Am J Physiol Lung Cell Mol Physiol
November 2023
Although PAH is partially attributed to disordered metabolism, previous human studies have mostly examined circulating metabolites at a single time point, potentially overlooking crucial disease biology. Current knowledge gaps include an understanding of temporal changes that occur within and across relevant tissues, and whether observed metabolic changes might contribute to disease pathobiology. We utilized targeted tissue metabolomics in the Sugen hypoxia (SuHx) rodent model to investigate tissue-specific metabolic relationships with pulmonary hypertensive features over time using regression modeling and time-series analysis.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
June 2023
Right ventricular (RV) adaptation is the principal determinant of outcomes in pulmonary arterial hypertension (PAH), however, RV function is challenging to assess. RV responses to hemodynamic stressors are particularly difficult to interrogate without invasive testing. This study sought to identify metabolomic markers of in vivo right ventricular function and exercise performance in PAH.
View Article and Find Full Text PDFIn pulmonary artery hypertension (PAH), emerging evidence suggests that metabolic abnormalities may be contributing to cellular dysfunction in PAH. Metabolic abnormalities such as glycolytic shift have been observed intracellularly in several cell types in PAH, including microvacular endothelial cells (MVECs). Concurrently, metabolomics of human PAH samples has also revealed a variety of metabolic abnormalities; however the relationship between the intracellular metabolic abnormalities and the serum metabolome in PAH remains under investigation.
View Article and Find Full Text PDFD-Amino acids are regulatory molecules that affect biological processes. Therefore, being able to accurately detect and quantify these compounds is important for understanding their impact on nutrition and health. There is a paucity of information regarding D-amino acids in human milk.
View Article and Find Full Text PDFWallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability of these events to therapeutic interventions remain unclear.
View Article and Find Full Text PDFNewborn screening using dried plasma spots offers preanalytical advantages over conventional cards for plasma-associated targets of interest. Herein we present dried plasma spot-based methods for measuring metabolites using a 250+ compound liquid chromatography tandem mass spectrometry library. Quality assurance reduced this library to 134, and from these, 30 compounds determined the normal newborn reference ranges.
View Article and Find Full Text PDFBackground: To investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS) from healthy term neonates or neonates with NE.
Methods: Plasma samples from the NE (n = 45, day of life 0-1) or healthy neonatal (n = 30, ≥36 weeks gestation) cohorts had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to 2-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III).
Protein glycosylation is one of the most common protein modifications, and the quantitative analysis of glycoproteins has the potential to reveal biological functions and their association with disease. However, the high throughput accurate quantification of glycoproteins is technically challenging due to the scarcity of robust assays to detect and quantify glycoproteins. Here we describe the development of multiplexed targeted MS assays to quantify N-linked glycosite-containing peptides in serum using parallel reaction monitoring (PRM).
View Article and Find Full Text PDFNew technologies in mass spectrometry are beginning to mature and show unique advantages for the identification and quantitation of proteins. In recent years, one of the significant goals of clinical proteomics has been to identify biomarkers that can be used for clinical diagnosis. As technology has progressed, the list of potential biomarkers has grown.
View Article and Find Full Text PDFProteomics analysis is important for characterizing tissues to gain biological and pathological insights, which could lead to the identification of disease-associated proteins for disease diagnostics or targeted therapy. However, tissues are commonly embedded in optimal cutting temperature medium (OCT) or are formalin-fixed and paraffin-embedded (FFPE) in order to maintain tissue morphology for histology evaluation. Although several tissue proteomic analyses have been performed on FFPE tissues using advanced mass spectrometry (MS) technologies, high-throughput proteomic analysis of OCT-embedded tissues has been difficult due to the interference of OCT in the MS analysis.
View Article and Find Full Text PDFGlycans play significant roles in physiological and pathological processes. Therefore, quantitative analysis of glycans from normal and disease specimens can provide insight into disease onset and progression. Relative glycan quantification usually requires modification of the glycans with either chromogenic or fluorogenic tags for optical measurement or isotopic tags for mass spectrometric analysis.
View Article and Find Full Text PDFBackground: The addition of a calibration curve with every run is both time-consuming and expensive for clinical mass spectrometry assays. We present alternative calibration strategies that eliminate the need for a calibration curve except as required by laboratory regulations.
Methods: We measured serum nortriptyline concentrations prospectively in 68 patients on 16 days over a 2-month period using a method employing calibration schemes that relied on the measurement of the response ratio (RR) corrected by the response factor (RF), i.
Infect Control Hosp Epidemiol
April 2011
We collected serial blood samples from children in the intensive care unit who underwent daily bathing with 2% chlorhexidine gluconate (CHG)-impregnated cloths. Low concentrations of CHG were detected in a few blood samples, indicating absorption through intact skin. There was no suggestion that CHG accumulated in the blood with repeated exposures.
View Article and Find Full Text PDFBackground: When creatinine concentrations determined by routine clinical assays are in question, reference methods can aid investigation. Currently available reference methods are significantly labor-intensive, which prevents implementation in a routine clinical laboratory.
Methods: Creatinine D-3 internal standard was added to serum prior to chromatographic separation.
Background: We describe a fully-automated turbulent-flow liquid chromatography-tandem mass spectrometry method for the detection of tricyclic antidepressant drugs (amitriptyline, desipramine, imipramine, and nortriptyline) in serum.
Methods: Human serum and an internal standard were injected directly onto a Cyclone-P online solid-phase extraction (SPE) column (0.5 x 50 mm).
Evid Based Complement Alternat Med
June 2008
Avocado/soy unsaponifiable (ASU) components are reported to have a chondroprotective effect by virtue of anti-inflammatory and proanabolic effects on articular chondrocytes. The identity of the active component(s) remains unknown. In general, sterols, the major component of unsaponifiable plant material have been demonstrated to be anti-inflammatory in vitro and in animal models.
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