{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:17:48Z","timestamp":1781932668371,"version":"3.54.5"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["ICMx"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma inhibition in clinical and experimental sepsis. We specifically hypothesized that plasma HYAL acts as endothelial glycocalyx shedding enzyme, sheddase.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Plasma hyaluronan, effective HYAL activity and HYAL inhibition were measured in healthy volunteers (<jats:italic>n<\/jats:italic>\u2009=\u200920), in patients with septic shock (<jats:italic>n<\/jats:italic>\u2009=\u200917, day 1 and day 4), in patients with acute pancreatitis (<jats:italic>n<\/jats:italic>\u2009=\u20097, day 1 and day 4) and in anesthetized and mechanically ventilated pigs (<jats:italic>n<\/jats:italic>\u2009=\u200916). Sixteen pigs were allocated (unblinded, open label) into three groups: Sepsis-1 with infusion of live <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) 1\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>\u00a0CFU\/h of 12\u00a0h (<jats:italic>n<\/jats:italic>\u2009=\u20095), Sepsis-2 with infusion of <jats:italic>E. coli<\/jats:italic> 1\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>\u00a0CFU\/h of 6\u00a0h followed by 1\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\u00a0CFU\/h of the remaining 6\u00a0h (<jats:italic>n<\/jats:italic>\u2009=\u20095) or Control with no <jats:italic>E. coli<\/jats:italic> infusion (<jats:italic>n<\/jats:italic>\u2009=\u20096).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In experimental <jats:italic>E. coli<\/jats:italic> porcine sepsis and in time controls, plasma hyaluronan increases with concomitant decrease in effective plasma HYAL activity and increase of endogenous HYAL inhibition. Plasma hyaluronan increased in patients with septic shock but not in acute pancreatitis. Effective plasma HYAL was lower in septic shock and acute pancreatitis as compared to healthy volunteers, while plasma HYAL inhibition was only increased in septic shock.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Elevated plasma hyaluronan levels coincided with a concomitant decrease in effective plasma HYAL activity and increase of endogenous plasma HYAL inhibition both in experimental and clinical sepsis. In acute pancreatitis, effective plasma HYAL activity was decreased which was not associated with increased plasma hyaluronan concentrations or endogenous HYAL inhibition. The results suggest that plasma HYAL does not act as sheddase in sepsis or pancreatitis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40635-021-00418-3","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T23:03:16Z","timestamp":1633906996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-7131","authenticated-orcid":false,"given":"Jaap","family":"van der Heijden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Kolliopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Skorup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Sallisalmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Heldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hultstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyrki","family":"Tenhunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"418_CR1","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","volume":"193","author":"C Fleischmann","year":"2016","unstructured":"Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P et al (2016) Assessment of global incidence and mortality of hospital-treated sepsis. 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Clinical study\u2014The institutional ethics committee of the Helsinki University Central Hospital approved the study (permit number 101\/13\/03\/02\/08). Written consent for participation in the study was obtained from either the patient or their next of kin prior to enrolment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"53"}}