关节腔内注射透明质酸钠与富血小板血浆治疗膝关节骨性关节炎的比较

文题释义： 富血小板血浆：1993年HOOD等首先提出富血小板血浆的概念,人全血经过离心后获得富含血小板的血浆,在其中加入凝血酶后可变为胶状物,因此也被称为富血小板凝胶。富血小板血浆中含有大量的生长因子如血小板源性生长因子、转化生长因子β、胰岛素样生长因子1等,可促进骨再生。富血小板血浆的制备方法尚未形成统一的标准,主要有血浆分离置换法和密度梯度离心法2种方法。 透明质酸钠：是一种葡聚糖醛酸,广泛存在于胎盘、羊水、晶状体、关节软骨、皮肤真皮层等组织。它是关节腔滑液的主要成分,对关节起润滑作用,可以减少组织间的磨擦,关节腔内注入透明质酸钠的作用：明显改善滑液组织的炎症反应,增强关节液的黏稠性和润滑功能,保护关节软骨,促进关节软骨的愈合与再生,缓解疼痛,增加关节的活动度。  背景：富血小板血浆因其富含生长因子,在组织修复及再生中起促进作用,其已逐渐应用于临床治疗骨性关节炎。透明质酸钠可改善滑液组织的炎症反应,保护关节软骨,促进关节软骨的愈合与再生,缓解疼痛。 目的：对比观察富血小板血浆、透明质酸钠治疗膝关节骨性关节炎的疼痛和功能改善程度。 方法：符合标准的膝关节骨性关节炎患者被随机分配到富血小板血浆组和透明质酸钠组。富血小板血浆组患者在21 d内接受3次关节穿刺注射富血小板血浆治疗,透明质酸钠组患者在35 d内接受5次关节穿刺注射透明质酸钠治疗。注射前以及注射后2,4,6个月随访评估疼痛及功能的改善程度,所使用的评估量表包括可视量化分级量表、膝关节和骨性关节炎症状系统分级表、HSS评分量表。 结果与结论：富血小板血浆组最终有35例患者,透明质酸钠组有36例患者进入结果分析。在6个月的随访期末,两组患者的疼痛、功能症状都有所减轻。膝关节损伤和骨性关节炎症状系统分级评分表明,相对于透明质酸钠组,富血小板血浆治疗关节炎分级Ⅱ级患者更有效。最后1次治疗后,富血小板血浆治疗组患者可视量化分级量表分值相对于初始值减少50%的患者数明显多于透明质酸钠组。两组患者治疗后2,4,6个月HSS评分差异无显著性意义(P > 0.05)。结果表明,富血小板血浆治疗方法适用于骨性关节炎分级较低的患者。 ORCID: 0000-0003-4453-6221(孙仁义) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Applications and emerging trends of hyaluronic acid in tissue engineering,as a dermal filler and in osteoarthritis treatment

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine, including scaffolding for tissue engineering, dermatological fillers and viscosupplementation for osteoarthritis treatment. HA is available in most connective tissues in body fluids such as synovial fluid and the vitreous humor of the eye. HA is responsible for several structural properties of tissues as a component of extracellular matrix and is involved in cellular signaling. Degradation of HA is a stepwise process that can occur via enzymatic or non-enzymatic reactions. A reduction in HA mass or molecular weight via degradation or slowing of synthesis affects physical and chemical properties such as tissue volume, viscosity and elasticity. This review addresses the distribution, turnover and tissue-specific properties of HA. This information is used as the context for considering recent products and strategies for modifying the viscoelastic properties of HA in tissue engineering, as a dermal filler and in osteoarthritis treatment.     

透明质酸钠治疗骨性关节炎的临床与实验研究

目的 探讨透明质酸钠关节腔注射对骨性关节炎的临床疗效、安全耐受性及对血清与滑膜液中ＩＬ－１、ＩＬ＿６水平的影响。方法 取３４例有膝关节腔积液的一关节炎患者随机分成两组,分别给予关节腔注身南酸钠与非甾体药治疗,观察治疗前后关节休息痛、活动痛、压痛、肿胀与功能改善程度,并分析其安全耐受性;同时测定前后血清与 膜液中ＩＬ－１、ＩＬ－６水平变化。结果 治疗组关节各种症状均有改善,尤以活动痛与肿胀改善显著,     

富血小板血浆与透明质酸钠关节腔内注射治疗膝骨关节炎的疗效比较

目的：比较自体富血小板血浆（PRP）与透明质酸（HA）钠关节腔内注射治疗膝骨关节炎的临床效果。方法2011年10月至2013年11月,盐城市第一人民医院门诊205例（278膝）膝关节炎患者纳入了本研究,根据患者选择进行分组,186例（230膝）完成治疗及随访,HA组82例96膝、PRP组104例124膝,二组分别采用药物2 mL HA钠、3 mL自体PRP加4 mL 5％利多卡因关节腔注射,每周1次,共3次。治疗前和治疗后3、6、12个月对患者进行随访并进行安大略西部和麦克马斯特大学骨关节炎指数（WOMAC ）评分评估,对膝关节肿胀消退情况进行观察。两组间各时相点WOMAC评分比较采用t检验,组内不同时间点比较采用重复测量方差分析,组内不同时间点两两比较采用Bonferroni检验。结果 PRP 组和 HA 组患者治疗后 WOMAC 评分均得到显著改善（F＝206．430、122．984,P＜0．05）。治疗后3个月,两组间 WOMAC 评分比较差异无统计学意义（t ＝－0．046,P＞0．05）,治疗后6个月和治疗后12个月,PRP 组 WOMAC 评分[（21．43±4．92）分、（21．57±7．32）分]与HA组[（23．44±5．41）分、（29．12±8．27）分]比较,差异有统计学意义（t＝－2．519、－5．768,P＜0．05）。HA组与PRP组膝关节肿胀治疗后消退情况分别为22膝（31．4％）与41膝（56．9％）,两组比较差异有统计学意义（χ2＝9．362,P＜0．05）。结论 PRP关节腔注射治疗膝骨关节炎获得了更持久的症状缓解效果,更多患者膝关节肿胀消退。     

富血小板血浆与透明质酸治疗膝骨关节炎疗效对比的Meta分析

文题释义：透明质酸：是细胞外基质的主要成分,是一种由氨基葡萄糖组成的多糖,主要分布于关节软骨、滑液、皮肤和房水中,具有调节生物化学过程、提供支持和润滑的功效,在维持关节的正常功能方面具有重要的作用。富血小板血浆：是自体外周血经离心后得到的血制品,对于自身无免疫排斥反应,含有大量生长因子,如血小板源性生长因子、血管内皮生长因子、转化生长因子等,这些因子能够刺激软骨细胞的增殖分化,诱导血管生成,对软组织损伤修复起着积极的作用。背景：透明质酸是治疗膝骨关节炎的常用药物,富血小板血浆治疗膝骨关节炎则是近年来的研究热点,对于这两者之间的有效性和安全性的比较尚存在争议。目的：系统评价富血小板血浆与透明质酸治疗膝骨关节炎的有效性及安全性。方法：按照Cochrane系统评价的方法,应用计算机检索CNKI、维普网、万方数据知识服务平台、中国生物医学文献数据库(CBM)、PubMed、Cochrane Library、Embase等数据库,检索有关富血小板血浆与透明质酸治疗膝骨关节炎的随机对照试验,文献发表时间为建库至2020年1月。对所有符合纳入标准的文献进行质量评价,采用Revman 5.3软件对其WOMAC评分、IKDC评分、目测类比评分、Lequesne指数及不良事件进行Meta分析。结果与结论：①纳入21篇文献,共1 872例患膝,其中富血小板血浆组963例,透明质酸组909例;②Meta分析结果显示,富血小板血浆组治疗后3,6,12个月的WOMAC评分明显低于透明质酸组[MD=-5.84,95%CI(-10.11,-1.57),P=0.007;MD=-9.48,95%CI(-13.02,-5.95),P < 0.000 01;MD=-10.47,95%CI(-13.95,-7.00),P < 0.000 01],治疗后6,12个月的目测类比评分低于透明质酸组[MD=-5.02,95%CI(-8.87,-1.18),P=0.01;MD=-3.33,95%CI(-4.89,-1.76),P< 0.000 1],治疗后3,6,12个月的IKDC评分高于透明质酸组[MD=7.10,95%CI(3.88,10.32),P < 0.000 1;MD=7.88,95%CI(5.12,10.65),P < 0.000 01;MD=6.85,95%CI(2.50,11.19),P=0.002],治疗后6,12个月的Lequesne指数低于透明质酸组[MD=-0.82,95%CI(-1.31,-0.32),P=0.001;MD=-2.37,95%CI(-2.93,-1.81),P < 0.000 01];两组不良事件发生率比较差异无显著性意义[OR=1.46,95%CI(0.94,2.24),P=0.09];③结果表明相较于透明质酸,富血小板血浆治疗膝骨关节炎更能缓解疼痛、改善功能、提高患者生活质量,疗效更持久。ORCID: 0000-0003-4045-0340(王养发)中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

The effect of hyaluronic acid on silk fibroin conformation

The molecular conformation of silk fibroin drastically changes the physical properties of this biomaterial. Herein, we investigated the capacity of hyaluronic acid to modify the conformational transition of silk fibroin into its crystalline beta-sheet form. For this aim, matrices composed of these two polymers were prepared and studied. Instrumental analysis confirmed the presence of two intermixed phases: one of pure hyaluronic acid, and another consisting of a molecular dispersion of silk fibroin and hyaluronic acid. Studies performed with silk fibroin/hyaluronic acid matrices indicated that hyaluronic acid induces molecular transition of silk fibroin into a beta-sheet structure when incubated in water, and that it synergistically enhances beta-sheet formation together with methanol treatment. The enhancement of beta-sheet content observed for silk fibroin/hyaluronic acid matrices correlated with improved mechanical properties: blended matrices had higher compressive moduli and higher breaking strengths than pure silk fibroin matrices. These new properties, together with the capacity of silk fibroin/hyaluronic acid to form partially insoluble matrices without any treatment with organic solvents, make this blend composition an interesting material for biomedical applications.     

The effect of hyaluronic acid on brushite cement cohesion

The improvement of calcium phosphate cement (CPC) cohesion is essential for its application in highly blood perfused regions. This study reports the effectiveness of hyaluronic acids of different molecular weights in the enhancement of brushite cement cohesion. The cement was prepared using a powder phase composed of a mixture of β-tricalcium phosphate and monocalcium phosphate monohydrate, whereas the liquid phase was formed by 0.5 M citric acid solution modified by the addition of hyaluronic acid of different molecular weights. It was found that medium and high molecular weight hyaluronic acid enhances the cement cohesion and scarcely affects the cement mechanical properties. However, concentrations >0.5% (w/v) were less efficient to prevent the cement disintegration. It is concluded that hyaluronic acid could be applied efficiently to reduce brushite cement disintegration.     

中医疗法与透明质酸治疗膝骨性关节炎有效性的网状Meta分析

BACKGROUND: Comparative study results between the efficacies of traditional Chinese medicine (TCM) therapy with Western medicine therapy in the treatment of knee osteoarthritis remain controversial. Currently, meta-analysis studies mainly focus on comparison of the efficacy between TCM and Western medicine, but lack investigations among TCM therapies. It makes us difficult to fully understand the efficacy of TCM therapy for knee osteoarthritis. OBJECTIVE: To compare the efficacies of TCM therapy with intra-articular injection of hyaluronic acid for knee osteoarthritis using a network Meta-analysis method. METHODS:PubMed, The Cochrane Library (tissue 10, 2015), EMbase, CNKI, CBM, VIP, Wangfang databases were searched up to October 20, 2015 for relevant randomized controlled trials addressing the efficacies of TCM therapy versus intra-articular injection of hyaluronic acid for knee osteoarthritis. Two reviewers independently selected the studies, extracted information, and assessed the quality of included trials. Data extraction from eligible studies was pooled and meta-analyzed using Stata12.0 and WinBUGS1.4.3 softwares. Odd ratios with their 95% confidence interval were estimated as effect size between treatments. RESULTS AND CONCLUSION: A total of 59 randomized controlled trials involving 6 155 patients with knee osteoarthritis and 12 treatment strategies were included. The results of network meta-analysis showed that TCM comprehensive therapy was superior to the TCM monotherapy and intra-articular injection of hyaluronic acid. Among these therapies, the efficacy of needle scalpel combined with acupuncture is optimal. TCM comprehensive therapies may be the best choice to treat patients with knee osteoarthritis of Kellgren-Lawrence II-III. More large-scale and well-designed randomized controlled trials are still warranted due to the limitation of the present study. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes

Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in clinical practice in the treatment of osteoarthritis. There have been no reports regarding cross-talk between HA and COX-2 inhibitors in articular human chondrocytes. The purpose of this study was to investigate whether HA, COX-2 inhibitors or a combination of COX-2 inhibitors and HA have different effects in human articular between lower and highly degenerated chondrocytes. Isolated lower and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or no additive. After incubating for 48 h, mitochondrial membrane potential analysis and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK) were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA resulted in dendritic, proliferating chondrocytes with strong red fluorescence enriched in the mitochondrial membrane, and indicated reduction of apoptosis in chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA inhibited the activation of p38 in highly degenerated chondrocytes. A combination of COX-2 inhibitors and HA decreased NO production in highly degenerated chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had no effect on PGE2 production. The present study demonstrated that COX-2 inhibitors and HA interacted synergistically the MAPK pathway and inhibition of NO production in highly degenerated chondrocytes. Administration of COX-2 inhibitors plus HA could be used as a new alternative way of treating osteoarthritis.     

The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel

Degradation of proteoglycan is the key early event in the development of osteoarthritis (OA). The aggrecanase ADAMTS-5 has been identified as the major enzyme responsible for the degradation and thus is an attractive therapeutic target for OA. However, currently there is no report on using an ADAMTS-5 inhibition strategy for OA treatment. The present study aimed to investigate the synergic effect of combining an ADAMTS-5 inhibitor (114810) with a hyaluronic acid hydrogel (HAX) for OA therapeutics. Two OA models were induced by surgically creating an osteochondral defect or removing the anterior cruciate ligament (ACL) in Sprague–Dawley rats. Human OA cartilage was obtained from total joint replacement patients. Both human and rat OA cartilage showed marked proteoglycan loss with significantly increased ADAMTS-5 expression. The effectiveness of ADAMTS-5 inhibition by 114810 was confirmed by a cartilage explants assay in vitro, which showed that the 114810 halted the aggrecanase-mediated ³⁷⁴ARGS neoepitope released from aggrecan induced by IL-1β stimulation. The in vivo effect of ADAMTS-5 inhibition was assessed by the articular injection of HAX with 114810 into OA knee joints. Evaluated eight weeks after injection, 114810 with HAX significantly promoted the in vivo cartilage healing in the osteochondral defect model, and prevented the progression of degenerative changes in the ACL model. Our results confirmed that ADAMTS-5 is an effective target for OA treatment, and the intra-articular injection of an ADAMTS-5 inhibitor within HAX gel could be a promising strategy for OA treatment.     

Improved synthesis of hyaluronic acid hydrogel and its effect on tissue augmentation

HA-HMDA hydrogels were developed by direct amide bond formation between the carboxyl groups of hyaluronic acid (HA) and hexamethylenediamine (HMDA) with an optimized carboxyl group modification in the preliminary experiment. However, these HA-HMDA hydrogels transformed into an unstable liquid form after steam sterilization, and were problematic for application to actual dermal filler. A new method to overcome the problem of the previously developed HA-HMDA hydrogels is to prepare them by adjusting the pH in this study. Not only are these improved HA-HMDA hydrogels prepared with lower amounts of cross-linking and activation agents compared to the previously developed hydrogels, but they also maintain a stable form after steam sterilization. These improved HA-HMDA hydrogels showed higher viscoelasticity and longer lasting effects than the previous ones, despite the fact that the amount of the HMDA used as a cross-linking agent as well as 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrated (HOBt) used as activation agents were substantially reduced. According to an in?vivo test using a wrinkled mouse model, the improved HA-HMDA hydrogels exhibited significantly improved tissue augmentation effects compared to a positive control of Restylane, which is widely used for the tissue augmentation throughout the world. Furthermore, histological analysis revealed excellent biocompatibility and safety of the improved synthesized HA-HMDA hydrogels.     

牛磺酸联合安定治疗脑缺血再灌注损伤的实验研究

目的:研究牛磺酸联合安定对实验性脑缺血再灌注损伤大鼠的神经保护作用。方法:SD雄性大鼠随机分为假手术组、脑缺血再灌注损伤组、牛磺酸治疗组(200mg·kg-1)、安定治疗组(10mg·kg-1)、联合治疗组(牛磺酸100mg·kg-1+安定5mg·kg-1),每组12只。采用大脑中动脉栓塞法(MCAO)建立大鼠局灶性脑缺血模型,2h后拔出栓线形成再灌注,再灌注时各组分别给药,脑缺血再灌注损伤组注射等剂量的生理盐水,12h后各组重复注射1次。另分批实验同样5组动物,每组16只,分别于再灌注后10h给药,12h后重复治疗1次。各组中12只动物同先前5组于再灌注后48h观测神经行为学评分、脑梗死体积以及脑含水量测定。每组中余下4只大鼠,2周后行尼氏染色观察脑组织病理学改变。结果:与脑缺血再灌注损伤组相比,缺血后2h、12h联合治疗均能显著降低大鼠神经行为学评分、减少脑含水量、缩小脑梗死体积,同时能明显减轻海马神经元变性坏死(P0.01或P0.05),且其保护作用优于牛磺酸或安定单用组。结论:缺血性脑损害所致急、慢性损伤时牛磺酸联合安定具有明显的神经保护作用。     

Hyaluronic acid hydrogel in the treatment of osteoarthritis

In order to overcome the problem of rapid clearance of the polysaccharide hyaluronic acid (Hyal) in the treatment of osteoarthritis (OA), a 50% cross-linked Hyal hydrogel (Hyal 50%) was synthesised. The 50% refers to the amount of COOH groups of the polysaccharide involved in the cross-linking reaction. i.e. 50% of the total amount. The rheological behaviour of the Hyal 50% hydrogel, and in particular the possibility to inject it through a needle, was studied. The results obtained demonstrated that the hydrogel injected through the needle still behaved like a gel, although it showed a reduction of the dynamic moduli. The most appropriate sterilisation technique for this kind of hydrogel was also evaluated. Liophilised Hyal 50% samples were sterilised by steam, Ethylene Oxide (EtO) and gamma-rays. EtO and gamma-rays did not modify the characteristics of the hydrogel in terms of swellability and morphology. Lastly, the in vivo effect of Hyal 50% hydrogel in the treatment of chondral defect in rabbit knee was also studied. The results obtained showed the Hyal 50% injections improved chondrocytes density and matrix appearance. Furthermore, the permanence in situ of the hydrogel was longer than that of the linear Hyal.     

The synergistic effect of lactic acid bacteria and alkylglycerols on humoral immunity in mice

Investigations on immune suppression and reconstitution of immune functions dependent on the presence of physiological microflora allow us to conclude that symbiotic microorganisms such as Lactobacillus sp. are essential for adequate activity of the defense system in humans. In addition to their beneficial influence on the intestinal microbial balance, these microorganisms exert a variety of immunomodulatory effects on the host immune system. On the other hand, immunostimulatory animal-derived substances rich in alkylglycerols have been shown to enhance lactic acid bacteria proliferation. Therefore, the aim of the present study was to evaluate the effects on murine humoral response of the combined administration of lyophilized combination of three lactic acid bacteria: L. acidophilus, L. bulgaricus and Bifidobacterium bifidum together with alkylglycerol-rich shark liver oil. The lactic acid bacteria mixture induced markedly stronger enhancement of the humoral response than alkylglycerols did. A significant synergistic stimulatory effect of lactic acid bacteria and alkylglycerols was observed in both treatment schedules: post- as well as in preimmunization with sheep red blood cells. However, their concomitant administration exerted stronger immunomodulatory effect than did the alternative route of treatment.     

The effect of hyaluronic acid and phospholipid based lubricants on friction within a human cartilage damage model

The lubricating abilities of different formulations of high molecular weight hyaluronic acid (HA), dipalmitoyl phosphatidylcholine (DPCC) and mixtures of both HA and DPCC were assessed in an in vitro model. Levels of start-up friction were determined using an osteoarthritis (OA) damaged human cartilage model set within a specially designed friction rig. To examine the long term benefits of HA, the extent of penetration of HA into cartilage tissue was investigated using fluorescently labelled HA and confocal microscopy. It was found that in this model, all formulations of HA and the majority of DPCC lubricants reduced friction (HA 5 and 10 mg ml(-1), DPPC 200 mg ml(-1) reductions of 51.9%, 46.7% and 46.5% respectively), compared to a Ringers solution control. Lubrication was found not to be concentration dependent for HA formulations, but concentration was key for DPCC lubrication (100 mg ml(-1) reduced friction by only 15.9%). By combining HA and DPCC (HA/DPPC; 5 mg ml(-1)/100 mg ml(-1) and 10 mg ml(-1)/200 mg ml(-1)), a further improvement was noted (69.5% and 61.9%, respectively) as the mean levels of friction were reduced by up to a further 17% than the most effective individual formulation (HA 5 mg ml(-1)). Penetration of HA into bovine cartilage by up to 300 microm from the surface was observed over a 48 h period. It was observed that HA specifically targeted the chondrocytes as it was primarily found within the lacunae surrounding the cells.     

透明质酸影响人膝骨关节炎滑膜成纤维样细胞骨桥蛋白和CD44的表达

背景：在骨关节炎病程中,透明质酸水平的改变可以使一系列细胞因子和酶表达水平改变,但是滑膜组织中骨桥蛋白、CD44的高表达是否与透明质酸水平改变相关目前尚不清楚。 目的：通过透明质酸干预体外培养的人膝骨关节炎滑膜成纤维样细胞,观察透明质酸对骨关节炎滑膜成纤维样细胞骨桥蛋白和CD44表达的影响。 方法：选取接受膝关节镜手术和膝关节置换的原发性膝关节骨关节炎患者滑膜标本10例,进行体外培养获取纯化的滑膜成纤维细胞,取第4~6代滑膜成纤维细胞,分为3组：空白对照组不进行任何干预;透明质酸组用100 mg/L透明质酸干预24 h;透明质酸酶组用300 mg/L透明质酸酶干预24 h。 结果与结论：与空白对照组相比,透明质酸组滑膜成纤维细胞骨桥蛋白mRNA表达水平上升(P < 0.05),透明质酸酶组滑膜成纤维细胞骨桥蛋白mRNA表达水平下降(P < 0.05)。透明质酸组和透明质酸酶组之间膜成纤维细胞骨桥蛋白mRNA表达水平差异有显著性意义(P < 0.05)。空白对照组、透明质酸组和透明质酸酶组滑膜成纤维细胞CD44 mRNA表达水平差异均无显著性意义(P > 0.05)。提示透明质酸可以使骨关节炎滑膜成纤维细胞骨桥蛋白mRNA表达增高,对CD44 mRNA表达没有影响。     

N-acetylated-alpha-linked-acidic dipeptidase inhibitor has a neuroprotective effect on mouse retinal ganglion cells after pressure-induced ischemia

Excessive glutamate receptor activation is thought to be involved in the retinal ganglion cell (RGC) death after ischemic injury. In this study, we examined the effect of 2-PMPA (2-(phosphonomethyl)pentanedioic acid) on RGC survival in an ischemia-reperfusion model using C57BL/6 mouse eyes. 2-PMPA is a NAALADase (N-acetylated-alpha-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. 100mg/kg 2-PMPA were given with intraperitoneal injections 30 min before ischemia followed per hour injection for 3h. 2-PMPA increased surviving RGCs as well as retinal thickness after pressure-induced retinal ischemia. In addition, neuroprotection afforded by 2-PMPA was greater than that of N-methyl-D-aspartate receptor blocker. These data indicate that NAALADase inhibition may be useful in retinal disorders in which excessive amino acid transmission is pathogenic.     

Combination of a dual 5-lipoxygenase/cyclooxygenase inhibitor with a glucocorticoid results in synergistic topical antiinflammatory activity without inducing skin atrophy

Synthetic glucocorticosteroids are widely used in clinical dermatology in the treatment of a number of inflammatory skin disorders. However, cutaneous side effects such as induction of skin atrophy are among the factors that limit the chronic use of this class of agents. We have found that a combination of a dual 5-lipoxygenase/cyclooxygenase inhibitor (9-phenylnonanohydroxamic acid, BMY 30094) and a glucocorticosteroid (hydrocortisone valerate) has synergistic antiinflammatory activity. Topical application of a 0.2% solution of hydrocortisone valerate alone inhibited phorbol ester-induced mouse skin inflammation by 92%. A 1% solution of BMY 30094 alone or a low dose of hydrocortisone valerate (0.005%) had no significant effect on the inflammatory reaction. A combination of 1% BMY 30094 and 0.005% hydrocortisone valerate inhibited the inflammation by 76%. This latter combination produced no signs of skin atrophy in rats after 28 days of application. In contrast, a 0.1% dose of hydrocortisone valerate produced significant skin atrophy. These findings suggest that it is possible to reduce the skin atrophy potential of glucocorticoids while maintaining the antiinflammatory activity using a novel drug combination.     

Synthesis and characterization of a novel hyaluronic acid hydrogel

Hyaluronic acid (hyaluronan, HA) has many medical applications as a biomaterial. To enhance its biostability, a novel hydrogel of cross-linked hyaluronic acid was prepared using a double cross-linking process, which involves building cross-linkages between hydroxyl group pairs and carboxyl group pairs. The present study explored a number of cross-linking processes in order to obtain different degrees of cross-linking, which were evaluated by the measurement of water absorption capacity as an index of the gel network density. To gain a better understanding of the stability of the gel, the chemical structure and particularly the rheological behaviour of the cross-linked HA, which included the influences of factors, such as degree of cross-linking, HA concentration and gel particle size, were investigated. The in vitro biostability against hyaluronidase and free radical degradation was tested to show that the cross-linked hydrogel had improved resistance to in vitro hyaluronidase and free radical degradation.