Uridine Triphosphate

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Richard J Wurtman - One of the best experts on this subject based on the ideXlab platform.

  • oral Uridine 5 monophosphate ump increases brain cdp choline levels in gerbils
    Brain Research, 2005
    Co-Authors: Mehmet Cansev, Carol Watkins, Eline M Van Der Beek, Richard J Wurtman
    Abstract:

    We examined the biochemical pathways whereby oral Uridine-5'-monophosphate (UMP) increases membrane phosphatide synthesis in brains of gerbils. We previously showed that supplementing PC12 cells with Uridine caused concentration-related increases in CDP-choline levels, and that this effect was mediated by elevations in intracellular Uridine Triphosphate (UTP) and cytidine Triphosphate (CTP). In the present study, adult gerbils received UMP (1 mmol/kg), a constituent of human breast milk and infant formulas, by gavage, and plasma samples and brains were collected for assay between 5 min and 8 h thereafter. Thirty minutes after gavage, plasma Uridine levels were increased from 6.6 +/- 0.58 to 32.7 +/- 1.85 microM (P < 0.001), and brain Uridine from 22.6 +/- 2.9 to 89.1 +/- 8.82 pmol/mg tissue (P < 0.001). UMP also significantly increased plasma and brain cytidine levels; however, both basally and following UMP, these levels were much lower than those of Uridine. Brain UTP, CTP, and CDP-choline were all elevated 15 min after UMP (from 254 +/- 31.9 to 417 +/- 50.2, [P < 0.05]; 56.8 +/- 1.8 to 71.7 +/- 1.8, [P < 0.001]; and 11.3 +/- 0.5 to 16.4 +/- 1, [P < 0.001] pmol/mg tissue, respectively), returning to basal levels after 20 and 30 min. The smallest UMP dose that significantly increased brain CDP-choline was 0.05 mmol/kg. These results show that oral UMP, a Uridine source, enhances the synthesis of CDP-choline, the immediate precursor of PC, in gerbil brain.

  • Uridine enhances neurite outgrowth in nerve growth factor differentiated pheochromocytoma cells
    Neuroscience, 2005
    Co-Authors: Amy M Pooler, D H Guez, R Benedictus, Richard J Wurtman
    Abstract:

    During rapid cell growth the availability of phospholipid precursors like cytidine Triphosphate and diacylglycerol can become limiting in the formation of key membrane constituents like phosphatidylcholine. Uridine, a normal plasma constituent, can be converted to cytidine Triphosphate in PC12 [corrected] cells and intact brain, and has been shown to produce a resulting increase in phosphatidylcholine synthesis. To determine whether treatments that elevate Uridine availability also thereby augment membrane production, we exposed PC12 [corrected] cells which had been differentiated by nerve growth factor to various concentrations of Uridine, and measured the numbers of neurites the cells produced. After 4 but not 2 days Uridine significantly and dose-dependently increased the number of neurites per cell. This increase was accompanied by increases in neurite branching and in levels of the neurite proteins neurofilament M [corrected] and neurofilament 70. Uridine treatment also increased intracellular levels of cytidine Triphosphate, which suggests that Uridine may affect neurite outgrowth by enhancing phosphatidylcholine synthesis. Uridine may also stimulate neuritogenesis by a second mechanism, since the increase in neurite outgrowth was mimicked by exposing the cells to Uridine Triphosphate, and could be blocked by various drugs known to antagonize P2Y receptors (suramin; Reactive Blue 2; pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid). Treatment of the cells with Uridine or Uridine Triphosphate stimulated their accumulation of inositol phosphates, and this effect was also blocked by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid. Moreover, degradation of nucleotides by apyrase blocked the stimulatory effect of Uridine on neuritogenesis. Taken together these data indicate that Uridine can regulate the output of neurites from differentiating PC12 [corrected] cells, and suggest that it does so in two ways, i.e. both by acting through cytidine Triphosphate as a precursor for phosphatidylcholine biosynthesis and through Uridine Triphosphate as an agonist for P2Y receptors.

  • dietary Uridine 5 monophosphate supplementation increases potassium evoked dopamine release and promotes neurite outgrowth in aged rats
    Journal of Molecular Neuroscience, 2005
    Co-Authors: Lei Wang, Amy M Pooler, Meredith A Albrecht, Richard J Wurtman
    Abstract:

    Membrane phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by cellular levels of its precursor, cytidine-5′-diphosphate choline (CDP-choline), which is produced from cytidine Triphosphate (CTP) and phosphocholine. In rat PC12 cells exogenous Uridine was shown to elevate intracellular CDP-choline levels, by promoting the synthesis of Uridine Triphosphate (UTP), which was partly converted to CTP. In such cells Uridine also enhanced the neurite outgrowth produced by nerve growth factor (NGF). The present study assessed the effect of dietary supplementation with Uridine-5′-monophosphate disodium (UMP-2Na+, an additive in infant milk formulas) on striatal dopamine (DA) release in aged rats. Male Fischer 344 rats consumed either a control diet or one fortified with 2.5% UMP for 6 wk, ad libitum. In vivo microdialysis was then used to measure spontaneous and potassium (K+)-evoked DA release in the right striatum. Potassium (K+)-evoked DA release was significantly greater among UMP-treated rats, i.e., 341±21% of basal levels vs. 283 ± 9% of basal levels in control rats (p<0.05); basal DA release was unchanged. In general, each animal’s K+-evoked DA release correlated with its striatal DA content, measured postmortem. The levels of neurofilament-70 and neurofilament-M proteins, biomarkers of neurite outgrowth, increased to 182±25% (p<0.05) and 221 ± 34% (p<0.01) of control values, respectively, with UMP consumption. Hence, UMP treatment not only enhances membrane phosphatide production but also can modulate two membrane-dependent processes, neurotransmitter release and neurite outgrowth, in vivo.

Fernanda Wajnsztajn - One of the best experts on this subject based on the ideXlab platform.

  • a double blind randomized comparative study of the use of a combination of Uridine Triphosphate trisodium cytidine monophosphate disodium and hydroxocobalamin versus isolated treatment with hydroxocobalamin in patients presenting with compressive neu
    Journal of Pain Research, 2017
    Co-Authors: Henrique Goldberg, Stephanie Wrobel Goldberg, Luiz Buchman, Helio Rzetelna, Marco Antonio Mibielli, Carlos Pereira Nunes, Mauro Geller, Lisa Oliveira, Spyros G.e. Mezitis, Fernanda Wajnsztajn
    Abstract:

    CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (Uridine Triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. METHODS: A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS: The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION: The combination of Uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

Henrique Goldberg - One of the best experts on this subject based on the ideXlab platform.

  • a double blind randomized comparative study of the use of a combination of Uridine Triphosphate trisodium cytidine monophosphate disodium and hydroxocobalamin versus isolated treatment with hydroxocobalamin in patients presenting with compressive neu
    Journal of Pain Research, 2017
    Co-Authors: Henrique Goldberg, Stephanie Wrobel Goldberg, Luiz Buchman, Helio Rzetelna, Marco Antonio Mibielli, Carlos Pereira Nunes, Mauro Geller, Lisa Oliveira, Spyros G.e. Mezitis, Fernanda Wajnsztajn
    Abstract:

    CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (Uridine Triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. METHODS: A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS: The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION: The combination of Uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

Mauro Geller - One of the best experts on this subject based on the ideXlab platform.

  • a double blind randomized comparative study of the use of a combination of Uridine Triphosphate trisodium cytidine monophosphate disodium and hydroxocobalamin versus isolated treatment with hydroxocobalamin in patients presenting with compressive neu
    Journal of Pain Research, 2017
    Co-Authors: Henrique Goldberg, Stephanie Wrobel Goldberg, Luiz Buchman, Helio Rzetelna, Marco Antonio Mibielli, Carlos Pereira Nunes, Mauro Geller, Lisa Oliveira, Spyros G.e. Mezitis, Fernanda Wajnsztajn
    Abstract:

    CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (Uridine Triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. METHODS: A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS: The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION: The combination of Uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

  • symptomatic improvement in an acute non traumatic spine pain model with a combination of Uridine Triphosphate cytidine monophosphate and hydroxocobalamin
    Conference on Privacy Security and Trust, 2014
    Co-Authors: Marco Antonio Mibielli, Carlos Pereira Nunes, Lisa Oliveira, Ari Boulanger Scussel, Mendel Suchmacher Neto, Mauro Geller
    Abstract:

    Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.

  • treatment of acute non traumatic pain using a combination of diclofenac cholestyramine Uridine Triphosphate cytidine monophosphate and hydroxycobalamin
    Proceedings of the Western Pharmacology Society, 2010
    Co-Authors: Marco Antonio Mibielli, Carlos Pereira Nunes, Lisa Oliveira, Jose Carlos Cohen, Ari Boulanger Scussel, Rafael Higashi, Gabriel Gherman Bendavit, Mauro Geller
    Abstract:

    : This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (Uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + Uridine + cytidine + vitamin B12 (Group DN, n=40) or Uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with Uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.

Marco Antonio Mibielli - One of the best experts on this subject based on the ideXlab platform.

  • a double blind randomized comparative study of the use of a combination of Uridine Triphosphate trisodium cytidine monophosphate disodium and hydroxocobalamin versus isolated treatment with hydroxocobalamin in patients presenting with compressive neu
    Journal of Pain Research, 2017
    Co-Authors: Henrique Goldberg, Stephanie Wrobel Goldberg, Luiz Buchman, Helio Rzetelna, Marco Antonio Mibielli, Carlos Pereira Nunes, Mauro Geller, Lisa Oliveira, Spyros G.e. Mezitis, Fernanda Wajnsztajn
    Abstract:

    CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (Uridine Triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. METHODS: A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. RESULTS: The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. CONCLUSION: The combination of Uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

  • symptomatic improvement in an acute non traumatic spine pain model with a combination of Uridine Triphosphate cytidine monophosphate and hydroxocobalamin
    Conference on Privacy Security and Trust, 2014
    Co-Authors: Marco Antonio Mibielli, Carlos Pereira Nunes, Lisa Oliveira, Ari Boulanger Scussel, Mendel Suchmacher Neto, Mauro Geller
    Abstract:

    Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.

  • treatment of acute non traumatic pain using a combination of diclofenac cholestyramine Uridine Triphosphate cytidine monophosphate and hydroxycobalamin
    Proceedings of the Western Pharmacology Society, 2010
    Co-Authors: Marco Antonio Mibielli, Carlos Pereira Nunes, Lisa Oliveira, Jose Carlos Cohen, Ari Boulanger Scussel, Rafael Higashi, Gabriel Gherman Bendavit, Mauro Geller
    Abstract:

    : This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (Uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + Uridine + cytidine + vitamin B12 (Group DN, n=40) or Uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with Uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.