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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
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J Andrew Derbyshire Smita Sampath Elliot R McVeigh 《Magnetic resonance in medicine》2007,58(1):206-210
Fully inverting spins, instead of merely saturating them, provides superior contrast for tagging procedures. The resulting improvement in tag contrast-to-noise ratio (CNR) yields higher-precision tag detection. Also, thinner slices and hence reduced tag separations can be employed, providing displacement and strain measurements with better spatial resolution. Alternatively, the improved tag contrast can be used to obtain cine images covering a greater portion of the cardiac cycle. The use of standard magnitude reconstruction for images of these inversion tags causes rectification of the negative-valued signals from the tags, confounding the image interpretation. Therefore, a phase-sensitive reconstruction scheme of the inverted tags must be employed. Here we demonstrate the implementation of inverted tags with phase-sensitive reconstruction in a ramped-flip-angle, steady-state free precession (SSFP) sequence. 相似文献
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AP de Moraes† ÉÂG de Arruda† MAV Vitoriano† MO de Moraes Filho‡ FÂF Bezerra‡ E de Magalhães Holanda§ MEA de Moraes‡ 《Journal of the European Academy of Dermatology and Venereology》2007,21(5):596-601
BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients. 相似文献
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Cardiac injuries--a clinical and autopsy profile 总被引:3,自引:0,他引:3
P Kulshrestha B Das K S Iyer K A Sampath M L Sharma I M Rao P Venugopal 《The Journal of trauma》1990,30(2):203-207
One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries. 相似文献
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In-vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium 总被引:21,自引:6,他引:21
Goud PT; Goud AP; Qian C; Laverge H; Van der Elst J; De Sutter P; Dhont M 《Human reproduction (Oxford, England)》1998,13(6):1638-1644
In-vitro maturation (IVM) of oocytes is a promising technique to reduce the
costs and avert the side-effects of gonadotrophin stimulation for in-vitro
fertilization (IVF). The pregnancy rates from oocytes matured in vitro are
much lower than those of in-vivo stimulation cycles indicating that
optimization of IVM remains a challenge. Therefore, we investigated the
effect of supplementation of the medium with gonadotrophins, oestradiol and
epidermal growth factor (EGF) and the effect of retaining or removing the
cumulus cells on nuclear and cytoplasmic maturation of immature oocytes.
Human germinal vesicle (GV) oocytes obtained after gonadotrophin
stimulation for intracytoplasmic sperm injection (ICSI) were cultured in a
complex defined medium either supplemented with gonadotrophins, oestradiol
and physiological concentrations of EGF (2 ng/ml) or gonadotrophins and
oestradiol alone. The cumulus cells were either removed or kept intact. In
GV stage oocytes cultured without cumulus (group I) significantly more
oocytes reached the metaphase II (MII) stage at 30 h in media supplemented
with EGF (64.3 versus 33.9%, P < 0.003). For oocytes cultured with
intact cumulus (group II), more oocytes reached MII at 30 h than in group
I, but there was no difference in medium with or without EGF
supplementation (81.8 and 79.8% respectively). Cytoplasmic maturation of
MII oocytes was judged from their capability to activate and fertilize
after ICSI. In group I, the rates of activation and normal fertilization
were similar. However, in group II, significantly more oocytes underwent
normal fertilization in the EGF-supplemented than the unsupplemented group
(71.7 versus 45.6%, P < 0.05). The cleavage rates of the fertilized
oocytes were similar in the sibling oocyte subgroups cultured with or
without EGF supplementation, but the overall cleavage rates were higher in
cumulus-intact compared to cumulus-denuded oocytes (88.9 versus 47.8%, P
< 0.001). Thus, supplementation of the maturation medium with EGF and
maintenance of the cumulus during culture improve the nuclear and
cytoplasmic maturation of human oocytes in vitro.
相似文献