Mass spectrometry for steroids, immunosuppressants, and other clinical applications

PresentationPresentation slides on matching mass spectrometry technology to clinical applications

Efficient Calculation of Accurate Masses of Isotopic Peaks

This paper presents a new method for calculating accurate masses of isotopic peaks. It is based on breaking the calculation into a binary series of calculations. The molecule is built up by a series of such calculations. At each step the accurate masses are calculated as a probability weighted sum of the masses of the contributing peaks. The method is computationally efficient and accurate for both mass and relative abundance

Corporate Planning Versus Government Planning

This paper discusses the differences between business planning and national planning and how to decide which works best for the overall economy.https://openscholarship.wustl.edu/mlw_papers/1043/thumbnail.jp

Immune compromise in HIV-1/HTLV-1 coinfection with paradoxical resolution of CD4 lymphocytosis during antiretroviral therapy: a case report

Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity

Accumulation of non-traditional risk factors for coronary heart disease is associated with incident coronary heart disease hospitalization and death

Assessing multiple traditional risk factors improves prediction for late-life diseases, including coronary heart disease (CHD). It appears that non-traditional risk factors can also predict risk. The objective was to investigate contributions of non-traditional risk factors to coronary heart disease risk using a deficit accumulation approach.Community-dwelling adults with no known history of CHD (n = 2195, mean age 46.9±18.7 years, 51.8% women) participated in the 1995 Nova Scotia Health Survey. Three risk factor indices were constructed to quantify the proportion of deficits present in individuals: 1) a 17-item Non-Traditional Risk Factor Index (e.g. sinusitis, arthritis); 2) a 9-item Traditional Risk Factor Index (e.g. hypertension, diabetes); and 3) a frailty index (25 items combined from the other two index measures). Ten-year risks of CHD events (defined as CHD-related hospitalization and CHD-related mortality) were evaluated.The Non-Traditional Risk Factor Index, made up of health deficits unrelated to CHD, was independently associated with incident CHD events over 10 years after controlling for age, sex, and the Traditional Risk Factor Index [adjusted {adj.} Hazard Ratio {HR} = 1.31; Confidence Interval {CI} 1.14-1.51]. When all health deficits, both those related and unrelated to CHD, were included in a frailty index the corresponding adjusted hazard ratio was 1.61; CI 1.40-1.85.Both traditional and non-traditional risk factor indices are independently associated with incident CHD events. CHD risk assessment may benefit from consideration of general health information as well as from traditional risk factors.Lindsay M. K. Wallace, Olga Theou, Susan A. Kirkland, Michael R. H. Rockwood, Karina W. Davidson, Daichi Shimbo, Kenneth Rockwoo

Performance enhancement in the measurement of 5 endogenous steroids by LC-MS/MS combined with differential ion mobility spectrometry

pre-printBackground: Challenges for steroid analysis by LC-MS/MS include low ionization efficiency, endogenous isobars with similar fragmentation patterns and chromatographic retention. Differential ion mobility spectrometry (DMS) provides an additional degree of separation prior to MS/MS detection, and shows promise in improving specificity of analysis. We developed a sensitive and specific method for measurement of corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone and progesterone in human serum and plasma using an ABSciex 5500 mass spectrometer equipped with a differential ion mobility interface. Methods: 250 μL aliquots of serum were spiked with deuterated internal standards and extracted with MTBE. The samples were analyzed using positivemode electrospray LC-DMS-MS/MS. Themethod was validated and compared with immunoassays and LC-MS/MS methods of reference laboratories. Results: Inter and intra assay imprecision was b10%. Limits of quantification and detection in nmol/L were 0.18, 0.09 for corticosterone and 17-hydroxyprogesterone, 0.30, 0.16 for 11-deoxycortisol, 0.12, 0.06 for progesterone and 0.06, 0.03 for 11-deoxycorticosterone. Comparison for progesterone and 17-hydroxyprogesterone with immunoassay showed slopes of 0.97 and 1.0, intercepts of 0.16 and 0.10 and coefficients of determination (r2) of 0.92 and 0.97, respectively. Progesterone by immunoassay showed positive bias in samples measuring b3.18 nmol/L. Reference intervals for progesterone and 11-deoxycorticosterone in post-menopausal women were found to be b2.88 and b0.28 nmol/L respectively. Conclusions: We developed and validated an LC-DMS-MS/MS method for analysis of five endogenous steroids suitable for routine measurements in clinical diagnostic laboratories. Specificity gained with DMS allows reducing the complexity of sample preparation, decreasing LC run times and increasing speed of the analysis

Microclimate modification by tree windbreaks in Florida farms

Paper presented at the 11th North American Agroforesty Conference, which was held May 31-June 3, 2009 in Columbia, Missouri.In Gold, M.A. and M.M. Hall, eds. Agroforestry Comes of Age: Putting Science into Practice. Proceedings, 11th North American Agroforestry Conference, Columbia, Mo., May 31-June 3, 2009.Florida citrus and vegetable crops generate billions in revenue every year. However, winds, freezes, hurricanes, and citrus canker (Xanthomonas campestris) impact production. Windbreaks located perpendicular to the prevailing wind can reduce soil erosion and increase irrigation efficiency and farm production mostly by simply modifying microclimate. Windbreaks can also control the spread of pathogens such as citrus canker. To study how tree windbreaks modify microclimate in southern Florida, weather stations were established in 2008 along transects behind a 1-row eastern redcedar (Juniperus virginiana) windbreak at the Southwest Florida Research and Education Center (SWFREC/University of Florida) at Immokalee, and a 1-row cadaghi (Corymbia torelliana) windbreak at C&B Farms, Clewiston, to assess spatial variation in wind speed, temperature, and relative humidity at 2m above the ground. The windbreaks significantly reduced wind speed; minimum wind speed was at two times the windbreak height (2H) behind dense (17 [percent] porosity) redcedar and at 6H behind relatively porous (20 [percent] porosity) cadaghi when the wind direction was nearly perpendicular to the windbreak. Wind speed at 2H behind eastern redcedar was approximately 5 [percent] of the open wind speed and at 6H behind cadaghi was approximately 3-30 [percent]. Wind speed at 14H behind cadaghi and redcedar windbreak was approximately 60 [percent] and 80 [percent] of the open wind speed, respectively. Temperature behind both windbreaks was relatively warmer than in the open. However, the extent of temperature and relative humidity modification was less compared to wind speed. Windbreaks are an effective use of forest trees to modify microclimate and appreciably enhance Florida farm production.Bijay Tamang (1), Donald L Rockwood1 and Michael G. Andreu (2) ; 1. PO Box 110410, School of Forest Resources and Conservation, University of Florida, Gainesville, FL 32611. 2. SFRC, University of Florida, Gulf Coast REC - Plant City, 1200 N Park Road, Plant City, FL 33563.Includes bibliographical references

The Analysis of Protein-Bound Thiocyanate in Plasma of Smokers and Non-Smokers as a Marker of Cyanide Exposure

When cyanide is introduced into the body, it quickly transforms through a variety of chemical reactions, normally involving sulfur donors, to form more stable chemical species. Depending on the nature of the sulfur donor, cyanide may be transformed into free thiocyanate, the major metabolite of cyanide transformation, 2-amino-2-thiazoline-4-carboxylic acid or protein-bound thiocyanate (PB-SCN) adducts. Because protein adducts are generally stable in biological systems, it has been suggested that PB-SCN may have distinct advantages as a marker of cyanide exposure. In this study, plasma was analyzed from 25 smokers (chronic low-level cyanide exposure group) and 25 non-smokers for PB-SCN. The amount of PB-SCN found in the plasma of smokers, 1.35 µM, was significantly elevated (p \u3c 0.0001) when compared to non-smokers, 0.66 µM. Differences in sub-groups of smokers and non-smokers were also evaluated. The results of this study indicate the effectiveness of analyzing PB-SCN in determining instances of chronic cyanide exposure with possible extension to confirmation of acute cyanide exposure

Quantification of α-ketoglutarate cyanohydrin in Swine Plasma by Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry

Determination of exposure to cyanide can be accomplished by direct cyanide analysis or indirectly by analysis of cyanide detoxification products, such as thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid. A potentially important marker and detoxification product of cyanide exposure, α-ketoglutarate cyanohydrin (α-KgCN), is produced by the reaction of cyanide and α-ketoglutarate. Therefore, an ultra high-performance liquid chromatography tandem mass spectrometry method to determine α-KgCN in plasma was developed. Swine plasma was spiked with α-KgCN and α-KgCN-d4 (internal standard) and proteins were precipitated with 1% formic acid in acetonitrile. After centrifugation, the supernatant was dried, reconstituted, separated by reversed phase high performance liquid chromatography and analyzed by tandem mass spectrometry. The method produced a dynamic range of 0.3–50 μM and a detection limit of 200 nM for α-KgCN. Furthermore, the method produced a %RSD of less than 13% for all intra- and inter-assay analyses. The stability of α-KgCN was poor for most storage conditions tested, except for −80 °C, which produced stable concentrations of α-KgCN for the 30 days tested. The validated method was tested by analysis of α-KgCN in the plasma of cyanide-exposed swine. α-KgCN was not detected pre-exposure, but was detected in all post-exposure plasma samples tested. To our knowledge, this method is the first reported analytical method for detecting α-KgCN in any matrix