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Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor.

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The hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) enzymes represent novel targets for the treatment of anemia, ulcerative colitis, and ischemic and metabolic disease inter alia. We have identified a novel small-molecule inhibitor of PHD,

Many amino acid substitutions in a hypoxia-inducible transcription factor (HIF)-1alpha-like peptide cause only minor changes in its hydroxylation by the HIF prolyl 4-hydroxylases: substitution of 3,4-dehydroproline or azetidine-2-carboxylic acid for the proline leads to a high rate of uncoupled 2-oxoglutarate decarboxylation.

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Three human prolyl 4-hydroxylases (P4Hs) regulate the hypoxia-inducible transcription factors (HIFs) by hydroxylating a Leu-Xaa-Xaa-Leu-Ala-Pro motif. We report here that the two leucines in the Leu-Glu-Met-Leu-Ala-Pro core motif of a 20-residue peptide corresponding to the sequence around Pro(564)

L-2-Oxothiazolidine-4-carboxylic acid or α-lipoic acid attenuates airway remodeling: involvement of nuclear factor-κB (NF-κB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and hypoxia-inducible factor (HIF).

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Reactive oxygen species (ROS) play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on

Teratogenicity of the class III antiarrhythmic drug almokalant. Role of hypoxia and reactive oxygen species.

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The class III antiarrhythmic drug almokalant (ALM) was given to pregnant rats on Gestation Day 11 (125 micromol/kg) or 13 (25 micromol/kg). Other groups were pretreated with alpha-phenyl-N-t-butylnitrone, (PBN; 850 micromol/kg intraperitoneally) 1 h before administration of ALM or given

A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma.

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Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Oxidative stress plays critical roles in airway inflammation. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce increased

YM-244769, a novel Na+/Ca2+ exchange inhibitor that preferentially inhibits NCX3, efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage.

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We investigated the pharmacological properties and interaction domains of N-(3-aminobenzyl)-6-{4-[(3-fluorobenzyl)oxy]phenoxy} nicotinamide (YM-244769), a novel potent Na(+)/Ca(2+) exchange (NCX) inhibitor, using various NCX-transfectants and neuronal and renal cell lines. YM-244769 preferentially

Characteristics of the NMDA receptor modulating hypoxia/hypoglycaemia-induced rat striatal dopamine release in vitro.

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We investigated the functional characteristics of the NMDA receptor that modulates hypoxia/hypoglycaemia-induced striatal dopamine release. Dopamine release was detected by fast cyclic voltammetry in rat neostriatal slices. Four variables were measured: T(on) -- time from initiation of

Ramiprilat attenuates hypoxia/reoxygenation injury to cardiac myocytes via a bradykinin-dependent mechanism.

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Isolated rat neonatal cardiac myocytes were subjected to immersion in hypoxic (PO2 < 2 mm Hg), glucose-free Tyrode's solution for 5 h followed by concomitant reoxygenation and staining with the membrane-impermeant fluorophore, propidium iodide, in normoxic (PO2 > 150 mm Hg), serum-free culture media

Hypoxia and bicarbonate could limit the expression of iron acquisition genes in Strategy I plants by affecting ethylene synthesis and signaling in different ways.

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In a previous work, it was shown that bicarbonate (one of the most important factors causing Fe chlorosis in Strategy I plants) can limit the expression of several genes involved in Fe acquisition. Hypoxia is considered another important factor causing Fe chlorosis, mainly on calcareous soils.

The "anti-pyrimidine effect" of hypoxia and brequinar sodium (NSC 368390) is of consequence for tumor cell growth.

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The rationale of the present study was to investigate the simultaneous effect of hypoxia and drugs with an "anti-pyrimidine effect" on tumor cell proliferation to evaluate putative changes in the sensitivity of cells to these kinds of chemotherapeutic treatment on reduced O2 tension. Pyrimidine de

Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates.

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Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using

The protective effects of Trolox-loaded chitosan nanoparticles against hypoxia-mediated cell apoptosis.

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Antioxidants have potentials to treat hypoxia-mediated oxidative stress related diseases. However, their therapeutic efficacy is restricted due to its poor cellular uptake efficiency and poor cell membrane permeability. To resolve these issues, we prepare the hydroxyethylated chitosan nanoparticles

L-leucine transport in rat heart under normal conditions and effects of a simulated hypoxia.

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L-leucine plays a central role in the regulation of protein metabolism in heart and has been implicated in myocardial protection, but little is known about the relationship between these phenomena and leucine transport across the cardiac sarcolemma. In this study we used sarcolemmal vesicles and

A new phthalidyl derivative of apovincaminic acid: (3 alpha,16 alpha)-eburnamenine-14 carboxylic acid phthalidyl ester (AF 698). A preliminary report on its chemical and pharmacological properties.

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A new phthalidyl derivative of apovincamine, (3 alpha,16 alpha)-eburnamenine-14 carboxylic acid phthalidyl ester (AF 698), has been synthesized as hydrochloride. Its chemical and physical properties are described and its acute toxicity and vasodilator effect assayed in comparison with vincamine

Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia.

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The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury. We hypothesized that maternal infusion of Trolox and AA, would reduce the fetal bradycardia and

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Herbal & Natural Medicine

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