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Kihoon Nam, Christina L Maruyama, Ching-Shuen Wang, Bryan G Trump, Pedro Lei, Stelios T Andreadis, Olga J Baker
Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization...
2017: PloS One
Anna Greta Barbe
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Mercadante V, Hamad AA, Lodi G, Porter S, Fedele S. Oral Oncol 2017;66:64-74. SOURCE OF FUNDING: The authors reported that no external funding sources directly supported this study TYPE OF STUDY/DESIGN: Systematic review and meta-analysis.
September 2017: Journal of Evidence-based Dental Practice
Yoshihiro Mitoh, Hirotaka Ueda, Hiroyuki Ichikawa, Masako Fujita, Motoi Kobashi, Ryuji Matsuo
The superior salivatory nucleus (SSN) contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, is a sialogogue that possibly stimulates SSN neurons in addition to the salivary glands themselves because it can cross the blood-brain barrier (BBB). In the present study, we examined immunoreactivities for mAChR subtypes in SSN neurons retrogradely labeled with a fluorescent tracer in neonatal rats...
September 2017: Autonomic Neuroscience: Basic & Clinical
Valeria Mercadante, Arwa Al Hamad, Giovanni Lodi, Stephen Porter, Stefano Fedele
INTRODUCTION: Salivary gland hypofunction is a common and permanent adverse effect of radiotherapy to the head and neck. Randomised trials of available treatment modalities have produced unclear results and offer little reliable guidance for clinicians to inform evidence-based therapy. We have undertaken this systematic review and meta-analysis to estimate the effectiveness of available interventions for radiotherapy-induced xerostomia and hyposalivation. METHODS: We searched MEDLINE, Cochrane Central, EMBASE, AMED, and CINAHL database through July 2016 for randomised controlled trials comparing any topical or systemic intervention to active and/or non-active controls for the treatment of radiotherapy-induced xerostomia...
March 2017: Oral Oncology
K Nam, C-S Wang, C L M Maruyama, P Lei, S T Andreadis, O J Baker
Hyposalivation contributes to dental caries, periodontitis, and microbial infections. Additionally, it impairs activities of daily living (e.g., speaking, chewing, and swallowing). Treatments for hyposalivation are currently limited to medications (e.g., the muscarinic receptor agonists pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells and the use of saliva substitutes. However, given that these therapies provide only temporary relief, the development of alternative treatments to restore gland function is essential...
July 2017: Journal of Dental Research
Marta Tanasiewicz, Tomasz Hildebrandt, Izabela Obersztyn
This paper presents the etiopathogenesis, symptomatology, evaluation and treatment of mouth dryness. Xerostomia affects 1-29% of the population, mostly women. It is observed in geriatric patients and in individuals using certain medications, those subjected to radiotherapy of the head and neck region or affected with autoimmune conditions. The main signs of xerostomia include the impression of a dry mouth, problems with food ingestion and dryness of the oral mucosa and skin. Evaluation is based on structured interviews (the Fox test) and determinations of unstimulated and stimulated salivary volume...
January 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Dmitrijs Stepanovs, Zenta Tetere, Irisa Rāviņa, Viktors Kumpiņš, Daina Zicāne, Ērika Bizdēna, Jānis Bogans, Irina Novosjolova, Agnese Grigaloviča, Remo Merijs Meri, Juris Fotins, Maksims Čerkasovs, Anatoly Mishnev, Māris Turks
Cevimeline is muscarinic receptor agonist which increases secretion of exocrine glands. Cevimeline base is a liquid (m.p. 20-25 °C) at ambient conditions, therefore its pharmaceutical formulation as a solid hydrochloride hemihydrate has been developed. The synthesis of cevimeline yields its cis- and trans-isomers and only the cis-isomer is recognized as the API and used in the finished formulation. In this study structural and physicochemical investigations of hydrochloride hemihydrates of cis- and trans-cevimelines have been performed...
January 25, 2016: Journal of Pharmaceutical and Biomedical Analysis
C L M Maruyama, N J Leigh, J W Nelson, A D McCall, R E Mellas, P Lei, S T Andreadis, O J Baker
Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients...
November 2015: Journal of Dental Research
Amira Moustafa, Yoshiaki Habara
In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist upregulated endothelial NO synthase in parotid tissue. NO and H2S donors increased the intracellular Ca(2+) concentration ([Ca(2+)]i)...
October 1, 2015: American Journal of Physiology. Cell Physiology
Coziana Ciurtin, Anca Ostas, Viorica M Cojocaru, Stephen B Walsh, David A Isenberg
BACKGROUND: Sjögren´s syndrome (SS) is an autoimmune rheumatic disease that is characterised by decreased exocrine gland function and frequent ocular symptoms associated with eye dryness. Significantly, dry eyes can lead to corneal abrasions, infection, ulceration, chronic scarring and, in severe cases, perforation. The available conventional therapies have limited efficacy and there are no biologic therapies licensed for use in SS patients. MATERIALS AND METHODS: A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was performed covering the period from January 1994 to September 2014...
December 2015: Seminars in Arthritis and Rheumatism
Xin Cong, Yan Zhang, Jing Li, Mei Mei, Chong Ding, Ruo-Lan Xiang, Li-Wei Zhang, Yun Wang, Li-Ling Wu, Guang-Yan Yu
The epithelial cholinergic system plays an important role in water, ion and solute transport. Previous studies have shown that activation of muscarinic acetylcholine receptors (mAChRs) regulates paracellular transport of epithelial cells; however, the underlying mechanism is still largely unknown. Here, we found that mAChR activation by carbachol and cevimeline reduced the transepithelial electrical resistance (TER) and increased the permeability of paracellular tracers in rat salivary epithelial SMG-C6 cells...
June 15, 2015: Journal of Cell Science
Anusha Rangare Lakshman, G Subhas Babu, Suresh Rao
CONTEXT: Xerostomia is a common sequel in patients undergoing irradiation of malignant tumors of the head and neck. Palliative treatments of xerostomia like topical agents such as ice-chips, saliva substitutes, systemic sialogogues like pilocarpine and cevimeline work well for some patients. Electrostimulation was studied in the past and showed moderate promise but never became part of the mainstream therapy for better management of xerostomia patients. AIMS: The aim of the following study is to evaluate the effectiveness of a transcutaneous electrical nerve stimulation (TENS) unit in stimulating the whole salivary flow rate in radiation induced xerostomia patients...
January 2015: Journal of Cancer Research and Therapeutics
Carlo Matera, Ada M Tata
The presence of cholinergic system markers and muscarinic receptor subtypes in several tissues also of nonneuronal type has been largely demonstrated. Acetylcholine, synthesized in the nervous system, can locally contribute to modulate cell proliferation, survival and apoptosis. Considering that the cholinergic system functions are impaired in a number of disorders, the identification of new drugs regulating these functions appears of great clinical relevance. The possible involvement of muscarinic acetylcholine receptors in different pathologies has been proposed in recent years and is becoming an important area of study...
2014: Recent Patents on CNS Drug Discovery
Ghaith Noaiseh, Joshua F Baker, Frederick B Vivino
OBJECTIVES: There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. METHODS: We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting...
July 2014: Clinical and Experimental Rheumatology
Fabio Del Bello, Alessandro Bonifazi, Wilma Quaglia, Angelica Mazzolari, Elisabetta Barocelli, Simona Bertoni, Rosanna Matucci, Marta Nesi, Alessandro Piergentili, Giulio Vistoli
The methyl group in cis stereochemical relationship with the basic chain of all pentatomic cyclic analogues of ACh is crucial for the agonist activity at mAChR. Among these only cevimeline (1) is employed in the treatment of xerostomia associated with Sjögren's syndrome. Here we demonstrated that, unlike 1,3-dioxolane derivatives, in the 1,4-dioxane series the methyl group is not essential for the activation of mAChR subtypes. Docking studies, using the crystal structures of human M2 and rat M3 receptors, demonstrated that the 5-methylene group of the 1,4-dioxane nucleus of compound 10 occupies the same lipophilic pocket as the methyl group of the 1,3-dioxolane 4...
August 1, 2014: Bioorganic & Medicinal Chemistry Letters
Tiffany L Lovelace, Nyssa F Fox, Amit J Sood, Shaun A Nguyen, Terry A Day
OBJECTIVE: To analyze the efficacy of various treatment options for radiation-induced hyposalivation in patients with head and neck cancer. STUDY DESIGN: A literature review and meta-analysis was performed on all appropriate literature identified via MEDLINE/PubMed. RESULTS: Fourteen articles were identified that met inclusion criteria for review, and 8 articles qualified for inclusion in the meta-analysis. The available literature addressed both objective and subjective responses of hyposalivation, xerostomia, or both to cholinergic agonists (such as pilocarpine and cevimeline), salivary substitutes, hyperbaric oxygen, and acupuncture...
May 2014: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Matthew B Young, Steven A Thomas
Neuromodulators released during and after a fearful experience promote the consolidation of long-term memory for that experience. Because overconsolidation may contribute to the recurrent and intrusive memories of post-traumatic stress disorder, neuromodulatory receptors provide a potential pharmacological target for prevention. Stimulation of muscarinic receptors promotes memory consolidation in several conditioning paradigms, an effect primarily associated with the M1 receptor (M1R). However, neither inhibiting nor genetically disrupting M1R impairs the consolidation of cued fear memory...
January 29, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Moriyoshi Nakamura, Tsuyoshi Saga, Koichi Watanabe, Nagahiro Takahashi, Yoko Tabira, Jingo Kusukawa, Koh-Ichi Yamaki
Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that produce saliva are destroyed. Cevimeline is thought to affect the composition of saliva in part by regulating the localization of aquaporins (AQPs). In this study, we investigated the effects of chronic Cevimeline administration in the salivary glands of SS mice on the immunohistochemical localization of aquaporin (AQP)-1, 3, 4, 5 and 8. We used Cevimeline-untreated SS mice, treated SS mice, discontinued SS mice and untreated normal mice...
2013: Kurume Medical Journal
Hiroto Tsuboi, Mana Iizuka, Hiromitsu Asashima, Takayuki Sumida
Sjögren's syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. It is characterized by lymphocytic infiltration into exocrine glands, leading to dry mouth and eyes. A number of auto-antibodies are detected in patients with SS. However, no SS-specific pathologic auto-antibodies have yet been found in this condition. M3 muscarinic acetylcholine receptor (M3R) plays a crucial role in the secretion of saliva. It is reported that some patients with SS carried inhibitory auto-antibodies against M3R...
2013: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Jae Brimhall, Malhar A Jhaveri, Juan F Yepes
OBJECTIVES: To determine the efficacy and compare the side-effects of cevimeline and pilocarpine in the secretion of saliva in patients with xerostomia. METHODS: A randomized, cross-over, double blind study was designed. Fifteen patients with diagnosis of xerostomia were assigned to take either 5 mg of pilocarpine or 30 mg of cevimeline three times a day for four weeks. Salivary flow rates were measured during the initial baseline, first and second month appointments...
May 2013: Special Care in Dentistry
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