Safety and Efficacy of Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase 1/2 Trial (MESRIX).

BACKGROUND: Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. PATIENT AND METHODS: This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration. RESULTS: No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05). CONCLUSIONS: ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.

Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels.

INTRODUCTION: Management of phenylketonuria (PKU) is achieved through low-phenylalanine (Phe) diet, supplemented with low-protein food and mixture of free-synthetic (FS) amino acid (AA). Casein glycomacropeptide (CGMP) is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides. OBJECTIVE: The purpose of this study was to compare absorption of CGMP-20 to FSAA with the aim of evaluating short-term effects on plasma AAs as well as biomarkers related to food intake. METHODS: This study included 8 patients, who had four visits and tested four drink mixtures (DM1-4), consisting of CGMP, FSAA, or a combination. Plasma blood samples were collected at baseline, 15, 30, 60, 120, and 240 minutes (min) after the meal. AA profiles and ghrelin were determined 6 times, while surrogate biomarkers were determined at baseline and 240 min. A visual analogue scale (VAS) was used for evaluation of taste and satiety. RESULTS: The surrogate biomarker concentrations and VAS scores for satiety and taste were nonsignificant between the four DMs, and there were only few significant results for AA profiles (not Phe). CONCLUSION: CGMP and FSAA had the overall same nonsignificant short-term effect on biomarkers, including Phe. This combination of FSAA and CGMP is a suitable supplement for PKU patients.

Caries affected by calcium and fluoride in drinking water and family income.

Water quality and socioeconomics influence caries in populations. This study broadens previous studies on how caries is associated with fluoride and calcium in drinking water and with family income by quantifying the combined effect of the three independent variables. The effects of calcium and fluoride can be described as independent effects of the two ions or, alternatively, in the form of saturation with respect to fluorite (CaF2). A general linear model describes this relationship with high significance and the model confirms the important protective effect of calcium and fluoride, independently against caries. From the model, the relative importance of fluoride and calcium to protect against caries is quantified. The relationship between caries and family income is also highly significant. It is illustrated how the linear model can be applied in planning and analyzing drinking water softening in relation to caries.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

BACKGROUND: Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. METHODS: This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. DISCUSSION: The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. TRIAL REGISTRATION: EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

Salivary microbiota in individuals with different levels of caries experience.

This study compared salivary bacterial profiles in two groups having a 10-fold difference in levels of caries experience, as it was hypothesized that the composition of the salivary microbiota might associate with the levels of caries experience. Bacterial profiles in stimulated saliva samples from 85 individuals with low levels of caries experience (healthy group) and 79 individuals with high levels of caries experience (caries group) were analyzed by means of the Human Oral Microbiome Identification Next Generation Sequencing (HOMINGS) technique. Subsequently, saliva samples from caries-free individuals in the healthy group (n = 57) and the caries group (n = 31) were compared. A significantly higher α-diversity (p < 0.0001) and a twofold higher relative abundance of Neisseria, Haemophilus, and Fusobacterium were recorded in saliva samples from the healthy group compared with the caries group. Differences observed were more pronounced when limiting the analyses to caries-free individuals in each group. Data from this cross-sectional analysis suggest that low levels of caries experience might associate with a characteristic salivary bacterial composition different from that in individuals with high caries experience. Consequently, longitudinal studies are required to determine if the composition of the salivary microbiota might be a predictive factor of caries risk at the individual level.

Is parotid saliva sterile on entry to the oral cavity?

CONCLUSION: The present study indicates that parotid saliva is sterile on entry to the oral cavity. OBJECTIVES: The objective was to investigate if parotid saliva is sterile on entry to the oral cavity and, thus, prior to contamination by oral bacteria. METHOD: Forty healthy volunteers were included in sterile parotid saliva collection. Parotid saliva was collected using a sterile Lashley cup, placed over the papilla of the Stensen´s duct, as well as sterile tubes and syringes for collection. All collections were followed by collection of a positive control sample where some of the sterile obtained parotid saliva had been exposed to the contralateral mucosal membranes. All samples parotid saliva, as well as the positive controls, were cultivated, and 10 randomly selected parotid saliva samples underwent polymerase chain reaction (PCR) analyses. RESULTS: In 33 of 40 parotid saliva samples there were no cultivable bacteria, whereas bacteria were cultivated in all positive control samples. In eight of 10 PCR samples no bacterial DNA was detected. The most frequent bacteria in the remaining non-sterile parotid saliva samples and positive control samples were non-haemolytical streptococci and the coagulase negative staphylococci.

Incidence of sialolithiasis in Denmark: a nationwide population-based register study.

Sialolithiasis is a frequent disorder affecting the salivary glands. The incidence rate (IR) has been reported to be 2.9-5.5 per 100,000 person-years, but all previous studies have been based on selected hospital data. In this study, we conducted a population-based study evaluating the IR of sialolithiasis and the IR variation according to age, gender and geography in Denmark. We included data from hospitals as well as from private ear, nose and throat (ENT) clinics. The study was based on registry data on all sialolithiasis cases in Denmark between 2003 and 2009 extracted from the Danish National Patient Registry (hospital cohort) and the Danish Regions Centre for Healthcare Statistics (private ENT clinic cohort). To validate the diagnosis, the proportion of visually confirmed cases was estimated based on patient records from subsamples of the two cohorts. The IR was 7.27 and 14.10 per 100,000 person-years based on visually confirmed cases only and on all cases, respectively. The highest IR was observed among 60- to 70-year-olds, in the North Denmark region and among females. In the validation subsamples, 35% of assumed sialoliths were visually confirmed in the private ENT clinic cohort and 59% in the hospital cohort. In this first population-based study of IR on sialolithiasis, we found a substantially higher IR. With respect to both visually confirmed cases and all cases, this is higher than previously reported from studies based on selected hospital data.

Comparative analysis of bacterial profiles in unstimulated and stimulated saliva samples.

BACKGROUND AND OBJECTIVE: The microbial profiles of stimulated saliva samples have been shown to differentiate between patients with periodontitis, patients with dental caries, and orally healthy individuals. Saliva was stimulated to allow for easy and rapid collection; however, microbial composition may not reflect the more natural, unstimulated state. The purpose of this study was to validate whether stimulated saliva is an adequate surrogate for unstimulated saliva in determining salivary microbiomes. DESIGN: Unstimulated (n=20) and stimulated (n=20) saliva samples were collected from 20 orally and systemically healthy, non-smoking participants. Salivary bacterial profiles were analyzed by means of the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using Mann-Whitney test with Benjamini-Hochberg's correction for multiple comparison, cluster analysis, principal component analysis, and correspondence analysis. RESULTS: From a total of 40 saliva samples, 496 probe targets were identified with a mean number of targets per sample of 203 (range: 146-303), and a mean number of probe targets of 206 and 200 in unstimulated and stimulated saliva samples, respectively (p=0.62). Based on all statistical methods used for this study, the microbial profiles of unstimulated and stimulated saliva samples collected from the same person were not statistically significantly different. CONCLUSIONS: Analysis of bacterial salivary profiles in unstimulated and stimulated saliva samples collected from the same individual showed comparable results. Thus, the results verify that stimulated saliva is an adequate surrogate of unstimulated saliva for microbiome-related studies.

Salivary bacterial fingerprints of established oral disease revealed by the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) technique.

BACKGROUND AND OBJECTIVE: The composition of the salivary microbiota, as determined using various molecular methods, has been reported to differentiate oral health from diseases. Thus, the purpose of this study was to utilize the newly developed molecular technique HOMINGS (Human Oral Microbe Identification using Next Generation Sequencing) for comparison of the salivary microbiota in patients with periodontitis, patients with dental caries, and orally healthy individuals. The hypothesis was that this method could add on to the existing knowledge on salivary bacterial profiles in oral health and disease. DESIGN: Stimulated saliva samples (n=30) were collected from 10 patients with untreated periodontitis, 10 patients with untreated dental caries, and 10 orally healthy individuals. Salivary microbiota was analyzed using HOMINGS and statistical analysis was performed using Kruskal-Wallis test with Benjamini-Hochberg's correction. RESULTS: From a total of 30 saliva samples, a mean number of probe targets of 205 (range 120-353) were identified, and a statistically significant higher mean number of targets was registered in samples from patients with periodontitis (mean 220, range 143-306) and dental caries (mean 221, range 165-353) as compared to orally healthy individuals (mean 174, range 120-260) (p=0.04 and p=0.04). Nine probe targets were identified with a different relative abundance between groups (p<0.05). CONCLUSIONS: Cross-sectional comparison of salivary bacterial profiles by means of HOMINGS analysis showed that different salivary bacterial profiles were associated with oral health and disease. Future large-scale prospective studies are needed to evaluate if saliva-based screening for disease-associated oral bacterial profiles may be used for identification of patients at risk of acquiring periodontitis and dental caries.

Temporal Stability of the Salivary Microbiota in Oral Health.

OBJECTIVES: Saliva is a biological fluid suitable for biomarker analysis, and differences in the salivary microbiota in oral health and disease have been reported. For such comparative analyses, time of sampling is critical since the bacterial composition may vary throughout the day, i.e., diurnal variation. The purpose of this study is to compare the salivary microbiome over time to determine the optimal time for sampling. DESIGN: Stimulated saliva samples were collected from 5 orally healthy individuals in 4 h intervals for 24 h, and collection was repeated 7 days later (number of samples per person, n = 12, total number of samples, n = 60). Salivary microbiota was analyzed using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using the Kruskal-Wallis test with Benjamini-Hochberg's correction for multiple comparisons, cluster analysis, principal component analysis and correspondence analysis. RESULTS: From a total of 60 saliva samples, 477 probe targets were collectively identified with a mean number of probes per sample of 207 (range: 153-307). Little or no variation in microbial profiles within subjects was observed over time. CONCLUSIONS: Although there was considerable variation between subjects, microbial profiles within subjects were stable throughout a 24 hour period and after 1 week. Since there is little or no evidence of diurnal variation of the salivary microbiome, time of sampling of saliva is not critical for perturbation or other microbial studies.

Whole-Saliva Fluoride Levels and Saturation Indices in 65+ Elderly during Use of Four Different Toothpaste Regimens.

BACKGROUND: Elderly individuals suffering from subnormal saliva secretion combined with inadequate oral hygiene may develop rampant caries and caries in parts of the dentition not normally affected by caries if preventive measures are not undertaken. Such measures include elevating fluoride levels at the saliva/biofilm/tooth interface. AIM: To analyse whole-saliva fluoride levels and mineral saturation indices during different fluoride toothpaste regimens in home-living elderly. MATERIALS AND METHODS: Whole saliva was collected from 27 subjects (7 males and 20 females, mean age 73.5±6.1 years) at ten time points covering the whole day during five 2-week periods. During the first period, participants used their normal toothpaste without instructions (baseline). This was followed by TP1: 1,450-ppm NaF toothpaste; TP2: 1,450-ppm monofluorophosphate (MFP) toothpaste with addition of calcium; TP3: 5,000-ppm NaF toothpaste, and TP4: the same toothpaste with additional 'smearing' of toothpaste on the teeth, twice daily. During TP1-TP4, the participants were instructed to brush 3 times per day using 1.5 g of toothpaste without rinsing. RESULTS: Salivary fluoride levels increased with toothpaste fluoride content (p<0.001), although major interindividual and intraindividual variations were observed. The highest fluoride values appeared in the morning and at night (p<0.001). Saturation indices for calcium fluoride were affected by the fluoride content in pastes (p<0.05). Concerning hydroxyapatite and fluorapatite, indices were highest with the MFP toothpaste and extra calcium (NS to p<0.05). CONCLUSIONS: Use of a high-fluoride toothpaste resulted in significantly increased fluoride levels in whole saliva and mineral saturation indices were indeed influenced by choice of toothpaste.

Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study.

The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect was assessed 2, 4, 8, 12, and 20 weeks after A/Ona (drooling problems (VAS), impact (0-7), treatment effect (0-5), unstimulated whole saliva (UWS) flow and composition)) and analyzed by two-way ANOVA. The effect was unchanged-moderate in A to moderate-marked in F. Changes in all parameters were significant in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response.

Does drinking water influence hospital-admitted sialolithiasis on an epidemiological level in Denmark?

OBJECTIVES: Sialolithiasis, or salivary stones, is not a rare disease of the major salivary glands. However, the aetiology and incidence remain largely unknown. Since sialoliths are comprised mainly of calcium phosphate salts, we hypothesise that drinking water calcium levels and other elements in drinking water could play a role in sialolithiasis. Owing to substantial intermunicipality differences in drinking water composition, Denmark constitutes a unique environment for testing such relations. DESIGN: An epidemiological study based on patient data extracted from the National Patient Registry and drinking water data from the Geological Survey of Denmark and Greenland retrieved as weighted data on all major drinking water constituents for each of the 3364 waterworks in Denmark. All patient cases with International Statistical Classification of Diseases 10th Revision (ICD-10) codes for sialolithiasis registered between the years 2000 and 2010 were included in the study (n=3014) and related to the drinking water composition on a municipality level (n=98). PRIMARY AND SECONDARY OUTCOME MEASURES: Multiple regression analysis using iterative search and testing among all demographic and drinking water variables with sialolithiasis incidence as the outcome in search of possible relations among the variables tested. RESULTS: The nationwide incidence of hospital-admitted sialolithiasis was 5.5 cases per 100,000 citizens per year in Denmark. Strong relations were found between the incidence of sialolithiasis and the drinking water concentration of calcium, magnesium and hydrogen carbonate, however, in separate models (p<0.001). Analyses also confirmed correlations between drinking water calcium and magnesium and their concentration in saliva whereas this was not the case for hydrogen carbonate. CONCLUSIONS: Differences in drinking water calcium and magnesium may play a role in the incidence of sialolithiasis. These findings are of interest because many countries have started large-scale desalination programmes of drinking water.

Root caries, root surface restorations and lifestyle factors in adult Danes.

AIM: To investigate selected lifestyle factors in relation to active caries and restored root surface lesions in adults. MATERIALS AND METHODS: Based on clinical examinations and questionnaires, data on root caries, socioeconomic status, body mass index, dietary habits, alcohol consumption, tobacco use and oral hygiene routines were collected from 4369 adults aged 21-89 who took part in a survey covering 13 municipalities across Denmark. Uni- and multivariate logistic regression analyses were applied to analyse the relationship between the independent lifestyle variables and active caries and restored root surface lesions, respectively. RESULTS: The prevalence of active root caries was 4%, while 26% displayed restored root surfaces. The sugar intake was not related to root caries. A multivariate logistic regression analysis revealed that, in subjects aged 45 or over, smoking and wearing dentures were significantly associated with presence of active root caries (p<0.01). The intake of 15 drinks or more per week was associated with higher odds of root surface restorations compared with no alcohol intake (OR=1.7; p<0.001). CONCLUSIONS: Lifestyle factors such as tobacco use and alcohol consumption, as well as wearing dentures, were significantly associated with the occurrence of untreated caries and restored root surface lesions, especially in persons over 45. Thus, such lifestyle factors should be taken into consideration, identifying persons with a need of preventive dental services. In addition, oral health education should focus on the possible risks of smoking and a high alcohol intake.

Mesenchymal stem cell therapy for salivary gland dysfunction and xerostomia: a systematic review of preclinical studies.

The most severe forms of xerostomia and salivary gland dysfunction, as well as a severely reduced quality of life, are seen in Sjögren syndrome (SS) and after radiotherapy for head and neck cancer. For both conditions, no effective regenerative therapies yet exist. Thus, the aim of this article was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization Clinical Trials Registry Platform, and Google Scholar. We identified 6 separate study comparisons eligible for inclusion. Owing to the limited number of studies, we conclude that more randomized, adequately powered clinical trials are needed to validate the potential beneficial effect of MSCs on salivary gland dysfunction and xerostomia. Nonetheless, the preliminary studies identified in the present review were encouraging for further research.

Saliva composition in three selected groups with normal stimulated salivary flow rates, but yet major differences in caries experience and dental erosion.

OBJECTIVE: It was hypothesized that, by comparing matched subjects with major differences in these dental diseases, but yet normal saliva flow rates, it would be possible to obtain data on the effect of saliva composition on dental disease isolated from the effect of the flow rate. Thus, the aim of the study was to compare the major physicochemical characteristics of stimulated whole saliva in three groups of 85 subjects, each with normal saliva flow rates and at least 24 remaining teeth. MATERIALS AND METHODS: A group with very little dental disease (healthy), a group with dental erosion (erosion) and a group with very high caries experience (caries) were chosen. Furthermore, the aim was to determine whether differences among groups could also be found on an individual level. RESULTS: Although it was not possible to retrieve three groups whose members were completely identical, the present study points in the direction that, on a group level, subjects with very little dental disease seemed to have a more favorable physicochemical saliva composition with respect to higher calcium, phosphate, bicarbonate, pH, degree of saturation with respect to hydroxyapatite and a lower critical pH (p < 0.05 or less). However, on an individual level the explanatory power for the saliva composition was only 10% for caries experience and only 11% for dental erosion (p < 0.001). CONCLUSION: The compositional analyses performed in this study on stimulated whole saliva, including major physicochemical characteristics of saliva, will most likely have little predictive value for future dental caries and erosion in single individuals.

Findings from the oral health study of the Danish Health Examination Survey 2007-2008.

OBJECTIVE: The aims of the oral part of the Danish Health Examination Survey (DANHES 2007-2008) were (1) to establish an oral health database for adult Danes and (2) to explore the influence of general diseases and lifestyle on oral health. This paper presents the study population, examination methods, questionnaire and baseline results. MATERIALS AND METHODS: The study population comprised 4402 subjects, aged 18-96, consecutively enrolled from 18 065 DANHES participants from 13 municipalities in Denmark. The oral part consisted of a validated questionnaire and a clinical examination, carried out in mobile units by three trained and calibrated dental hygienists. The data were processed with descriptive statistics and mono- and bivariate analyses. RESULTS: The mean age was 54.1 years and 60% were women. The mean number of natural teeth was 26.6; the mean DMFT/DMFS values were 18.9 and 61.0, and varied with age (DMFT 8.7-24.3). A higher proportion of females suffered from dental erosion in the younger age groups. Forty per cent of all subjects had a mean clinical attachment loss ≥ 3 mm, varying from 4% among those aged 18-34 to 80% in those over 75. A sub-optimal saliva secretion rate was more common among females than males (17.7% vs 10.4%) and this was reflected by the reported frequency of dry mouth. CONCLUSION: This extensive cross-sectional study provides a platform for obtaining future knowledge of the impact of health- and lifestyle-related factors on oral diseases. The validated questionnaire and the clinical characteristics enable robust analyses, although the conclusions may be hampered by limited external validity.

Saliva in relation to dental erosion before and after radiotherapy.

OBJECTIVE: Low saliva flow and abnormal saliva composition are common conditions after radiotherapy for oral cavity and pharyngeal cancer. Both conditions increase the susceptibility to dental caries and erosion, which may be further accelerated by changes in food preferences. The aim of this study was to determine changes in saliva flow and susceptibility to erosive challenges in pharyngeal cancer patients before and after radiotherapy to the head and neck. MATERIALS AND METHODS: The erosive potential of sucking acidic candies with and without calcium was determined in nine patients (50-68 years) before and after receiving a radiation dose of 66 Gy to the head and neck area. The erosive potential was evaluated from saliva degree of saturation with respect to hydroxyapatite (HAp) and by dissolution of HAp in candy-stimulated saliva. RESULTS: Sucking acidic candies increased saliva flow rates ≈ 17-fold before as well as after radiotherapy (p < 0.001). However, significantly lower unstimulated (p < 0.05) and stimulated (p < 0.01) saliva flow rates were obtained after radiotherapy. Also, saliva became more under-saturated with respect to HAp during (p < 0.01) and in a period after sucking the candies (p < 0.01). HAp dissolution was significantly lower with the candy containing calcium compared with the control candy, both before and after radiotherapy (p < 0.001 and p < 0.05). CONCLUSIONS: Radiotherapy to the head and neck area significantly reduced saliva flow and altered saliva composition in a way that may increase the susceptibility to dental disease. However, saliva could be stimulated by acidic candies, which could be made nearly non-erosive even in irradiated patients.

Effect of chewing gums containing the probiotic bacterium Lactobacillus reuteri on oral malodour.

OBJECTIVE: To evaluate the effect of chewing gums containing probiotic bacteria on oral malodour. The null hypothesis was that no difference would be displayed compared with placebo gums. MATERIALS AND METHODS: Twenty-five healthy young adults with self-reported malodorous morning breath completed this randomized double-blind placebo-controlled cross-over trial. The design included run-in and wash-out periods interspersed by two intervention periods of 14 days each. The subjects were instructed to chew one gum in the morning and one in the evening containing either two strains of probiotic lactobacilli (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289) or placebo. The outcome measures were (i) organoleptic scores (0-5) by a certified test panel, (ii) concentration of volatile sulphur compounds (VSC) measured with a Halimeter and (iii) concentration of VSC after a cysteine rinse. Registrations were made at baseline and after each intervention period. Differences between the groups were assessed by non-parametric paired statistics and chi-square test. RESULTS: The median organoleptic score was similar (score 2) in both groups at baseline. After 14 days of treatment, the organoleptic scores were significantly lower in the probiotic group compared with the placebo group (p < 0.05). Assessments of the VSC levels displayed no significant differences between the groups, either before or after rinsing with L-cysteine. No adverse effects were registered. CONCLUSION: The results demonstrated that probiotic chewing gums may have some beneficial effect on oral malodour assessed by organoleptic scores. The results indicate that the probiotic gum may affect bacteria that produce malodourous compounds other than VSCs.

Treatment of severe drooling with botulinum toxin in amyotrophic lateral sclerosis and Parkinson's disease: efficacy and possible mechanisms.

OBJECTIVE: Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A). MATERIAL AND METHODS: This open, prospective study deals with treatment of drooling in 12 patients with amyotrophic lateral sclerosis and three with Parkinson's disease. Injections of BTX-A (Botox) were given into the parotid (25-40 units) and submandibular (15-30 units) glands with ultrasonographic guidance. After BTX-A treatment, the patients were followed for 2 months with evaluations every second week by means of self-assessed rating scales for drooling intensity, discomfort and treatment effect, and determination of unstimulated whole saliva (UWS) flow rate, and inorganic and organic UWS composition. The treatment was repeated up to four times, but seven patients dropped out shortly after the first treatment due to marked worsening of their disease-related condition. RESULTS: Drooling and flow were reduced (P < 0.05) 2 weeks after treatment, without side-effects. The maximal reductions during the observation period were 40% for drooling and 30% for flow. There was a systematic variation in flow during the observation period, with an initial decrease and then an increase followed by a second decrease. Amylase activity and total protein concentration generally increased with decreasing flow (P ≤ 0.03). CONCLUSION: Inhibition of acetylcholine release from postganglionic parasympathetic nerve endings by injection of BTX-A into salivary glands seemed useful for secondary sialorrhoea, although cyclic variations in flow may occur, possibly due to transitory sprouting and regeneration.