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Jesus Pintor - One of the best experts on this subject based on the ideXlab platform.
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Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology
2020Co-Authors: Nery García-porta, Jesus Pintor, Gonzalo Carracedo, Laura Rico-del-viejo, Alba Martin-gil, José Manuel González-méijomeAbstract:properly cited. Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide Diadenosine Tetraphosphate (Ap 4 A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day ( < 0.05, 2 ) was observed. No significant changes were observed in Ap 4 A concentration in any group. Bulbar redness, limbal redness, and conjunctival staining increased significantly in the Si-Hy group ( < 0.05, Kruskal-Wallis test). Conclusion. Discomfort and dryness symptoms at the end of the day are lower in the OK CL group than in the Si-Hy CL group
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understanding the presence and roles of ap4a Diadenosine Tetraphosphate in the eye
Journal of Ocular Pharmacology and Therapeutics, 2017Co-Authors: Almudena Crooke, Gonzalo Carracedo, Ana Guzmanaranguez, Maria Perez J De Lara, Jesus PintorAbstract:Diadenosine Tetraphosphate abbreviated Ap4A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap4A are mostly carried out by P2Y2 receptors, but the participation of P2X2 and P2Y6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y2, is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap4A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap4A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.
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Diadenosine Tetraphosphate as a potential therapeutic nucleotide to treat glaucoma
Purinergic Signalling, 2017Co-Authors: Begoña Fonseca, Alejandro Martínez-Águila, María J. Pérez Lara, Jesus PintorAbstract:Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide Diadenosine Tetraphosphate AKA Ap_4A to reduce IOP. The topical application of Ap_4A when IOP is maximal (9–12 months) reduced IOP 30.6 ± 6.6% in the DBA/2J and 17.9 ± 4.0% in the C57BL/6J mice. Concentration response curves in both animal strains produced similar pD2 values; these being 4.9 ± 0.5 and 5.1 ± 0.4 for the normotensive C57BL/6J and the glaucomatous DBA/2J respectively. Antagonist studies showed differences between the control and the glaucomatous animals. In particular, the main receptor reducing IOP in the control animal was the P2Y_1 receptor and in the glaucomatous model the P2Y_6, although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap_4A applied three times a week for 3 months showed a clear stop in the elevation of IOP in the glaucomatous model, thus indicating the possibility of using Ap_4A as an effective compound for the treatment of glaucoma.
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Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology
BioMed research international, 2016Co-Authors: Nery García-porta, Jesus Pintor, Gonzalo Carracedo, Laura Rico-del-viejo, Alba Martin-gil, José Manuel González-méijomeAbstract:Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide Diadenosine Tetraphosphate (Ap4A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day (, ) was observed. No significant changes were observed in Ap4A concentration in any group. Bulbar redness, limbal redness, and conjunctival staining increased significantly in the Si-Hy group (, Kruskal–Wallis test). Conclusion. Discomfort and dryness symptoms at the end of the day are lower in the OK CL group than in the Si-Hy CL group.
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2 Spanish Cooperative Thematic Research Network in Ocular Prevalent and Chronic Pathology (RETIC),
2016Co-Authors: Ana Guzman-aranguez, Xavier Gasull, A Diebold, Jesus PintorAbstract:Copyright © 2014 Ana Guzman-Aranguez et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited. Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned, ” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-Diadenosine Tetraphosphate (Ap 4 A), and P1,P5-Diadenosine pentaphosphate (Ap 5 A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A 2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A
Alexander G Mclennan - One of the best experts on this subject based on the ideXlab platform.
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re evaluation of Diadenosine Tetraphosphate ap4a from a stress metabolite to bona fide secondary messenger
Frontiers in Molecular Biosciences, 2020Co-Authors: Freya Ferguson, Alexander G Mclennan, Nigel J Jones, Michael D Urbaniak, Nikki A CopelandAbstract:Cellular homeostasis requires adaption to environmental stress. In response to various environmental and genotoxic stresses, all cells produce dinucleoside polyphosphates (NpnNs), the best studied of which is Diadenosine Tetraphosphate (Ap4A). Despite intensive investigation, the precise biological roles of these molecules have remained elusive. However, recent studies have elucidated distinct and specific signaling mechanisms for these nucleotides in prokaryotes and eukaryotes. This review summarizes these key discoveries and describes the mechanisms of Ap4A and Ap4N synthesis, the mediators of the cellular responses to increased intracellular levels of these molecules and the hydrolytic mechanisms required to maintain low levels in the absence of stress. The intracellular responses to dinucleotide accumulation are evaluated in the context of the "friend" and "foe" scenarios. The "friend (or alarmone) hypothesis" suggests that ApnN act as bona fide secondary messengers mediating responses to stress. In contrast, the "foe" hypothesis proposes that ApnN and other NpnN are produced by non-canonical enzymatic synthesis as a result of physiological and environmental stress in critically damaged cells but do not actively regulate mitigating signaling pathways. In addition, we will discuss potential target proteins, and critically assess new evidence supporting roles for ApnN in the regulation of gene expression, immune responses, DNA replication and DNA repair. The recent advances in the field have generated great interest as they have for the first time revealed some of the molecular mechanisms that mediate cellular responses to ApnN. Finally, areas for future research are discussed with possible but unproven roles for intracellular ApnN to encourage further research into the signaling networks that are regulated by these nucleotides.
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nudt2 disruption elevates Diadenosine Tetraphosphate ap4a and down regulates immune response and cancer promotion genes
PLOS ONE, 2016Co-Authors: Andrew S Marriott, Alexander G Mclennan, Nikki A Copeland, Olga Vasieva, Yongxiang Fang, Nigel J JonesAbstract:Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide Diadenosine Tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis.
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structure and substrate binding mechanism of human ap4a hydrolase
Journal of Biological Chemistry, 2005Co-Authors: James D Swarbrick, Alexander G Mclennan, Kenwyn R Gayler, S Buyya, Dilantha Gunawardana, Paul R GooleyAbstract:Asymmetric Diadenosine 5',5'''-P(1),P(4)-Tetraphosphate (Ap(4)A) hydrolases play a major role in maintaining homeostasis by cleaving the metabolite Diadenosine Tetraphosphate (Ap(4)A) back into ATP and AMP. The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP. The adenine moiety of the nucleotide predominantly binds in a ring stacking arrangement equivalent to that observed in the x-ray structure of the homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class of enzymes, opening avenues for the exploration of specific therapeutics. Binding of ATP induces substantial conformational and dynamic changes that were not observed in the C. elegans structure. In contrast to the C. elegans homologue, important side chains that play a major role in substrate binding do not have to reorient to accommodate the ligand. This may have important implications in the mechanism of substrate recognition in this class of enzymes.
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nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5 phosphoribosyl 1 pyrophosphate prpp pyrophosphatase activity that generates the glycolytic activator ribose 1 5 bisphosphate
Journal of Biological Chemistry, 2002Co-Authors: D Fisher, Alexander G Mclennan, Stephen T Safrany, Peter Strike, Jared L CartwrightAbstract:Abstract A total of 17 Nudix hydrolases were tested for their ability to hydrolyze 5-phosphoribosyl 1-pyrophosphate (PRPP). All 11 enzymes that were active toward dinucleoside polyphosphates with 4 or more phosphate groups as substrates were also able to hydrolyze PRPP, whereas the 6 that could not and that have coenzyme A, NDP-sugars, or pyridine nucleotides as preferred substrates did not degrade PRPP. The products of hydrolysis were ribose 1,5-bisphosphate and Pi. Active PRPP pyrophosphatases included the diphosphoinositol polyphosphate phosphohydrolase (DIPP) subfamily of Nudix hydrolases, which also degrade the non-nucleotide diphosphoinositol polyphosphates. K m andk cat values for PRPP hydrolysis for theDeinococcus radiodurans DR2356 (di)nucleoside polyphosphate hydrolase, the human Diadenosine Tetraphosphate hydrolase, and human DIPP-1 (Diadenosine hexaphosphate and diphosphoinositol polyphosphate hydrolase) were 1 mm and 1.5 s−1, 0.13 mm and 0.057 s−1, and 0.38 mm and 1.0 s−1, respectively. Active site mutants of theCaenorhabditis elegans Diadenosine Tetraphosphate hydrolase had no activity, confirming that the same active site is responsible for nucleotide and PRPP hydrolysis. Comparison of the specificity constants for nucleotide, diphosphoinositol polyphosphate, and PRPP hydrolysis suggests that PRPP is a significant substrate for theD. radiodurans DR2356 enzyme and for the DIPP subfamily. In the latter case, generation of the glycolytic activator ribose 1,5-bisphosphate may be a new function for these enzymes.
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Human Diadenosine 5',5"'-P1,P4-Tetraphosphate pyrophosphohydrolase is a member of the MutT family of nucleotide pyrophosphatases.
Biochemical Journal, 1995Co-Authors: N M H Thorne, Steven Hankin, Mark C. Wilkinson, Carmen Nunez, Roger Barraclough, Alexander G MclennanAbstract:The cDNA and derived amino acid sequence of human Diadenosine 5',5"'-P1,P4-Tetraphosphate pyrophosphohydrolase have been determined with the aid of the GenBank Expressed Sequence Tag database. This enzyme possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. It is unrelated to the enzymes of Diadenosine Tetraphosphate catabolism found in prokaryotes and fungi.
Pedro Rotllan - One of the best experts on this subject based on the ideXlab platform.
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DDR Strategy, Management and Health Policy Venture Capital Enabling
2014Co-Authors: Functions Of Diadenosine Polyphosphates, Andrzej Guranowski, Pedro Rotllan, Larry D. Barnes, Charles Brenner, Er G. Mclennan, Michael G. Blackburn, Andrew D. Miller, Juan Manuel Rovira, Bernat SoriaAbstract:ABSTRACT Recent developments in the effort to understand the metabolism and function of the intracellular dinucleoside polyphosphates were described by nine speakers from some of the world’s leading laboratories in this field in a workshop at the Purines 2000 International Symposium on Nucleosides and Nucleotides held in Madrid in July, 2000. Topics were wide-ranging and included phenotypic analyses of yeast mutants defective in enzymes of dinucleoside polyphosphate degradation, virally encoded catabolic enzymes, the structure and function of the Fhit tumor suppressor and Fhit-nitrilase fusion proteins and the relationship of Fhit to human Diadenosine triphosphate hydrolase, site-directed mutagenesis of Diadenosine Tetraphosphate hydrolase, novel nucleotide analogs for studying hydrolase function, the synthesis of dinucleoside polyphosphates by ligases, and the possible roles of Diadenosine tri- and Tetraphosphates i
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binding of 5 o 2 thiodiphosphate to rat brain membranes is prevented by Diadenosine Tetraphosphate and correlates with ecto nucleotide pyrophosphatase phosphodiesterase 1 npp1 activity
Neuroscience Letters, 2008Co-Authors: Sol Oaknin, Jose S Aguilar, Carmen R Rodriguezferrer, Antonio Ramos, Pedro RotllanAbstract:Abstract The distribution of binding sites for [ 35 S]5′- O -(2-thiodiphosphate) ([ 35 S]ADPβS), a radioligand of P2Y 1,12,13 receptors, and of ecto-nucleotide pyrophosphatase phosphodiesterase activity were analyzed in the rat forebrain. Binding sites for the radilogand are widespreadly distributed in the rat forebrain, showing the highest density in hypothalamus. K d values were in the range 1–2 nM. Diadenosine Tetraphosphate (Ap 4 A) and diethenoadenosine Tetraphosphate, ɛ-(Ap 4 A), displaced the radioligand, indicating dinucleotide binding to ADPβS-recognizing P2Y receptors. Activity ecto-nucleotide pyrophosphatase phosphodiesterase 1 (NPP1), able to hydrolyze Ap 4 A and other Diadenosine polyphosphates, is also widely distributed through the rat forebrain, with the highest activity in hypothalamus. These results suggests that Ap 4 A signalling mediated by P2Y 1,12,13 receptors and enzymatically regulated by NPP1 activity may be particularly important in hypothalamus and add new support for neurotransmitter/neuromodulatory functions of Diadenosine polyphosphates in brain.
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Potent inhibition of specific Diadenosine polyphosphate hydrolases by suramin
FEBS Letters, 1998Co-Authors: Pedro Rotllan, Carmen R. Rodríguez-ferrer, Aaron C. Asensio, Sol OakninAbstract:Abstract The cytosolic enzymes asymmetrical Diadenosine Tetraphosphate hydrolase (EC 3.6.1.17, Ap4Aase) and Diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap3Aase) are inhibited competitively by suramin. Ap4Aase and Ap3Aase were assayed in cytosolic rat brain extracts using fluorogenic analogues of the respective substrates Diadenosine Tetraphosphate (Ap4A) and Diadenosine triphosphate (Ap3A). Ki values for suramin as inhibitor of Ap4Aase and Ap3Aase were 5×10−6 M and 3×10−7 M, respectively. Results indicate that suramin or suramin-like derivatives may be useful tools to investigate Diadenosine polyphosphate cleaving enzymes and that the intracellular Diadenosine polyphosphate metabolism may be a pharmacological target of suramin with biological and clinical implications.
Sol Oaknin - One of the best experts on this subject based on the ideXlab platform.
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binding of 5 o 2 thiodiphosphate to rat brain membranes is prevented by Diadenosine Tetraphosphate and correlates with ecto nucleotide pyrophosphatase phosphodiesterase 1 npp1 activity
Neuroscience Letters, 2008Co-Authors: Sol Oaknin, Jose S Aguilar, Carmen R Rodriguezferrer, Antonio Ramos, Pedro RotllanAbstract:Abstract The distribution of binding sites for [ 35 S]5′- O -(2-thiodiphosphate) ([ 35 S]ADPβS), a radioligand of P2Y 1,12,13 receptors, and of ecto-nucleotide pyrophosphatase phosphodiesterase activity were analyzed in the rat forebrain. Binding sites for the radilogand are widespreadly distributed in the rat forebrain, showing the highest density in hypothalamus. K d values were in the range 1–2 nM. Diadenosine Tetraphosphate (Ap 4 A) and diethenoadenosine Tetraphosphate, ɛ-(Ap 4 A), displaced the radioligand, indicating dinucleotide binding to ADPβS-recognizing P2Y receptors. Activity ecto-nucleotide pyrophosphatase phosphodiesterase 1 (NPP1), able to hydrolyze Ap 4 A and other Diadenosine polyphosphates, is also widely distributed through the rat forebrain, with the highest activity in hypothalamus. These results suggests that Ap 4 A signalling mediated by P2Y 1,12,13 receptors and enzymatically regulated by NPP1 activity may be particularly important in hypothalamus and add new support for neurotransmitter/neuromodulatory functions of Diadenosine polyphosphates in brain.
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Potent inhibition of specific Diadenosine polyphosphate hydrolases by suramin
FEBS Letters, 1998Co-Authors: Pedro Rotllan, Carmen R. Rodríguez-ferrer, Aaron C. Asensio, Sol OakninAbstract:Abstract The cytosolic enzymes asymmetrical Diadenosine Tetraphosphate hydrolase (EC 3.6.1.17, Ap4Aase) and Diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap3Aase) are inhibited competitively by suramin. Ap4Aase and Ap3Aase were assayed in cytosolic rat brain extracts using fluorogenic analogues of the respective substrates Diadenosine Tetraphosphate (Ap4A) and Diadenosine triphosphate (Ap3A). Ki values for suramin as inhibitor of Ap4Aase and Ap3Aase were 5×10−6 M and 3×10−7 M, respectively. Results indicate that suramin or suramin-like derivatives may be useful tools to investigate Diadenosine polyphosphate cleaving enzymes and that the intracellular Diadenosine polyphosphate metabolism may be a pharmacological target of suramin with biological and clinical implications.
Gonzalo Carracedo - One of the best experts on this subject based on the ideXlab platform.
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Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology
2020Co-Authors: Nery García-porta, Jesus Pintor, Gonzalo Carracedo, Laura Rico-del-viejo, Alba Martin-gil, José Manuel González-méijomeAbstract:properly cited. Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide Diadenosine Tetraphosphate (Ap 4 A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day ( < 0.05, 2 ) was observed. No significant changes were observed in Ap 4 A concentration in any group. Bulbar redness, limbal redness, and conjunctival staining increased significantly in the Si-Hy group ( < 0.05, Kruskal-Wallis test). Conclusion. Discomfort and dryness symptoms at the end of the day are lower in the OK CL group than in the Si-Hy CL group
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understanding the presence and roles of ap4a Diadenosine Tetraphosphate in the eye
Journal of Ocular Pharmacology and Therapeutics, 2017Co-Authors: Almudena Crooke, Gonzalo Carracedo, Ana Guzmanaranguez, Maria Perez J De Lara, Jesus PintorAbstract:Diadenosine Tetraphosphate abbreviated Ap4A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap4A are mostly carried out by P2Y2 receptors, but the participation of P2X2 and P2Y6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y2, is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap4A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap4A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.
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Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology
BioMed research international, 2016Co-Authors: Nery García-porta, Jesus Pintor, Gonzalo Carracedo, Laura Rico-del-viejo, Alba Martin-gil, José Manuel González-méijomeAbstract:Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide Diadenosine Tetraphosphate (Ap4A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day (, ) was observed. No significant changes were observed in Ap4A concentration in any group. Bulbar redness, limbal redness, and conjunctival staining increased significantly in the Si-Hy group (, Kruskal–Wallis test). Conclusion. Discomfort and dryness symptoms at the end of the day are lower in the OK CL group than in the Si-Hy CL group.
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Differences in Dry Eye Questionnaire Symptoms in Two Different Modalities of Contact Lens Wear: Silicone-Hydrogel in Daily Wear Basis and Overnight Orthokeratology
Hindawi Limited, 2016Co-Authors: Nery García-porta, Jesus Pintor, Gonzalo Carracedo, Laura Rico-del-viejo, Alba Martin-gil, José Manuel González-méijomeAbstract:Purpose. To compare the ocular surface symptoms and signs in an adult population of silicone-hydrogel (Si-Hy) contact lens (CL) wearers with another modality of CL wear, overnight orthokeratology (OK). Materials and Methods. This was a prospective and comparative study in which 31 myopic subjects were fitted with the same Si-Hy CL and 23 underwent OK treatment for 3 months. Dry eye questionnaire (DEQ) was filled in at the beginning of the study and then after 15 days, 1 month, and 3 months using each CL modality. The tear quality was evaluated with noninvasive tear break-up time. Tear production was measured with Schirmer test. Tear samples were collected with Schirmer strips being frozen to analyze the dinucleotide Diadenosine Tetraphosphate (Ap4A) concentration with High-Performance Liquid Chromatography (HPLC). Results. After refitting with ortho-k, a reduction in discomfort and dryness symptoms at the end of the day (p
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in vitro and in vivo delivery of the secretagogue Diadenosine Tetraphosphate from conventional and silicone hydrogel soft contact lenses
Journal of Optometry, 2013Co-Authors: C O Dominguezgodinez, Jesus Pintor, Gonzalo Carracedo, Ana Guzmanaranguez, Alba Martingil, Jose Manuel GonzalezmeijomeAbstract:Purpose: To evaluate the possible use of soft contact lenses (CL) to improve the secretagogue role of Diadenosine Tetraphosphate (Ap4A) promoting tear secretion. Methods: Two conventional hydrogel CL (Omafilcon A and Ocufilcon D) and two silicone hydrogel (SiH) CL (Comfilcon A and Balafilcon A) were used. Ap4A was loaded into the lenses by soaking in a 1 mM Ap4A solution during 12 h. In vitro experiments were performed by placing the lenses in multi-wells during 2 h containing 1 ml of ultrapure water. 100 l aliquots were taken at time zero and every minute for the first 10 min, and then every 15 min. In vivo experiments were performed in New Zealand rabbits and both the dinucleotide release from SiH and tear secretion were measured by means of Schirmer strips and high-pressure liquid chromatography (HPLC) analysis.