Effect of Selective Estrogen Receptor Modulator/Raloxifene Analogue on Proliferation and Collagen Metabolism of Tendon Fibroblast

The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17β-Estradiol (E₂; 10^?11–10^?9 M) and LY117018 (10^?9–10^?7 M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2′-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E₂ nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E₂ and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E₂ and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E₂ or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels.     

Prevention of Venous Thromboembolism in Medical Intensive Care Unit: A Multicenter Observational Study in Korea

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.     

Venous Thromboembolism Following Hip and Knee Replacement Arthroplasty in Korea: A Nationwide Study Based on Claims Registry

The aim of this study was to examine the incidence and trends of clinically relevant venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) after hip and knee replacement arthroplasty (HKRA) in Korea. Between January 1 and December 31, 2010, 22,127 hip replacement arthroplasty (HRA) patients and 52,882 knee replacement arthroplasty (KRA) patients were enrolled in the analysis using the administrative claims database of the Health Insurance Review and Assessment Service (HIRA). All available parameters including procedure history and clinically relevant VTE during the 90 days after HKRA were identified based on diagnostic and electronic data interchange (EDI) codes. The overall incidence of VTE, DVT, and PE during the 90 days was 3.9% (n=853), 2.7% (n=597), and 1.5% (n=327) after HRA, while the incidence was 3.8% (n=1,990), 3.2% (n=1,699), and 0.7% (n=355) after KRA. The incidence of VTE after HKRA was significantly higher in patients who had previous VTE history (odds ratio [OR], 10.8 after HRA, OR, 8.5 after KRA), chronic heart failure (2.1, 1.3), arrhythmia (1.8, 1.7), and atrial fibrillation (3.4, 2.1) than in patients who did not. The VTE incidence in patients with chemoprophylaxis was higher than that in patients without chemoprophylaxis. The incidence of VTEs revealed in this retrospective review was not low compared with the results of the studies targeting other Asian or Caucasian populations. It may warrant routine prevention including employment of chemoprophylaxis. However, the limitation of the reviewed data mandates large scale prospective investigation to affirm this observation.     

Prevention of Venous Thromboembolism, 2nd Edition: Korean Society of Thrombosis and Hemostasis Evidence-Based Clinical Practice Guidelines

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Graphical Abstract

相似文献   

Transgenic Models of Metabolic Bone Disease: Impact of Estrogen Receptor Deficiency on Skeletal Metabolism

Estrogen has protective effects on the skeleton via its inhibition of bone resorption. Mechanisms for these effects and the selectivity to the estrogen receptor &#102 (ER &#102 ) or ER &#103 are unclear. The purpose of our study was to determine the impact of the ER &#102 on skeletal metabolism using murine models with targeted disruption of the ER &#102 and &#103 . Mice generated by homologous recombination and Cre/ lox P technology yielding a deletion of the ER &#102 exon 3 were evaluated and also crossed with mice with a disruption of the exon 3 of the ER &#103 to result in double ER &#102 and ER &#103 knockout mice. Skeletal analysis of long bone length and width, radiographs, dual X-ray absorptiometry, bone histomorphometry, micro computerized tomography, biomechanical analysis, serum biochemistry, and osteoblast differentiation were evaluated. Male ER &#102 knockout mice had the most dramatic phenotype consisting of reduced bone mineral density (BMD), and bone mineral content (BMC) of femurs at 10 and 16 weeks and 8-9 months of age. Female ER &#102 knockout mice also had reduced density of long bones but to a lesser degree than male mice. The reduction of trabecular and cortical bone in male ER &#102 knockout mice was statistically significant. Male double ER &#102 and ER &#103 knockouts had similar reductions in bone density versus the single ER &#102 knockout mice suggesting that the ER &#102 is more protective than the ER &#103 in bone. In vitro analysis revealed no differences in osteoblast differentiation or mineralized nodule formation among cells from ER &#102 genotypes. These data suggest that estrogens are important in skeletal metabolism in males; the ER &#102 plays an important role in estrogen protective effects; osteoblast differentiation is not altered with loss of the ER &#102 ; and compensatory mechanisms are present in the absence of the ER &#102 and/or another receptor for estrogen exists that mediates further effects of estrogen on the skeleton.     

Venous Thromboembolism in Korean Patients Undergoing Major Orthopedic Surgery: A Prospective Observational Study using Computed Tomographic (CT) Pulmonary Angiography and Indirect CT Venography

In patients undergoing major orthopedic surgery, data of deep venous thrombosis (DVT) and pulmonary embolism (PE) are lacking as studied by computed tomographic (CT) pulmonary angiography and indirect CT venography (CTPA-CTV). A prospective observational study was performed for 363 Korean patients undergoing major orthopedic surgery to determine the incidence of venous thromboembolism (VTE), especially proximal DVT and PE. The incidence of VTE was 16.3% (n=59). Of them, 8 patients (2.2%) were symptomatic. The rate of VTE was the highest in patients who underwent total knee replacement (40.4%), followed by hip fracture surgery (16.4%), and total hip replacement (8.7%; P<0.001). The incidence of PE was 6.6% (n=24). Of them, 4 patients (1.1%) were symptomatic. Forty-one patients (11.3%) were in the proximal DVT or PE group. Based on multivariate analysis, total knee replacement and age ≥65 yr were significant risk factors for proximal DVT or PE in patients undergoing major orthopedic surgery (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1; P=0.025; and OR, 2.1; 95% CI, 1.0-4.4; P=0.046, respectively). Taken together, the overall incidence of PE was 6.6% and rate of symptomatic PE rate was 1.1%. Knee joint replacement and age ≥65 yr were significant risk factors for proximal DVT or PE.     

Venous Thromboembolism in a Single Korean Trauma Center: Incidence,Risk Factors,and Assessing the Validity of VTE Diagnostic Tools

PurposeTrauma increases the risk of venous thromboembolism (VTE) in hospitalized patients. However, the risk and incidence of VTE in Korean trauma patients are limited. Therefore, we aimed to evaluate the incidence and identify potential predictors of VTE occurrence in Korean trauma patients. Moreover, we assessed the validity of the Greenfield risk assessment profile (RAP) and the trauma embolic scoring system (TESS) in these patients.Materials and MethodsThis retrospective cohort study used the data of trauma patients who were admitted to a regional trauma center between 2010 and 2016 and were eligible for entry into the Korea Trauma Data Bank. Clinical data were collected from hospital medical records. The patient''s baseline characteristics and clinical data were compared between VTE and non-VTE groups.ResultsWe included 9472 patients. The overall VTE rate was 0.87% (n=82), with 56 (0.59%) events of deep vein thrombosis and 39 (0.41%) of pulmonary embolism. Multiple regression analysis revealed that variables, including VTE history, pelvic-bone fracture, ventilator use, and hospitalization period, were significant, potential predictors of VTE occurrence. This study showed that increased RAP and TESS scores were correlated with increased VTE rate, with rates of 1% and 1.5% for the RAP and TESS scores of 6, respectively. The optimal cut-off value for RAP and TESS scores was 6.ConclusionRAP and TESS, which are well-known diagnostic tools, demonstrated potentials in predicting the VTE occurrence in Korean trauma patients. Additionally, patients with pelvic-bone fractures and long-term ventilator treatment should be carefully examined for possible VTE.     

雌激素、雌激素受体与膀胱癌间关系的研究进展

目的:探讨雌激素与雌激素受体对膀胱癌发生、发展的影响,为膀胱癌的内分泌治疗提供新的思路.方法:查阅近年来国内外膀胱癌与雌激素、雌激素受体间关系的相关文献,对其进行研究总结.结果:膀胱癌的病因、发病机理、复发机理还不十分明确,治疗方法也不完善.雌激素、雌激素受体可能对膀胱癌的发生发展有一定作用.结论:研究雌激素、雌激素受体与膀胱癌发生、发展的关系,对膀胱癌的诊断与治疗方面有重要意义.     

雌激素防治骨质疏松症的研究进展

１９４１年Ａｌｂｒｉｇｈｔ首先提出绝经与骨质疏松之间的关系，５０多年来，大量的临床与实验研究证实，雌激素缺乏是绝经后骨质疏松的重要发病因素。低雌激素状态或绝经后补充雌激素，可以预防雌激素低下引起的骨丢失，并对绝经后的多种改变有防治作用，例如绝经后症状...     

雌激素及运动对老年性骨质疏松症的影响及防治

研究阐述了雌激素及运动对老年性骨质疏松症的影响及机制,并就目前研究,提出进一步研究的方向,雌激素和运动作为影响骨密度的两个独立而又相互交叉的因素,前者作为内源性物质,随着年龄的降低能否成为骨质疏松症发生的预测指标,后者作为外在因素,能够多大限度的抵消雌激素降低带来的负性效果,有待于进一步验证。     

分子成像在静脉血栓栓塞诊断中的研究与应用进展

静脉血栓栓塞(venous thromboembolism,VTE)主要表现为深静脉血栓形成(deep vein thrombosis,DVT)和肺栓塞(pulmonary embolism,PE),由于症状的非特异性,该疾病很难被确诊.此外,治疗DVT的副作用明显,因此正确诊断静脉血栓栓塞具有重要的临床意义.目前临床上用于诊断静脉血栓栓塞的主要手段包括超声、计算机断层扫描和磁共振成像.近年来,随着分子影像学的快速发展,分子成像在静脉血栓栓塞的诊断中将发挥越来越重要的作用.本文对分子成像的靶点、示踪剂及其用于诊断静脉血栓栓塞的研究进展进行综述.     

Graves病患者外周血白细胞雌,雄激素受体变化的初步研究

应用放射配体结合法，测定了３５例ＧＤ病人外周血白细胞雌激素受体（ＥＲ）和雄激素受体（ＡＲ）等指标。结果：病人血清Ｅ２、Ｔ、白细胞ＥＲ明显增高（Ｐ〈０．０５），ＡＲ明显降低。提示：ＧＤ病人性激素异常、外周血白细胞ＥＲ、ＡＲ的异常可能与ＧＤ发病和／或演变有关。     

ER、PR及其相应拮抗剂与甲状腺癌的相关性研究进展

雌激素受体(ER)、孕激素受体(PR)在甲状腺癌中的异常表达说明性激素受体在甲状腺癌的发病机制中起重要作用.ER、PR通过经典的基因途径及非基因途径对甲状腺癌的发生、发展及生物学特征产生重要影响.性激素受体拮抗剂抑制甲状腺癌细胞增殖作用的研究,将为甲状腺癌的治疗提供新的选择方案.     

Comparative effects of risedronate,atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats

Objective

The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats.

Methods

Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17β-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test.

Results

Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group (p = 0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group (p = 0.047). In ovariectomy + atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group (p = 0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene (p = 0.602, 0.602, 0.75, and 0.927). In ovariectomy + risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group (p = 0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene (p = 0.306, 0.808, and 0.095).

Conclusions

While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium.     

In Vivo Effects of Ovarian Steroid Hormones on the Expressions of Estrogen Receptors and the Composition of Extracellular Matrix in the Anterior Cruciate Ligament in Rats

Female athletes have a significantly higher rate of anterior cruciate ligament (ACL) injury than their male counterparts. Sex steroid hormones are considered to have an influence as risk factors for female ACL injuries. We hypothesized that estrogen and progesterone have specific and synergistic influences on the composition of extracellular matrix in ACL. By ovariectomy (OVX) followed by subcutaneous estradiol (E2) and/or progesterone (P4) replacement, 40 female rats were divided into 5 groups: E2, P4, combined E2 and P4 (EP), OVX control, and sham group. After 30 days, using undecalcified sections of knee joints in conjunction with immunofluorescence staining of estrogen receptor α and β (ERα and ERβ), collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP), the immunoreactivities of these proteins in two distinct parts of ACL, proximal and middle portions, were compared semiquantitatively among experimental groups. By E2 replacement, the expressions of ERα in ACL fibroblasts were elevated compared to the OVX group. At the proximal portion, the immunoreactivities of type 1 collagen by E2 replacement, type 3 collagen by P4 replacement, and COMP by E2 or P4 replacement were significantly reduced. At the middle portion, the immunoreactivity of type 3 collagen was significantly elevated by E2 replacement. However, no differences were observed between the sham and OVX groups. These findings suggest that ACL is ER-dependent and that ovarian hormones alter ligament tissue composition, especially at the proximal portion. Female hormonal influences are partly involved in the biological properties of ACL.     

Venous thromboembolism in Latin America: a review and guide to diagnosis and treatment for primary care

There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America.