Magdalena Alonso‐Galicia

24-Hour Profile of Microvascular Liver Perfusion in Sickle Cell Disease Mice Following Hypoxia-Induced Vaso-Occlusion

Keith Abe, Michael Wright, Derek Sim, Magdalena Alonso‐Galicia et autres

Abstract Introduction: Sickle cell disease (SCD) is a debilitating genetic disorder of the red blood cells, leading to acute vaso-occlusive (VOC) events and chronic disease in multiple organs. In the liver, VOC events in the hepatic sinusoids can lead to fatal sickle …

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Discovery of a potent and selective ROMK inhibitor with improved pharmacokinetic properties based on an octahydropyrazino[2,1-c][1,4]oxazine scaffold

Yuping Zhu, Reynalda K. de Jesus, Haifeng Tang, Shawn P. Walsh et autres

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The Renal Outer Medullary Potassium Channel Inhibitor, MK-7145, Lowers Blood Pressure, and Manifests Features of Bartter’s Syndrome Type II Phenotype

Caryn Hampton, Xiaoyan Zhou, Birgit T. Priest, Lee-Yuh Pai et autres

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Discovery of MK-7145, an Oral Small Molecule ROMK Inhibitor for the Treatment of Hypertension and Heart Failure

Haifeng Tang, Yuping Zhu, Nardos Teumelsan, Shawn P. Walsh et autres

ROMK, the renal outer medullary potassium channel, is involved in potassium recycling at the thick ascending loop of Henle and potassium secretion at the cortical collecting duct in the kidney nephron. Because of this dual site of action, selective inhibitors of ROMK …

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Differentiation of ROMK potency from hERG potency in the phenacetyl piperazine series through heterocycle incorporation

Shawn P. Walsh, Aurash Shahripour, Haifeng Tang, Reynalda K. de Jesus et autres

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Protection of Microvascular Liver Perfusion with 5-Hydroxymethylfurfural in Sickle Cell Disease Mice Following Hypoxia-Induced Vasoocclusion

Michael Wright, Derek Sim, Magdalena Alonso‐Galicia, Katalin Kauser et autres

Abstract Introduction: Sickle cell disease (SCD) is a debilitating genetic disorder, and the resultant "sickling" deformity of red blood cells leads to acute vasoocclusive (VOC) events and chronic disease in multiple organs. Sickle cell hepatopathy, arising from VOC events in the hepatic …

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Discovery of a Potent and Selective ROMK Inhibitor with Pharmacokinetic Properties Suitable for Preclinical Evaluation

Shawn P. Walsh, Aurash Shahripour, Haifeng Tang, Nardos Teumelsan et autres

A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a …

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Pharmacological activities of roflumilast N-oxide, dexamethasone and formoterol in human neutrophils from healthy non-smokers and COPD patients

Javier Milara, Javier Lluch, Adela Serrano, Jose Freire et autres

Introduction: Roflumilast N-oxide (RNO) has anti-inflammatory activities and reverses corticosteroid resistance in COPD neutrophils. This study further explored the anti-inflammatory effects of RNO, dexamethasone (DEX) and formoterol and their combinations in human neutrophils from healthy non-smokers and COPD patients. Methods: Neutrophils were …

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Pharmacologic Inhibition of the Renal Outer Medullary Potassium Channel Causes Diuresis and Natriuresis in the Absence of Kaliuresis

María L. García, Birgit T. Priest, Magdalena Alonso‐Galicia, Xiaoyan Zhou et autres

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Discovery of a novel sub-class of ROMK channel inhibitors typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one

Haifeng Tang, Reynald K. de Jesus, Shawn P. Walsh, Yuping Zhu et autres

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Anti-inflammatory effects of roflumilast N-oxide and dexamethasone in human bronchial epithelial cells stimulated with toll-like receptor agonists

Javier Milara, Javier Lluch, Patricia Almudéver, Teresa Peiró et autres

Objective Bacterial and viral infections in COPD contribute to inflammation and exacerbations, and toll-like receptors (TLR) modulate the innate immune response to these infectious agents. This study explored the anti-inflammatory effects of dexamethasone (DEX) and roflumilast N-oxide (RNO) following TLR stimulation and …

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Roflumilast aids airway surface liquid recovery after cigarette smoke exposure in primary human bronchial epithelia cultures

Jean Tyrrell, Maohua Qian, Magdalena Alonso‐Galicia, Jose Freire et autres