硫化氢供体对大鼠高肺血流性肺动脉高压中内皮素-1及结缔组织生长因子表达的影响

目的：探讨硫氢化钠（NaHS）对大鼠高肺血流性肺动脉高压中内皮素-1(ET-1)及结缔组织生长因子(CTGF)表达的影响。方法:32只雄性SD大鼠随机分为分流组（n=8）、分流+NaHS组（n=8）、假手术组（n=8）和假手术+NaHS组（n=8）。对分流组和分流+NaHS组大鼠行腹主动脉-下腔静脉穿刺建立高肺血流动物模型。分流11周后，分别测定大鼠肺动脉收缩压（SPAP）、血浆ET-1含量、肺组织硫化氢（H2S）含量、肺组织ET-1mRNA的表达及肺动脉CTGF蛋白的表达。结果:分流11周，大鼠SPAP明显高于假手术组(P<0.05)；分流组大鼠肺组织ET-1mRNA表达、血浆ET-1含量以及肺腺泡肌型动脉CTGF表达明显高于假手术组；肺组织H2S含量明显低于假手术组(P<0.05)；应用NaHS干预11周，分流+NaHS组大鼠H2S含量明显高于、而SPAP明显低于假手术组(P<0.05)；分流+NaHS组大鼠血浆ET-1含量及肺组织ET-1mRNA的表达明显低于分流组(P<0.05)；分流+NaHS组大鼠肺动脉CTGF蛋白表达明显低于分流组(P<0.05)。结论: NaHS可能通过降低血管活性肽ET-1 及CTGF在肺组织的表达参与调节高肺血流性肺动脉高压的形成。     

内源性硫化氢抑制高肺血流大鼠肺动脉弹力蛋白的表达

目的探讨内源性硫化氢(H2S)对高肺血流所致肺血管重构大鼠肺动脉弹力蛋白的调节作用。方法将雄性SD大鼠随机分为4组:分流组、分流 炔丙基甘氨酸(PPG)组、假手术组和假手术 PPG组,每组8只。分流组及分流 PPG组大鼠经腹主动脉-下腔静脉穿刺建立高肺血流动物模型。4周后,测定大鼠肺动脉平均压(mPAP),显微镜下观察肺血管结构变化;用免疫组化方法测定α-平滑肌肌动蛋白(α-SM-actin)、弹力蛋白、转化生长因子-β(TGF-β)和结缔组织生长因子(CTGF)在肺动脉平滑肌细胞的表达。结果分流 PPG组mPAP较分流组和假手术组明显升高(P<0.05);在分流组,小型肺动脉中肌型动脉和部分肌型动脉所占百分比明显高于假手术组(均P<0.05),非肌型动脉所占百分比明显低于假手术组(P<0.01);在分流 PPG组,小型肺动脉中肌型动脉所占百分比明显高于分流组(P<0.01),非肌型动脉所占百分比明显低于分流组(P<0.01)。分流组肺中,小型肺动脉平滑肌细胞α-SM-actin、弹力蛋白、TGF-β和CTGF含量明显高于假手术组(均P<0.01),分流 PPG组上述指标明显高于分流组(均P<0.01)。结论内源性硫化氢可能通过抑制高肺血流大鼠肺动脉弹力蛋白的表达,调节其肺血管结构重构。     

硫化氢在脂多糖所致大鼠急性肺损伤中的作用

目的探讨硫化氢(H2S)在脂多糖(LPS)所致大鼠急性肺损伤(ALI)中的作用及可能的机制。方法将64只SD大鼠随机分为对照组、LPS组(经气管内滴注LPS复制ALI)、NaHS LPS组和炔丙基甘氨酸(PPG) LPS组。给药后4 h或8 h处死,测定肺系数;光镜观察肺组织形态学改变;化学法检测血浆H2S和CO含量、肺组织丙二醛(MDA)含量、胱硫醚-γ-裂解酶(CSE)和血红素加氧酶(HO)活性;用免疫组织化学法检测肺组织HO-1蛋白表达及吸光度值。结果气管内滴注LPS可引起肺组织明显的形态学改变;肺系数和肺组织MDA含量增加;血浆H2S含量和肺组织CSE活性下降;肺组织HO活性和HO-1蛋白表达增强;血浆CO含量增加。预先给予NaHS可显著减轻LPS所致上述指标的改变。而预先给予PPG可加重LPS所致肺损伤,但对CO含量、HO活性和HO-1蛋白表达无明显影响。结论H2S/CSE体系的下调在LPS所致ALI的发病学中有一定作用,而外源性给予一定量的NaHS对肺组织具有保护作用,该作用可能与其抗氧化效应和上调CO/HO-1体系有一定关系。     

内源性H2S在CCK-8减轻脂多糖所致急性肺损伤中的作用

目的：探讨内源性硫化氢(H₂S)在八肽胆囊收缩素(CCK-8)减轻脂多糖（LPS）所致急性肺损伤(ALI)中的作用。方法: 将84只SD大鼠随机分为正常对照组、LPS组（经气管内滴注LPS复制ALI）、NaHS(H₂S供体)+LPS组、炔丙基甘氨酸［胱硫醚-γ-裂解酶（CSE）抑制剂，PPG］+LPS组、CCK-8+LPS组、PPG+CCK-8+LPS组和CCK- 8组。给药后分别于4 h和8 h处死动物，测定肺湿/干比值；光镜观察肺组织形态学改变；化学法检测血浆H₂S含量，肺组织MDA含量、MPO活性和CSE活性；放免法检测肺组织P-selectin含量；RT-PCR检测肺组织CSE mRNA的表达；并行支气管肺泡灌洗，检测支气管肺泡灌洗液(BALF)中蛋白含量。结果: 气管内滴注LPS可引起肺组织明显的形态学改变；肺湿/干比值、BALF中蛋白含量及肺组织MDA、MPO活性和P-selectin水平增高；血浆H2S含量、肺组织CSE活性及CSE mRNA表达下降。预先给予NaHS或CCK-8可显著减轻LPS所致的上述改变，且血浆H₂S含量、肺组织CSE活性及CSE mRNA表达高于相应的LPS组；预先给予PPG可加重LPS所致的肺损伤，而血浆H₂S含量、肺组织CSE活性及CSE mRNA表达分别低于相应的LPS组和CCK-8+LPS组。结论: CCK-8可通过内源性H₂S介导的抗氧化、抑制PMN黏附聚集等效应发挥减轻LPS所致肺损伤的作用。     

脂多糖性休克大鼠血浆和主要器官中硫化氢含量的变化和意义

目的：探讨内毒素休克（endotoxic shock，ES）大鼠血浆及肝、肾、心、肺、主动脉等主要器官组织中内源性硫化氢（hydrogen sulfide，H2S）的含量变化及意义。方法：用静脉注射脂多糖（lipopolysaccharide，LPS）法制备LPS攻击大鼠模型，将雄性Wistar大鼠随机分为正常对照组、LPS组、LPS+硫氢化钠（NaHS，H2S供体）组、LPS+炔丙基甘氨酸（PPG，H2S代谢酶抑制剂）组。观察给药后240 min内大鼠平均动脉压（mean arterial pressure，MAP）的变化及测定血浆和以上主要器官中H2S含量，并分析其相关性；光镜观察主要器官的形态学变化。结果：与正常对照组相比，LPS组大鼠血压迅速下降，血浆H2S含量于LPS注射后显著增高，肝、肾、心、肺和主动脉组织中H2S含量亦明显增高（均P<0.05），并出现组织结构损伤；给予PPG能显著抑制血浆以及各组织中H2S含量的增高，并可显著减轻LPS所致的血压下降（均P<0.05）和组织损伤；而给予H2S供体NaHS后，与LPS组相比，大鼠血浆以及各组织中H2S含量显著增高，血压明显下降（均P<0.05），组织损伤加重。LPS攻击大鼠血浆及组织中H2S含量与血压呈高度负相关（均P<0.05）。结论：H2S是一种新的内源性介质，可能参与了ES的一系列病理生理过程。     

硫化氢在休克肠淋巴液致肝损伤中的作用与机制

 目的： 应用硫化氢（H2S）合成酶胱硫醚γ-裂解酶（CSE）抑制剂DL-炔丙基甘氨酸（PPG）和H2S供体硫氢化钠（NaHS）作用于行肠淋巴液引流的大鼠,探讨H2S在肠淋巴液引流减轻休克大鼠肝损伤中的作用。方法：休克组、休克+引流组、休克+引流+PPG组（45 mg/kg,放血前0.5 h,ip）和休克+引流+NaHS（28 μmol/kg,放血前0.5 h,ip）组大鼠复制失血性休克模型,低血压1 h后行液体复苏,休克+引流组、休克+引流+PPG组和休克+引流+NaHS组在输液结束后,行肠淋巴液引流至液体复苏结束后3 h。观察肝组织形态,检测血浆肝功能生化指标以及肝组织H2S、CSE、Toll样受体4（TLR4）、白细胞介素（IL）-10、IL-12和肿瘤坏死因子α（TNF-α）水平。结果：休克组大鼠血浆天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆汁酸（TBA）以及肝组织H2S、CSE、TLR4、IL-10、IL-12、TNF-α含量均显著高于假手术组;肠淋巴液引流显著降低了休克组大鼠血浆AST、ALT、TBA以及肝组织H2S、CSE、IL-10、IL-12、TNF-α含量;PPG使休克+引流组大鼠血浆AST、ALT、TBA以及肝组织H2S、TLR4、IL-10、IL-12、TNF-α含量进一步降低;NaHS则提高了休克+引流组大鼠血浆AST、ALT与肝组织H2S、TLR4、IL-10、IL-12、TNF-α的含量。组织形态学观察表明,休克组和休克+引流+NaHS组大鼠出现了肝细胞损伤,假手术组、休克+引流组、休克+引流+PPG组大鼠肝细胞形态基本正常。结论：肠淋巴液引流减轻失血性休克大鼠肝损伤的作用机制与抑制H2S生成、减轻H2S介导的炎症反应有关。     

L-精氨酸对大鼠高肺血流所致肺血管结构重建及内源性硫化氢的影响

探讨L 精氨酸 (L Arg)对高肺血流量所致大鼠肺血管结构重建和内源性硫化氢的影响及其机制。 2 1只SD大鼠随机分为对照组 (n =7) ,分流组 (n =7) ,分流 +L 精氨酸组 (n =7)。对后两组大鼠行腹主动脉、下腔静脉分流术。对分流 +L 精氨酸组大鼠每天灌胃L Arg 1g kg。 1 1周后观察肺动脉平均压 (mPAP)和右心室肥厚的改变。并且在光学显微镜和电子显微镜下观测肺血管结构的变化。测定血浆硫化氢含量和肺组织硫化氢产出率。结果表明 ,分流组大鼠mPAP、右心室 /体重 (RV BW)及右心室 /左心室 +室间隔 [RV (LV +S) ]比值明显高于对照组 (P <0 0 1 ) ,光镜下肺小血管肌化程度明显增强 ,电镜下 ,肺中、小肌型动脉内皮细胞增生、肥厚 ,平滑肌细胞由收缩表型向合成表型转化。分流组大鼠的血浆H2 S含量及肺组织CSE活性 (肺组织H2 S产出率 )明显低于对照组 (P <0 0 1 ) ,肺动脉平均压与血浆H2 S浓度呈负相关。同时L Arg缓解了肺动脉结构重建的形成 ,同时提高了内源性硫化氢水平 ,这可能是L Arg缓解高肺血流量所致肺动脉高压形成的机制之一。     

中介素抑制高肺血流性肺动脉高压大鼠肺组织胶原生成

 目的:研究中介素（IMD）对高肺血流性肺动脉高压大鼠肺组织胶原生成和沉积的调节作用及其机制。方法: 健康雄性SD大鼠20只,随机分为对照组（n=7）、分流组（n=7）和分流+IMD组（n=6）。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+IMD组大鼠,皮下埋微量渗透泵持续给予IMD 1.5 μg·kg-1·h-1。继续饲养2周后,比较各组大鼠肺动脉平均压（mPAP）、肺中、小动脉相对中膜厚度（RMT）,肺组织羟脯氨酸、Ⅰ和Ⅲ 型胶原、骨形成蛋白-2（BMP-2）含量和I、III型前胶原mRNA表达水平。结果: 与对照组相比,分流组大鼠mPAP明显上升,肺中、小动脉RMT明显增加,肺组织羟脯氨酸和Ⅰ、Ⅲ型胶原含量明显增多,Ⅰ、Ⅲ型前胶原mRNA表达上调,BMP-2含量明显增多。IMD则使分流大鼠肺动脉压力明显回降,肺血管结构改变缓解,胶原沉积减少,BMP-2含量降低,Ⅰ、Ⅲ 型前胶原mRNA表达下调。结论: IMD可通过抑制高肺血流大鼠肺组织胶原生成和沉积,缓解高肺血流性肺动脉高压和肺血管结构重构形成,该作用可能与BMP-2途径有关。     

内源性硫化氢对实验性肝硬化门静脉高压的影响及其与一氧化氮的相互作用

目的：探讨硫化氢（ H2 S）对实验性肝硬化门静脉高压的影响及H2 S与一氧化氮（ NO）的相互作用。方法：将32只雌性SD大鼠,随机分为肝硬化组、肝硬化＋炔丙基甘氨酸（ PPG）组、肝硬化＋硫氢化钠（ NaHS）组和正常组4组,每组8只。肝硬化组、肝硬化＋PPG组及肝硬化＋NaHS组大鼠采用四氯化碳（CCl4）复合法制备肝硬化门静脉高压动物模型。造模结束第2天,肝硬化＋PPG组大鼠腹腔注射PPG 30 mg/（kg．d）,肝硬化＋NaHS组大鼠腹腔注射NaHS 56μmol/（kg．d）,肝硬化组及正常组大鼠腹腔给予10 ml/（ kg．d）生理盐水。给药干预1周后,测定各组大鼠门静脉压力（ PVP）、大鼠门静脉血浆H2 S、NO含量。结果：实验结束,经病理学观察证实肝硬化大鼠模型制备成功,PVP均大于11．80 mmHg,显示门静脉高压形成。肝硬化组、肝硬化＋PPG组和肝硬化＋NaHS组PVP和门静脉血浆NO含量均高于正常组,门静脉血浆H2S含量均低于正常组（P＜0．05）。肝硬化＋PPG组PVP和门静脉血浆NO含量高于肝硬化组,门静脉血浆H2 S含量低于肝硬化组;肝硬化＋NaHS组PVP和门静脉血浆NO含量低于肝硬化组,门静脉血浆H2S含量高于肝硬化组（P＜0．05）。结论：内源性H2S对肝硬化门静脉高压发挥保护性调节作用。内源性H2 S与NO在肝硬化门静脉高压形成中可能呈现相互的负性调节作用,共同参与肝硬化门静脉高压形成的调控机制。     

构建截肢创伤模型大鼠肝脏功能变化及硫化氢的影响

背景：截肢是一种特殊类型的创伤,创伤导致肝脏损害的机制及硫化氢对肝脏的作用目前尚不明确。 目的：探索构建截肢创伤模型大鼠的肝脏损伤,以硫化氢(H2S)对其的影响。 方法：将Wistar大鼠和SD大鼠分别随机等分为正常组、截肢后6,12,24,72 h组、硫氢化钠(NaHS)组、炔丙基甘氨酸组和为正常组、截肢后6 h组、NaHS组、炔丙基甘氨酸组。除正常组外所有大鼠完全截断左侧于膝关节上方1.2-1.4 cm处结构,并在结扎血管后剪断左侧股静、动脉,建立左后肢的截肢模型大鼠。NaHS组及炔丙基甘氨酸组大鼠分别于截肢后即刻腹腔注射28 μmol/kg NaHS和50 mg/kg炔丙基甘氨酸。 结果与结论：与正常组相比,截肢后6 h组大鼠肝脏和线粒体结构出现了损伤性改变,血浆及肝脏髓过氧化物酶、丙二醛、H2S/胱硫醚γ-裂解酶水平、血浆及肝脏髓过氧化物酶、丙二醛、肝脏线粒体呼吸控制率、膜电位及ATP酶活性明显降低(P < 0.05),NaHS干预后H2S/胱硫醚γ-裂解酶水平及以上指标明显升高(P < 0.05),但血浆转氨酶并未明显变化(P > 0.05)。应用炔丙基甘氨酸后,以上除线粒体指标无明显变化外,多表现为进一步降低,转氨酶也明显下降(P < 0.05)。说明H2S可减轻截肢模型大鼠肝脏组织脂质过氧化、炎症反应,并使线粒体功能明显改善,但并未减轻肝脏功能的受损。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

P63 in pulmonary epithelium,pulmonary squamous neoplasms,and other pulmonary tumors

p63 is a p53-homologous nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with citric acid (pH 6.0) for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as chromagen, and were counterstained with hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). In some well-differentiated carcinomas, staining was found at the periphery of tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All small-cell carcinomas were p63 negative (n = 9). Staining of bronchioloalveolar carcinomas (n = 7) and adenocarcinomas (n = 23) was variable: some tumors showed no detectable staining, others showed heterogeneously positive staining. Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern. Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated squamous carcinoma versus small-cell carcinoma. A stem cell biology-based classification system for squamous carcinomas is proposed.     

肺部超声对重症肺部感染患者肺通气的评估价值

目的:探讨肺部超声评价重症肺部感染患者通气情况的应用价值。方法:选取88例重症肺部感染患者,采用半定量方法对肺部超声征象进行评分,以CT检查结果为金标准,分析肺部超声评分与患者肺通气的关系;同时分析存活和死亡患者临床资料、肺部超声评分的差异,以及肺部超声评分预测患者死亡的价值。结果:88例患者全肺超声评分平均为（18.50±2.12）分,全肺CT值平均为（-620.50±88.13） HU,不通气/低通气肺组织比例平均为（10.41±3.35）%,正常通气肺组织比例平均为（71.54±6.69）%,过度通气肺组织比例平均为（17.65±4.11）%;患者肺部超声评分与全肺CT值、不通气/低通气肺组织比例呈正相关（r=0.775、0.648, P<0.05）,与正常通气肺组织比例、过度通气肺组织比例无明显相关性（r=-0.170、0.046, P>0.05）;死亡组患者年龄、糖尿病比例、APACHEⅡ评分、肺泡-动脉氧分压差、机械通气治疗和肺部超声评分分别为（59.28±8.12）岁、44.83%、（22.19±2.40）分、（344.40±82.29） mmHg、72.41%和（20.20±1.72）分,明显高于存活组（P<0.05）,而氧合指数为（104.42±21.18）,明显低于存活组（P<0.05）;Logistic回归分析结果显示:年龄、APACHEⅡ、肺部超声评分是重症肺部感染患者死亡的影响因素（OR=1.758、2.841、2.440, P<0.05）;肺部超声评分预测重症肺部感染患者死亡的ROC曲线下面积为0.901（95%CI:0.836~0.966）,截断值为20分,灵敏性和特异性分别为82.80%和84.70%。结论:肺部超声可以作为重症肺部感染患者肺通气的评估指标,同时其在预测患者预后方面有一定应用价值。     

The pulmonary matrix, glycosaminoglycans and pulmonary emphysema

This paper reviews recent evidence of the effect of intratracheal hyaluronan (HA) to limit the induction of experimental emphysema in hamsters. Experimental emphysema was induced by both neutrophil and pancreatic elastase instilled intratracheally. Emphysema was quantified anatomically by measurement of alveolar mean linear intercept. Hyaluronidase, instilled intratracheally, enhanced the induction of experimental emphysema. Air-space size measured one week after intratracheal instillation of elastase showed that administration of 1 mg HA immediately following elastase administration resulted in a marked reduction in air-space enlargement (82 microM vs 122 microM, p < 0.01). Similarly, animals given either 1 or 2 mg HA 2 h before elastase or 2mg HA 1 h after elastase showed a significant decrease in air-space enlargement compared to controls (96 microM, 88 microM vs 120 microM and 66 microM vs 104 microM, respectively; p < 0.05. Experimental emphysema induced by neutrophil elastase was also limited by the administration of 1 or 4 mg of HA, administered 2 h prior to elastase (57 and 59 microM, respectively vs 64 for controls, p < 0.05). Characterization of administered HA showed a mean molecular weight of 104,800 Da, less than 5% protein and a uronic acid/hexosamine ratio of 1, which is characteristic of HA. Studies using fluorescein-labeled hyaluronan (HA) showed fluorescence associated with interstitial, pleural and vascular elastic fibers. The mechanism of attachment of the administered HA to elastin remains unknown. Fluorescein labeling of elastin was visible for at least 4 h post-instillation. These studies indicate a protective effect of hyaluronan against elastase degradation of pulmonary elastin in vivo by both pancreatic and neutrophil elastases. The anatomical studies further suggest a mechanism of protective coating of hyaluronan which may limit access to pulmonary elastin from neutrophils and alveolar macrophages. Results also suggest that a reduction in pulmonary hyaluronan content increases the susceptibility of elastin to degradation by elastases. These studies provide evidence for an antielastase effect of hyaluronan which is not dependent upon enzyme inhibition but on anatomical protection of pulmonary elastin by other mechanisms.     

Changes in pulmonary hemodynamics in acute pulmonary edema

Summary Experiments were made on dogs to study the hemodynamic changes following intravenous injections of chloramine and adrenaline. Chloramine injections were followed by the development of a severe pulmonary edema in an of the dogs. In most of them, however, the capillary pressure in the pulmonary circulation increased, but insignificantly. The great increase in the pulmonary capillary pressure following adrenaline injection did not culminate in the development of edema or caused very slight edema. The conclusion is drawn that increase of filtration pressure is not an indispensable decisive factor for the development of pulmonary edema, even if it is concurrent with considerable disturbances in the pulmonary circulation.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 25–29, August, 1965     

Mycobacterial pulmonary infections in patients with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

A case of pulmonary capillary hemangiomatosis with pulmonary fibrosis associated with MMP-9 related pulmonary remodeling

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. It is characterized capillary proliferation within the alveolar septa. Here, we report a case of PCH with extensive pulmonary fibrosis. A 52-year-old man with a clinical diagnosis of non-specific interstitial pneumonia died of respiratory failure with severe pulmonary hypertension. Autopsy revealed pronounced right ventricle hypertrophy and pulmonary fibrosis. Consistent with clinical diagnosis, histological examination revealed diffuse pulmonary fibrosis, in addition, it also disclosed marked capillary proliferation within the alveolar septa as well as the fibrotic pulmonary stroma, suggesting the presence of PCH. Hemosiderin-laden macrophages had accumulated in the capillary proliferative area, and bronchiolar-type metaplasia was conspicuous in the fibrotic lesion. Proliferated capillaries were surrounded by fine collagen and α-smooth muscle actin-positive myofibroblasts. Immunohistochemistry revealed that type IV collagen around capillaries in the area of the PCH without inflammation disappeared in the area with inflammation. In addition, the PCH lesion contained significant numbers of macrophages expressing matrix metalloproteinase (MMP) 9 and type II pneumocytes positive for vascular endothelial growth factor. Although pulmonary fibrosis is a distinctive disease entity, different from PCH, MMP-9-driven destruction of the basement membrane may promote unusual pulmonary remodeling, which, in this case, resulted in extensive pulmonary fibrosis.