Control of the intracellular levels of prostaglandin E2 through inhibition of the 15-hydroxyprostaglandin dehydrogenase for wound healing

Excessive scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Much experimental data suggests that prostaglandin E₂ (PGE₂) plays a role in the prevention of excessive scarring. However, it has a very short half-live in blood, its oxidization to 15-ketoprostaglandins is catalyzed by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, we reported that 15-PGDH inhibitors significantly increased PGE₂ levels in A549 cells. In our continuing attempts to develop highly potent 15-PGDH inhibitors, we newly synthesized various thiazolidine-2,4-dione derivatives. Compound 27, 28, 29, and 30 demonstrated IC₅₀ values of 0.048, 0.020, 0.038 and 0.048 μM, respectively. They also increased levels of PGE₂ in A549 cells. Especially, compound 28 significantly increased level of PGE₂ at 260 pg/mL, which was approximately fivefold higher than that of control. Scratch wounds were analyzed in confluent monolayers of HaCaT cells. Cells exposed to compound 28 showed significantly improved wound healing with respect to control.     

Passive myocardial mechanical properties: meaning,measurement, models

Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.     

血府逐瘀汤与赛庚啶治疗瘢痕成熟期瘙痒的比较研究

目的：比较血府逐瘀汤与赛庚啶治疗瘢痕成熟期瘙痒的效果。方法：将患者随机分为治疗组和对照组,治疗组口服血府逐瘀汤治疗瘢痕瘙痒,对照组口服赛庚啶,比较两组患者服药后的瘙痒评分及P物质浓度。结果：治疗组服药后的瘙痒评分及P物质浓度均低于对照组,差异有统计学意义（P〈0．05）.结论：血府逐瘀汤治疗瘢痕成熟期瘙痒的效果优于赛庚啶。     

剖宫产疤痕妊娠30例临床分析

摘要目的：探讨子宫剖宫产疤痕妊娠（CSP）的诊断和最佳治疗方法,为后续的临床研究工作提供理论依据和临床资料。方法：回顾性分析我院2010年2月．2012年2月收治的30例CSP患者的临床资料。结果：30例患者中,有25例行双侧子宫动脉栓塞（UAE）＋MTX灌注术后,再行清宫术,手术均获得成功,术后无任何并发症出现;另外5例患者因误诊为宫内妊娠后行人工流产术时发生大出血转至我院进行抢救,其中,4例成功实施了子宫动脉栓塞术,达到了止血目的,1例因子宫破裂直接行全子宫切除术。结论：对子宫剖宫产疤痕妊娠（CSP）患者实施双侧子宫动脉栓塞术＋MTX灌注术后,借助B超监测,再行刮宫术,是治疗剖宫产切口妊娠的有效方法。     

疤痕组织中FGF变化的免疫组织化学观察

为探讨疤痕形成机理,我们对疤痕的不同部位分别行组织学和免疫组织化学观察,了解成纤维细胞生长因子（ＦＧＦ）在疤痕组织的分布特点。结果发现：同一部位的疤痕,其增生明显处的真皮内ＦＧＦ表达明显;疤痕边缘或萎缩部位的真皮内ＦＧＦ表达中等;正常真皮内ＦＧＦ阴性表达;ＦＧＦ阳性细胞较多,为成纤维细胞;增生明显处疤痕的中层有较多的ＦＧＦ阳性细胞。本文认为：疤痕形成与ＦＧＦ表达密切相关,增生性疤痕真皮的中心部位可能是组织增生最活跃的部位。     

氯胺酮对小鼠Ⅲ度烧伤死亡率和瘢痕形成的作用

目的观察氯胺酮对小鼠Ⅲ度烧伤死亡率和疤痕形成的作用,为临床应用提供实验依据。方法小鼠背部用95%酒精造成Ⅲ度火焰烧伤,烧伤面积7cm2,烧伤时间30s;氯胺酮用量10～20mg/kg,分别于烧伤后或烧伤前后腹腔注射,对照组注射等量生理盐水,通过烧伤小鼠早期死亡率和烧伤后期瘢痕面积观察其作用。结果 BALB/c和C57BL/6小鼠烧伤后立即、4h、24h腹腔注射氯胺酮20mg/kg,小鼠死亡率分别为42.8%和100%,与对照组无明显差别（P〉0.05）;C57BL/6小鼠烧伤前10min和烧伤后4h、24h注射氯胺酮10mg/kg,小鼠死亡率为100%,与对照组也无差别。烧伤时间减为20s,于烧伤烧伤后立即和24h注射氯胺酮20mg/kg,35d后测定瘢痕面积,治疗组明显小于对照组（P〈0.05）。结论氯胺酮无明显降低小鼠烧伤早期死亡率的效果,但有减少烧伤瘢痕面积的作用,可能与氯胺酮抗炎作用有关。     

子宫动脉栓塞术对于难治性子宫下段瘢痕妊娠的影响分析

目的:探讨子宫动脉栓塞术对于难治性子宫下段瘢痕妊娠的影响。方法:回顾性分析2009年8月至2013年4月经我院收治的85例难治性子宫下段瘢痕妊娠患者,其中41例行子宫动脉栓塞术治疗(观察组),44例行孕囊穿刺术治疗(对照组)。记录两组患者术中出血量、住院时间、转经时间、β-HCG下降至正常时间及激素水平,并比较两种治疗方法的效果。结果:观察组与对照组痊愈率分别为92.68%和90.91%,两组治疗效果比较无显著性差异(P0.05)。与对照组比较,观察组术中出血量显著降低、住院时间及β-HCG下降至正常时间均显著缩短(P0.05);但两组治疗前后激素水平变化比较无显著性差异(P0.05)。术后随访1-3个月,观察组患者转经时间为(32.18±11.46)d,显著低于对照组的(50.03±8.04)d,两组比较差异有统计学意义(P0.05)。结论:子宫动脉栓塞术有效性和安全性更高,与孕囊穿刺术比较能减少术中出血量,缩短住院时间、转经时间及β-HCG下降至正常时间。     

Intrinsic fibroblast-mediated remodeling of damaged collagenous matrices in vivo

Numerous studies have examined wound healing and tissue repair after a complete tissue rupture and reported provisional matrix and scar tissue formation in the injury gap. The initial phases of the repair are largely mediated by the coagulation response and a principally extrinsic inflammatory response followed by type III collagen deposition to form scar tissue that may be later remodeled. In this study, we examine subfailure (Grade II sprain) damage to collagenous matrices in which no gross tissue gap is present and a localized concentration of provisional matrix or scar tissue does not form. This results in extracellular matrix remodeling that relies heavily upon type I collagen, and associated proteoglycans, and less heavily on type III scar tissue collagen. For instance, following subfailure tissue damage, collagen I and III expression was suppressed after 1 day, but by day 7 expression of both genes was significantly increased over controls, with collagen I expression significantly larger than type III expression. Concurrent with increased collagen expression were significantly increased expression of the collagen fibrillogenesis supporting proteoglycans fibromodulin, lumican, decorin, the large aggregating proteoglycan versican, and proteases cathepsin K and L. Interestingly, this remodeling process appears intrinsic with little or no inflammation response as damaged tissues show no changes in macrophage or neutrophils levels following injury and expression of the inflammatory markers, tumor necrosis factor-alpha and tartrate-resistant acid phosphatase were unchanged. Hence, since inflammation plays a large role in wound healing by inducing cell migration and proliferation, and controlling extracellular matrix scar formation, its absence leaves fibroblasts to principally direct tissue remodeling. Therefore, following a Grade II subfailure injury to the collagen matrix, we conclude that tissue remodeling is fibroblast-mediated and occurs without scar tissue formation, but instead with type I collagen fibrillogenesis to repair the tissue. As such, this system provides unique insight into acute tissue damage and offers a potentially powerful model to examine fibroblast behavior.     

Fourier transform infrared evaluation of microscopic scarring in the cardiomyopathic heart: effect of chronic AT1 suppression

Our primary aim was to investigate the use of Fourier transform infrared (FTIR) spectromicroscopy as an accurate assay of cardiac extracellular matrix remodeling. Abnormal rearrangement or remodeling of the cardiac extracellular matrix is known to contribute to cardiac dysfunction. The microscopic multifocal necrosis and scarring are modulated by chronic AT(1) receptor blockade in experimental cardiomyopathy; thus, we also wished to rationalize the spectromicroscopic differences among control, untreated cardiomyopathic (CMP), and losartan-treated cardiomyopathic (LOS) hearts according to the pathogenesis of experimental cardiomyopathy. Male UM-X7.1 cardiomyopathic Syrian hamsters at early and late (65 and 200 days) stages of cardiomyopathy were subjected to 4-week losartan (15 mg/kg/day continuous infusion) treatment. Focal collagen microdomain distribution was confirmed spectroscopically by observation of the collagen IR fingerprint in the 1000-1800 cm(-1) region. Synchrotron FTIR spectromicroscopic map data were obtained from control (F1-beta strain) hamsters, nontreated cardiomyopathic, and losartan-treated CMP animals and imaged with mapping software, according to intensity of collagen fingerprint. Compared to controls, untreated late-stage CMP myocardium was characterized by elevated levels of fibrillar collagens and this was partially normalized with a 4-week losartan treatment. FTIR spectromicroscopy revealed that elevated collagen expression in focal microdomains is present in late-stage cardiomyopathy, and 4-week AT(1) blockade is associated with attenuation of collagen absorption in these lesions.