The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Nilza Nelly Fontana Lopes - One of the best experts on this subject based on the ideXlab platform.
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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact
Supportive Care in Cancer, 2010Co-Authors: Siri Beier Jensen, Anne Marie Lynge Pedersen, Arjan Vissink, Elo Andersen, Carlton G Brown, J Dutilh, Janet S Fulton, Ljiljana Jankovic, A. N. Davies, Nilza Nelly Fontana LopesAbstract:Purpose This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. Methods The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Results Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Conclusions There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
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a systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies management strategies and economic impact
Supportive Care in Cancer, 2010Co-Authors: Siri Beier Jensen, Anne Marie Lynge Pedersen, Arjan Vissink, Elo Andersen, Carlton G Brown, Andrew Davies, J Dutilh, Janet S Fulton, Ljiljana Jankovic, Nilza Nelly Fontana LopesAbstract:This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
Jurgen Wess - One of the best experts on this subject based on the ideXlab platform.
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cholinergic stimulation of salivary secretion studied with m1 and m3 Muscarinic receptor single and double knockout mice
Molecular Pharmacology, 2004Co-Authors: Dinesh Gautam, Thomas S Heard, Yinghong Cui, Georgina Miller, Lanh M Bloodworth, Jurgen WessAbstract:Identification of the specific Muscarinic acetylcholine receptor (mAChR) subtypes mediating stimulation of salivary secretion is of considerable clinical interest. Recent pharmacological and molecular genetic studies have yielded somewhat confusing and partially contradictory results regarding the involvement of individual mAChRs in this activity. In the present study, we re-examined the roles of M(1) and M(3) mAChRs in Muscarinic Agonist-mediated stimulation of salivary secretion by using M(1) and M(3) receptor single-knockout (KO) mice and newly generated M(1)/M(3) receptor double-KO mice. When applied at a low dose (1 mg/kg, s.c.), the Muscarinic Agonist pilocarpine showed significantly reduced secretory activity in both M(1) and M(3) receptor single-KO mice. However, when applied at higher doses, pilocarpine induced only modestly reduced (5 mg/kg, s.c.) or unchanged (15 mg/kg, s.c.) salivation responses, respectively, in M(1) and M(3) receptor single-KO mice, indicating that the presence of either M(1) or M(3) receptors is sufficient to mediate robust salivary output. Quantitative reverse transcriptase-polymerase chain reaction studies with salivary gland tissue showed that the inactivation of the M(1) or M(3) mAChR genes did not lead to significantly altered mRNA levels of the remaining mAChR subtypes. Strikingly, the sialagogue activity of pilocarpine was abolished in M(1)/M(3) receptor double-KO mice. However, salivary glands from M(1)/M(3) receptor double-KO mice remained responsive to stimulation by the beta-adrenergic receptor Agonist, (S)-isoproterenol. Taken together these studies support the concept that a mixture of M(1) and M(3) receptors mediates cholinergic stimulation of salivary flow.
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cholinergic stimulation of salivary secretion studied with m1 and m3 Muscarinic receptor single and double knockout mice
Molecular Pharmacology, 2004Co-Authors: Dinesh Gautam, Thomas S Heard, Georgina Miller, Lanh M Bloodworth, Jurgen WessAbstract:Identification of the specific Muscarinic acetylcholine receptor (mAChR) subtypes mediating stimulation of salivary secretion is of considerable clinical interest. Recent pharmacological and molecular genetic studies have yielded somewhat confusing and partially contradictory results regarding the involvement of individual mAChRs in this activity. In the present study, we re-examined the roles of M1 and M3 mAChRs in Muscarinic Agonist-mediated stimulation of salivary secretion by using M1 and M3 receptor single-knockout (KO) mice and newly generated M1/M3 receptor double-KO mice. When applied at a low dose (1 mg/kg, s.c.), the Muscarinic Agonist pilocarpine showed significantly reduced secretory activity in both M1 and M3 receptor single-KO mice. However, when applied at higher doses, pilocarpine induced only modestly reduced (5 mg/kg, s.c.) or unchanged (15 mg/kg, s.c.) salivation responses, respectively, in M1 and M3 receptor single-KO mice, indicating that the presence of either M1 or M3 receptors is sufficient to mediate robust salivary output. Quantitative reverse transcriptase-polymerase chain reaction studies with salivary gland tissue showed that the inactivation of the M1 or M3 mAChR genes did not lead to significantly altered mRNA levels of the remaining mAChR subtypes. Strikingly, the sialagogue activity of pilocarpine was abolished in M1/M3 receptor double-KO mice. However, salivary glands from M1/M3 receptor double-KO mice remained responsive to stimulation by the β-adrenergic receptor Agonist, (S)-isoproterenol. Taken together these studies support the concept that a mixture of M1 and M3 receptors mediates cholinergic stimulation of salivary flow.
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role of specific Muscarinic receptor subtypes in cholinergic parasympathomimetic responses in vivo phosphoinositide hydrolysis and pilocarpine induced seizure activity
European Journal of Neuroscience, 2003Co-Authors: Frank P Bymaster, Neil M Nathanson, Jurgen Wess, Masahisa Yamada, Petra A Carter, Jesus Gomeza, Susan E Hamilton, David L Mckinzie, Christian C FelderAbstract:Muscarinic Agonist-induced parasympathomimetic effects, in vivo phosphoinositide hydrolysis and seizures were evaluated in wild-type and Muscarinic M 1 -M 5 receptor knockout mice. The Muscarinic Agonist oxotremorine induced marked hypothermia in all the knockout mice, but the hypothermia was reduced in M 2 and to a lesser extent in M 3 knockout mice. Oxotremorine-induced tremor was abolished only in the M 2 knockout mice. Muscarinic Agonist-induced salivation was reduced to the greatest extent in M 3 knockout mice, to a lesser degree in M 1 and M 4 knockout mice, and was not altered in M 2 and M 5 knockout mice. Pupil diameter under basal conditions was increased only in the M 3 knockout mice. Pilocarpine-induced increases in in vivo phosphoinositide hydrolysis were completely absent in hippocampus and cortex of M 1 knockout mice, but in vivo phosphoinositide hydrolysis was unaltered in the M 2 -M 5 knockout mice. A high dose of pilocarpine (300 mg/kg) caused seizures and lethality in wild-type and M 2 -M 5 knockout mice, but produced neither effect in the M 1 knockout mice. These data demonstrate a major role for M 2 and M 3 Muscarinic receptor subtypes in mediating parasympathomimetic effects. Muscarinic M 1 receptors activate phosphoinositide hydrolysis in cortex and hippocampus of mice, consistent with the role of M 1 receptors in cognition. Muscarinic M 1 receptors appear to be the only Muscarinic receptor subtype mediating seizures.
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Evaluation of Muscarinic Agonist-Induced Analgesia in Muscarinic Acetylcholine Receptor Knockout Mice
Molecular pharmacology, 2002Co-Authors: Alokesh Duttaroy, Jesus Gomeza, Christian C Felder, Jai-wei Gan, Nasir A. Siddiqui, Anthony S. Basile, W. Dean Harman, Philip L. Smith, Allan I. Levey, Jurgen WessAbstract:Centrally active Muscarinic Agonists display pronounced analgesic effects. Identification of the specific Muscarinic acetylcholine receptor (mAChR) subtype(s) mediating this activity is of considerable therapeutic interest. To examine the roles of the M 2 and M 4 receptor subtypes, the two G i /G o -coupled mAChRs, in mediating Agonist-dependent antinociception, we generated a mutant mouse line deficient in both M 2 and M 4 mAChRs [M 2 /M 4 double-knockout (KO) mice]. In wild-type mice, systemic, intrathecal, or intracerebroventricular administration of centrally active Muscarinic Agonists resulted in robust analgesic effects, indicating that Muscarinic analgesia can be mediated by both spinal and supraspinal mechanisms. Strikingly, Muscarinic Agonist-induced antinociception was totally abolished in M 2 /M 4 double-KO mice, independent of the route of application. The nonselective Muscarinic Agonist oxotremorine showed reduced analgesic potency in M 2 receptor single-KO mice, but retained full analgesic activity in M 4 receptor single-KO mice. In contrast, two novel Muscarinic Agonists chemically derived from epibatidine, CMI-936 and CMI-1145, displayed reduced analgesic activity in both M 2 and M 4 receptor single-KO mice, independent of the route of application. Radioligand binding studies indicated that the two CMI compounds, in contrast to oxotremorine, showed >6-fold higher affinity for M 4 than for M 2 receptors, providing a molecular basis for the observed differences in Agonist activity profiles. These data provide unambiguous evidence that Muscarinic analgesia is exclusively mediated by a combination of M 2 and M 4 mAChRs at both spinal and supraspinal sites. These findings should be of considerable relevance for the development of receptor subtype-selective Muscarinic Agonists as novel analgesic drugs.
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m3 receptor knockout mice Muscarinic receptor function in atria stomach fundus urinary bladder and trachea
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2002Co-Authors: Peter W Stengel, Jurgen Wess, Masahisa Yamada, Marlene L CohenAbstract:Negative chronotropic and smooth muscle contractile responses to the nonselective Muscarinic Agonist carbamylcholine were compared in isolated tissues from M3-Muscarinic receptor knockout and wild-...
Siri Beier Jensen - One of the best experts on this subject based on the ideXlab platform.
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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact
Supportive Care in Cancer, 2010Co-Authors: Siri Beier Jensen, Anne Marie Lynge Pedersen, Arjan Vissink, Elo Andersen, Carlton G Brown, J Dutilh, Janet S Fulton, Ljiljana Jankovic, A. N. Davies, Nilza Nelly Fontana LopesAbstract:Purpose This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. Methods The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Results Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Conclusions There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
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a systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies management strategies and economic impact
Supportive Care in Cancer, 2010Co-Authors: Siri Beier Jensen, Anne Marie Lynge Pedersen, Arjan Vissink, Elo Andersen, Carlton G Brown, Andrew Davies, J Dutilh, Janet S Fulton, Ljiljana Jankovic, Nilza Nelly Fontana LopesAbstract:This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, Muscarinic Agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
Harlan E. Shannon - One of the best experts on this subject based on the ideXlab platform.
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The Muscarinic Agonist xanomeline increases monoamine release and immediate early gene expression in the rat prefrontal cortex.
Biological Psychiatry, 2001Co-Authors: Kenneth W. Perry, Christian C Felder, Laura Nisenbaum, Carolyn A George, Harlan E. Shannon, Frank P BymasterAbstract:Abstract Background: The Muscarinic Agonist xanomeline has been shown to reduce antipsychotic-like behaviors in patients with Alzheimer’s disease. Because atypical antipsychotic agents increase dopamine release in prefrontal cortex and induce immediate early gene expression in prefrontal cortex and nucleus accumbens, the effect of xanomeline was determined on these indices. Methods: The effect of xanomeline on extracellular levels of monoamines in brain regions was determined using a microdialysis technique, and changes in expression of the immediate early genes c-fos and zif/268 in brain regions were evaluated using in situ hybridization histochemistry. Results: Xanomeline increased extracellular levels of dopamine in prefrontal cortex and nucleus accumbens but not in striatum. Xanomeline increased expression of c-fos and zif/268 in prefrontal cortex and nucleus accumbens. There was no change in immediate early gene expression in striatum. Conclusions: Xanomeline increased extracellular levels of dopamine, which is similar to the effects of the atypical antipsychotics clozapine and olanzapine. The regional pattern of immediate early gene expression induced by xanomeline resembled that of atypical antipsychotic agents. Based on the antipsychotic-like activity of xanomeline in Alzheimer’s patients and the similarity to atypical antipsychotic agents, we suggest that xanomeline may be a novel antipsychotic agent.
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1,2,5-Thiadiazole Analogues of Aceclidine as Potent m1 Muscarinic Agonists
Journal of medicinal chemistry, 1998Co-Authors: John S. Ward, Harlan E. Shannon, Charles H. Mitch, Franklin Porter Bymaster, David O. Calligaro, Malcolm J. Sheardown, Leander Merritt, Celia Ann Whitesitt, David Brunsting, Preben H. OlesenAbstract:The acetyl group of the Muscarinic Agonist aceclidine 4 was replaced by various 1,2,5-thiadiazoles to provide a new series of potent m1 Muscarinic Agonists 17 and 18. Optimal m1 Muscarinic Agonist potency was achieved when the 1,2,5-thiadiazole substituent was either a butyloxy, 17d, or butylthio, 18d, group. Although 1,2,5-oxadiazole 37 and pyrazine 39 are iso-pi-electronic with 1,2,5-thiadiazole 17d, both analogues were substantially less active than 17d. Compounds with high Muscarinic affinity and/or m1 Muscarinic Agonist efficacy were also obtained when the 3-oxyquinuclidine moiety of 17d or 18c was replaced by ethanolamines, hydroxypyrrolidines, hydroxyazetidine, hydroxyisotropanes, or hydroxyazanorbornanes. The structure-activity data support the participation of the oxygen or sulfur atom in the substituent on the 1,2,5-thiadiazole in the activation of the m1 receptor. Several of these new 1,2,5-thiadiazoles have m1 Agonist efficacy, potency, and selectivity comparable to those of xanomeline 2 in the Muscarinic tests investigated.
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Xanomeline: A Potent and Selective M1 Muscarinic Agonist in Vitro
Neurobiology of Aging, 1994Co-Authors: Charles H. Mitch, Harlan E. Shannon, Franklin Porter Bymaster, David O. Calligaro, Steven James Quimby, B.d. Sawyer, John S. Ward, P. H. Olesen, P. Sauerberg, M. J. SheardownAbstract:Xanomeline (3-(4-Hexyloxy-1,2,5-thiadiazole-3-yl)-1,2,5,6-tetrahydro-1- methylpyridine), (hexyloxy-TZTP) was discovered in the course of investigations on the structure activity relationship of a series of thiadiazole based analogs of the Muscarinic Agonist arecoline. The compound demonstrated functional selectivity for M1 receptors when tested in isolated tissue preparations and in cloned cell lines expressing specific Muscarinic receptor subtypes.
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Synthesis and structure-activity relationships of heterocyclic analogues of the functional M1 selective Muscarinic Agonist hexyloxy-TZTP
Bioorganic & Medicinal Chemistry Letters, 1992Co-Authors: Per Sauerberg, Charles H. Mitch, B.d. Sawyer, Preben H. Olesen, Peter D. Suzdak, Malcolm J. Sheardown, Harlan E. ShannonAbstract:Abstract Isothiazole ( 8a,b ), isoxazole ( 14 ) and thiophene ( 19a,b ) analogues of the potent, M 1 selective Muscarinic Agonist, hexyloxy-TZTP, 1b , were synthesized and tested |in vitro for Muscarinic receptor affinity and M 1 efficacy. All the analogues had lower affinity and efficacy at the M 1 Muscarinic receptors than 1b .
Martin C Michel - One of the best experts on this subject based on the ideXlab platform.
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Muscarinic receptor subtypes and signalling involved in the attenuation of isoprenaline induced rat urinary bladder relaxation
Naunyn-schmiedebergs Archives of Pharmacology, 2011Co-Authors: Lambertus P W Witte, Noach De Haas, Mathai Mammen, Eric L Stangeland, Tod Steinfeld, Jayashree Aiyar, Martin C MichelAbstract:β-Adrenoceptors are important mediators of smooth muscle relaxation in the urinary bladder, but the concomitant presence of a Muscarinic Agonist, e.g., carbachol, can attenuate relaxation responses by reducing potency and/or efficacy of β-adrenoceptor Agonists such as isoprenaline. Therefore, the present study was designed to explore the subtypes and signalling pathways of Muscarinic receptors involved in the attenuation of isoprenaline-induced isolated rat detrusor preparations using novel subtype-selective receptor ligands. In radioligand binding studies, we characterized BZI to be a M3-sparing Muscarinic Agonist, providing selective M2 stimulation in rat bladder, and THRX-182087 as a highly M2-selective antAgonist. The use of BZI and of THRX-182087 in the presence of carbachol enabled experimental conditions with a selective stimulation of only M2 or M3 receptors, respectively. Confirming previous findings, carbachol attenuated isoprenaline-induced detrusor relaxation. M2-selective stimulation partly mimicked this attenuation, indicating that both M2 and M3 receptors are involved. During M3-selective stimulation, the attenuation of isoprenaline responses was reduced by the phospholipase C inhibitor U 73,122 but not by the protein kinase C inhibitor chelerythrine. We conclude that both M2 and M3 receptors contribute to attenuation of β-adrenoceptor-mediated relaxation of rat urinary bladder; the signal transduction pathway involved in the M3 component of this attenuation differs from that mediating direct contractile effects of M3 receptors.
