巴卡亭III对心房纤维化的作用及其机制研究

为探讨巴卡亭III对心衰诱导的心房纤维化是否有效及潜在作用机制, 本研究对C57BL/6小鼠行胸主动脉缩窄手术, 构建心衰模型, 进一步腹腔注射巴卡亭III, 以观察心房纤维化程度及相应信号通路的改变. 在体外使用血管紧张素II刺激成年小鼠心房成纤维细胞, 巴卡亭III处理后观察心房成纤维细胞分化、迁移和分泌细胞外基质的能力及TGF-β1/Smad2/3信号通路的改变. 临床样本表明, 心衰可以加重心房纤维化的程度(P<0.05). 动物实验表明, 巴卡亭III可以减轻心衰诱导的小鼠心功能不全及左心房扩大和纤维化, 并减轻心房组织TGF-β1/Smad2/3信号通路的激活(P<0.01). 细胞实验表明, 巴卡亭III可以抑制Ang-II所诱导的心房成纤维细胞分化、迁移和分泌细胞外基质的能力和减轻心房成纤维细胞TGF-β1/Smad2/3信号通路的激活(P<0.01). 表明巴卡亭III可通过TGF-β1/Smad2/3信号通路抑制心房成纤维细胞的活动, 从而减轻心衰诱导的心房纤维化的发生发展.     

Evaluation of imatinib mesylate as a possible treatment for nephrogenic systemic fibrosis in a rat model

Introduction

The purpose of the study was to evaluate the efficacy of imatinib mesylate in the treatment of nephrogenic systemic fibrosis (NSF) in a rat model administered high-dose gadodiamide, erythropoietin (Epo) and intravenous iron (IV iron).

Materials and methods

The local committee for animal research approved this study. Four groups of six Hannover–Wistar rats were studied. Group A received normal saline; Group B, IV iron and Epo; Group C, gadodiamide, IV iron and Epo; and Group D, gadodiamide, IV iron, Epo and imatinib. Gadodiamide was administered at 10 mmol/kg of body weight for 5 consecutive days. Imatinib was administered at 50 mg/kg starting 3 days before gadodiamide injections and was continued for 50 days afterwards. Biopsies were taken 3 and 7 weeks after gadodiamide injection, and dermal histology was analyzed as well as gadolinium deposition as measured by inductively coupled plasma mass spectrometry. Additionally, rats treated with gadodiamide were observed for a total of 16 weeks. For comparison of cellularity, a linear mixed-effects model was used, and for metal deposition, an analysis of variance was used, which was corrected with a Tamhane correction for unequal variances.

Results

Rats treated with gadodiamide in addition to IV iron and Epo (group C) had worse skin lesions on histology (P<.001) compared to control animals (groups A and B). Treatment with imatinib resulted in decreased cellularity (group D vs C, P<.001), although there was no difference in the amount of deposited gadolinium (P>.5). Histology at 16 weeks demonstrated increased fibrosis and dermal calcifications, consistent with the clinical presentation of NSF.

Conclusions

The administration of imatinib to rats treated with high-dose gadodiamide resulted in decreased lesion severity.     

Safety aspects of gadofosveset in clinical practice – analysis of acute and long-term complications

Purpose

The purpose of this retrospective study was to systematically search for acute adverse reactions and long-term complications in all patients that had been administered gadofosveset at our hospital.

Materials and methods

We identified 67 gadofosveset administrations during 2006–2009 in 62 patients from 8 to 84 years of age. Radiological information system (RIS) and clinical patient records were analyzed for suspected acute adverse reactions and long-term complications including nephrogenic systemic fibrosis (NSF).The gadofosveset doses ranged between 0.024 and 0.060 mmol/kg bodyweight with a mean dose of 0.031-mmol/kg bodyweight. Follow-up time of the patients ranged from less than 1 year up to 4 years with a mean follow-up time of 2.1 years.

Results

No acute adverse events or technical failures related to the contrast medium were recorded in the RIS. No dermatological and nephrological diseases related to the gadofosveset administration were found in the clinical patient records. Four patients died during follow-up without any apparent relation to the gadofosveset exposure.

Conclusions

Based on our clinical material we conclude that gadofosveset is safe for a mixed patient population with no acute adverse events or any indications of long-term complications during the follow-up time up to four years.     

Messung der Leberschädigung durch Perchlorethen mit Hilfe des in vivo [15N]Methacetin-Urintests

Es wird gezeigt, daß der [¹⁵N]Methacetin-Urintest ein empfindliches, einfaches und nicht belastendes Verfahren ist, mit dem hepatozelluläre Schädigungen als Folge bestimmter Umwelteinflüsse am Arbeitsplatz gemessen werden können.

Die Methode wird an 13 Textilreinigerinnen demonstriert, die bis zu 39 Jahre in ihrem Betrieb Perchlorethendämpfen ausgesetzt waren.

Mit zunehmenden Expositionszeiten der Arbeiterinnen nehmen die ¹⁵N-Eliminations-geschwindigkeiten absinkenden hepatozellulären Monooxygenasen-Kapazitäten. Dies entspricht.

It is shown that the [¹⁵N]methacetin urine test is a sensitive, simple, and non-distressing tool to measure hepatocellular injury as a consequence of certain environmental factors at the workplace.

The method is demonstrated with 13 female textile cleaners who have been exposed to perchlorethylene for up to 39 years in their shop.

Decreasing ¹⁵N elimination rates – equal to decreasing monooxygenase capacities – are seen to be correlated with increasing exposure times of the workers.     

The blooming intersection of transcatheter hepatic artery chemoembolization and nanomedicine

Transcatheter hepatic artery chemoembolization(TACE) is a universal treatment for patients with hepatocellular carcinoma(HCC) that inhibits tumor growth by cutting off the blood supply and provides chemotherapeutics locally to the tumor.The strategy of combining TACE formulation with image-guided ablation holds tremendous potential,but patient tolerance and undesired toxicity/immunosuppression remains a challenge.The application of nanotechnology in TACE opens new doors for the treatment of HCC.Strikingly,nanomaterials or nano-drugs dispersed in the TACE formulation can effectively improve the delivery efficiency of drugs by achieving both controlled and continuous release.In addition,the utilization of multifunctional nanoparticles can provide guidance and monitoring for various advanced imaging methods for TACE treatment,and can realize the combination therapy of thermal ablation,microwave ablation,in situ radiotherapy,and other therapies,greatly expanding the therapeutic strategies available for HCC treatment.Here,the current exploration of nanotechnology in TACE of HCC is briefly summarized and the challenges of TACE with nanoformulations for clinical translation are comprehensively discussed.     

超声造影联合增强CT诊断不典型肝血管平滑肌脂肪瘤的临床价值

选取2011年6月~2017年6月于我院就诊的经病理学检查明确确诊为肝血管平滑肌脂肪瘤(HAML)的43例患者,通过对纳入患者的49个HAML病灶的超声造影(CEUS)及增强CT(CECT)的影像学表现及术前诊断结果进行分析,探讨CEUS联合CECT在诊断不典型HAML中的临床价值。结果显示,HAML在女性中的发病率显著高于男性(P<0.001),且HAML多为单发病灶(P<0.001)。术前经CECT准确诊断HAML者有34.69%,经CEUS准确诊断HAML者有57.14%,二者联合准确诊断HAML者有77.55%,联合诊断的准确性显著高于单独应用CECT或CEUS(P<0.05)。HAML在CECT和CEUS上的表现具有一定的特征性,二者联合应用可以提高HAML诊断正确率。     

A neutral polysaccharide from <Emphasis Type="Italic">Glycyrrhiza inflata</Emphasis>

A neutral polysaccharide Gi-A1 was isolated from the roots of Glycyrrhiza inflata Bat. It had a molecular mass of over 2000 kDa and showed [α]_D²⁰ + 81.4° (c 1.05, H₂O). Acid hydrolysis and methylation analysis indicated that Gi-A1 was mainly composed of α-D-glucose, α-L-arabinose, and α-D-galactose with a molar ratio of 8.0:1.8:1.0. It can significantly stimulate spleen cell proliferation in vitro (P < 0.01). Published in Khimiya Prirodnykh Soedinenii, No. 1, pp. 13–14, January–February, 2009.     

尼达尼布的合成新方法

以N-甲基-4-硝基苯胺作为起始原料,依次经氯乙酰化、取代及氢化还原反应制得关键中间体N-(4-氨基苯基)-甲基-2-(4-甲基-1-哌嗪基)乙酰胺（4）;以4-氯-3-硝基苯甲酸为原料,依次经酯化、取代、氢化还原及环合反应制得6-甲氧羰基-2-吲哚酮（8）; 8与原苯甲酸三乙酯和乙酸酐经“一锅煮”反应制得中间体1-乙酰基-3-甲氧基(苯基)亚甲烯基-2-氧代吲哚环-6-羧酸甲酯（9）; 4和9进行取代反应的同时脱除保护,经“一锅煮”反应合成尼达尼布,总收率57.2%,其结构经¹H NMR,¹³C NMR和MS(ESI)确证。     

Polyphenolic characterisation of plant mixture (Lisosan® Reduction) and its hypocholesterolaemic effect in high fat diet-fed mice

Lisosan® Reduction is a plant mixture produced from powder of fermented Triticum aestivum (Lisosan® G), Desmodium adscendens, Malus domestica, Picrorhiza kurroa and Hordeum vulgare. The aim of this study was to characterise the phenolic profile of Lisosan® Reduction and to evaluate the effects of aqueous extract on mice fed a high fat diet (HFD). Syringic acid, trans sinapic acid and neochlorogenic acid were identified by HPLC-DAD to be the dominant polyphenols of Lisosan® Reduction, followed by vitexin, trans p-coumeric acid and trans ferulic acid. Mice treated with aqueous extract of Lisosan® Reduction (60 mg/kg b.w.) showed a significant decrease of serum cholesterol, glucose and triglycerides level and a significant increase of CYP7A1 gene expression, compared to HFD group.     

Collection and X-ray microanalysis of airway surface liquid in the mouse using ion exchange beads

The airway surface liquid (ASL) is a thin layer of liquid covering the airway epithelium. The ionic composition of the ASL is assumed to be important for airway function and may be altered in diseases such as cystic fibrosis and exercise-induced asthma. A method for collection of ASL is presented in which the fluid is collected using small dextran ion-exchange beads. The beads are equilibrated with the ASL in a humidity chamber, collected under silicon oil, dried and analyzed by X-ray microanalysis. Analysis of standard beads prepared by exposure to different salt solutions shows that linear calibration lines can be obtained, but that beads absorb different elements to a different extent. The results show that the ASL in mice is hypotonic, and that the mucus component of the ASL has an elemental composition that is different from that of the periciliary fluid.