Paul Vogel, Ph.D.
Raleigh-Durham-Chapel Hill Area
3K followers
500+ connections
About
Innovative and exceptionally driven scientific professional with demonstrated ability to…
Education
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Michigan State University
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Activities and Societies: Younger Chemist's Committee, Orientation Committee, Michigan Science Olympiad Laboratory Supervisor
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Activities and Societies: Chem Club
Publications
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Effect of inhaled nitric oxide on oxygen therapy, mechanical ventilation, and hypoxic respiratory failure
Minerva Pediatrica
To assess the role of inhaled nitric oxide (iNO) in reducing the need for oxygen therapy, decreasing time on mechanical ventilatory support, and attenuating probability of hypoxic respiratory failure severity progression, we reviewed published reports of phase III iNO studies in neonates with hypoxic respiratory failure and pulmonary hypertension, as well as a novel post hoc analysis of data from the Clinical Inhaled Nitric Oxide Research Group Initiative (CINRGI) study population not been…
To assess the role of inhaled nitric oxide (iNO) in reducing the need for oxygen therapy, decreasing time on mechanical ventilatory support, and attenuating probability of hypoxic respiratory failure severity progression, we reviewed published reports of phase III iNO studies in neonates with hypoxic respiratory failure and pulmonary hypertension, as well as a novel post hoc analysis of data from the Clinical Inhaled Nitric Oxide Research Group Initiative (CINRGI) study population not been previously reported. The post hoc analysis of the CINRGI study showed that iNO shortens the duration of oxygen therapy versus placebo (17 vs. 34 days; P<0.05); the CINRGI retrospective analysis by Konduri et al showed earlier administration of iNO (oxygenation index [OI]=15‒25) yielded a 48% relative reduction vs. placebo in number of patients who progressed to OI ≥30 (16.7% vs. 32.2%; P=0.002). Golombek and Young’s pooled analysis of phase III studies showed a rapid improvement in oxygenation after initiation of iNO therapy versus controls in each study, and a significant reduction in median ventilation duration (11 vs. 14 days; P=0.003). The Gonzalez et al study revealed that earlier iNO administration in infants with mild to moderate hypoxic respiratory failure (OI=10–30) resulted in a decreased duration of oxygen therapy vs. placebo (11.5 vs. 18.0 days; P<0.03) and reduced the probability of developing severe hypoxic respiratory failure.
Other authorsSee publication -
Superoxide Enhances Ca2+ Entry Through L-Type Channels in the Renal Afferent Arteriole
Hypertension
Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in…
Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (P<0.001) and doubled the plateau response. These effects were abolished by tempol and nitroblue tetrazolium, but not by catalase, confirming actions of superoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor–mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor–mediated calcium mobilization.
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Thromboxane-Induced Renal Vasoconstriction is Mediated by the ADP-Ribosyl Cyclase CD38 and Superoxide Anion.
American Journal of Physiology Renal Physiology
Renal hemodynamic studies tested the hypothesis that CD38 and superoxide anion (O2.-) participate in vasoconstriction produced by activation of thromboxane prostanoid (TP) receptors in the mouse kidney. CD38 is the major mammalian ADP-ribosyl cyclase contributing to vasomotor tone through generation of cyclic ADP-ribose, a second messenger that activates ryanodine receptors to release Ca2+ from the sarcoplasmic reticulum in vascular smooth muscle cells. We evaluated whether the stable…
Renal hemodynamic studies tested the hypothesis that CD38 and superoxide anion (O2.-) participate in vasoconstriction produced by activation of thromboxane prostanoid (TP) receptors in the mouse kidney. CD38 is the major mammalian ADP-ribosyl cyclase contributing to vasomotor tone through generation of cyclic ADP-ribose, a second messenger that activates ryanodine receptors to release Ca2+ from the sarcoplasmic reticulum in vascular smooth muscle cells. We evaluated whether the stable thromboxane mimetic U-46619 causes less pronounced renal vasoconstriction in CD38 deficient mice and the involvement of O2.- in U-46619-induced renal vasoconstriction. Our results indicate that U-46619 activation of TP receptors causes renal vasoconstriction in part by activating cADP-ribose signaling in renal resistance arterioles. Based on maximal renal blood flow and renal vascular resistance responses to bolus injections of U-46619, CD38 contributes 30-40% of the TP receptor-induced vasoconstriction. We also found that the anti-oxidant superoxide dismutase mimetic tempol attenuated the magnitude of vasoconstriction by U-46619 in both groups of mice, suggesting mediation by O2.-. The degree of tempol blockage of U-46619-induced renal vasoconstriction was greater in wild-type mice, attenuating renal vasoconstriction by 40% as compared to 30% in CD38 null mice. In other studies U-46619 rapidly stimulated O2.- production (DHE fluorescence) in isolated mouse afferent arterioles, an effect abolished by tempol. These observations provide the first in vivo demonstration of CD38 and O2.- involvement in the vasoconstrictor effects of TP receptor activation in the kidney and in vitro evidence for TP receptor stimulation of O2.- production by the afferent arteriole.
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C-peptide-stimulated nitric oxide production in a cultured pulmonary artery endothelium is erythrocyte mediated and requires Zn2+
Diabetes/Metabolism Research and Reviews
C-peptide has been shown to stimulate the production of nitric oxide (NO) in aortic endothelial cells via activation of endothelial nitric oxide synthase (eNOS) through an increased calcium influx. Here, results obtained using cultured bovine pulmonary artery endothelial cells (bPAECs) suggest that C-peptide does not induce eNOS activation directly in cultured pulmonary artery endothelium. However, C-peptide has been shown to stimulate the release of ATP from erythrocytes, a well-documented…
C-peptide has been shown to stimulate the production of nitric oxide (NO) in aortic endothelial cells via activation of endothelial nitric oxide synthase (eNOS) through an increased calcium influx. Here, results obtained using cultured bovine pulmonary artery endothelial cells (bPAECs) suggest that C-peptide does not induce eNOS activation directly in cultured pulmonary artery endothelium. However, C-peptide has been shown to stimulate the release of ATP from erythrocytes, a well-documented stimulus of eNOS activity in the pulmonary endothelium. Therefore, studies were performed to examine if C-peptide can indirectly stimulate NO production in a cultured pulmonary endothelium that is erythrocyte mediated. C-peptide does not affect NO production in bPAECs directly but can impact NO production through an erythrocyte-mediated mechanism. Furthermore, in the absence of Zn2+, C-peptide does not stimulate this NO production directly or indirectly. These results suggest that C-peptide, in the presence of Zn2+, may be a determinant in purinergic receptor signalling via its ability to stimulate the release of ATP from erythrocytes.
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Microfluidic Transendothelial Electrical Resistance Measurement Device that Enables Blood Flow and Postgrowth Experiments
Analytical Chemistry - Featured Article
Transendothelial electronic resistance (TEER) measurements are performed across a cell layer immobilized on a microfluidic device that also enables the cell layer to interact with a flowing stream of red blood cells (RBCs). A bipolar pulsed square wave potential is applied across a monolayer of bovine pulmonary artery endothelial cells, and the resulting current response is measured and integrated. The overall impedance of the cell layer provides an indicator of cell layer integrity. After cell…
Transendothelial electronic resistance (TEER) measurements are performed across a cell layer immobilized on a microfluidic device that also enables the cell layer to interact with a flowing stream of red blood cells (RBCs). A bipolar pulsed square wave potential is applied across a monolayer of bovine pulmonary artery endothelial cells, and the resulting current response is measured and integrated. The overall impedance of the cell layer provides an indicator of cell layer integrity. After cell seeding on the device, a decrease in TEER signal from 22.3 ± 1.6 μC to 3.5 ± 0.4 μC (corresponding to a resistance of 40.9 ± 2.9 Ω·cm2 to 259.1 ± 27.4 Ω·cm2) was observed after 8 h of cell growth. Intracellular nitric oxide (NO) production by the immobilized endothelial cells that had reached confluence was 34% higher than those cells that had not reached confluence, as indicated by the integrated TEER system. Importantly, this NO production by the confluent endothelium was stimulated by ATP released from RBCs flowing under the endothelial cells. In this construct, the described microfluidic device enables both a TEER-based evaluation of cell layer integrity and molecularly communicated interactions of these cells with a flowing stream of blood components.
Other authorsSee publication -
The Red Blood Cell and Nitric Oxide: Derived, Stimulated, or Both?
The Open Nitric Oxide Journal
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