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Erwin E.w. Jansen - One of the best experts on this subject based on the ideXlab platform.
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anserine inhibits carnosine degradation but in human serum carnosinase cn1 is not correlated with histidine dipeptide concentration
Clinica Chimica Acta, 2011Co-Authors: Verena Peters, Erwin E.w. Jansen, Cornelis Jakobs, Eva Riedl, Bart Janssen, Benito A Yard, Johannes Wedel, Georg F Hoffmann, Johannes Zschocke, Daniel GotthardtAbstract:Abstract Background We reported an association of a particular allele of the carnosinase ( CNDP1 Mannheim ) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low. Methods We measured the concentration of two further histidine dipeptides, anserine and Homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA. Results We found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and Homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n = 7 males; normal range: 3.2 ± 1.1, n = 104; p p Conclusions Serum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues.
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relevance of allosteric conformations and Homocarnosine concentration on carnosinase activity
Amino Acids, 2010Co-Authors: Verena Peters, Erwin E.w. Jansen, Cornelis Jakobs, Moustafa Kebbewar, Eva Riedl, Hannes Koeppel, Dirk Frey, Katja Adelmann, Kristina Klingbeil, Matthias MackAbstract:Activity of carnosinase (CN1), the only dipeptidase with substrate specificity for carnosine or Homocarnosine, varies greatly between individuals but increases clearly and significantly with age. Surprisingly, the lower CN1 activity in children is not reflected by differences in CN1 protein concentrations. CN1 is present in different allosteric conformations in children and adults since all sera obtained from children but not from adults were positive in ELISA and addition of DTT to the latter sera increased OD450 values. There was no quantitative difference in the amount of monomeric CN1 between children and adults. Further, CN1 activity was dose dependently inhibited by Homocarnosine. Addition of 80 microM Homocarnosine lowered V (max) for carnosine from 440 to 356 pmol/min/microg and increased K (m) from 175 to 210 microM. The estimated K (i) for Homocarnosine was higher (240 microM). Homocarnosine inhibits carnosine degradation and high Homocarnosine concentrations in cerebrospinal fluid (CSF) may explain the lower carnosine degradation in CSF compared to serum. Because CN1 is implicated in the susceptibility for diabetic nephropathy (DN), our findings may have clinical implications for the treatment of diabetic patients with a high risk to develop DN. Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels.
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a novel quantitative assay for Homocarnosine in cerebrospinal fluid using stable isotope dilution liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2006Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, Michael K Gibson, Yosuke Shigematsu, N M VerhoevenAbstract:Abstract We describe a rapid and sensitive method for the quantification of Homocarnosine in physiological fluids, with particular emphasis on cerebrospinal fluid (CSF). Homocarnosine was quantified as the butyl derivative, with 2 H 2 - l -Homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6 M HCl in butanol. Samples were chromatographed on a C 18 column and detected by liquid chromatography–tandem mass spectrometry (LC–MS/MS) operating in the multiple reaction monitoring mode. The intra- and inter-assay variations were 4.6 and 10.9%, respectively. Mean recovery of Homocarnosine at two concentrations was 105%. The limit of detection in CSF approximated 20 nmol/L. CSF Homocarnosine is age dependent and ranges from
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a novel quantitative assay for Homocarnosine in cerebrospinal fluid using stable isotope dilution liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2006Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, Michael K Gibson, Yosuke Shigematsu, N M VerhoevenAbstract:We describe a rapid and sensitive method for the quantification of Homocarnosine in physiological fluids, with particular emphasis on cerebrospinal fluid (CSF). Homocarnosine was quantified as the butyl derivative, with (2)H(2)-l-Homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6M HCl in butanol. Samples were chromatographed on a C(18) column and detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) operating in the multiple reaction monitoring mode. The intra- and inter-assay variations were 4.6 and 10.9%, respectively. Mean recovery of Homocarnosine at two concentrations was 105%. The limit of detection in CSF approximated 20 nmol/L. CSF Homocarnosine is age dependent and ranges from <0.02 to 10 micromol/L. Our method is applicable to the analysis of CSF derived from patients with heritable defects in the GABA pathway, patients with homocarnosinosis or serum carnosinase deficiency, and should be applicable to other model systems in order to further explore the biological role and significance of Homocarnosine in mammalian systems.
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GABA, Homocarnosine, and β-Alanine
Laboratory Guide to the Methods in Biochemical Genetics, 2026Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, K. Michael GibsonAbstract:GABA (gamma-aminobutyric acid; 4-aminobutyric acid), β-alanine (2-aminopropanoic acid), and Homocarnosine (γ-aminobutyryl-L-histidine) represent bioactive amines with diverse roles in intermediary metabolism and central neurotransmission. These neuromodulatory compounds are known (or suspected) to be increased in cerebrospinal fluid (CSF) derived from patients with several heritable neurometabolic disorders. The latter include succinate semialdehyde dehydrogenase (SSADH, or aldehyde dehydrogenase 5a1 (Aldh5a1)) deficiency (also known as gamma-hydroxybutyric aciduria), GABA-transaminase deficiency, homocarnosinosis, hyper-β-alaninemia, and a putative combined semialdehyde dehydrogenase deficiency. The current chapter describes highly sensitive, quantitative methodology for determination of these species in CSF, with the potential for adaptation to other physiological fluids. GABA and β-alanine are quantified as the methylformate-pentafluorobenzyl derivatives employing isotope dilution gas chromatography-mass spectrometry. Conversely, Homocarnosine is quantified as the butyl derivative utilizing isotope-dilution liquid chromatography-tandem mass spectrometry.
Douglas L. Rothman - One of the best experts on this subject based on the ideXlab platform.
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elevated Homocarnosine and gaba in subject on isoniazid as assessed through 1h mrs at 7t
Analytical Biochemistry, 2020Co-Authors: Karl Landheer, Ognen A. C. Petroff, Douglas L. Rothman, Hetty Prinsen, Christoph JuchemAbstract:Typical magnetic resonance spectroscopy J-editing methods designed to quantify GABA suffer from contamination of both overlapping macromolecules and Homocarnosine signal, introducing potential confounds. The aim of this study was to develop a novel method to assess accurately both the relative concentrations of Homocarnosine as well as GABA free from overlapping creatine, Homocarnosine and macromolecule signal. A novel method which utilized the combination of echo time STEAM and MEGA-sLASER magnetic resonance spectroscopy experiments at 7T were used to quantify the concentration of GABA and homocarnsoine independently, which are typically quantified in tandem. The metabolites GABA and Homocarnosine were measured in brain of 6 healthy control subjects, and in a single subject medicated with isoniazid. It was found that (16.6±10.2)% of the supposed GABA signal in the brain originated from Homocarnosine, and that isoniazid caused significantly elevated concentration of GABA and Homocarnosine in a single subject compared to controls.
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brain Homocarnosine and seizure control of patients taking gabapentin or topiramate
Epilepsia, 2006Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: To assess the relation between seizure control and brain Homocarnosine and γ-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy. Methods: In vivo measurements of GABA and Homocarnosine were made of a 14-cc volume in the occipital cortex by using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied. Results: Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not. Conclusions: In the visual neocortex, which is remote from the presumed seizure-onset zone, higher Homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.
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Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures
Neurology, 2001Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Objective: To assess the relationship between seizure control and gamma-aminobutyric acid (GABA), Homocarnosine, and pyrrolidinone levels in the visual cortex of patients with epilepsy taking valproate or lamotrigine. Previous studies suggested that poor seizure control was associated with low GABA and Homocarnosine levels. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made in a 14-cm 3 volume of the occipital cortex using 1 H spectroscopy with a 2.1-Tesla MR spectrometer and an 8-cm surface coil. Twenty-six adults (eight men) taking valproate or lamotrigine were recruited; 12 had complex partial seizures (CPS) and 14 had juvenile myoclonic epilepsy (JME). Results: Median Homocarnosine levels were normal for patients with JME and below normal for patients with CPS. Better seizure control was associated with higher Homocarnosine levels for both groups. Median GABA was below normal for patients with JME, lower than for patients with CPS. Brain GABA was lowest in patients with JME even when seizure control was excellent. Pyrrolidinone levels were above normal in almost all patients with JME. Conclusions: Low GABA levels are associated with poor seizure control in patients with CPS, but not in JME. Higher Homocarnosine levels are associated with better seizure control in both types of epilepsy.
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Effects of gabapentin on brain GABA, Homocarnosine, and pyrrolidinone in epilepsy patients.
Epilepsia, 2000Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain γ-aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, Homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex by using a 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200–2,000 mg) of GBP were rechal-lenged with a single high dose (2,400 mg). Results: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4–1.8 mM) within 1 h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM;95% CI, 0.2–0.9), Homocarnosine (0.3 mM; 95% CI, 0.2–0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06–0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3–0.5) within 1 h. Conclusions: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased Homocarnosine and pyrrolidinone with daily therapy.
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clinical research effects of gabapentin on brain gaba Homocarnosine and pyrrolidinone in epilepsy patients
2000Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain y-aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, Homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex by using a 'H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200-2,000 mg) of GBP were rechallenged with a single high dose (2,400 mg). Results: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4-1.8 mM) within I h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM; 95% CI, 0.20.9), Homocarnosine (0.3 mM; 95% C1, 0.2-0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06-0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3-0.5) within 1 h. Conclusions: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased Homocarnosine and
Cornelis Jakobs - One of the best experts on this subject based on the ideXlab platform.
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anserine inhibits carnosine degradation but in human serum carnosinase cn1 is not correlated with histidine dipeptide concentration
Clinica Chimica Acta, 2011Co-Authors: Verena Peters, Erwin E.w. Jansen, Cornelis Jakobs, Eva Riedl, Bart Janssen, Benito A Yard, Johannes Wedel, Georg F Hoffmann, Johannes Zschocke, Daniel GotthardtAbstract:Abstract Background We reported an association of a particular allele of the carnosinase ( CNDP1 Mannheim ) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low. Methods We measured the concentration of two further histidine dipeptides, anserine and Homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA. Results We found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and Homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n = 7 males; normal range: 3.2 ± 1.1, n = 104; p p Conclusions Serum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues.
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relevance of allosteric conformations and Homocarnosine concentration on carnosinase activity
Amino Acids, 2010Co-Authors: Verena Peters, Erwin E.w. Jansen, Cornelis Jakobs, Moustafa Kebbewar, Eva Riedl, Hannes Koeppel, Dirk Frey, Katja Adelmann, Kristina Klingbeil, Matthias MackAbstract:Activity of carnosinase (CN1), the only dipeptidase with substrate specificity for carnosine or Homocarnosine, varies greatly between individuals but increases clearly and significantly with age. Surprisingly, the lower CN1 activity in children is not reflected by differences in CN1 protein concentrations. CN1 is present in different allosteric conformations in children and adults since all sera obtained from children but not from adults were positive in ELISA and addition of DTT to the latter sera increased OD450 values. There was no quantitative difference in the amount of monomeric CN1 between children and adults. Further, CN1 activity was dose dependently inhibited by Homocarnosine. Addition of 80 microM Homocarnosine lowered V (max) for carnosine from 440 to 356 pmol/min/microg and increased K (m) from 175 to 210 microM. The estimated K (i) for Homocarnosine was higher (240 microM). Homocarnosine inhibits carnosine degradation and high Homocarnosine concentrations in cerebrospinal fluid (CSF) may explain the lower carnosine degradation in CSF compared to serum. Because CN1 is implicated in the susceptibility for diabetic nephropathy (DN), our findings may have clinical implications for the treatment of diabetic patients with a high risk to develop DN. Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels.
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a novel quantitative assay for Homocarnosine in cerebrospinal fluid using stable isotope dilution liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2006Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, Michael K Gibson, Yosuke Shigematsu, N M VerhoevenAbstract:Abstract We describe a rapid and sensitive method for the quantification of Homocarnosine in physiological fluids, with particular emphasis on cerebrospinal fluid (CSF). Homocarnosine was quantified as the butyl derivative, with 2 H 2 - l -Homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6 M HCl in butanol. Samples were chromatographed on a C 18 column and detected by liquid chromatography–tandem mass spectrometry (LC–MS/MS) operating in the multiple reaction monitoring mode. The intra- and inter-assay variations were 4.6 and 10.9%, respectively. Mean recovery of Homocarnosine at two concentrations was 105%. The limit of detection in CSF approximated 20 nmol/L. CSF Homocarnosine is age dependent and ranges from
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a novel quantitative assay for Homocarnosine in cerebrospinal fluid using stable isotope dilution liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2006Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, Michael K Gibson, Yosuke Shigematsu, N M VerhoevenAbstract:We describe a rapid and sensitive method for the quantification of Homocarnosine in physiological fluids, with particular emphasis on cerebrospinal fluid (CSF). Homocarnosine was quantified as the butyl derivative, with (2)H(2)-l-Homocarnosine as internal standard. Following deproteinization of CSF samples, supernatants were evaporated to dryness and derivatized with 10% 6M HCl in butanol. Samples were chromatographed on a C(18) column and detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) operating in the multiple reaction monitoring mode. The intra- and inter-assay variations were 4.6 and 10.9%, respectively. Mean recovery of Homocarnosine at two concentrations was 105%. The limit of detection in CSF approximated 20 nmol/L. CSF Homocarnosine is age dependent and ranges from <0.02 to 10 micromol/L. Our method is applicable to the analysis of CSF derived from patients with heritable defects in the GABA pathway, patients with homocarnosinosis or serum carnosinase deficiency, and should be applicable to other model systems in order to further explore the biological role and significance of Homocarnosine in mammalian systems.
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GABA, Homocarnosine, and β-Alanine
Laboratory Guide to the Methods in Biochemical Genetics, 2026Co-Authors: Erwin E.w. Jansen, Cornelis Jakobs, K. Michael GibsonAbstract:GABA (gamma-aminobutyric acid; 4-aminobutyric acid), β-alanine (2-aminopropanoic acid), and Homocarnosine (γ-aminobutyryl-L-histidine) represent bioactive amines with diverse roles in intermediary metabolism and central neurotransmission. These neuromodulatory compounds are known (or suspected) to be increased in cerebrospinal fluid (CSF) derived from patients with several heritable neurometabolic disorders. The latter include succinate semialdehyde dehydrogenase (SSADH, or aldehyde dehydrogenase 5a1 (Aldh5a1)) deficiency (also known as gamma-hydroxybutyric aciduria), GABA-transaminase deficiency, homocarnosinosis, hyper-β-alaninemia, and a putative combined semialdehyde dehydrogenase deficiency. The current chapter describes highly sensitive, quantitative methodology for determination of these species in CSF, with the potential for adaptation to other physiological fluids. GABA and β-alanine are quantified as the methylformate-pentafluorobenzyl derivatives employing isotope dilution gas chromatography-mass spectrometry. Conversely, Homocarnosine is quantified as the butyl derivative utilizing isotope-dilution liquid chromatography-tandem mass spectrometry.
Ognen A. C. Petroff - One of the best experts on this subject based on the ideXlab platform.
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elevated Homocarnosine and gaba in subject on isoniazid as assessed through 1h mrs at 7t
Analytical Biochemistry, 2020Co-Authors: Karl Landheer, Ognen A. C. Petroff, Douglas L. Rothman, Hetty Prinsen, Christoph JuchemAbstract:Typical magnetic resonance spectroscopy J-editing methods designed to quantify GABA suffer from contamination of both overlapping macromolecules and Homocarnosine signal, introducing potential confounds. The aim of this study was to develop a novel method to assess accurately both the relative concentrations of Homocarnosine as well as GABA free from overlapping creatine, Homocarnosine and macromolecule signal. A novel method which utilized the combination of echo time STEAM and MEGA-sLASER magnetic resonance spectroscopy experiments at 7T were used to quantify the concentration of GABA and homocarnsoine independently, which are typically quantified in tandem. The metabolites GABA and Homocarnosine were measured in brain of 6 healthy control subjects, and in a single subject medicated with isoniazid. It was found that (16.6±10.2)% of the supposed GABA signal in the brain originated from Homocarnosine, and that isoniazid caused significantly elevated concentration of GABA and Homocarnosine in a single subject compared to controls.
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brain Homocarnosine and seizure control of patients taking gabapentin or topiramate
Epilepsia, 2006Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: To assess the relation between seizure control and brain Homocarnosine and γ-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy. Methods: In vivo measurements of GABA and Homocarnosine were made of a 14-cc volume in the occipital cortex by using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied. Results: Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not. Conclusions: In the visual neocortex, which is remote from the presumed seizure-onset zone, higher Homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.
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Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures
Neurology, 2001Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Objective: To assess the relationship between seizure control and gamma-aminobutyric acid (GABA), Homocarnosine, and pyrrolidinone levels in the visual cortex of patients with epilepsy taking valproate or lamotrigine. Previous studies suggested that poor seizure control was associated with low GABA and Homocarnosine levels. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made in a 14-cm 3 volume of the occipital cortex using 1 H spectroscopy with a 2.1-Tesla MR spectrometer and an 8-cm surface coil. Twenty-six adults (eight men) taking valproate or lamotrigine were recruited; 12 had complex partial seizures (CPS) and 14 had juvenile myoclonic epilepsy (JME). Results: Median Homocarnosine levels were normal for patients with JME and below normal for patients with CPS. Better seizure control was associated with higher Homocarnosine levels for both groups. Median GABA was below normal for patients with JME, lower than for patients with CPS. Brain GABA was lowest in patients with JME even when seizure control was excellent. Pyrrolidinone levels were above normal in almost all patients with JME. Conclusions: Low GABA levels are associated with poor seizure control in patients with CPS, but not in JME. Higher Homocarnosine levels are associated with better seizure control in both types of epilepsy.
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Effects of gabapentin on brain GABA, Homocarnosine, and pyrrolidinone in epilepsy patients.
Epilepsia, 2000Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain γ-aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, Homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex by using a 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200–2,000 mg) of GBP were rechal-lenged with a single high dose (2,400 mg). Results: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4–1.8 mM) within 1 h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM;95% CI, 0.2–0.9), Homocarnosine (0.3 mM; 95% CI, 0.2–0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06–0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3–0.5) within 1 h. Conclusions: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased Homocarnosine and pyrrolidinone with daily therapy.
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clinical research effects of gabapentin on brain gaba Homocarnosine and pyrrolidinone in epilepsy patients
2000Co-Authors: Ognen A. C. Petroff, Fahmeed Hyder, Douglas L. Rothman, Richard H. MattsonAbstract:Summary: Purpose: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain y-aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, Homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. Methods: In vivo measurements of GABA, Homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex by using a 'H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200-2,000 mg) of GBP were rechallenged with a single high dose (2,400 mg). Results: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4-1.8 mM) within I h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM; 95% CI, 0.20.9), Homocarnosine (0.3 mM; 95% C1, 0.2-0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06-0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3-0.5) within 1 h. Conclusions: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased Homocarnosine and
Giorgia Meineri - One of the best experts on this subject based on the ideXlab platform.
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Effect of cooking method on carnosine and its homologues, pentosidine and thiobarbituric acid-reactive substance contents in beef and turkey meat.
Food chemistry, 2011Co-Authors: Pier Giorgio Peiretti, Claudio Medana, Sonja Visentin, Federica Dal Bello, Giorgia MeineriAbstract:Commercial samples of beef and turkey meat were prepared by commonly used cooking methods with standard cooking times: (1) broiled at 200°C for 10min, (2) broiled at a medium temperature (140°C) for 10min, (3) cooked by microwave (MW) for 3min and then grilled (MW/grill) for 7min, (4) cooked in a domestic microwave oven for 10min, and (5) boiled in water for 10min. The raw and cooked meats were then analysed to determine the carnosine, anserine, Homocarnosine, pentosidine, and thiobarbituric acid-reactive substance (TBARS) contents. It was observed that boiling beef caused a loss of approximately 50% of the carnosine, probably because of the high water solubility of carnosine and its homologues; cooking by microwave caused a medium loss of the anti-oxidants of approximately 20%; cooking by MW/grill led to a reduction in carnosine of approximately 10%. As far as the anserine and Homocarnosine contents were concerned, a greater loss was observed for the boiling method (approximately 70%) while, for the other cooking methods, the value ranged from 30% to 70%. The data oscillate more for the turkey meat: the minimum carnosine decrease was observed in the cases of MW/grill and broiling at high temperature (25%). Analogously, the anserine and Homocarnosine contents decreased slightly in the case of MW/grill and broiling at a high temperature (2-7%) and by 10-30% in the other cases. No analysed meat sample showed any traces of pentosidine above the instrumental determination limits. The cooked beef showed an increased TBARS value compared to the raw meat, and the highest values were found when the beef was broiled at a high temperature, cooked by microwave or boiled in water. The TBARS value of the turkey meat decreased for all the cooking methods in comparison to the TBARS value of the fresh meat.
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determination of carnosine anserine Homocarnosine pentosidine and thiobarbituric acid reactive substances contents in meat from different animal species
Food Chemistry, 2011Co-Authors: Pier Giorgio Peiretti, Claudio Medana, Sonja Visentin, Valeria Rachele Giancotti, Valentina Zunino, Giorgia MeineriAbstract:The aim of this research was to determine the content of the histidinic antioxidants, advanced glycation end products (pentosidine) and thiobarbituric acid reactive substance (TBARS) in the meat from different animal species. Carnosine, anserine, Homocarnosine and pentosidine were quantified by HPLC/MS, while TBARS was determined by photometric measurements. The total CRCs (carnosine + anserine + Homocarnosine) content was in the increasing order: beef < rabbit < pork < horse < chicken < turkey. The analysis showed traces of pentosidine above the instrumental determination limits in all the meat samples, while the susceptibility of these meat to lipid oxidation decreased from beef to chicken, with the exception of turkey meat, which presented a high TBARS content towards even though its total CRCs was the highest. The structure of Homocarnosine was elucidated by high resolving power multistage mass spectrometry.