Magnetic Resonance Imaging of Osteophytic,Chondral, and Subchondral Structures in a Surgically-Induced Osteoarthritis Rabbit Model

Objective

This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model.

Methods

The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons.

Results

The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05–0.15 to 1.15–1.30 to 1.90–1.97 to 3.00–3.35 at each successive time point, respectively (p<0.05). Subchondral bone lesions progressed from a grade of 0.00 to 0.78–0.90 to 1.27–1.58 to 1.95–2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87–1.06 to 1.24–1.87 to 2.21–3.21 at each successive time point, respectively (p = 0.000).

Conclusions

Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.     

The Correlation of Contrast-Enhanced Ultrasound and MRI Perfusion Quantitative Analysis in Rabbit VX2 Liver Cancer

Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time–intensity curve of rabbit VX2 liver cancer showed “fast in, fast out” model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.     

前交叉韧带损伤后软骨退变和骨性关节炎发生的分子变化

为了探讨凋亡酶的半胱天冬酶3 (Caspase 3)、促炎细胞因子interleukin-1β(IL-1β)、白细胞介素-6(IL-6)和基质金属蛋白酶降解酶-13 (MMP-13)的表达水平,来说明前交叉韧带(anterior cruciate ligament,ACL)损伤后软骨细胞的软骨变性和骨性关节炎的发展情况,本研究通过探讨软骨降解程度与损伤时间或患者年龄之间的关系,应用实时聚合酶链反应检测正常人(n=5)和ACL破裂患者(n=42)软骨细胞中IL-1β、IL-6和MMP-13 mRNA的表达水平,采用Western blotting检测MMP-13和Caspase 3蛋白表达水平。通过趋势分析和相关系数分析,分别得出MMP-13、IL-6、IL-1β基因表达与软骨缺损分级,MMP-13、IL-6、IL-1β基因表达与患者年龄的关系。结果表明,软骨降解程度与损伤时间之间存在相关性。与正常相比,ACL损伤的软骨细胞中,MMP-13、IL-6、IL-1β和Caspase 3的表达水平有显著上调。在ACL缺陷患者中,与ACL缺陷未到18个月的患者相比,在超过18个月的患者中发现MMP-13明显上调,而超过10月的患者软骨细胞中IL-6和IL-1β表达水平要高于未到10个月的ACL缺陷患者。同时,IL-1β、IL-6和MMP-13表达水平和软骨损伤或病人的年龄之间没有关联。研究发现,软骨细胞凋亡、炎症和分解代谢因子水平的升高与损伤时间有关,并可能导致ACL损伤后软骨退变和骨性关节炎的发生。     

Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) Shows No Change in Cartilage Structural Composition after Viscosupplementation in Patients with Early-Stage Knee Osteoarthritis

Introduction

Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA.

Methods

In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses.

Results

All KOOS subscales (‘pain’, ‘symptoms’, ‘daily activities’, ‘sports’ and ’quality of life’) and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee.

Conclusions

Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.     

血清生物标记物含量与膝关节单纯性滑膜炎的相关性研究

目的:探讨血清生物标记物与膝关节单纯性滑膜炎的严重程度及预后的相关性.方法:选取我科2011年6月至2012年9月收治的64例膝关节单纯性滑膜炎患者为滑膜炎组,60例同期健康志愿者作为对照组.采用酶联免疫吸附实验(ELISA)法检测其血清中透明质酸、软骨寡聚蛋白、血管内皮生长因子的含量.滑膜炎评分采用术中关节镜下Ayral评分,分别在术前及术后三周对所有患者进行膝关节lysholm评分及视觉模拟评分(VAS).结果:滑膜炎组血清透明质酸、血管内皮生长因子的含量均显著高于对照组(P＜0.05),但两组软骨寡聚蛋白含量比较无统计学差异(P＞0.05).Ayral滑膜炎评分≥60分组血清HA、VEGF含量显著高于Ayral滑膜炎评分＜60分组(P＜0.05).术后3周,滑膜炎患者的lysholm评分及VAS评分均较术前的明显改善(P＜0.05).HA含量的高低与lysholm评分差值具有相关性(P＜0.05,r=0.743).VEGF含量高低与lysholm评分差值呈负相关(P＜0.05,r=-0.494).结论:滑膜炎患者血清HA、VEGF的含量与滑膜炎的严重程度和预后均有关,对早期诊断膝关节单纯性滑膜炎的病情严重程度有一定的参考价值,可作为临床检查和影像学诊断的有益补充.     

Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.     

T1-Weighted Sodium MRI of the Articulator Cartilage in Osteoarthritis: A Cross Sectional and Longitudinal Study

Structural magnetic resonance imaging (MRI) has shown great utility in diagnosing soft tissue burden in osteoarthritis (OA), though MRI measures of cartilage integrity have proven more elusive. Sodium MRI can reflect the proteoglycan content of cartilage; however, it requires specialized hardware, acquisition sequences, and long imaging times. This study was designed to assess the potential of a clinically feasible sodium MRI acquisition to detect differences in the knee cartilage of subjects with OA versus healthy controls (HC), and to determine whether longitudinal changes in sodium content are observed at 3 and 6 months. 28 subjects with primary knee OA and 19 HC subjects age and gender matched were enrolled in this ethically-approved study. At baseline, 3 and 6 months subjects underwent structural MRI and a 0.4ms echo time 3D T1-weighted sodium scan as well as the knee injury and osteoarthritis outcome score (KOOS) and knee pain by visual analogue score (VAS). A standing radiograph of the knee was taken for Kellgren-Lawrence (K-L) scoring. A blinded reader outlined the cartilage on the structural images which was used to determine median T1-weighted sodium concentrations in each region of interest on the co-registered sodium scans. VAS, K-L, and KOOS all significantly separated the OA and HC groups. OA subjects had higher T1-weighted sodium concentrations, most strongly observed in the lateral tibial, lateral femoral and medial patella ROIs. There were no significant changes in cartilage volume or sodium concentration over 6 months. This study has shown that a clinically-feasible sodium MRI at a moderate 3T field strength and imaging time with fluid attenuation by T1 weighting significantly separated HCs from OA subjects.     

关节腔注射强力霉素对兔膝骨关节炎模型的影响

目的:研究关节腔内注射强力霉素对兔制动性骨关节炎模型的影响.方法:30只新西兰大白兔随机分成正常组6只及实验组24只,试验组左膝关节伸直位石膏固定4周随机选取6只处死左膝关节取材证实造模成功后剩余18只为左膝骨关节炎模型,随机分为治疗组、阴性对照组和模型对照组,治疗组每日给予1.33%的强力霉素0.3毫升左膝关节腔内注射,阴性对照组每日给予生理盐水0.3毫升左膝关节腔注射,模型对照组不做处理,于8周处死取材.观察指标包括关节软骨大体形态,软骨Mankin's评分,软骨细胞基质金属蛋白酶-3(MMP-3)表达及滑膜细胞白介素-1(IL-1)表达.结果:强力霉素治疗组软骨面退变明显轻于模型组及生理盐水对照组,软骨大体评分,Mankin评分,MMP-3表达及滑膜IL-1表达亦显著降低.结论:强力霉素关节腔内注射对兔制动性骨关节炎模型软骨退变有明显的缓解作用.     

In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model

Tissue engineering (TE) has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS) technology, we have fabricated an oriented cartilage extracellular matrix (ECM)-derived scaffold with a Young''s modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC)-scaffold constructs (cell-oriented and random) in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen) and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties.     

Three-Dimensional Quantitative Morphometric Analysis (QMA) for In Situ Joint and Tissue Assessment of Osteoarthritis in a Preclinical Rabbit Disease Model

This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (σ), an angle to indicate erosion between the lateral and medial femoral condyles (ρ), a vector defining altered angulation (λ, α, β, γ) and a twist angle (τ) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept (m, Χ) of joint contact to demonstrate altered loading with disease progression, as well as traditional bone and cartilage and histo-morphometry measures. We demonstrate correlation of microCT and histology, sensitive discrimination of OA change and robust reproducibility.     

Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a Rabbit Model of Atherothrombosis

IntroductionThe detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture.ConclusionsOur targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout.     

原发性高血压患者血浆ET-1含量与血小板参数相关性研究

目的:探讨血浆内皮素-1 (Endothelin-1,ET-1)含量变化和血小板功能异常在原发性高血压疾病进程中相关性及意义.方法:选择98例原发性高血压患者作为实验组和30例健康受试者作为正常对照组.实验组又根据高血压分级标准分为轻度高血压组(L组),中度高血压组(M组)和重度高血压组(S组),分别检测各组患者血浆ET-1含量和血小板各项参数值.结果:实验组血浆ET-1含量、平均血小板体积(mean platelet volume,MPV)、血小板分布宽度(platelet distribution width,PDW)明显高于对照组(P＜0.05),血小板计数(platelet count,PLT)和血小板压积(platelet hematocrit,PCT)明显低于对照组(P＜0.05);L组、M组和S组ET-1含量、MPV和PDW值呈进行性升高(P＜0.05),PLT和PCT值呈进行性降低(P＜0.05).结论:血浆ET-1含量和血小板各项参数变化与疾病的进展和危重程度存在相关性,对原发性高血压的诊断治疗及预后评估有重要意义.     

瑞舒伐他汀对兔动脉粥样硬化斑块及血清PAPP-A的影响

目的:探讨瑞舒伐他汀对兔动脉粥样硬化斑块及血清妊娠相关血浆蛋白(PAPP-A)的影响.方法:新西兰家兔18只,随机分为正常对照组(Normal组,n=6)、动物粥样梗化模型组(AS组,n=6)和瑞舒伐他汀治疗组(RSV组,n=6).于治疗前、治疗后,检测血清总胆固醇(TC)、三酰甘油(TG)、血清低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)含量,酶联免疲吸附法(ELISA)检测血清PAPP-A水平.同时,用血管内超声检查(IVUS)测定病变部位的血管外弹力膜面积(EEMA)、管腔面积(LA)和斑块面积(PA),计算管腔面积狭窄百分率(LAS%).结果:治疗前,AS组和RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较Normal组高(P<0.01),HDL-C的水平较Normal组低(P<0.01);治疗后,RSV组兔的血清TC、TG、LDL-C及PAPP-A比AS组低(P<0.01).HDL-C的水平比AS组高(P<0.01),且RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较治疗前低(P<0.01),HDL-C的水平较治疗前高(P<0.01).血管内超声检查结果显示,治疗后,RSV组兔的LAS%(30.87%±5.27%)比AS组低(37.42%±6.12%)(P<0.01).结论:瑞舒伐他汀能改善对AS兔血脂,减少AS斑块形成及降低血清PAPP-A水平.     

兔不同急性肝衰竭模型的建立与评价

目的:探讨一种理想的急性肝衰竭(AHF)模型建立方法.方法:36只实验兔随机分为3组:①改良药物手术诱导组(A组,n=12),先用D-氨基半乳糖(D-Gain)和脂多糖(LPS)腹腔注射,同时加用乳果糖,注射后2h以氟烷作为麻醉剂,切除约50%肝脏组织.术中经肝静脉注入5%葡萄糖氯化钠溶液10ml/kg体重;②传统手术诱导组(B组,n=12),切除约95%肝脏组织,术中不行肝静脉穿刺注射5%葡萄糖氯化钠溶液;③药物诱导组(C组,n=12),用D一氨基半乳糖(D-Gain)和脂多糖(LPS)一次性腹腔注射.比较建模死亡率、建模后24h兔存活率、血谷丙转氨酶(ALT)、血氨(NH3)、总胆红素(TB)和血糖(BS).结果:B组手术死亡率高于A组死亡率(41.77%vs0%),A组、B组兔建模成功后24h存活率及C组兔建模成功后72h存活率分别为0%,0%,25%,A组ALT和NH3水平显著高于C组(P＜0.05),TB和BG水平低于C组,但差异无显著性.结论:通过改进的50%肝切除术可建立较理想的兔AHF模型,以氟烷作为麻醉剂,药物诱导注射同时加用乳果糖,术中经中叶肝静脉注入5%葡萄糖氯化钠溶液可减少手术死亡率.     

兔膝关节损伤后软骨细胞中OPG与RANKL表达

目的:随着中国经济的高速发展,人民生活水平日益增高。体育运动,高能量机动车造成的膝关节损伤数量不断增加,关节软骨的损伤恢复一直不是很理想。针对其后期的恢复研究做了许多相关的实验。本实验通过对兔膝关节软骨细胞损伤后软骨细胞中OPG(骨保护素)与RANKL(核激活因子受体配体)两种因子在损伤后与正常软骨细胞中的表达的比较,探讨损伤后软骨细胞中OPG和RANKL的表达。方法:25只大耳白兔随机分成5组,每组5只。前4组在10天完成20只兔左后腿膝关节软骨损伤动物模型,最后1组5只做手术对照组,术后处置相同。在术后1周,2周,4周,8周时取膝关节软骨损伤处关节软骨制成标本对照组取正常膝关节软骨制成标本。应用HE染色观察软骨细胞恢复情况及SP免疫组化法检测软骨细胞中OPG与RANKL的表达。在光镜下观察,通过医学图像分析软件(media cybernetics image-proplus6.0)图片分析,测定镜下相对灰度值并计算每个标本的平均灰度值,单因素方差分析法进行数据分析。结果:OPG在膝关节损伤后2-4周表达最高,4-8周有下降趋势。RANKL在膝关节软骨损伤后明显表达并逐步的呈升高趋势。实验组镜下观察表达较强烈,测定镜下平均灰度值与对照组有显著性差异(P0.05)。结论:1.OPG在膝关节软骨损伤后显著性表达。2-4周表达较高,4-8周趋于降低。2.RANKL在膝关节软骨损伤后显著表达,1-8周呈平稳上升趋势。     

Susceptibility-Weighted Imaging for the Noncontrast Evaluation of Hepatocellular Carcinoma: A Prospective Study with Histopathologic Correlation

Background

Specific morphologic features of hepatocellular carcinoma (HCC) on imaging have identifiable pathologic correlates as well as implications for altering surgical management and defining prognosis. In this study, we compared susceptibility-weighted imaging (SWI) to conventional techniques and correlated our findings with histopathology to determine the role of SWI in assessing morphologic features of HCC without using a contrast agent.

Methods

86 consecutive patients with suspected HCC were imaged with MRI (including T1, T2, T2*, and SWI) and subsequently CT. 59 histologically-proven HCC lesions were identified in 53 patients. Each lesion on each imaging sequence was evaluated by two radiologists, and classified with respect to lesion morphology, signal intensity relative to surrounding hepatic parenchyma, presence of a pseudocapsule, presence of venous invasion, and internal homogeneity.

Results

Histopathology confirmed pseudocapsules in 41/59 lesions. SWI was able to detect a pseudocapsule in 34/41 lesions; compared to conventional T1/T2 imaging (12/41) and T2* (27/41). Mosaic pattern was identified in 25/59 lesions by histopathology; SWI confirmed this in all 25 lesions, compared to T1/T2 imaging (13/25) or T2* (18/25). Hemorrhage was confirmed by histopathology in 43/59 lesions, and visible on SWI in 41/43 lesions, compared to T1/T2 (7/43) and T2* (38/43). Venous invasion was confirmed by histopathology in 31/59 patients; SWI demonstrated invasion in 28/31 patients, compared to T1/T2 (7/31) and T2* (24/31).

Conclusions

SWI is better at identifying certain morphologic features such as pseudocapsule and hemorrhage than conventional MRI without using a contrast agent in HCC patients.     

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

Purpose

To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.

Materials and Methods

Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.

Results

Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).

Conclusion

ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.     

Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis by Regulating Nitric Oxide and Inflammatory Cytokines

Objective

To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).

Materials and Methods

OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.

Results

Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.

Conclusion

CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.