The Experts below are selected from a list of 1623 Experts worldwide ranked by ideXlab platform

Fernando Scaglia - One of the best experts on this subject based on the ideXlab platform.

  • Arginine and citrulline for the treatment of MELAS Syndrome.
    Journal of Inborn Errors of Metabolism and Screening, 2017
    Co-Authors: Ayman W. El-hattab, Mohammed Almannai, Fernando Scaglia
    Abstract:

    MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) Syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS Syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS Syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes aspect of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS Syndrome.

  • Impaired nitric oxide production in children with MELAS Syndrome and the effect of arginine and citrulline supplementation.
    Molecular Genetics and Metabolism, 2016
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Mohammed Almannai, Jean W. Hsu, Farook Jahoor, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this Syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS Syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS Syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS Syndrome. When compared to control subjects, children with MELAS Syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS Syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS Syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS Syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS Syndrome are needed.

  • MELAS Syndrome: Clinical manifestations, pathogenesis, and treatment options.
    Molecular Genetics and Metabolism, 2015
    Co-Authors: Ayman W. El-hattab, Jeremy Y. Jones, Adekunle M Adesina, Fernando Scaglia
    Abstract:

    article i nfo Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS Syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS Syndrome is the m.3243ANG mutation in the MT-TL1 gene encoding the mitochondrial tRNA Leu(UUR) .

  • MELAS Syndrome: Clinical manifestations, pathogenesis, and treatment options.
    Molecular Genetics and Metabolism, 2015
    Co-Authors: Ayman W. El-hattab, Adekunle M Adesina, Jeremy Jones, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS Syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS Syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS Syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS Syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS Syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS Syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS Syndrome without proven efficacy.

  • Mitochondria: role of citrulline and arginine supplementation in MELAS Syndrome.
    The International Journal of Biochemistry & Cell Biology, 2014
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Fernando Scaglia
    Abstract:

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS Syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS Syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS Syndrome are needed.

Ayman W. El-hattab - One of the best experts on this subject based on the ideXlab platform.

  • Arginine and citrulline for the treatment of MELAS Syndrome.
    Journal of Inborn Errors of Metabolism and Screening, 2017
    Co-Authors: Ayman W. El-hattab, Mohammed Almannai, Fernando Scaglia
    Abstract:

    MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) Syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS Syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS Syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes aspect of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS Syndrome.

  • Impaired nitric oxide production in children with MELAS Syndrome and the effect of arginine and citrulline supplementation.
    Molecular Genetics and Metabolism, 2016
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Mohammed Almannai, Jean W. Hsu, Farook Jahoor, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this Syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS Syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS Syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS Syndrome. When compared to control subjects, children with MELAS Syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS Syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS Syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS Syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS Syndrome are needed.

  • MELAS Syndrome: Clinical manifestations, pathogenesis, and treatment options.
    Molecular Genetics and Metabolism, 2015
    Co-Authors: Ayman W. El-hattab, Jeremy Y. Jones, Adekunle M Adesina, Fernando Scaglia
    Abstract:

    article i nfo Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS Syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS Syndrome is the m.3243ANG mutation in the MT-TL1 gene encoding the mitochondrial tRNA Leu(UUR) .

  • MELAS Syndrome: Clinical manifestations, pathogenesis, and treatment options.
    Molecular Genetics and Metabolism, 2015
    Co-Authors: Ayman W. El-hattab, Adekunle M Adesina, Jeremy Jones, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS Syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS Syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS Syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS Syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS Syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS Syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS Syndrome without proven efficacy.

  • Mitochondria: role of citrulline and arginine supplementation in MELAS Syndrome.
    The International Journal of Biochemistry & Cell Biology, 2014
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Fernando Scaglia
    Abstract:

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS Syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS Syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS Syndrome are needed.

William J Craigen - One of the best experts on this subject based on the ideXlab platform.

  • Impaired nitric oxide production in children with MELAS Syndrome and the effect of arginine and citrulline supplementation.
    Molecular Genetics and Metabolism, 2016
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Mohammed Almannai, Jean W. Hsu, Farook Jahoor, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this Syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS Syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS Syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS Syndrome. When compared to control subjects, children with MELAS Syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS Syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS Syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS Syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS Syndrome are needed.

  • Arrhythmia as a cardiac manifestation in MELAS Syndrome.
    Molecular Genetics and Metabolism Reports, 2015
    Co-Authors: Tamara Thomas, William J Craigen, Ryan M. Moore, Richard J. Czosek, John L. Jefferies
    Abstract:

    A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) Syndrome had progressive left ventricular hypertrophy (LVH) on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS Syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.

  • Mitochondria: role of citrulline and arginine supplementation in MELAS Syndrome.
    The International Journal of Biochemistry & Cell Biology, 2014
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Fernando Scaglia
    Abstract:

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS Syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS Syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS Syndrome are needed.

  • the effect of citrulline and arginine supplementation on lactic acidemia in MELAS Syndrome
    Meta Gene, 2013
    Co-Authors: Kaitlin C Williamson, Lisa T Emrick, Ayman W Elhattab, William J Craigen, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS Syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS Syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS Syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

  • Restoration of impaired nitric oxide production in MELAS Syndrome with citrulline and arginine supplementation.
    Molecular Genetics and Metabolism, 2012
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Jean W. Hsu, Farook Jahoor, Lee-jun C. Wong, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS Syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS Syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

Lisa T Emrick - One of the best experts on this subject based on the ideXlab platform.

  • Impaired nitric oxide production in children with MELAS Syndrome and the effect of arginine and citrulline supplementation.
    Molecular Genetics and Metabolism, 2016
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Mohammed Almannai, Jean W. Hsu, Farook Jahoor, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this Syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS Syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS Syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS Syndrome. When compared to control subjects, children with MELAS Syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS Syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS Syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS Syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS Syndrome are needed.

  • Mitochondria: role of citrulline and arginine supplementation in MELAS Syndrome.
    The International Journal of Biochemistry & Cell Biology, 2014
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Sirisak Chanprasert, Fernando Scaglia
    Abstract:

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS Syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS Syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS Syndrome are needed.

  • the effect of citrulline and arginine supplementation on lactic acidemia in MELAS Syndrome
    Meta Gene, 2013
    Co-Authors: Kaitlin C Williamson, Lisa T Emrick, Ayman W Elhattab, William J Craigen, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS Syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS Syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS Syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

  • Restoration of impaired nitric oxide production in MELAS Syndrome with citrulline and arginine supplementation.
    Molecular Genetics and Metabolism, 2012
    Co-Authors: Ayman W. El-hattab, Lisa T Emrick, William J Craigen, Jean W. Hsu, Farook Jahoor, Lee-jun C. Wong, Fernando Scaglia
    Abstract:

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS Syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS Syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

Hideto Nakajima - One of the best experts on this subject based on the ideXlab platform.

  • Late-onset MELAS Syndrome with mtDNA 14453G→A mutation masquerading as an acute encephalitis: a case report.
    BMC Neurology, 2020
    Co-Authors: Yuki Yokota, Makoto Hara, Takayoshi Akimoto, Tomotaka Mizoguchi, Yu-ichi Goto, Ichizo Nishino, Satoshi Kamei, Hideto Nakajima
    Abstract:

    Background A unique patient with MELAS Syndrome, who initially masqueraded as having acute encephalitis and was eventually diagnosed with MELAS Syndrome harboring a mtDNA 14453G → A mutation, is described. Case presentation A 74-year-old Japanese man was admitted to another hospital due to acute onset of cognitive impairment and psychosis. After 7 days he was transferred to our hospital with seizures and deteriorating psychosis. The results of primary ancillary tests that included EEG, CSF findings, and brain MRI supported the diagnosis of an acute encephalitis. HSV-DNA and antibodies against neuronal surface antigens in the CSF were all negative. With the assistance of the lactate peak on the brain lesions in the magnetic resonance spectroscopy image and genetic analysis of the biopsied muscle, he was eventually diagnosed with MELAS Syndrome harboring mtDNA 14453G → A mutation in the ND6 gene. Conclusions This case provides a caveat that MELAS Syndrome can manifest in the symptoms and ancillary tests masquerading as an acute encephalitis caused by infection or autoimmunity. This is the first adult patient seen to harbor the mtDNA14453G → A with a unique onset, which broadens the phenotypic spectrum of MELAS Syndrome associated with ND6 gene mutation.

  • late onset MELAS Syndrome with mtdna 14453g a mutation masquerading as an acute encephalitis a case report
    BMC Neurology, 2020
    Co-Authors: Yuki Yokota, Makoto Hara, Takayoshi Akimoto, Tomotaka Mizoguchi, Yu-ichi Goto, Ichizo Nishino, Satoshi Kamei, Hideto Nakajima
    Abstract:

    Background A unique patient with MELAS Syndrome, who initially masqueraded as having acute encephalitis and was eventually diagnosed with MELAS Syndrome harboring a mtDNA 14453G → A mutation, is described. Case presentation A 74-year-old Japanese man was admitted to another hospital due to acute onset of cognitive impairment and psychosis. After 7 days he was transferred to our hospital with seizures and deteriorating psychosis. The results of primary ancillary tests that included EEG, CSF findings, and brain MRI supported the diagnosis of an acute encephalitis. HSV-DNA and antibodies against neuronal surface antigens in the CSF were all negative. With the assistance of the lactate peak on the brain lesions in the magnetic resonance spectroscopy image and genetic analysis of the biopsied muscle, he was eventually diagnosed with MELAS Syndrome harboring mtDNA 14453G → A mutation in the ND6 gene. Conclusions This case provides a caveat that MELAS Syndrome can manifest in the symptoms and ancillary tests masquerading as an acute encephalitis caused by infection or autoimmunity. This is the first adult patient seen to harbor the mtDNA14453G → A with a unique onset, which broadens the phenotypic spectrum of MELAS Syndrome associated with ND6 gene mutation.