The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Franco Valenza - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate treatment during transient or sustained Lactic Acidemia in normoxic and normotensive rats
PLOS ONE, 2012Co-Authors: Federico Polli, Sara Froio, Franco Valenza, Giorgio Chevallard, Tommaso Fossali, Valentina Salice, Marta Pizzocri, S Coppola, Stefano GattiAbstract:Introduction: Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of Lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of Lactic Acidemia per se without the confounding factor of an underlying organic cause of acidosis. Methodology: Sprague Dawley rats underwent a primed endovenous infusion of L(+) Lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n=8 per group): S) sustained infusion of Lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme’s activity were also measured. Principal Findings: Following Lactic acid infusion blood lactate rose (P,0.05), pH (P,0.05) and strong ion difference (P,0.05) drop. Some rats developed hemodynamic instability during the primed infusion of Lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of Lactic acid (from 7.2260.02 to 7.3660.04, P,0.05) while overshoot to alkalemic values when the infusion was transient (from 7.2460.01 to 7.5360.03, P,0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P,0.05) so that blood lactate was higher (2.961 mmol/l vs. 1.060.2, P,0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2=0.475, P,0.05). Conclusions: pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.
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Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats
PLoS ONE, 2012Co-Authors: Franco Valenza, Federico Polli, Sara Froio, Stefano Gatti, Giorgio Chevallard, Tommaso Fossali, Valentina Salice, Marta Pizzocri, S Coppola, Francesco FortunatoAbstract:Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of Lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of Lactic Acidemia per se without the confounding factor of an underlying organic cause of acidosis.
Yasuhiro Kuroda - One of the best experts on this subject based on the ideXlab platform.
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molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine responsive congenital Lactic Acidemia
Pediatric Research, 1994Co-Authors: Etsuo Naito, Eiji Takeda, Ichiro Yokota, Satoshi Yoshijima, Yasuhiro KurodaAbstract:Molecular Analysis of Abnormal Pyruvate Dehydrogenase in a Patient with Thiamine-Responsive Congenital Lactic Acidemia
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decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital Lactic Acidemia
Clinica Chimica Acta, 1992Co-Authors: Hideaki Kobashi, Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:Abstract We developed an assay method for pyruvate dehydrogenase phosphatase activity using [1- 14 C]pyruvate and measured pyruvate dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital Lactic Acidemia due to a defect in activation of the pyruvate dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the pyruvate dehydrogenase complex in these patients might be due to a reduction in pyruvate dehydrogenase phosphatase activity.
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Demonstration of an Unstable Variant of Pyruvate Dehydrogenase Protein (E_1) in Cultured Fibroblasts from a Patient with Congenital Lactic Acidemia
Pediatric Research, 1991Co-Authors: Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:ABSTRACT: The deficiency of pyruvate dehydrogenase enzyme complex causes congenital Lactic Acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E_1) component, which consists of two subunits, α and β. Whereas some patients are deficient of a single subunit, in other patients both subunits of E_1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E_1-α and E_1-β protein bands on Western blot. Radiolabeling-immunoprecipitation studies with ^35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E_1-α and E_1-β proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that α- and β-proteins were degraded rapidly compared to normal. Our findings proved that α- and β-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.
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demonstration of an unstable variant of pyruvate dehydrogenase protein e1 in cultured fibroblasts from a patient with congenital Lactic Acidemia
Pediatric Research, 1991Co-Authors: Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:ABSTRACT: The deficiency of pyruvate dehydrogenase enzyme complex causes congenital Lactic Acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, α and β. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1-α and E1-β protein bands on Western blot. Radiolabeling-immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-α and E1-β proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that α- and β-proteins were degraded rapidly compared to normal. Our findings proved that α- and β-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.
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a semiquantitative filter paper method for screening for Lactic Acidemia
The Tokushima journal of experimental medicine, 1990Co-Authors: Yasuhiro Kuroda, Etsuo Naito, Ichiro Yokota, Takahiko Saijo, T Watanabe, Eiji TakedaAbstract:: A specific semiquantitative measurement of lactate suitable for use in screening is described. In this method lactate in dried blood on filter paper is stained with an indicator dye.
Stefano Gatti - One of the best experts on this subject based on the ideXlab platform.
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sodium bicarbonate treatment during transient or sustained Lactic Acidemia in normoxic and normotensive rats
PLOS ONE, 2012Co-Authors: Federico Polli, Sara Froio, Franco Valenza, Giorgio Chevallard, Tommaso Fossali, Valentina Salice, Marta Pizzocri, S Coppola, Stefano GattiAbstract:Introduction: Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of Lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of Lactic Acidemia per se without the confounding factor of an underlying organic cause of acidosis. Methodology: Sprague Dawley rats underwent a primed endovenous infusion of L(+) Lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n=8 per group): S) sustained infusion of Lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme’s activity were also measured. Principal Findings: Following Lactic acid infusion blood lactate rose (P,0.05), pH (P,0.05) and strong ion difference (P,0.05) drop. Some rats developed hemodynamic instability during the primed infusion of Lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of Lactic acid (from 7.2260.02 to 7.3660.04, P,0.05) while overshoot to alkalemic values when the infusion was transient (from 7.2460.01 to 7.5360.03, P,0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P,0.05) so that blood lactate was higher (2.961 mmol/l vs. 1.060.2, P,0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2=0.475, P,0.05). Conclusions: pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.
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Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats
PLoS ONE, 2012Co-Authors: Franco Valenza, Federico Polli, Sara Froio, Stefano Gatti, Giorgio Chevallard, Tommaso Fossali, Valentina Salice, Marta Pizzocri, S Coppola, Francesco FortunatoAbstract:Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of Lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of Lactic Acidemia per se without the confounding factor of an underlying organic cause of acidosis.
Etsuo Naito - One of the best experts on this subject based on the ideXlab platform.
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Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency.
Journal of the Neurological Sciences, 2002Co-Authors: Etsuo Naito, Ichiro Yokota, Takahiko Saijo, Yukiko Ogawa, Kuroda YAbstract:Pyruvate dehydrogenase complex (PDHC) deficiency is a major cause of congenital Lactic Acidemia in children. PDHC catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment was effective for some patients with PDHC deficiency. We reexamined 30 patients with congenital Lactic Acidemia of unknown origin who had normal PDHC activity in their cultured fibroblasts using a routine assay with a high (0.4 mM) thiamine pyrophosphate (TPP) concentration. We measured the activity of PDHC in the presence of a low (1×10−4 mM) TPP concentration, and analyzed for mutations in the E1α subunit gene. Three males had low PDHC activity in the presence of 1×10−4 mM TPP. The DNA sequence of these three patients' X-linked E1α subunit revealed a substitution of alanine for valine at position 71 (V71A) in exon 3, phenylalanine for cysteine at position 101 (C101F) in exon 4, and glycine for arginine at position 263 (R263G) in exon 8, respectively. Thiamine treatment was effective in these three patients. Therefore, they had a thiamine-responsive PDHC deficiency due to a point mutation in the E1α subunit gene. PDHC activity should be measured at a low TPP concentration to detect thiamine-responsive PDHC deficiency so that thiamine treatment can be initiated as soon as possible.
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molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine responsive congenital Lactic Acidemia
Pediatric Research, 1994Co-Authors: Etsuo Naito, Eiji Takeda, Ichiro Yokota, Satoshi Yoshijima, Yasuhiro KurodaAbstract:Molecular Analysis of Abnormal Pyruvate Dehydrogenase in a Patient with Thiamine-Responsive Congenital Lactic Acidemia
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decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital Lactic Acidemia
Clinica Chimica Acta, 1992Co-Authors: Hideaki Kobashi, Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:Abstract We developed an assay method for pyruvate dehydrogenase phosphatase activity using [1- 14 C]pyruvate and measured pyruvate dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital Lactic Acidemia due to a defect in activation of the pyruvate dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the pyruvate dehydrogenase complex in these patients might be due to a reduction in pyruvate dehydrogenase phosphatase activity.
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Demonstration of an Unstable Variant of Pyruvate Dehydrogenase Protein (E_1) in Cultured Fibroblasts from a Patient with Congenital Lactic Acidemia
Pediatric Research, 1991Co-Authors: Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:ABSTRACT: The deficiency of pyruvate dehydrogenase enzyme complex causes congenital Lactic Acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E_1) component, which consists of two subunits, α and β. Whereas some patients are deficient of a single subunit, in other patients both subunits of E_1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E_1-α and E_1-β protein bands on Western blot. Radiolabeling-immunoprecipitation studies with ^35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E_1-α and E_1-β proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that α- and β-proteins were degraded rapidly compared to normal. Our findings proved that α- and β-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.
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demonstration of an unstable variant of pyruvate dehydrogenase protein e1 in cultured fibroblasts from a patient with congenital Lactic Acidemia
Pediatric Research, 1991Co-Authors: Etsuo Naito, Eiji Takeda, Takahiko Saijo, Yasuhiro KurodaAbstract:ABSTRACT: The deficiency of pyruvate dehydrogenase enzyme complex causes congenital Lactic Acidemia and devastating neurologic abnormalities in newborns and children. In the majority of cases, the basic defect appears to be in the pyruvate dehydrogenase (E1) component, which consists of two subunits, α and β. Whereas some patients are deficient of a single subunit, in other patients both subunits of E1 are missing. To find out why two proteins were deficient, we investigated the cultured fibroblasts of a female patient who had missing E1-α and E1-β protein bands on Western blot. Radiolabeling-immunoprecipitation studies with 35S-methionine revealed that patient fibroblasts synthesized normal sized precursor E1-α and E1-β proteins, which were presumably transported into mitochondria and processed into normal sized mature proteins. However, pulse-chase analysis showed that α- and β-proteins were degraded rapidly compared to normal. Our findings proved that α- and β-subunits were synthesized and processed normally but failed to form a stable structure for incorporation into the pyruvate dehydrogenase complex.
Alison G Cahill - One of the best experts on this subject based on the ideXlab platform.
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umbilical cord venous lactate for predicting arterial Lactic Acidemia and neonatal morbidity at term
Obstetrics & Gynecology, 2016Co-Authors: Methodius G Tuuli, Molly J Stout, George A Macones, Alison G CahillAbstract:OBJECTIVE: To estimate the utility of umbilical venous lactate, more readily available than umbilical cord arterial lactate, for predicting arterial Lactic Acidemia and neonatal outcomes at term. METHODS: This was a prospective cohort study of consecutive, nonanomalous, singleton, term births after labor in a large academic medical center (2009-2014). Umbilical arterial and venous lactate were measured immediately after delivery, before knowledge of neonatal outcomes. The outcome measures were arterial Lactic Acidemia (greater than 3.9 mmol/L) and a composite neonatal outcome consisting of neonatal death and any of a number of neonatal morbidities including intubation, mechanical ventilation, meconium aspiration syndrome, hypoxic-ischemic encephalopathy, and therapeutic hypothermia. Predictive ability of venous lactate was estimated using the area under the receiver operating characteristic curve. RESULTS: Among 7,741 births, venous lactate was strongly predictive of arterial Lactic Acidemia (area under the curve 0.958). The "optimal" cut point of venous lactate for predicting both arterial Lactic Acidemia and the composite neonatal outcome was 3.4 mmol/L. This predicted arterial Lactic Acidemia with sensitivity of 87.0% and specificity of 91.3%. Positive and negative predictive values were 79.9% and 94.7%, respectively. The composite neonatal outcome occurred in 104 neonates (1.3%). Compared with arterial lactate, venous lactate predicted the composite neonatal outcome with comparable sensitivity (75.0% compared with 74.0%, P>.99) but slightly lower specificity (69.7% compared with 72.2%, P<.01). CONCLUSION: Umbilical venous lactate strongly predicts arterial Lactic Acidemia and is comparable with arterial lactate for predicting neonatal morbidity at term. It could be used as a measure of neonatal morbidity when arterial blood is not available.
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Umbilical Cord Venous Lactate for Predicting Arterial Lactic Acidemia and Neonatal Morbidity at Term.
Obstetrics & Gynecology, 2016Co-Authors: Methodius G Tuuli, Molly J Stout, George A Macones, Alison G CahillAbstract:OBJECTIVE: To estimate the utility of umbilical venous lactate, more readily available than umbilical cord arterial lactate, for predicting arterial Lactic Acidemia and neonatal outcomes at term. METHODS: This was a prospective cohort study of consecutive, nonanomalous, singleton, term births after labor in a large academic medical center (2009-2014). Umbilical arterial and venous lactate were measured immediately after delivery, before knowledge of neonatal outcomes. The outcome measures were arterial Lactic Acidemia (greater than 3.9 mmol/L) and a composite neonatal outcome consisting of neonatal death and any of a number of neonatal morbidities including intubation, mechanical ventilation, meconium aspiration syndrome, hypoxic-ischemic encephalopathy, and therapeutic hypothermia. Predictive ability of venous lactate was estimated using the area under the receiver operating characteristic curve. RESULTS: Among 7,741 births, venous lactate was strongly predictive of arterial Lactic Acidemia (area under the curve 0.958). The "optimal" cut point of venous lactate for predicting both arterial Lactic Acidemia and the composite neonatal outcome was 3.4 mmol/L. This predicted arterial Lactic Acidemia with sensitivity of 87.0% and specificity of 91.3%. Positive and negative predictive values were 79.9% and 94.7%, respectively. The composite neonatal outcome occurred in 104 neonates (1.3%). Compared with arterial lactate, venous lactate predicted the composite neonatal outcome with comparable sensitivity (75.0% compared with 74.0%, P>.99) but slightly lower specificity (69.7% compared with 72.2%, P
