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31.
32.
Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. 总被引:2,自引:0,他引:2
T Kuber Sampath Petra Simic Rebecca Sendak Natasa Draca Ann E Bowe Stephen O'Brien Susan C Schiavi John M McPherson Slobodan Vukicevic 《Journal of bone and mineral research》2007,22(6):849-859
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. 相似文献
33.
Shreyasee Amin B Lawrence Riggs Elizabeth J Atkinson Ann L Oberg L Joseph Melton Sundeep Khosla 《Journal of bone and mineral research》2004,19(7):1075-1083
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. 相似文献
34.
Prediction of Remission of Acute Posttraumatic Stress Disorder in Motor Vehicle Accident Victims 总被引:1,自引:0,他引:1
Edward B. Blanchard Edward J. Hickling Catherine A. Forneris Ann E. Taylor Todd C. Buckley Warren R. Loos James Jaccard 《Journal of traumatic stress》1997,10(2):215-234
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. 相似文献
35.
36.
Rachel Yehuda Ann Steiner Boaz Kahana Karen Binder-Brynes Steven M. Southwick Shelly Zemelman Earl L. Giller 《Journal of traumatic stress》1997,10(1):93-100
Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma. 相似文献
37.
38.
Ann Bowling Morag Farquhar Emily Grundy Juliet Formby 《International journal of geriatric psychiatry》1992,7(5):307-321
This article reports findings from a longitudinal survey of very elderly people living at home in London. The research aimed to identify social, psychological and physical characteristics associated with positive ageing and successful survival in the community in later life and its converse—negative ageing—as well as the associated policy implications. Associations with psychiatric morbidity, measured using the General Health Questionnaire, among sample members without cognitive impairment between the baseline interviews in 1987 and at follow-up, two and a half years later in 1990, are reported. Twenty-five per cent of survivors scored over the threshold of the GHQ in 1987 and 30% scored over the threshold in 1990. Half of those with a score over the threshold in 1990 also scored over the threshold in 1987. Hierarchical regression (using residualized change analysis) was used to estimate the effects of the independent variables on changes in psychiatric morbidity. The most significant predictor of psychiatric morbidity (GHQ score) in 1990 was baseline GHQ score, followed by health and functional status scores. Health and functional status were also the strongest predictors of baseline (1987) GHQ scores. The uniqueness of the study lies in the collection of follow-up data on a sample of very elderly people, given that most surveys are corss-sectional and contain too few people aged 85+ to merit separate analysis. It contributes to the small body of literature on outcome of depression. The lack of consistent associations with recovery from psychiatric morbidity in the literature enhances the importance of studies aiming to identify factors associated with different outcomes. 相似文献
39.
40.
T Nagatake V T Hoang T Tegoshi J Rabbege T K Ann M Aikawa 《The American journal of tropical medicine and hygiene》1992,47(2):259-264
Autopsy samples from the brains of 20 patients who died of falciparum malaria were examined by light microscopy and by an immunohistologic method. Particular attention was paid to a comparison of the pathologic features of the white matter and the cortex. In the high-sequestration (greater than 50%) group (n = 8), the mean +/- SD percentage of cerebral microvessels that showed parasitized red blood cell (PRBC) sequestration was 71.2 +/- 8.1% in the cortex and 84.0 +/- 6.7% in the white matter. The difference in the PRBC sequestration rate between cortex and white matter was statistically significant (P less than 0.01). Perivascular and ring hemorrhages were seen more frequently in the white matter than in the cortex. Deposition of IgG and Plasmodium falciparum antigen in the cerebral microvessels was more highly significant in the white matter than in the cortex (P less than 0.01). Our study demonstrated that the localized concentration of PRBC sequestration in the brain correlated with the marked immunohistologic differences in the microvessels of cortex and white matter. 相似文献