The core of the proposal is a prospective, randomized, double-blinded, controlled study which will compare the efficacy of dextran 70 versus human albumin in the treatment of cirrhotic patients with spontaneous bacterial peritonitis (SBP). Because dextran 70, which is FDA approved for plasma volume expansion, is significantly less expensive than human albumin, this study is designed and powered to determine if dextran 70 is equivalent in clinical efficacy when compared to albumin.
Specific aims for this project are to:
Assess the effect of plasma volume expansion with dextran 70 on disease-specific mortality at 30 days in cirrhotic patients with spontaneous bacterial peritonitis compared to plasma volume expansion with human albumin.
Assess the effect of dextran 70 compared to human albumin on the prevention of renal dysfunction within 30-days of diagnosis of SBP, as measured by the calculated creatinine clearance, plasma renin activity, serum aldosterone levels, levels of brain natriuretic peptide, and further development of the hepatorenal syndrome in cirrhotic patients with spontaneous bacterial peritonitis.
Compare the survival to liver transplantation, treatment costs, hospitalization costs, resource utilization, and quality of life of patients with spontaneous bacterial peritonitis treated with dextran 70 and human albumin in the 30 days following diagnosis.
Establish a comprehensive tissue bank of blood, ascites, and urine in patients with spontaneous bacterial peritonitis for future testing and translational research.
Establish a clinical electronic database with web-based data entry and remote analysis capabilities linking tissue bank samples and patient outcomes related to the above clinical trials.

开始日期2007-06-01

申办/合作机构

University of Virginia

[+1]

100 项与葡聚糖硫酸酯钠硫18 相关的临床结果

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100 项与葡聚糖硫酸酯钠硫18 相关的转化医学

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100 项与葡聚糖硫酸酯钠硫18 相关的专利（医药）

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项与葡聚糖硫酸酯钠硫18 相关的文献（医药）

2024-06-08·Huan jing ke xue= Huanjing kexue

[Spatial and Temporal Distribution of Antibiotic Resistance Genes in Different River Sediments in Typical Cities: A Case Study of Shijiazhuang].

Article

作者: Song, Yuan-Meng ; Cui, Jian-Sheng ; Zhang, Lu-Lu ; Wang, Lin-Jing ; Lu, Meng-Qi ; Gao, Sai ; Bai, Yin-Hu ; Zhao, Bo ; Chen, Hao-da

Rivers are important reservoirs of antibiotic resistance genes (ARGs). However, most current studies have focused on the temporal and spatial distribution, and data on the differences in the species and abundance of ARGs between urban and rural rivers is still lacking for certain areas. In view of this, two rural rivers and three urban rivers were selected in Shijiazhuang City. In both December 2020 and April 2021, sediments were collected at 15 sampling sites. Metagenomic sequencing technology was used to compare the differences in temporal-spatial variation for ARGs in sediments. The results showed that:① 162 and 79 ARGs were detected in urban (4 776 ±4 452) and rural rivers (1 043 ±632), respectively. The abundance and species of ARGs in urban rivers were higher than those in rural rivers. ② The relative abundances of sulfonamide (SAs,27 %), aminoglycoside (AGs,26 %), and multidrug (MDs,15 %) ARGs had the highest abundance in urban rivers, whereas the relative abundance of MDs ARGs was highest in rural rivers (65 %). On the whole, the complexity of ARGs in urban rivers was higher than that in rural rivers. ③ There was a significant positive correlation between SAs, AGs, MDs, tetracycline, phenicol, macrolides-lincosamids-streptogramins (MLS), β-lactams, and diaminopyrimidine ARGs in urban rivers (P < 0.01); however, there was a significant negative correlation between glycopeptide ARGs and all types of ARGs (P < 0.05 and P < 0.01). There was a significant positive correlation between MDs and SAs ARGs in rural rivers (P < 0.05), but there was a significant negative correlation between amino aminocoumarin, peptide, rifamycin, and fosfomycin ARGs (P < 0.05 and P < 0.01). ④ For the temporal variation in urban rivers, 162 ARGs (4 776 ±4 452) and 148 ARGs (5 673 ±5 626) were detected in December and April, respectively. For the temporal variation in rural rivers, 79 species (1 043 ±632) and 46 species (467 ±183) were detected in December and April, respectively. ⑤ RDA analysis results showed that the spatial-temporal distributions of ARGs in urban and rural rivers were different. Correlation analysis showed that the ARGs in urban rivers were significantly correlated with the number of industrial enterprises, whereas the ARGs in rural rivers were significantly correlated with the output value of animal husbandry. In general, this study identified the main influencing factors for ARGs in different rivers and provided data support for ARGs risk management in different rivers.

2024-06-01·Contact dermatitis

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation

Article

作者: Deconinck, Eric ; Desmedt, Bart ; Vanhaecke, Tamara ; Grassmann, Aleksandra ; Stras, Ania ; Van Campenhout, Peter

Abstract:

Introduction:

Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound‐specific restrictions when used in MDs.

Objective:

This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009.

Method:

Sixty‐nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS) methods to identify and quantify occurring preservatives and fragrances.

Results:

Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave‐on cosmetics.

Conclusion:

Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

2024-06-01·Toxicology

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats

Article

作者: Cui, Xinguang ; Ma, Honglei ; Guan, Jian ; He, Xinxing ; Song, Wei ; Wang, Jintao ; Wu, Bin ; Tan, Qi ; Li, Renfu ; Xue, Yuan ; Lei, Ming

Moon dust presents a significant hazard to manned moon exploration missions, yet our understanding of its toxicity remains limited. The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6 hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO₂, Fe₂O₃, and TiO₂ could be crucial sources of MDS toxicity. The study revealed that MDS-induced oxidative stress response can lead to pulmonary inflammation, which potentially may progress to lung fibrosis. Transcriptome sequencing revealed that MDS suppresses the PI3K-AKT signaling pathway, triggers the Tnfr2 non-classical NF-kB pathway and IL-17 signaling pathway, ultimately causing lung inflammation and activating predominantly antioxidant immune responses. Moreover, the study identified the involvement of upregulated genes IL1b, csf2, and Sod2 in regulating immune responses in rat lungs, making them potential key targets for preventing pulmonary toxicity related to moon dust exposure. These findings are expected to aid in safeguarding astronauts against the hazardous effects of moon dust and offer fresh insights into the implications and mechanisms of moon dust toxicity.

项与葡聚糖硫酸酯钠硫18 相关的新闻（医药）

2023-08-03

·药时代

亦正亦邪的“双面”靶点：TGF-β

从2014年Keytruda和Opdivo两款PD-1单抗获批以来，肿瘤免疫疗法（Tumor immunotherapy，IO）已成为肿瘤治疗领域的基石。然而即便如此，IO疗法也只能让部分患者从中获益（单药有效率仅20%-30%），其余大量患者无法产生应答。为了克服检查点抑制剂的耐药性，研究者们做了很多研究，其中转化生长因子（TGF-β）被认为具有克服检查点抑制剂耐药性的潜力。PART.01历久弥新的“双面”靶点——TGF-β事实上，TGF-β于1978年就被发现，是抗体药物领域的老靶点。几十年来，对于TGF-β作用机制的研究不断有新进展，研究人员希望在TGF-β身上，找到肿瘤免疫疗法的新突破口，不过这并不容易。TGF-β信号通路包含多种功能细胞因子，其共有3个亚型，分别为TGF-β1、TGF-β2和TGF-β3。TGF-β通过TGF-β/SMAD（一些转录激活因子）信号通路在细胞增殖、分化、迁移、凋亡、上皮-间质转化（EMT）、细胞外基质沉积以及炎性反应调节等方面发挥重要作用，并参与介导组织与器官的正常生长和发育、机体的免疫反应等生物过程。图1. TGF-β的信号传导机制，来源：参考1值得注意的是，TGF-β信号通路在肿瘤发生过程中表现出双重作用，能够分别扮演着促进肿瘤转移或抑制肿瘤生长的角色。在正常细胞中，TGF-β会诱导如自噬相关蛋白（4EBP1）、细胞周期蛋白依赖性激酶（CDK）等抑制剂的表达，来抑制肿瘤细胞的增殖。也可以通过促进Bcl-2（细胞凋亡蛋白家族成员之一）、DAPK（细胞死亡相关蛋白激酶）、GADD45b（生长停滞与DNA损伤诱导蛋白）等因子的表达，来诱导肿瘤细胞凋亡；以及抑制血管内皮细胞的生长和血管的成熟，从而阻断肿瘤营养的供给。这些作用维持了正常组织内的动态平衡，在早期阶段防止肿瘤形成。不过，TGF-β对恶变前癌细胞施加的压力，会迫使肿瘤细胞通过突变等手段避开TGF-β的抑制作用。这时候，TGF-β就变成了协助肿瘤细胞进行免疫逃逸的“叛军”。TGF-β首先会影响肿瘤微环境，即肿瘤在发生和发展过程中所处的内环境。TGF-β对于肿瘤微环境中所有免疫细胞，如T细胞、巨噬细胞、中性粒细胞等都表现出了免疫抑制，宿主抵抗肿瘤的能力也因此受到影响。另外，TGF-β可以通过诱导HMGA2（高迁移率族蛋白A2）、Snail1/2（肿瘤相关成纤维细胞活化相关蛋白）等转录因子的表达，诱发EMT，通过EMT肿瘤细胞得以实现扩散，侵入淋巴管和血管。不仅如此，TGF-β表达上调会促使VEGF-A（血管内皮生长因子A）等因子分泌，刺激血管生成，新生成的血管将为癌细胞的生长提供营养物质，助力癌细胞的生长和转移。研究还发现，TGF-β信号通路还与肿瘤细胞的耐药性相关。它可以通过上调PKCα（蛋白激酶Cα）表达增强肿瘤细胞的耐药性。总之，“叛变”后的TGF-β变成了肿瘤细胞的得力助手。PART.02靶向TGF-β的药物研发针对TGF-β促进肿瘤转移的机制，研究者们展开了TGF-β抑制剂的开发。其中，抗体药物因为拥有更好的靶向特异性和更好的药代动力学性质而备受关注。从正在开发的TGF-β靶向候选药来看，主要包括TGF-β单抗、双抗靶向药以及细胞治疗产品三大类。 01 TGF-β单抗靶向药NIS793是诺华旗下一款潜在的FIC（同类首创）全人源抗TGF-β IgG2单克隆抗体，可抑制肿瘤细胞的TGF-β通路，并调控肿瘤微环境，逆转免疫抑制和纤维化。目前，诺华正在全球范围内开展多项NIS793的临床试验，涉及的适应症包括转移性胰腺导管腺癌、转移性结直肠癌、肺癌等。其中，NIS793治疗胰腺导管腺癌的研究已进入到III期临床阶段。图2. NIS793（尼斯奇塔单抗）知识图谱，来源：药渡数据Galunisertib由礼来公司研发，是礼来在TGF-β领域抑制剂开发的先导，临床适应症主要指向骨髓增生异常综合征（MDS）、肝细胞癌（HCC），2014年即启动了MDS的II/III期临床，并于2017年完成；2011年启动的转移性胰腺癌Ib/IIa期试验，也于2016年完成；2017年8月发起的一项子宫/卵巢癌肉瘤患者的Ib期试验，目前暂未完成。图3. Galunisertib知识图谱，来源：药渡数据GFH018是劲方医药研发的一款口服小分子TGF-β抑制剂，于2019年进入临床试验，其在多种人体细胞系和疾病动物模型中显示出了良好的抗肿瘤药效和成药性，并显示了与免疫检查点抑制剂协同增效的作用。目前GFH018联合PD-1抑制剂（特瑞普利单抗）的全球多中心试验在中国大陆、中国台湾、澳大利亚进行，GFH018联合PD-1抑制剂及同步放化疗的联合疗法也在中国大陆进行。图4. GFH018（GF-101）知识图谱，来源：药渡数据YL-13027由璎黎药业研发，主要用于肝细胞癌等实体瘤适应症以及多发性骨髓瘤和MDS的治疗。临床前研究表明，YL-13027具有很高的体内外活性，优良的动物体内药代特性，显著的抗肿瘤效果和很高的安全性。在多种肿瘤模型药效试验中，YL-13027显示出了作为免疫抗肿瘤药物的能力，它通过显著增加肿瘤中肿瘤浸润淋巴细胞的数量来抑制肿瘤的生长，且和抗PD-L1抗体有很好的协同效果。YL-13027目前正在开展I期临床试验。图5. YL-13027知识图谱，来源：药渡数据 02 TGF-β双抗靶向药除了单抗药物，靶向TGF-β的双抗药物也是一个重要研发方向，其中以PD-L1/TGF-β双抗居多，它可通过同时阻断PD-L1和TGF-β这两个免疫抑制信号通路，从而恢复和增强机体的抗肿瘤反应。表1. 处于临床阶段的TGF-β双抗药物，来源：公开资料整理M7824在众多正在研发的TGF-β双抗药物中，默克/GSK的PD-L1/TGF-β双抗M7824（bintrafusp alfa）本来是进展最快的，但是在后续研发中却遭遇了一连串打击。M7824曾被认为是“PD-1 2.0”潜力选手，这是因为在2018年的ASCO大会上，M7824的I期临床数据非常优秀。研究显示，在使用1200mg剂量组的40例非小细胞肺癌（NSCLC）患者中，PD-L1阳性患者的客观缓解率（ORR）达到了惊人的40.7%，PD-L1高表达患者的ORR则高达71.4%，而在使用PD-1患者群体中，这个数值则为29-44%，有效率明显高于PD-1。图6. M7824作用机制示意图，来源：药渡数据在后面的ESMO大会上，M7824在含铂化疗一线治疗后病情进展的亚洲胆管癌患者中，ORR为23%。FDA因此授予M7824治疗胆管癌的孤儿药资格认定。2019年2月，GSK与默克宣布，双方达成全球战略合作联盟，共同负责M7824在全球范围内的临床开发及商业推广，交易总额高达37亿欧元。M7824凭一己之力使PD-L1/TGF-β成为医药界的新星。国内药企也抓住这一机会纷纷入局，其中恒瑞医药遥遥领先。不过好景不长，2021年，M7824接连遭遇多次失败。2021年1月份，M7824在微卫星高度不稳定（MSI-H）/错配修复缺陷（dMMR）实体瘤II期临床以及NSCLC III期临床研究中失败；2021年3月，M7824单药二线治疗局部晚期或转移性胆道癌（BTC）的II期临床试验失败：ORR为10.1%，未达到预先设置的阈值；2021年8月，M7824联合吉西他滨和顺铂一线治疗BTC患者的研究也宣告失败。2021年9月，默克宣布与GSK达成协议，终止M7824相关的合作。至此，默克对M7824的研发热情大大下降。从默克发布的2022年年报中，已经看不到M7824的身影。PD-LI/TGF-β的未来充满阴霾。表2. 默克公司的肿瘤研发管线，来源：默克2022年年报SHR-1701不过，国内研发进度靠前的恒瑞医药并未选择放弃，其自主研发的抗PD-L1/TGF-β双抗SHR-1701于2018年7月获得国家药监局的I期临床试验批件，成为国内第一个进入临床阶段的PD-L1/TGF-β双抗。根据恒瑞医药2022年年报显示，目前仍有12项关于SHR-1701的临床试验在推进，其中绝大多数为与其他药物的联用。PM8001、TQB2858 & LBL-015除恒瑞外，国内还有普米斯生物的PM8001、正大天晴的TQB2858以及维立志博的LBL-015，临床进度靠前。其中PM8001以分子量小、稳定性好的单域抗体为基础，同时靶向包括PD-L1的两个肿瘤相关靶点，从而提高抗肿瘤活性及疗效。目前，PM8001正处于临床II期阶段。 03 靶向TGF-β的细胞治疗产品除了单抗和双抗产品外，也有公司针对TGF-β开发细胞治疗产品。迪诺仑赛注射液永泰生物的迪诺仑赛注射液（原称CAR-T-19-D2、CART-19-DNR）即为靶向CD19抗原且拮抗TGF-β下游信号通路的一款CAR-T产品。在这款产品中，经过改造的T细胞可以直接识别CD19分子并杀伤携带靶标的细胞，从而达成治疗肿瘤的目的。此外，同步转录翻译表达细胞内部拮抗TGF-β下游信号通路的蛋白，具有阻遏肿瘤微环境中存在TGF-β所导致的免疫抑制效应的潜力，防止CAR-T细胞免疫杀伤能力的削弱与耗竭，从而进一步提高治疗效果。迪诺仑赛注射液旨在于解决CAR-T细胞对实体瘤治疗持久性不够、治疗效果欠佳的痛点。PART.03小结总的来说，由于TGF-β作用机制相对复杂，靶向TGF-β产品的开发仍有很多问题待解决。目前在最有前景的双抗领域，默克减缓M7824的研发进展到底是对是错？恒瑞医药能否“弯道超车”？都值得我们期待……参考资料：1. Rik Derynck et al. TGFβ biology in cancer progression and immunotherapy. Nature Reviews Clinical Oncology (2020).2. Zhai T, Wang C, Xu Y, et alGeneration of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer. Journal for ImmunoTherapy of Cancer 2021;9:e002131. doi: 10.1136/jitc-2020-002131.3. Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib.4. http://www.cninfo.com.cn/new/disclosure/detail?stockCode= 06978& announcementId= 1216181462& orgId=9900044697&announcementTime =2023-03-21.封面图来源：123rf精彩推荐FDA亲自帮忙修改临床终点，结果还是没打过安慰剂...药时代路演第三期 | 抗体领域龙头企业优质系列双抗对外授权7月“裁报季”，15家药企宣布裁员！73亿美元并购，刚宣布裁员节流的Biogen，就把手里的现金全花了......点击这里，与药时代一起快乐学习！

免疫疗法临床研究临床结果

100 项与葡聚糖硫酸酯钠硫18 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	B05AA05	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
高甘油三酯血症	日本	Kowa Co., Ltd.	1963-04-27

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00570960 (CTgov)	临床4期	自发性细菌性腹膜炎	8	Dextran (Dextran Therapy Arm)	鑰膚簾選糧積構蓋襯憲(願醖網醖積網糧糧膚網) = 鑰壓構壓鹽壓獵選顧網窪鏇淵膚憲蓋醖鑰觸鑰 (築鏇蓋糧醖範淵築構糧, 鏇廠鑰繭憲積觸製艱築 ~ 齋夢遞醖廠製鹽窪願遞) 更多	-	2014-12-03
				Albumin (Standard of Care Albumin Arm)	鑰膚簾選糧積構蓋襯憲(願醖網醖積網糧糧膚網) = 遞糧窪淵襯窪憲蓋醖鹽窪鏇淵膚憲蓋醖鑰觸鑰 (築鏇蓋糧醖範淵築構糧, 構選蓋鹽夢鏇選淵築獵 ~ 鹽蓋憲鹽積蓋壓鹽簾簾) 更多
Pubmed \| Crit Care Med	临床2期	疟疾	79	Dextran 70	鑰網壓鏇淵簾艱襯遞壓(餘夢鏇淵廠膚壓衊構鑰) = 鬱積簾廠範網膚繭範顧簾夢餘壓選壓鬱廠願網 (鑰艱襯壓範鏇夢膚觸襯 )	-	2010-08-01
				Hydroxyethyl starch	鑰網壓鏇淵簾艱襯遞壓(餘夢鏇淵廠膚壓衊構鑰) = 選鏇繭襯構簾構襯衊糧簾夢餘壓選壓鬱廠願網 (鑰艱襯壓範鏇夢膚觸襯 )