Salivary Electrostimulation in the Treatment of Radiation Therapy-Induced Xerostomia (LEONIDAS-2): A Multicenter, Randomized, Double-Masked, Sham-Controlled, Phase 3 Trial.

PURPOSE: Radiation therapy-induced xerostomia significantly affects quality of life in head and neck cancer survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms. METHODS AND MATERIALS: This multicenter, double-masked, randomized, sham-controlled clinical trial assessed the long-term effects of a commercially available intraoral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow, and improving quality of life in individuals with radiation therapy-induced xerostomia. Using a computer-generated randomization list, participants were assigned (1:1) to an active intraoral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia visual analog scale at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and visual analog scale) and quality-of-life questionnaires (EORTC QLQ-H&N35, OH-QoL16, and SF-36). RESULTS: As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality-of-life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth subscale score of the EORTC QLQ-H&N35 in favor of the active intervention. CONCLUSIONS: LEONIDAS-2 did not meet the primary and secondary outcomes.

The Mechanism of Core Chinese Medicine Combination in Treating Salivation.

OBJECTIVE: To analyze the regularity of modern Chinese herbal compound in the treatment of salivation based on data mining technology, and to study the potential mechanism of core Chinese herbal medicine in the treatment of salivation using network pharmacology and molecular docking. METHODS: CNKI, VIP and Wanfang literature databases were searched.Choose a prescription for salivation.Excel2019 was used to establish a database of formulas for the treatment of salivation.The included TCM compounds were analyzed by frequency statistics and association rules using the ancient and modern medical record cloud platform to obtain the core drug pairs.TCMSP and Uniprot were used to search the components and targets of the core drug pairs, and intersected with the disease targets obtained from Genecards, OMIM, TTD, PharmgKb, and DrugBank platforms.Complex networks were constructed by cytoscape3.9.1; PPI networks were completed by STRING platform; GO and KEEG pathway enrichment analysis was performed by R language; finally molecular docking validation was performed using AutoDockTools software; and the results were visualized by Pymol software. RESULTS: 122 prescriptions were obtained, 194 herbs were used, the total frequency was 1047, and the top ten drugs used were Atractylodes macrocephala Koidz, Poria cocos, Glycyrrhiza uralensis, Yizhiren, Citrus sinensis, Codonopsis pilosula, Yam, Pinellia ternate, Zingiber officinale, and Coptis chinensis.After association rule analysis, the core drug pair Codonopsis pilosula - Atractylodes macrocephala Koidz was obtained.Twenty-seven effective active components of core drug pairs were screened, corresponding to 62 targets for the treatment of salivation, and four core targets were MAPK1, TP53, MAPK14, and ESR1.GO enrichment analysis yielded 1789 biological process entries, 81 cellular component entries and 111 molecular function entries.KEGG enrichment analysis resulted in 157 pathways, and the first 30 were selected for visualization.Molecular docking of luteolin, 7-Methoxy-2-methyl isoflavone, Stigmasterol, 3ß-acetoxyatractylone, Frutinone A, 3betaHydroxymethyllenetanshiquinone, glycitein to the core target showed that the key active components had good binding activity to the core target. CONCLUSION: The key active components of Codonopsis pilosula and Atractylodes macrocephala Koidz in the treatment of salivation act on MAPK1, TP53, MAPK14 and ESR1 through Calcium, PI3K Akt and IL-17 signaling pathways to regulate the physiological processes of nerve, muscle, endocrine and reproductive systems and the physiological functions of nerve cells, providing a theoretical reference for the later study of integrated traditional Chinese and western medicine in the treatment of salivation.

[Effect of intradermal needling combined with oral motor therapy for salivation in children with cerebral palsy: a randomized controlled trial].

OBJECTIVE: To compare the effect of combination of intradermal needling with oral motor therapy and simple oral motor therapy on salivation in children with cerebral palsy. METHODS: A total of 60 children with salivation in cerebral palsy were randomized into an observation group and a control group, 30 cases in each group. The observation group was treated with intradermal needling (kept for 24 hours each time at Jiache [ST 6], Dicang [ST 4], tongue three needles, etc. ) and oral motor therapy, while the control group was only given oral motor therapy. The intradermal needling was performed 3 times a week, and oral motor therapy was performed 5 times a week, 4 weeks as a course, totally 3 courses of treatment were required. The classification of teacher drooling scale (TDS), drooling severity and Kubota water swallow test, dysphagia disorders survey (DDS) score were compared before treatment and after 4, 8 and 12 weeks of treatment in both groups, and the clinical efficacy was evaluated. RESULTS: After 8 weeks of treatment in the observation group and after 12 weeks of treatment in the two groups, the classification of TDS and drooling severity were improved (P<0.05), and the observation group was better than the control group after 12 weeks of treatment (P<0.05). After 8 and 12 weeks of treatment, the DDS scores of oral period in the observation group were lower than those before treatment (P<0.05). The total effective rate in the observation group was 83.3% (25/30), which was higher than 53.3% (16/30) in the control group (P<0.05). CONCLUSION: The combination of intradermal needling with oral motor therapy can improve salivation symptoms and swallowing function in children with cerebral palsy, the effect is better than oral motor therapy alone, and the effect is earlier.

Effect of intradermal needling combined with oral motor therapy for salivation in children with cerebral palsy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the effect of combination of intradermal needling with oral motor therapy and simple oral motor therapy on salivation in children with cerebral palsy.@*METHODS@#A total of 60 children with salivation in cerebral palsy were randomized into an observation group and a control group, 30 cases in each group. The observation group was treated with intradermal needling (kept for 24 hours each time at Jiache [ST 6], Dicang [ST 4], tongue three needles, etc. ) and oral motor therapy, while the control group was only given oral motor therapy. The intradermal needling was performed 3 times a week, and oral motor therapy was performed 5 times a week, 4 weeks as a course, totally 3 courses of treatment were required. The classification of teacher drooling scale (TDS), drooling severity and Kubota water swallow test, dysphagia disorders survey (DDS) score were compared before treatment and after 4, 8 and 12 weeks of treatment in both groups, and the clinical efficacy was evaluated.@*RESULTS@#After 8 weeks of treatment in the observation group and after 12 weeks of treatment in the two groups, the classification of TDS and drooling severity were improved (P<0.05), and the observation group was better than the control group after 12 weeks of treatment (P<0.05). After 8 and 12 weeks of treatment, the DDS scores of oral period in the observation group were lower than those before treatment (P<0.05). The total effective rate in the observation group was 83.3% (25/30), which was higher than 53.3% (16/30) in the control group (P<0.05).@*CONCLUSION@#The combination of intradermal needling with oral motor therapy can improve salivation symptoms and swallowing function in children with cerebral palsy, the effect is better than oral motor therapy alone, and the effect is earlier.

Mechanism of cAMP-PKA Signaling Pathway Mediated by Shaoyao Gancao Decoction () on Regulation of Aquaporin 5 and Muscarinic Receptor 3 Levels in Sjögren's Syndrome.

OBJECTIVE: To investigate the mechanism of cAMP-PKA signaling pathway mediated by Chinese medicine formula Shaoyao Gancao Decoction (, SGD) on the regulation of aquaporin 5 (AQP5) and muscarinic receptor 3 (M3R) levels in Sjögren's syndrome (SS). METHODS: Of the 30 mice, 5 were randomly selected as control, and others were used for creating SS model. After successful modeling, mice were randomly divided into 5 groups (n=5 per group) and intragastrically administered with saline (8 mL/kg), pilocarpine (1.4 mg/kg), or low, medium and high doses SGD (0.14, 0.21, 0.35 g/kg Radix paeoniae with 0.01 g/kg Radix glycyrrhizae, respectively) for 6 weeks. Human labial gland acinar cells were treated with pilocarpine or varying doses of SGD with saline as the placebo. Hematoxylin and eosin staining was used to observe the histopathological changes of the submandibular glands of mice. The serum levels of anti-SS antigen A (SS-A), anti-SS antigen B (SS-B), M3R, and α-fodrin in submandibular glands of mice were measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to observe the spatial localization of AQP5 and M3R in acinar cells. Reverse transcriptase polymerase chain reaction and Western blot were used to detect the expressions of PKA, cAMP, Epac1, AQP5, M3R, nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF)-α in submandibular gland tissues and cells of each group. RESULTS: Compared to normal mice, body weight, 5-min salivary secretion, 30-min secretion of tears and breakup time of tear film of model mice decreased at 1-6 weeks after immunization (all P<0.05), whereas water intake increased (all P<0.05). In the model group, glands of the submandibular glands showed atrophy, accompanied by acini of different sizes, decreased numbers and loose arrangement, with catheter dilatation and different degrees of lymphocyte infiltration. Conditions of mice in SGD groups were improved. The positive expression of AQP5 and M3R were higher in the acinar cells treated with all doses SGD compared to the normal group; serum levels of SS-A, SS-B, and α-fodrin were lower, and that of M3R was higher in all doses SGD treated animals than the model or pilocarpine treated ones (all P<0.05). Compared to the model and pilocarpine groups, the mRNA and protein levels of NF-κB and TNF-α were lower in mice or cells treated with medium or high-dose SGD (all P<0.05), while those of PKA, Epac1, AQP5 and M3R were higher (all P<0.05). CONCLUSION: SGD can improve symptoms of SS by regulating the cAMP-PKA signaling pathway and increasing AQP5 and M3R levels.

Sauce it up: influence of condiment properties on oral processing behavior, bolus formation and sensory perception of solid foods.

Condiments are rarely consumed on their own. Although addition of condiments to carrier foods is known to affect oral processing behavior and sensory perception, an understanding of how different condiment properties impact oral processing behavior and sensory perception of solid carrier foods is lacking. This study aimed to understand the role of condiments varying in composition and/or rheological properties in bolus formation facilitation, and how they influence oral processing behavior and sensory perception of solid carrier foods. Two carriers (bread, cooked potato) were combined with mayonnaises differing in fat content and viscosity. Addition of mayonnaises changed bolus properties of solid carrier foods considerably (i.e. decreased bread firmness, increased potato cohesiveness, increased lubrication of both bread and potato bolus) and, consequently, facilitated faster bolus formation. While addition of mayonnaises to bread and potatoes decreased the number of chewing cycles before swallowing, consumers did not change muscle activities or jaw movements per chew. No effect of mayonnaise fat content on oral processing behavior of composite foods was observed. Low viscosity mayonnaise resulted in faster bolus formation and swallowing compared to high viscosity mayonnaise. Low viscosity mayonnaise penetrated faster into bread boli leading to faster softening of bread boli. Also in the case of potato, low viscosity mayonnaise lead to faster bolus formation than for high viscosity mayonnaise. The low viscosity mayonnaise mixed more easily with potato bolus pieces, enhancing adhesion between pieces. Both mayonnaise fat content and viscosity influenced sensory perception of composite foods considerably, especially in terms of fattiness and creaminess. We conclude that oral processing behavior, bolus formation and sensory perception of solid carrier foods can be modified considerably by condiments. While composition and rheological properties of condiments have a large effect on bolus formation and sensory perception of solid carrier foods, these aspects have a limited effect on oral processing behavior of composite foods. Oral processing behavior is dominated by the properties of the solid carrier food. Tailoring condiment-carrier combinations could be an effective strategy to increase healthy eating, alter food intake for populations such as the elderly, and increase food appreciation.

Ixeris dentata and Lactobacillus gasseri Extracts Improve Salivary Secretion Capability in Diabetes-Associated Dry Mouth Rat Model.

Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there has been no way to relieve these symptoms. This study's aim was to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin (STZ)-induced diabetes model, the dry mouth condition was established as a model. Here, rats were treated with water or IXD through the sublingual spray, and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na+/H+ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than in each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes, glutathione assay (GSH: GSSG) ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx), were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia.

Evaluation of photobiomodulation in salivary production of patients with xerostomy induced by anti-hypertensive drugs: Study protocol clinical trial (SPIRIT compliant).

INTRODUCTION: Hypertension (systemic arterial hypertension [SAH]) is a systemic condition that affects about 30% of the world population, according to data from the World Health Organization (WHO). Drugs used to control this disease have the potential to induce xerostomia, an oral condition in which the decrease of the salivary flow is observed and whose presence leads to the increase of the index of caries, periodontal disease, loss of the teeth, dysgeusia, difficulty of mastication, dysphagia, bad breath and oral burning and impairment of prothesis installed in the buccal cavity, including retention of removable and total dentures. METHODS: This is a randomized, placebo-controlled, blind clinical protocol that aims to analyze the impact of phobiomodulation (PBM) on salivary glands of patients with antihypertensive drug induced xerostomia. Patients will be divided into 2 groups: G1: older adults with xerostomia induced by antihypertensive drugs and treatment with PBM (n = 30); G2: placebo PBM (n = 30). The irradiation will be made using a diode laser emitting at 808 nm with 100 mW and 40 seconds of exposure per site at the salivary glands. Twenty sites will be irradiated weekly for 4 weeks. Non-stimulated and stimulated salivary flow will be analyzed before and after the treatment. RESULTS: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. CONCLUSION: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. TRIAL REGISTRATION: Clinicaltrials.gov - NCT03632096.

Effect of homeopathy in the function and morphology of salivary parotid glands of irradiated rats / Efeito da homeopatia na função e morfologia das glândulas parótidas de ratos irradiados

Objective: To evaluate the radioprotective effect of a homeopathic solution in salivary function and parotid glands morphology of irradiated rats. Materials and Methods: The sample consisted of 150 rats randomly divided into 6 groups. The groups were named based on the substance administered: Control- saline solution; Irradiated Control- saline solution and 15 Gy of X radiation; Alcohol-hydroalcoholic solution dynamized at 15 CH; Irradiated Alcohol- hydroalcoholic solution dynamized at 15 CH and 15 Gy of X radiation; Homeopathy- 0.25 ml (1mL/kg) of the irradiated hydroalcoholic solution and dynamized at 15 CH; Irradiated homeopathy- homeopathic solution and 15 Gy of X radiation. Each group was subdivided into 5 different subgroups, based on the time point of euthanasia: 12 hours, 3, 10, 17, and 24 days. The medication was administered for 7 days before and 7 days after the radiation treatment. On the day of euthanasia, salivation was induced with pilocarpine and collected. The animals were then sacrificed and the parotid glands were removed. Results: Salivary function analysis showed that only group irradiated homeopathy euthanized on day 17 had a statistically significant difference when compared to other irradiated groups, presenting a higher salivation flow rate. The only group that showed a statistically significant difference in the number of acini over time was the irradiated alcohol group, which presented a tendency of reduction. Conclusion: The homeopathic solution presented a late radioprotective effect based on salivary function and morphological analysis of the parotid gland.

Objetivo: Avaliar o efeito radioprotetor de uma solução homeopática na função salivar e na morfologia das glândulas parótidas de ratos irradiados. Materiais e Métodos: A amostra foi composta por 150 ratos divididos aleatoriamente em 6 grupos. Os grupos foram nomeados com base na substância administrada: solução salina controle; Solução salina controle irradiada e 15 Gy de radiação X; Solução álcool-hidroalcoólica dinamizada a 15 CH; Solução hidroalcoólica de álcool irradiado dinamizada a 15 CH e 15 Gy de radiação X; Homeopatia - 0,25 ml (1mL / kg) da solução hidroalcoólica irradiada e dinamizada a 15 CH; Homeopatia irradiada - solução homeopática e 15 Gy de radiação X. Cada grupo foi subdividido em 5 subgrupos diferentes, com base no tempo da eutanásia: 12 horas, 3, 10, 17 e 24 dias. O medicamento foi administrado por 7 dias antes e 7 dias após o tratamento com radiação. No dia da eutanásia, a salivação foi induzida com pilocarpina e coletada. Os animais foram então sacrificados e as glândulas parótidas foram removidas. Resultados: A análise da função salivar mostrou que apenas a homeopatia irradiada por grupo sacrificada no dia 17 apresentou diferença estatisticamente significante quando comparada a outros grupos irradiados, apresentando maior taxa de fluxo de salivação. O único grupo que apresentou diferença estatisticamente significante no número de ácinos ao longo do tempo foi o grupo álcool irradiado, o qual apontou uma tendência de redução. Conclusão: A solução homeopática apresentou efeito radioprotetor tardio baseado na função salivar e na análise morfológica da glândula parótida.

Study on the salivation effect of encapsulated food products containing Sichuan pepper oil.

Sichuan pepper is a plant belonging to the genus Zanthoxylum and family rue. To evaluate whether Sichuan pepper oil boosts saliva secretion using an encapsulated food product containing the oil in subjects presenting with mouth dryness. We evaluated subjective symptoms that changed with a decrease in salivary secretion in the subjects by evaluating the number of Candida colonies and by conducting interviews. The study results demonstrated that salivary secretion increased by 39.4% ± 37.6% after single ingestion of the product, and an additional 8.7% ± 13.2% and 6.3% ± 31.2% following continuous ingestion over 2 and 4 weeks, respectively. These findings suggested that the product rapidly promotes and maintains salivation. Regarding the proliferation of Candida colonies in subjects with mouth dryness, a negative correlation was observed between Candida colony number and salivary secretion quantity. Additionally, interviews revealed that subjective symptoms, such as mouth dryness, discomfort and pain in the mouth, difficulty swallowing the saliva, and feeling of stickiness in the mouth, improved shortly after single ingestion of the product, and mouth dryness was reduced by continuous consumption of the product. These findings indicated that the product studied promotes rapid salivary secretion, is effective in reducing the number of oral Candida colonies, and improves subjective symptoms such as mouth dryness.

Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjögren's syndrome mouse model.

OBJECTIVES: SS is characterized by chronic inflammation of the salivary glands leading to loss of secretory function, thereby suggesting specialized pro-resolving mediators targeting inflammation to be a viable option for treating SS. Previous studies demonstrated that aspirin-triggered resolvin D1 (AT-RvD1) prevents chronic inflammation and enhances saliva secretion in a SS-like mouse model when applied before disease onset. However, this therapy cannot be used in SS patients given that diagnosis occurs post-disease onset and no reliable screening methods exist. Therefore, we examined whether treatment with AT-RvD1 reduces SS-like features in a mouse model post-disease onset. METHODS: Tail vein injections were performed in a SS-like mouse model both with and without AT-RvD1 post-disease onset for 8 weeks, with salivary gland function and inflammatory status subsequently determined. RESULTS: Treatment of a SS-like mouse model with AT-RvD1 post-disease onset restores saliva secretion in both females and males. Moreover, although AT-RvD1 treatment does not reduce the overall submandibular gland lymphocytic infiltration, it does reduce the number of T helper 17 cells within the infiltrates in both sexes. Finally, AT-RvD1 reduces SS-associated pro-inflammatory cytokine gene and protein expression levels in submandibular glands from female but not male mice. CONCLUSION: AT-RvD1 treatment administered post-disease onset reduces T helper 17 cells and successfully restores salivary gland function in a SS mouse model with variable effects noted by sex, thus warranting further examination of both the causes for the sex differences and the mechanisms responsible for the observed treatment effect.

Treatment Strategies for Clozapine-Induced Sialorrhea: A Systematic Review and Meta-analysis.

BACKGROUND: Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea. METHODS: We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm. RESULTS: 19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1). CONCLUSION: Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.

The effect of transcutaneous electrical nerve stimulation on increasing salivary flow rate in hemodialysis patients.

OBJECTIVE: To evaluate the impact of a transcutaneous electrical nerve stimulation (TENS) program for hemodialysis on patients' dry mouth and salivary flow rates. SUBJECTS AND METHODS: A single-blinded repeated measures study design was used. A total of 80 subjects were randomly assigned to a treatment group receiving a 250 µs; 50 Hz TENS program and a control group receiving a 50 µs; 2 Hz TENS program at acupoints ST 6 and TE17 three times a week for 3 weeks. Whole salivary flow rate and dry mouth intensity were measured totally five times for both groups, at pretreatment, after three, six, nineTENS sessions, and 1 week after the treatment was completed. RESULTS: After six TENS sessions were completed, whole salivary flow rates increased stably until the end of nine TENS sessions for the treatment group. In the follow-up week after treatment, there was significant increase as well. However, significant improvement in dry mouth intensity was observed at all post-tests than that at pretreatment in both groups. CONCLUSION: Whole salivary flow rates and improvement in dry mouth intensity were only observed during and 1 week after the TENS sessions. Further studies are needed to evaluate whether this method can offer a long-term effective nonpharmacological therapy for dry mouth-disturbed hemodialysis patients.

Effects of Acute Deltamethrin Exposure in Adult and Developing Sprague Dawley Rats on Acoustic Startle Response in Relation to Deltamethrin Brain and Plasma Concentrations.

Deltamethrin (DLM) is a commonly used pesticide that helps to control crop destruction, disease, and nuisance insects. In rodents DLM can produce choreoathetosis, salivation, and decreased acoustic startle responses (ASR). Herein, adult Sprague Dawley rats were assessed for ASR 2 h after DLM delivered in 5 ml/kg corn oil, however no decrease was observed. Therefore, a test-retest protocol was used to reduce variability, and the effects on ASR on postnatal day 15 (P15) and adult rats were assessed 2, 4, 6, and 8 h after DLM administration (0, 1, 2, or 4 mg/kg for P15 rats and 0, 2, 8, or 25 mg/kg for adults). In a separate set of rats identically treated, DLM levels were determined in blood and brain. DLM (8 or 25 mg/kg) in adult rats decreased ASR up to 4 h, whereas in P15 rats decreases were observed between 2 and 8 h. The adult 25 mg/kg group showed consistent signs of salivation and tremor, whereas in P15 rats salivation was observed in the 2 and 4 mg/kg groups and tremor was observed at all doses over the 8-h period. Mortality was observed in all P15 dose groups but not in adults. Dose-dependent increases of DLM in blood and brain regardless of age were observed. At approximately equivalent whole brain concentrations, effects were more pronounced in P15 rats than in adult rats. Comparable brain levels of DLM do not explain differences in ASR and tremor between the P15 and adult rats. These data indicate age-dependent differences in sensitivity to DLM.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice.

OBJECTIVE: To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice. METHODS: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction. RESULTS: Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05). CONCLUSIONS: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Protective Effect of Zengye Decoction () on Submandibular Glands in Nonobese Diabetic Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.@*METHODS@#Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction.@*RESULTS@#Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05).@*CONCLUSIONS@#ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.

Newly Distinguished Cell Punctures Associated with Transmission of the Semipersistent Phloem-Limited Beet Yellows Virus.

Here we report on plant penetration activities (probing) by the aphid Myzus persicae (Sulzer, 1776) in association with the transmission, acquisition, and inoculation of the semipersistent Beet yellows virus (BYV; Closterovirus) in sugar beet. During electrical penetration graph (EPG) recording of stylet pathways, standard intracellular stylet punctures occur which are called potential drop (pd) waveforms. In addition to the standard pd, there also appeared to be a unique type of intracellular stylet puncture that always preceded the phloem salivation phase (waveform E1). This type of pd, the phloem-pd, showed properties distinct from those of the standard pds and has never been described before. We manually ended EPG recordings during the acquisition and inoculation tests by removing aphids from the source or test plant after specific waveforms were recorded. Inoculation of BYV occurred at the highest rate when probing was interrupted just after a single or various phloem-pds. In contrast, BYV acquisition showed an intimate association with sustained phloem sap ingestion from phloem sieve elements (SEs) (E2 waveform). Our work shows for the first time that the inoculation of a phloem-limited virus occurs during specific intracellular stylet punctures and before phloem salivation (waveform E1). Further studies are needed to establish in what cells this novel phloem-pd occurs: phloem parenchyma, companion, or SE cells. The role of the different stylet activities in the acquisition and inoculation of BYV by M. persicae is discussed.IMPORTANCE We discovered the specific feeding activities of Myzus persicae (Sulzer, 1776) associated with the transmission of Beet yellows virus (BYV; Closterovirus). Our work strongly suggests that aphids can insert their stylets into the membranes of phloem cells-visualized as a unique type of waveform that is associated with the inoculation of BYV. This intracellular puncture (3 to 5 s) occurs just before the phloem salivation phase and can be distinguished from other nonvascular stylet cell punctures. This is the first time that the transmission of a phloem-limited semipersistent virus has been shown to be associated with a unique type of intracellular puncture. Our work offers novel information and strongly contributes to the existing literature on the transmission of plant viruses. Here we describe a new kind of aphid behavioral pattern that could be key in further works, such as studying the transmission of other phloem-limited viruses (e.g., luteoviruses).

[Effect of acupuncture at proximal and distal acupoints combined with neuromuscular electrical stimulation on children with cerebral palsy salivation].

OBJECTIVE: To explore the effect of acupuncture at the proximal and distal acupoints combined with neuromuscular electrical stimulation (NMES) for the children with cerebral palsy salivation on the basis of oral function training. METHODS: A total of 124 children were randomized into an observation group and a control group, 62 cases in each one. Oral function training (30 min a time) and NMES (20 min a time) were used in the two groups. Acupuncture was applied after NMES in the observation group. The main acupoints were Baihui (GV 20), Sishencong (EX-HN 1), Speech AreaⅠ, Dicang (ST 4), Jiache (ST 6), Hegu (LI 4), Zusanli (ST 36), etc. Scalp acupuncture was for 1 h, and body acupuncture was for 30 min. Pricking blood was used at Jinjin (EX-HN 12) and Yuye (EX-HN 13) for the patients of Ⅴ in teacher salivation grading (TDS). All the treatment was given for 3 courses, 30 days as a course, 5 times a week, once a day. TDS, safety, dysphagia and Gesell development scale were assessed before and after treatment. RESULTS: After treatment, the total effective rate of TDS in the observation group was 83.9% (52/62), which was better than 58.1% (36/62) in the control group (P<0.05). The total effective rate of dysphasia in the observation group was 88.7% (55/62), which was better than 69.4% (43/62) in the control group (P<0.05). The lip and tongue movement, chewing and swallowing after treatment in the observation group were superior to those in the control group (all P<0.05). After treatment, the Gesell development scale of adaptability, language behavior and personal social development quotient were better compared with those before treatment in the observation group (all P<0.05); the language behavior improved after treatment in the control group (P<0.05). The adaptability, language behavior and personal social development quotient after treatment in the observation group were superior to those in the control group (P<0.05，P<0.01). The adverse reactions in the observation group were less than those in the control group. CONCLUSION: Acupuncture at the proximal and distal acupoints combined with NMES are better than simple NMES for children with cerebral palsy salivation. The methods could not only improve children's behavior cognitive ability, but also improve the sensation and motor coordination of the lip, tongue, pharynx, etc. As a result, the salivation and swallowing function improve.

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.

Effect of oral functional training on immunological abilities of older people: a case control study.

BACKGROUND: Oral functional ability decreases with age, and systemic immunological ability and quality of life can also deteriorate. Continuous moderate whole-body exercise for older people is known to improve oral functional and their immunological abilities. Here, we evaluated the effect of oral exercise as an alternative training method for highly older people who cannot perform whole-body exercises. METHODS: Unstimulated whole saliva samples had been collected for three times before training as baseline data and one time after 3 and 6 weeks of training each. Participants were instructed to conduct self-massage; their tongues were used to press their orbicularis oris muscle and buccinators, and instructed to perform bilateral massage of three major glands for facilitating saliva secretion. Medical histories, daily life habits and characteristics were also collected. RESULTS: Totally 30 participants (84.2 ± 8.5 years) were enrolled. In contrast to previous researches, increase in salivary Immunoglobulin A (IgA) after the training was not observed. Interestingly, hierarchical clustering analyses revealed clear individual variations as two prominent clusters and a strong positive correlation between stimulated saliva flow rate and IgA flow rate, regardless of the continuous oral functional exercise. Only body mass index (BMI) showed significant differences between the two groups (Z = 2.06, P = 0.039, Wilcoxon rank-sum test) among all collected parameters. CONCLUSION: Oral functional training limitedly effects on salivary parameters of highly older people. On the other hand, BMI characterized salivary features more than any other parameters, such as the presence of diseases or medication use in these people. TRIAL REGISTRATION: UMIN-CTR Clinical Trial UMIN000028394 on 27/July 2017, retrospectively registered.