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Introduction: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate‐to‐severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post‐tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post‐tonsillectomy pain. Methods: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. Results: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post‐tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post‐tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. Conclusion: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post‐tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries. [ABSTRACT FROM AUTHOR]

Background Serum vitamin B-12 is measured to evaluate vitamin B-12 status. Serum methylmalonic acid (MMA) is a specific functional indicator of vitamin B-12 status; however, concentrations increase with impaired renal function. Objective The aim of this study was to describe the distribution of serum vitamin B-12 and MMA in US adults, and estimate age-specific reference intervals for serum MMA in a healthy subpopulation with replete vitamin B-12 status and normal renal function. Methods We examined cross-sectional data for serum vitamin B-12 and MMA in adults participating in the NHANES from 2011 to 2014. Vitamin B-12 was measured by electrochemiluminescence assay and MMA by isotope-dilution liquid chromatography–tandem mass spectrometry. Results In both bivariate and multivariate analyses, age, race/Hispanic origin, and vitamin B-12 supplement use were generally significantly associated with serum vitamin B-12 and MMA concentrations. Serum MMA concentrations increased with age, particularly in persons aged ≥70 y. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations than non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were widest for persons aged ≥70 y compared with younger age groups. Compared with the overall population, the central 95% reference intervals for serum MMA concentrations were considerably narrower for a vitamin B-12–replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, whereas serum MMA showed notable, increases with impaired renal function. Conclusions The higher serum MMA concentrations throughout the entire distribution in older persons (especially persons aged ≥70 y) who are vitamin B-12–replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret vitamin B-12 status in epidemiologic research. [ABSTRACT FROM AUTHOR]

Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n=14); RMR + CAA: RMR rats treated with CAA (n=13); SO: SO rats without treatment (n=13); and SO + CAA: SO rats treated with CAA (n=13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p<0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p<0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress. [ABSTRACT FROM AUTHOR]

Abstract: 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a complex mixture of nine carbon branched-chain isomers. It has been used in Europe since 2002 as a plasticizer to replace phthalates such as di(2-ethylhexyl)phthalate (DEHP) and diisononyl phthalate (DINP). Urinary concentrations of the oxidative metabolites of DINCH, namely cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (MCOCH); cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (MONCH); and cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (MHNCH), can potentially be used as DINCH exposure biomarkers. The concentrations of MCOCH, MONCH and MHNCH were measured by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry in urine collected in 2000 (n=114), 2001 (n=57), 2007 (n=23), 2009 (n=118), 2011 (n=94) and 2012 (n=121) from convenience groups of anonymous U.S. adult volunteers with no known DINCH exposure. None of the DINCH metabolites were detected in samples collected in 2000 and 2001. Only one sample collected in 2007 had measureable concentrations of DINCH metabolites. The detection rate for all three metabolites increased from 2007 to 2012. The presence of oxidative metabolites of DINCH in urine suggests that these oxidative metabolites can be used as DINCH biomarkers for exposure assessment even at environmental exposure levels. [Copyright &y& Elsevier]

Objective: The aim of this study is to investigate the effect of ionization and vehicle of topical formulations on skin absorption and penetration of azelaic acid (AZA). Materials and methods: In vitro transport of AZA was determined for two topical formulations containing AZA with pH values of 3.9 and 4.9, respectively. FINACEA® (15% AZA gel), a US Food and Drug Administration approved drug for treatment of acne and rosacea, was also used for comparison. Release profile and flux of AZA were determined in an in vitro hairless mouse skin model using Franz Diffusion Cell. Results: The data have shown that a higher concentration of AZA is retained in the epidermis/dermis layer and the whole skin for the formulation with pH = 4.9 as compared to that with pH = 3.9 at an active loading level of 2.82 mg/cm2. In addition, the flux of ionized species of AZA in the pH 4.9 formulation (128.4 ± 35.9 μg/cm2/h) is approximately five-fold greater than that in the pH 3.9 formulation (27.7 ± 4.0 μg/cm2/h). The results suggest that the ionized AZA penetrates through the skin and accounts for majority of the total flux. Discussion and conclusion: This study has demonstrated that the penetration and absorption of AZA show a strong pH- and vehicle-dependency. Solubilization is the rate-limiting step in percutaneous absorption of AZA. [ABSTRACT FROM AUTHOR]