428 results on '"S. Mcdonald"'
Search Results
2. MR Imaging Safety Considerations of Gadolinium-Based Contrast Agents
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Jennifer S. McDonald and Robert J. McDonald
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medicine.medical_specialty ,business.industry ,Gadolinium ,chemistry.chemical_element ,Medical information ,medicine.disease ,Mr imaging ,030218 nuclear medicine & medical imaging ,Imaging modalities ,03 medical and health sciences ,Safety profile ,0302 clinical medicine ,chemistry ,Nephrogenic systemic fibrosis ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
Gadolinium (Gd)-based contrast agents (GBCAs) have revolutionized of MR imaging, enabling physicians to obtain life-saving medical information that often cannot be obtained with unenhanced MR imaging or other imaging modalities. Since regulatory approval in 1988, more than 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile. Recent evidence has demonstrated, however, that a small fraction of Gd is retained in human tissues. No direct correlation between Gd retention and clinical effects has been confirmed; however, a subset of patients have attributed various symptoms to GBCA exposure. This review details current knowledge regarding GBCA safety.
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- 2020
3. Author response: Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
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Ingvar Betner, Matthew E. Pope, Andreas Hober, Sigurd Hermansson, Lisa Calton, Thomas S. McDonald, Rebecca Pattison, Richard Yip, Fredrik Edfors, Amy Bartlett, Jessica J. Alm, Terry W. Pearson, Morteza Razavi, Samantha Ferries, Dominic Foley, Lars Engstrand, Mathias Uhlén, Leigh N Andersson, Khue Hua Tran-Minh, and Johannes P. C. Vissers
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chemistry.chemical_classification ,Liquid chromatography–mass spectrometry ,Chemistry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Peptide ,Virology - Published
- 2021
4. High-throughput UHPLC/MS/MS-based metabolic profiling using a vacuum jacketed column
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Thomas S. McDonald, Paul D. Rainville, Kelly A. Johnson, Jason F. Hill, Lee A. Gethings, Ian D. Wilson, and Robert S. Plumb
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Electrospray ,Vacuum ,Mass spectrometry ,Uhplc ms ms ,Analytical Chemistry ,Diffusion ,Column chromatography ,Tandem Mass Spectrometry ,0399 Other Chemical Sciences ,Column (data store) ,Chromatography, High Pressure Liquid ,Detection limit ,Chromatography ,Science & Technology ,UPLC ,Chemistry ,Chemistry, Analytical ,MASS-SPECTROMETRY ,HPLC-MS ,RESOLUTION ,Radial diffusion ,Physical Sciences ,Dispersion (chemistry) ,0301 Analytical Chemistry ,GENERATION ,Chromatography, Liquid - Abstract
In UHPLC, frictional heating from the eluent flowing through the column at pressures of ca. 10-15 Kpsi causes radial diffusion via temperature differences between the center of the column and its walls. Longitudinal dispersion also occurs due to temperature gradients between the inlet and outlet. These effects cause band broadening but can be mitigated via a combination of vacuum jacketed stainless steel tubing, reduced column end nut mass, and a constant temperature in the column from heating the inlet fitting. Here, vacuum jacketed column (VJC) technology, employing a novel column housing located on the source of the mass spectrometer and minimized tubing from the column outlet to the electrospray probe, was applied to profiling metabolites in urine. For a 75 s reversed-phase gradient separation, the average peak widths for endogenous compounds in urine were 1.2 and 0.6 s for conventional LC/MS and VJC systems, respectively. The peak tailing factor was reduced from 1.25 to 1.13 when using the VJC system compared to conventional UHPLC, and the peak capacity increased from 65 to 120, with a 25% increase in features detected in urine. The increased resolving power of the VJC system reduced co-elution, simplifying MS and MS/MS spectra, providing a more confident metabolite identification. The increased LC performance also gave more intense MS peaks, with a 10-120% increase in response, improving the quality of the MS data and detection limits. Reducing the LC gradient duration to 37 s gave peak widths of ca. 0.4 s and a peak capacity of 84.
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- 2021
5. Glucose clearance and uptake is increased in the SOD1G93Amouse model of amyotrophic lateral sclerosis through an insulin‐independent mechanism
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John D. Lee, Jenny Nt Fung, Tanya S. McDonald, Trent M. Woodruff, and Vinod Kumar
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0301 basic medicine ,medicine.medical_specialty ,animal diseases ,medicine.medical_treatment ,Glucose uptake ,Biochemistry ,Glucagon ,Energy homeostasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Glucose homeostasis ,Molecular Biology ,Glycogen ,Insulin ,Pancreatic islets ,nutritional and metabolic diseases ,nervous system diseases ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,030217 neurology & neurosurgery ,Homeostasis ,Hormone ,Biotechnology - Abstract
Metabolic disturbances are associated with the progression of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS). However, the molecular events that drive energy imbalances in ALS are not completely understood. In this study, we aimed to elucidate deficits in energy homeostasis in the SOD1G93A mouse model of ALS. SOD1G93A mice and their wild-type littermates underwent indirect calorimetry and intraperitoneal glucose/insulin tolerance tests at both the onset and mid-symptomatic stages of the disease. Glucose uptake and the plasma glucoregulatory hormone profiles were analyzed. Pancreatic islet cell mass and function were assessed by measuring hormone concentrations and secretion in isolated islets, and pancreatic α- and β-cell immunoreactive areas. Finally, we profiled liver glycogen metabolism by measuring glucagon concentrations and liver metabolic gene expressions. We identified that mid-symptomatic SOD1G93A mice have increased oxygen consumption and faster exogenous glucose uptake, despite presenting with normal insulin tolerance. The capacity for pancreatic islets to secrete insulin appears intact, however, islet cell insulin concentrations and β-cell mass were reduced. Fasting glucose homeostasis was also disturbed, along with increased liver glycogen stores, despite elevated circulating glucagon, suggesting that glucagon signaling is impaired. Metabolic gene expression profiling of livers indicated that glucose cannot be utilized efficiently in SOD1G93A mice. Overall, we demonstrate that glucose homeostasis and uptake are altered in SOD1G93A mice, which is linked to an increase in insulin-independent glucose uptake, and a loss of β-cells, insulin production, and glucagon sensitivity. This suggests that the hormonal regulation of glucose concentrations may contribute to the progression of disease in this ALS mouse model.
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- 2021
6. Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
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Matthew E. Pope, Johannes P. C. Vissers, Thomas S. McDonald, Sigurd Hermansson, Rebecca Pattison, Ingvar Betner, Amy Bartlett, Fredrik Edfors, Terry W. Pearson, Dominic Foley, Jessica J. Alm, Samantha Ferries, Richard Yip, Tran-Minh Khue Hua, Lisa Carlton, N. Leigh Anderson, Lars Engstrand, Mathias Uhlén, Morteza Razavi, and Andreas Hober
- Subjects
Proteomics ,Coronavirus disease 2019 (COVID-19) ,QH301-705.5 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Science ,SARS CoV-2 ,Peptide ,Mass spectrometry ,Sensitivity and Specificity ,Mass Spectrometry ,Viral Proteins ,Immunology and Inflammation ,Nasopharynx ,Lc ms ms ,diagnostics ,Humans ,SISCAPA ,Biology (General) ,Pandemics ,chemistry.chemical_classification ,Microbiology and Infectious Disease ,Chromatography ,Chemistry ,SARS-CoV-2 ,Pandemic preparedness ,COVID-19 ,Reproducibility of Results ,Peptide Fragments ,Virus detection ,Targeted proteomics ,Molecular Diagnostic Techniques ,Linear Models ,Medicine ,Public Health ,Insight ,Research Article ,Chromatography, Liquid ,Human - Abstract
Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.
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- 2021
7. Fructose 1,6-bisphosphate is anticonvulsant and improves oxidative glucose metabolism within the hippocampus and liver in the chronic pilocarpine mouse epilepsy model
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Karin Borges, Elliott S. Neal, and Tanya S. McDonald
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medicine.medical_specialty ,Fructose 1,6-bisphosphate ,medicine.medical_treatment ,Status epilepticus ,Fructose ,Carbohydrate metabolism ,Hippocampus ,Behavioral Neuroscience ,chemistry.chemical_compound ,Epilepsy ,Mice ,Status Epilepticus ,Internal medicine ,medicine ,Fructosediphosphates ,Animals ,Seizure threshold ,Pilocarpine ,medicine.disease ,Disease Models, Animal ,Oxidative Stress ,Anticonvulsant ,Endocrinology ,Glucose ,Neurology ,chemistry ,Liver ,Anticonvulsants ,Neurology (clinical) ,medicine.symptom ,Ketogenic diet ,medicine.drug - Abstract
Glucose metabolism is altered in epilepsy, and this may contribute to seizure generation. Recent research has shown that metabolic therapies including the ketogenic diet and medium chain triglycerides can improve energy metabolism in the brain. Fructose 1,6-bisphosphate (F16BP) is an intermediate of glycolysis and when administered exogenously is anticonvulsant in several rodent seizure models and may alter glucose metabolism. Here, we showed that F16BP elevated the seizure threshold in the acute 6-Hz mouse seizure model and investigated if F16BP could restore impairments in glucose metabolism occurring in the chronic stage of the pilocarpine mouse model of epilepsy. Two weeks after the pilocarpine injections, mice that experienced status epilepticus (SE, “epileptic”) and did not experience SE (no SE, “nonepileptic”) were injected with vehicle (0.9% saline) or F16BP (1 g/kg in 0.9% saline) daily for 5 consecutive days. At 3 weeks, mice were injected with [U-13C6]-glucose and the % enrichment of 13C in key metabolites in addition to the total levels of each metabolite was measured in the hippocampal formation and liver. Fructose 1,6-bisphosphate increased total GABA in the hippocampal formation, regardless of whether mice had experienced SE. In the hippocampal formation, F16BP prevented reductions in the % 13C enrichment of citrate, succinate, malate, glutamate, GABA and aspartate that occurred in the chronic stage of the pilocarpine model. Interestingly, % 13C enrichment in glucose-derived metabolites was reduced in the liver in the chronic stage of the pilocarpine model. Fructose 1,6-bisphosphate was also beneficial in the liver, preventing reductions in % 13C enrichment of lactate and alanine that were associated with SE. This study confirmed that F16BP is anticonvulsant and can improve elements of glucose metabolism that are dysregulated in the chronic stage of the pilocarpine model, which may be due to reduction of spontaneous seizures. Our results highlight that F16BP may be therapeutically beneficial for epilepsies refractory to treatment.
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- 2021
8. Use of metham sodium to eliminate Phytophthora spp. from roading gravel
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S. McDonald, N. West, Elaine Davison, B. Warton, S. Kazemi, Francis Tay, and S. Paton
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0106 biological sciences ,0301 basic medicine ,Biocide ,Metham sodium ,biology ,food and beverages ,Plant Science ,Pesticide ,Phytophthora cinnamomi ,biology.organism_classification ,01 natural sciences ,Plant disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Agronomy ,Methyl isothiocyanate ,chemistry ,Phytophthora ,Application methods ,010606 plant biology & botany - Abstract
Lateritic gravel is used for road building in Western Australia, with about 8 million m3 required annually. The introduced, soil-borne pathogen Phytophthora cinnamomi, which is associated with mortality of native plants, has been widely spread by using gravel from infested pits. Uninfested gravel is in demand, and in short supply. The biocide metham sodium is registered by the Australian Pesticides and Veterinary Medicine Authority (APVMA) as a soil fumigant, but the registered application method is unsuitable for treating gravel. In moist soil metham sodium decomposes into the fumigant-like pesticide, methyl isothiocyanate (MITC). Field experiments in which metham sodium was applied during the construction of 4 m3 gravel stockpiles, showed Phytophthora spp. are killed within 2 weeks of treatment with 80 mL m3–1 metham sodium. MITC is sealed within the stockpile by surface crusting; it was only detected 5 m downwind within the first 24 h of treatment. It was not detected in gravel 28 days after treatment. This application method that can safely eliminate Phytophthora spp. from infested gravel has been registered by the APVMA, allowing scaling-up trials to be considered.
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- 2019
9. Triheptanoin alters [U-13C6]-glucose incorporation into glycolytic intermediates and increases TCA cycling by normalizing the activities of pyruvate dehydrogenase and oxoglutarate dehydrogenase in a chronic epilepsy mouse model
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Mark P. Hodson, Michelle Puchowicz, Ilya Bederman, Tanya S. McDonald, and Karin Borges
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0303 health sciences ,Glycogenolysis ,Dehydrogenase ,Metabolism ,Pyruvate dehydrogenase complex ,Triheptanoin ,Citric acid cycle ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neurology ,chemistry ,Biochemistry ,Glycolysis ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Oxoglutarate dehydrogenase complex ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Triheptanoin is anticonvulsant in several seizure models. Here, we investigated changes in glucose metabolism by triheptanoin interictally in the chronic stage of the pilocarpine mouse epilepsy model. After injection of [U-13C6]-glucose (i.p.), enrichments of 13C in intermediates of glycolysis and the tricarboxylic acid (TCA) cycle were quantified in hippocampal extracts and maximal activities of enzymes in each pathway were measured. The enrichment of 13C glucose in plasma was similar across all groups. Despite this, we observed reductions in incorporation of 13C in several glycolytic intermediates compared to control mice suggesting glucose utilization may be impaired and/or glycogenolysis increased in the untreated interictal hippocampus. Triheptanoin prevented the interictal reductions of 13C incorporation in most glycolytic intermediates, suggesting it increased glucose utilization or – as an additional astrocytic fuel – it decreased glycogen breakdown. In the TCA cycle metabolites, the incorporation of 13C was reduced in the interictal state. Triheptanoin restored the correlation between 13C enrichments of pyruvate relative to most of the TCA cycle intermediates in “epileptic” mice. Triheptanoin also prevented the reductions of hippocampal pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities. Decreased glycogen breakdown and increased glucose utilization and metabolism via the TCA cycle in epileptogenic brain areas may contribute to triheptanoin's anticonvulsant effects.
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- 2019
10. Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C
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Aikaterini Kontrogianni-Konstantopoulos, Laurin M. Hanft, Kerry S. McDonald, Joel C. Robinett, and Janelle Geist
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Male ,Sarcomeres ,0301 basic medicine ,Myofilament ,Contraction (grammar) ,Physiology ,Myosins ,Microfilament ,Sarcomere ,Rats, Sprague-Dawley ,Protein filament ,03 medical and health sciences ,0302 clinical medicine ,Myofibrils ,Commentaries ,Myosin ,Animals ,Phosphorylation ,Protein kinase A ,Research Articles ,Actin ,Chemistry ,musculoskeletal system ,Cyclic AMP-Dependent Protein Kinases ,Rats ,Actin Cytoskeleton ,030104 developmental biology ,Muscle Fibers, Fast-Twitch ,Commentary ,Biophysics ,Calcium ,Carrier Proteins ,030217 neurology & neurosurgery ,Research Article ,Protein C ,Muscle Contraction - Abstract
Myosin binding protein C (MyBP-C) is thought to regulate the contraction of skeletal muscle. Robinett et al. show that phosphorylation of slow skeletal MyBP-C modulates contraction by recruiting cross-bridges, modifying cross-bridge kinetics, and altering internal drag forces in the C-zone., Myosin binding protein C (MyBP-C) is a 125–140-kD protein located in the C-zone of each half-thick filament. It is thought to be an important regulator of contraction, but its precise role is unclear. Here we investigate mechanisms by which skeletal MyBP-C regulates myofilament function using rat permeabilized skeletal muscle fibers. We mount either slow-twitch or fast-twitch skeletal muscle fibers between a force transducer and motor, use Ca2+ to activate a range of forces, and measure contractile properties including transient force overshoot, rate of force development, and loaded sarcomere shortening. The transient force overshoot is greater in slow-twitch than fast-twitch fibers at all Ca2+ activation levels. In slow-twitch fibers, protein kinase A (PKA) treatment (a) augments phosphorylation of slow skeletal MyBP-C (sMyBP-C), (b) doubles the magnitude of the relative transient force overshoot at low Ca2+ activation levels, and (c) increases force development rates at all Ca2+ activation levels. We also investigate the role that phosphorylated and dephosphorylated sMyBP-C plays in loaded sarcomere shortening. We test the hypothesis that MyBP-C acts as a brake to filament sliding within the myofilament lattice by measuring sarcomere shortening as thin filaments traverse into the C-zone during lightly loaded slow-twitch fiber contractions. Before PKA treatment, shortening velocity decelerates as sarcomeres traverse from ∼3.10 to ∼3.00 µm. After PKA treatment, sarcomeres shorten a greater distance and exhibit less deceleration during similar force clamps. After sMyBP-C dephosphorylation, sarcomere length traces display a brief recoil (i.e., “bump”) that initiates at ∼3.06 µm during loaded shortening. Interestingly, the timing of the bump shifts with changes in load but manifests at the same sarcomere length. Our results suggest that sMyBP-C and its phosphorylation state regulate sarcomere contraction by a combination of cross-bridge recruitment, modification of cross-bridge cycling kinetics, and alteration of drag forces that originate in the C-zone.
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- 2019
11. Cardiac MyBP-C phosphorylation regulates the Frank–Starling relationship in murine hearts
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Laurin M. Hanft, Richard L. Moss, Timothy A. Hacker, Daniel P. Fitzsimons, and Kerry S. McDonald
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Sarcomeres ,0301 basic medicine ,Myofilament ,Contraction and cell motility ,Physiology ,Mice, Transgenic ,Myofilament Special Issue, 2020 ,030204 cardiovascular system & hematology ,Sarcomere ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Myosin ,Animals ,Myocyte ,Phosphorylation ,Molecular physiology ,Frank–Starling law of the heart ,Chemistry ,Myocardium ,Cyclic AMP-Dependent Protein Kinases ,Myocardial Contraction ,Cell biology ,030104 developmental biology ,Starlings ,cardiovascular system ,Ventricular pressure ,Carrier Proteins ,Myofibril - Abstract
Cardiac myosin-binding protein C (cMyBP-C) is thought to regulate cardiac muscle and heart contraction. Hanft et al. show that cMyBP-C phosphorylation regulates length dependence of power output in murine permeabilized cardiac myocytes, which translates to in vivo Frank–Starling relationships., The Frank–Starling relationship establishes that elevated end-diastolic volume progressively increases ventricular pressure and stroke volume in healthy hearts. The relationship is modulated by a number of physiological inputs and is often depressed in human heart failure. Emerging evidence suggests that cardiac myosin-binding protein-C (cMyBP-C) contributes to the Frank–Starling relationship. We measured contractile properties at multiple levels of structural organization to determine the role of cMyBP-C and its phosphorylation in regulating (1) the sarcomere length dependence of power in cardiac myofilaments and (2) the Frank–Starling relationship in vivo. We compared transgenic mice expressing wild-type cMyBP-C on the null background, which have ∼50% phosphorylated cMyBP-C (Controls), to transgenic mice lacking cMyBP-C (KO) and to mice expressing cMyBP-C that have serine-273, -282, and -302 mutated to aspartate (cMyBP-C t3SD) or alanine (cMyBP-C t3SA) on the null background to mimic either constitutive PKA phosphorylation or nonphosphorylated cMyBP-C, respectively. We observed a continuum of length dependence of power output in myocyte preparations. Sarcomere length dependence of power progressively increased with a rank ordering of cMyBP-C KO = cMyBP-C t3SA < Control < cMyBP-C t3SD. Length dependence of myofilament power translated, at least in part, to hearts, whereby Frank–Starling relationships were steepest in cMyBP-C t3SD mice. The results support the hypothesis that cMyBP-C and its phosphorylation state tune sarcomere length dependence of myofibrillar power, and these regulatory processes translate across spatial levels of myocardial organization to control beat-to-beat ventricular performance.
- Published
- 2021
12. Alterations in mitochondrial glucose carbon metabolism in epilepsy and targeted metabolic treatments
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Tanya S. McDonald, Karin Borges, Felicity Y. Han, and Weizhi Xu
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Citric acid cycle ,chemistry.chemical_compound ,Biochemistry ,Chemistry ,Glycolysis ,Metabolism ,Mitochondrion ,Carbohydrate metabolism ,Pyruvate dehydrogenase complex ,Energy source ,Triheptanoin - Abstract
There is increasing evidence showing that oxidative glucose metabolism in mitochondria is impaired in epilepsy and the involved metabolic mechanisms have been further characterized by recent work. Glucose is the main energy source in brain in people who eat a conventional mixed diet with carbohydrates, fats, and proteins. In the cytoplasm, glucose is metabolized to pyruvate by glycolysis, which produces small amounts of energy. Entry of pyruvate into mitochondria and subsequent metabolism via the tricarboxylic acid cycle generates large amounts of adenosine triphosphate as well as precursors for cellular biosynthesis of lipids and amino acids. Sufficient energy is important for the brain to be able to signal normally and to keep the sodium and potassium gradients stable across cellular membranes. In contrast, insufficient energy can contribute to surges in extracellular potassium levels, which destabilizes membrane potentials and signaling and can result in seizure generation in the chronic epileptic brain. The known biochemical mechanisms leading to mitochondrial impairments of glucose carbon metabolism in epilepsy are summarized in this chapter, including reduced glucose utilization, decreases in enzyme activities, such as pyruvate dehydrogenase, as well as increased anaplerotic demand. Based on this current knowledge, auxiliary brain fuels would be useful to provide extra energy to the epileptic brain. This includes ketones, tricarboxylic acid cycle intermediates, and precursors as well as even medium chain fatty acids and triheptanoin.
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- 2021
13. Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients
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Taxiarchis Kourelis, Suzanne R. Hayman, Nelson Leung, John A. Lust, Eli Muchtar, Harsh Parmar, Prashant Kapoor, Iuliana Vaxman, Angela Dispenzieri, Abdullah S. Al Saleh, Yi L. Hwa, David Dingli, Miriam Hobbs, Amie Fonder, Jennifer S. McDonald, Wilson I. Gonsalves, Martha Q. Lacy, John C. Lieske, Morie A. Gertz, Shaji Kumar, Robert A. Kyle, Alissa Visram, S. Vincent Rajkumar, Rahma Warsame, Mustaqeem A. Siddiqui, and Francis K. Buadi
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Male ,medicine.medical_specialty ,Urology ,Urine ,030204 cardiovascular system & hematology ,lcsh:RC254-282 ,Article ,Urine collection device ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Diagnosis ,AL amyloidosis ,medicine ,Albuminuria ,Humans ,Immunoglobulin Light-chain Amyloidosis ,Signs and symptoms ,Aged ,Retrospective Studies ,Creatinine ,Proteinuria ,business.industry ,Retrospective cohort study ,Hematology ,Gold standard (test) ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business ,Haematological diseases - Abstract
A 24-h urine protein collection (24hUP), the gold standard for measuring albuminuria in systemic AL amyloidosis, is cumbersome and inaccurate. We retrospectively reviewed 575 patients with systemic AL amyloidosis to assess the correlation between a urine albumin to creatinine ratio (uACR) and the 24hUP. The uACR correlated strongly with 24hUP at diagnosis (Pearson’s r = 0.87, 95% CI 0.83–0.90) and during the disease course (Pearson’s r = 0.88, 95% CI 0.86–0.90). A uACR ≥300 mg/g estimated a 24hUP ≥ 500 mg with a sensitivity of 92% and specificity of 97% (area under the receiver operating curve = 0.938, 95% CI 0.919–0.957). A uACR cutoff of 3600 mg/g best predicted a 24hUP > 5000 g (sensitivity 93%, specificity 94%), and renal stage at diagnosis was strongly concordant using either 24hUP or uACR as the proteinuria measure (k = 0.823, 95% CI 0.728–0.919). In patients with serial urine collections, a > 30% decrease in uACR predicted a > 30% decrease in 24hUP with a sensitivity of 94%. In conclusion, the uACR is a reliable and convenient method for ruling out proteinuria >500 mg per day, prognosticating renal outcomes, and assessing renal response to therapy. Further studies are needed to validate the uACR cutoffs proposed in this study.
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- 2020
14. Gadolinium retention within multiple rat organs after intra-articular administration of gadolinium-based contrast agents
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Nicholas G. Rhodes, Jennifer S. McDonald, Michael D. Ringler, Robert J. McDonald, David F. Kallmes, Jennifer R. Ayers-Ringler, and Daniel R. Jakaitis
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Gadolinium DTPA ,Biodistribution ,Gadolinium ,medicine.medical_treatment ,chemistry.chemical_element ,Urine ,030218 nuclear medicine & medical imaging ,Gadobutrol ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Organometallic Compounds ,Animals ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,Scientific Article ,Rats, Wistar ,Arthrography ,Saline ,Kidney ,medicine.diagnostic_test ,business.industry ,Gadodiamide ,Contrast media ,Brain ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Rats ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Nuclear medicine ,business ,medicine.drug - Abstract
Objective To characterize the extent of retention and biodistribution of gadolinium (Gd) following intra-articular (IA) injection of linear and macrocyclic gadolinium-based contrast agents (GBCAs) into the knee joint of a rat model. Materials and methods Fifteen Wistar rats were divided into five groups and underwent fluoroscopically-guided injections of both knee joints of (1) clinical 1:200 dilution (low dose, LD) gadodiamide (linear GBCA), (2) LD gadobutrol (macrocyclic GBCA), (3) undiluted (high dose, HD) gadodiamide, (4) HD gadobutrol, and (5) saline. Gd concentrations were quantified by inductively coupled plasma mass spectrometry in (1) blood and urine samples obtained over a 72 h period and (2) knee joint tissues, brain, kidney, and bone marrow at 3 days post-injection. Results Both HD and LD gadodiamide and gadobutrol were rapidly absorbed from the joint with peak serum and urine concentration at 1 h post-injection, with relatively faster clearance of gadobutrol. All GBCA-exposed groups had detectable levels of Gd in the joint tissues, bone marrow, and/or kidneys (median tissue gadolinium range: 0.1–71 μg Gd/g tissue), with higher amounts observed with gadodiamide versus gadobutrol. Retention within brain tissues was only detected following HD gadodiamide administration but not LD gadodiamide nor HD or LD gadobutrol. Conclusion There was rapid systemic absorption, redistribution, and widespread multi-organ retention of Gd following IA injection of both linear and macrocyclic GBCAs, despite substantial amounts of urinary excretion. Higher concentrations of Gd were observed with administration of gadodiamide compared to gadobutrol in most tissues and biofluids.
- Published
- 2020
15. Regulation of Myofilament Contractile Function in Human Donor and Failing Hearts
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Kerry S. McDonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, and Kenneth S. Campbell
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0301 basic medicine ,Myofilament ,medicine.medical_specialty ,Physiology ,Biophysics ,heart failure ,PNPO ,Isometric exercise ,030204 cardiovascular system & hematology ,Sarcomere ,lcsh:Physiology ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Myocyte ,human cardiac myocytes ,loaded shortening ,Original Research ,sarcomere length ,lcsh:QP1-981 ,Chemistry ,Cardiac myocyte ,medicine.disease ,030104 developmental biology ,Endocrinology ,contractile properties ,power output ,Heart failure ,Myofibril ,rate of force development - Abstract
Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca2+ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was similar between groups (donor: length 148 ± 10 μm, width 21 ± 2 μm, n = 13; HF: length 131 ± 9 μm, width 23 ± 1 μm, n = 16). The maximal Ca2+-activated isometric force was also similar between groups (donor: 47 ± 4 kN⋅m-2; HF: 44 ± 5 kN⋅m-2), which implicates that previously reported force declines in multi-cellular preparations reflect, at least in part, tissue remodeling. Maximal force development rates were also similar between groups (donor: k tr = 0.60 ± 0.05 s-1; HF: k tr = 0.55 ± 0.04 s-1), and both groups exhibited similar Ca2+ activation dependence of k tr values. Human cardiac myocyte preparations exhibited a Ca2+ activation dependence of loaded shortening and power output. The peak power output normalized to isometric force (PNPO) decreased by ∼12% from maximal Ca2+ to half-maximal Ca2+ activations in both groups. Interestingly, the SL dependence of PNPO was diminished in failing myocyte preparations. During sub-maximal Ca2+ activation, a reduction in SL from ∼2.25 to ∼1.95 μm caused a ∼26% decline in PNPO in donor myocytes but only an ∼11% change in failing myocytes. These results suggest that altered length-dependent regulation of myofilament function impairs ventricular performance in failing human hearts.
- Published
- 2020
16. Positron Emission Tomography Imaging of Poly-(Adenosine Diphosphate-Ribose) Polymerase 1 Expression in Breast Cancer: A Nonrandomized Clinical Trial
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Robert K. Doot, Elizabeth S. McDonald, Michael D. Farwell, Kara N. Maxwell, Robert H. Mach, David A. Mankoff, and Austin R. Pantel
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Cancer Research ,Fluorine Radioisotopes ,Poly (ADP-Ribose) Polymerase-1 ,Breast Neoplasms ,Poly(ADP-ribose) Polymerase Inhibitors ,chemistry.chemical_compound ,Breast cancer ,medicine ,Research Letter ,Humans ,skin and connective tissue diseases ,Polymerase ,biology ,medicine.diagnostic_test ,Adenosine diphosphate ribose ,business.industry ,Poly Adenosine Diphosphate Ribose ,medicine.disease ,Adenosine ,Clinical trial ,Oncology ,chemistry ,Positron emission tomography ,Positron-Emission Tomography ,biology.protein ,Cancer research ,Biomarker (medicine) ,Female ,business ,medicine.drug - Abstract
This nonrandomized clinical trial tested [(18)F]FluorThanatrace as a method for measuring regional poly–(adenosine diphosphate–ribose) polymerase 1 expression in breast cancer and as a potential functional biomarker for breast cancer poly–(adenosine diphosphate–ribose) polymerase inhibitor response.
- Published
- 2020
17. Blending studies using wheat and lentil cotyledon flour-Effects on rheology and bread quality
- Author
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John Mawson, Linda S. McDonald, Drew Portman, Joe Panozzo, Pankaj Maharjan, Mani Naiker, and Christopher Blanchard
- Subjects
chemistry.chemical_classification ,extensibility ,food.ingredient ,Chemistry ,fungi ,Organic Chemistry ,loaf volume ,food and beverages ,04 agricultural and veterinary sciences ,crumb firmness ,040401 food science ,Gluten ,food.food ,Yeast ,crumb color ,0404 agricultural biotechnology ,food ,Rheology ,Food products ,Food science ,High ratio ,Food quality ,Gram flour ,Cotyledon ,Food Science - Abstract
Background and objectives Lentil (Lens Culinaris. Medik) is a highly nutritious food staple widely consumed within India subcontinent and the Mediterranean region. Although gaining popularity in western diets, wheat will continue to be a major crop as it can be used to manufacture a wide range of products. The nutritional benefits of lentils are acknowledged, particularly as a source of high protein so the incorporation of lentil flour into wheat‐based foods has the potential to improve the nutritive value of range food products. Twelve blended flours were made using different concentrations of red lentil cotyledon, wheat, and additional gluten. A blending study was undertaken to access yeast vitality, rheological properties of dough and baking characteristic of resulting bread. Findings High ratio blends of lentil flour had no negative effect on yeast vitality even at the highest concentration of 40%. Increasing substitution of lentil flour was highly correlated to increased protein (r = 0.98) and ash (r = 0.95) and a concomitant decrease in dough strength but not extensibility. Loaf volume and baking quality were also compromised at higher concentrations. At a concentration of 5% lentil flour, there were no deleterious effects on dough quality traits or on baking quality. The addition of bakers’ gluten 0.1 g/gram flour had a restorative effect on the rheological and baking characteristics of wheat–lentil composites at higher concentrations of up to 20%. Conclusions Our results show that optimal baking quality of wheat–lentil flour can be achieved using either low concentrations of up to 5% lentil flour or up to 20% lentil flour with the addition of gluten which maintained a superior loaf and crumb quality. Significance and novelty The protein and ash content of baked breads significantly increased when wheat was partially substituted with lentil flour. The concentration of lentil flour decreased dough strength and dough development time and decreased loaf volume while increasing crumb firmness in resulting bread. The addition of gluten improved the rheological and product quality of bread which allowed higher concentrations of lentil flour to be used in bread making. Balancing the ratio of lentil flour and gluten to optimize the rheological properties will result in a composite wheat–lentil bread with acceptable baking performance and enhanced nutritional benefits for consumers.
- Published
- 2018
18. Semi-preparative high-resolution recycling liquid chromatography
- Author
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Thomas S. McDonald, Qi Yan, Fabrice Gritti, Basile Mark J, Sylvain Cormier, Frank Riley, Martin Gilar, and Fogwill Michael O
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Acetonitriles ,Magnetic Resonance Spectroscopy ,Chemistry, Pharmaceutical ,Fraction (chemistry) ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Diluent ,Spectral line ,Analytical Chemistry ,Impurity ,Pressure ,Particle Size ,Pressure drop ,Chromatography ,Chemistry ,Methanol ,010401 analytical chemistry ,Organic Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Particle size ,Drug Contamination ,0210 nano-technology ,Selectivity ,Stock solution ,Chromatography, Liquid - Abstract
A semi-preparative high-resolution system based on twin column recycling liquid chromatography was built. The integrated system includes a binary pump mixer, a sample manager, a two-column oven compartment, two low-dispersion detection cells, and a fraction manager (analytical). It addresses challenges in drug/impurity purification, which involve several constraints simultaneously: (1) small selectivity factors (α 1.2, poor resolution), (2) mismatch of elution strength between the sample diluent and the eluent causing severe band fronting or tailing, (3) diluent-to-eluent mismatch of viscosity causing viscous fingering and unpredictable band deformation, (4) low abundance of the impurity relative to the active pharmaceutical ingredient (API) (1/100), and (5) yield and purity levels to be larger than 99% and 90%, respectively. The prototype system was tested for the preparation of a trace impurity present in a concentrated solution of an API, estradiol. The ultimate goal was to collect ∼1 mg of impurity (90% purity) for unambiguous structure elucidation by liquid state nuclear magnetic resonance (NMR 600 MHz and above). First, the particle size (3.5 μm) used to pack the 4.6 mm × 150 mm long twin columns is selected so that the speed-resolution of the recycling process is maximized at 4000 psi pressure drop. Next, the production rate of the process is also maximized by determining the optimum number (7) of cycles and the corresponding largest sample volume (160 μL) to be injected. Finally, the process is fully automated by programming the time events related to (1) sample cleaning, (2) transfer of the targeted impurity from one to the second twin column, and (3) impurity collection. The process was tested without interruption during one week for the collection of a trace impurity (α = 1.166, strong acetonitrile-methanol sample diluent, concentration ∼2 mg/L) from a concentrated (10 g/L) stock solution (60 mL total) of estradiol. The process enriches the impurity content relative to the API by about a factor ∼5000. For the lack of a sufficient collected amount (∼120 μg only) of the pure impurity (purity 50% only), NMR experiments could not provide reliable results. Instead, the combination of LC-MS (single ion monitoring) and UV absorption spectra (λ
- Published
- 2018
19. Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study
- Author
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Laurence J. Eckel, Jennifer S. McDonald, Paul J. Jannetto, David L. Murray, Avinash Nehra, Robert J. McDonald, David F. Kallmes, Amy M. Bluhm, and Tina M. Gunderson
- Subjects
Adult ,Male ,Gadolinium ,Contrast Media ,chemistry.chemical_element ,Spinal Puncture ,030218 nuclear medicine & medical imaging ,Gadobutrol ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Organometallic Compounds ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Aged ,business.industry ,Spectrophotometry, Atomic ,Middle Aged ,Image Enhancement ,Magnetic Resonance Imaging ,Mr imaging ,chemistry ,Female ,Nuclear medicine ,business ,030217 neurology & neurosurgery ,medicine.drug ,Cohort study - Abstract
Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P.001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.
- Published
- 2018
20. Chromatographic performance of microfluidic liquid chromatography devices: Experimental evaluation of straight versus serpentine packed channels
- Author
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Fabrice Gritti, Robert A. Collamati, Geoff C. Gerhardt, Bernard Bunner, Thomas S. McDonald, Martin Gilar, Tad A. Dourdeville, Joseph D. Michienzi, Jay S. Johnson, Robert A. Jencks, Jim Murphy, Matthew P. Bannon, Gregory T. Roman, Devesh D. Satpute, Dennis Dellarovere, and Keith Fadgen
- Subjects
Titanium ,Sorbent ,Chromatography ,Capillary action ,Chemistry ,Microfluidics ,010401 analytical chemistry ,Organic Chemistry ,Tapering ,02 engineering and technology ,General Medicine ,Channel width ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,Chemistry Techniques, Analytical ,0104 chemical sciences ,Analytical Chemistry ,Planar ,Lab-On-A-Chip Devices ,Dispersion (optics) ,Turn (geometry) ,0210 nano-technology ,Chromatography, Liquid - Abstract
We prepared a series of planar titanium microfluidic (μLC) columns, each 100 mm long, with 0.15, 0.3 and 0.5 mm i.d.’s. The microfluidic columns were packed with 1.8 μm C18 sorbent and tested under isocratic and gradient conditions. The efficiency and peak capacity of these devices were monitored using a micro LC instrument with minimal extra column dispersion. Columns with serpentine channels were shown to perform worse than those with straight channels. The loss of efficiency and peak capacity was more prominent for wider i.d. columns, presumably due to on-column band broadening imparted by the so-called “race-track” effect. The loss of chromatographic performance was partially mitigated by tapering the turns (reduction in i.d. through the curved region). While good performance was obtained for 0.15 mm i.d. devices even without turn tapering, the performance of 0.3 mm i.d. columns could be brought on par with capillary LC devices by tapering down to 2/3 of the nominal channel width in the turn regions. The loss of performance was not fully compensated for in 0.5 mm devices even when tapering was employed; 30% loss in efficiency and 10% loss in peak capacity was observed. The experimental data for various devices were compared using the expected theoretical relationship between peak capacity Pc and efficiency N; (Pc−1) = N0.5 × const. While straight μLC columns showed the expected behavior, the devices with serpentine channels did not adhere to the plot. The results suggest that the loss of efficiency due to the turns is more pronounced than the corresponding loss of peak capacity.
- Published
- 2018
21. Hydrogen Uptake on Coordinatively Unsaturated Metal Sites in VSB-5: Strong Binding Affinity Leading to High-Temperature D2/H2 Selectivity
- Author
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Amit Sharma, Jesse L. C. Rowsell, Christopher T. Eckdahl, Keith V. Lawler, Jarod J. Wolffis, Cooper S. McDonald, Paul M. Forster, and Stephen A. FitzGerald
- Subjects
Hydrogen ,Chemistry ,Nanoporous ,Inorganic chemistry ,chemistry.chemical_element ,Sorption ,02 engineering and technology ,Surfaces and Interfaces ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Metal ,Adsorption ,Deuterium ,Molecular vibration ,visual_art ,Electrochemistry ,visual_art.visual_art_medium ,General Materials Science ,0210 nano-technology ,Selectivity ,Spectroscopy - Abstract
We examine the adsorption of hydrogen and deuterium into the nanoporous nickel phosphate, VSB-5. On the basis of gas sorption analysis, VSB-5 exhibits one of the highest measured H2 heats of adsorption (HOA) for hydrogen (16 kJ/mol) yet reported. This high HOA is consistent with an unusually large red shift in the Q(1) and Q(0) hydrogen vibrational modes as measured with in situ infrared spectroscopy. The HOA for D2 is measured to be 2 kJ/mol higher than that for H2. “Ideal adsorbed solution theory” analysis of H2 and D2 isotherms provides selectivities above 4 for deuterium at 140 K, suggesting that VSB-5 is a promising adsorbent for pressure-swing adsorption-type separations of hydrogen isotopes.
- Published
- 2017
22. An unattended verification station for UF6 cylinders: Field trial findings
- Author
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Jonathan A. Kulisek, S.J. Branney, Lindsay C. Todd, Leon E. Smith, Scott Stewart, Benjamin S. McDonald, Heather Ann Nordquist, James R Garner, Martyn T. Swinhoe, Mital A. Zalavadia, Karen A. Miller, Nikhil Deshmukh, and Jennifer B. Webster
- Subjects
Nuclear fuel cycle ,Physics ,Nuclear and High Energy Physics ,010308 nuclear & particles physics ,010401 analytical chemistry ,chemistry.chemical_element ,Uranium ,Enriched uranium ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Uranium hexafluoride ,chemistry ,Field trial ,0103 physical sciences ,Systems engineering ,Metre ,European commission ,Nondestructive assay ,Instrumentation - Abstract
In recent years, the International Atomic Energy Agency (IAEA) has pursued innovative techniques and an integrated suite of safeguards measures to address the verification challenges posed by the front end of the nuclear fuel cycle. Among the unattended instruments currently being explored by the IAEA is an Unattended Cylinder Verification Station (UCVS), which could provide automated, independent verification of the declared relative enrichment, 235 U mass, total uranium mass, and identification for all declared uranium hexafluoride cylinders in a facility (e.g., uranium enrichment plants and fuel fabrication plants). Under the auspices of the United States and European Commission Support Programs to the IAEA, a project was undertaken to assess the technical and practical viability of the UCVS concept. The first phase of the UCVS viability study was centered on a long-term field trial of a prototype UCVS system at a fuel fabrication facility. A key outcome of the study was a quantitative performance evaluation of two nondestructive assay (NDA) methods being considered for inclusion in a UCVS: Hybrid Enrichment Verification Array (HEVA), and Passive Neutron Enrichment Meter (PNEM). This paper provides a description of the UCVS prototype design and an overview of the long-term field trial. Analysis results and interpretation are presented with a focus on the performance of PNEM and HEVA for the assay of over 200 “typical” Type 30B cylinders, and the viability of an “NDA Fingerprint” concept as a high-fidelity means to periodically verify that material diversion has not occurred.
- Published
- 2017
23. Impact of instrument and column parameters on high-throughput liquid chromatography performance
- Author
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Fabrice Gritti, Martin Gilar, and Thomas S. McDonald
- Subjects
Void (astronomy) ,Chromatography ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Analytical chemistry ,General Medicine ,01 natural sciences ,Biochemistry ,Mass Spectrometry ,Time ,0104 chemical sciences ,Analytical Chemistry ,Volumetric flow rate ,Cycle time ,Duty cycle ,Void volume ,Chromatography, High Pressure Liquid ,Production rate ,Delay time - Abstract
The speed and separation performance of high-throughput liquid chromatography (HT LC) was investigated. We evaluated the contributions of various experimental parameters to the total analysis cycle time, including column length (column void time), gradient delay, flow rate, auto-sampler (A/S) speed, and software related delays. The best case injection-to-injection cycle time of 22s was achieved using 12s gradient time and 2.1×20mm columns packed with 1.7μm C18 particles. The total 22s analytical duty cycle consisted of 2.5s column void time, 1.8s gradient delay, 12s gradient time, and approximately 5.7s for software setup delay time that served as column re-equilibration time. The achieved peak capacity for an alkylphenone sample was approximately 35, giving a peak production rate of 95 peaks per minute. We estimated the impact of LC system dispersion on peak capacity and peak production rate (peak capacity per unit of time). For HT LC scenarios (5-50mm columns and 4.8-120s long gradients) we observed that even a minor amount of system dispersion (2μL2) reduces the achievable peak capacity and peak productivity rate significantly. HT LC-MS analysis using 2.1×5mm guard column with duty cycle of 22s was successfully demonstrated.
- Published
- 2017
24. Comparison of Gadolinium Concentrations within Multiple Rat Organs after Intravenous Administration of Linear versus Macrocyclic Gadolinium Chelates
- Author
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David L. Murray, Jennifer S. McDonald, Dana Schroeder, Laurence J. Eckel, Ramanathan Kadirvel, David F. Kallmes, Mark E. Jentoft, Daying Dai, and Robert J. McDonald
- Subjects
Liver chemistry ,medicine.diagnostic_test ,business.industry ,Gadolinium ,Radiochemistry ,chemistry.chemical_element ,Magnetic resonance imaging ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,chemistry ,medicine ,High doses ,Radiology, Nuclear Medicine and imaging ,Chelation ,Tissue distribution ,Nuclear medicine ,business ,030217 neurology & neurosurgery - Abstract
Intravenous administration of high doses of gadolinium-based contrast agents (GBCAs) is associated with extensive multiorgan deposition that is reduced but not eliminated by use of macrocyclic GBCA chelates in lieu of linear chelates.
- Published
- 2017
25. Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities
- Author
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David F. Kallmes, Robert J. McDonald, David L. Murray, Laurence J. Eckel, Jennifer S. McDonald, Eric E. Williamson, Mark E. Jentoft, and Michael A. Paolini
- Subjects
Pathology ,medicine.medical_specialty ,media_common.quotation_subject ,Gadolinium ,Contrast Media ,chemistry.chemical_element ,Models, Biological ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,cardiovascular diseases ,Aged ,Retrospective Studies ,media_common ,Aged, 80 and over ,Brain Chemistry ,Adult patients ,business.industry ,Human brain ,Middle Aged ,Magnetic Resonance Imaging ,Mr imaging ,medicine.anatomical_structure ,chemistry ,cardiovascular system ,business ,030217 neurology & neurosurgery - Abstract
Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate45 mL/min/1.73 m
- Published
- 2017
26. Spectroscopic and neutron detection properties of rare earth and titanium doped LiAlO2 single crystals
- Author
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Peter T. Dickens, Benjamin S. McDonald, Kelvin G. Lynn, José Marcial, and John S. McCloy
- Subjects
010302 applied physics ,Materials science ,Dopant ,Astrophysics::High Energy Astrophysical Phenomena ,Radiochemistry ,Biophysics ,Analytical chemistry ,chemistry.chemical_element ,02 engineering and technology ,General Chemistry ,Compton edge ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Biochemistry ,Atomic and Molecular Physics, and Optics ,Crystal ,chemistry ,0103 physical sciences ,Neutron detection ,Neutron source ,Neutron ,Lithium ,0210 nano-technology ,Luminescence - Abstract
In this study, LiAlO2 crystals doped with rare-earth elements and Ti were produced by the CZ method and spectroscopic and neutron detection properties were investigated. Photoluminescence revealed no clear luminescent activation of LiAlO2 by the rare-earth dopants though some interesting luminescence was observed from secondary phases within the crystal. Gamma-ray pulse height spectra collected using a 137Cs source exhibited only a Compton edge for the crystals. Neutron modeling using Monte Carlo N-Particle Transport Code revealed most neutrons used in the detection setup are thermalized, and while using natural lithium in the crystal growth, which contains 7.6% 6Li, a 10 mm O by 10 mm sample of LiAlO2 has a 70.7% intrinsic thermal neutron capture efficiency. Furthermore, the pulse height spectra collected using a 241Am-Be neutron source demonstrated a distinct neutron peak.
- Published
- 2017
27. Analysis of an indirect neutron signature for enhanced UF6 cylinder verification
- Author
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Jonathan A. Kulisek, Mital A. Zalavadia, Jennifer B. Webster, Leon E. Smith, and Benjamin S. McDonald
- Subjects
Physics ,Nuclear and High Energy Physics ,Spectrometer ,010308 nuclear & particles physics ,Astrophysics::High Energy Astrophysical Phenomena ,020209 energy ,Nuclear engineering ,Monte Carlo method ,02 engineering and technology ,Enriched uranium ,01 natural sciences ,Cylinder (engine) ,law.invention ,Nuclear physics ,chemistry.chemical_compound ,Uranium hexafluoride ,chemistry ,law ,0103 physical sciences ,0202 electrical engineering, electronic engineering, information engineering ,Neutron detection ,Neutron ,Nuclide ,Instrumentation - Abstract
The International Atomic Energy Agency (IAEA) currently uses handheld gamma-ray spectrometers combined with ultrasonic wall-thickness gauges to verify the declared enrichment of uranium hexafluoride (UF6) cylinders. The current method provides relatively low accuracy for the assay of 235U enrichment, especially for natural and depleted UF6. Furthermore, the current method provides no capability to assay the absolute mass of 235U in the cylinder due to the localized instrument geometry and limited penetration of the 186-keV gamma-ray signature from 235U. Also, the current verification process is a time-consuming component of on-site inspections at uranium enrichment plants. Toward the goal of a more-capable cylinder assay method, the Pacific Northwest National Laboratory has developed the hybrid enrichment verification array (HEVA). HEVA measures both the traditional 186-keV direct signature and a non-traditional, high-energy neutron-induced signature (HEVANT). HEVANT enables full-volume assay of UF6 cylinders by exploiting the relatively larger mean free paths of the neutrons emitted from the UF6. In this work, Monte Carlo modeling is used as the basis for characterizing HEVANT in terms of the individual contributions to HEVANT from nuclides and hardware components. Monte Carlo modeling is also used to quantify the intrinsic efficiency of HEVA for neutron detection in a cylinder-assay geometry. Modeling predictions are validated against neutron-induced gamma-ray spectra from laboratory measurements and a relatively large population of Type 30B cylinders spanning a range of enrichments. Implications of the analysis and findings on the viability of HEVA for cylinder verification are discussed, such as the resistance of the HEVANT signature to manipulation by the nearby placement of neutron-conversion materials.
- Published
- 2017
28. Acute Kidney Injury After Intravenous Versus Intra-Arterial Contrast Material Administration in a Paired Cohort
- Author
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David F. Kallmes, Robert J. McDonald, Jennifer S. McDonald, Richard W. Katzberg, Rajiv Gulati, Caleb B. Leake, and Eric E. Williamson
- Subjects
Male ,Cardiac Catheterization ,medicine.medical_specialty ,medicine.medical_treatment ,Contrast-induced nephropathy ,Contrast Media ,Renal function ,Kidney Function Tests ,urologic and male genital diseases ,030218 nuclear medicine & medical imaging ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Dialysis ,Aged ,Retrospective Studies ,Cardiac catheterization ,Creatinine ,business.industry ,Acute kidney injury ,Retrospective cohort study ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Radiographic Image Enhancement ,Injections, Intra-Arterial ,chemistry ,030220 oncology & carcinogenesis ,Anesthesia ,Administration, Intravenous ,Female ,Radiology ,Tomography, X-Ray Computed ,business ,Glomerular Filtration Rate ,Cohort study - Abstract
Objectives The aim of this study was to determine whether intra-arterial administration of contrast material is associated with a higher risk of acute kidney injury (AKI) compared with that of intravenous (IV) administration in a cohort of patients that received both routes of administration. Materials and methods All patients who received both a contrast-enhanced computed tomography (CT) and a diagnostic or interventional cardiac catheterization between 2000 and 2014 were identified. Patients who lacked sufficient preprocedure and postprocedure serum creatinine results, who were on preexisting renal dialysis, or who underwent additional contrast-enhanced procedures within 7 days of either procedure were excluded. The rate of AKI (serum creatinine ≥0.3 mg/dL or 50% above baseline) was compared after CT scan and cardiac catheterization using McNemar test. Results A total of 1969 patients met all study inclusion criteria. The rate of AKI after CT scan was similar to the rate after catheterization when examining all patients (9.9% CT vs 11% catheterization, P = 0.12). A similar rate of AKI after both procedures was observed regardless of procedure order, catheterization type, and patient baseline estimated glomerular filtration rate. Conclusions Intra-arterial administration of contrast material during cardiac catheterization had a similar risk of AKI as compared with that of CT scanning involving IV administration in a cohort of patients who underwent both procedures. These findings suggest that previously reported much higher rates of AKI after cardiac catheterization compared with that of IV contrast administration reflect higher baseline clinical risk factors for AKI in the former cohort compared with that in the latter.
- Published
- 2016
29. Utility of linear and nonlinear models for retention prediction in liquid chromatography
- Author
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Fabrice Gritti, Thomas S. McDonald, Martin Gilar, and Jason F. Hill
- Subjects
Work (thermodynamics) ,Chromatography, Reverse-Phase ,Chromatography ,Chemistry ,Elution ,010401 analytical chemistry ,Organic Chemistry ,Solvation ,General Medicine ,Reversed-phase chromatography ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Analytical Chemistry ,Nonlinear system ,Column chromatography ,Nonlinear Dynamics ,Phase (matter) ,Range (statistics) ,Linear Models ,Algorithms ,Chromatography, High Pressure Liquid ,Chromatography, Liquid - Abstract
Linear solvation strength model in reversed-phase liquid chromatography assumes linear relationship between ln k and Φ. In this work we show that this assumption is true only in narrow range of mobile phase strength. The ln k versus Φ relationship could be more accurately described by three-parametric non-linear model in a wide range of eluent strength. We investigated the consequences of non-linearity on retention prediction accuracy and analyte retention behavior in reversed-phase chromatography. When the ln k versus Φ is measured in narrow range of mobile phase strength (ΔΦ ~ 0.1-0.2) both linear and nonlinear models provide comparable retention prediction results. We propose that the linear trend of ln k versus Φ relationship is obtained in the range flanking the elution factor ke (value of retention factor at the column end). We calculated and plotted changes of retention factor of analytes along the column. The visualization illustrates the ranges of retention factor values participating in separation during gradient. For typical gradient slopes employed in liquid chromatography practice and small molecules the elution factor ke value is between 2 and 8. As a simplified generalization for typical gradient slopes we propose using linear ln k versus Φ trend in the k range between 1 and 30. The spreadsheet was utilized to compare the retention prediction accuracy of linear and non-linear retention models. When fitting ln k versus Φ trend in k range 1-30 the simple linear model is in good agreement with nonlinear model with retention time prediction error 0.3-4.7% (for gradient slope 0.013-0.260).
- Published
- 2019
30. Analysis of Dextromethorphan and Three Metabolites in Decomposed Skeletal Tissues by UPLC-QToF-MS: Comparison of Acute and Repeated Drug Exposures
- Author
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Claire S McDonald, Heather M. Cornthwaite, and James H. Watterson
- Subjects
Drug ,Analyte ,Health, Toxicology and Mutagenesis ,media_common.quotation_subject ,Electrospray ionization ,Toxicology ,Mass spectrometry ,01 natural sciences ,Dextromethorphan ,Bone and Bones ,Mass Spectrometry ,Analytical Chemistry ,Skeletal tissue ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Environmental Chemistry ,Animals ,030216 legal & forensic medicine ,media_common ,Chemical Health and Safety ,Chromatography ,Dextrorphan ,Chemistry ,010401 analytical chemistry ,Skeleton (computer programming) ,0104 chemical sciences ,Body Remains ,Rats ,Uplc qtof ms ,medicine.drug ,Chromatography, Liquid - Abstract
Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC–QToF–MS) analysis of dextromethorphan (DXM) and its metabolites—dextrorphan, 3-methoxymorphinan (3-MEM) and 3-hydroxymorphinan—in skeletal remains of rats exposed to DXM under different dosing patterns is described. Rats (n = 20) received DXM in one of four dosing patterns: acute (ACU1 or ACU2—100 or 200 mg/kg, i.p.; n = 5, respectively) or repeated (REP1 or REP2—3 doses of 25 or 50 mg/kg, i.p., 30 min apart; n = 5, respectively). Drug-free animals (n = 5) served as negative controls. Following euthanasia, the animals decomposed to skeleton outdoors. Bones were sorted by animal and skeletal element (vertebra, femur, pelvis, tibia, rib and skull), washed, air-dried and pulverized prior to dynamic methanolic drug extraction, filtration/pass-through extraction and analysis by UPLC–QToF–MS in positive electrospray ionization mode. Analyte levels (expressed as mass-normalized response ratios, RR/m) differed significantly between ACU1 and ACU2 (Mann–Whitney (MW), P
- Published
- 2019
31. Nutritional and functional properties of cookies made using down-graded lentil – A candidate for novel food production and crop utilization
- Author
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Heidi Irvin, Pankaj Maharjan, Christopher Blanchard, Mani Naiker, C.K. Walker, Joe Panozzo, Drew Portman, Linda S. McDonald, and Slavica Laskovska
- Subjects
Adverse weather ,kaempferol ,Chemistry ,Organic Chemistry ,Wheat flour ,Novel food ,Raw material ,Wholemeal flour ,food.food ,lentil ,Crop ,food ,oligosaccharides ,procyanidin ,Production (economics) ,Food science ,frost ,protein ,Food Science ,Total protein ,fiber - Abstract
Background and objectives Lentil (Lens culinaris M.) is a high-value grain used traditionally as a minimally processed product. Lentil crops are well-suited to Mediterranean-type climates with mild winters and hot dry summers which results in the production of high-value grain. However, extreme weather conditions, such as frost, can impact the lentil seed, for example, a darkened seed color and distorted seed shape resulting in a downgrade of its market value. The quality parameters of lentil when milled as wholemeal flour is not reliant on visual or physical seed traits such as seed size and color which impact on the market value in traditional market specifications. Instead, quality parameters such as those applied in the assessment of wheat, these include flour yield and color would be appropriate parameters to determine the value of lentil flour. It is proposed that flour, even from down-graded lentil could be supplemented with wheat flour and used to enhance the quality profile of baked products including breads, pastas, and cookies. Findings This study investigated the use of premium and frost-damaged lentil flour in cookie making. Overall cookies made from wheat–lentil composite blends resulted in flatter and wider cookies that were darker than the cookies made from 100% wheat flour. Cookies made by incorporating lentil and wheat flour resulted in a significant increase in total protein, insoluble fiber, and oligosaccharides (p < .05). In addition, the phenolic acids kaempferol and procyanidin were detected in cookies made using wheat–lentil contributing to an increase in antioxidant activity (p < .05). These phenolic acids were not detected in cookies made from 100% wheat flour. Our results show that using concentrations of up to 25% lentil flour resulted in cookies that had expectable hardness and color characteristics in comparison with a 100% wheat biscuit. Conclusion This research showed that the nutritional value and functional properties of cookies can be significantly enhanced by using either premium or down-graded lentil and the quality of the cookies was not impacted by the market-grade of the raw material. Significance and novelty Investigations into the use of pulse flours such as lentil in novel food products including pasta and snack foods are gaining popularity particularly by the health-conscious consumer. The visual appearance of lentil is not critical when utilized in such products. Lentil that has been visually or physically affected by adverse weather conditions, but its nutritional and functional values have not been compromised may prove a viable inclusion in the creation of highly nutritious food alternatives. The use of down-graded lentil as flour in novel food production could ultimately add value to pulse grain affected by adverse environmental conditions.
- Published
- 2019
32. Cardiac Troponin I N-Terminal Pseudo-Phosphorylation Regulates Power Output and Stretch Activation
- Author
-
Brandon J. Biesiadecki, Joel C. Robinett, Kerry S. McDonald, and Laurin M. Hanft
- Subjects
Cardiac troponin ,Terminal (electronics) ,Chemistry ,Biophysics ,Phosphorylation ,Power output - Published
- 2021
33. Molecule specific effects of PKA-mediated phosphorylation on rat isolated heart and cardiac myofibrillar function
- Author
-
Craig A. Emter, Michael J. Rovetto, Laurin M. Hanft, Colin A. McDonald, Timothy D. Cornell, and Kerry S. McDonald
- Subjects
Male ,Sarcomeres ,0301 basic medicine ,medicine.medical_specialty ,Myofilament ,Biophysics ,macromolecular substances ,Biochemistry ,Sarcomere ,Article ,Rats, Sprague-Dawley ,Contractility ,03 medical and health sciences ,Myofibrils ,Isometric Contraction ,Internal medicine ,medicine ,Animals ,Myocyte ,Calcium Signaling ,Phosphorylation ,Muscle, Skeletal ,Molecular Biology ,Chemistry ,Myocardium ,Cardiac myocyte ,Hemodynamics ,Heart ,Cyclic AMP-Dependent Protein Kinases ,Recombinant Proteins ,Rats ,030104 developmental biology ,Endocrinology ,cardiovascular system ,Calcium ,Stress, Mechanical ,Myofibril ,PRKCE ,Signal Transduction - Abstract
Increased cardiac myocyte contractility by the β-adrenergic system is an important mechanism to elevate cardiac output to meet hemodynamic demands and this process is depressed in failing hearts. While increased contractility involves augmented myoplasmic calcium transients, the myofilaments also adapt to boost the transduction of the calcium signal. Accordingly, ventricular contractility was found to be tightly correlated with PKA-mediated phosphorylation of two myofibrillar proteins, cardiac myosin binding protein-C (cMyBP-C) and cardiac troponin I (cTnI), implicating these two proteins as important transducers of hemodynamics to the cardiac sarcomere. Consistent with this, we have previously found that phosphorylation of myofilament proteins by PKA (a downstream signaling molecule of the beta-adrenergic system) increased force, slowed force development rates, sped loaded shortening, and increased power output in rat skinned cardiac myocyte preparations. Here, we sought to define molecule-specific mechanisms by which PKA-mediated phosphorylation regulates these contractile properties. Regarding cTnI, the incorporation of thin filaments with unphosphorylated cTnI decreased isometric force production and these changes were reversed by PKA-mediated phosphorylation in skinned cardiac myocytes. Further, incorporation of unphosphorylated cTnI sped rates of force development, which suggests less cooperative thin filament activation and reduced recruitment of non-cycling cross-bridges into the pool of cycling cross-bridges, a process that would tend to depress both myocyte force and power. Regarding MyBP-C, PKA treatment of slow-twitch skeletal muscle fibers caused phosphorylation of MyBP-C (but not slow skeletal TnI (ssTnI)) and yielded faster loaded shortening velocity and ~30% increase in power output. These results add novel insight into the molecular specificity by which the β-adrenergic system regulates myofibrillar contractility and how attenuation of PKA-induced phosphorylation of cMyBP-C and cTnI may contribute to ventricular pump failure.
- Published
- 2016
34. Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-l-Carnitine
- Author
-
Olav B. Smeland, Haytham Eloqayli, Tore Wergeland Meisingset, Saied A. Jaradat, Karin Borges, Mussie Ghezu Hadera, Ursula Sonnewald, and Tanya S. McDonald
- Subjects
0301 basic medicine ,Neurological disorder ,Pharmacology ,Biology ,Inhibitory postsynaptic potential ,Biochemistry ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Epilepsy ,0302 clinical medicine ,medicine ,Animals ,Humans ,Amino Acids ,Acetylcarnitine ,Triglycerides ,Neurotransmitter Agents ,Glutamate receptor ,General Medicine ,medicine.disease ,Triheptanoin ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,chemistry ,Astrocytes ,Anticonvulsants ,Kindling model ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug ,Astrocyte - Abstract
Epilepsy is a severe neurological disorder characterized by altered electrical activity in the brain. Important pathophysiological mechanisms include disturbed metabolism and homeostasis of major excitatory and inhibitory neurotransmitters, glutamate and GABA. Current drug treatments are largely aimed at decreasing neuronal excitability and thereby preventing the occurrence of seizures. However, many patients are refractory to treatment and side effects are frequent. Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults. In rodents, the pilocarpine-status epilepticus model reflects the pathology and chronic spontaneous seizures of TLE and the pentylenetetrazole kindling model exhibits chronic induced limbic seizures. Accumulating evidence from studies on TLE points to alterations in astrocytes and neurons as key metabolic changes. The present review describes interventions which alleviate these disturbances in astrocyte-neuronal interactions by supporting mitochondrial metabolism. The compounds discussed are the endogenous transport molecule acetyl-L-carnitine and the triglyceride of heptanoate, triheptanoin. Both provide acetyl moieties for oxidation in the tricarboxylic acid cycle whereas heptanoate is also provides propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis-the refilling of the tricarboxylic acid cycle.
- Published
- 2015
35. Correlation between 24-hour proteinuria and spot urine albumin to creatinine ratio in systemic light chain amyloidosis
- Author
-
Eli Muchtar, Harsh Parmar, Morie A. Gertz, Alissa Visram, Abdullah S. Al Saleh, Nelson Leung, Francis K. Buadi, Jennifer S. McDonald, Iuliana Vaxman, and Angela Dispenzieri
- Subjects
Cancer Research ,medicine.medical_specialty ,Creatinine ,Proteinuria ,business.industry ,Amyloidosis ,Urology ,Albumin ,Gold standard (test) ,medicine.disease ,Immunoglobulin light chain ,Spot urine ,chemistry.chemical_compound ,Oncology ,chemistry ,Medicine ,medicine.symptom ,business - Abstract
8549 Background: Proteinuria evaluation is essential for diagnosing and monitoring of renal involvement in light chain (AL) amyloidosis. A 24 hour protein collection (24h UP) is the gold standard for proteinuria assessment however it is cumbersome and can be inaccurate. A spot urine albumin to creatinine ratio (uACR) has been proposed as a convenient method to estimate 24hUP. We aimed to validate the correlation between uACR and 24hUP in a large cohort of patients. Methods: We retrospectively studied systemic AL amyloidosis patients evaluated between 2010 and 2019 at Mayo Clinic, with a uACR and 24hUP collected less than 7 days apart. Linear regression analysis was used to construct a prediction model for 24hUP with uACR as the primary predictor. Possible confounders (age, gender, body mass index, morning versus afternoon spot urine collection, estimated glomerular filtration rate) for the primary relationship between uACR and 24h UP were evaluated in the model. We used receiver operating characteristic (ROC) analysis to identify the best uACR cutoff to predict significant proteinuria (defined as a 24hUP > 500mg). Results: We included 665 patients, with a median age of 66 years (IQR 59-72). The spot urine was collected in the morning (before 1200 hours) in 382 (57%) patients, and in the afternoon in 283 (43%) patients. The median 24hUP was 321 (IQR 129-2512.5) mg, median uACR was 107 (IQR 13.5-1845) mg/g, and median serum creatinine was 1.2 (IQR 1-1.8) mg/dL. The uACR correlated well with 24h UP (Pearson’s r= 0.83, 95% CI 0.80-0.85). Linear regression showed that E (24h UPi) = 362 + 1.05(uACRi), and this model was statistically and clinically significant (p < 0.001 and R2 of 0.68, respectively). Age, gender, body mass index, eGFR, and time of day of spot urine collection did not confound the primary relationship between uACR and 24hUP, and no collinearity was observed. A uACR cutoff of > 280 mg/g was the best predictor of a 24hUP > 500 mg (area under the ROC curve 0.98, sensitivity 92%, specificity 97%). For simplicity, we assessed the predictive value of uACR > 300 mg/g for 24h UP > 500 mg. Among patients with 24huACR > 300 mg/g 264 (96%) had a 24hUP > 500 mg, and 31 (7%) of patients with uACR < 300 mg/g had a 24h UP > 500 mg (p < 0.001). Conclusions: In systemic AL amyloid patients, we showed that uACR on a random urine sample correlated well with 24h UP, and can be used to estimate proteinuria with a linear regression model. Based on these findings, and the convenience of uACR testing for patients, we propose that uACR should be used to monitor renal response to AL amyloidosis therapy.
- Published
- 2020
36. Gamma-ray spectrum variations for surface measurements of uranium hexafluoride cylinders
- Author
-
Benjamin S. McDonald, Bonnie Canion, Noah McFerran, Andreas Enqvist, Jonathan A. Kulisek, Jonathan Dreyer, and Simon E. Labov
- Subjects
Physics ,Surface (mathematics) ,Nuclear and High Energy Physics ,Work (thermodynamics) ,010308 nuclear & particles physics ,0211 other engineering and technologies ,Gamma ray ,02 engineering and technology ,Geometric distribution ,01 natural sciences ,Spectral line ,Computational physics ,Cylinder (engine) ,law.invention ,Physics::Fluid Dynamics ,chemistry.chemical_compound ,Uranium hexafluoride ,chemistry ,law ,0103 physical sciences ,021108 energy ,Spectroscopy ,Instrumentation - Abstract
This work aims to characterize features that contribute to the spectral variations that appear in gamma-ray spectra of filled uranium hexafluoride (UF6) cylinders. While the enrichment of the UF6 in a cylinder can greatly affect gamma-ray spectra at peaks such as the 185.7 keV peak and be used to verify enrichment, many other characteristics of a filled UF6 cylinder can affect the spectra. These characteristics vary on a per-cylinder basis and can include: the time between when a cylinder was filled and when it was measured; the previous fill history of a cylinder; how the cylinder was most recently filled; the UF6 geometric distribution within the cylinder; and the measurement location along the cylinder. This work explores spectral variations seen in measurement data and uses validated simulation models to find trends in these uncertainties. These trends are analyzed to observe how each parameter can contribute to the overall uncertainty of UF6 spectral measurements.
- Published
- 2020
37. Detector characterization for quantitative spectral radiography of uranium powder samples
- Author
-
Andrew J. Gilbert, Dustin M. Kasparek, Benjamin S. McDonald, and Rick Wittman
- Subjects
Physics ,Nuclear and High Energy Physics ,Fabrication ,Nuclear fuel ,Nuclear engineering ,Detector ,Pellets ,chemistry.chemical_element ,Scrap ,Uranium ,Characterization (materials science) ,chemistry ,Calibration ,Instrumentation - Abstract
The International Atomic Energy Agency (IAEA) is responsible for verifying the mass of elemental uranium in various forms (powders, pellets, scrap) as part of inspections at nuclear fuel fabrication facilities. Current methods require in-field dissolution chemistry, which is time consuming and imposes operational challenges. Pacific Northwest National Laboratory (PNNL) is developing a prototype spectral x-ray radiography (SpecX) nondestructive assay system for noninvasive material mass quantification of uranium-bearing powders. The SpecX system uses a custom material estimation algorithm, which requires a high-fidelity pixel-by-pixel detector response model for accurate quantification. We performed a detailed characterization and built a model of a High-Energy X-ray Imaging Technology (HEXITEC) CdTe pixelated spectral detector. Here we present the detector characterization which led to that model, including a determination of the pixel-wise energy calibration, the detection efficiency, the detector uniformity, the detector stability, and a comparison of methods to remove charge-shared events.
- Published
- 2020
38. Energy metabolism in epilepsy: biochemical changes in glucose metabolism and the effects of metabolic treatments in murine seizure models
- Author
-
Tanya S. McDonald
- Subjects
medicine.medical_specialty ,Epilepsy ,Endocrinology ,Chemistry ,Internal medicine ,medicine ,Energy metabolism ,Carbohydrate metabolism ,medicine.disease - Published
- 2018
39. Acquisition parameters for dual-energy contrast-enhanced digital mammography using a micelle-based all-in-one nanoparticle (AION) contrast agent: a phantom study
- Author
-
Peter Chhour, David P. Cormode, Andrew D. A. Maidment, Renee Hastings, Joel M. Stein, Kristen C. Lau, Jessica C. Hsu, Elizabeth S. McDonald, and Pratap C. Naha
- Subjects
Materials science ,Digital mammography ,Breast imaging ,Silver sulfide ,media_common.quotation_subject ,Nanoparticle ,Imaging phantom ,Silver nanoparticle ,chemistry.chemical_compound ,chemistry ,Contrast Enhanced Digital Mammography ,Contrast (vision) ,Biomedical engineering ,media_common - Abstract
The objective of our study is to optimize the acquisition parameters for imaging Ag2S nanoparticles using contrast-enhanced digital mammography (CE-DM) by varying parameters such as kV, mAs, and filtration. The efficacies of three different contrast materials (Ag2S nanoparticles, silver nanoparticles, and iodine) were assessed using a contrast-embedded gradient phantom. The phantom was constructed using tissue-equivalent materials and varied continuously in composition from 100% glandular tissue to 100% adipose tissue. Each contrast agent was prepared at six different concentrations (1, 2, 5, 10, 15, and 25 mg/mL). Holes were bored through the phantom in the direction of varying glandularity, and tubes of contrast agents were inserted into the holes. Phantoms were imaged at four different energies (26 kV, 32 kV, 45 kV, and 49 kV); 5 energy pairs were considered in this study. Our results demonstrate that for a given contrast agent, the contrast-to-noise ratio is linearly proportional to concentration, and its magnitude is dependent on the energy of the low-energy (LE) image. In our study, it was shown that the LE images at 26 kV are better suited for imaging silver-based nanoparticles, and the LE images at 32 kV are better suited for imaging iodine contrast. Thus, the energy of the LE image should be chosen so that it is as close as possible to the k-edge of the contrast material. Preliminary results from CE-DM imaging indicate that silver contrast has a significantly higher signal than iodine contrast when imaging at lower energies, thus demonstrating the feasibility of using silver-based nanoparticles in breast imaging.
- Published
- 2018
40. Contact Dermatitis Reaction to 2-Octyl Cyanoacrylate Following 3 Orthopedic Procedures
- Author
-
James E Toledano, Nicholas H Lake, Brian T. Barlow, Lucas S. McDonald, and Johannah Valentine
- Subjects
Adult ,Male ,medicine.medical_specialty ,Triamcinolone acetonide ,Adolescent ,030230 surgery ,Dermatitis, Contact ,Triamcinolone ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hematoma ,law ,medicine ,Humans ,Orthopedic Procedures ,Orthopedics and Sports Medicine ,Cyanoacrylates ,Child ,Allergic contact dermatitis ,Wound Closure Techniques ,business.industry ,medicine.disease ,Dermatology ,Surgery ,2-Octyl cyanoacrylate ,chemistry ,Cyanoacrylate ,Orthopedic surgery ,Female ,Tissue Adhesives ,business ,Contact dermatitis ,medicine.drug - Abstract
Two-octyl cyanoacrylate is a popular skin adhesive used for closing surgical incisions. Since Food and Drug Administration approval in 1998, the few reports of adverse reactions following its use have primarily been limited to the nonorthopedic literature. The authors present a case series of contact dermatitis associated with 2-octyl cyanoacrylate following orthopedic surgery and a review of the literature on the diagnosis and treatment of this complication. All 3 patients presented with blistering around their incisions within 2 weeks of surgery and responded to treatment involving removal of the offending agent and use of oral diphenhydramine and hydroxyzine and topical triamcinolone. One case was complicated by a draining hematoma, requiring irrigation and debridement. Complete resolution occurred in all cases. This case series is intended to increase awareness in the orthopedic community of allergic contact dermatitis to 2-octyl cyanoacrylate and its appropriate treatment. [ Orthopedics. 2018; 41(2):e289–e291.]
- Published
- 2018
41. The effect of dichloroacetate in mouse models of epilepsy
- Author
-
Tanya S. McDonald, Karin Borges, and Dylan Durie
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Pyruvate dehydrogenase kinase ,Protein subunit ,Convulsants ,03 medical and health sciences ,Epilepsy ,Mice ,0302 clinical medicine ,Internal medicine ,Flurothyl ,medicine ,Animals ,Chronic stage ,Analysis of Variance ,Dichloroacetic Acid ,Chemistry ,Pilocarpine ,Ketone Oxidoreductases ,Pyruvate dehydrogenase complex ,medicine.disease ,Electric Stimulation ,Mitochondria ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Neurology ,Phosphorylation ,Anticonvulsants ,Neurology (clinical) ,030217 neurology & neurosurgery ,medicine.drug - Abstract
A recent report has found that glucose oxidation and the activity of pyruvate dehydrogenase (PDH) are reduced in the chronic stage of the pilocarpine mouse epilepsy model. This is likely caused by increased phosphorylation by PDH kinase of the E1α subunit of PDH, downregulating its activity. Inhibition of this phosphorylation has not yet been explored as a possible approach to treat epilepsy. Chronic dichloroacetate (DCA, 50 and 100 mg/kg/day) treatment was tested in acute seizure and the chronic pilocarpine models. We also determined the effects on phosphorylation state, activity and protein levels of PDH in the chronic stage of the pilocarpine model. DCA treatment did not increase latencies to seizures in the acute flurothyl seizure test and was slightly proconvulsant in the 6 Hz test. The latencies to seizures in a second-hit flurothyl test were decreased in SE vs. No SE mice in the chronic stage, but were not restored by DCA. In mice that had experienced pilocarpine-induced SE and were in the chronic “epileptic” stage of the model, PDH activity was reduced by 65% compared to “healthy” No SE mice. This was partially alleviated with DCA treatment. Also, PDH protein levels were decreased by 37% and phosphorylation at Ser300 of PDH was increased by 52% in SE mice, but were not significantly changed with DCA. Moreover DCA treatment decreased the amounts of total PDH by 23% in No SE mice, which may explain the proconvulsant effects in the 6 Hz test. The reduction in PDH protein levels during the chronic epileptic stage suggests increased degradation of the protein, which may contribute to the deficient glucose oxidation found in epilepsy. Taken together, DCA did not have any anti-convulsant effects in the tested models. Future studies utilising other PDH kinase inhibitors are required to determine whether this treatment approach is viable.
- Published
- 2018
42. Chronic low-intensity exercise attenuates cardiomyocyte contractile dysfunction and impaired adrenergic responsiveness in aortic-banded mini-swine
- Author
-
Adam B. Veteto, Jessica A. Hiemstra, Timothy L. Domeier, T. Dylan Olver, Kerry S. McDonald, Craig A. Emter, Michelle D. Lambert, and Brian S. Ferguson
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Physiology ,Swine ,chemistry.chemical_element ,Adrenergic ,030204 cardiovascular system & hematology ,Calcium ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Physical Conditioning, Animal ,Medicine ,Animals ,Myocytes, Cardiac ,Excitation Contraction Coupling ,Heart Failure ,business.industry ,Excitation–contraction coupling ,medicine.disease ,Myocardial Contraction ,030104 developmental biology ,chemistry ,Heart failure ,Low intensity exercise ,Cardiology ,Swine, Miniature ,Heart failure with preserved ejection fraction ,business ,Research Article - Abstract
Exercise improves clinical outcomes in patients diagnosed with heart failure with reduced ejection fraction (HFrEF), in part via beneficial effects on cardiomyocyte Ca2+ cycling during excitation-contraction coupling (ECC). However, limited data exist regarding the effects of exercise training on cardiomyocyte function in patients diagnosed with heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to investigate cardiomyocyte Ca2+ handling and contractile function following chronic low-intensity exercise training in aortic-banded miniature swine and test the hypothesis that low-intensity exercise improves cardiomyocyte function in a large animal model of pressure overload. Animals were divided into control (CON), aortic-banded sedentary (AB), and aortic-banded low-intensity trained (AB-LIT) groups. Left ventricular cardiomyocytes were electrically stimulated (0.5 Hz) to assess Ca2+ homeostasis (fura-2-AM) and unloaded shortening during ECC under conditions of baseline pacing and pacing with adrenergic stimulation using dobutamine (1 μM). Cardiomyocytes in AB animals exhibited depressed Ca2+ transient amplitude and cardiomyocyte shortening vs. CON under both conditions. Exercise training attenuated AB-induced decreases in cardiomyocyte Ca2+ transient amplitude but did not prevent impaired shortening vs. CON. With dobutamine, AB-LIT exhibited both Ca2+ transient and shortening amplitude similar to CON. Adrenergic sensitivity, assessed as the time to maximum inotropic response following dobutamine treatment, was depressed in the AB group but normal in AB-LIT animals. Taken together, our data suggest exercise training is beneficial for cardiomyocyte function via the effects on Ca2+ homeostasis and adrenergic sensitivity in a large animal model of pressure overload-induced heart failure. NEW & NOTEWORTHY Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Our findings show chronic low-intensity exercise training can prevent cardiomyocyte dysfunction and impaired adrenergic responsiveness in a translational large animal model of chronic pressure overload-induced heart failure with relevance to human HFpEF.
- Published
- 2018
43. Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX
- Author
-
David F. Kallmes, Sylvain V. Costes, Tamara M. Hudson, Dana Schroeder, Jennifer S. McDonald, Philip M. Young, Jacob B. Ekins, Anthony S. Tin, Robert J. McDonald, Aiming Lu, Ramanathan Kadirvel, Scott H. Kaufmann, and Kevin M. Kallmes
- Subjects
0301 basic medicine ,Male ,Pathology ,DNA Repair ,Physiology ,medicine.medical_treatment ,lcsh:Medicine ,Gadolinium ,030204 cardiovascular system & hematology ,Biochemistry ,Diagnostic Radiology ,Histones ,White Blood Cells ,0302 clinical medicine ,Animal Cells ,Medicine and Health Sciences ,Lymphocytes ,Prospective Studies ,Prospective cohort study ,lcsh:Science ,Multidisciplinary ,medicine.diagnostic_test ,Radiology and Imaging ,Heart ,Middle Aged ,Magnetic Resonance Imaging ,Body Fluids ,Nucleic acids ,Chemistry ,Blood ,Physical Sciences ,Female ,Cellular Types ,Anatomy ,Cardiomyopathies ,Tumor Suppressor p53-Binding Protein 1 ,Research Article ,Chemical Elements ,Adult ,medicine.medical_specialty ,DNA damage ,Imaging Techniques ,Immune Cells ,Immunology ,Cardiology ,Malignancy ,Research and Analysis Methods ,Drug Absorption ,Peripheral blood mononuclear cell ,03 medical and health sciences ,Diagnostic Medicine ,medicine ,Genetics ,Humans ,Clinical significance ,Pharmacokinetics ,Aged ,Retrospective Studies ,Pharmacology ,Chemotherapy ,Blood Cells ,Biology and life sciences ,business.industry ,lcsh:R ,Correction ,Magnetic resonance imaging ,DNA ,Cell Biology ,medicine.disease ,Radiation therapy ,030104 developmental biology ,lcsh:Q ,business ,Biomarkers ,DNA Damage - Abstract
Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.
- Published
- 2018
44. Gadolinium Deposition in the Pediatric Brain-Reply
- Author
-
Laurence J. Eckel, Robert J. McDonald, and Jennifer S. McDonald
- Subjects
business.industry ,Gadolinium ,chemistry.chemical_element ,Brain ,Contrast Media ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,chemistry ,Pediatric brain ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Medicine ,Humans ,business ,Nuclear medicine ,Child ,Deposition (chemistry) - Published
- 2017
45. Bilateral Sustained Nephrograms After Parenteral Administration of Iodinated Contrast Material: A Potential Biomarker for Acute Kidney Injury, Dialysis, and Mortality
- Author
-
Richard W. Katzberg, Robert J. McDonald, Kamel A. Gharaibeh, Jennifer S. McDonald, Eric E. Williamson, Erik M. Steckler, Nelson Leung, Abdurrahman M. Hamadah, Joseph G. Cernigliaro, and David F. Kallmes
- Subjects
Male ,medicine.medical_specialty ,Cardiac Catheterization ,medicine.medical_treatment ,Iohexol ,Urology ,Renal function ,Contrast Media ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Iodinated contrast ,Renal Dialysis ,Risk Factors ,medicine ,Humans ,Dialysis ,Cardiac catheterization ,Aged ,Retrospective Studies ,Creatinine ,business.industry ,Acute kidney injury ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,Administration, Intravenous ,Female ,business ,Tomography, X-Ray Computed ,Biomarkers ,medicine.drug ,Kidney disease ,Glomerular Filtration Rate - Abstract
To determine whether persistent bilateral global nephrograms are associated with acute kidney injury (AKI), dialysis, and mortality.All patients who underwent (1) contrast-enhanced computed tomography (CT) or cardiac catheterization with iohexol between January 1, 2000, and December 31, 2014, and (2) noncontrast abdominal CT in the subsequent 24±6 hours were identified. Patients without preprocedure and postprocedure creatinine measurements or who received additional contrast material were excluded. Nephrograms were identified by radiologist review and CT attenuation measurements. Univariate and multivariate analyses were performed to determine nephrogram risk factors. Acute kidney injury (defined as a creatinine level of ≥0.5 mg/dL or Kidney Disease: Improving Global Outcomes stages 1-3), dialysis, and mortality proportions were compared between patients with and without bilateral global nephrograms using the Fisher's exact test.A total of 123 patients met all inclusion criteria. The proportion of patients with a nephrogram was 37.4% (n=46), with a higher proportion following interventional (67% [18 of 30]) vs diagnostic (27.3% [9 of 33]) catheterization or contrast-enhanced computed tomography (31.7% [19 of 60]). Age (P=.002), chronic kidney disease (P=.05), and acute hypotension or shock (P=.02) were significant risk factors for nephrogram development. Patients with nephrogram had significantly higher rates of AKI (37.0% [17 of 46] vs 5.2% [4 of 77]; odds ratio [OR], 10.7 [95% CI, 3.31-34.5]; P.001), dialysis (17.4% [8 of 46] vs 1.3% [1 of 77]; OR, 16.0 [95% CI, 1.93-133]; P=.001), and mortality (15.2% [7 of 46] vs 1.3% [1 of 77]; OR, 13.6 [1.62-115]; P=.003) than patients without nephrogram.The presence of persistent bilateral global nephrograms suggests an increased risk of AKI, dialysis, and mortality when compared with patients whose kidneys fully eliminated the contrast material.
- Published
- 2017
46. Accurate measurement of dispersion data through short and narrow tubes used in very high-pressure liquid chromatography
- Author
-
Thomas S. McDonald, Martin Gilar, and Fabrice Gritti
- Subjects
Chromatography ,Aspect ratio ,Chemistry ,Organic Chemistry ,Taylor dispersion ,General Medicine ,Péclet number ,Biochemistry ,Analytical Chemistry ,Diffusion ,symbols.namesake ,Volume (thermodynamics) ,Dispersion (optics) ,symbols ,Tube (fluid conveyance) ,Diffusion (business) ,Chromatography, High Pressure Liquid ,Dimensionless quantity - Abstract
An original method is proposed for the accurate and reproducible measurement of the time-based dispersion properties of short L50cm and narrow rc50μm tubes at mobile phase flow rates typically used in very high-pressure liquid chromatography (vHPLC). Such tubes are used to minimize sample dispersion in vHPLC; however, their dispersion characteristics cannot be accurately measured at such flow rates due to system dispersion contribution of vHPLC injector and detector. It is shown that using longer and wider tubes (10μL) enables a reliable measurement of the dispersion data. We confirmed that the dimensionless plot of the reduced dispersion coefficient versus the reduced linear velocity (Peclet number) depends on the aspect ratio, L/rc, of the tube, and unexpectedly also on the diffusion coefficient of the analyte. This dimensionless plot could be easily obtained for a large volume tube, which has the same aspect ratio as that of the short and narrow tube, and for the same diffusion coefficient. The dispersion data for the small volume tube are then directly extrapolated from this plot. For instance, it is found that the maximum volume variances of 75μm×30.5cm and 100μm×30.5cm prototype finger-tightened connecting tubes are 0.10 and 0.30μL(2), respectively, with an accuracy of a few percent and a precision smaller than seven percent.
- Published
- 2015
47. Attenuated sarcomere lengthening of the aged murine left ventricle observed using two-photon fluorescence microscopy
- Author
-
Justin T. Whitfield, Gerald A. Meininger, Michael E. Nance, Steven S. Segal, Yi Zhu, Kenneth S. Campbell, Laurin M. Hanft, Anne K. Gibson, Timothy L. Domeier, and Kerry S. McDonald
- Subjects
Sarcomeres ,Physiology ,Chemistry ,Heart Ventricles ,Age Factors ,Anatomy ,Two photon fluorescence ,Sarcomere ,Mice, Inbred C57BL ,Mice ,Microscopy, Fluorescence, Multiphoton ,medicine.anatomical_structure ,Ventricle ,Elastic Modulus ,Physiology (medical) ,Microscopy ,cardiovascular system ,medicine ,Animals ,Cardiology and Cardiovascular Medicine ,Ventricular filling ,Muscle Mechanics and Ventricular Function ,Fluorescent Dyes - Abstract
The Frank-Starling mechanism, whereby increased diastolic filling leads to increased cardiac output, depends on increasing the sarcomere length ( Ls) of cardiomyocytes. Ventricular stiffness increases with advancing age, yet it remains unclear how such changes in compliance impact sarcomere dynamics in the intact heart. We developed an isolated murine heart preparation to monitor Ls as a function of left ventricular pressure and tested the hypothesis that sarcomere lengthening in response to ventricular filling is impaired with advanced age. Mouse hearts isolated from young (3–6 mo) and aged (24–28 mo) C57BL/6 mice were perfused via the aorta under Ca2+-free conditions with the left ventricle cannulated to control filling pressure. Two-photon imaging of 4-{2-[6-(dioctylamino)-2-naphthalenyl]ethenyl}1-(3-sulfopropyl)-pyridinium fluorescence was used to monitor t-tubule striations and obtain passive Ls between pressures of 0 and 40 mmHg. Ls values (in μm, aged vs. young, respectively) were 2.02 ± 0.04 versus 2.01 ± 0.02 at 0 mmHg, 2.13 ± 0.04 versus 2.23 ± 0.02 at 5 mmHg, 2.21 ± 0.03 versus 2.27 ± 0.03 at 10 mmHg, and 2.28 ± 0.02 versus 2.36 ± 0.01 at 40 mmHg, indicative of impaired sarcomere lengthening in aged hearts. Atomic force microscopy nanoindentation revealed that intact cardiomyocytes enzymatically isolated from aged hearts had increased stiffness compared with those of young hearts (elastic modulus: aged, 41.9 ± 5.8 kPa vs. young, 18.6 ± 3.3 kPa; P = 0.006). Impaired sarcomere lengthening during left ventricular filling may contribute to cardiac dysfunction with advancing age by attenuating the Frank-Starling mechanism and reducing stroke volume.
- Published
- 2015
48. Risk of Acute Kidney Injury, Dialysis, and Mortality in Patients With Chronic Kidney Disease After Intravenous Contrast Material Exposure
- Author
-
John C. Lieske, Richard W. Katzberg, Eric E. Williamson, Jennifer S. McDonald, David E. Kallmes, Rickey E. Carter, and Robert J. McDonald
- Subjects
medicine.medical_specialty ,Creatinine ,business.industry ,Urology ,Acute kidney injury ,Contrast-induced nephropathy ,Renal function ,Retrospective cohort study ,General Medicine ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,chemistry.chemical_compound ,chemistry ,Iodinated contrast ,Cohort ,medicine ,business ,Intensive care medicine ,Kidney disease - Abstract
Objective To examine the effect of intravenous iodinated contrast material administration on the subsequent development of acute kidney injury (AKI), emergent dialysis, and short-term mortality using a propensity score–adjusted analysis of computed tomographic scan recipients with chronic kidney disease (CKD). Patients and Methods In this institutional review board–approved retrospective study, all patients with CKD who received a contrast-enhanced (contrast group) or unenhanced (noncontrast group) computed tomographic scan from January 1, 2000, to August 1, 2013 were identified. Patients were subdivided into CKD stage III (baseline estimated glomerular filtration rate, 30-59 mL/min per 1.73 m 2 ) and CKD stage IV-V (baseline estimated glomerular filtration rate, 2 ) subgroups and separately underwent propensity score generation, stratification, and 1:1 matching. Rates of AKI, 30-day emergent dialysis, and mortality were compared between contrast and noncontrast groups. Sensitivity analyses examining only patients with stable prescan serum creatinine levels and incorporating intravenous fluid administration at the time of the CT scan into the model were also performed. Results A total of 6902 patients (4496 CKD stage III, matched: 1220 contrast and 1220 noncontrast; 2086 CKD stage IV-V, matched: 491 contrast and 491 noncontrast) were included in the study. After propensity score adjustment, rates of AKI, emergent dialysis, and mortality were not significantly higher in the contrast group than in the noncontrast group in either CKD subgroup (CKD stage III: OR, 0.65-1.00; P P =.22-.99). Both sensitivity analyses revealed similar results. Conclusion Intravenous contrast material administration was not associated with an increased risk of AKI, emergent dialysis, and short-term mortality in a cohort of patients with diminished renal function.
- Published
- 2015
49. Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging
- Author
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Eric E. Williamson, Jennifer S. McDonald, David F. Kallmes, Robert J. McDonald, Mark E. Jentoft, Laurence J. Eckel, Kent R. Thielen, and David L. Murray
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Gadolinium ,chemistry.chemical_element ,Renal function ,Mr imaging ,Gadolinium-based Contrast Agent ,chemistry.chemical_compound ,chemistry ,medicine ,Gadoteric acid ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Tissue distribution ,business ,Deposition (chemistry) ,media_common - Abstract
Intravenous administration of gadolinium-based contrast material is associated with dose-dependent deposition in neuronal tissues that is unrelated to renal function, age, or time between exposure and death.
- Published
- 2015
50. Wide injection zone compression in gradient reversed-phase liquid chromatography
- Author
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Thomas S. McDonald, Martin Gilar, James W. Jorgenson, Jay S. Johnson, and James P. Murphy
- Subjects
Chromatography, Reverse-Phase ,Chromatography ,Chemistry ,Organic Chemistry ,Microfluidics ,Analytical chemistry ,General Medicine ,Reversed-phase chromatography ,Compression (physics) ,Tracking (particle physics) ,Biochemistry ,Sample (graphics) ,Analytical Chemistry ,Volume (thermodynamics) ,Column (typography) ,Void volume ,Oligopeptides - Abstract
Chromatographic zone broadening is a common issue in microfluidic chromatography, where the sample volume introduced on column often exceeds the column void volume. To better understand the propagation of wide chromatographic zones on a separation device, a series of MS Excel spreadsheets were developed to simulate the process. To computationally simplify these simulations, we investigated the effects of injection related zone broadening and its gradient related zone compression by tracking only the movements of zone boundaries on column. The effects of sample volume, sample solvent, gradient slope, and column length on zone broadening were evaluated and compared to experiments performed on 0.32mm I.D. microfluidic columns. The repetitive injection method (RIM) was implemented to generate experimental chromatograms where large sample volume scenarios can be emulated by injecting two discrete small injection plugs spaced in time. A good match between predicted and experimental RIM chromatograms was observed. We discuss the performance of selected retention models on the accuracy of predictions and use the developed spreadsheets for illustration of gradient zone focusing for both small molecules and peptides.
- Published
- 2015
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