{"title":"Cardiac vagal activity and daily clinical practice.","authors":"Luc Quintin, John M Karemaker, Robin M McAllen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":94073,"journal":{"name":"Journal of clinical and translational research","volume":"2 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2016-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuchao Xie, Benjamin L Woolbright, Milan Kos, Mitchell R McGill, Kenneth Dorko, Sean C Kumer, Timothy M Schmitt, Hartmut Jaeschke
{"title":"Lack of direct cytotoxicity of extracellular ATP against hepatocytes: role in the mechanism of acetaminophen hepatotoxicity.","authors":"Yuchao Xie, Benjamin L Woolbright, Milan Kos, Mitchell R McGill, Kenneth Dorko, Sean C Kumer, Timothy M Schmitt, Hartmut Jaeschke","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Acetaminophen (APAP) hepatotoxicity is a major cause of acute liver failure in many countries. Mechanistic studies in mice and humans have implicated formation of a reactive metabolite, mitochondrial dysfunction and oxidant stress as critical events in the pathophysiology of APAP-induced liver cell death. It was recently suggested that ATP released from necrotic cells can directly cause cell death in mouse hepatocytes and in a hepatoma cell line (HepG2).</p><p><strong>Aim: </strong>To assess if ATP can directly cause cell toxicity in hepatocytes and evaluate their relevance in the human system.</p><p><strong>Methods: </strong>Primary mouse hepatocytes, human HepG2 cells, the metabolically competent human HepaRG cell line and freshly isolated primary human hepatocytes were exposed to 10-100 µM ATP or ATγPin the presence or absence of 5-10 mM APAP for 9-24 h.</p><p><strong>Results: </strong>ATP or ATγP was unable to directly cause cell toxicity in all 4 types of hepatocytes. In addition, ATP did not enhance APAP-induced cell death observed in primary mouse or human hepatocytes, or in HepaRG cells as measured by LDH release and by propidium iodide staining in primary mouse hepatocytes. Furthermore, addition of ATP did not cause mitochondrial dysfunction or enhance APAP-induced mitochondrial dysfunction in primary murine hepatocytes, although ATP did cause cell death in murine RAW macrophages.</p><p><strong>Conclusions: </strong>It is unlikely that ATP released from necrotic cells can significantly affect cell death in human or mouse liver during APAP hepatotoxicity.</p><p><strong>Relevance for patients: </strong>Understanding the mechanisms of APAP-induced cell injury is critical for identifying novel therapeutic targets to prevent liver injury and acute liver failure in APAP overdose patients.</p>","PeriodicalId":94073,"journal":{"name":"Journal of clinical and translational research","volume":"1 2","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dara R Pabittei, Wadim de Boon, Michal Heger, Rowan F van Golen, Ron Balm, Dink A Legemate, Bas A de Mol
{"title":"Laser-assisted vessel welding: state of the art and future outlook.","authors":"Dara R Pabittei, Wadim de Boon, Michal Heger, Rowan F van Golen, Ron Balm, Dink A Legemate, Bas A de Mol","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Laser-assisted vascular welding (LAVW) is an experimental technique being developed as an alternative to suture anastomosis. In comparison to mechanical anastomosis, LAVW is less traumatic, non-immunogenic, provides immediate water tight sealant, and possibly a faster and easier procedure for minimally invasive surgery. This review focuses on technical advances to improve welding strength and to reduce thermal damage in LAVW. In terms of welding strength, LAVW has evolved from the photothermally-induced microvascular anastomosis, requiring stay sutures to support welding strength, to sutureless anastomoses of medium-sized vessels, withstanding physiological and supraphysiological pressure. Further improvements in anastomotic strength could be achieved by the use of chromophore-containing albumin solder and the employment of (biocompatible) polymeric scaffolds. The anastomotic strength and the stability of welds achieved with such a modality, referred to as scaffold- and solder-enhanced LAVW (ssLAVW), are dependent on the intermolecular bonding of solder molecules (cohesive bonding) and the bonding between solder and tissue collagen (adhesive bonding). Presently, the challenges of ssLAVW include (1) obtaining an optimal balance between cohesive and adhesive bonding and (2) minimizing thermal damage. The modulation of thermodynamics during welding, the application of semi-solid solder, and the use of a scaffold that supports both cohesive and adhesive strength are essential to improve welding strength and to limit thermal damage.</p>","PeriodicalId":94073,"journal":{"name":"Journal of clinical and translational research","volume":"1 2","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}