Red, infrared, and simultaneous laser-wavelengths irradiation effects on 5-fluorouracil-induced oral mucositis in hamsters.

The association of more than one wavelength for photobiomodulation therapy (PBMT) to treat oral mucositis (OM) is unusual in the literature. Thus, this study aims to compare the simultaneous irradiation effects with their isolated application to treat OM. In order of that, 48 male Syrian hamsters were divided into 4 groups: Chemotherapy (Ch), which received only a OM induction protocol (5-fluorouracil chemotherapy and superficial oral mucosa scratches); red laser (RL), which received the OM induction and a PBMT protocol at 660 nm; infrared laser (IRL), which received the OM induction, and a PBMT protocol at 808 nm; and the RL + IRL group, which received the simultaneous application, of 660 and 808 nm wavelengths. Clinical (OM grade classification), histological (light microscopy analysis with H&E and collagen staining), immunohistochemical (TNF-α expression), and biochemical (TNF-α and hydroxyproline concentration) analyzes were performed after 7 and 10 days. Mainly on the 10th day, the RL and IRL groups showed lower OM grades and faster microscopic repair process, with greater expression of collagen fibers and lower TNF-α levels, besides the higher hydroxyproline concentrations, mainly in comparison with the Ch group. In conclusion, in this study, the simultaneous protocol did not present superior results than the isolated irradiations.

Impacto na deglutição e manejo da mucosite hipofaríngea em pacientes submetidos à quimiorradioterapia na região de cabeça e pescoço: uma revisão integrativa da literatura / Management of hypopharyngeal mucositis in patients undergoing chemoradiotherapy in the head and neck region and its impact on swallowing: an integrative literature review

RESUMO Objetivo Investigar o impacto da mucosite hipofaríngea quimiorradioinduzida na deglutição e o seu manejo, a partir de uma revisão integrativa de literatura. Estratégia de pesquisa A busca e a seleção dos artigos foram realizadas nas seguintes bases de dados: PubMed, Embase, Scopus, ScienceDirect e LILACS. Critérios de seleção Os termos de busca utilizados foram ''Pharyngeal Mucositis", ''Radiotherapy" e ''Esophagitis", com auxílio do operador booleano (AND). A equação de busca utilizada foi: ''Pharyngeal Mucositis" AND "Radiotherapy" AND "Esophagitis". A seguinte questão central orientou o estudo: "Qual a forma de avaliação e manejo da mucosite hipofaríngea induzida pela radiação na região de cabeça e pescoço e seu impacto na deglutição?". Resultados Foram identificados 75 estudos, sendo que 6 foram excluídos devido à duplicidade e 60 foram excluídos por não se encaixarem nos critérios de inclusão; os artigos restantes foram lidos na íntegra e 4 foram selecionados para fazerem parte desta revisão integrativa da literatura. Conclusão Apesar da escassa literatura e das poucas informações sobre os métodos de avaliação da mucosite hipofaríngea, os artigos apontam que, independentemente da dose de radiação, a radioterapia na região cervical causa mucosite hipofaríngea. A mucosite hipofaríngea provoca grande impacto na deglutição, resultando na necessidade de uso de via alternativa de alimentação. Além da ausência de informações quanto à avaliação e graduação da mucosite hipofaríngea, os estudos não discutem o tratamento direto ou a prevenção desse tipo de doença.

ABSTRACT Purpose To investigate the impact of chemoradiation-induced hypopharyngeal mucositis on swallowing and its management, based on an integrative literature review. Research strategy Two researchers were responsible for the search and selection of articles, within the following databases: PubMed, Embase, Scopus, Science Direct, and Lilacs. Selection criteria The search terms used were "Pharyngeal Mucositis", "Radiotherapy" and "Esophagitis", with the aid of the Boolean operator (AND). The search equation used was "Pharyngeal Mucositis" AND Radiotherapy AND Esophagitis. The following central question guided the study: "What is the assessment and management of radiation-induced hypopharyngeal mucositis in the head and neck region and its impact on swallowing?" Results 75 studies were identified, of which 6 were excluded due to duplicity and 60 were excluded for not meeting the inclusion criteria; the remaining articles were read in full and 4 were selected to be part of the integrative literature review. Conclusion Despite the scarce literature and little information on methods for evaluating hypopharyngeal mucositis, the articles point out that, regardless of the radiation dose, radiotherapy in the cervical region causes hypopharyngeal mucositis. Hypopharyngeal mucositis causes a great impact on swallowing, resulting in the need to use an alternative feeding route. In addition to the lack of information regarding the assessment and grading of hypopharyngeal mucositis, the studies do not discussitsdirect treatment or prevention.

High-power laser for oral excisional biopsy in an oncologic patient with pancytopenia.

Oral surgical procedures are a great challenge in cancer patients, especially those with pancytopenia, given the risk of both hemorrhage and opportunistic infection. Thus, we report herein a case of a patient with refractory acute myeloid leukemia, severe pancytopenia, and some episodes of febrile neutropenia, who presented asymptomatic, bilateral lesions on the tongue, requiring excisional biopsy. Considering the high risk of bleeding, surgical intervention was proposed with a high-power laser (HPL) at the bedside. There was no considerable bleeding and stitches were not needed. Within 48 h postoperatively, the patient reported neither pain nor further bleeding and her tongue presented normal function. The patient was under a follow-up period of about 8 months, with no lesion relapse. The HPL seems to be of great value for preventing excessive bleeding and late infection in patients with pancytopenia submitted to minor oral surgeries.

Determining the Presence of 5-Fluorouracil in Hamster Saliva by HPLC / Determinação, por CLAE, da Presença do 5-Fluorouracil em Saliva de Hamsters

Abstract Introduction: Various methods of analysis for the assay of chemotherapeutic agent 5-Fluorouracil (5-FU) in human and animal biological fluids have previously been reported. However, there is no standardization for detecting 5-FU in the hamsters' saliva that received the chemotherapeutic agent. Objective: Considering that the administration of 5-FU in some way changes the morphology and function of the salivary glands, and that the presence of the chemotherapeutic agents in the oral mucosa may lead to some oral complications, the aim of this study was to determine the presence of 5-FU in the hamsters' saliva that received the chemotherapeutic agent, by means of the High Performance Liquid Chromatography technique (HPCL) since this animal model is used in studies of 5-FU induced oral mucositis and glandular hypofunction. Methods: Twelve animals were divided into 4 groups: CP and CPI, in which the animals received pilocarpine (CP) or pilocarpine + isoproterenol (CPI) and the chemotherapy vehicle intraperitoneally; and Groups QP and QPI, in which the animals received the same secretagogues listed above, and the chemotherapeutic agent 5-FU, respectively. After the secretagogue administration, saliva was collected from all the animals for a period of 60 mins. Subsequently, the saliva was frozen at -80 ˚C for later determination of the chemotherapeutic agent by HPLC. After the the chromatograms analysis, and based on the results obtained, it was possible to identify the presence of 5-FU in the saliva samples from hamsters that received the chemotherapeutic agent intraperitonally, by the HPLC technique. (AU)

Resumo Vários métodos de análise para o ensaio do quimioterápico 5-Fluorouracil (5-FU) em fluidos biológicos de humanos e animais, foram previamente relatados. No entanto, não há uma padronização para detecção de 5-FU na saliva de hamsters que receberam o quimioterápico. Considerando que a administração do 5-FU altera de alguma maneira a morfologia e função das glândulas salivares, e que a presença do quimioterápico na mucosa oral pode levar a algumas complicações orais, este trabalho teve como objetivo de determinar a presença de 5-FU na saliva de hamsters que receberam o quimioterápico pela técnica de Cromatografia Líquida de Alta Eficiência (CLAE), uma vez que este modelo animal é usado nos estudos com mucosite oral e hipofunção glandular, induzidas por 5-FU. Doze animais foram divididos em 4 grupos: CP e CPI, onde os animais receberam intraperitonealmente pilocarpina (CP) ou pilocarpina + isoproterenol (CPI) e o veículo do quimioterápico, e os grupos QP e QPI, onde os animais receberam, respectivamente, os mesmos secretagogos listados acima e o quimioterápico 5-FU. Após a administração do secretagogo, foi coletada a saliva de todos os animais, por um período de 60 min. Em seguida, a saliva foi congelada a -80 ˚C para posterior determinação do quimioterápico por CLAE. Após análise dos cromatogramas, e com base nos resultados obtidos, foi possível identificar a presença do 5-FU nas amostras de saliva de hamsters que receberam o quimioterápico via intraperitoneal pela técnica da CLAE. (AU)

Management of orofacial lesions with antimicrobial photodynamic therapy and photobiomodulation protocols in patients with COVID-19: A multicenter case series.

Several oral lesions related to COVID-19 have been described in the scientific literature. The COVID-19 pandemic highlighs importance of supportive protocols, which can reduce the inflammation and aid in tissue repair in severe cases. Photobiomodulation therapy (PBMT) alone or in combination with antimicrobial photodynamic therapy (aPDT) can be used to manage orofacial lesions in confirmed cases of COVID-19. Here, we sought to describe the clinical presentation and specificities of three cases in which aPDT and PBMT were used to manage orofacial lesions in patients with COVID-19. The laser protocols were effective with improvement of the orofacial lesions within a few days.

Wound healing process with different photobiomodulation therapy protocols to treat 5-FU-induced oral mucositis in hamsters.

OBJECTIVES: The aim of this study was to analyze the effects of three different Photobiomodulation Therapy (PBMT) protocols in the treatment of 5-fluorouracil-induced oral mucositis in hamsters. DESIGN: 60 hamsters were divided into five groups: group "C", which did not receive oral mucosa scratching, 5-fluorouracil (5-FU) or PBMT; group "Ch", which received anesthesia, superficial oral mucosa scratching and 5-FU (oral mucositis induction); and three groups that received oral mucositis induction and a PBMT protocol: groups ChLI, ChLII and ChLIII that received 0.24 J (one point), 1 J (one point) and 1.2 J (five points of 0.24 J) of energy, respectively. The laser equipment used had λ = 660 nm and 0.04 cm2 of spot area (0.226 cm diameter). The animals were euthanized on days 7 and 10 of the experiment, and their oral mucosas were removed for histological (light microscopy and collagen staining), immunohistochemical (NF-kB and TNF-α), and biochemical (TNF-α, NF-kB and hydroxyproline) analysis. RESULTS: Group ChLI (less energy), showed the most accelerated repair rates and a lower concentration of inflammatory biomarkers than group Ch. Comparing the three PBMT protocols for treatment of 5-FU-induced oral mucositis in hamsters, the one with low energy (0.24 J) showed better results, regarding reduction of inflammatory biomarkers and tissue repair, than the ones with higher energy (1 and 1.2 J).

Antimicrobial photodynamic therapy to oral candidiasis not responsive to micafungin in a patient undergoing hematopoietic cell transplantation.

In hematopoietic cell transplants (HCT) patients, opportunistic fungal infections - especially candidiasis - are typical and, due to the immunosuppressed condition, severe and fatal clinical conditions may occur. Many antifungal agents are used for treating candidiasis; however, there are non-responsive, drug-resistant cases in which alternative antimicrobial therapies are strongly needed. The present study aimed to report a clinical case in which antimicrobial photodynamic therapy (aPDT) was used for extensive oral pseudomembranous candidiasis not responsive to micafungin in a patient undergoing HCT. Thus, 0.01 % methylene blue solution was applied for 3 min onto the infected area, followed by 660-nm laser irradiation. Within 72 h, there was neither a symptom nor a sign of the fungal infection. According to the current case report, aPDT seems to be highly effective for HCT patients presenting oral candidiasis not responsive to micafungin; however, further studies are necessary.

Effect of Tungstate Administration on the Lipid Peroxidation and Antioxidant Parameters in Salivary Glands of STZ-Induced Diabetic Rats.

Sodium tungstate is an alternative to reduce hyperglycemia for the treatment of diabetes. In previous work, we showed that the administration of sodium tungstate increased the specific activity of salivary amylase in the parotid gland. Here, we investigated the effect of the administration of sodium tungstate on the lipid peroxidation and some antioxidant parameters in the submandibular (SM) and parotid (PA) salivary glands of streptozotocin (STZ)-induced diabetic rats. Thirty-two male Wistar rats were divided into four groups (n = 8, each): control (C), control treated with sodium tungstate (CT), diabetic (D), and diabetic treated with sodium tungstate (CT). Sodium tungstate (2 mg/ml) was administered to the STZ-induced diabetic rats for 15 days. Malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione, and blood glucose concentrations were quantified. In addition, superoxide dismutase (SOD) and catalase (CAT) activities were assessed. Results revealed that diabetes caused an increase in MDA concentration in both glands, a reduction in the SOD activity in SM, and an increase in catalase activity in PA glands. Administration of sodium tungstate reduced the blood glucose levels and normalized the SOD activity in the SM and MDA levels in both glands of the STZ-induced diabetic rats. Catalase activity was increased in PA glands of diabetic and tungstate-treated animals (p < 0.05). The GSH/GSSG ratio was increased in SM glands of tungstate-treated animals (p < 0.05). Overall, the reduction of hyperglycemia by sodium tungstate reduced lipid peroxidation and caused alterations in the antioxidant system in the salivary glands of STZ-induced diabetic rats.

Local management of neutropenic ulcer in a patient under breast cancer treatment.

Neutropenic ulcers are characterized by regular margins with a yellowish membrane, and are usually associated with severe pain and signs of inflammation due to opportunistic infections. Considering the immunosuppressed condition of these patients, local management of these lesions is a challenge. Antimicrobial photodynamic therapy (aPDT) is the association of light, which can be a low-power laser, with a photosensitizing agent and oxygen, whose synergy produces reactive oxygen species capable of reducing non-specific microbial contamination without causing side effects. The aim of this paper is to report a case of oral neutropenic ulcer treated with aPDT. A 50-year-old diabetic woman undergoing breast cancer treatment, presented with a malodorous malodorous and painful ulcer, which limited her basic oral functions. It was located in the maxillary alveolar ridge in the left first upper molar region and did not present bone involvement. Blood tests showed grade 2 of neutropenia. Thus, conservative treatment with aPDT technique was proposed. After one week, the lesion showed an improvement and pain had halved. The region was totally healed after three weeks. Local and non-invasive management of these lesions is of utmost importance for immunosuppressed patients, because it avoids systemic side effects and bacterial resistance resulting from overuse of antibiotics.

Early effect of laser irradiation in signaling pathways of diabetic rat submandibular salivary glands.

Low-power laser irradiation (LPLI) is clinically used to modulate inflammation, proliferation and apoptosis. However, its molecular mechanisms are still not fully understood. This study aimed to describe the effects of LPLI upon inflammatory, apoptotic and proliferation markers in submandibular salivary glands (SMGs) in an experimental model of chronic disorder, 24h after one time irradiation. Diabetes was induced in rats by the injection of streptozotocin. After 29 days, these animals were treated with LPLI in the SMG area, and euthanized 24h after this irradiation. Treatment with LPLI significantly decreased diabetes-induced high mobility group box 1 (HMGB1) and tumor necrosis factor alpha (TNF-α) expression, while enhancing the activation of the transcriptional factor cAMP response element binding (CREB) protein. LPLI also reduced the expression of bax, a mitochondrial apoptotic marker, favoring the cell survival. These findings suggest that LPLI can hamper the state of chronic inflammation and favor homeostasis in diabetic rats SMGs.

Photobiomodulation and antimicrobial photodynamic therapy for oral cytomegalovirus reactivation following acute graft-versus-host disease.

The relationship between cytomegalovirus (CMV), a severe complication in immunocompromised patients, and graft-versus-host disease (GVHD) has already been reported but remains without complete elucidation, especially concerning oral lesions. Considering that antimicrobial photodynamic therapy (aPDT) has an antimicrobial effect and photobiomodulation therapy (PBM) provides analgesia and modulation of inflammatory processes, the present study aimed to report a clinical case in which oral CMV reactivation following acute GVHD was treated by a combination of aPDT and PBMT concomitantly with conventional drug treatment. Intense and uninterrupted oral pain and consequent impairment of the patient's oral functions were present due to ulcerated lesions in the tongue, soft palate, and labial mucosa. After 72 hours from the first laser session, a marked decrease in the severity of the lesions and pain relief was observed. All oral lesions were repaired within 30 days. Based on this case report, when used concomitantly with conventional drug treatment, the combination of aPDT and PBMT seems to play a crucial role in treating CMV associated with GVHD.

Improvement of full-thickness rat skin wounds by photobiomodulation therapy (PBMT): A dosimetric study.

Basic dosimetric studies are necessary to support the use of photobiomodulation therapy (PBMT), since the great variety of laser parameters that are reported in the literature have created an obstacle to identifying reproducible results. Thus, the present study evaluates the process of tissue repair after the photobiomodulation therapy, taking into consideration the dose, frequency and the mode of energy delivery used. For this, 6 mm diameter wounds were created on dorsal skin of Wistar rats, and the animals were divided in control and irradiated groups, where L1 and L4 (irradiated with 1 point of 10 J/cm2), L2 and L5 (5 points of 10 J/cm2), L3 and L6 (1 point of 50 J/cm2), respectively for one or multiple days of irradiations. A diode laser, λ 660 nm, 40 mW of power and 0.028 cm2 of spot area was used. Our data showed that the group receiving multiple treatments over the first week post wounding, applied at 10 J/cm2 at each of 5 points on and around the wound (group L5) presented the best improvement of wound closure, higher cytokeratin 10, lower macrophage infiltration, and greater tissue resistance to rupture. We conclude that PBMT improves the skin wound healing process, and the outcomes were directly related to the chosen laser parameters and irradiation mode.

Site-Specific Expression Pattern of PIWI-Interacting RNA in Skin and Oral Mucosal Wound Healing.

The oral mucosa exhibits exceptional healing capability when compared to skin. Recent studies suggest that intrinsic differences in coding genes and regulatory small non-coding RNA (sncRNA) genes (e.g., microRNAs) may underlie the exceptional healing that occurs in the oral mucosa. Here, we investigate the role of a novel class of sncRNA-Piwi-interacting RNA (piRNA)-in the tissue-specific differential response to injury. An abundance of piRNAs was detected in both skin and oral mucosal epithelium during wound healing. The expression of PIWI genes (the obligate binding partners of piRNAs) was also detected in skin and oral wound healing. This data suggested that PIWI-piRNA machinery may serve an unknown function in the highly orchestrated wound healing process. Furthermore, unique tissue-specific piRNA profiles were obtained in the skin and oral mucosal epithelium, and substantially more changes in piRNA expression were observed during skin wound healing than oral mucosal wound healing. Thus, we present the first clue suggesting a role of piRNA in wound healing, and provide the first site-specific piRNA profile of skin and oral mucosal wound healing. These results serve as a foundation for the future investigation of the functional contribution(s) of piRNA in wound repair and tissue regeneration.

Phototherapy With LED as an Effective Treatment for Chemotherapy-Induced Oral Mucositis in Hamsters.

Introduction: Oral mucositis (OM) has been considered one of the most feared collateral effects of oncological treatments. Some therapies have been used, such as light-emitting diode (LED), with promising results, but with no sufficient evidence in the literature. Objective: Our study aimed to evaluate, by clinical and histological analysis, the effect of LED on the treatment of chemotherapy-induced OM (CIOM) in an animal model. Methods: Twenty male hamsters were equally distributed to two groups: control (C), which received anesthesia and CIOM induction; and LED (L), which received anesthesia, CIOM induction, and LED treatment (635 nm, 120 mW, 0.48 J). The clinical analysis was performed through two specific scales for OM analysis on days 5, 7 and 10 of the experiment. In addition, the injured area of all hamsters check pouch mucosa was removed and processed for histological analysis on the last experimental day. Results: After statistical analysis, group L showed less severity of OM when compared with the C group (P <0.05); beyond that, both healed completely on day 10. Conclusion: Our results suggested that the phototherapy with LED had a positive effect on accelerating repair, reducing the severity of CIOM.

Treating Acute Cervical Radiodermatitis with Photobiomodulation Therapy: A Report of Two Cases.

Objective: The objective of this study was to report the application of photobiomodulation therapy (PBMT) in the treatment of two patients diagnosed with acute cervical radiodermatitis (RD) induced by radiotherapy. Background data: An undesirable effect of radiotherapy, RD often poses a limitation to the continuity of treatment that can negatively affect the control and prognosis of the disease. RD is frequently associated with pain and aesthetic impairment and can significantly influence quality of life. Many agents used to prevent and treat RD do not have sufficient scientific evidence to support its use. Materials and methods: In both clinical cases, the patients presented RD degree 3 and were in drug treatment, with no satisfactory response, and PBMT was started. Two diode lasers were used, with a dose of 35.71 J/cm2, 10 sec/point, 100 mW of power, and a beam area of 0.028 cm2 and dose of 27.77 J/cm2, 25 sec/point, 40 mW, and 0.036 cm2 beam area. Both lasers were applied at the wavelength of red, daily, in contact and perpendicular to the skin, to deliver 1 J/point/1.5 cm, which covered the entire area affected with RD. Results: The PBMT made possible an expressive improvement in the healing process and reduction of painful symptoms associated with RD. Conclusions: Although PBMT facilitated healing and reduced pain experienced with RD, randomized controlled trials are needed to evaluate all of its possible benefits.

Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure.

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

Differential microRNA profile underlies the divergent healing responses in skin and oral mucosal wounds.

Oral mucosal wounds heal faster than skin wounds, yet the role of microRNAs in this differential healing has never been examined. To delineate the role of microRNAs in this site-specific injury response, we first compared the microRNAome of uninjured skin and oral mucosa in mice. A total of 53 tissue-specific microRNAs for skin and oral mucosa epithelium were identified. The most striking difference was the high abundance of miR-10a/b in skin (accounting for 21.10% of the skin microRNAome) as compared to their low expression in oral mucosa (2.87%). We further examined the dynamic changes of microRNAome throughout the time course of skin and oral mucosal wound healing. More differentially expressed microRNAs were identified in skin wounds than oral wounds (200 and 33, respectively). More specifically, miR-10a/b was significantly down-regulated in skin but not oral wounds. In contrast, up-regulation of miR-21 was observed in both skin and oral wounds. The therapeutic potential of miR-10b and miR-21 in accelerating wound closure was demonstrated in in vitro assays and in a murine skin wound model. Thus, we provided the first site-specific microRNA profile of skin and oral mucosal wound healing, and demonstrate the feasibility of a microRNA-based therapy for promoting wound closure.