Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Shielded and unshielded geometries in the search for orphan sources.

A car-borne NaI(Tl) spectrometric system was used together with a 137Cs source to obtain realistic data in the search for unshielded and semi-shielded orphan sources. The potassium-stripped counts (PSC) method was used to estimate the influence by the shielding on the detection ability. A reduction of about 5% in the critical distance was obtained for the semi-shielded source. A curve fitting method was also developed and evaluated. Results from the curve fitting method showed inferior ability to find the source compared to the PSC method. However, it can be a useful complementary tool, for characterisation of the source shielding, and estimation of the distance from the road.     

A potentially deleterious role of IGFBP-2 on bone density in aging men and women.

The role of the IGFs and IGFBPs on age-related changes in BMD in adult men and women is not well understood. Studying an age-stratified community based sample of 344 men and 276 women, we found higher IGFBP-2 levels to be associated with lower BMD. IGFBP-2, which increases with age in both men and women, was the strongest, most consistent predictor of BMD among the IGF/IGFBPs studied. INTRODUCTION: Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators of tissue growth and metabolism, but their association with BMD in adult men and women is controversial. MATERIALS AND METHODS: In an age-stratified, random sample of the community population, we examined the role of serum levels of IGF-I, IGF-II, and IGFBP-1, -2, and -3 on BMD of the proximal femur (total hip), lateral spine, midshaft, and ultradistal radius as measured by DXA. We explored the association before and after adjustment for potential confounders, including age, bioavailable estradiol and testosterone, sex hormone binding globulin (SHBG), and measures of total fat and skeletal muscle mass. RESULTS: We studied 344 men (age, 23-90 years) and 276 women (age, 21-93 years; 166 postmenopausal) not on hormone replacement or oral contraceptives. In both men and women, IGF-I and IGFBP-3 levels fell with advancing age, whereas IGFBP-2 levels tended to rise with age. There was an inverse association of IGFBP-2 with BMD at most skeletal sites in men and both premenopausal and postmenopausal women, whereas lower IGF-I and IGFBP-3 were associated with lower BMD in men and postmenopausal women only. Lower IGF-II was associated with lower BMD in men only. There were no associations between IGFBP-1 and BMD in either sex. After adjustment for age, in most cases, we found no further associations between IGF-I, IGF-II, or IGFBP-3 and BMD. In contrast, after age adjustment, higher IGFBP-2 remained a predictor of lower BMD in men and postmenopausal women at all sites except for the lateral spine (for men: r = -0.21, -0.20, and -0.19, all p < 0.001; and for postmenopausal women: r = -0.34, -0.24, and -0.25, all p < 0.01, for the total hip, midshaft, and ultradistal radius, respectively). IGFBP-2 remained an independent negative predictor of BMD in men, postmenopausal women, and all women combined after additional adjustment for bioavailable sex steroids, but not at all sites after adjustment for SHBG and muscle mass. In premenopausal women, IGFBP-2 had similar associations as seen in postmenopausal women, but they were weaker and not statistically robust. CONCLUSIONS: Among the IGF/IGFBPs in our study, IGFBP-2 was a key negative predictor of BMD among men and women, particularly postmenopausal women. Our findings suggest a potential role of the IGF/IGFBP system in regulating bone loss in aging men and women and identify a previously under-recognized, potentially deleterious role for IGFBP-2, a known inhibitor of IGF action that increases with age in both sexes. Whether the action of the IGF/IGFBP system on bone metabolism is mediated partly through its effects on muscle mass or SHBG deserves further study.     

GnRH receptor signalling to ERK: kinetics and compartmentalization.

Many hormones, neurotransmitters and growth factors influence their target cells by activation of mitogen-activated protein kinase cascades. The consequences of such activation reflect not only the magnitude, but also the kinetics and cellular compartmentalization of kinase activity. Gonadotropin-releasing hormone (GnRH) receptors are seven-transmembrane receptors that have undergone a period of rapidly accelerated molecular evolution in which the advent of type I mammalian GnRH receptors has been associated with the loss of the carboxyl-terminal tail, a structure present in all other seven-transmembrane receptors. Here, we review spatiotemporal aspects of extracellular-signal-regulated kinase activation by gonadotropin-releasing hormone receptors, emphasizing how the absence or presence of the carboxyl-terminal tail dictates the receptors' ability to engage and signal via arrestins.     

Prediction of Remission of Acute Posttraumatic Stress Disorder in Motor Vehicle Accident Victims

One hundred forty five individuals who sought medical attention as a result of a motor vehicle accident (MVA), and who were initially assessed 1 to 4 months post-MVA, were followed up prospectively for 6 months to determine how many of the 55 with posttraumatic stress disorder (PTSD) and the 43 with sub-syndromal PTSD would remit and what variables would predict remission. Thirty (55%) of those with initial PTSD had remitted at least in part by 6 months while 67% of those with sub-syndromal PTSD had remitted (and 5% had worsened). Four variables, including severity of initial symptoms, degree of initial physical injury, relative degree of physical recovery by 4 months and whether a close family member suffered a trauma during the follow-up interval, combined to classify 6-month clinical status of 84% of those with initial PTSD secondary to MVAs.     

What should nurse teachers be doing? A preliminary study

There is little doubt that the role of the nurse teacher is complex and multifaceted in nature. The apparently conflicting demands of NHS trusts and education in the United Kingdom, at the time of integration of nurse education into the higher education sector, further complicates the role. This recognition underlines the need to capture and measure key aspects of nurse teacher function in order to maximize educational gain. Using a comprehensive literature review, focus group discussions and a small number of individual semi-structured interviews, this preliminary study explored the issue of teacher workload, from the perspective of the principal stakeholders in nurse and higher education. Competing research and clinical practice objectives for nurse teachers are identified against a background of changing health care provision, reduced availability of placements and an increased need for evidence-based practice.     

Lewis Histo-Blood Group System and Associated Secretory Phenotypes

This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histoblood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual's Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone's Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis-negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b–) phenotype, the secretor genotype causes the Le(a–b+) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.