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111.
Sanjeev Kakar Thomas A Einhorn Siddharth Vora Lincoln J Miara Gregory Hon Nathan A Wigner Daniel Toben Kimberly A Jacobsen Maisa O Al-Sebaei Michael Song Philip C Trackman Elise F Morgan Louis C Gerstenfeld George L Barnes 《Journal of bone and mineral research》2007,22(12):1903-1912
Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. 相似文献
112.
罗格列酮对糖尿病大鼠肾脏保护作用机制的探讨 总被引:7,自引:1,他引:6
目的 探讨罗格列酮对糖尿病大鼠肾脏的保护作用机制。方法 将大鼠分为正常组、糖尿病组、小剂量罗格列酮组、大剂量罗格列酮组。药物干预4周后,检测各组大鼠的血糖(BS)、三酰甘油(TG)、胆固醇(TC)、肌酐(Scr)水平及尿白蛋白定量(24h)。随后处死大鼠,测定肾组织中丙二醛(MDA)含量、总抗氧化能力(T-AOC)及铜锌超氧化物歧化酶(Cu-ZnSOD)、谷胱甘肽过氧化酶(GSH-Px)、核转录因子-κB(NF-κB)的活性。同时留取。肾脏组织作PAS染色行病理检查。RT-PCR和免疫组化法检测。肾组织中单核细胞化学吸引蛋白质1(MCP-1)mRNA及蛋白质的表达。结果 与糖尿病组相比,大剂量罗格列酮干预组BS、TC、TG差异无统计学意义;而。肾组织MDA含量、MCP-1mRNA及蛋白质表达、NF-κB活性差异有统计学意义(P〈0.05),SOD、GSH-Px、T-AOC活性显著上升;肾小球面积及体积减小。结论大剂量的罗格列酮可显著改善糖尿病大鼠的。肾脏损害,其机制可能与其抗氧化,抑制NF-κB活性,降低MCP-1的含量有关。 相似文献
113.
Ted T Song Michael R Nelson James H Chang Renata J M Engler Badrul A Chowdhury 《Annals of allergy, asthma & immunology》2005,94(5):539-542
BACKGROUND: Epinephrine injected by an autoinjector in the anterolateral aspect of the thigh is the standard of care in the emergency self-treatment of anaphylaxis. In the United States, the autoinjector EpiPen is widely used for the self-treatment of anaphylaxis. OBJECTIVE: To investigate whether EpiPen autoinjector, with a needle length of 1.43 cm, is sufficient for intramuscular delivery of epinephrine in men and women. METHODS: The distance from skin to muscle in the anterolateral aspect of the thigh was measured in 50 men and 50 women who had undergone computed tomography of the thighs for other medical reasons. For each individual, body mass index (BMI; a measure of weight in kilograms divided by the square of height in meters) was also calculated, and the individuals were classified as underweight (BMI, < 18.5), normal (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) using standard definition. RESULTS: In the study participants the mean +/- SD distance from skin to muscle was 0.66 +/- 0.47 cm for men and 1.48 +/- 0.72 cm for women (P < .001). One man (obese at a BMI of 42.2) and 21 women (11 obese with a mean BMI of 35.2, 6 overweight with a mean BMI of 30.1, and 4 normal with a mean BMI of 24.5) had a greater distance from skin to muscle than the EpiPen needle length of 1.43 cm. CONCLUSION: The distance from skin to muscle for the anterolateral aspect of the thigh is higher in women compared with men. This difference suggests that EpiPen may not deliver epinephrine to the intramuscular tissue in many women. 相似文献
114.
Yusen Chen Jun Nakura Jing-Ji Jin Zhihong Wu Miyuki Yamamoto Michiko Abe Yasuharu Tabara Yoshikuni Yamamoto Michiya Igase Xiao Bo Katsuhiko Kohara Tetsuro Miki 《Hypertension research》2003,26(6):439-444
The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension. 相似文献
115.
蛋白酶对降低异常精液粘稠度的实验对比研究 总被引:1,自引:0,他引:1
目的通过不同蛋白酶类对降低高粘稠度精液的粘稠度效果对比,寻找理想的降低精液粘稠度的药物。方法将高粘稠度精液标本分为两组,A组:31例采用α-糜蛋白酶降低精液粘稠度:B组:32例采用尿激酶降低精液粘稠度;两组均观察用药前后的精子活动力。采用配对t检验和单因素方差分析对所得数据作统计学处理。结果高粘稠度精液用药物(α-糜蛋白酶或者尿激酶)液化精液后,精子的活动力较用药前有明显提高(P<0.001);用药前后精液的粘稠度都存在着明显的差异,精液的粘稠度分别下降44.83%和55.45%(P<0.001);在A组和B组的对比研究中,单因素方差分析检验提示:用药后两组间粘稠度数据有显著的差异(P<0.001£(?)。结论蛋白酶可以有效地降低异常精液粘稠度的精液,从实验结果提示尿激酶降低精液粘稠度的效果优于α-糜蛋白酶,这有助于临床开展应用性研究和治疗。 相似文献
116.
M Javaid F Song S Leinster M G Dickson N K James 《Journal of plastic, reconstructive & aesthetic surgery》2006,59(1):16-26
OBJECTIVE: To conduct a systematic review to gather the available evidence on the optimum timing of the radiotherapy in relation to autologous breast reconstruction. MATERIAL AND METHODS: The data was extracted from scientific databases, and a manual follow-up of references. The studies were selected which included at least 20 patients with any method of autologous breast reconstruction who were treated with adjuvant radiotherapy either before or after their reconstruction, and had addressed the effects of radiotherapy on the cosmetic outcome in their results. The principal outcome was cosmetic appearance. Secondary outcomes were immediate and delayed complications. RESULTS: We could not find any randomised controlled trial on this topic. Ten studies were included, most were retrospective, heterogeneous in terms of control groups, radiation doses, follow-up duration, and outcome measurements. Two studies included no control groups, and four studies compared the outcomes of patients with radiotherapy either before (n=3) or after (n=1) autologous breast reconstruction. The overall incidence of complications was increased in patients with radiotherapy in three out of these four studies. Only four studies directly compared the outcomes of patients who received radiotherapy before with patients who received radiotherapy after autologous breast reconstruction and two out of these reported worse outcomes associated with post-reconstruction radiotherapy. CONCLUSIONS: Despite the paucity of the published data, the current evidence suggests that the radiation has a deleterious effect on autologous flap reconstruction. Until better methods of radiation delivery can be devised to minimise the long term radiation sequelae in the irradiated tissue, delayed reconstruction seems to be a safe option in most of the cases. However, the findings from these studies should be interpreted with great caution before generalising from their results. 相似文献
117.
118.
119.
OBJECTIVE: To optimize the process of extracting flavonoids from Smilax glabra. METHODS: Flavonoids were extracted from Smilax glabra by microwave-assisted method, and the extracting time, microwave power, ethanol concentration, solid-solvent ratio and extracting temperature were optimized through single factor experiment and orthogonal test. RESULTS: The optimun process parameters of extracting flavonoids were as follows: the extracting time, microwave power, ethanol concentration, solid-liquid ratio and extracting temperature were 5 minutes, 600 W, 60%, 1:30 and 80 degrees C, respectively. CONCLUSION: The proposed method has been applied stably and reliably to the extraction of flavonoids from Smilax glabra which has the advantages of high recovery and short extraction time. The recovery, the yield and the content of falvonoids are 93.2%, 2.66% and 32.6%, respectively. 相似文献
120.