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Papers by Mario Figueroa

Research paper thumbnail of Vasorelaxant effect of flavonoids through calmodulin inhibition: Ex vivo, in vitro, and in silico approaches

Bioorganic & Medicinal Chemistry, 2011

In our search for potential antihypertensive agents, a series of structurally-related flavonoids ... more In our search for potential antihypertensive agents, a series of structurally-related flavonoids was screened. Ex vivo and in vitro biological evaluations indicated that compounds 1-7 displayed an important vasorelaxant effect on the endothelium-intact (E + ) and -denuded (E À ) aortic rings test. Their in vitro anti-calmodulin (CaM) properties were determined by means of the inhibitory effect on the activation of the calmodulin-sensitive cAMP phosphodiesterase (PDE1) assay. Molecular modeling experiments were also performed in order to explore the probable binding site of 1-7 with CaM, and the results indicated that they could bind to the protein in the same pocket as trifluoperazine (TFP), a well-known CaM inhibitor.

Research paper thumbnail of Albumin and Hydroxyethyl Starch Modulate Oxidative Inflammatory Injury to Vascular Endothelium

Anesthesiology, 2004

Background: Human serum albumin is used clinically to maintain colloid osmotic pressure and is vi... more Background: Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury.

Research paper thumbnail of Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Journal of Clinical Investigation, 2001

Research paper thumbnail of Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury

Appreciating that CO 2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory... more Appreciating that CO 2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n ϭ 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa CO 2 at approximately 35-40 mm Hg), eucapnia ϩ lipopolysaccharide (LPS), eucapnia ϩ LPS ϩ inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa CO 2 at approximately 60 mm Hg), hypercapnia ϩ LPS, and hypercapnia ϩ LPS ϩ iNO. The hypercapnia ϩ LPS groups compared with groups exposed to eucapnia ϩ LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p Ͻ 0.05), lung wet-to-dry ratios (p Ͻ 0.05), bronchoalveolar lavage fluid cell counts (p Ͻ 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p Ͻ 0.05), tissue myeloperoxidase content (p Ͻ 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p Ͻ 0.05) was greatest under conditions of hypercapnia ϩ LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes.

Research paper thumbnail of Vasorelaxant effect of flavonoids through calmodulin inhibition: Ex vivo, in vitro, and in silico approaches

Bioorganic & Medicinal Chemistry, 2011

In our search for potential antihypertensive agents, a series of structurally-related flavonoids ... more In our search for potential antihypertensive agents, a series of structurally-related flavonoids was screened. Ex vivo and in vitro biological evaluations indicated that compounds 1-7 displayed an important vasorelaxant effect on the endothelium-intact (E + ) and -denuded (E À ) aortic rings test. Their in vitro anti-calmodulin (CaM) properties were determined by means of the inhibitory effect on the activation of the calmodulin-sensitive cAMP phosphodiesterase (PDE1) assay. Molecular modeling experiments were also performed in order to explore the probable binding site of 1-7 with CaM, and the results indicated that they could bind to the protein in the same pocket as trifluoperazine (TFP), a well-known CaM inhibitor.

Research paper thumbnail of Albumin and Hydroxyethyl Starch Modulate Oxidative Inflammatory Injury to Vascular Endothelium

Anesthesiology, 2004

Background: Human serum albumin is used clinically to maintain colloid osmotic pressure and is vi... more Background: Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury.

Research paper thumbnail of Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration

Journal of Clinical Investigation, 2001

Research paper thumbnail of Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury

Appreciating that CO 2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory... more Appreciating that CO 2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n ϭ 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa CO 2 at approximately 35-40 mm Hg), eucapnia ϩ lipopolysaccharide (LPS), eucapnia ϩ LPS ϩ inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa CO 2 at approximately 60 mm Hg), hypercapnia ϩ LPS, and hypercapnia ϩ LPS ϩ iNO. The hypercapnia ϩ LPS groups compared with groups exposed to eucapnia ϩ LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p Ͻ 0.05), lung wet-to-dry ratios (p Ͻ 0.05), bronchoalveolar lavage fluid cell counts (p Ͻ 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p Ͻ 0.05), tissue myeloperoxidase content (p Ͻ 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p Ͻ 0.05) was greatest under conditions of hypercapnia ϩ LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes.

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