Salivary Output Research Articles

Whole salivary flow rates following submandibular gland resection

Background Patients with head and neck neoplasms receive therapeutic neck dissections which may include the submandibular gland unilaterally or bilaterally. The clinical consequences of salivary gland resection could be reduced salivary output, altered cariogenic microflora, and increased incidence of dental caries. Methods This investigation evaluated whole salivary flow rates of patients who had received unilateral (n = 29) or bilateral (n = 8) submandibular gland resections and compared them with noncancer control subjects (n = 29). Results Unstimulated and stimulated (paraffin) flow rates were significantly lower in both resection groups compared with those of the noncancer group, ranging from p < .002 to p < .02. Although flow rates were lower in the bilateral group than in the unilateral group, the differences between these two groups were statistically significant (p < .02) only for stimulated saliva. Xerostomia was reported by one third of the resection subjects. Conclusions In view of the significantly lower flow rates observed in the resection groups (especially for unstimulated saliva), topical fluoride therapy should be considered for those patients whose past carries activity would indicate an increased carries risk associated with partial loss of salivary function. © 1996 John Wiley & Sons, Inc.

Enhancement of salivary esophagoprotection: Rationale for a physiological approach to gastroesophageal reflux disease

BACKGROUND & AIMS: Secretion of salivary protective factors in patient s with gastroesophageal reflux disease is impaired. However, the impact of physiological stimulus mastication on salivary protective factors output remains largely unknown. The aim of this study was to measure salivary volume, pH, HCO3-, peptide growth factors, prostaglandin, mucin, protein, and viscosity during mastication. METHODS: In 31 asymptomatic volunteers and 36 patients with endoscopic reflux esophagitis, in basal and parafilm chewing-stimulated saliva, its volume, pH, bicarbonate, epidermal growth factor, transforming growth factor alpha, prostaglandin E2, mucin, protein, and viscosity were investigated. RESULTS: Masticatory stimulation in controls resulted in a significantly increased salivary volume by 205%, pH by 7.6%, bicarbonate by 335%, mucin by 137%, protein by 98%, epidermal growth factor by 123%, and prostaglandin E2 by 132%, accompanied by an increase in transforming growth factor alpha by 80% with 19% decline in viscosity vs. basal values. Mastication in reflux esophagitis significantly increased salivary volume by 215%, pH by 6.8%, bicarbonate by 257%, mucin by 135%, protein by 94%, epidermal growth factor by 207%, and prostaglandin E2 by 240%, whereas transforming growth factor alpha increased by 225% and viscosity by 64% when compared with corresponding basal values. CONCLUSIONS: A profound and significant increase in the secretion rate of inorganic and organic protective components in saliva during masticatory stimulation suggests its potential value as a therapeutic approach to the treatment of patients with gastroesophageal reflux disease. (Gastroenterology 1996 Mar;110(3):675-81)

Longitudinal Analysis of Parotid and Submandibular Salivary Flow Rates in Healthy, Different-Aged Adults

Early studies suggested that salivary gland dysfunction was a normal sequela of aging. Recent research on healthy, different-aged adults has led to a revision of these former conclusions. Parotid gland function appears to be age-stable, yet there is no consensus on submandibular/sublingual output. To date, there have only been two longitudinal studies utilizing healthy individuals examining parotid function, and no published longitudinal studies on submandibular/sublingual output. The purpose of this study was to examine unstimulated and stimulated major salivary gland flow rates in unmedicated, essentially healthy subjects, over a 3-year period. Thirty-seven males and females, aged 26-90 years of age, were examined twice over a 3-year period at the Clinical Center of the National Institutes of Health. All were healthy, community-dwelling adults, without systemic diseases, and not taking any medications. Unstimulated and 2% citrate-stimulated parotid and submandibular/sublingual salivary gland flow rates were assessed at both visits, and changes over time were evaluated according to the subject's age at initial visit. There were no significant flow rate differences over a 3-year time period for unstimulated and stimulated parotid and submandibular/sublingual flow rates. Major salivary gland output is aged-stable in healthy persons over a 3-year period. The data from this study suggest that salivary gland dysfunction in an older person should not be considered a normal process of aging.

Dental findings in geriatric populations with diverse medical backgrounds

Objective To determine whether there is a difference in the oral/dental health in older persons with different life styles and medical status. Study design Survey (cross-sectional study) included four groups: (1) subjects (n=123) living in a residential retirement home or community dwelling; (2) subjects (n=218) seeking dental treatment at a Veterans Affairs Dental Outpatient Clinic; (3) subjects (n=132) resident in a VA long-term care facility; and (4) subjects (n=81) recently admitted to a VA acute care ward with a diagnosis of cerebral vascular accident or other neurologic problem. Each subject answered questions on medical and dental health and dietary preferences in a comprehensive interview. They were given a comprehensive dental examination that included measurements of stimulated salivary flow and minor salivary gland output. Results The data from groups 2 and 3 confirmed previous reports that independent living subjects have better oral/dental health than dependent living subjects. The data from groups 1 and 4, obtained from geriatric populations on the opposite ends of the medical health/disease continuum provide new information that suggests that good medical health and good oral/dental health are linked. The subjects in group 1 were very healthy as judged by their longevity; 54% were ≥80 years and they had low reported prevalence of medical disease. Only 6% were edentulous and the dentate persons were missing 4.5 teeth. In contrast, over 50% of the patients in group 4 were <70 years; they had an edentulous rate of 49% and among the dentate persons had an average 12 missing and 5 decayed teeth. Conclusions The medically healthy persons had excellent dental health whereas the sickest persons were either edentulous or had many missing teeth.

Depletion of total salivary gland protein in blood-fed Anopheles mosquitoes.

Reduction in total salivary gland protein from four anopheline vectors of human malaria, Anopheles stephensi Liston, An. albimanus Wiedmann, An. gambiae Giles, and An. freeborni Aitken, was quantified after mosquitoes blood-fed to repletion on human volunteers, hamsters or through a Baudruche artificial membrane. Total salivary gland protein from pools of six unfed mosquitoes ranged from 4.33 to 7.91 micrograms/ml. The difference between the total protein of glands from unfed and blood-fed mosquitoes for all species ranged from 1.77 to 3.12 (micrograms/ml for six pooled salivary glands. Total salivary gland protein for mosquitoes blood-fed to repletion was significantly less than that of unfed controls from the same cohort. Reduction in total salivary gland protein for An. freeborni and An stephensi blood fed to repletion on human volunteers, hamsters, and a Baudruche membrane ranged from 24 to 46%, from 43 to 56%, and from 24 to 51%, respectively. An. stephensi mosquitoes were allowed to blood feed on humans for 0 (unfed), 0.5-, 1.0-, 2.0-min time periods or to repletion (> 2-5 min). As feeding time increased, there was a significant decrease in total amount of protein in the salivary glands. This decrease was proportional over time, indicating that salivation occurred continuously from the beginning (probing) of blood feeding to withdrawal of the mosquito mouthparts at repletion. These data indicate that during blood feeding there difference between species in the salivary gland output measured as amount of protein depleted from the salivary glands and that depletion of salivary protein from the glands occurred continuously as mosquitoes fed to repletion.

Influences of secretory activities in rat submandibular glands on tissue kallikrein circulating in the blood

Changes in serum levels of rat tissue kallikrein (rK1) in venous blood were measured, using a newly developed radioimmunoassay, before and after autonomic nerve stimulations of submandibular salivary secretion. rK1 secreted into saliva under these conditions was measured by radioimmunoassay and by enzymic activity assay, using the fluorogenic peptide substrate D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC). Following an overnight fast, serum rK1 concentration was 30-40 ng ml-1. Unilateral electrical stimulation of the submandibular sympathetic nerve supply (at 50 Hz in bursts of 1 s every 10 s for 60 min) evoked a small flow of saliva with a very high rK1 concentration, resulting in a large output of rK1 of 2104.4 +/- 603.5 micrograms (n = 6). Such stimulation caused a large degranulation of granular duct cells and a corresponding reduction in glandular rK1 content. Unilateral electrical stimulation of the parasympathetic nerve supply (at 5 Hz continuously for 60 min) evoked a copious flow of saliva with a very low rK1 concentration, resulting in a low output of rK1 (18.1 +/- 4.9 micrograms; n = 6). Despite these large differences in salivary outputs of rK1, serum concentrations of rK1 were increased similarly following either sympathetic or parasympathetic stimulation by 48 and 46%, respectively. If the submandibular duct was briefly obstructed during sympathetic stimulation, inducing leakage and glandular oedema, then serum rK1 increased greatly (40-fold); a similar increase to that seen by others in previous studies without deliberate obstruction. Four days after bilateral submandibular-sublingual sialadenectomy serum rK1 concentration was reduced by approximately 50%. The results indicate that submandibular glands normally contribute to circulating levels of rK1 in rats, but this contribution is independent of the amounts of rK1 secreted into saliva by sympathetically induced exocytosis, and is likely to arise from basal vesicular transport. However, if glandular leakage occurs during sympathetic stimulation of submandibular secretion this then causes increases in the circulating levels of rK1 that correlate with the large amounts being secreted into saliva.

Comparison of the number and type of dental functional units in geriatric populations with diverse medical backgrounds

Elderly subjects (N 430) from four convenience populations that represented different levels of medical health--independent living (Veterans Affairs and non-Veterans Affairs), nursing home, and hospitalized acute care--were given dental examinations. The independent living groups had significantly higher numbers of functional units (opposing natural or prosthetic tooth pairs) and of contiguous functional units compared with the nursing home and hospitalized groups. There was a shift from functional units that consisted of natural teeth to functional units that consisted of prosthetic teeth in the nursing home and hospitalized groups. Numbers of functional units were negatively correlated to plaque index, papillary bleeding scores, and minor salivary gland output. This study suggests a strong relationship between functional integrity of the dentition and general health.

Late effects of radiation therapy in the head and neck region

The head and neck region is composed of numerous structures, each with an inherent response to radiation that is largely governed by the presence or absence of mucosa, salivary glands, or specialized organs within that site. Irradiated mucocutaneous tissues demonstrate increased vascular permeability that leads to fibrin deposition, subsequent collagen formation, and eventual fibrosis. Irradiated salivary tissue degenerates after relatively small doses, leading to markedly diminished salivary output. This, in turn, effects the teeth by promoting dental decay which, in turn, effects the integrity of the mandible. Details of these changes are presented, including their pathophysiology, clinical syndromes, and potential treatment.

Do salivary organic components play a protective role in health and disease of the esophageal mucosa?

Aggressive factors operating within the esophageal lumen during gastroesophageal reflux are balanced by adequately mobilized protective mechanisms. Esophageal mucosal protection operates at three different although complementary dimensions: (1) preepithelial, (2) epithelial and (3) postepithelial. Since aggressive factors predominantly operate within the esophageal lumen, preepithelial defense is pivotal in mucosal protection. The preepithelial barrier is significantly enhanced by the quantity and the quality of salivary organic components such as salivary mucin, nonmucin protein, salivary epidermal growth factor (EGF) and salivary prostaglandin E2. The rate of secretion of salivary mucin, nonmucin protein and EGF under the impact of intraesophageal mechanical (bolus) and chemical (HCl/pepsin) stimulation, mimicking the natural gastroesophageal reflux scenario, is significantly impaired in patients with RE, whereas the rate of salivary PGE2 output remains essentially unchanged. Salivary secretory response to esophageal mechanical and chemical stimuli in terms of organic components, mediated by the esophagosalivary reflex pathway, exhibits a significant impairment in patients with reflux esophagitis.

The Effect of Esophageal Mechanical and Chemical Stimuli on Salivary Mucin Secretion in Healthy Individuals

Because of a newly developed model of esophageal perfusion in humans, the authors could study the role of esophago-salivary reflex in salivary neutral and acidic mucin output. The basal rate of neutral mucin output was 0.24 +/- 0.06 mg per minute. Placement of intraesophageal tubing and inflation of balloons resulted in a highly significant increase in salivary mucin output (2.10 +/- 0.22 mg per minute; p < 0.00001). However, implementation of esophageal perfusion with saline resulted in a significant decline of salivary mucin output (1.28 +/- 0.10 mg/mL NaCl4 versus 2.08 +/- 0.24 mg/mL NaCl1; p < 0.001). Esophageal perfusion with hydrochloric acid prevented the decline of salivary mucin output observed during perfusion with saline, whereas infusion of hydrochloric acid/pepsin resulted in a significant enhancement of salivary mucin output (2.89 +/- 0.31 mg per minute; p < 0.01). Therefore, mechanical and chemical stimulations resulted in an overall 9-fold and 12-fold increase in the rate of salivary mucin output over the basal value, respectively. The basal rate of acidic mucin secretion was 0.26 +/- 0.06 mg per minute. After placement of intraesophageal tubing, inflation of balloons, perfusion hydrochloric acid, or hydrochloric acid-pepsin solution, a significant enhancement in the rate of salivary acidic mucin output, similar to that observed during measurement of neutral mucin, was observed. Therefore, during mechanical and chemical stimulation, the rate of salivary acidic mucin output increased 7.3-fold and 11.1-fold over the basal value, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural and functional changes in salivary glands during aging

Various salivary glands in senescent humans and other animals have been examined extensively to characterize the structural and functional changes that occur during aging. Although a wide range of different structural changes, involving both the parenchymal and stromal tissues, have been described, it is unclear how any of these changes affects the function of the salivary glands. One major change in structure is the reduction in the volume of acini with a concomitant increase in the ductal volume. Despite this loss of functional acini, the salivary output and the contents seem to be unaltered, or minimally altered, due to aging. One consistent change observed in many salivary glands of aged animals is the decline in the rate of synthesis of proteins and their messenger RNA (mRNA). However, the salivary acinar cells from aged animals can synthesize secretory proteins at an elevated rate just as effectively as those from their younger counterparts in response to external stimuli, which are known to enhance the rate of protein synthesis. Thus, it appears that the salivary acinar cells, which remain structurally intact during aging, seem to retain their functional efficiency. Furthermore, these acinar cells, although reduced in number, are sufficient in quantity to carry out most of the salivary gland functions.

Salivary Gland Dysfunction

Clinically significant declines of salivary output are not a function of aging. Complaints of oral dryness (xerostomia) are common in the elderly patient, however. This complaint is most often a consequence of medications; tricyclic antidepressants, certain antihypertensives, and anticholinergics can cause marked decreases in salivary flow rates. Other medications such as diuretics may cause xerostomia without decreasing salivary output. Systemic diseases such as Sjögren's syndrome can destroy salivary glands. Specific serologic, ophthalmologic, and salivary findings are necessary for the diagnosis of Sjögren's syndrome. Radiation therapy for treatment of head and neck cancers also can damage salivary glands permanently. Infectious agents such as mycobacteria, Epstein-Barr virus, and various oral bacteria can infect human salivary glands. Diminished salivary output can lead to serious oral sequelae. Rapidly progressing dental caries and oral candidiasis are found frequently in this age group. Close supervision of the geriatric patient's oral and dental health is essential.

Salivary gland involvement in HIV-1 infection

After infection with human immunodeficiency virus (HIV)-1, virus can be recovered from both whole saliva (the total fluid contents of the mouth) and individual major salivary gland secretions. The concentration of virus is low, and recovery is infrequent. Antibodies (primarily of the IgA class) to HIV-1 are found in saliva. Despite the presence of virus, the oral cavity does not appear to be a route of transmission for HIV-1. This may relate to protective properties of saliva. It has been reported that whole saliva and mixed submandibular / sublingual secretions inhibit the infectivity of the virus in vitro. HIV infection also induces alterations in salivary gland function. Both salivary output and composition may be affected.

The Effect of Increased Mastication by Daily Gum-chewing on Salivary Gland Output and Dental Plaque Acidogenicity

The effect of increased mastication on plaque metabolism and salivary gland function was determined in 11 human subjects who chewed a sugarless gum for ten minutes of each waking hour for two weeks. Prior to and at the conclusion of the gum-chewing regimen, unstimulated whole saliva and 2% citric-acid-stimulated parotid saliva were collected. Flow rates, pH, and buffer capacity were determined on all saliva samples. In addition, parotid saliva was analyzed for protein concentration and the proteins further studied by SDS-PAGE. The plaque pH response to a 10% sucrose rinse was also measured before and after the regimen. Significant increases were observed in the pH and buffer capacity of unstimulated whole saliva as were similar increases in the flow rate, pH, and buffer capacity of stimulated parotid saliva. Protein concentrations and profiles remained unaffected. In addition, the resting plaque pH and minimum plaque pH reached after a sucrose challenge were both raised significantly, with a significant reduction in the cH area. The results of this study indicate that increased masticatory effort by frequent consumption of sugar-free chewing gum over a prolonged time period resulted in a functional increase in the output of stimulated parotid saliva, as well as in increases in pH and buffer capacity of whole and parotid saliva, which may help to reduce plaque acidogenicity.

An assessment of salivary function in healthy premenopausal and postmenopausal females : J. Gerontol. 1991 46/1 (M11–M15)

The elderly represent the most rapidly growing segment of the U.S. population, and the majority of this group are females. The average woman can anticipate living about a third of her life beyond menopause, and many U.S. women undergo hormonal replacement in an attempt to relieve menopausal symptoms. Little is understood about the relationship between menopause, hormonal replacement therapy, and the oral structures, although oral discomfort, xerostomia, and salivary hypofunction have been associated with postmenopausal women. The effects of menopausal status and estrogen therapy on subjective reports of oral dryness and discomfort and objective measurements of major salivary gland output were assessed in 43 healthy premenopausal and postmenopausal females. No complaints of xerostomia or burning mouth and no alterations in the quantity of saliva occurred in this population. This study suggests that among healthy women salivary gland function is not significantly influenced by menopause or hormonal replacement therapy.

Pilocarpine Treatment of Salivary Gland Hypofunction and Dry Mouth (Xerostomia)

We studied the effects of pilocarpine hydrochloride, a para-sympathomimetic agent, on major salivary gland output and subjective responses in 31 patients with salivary hypofunction. Pilocarpine hydrochloride (5-mg capsules, three times daily) was given for 5 months and a placebo was randomly assigned for 1 month in a double-blind fashion. Objective measurements of major salivary gland output, subjective impressions of oral moisture, treatment-related side effects, and a number of physiologic measures were assessed monthly. Pilocarpine significantly increased salivary output in 21 of the 31 patients. Subjective improvement in the feeling of oral dryness, speaking, chewing, and swallowing were reported by 27 individuals. Side effects, while common, generally were mild and tolerable. There were no significant alterations in cardiovascular or other physiologic measures. We conclude that pilocarpine is an effective and safe treatment for salivary gland hypofunction and xerostomia in selected patients. The increase in major gland output provides beneficial natural secretions and relief of oral dryness.

Atropine‐resistant submandibular responses to stimulation of the parasympathetic innervation in the anaesthetized ferret.

1. Submandibular salivary and vascular responses to stimulation of the peripheral end of the chorda-lingual nerve at 20 Hz continuously for 60 min were investigated in anaesthetized ferrets, in which the sympathetic innervation to the gland was cut, in the presence and absence of atropine (2.0 mg kg-1). 2. Both the increase in submandibular salivary flow and protein output, which occurred in response to nerve stimulation, were substantially reduced following the administration of atropine, the latency was greatly increased thereby, and both responses were more transient but neither was abolished by atropine. The fall in submandibular vascular resistance was not significantly affected by atropine, either in respect of extent or duration. 3. Chorda-lingual stimulation produced an increase in the output of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the submandibular venous effluent blood. Each of these responses was maximal within the first 10 min after the onset of stimulation and declined thereafter. The time-scales of both the CGRP and SP responses were similar to those of the atropine-resistant secretory responses, both being quite short-lived, whereas the output of VIP (like the atropine-resistant vascular response) was significantly greater than the basal value throughout the whole of the 60 min period of stimulation. 4. The CGRP response was completely abolished by pre-treatment with atropine, whereas the outputs of both VIP and SP were significantly enhanced thereby. Both the submandibular vascular and secretory responses to chorda-lingual stimulation were almost completely suppressed following the administration of hexamethonium, and there was then no detectable release of peptidergic agonists from the gland. 5. The atropine-resistant submandibular salivary secretory responses were completely abolished by pre-treatment with a tachykinin inhibitor [( D-Arg1, D-Cl2 Phe5, Asn6, D-Trp7,9, Nle11]-SP; 0.75 mg kg-1) without affecting the fall in submandibular vascular resistance. 6. Following pre-treatment with hexamethonium, I.V. bolus injections of methacholine, SP and CGRP elicited increases in submandibular blood flow and secretion of saliva. VIP caused an increase in blood flow without overt secretion, although it is known to increase secretion of protein and to potentiate the secretory response to SP. Taken together, all these results are consistent with the contention that VIP contributes to the vasodilator response to stimulation of the para-sympathetic innervation in this gland and that both SP and CGRP are likely to contribute to the secretory response.

How Much Saliva is Enough?

Saliva is important for the preservation and maintenance of oral health. It is unclear, however, how much saliva is required to maintain normal oral function. Major salivary gland flow rates, objective measurements of oral health, and subjective complaints of oral problems were assessed in different-aged, healthy persons. Results suggest that the comparison of major salivary gland flow rates of an individual with population standards to identify patients susceptible to the effects of salivary dysfunction is unreliable. Changes in salivary function over time are a more meaningful gauge of the impact of saliva on oral health. The clinician should monitor salivary production to identify patients with declining salivary gland output.

An Assessment of Salivary Function in Healthy Premenopausal and Postmenopausal Females

The elderly represent the most rapidly growing segment of the U.S. population, and the majority of this group are females. The average woman can anticipate living about a third of her life beyond menopause, and many U.S. women undergo hormonal replacement in an attempt to relieve menopausal symptoms. Little is understood about the relationship between menopause, hormonal replacement therapy, and the oral structures, although oral discomfort, xerostomia, and salivary hypofunction have been associated with postmenopausal women. The effects of menopausal status and estrogen therapy on subjective reports of oral dryness and discomfort and objective measurements of major salivary gland output were assessed in 43 healthy premenopausal and postmenopausal females. No complaints of xerostomia or burning mouth and no alterations in the quantity of saliva occurred in this population. This study suggests that among healthy women salivary gland function is not significantly influenced by menopause or hormonal replacement therapy.

Effects of diabetes and dietary manipulation on rat parotid gland secretory response to sympathetic nerve stimulation

1. 1. The effects of streptozotocin-diabetes, bulk-diet, low protein diet (8%) and protein-calorie malnutrition on parotid gland response to sympathetic nerve stimulation were studied in male Wistar rats. 2. 2. Mean body weights were considerably less in diabetic and protein-calorie malnourished rats than in the other groups, but parotid gland weight was reduced only in animals placed on a low-protein diet. 3. 3. Salivary flow rate (μ1/min/g tissue) and total protein output (mg secreted/g tissue) were reduced in diabetic rats. 4. 4. Salivary composition was altered in diabetes and protein-calorie restriction, and the specifie changes were unique to each condition. 5. 5. Thus, with the possible exception of gland weight the effects of diabetes on parotid gland structure and function are not related to either hyperphagia or nutritional status.