was to describe strategies used in postoperative pain assessment among a group of nurses in South Africa. A mixed qualitative and quantitative study was conducted in a 950-bed academic hospital complex. Surgical nurses (n = 12) carried out pain assessments of postoperative patients (n = 36) in pain. Data were collected using detailed interviews and pain intensity was estimated on a visual analogue scale (VAS, 0-10 cm). Nurses used four categories of criteria (a) how the patient looks, (b) what the patient says, (c) the patient's way of talking, and (d) experience of similar circumstances and drew on their past experiences in five different ways: (a) some patients report lower pain intensity than expected, (b) a typology of patients, (c) a focus on listening to patients, (d) what to look for, and (e) what to do for patients were identified.The system of categories described by Sjöström [Sjöström B. Assessing acute postoperative pain. Assessment strategies and quality of clinical experience and professional role. Göteborg: Acta Universitatis Gothoburgensis; 1995] was valid for this sample with an additional category. The different categories seem to be complementary and necessary for assessing pain in others. The findings have implications for professionals who provide care for patients in pain. [ABSTRACT FROM AUTHOR]

Abstract: Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls (P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased (P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased (P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified. [Copyright &y& Elsevier]

The introduction of transgenic mice as animal models in medical research has increased the need for methods to study the phenotype of mice. The aim of the present study was to develop and evaluate a method for in vivo prediction of fat content in living mice. We combined a modified dual-energy X-ray technique with an image analysis procedure. This combined procedure calculates the percentage of fat area, defined as the percentage of the total area of the mice consisting of >50% fat. A high correlation between the percentage of fat area and dissected adipose tissue was seen in both male and female mice (males, r = 0.92, P < 0.001; females, r = 0.88, P < 0.001). A high correlation was also seen between the percentage of fat area and serum levels of leptin (males, r = 0.95, P < 0.001; females, r = 0.86, P < 0.001). An additional experiment demonstrated a very strong correlation between the percentage of fat area and total body fat as determined by chemical extraction (r = 0.97, P < 0.001). In summary, the percentage of fat area, as measured with the dual-energy X-ray/image combined procedure, provides a good in vivo estimation of total body fat content in mice. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Genetic differences of VDR receptor do not influence muscle strength in elderly men. • Difference in incidence of falls between alleles of the SNP rs7136534. • 25(OH)D3 levels in blood were associated with time to do physical function tests. Abstract The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69–81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear. [ABSTRACT FROM AUTHOR]

Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for two weeks. During the treatment, right tibiae were subjected to short periods of cyclic compressive loading three times weekly, while left tibiae were used as physiologically loaded controls. The bones were analyzed using peripheral quantitative computed tomography, histomorphometry, real-time PCR, three-point bending and Fourier transform infrared micro-spectroscopy. Loading alone increased trabecular volumetric bone mineral density (vBMD), cortical thickness, cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast number, and bone strength. Prednisolone alone decreased cortical area and thickness and osteoblast-associated gene expression. Importantly, prednisolone treatment decreased the load-induced increase in trabecular vBMD by 57% (p < 0.001) and expression of osteoblast-associated genes, while completely abolishing the load-induced increase in cortical area, cortical thickness, number of osteocytes and osteoclasts, and bone strength. When combined, loading and prednisolone decreased the collagen content. In conclusion, high-dose prednisolone treatment strongly inhibits the loading-induced increase in trabecular BMD, and abolishes the loading-induced increase in cortical bone mass. This phenomenon could be due to prednisolone inhibition of osteoblast differentiation and function. [ABSTRACT FROM AUTHOR]

Abstract: We explored the role of transient receptor potential vanilloid 4 (TRPV4) in murine bone metabolism and association of TRPV4 gene variants with fractures in humans. Urinary and histomorphometrical analyses demonstrated reduced osteoclast activity and numbers in male Trpv4−/− mice, which was confirmed in bone marrow-derived osteoclast cultures. Osteoblasts and bone formation as shown by serum procollagen type 1 amino-terminal propeptide and histomorphometry, including osteoid surface, osteoblast and osteocyte numbers were not affected in vivo. Nevertheless, osteoblast differentiation was enhanced in Trpv4−/− bone marrow cultures. Cortical and trabecular bone mass was 20% increased in male Trpv4−/− mice, compared to sex-matched wild type (Trpv4+/+ ) mice. However, at the same time intracortical porosity was increased and bone matrix mineralization was reduced. Together, these lead to a maximum load, stiffness and work to failure of the femoral bone, which were not different compared to Trpv4+/+ mice, while the bone material was less resistant to stress and less elastic. The differential impacts on these determinants of bone strength were likely responsible for the lack of any changes in whole bone strength in the Trpv4−/− mice. None of these skeletal parameters were affected in female Trpv4−/− mice. The T-allele of rs1861809 SNP in the TRPV4 locus was associated with a 30% increased risk (95% CI: 1.1–1.6; p=0.013) for non-vertebral fracture risk in men, but not in women, in the Rotterdam Study. Meta-analyses with the population-based LASA study confirmed the association with non-vertebral fractures in men. This was lost when the non-population-based studies Mr. OS and UFO were included. In conclusion, TRPV4 is a male-specific regulator of bone metabolism, a determinant of bone strength, and a potential risk predictor for fractures through regulation of bone matrix mineralization and intra-cortical porosity. This identifies TRPV4 as a unique sexually dimorphic therapeutic and/or diagnostic candidate for osteoporosis. [Copyright &y& Elsevier]

Abstract: Introduction : Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. Materials and methods : Mice with adult liver-specific IGF-I inactivation (LI-IGF-I−/−) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. Results : Ovx resulted in a pronounced reduction in trabecular bone mineral density (−52%, P < 0.001), number (−45%, P < 0.01) and thickness (−13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I−/− mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I−/− mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-κB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I−/− mice. Conclusions : Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow. [Copyright &y& Elsevier]

Abstract: Feather pecking (FP) is a detrimental behaviour in chickens, which is performed by only some individuals in a flock. FP was studied in 54 red junglefowl (ancestor of domestic chickens), 36 White Leghorn laying hens, and 762 birds from an F2-intercross between these two lines. From all F2-birds, growth and feed consumption were measured. Age at sexual maturity and egg production in females, and corticosterone levels in males were also measured. From 333 F2-birds of both sexes, and 20 parental birds, body composition with respect to bone mineral content, muscle and fat was obtained by post-mortem examinations using Dual X-Ray Absorptiometry (DXA). In femurs of the same birds, the bone density and structure were analysed using DXA and Peripheral Quantitative Computerized Tomography (pQCT), and a biomechanical analysis of bone strength was performed. Furthermore, plumage condition was determined in all birds as a measure of being exposed to feather pecking. Using 105 DNA-markers in all F2-birds, a genome-wide scan for Quantitative Trait Loci (QTL), associated with the behaviour in the F2-generation was performed. FP was at least as frequent in the red junglefowl as in the White Leghorn strain studied here, and significantly more common among females both in the parental strains and in the F2-generation. In the F2-birds, FP was phenotypically linked to early sexual maturation, fast growth, weak bones, and, in males, also high fat accumulation, indicating that feather peckers have a different resource allocation pattern. Behaviourally, F2 feather peckers were more active in an open field test, in a novel food/novel object test, and in a restraint test, indicating that feather pecking might be genetically linked to a proactive coping strategy. Only one suggestive QTL with a low explanatory value was found on chromosome 3, showing that many genes, each with a small effect, are probably involved in the causation of feather pecking. There were significant effects of sire and dam on the risk of being a victim of feather pecking, and victims grew faster pre- and post-hatching, had lower corticosterone levels and were less active in a restraint test. Hence, a wide array of behavioural and developmental traits were genetically linked to FP. [Copyright &y& Elsevier]