帕瑞昔布联合股神经阻滞用于膝关节置换术后镇痛的效果评价及其对患者免疫功能的影响

目的:探讨帕瑞昔布联合股神经阻滞用于膝关节置换术后镇痛的效果及对患者免疫功能的影响。方法:选择2016年10月-2017年10月我院骨科住院部收治并行单侧膝关节置换的患者108例,按镇痛方式分为对照组和观察组各54例。对照组患者采用单纯股神经阻滞,观察组采用股神经阻滞联合帕瑞昔布。比较两组静息及活动状态下术后VAS评分、术后膝关节HSS评分、不良反应的发生情况及免疫指标的变化情况。结果:静息及活动状态下,观察组术后VAS评分均明显低于对照组(P均0.05),膝关节HSS评分显著高于对照组(P0.05)。两组术后不良反应的发生情况比较差异无统计学意义(P0.05)。手术结束时,两组CD4~+较麻醉前均显著下降(P均0.05);术后72 h,两组CD4~+、CD8~+及CD4~+/CD8~+较麻醉前均无显著差异(P均0.05)。观察组术后72 h CD4~+比对照组高(P0.05),而CD4~+/CD8~+显著低于对照组(P0.05)。结论:帕瑞昔布联合股神经阻滞对膝关节置换术后镇痛临床效果好,利于保护和改善患者免疫功能,促进膝关节功能的康复。     

A Simple Method for Measuring the Changeable Mechanical Action of Unloader Knee Braces for Osteoarthritis

Purpose

Today's orthotics should be designed to apply the external orthosis moment to the knee joint solely during the stance phase instead of the entire gait cycle. The aim of this study was to validate the reliability of a simple device for measuring forces at the leg–orthosis interface and describe the behavior of an innovating dynamic unloader knee brace built to interrupt its mechanical action during large knee flexion (swing phase of gait).

Extracellular matrix content and WNT/β-catenin levels of cartilage determine the chondrocyte response to compressive load

During osteoarthritis (OA)-development extracellular matrix (ECM) molecules are lost from cartilage, thus changing gene-expression, matrix synthesis and biomechanical competence of the tissue. Mechanical loading is important for the maintenance of articular cartilage; however, the influence of an altered ECM content on the response of chondrocytes to loading is not well understood, but may provide important insights into underlying mechanisms as well as supplying new therapies for OA. Objective here was to explore whether a changing ECM-content of engineered cartilage affects major signaling pathways and how this alters the chondrocyte response to compressive loading.Activity of canonical WNT-, BMP-, TGF-β- and p38-signaling was determined during maturation of human engineered cartilage and followed after exposure to a single dynamic compression-episode. WNT/β-catenin- and pSmad1/5/9-levels declined with increasing ECM-content of cartilage. While loading significantly suppressed proteoglycan-synthesis and ACAN-expression at low ECM-content this catabolic response then shifted to an anabolic reaction at high ECM-content. A positive correlation was observed between GAG-content and load-induced alteration of proteoglycan-synthesis. Induction of high β-catenin levels by the WNT-agonist CHIR suppressed load-induced SOX9- and GAG-stimulation in mature constructs. In contrast, the WNT-antagonist IWP-2 was capable of attenuating load-induced GAG-suppression in immature constructs.In conclusion, either ECM accumulation-associated or pharmacologically induced silencing of WNT-levels allowed for a more anabolic reaction of chondrocytes to physiological loading. This is consistent with the role of proteoglycans in sequestering WNT-ligands in the ECM, thus reducing WNT-activity and also provides a novel explanation of why low WNT-activity in cartilage protects from OA-development in mechanically overstressed cartilage.     

Peak power and pulmonary oxygen uptake during knee extension exercise – comparisons among different incremental protocols

Four incremental protocols of knee extension exercise of different stage durations were compared to study the effect of the protocol upon power output at the last stage (P _peak). Previous studies of knee extension have found very different power outputs with similar ergometers and these large differences have been interpreted as being the result of the fatigue due to the durations of the protocols. The knee extension device used in previous studies was modified to avoid the action of the knee and hip flexors: the subjects pushing on a lever instead of pulling a rod. In the present study five subjects performed four incremental knee extension exercises which differed with regard to stage duration (60, 90, 180 or 360 s) on this ergometer. The P _peak, peak oxygen uptake (V˙O_2peak) and peak heart rate (HR_peak) were measured at the end of each of these four incremental protocols. In eight subjects, the reliability of the protocols with the two shortest increments (60 and 90-s stages) was verified by measuring P _peak at 60 s and 90 s (P _peak60, P _peak90) twice. The knee ergometer proposed in the present paper was easy to use without any special training and should improve the measurement of P _peak. The P _peak60 [49.4 (SD 5.6) W] was higher than at 180 s [P _peak180, 43.6 (SD 5.8) W, P < 0.05] and at 360 s [P _peak360, 43.4 (SD 5.3) W, P < 0.05]. All the other differences in P _peak, V˙O_{2 peak} and HR_peak were not significant. All correlations between P _peak60, P _peak90, P _peak180 and P _peak360 were significant, except those between P _peak360 and P _peak90 or P _peak180. The effect of the stage duration on power output and oxygen uptake at the end of the knee extension exercises was not great. Consequently, the large differences in power output and oxygen uptake observed in previous studies cannot be explained by the protocol only. The significant difference between P _{peak 60} and P _peak90 was of the order of 10% in agreement with findings in the literature using cycle ergometry. The reliability of P _peak60 and P _peak90 was high and the use of these protocols can be recommended if further studies show that the measurement of P _peak, is useful in the evaluation of local endurance. Accepted: 2 April 1998     

Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress

Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well.     

Regional differences in prostaglandin E2 and nitric oxide production in the knee meniscus in response to dynamic compression

Injury or loss of the knee meniscus is associated with altered joint stresses that lead to progressive joint degeneration. The goal of this study was to determine if dynamic mechanical compression influences the production of inflammatory mediators by meniscal cells. Dynamic compression increased prostaglandin E2 (PGE(2)) and nitric oxide (NO) production over a range of stress magnitudes (0.0125-0.5 MPa) in a manner that depended on stress magnitude and zone of tissue origin. Inner zone explants showed greater increases in PGE(2) and NO production as compared to outer zone explants. Meniscal tissue expressed NOS2 and NOS3 protein, but not NOS1. Mechanically induced NO production was blocked by NOS inhibitors, and the non-selective NOS inhibitor L-NMMA augmented PGE(2) production in the outer zone only. These findings suggest that the meniscus may serve as an intra-articular source of pro-inflammatory mediators, and that alterations in the magnitude or distribution of joint loading could significantly influence the production of these mediators in vivo.     

Utility of peak torque and rate of torque development characteristics to identify walking performance ability in older women

Objectives:It is unclear whether peak torque and rate of torque development (RTD) measurements can characterize functional differences in older adults according to their performance on a six-minute walk test. This study aimed to examine the efficacy of isometric peak torque and RTD characteristics of the knee extensors to differentiate between functional status in older women who are able (higher functioning) versus those who are unable (lower functioning) to walk 550 m in six minutes.Methods:Ten higher functioning (67±4 years) and 10 lower functioning (68±4 years) older women performed three isometric knee extension maximal voluntary contractions followed by a six-minute walk test. Peak torque and early (RTD100), late (RTD200), and maximum (Peak RTD) RTD measurements were obtained from each contraction.Results:The higher functioning group exhibited greater peak torque, Peak RTD, RTD100, and RTD200 compared to the lower functioning group (P≤0.011), with larger differences occurring for RTD characteristics (39.9-54.9%) than peak torque (20.3%). Multiple regression analysis indicated that RTD200 was the single best predictor of the distance covered during the six-minute walk test (R²=0.437, P=0.002).Conclusions:These findings suggest that knee extensor muscle strength, and in particular RTD, may be an effective discriminator and predictor of walking performance ability in older women.     

Avenanthramide C as a novel candidate to alleviate osteoarthritic pathogenesis

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.