Aprepitant exerts anti-fibrotic effect via inhibition of TGF-β/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats

Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway.     

Bleomycin sclerotherapy in lymphangiomas of the head and neck region: a prospective study

Intralesional sclerotherapy for lymphatic malformations (LMs) has become a modality of choice because of the high morbidity and recurrence rates with surgical excision. Traditionally, the macrocystic variant has shown good results with sclerotherapy. This prospective study was performed to evaluate the role of bleomycin sclerotherapy in the management of different radiological variants of LM. A total of 142 patients were included in this study. The lesions were classified as macrocystic, microcystic, or mixed LMs on the basis of ultrasonography. All patients were managed by intralesional injection of bleomycin and were recalled after 4 weeks for evaluation. Colour photographs of the patients were taken before the onset of treatment and at each monthly visit, and were utilized to assess the response. Following the second, third, and fourth doses, the response was better in patients with the macrocystic variant than in those with the other two variants. However, after the completion of six doses, 80.3% of patients with the macrocystic variant, 67.4% with the microcystic variant, and 71.4% with the mixed type had a complete response. There was no difference in the overall response between the three types (P = 0.28). Oedema, erythema, and local induration with fever were the most common adverse effects and were more common in younger children.     

Protective effect of Alstonia scholaris Linn. R. Br. against Bleomycin induced chromosomal damage in cultured human lymphocytes,in vitro

It is both interesting and necessary to identify and develop nontoxic radioprotective compounds. Bleomycin (BLM), a known radiomimetic drug was used as a clastogen in the present study. The possible protective effects against BLM (15?μg/ml) induced clastogenicity by aqueous and methanolic extracts from Alstonia scholaris bark, stem and leaves were compared. The treatment of bark extracts significantly (p?2 assay was performed. Lymphocyte cultures from 12 healthy volunteers were exposed to aqueous (50?μg/ml) and methanolic (50?μg/ml) extracts of A. scholaris bark alone as well as in combination with Bleomycin under two different growth phases, G₀ and G₂. There was a statistically significant reduction (p?2 phase as compared to respective cultures exposed at G₀ phase. The highest level (p?2 phase than those at G₀ phase. This indicated that there could be certain compound(s) present in aqueous bark extracts which enhance DNA repair capacity. Therefore, the bark of A. scholaris could be further utilized to identify and bring out front line radio protective agents in the market with effective formulations.     

平阳霉素地塞米松联合治疗口腔颌面部脉管畸形

目的 评价平阳霉素(PYM)与地塞米松联合应用病变内注射治疗口腔颌面部各种脉管畸形的疗效。方法 采用PYM和地塞米松联合病变内注射治疗口腔颌面部脉管畸形患者200例(225个瘤体)5～7d注射一次，3～5次为一个疗程。结果 200例患者治疗1～5次后，经过6～36m随诊，治愈率和基本治愈率为86．5％，好转为11％，总有效率达97．5％。静脉畸形、淋巴管畸形、混合性畸形、微静脉畸形的治愈率和基本治愈率分别为91．4％、80％、90．5％、36．3％，而动静脉畸形应用PYM与地塞米松联合治疗基本无效，2．5％的患者在治疗过程中出现溃疡，3．5％出现发热副反应。结论 PYM和地塞米松联合瘤内注射是治疗口腔颌面部脉管畸形一种较佳的治疗方法，疗效高，安全可靠，但应对脉管畸形病变进行正确分类，掌握其适应证。     

平阳霉素对颊囊癌金黄地鼠肺毒性的实验研究

目的 探讨平阳霉素对颊囊癌金黄地鼠肺组织的毒副作用。立法 将75只金黄地鼠用5％DM—BA涂擦颊囊诱发颊囊癌后分别用0．2mg/kg、0．4mg/kg和0．5mg／kg三种剂量的平阳霉素行腹腔注射；对照组每日灌服消炎痛拮抗。结果 随平阳霉素用量的增加，金黄地鼠肺炎样变及肺纤维化呈上升趋势；消炎痛具有良好的拮抗作用，可对抗平阳霉素的肺毒性。结论 平阳霉素用量较大时(超过0．4mg/kg)可出现肺炎样变及肺纤维化，如果同时使用消炎痛，则可有效地抑制肺纤维化的发生。     

喉部巨大血管瘤的微创治疗

目的：探讨安全有效的咽喉部血管瘤的治疗方法。方法总结2013年10月－2013年11月内蒙古医科大学附属医院耳鼻咽喉科在支撑喉镜下使用一次性注射针头注射平阳霉素治疗喉部巨大血管瘤1例的治疗效果。结果本例患者在历经1个月3次注射后,成功治愈。结论使用一次性注射针头支撑喉镜下喉部巨大血管瘤的注射治疗方法简单,疗效明确。是治疗咽喉部血管瘤的一种理想的微创治疗方法。     

Biochemical and histological changes in pulmonary fibrosis induced in rabbits with intratracheal bleomycin

Pulmonary fibrosis was induced in rabbits by an intratracheal instillation of bleomycin. Histologically, at 2 weeks there was inflammation but only limited evidence of increased collagen deposition; at 8 weeks the inflammatory response had subsided and increased collagen deposition, characteristic of early interstitial fibrosis, was observed. Biochemical analyses showed bleomycin treatment caused marked increases in the total amounts of RNA, DNA, mixed protein, collagen and elastin when compared to controls (P less than 0.001 in all cases). Furthermore the increases were essentially complete by 2 weeks where the contents had increased by 110 +/- 13%, 60 +/- 11%, 148 +/- 12%, 94 +/- 15% and 89 +/- 11% respectively (P less than 0.001 in all cases). When collagen and elastin were expressed as concentrations with respect to wet weight, total protein or DNA content, the changes were not statistically significant. No changes were observed in the relative amounts of type I and type III collagen. It is concluded that: (1) compared to biochemical analysis, histology is relatively insensitive in detecting the early increases in connective tissue proteins; (2) measurements of lung collagen and elastin should be expressed as total lung contents wherever possible; the concentration of these proteins may remain unchanged, especially in the early stages of fibrosis, due to concomitant increases in other lung constituents; (3) changes in the relative amounts to types I and III collagens do not play a major role in the pathology of this form of pulmonary fibrosis.     

丹参酮对鼠肺纤维化过程中组织学变化的影响

观察了ＳＤ大白鼠腹腔内注射丹参酮ＩＩ＿Ａ磺酸钠（１５ｍｇ／ｋｇ）对博莱霉素致鼠肺纤维化的影响，通过动态测定各实验组与肺纤维化形成相关的第３、７、１４、２８灭肺组织匀浆内羟脯氨酸、脂质过氧化物的含量，表明丹参酮ＩＩ＿Ａ磺酸钠组较单纯博莱霉素组明显减低，同时也观察了肺组织病理学变化及形态学定量测量，结果表明丹参酮ＩＩ＿Ａ磺酸钠减轻了博菜霉素致肺纤维化的程度，初步探讨了丹参酮ＩＩ＿Ａ磺酸钠的作用机制。     

99 Tcm-六甲基丙二胺肟肺显像早期诊断博莱霉素所致肺损伤的临床价值

目的探讨^99Tc^m-六甲基丙二胺肟（HMPAO）肺显像早期诊断博莱霉素所致肺损伤的临床价值及损伤肺异常摄取^99Tc^m-HMPAO的机制。方法24只兔随机分成Ⅰ、Ⅱ、Ⅲ、Ⅳ四组，Ⅰ组为空白对照组，正常饮食，Ⅱ、Ⅲ、Ⅳ组隔天分别经耳缘静脉给予0．2mg／kg、0.3mg／kg及0．5mg／kg的博莱霉素。服药前及服药8、16、24、32d后均行孵^99Tc^m-HMPAO SPECT显像，勾画右肺感兴趣区，计算注入^99Tc^m-HMPAO后60s（A60）和最高峰（Apeak）的活性比A60／Apeak，并绘制时间活度曲线。Ⅳ组给药16d后，Ⅰ、Ⅱ、Ⅲ组给药32d后将兔全部处死，取肺组织做光、电镜检查。结果Ⅱ、Ⅲ、Ⅳ给药组A60／Apeak值与对照组比较均有显著相差异（P〈0．05）。光镜下肺组织呈轻微间质性肺炎改变，电镜下显示内皮细胞胞浆有水肿性改变，并可在胞浆内见大量吞银小泡。结论^99Tc^m-HMPAO肺显像能早期显示博莱霉素所致的肺损伤，肺毛细血管内皮细胞可能是^99Tc^m-HMPAO异常聚集的主要部位。