Stimulated Saliva Secretion Research Articles

Intragland Shh gene delivery mitigated irradiation-induced hyposalivation in a miniature pig model

Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found recently in mouse models that transient activation of Hedgehog pathway following irradiation rescued salivary gland function by preserving salivary stem/progenitor cells, parasympathetic innervation and microvessels. Due to huge differences between salivary glands of rodents and humans, to examine the translational potential of this approach, we evaluated effects of Shh gene transfer in a miniature pig model of irradiation-induced hyposalivation.Methods: The right parotid of each pig was irradiated with a single dose of 20 Gray. Shh and control GFP genes were delivered into irradiated parotid glands by noninvasive retrograde ductal instillation of corresponding adenoviral vectors 4 or 16 weeks after irradiation. Parotid saliva was collected every two weeks. Parotid glands were collected 5 or 20 weeks after irradiation for histology, Western blot and qRT-PCR assays.Results: Shh gene delivery 4 weeks after irradiation significantly improved stimulated saliva secretion and local blood supply up to 20 weeks, preserved saliva-producing acinar cells, parasympathetic innervation and microvessels as found in mouse models, and also activated autophagy and inhibited fibrogenesis in irradiated glands.Conclusion: These data indicate the translational potential of transient activation of Hedgehog pathway to preserve salivary function following irradiation.

Daily voluntary exercise enhances pilocarpine-induced saliva secretion and aquaporin 1 expression in rat submandibular glands.

Saliva—a water‐based fluid containing electrolytes, immunoglobulins, and enzymes—has many functions, including the protection and hydration of mucosal structures within the oral cavity and the initiation of digestion. Aquaporins (AQPs) are proteins that act as water channels through membranes. We have previously reported upregulation of the expression levels of AQP 1 and 5 in the submandibular glands (SMGs) in heat‐acclimated rats. In this study, we investigated pilocarpine‐induced saliva secretion and AQP expression in rats after voluntary exercise. Male, 10‐week‐old Wistar rats were initially maintained at an ambient temperature of 24 °C for 10 days and were then kept for 40 days in cages either with a running wheel (exercise rats, n = 6) or with a locked wheel [control rats (CN), n = 6]. After the training period, the rats were anesthetized and pilocarpine, an M3 muscarinic receptor agonist, was intraperitoneally injected (0.5 mg·kg−1) to stimulate saliva secretion. Saliva was collected, and the SMGs were sampled and subjected to western blot, RT‐PCR, and immunohistochemical analyses. Pilocarpine induced a greater amount of saliva in the exercised rats than in the CN. Expression levels of AQP1 mRNA and protein were significantly higher in SMGs of exercised rats than in those of the CN, but the expression of AQP5 was not affected by voluntary exercise. Voluntary exercise increased the expression of vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31), a marker for endothelial cells, in the SMGs. Voluntary exercise promoted pilocarpine‐induced saliva secretion, probably via an increase in the expression level of AQP1 due to VEGF‐induced CD31‐positive angiogenesis in the SMG.

Probiotic intervention influences the salivary levels of Matrix Metalloproteinase (MMP)-9 and Tissue Inhibitor of metalloproteinases (TIMP)-1 in healthy adults

ObjectiveTo study the effect of orally administered Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG on the salivary levels of Matrix Metalloproteinases (MMP)-8, MMP-9 and of Tissue Inhibitor of Metalloproteinases (TIMP)-1 in healthy adults. Furthermore, the correlations between MMP-8, MMP-9 and TIMP-1 and plaque and gingival indices, salivary mutans streptococci and lactobacilli counts, and stimulated saliva secretion rate were analysed. DesignThe salivary samples originated from a randomized controlled trial where healthy student volunteers consumed probiotic or placebo lozenges twice a day for four weeks. The saliva samples were collected and clinical parameters measured at the baseline and at the end of the original study. For this study, the salivary levels of MMP-8, MMP-9 and TIMP-1 were analysed with immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). ResultsIn the probiotic group (n=29), salivary MMP-9 levels increased (p<0.01) and TIMP-1 levels decreased (p<0.01) significantly during the intervention. Furthermore, MMP-9/TIMP-1 ratio differed significantly from the baseline level (p<0.01). These changes were not observed in the control group (n=31). In the whole data, salivary MMP-9 and gingival index correlated (r=0.260, p<0.05 at baseline and r=0.354, p<0.01 at the end of the study). Intergroup differences or correlations with other clinical parameters were not found. Probiotic consumption did not affect the saliva flow rate. ConclusionsIncreased MMP-9 and decreased TIMP-1 levels in saliva may indicate that probiotics have immunomodulatory effects in the oral cavity. Furthermore, increased salivary MMP-9 levels may be an indication of the defensive potential of matrix metalloproteinases.

Localized WR-1065 Delivery to Murine Salivary Glands has Radioprotective Effect and Hemodynamic Benefit Over Systemic Administration

There are over 50,000 cases of head and neck cancer (HNC) diagnosed each year in the United States. Approximately 75% of these patients will undergo radiation at some point during their treatment, and of those patients over 50% will go on to develop permanent xerostomia. Amifostine is the only FDA approved drug for use in xerostomia radioprophylaxis, but suffers from a narrow therapeutic window and systemic toxicities including severe nausea and hypotension that severely limit its clinical utility. To overcome challenges of systemic administration and potentially increase effectiveness, local delivery via Wharton’s duct of WR-1065 (the active metabolite of Amifostine) was utilized. Our hypothesis is that retroductal delivery of WR-1065 to the murine submandibular gland (SMG) will improve salivary gland function while reducing drug side effects such as hypotension at 90 days following a single xerogenic dose (15.0 Gy) of irradiation. All studies used n = 5 C57BL/6 female mice per treatment group. To assess blood pressure response, anesthetized mice underwent bilateral femoral catheterization and aortic placement of a pressure transducer. Mice received either IV or retroductal doses of Amifostine or WR-1065. Baroreflex was subsequently measured by bolus administration of phenylephrine. For radiation studies, mice received unilateral SMG injection with WR-1065 or saline. A single dose of 15.0 Gy was then delivered to the submandibular glands using a Cs137 irradiator with a slit collimator. Study endpoints include volume of stimulated saliva secretion 90 days post irradiation, SMG histology, and immunohistochemical staining compared to irradiated and nonirradiated control groups. Hemodynamic data show retained baroreflex sensitivity and mean arterial pressure following retrograde WR-1065 injection. Furthermore, mice receiving retrograde WR-1065 show significantly higher volumes of stimulated saliva secretion (61±29 μL) compared to irradiated (14±8 μL) and saline treated controls (19 ±7 μL) at 90 days (p<0.05). Furthermore, no significant difference exists in gland secretion between irradiated WR-1065 treated mice and non-irradiated mice. Preliminary data shows improvement in stimulated saliva secretion and gland histology in WR-1065 retroductally treated mice 90 days post irradiation. Hemodynamic data further supports development of this drug delivery modality for SMG radioprotection, as blood pressure and baroreflex sensitivity are retained following retrograde WR-1065 injection.

Interdisciplinary, Comprehensive Oral and Ocular Evaluation of Patients with Primary Sj\xf6gren\u2019s Syndrome

A comprehensive evaluation of oral and ocular symptoms and findings in primary Sjögren’s syndrome (pSS) patients may provide valuable information for management. Medical history was obtained from female pSS patients, and sex- and age-matched non-SS patients with sicca symptoms (non-SS sicca controls) as well as healthy subjects without sicca complaints (healthy controls). Oral (Summated Xerostomia Inventory, SXI) and ocular (McMonnies Dry Eye questionnaire, MDEIS, and Ocular Surface Disease Index, OSDI) subjective complaints were recorded. Objective findings including clinical oral dryness scores (CODS), unstimulated and stimulated saliva secretion rates (UWS/SWS), Schirmer I test, tear osmolarity, tear film break-up time (TFBUT), and ocular surface staining (OSS) were determined. The pSS and non-SS sicca controls were extensively troubled by subjective dryness, while the pSS group had higher CODS, significantly lower saliva and tear secretion, shorter TFBUT and higher OSS than both control groups. Furthermore, candida counts were significantly higher in the pSS patients. In the pSS group, subjective oral dryness significantly correlated with ocular dryness (MDEIS: r = 0.5, OSDI: r = 0.413) and SWS was significantly correlated with Schirmer I (r = 0.419). The findings imply that interdisciplinary subjective and objective evaluation of patients with xerostomia and xerophthalmia not only have implications for patient care, but also may guide clinicians in differentiating between pSS and non-SS sicca patients.

Quantification of the salivary volume flow rate in the parotid duct using the time-spatial labeling inversion pulse (Time-SLIP) technique at MRI: A feasibility study.

We developed a method to quantify the volume flow rate (VFR) using the time-spatial labeling inversion pulse (Time-SLIP) technique to evaluate salivary function. To investigate the accuracy of quantification of the salivary VFR using the Time-SLIP technique in phantoms and to examine the feasibility of its use in human subjects. This was a prospective phantom and volunteer study. A phantom and 23 normal volunteers who fasted at least 2 hours study was performed. Flow images of the phantom and the parotid duct of 23 volunteers were acquired on a 3T-MRI scanner using the Time-SLIP technique. Hypothesizing that flow aggregates in the conducting duct, we measured the VFR on flow images. In the phantom study, the actual VFR (slow, medium, fast flow) was controlled by an automatic pump system and the measured VFR was compared with the actual VFR on flow images. In the human study we injected citric acid into the mouth of healthy volunteers to stimulate saliva secretion and recorded the VFR. As this study was a feasibility study, statistical tests were not performed. In the phantom study, the VFR at slow, medium, and fast flow was 5.7 ± 0.4 (SD), 8.4 ± 0.3, and 12.2 ± 1.1 mm3 /sec, respectively. The error between the measured and actual VFR values was 2.8-3.7%. Salivary flow in the parotid duct was visualized in 22 of the 23 volunteers. The mean VFR was 8760 mm3 /10 min. When salivary flow was stimulated with citric acid in normal volunteers, the salivary VFR could be obtained using the Time-SLIP technique. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:928-935.

Rescue Effects and Underlying Mechanisms of Intragland Shh Gene Delivery on Irradiation-Induced Hyposalivation.

Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found in an inducible sonic hedgehog (Shh) transgenic mouse model that transient activation of the Hedgehog pathway after irradiation rescued salivary gland function in males by preserving salivary stem/progenitor cells and parasympathetic innervation. To translate these findings into feasible clinical application, we evaluated the effects of Shh gene transfer to salivary glands of wild-type mice on irradiation-induced hyposalivation. Shh or control GFP gene was delivered by noninvasive retrograde ductal instillation of corresponding adenoviral vectors. In both male and female mice, Shh gene delivery efficiently activated Hedgehog/Gli signaling, and significantly improved stimulated saliva secretion and preserved saliva-producing acinar cells after irradiation. In addition to preserving parasympathetic innervation through induction of neurotrophic factors, Shh gene delivery also alleviated the irradiation damage of the microvasculature, likely via inducing angiogenic factors, but did not expand the progeny of cells responsive to Hedgehog/Gli signaling. These data indicate that transient activation of the Hedgehog pathway by gene delivery is promising to rescue salivary function after irradiation in both sexes, and the Hedgehog/Gli pathway may function mainly in cell nonautonomous manners to achieve the rescue effect.

EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation.

BackgroundMutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function.MethodsIndividuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S.ResultsThe mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4–17) in the mutation group and 0.1 ± 0.3, (range 0–1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0–6) in the mutation group and 1.5 ± 1.1 (range 0–5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group.ConclusionsIndividuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures.

Study on factors that affect caries susceptibility in mice

In our previous research, we discovered a C57BL/6CrSlc mouse strain (B6) that is highly susceptible to caries and a C3H/HeSlc mouse strain (C3H) that is highly resistant to caries, and reported that genetic factors play a role in caries susceptibility. In a study on the B6 and C3H mouse strains, a difference was found in their saliva flow rates, as well as their caries scores. In the present study, we focused on saliva secretion, which may influence differences in caries susceptibility. We examined temporal changes in stimulated saliva secretion volume in B6 and C3H mice, and found that secretion volume was significantly higher in C3H mice than in B6 mice even at 30 min after stimulation, and that total saliva volume was significantly higher in C3H mice. In addition, histological comparisons of the submandibular gland in the two strains revealed the ratio of acinar cells area to be significantly higher in C3H mice than in B6 mice. We then examined the gene expression of the muscarinic acetylcholine receptors M1R, M2R and M3R, which are thought to be regulatory factors of water secretion from acinar cells in the parasympathetic nervous system, but did not find any significant differences between the two strains. Enamel hardness was significantly higher in C3H mice than in B6 mice. The acinar cell ratio in the submandibular gland may be a factor associated with differences in salivary flow rate, and enamel hardness may be a determining factor of tooth decalcification; two factors that affect caries susceptibility.

Muscarinic Type 3 Receptor Induces Cytoprotective Signaling in Salivary Gland Cells through Epidermal Growth Factor Receptor Transactivation

Muscarinic type 3 receptor (M3R) plays a pivotal role in the induction of glandular fluid secretions. Although M3R is often the target of autoantibodies in Sjögren's syndrome (SjS), chemical agonists for M3R are clinically used to stimulate saliva secretion in patients with SjS. Aside from its activity in promoting glandular fluid secretion, however, it is unclear whether activation of M3R is related to other biological events in SjS. This study aimed to investigate the cytoprotective effect of chemical agonist-mediated M3R activation on apoptosis induced in human salivary gland (HSG) cells. Carbachol (CCh), a muscarinic receptor-specific agonist, abrogated tumor necrosis factor α/interferon γ-induced apoptosis through pathways involving caspase 3/7, but its cytoprotective effect was decreased by a M3R antagonist, a mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) inhibitor, a phosphatidylinositol 3-kinase/Akt inhibitor, or an epidermal growth factor receptor (EGFR) inhibitor. Ligation of M3R with CCh transactivated EGFR and phosphorylated ERK and Akt, the downstream targets of EGFR. Inhibition of intracellular calcium release or protein kinase C δ, both of which are involved in the cell signaling of M3R-mediated fluid secretion, did not affect CCh-induced ERK or Akt phosphorylation. CCh stimulated Src phosphorylation and binding to EGFR. A Src inhibitor attenuated the CCh/M3R-induced cytoprotective effect and EGFR transactivation cascades. Overall, these results indicated that CCh/M3R induced transactivation of EGFR through Src activation leading to ERK and Akt phosphorylation, which in turn suppressed caspase 3/7-mediated apoptotic signals in HSG cells. This study, for the first time, proposes that CCh-mediated M3R activation can promote not only fluid secretion but also survival of salivary gland cells in the inflammatory context of SjS.

Function of the Membrane Water Channel Aquaporin-5 in the Salivary Gland

The process of saliva production in the salivary glands requires transepithelial water transfer from the interstitium to the acinar lumen. There are two transepithelial pathways: the transcellular and paracellular. In the transcellular pathway, the aquaporin water channels induce passive water diffusion across the membrane lipid bilayer. It is well known that aquaporin-5 (AQP5) is expressed in the salivary glands, in which it is mainly localized at the apical membrane of the acinar cells. This suggests the physiological importance of AQP5 in transcellular water transfer. Reduced saliva secretion under pilocarpine stimulation in AQP5-null mice compared with normal mice further indicates the importance of AQP5 in this process, at least in stimulated saliva secretion. Questions remain therefore regarding the role and importance of AQP5 in basal saliva secretion. It has been speculated that there would be some short-term regulation of AQP5 such as a trafficking mechanism to regulate saliva secretion. However, no histochemical evidence of AQP5-trafficking has been found, although some of biochemical analyses suggested that it may occur. There are no reports of human disease caused by AQP5 mutations, but some studies have revealed an abnormal subcellular distribution of AQP5 in patients or animals with xerostomia caused by Sjögren’s syndrome and X-irradiation. These findings suggest the possible pathophysiological importance of AQP5 in the salivary glands.

α-Amylase as a reliable and convenient measure of sympathetic activity: don’t start salivating just yet!

Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which provides a simple means of quantification by measuring its enzymatic activity. This commentary will address a number of common misconceptions and methodological issues that surround the use of sAA as a marker of SNS activity and limit its utility in biobehavioral research. The usefulness of sAA as an SNS marker is undermined by the fact that the parasympathetic nerves also play a significant role in sAA release. Local parasympathetic nerves regulate sAA activity via: (1) α-amylase release from glands that are solely or mainly parasympathetically innervated; (2) via synergistic sympathetic-parasympathetic effects on protein secretion (known as 'augmented secretion'); and (3) via effects on salivary flow rate. Regarding methodology, we discuss why it is problematic: (1) to ignore the contribution of salivary flow rate; (2) to use absorbent materials for saliva collection, and; (3) to stimulate saliva secretion by chewing. While these methodological problems can be addressed by using standardized and timed collection of unstimulated saliva, the physiological regulation of sAA secretion presents less resolvable issues. We conclude that at present there is insufficient support for the use and interpretation of sAA activity as a valid and reliable measure of SNS activity.

Application of near-infrared spectroscopy to measurement of hemodynamic signals accompanying stimulated saliva secretion

We aim to test the feasibility of using near-infrared spectroscopy (NIRS) for indirect measurement of human saliva secretion in response to taste stimuli for potential application to organoleptic testing. We use an NIRS system to measure extracranial hemodynamics (Hb-signals around the temples) of healthy participants when taste stimuli are taken in their mouths. First, the Hb-signals and volume of expelled saliva (stimulated by distilled-water or sucrose-solution intake) are simultaneously measured and large Hb-signal changes in response to the taste stimuli (Hb-responses) are found. Statistical analysis show that both the Hb response and saliva volume are larger for the sucrose solution than for the distilled water with a significant correlation between them (r = 0.81). The effects of swallowing on the Hb-signals are investigated. Similar Hb responses, differing from the sucrose solution and distilled water, are obtained even though the participants swallow the mouth contents. Finally, functional magnetic resonance imaging is used to identify possible sources of the Hb signals corresponding to salivation. Statistical analysis indicates similar responses in the extracranial regions, mainly around the middle meningeal artery. In conclusion, the identified correlation between extracranial hemodynamics and the saliva volume suggests that NIRS is applicable to the measurement of hemodynamic signals accompanying stimulated saliva secretion.

Inhibition of Salivary Secretion by Activation of Cannabinoid Receptors

It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that AEA injected intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection of AM251 increased saliva secretion induced by lower doses of NE or MC. This increase was synergized after coinjection with AM630. Therefore, we concluded that AEA decreases saliva secretion in the SMG acting through CB1 and CB2 receptors.

Oral and nutritional status in frail elderly.

This article describes associations between oral health and nutritional status among chronically ill older adults who were living at home and receiving regular professional home care services. A structured questionnaire, oral examination, and Mini-Nutritional Assessment were completed for 51 subjects (mean age 83.7 years). Two-thirds of the sample were edentulous, and one-third had between 2 and 23 teeth (mean 10.59, SD +/- 6.92). Sixty percent of subjects complained of xerostomia, while dentists found only 48% to have clinical signs of dry mouth. More than half of the subjects had stimulated saliva rates of < 0.8 ml/min. Stimulated saliva secretion rates were lower for persons with no functional natural dentition or prostheses (p = 0.012). Subjects assessed their dentures to be more functional than did the dentist (Kappa 0.338). No one was considered malnourished. 47% were at risk of malnutrition, and 52% were well nourished. The dentist's estimation of dry mouth and eating problems were significantly associated to lower MNA scores (p = 0.049 and p = 0.015, respectively). Subjects with a natural functioning dentition had higher BMI scores (p = 0.0485).

The changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy.

To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy. Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva. With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy. When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

Saliva Flow, pH, Buffer Capacity, and Colonization by Streptococcus mutans during and after Radical Radiotherapy of Head and Neck Tumours

Background: How does oral health (saliva pH, buffer capacity, and colonization with Streptococcus mutans) change because of reduced salivary flow during and after radical radiotherapy of head and neck carcinoma dependent on ipsilateral or bilateral parotid irradiation? Patients and Methods: 20 consecutive patients who were radically irradiated because of head and neck carcinomas were studied. They were evaluated before radiotherapy, weekly during therapy, and 6 weeks after the end of treatment. Flow rate, pH and buffer capacity of saliva, and colonization with S. mutans were tested. Results: Stimulated saliva secretion rate dropped in the first radiotherapy week in both groups (p < 0.006). This effect was more pronounced in patients with bilateral parotid gland radiation (BPR) in comparison with unilateral parotid gland radiation (UPR). Depending on dose saliva production declined exponentially up to the end of treatment. No rebound was found up to 6 weeks after the end of therapy, a trend towards a further saliva production was observed. Stimulated saliva was significantly diminished when compared to production before the start of treatment (p < 0.003 for UPR and p < 0.001 for BPR). Buffer capacity was reduced parallel to the saliva deficit. The pH of saliva decreased from a mean of 7.3 before treatment to 6.3 at the end of radiotherapy and did not recover for patients with BPR. For patients with UPR, the pH decreased from a mean of 7.8 to 7.4 and remained constant. Colonization with S. mutans increased during treatment and stayed high after the end of radiotherapy. Conclusion: Saliva production is exponentially reduced during radiotherapy, starting in the first week of treatment. Recovery is not observed up to 6 weeks after therapy. Buffer capacity and pH decline during radiotherapy in relation to saliva loss. Colonization by S. mutans increases markedly during radiotherapy and remained high afterwards.

Saliva in non-insulin-dependent diabetic patients and control subjects: The role of the autonomic nervous system

Objective. The purpose of this investigation was to study the flow rate and organic constituents of whole saliva in relation to autonomic nervous function in patients with non-insulin-dependent diabetes. Study design. We studied the associations of saliva factors and autonomic nervous function in 45 patients with non-insulin-dependent diabetes (mean age, 68 ± 6 years) and 77 control subjects (mean age, 67 ± 5 years). The metabolic evolution was well known over a 10-year period from the time of diagnosis. Resting and paraffin-wax-stimulated whole saliva samples were collected and analyzed. Autonomic nervous function was evaluated by measuring heart rate variation during deep breathing and change in systolic blood pressure during orthostatic testing and by means of power spectral analysis of heart rate variability while standing. The effect of drugs used on saliva was also studied. Results. No difference was seen in flow rate between the patients with diabetes and the control subjects; resting flow rates were 0.3 ± 0.3 ml/min in the patients with diabetes and 0.3 ± 0.2 ml/min in the control subjects, and stimulated flow rates were 1.2 ± 1.4 ml/min in the patients with diabetes and 1.2 ± 0.8 ml/min in the control subjects. The number of drugs used daily correlated with salivary flow rates of the control subjects ( p < 0.001) but not with flow rates of the patients with diabetes. The effect of xerogenic medication on salivary flow rates was stronger in patients with diabetes than in control subjects, however. There were no statistically significant differences between patients with diabetes and control subjects in the organic constituents of saliva. The stimulated saliva secretion was associated with total power ( r s = 0.343; p = 0.035), medium-frequency power ( r s = 0.375; p = 0.020), and high-frequency power ( r s = 0.414; p = 0.010) of heart rate variability in patients with diabetes. Conclusion. Saliva secretion might be more affected by xerogenic drugs and autonomic nervous dysfunction in patients with non-insulin-dependent diabetes than in nondiabetic control subjects.

Salivary levels of mutans streptococci and lactobacilli in dentate 80‐ and 85‐year‐old Swedish men and women

The number of Streptococcus mutans, Streptococcus sobrinus, and lactobacilli in whole stimulated saliva was examined in 130 dentate 80- and 85-yr-old persons. 88.5% were positive for mutans streptococci and 29% carried greater than 10(6) cfu per ml saliva. S. mutans was most frequently isolated and was found in 114 persons (88%) alone or in combination with S. sobrinus. S. sobrinus was detected in 33 persons (25%), who also showed significantly higher salivary numbers of both mutans streptococci and lactobacilli than persons from whom S. sobrinus was not isolated. The S. sobrinus carriers also had significantly lower stimulated saliva secretion rates than the non-carriers. 95% of the subjects had detectable levels of lactobacilli in saliva with 35% having greater than 10(5) cfu per ml saliva. When the subjects were divided into classes according to the number of intermaxillary contacts, i.e. the Eichner classification, the distribution of subjects with high and low salivary counts of cariogenic bacteria varied. Thus fewer subjects belonging to Eichner class A showed higher salivary numbers of mutans streptococci (14% had greater than 10(6) cfu/ml) as well as lactobacilli (21% had greater than 10(5) cfu/ml) than, for example, subjects belonging to Eichner class B (26% had greater than 10(6) cfu/ml of mutans streptococci, 35% had greater than 10(5) cfu/ml of lactobacilli). Subjects who carried a removable denture(s) had significantly higher salivary numbers of both mutans streptococci and lactobacilli than subjects without removable dentures.

The effect of a chewing gum on salivary secretion, oral mucosal friction, and the feeling of dry mouth in xerostomic patients

A new chewing gum (PTC) with the ability to release flavoring substances for a rather long time was tested for its ability to stimulate saliva secretion. The chewing gum is mildly flavored and contains non-cariogenic sweeteners (xylitol and sorbitol). Measurements of saliva secretion rate and oral mucosal sliding friction and subjective evaluations on visual analog scales were made in relation to chewing and compared with those when chewing a commercially available gum (V6). The study was a randomized, crossover comparison with blind evaluation. Both chewing gums stimulated saliva secretion and decreased oral mucosal friction. The PTC gum gave consistently higher mean values of saliva secretion rate and lower oral mucosal friction values than V6. The difference was statistically significant for the saliva secretion rate and most pronounced after 5-10 min of chewing. There was also a statistically significant difference between the subjective evaluations of V6 and PTC with regard to saliva-stimulating ability and taste in favor of the PTC gum.