Evaluation of photobiomodulation in the salivary production of patients with hyposalivation induced by antihypertensive drugs - A blind, randomized, controlled clinical trial.

BACKGROUND: Arterial hypertension is a systemic condition that affects about 35% of the world population. The drugs that are used for its control can produce hyposalivation. This work evaluated the effect of photobiomodulation on salivary flow rate, salivary pH, total protein concentration, and calcium concentration in individuals using antihypertensive medications. MATERIAL AND METHODS: 41 subjects were randomly allocated in one of two groups: control (placebo) and photobiomodulation. The subjects had their salivary glands (20 sites) irradiated with a laser emitting at 808 nm, 4J/site once a week for 4 weeks and had their salivary flow measured before and after the whole treatment. RESULTS: The intragroup analysis (before and after treatment) shows a significant difference for both non-stimulated and stimulated salivary flow in the photobiomodulation group (p = 0.0007 and p = 0.0001, respectively). Comparing the placebo with the photobiomodulation group, significant differences were found for both non-stimulated (p = 0.0441) and stimulated salivary flow (p = 0.0441) after the treatment. No significant differences were found in pH, total protein concentration, calcium concentration. CONCLUSION: Despite the usage of drugs that influence the nervous system and typically result in a reduction of saliva production, photobiomodulation demonstrated a remarkable ability to enhance saliva production by a significant 75%.

The effect of selenium supplementation on sonographic findings of salivary glands in papillary thyroid cancer (PTC) patients treated with radioactive iodine: study protocol for a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted. METHODS: This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation. DISCUSSION: Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 µg/day, it has not had any significant side effects in many types of cancer under radiation therapy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021.

Effects of low-level light therapy on xerostomia related to hyposalivation: a systematic review and meta-analysis of clinical trials.

Hyposalivation is a condition represented by a reduced salivary flow and may include symptoms such as mouth dryness (xerostomia), loss of taste, pain, dysphagia, and dysphonia, all of which greatly affect an individual's quality of life.The aim of the present study was to systematically review the effects of low-level light therapy irradiation (photobiomodulation) on salivary gland function in patients with hyposalivation.The main question of the systematic review was: "Does low-level light irradiation therapy of the salivary glands affect salivary flow rate or indicators of salivary function (ion and protein concentrations) in patients with xerostomia or hyposalivation?" The question was based on the PICO (participant, intervention, control, outcome) principle and followed the PRISMA guidelines. Databases were explored and papers published between the years 1997 and 2020 were reviewed for the following Mesh-term keywords and their corresponding entry terms in different combinations: "Low-level light therapy," "Xerostomia," "Saliva," "Salivary glands," "Salivation."The initial sample consisted of 220 articles. Of those, 47 articles were used for full-text analysis and 18 were used for a systematic review, 14 were used in meta-analysis. According to their individual quality, most articles were classified as high quality of evidence according to the GRADE score. Meta-analysis of the evidence observed increase of unstimulated salivary flow 0.51 SMD compared to placebo (95% CI: 0.16-0.86), I2 = 50%, p = 0.005.The findings of our review revealed evidence of a beneficial effect of photobiomodulation therapy on salivary gland function. The therapy alleviates xerostomia and hyposalivation. However, these effects are reported short term only and did not induce lasting effects of photobiomodulation therapy on patients' quality of life.

Research status and prospects of acupuncture for prevention and treatment of chemo- and radiotherapy-induced salivary gland dysfunction in head and neck cancer.

Salivary gland dysfunction (SGD) induced by chemo- and radiotherapy for head and neck cancer (HNC) has always been a difficult problem in modern medicine. The quality of life of a large number of HNC patients is severely impaired by SGD such as xerostomia and dysphagia. In recent years, several studies have found that acupuncture can improve patients' salivary secretion, but it has not yet been approved as an alternative therapy for SGD. For this reason, we collected the clinical study reports on acupuncture in the treatment of SGD induced by chemo- and radiotherapy in HNC patients in the past 20 years, and analyzed and discussed the advantages and disadvantages of these studies with respect to tumor types, group setting, intervention modality, acupoints selection, outcome evaluation, and safety. We believed that acupuncture is beneficial for SGD, but the existing objective evidence is insufficient to support its effectiveness. Therefore, improving the Standards for Reporting Interventions in Clinical Trials of Acupuncture, selecting the optimal combination of acupoints through scientific and rigorous study design, and exploring the potential mechanism of acupuncture in the treatment of diseases combined with the meridian theory may be effective ways to promote the acceptance of acupuncture as an alternative therapy for SGD in future. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of SGD in future from the perspective of the combination of modern medicine and traditional Chinese medicine.

Effects of photobiomodulation in salivary glands of chronic kidney disease patients on hemodialysis.

This randomized placebo-controlled trial evaluates the impact of photobiomodulation (PBMT) on the salivary flow and biochemistry of patients with chronic kidney disease (CKD) on hemodialysis. Forty-four patients on hemodialysis self-responded two questionnaires for oral health and salivary gland function perception. The subjects were evaluated for function of salivary glands and randomly allocated to two groups: PBMT group (three irradiations at 808 nm, 100 mW, 142 J/cm2, and 4 J per site); and placebo group. Patients were submitted to non-stimulated and stimulated sialometry and after the treatment at baseline and 14 days. Salivary volume and biochemical of the saliva were analyzed. At baseline, most subjects had self-perception of poor oral health (52.6%) and salivary dysfunction (63.1%). Clinical exam revealed that 47.3% of subjects presented dry mucosa. PBMT promoted increase of the non-stimulated (p = 0.027) and stimulated saliva (p = 0.014) and decrease of urea levels in both non-stimulated (p = 0.0001) and stimulated saliva (p = 0.0001). No alteration was detected in total proteins and calcium analysis. Patients with kidney disease can present alteration in flow, concentrations, and composition of saliva, affecting oral health, but our findings suggest that PBMT is effective to improve hyposalivation and urea levels in saliva of patients with CKD.

Development of a functional salivary gland tissue chip with potential for high-content drug screening.

Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

MnTnBuOE-2-PyP treatment protects from radioactive iodine (I-131) treatment-related side effects in thyroid cancer.

Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085-0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.

Photobiomodulation and salivary glands: a systematic review.

To date, there is no compilation of evidence-based information associating photobiomodulation effect and salivary glands. This systematic review aims to assess photobiomodulation effect of low intensity laser on salivary glands in the presence of systemic diseases. MEDLINE databases were searched in duplicate through December 2018. In vivo studies and clinical trials were included if photobiomodulation was performed in salivary glands of animal (rat or mice) or human in the presence of systemic disease. The methodological quality was assessed in duplicate using the modified Newcastle-Ottawa scale (NOS). Search strategy identified 483 potentially eligible articles, and 449 were included. The Boolean search naturally leads to a high amount of works the majority of which were excluded because the analysis of the title and abstract demonstrated it was not focusing on PBM. Only 34 studies were selected for the full-text analysis, of which 5 were excluded due to non-use of photobiomodulation, 4 due to lack of control group, 2 because they were studies of cell cultures and 1 because they did not have the total of animals used. Thus, 21 papers were included for the critical evaluation of the impact of photobiomodulation on the major salivary glands; the studies used rats (n = 10) and humans (n = 11). Although studies reported an increase in the salivary rate, decrease in pain, and increase in quality of life after the PBM, the lack of standards for the application of light and reporting of the parameters, make it hard to reproduce the results. This topic is still in need for further research.

The impact of photobiomodulation of major salivary glands on caries risk.

Dental caries is a complex multifactorial chronic infectious disease guided by several risk or protective factors. Saliva has an important role in caries and the remineralization process. Caries risk assessment is defined as the probability of new caries lesion development or the existing lesion progression in a given time period. Caries diagnostics and risk factor assessment are followed by targeted elimination of risk factors and less conservative but abundant preventive therapeutic measures. The aim of our prospective randomized study was to elucidate on how photobiomodulation of major salivary glands with polychromatic light or LED light affects caries risk factors in high caries-risk patients. Thirty-six patients were assigned to one of the following three experimental groups: the first, irradiated with polarized polychromatic light (40 mW/cm2, wavelengths 480-3400 nm); the second, a continuous LED light (16 mW/cm2, wavelengths 625, 660, 850 nm); the third, same LED light in a pulsed mode. The fourth group was the control, for which a non-therapeutic visible light was used. Light was administered extra-orally bilaterally above the parotid and submandibular glands for 10 min and intra-orally above the sublingual glands for 5 min, 3 times a week, for 4 consecutive weeks. Each patient's caries risk was assessed according to Cariogram before and after therapy. Caries risk factors were determined from samples of saliva before therapy, two weeks after it commenced, at the end of therapy, and four weeks after the end of therapy. At the end of treatment, the following findings were obtained: In the group irradiated with polarized polychromatic light and in the group irradiated with continuous LED light, the Streptococcus mutans and Lactobacillus counts decreased and salivary buffering capacity increased (p < 0.05). In the group irradiated with pulsed LED light, Streptococcus mutans counts decreased and unstimulated salivary flow and salivary buffering capacity increased (p < 0.05). In all three experimental groups, caries risk was lower (p < 0.05). In the placebo control group, there were no statistically significant differences between parameters before and after therapy. We concluded that photobiomodulation of major salivary glands in high caries-risk patients can reduce the cariogenic bacteria in saliva and improve some salivary parameters, thus reducing caries risk.

The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer: A Randomized Clinical Trial.

PURPOSE: To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after I therapy. MATERIALS AND METHODS: One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after I therapy, and the SGSs were also taken just before and at 8 months after the I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups. RESULTS: The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P = 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704; P = 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial = -0.2741, P = 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the I therapy, and I dose). CONCLUSIONS: PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to I therapy.

In vitro biological response of cancer and normal tissue cells to proton irradiation not affected by an added magnetic field.

To optimize beam delivery and conformality of proton therapy, MRI integration has been proposed. Therefore, we investigated if proton irradiation in a magnetic field would change biological responses. Our data in cancer cell lines and stem cell-derived organoid models suggest that a magnetic field does not modify the biological response.

Protective Effect of Whortleberry Extract on Salivary Gland Damage Induced by Neck Irradiation in Rats.

Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased (P < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.

Effect of photobiomodulation on the severity of oral mucositis and molecular changes in head and neck cancer patients undergoing radiotherapy: a study protocol for a cost-effectiveness randomized clinical trial.

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.

Monosodium Glutamate Reduces 68Ga-PSMA-11 Uptake in Salivary Glands and Kidneys in a Preclinical Prostate Cancer Model.

We evaluated the ability of monosodium glutamate (MSG) to reduce salivary and kidney uptake of a prostate-specific membrane antigen (PSMA) radioligand without affecting tumor uptake. Methods: LNCaP tumor-bearing mice were intraperitoneally injected with MSG (657, 329, or 164 mg/kg) or phosphate-buffered saline (PBS). Fifteen minutes later, the mice were intravenously administered 68Ga-PSMA-11. PET/CT imaging and biodistribution studies were performed 1 h after administration. Results: Tumor uptake (percentage injected dose per gram [%ID]) was not statistically different between groups, at 8.42 ± 1.40 %ID in the 657 mg/kg group, 7.19 ± 0.86 %ID in the 329 mg/kg group, 8.20 ± 2.44 %ID in the 164 mg/kg group, and 8.67 ± 1.97 %ID in the PBS group. Kidney uptake was significantly lower in the 657 mg/kg group (85.8 ± 24.2 %ID) than in the 329 mg/kg (159 ± 26.2 %ID), 164 mg/kg (211 ± 27.4 %ID), and PBS groups (182 ± 33.5 %ID) (P < 0.001). Salivary gland uptake was lower in the 657 mg/kg (3.72 ± 2.12 %ID) and 329 mg/kg (5.74 ± 0.62 %ID) groups than in the PBS group (10.04 ± 2.52 %ID) (P < 0.01). Conclusion: MSG decreased salivary and kidney uptake of 68Ga-PSMA-11 in a dose-dependent manner, whereas tumor uptake was unaffected.

Transcutaneous Electrical Nerve Stimulation (TENS) on hyposalivation induced by radiotherapy in the head and neck region: a preliminary study. / Efeito agudo da Transcutaneous Electric Nerve Stimulation (TENS) sobre a hipossalivação induzida pela radioterapia na região de cabeça e pescoço: um estudo preliminar.

PURPOSE: To verify the acute effect of electrostimulation on the salivary flow of patients with hyposalivation. METHODS: Uncontrolled clinical trial evaluating 15 patients with hyposalivation induced by radiotherapy (RT) used for head and neck cancer treatment. Mean age of the patients was 56.8 ± 6.46 years. Males outnumbered females (73%). Transcutaneous Electrical Nerve Stimulation (TENS) was adjusted with 50Hz of frequency and 250µs of pulse width. Intensity was adjusted over a 20-minute period according to maximum tolerance. The electrodes were attached bilaterally on the region of the salivary glands. Evaluation of the salivary flow was performed through sialometry before and immediately after application of TENS. RESULTS: The most prevalent region for RT was the oropharynx (80.0% of cases). The mean dose used in RT was 64.6 ± 7.27 Gy. After TENS, salivary flow increased significantly (p = 0.0051) from 0.05 (0.00; 0.40) mL/min to 0.10 (0.07: 0.40) mL/min. The response to TENS was directly correlated with the intensity of the tolerated electric current (r = 0.553; p = 0.032) and the dose used in RT (r = -0.514; p = 0.050). CONCLUSION: TENS was able to increase the salivary flow rate of patients with RT-induced hyposalivation.

OBJETIVO: Verificar o efeito agudo da eletroestimulação sobre o fluxo salivar de pacientes com hipossalivação. MÉTODO: Ensaio clínico não controlado que avaliou o efeito de uma única aplicação da Transcutaneous Electric Nerve Stimulation (TENS) sobre o fluxo salivar de 15 pacientes com hipossalivação induzida por radioterapia (RT), utilizada no tratamento de câncer de cabeça e pescoço. A média de idade dos pacientes foi de 56,8 ± 6,46 anos e o gênero masculino foi predominante (73%). A TENS foi programada com 50Hz de frequência, 250µs de largura de pulso e a intensidade foi ajustada ao longo dos 20 minutos conforme máxima tolerância. Os eletrodos foram fixados bilateralmente sobre a região das glândulas salivares. A avaliação do fluxo salivar foi realizada por meio de sialometria estimulada, antes e imediatamente após a aplicação da TENS. RESULTADOS: Em 80% dos casos, o tratamento oncológico incluiu quimioterapia. A RT foi aplicada em 80% dos casos na região e orofaringe, com intensidade média de 64,6 ± 7,27 Gy. Após a TENS, o fluxo salivar aumentou significativamente (p = 0,0051), passando de 0,05 (0,00; 0,40) mL/min para 0,10 (0,07;0,40) mL/min. A resposta à TENS foi diretamente correlacionada à intensidade da corrente elétrica tolerada (r = 0,553; p = 0,032) e à dose utilizada na RT (r = -0,514; p = 0,050). CONCLUSÃO: A TENS aumentou significativamente o fluxo salivar de pacientes com hipossalivação induzida pela RT.

Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes.

Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1-/- adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.

Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca2+ overload and ER stress during hyperglycemia.

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm2) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm2) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation.

Use of low-level laser therapy on children aged 1 to 5 years with energy-protein malnutrition: A clinical trial.

BACKGROUND: Episodes of malnutrition in early childhood can produces alterations in the salivary glands. The investigation of mechanisms that can reduce the impact of malnutrition on the defenses of the organism is of the utmost important and interest to public health. The aim of this study is to evaluate the effect of low-level laser on the saliva of children aged 1 to 5 years with energy-protein malnutrition. METHODS: Mandatory inclusion criteria are diagnosis of malnutrition. The sample will consist of 50 men and women malnourished children aged 12 to 71 months. Saliva will be collected and the volume of saliva will be measured and the salivary flow rate will be determined (mL/min). Concentrations of salivary IgA in all samples will be measured using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Low-level laser (laser diode) will be administered in the region of the parotid glands bilaterally as well as in the regions of the submandibular and sublingual glands. DISCUSSION: This study will be the first that investigate the effects of local laser therapy on the salivary glands of malnourished children. TRIAL REGISTRATION: Clinical.trials.gov as NCT03355313, first received in 21 November 2017.

Differentiated thyroid cancer and selenium supplements for protection of salivary glands from 131I treatment.

Dear Editor, I read with great interest the article by Son et al about the radioprotective effect of selenium (Se) supplementation for the salivary glands from 131I treatment in patients with differentiated thyroid cancer (DTC). In this study, 8 patients received 300µg of Se (as inorganic sodium selenite; selenase®) orally for 10 days, 3 days before to 6 days after 131I treatment. On the occasion of the use of Se among these patients, I want with this letter to remind the differences among the prescribed Se supplements in clinical practice, such as the possible health consequences of Brazil nut consumption as another choice for the preparation of DTC patients for radioactive iodine (RAI) therapy. Selenium is an essential element with many pleiotropic effects that can be found in foods and supplements in organic form (as selenomethionine, selenocysteine, γ-glutamyl-Se-methylselenocysteine) or/and in inorganic form (as sodium selenate and sodium selenite). Selenium in multivitamin/multimineral supplements or in a stand-alone supplement is often available in the forms of L-selenomethionine, Se-enriched yeast (grown in a high-Se medium), mustard seed-derived Se, or as sodium selenite or sodium selenate. Because these two (organic and inorganic) forms of Se are absorbed and metabolized differently, it is very important for the physicians, when prescribe a Se supplement, to know the contained form of Se. Inorganic forms of Se are easily absorbed through the intestine but poorly retained. Once they reach the blood, inorganic Se is quickly filtered out by the kidneys and excreted in the urine. So, the consumption of supplements with inorganic forms of Se does not offer the maximum health benefits of the element. Conversely, Se-containing amino acids, such as selenomethionine and selenocysteine, are introduced directly into proteins, including muscle proteins. These organic proteins-bound Se (selenoproteins) are better retained, utilized, and incorporated by the human body. About 90% of the received selenomethionine is actually absorbed in the intestinal tract, and about half of that remains in the body. The higher degree of absorption of selenomethionine against selenite was described in a recently published systematic review and meta-analysis by Wichman et al. In this review, a significant decrease in serum thyroid peroxidase antibodies (TPO-Ab) levels was found among patients receiving 200µg selenomethionine, but not among those receiving 200µg sodium selenite. In another investigation, 10 groups of Se-replete subjects were randomly assigned to receive a placebo or either 200 or 400 or 600µg/day Se as selenomethionine, sodium selenite, or high-selenium yeast (in which an estimated 75% of Se was in the form of selenomethionine) for 16 weeks. Selenium bioavailability, based on urinary excretion, was greatest for selenomethionine and lowest for selenite. However, supplementation with any of these forms only affected plasma Se levels and not glutathione peroxidase activity or selenoprotein P concentration, suggesting that study participants were selenium replete before they began taking Se supplements. Because the absorption of selenite was approximately two-thirds of the absorption of selenomethionine in this study, we can assume that the daily dose of 300µg of sodium selenite in the study of Son et al corresponded to 200µg of selenomethionine which is the most frequently used dose in intervention trials. However, in our opinion, the prescription of supplements with organic forms of Se must be preferred, when required. It is also worth mentioning that the prescribed Se supplements should not contain iodine considering that for a successful RAI therapy after thyroidectomy, DTC patients must, not only increase their thyroid-stimulating hormone (TSH) levels, but also deplete the whole body iodine pool through a low-iodine diet (low-quality evidence). One of the richest known food sources of bioavailable Se, in the organic form of selenomethionine, are the Brazil nuts. Brazil nuts grow on massive tropical trees, the Bertholletia excelsa of the Lecythidaceae family, some reaching heights over 45m. The average Se content of each Brazil nut in most elemental analyses varies ranging from 2.7 to 11µg Se/g, and the average weight of each nut varies between 3 and 4 g. Their consumption can increase the likelihood of Se toxicity, regardless of the quantity of the nuts consumed, and thus is not be a safe dietary choice. Moreover, Brazil nuts may be infected externally by aflatoxins or can trigger allergic reactions in sensitive people. However, raw Brazil nuts don't contain iodine and thus their consumption would not undermine the dietary efforts of DTC patient in the framework of the required low-iodine diet. The consumption of 2-3 unshelled and raw (unsalted) Brazil nuts daily could be another choice for the post-thyroidectomy period up to 10 days after RAI therapy among DTC patients who do not want to receive supplements as source of Se. We must emphasize that some patients having DTC and also Hashimoto's thyroiditis may had previously received Se supplements or Brazil nuts for a long period of time before DTC was diagnosed and thyroidectomy had followed. In conclusion, the prescription of supplements with organic forms of Se must be preferred against of supplements with inorganic forms of Se among DTC patients for the protection of their salivary glands from 131I treatment and Brazil nuts could be another choice.

Radioactive iodine: An unappreciated threat to salivary gland function.

Thyroid cancer is an endocrine malignancy whose prevalence is increasing in the United States. Nearly 57,000 new cases of thyroid cancer are estimated to be diagnosed in 2017. The standard of care for differentiated thyroid cancer is thyroidectomy followed by ablation of thyroid remnants with high-dose radioactive iodine (131 I). Apart from thyroid glands, 131 I accumulates in cells of salivary glands and compromises its function. Xerostomia is, therefore, a frequent and often persistent complaint of patients. Despite adoption of standard preventive measures, parenchymal damage and chronic salivary dysfunction are observed in a substantial number of patients. Saliva is important for oral homeostasis, and its reduction increases the risk of oral morbidity. As differentiated thyroid cancer patients have an excellent survival rate, preservation of salivary gland function carries added significance. A focus on treatments that preserve or restore long-term salivary flow can significantly improve the quality of life of thyroid cancer survivors.