Relationship of plasma and synovial fluid BMP-7 with disease severity in knee osteoarthritis patients: a pilot study

The objective of this study was to investigate bone morphogenetic protein-7 (BMP-7) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to disease severity. Thirty-two patients with knee OA and 15 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. BMP-7 levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The mean plasma BMP-7 concentration of the knee OA patients was significantly higher compared with that of healthy controls (12.1 ± 1.6 vs 3.5 ± 0.9 pg/ml, P = 0.001). Although BMP-7 levels in plasma were higher with respect to paired synovial fluid samples, the difference was not statistically significant (12.1 ± 1.6 vs 10.5 ± 2.2 pg/ml, P = 0.3). Subsequent analysis showed that plasma BMP-7 levels significantly correlated with disease severity (r = 0.77, P < 0.001). Furthermore, the synovial fluid levels of BMP-7 also correlated with disease severity (r = 0.60, P < 0.001). In addition, plasma BMP-7 levels showed a positive correlation with synovial fluid BMP-7 levels (r = 0.71, P < 0.001). Overexpression of BMP-7 in plasma and synovial fluid is related to progressive joint damage in knee OA. These findings suggest that BMP-7 might serve as a biochemical parameter for determining disease severity in primary knee OA and could play a potential role in cartilage protection and repair of OA.     

Effect of combined laser acupuncture on knee osteoarthritis: a pilot study

Our objective was to assess the efficacy and safety of combined 10.6 μm and 650 nm laser irradiation on patients with knee osteoarthritis (OA). Forty patients with OA were randomly allocated to an active laser group or to a placebo laser group (20 per group). They either received active or sham laser treatment at acupoint Dubi (ST 35) in a total of 12 sessions. There was significant difference between the two groups in the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score change from baseline after 2 weeks of treatment (P = 0.047). The pain reduction of the active laser treatment group was 49%, whereas that of the placebo control group was only 13%. However, due to the high patient drop-out rate, the 4-week assessment could not be analyzed. Combined laser treatment seems beneficial to patients with knee OA. However, due to the small sample size and the high drop-out rate of patients in the placebo group, a large sample-size clinical trial is warranted to determine further the therapeutic efficacy of the device.     

Effect of carbon dioxide pneumoperitoneum on the severity of acute pancreatitis: An experimental study in rats

Background In the management of mild acute biliary pancreatitis, it is generally recommended to perform laparoscopic cholecystectomy after the subsidence of the attack during the same hospital admission. The effect of laparoscopy on abdominal organs has been widely investigated but not in acute pancreatitis. This study used an animal model of mild acute pancreatitis to examine the effects of CO₂ pneumoperitoneum on acute pancreatitis in rats.Methods Mild acute pancreatitis was induced in 30 male Sprague-Dawley rats by surgical ligation of the biliopancreatic duct. After 2 days, animals were assigned to three groups: sham operation (animals were anesthetized for 30 min without undergoing laparotomy), CO₂ pneumoperitoneum (applied for 30 min at a pressure of 12 mmHg), and laparotomy (performed for 30 min, and then the abdomen was closed). Two hours after the surgical procedures, animals were killed and levels of lactate dehydrogenase, aspartate aminotransferase, glucose, urea, hematocrit, and leukocyte count among Ransons criteria and levels of amylase, lipase, and total bilirubin were measured to determine the severity of acute pancreatitis. Histopathologic examination of the pancreas was done, and malondialdehyde and glutathione levels of the pancreas and lung were determined.Results The only significant differences between the groups were in lactate dehydrogenase and aspartate aminotransferase levels, which were significantly higher in the pneumoperitoneum group compared to the sham operation group.Conclusion CO₂ pneumoperitoneum for 30 min at a pressure of 12 mmHg did not affect the severity of acute pancreatitis induced by ligation of the biliopancreatic duct in rats.Paper presented as an abstract at the 12th World Congress of the International Association of Surgeons and Gastroenterologists, Istanbul, 2002     

Changes in the integrins expression are related with the osteoarthritis severity in an experimental animal model in rats

We identify changes in the expression and localization of α5, α4, and α2 integrins during osteoarthritis (OA) pathogenesis in a rat experimental model. The changes were concomitant with variations in the extracellular matrix (ECM) content and the increase of metalloproteinases (MMPs) activity during OA pathogenesis, which were analyzed by immunofluorescence and Western blot assays. Our results showed an increased expression of α5 and α2 integrins at OA late stages, which was co‐related with changes in the ECM content, as a consequence of the MMPs activity. In addition, this is the first report that has shown the presence of α4 integrin since OA early stages, which was co‐related with the loss of proteoglycans and clusters formation. However, at late OA stages, the increased expression of α4 integrin in the middle and deep zones of the cartilage was also co‐related with the abnormal endochondral ossification of the cartilage through its interaction with osteopontin. Finally, we conclude that ECM‐chondrocytes interaction through specific cell receptors is essential to maintain the cartilage homeostasis. However, due to integrins cell signaling is ligand‐dependent; changes in the ECM contents could induce activation of either anabolic or catabolic processes, which limits the reparative capacity of chondrocytes, favoring OA severity. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1161–1166, 2014.     

Dose-response study of nebulised nedocromil sodium in exercise induced asthma.

Ten patients with exercise induced asthma, in whom inhaled nedocromil sodium 4 mg by metered dose inhaler attenuated the exercise fall in forced expiratory volume in one second (FEV1) by at least 40%, participated in a double blind dose response study to compare the protective effect of nedocromil sodium given 15 minutes before exercise challenge via a nebuliser (Wright) in concentrations of 0.5, 5, 10, and 20 mg/ml with that of placebo (saline). Response was assessed as the maximum fall in FEV1 after the patient had run on a treadmill for six to eight minutes. Plasma concentrations of nedocromil sodium were measured at the time of challenge. After exercise challenge the mean (SEM) maximum percentage falls in FEV1 were 30.3 (1.6) for the control run and 28.0 (4.1) after placebo. The percentage fall was attenuated by pretreatment with all concentrations of nedocromil sodium to 12.8 (2.8), 11.2 (2.1), 12.8 (2.1), and 14.1 (3.5) for the 0.5, 5, 10, and 20 mg/ml concentrations respectively (p less than 0.001). There were no significant differences between the different nedocromil concentrations. Mean plasma concentrations of nedocromil were proportional to dose. Thus concentrations of nebulised nedocromil sodium that ranged from 0.5 to 20 mg/ml gave a similar degree of protection (50-60%) against exercise induced asthma. This appears to be the maximum protection that can be achieved with nedocromil sodium and is similar to the protection obtained with 4 mg nedocromil administered by metered dose aerosol.     

Dose-response relationship of mannitol and intracranial pressure: a metaanalysis

OBJECTIVE: Brain edema can increase intracranial pressure (ICP), potentially leading to ischemia, herniation, and death. Edema and elevated ICP are often treated with osmotic agents to remove water from brain tissue. Mannitol is the osmotic diuretic most commonly used in the intensive care unit; however, despite its clinical importance, treatment protocols vary from center to center, and the dose-response relationship is not understood. The goal of this metaanalysis was to aggregate and analyze data from studies in which authors have described the dose-response relationship between mannitol and ICP. METHODS: The authors identified 18 studies that quantitatively characterized the dose-response relationship of mannitol and ICP. We also examined study designs and mannitol administration protocols. RESULTS: Meta-regression found a weak linear relationship between change in ICP (delta ICP) and dose (delta ICP = 6.6 x dose - 1.1; p = 0.27, R(2) = 0.05). The lack of statistical significance could reflect the variation in protocols among studies and the variation in patients both within and among studies. However, the authors found a highly significant difference (p < 0.001) in decrease in ICP when the initial ICP was higher or lower than 30 mm Hg. Nonlinear regression suggested that ICP decrease is greatest shortly after mannitol is given (R(2) = 0.63). Finally, the authors found that recent studies tend to include fewer patients and set a lower ICP threshold for mannitol administration but report more parameters of interest; the duration of mannitol's effect was the most frequently unreported parameter. CONCLUSIONS: Despite its clinical importance, the determination of the mannitol dose-response curve continues to be challenging for many reasons. This metaanalysis highlights the need for a consensus of methods and results required to determine this important relationship.     

Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study

BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) impairs cardiovascular autonomic responses to exercise and, depending on the level of injury, may result in hypotension and pathologic fatigue with exertion. Other clinical populations with sympathetic regulatory dysfunction, but without skeletal muscle paralysis, exhibit similar signs and symptoms. Their ability to engage in physical activity improves with elevation of blood pressure through pharmacologic treatment: Midodrine, an oral alpha-sympathomimetic agent, has been shown to be safe and efficacious for this purpose. Use of this medication in individuals with SCI merits investigation. METHODS: Double-blind, placebo-controlled, randomized, crossover, within-subjects protocol. Four participants with chronic, motor-complete injuries from C6 to C8 underwent 4 peak exercise tests (PXT) using a wheelchair ergometer, following administration of midodrine, 5 mg, 10 mg, and placebo, in random order. Heart rate, blood pressure, oxygen consumption (VO2), and perceived exertion were measured. RESULTS: Treatment with midodrine, 10 mg, was associated with elevated systolic blood pressure during peak exercise in 3 participants. Two participants showed a concurrent decrease in perceived exertion and increase in VO2. No adverse effects of midodrine were evident. CONCLUSION: Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction.     

Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study

Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end‐stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra‐articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T_1ρ and T₂) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX‐I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro‐computed tomography (micro‐CT) and histology. KGN treatment significantly lowered the T_1ρ and T₂ relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX‐I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post‐traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780–1789, 2016.     

Urate and osteoarthritis: Evidence for a reciprocal relationship

Hyperuricemia is a common condition, and in a subset of patients leads to gout, the most common inflammatory arthritis. Osteoarthritis is the most common form of arthritis overall, and gout and osteoarthritis frequently coexist in the same patient. However, the relationship between the two remains poorly defined. More particularly, the impact of osteoarthritis on the development of gout, and the impact of gout on the development of osteoarthritis, remain to be determined. Additionally, whether hyperuricemia mediates osteoarthritis in the absence of gout is uncertain. Here, we review the evidence linking gout and osteoarthritis, with a special focus on the role of hyperuricemia in the presence or absence of gout. Since disease modifying agents are currently available for hyperuricemia and gout but not for osteoarthritis, a contributory role for urate in the pathogenesis of osteoarthritis could have important clinical implications.     

Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study

OBJECTIVE: This preliminary study sought to determine whether using 1500/1200mg of glucosamine hydrochloride and chondroitin sulfate (GH/CS) is effective, both separately and combined with exercise, compared to a placebo plus exercise program in improving physical function, pain, strength, balance, and mobility in older adults with knee osteoarthritis (OA). METHODS: This double-blind, placebo-controlled, randomized clinical trial lasted 12 months. Participants included 89 older adults (age>/=50 years) with knee OA randomized to either GH/CS or placebo group. Phase I was a 6-month trial comparing the effects of assignment to either GH/CS or placebo. Phase II added 6 months of exercise for both groups. The primary outcome measure was Western Ontario and McMaster University Osteoarthritis Index (WOMAC) function, and secondary outcome measures included WOMAC pain, 6-min walk, balance, and knee strength. RESULTS: Of the 89 randomized participants, 72 (81%) completed the study. The median pill compliance was 94% and 95% in Phase I, and, in Phase II, 97% and 91% for the GH/CS and placebo groups, respectively. Median exercise compliance during Phase II was 77% for the GH/CS group and 78% for the placebo group. WOMAC function and pain did not differ significantly between the groups at 6- or 12-month follow-up. There were also no significant differences between the groups in 6-min walk or knee strength; however, balance was better in the placebo group with approximately a 10% difference compared to the GH/CS group. CONCLUSIONS: The GH/CS group was not superior to the placebo group in function, pain, or mobility after both phases of the intervention (pill only and pill plus exercise).     

社区医疗中运动疗法治疗膝骨关节炎的疗效分析

目的评价运动疗法治疗膝骨关节炎患者的疗效。 方法北京市东城区第一人民医院从2019年1月至10月纳入76例膝骨关节炎患者(114膝),进行为期6周的运动疗法,训练地点为社区居委会或社区养老驿站。该研究纳入标准为确诊为膝关节骨关节炎且可配合完成6周运动疗法课程的患者;排除标准为膝关节屈伸肌肌力2级及以下或存在炎症性膝关节炎或重要脏器功能衰竭者。分别于治疗开始前、6周和12周后对患者进行疗效评定,评定内容包括膝关节主动活动度(AROM)、40 m步行试验、30 s椅子坐起试验;并利用量表对膝关节功能(HSS)、欧洲5维健康量表(EQ-5D)评分、疼痛视觉模拟评分(VAS)进行评价,使用单因素重复测量方差分析比较基线与6周、12周随访的结果变化,组间比较则采用Bonferroni检验。此外在治疗结束时询问患者对治疗课程的满意度,并使用秩和检验进行统计学分析。 结果在76例患者中,71例患者(109膝)完成了12周随访。109膝不同时点膝关节AROM(F＝137.55,P<0.001)、HSS评分(F＝108.81,P<0.001)及VAS评分(F＝179.72,P<0.001)治疗后均比治疗前有改善;71例患者不同时点的EQ-5D生活质量评分(F＝99.53,P<0.001)、40 m步行试验(F＝199.54,P<0.001)、30 s椅子坐起试验(F＝170.62,P<0.001)治疗后均比治疗前有改善,差异有统计学意义。患者总体满意率达100%,K/L分级为Ⅰ、Ⅱ级患者与Ⅲ、Ⅳ级患者相比,对该项目的满意度更高(U＝401.5,P＝0.044)。 结论运动疗法可缓解膝关节疼痛,改善膝关节功能,提高患者的生活质量,且在社区训练中取得良好效果,利于在社区的推广普及。     

Efficacy of exercise for end-stage renal disease patients immediately following high-efficiency hemodialysis: a pilot study

Nine patients receiving maintenance high-efficiency hemodialysis were studied before and after a 12-week conditioning program to determine the efficacy of exercise immediately following hemodialysis. Each patient performed a combination of bicycle ergometry on the Schwinn Air-Dyne ergometer (SAE) and treadmill walking three times a week for a total exercise time of 15-35 min per session. A low-level Bruce treadmill test and an exercise test on the SAE were administered before and after training. Hematological, serum electrolyte, and serum lipid profiles were also determined before and after training. Following training, there were improvements in exercise capacities for both treadmill walking and ergometry on the SAE. Although a significant increase in serum apolipoprotein A1 was seen following exercise, no significant changes were observed for total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol or apolipoprotein B. Additionally, no significant changes were seen in hematological parameters and serum electrolyte profiles following the exercise program. The 9 patients demonstrated an average compliance record of 74%. This study demonstrated that patients on high-efficiency hemodialysis can safely engage in an exercise program immediately following dialysis at intensities and frequencies that can improve their physical work capacities.     

Acupuncture for pain and osteoarthritis of the knee: a pilot study for an open parallel-arm randomised controlled trial

Background  

There is some evidence that acupuncture for pain and osteoarthritis (OA) of the knee is more than a placebo, and short term clinical benefits have been observed when acupuncture is compared to usual care. However there is insufficient evidence on whether clinical benefits of acupuncture are sustained over the longer term. In this study our key objectives are to inform the design parameters for a fully powered pragmatic randomised controlled trial. These objectives include establishing potential recruitment rates, appropriate validated outcome measures, attendance levels for acupuncture treatment, loss to follow up and the sample size for a full scale trial.     

Effects of acute resistance exercise on acyl-ghrelin and obestatin levels in hemodialysis patients: a pilot study

Abstract

Chronic physical exercises may be beneficial to modulate appetite hormones as acyl-ghrelin (orexigenic) and obestatin (anorexigenic) in chronic kidney disease (CKD) patients; however, there are no data about the effects of acute exercises on these hormones. Thus, the aim of the present study was to assess the effect of acute resistance exercise on appetite hormones (acyl-ghrelin and obestatin) of patients undergoing hemodialysis (HD). Twenty-five patients (44.7?±?12.9 years, 68% women) on regular HD program were enrolled into two groups, 16 patients performed exercises and 9 patients comprised the control group. The patients performed the exercises in both lower limbs with ankle-cuffs and elastic bands, 30?min after the initiation of hemodialysis session. Blood samples of both the groups were drawn in the morning before and after 30?min with exercise session (exercise group) and, before and after the same time without exercise (control group). Acyl-ghrelin and obestatin plasma levels were measured using an enzyme immunometric assay. Acyl-ghrelin plasma levels did not change in both the groups. However, when stratified by gender the acyl-ghrelin increased significantly right after exercise in men [32.1?pg/mL (25.6–41.2) to 46.0?pg/mL (39.0–59.5)] (p?=?0.04). Obestatin plasma levels reduced after a single bout of exercise and changes remained significantly when the sample was stratified by gender. There was no change in obestatin plasma levels in control group. A single bout of resistance exercise seems to modulate the levels of appetite hormones in HD patients.     

当归阿魏酸钠局部用药治疗骨关节炎的实验研究

[目的]探讨当归、阿魏酸钠关节腔注射对大鼠骨关节炎(OA)的疗效.[方法]40只大鼠木瓜蛋白酶法建立双膝OA模型,造模后分为模型对照组,25%及5%当归治疗组,0.5%及0.1%阿魏酸钠治疗组,另取8只大鼠作正常对照;各组关节腔注射相应浓度药物或生理盐水0.1 ml,3日一次;6周后检测血浆、关节液SOD、MDA,关节软骨取材光镜观察,检测软骨MMP-1、TIMP-1、Bcl-2、Bax的表达.[结果]25%当归和0.5%阿魏酸钠可增加血浆、关节液SOD活性(均P＜0.05)并降低其MDA水平(均P＜0.01);降低关节软骨Mankin's评分(均P＜0.01),降低软骨细胞MMP-1、Bax的表达(P＜0.05或P＜0.01),同时使TIMP-1、Bcl-2的表达增加(P＜0.05或P＜0.01);5%当归无显著效果,0.1%阿魏酸钠对部分检测指标有统计意义.[结论]当归、阿魏酸钠关节腔注射治疗大鼠OA均有疗效,其作用具有剂量依赖性,阿魏酸是当归注射液治疗OA的有效单体成分.