5 results on '"Harnisch, Lars-Olav"'
Search Results
2. Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial.
- Author
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Harnisch, Lars-Olav, Neugebauer, Sophie, Mihaylov, Diana, Eidizadeh, Abass, Zechmeister, Bozena, Maier, Ilko, and Moerer, Onnen
- Subjects
BILE acids ,CEREBROSPINAL fluid ,DEOXYCHOLIC acid ,CENTRAL nervous system ,BLOOD-brain barrier - Abstract
(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [−0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood–brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood–brain barrier. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value
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Harnisch, Lars-Olav, Baumann, Sophie, Mihaylov, Diana, Kiehntopf, Michael, Bauer, Michael, Moerer, Onnen, and Quintel, Michael
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bile acids ,Medicine (General) ,R5-920 ,ARDS ,cholestasis ,digestive system ,Article ,liver injury ,GGT - Abstract
Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels.
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- 2021
4. Determination of individual bile acids in acute respiratory distress syndrome reveals a specific pattern of primary and secondary bile acids and a shift to the acidic pathway as an adaptive response to the critical condition.
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Harnisch, Lars-Olav, Mihaylov, Diana, Bein, Thomas, Apfelbacher, Christian, Kiehntopf, Michael, Bauer, Michael, Moerer, Onnen, and Quintel, Michael
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ADULT respiratory distress syndrome , *BILE acids , *BILE , *CONDITIONED response , *ENTEROHEPATIC circulation , *GLUCAGON-like peptide-1 agonists , *FARNESOID X receptor - Abstract
Above that, sequential testing could help estimate the course of the disease in terms of resolution (bile acid profile returns to normal) or deterioration (bile acid profile displays the specific adaptive response further or even changes to a "maladaptive profile" most likely reflected by increases in secondary bile acids) of the disease. Currently, it is unknown whether mentioned treatment measures interfere with bile acid metabolism (detectable as cholestasis/increased levels of bile acid in serum) or rather a specific adaptive regulatory response leads to such a specific bile acid pattern. Keywords: acidic pathway; adaptive response; ARDS; bile acid pattern; bile acids EN acidic pathway adaptive response ARDS bile acid pattern bile acids 891 900 10 05/12/22 20220501 NES 220501 Introduction Cholestasis, defined as impaired or blocked bile flow from the liver, is a common finding in approximately 20% of critically ill patients [[1]], [[2]], [[3]]. [Extracted from the article]
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- 2022
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5. The Specific Bile Acid Profile of Shock: A Hypothesis Generating Appraisal of the Literature.
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Harnisch, Lars-Olav and Moerer, Onnen
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BILE acids , *DEOXYCHOLIC acid , *CARDIOGENIC shock , *SEPTIC shock , *METABOLIC regulation , *CRITICALLY ill - Abstract
Background: Bile acid synthesis and regulation of metabolism are tightly regulated. In critical illness, these regulations are impaired. Consequently, the physiologic bile acid pattern in serum becomes disturbed and a disease-specific bile acid profile seems to become evident. Methods: A literature review was performed and trials reporting the broken-down bile acid pattern were condensed with regard to percent differences in bile acid profiles of defined diseases compared to a human control. Results: Ten articles were identified. Most of the studied bile acid profiles differ statistically significant between disease states, furthermore, neither of the reported disease entities show the same broken-down pattern of individual bile acids. Deoxycholic acid (DCA) was found to be decreased in almost all diseases, except for the two shock-states investigated (cardiogenic shock, septic shock) where it was elevated by about 100% compared to the control. Moreover, the pattern of both examined shock-states are very similar, rendering a specific shock-pattern possible, that we argue could eventually maintain or even worsen the pathological state. Conclusion: The specific broken-down bile acid profile of defined diseases might aid in gaining insight into the body's adaptive reaction and the differential diagnosis, as well as in the therapy of disease states in the early course of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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