Randomized Control Study of the Effects of Turmeric Mouthwash on Oral Health Status, Treatment-Induced Mucositis, and Associated Oral Dysfunctions Among Patients With Head and Neck Cancer.

BACKGROUND: Oral mucositis is the most severe and debilitating adverse effect of cancer treatment, resulting in inadequate nutritional intake, treatment disruptions, and dose alteration, leading to increased hospital costs and decreased tumor control. OBJECTIVE: The aim of this study was to determine the effectiveness of turmeric mouthwash on oral health status and onset and severity of treatment-induced oral mucositis and associated oral dysfunctions among head and neck cancer patients. METHODS: A randomized controlled design was adopted (CTRI/2018/06/014367). Turmeric mouthwash was administered to the experimental group (n = 46) and benzydamine mouthwash was given to the control group (n = 46). Oral health status and mucositis were graded using the Oral Health Assessment Tool and the World Health Organization oral toxicity criteria, respectively. Oral dysfunctions were measured by a patient-reported oral mucositis symptom scale and xerostomia short-form inventory. All outcome variables were measured weekly during the entire course of radiation therapy. RESULTS: Both groups were comparable with regard to their demographic and outcome variables ( P > .05). The incidence of intolerable mucositis in the control group was 100% compared with 17.8% in the experimental group. Repeated-measures analysis of variance demonstrated significant differences in the onset and severity of oral mucositis ( P = .001), oral health status ( P = .001), and oral dysfunctions ( P = .001) between the experimental and control groups. CONCLUSION: Turmeric mouthwash was effective in reducing the severity of oral mucositis and associated oral dysfunctions as compared with benzydamine mouthwash. IMPLICATIONS: Use of turmeric, a nontoxic and cost-effective intervention, can be an alternative to the traditional management of oral mucositis.

Effect of Honey-Lemon Spray Versus Benzydamine Hydrochloride Spray on Radiation-Induced Acute Oral Mucositis in Head and Neck Cancer Patients: A Pilot, Randomized, Double-Blind, Active-Controlled Clinical Trial.

Introduction: Oral mucositis (OM) is the most prevalent side effect in patients with head and neck cancer (HNC). It causes an obvious decrease in quality of life (QoL) in these patients, so different medications have been recommended for OM, however, without optimal response. This randomized trial aimed to assess the effects of a honey-lemon spray compared with benzydamine hydrochloride in prevention of radiation-induced OM in patients with HNC. Materials and Methods: Forty-six patients with HNC received external beam radiotherapy for 5 days per week. Patients were randomized to treatment with either benzydamine hydrochloride spray or honey-lemon spray for 5 weeks and continued for 1 week after the end of treatment. The oral cavity was examined weekly, with a score given to each site based on the degree of mucositis using a 4-point scale, and a mean mucositis score was calculated as the primary outcome. Occurrence of OM, pain, QoL, and adverse effects were defined as secondary outcomes. Patients, therapists, and outcome assessors were blinded to group allocation. Results: No significant group differences occurred in the mucositis score, pain, or QoL. Mucositis occurrence rates were higher in the benzydamine hydrochloride group compared with the honey-lemon group (hazard ratio = 2.1, 95% confidence interval: 1.1 to 4.2). Two patients in the honey-lemon group had mild nausea and burning throat; no adverse effects occurred in the benzydamine hydrochloride group. Conclusions: There were no significant group differences in mucositis severity between patients treated with honey-lemon spray and benzydamine hydrochloride. The potential preventive effects of honey-lemon spray need to be confirmed in further trials. The trial registration number is IRCT20161024030467N1.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium.

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: A Turkish study - NON-RANDOMISED TRIAL.

OBJECTIVE: To evaluate the effect of different solutions administered to patients undergoing stem cell transplantation on oral mucositis. METHODS: The non-randomised controlled trial was conducted at a Istanbul Medipol Mega university hospital in Turkey between May 2014 and June 2016, and comprised patients undergoing stem cell transplantation. They were divided into three groups. Group 1 had patients using chlorhexidine gluconate and benzydamine hydrochloride solution. Group 2 had those using calcium and phosphate solution. Group 3 patients were using black mulberry syrup. Data was collected using a structured questionnaire and the World Health Organisation mucositis assessment scale. Assessment was done on days 7, 14 and 21. Clinical significance of oral solutions was statistically determined. RESULTS: Of the 83 patients, 30(36%) were in group 1, 28(34%) in group 2, and 25(30%) in group 3. On day 7, there was no significant difference in terms of grades among the groups (p>0.05). On day 14, grade 2 mucositis was seen in 2(8%) patents in group 3, 5(17.9%) in group 2 and 5(16.7%) in group 1; Grade 3 mucositis was seen in 2(6.7%) patients in group 1, but none in the other two groups. On day 21, grade 3 mucositis was present in 2(8.0%) in group 3, 2(7.1%) in group 2, and 4(13.3%) in group 1. CONCLUSIONS: The use of black mulberry and calcium-phosphate solutions was found to be beneficial in preventing and treating oral mucositis.

Pharmacological modulation of radiation-induced oral mucosal complications.

Radiation-induced mucositis is a common toxicity, especially in patients with head and neck cancers. Despite recent technological advances in radiation therapy, such as intensity-modulated radiotherapy, radiation-induced mucositis is still causing treatment disruptions, negatively affecting patients' long and short term quality of life, and impacting medical resources use with economic consequences. The objective of this article was to review the latest updates in the management of radiation-induced mucositis, with a focus on pharmaceutical strategies for the prevention or treatment of mucositis. Although numerous studies analysing the prevention and management of oral radiation-induced mucositis have been conducted, there are still few reliable data to guide daily clinical practice. Furthermore, most of the tested drugs have shown no (anti-inflammatory cytokine, growth factors) or limited (palifermin) effect. Therapies for acute oral mucositis are predominantly focused on improving oral hygiene and providing symptoms control. Although low-level laser therapy proved efficient in preventing radiation-induced oral mucositis in patients with head and neck cancer, this intervention requires equipment and trained medical staff, and is therefore insufficiently developed in clinical routine. New effective pharmacological agents able to prevent or reverse radio-induced mucositis are required.

Marmoset Flavin-Containing Monooxygenase 3 in the Liver Is a Major Benzydamine and Sulindac Sulfide Oxygenase.

Common marmosets (Callithrix jacchus) are potentially primate models for preclinical drug metabolism studies because there are similarities in the molecular characteristics of cytochrome P450 enzymes between this species and humans. However, characterization of non-cytochrome P450 enzymes has not been clarified in marmosets. Here, we report characterization of flavin-containing monooxygenases FMO1-FMO5 identified in marmoset tissues. Marmoset FMO forms shared high amino acid sequence identities (93%-95%) and phylogenetic closeness with human homologous FMO forms. FMO1 and FMO3 mRNA were abundantly expressed in the liver and kidneys among five marmoset tissues examined, where FMO3 protein was detected by immunoblotting. FMO inhibition assays using preheated tissue microsomes indicated that benzydamine N-oxygenation and sulindac sulfide S-oxygenation in the marmoset liver was mainly catalyzed by FMO3, the major hepatic FMO. Marmoset FMO3 protein heterologously expressed in Escherichia coli effectively catalyzed benzydamine N-oxygenation and sulindac sulfide S-oxygenation comparable to marmoset liver microsomes. These results indicate that the FMO3 enzyme expressed in marmoset livers mainly metabolizes benzydamine and sulindac sulfide (typical human FMO substrates), suggesting its importance for FMO-dependent drug metabolism in marmosets.

Lidocaine versus lidocaine plus benzydamine as a topical anesthesia regimen for unsedated upper gastrointestinal endoscopy: A comparison study.

BACKGROUND/AIMS: The aim was to assess the efficacy of adding benzydamine (B) spray to standard treatment with a lidocaine (L) spray before upper gastrointestinal endoscopy (UGE) as a topical anaesthetic regimen. MATERIALS AND METHODS: A total of 118 adult patients undergoing outpatient UGE were randomly assigned to receive L (n=44), LB (n=38) or B (n=36) before the procedure. The primary outcome was the patient tolerance score, which represents a summative evaluation of the taste of the anesthetic agent, the intensity of pharyngeal numbness, the amount of coughing or gagging and the degree of discomfort during oesophageal intubation. RESULTS: The median (min-max) patient tolerance scores were comparable between groups LB (10.5; range 5-12) and L (10; range 4-13) (p=0.235) and significantly lower in group B (7.5; range 3-12) (p<0.01). LB improved several secondary outcomes. Oesophageal intubation was less difficult (5 [range 2-10] vs 3 [range 0-8], p<0.001), and a lower proportion of patients developed postprocedural sore throat (4 [10.5%] vs 15 [34.1%], p=0.011) in LB compared to L. CONCLUSION: LB is not superior to L in terms of overall patient tolerance, but LB may be preferred over L in cases with difficult oesophageal intubation or a previous history of postprocedural sore throat.

Actualización del tratamiento del síndrome de boca ardiente / Upgrade treatment of burning mouth syndrome

El síndrome de boca ardiente se considera un 'dolor urente en la lengua o en otra localización de la mucosa oral sin signos patológicos específicos con evolución de al menos 4-6 meses', según la Asociación Internacional para el estudio del Dolor (IASP). La prevalencia oscila entre el 0,7% - 4,6%, siendo más frecuente en el sexo femenino (7:1) en la etapa peri-postmenopáusica. La etiología es multifactorial, por lo que debemos eliminar los factores locales, sistémicos y psicológicos que como factores precipitantes o consecuentes, están siempre presentes en esta entidad. En cuanto al tratamiento hemos de retirar los agentes causantes de la patología y disminuir en la medida de lo posible la sintomatología. A pesar de haber obtenido resultados con las terapias descritas en las revisiones sistemáticas y en los estudios clínicos son necesarios más ensayos clínicos aleatorizados, con muestras homogéneas, diseños apropiados y periodos de seguimiento prolongados que permitan evaluar la eficacia clínica y los posibles efectos adversos a largo plazo (AU)

Burning mouth syndrome is considered a burning pain in the tongue or in another location of the oral mucosa without specific pathological features with the development in at least 4-6 months, according to the International Association for the Study of Pain (IASP). The prevalence ranges from 0.7% - 4.6%, being more common in females (7:1) in the peri-menopausal stage. The etiology is multifactorial, so we must delete local, systemic and psychological factors as precipitating or consequential factors are always present in this entity. Despite of the results obtained with the therapies described in systematic reviews and clinical studies more randomized clinical trials with homogeneous samples, appropriate designs and longer follow-up periods to evaluate the clinical efficacy and potential adverse effects are needed long term (AU)

Human flavin-containing monooxygenase 3 on graphene oxide for drug metabolism screening.

Human flavin-containing monooxygenase 3 (hFMO3), a membrane-bound hepatic protein, belonging to the second most important class of phase-1 drug-metabolizing enzymes, was immobilized in its active form on graphene oxide (GO) for enhanced electrochemical response. To improve protein stabilization and to ensure the electrocatalytic activity of the immobilized enzyme, didodecyldimethylammonium bromide (DDAB) was used to mimic lipid layers of biological membranes and acted as an interface between GO nanomaterial and the hFMO3 biocomponent. Grazing angle attenuated total reflectance Fourier transform infrared (GATR-FT-IR) experiments confirmed the preservation of the protein secondary structure and fold. Electrochemical characterization of the immobilized enzyme with GO and DDAB on glassy carbon electrodes was carried out by cyclic voltammetry, where several parameters including redox potential, electron transfer rate, and surface coverage were determined. This system's biotechnological application in drug screening was successfully demonstrated by the N-oxidation of two therapeutic drugs, benzydamine (nonsteroidal anti-inflammatory) and tamoxifen (antiestrogenic widely used in breast cancer therapy and chemoprevention), by the immobilized enzyme.

Comparative Efficacy of Aloe vera and Benzydamine Mouthwashes on Radiation-induced Oral Mucositis: A Triple-blind, Randomised, Controlled Clinical Trial.

PURPOSE: To compare the efficacy of an Aloe vera mouthwash with a benzydamine mouthwash in the alleviation of radiation- induced mucositis in head and neck cancer patients using a triple-blind, randomised controlled trial. MATERIALS AND METHODS: Twenty-six eligible head and neck cancer patients who were to receive conventional radiation therapy at the radiation oncology department were randomised to receive an Aloe vera mouthwash or a benzydamine mouthwash. Mucositis severity was assessed during the course of radiation therapy using the WHO grading system. RESULTS: At baseline, there was no difference in the distribution of mucositis severity between the two groups. The mean interval between radiation therapy and onset of mucositis was similar for both groups (Aloe vera 15.69±7.77 days, benzydamine 15.85±12.96 days). The mean interval between the start of radiation therapy and the maximum severity of mucositis were was also similar in both the Aloe vera and benzydamine groups (Aloe vera 23.38±10.75 days, benzydamine 23.54±15.45 days). Mean changes of mucositis severity over time in both groups were statistically similar and the effect of both treatments did not change signficantly with time (p=0.09). CONCLUSION: Aloe vera mouthwash was as beneficial as benzydamine mouthwash in alleviating the severity of radiation-induced mucositis and showed no side effects. The Aloe vera mouthwash could be an alternative agent in the treatment of radiation-induced mucositis in patients with head and neck cancers.