Effect of Honey-Lime Spray as Add-On Therapy on Chemotherapy-Induced Xerostomia in Breast Cancer Patients: A Pilot Randomized Double-Blinded Controlled Trial.

INTRODUCTION: Xerostomia (dry mouth) is a common side effect among patients with cancer undergoing chemotherapy. There is no standard treatment for this symptom yet, although Persian medicine textbooks suggested some products to relieve xerostomia. We aimed to assess the efficacy of honey-lime spray in treating chemotherapy-induced xerostomia in breast cancer patients through a controlled study. METHODS: In this pilot, randomized, double-blinded clinical trial conducted in Shohadaye Tajrish Hospital, Iran, the intervention group received honey-lime spray and nystatin, while the control group used distilled water plus nystatin for 2 weeks. The six-item dry mouth form and visual analog score (VAS) were used to evaluate xerostomia extent and pain, respectively. RESULTS: The standardized value of the difference between the mean scores before and after the study was -10.21 (p < 0.001), and the effect size was estimated at 55%. Also, VAS showed a significant decrease in pain for the intervention group compared with the control group (p < 0.001). There were no serious side effects. CONCLUSION: Honey-lime spray may be a good treatment choice for xerostomia in chemotherapy-induced breast cancer patients, but robust trials with larger samples and prolonged follow-ups are highly recommended.Mundtrockenheit (Xerostomie) ist eine häufige Nebenwirkung bei Krebspatienten, die sich einer Chemotherapie unterziehen. Es gibt bisher keine Standardtherapie für dieses Symptom, doch Lehrbücher der persischen Medizin schlagen einige Mittel zur Linderung von Mundtrockenheit vor. Unser Ziel war es, die Wirksamkeit von Honig-Limetten-Spray zur Behandlung von chemotherapiebedingter Mundtrockenheit bei Patientinnen mit Brustkrebs im Rahmen einer kontrollierten Studie zu untersuchen.In dieser randomisierten, doppelt verblindeten klinischen Pilotstudie, die im Shohadaye Tajrish Hospital im Iran durchgeführt wurde, erhielt die Interventionsgruppe zwei Wochen lang Honig-Limetten-Spray und Nystatin und die Kontrollgruppe destilliertes Wasser plus Nystatin. Ein Mundtrockenheits-Fragebogen mit sechs Items wurde zur Beurteilung der Schwere der Mundtrockenheit verwendet und eine visuelle Analogskala zur Beurteilung der Schmerzen.Der standardisierte Wert der Differenz zwischen den mittleren Scores vor und nach der Studie betrug −10,21 (p < 0,01), und die geschätzte Effektstärke betrug 55%. Zudem zeigte die VAS eine signifikante Abnahme der Schmerzen in der Interventionsgruppe im Vergleich zur Kontrollgruppe (p < 0,01). Es traten keine schwerwiegenden Nebenwirkungen auf.Honig-Limetten-Spray könnte eine gute Wahl für die Behandlung von Mundtrockenheit bei Brustkrebspatientinnen unter Chemotherapie sein, doch hierzu werden belastbare Studien mit größerem Probenumfang und längerer Nachbeobachtung nachdrücklich empfohlen.

Impact of low-level laser therapy on the quality of life of patients with xerostomia undergoing head and neck radiotherapy: a systematic review.

PURPOSE: To carry out a systematic review to assess whether low-level laser therapy can improve the quality of life of patients with xerostomia undergoing head and neck radiotherapy. METHODS: A systematic search was performed through Embase, Medline/PubMed, Cochrane, Scopus, Web of Science, nonpeer-reviewed clinicaltrials.gov and LILACS. The strategy included clinical studies were selected that prospectively followed or evaluated the quality of life by directly comparing the use of low-level laser therapy for xerostomia induced by head and neck radiotherapy with alternative therapies without the use of a laser. The risk of bias in the studies was assessed by RoB 2.0 and Robins I. RESULTS: After all application of the predetermined criteria, four studies were included, dated between the years 2014 and 2023. Three studies described as randomized clinical trials were included, one of which was a randomized pilot study and only one was a prospective clinical trial. A total of 126 patients were evaluated, all four studies used the infrared wavelength, with two studies using the combination with the red wavelength. It was observed that low-level laser therapy can change the sensation of dry mouth, improving patients' quality of life. In addition, changes related to increased stimulated and unstimulated salivary flow were also identified. CONCLUSION: The use of low-level laser therapy has promising results on xerostomia, consequently improving the quality of life of patients undergoing radiotherapy in the head and neck region.

The Photobiomodulation effect of 980 nm Diode Laser on Patients with Xerostomia.

PURPOSE: Xerostomia is not a disease in itself. This condition is associated with systemic diseases, medication use, and radiotherapy. Oral and general health suffer when the salivary gland´s function is reduced. The effectiveness of therapeutic methods in resolving this issue thus far has been inadequate. This study aimed to determine the photobiomodulation (PBM) effect of a 980 nm laser on xerostomia. METHODS: A quasi-experimental study was carried out using a 980 nm diode laser on 28 patients with xerostomia. A diode laser (980 nm) was used extortionally over the submandibular glands and parotids and it was used internally in the sublingual glands. The laser beam (extrorally 6 J, 300mW, 20 s, and introrally 4 J, 200mW, 20 s) was applied bilaterally every other day for 10 sessions. It should be noted that 8 points of the parotid, 2 points of the submandibular glands, and 2 points of the sublingual glands were irradiated. The saliva was collected each session using the Navazesh technique, 5 min before and after PBM. The Wilcoxon test was used to study the effect of laser therapy on saliva flow rate (volume and weight). The P < 0.05 level was considered a significant level. RESULTS: The volume (P < 0.0001) and the weight (P < 0.0001) of the saliva were increased by using a 980 nm diode laser. While, in smokers and diabetic patients with hypertension, no significant difference was observed in either saliva volume (P = 0.593, P = 0.092) or weight (P = 0.785, P = 0.089). CONCLUSION: In this study, the volume and weight of the unstimulated saliva in most patients with xerostomia increased with using PBM.

Evaluating the Efficacy and Safety of Therapeutic Interventions in Sjögren's Syndrome: A Systematic Review Literature.

In strict accordance with PRISMA 2020 guidelines, our research team conducted a comprehensive systematic literature review (SLR) to explore the treatment and preventive strategies for Sjögren's Syndrome (SS). Leveraging a meticulous search strategy, we scoured reputable databases such as PubMed, PubMed Central, Google Scholar, Web of Science, and The Cochrane Library. Our analysis zeroed in on 10 seminal articles that met our stringent inclusion criteria, providing a holistic view of the existing treatment landscape for SS, along with emerging diagnostic tools and associated biomarkers indicative of lymphoma risk. From a clinical standpoint, our findings unequivocally highlight the detrimental effects of SS on patients' overall well-being. Of particular interest is the growing body of evidence that underscores the effectiveness of natural remedies and over-the-counter supplements rich in antioxidants as viable therapeutic interventions. Contrary to expectations, no single laboratory marker emerged as highly sensitive for the diagnosis of SS. On a promising note, dental implants have been demonstrated to offer lasting benefits with minimal side effects, emphasizing their potential utility in enhancing the oral health of individuals affected by SS. Given the evolving nature of treatment approaches for SS, our review strongly calls for further investigations. Such research endeavors are imperative for validating the effectiveness of these treatment options, whether they serve as primary or preventive care solutions, with the overarching aim of improving the quality of oral health among those suffering from SS.

A New Model of Salivary Pacemaker-A Proof of Concept and First Clinical Use.

Background and Objectives: Saliva is of utmost importance for maintaining oral health. Management of saliva flow rate deficiency recently includes salivary neuro-electrostimulation. The aim of this paper is to present a new model of salivary pacemaker-the MICROSAL device (MD), an intelligent, miniaturized, and implant-supported oral device used for salivary stimulation. Materials and Methods: This report presents the development, calibration, and first clinical tests which involved the MD. The novel features of this device are the pH sensor and the fact that it communicates with the patient's smartphone, where oral wetness and pH are graphically exposed. Saliva samples were taken before and after the MD was used on a 68-year-old patient suffering from post-irradiation xerostomia, and albumin and total protein were analyzed. Results: The device uses up to 3 V and time intervals of 2 s seconds for stimulation. The total volume of all saliva samples collected during the clinical trial was almost seven times higher after the device was used. Albumin decreased from a maximum of 0.15 g/dL to 0.04 g/dL, and total proteins from 0.65 g/dL to 0.21 g/dL, after salivary stimulation. Conclusions: The MD increased saliva secretion of the patient, and we are confident it will be a good solution for future management of salivary gland hypofunction.

Protective Effect of Electroacupuncture on Chemotherapy-Induced Salivary Gland Hypofunction in a Mouse Model.

Radiotherapy and chemotherapy can impair salivary gland (SG) function, which causes xerostomia and exacerbate other side effects of chemotherapy and oral infection, reducing patients' quality of life. This animal study aimed to assess the efficacy of electroacupuncture (EA) as a means of preventing xerostomia induced by 5-fluorouracil (5-FU). A xerostomia mouse model was induced via four tail vein injections of 5-FU (80 mg/kg/dose). EA was performed at LI4 and LI11 for 7 days. The pilocarpine-stimulated salivary flow rate (SFR) and salivary glands weight (SGW) were recorded. Salivary immunoglobulin A (SIgA) and lysozyme were determined via enzyme-linked immunosorbent assay (ELISA). SG was collected for hematoxylin and eosin staining to measure acini number and acinar cell size. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and aquaporin 5 (AQP5) mRNA expressions in SG were quantified via RT-qPCR. 5-FU caused significant decreases in SFR, SGW, SIgA, lysozyme, AQP5 expression, and acini number, while TNF-α and IL-1ß expressions and acinar cell size were significantly increased. EA treatment can prevent 5-FU damage to the salivary gland, while pilocarpine treatment can only elevate SFR and AQP5 expression. These findings provide significant evidence to support the use of EA as an alternative treatment for chemotherapy-induced salivary gland hypofunction and xerostomia.

Effects of the salivary gland massage program in older type 2 diabetes patients on the salivary flow rate, xerostomia, swallowing and oral hygiene: A randomized controlled trial.

AIM: To evaluate the effect of a salivary gland massage program to improve salivary flow, swallowing, and oral hygiene in older type 2 diabetes patients. METHODS: This randomized control trial consisted of 73 older diabetes patients with a low salivary flow; 39 and 34 in intervention and control groups, respectively. The intervention group received a salivary gland massage from a trained dental nurse, whereas the control group received a dental education. The salivary flow rates were collected using spit methods at baseline, 1-month and 3-month follow up. All participants were examined for the objective and subjective symptoms of xerostomia, the Simplified Debris Index and the Repetitive Saliva Swallowing Test. RESULTS: After 3 months, the resting (0.32 vs 0.14 mL/min, P < 0.001) and stimulating salivary flow (3.66 vs 2.83 mL/min, P = 0.025) in the intervention group was significantly higher than the control group. The objective symptoms in the intervention group were significantly lower than the control group after 3 months (1.41 vs 2.26, P = 0.001). The participants who were able to swallow least three times in the Repetitive Saliva Swallowing Test in the intervention group increased by 35.89% after 3 months, whereas the control group increased by 8.82%. Oral hygiene was improved in both groups, but the changes in the intervention were significantly greater than in the control group. CONCLUSIONS: The 3-month salivary glands massage program increases the salivary flow rate, and affects swallowing, objective dry mouth symptoms and oral hygiene in older patients with type 2 diabetes. Geriatr Gerontol Int 2023; 23: 549-557.

Salivary stimulatory effect of novel low level transcutaneous electro neurostimulator in geriatric patients with xerostomia.

BACKGROUND: Xerostomia (dryness of the mouth) is one of the most common long-term consequences of ageing, and it causes a tremendous impact on the function and morphology of the salivary ductal system. As a consequence, it leads to a decrease in the amount of salivary output and also affects the overall quality of life. The purpose of this study was to determine whether electrostimulation using a custom designed transcutaneous electrical nerve stimulation (TENS) device will help to improve the quality of secreted saliva following electrostimulation. METHODS: One hundred thirty-five participants underwent the intervention for three months, twice daily (80 Hz). Pre-intervention and post-intervention unstimulated saliva were collected. Parameters such as salivary pH, cortisol level, salivary antioxidants, total protein, the viscosity of saliva, and microbial carriage were analysed. RESULTS: Salivary pH, cortisol, microbial cultures, viscosity, and antioxidants showed a significant difference at the end of the 3rd month (p < 0.05). Irrespective of the patient's age, gender, and common underlying systemic illnesses (diabetes and hypertension), a significant change in the quality of the salivary analytes was observed. CONCLUSION: The study emphasises the use of a custom designed TENS device in improving the quality of secreted saliva among old patients with oral dryness.

Photobiomodulation for the management of xerostomia and oral mucositis in patients with cancer: a randomized clinical trial.

To evaluate the applicability of photobiomodulation therapy (PBM-T) in the management of xerostomia and OM. Fifty-three patients with head and neck squamous cell carcinoma were randomized into two groups: Sham and PBM-T. The Sham group received artificial saliva and laser simulation, while the PBM-T group received artificial saliva and PBM-T. Xerostomia-related quality of life (QoL), the presence or absence of OM lesions, the decayed-missing-filled teeth (DMFT) index, and periodontal charts were evaluated. The results of the QoL questionnaire, DMFT index, and periodontal chart were analyzed with the Kruskal-Wallis test, followed by the Student-Newman-Keuls test, while OM findings were compared using the Mann-Whitney test. QoL scores significantly increased in the Sham group (p < 0.0001), denoting more severe xerostomia symptoms (p = 0.0074), and decreased in the PBM-T group, indicating no or very mild xerostomia. Higher grades of OM were found in the Sham group than the PBM-T group (p = 0.0001). There was no significant difference in DMFT index or periodontal charts between the groups (p > 0.05). PBM-T improved QoL in patients with head and neck cancer treated with radiotherapy, whether as radiation alone or as an adjunct to chemotherapy and surgery.

Umbrella review: Summary of findings for acupuncture as treatment for radiation-induced xerostomia.

Acupuncture is a common part of complementary medicine. However, traditional Chinese acupuncture has been built on concepts which are not in accordance with science-based medicine. Our aim was to critically assess the evidence presented in systematic reviews (SRs) and meta-analyses (MAs) about the effectiveness of acupuncture on radiotherapy induced xerostomia. A systematic search was conducted in February 2022. We evaluated all SRs/MAs using the AMSTAR-2 instrument. Eight SRs, with 12 controlled studies were included. All SRs summarize that the methodological drawbacks do not allow to give a clear statement about the effectiveness of acupuncture. While objective assessments in most SRs/MAs reported no difference between real and sham acupuncture, some favorable effects on subjective xerostomia symptoms are found. No clinical meaningful effectiveness of acupuncture on xerostomia has been proven so far, but positive subjective findings need to be explored more. While most SRs recommend further studies, studies involving patients with a serious cancer diagnosis are ethically questionable.

Efficacy of auricular acupuncture in improving dry mouth among an institutionalised older population: A randomised controlled study.

AIMS: To investigate the efficacy of applying auricular acupuncture (AA) treatment in improving dry mouth in institution-dwelling older adults. BACKGROUND: Dry mouth (xerostomia) is a common distressing problem in older populations, especially for institution-dwelling older adults that can affect oral health and quality of life. DESIGN: A randomised controlled trial was conducted from December 2020 to March 2021 and performed according to STRICTA guidelines extended from the CONSORT statement. METHODS: Older adults aged more than 65 years were randomly allocated to an AA group (n = 37) with an 8-week actual auricular points treatment or a control group (n = 38) receiving sham auricular point acupuncture. Measurements comprised a subjective assessment of the level of dry mouth as assessed by a visual analogue scale in a xerostomia questionnaire, and an objective assessment of the physiological wetness of the lingual mucosa measured with a moisture-checking device. A generalised estimating equation model was used for data analyses. RESULTS: After completing an 8-week AA intervention stimulating the Shenmen, Point Zero and Salivary Gland 2-prime points, the AA group exhibited significantly improved subjective symptoms of dry mouth comprised of difficulty speaking (B = -6.47, p < .001), difficulty swallowing (B = -6.73, p < .001), the amount of oral saliva (B = -5.38, p < .001), a dry throat (B = -7.53, p < .001) and thirst (B = -8.06, p < .001) compared with the control group. Moreover, the AA group had higher objective oral saliva flow than the control group (B = 4.73, p < .001). CONCLUSION: AA is an effective non-pharmacological method for improving subjective symptoms of dry mouth and objective saliva secretion in older populations living in nursing homes. RELEVANT TO CLINICAL PRACTICE: Performing regular AA on the Shenmen, Point Zero and Salivary Gland 2-prime auricular points can be considered an alternative treatment approach to improve dry mouth in institution-dwelling older adults.

Effect of Sustained Systemic Administration of Ginger (Z officinale) Rhizome Extracts on Salivary Flow in Mice.

OBJECTIVE: This study aimed to evaluate the effect of methanol (70% v/v), ethanol (80% v/v), dimethyl sulfoxide (DMSO; 100% v/v) extracts of ginger rhizome (GR), and 6-shogaol on the pilocarpine-stimulated salivary flow rate in C57BL/6 mice. METHODS: Three extracts of ginger (Zingiber officinale) rhizome prepared by maceration using the respective solvents and 6-shogoal were reconstituted in normal saline with 0.2% DMSO. Thirty C57BL/6 15-week-old mice were divided into 5 groups: Group 1, saline; Group 2, 70% methanol extract; Group 3, 80% ethanol extract; Group 4, 100% DMSO extract; and Group 5, 6-shogaol. The baseline pilocarpine-stimulated salivary flow rate was measured at the age of 15 weeks (15th week), and treatment solutions were administered by intraperitoneal injection from the 16th to 18th week. The stimulated salivary flow rate during treatment weeks was recorded for each group, and its difference with baseline was analysed using paired-sample t test. The change in salivary flow rate between the treatment groups and the control group was analysed using one-way analysis of variance. RESULTS: Groups 2, 3, 4, and 5 showed a significant increase in salivary flow rate when compared to baseline (P < .05). The increase in salivary flow rate in all 4 treatment groups was significant when compared to the control group (P < .05). Group 4 produced the highest increase in salivary flow rate; however, the differences amongst the treatment groups did not reach statistical significance (P > .05). CONCLUSIONS: All GR extracts (70% methanol, 80% ethanol, 100% DMSO) and 6-shogaol were equally effective in increasing the pilocarpine-stimulated salivary flow rate in C57BL/6 mice when administered systemically as a sustained dose for 3 weeks.

Effect of recombinant human thyroid stimulating hormone on long-term salivary gland dysfunction in thyroid cancer patients treated with radioactive iodine. A systematic review.

Adjuvant radioactive iodine (RAI) is administered to thyroid cancer patients following thyroidectomy for remnant tissue ablation and metastatic disease management. Patients are prepared with thyroid hormone withdrawal (THW) or recombinant human thyroid stimulating hormone (rhTSH). Long-term salivary gland dysfunction (LT-SGD) is a common, dosage-dependent, RAI adverse effect. Although rhTSH preparation seems to reduce LT-SGD, this effect could be due to lower RAI activity generally used in rhTSH-prepared patients. Therefore, this meta-analysis investigated the effect of preparation type on LT-SGD development. Literature search (PubMed, Medline, EmBase, Cochrane, Web of Science, LILACS, Google Scholar) was performed four times (January-November 2022) and studies reporting LT-SGD incidence ≥1 year after RAI in patients prepared with rhTSH/THW were identified. The LT-SGD risk ratio (RR) was estimated with various models considered for sensitivity analysis (fixed-effect, random-effects, study-quality adjusted, publication-bias adjusted, individual-patient-data meta-analysis adjusted for RAI). Subgroup analysis according to RAI activity (<3.7/≥3.7 GBq) also was performed. Literature search resulted in five studies (321 rhTSH, 632 THW patients). The pooled RRs according to various models were 0.65 (95% confidence interval -95CI, 0.49-0.86; fixed-effect); 0.62 (95CI, 0.38-1.02; random-effects); 0.72 (95CI, 0.54-0.96; quality adjusted); 0.76 (95CI, 0.58-0.99; publication-bias adjusted); 0.0.80 (95CI, 0.55-1.14; individual-patient-data meta-analysis). The pooled RRs stratified for RAI activity were 0.26 (95CI, 0.05-1.30) for <3.7 GBq; 0.75 (95CI, 0.57-0.98) for ≥3.7 GBq. The number of patients needed to be prepared with rhTSH to prevent one case of LT-SGD ranged between seven and thirty-seven. There is moderate-quality scientific evidence that rhTSH preparation may consistently protect salivary gland function.

Exploring the Target and Mechanism of Radix Paeoniae Alba on Sjogren's Syndrome.

BACKGROUND: Radix Paeoniae Alba is a traditional Chinese herbal medicine. It can accelerate salivary secretion and alleviate the dry mouth of patients with Sjogren's syndrome (SS). Although it is widely used in clinical treatment, its target and mechanism remain unclear. OBJECTIVE: This study aims to analyze the main components of Radix Paeoniae Alba, explore the target genes, and propose the possible mechanism for Radix Paeoniae Alba's acceleration of salivary secretion. METHODS: The main active components and potential targets of Radix Paeoniae Alba were searched through the TCMSP database. Efforts were made to search for the related genes of Sjogren's syndrome in OMIM and GeneCards databases. Cytoscape v3.8.0 software was used to link target genes of active components and key genes of the disease. The software Autodock vina1.1.2. was adopted to simulate the interaction between active components and target genes. Human submandibular gland (HSG) cells were used in vitro experiments to verify the results of our analysis. RESULTS: ß-Sitosterol, the main component of Radix Paeoniae Alba, may intervene in the disease through CHRM3. Molecular docking shows ß-Sitosterol has a high affinity with CHRM3, and the interaction between CHRM3 and ß-Sitosterol is the basis of biological activity. The in vitro experiments showed that ß-Sitosterol could significantly up-regulate the mRNA and protein expression levels of both CHRM3 and secretion-related genes in HSG cells. CONCLUSION: Our study shows that the chemical components of Radix Paeoniae Alba have a positive effect on the related mechanism of salivary secretion. We found that ß-Sitosterol can promote the expression of CHRM3, stimulate salivary secretion, treat Sjogren's syndrome and potentially improve its prognosis.

Prevention of salivary gland dysfunction in patients treated with radioiodine for differentiated thyroid cancer: A systematic review of randomized controlled trials.

Introduction: Salivary gland dysfunction (e.g., sialadenitis and xerostomia) is the most common complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC). Several methods have been used to reduce/prevent this adverse effect. We aimed to systematically review the effectiveness of non-pharmacological and pharmacological interventions in preventing RAI-induced salivary gland dysfunction in patients with DTC. Methods: A systematic review was conducted, according to PRISMA guidelines. The protocol was registered (PROSPERO: CRD42022295229). PubMed, Embase, Scopus, and the Cochrane Library electronic databases were searched from inception to November 2021. Inclusion criteria were randomized controlled trials of DTC patients who were older than 18 years and underwent RAI after thyroidectomy in which at least one studied group received an intervention to prevent salivary gland dysfunction. Results: Twelve studies (a total of 667 participants) were included. Among DTC patients who were treated with RAI, nonpharmacological treatment such as parotid gland massage and aromatherapy ameliorated salivary gland dysfunction. Antioxidants such as vitamin E and selenium demonstrated radioprotective effects on the salivary gland, while other antioxidants did not show radioprotective benefits. Vitamin C showed no significant effects on preventing salivary gland dysfunction. Amifostine had inconsistent outcomes among studies. Among cholinergic agonists, pilocarpine did not demonstrate the radioprotective effect on parotid glands, while bethanechol lowered salivary gland dysfunction. However, the negative results from pilocarpine may be explained by the strong sialorrheic effect of the Cincinnati regimen in both study arms. Conclusion: Among non-pharmacological and pharmacological methods, parotid gland massage, aromatherapy, vitamin E, selenium, amifostine, and bethanechol may have benefits in minimizing RAI-induced salivary gland dysfunction in patients with DTC. The results are limited by a small number of patients and should be confirmed in future larger randomized controlled trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=295229, PROSPERO, identifier CRD42022295229.

Resveratrol alleviates salivary gland dysfunction induced by ovariectomy in rats.

Resveratrol (Res), found abundant in many medicinal plants, exerts multiple biological functions in the body, including anti-inflammatory, antioxidant, and anti-aging properties. Xerostomia is a major symptom of salivary gland dysfunction in menopausal women, which significantly compromises the quality of life. Here, we investigated the effect of Res on estrogen deficiency-induced salivary gland dysfunction in rats. We found that Res administration could reduce body weight and water consumption, and increase salivary fluid secretion and blood flow of the submandibular gland. Furthermore, Res therapy alleviated histological lesions, increased AQP5 expression, and inhibited cell apoptosis in submandibular gland tissue. Meanwhile, the action of antioxidants was restored and the levels of inflammatory cytokines were attenuated by Res supplementation. Collectively, Res effectively improved estrogen deficiency-induced hyposalivation, which may provide a novel, safe, and practical approach to protect the salivary glands of estrogen-deficient females against xerostomia.

Cross-Cultural Brain Activity Differences Between True and Sham Acupuncture for Xerostomia During Head and Neck Cancer Radiotherapy.

BACKGROUND: A prior phase III, multicenter (United States and China), clinical trial found true acupuncture (TA) resulted in lower xerostomia scores 12 months after radiotherapy than that of a standard care control group. This small pilot study examined brain function changes comparing TA to sham acupuncture (SA) in US and Fudan patients undergoing head and neck radiotherapy. METHODS: To determine cerebral activity during TA versus SA acupuncture, patients underwent electroencephalogram evaluation (EEG) immediately prior, during and after both conditions. Acupuncture occurred during weeks 3 to 5 of radiotherapy, with patients receiving either TA or SA, followed 2 to 3 days later by the other treatment in a counterbalanced manner. RESULTS: In the TA minus SA condition (N = 14 Fudan; N = 13 US), most changes were in the delta (0.5-3.5 Hz) and alpha (8-12 Hz) bandwidths. Delta was present in the frontal gyrus and parahippocampal gyrus. Alpha was present in the anterior and posterior cingulate, lingual gyrus, amygdala, precuneus, medial frontal gyrus, fusiform gyrus, and superior frontal gyrus. Maximal cortical differences in the Fudan cohort between TA and SA were in areas previously shown to be associated with (TA). In the US cohort, maximal differences between TA and SA were associated with areas which are usually decreased in TA conditions. CONCLUSIONS: There were distinct differences in brain function between those receiving TA and SA and there were clear differences between cultures, helping to explain the lack of placebo effect in the Fudan participants and strong placebo effect in the US patients.

Análise comparativa do tratamento do ardor bucal com terapia a laser de baixa intensidade e estimulação elétrica nervosa transcutânea: um ensaio clínico randomizado / Comparative analysis of the treatment of burning mouth with low-intensity laser therapy and transcutaneous electrical nerve stimulation: a randomized clinical trial

Introdução: O manejo de pacientes com ardor bucal é um desafio no cotidiano clínico da odontologia. Objetivo: Comparar o efeito da Terapia a Laser de Baixa Intensidade (LLLT) e da Estimulação Elétrica Nervosa Transcutânea (TENS) no tratamento do ardor bucal. Metodologia: Ensaio clínico randomizado constituído por 25 pacientes com ardor bucal que foram tratados por TENS (n=12) e por LLLT (n=13). Os protocolos de tratamento foram aplicados semanalmente por 8 semanas. O teste análise de variância (ANOVA) dois fatores foi usado para verificar se existia diferença significativa entre os tempos T0 (antes de iniciar o tratamento), T1 (após a 4ª sessão de tratamento), T2 (após a 8ª sessão de tratamento) e T3 (30 dias após o término do tratamento) em relação aos sintomas, analisados por meio da Escala Visual Analógica (EVA), fluxo salivar não estimulado, xerostomia e disgeusia com as intervenções de TENS e LLLT. Resultados: A maioria dos pacientes foi do sexo feminino no período pós-menopausa com média de idade no grupo TENS de 59,25 anos e no grupo LLLT de 62,08. Hipertensão e dislipidemia foram as alterações sistêmicas mais frequentes. Ansiedade e depressão foram os únicos transtornos psiquiátricos relados. A maioria dos pacientes fazia uso de medicamentos como anti-hipertensivos e antidepressivos. Não foram observadas variações expressivas no que se refere a xerostomia e a disgeusia nos dois grupos analisados. A TENS e a LLLT foram eficazes na redução dos sintomas relatados pelos pacientes (p˂0,001), entretanto, observou-se entre os tempos T2 e T3 que o grupo LLLT apresentou uma melhor resposta quando comparado ao TENS (p=0,003). Os pacientes do grupo TENS apresentaram aumento do fluxo salivar entre os tempos T1 e T2, enquanto o grupo LLLT apresentou uma diminuição (p=0,052). Conclusão: A TENS e a LLLT foram eficazes na redução dos sintomas do ardor bucal durante o tratamento e 30 dias após o término do tratamento, sendo que o grupo LLLT apresentou uma melhor resposta na sessão de acompanhamento pós-tratamento quando comparado ao grupo TENS (AU).

Introduction: The management of patients with burning mouth is a challenge in the clinical routine of dentistry. Objective: To compare the effect of Low Intensity Laser Therapy (LLLT) and Transcutaneous Electrical Nerve Stimulation (TENS) in the treatment of burning mouth. Methodology: Randomized clinical trial consisting of 25 patients with burning mouth who were treated with TENS (n=12) and LLLT (n=13). Treatment protocols were applied weekly for 8 weeks. The two-way analysis of variance (ANOVA) test was used to verify whether there was a significant difference between the times T0 (before starting treatment), T1 (after the 4th treatment session), T2 (after the 8th treatment session) and T3 (30 days after the end of treatment) in relation to symptoms, analyzed using the Visual Analogue Scale (VAS), unstimulated salivary flow, xerostomia and dysgeusia with TENS and LLLT interventions. Results: Most patients were female in the postmenopausal period, with a mean age of 59.25 years in the TENS group and 62.08 in the LLLT group. Hypertension and dyslipidemia were the most frequent systemic alterations. Anxiety and depression were the only psychiatric disorders reported. Most patients used drugs such as antihypertensives and antidepressants. Significant variations were not observed with regard to xerostomia and dysgeusia in the two groups analyzed. TENS and LLLT were effective in reducing the symptoms reported by patients (p˂0.001), however, it was observed between times T2 and T3 that the LLLT group showed a better response when compared to TENS (p=0.003). Patients in the TENS group showed an increase in salivary flow between times T1 and T2, while the LLLT group showed a decrease (p=0.052). Conclusion: TENS and LLLT were effective in reducing the symptoms of burning mouth during treatment and 30 days after the end of treatment, and the LLLT group showed a better response in the posttreatment follow-up session when compared to the TENS group (AU).

Apigenin, a Single Active Component of Herbal Extract, Alleviates Xerostomia via ERα-Mediated Upregulation of AQP5 Activation.

Xerostomia is a common symptom in menopausal women, suggesting the role of sex steroids in disease development. Shreds of literature had reported the potential use of herbal extracts to relieve xerostomia. However, a cocktail of multiple components in herbal extract makes it difficult to understand the exact mechanism of action. Aquaporin5 (AQP5), the specific aquaporin expressed in salivary glands, plays an important role in salivary secretion as a downstream of estrogen signaling. In this study, we aimed to unravel a single active herbal component as a therapeutic for xerostomia and investigate its mechanism of action. The effects of apigenin (flavonoid), dauricine (alkaloids), protopine (alkaloids), and lentinan (polysaccharides) on AQP5 transcription were screened in vitro. Only apigenin robustly induced AQP5 transcription and expression, and this effect was even robust compared to the effect of estradiol (E2, a positive control). Overexpression of estrogen receptor α (ERα) in the human salivary gland cell line (HSG) upregulated the AQP5 transcription and expression and the knockdown ERα reversed this effect, suggesting the role of ERα signaling on AQP5 activation in HSG cells. Docking results showed apigenin-specific binding sites in ERα. We further analyzed the therapeutic effect of apigenin on ovariectomized mice as a xerostomia model. The saliva secretion in the xerostomia group was reduced to one-third of the sham group, whereas the apigenin or E2 treatment for 12 weeks reversed this effect. Meanwhile, the water consumption in the xerostomia group was augmented obviously compared to the sham group, whereas the water consumption in the apigenin and E2 group was declined to the level of the sham group. Immunohistochemistry of submandibular glands revealed the downregulation of AQP5 expression in xerostomia mice compared to control. Apigenin, or E2 treatment, upregulated AQP5 expression in xerostomia mice. In conclusion, apigenin, a single active component of herbal extract, upregulated AQP5 expression in HSG cells via activation of ERα signaling and restored saliva flow rates in OVX mice. These results revealed apigenin as a single active component of herbal extract with the potential to treat xerostomia.

Sjogren's syndrome-An interesting case.

OBJECTIVE: To present a case of Sjogren syndrome with pulmonary manifestations in an adult female and discuss its assessment and management. DESIGN: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: A 50 yrs female admitted with complaints of dryness of eyes with decreased salivation causing difficulty in swallowing since last 3 years, with persistent dry cough since 10-15 days and progressive dyspnea since 4-5 days. Anti-nuclear antibody (ANA) profile revealed Anti- Ro/SS-A and Anti- La/SS-B Positive. Also, sub-lingual excisional biopsy was done which was consistent with findings of Sjogren's syndrome. Patient showed significant improvement after starting oral glucocorticoids, systemic anti inflammatory agents (Tab. HCQS), artificial tear drops, oral iron supplements and other supportive treatment. CONCLUSION: Sjögren syndrome (SS) is a chronic inflammatory disorder characterized by diminished lacrimal and salivary gland function and associated with lymphocytic infiltration of exocrine glands, and can affect extraglandular organ systems including the skin, lung, heart, kidney, neural, and hematopoietic systems. We present a case of Sjogren syndrome in an adult female presenting with xerostomia and dyspnea and was diagnosed upon detection of anti-Ro and anti-La antibodies and confirmed by histopathological examination of lip biopsy. Patient was started on oral steroids and other supportive treatment, General condition improved significantly and is doing very well on regular follow-up.