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Fibromyalgia syndrome (FS) is a disorder characterized by widespread musculoskeletal pain and psychopathological symptoms, often associated with central pain modulation failure and dysfunctional adaptive responses to environmental stress. The Radio Electric Asymmetric Conveyer (REAC) technology is a neuromodulation technology. The aim of this study was to evaluate the effects of some REAC treatments on psychomotor responses and quality of life in 37 patients with FS. Tests were conducted before and after a single session of Neuro Postural Optimization and after a cycle of 18 sessions of Neuro Psycho Physical Optimization (NPPO), using evaluation of the functional dysmetria (FD) phenomenon, Sitting and Standing (SS), Time Up and Go (TUG) tests for motor evaluation, Fibromyalgia Impact Questionnaire (FIQ) for quality of life. The data were statistically analyzed, and the results showed a statistically significant improvement in motor response and quality of life parameters, including pain, as well as reduced FD measures in all participants. The study concludes that the neurobiological balance established by the REAC therapeutic protocols NPO and NPPO improved the dysfunctional adaptive state caused by environmental and exposomal stress in FS patients, leading to an improvement in psychomotor responses and quality of life. The findings suggest that REAC treatments could be an effective approach for FS patients, reducing the excessive use of analgesic drugs and improving daily activities.
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BACKGROUND: Chronic post-herpetic neuralgia (CPHN) is a symptomatic condition that afflicts adults and elderly individuals. The chronicity of this symptomatology can be conditioned by the epigenetic modifications induced by the virus on the processes of neurotransmission and sensitivity to pain. The aim of this study is to investigate whether manipulating endogenous bioelectrical activity (EBA), responsible for neurotransmission processes and contributing to the induction of epigenetic modifications, can alleviate pain symptoms. METHODS: This manipulation was carried out with the antalgic neuromodulation (ANM) treatment of radioelectric asymmetric conveyer (REAC) technology. Pain assessment before and after treatment was performed using a numerical analog scale (NAS) and a simple descriptive scale (SDS). RESULTS: The results of the analysis showed an over four-point decrease in NAS scale score and over one point decrease in SDS scale score, with a statistical significance for both tests of p < 0.005. CONCLUSIONS: The results obtained in this study demonstrate how REAC ANM manipulation of EBA can lead to improvement in epigenetically conditioned symptoms such as CPHN. These results should prompt further research to expand knowledge and ensure optimized therapeutic outcomes.
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INTRODUCTION: The purpose of this retrospective study was to compare the effects of two different modalities of administration of the neuro psycho physical optimization (NPPO) neuromodulation treatment, applied with radio electric asymmetric conveyer (REAC) biotechnology devices. Both the modalities are aimed at improving the strategies to deal with and optimize the allostatic response to environmental stressors and exposome. This allows to reduce the dysfunctional adaptive behavior patterns, which underlie many neuropsychological symptoms and pathologies, and to improve the symptoms of depression, anxiety and stress. MATERIALS AND METHODS: From a population of subjects experiencing at least two of the three symptoms depression, anxiety and stress, the selection of pre and post-treatment Depression, Anxiety, Stress 21 items scale (DASS 21) data was made proceeding with a reverse chronological recruitment mechanism, until reaching 150 subjects for each of the 2 groups. The first group was treated with the neuro psycho physical optimization treatment (NPPO), which is the punctiform modality of administration on the auricle pavilion, and the second group was treated with the neuro psycho physical optimization treatment, which is the area modality of administration applied by the planar probe on the cervicobrachial area (NPPO-CB). RESULTS: The Wilcoxon signs test confirmed the differences in scores in pre and post-treatment DASS-21. The comparison between the two groups data and the comparison across groups data showed that NPPO and NPPO-CB have the same efficacy in reducing the symptoms of depression, anxiety and stress, after a single treatment cycle. Statistical significance was set at p <0.05. DISCUSSION: This is the first efficacy descriptive comparison between the two different modalities of administration of the NPPO treatment, as different options for the same clinical indication.
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INTRODUCTION: In addition to the effects of coronavirus infection, the Covid-19 pandemic has induced widespread psychosocial distress, which has triggered the onset of anxious and depressive states, reactive to the socio-relational and economic situation induced by the pandemic. Some of our participants showed depressive and anxious attitudes even in the absence of real pictures of depression and anxiety. This phenomenon, combined with mechanisms of emulation and conditioning, can trigger a vicious cycle within interpersonal relationships and promote the administration of unnecessary treatments. Various approaches have been proposed to help populations suffering from psychosocial problems induced by the Covid-19 pandemic, but there is an objective difficulty in treating a large population. METHODS: To contain and reduce this widespread psychosocial unease, in this study we used two radio electric asymmetric conveyer (REAC) technology neuromodulation treatments, neuro postural optimization (NPO) and neuropsychophysical optimization-cervicobrachial (NPPO-CB), aimed at optimizing an individual's response to the effects of environmental stressors. These treatments are quick and easy to administer; therefore, they can be administered to a large cohort of participants in a short time. To evaluate the effects of the REAC NPO and NPPO-CB treatments, the DASS-21 psychometric test was used because it has already been used to test depression, anxiety, and stress during the Covid-19 pandemic. RESULTS: The results of the study confirm the usefulness of REAC NPO and NPPO-CB treatments in helping participants to have better coping strategies for the environmental pressures and reduce the neuropsychological and behavioral effects induced by the Covid-19 pandemic. DISCUSSION: The results obtained in this study are consistent with previous clinical studies confirming the usefulness of the treatments to face neuropsychological and behavioral effects induced by exposome pressure.
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OBJECTIVE: Physical traumas can lead to unconscious neuropsychical alterations, which can compromise rehabilitation result and functional recovery. Aim of this interventional study is to verify if neurobiological Radio Electric Asymmetric Conveyer (REAC) treatments Neuro Postural Optimization (NPO) and Tissue Optimization (TO) are able respectively to improve neuro psychomotor strategies and facilitate recovery process in medial collateral ligaments (MCL) lesions of the knee. PATIENTS AND METHODS: 45 healthy subjects, 32 males and 13 females, with knee MCL lesion, diagnosed with MRI or ultrasound. Within 4 days after the trauma, subjects were clinically evaluated (T0), both through medical and subjective assessments. Clinical evaluation was repeated after the REAC NPO treatment (T1) and at the end of 18 REAC TO treatments (T2) and at the 30 days follow-up (T3). RESULTS: In comparison with the results commonly found in clinical practice, all REAC treated patients recovered much faster. They reported functional recovery, pain relief and joint stability, regardless of the severity of the lesion. CONCLUSION: The combined use of REAC NPO and TO can envisage a new rehabilitative approach, which aims not only at recovering the outcomes of the physical trauma, but also at improving the neuropsychical state that can condition the rehabilitation result.
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OBJECTIVE: The 4-nitroquinoline 1-oxide (4-NQO) model for carcinogenesis has been used to investigate cancer stem cells (CSC), but no study has addressed the role of the p75 neurotrophin receptor (p75NTR) in 4-NQO-induced oral dysplasia and oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the immunohistochemistry profile of the p75NTR during 4-NQO-induced oral carcinogenesis in rats and to verify whether this profile has an association with proliferating cell nuclear antigen (PCNA) immunolabeling. DESIGN: For 28 weeks, rats were exposed to 4-NQO, which was diluted in the drinking water. After 3, 5, 7, 16, and 28 weeks, the animals were euthanized and their tongues were histologically analyzed using p75NTR and PCNA immunolabeling. RESULTS: In animals without 4-NQO exposure, the p75NTR and PCNA were expressed only in the basal epithelial layer and in a clustered manner. The oral epithelium showed dysplasia and a significant increase in the number of p75NTR- and PCNA-positive cells, which were localized mainly in the basal and suprabasal epithelial layers during weeks 5-16 of 4-NQO exposure. When the epithelium invaded the lamina propria and well-differentiated OSCC began, the p75NTR-positive cell frequency drastically decreased in epithelial cords and nests, showing a negative correlation with PCNA expression. p75NTR immunolabeling during 4-NQO-induced carcinogenesis was similar to that described for human head and neck dysplasia and neoplasia. CONCLUSIONS: p75NTR immunolabeling observed in 4-NQO-induced oral dysplastic and OSCC lesions were related to the early phases of oral carcinogenesis and may help predict cell dysplasia and malignant transformation.
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Biomarcadores Tumorais , Carcinoma de Células Escamosas , Neoplasias Bucais , Lesões Pré-Cancerosas , Receptor de Fator de Crescimento Neural , Animais , Masculino , Ratos , 4-Nitroquinolina-1-Óxido , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Ratos Wistar , Receptor de Fator de Crescimento Neural/metabolismoRESUMO
Impairment of vascular functions after photodynamic therapy (PDT) is frequently associated with tumor remission and is considered one of the main antineoplastic PDT effects. Vascular alterations in oral leukoplakia (OL) treated with PDT have not yet been described. The aim of this study was to evaluate the effect of topical 5-ALA-mediated PDT on the vascular network of 4NQO-induced OL in rats. After applying 4NQO topically on the tongue during 16 weeks, there was induction of dysplastic lesions, which were treated with two PDT sessions (with an interval of 72 h between them), using topical application of 5-ALA and posterior irradiation with a laser (90 J/cm2 fluency). Histological sections of the tongues were obtained and analyzed concerning plasmatic exudation and microvessel density after immunolabeling with CD31 and CD34 vessel markers. There was intense plasmatic exudation after 6 h of the first PDT session; at 6 h of the second PDT session, there was a significant reduction in the density of CD31- and CD34-positive microvessels in comparison to controls (p < 0.05). In the PDT intervals, there was an increase in the density of CD31 and CD34 microvessels, suggesting angiogenesis. Topical application of 5-ALA-mediated PDT caused an immediate deleterious effect on the vascular network, increasing vessel permeability and reducing vessel density, mainly after two sessions of the treatment. However, secondary angiogenesis emerged in these lesions during intervals of the PDT session. This fact may be considered during the adoption of a PDT protocol, to avoid OL resistance and recurrence after the treatment.
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Ácido Aminolevulínico/uso terapêutico , Leucoplasia Oral/tratamento farmacológico , Microvasos/patologia , Fotoquimioterapia/efeitos adversos , 4-Nitroquinolina-1-Óxido , Ácido Aminolevulínico/farmacologia , Animais , Humanos , Imuno-Histoquímica , Leucoplasia Oral/patologia , Masculino , Microvasos/efeitos dos fármacos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Tamanho do Órgão , Fármacos Fotossensibilizantes/farmacologia , Quinolonas , Ratos Wistar , Língua/efeitos dos fármacos , Língua/patologiaRESUMO
Acute inflammatory response after photodynamic therapy is frequently described, and increase on mast cell degranulation is also present during this process. The mast cell activation may improve angiogenesis, and this fact has been associated with progression of oral premalignant lesions (OPL). The aim of this study was to evaluate whether photodynamic therapy (PDT) increases mast cell density (MCD) and microvessels density (MVD) in 4-nitroquinoline-1-oxide(4NQO)-induced OPL in rats. 4NQO-induced OPL were treated or not with 5-ALA followed by laser irradiation (PDT group and 4NQO groups, respectively). Mast cells and CD34+ microvessels were counted. Both PDT and 4NQO groups had MCD and MVD that were higher than normal mucosa (p b 0.05). The 4NQO group had the lowest number of non-degranulated MCD in comparison to experimental periods of PDT (PDT 6 h p=0.020; 24 h p=0.016; 48 h p=0.003; 72 h p=0.033). Only in the PDT group did MCD and MVD have a significant correlation (r= 0.6219, p = 0.010). 5-ALA-mediated PDT modified the MCD and MVD in the induced OPL, leading to degranulation of mast cells and angiogenesis. A PDT protocol with an efficient eradication of the OPL must be adopted considering the angiogenesis potential associated with the mast cell activation after the therapy.
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Ácido Aminolevulínico/uso terapêutico , Mastócitos/fisiologia , Microvasos/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Língua/tratamento farmacológico , 4-Nitroquinolina-1-Óxido/toxicidade , Ácido Aminolevulínico/farmacologia , Animais , Antígenos CD34/metabolismo , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/efeitos da radiação , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Lasers , Mastócitos/citologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Ratos , Ratos Wistar , Língua/patologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/veterináriaRESUMO
BACKGROUND: Most studies have demonstrated 4-NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4-NQO topical application during early phases of oral cancer induction. METHODS: A 4-NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry. RESULTS: Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected. CONCLUSIONS: 4-NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.
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Carcinogênese/induzido quimicamente , Carcinógenos/toxicidade , Quinolonas/toxicidade , 4-Nitroquinolina-1-Óxido/toxicidade , Administração Tópica , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Análise Química do Sangue , Feminino , Queratinócitos/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Contagem de Leucócitos , Leucoplasia Oral/induzido quimicamente , Fígado/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Ratos , Ratos Wistar , Albumina Sérica/efeitos dos fármacos , Baço/citologia , Baço/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacos , Língua/efeitos dos fármacos , Neoplasias da Língua/induzido quimicamente , Aumento de Peso/efeitos dos fármacosRESUMO
Objetivos: Verificar alterações histológicas no disco epifisário da tíbia em crescimento de camundongos em exposição a ondas ultrassônicas de frequência de 1 MHz.Métodos: Estudo experimental de natureza quantitativa e randomizado. Para tanto, 16 camundongos albinos da linhagem Swiss Webster, em fase de crescimento, com idade de três semanas e peso entre 10-15 g foram distribuídos aleatoriamente em dois grupos de oito animais cada um, e expostos a ondas ultrassônicas na tíbia direita. Os grupos foram designados D1 (exposto à dose de 0,1 w/cm2) e D2 (exposto à dose de 0,5 w/cm2). O grupo controle, designado C, foi representado por 16 amostras referentes ao lado contralateral de cada animal dos grupos D1 e D2. Os procedimentos ocorreram em uma aplicação/dia, totalizando ao final, 10 aplicações sem interrupção. Analise histológica ocorreu pelas técnicas de hematoxilina-eosina, alcian blue e von kossa, visando medir a área da cabeça da tíbia versus disco epifisário e as espessura das zonas proliferativa e hipertrófica. Para análise estatística foi utilizado teste de Friedman com correção de Bonferroni.Resultados: O tecido ósseo foi influenciado pelas ondas ultrassônicas, assim como o disco epifisário, em que o grupo de maior parâmetro teve a área total do disco maior do que os demais. A zona calcificada não sofreu influência das ondas ultrassônicas, porém a zona proliferativa foi sensível a essa terapia, principalmente na menor dose. Não foi encontrada nenhuma alteração anatomopatológica nos grupos tratados econtrole.Conclusões: Nos parâmetros utilizados neste estudo foi observada ação positiva do ultrassom na cartilagem, e no tecido ósseo em formação, não sendo possível precisar qual foi o nível de intensidade da aplicação do ultrassom mais significativo estatisticamente...
AIMS: To evaluate the histological changes in the epiphyseal disk of the tibia in growing mice during exposure to ultrasonic waves of 1MHz frequency.METHODS: Experimental study of quantitative and randomized nature. For this purpose, 16 Swiss albino mice of the Webster strain, during growth, aged 3 weeks and weighing 10-15 g were randomly divided into two groups of eight animals each and exposed to ultrasonic waves in the right tibia. Groups D1 (exposed to a dose of 0.1 W/cm2) and D2 (exposed dose of 0.5 W/cm2) were assigned. The control group, designated C, was represented by 16 samples relating to the contralateral side of each animal of groups D1 and D2. Procedures occurred in an application/day, totaling 10 applications without interruption. The samples were analyzed histological by hematoxylin-eosin staining techniques, Alcian blue and Von Kossa stains, in order to measure the area of the head versus the tibia epiphysial disc, beyond the thickness of the proliferative and hypertrophic zones. For statistical analysis we used the Friedman test with Bonferroni correction.RESULTS: The bone tissue was influenced by ultrasonic waves, as well as the epiphyseal plate, where the group had the largest parameter of the total area larger than the other disc. The calcified zone was not influenced by the ultrasonic waves, but the proliferative zone was sensitive to this therapy, especially at the lowest dose. No pathological changes were found in the treated and control groups.CONCLUSIONS: With the parameters used in this study positive action of ultrasound was observed in the cartilage and bone tissue formation, not being possible to determine what was the intensity level of the application of ultrasound statistically more significant...
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Camundongos , Desenvolvimento Ósseo , Histologia , Terapia por UltrassomRESUMO
Fractionation can improve photodynamic therapy (PDT) efficacy for potentially malignant oral lesion treatment. The aim of this study was to demonstrate the apoptosis/proliferation index of oral keratinocytes after two sessions of topical 5-ALA-mediated PDT in 4-Nitroquinoline-1-oxide-induced potentially malignant oral lesion, and to suggest the ideal interval between PDT sessions. Immuno-histochemical tests for proliferating cell nuclear antigen and caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed at 6h, 24h, 48h, and 72h time intervals after PDT. The number of positive cells showing caspase-3 expression was significantly higher, mainly at 6h after PDT. In the first cycle of PDT, the highest frequency of positive cells for TUNEL was found at 24h. At 72h after PDT, proliferating cell nuclear antigen positive cells increased significantly, indicating that there was an epithelial response in direction towards DNA repair and cell proliferation at this time. Because cell proliferation increases and cell death index decreases at 72h after PDT, it is recommended that the interval between the PDT sessions must not be longer than 2days up to total lesion remission.
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Ácido Aminolevulínico/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/tratamento farmacológico , Fotoquimioterapia , Quinolonas/efeitos adversos , 4-Nitroquinolina-1-Óxido/efeitos adversos , Administração Tópica , Ácido Aminolevulínico/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Epitélio/efeitos dos fármacos , Epitélio/patologia , Epitélio/efeitos da radiação , Feminino , Queratinócitos/patologia , Neoplasias Bucais/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ratos WistarRESUMO
As lesões potencialmente malignas orais (LPMO) constituem processos com chances de malignização e, portanto, o acompanhamento rigoroso e a retirada das lesões em situações de displasia são mandatórios. A terapia fotodinâmica (PDT) tem sido apontada como uma alternativa promissora e não invasiva para o tratamento dessas lesões. O princípio terapêutico da PDT envolve a geração de altos níveis de estresse oxidativo, pela associação de uma substância fotoativa com a energia eletromagnética e o oxigênio tecidual. É capaz de inviabilizar, através de cascatas de morte ainda pouco esclarecidas, células com alterações metabólicas significativas. A maioria dos trabalhos aponta a necessidade de várias sessões de PDT para erradicar as LPMO, porém o intervalo entre as sessões ainda é discutível. O objetivo deste trabalho foi estabelecer a relação anatomocronológica de marcadores de morte celular (caspase 3, beclin 1 e RIP 1 ) e de proteína de reparo do DNA durante o ciclo celular (PCNA) presentes após a PDT, com o intuito de verificar a cinética morte/proliferação celular e sugerir o intervalo de tempo entre as sessões de PDT mais adequado para a repetição da terapia. Para tanto, LPMOs foram induzidas por intermédio da aplicação tópica de 4-nitroquinolina-1-óxido (4-NQO) na mucosa lingual de ratos e posteriormente tratadas com PDT mediada pela administração tópica do ácido 5-aminolevulínico (5-ALA) e laser comercial (660nm, 90J. cm-2, 1000mW. cm-2). O efeito da PDT foi analisado nos tempos experimentais de 6h, 24h, 48h e 72h após a primeira sessão de PDT, e em 6h e 72h após uma segunda sessão. Nesses períodos, as línguas foram avaliadas clinica e histopatologicamente em relação ao percentual de redução das lesões induzidas e à morfologia do tecido, bem como por meio de análise imuno-histoquímica para PCNA; caspase 3 clivada (presente na apoptose), Beclin 1 (presente na autofagia) e RIP 1 (presente na necroptose).
Foi determinada a porcentagem de células positivas para esses marcadores no epitélio da mucosa lingual. Não houve remissão completa das lesões nas duas sessões de PDT, mas a segunda sessão acarretou diminuição em torno de 50% no tamanho das lesões. O período de 6h após a PDT foi o que exibiu significativa atrofia epitelial, bem como a maior porcentagem de células positivas para todos os marcadores analisados, incluindo o PCNA, em ambas as sessões. Caspase 3, beclin 1 e RIP 1 exibiram significativa diminuição da expressão em 24h. O PCNA exibiu aumento significativo no período 72h, e nos dois períodos do segundo ciclo. Como não houve a presença de necrose, a expressão aumentada de RIP 1 foi associada ao processo de apoptose e autofagia. Concluiu-se que a PDT mediada pelo 5-ALA provocou aumento da expressão de caspase 3, beclin 1 e RIP 1 em LPMO nas primeiras 6h após a terapia. Nesse modelo de PDT, essas proteínas parecem interagir em mecanismos de morte por apoptose e por autofagia, mas não por necrose. Considera- se o intervalo de 24h como o mais adequado para novo ciclo com os presentes parâmetros, sem que se estenda além de 72h.
The potentially malignant oral lesions (PMOL) are processes with great chances for cancer transformation and therefore the close monitoring and removal of lesions in cases of dysplasia are mandatory. Photodynamic therapy (PDT) has been identified as a promising and noninvasive treatment for these injuries. The therapeutic principle of PDT involves the generation of high levels of oxidative stress, by association of a photoactive substance with electromagnetic energy and tissue oxygen. It can kill metabolically changed cells through cascades of death which are still unclear. Most studies indicate the need of several PDT sessions to eradicate PMOL, however the interval between sessions is not consensual. The aim of this study was to establish the anatomical and chronological relationship between cellular death biomarkers (caspase 3, beclin 1 and RIP 1 ) and a DNA repair protein during cell cycle (PCNA) present after PDT, aiming to check the kinetic death/cell proliferation and suggest the time interval between PDT sessions more suitable to repetition of the PDT. For this purpose, PMOLs were induced by 4-nitroquinoline-1-oxide (4-NQO) topical application on the lingual mucosa of rats and further treated with PDT mediated by topical administration of 5-aminolevulinic acid (5-ALA) and a commercial laser (Twin flex-MM Optics São Carlos-Brazil 660nm, 90J.cm-2,1000mW.cm-2).The effect of PDT was analyzed at 6h, 24h, 48h and 72h after the first session, and at 6h and 72h after a second session. In these periods, the tongues have been evaluated clinically and histopathologically regarding the percentage reduction of lesions induced and tissue morphology as well as by immunohistochemical analysis for PCNA, cleaved caspase 3 (present in apoptosis), Beclin 1 (present in autophagy) and RIP (present in necroptosis). The percentage of positive cells for these markers was determined in the epithelium of the tongue mucosa.
There was no complete remission of lesions after two PDT sessions, but the second session resulted in a decrease of around 50% in lesion size. The period of 6 hours after PDT was the one in which significant epithelial atrophy was exhibited, as well as the highest percentage of positive cells for all tested markers, including PCNA in both sessions. Caspase 3, beclin 1 and RIP 1 exhibited a significant decrease of the expression at 24 hours. PCNA showed significant increase in the 72-hour period and after 6h and 72h from the second session. As there was no necrosis, the increased expression of RIP 1 has been linked to apoptosis and autophagy. It was concluded that PDT mediated by 5-ALA promoted incresead expression of caspase 3, beclin 1 and RIP 1 at the PMOLs in the first 6 hours after therapy.
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Imuno-Histoquímica , Lesões Pré-Cancerosas/complicações , Patologia Bucal , FotoquimioterapiaRESUMO
OBJECTIVE: Antimicrobial photodynamic therapy (aPDT) has been used to combat local infections, and it consists of the combination of a photosensitizer, a light source, and reactive oxygen species (ROS) to kill microbial cells. In this study, we evaluated the effectiveness of aPDT in the treatment of candidiasis in HIV-infected patients. METHODS: Twenty-one patients were divided into three groups. Control group (CG) was treated with the conventional medication for candidiasis (fluconazole 100 mg/day during 14 days). Laser group (LG) was subjected to low-level laser therapy (LLLT), wavelength 660 nm, power of 30 mW, and fluence of 7.5 J/cm(2), in contact with mucosa during 10 sec on the affected point. An aPDT group (aPDTG) was treated with aPDT, that is, combination of a low-power laser and methylene blue 450 µg/mL. Pre-irradiation time was 1 min. Parameters of irradiation were the same ones as for the LG, and patients were single irradiated. Patients were clinically evaluated and culture analysis was performed before, immediately after, and 7, 15, and 30 days after the treatment. RESULTS: Our results showed that fluconazole was effective; however, it did not prevent the return of the candidiasis in short-term. LLLT per se did not show any reduction on Candida spp. aPDT eradicated 100% of the colonies of this fungus and the patients did not show recurrence of candidiasis up to 30 days after the irradiation. CONCLUSIONS: These findings suggest that aPDT is a potential approach to oral candidiasis treatment in HIV-infected patients.