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Browsing by Subject "Lipase"
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Item Does Hyperlipasemia Predict Worse Clinical Outcomes in COVID-19? A Multicenter Retrospective Cohort Study(Wolters Kluwer, 2022) Singh, Ritu R.; Chhabra, Puneet; Kumta, Nikhil A.; Medicine, School of MedicineGoal: We aim to perform a multicenter retrospective cohort study to determine if elevated serum lipase determines clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Background: Several cases of acute pancreatitis (AP) have recently been reported in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most of the evidence is based on elevated serum lipase values without objective demonstration of pancreatic inflammation or necrosis. Materials and methods: A population-based, multicenter, retrospective cohort study utilizing TriNetX was performed to obtain aggregated health records of ∼69 million patients from 49 health care organizations from January 1, 2020, to December 31, 2020. Adult patients (18 y and above) diagnosed with COVID-19 were identified using appropriate International Classification of Diseases, 10th Revision (ICD-10) codes and were stratified into 2 groups, with elevated (≥180 U/L) and with normal (≤80 U/L) serum lipase. The primary outcome was 30-day mortality; other outcomes were 30-day rehospitalization, need for mechanical ventilation, need for vasopressor use, acute kidney injury. Results: A total of 435,731 adult patients with COVID-19 were identified, and 1406 of them had elevated serum lipase which was associated with higher 30-day mortality [risk ratio (RR)=1.53, P<0.001], risk of acute kidney injury (RR=1.5, P=0.003), and vasopressor use (RR=1.69, P<0.001) without any difference in 30-day rehospitalization (RR=0.98, P=0.54), or need for mechanical ventilation (RR=1.20, P=0.26). The negative predictive value of normal serum lipase for 3-month mortality in patients with COVID-19 was 91%. Conclusions: Patients with COVID-19 who have elevated serum lipase experience worse clinical outcomes even in the absence of AP. If these findings can be replicated in prospective studies, serum lipase can be utilized as a marker of disease severity in patients with COVID-19.Item Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis(Editorial Office of Gut and Live, 2017-11) Oh, Hyoung-Chul; Kwon, Chang-Il; El Hajj, Ihab I.; Easler, Jeffrey J.; Watkins, James; Fogel, Evan L.; McHenry, Lee; Sherman, Stuart; Zimmerman, Michelle K.; Lehman, Glen A.; Medicine, School of MedicineBackground/Aims This study aimed to evaluate the diagnostic role of low serum amylase and lipase values in the detection of chronic pancreatitis. Methods Patients underwent endoscopic retrograde cholangiopancreatography and were diagnosed with non-calcific chronic pancreatitis (NCCP; n=99) and calcific chronic pancreatitis (CCP; n=112). Patient serum amylase and lipase values were compared with those of healthy controls (H; n=170). Results The median serum amylase (normal range, 19 to 86 U/L) and lipase values (7 to 59 U/L) (P25–P75) were 47.0 (39.8 to 55.3) and 25.0 (18.0 to 35.0) for H, 34.0 (24.5 to 49.0) and 19.0 (9.0 to 30.0) for NCCP, and 30.0 (20.0 to 40.8) and 10.0 (3.0 to 19.0) for CCP, respectively. The cutoff values with the highest diagnostic accuracy for discriminating NCCP from H were 40 U/L for amylase and 20 U/L for lipase, respectively, and for CCP from H were 38 U/L for amylase and 15 U/L for lipase, respectively. For the diagnosis of NCCP with a criterion of serum amylase <40 and lipase <20 U/L, the sensitivity, specificity, positive predictive value, and negative predictive values were 37.4%, 88.8%, 66.1%, and 70.9%, respectively. Conclusions Serum amylase and/or lipase levels below the normal serum range are highly specific for chronic pancreatitis patients. Clinicians should not ignore low serum pancreatic enzyme values.Item Lysosomal Acid Lipase Hydrolyzes Retinyl Ester and Affects Retinoid Turnover(American Society for Biochemistry & Molecular Biology, 2016-08-19) Grumet, Lukas; Eichmann, Thomas O.; Taschler, Ulrike; Zierler, Kathrin A.; Leopold, Christina; Moustafa, Tarek; Radovic, Branislav; Romauch, Matthias; Yan, Cong; Du, Hong; Haemmerle, Guenter; Zechner, Rudolf; Fickert, Peter; Kratky, Dagmar; Zimmermann, Robert; Lass, Achim; Department of Pathology and Laboratory Medicine, IU School of MedicineLysosomal acid lipase (LAL) is essential for the clearance of endocytosed cholesteryl ester and triglyceride-rich chylomicron remnants. Humans and mice with defective or absent LAL activity accumulate large amounts of cholesteryl esters and triglycerides in multiple tissues. Although chylomicrons also contain retinyl esters (REs), a role of LAL in the clearance of endocytosed REs has not been reported. In this study, we found that murine LAL exhibits RE hydrolase activity. Pharmacological inhibition of LAL in the human hepatocyte cell line HepG2, incubated with chylomicrons, led to increased accumulation of REs in endosomal/lysosomal fractions. Furthermore, pharmacological inhibition or genetic ablation of LAL in murine liver largely reduced in vitro acid RE hydrolase activity. Interestingly, LAL-deficient mice exhibited increased RE content in the duodenum and jejunum but decreased RE content in the liver. Furthermore, LAL-deficient mice challenged with RE gavage exhibited largely reduced post-prandial circulating RE content, indicating that LAL is required for efficient nutritional vitamin A availability. In summary, our results indicate that LAL is the major acid RE hydrolase and required for functional retinoid homeostasis.Item Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation(American Society for Biochemistry and Molecular Biology, 2017-07-28) Tuohetahuntila, Maidina; Molenaar, Martijn R.; Spee, Bart; Brouwers, Jos F.; Wubbolts, Richard; Houweling, Martin; Yan, Cong; Du, Hong; VanderVen, Brian C.; Vaandrager, Arie B.; Helms, J. Bernd; Medicine, School of MedicineActivation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters, and retinyl esters (REs). We previously provided evidence for the presence of two distinct LD pools, a preexisting and a dynamic LD pool. Here we investigate the mechanisms of neutral lipid metabolism in the preexisting LD pool. To investigate the involvement of lysosomal degradation of neutral lipids, we studied the effect of lalistat, a specific lysosomal acid lipase (LAL/Lipa) inhibitor on LD degradation in HSCs during activation in vitro The LAL inhibitor increased the levels of TAG, cholesteryl ester, and RE in both rat and mouse HSCs. Lalistat was less potent in inhibiting the degradation of newly synthesized TAG species as compared with a more general lipase inhibitor orlistat. Lalistat also induced the presence of RE-containing LDs in an acidic compartment. However, targeted deletion of the Lipa gene in mice decreased the liver levels of RE, most likely as the result of a gradual disappearance of HSCs in livers of Lipa-/- mice. Lalistat partially inhibited the induction of activation marker α-smooth muscle actin (α-SMA) in rat and mouse HSCs. Our data suggest that LAL/Lipa is involved in the degradation of a specific preexisting pool of LDs and that inhibition of this pathway attenuates HSC activation.Item Nature and function of cardiac lipase(1968) Christian, Dennis RayItem Studies on pancreatic lipase(1969) Yip, Yum Keung