The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
John R. Grider - One of the best experts on this subject based on the ideXlab platform.
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branched short chain fatty Acid Isovaleric Acid causes colonic smooth muscle relaxation via camp pka pathway
Digestive Diseases and Sciences, 2019Co-Authors: Bryan A. Blakeney, Molly S. Crowe, Sunila Mahavadi, Karnam S. Murthy, John R. GriderAbstract:Isovaleric Acid (IVA) is a 5-carbon branched-chain fatty Acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty Acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty Acids on gut smooth muscle and motility is unknown. To determine the effect of IVA on contractility of colonic smooth muscle. Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells. In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells. The branched-chain fatty Acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.
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Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway
Digestive diseases and sciences, 2018Co-Authors: Bryan A. Blakeney, Molly S. Crowe, Sunila Mahavadi, Karnam S. Murthy, John R. GriderAbstract:Isovaleric Acid (IVA) is a 5-carbon branched-chain fatty Acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty Acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty Acids on gut smooth muscle and motility is unknown. To determine the effect of IVA on contractility of colonic smooth muscle. Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells. In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells. The branched-chain fatty Acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.
Moacir Wajner - One of the best experts on this subject based on the ideXlab platform.
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creatine administration prevents na k atpase inhibition induced by intracerebroventricular administration of Isovaleric Acid in cerebral cortex of young rats
Brain Research, 2009Co-Authors: César Augusto João Ribeiro, Guilhian Leipnitz, Alexandre Umpierrez Amaral, Giorgia De Bortoli, Bianca Seminotti, Moacir WajnerAbstract:Abstract Isovaleric Acidemia (IVAcidemia) is an inborn error of metabolism due to deficiency of isovaleryl-CoA dehydrogenase activity, leading to predominant accumulation of Isovaleric Acid (IVA). Patients affected by IVAcidemia suffer from acute episodes of encephalopathy, whose underlying mechanisms are poorly known. In the present study we investigated whether an intracerebroventricular injection of IVA could compromise energy metabolism in cerebral cortex of young rats. IVA administration significantly inhibited 14 CO 2 production from acetate (22%) and citrate synthase activity (20%) in cerebral cortex homogenates prepared 24 h after injection. However, no alterations of these parameters were observed 2 h after injection. In contrast, no significant differences were found in the activities of succinate dehydrogenase, isocitrate dehydrogenase, electron transfer chain complexes or creatine kinase in rats sacrificed 2 or 24 h after IVA administration. Moreover, IVA injection significantly inhibited Na + ,K + -ATPase activity (25%) in cerebral cortex of rats 2 or 24 h after IVA administration, while pre-treatment of rats with creatine completely prevented the inhibitory effects of IVA on Na + ,K + -ATPase. In conclusion, in vivo administration of IVA inhibits the citric Acid cycle probably through the enzyme citrate synthase, as well as Na + ,K + -ATPase, a crucial enzyme responsible for maintaining the basal potential membrane necessary for a normal neurotransmission. It is presumed that inhibition of these activities may be involved in the pathophysiology of the neurological dysfunction of Isovaleric academic patients. The present findings are of particular interest because treatment with creatine supplementation may represent a potential novel adjuvant therapeutic strategy in IVAcidemia.
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Creatine administration prevents Na+,K+-ATPase inhibition induced by intracerebroventricular administration of Isovaleric Acid in cerebral cortex of young rats.
Brain research, 2009Co-Authors: César Augusto João Ribeiro, Guilhian Leipnitz, Alexandre Umpierrez Amaral, Giorgia De Bortoli, Bianca Seminotti, Moacir WajnerAbstract:Abstract Isovaleric Acidemia (IVAcidemia) is an inborn error of metabolism due to deficiency of isovaleryl-CoA dehydrogenase activity, leading to predominant accumulation of Isovaleric Acid (IVA). Patients affected by IVAcidemia suffer from acute episodes of encephalopathy, whose underlying mechanisms are poorly known. In the present study we investigated whether an intracerebroventricular injection of IVA could compromise energy metabolism in cerebral cortex of young rats. IVA administration significantly inhibited 14 CO 2 production from acetate (22%) and citrate synthase activity (20%) in cerebral cortex homogenates prepared 24 h after injection. However, no alterations of these parameters were observed 2 h after injection. In contrast, no significant differences were found in the activities of succinate dehydrogenase, isocitrate dehydrogenase, electron transfer chain complexes or creatine kinase in rats sacrificed 2 or 24 h after IVA administration. Moreover, IVA injection significantly inhibited Na + ,K + -ATPase activity (25%) in cerebral cortex of rats 2 or 24 h after IVA administration, while pre-treatment of rats with creatine completely prevented the inhibitory effects of IVA on Na + ,K + -ATPase. In conclusion, in vivo administration of IVA inhibits the citric Acid cycle probably through the enzyme citrate synthase, as well as Na + ,K + -ATPase, a crucial enzyme responsible for maintaining the basal potential membrane necessary for a normal neurotransmission. It is presumed that inhibition of these activities may be involved in the pathophysiology of the neurological dysfunction of Isovaleric academic patients. The present findings are of particular interest because treatment with creatine supplementation may represent a potential novel adjuvant therapeutic strategy in IVAcidemia.
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Isovaleric Acid reduces Na+, K+-ATPase activity in synaptic membranes from cerebral cortex of young rats.
Cellular and molecular neurobiology, 2007Co-Authors: César Augusto João Ribeiro, Fabrício Balestro, Vanessa Grando, Moacir WajnerAbstract:1. Patients affected by Isovaleric Acidemia (IVAcidemia) suffer from acute episodes of encephalopathy. However, the mechanisms underlying the neuropathology of this disease are poorly known. The objective of the present study was to investigate the in vitro effects of the metabolites that predominantly accumulate in IVAcidemia, namely Isovaleric Acid (IVA), 3-hydroxyIsovaleric Acid (3-OHIVA) and isovalerylglycine (IVG), on important parameters of energy metabolism, such as (14)CO(2) production from acetate and the activities of the respiratory chain complexes I-IV, creatine kinase and Na(+), K(+)-ATPase in synaptic plasma membranes from cerebral cortex homogenates of 30-day-old rats. 2. We observed that 3-OHIVA Acid and IVG did not affect all the parameters analyzed. Similarly, (14)CO(2) production from acetate (Krebs cycle activity), the activities of creatine kinase, and of the respiratory chain complexes was not modified by IVA. In contrast, IVA exposition to cortical homogenates provoked a marked inhibition of Na(+), K(+)-ATPase activity. However, this activity was not changed when IVA was directly exposed to purified synaptic plasma membranes, suggesting an indirect effect of this organic Acid on the enzyme. Furthermore, pretreatment of cortical homogenates with alpha-tocopherol and creatine totally prevented IVA-induced inhibition on Na(+), K(+)-ATPase activity from synaptic plasma membranes, whereas glutathione (GSH) and the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) did not alter this inhibition. 3. These data indicate that peroxide radicals were probably involved in this inhibitory effect. Since Na(+), K(+)-ATPase is a critical enzyme for normal brain development and functioning and necessary to maintain neuronal excitability, it is presumed that the inhibitory effect of IVA on this activity may be involved in the pathophysiology of the neurological dysfunction of Isovaleric Acidemic patients.
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Isovaleric Acid reduces na k atpase activity in synaptic membranes from cerebral cortex of young rats
Cellular and Molecular Neurobiology, 2007Co-Authors: César Augusto João Ribeiro, Fabrício Balestro, Vanessa Grando, Moacir WajnerAbstract:1. Patients affected by Isovaleric Acidemia (IVAcidemia) suffer from acute episodes of encephalopathy. However, the mechanisms underlying the neuropathology of this disease are poorly known. The objective of the present study was to investigate the in vitro effects of the metabolites that predominantly accumulate in IVAcidemia, namely Isovaleric Acid (IVA), 3-hydroxyIsovaleric Acid (3-OHIVA) and isovalerylglycine (IVG), on important parameters of energy metabolism, such as (14)CO(2) production from acetate and the activities of the respiratory chain complexes I-IV, creatine kinase and Na(+), K(+)-ATPase in synaptic plasma membranes from cerebral cortex homogenates of 30-day-old rats. 2. We observed that 3-OHIVA Acid and IVG did not affect all the parameters analyzed. Similarly, (14)CO(2) production from acetate (Krebs cycle activity), the activities of creatine kinase, and of the respiratory chain complexes was not modified by IVA. In contrast, IVA exposition to cortical homogenates provoked a marked inhibition of Na(+), K(+)-ATPase activity. However, this activity was not changed when IVA was directly exposed to purified synaptic plasma membranes, suggesting an indirect effect of this organic Acid on the enzyme. Furthermore, pretreatment of cortical homogenates with alpha-tocopherol and creatine totally prevented IVA-induced inhibition on Na(+), K(+)-ATPase activity from synaptic plasma membranes, whereas glutathione (GSH) and the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) did not alter this inhibition. 3. These data indicate that peroxide radicals were probably involved in this inhibitory effect. Since Na(+), K(+)-ATPase is a critical enzyme for normal brain development and functioning and necessary to maintain neuronal excitability, it is presumed that the inhibitory effect of IVA on this activity may be involved in the pathophysiology of the neurological dysfunction of Isovaleric Acidemic patients.
Bryan A. Blakeney - One of the best experts on this subject based on the ideXlab platform.
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branched short chain fatty Acid Isovaleric Acid causes colonic smooth muscle relaxation via camp pka pathway
Digestive Diseases and Sciences, 2019Co-Authors: Bryan A. Blakeney, Molly S. Crowe, Sunila Mahavadi, Karnam S. Murthy, John R. GriderAbstract:Isovaleric Acid (IVA) is a 5-carbon branched-chain fatty Acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty Acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty Acids on gut smooth muscle and motility is unknown. To determine the effect of IVA on contractility of colonic smooth muscle. Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells. In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells. The branched-chain fatty Acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.
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Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway
Digestive diseases and sciences, 2018Co-Authors: Bryan A. Blakeney, Molly S. Crowe, Sunila Mahavadi, Karnam S. Murthy, John R. GriderAbstract:Isovaleric Acid (IVA) is a 5-carbon branched-chain fatty Acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty Acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty Acids on gut smooth muscle and motility is unknown. To determine the effect of IVA on contractility of colonic smooth muscle. Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells. In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells. The branched-chain fatty Acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.
Anne Thierry - One of the best experts on this subject based on the ideXlab platform.
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Isovaleric Acid is mainly produced by Propionibacterium freudenreichii in Swiss cheese
International Dairy Journal, 2004Co-Authors: Anne Thierry, Romain Richoux, Jean-rené KerjeanAbstract:Abstract Isovaleric Acid (3-methylbutyric Acid) and 2-methylbutyric Acid contribute to Swiss cheese flavour. In order to determine the contribution of propionibacteria (PAB) to the production of methylbutyric Acids, mini-Swiss cheeses were manufactured with or without PAB as a secondary starter (25 Propionibacterium freudenreichii strains), associated with different cultures of thermophilic lactic starters. In the presence of PAB, the quantity of methylbutyric Acids was three to ten times greater, depending on PAB strain, than in the absence of PAB, regardless of the species and the strain of lactobacilli used (20–63 vs. −1 ripened cheese). PAB produced methylbutyric Acids concomitantly with acetic and propionic Acids, then kept on producing methylbutyric Acids after propionic fermentation. The increase in salt-in-moisture content of cheese from 1.0% to 1.8% induced a strain-dependent inhibition of Isovaleric Acid production. This study shows that P. freudenreichii is the main contributor to methylbutyric Acid production in Swiss cheese.
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A simple screening method for Isovaleric Acid production by Propionibacterium freudenreichii in Swiss cheese
International Dairy Journal, 2004Co-Authors: Anne Thierry, Romain Richoux, Jean-rené Kerjean, Sylvie LortalAbstract:Abstract Isovaleric Acid (3-methylbutyric Acid) and 2-methylbutyric Acid are cheese flavour compounds and are produced in Swiss cheese mainly by propionibacteria (PAB), with large variations in amounts depending on the strain. To evaluate the possibility of screening this property in vitro, the production of both Acids (referred to as methylbutyric Acids) was compared for eight Propionibacterium freudenreichii strains both in mini-Swiss cheeses and in liquid cultures (salted-yeast extract-peptone-lactate medium, pH 5.4, incubated at 24°C then at 6°C). Similar time courses of methylbutyric Acid production were observed in cheeses and in liquid cultures. PAB produced methylbutyric Acids during propionic fermentation at 24°C (8–37 mg kg−1, and 5–13 mg L−1, respectively, in cheeses and cultures), and during further storage at 6°C for 2 months (11–77 mg kg−1 and 5–17 mg L−1). PAB strains significantly (P
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Conversion of L-leucine to Isovaleric Acid by Propionibacterium freudenreichii TL 34 and ITGP23.
Applied and environmental microbiology, 2002Co-Authors: Anne Thierry, Marie-bernadette Maillard, Mireille YvonAbstract:Several branched-chain volatile compounds are involved in the flavor of Swiss cheese. These compounds are probably produced by enzymatic conversion of branched-chain amino Acids, but the flora and the pathways involved remain hypothetical. Our aim was to determine the ability of Propionibacterium freudenreichii, which is one of the main components of the secondary flora of Swiss cheese, to produce flavor compounds during leucine catabolism. Cell extracts and resting cells of two strains were incubated in the presence of l-leucine, α-ketoglutaric Acid, and cofactors, and the metabolites produced were determined by high-performance liquid chromatography and gas chromatography. The first step of leucine catabolism was a transamination that produced α-ketoisocaproic Acid, which was enzymatically converted to Isovaleric Acid. Both reactions were faster at pH 8.0 than at Acidic pHs. Cell extracts catalyzed only the transamination step under our experimental conditions. Small amounts of 3-methylbutanol were also produced by resting cells, but neither 3-methylbutanal norα-hydroxyisocaproic Acid was detected. l-Isoleucine and l-valine were also converted to the corresponding Acids and alcohols. Isovaleric Acid was produced by both strains during growth in a complex medium, even under conditions simulating Swiss cheese conditions (2.1% NaCl, pH 5.4, 24°C). Our results show that P. frendenreichii could play a significant role in the formation of Isovaleric Acid during ripening.
Aynur Senol - One of the best experts on this subject based on the ideXlab platform.
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optimization and modeling of extraction equilibria of the type 2 ternary systems containing water Isovaleric Acid solvent
The Journal of Chemical Thermodynamics, 2015Co-Authors: Aynur SenolAbstract:Abstract The extraction equilibria of the type 2 ternary systems containing (water + Isovaleric Acid + solvent) have been investigated at T = (298.2 ± 0.1) K and P = (101.3 ± 0.7) kPa. Aromatic solvents xylene, chlorobenzene and benzyl ether give the largest distribution ratios and separation factors, as compared to 1-phenyl ethanol, cyclohexanol and 1-decanol. The distribution data have been subjected to formulation of an optimization structure for an effective Acid separation. The optimization approach uses a derivative variation method to efficiently identify the optimization range through analyzing the first order derivatives of the optimized quantity and the non-linear deviation profile of the derivative value. Some aspects of selection of an appropriate criterion for designing optimum extraction are discussed. Modeling efforts based on the LSER (linear solvation energy relation) principles have shown considerable success. The proposed SERLAS model using six physical descriptors of the components has provided relatively reliable fits with a mean relative error of 10.1% and satisfies have established limiting behavior of the physical event. As well, the tie-lines of relevant systems have been predicted by the UNIFAC-original model.
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Optimization and modeling of extraction equilibria of the type 2 ternary systems containing (water + Isovaleric Acid + solvent)
The Journal of Chemical Thermodynamics, 2015Co-Authors: Aynur SenolAbstract:Abstract The extraction equilibria of the type 2 ternary systems containing (water + Isovaleric Acid + solvent) have been investigated at T = (298.2 ± 0.1) K and P = (101.3 ± 0.7) kPa. Aromatic solvents xylene, chlorobenzene and benzyl ether give the largest distribution ratios and separation factors, as compared to 1-phenyl ethanol, cyclohexanol and 1-decanol. The distribution data have been subjected to formulation of an optimization structure for an effective Acid separation. The optimization approach uses a derivative variation method to efficiently identify the optimization range through analyzing the first order derivatives of the optimized quantity and the non-linear deviation profile of the derivative value. Some aspects of selection of an appropriate criterion for designing optimum extraction are discussed. Modeling efforts based on the LSER (linear solvation energy relation) principles have shown considerable success. The proposed SERLAS model using six physical descriptors of the components has provided relatively reliable fits with a mean relative error of 10.1% and satisfies have established limiting behavior of the physical event. As well, the tie-lines of relevant systems have been predicted by the UNIFAC-original model.
