Search

Background: The empirical dietary inflammation pattern score (EDIP), which measures the ability of the diet to regulate chronic inflammation, is associated with both higher adiposity and breast cancer (BC) risk. Mammographic density (MD) is an important risk factor for BC., Objective: We examined the associations between EDIP and mammographic features overall and stratified by menopausal status, and assessed the extent to which these associations are mediated by adiposity., Methods: We included 4145 participants without BC in the Nurses' Health Study (NHS) and NHSII. Cumulative average EDIP was assessed by food frequency questionnaires every 4-6 y. We assessed MD parameters (percent MD, dense area, and nondense area) and V (measure of grayscale variation). MD parameters were square-root transformed. Multivariable-adjusted linear regression models were used to analyze the associations between EDIP score and MD parameters. Baron and Kenny's regression method was used to assess the extent to which the associations of EDIP and mammographic traits were mediated by BMI., Results: In multivariable-adjusted models, EDIP was significantly inversely associated with percent MD [top compared with bottom quartile, β = -0.57; 95% confidence interval (CI): -0.78, -0.36]. Additional adjustment for BMI attenuated the association (β = -0.15; 95% CI: -0.34, 0.03), with 68% (β = 0.68, 20; 95% CI: 0.54, 0.86) mediation via BMI. In addition, EDIP was positively associated with nondense area after adjusting for BMI and other covariates. No associations were observed for dense area and V measure. Results were similar when stratified by menopausal status., Conclusions: EDIP score was inversely associated with percent MD and positively associated with nondense area, and these associations were largely mediated by BMI., Competing Interests: Conflict of interest PS received salary from Merck & Co., Inc. However, this had no role in the study design, data collection, analyses, and data interoperation, in writing the paper or in the decision to submit the paper for publication. All other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Midazolam is an ultra short acting benzodiazepine derivative and a specific probe for phenotyping cytochrome P450 (P450) 3A4/5 activity. A rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantitation of midazolam and its metabolites (1'-hydroxymidazolam and 4-hydroxymidazolam). Deuterated (D5) analog of midazolam was utilized as an internal standard. Sample preparation either from human plasma (100 microL) or liver microsomal incubations involved a simple protein precipitation using acetonitrile (900 microL) with an average recovery of >90% for all compounds. The chromatographic separation was achieved using Zorbax-SB Phenyl, Rapid Resolution HT (2.1 mm x 100 mm, 3.5 microm) and a gradient elution with 10 mM ammonium acetate in 10% methanol (A) and acetonitrile (B). The flow rate was 0.25 mL/min and total run time was 5.5 min. Calibration curves were linear over the concentration range of 0.100-250 ng/mL. The lower limit of quantitation (LLOQ) was 0.1 ng/mL for all three analytes. The accuracy and precision, estimated at LLOQ and three concentration levels of quality control samples in six replicates, were within 85-115%. In conclusion, a robust, simple and highly sensitive analytical method was developed and validated for the analysis of midazolam and its metabolites. This method is suitable for characterizing the P450 3A4/5 activity in vitro or in human pharmacokinetic studies allowing administration of smaller doses of midazolam., (Copyright 2010 Elsevier B.V. All rights reserved.)

Iodixanol is a widely used iso-osmolar contrast medium agent. Similar to iohexol, it can also be a good exogenous marker for the measurement of glomerular filtration rate (GFR). This article describes the development and validation of an HPLC-UV method for quantification of iodixanol in human plasma. Internal standard, iohexol (20 microl, 1 mg/ml), and perchloric acid (30 microl, 20%, v/v) were added to plasma samples (300 microl), followed by neutralization with 10 microl potassium carbonate (5M). Samples were centrifuged and 10 microl of the supernatant was injected onto a C(18) EPS analytical column (3 microm particle size, 150 mm x 4.6 mm). The extraction method yielded >95% recovery for both iodixanol and iohexol. The mobile phase consisted of 0.1% (w/v) sodium formate buffer and acetonitrile. Iohexol and iodixanol peaks were eluted at approximately 5 and 9 min, respectively using a fast gradient method. The assay lower limit of detection was 2.0 microg/ml and lower limit of quantification was 10 microg/ml. The calibration curves, assessed in six replicates, were linear over an iodixanol concentration range of 10-750 microg/ml. Intra- and inter-day accuracy was >95% and precision expressed as % coefficient of variation was <10%. This method is simple, accurate, precise and robust and can potentially be used for iodixanol quantification in large-scale clinical studies.