Method for the quantitative assay of fatty acid-bile acid conjugates by tandem mass spectrometry

Fatty acid-bile acid conjugates and especially arachidyl amido cholic acid are synthetic molecules that were shown to prevent cholesterol gallstone formation in mice and hamsters as well as to dissolve pre-existing gallstones in mice. To measure these novel compounds we developed a liquid chromatography electrospray tandem mass spectrometry method based on the analysis of 100 mul of plasma with stearyl amido cholic acid (stamchol, 1.5 mumol/l) added as internal standard. Repeatable calibrations between 0 and 50 mumol/l exhibited consistent linearity and reproducibility. Inter- and intraassay C.V.s were 5.3-11.4% and 2.6-6.4%, respectively, at targeted concentrations of 0.1, 2.3 and 50 mumol/l. (C) 2003 Elsevier B.V. All rights reserve

No association between Helicobacter pylori infection or CagA-bearing strains and glaucoma

Background and Purpose: Accumulating evidence indicates that a variety of infections contribute to the pathogenesis of glaucoma. The role of Helicobacter pylori infection in glaucoma is controversial

Biomarker-Guided Assessment of Acute Kidney Injury Phenotypes E among ST-Segment Elevation Myocardial Infarction Patients

Recent practice guidelines recommended the use of new stress, functional, and damage biomarkers in clinical practice to prevent and manage acute kidney injury (AKI). Biomarkers are one of the tools used to define various AKI phenotypes and provide prognostic information regardless of an acute decline in renal function. We investigated the incidence and possible implications of AKI phenotypes among ST elevation myocardial infarction patient treated with primary coronary intervention. We included 281 patients with STEMI treated with PCI. Neutrophil gelatinase associated lipocalin (NGAL) was utilized to determine structural renal damage and functional AKI was determined using the KDIGO criteria. Patients were stratified into four AKI phenotypes: no AKI, subclinical AKI, hemodynamic AKI, and severe AKI. Patients were assessed for in-hospital adverse events (MACE). A total of 46 patients (44%) had subclinical AKI, 17 (16%) had hemodynamic AKI, and 42 (40%) had severe AKI. We observed a gradual and significant increase in the occurrence of MACE between the groups being highest among patients with severe AKI (10% vs. 19% vs. 29% vs. 43%; p p p = 0.004) for hemodynamic AKI, and 12.9 (95% CI 5.59–30.1, p < 0.001) for severe AKI. In conclusion, among STEMI patients, AKI is a heterogeneous condition consisting of distinct phenotypes, addition of novel biomarkers may overcome the limitations of sCr-based AKI definitions to improve AKI phenotyping and direct potential therapies

Early Detection of Inflammation-Prone STEMI Patients Using the CRP Troponin Test (CTT)

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p p p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents

Sepsis Related Mortality Associated with an Inflammatory Burst in Patients Admitting to the Department of Internal Medicine with Apparently Normal C-Reactive Protein Concentration

Background: Patients who are admitted to the Department of Internal Medicine with apparently normal C-reactive protein (CRP) concentration impose a special challenge due the assumption that they might not harbor a severe and potentially lethal medical condition. Methods: A retrospective cohort of all patients who were admitted to the Department of Internal Medicine with a CRP concentration of &le;31.9 mg/L and had a second CRP test obtained within the next 24 h. Seven day mortality data were analyzed. Results: Overall, 3504 patients were analyzed with a mean first and second CRP of 8.8 (8.5) and 14.6 (21.6) mg/L, respectively. The seven day mortality increased from 1.8% in the first quartile of the first CRP to 7.5% in the fourth quartile of the first CRP (p &lt; 0.0001) and from 0.6% in the first quartile of the second CRP to 9.5% in the fourth quartile of the second CRP test (p &lt; 0.0001), suggesting a clear relation between the admission CRP and in hospital seven day mortality. Conclusions: An association exists between the quartiles of CRP and 7-day mortality as well as sepsis related cause of death. Furthermore, the CRP values 24 h after hospital admission improved the discrimination

ABCA1-dependent but apoA-I-independent cholesterol efflux mediated by fatty acid-bile acid conjugates (FABACs)

FABACs (fatty acid-bile acid conjugates) are synthetic molecules that are designed to treat a range of lipid disorders. The compounds prevent cholesterol gallstone formation and diet-induced fatty liver, and increase reverse cholesterol transport in rodents. The aim of the present study was to investigate the effect of FABACs on cholesterol efflux in human cells. Aramchol (3beta-arachidylamido-7alpha,12alpha,5beta-cholan-24-oic acid) increased cholesterol efflux from human skin fibroblasts in a dose-dependent manner in the absence of known efflux mediators such as apoA-I (apolipoprotein A-I), but had little effect on phospholipid efflux. An LXR (liver X receptor) agonist strongly increased Aramchol-induced cholesterol efflux; however, in ABCA1 (ATP-binding cassette transporter A1)-deficient cells from Tangier disease patients, the Aramchol effect was absent, indicating that activity of ABCA1 was required. Aramchol did not affect ABCA1 expression, but plasma membrane levels of the transporter increased 2-fold. Aramchol is the first small molecule that induces ABCA1-dependent cholesterol efflux without affecting transcriptional control. These findings may explain the beneficial effect of the compound on atherosclerosi