Stimulation Of Salivary Secretion Research Articles

Alpha-synuclein as a biomarker in Parkinson's disease: focus on neural derived extracelluar vesicles.

Alpha-synuclein as a biomarker in Parkinson's disease: focus on neural derived extracelluar vesicles.

Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Patient-related outcomes in Sjögren syndrome treated with stimulants of salivary secretion: Randomized clinical trial.

To investigate the impact of gustatory stimulants of salivary secretion (GSSS) on Sjögren's syndrome patients' self-perception of xerostomia, oral health-related quality of life (OHRQoL) and salivary secretion. A total of 110 Sjögren's syndrome patients were randomly allocated to be treated with either a malic acid lozenge or a citric acid mouthwash and then crossed over. Before and after the interventions, the Xerostomia Inventory 5 (SXI-5-PL) and the Oral Health Impact Profile (OHIP-14-PT) questionnaires (both in the Portuguese language) were administered to patients. Unstimulated, mechanical and gustatory-stimulated salivary flows were determined. Repeated measures and between-subject analyses were performed. Statistical significance was set at 5%. After the intervention and within each group, both GSSS elicited a reduction in the SXI-5-PL and OHIP-14-PT scores and an increase in salivary output, significant in the malic acid lozenge group. The malic acid treatment resulted in a greater effect size and percentage improvement than citric acid mouthwash. The malic acid lozenge also produced a significant greater salivary output than the citric acid rising solution. In Sjögren's syndrome patients, lozenges containing malic acid increased saliva production and xerostomia relief, resulting in improved quality of life.

Evaluation of enamel demineralization and fluorine uptake caused by gustatory stimulants of salivary secretion (GSSS) using Raman spectroscopy and proton induced gamma‐ray emission (PIGE)

AbstractIn this work, two gustatory stimulants of salivary secretion (GSSS) were studied using Raman microscopy to evaluate their potential demineralization effect in human enamel samples and proton induced gamma‐ray emission (PIGE) to quantify fluorine uptake. These pharmaceutical products are usually administrated to patients who have revealed xerostomia, namely, caused by radiation therapy, chemotherapy, or diseases such as Sjögren's Syndrome. Traditional GSSS are composed of citric or malic acids that can promote enamel erosion by decreasing salivary pH below the critical level of hydroxyapatite demineralization (pH = 5.5). Recently, new GSSS composed of malic acid, fluorine, and xylitol were developed, which are supposed to decrease erosion potential risk and uptake fluorine in dental enamel. In this, in vitro study, 16 specimens of human enamel were randomized in two different groups exposed to two different GSSS: S group—SST® (with citric and malic acids, without fluorine) and X group—Xeros™ (with malic acid, fluorine, and xylitol) and analysed before and after treatment. The treatment simulated administration of four tablets per day during eight consecutive days. Statistically, significant increase in fluorine concentration was found in samples treated by Xeros™, whereas no significant differences were found in fluorine concentration for the ones treated using SST® treatment. No demineralization was found in dental enamel samples treated with either Xeros™ or SST®.

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PurposeA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E2 (PGE2), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL). Material/methodsSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario. ResultsSalivary pH in BE was significantly lower than in controls during mechanical (p<0.001) and chemical stimulations (p<0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p<0.05) and chemical stimulations (p<0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p<0.05) and during mechanical (p<0.05) and chemical stimulations (p<0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p<0.05). We observed a higher TGFα output during mastication (p<0.05) and PGE2 secretion during basal and masticatory condition (p<0.05) in BE. ConclusionsPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.

Clinical Updates on Substance-P Antagonist in Pain Management

Novel drug designing and development is the need and the decisive target of pharmaceutical industry, as the active life of a drug is not very extensive. Substance P (SP) is considered as the prototypic neuropeptide of the more than 50 known neuroactive molecules, and is also the member of a new neurotransmitter system that belongs to the family of three related peptides known as neurokinins and a member of the seven-transmembrane G-protein coupled family of receptors and is primarily associated with sensory neurons in the periphery and specific areas of the CNS [1,2]. The other two members are simply called neurokinin A and neurokinin B. Modulation of SP activity offered a radical new approach to the management of depression, anxiety, stress and is involved in several physiologic activities, including the vomiting reflex, defensive behavior, change in cardio-vascular tone, stimulation of salivary secretion, smooth muscle contraction and vasodilatation [3,4].

Efeitos dos estimulantes gustativos de secreção salivar e a sua libertação de flúor na saliva

ObjectivesTo compare salivary flow stimulation capacity, erosive potential and fluoride quantities released in saliva during the exposure to two different gustatory stimulants of salivary secretion (GSSS). MethodsA double blind randomized controlled trial in cross‐over. Sixty volunteers randomly both recruited and divided into two groups, according to the first GSSS tested. The groups were exposed to GSSS based on citric acid or GSSS containing malic acid, fluoride and xylitol. Unstimulated, mechanical and GSSS stimulated salivary secretions were measured within each group. The pH variations and fluoride release of all samples were measured using potenciometric techniques. Erosive potential was determined regarding salivary pH variations and counts of subjects with pH below 4.5 for over 1min. Results were presented as mean±95% confidence interval and analyzed with Student's t‐test or ANOVA as appropriate and only comparative findings for p<0.05 were accepted. ResultsThe malic acid, fluoride and xylitol GSSS presented an absolute risk reduction (ARR) for potential erosive phenomena's of 13.91% [1.67%; 26.15%] and a number needed to treat (NNT) of 8 when compared with the citric acid GSSS. The same GSSS released 87.75% [81.48%; 94.03%] of the total fluoride quantity announced by the producer into the saliva. ConclusionThe malic acid based GSSS presented similar salivary stimulation efficiency when compared to the GSSS containing citric acid. Moreover the malic acid based GSSS presented a decrease of erosion potential and fluorides release to the saliva, which in turn could potentially protect tooth structure from erosion episodes.

Review of pharmacological activities of Dendrobium officinale based on traditional functions

This review firstly made a summary of ancient literature on traditional functions of Dendrobium, combined with literature of modern pharmacological research and clinical application of D. officinale from CNKI search system, it was summarized that D. officinale had broad bioactivities including immunomodulation, antifatigue activity, antioxidation, digest-promotion, stimulation of salivary secretion, lowering hyperglycemia, anti-hypertension, anti liver injury and antitumor activity, etc. Furthermore, public healty needs and present situation of cooperative product development were analyzed base on tradtional functions, pharmacological actions and related clinical applications of D. officinale, could provide a reference for the further industrial development.

Effects of gustatory stimulants of salivary secretion on salivary pH and flow in patients with Sjögren’s syndrome: a randomized controlled trial

To compare salivary pH changes and stimulation efficacy of two different gustatory stimulants of salivary secretion (GSSS) in patients with primary Sjögren syndrome. Portuguese Institute for Rheumatological Diseases. Double-blind randomized controlled trial. Eighty patients were randomized to two intervention groups. Sample size was calculated using an alpha error of 0.05 and a beta of 0.20. Participants were randomly assigned to receive a new GSSS containing a weaker malic acid, fluoride and xylitol or a traditionally citric acid-based one. Saliva collection was obtained by established methods at different times. The salivary pH of the samples was determined with a pH meter and a microelectrode. Salivary pH variations and counts of subjects with pH below 4.5 for over 1 min and stimulated salivary flow were the main outcome measures. Both GSSS significantly stimulated salivary output without significant differences between the two groups. The new gustatory stimulant of salivary secretion presented an absolute risk reduction of 52.78% [33.42-72.13 (95% CI)] when compared with the traditional one. In Xerostomic Primary Sjögren syndrome patients, gustatory stimulants of salivary secretion based on acid mail only with fluoride and xylitol present similar salivary stimulation capacity when compared to citric acid-based ones, besides significantly reducing the number of salivary pH drops below 4.5. This could be related to a diminished risk for dental erosion and should be confirmed with further studies.

Effects of gustatory stimulants of salivary secretion on salivary pH and flow: a randomized controlled trial

To compare salivary pH changes and stimulation efficacy of two different gustatory stimulants of salivary secretion (GSSS). Portuguese Dental Faculty Clinic. Double blind randomized controlled trial. One hundred and twenty volunteers were randomized to two intervention groups. Sample sized was calculated using an alpha error of 0.05 and a beta of 0.20. Participants were randomly assigned to receive a new gustatory stimulant of secretory secretion containing a weaker malic acid, fluoride and xylitol or a traditionally citric acid-based one. Saliva collection was obtained by established methods at different times. The salivary pH of the samples was determined with a pH meter and a microelectrode. Salivary pH variations and counts of subjects with pH below 5.5 for over 1 min and stimulated salivary flow were the main outcome measures. Both GSSS significantly stimulated salivary output without significant differences between the two groups. The new gustatory stimulant of salivary secretion presented a risk reduction of 80 +/- 10.6% (95% CI) when compared with the traditional one. Gustatory stimulants of salivary secretion with fluoride, xylitol and lower acid content maintain similar salivary stimulation capacity while reducing significantly the dental erosion predictive potential.

Effects of Chinese herbs on salivary fluid secretion by isolated and perfused rat submandibular glands

To determine whether Chinese herbs (CHs) relieve xerostomia (dry mouth) by increasing salivary secretion. The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 mumol/L carbamylcholine (CCh) in the perfusate for 10 min, Chinese herb (CH) was added in the perfusion for 5 min. CCh was then overloaded at 0.2 mumol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH, overloading of CCh promoted fluid secretion in 15 of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH: Overall sustained phase was continuously raised (Yin-nourishing, fluid production-promoting and heat-clearing agents); The sustained secretion rose to reach a maximum then decreased (Qi-enhancing agent); Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline (swelling-reducing, phlegm-resolving and pus-expelling agents); Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level (blood activating agent). The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.

Conventional Therapy of Sjogren’s Syndrome

Sjogren's syndrome (SS) is a chronic autoimmune disorder affecting mainly middle-aged women. It is characterized by lymphocytic infiltration and destruction of the exocrine glands (mainly the salivary and lacrimal glands), resulting in dry mouth and eyes. Symptoms of SS are chronic and sometimes devastating, compromising the quality of life at a major extent. Despite its autoimmune nature, evidence for the use of immunosuppressive agents, which are the mainstay of therapy of diseases of autoimmune origin, is limited. Keratoconjunctivitis sicca (KCS), the main ocular manifestation of SS, is managed with tear substitutes, as well as local and systemic stimulators of tear secretion and supportive surgical procedures. Management of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline are the cornerstone of current therapy in SS. Corticosteroids, cyclophoshamide, and nucleoside analogues are reserved for severe extraglandular manifestations of SS. The role of anti-B-cell therapy is a promising option for glandular and extraglandular manifestations of the disease, as well as for the management of SS-associated lymphoma.

Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice

Background Physiologically, salivary secretion is controlled by cholinergic and adrenergic pathways but the role of ionic channels in this process is not yet clearly understood. In cystic fibrosis (CF), most exocrine glands failed to response to β-adrenergic agonists. Methods To determine the implication of CFTR in this process, we measured in vivo the salivary secretion of Cftr +/+ and Cftr −/− mice in the presence of 2 water-soluble benzo[ c]quinolizinium derivatives; MPB-07 a potentiator of CFTR Cl − channel and MPB-05 an inactive analogue. We also used genistein and its vehicle ethanol to confirm the implication of CFTR in salivary secretion. Results We showed that subcutaneous injection of MPB-07 in the mice cheek enhanced in a dose dependent manner the isoprenaline-induced salivary secretion in Cftr +/+ but not in Cftr −/− mice. By contrast, MPB-05 did not activate the salivary secretion in Cftr +/+ mice. The CFTR activator genistein (50 μM) significantly potentiated the secretory response of Cftr +/+ mice whereas its vehicle, ethanol, had no effect. Conclusions These results show for the first time in vivo pharmacological stimulation of salivary secretion by a water-soluble CFTR potentiator, MPB-07 and by the isoflavone, ethanol-soluble genistein and suggest that this chloride channel plays an important role in salivary gland physiology.

Intraoral stimulation of salivary secretion with the cholinesterase inhibitor physostigmine as a mouth spray: A pilot study in healthy volunteers

Dry mouth produces a deterioration in oral health and impairs quality of life. There is a need for a novel approach to the pharmacological treatment of dry mouth. With a view to enhancing the cholinergic drive on minor salivary glands, whilst at the same time minimising adverse systemic effects, the cholinesterase inhibitor physostigmine was therefore sprayed, in a fixed volume, onto the oral mucosa of seven healthy subjects. Three concentrations (0.5%, 1% and 2%) were tested. The mean salivary output over time (0–105 min) was higher than that of placebo ( p < 0.05), as the area under the curve increased by 61%, 91% and 66% at physostigmine 0.5%, 1% and 2%, respectively. Two subjects experienced nausea at the highest physostigmine concentration, thus reflecting systemic effects. Heart rate, blood pressure and respiration were unaffected by the physostigmine treatment.

The management of Sjögren's syndrome

Sjögren's syndrome is a chronic autoimmune disorder, characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. The syndrome can present either alone (primary Sjögren's syndrome) or in the context of an underlying connective tissue disease (secondary Sjögren's syndrome). Systemic features, resulting from cutaneous, respiratory, renal, hepatic, neurologic, and vascular involvement, often occur. Two types of primary Sjögren's syndrome are currently recognized: a benign disease that affects quality of life, and a systemic syndrome associated with increased morbidity and mortality owing to a high risk of malignant transformation, and that requires close follow-up. Ocular involvement, manifested as keratoconjunctivitis sicca, is managed with local and systemic stimulators of tear secretion and supportive surgical procedures. Treatment of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline, are helpful in patients with residual salivary function, and ciclosporin ocular drops seem to be of some benefit. Systemic immunosuppressives are reserved for treatment of severe extraglandular manifestations of Sjögren's syndrome. Anti-B-cell therapy is a new potential therapy for the glandular and extraglandular manifestations, such as glomerulonephritis or vasculitis, in addition to the management of lymphoma associated with Sjögren's syndrome. Induction of oral tolerance and gene-transfer modalities were recently attempted in animal models, with promising results.

Muscarinic receptors and salivary secretion

The release of acetylcholine from parasympathetic nerves and its interaction with muscarinic acetylcholine receptors (mAChRs) regulates many fundamental functions in the periphery (smooth muscle contraction, glandular secretion, modulation of cardiac output) and central nervous system (motor control

Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice.

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.

Current therapies for xerostomia and salivary gland hypofunction associated with cancer therapies

In cancer patients, as in the general population, medication is the most common cause of xerostomia. In general, saliva flow in these patients can be stimulated by mechanical or pharmacological stimulation of the salivary glands. Painful damaged oral mucosa can be treated by softening, lubricating mouthwashes or gels. A specific group of patients are those receiving radiotherapy for malignant tumours in the head and neck region. This treatment is inevitably associated with damages to the oral tissues, including the salivary glands, resulting in salivary gland hypofunction. When residual secretory capacity is present, it is advisable to stimulate the salivary glands by mechanical or gustatory stimuli regularly in these patients as supportive oral care. Alternatively, salivary flow can be stimulated by the use of cholinergic pharmaceutical preparations, such as pilocarpine or cevimeline. After the radiation therapy is ended, a dental check-up should be done every 3 months to allow control of any incipient oral inflammation and dental decay. For daily use, a special dentifrice (e.g. children's toothpaste) is recommended, since the taste of a regular dentifrice may be too strong for these patients. Nocturnal oral dryness can be alleviated by spraying the oral surfaces with water, or by applying a small amount of dentifrice on the dental smooth surfaces. When stimulation of salivary secretion fails, patients can be given palliative oral care in the form of application of mouthwashes and saliva substitutes. The daily use of a mouthwash, e.g. Biotène, Oral Balance or Zendium, or one of the saliva substitutes is indicated. Different types of saliva substitutes are now commercially available, containing different polymers as thickening agents, e.g. carboxymethylcellulose (Oralube and Glandosane), polyacrylic acid, and xanthan gum (Xialine). Recent developments, which are, however, still in the experimental stage, are bio-active saliva substitutes and mouthwashes containing antimicrobial peptides to protect the oral tissues against microbial colonization and to suppress and to cure mucosal and gingival inflammation.

Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats.

1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.

Is intraesophageal exposure to acid, pepsin and bile acids capable to ellicit stimulation of salivary secretion, mediated by the esophago-salivary reflex, in asymptomatic volunteers?

Is intraesophageal exposure to acid, pepsin and bile acids capable to ellicit stimulation of salivary secretion, mediated by the esophago-salivary reflex, in asymptomatic volunteers?