17 research outputs found
Op-Ed -- The True University These Days Is a Collection of… eBooks?!
An efficient stereoselective synthesis of furanoverrillin (<b>5</b>), a highly functionalized core of verrillin (<b>1</b>), is reported. The synthetic strategy is based on constructing bicyclic lactone <b>17</b> prior to the 10-membered ring macrocyclization. The effect of the C<sub>4</sub> methyl group on the furan reactivity is also discussed
How the VALID Act could affect patient access to laboratory developed testing for therapeutic drug monitoring
Comparative analysis of hospital and forensic laboratory ethanol concentrations: A 15 month investigation of antemortem specimens
Synthetic Explorations of Structurally Complex Bioactive Cembrenolides /
The work described herein is a culmination of synthetic studies in the area of cembrenolide natural products, compounds that are synthetically intriguing not only for their highly intricate structures, but also for their array of bioactivities. The synthetic studies toward this family of natural products is divided into 4 chapters : (1) an overview of the first generation of the synthesis with discussion of the total synthesis of norcem- brenolide B and scabrolide D; (2) a discussion of the second generation of the synthe- sis of the family of cembrenolides, specifically, the introduction of the C13 hydroxy functionality and its oxidative rearrangement patterns; (3) an overview of the third gen- eration which involves further carbon skeletal rearrangements toward the synthesis of highly complex cembrenolides such as verrillin; (4) concluding remarks which describe the evolution of each generation and highlight each generation's strengths. Discussions of synthetic strategies and design are also discussed in great detai
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Comparative analysis of hospital and forensic laboratory ethanol concentrations: A 15 month investigation of antemortem specimens.
Quantitative serum alcohol concentrations from regional hospitals (from specimens collected at time of hospital admission) were compared to results from whole blood (from specimens collected at the time of hospital admission) concentrations measured at the San Diego County Medical Examiner's Office (SDCMEO). Over a 15 month period (January 2012 to March 2013), the postmortem forensic toxicology laboratory analyzed a total of 2,321 cases. Of these, 280 were hospital cases (antemortem) representing 12% of the overall Medical Examiner toxicology casework. 59 of the 280 hospital cases (or 21%) screened positive for alcohol (ethanol). 39 of these 59 cases were included in the study based on available specimens for quantitative analyses. This investigation indicated that serum hospital ethanol concentrations correlated well (R(2)Â =Â 0.942) with ethanol values determined at SDCMEO (generally measured in whole blood). There was an observed negative bias with an average of -14.1%. A paired t-test was applied to the data and it was shown that this observed bias is statistically significant. These differences in ethanol concentrations could result from differences in specimen, analytical techniques, and/or calibration. The potential for specimen contamination is also discussed
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Evaluation of the Waters MassTrak LC-MS/MS Assay for Tacrolimus and a Comparison to the Abbott Architect Immunoassay.
BackgroundTacrolimus (Prograf, Advagraf, and FK-506) is the most commonly prescribed calcineurin inhibitor after kidney and liver transplantation. The use of tacrolimus (in conjunction with other drugs) has successfully contributed to the maintenance of solid organ allografts; however, it also exhibits toxic side effects. Therapeutic drug monitoring of tacrolimus is used as an aid to achieve drug concentrations within a narrow therapeutic window.MethodsThe Waters MassTrak Immunosuppressants assay (LC-MS/MS) for the quantification of tacrolimus in whole blood was evaluated for precision, linearity, lower limit of quantification, matrix effects, and accuracy. A method comparison with the Abbott Architect Tacrolimus immunoassay was also performed.ResultsThe mean concentration (nanograms per milliliter) and coefficient of variation for low, mid, and high patient pools were 0.6% ± 19.9%, 16.0% ± 5.4%, and 31.2% ± 5.8%, respectively. The MassTrak assay was linear from 0.5 to 30.0 ng/mL. Although the MassTrak and Architect assays correlated well (R = 0.97) for patient samples, the MassTrak assay displayed an average negative bias of 18.5% versus Architect (range of 0.0%-36.7%). Analysis of a certified tacrolimus reference material in human whole blood [European Reference Materials (ERM)-DA110a, LGC Standards] on both platforms failed to completely explain the observed difference for patient samples.ConclusionsTwo widely used assays for therapeutic drug monitoring of tacrolimus are not in agreement with one another. Care should be exercised when interpreting results generated on these 2 assay platforms
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Evaluation of the Waters MassTrak LC-MS/MS Assay for Tacrolimus and a Comparison to the Abbott Architect Immunoassay.
BackgroundTacrolimus (Prograf, Advagraf, and FK-506) is the most commonly prescribed calcineurin inhibitor after kidney and liver transplantation. The use of tacrolimus (in conjunction with other drugs) has successfully contributed to the maintenance of solid organ allografts; however, it also exhibits toxic side effects. Therapeutic drug monitoring of tacrolimus is used as an aid to achieve drug concentrations within a narrow therapeutic window.MethodsThe Waters MassTrak Immunosuppressants assay (LC-MS/MS) for the quantification of tacrolimus in whole blood was evaluated for precision, linearity, lower limit of quantification, matrix effects, and accuracy. A method comparison with the Abbott Architect Tacrolimus immunoassay was also performed.ResultsThe mean concentration (nanograms per milliliter) and coefficient of variation for low, mid, and high patient pools were 0.6% ± 19.9%, 16.0% ± 5.4%, and 31.2% ± 5.8%, respectively. The MassTrak assay was linear from 0.5 to 30.0 ng/mL. Although the MassTrak and Architect assays correlated well (R = 0.97) for patient samples, the MassTrak assay displayed an average negative bias of 18.5% versus Architect (range of 0.0%-36.7%). Analysis of a certified tacrolimus reference material in human whole blood [European Reference Materials (ERM)-DA110a, LGC Standards] on both platforms failed to completely explain the observed difference for patient samples.ConclusionsTwo widely used assays for therapeutic drug monitoring of tacrolimus are not in agreement with one another. Care should be exercised when interpreting results generated on these 2 assay platforms
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A Young Woman With Recurrent Gestational Hypercalcemia and Acute Pancreatitis Caused by CYP24A1 Deficiency.
The CYP24A1 gene encodes a mitochondrial 24-hydroxylase that inactivates 1,25(OH)2 D. Loss-of-function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia. Her first pregnancy, at age 20, resulted with the intrauterine demise of twin fetuses. Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)2 D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively). Between one and three months postpartum, her serum calcium decreased from 11.4 to 10.2 mg/dL while her 1,25(OH)2 D level decreased from 83 to 24 pg/mL. Her 24-hour urine calcium was 277 mg. Six months postpartum, she became pregnant again. At 14 weeks, her albumin-corrected calcium level was 10.4 mg/dL and her 1,25(OH)2 D level exceeded 200 pg/mL. To establish the diagnosis of CYP24A1 deficiency, we showed her 24,25(OH)2 D level to be undetectable (<2 ng/mL). Exon sequencing of the CYP24A1 gene revealed a homozygous, 8-nucleotide deletion in exon 8, causing an S334V substitution and premature termination due to a frame shift (c.999_1006del, p.Ser334Valfs*9). To prevent hypercalcemia, she was advised to discontinue prenatal vitamins, avoid sun exposure and calcium-rich foods, and start omeprazole and a calcium binder (250 mg K-Phos-neutral with meals). Despite these measures, both hypercalcemia (11.5 mg/dL) and acute pancreatitis recurred. Labor was induced and a healthy, normocalcemic boy was delivered. In the absence of lactation, maternal hypercalcemia resolved within 2 months. This report shows that CYP24A1-deficient subjects may be normocalcemic at baseline. Hypercalcemia may be unmasked by pregnancy through the routine use of calciferol-containing prenatal vitamins, increased 1-alpha hydroxylation of VitD by the placenta and maternal kidney, and production of PTHrP by the uteroplacental unit. CYP24A1 deficiency should be considered in patients with unexplained vitamin D-mediated hypercalcemia. © 2016 American Society for Bone and Mineral Research