REAC Antalgic Neuro Modulation in Chronic Post Herpetic Neuralgia.

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.

Melatonin finely tunes proliferation and senescence in hematopoietic stem cells.

Human hematopoietic stem/progenitor cells (HSPCs) are pluripotent cells that gradually lose their self-renewal and regenerative potential, to give rise to mature cells of the hematopoietic system by differentiation. HSPC infusion is used to restore hematopoietic function in patients with a variety of onco-hematologic and immune-mediated disorders. The functionality of these cells is therefore of great importance to ensure the homeostasis of the hematopoietic system. Melatonin plays an important role as immunomodulatory and oncostatic hormone. In the present manuscript, we aimed at evaluating the activity of melatonin in modulating HSPC senescence, in the attempt to improve their hemopoietic regenerative potential. We exposed HSPCs to melatonin, in different conditions, and then analyzed the expression of genes regulating cell cycle and cell senescence. Moreover, we assessed cell senescence by ß-galactosidase and telomerase activity. Our results showed the ability of melatonin to counteract HSPC senescence, thus paving the way for enhanced efficiency in their clinical application.

Myrtle-Functionalized Nanofibers Modulate Vaginal Cell Population Behavior While Counteracting Microbial Proliferation.

Vaginal infections affect millions of women annually worldwide. Therapeutic options are limited, moreover drug-resistance increases the need to find novel antimicrobials for health promotion. Recently phytochemicals were re-discovered for medical treatment. Myrtle (Myrtus communis L.) plant extracts showed in vitro antioxidant, antiseptic and anti-inflammatory properties thanks to their bioactive compounds. The aim of the present study was to create novel nanodevices to deliver three natural extracts from leaves, seeds and fruit of myrtle, in vaginal milieu. We explored their effect on human cells (HeLa, Human Foreskin Fibroblast-1 line, and stem cells isolated from skin), resident microflora (Lactobacillus acidophilus) and on several vaginal pathogens (Trichomonas vaginalis, Escherichia coli, Staphylococcus aureus, Candida albicans, Candida kefyr, Candida glabrata, Candida parapsilosis, Candida krusei). Polycaprolactone-Gelatin nanofibers encapsulated with leaves extract and soaked with seed extracts exhibited a different capability in regard to counteracting microbial proliferation. Moreover, these nanodevices do not affect human cells and resident microflora viability. Results reveal that some of the tested nanofibers are interesting candidates for future vaginal infection treatments.

REAC neurobiological treatments in acute post-traumatic knee medial collateral ligament lesion.

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.

Radio electric asymmetric conveyer neuromodulation in depression, anxiety, and stress.

BACKGROUND: The purpose of this study was to assess the efficacy of specific neuromodulation treatments performed with radio electric asymmetric conveyer (REAC) technology in the treatment of the symptomatic triad depression, anxiety, and stress by the use of a specific psychometric test such as the Depression Anxiety Stress Scale-42 items (DASS-42) version, which assesses simultaneously the severity of expression of this triad. PATIENTS AND METHODS: The design of this study was planned to compare two populations that performed DASS-42 test twice within a similar period of time. The first population performed the first DASS test before the treatment and the second test about 3 months later, at the end of two specific REAC neuromodulation treatments, neuropostural optimization (NPO) and neuropsychophysical optimization (NPPO), that have previously shown an efficacy in the treatment of depression, anxiety and stress. The second population (untreated), used as the randomized control group, consisted of a similar group by gender and age, who performed the DASS-42 test in an online platform twice, with an interval of about 3 months between the first and second tests, similar to the interval between the two tests in the treated group. RESULTS: The comparison between the treated group and the control group points out the REAC treatment efficacy in improving the quality of life. At the second DASS-42 test, self-administered about 3 months after the treatments, treated patients were positioned on average values of much milder severity in all the three clusters, depression, anxiety, and stress, while in untreated patients there was no significant difference between the mean values of the first and second DASS tests. CONCLUSION: The results obtained in this study, evaluated with the DASS-42 test, confirm that REAC-NPO and REAC-NPPO neuromodulation treatments can be useful tools for the clinical treatment of depression, anxiety, and stress, as already proven by previous results evaluated with different psychometric tests.

Avaliação da terapia fotodinâmica mediada por azul de metileno na cicatrização: estudo experimental in vivo / Evaluation of methylene blue mediated photodynamic therapyin wound healing: in vivo experimental study

Objetivo: Avaliar os efeitos tissulares de uma única aplicação da Terapia Fotodinâmica em lesões induzidas em modelos experimentais, determinando sua influência na formação colagênica e na duração do ciclo celular. Método: Cinquenta lesões induzidas em camundongos Mus Musculus foram randomicamente tratadas com Terapia Fotodinâmica mediada por Azul de Metileno a 0,01% ativado por Laser vermelho 660 nm (G1), Laserterapia sem fotossensibilizador (G2), Azul de Metileno a 0,01% (G3), Pomada dermatológica como controle positivo (G4) e água destilada como controle negativo (G5), sendo avaliados histologicamente quanto à deposição colagênica e áreas de organização nucleolar após 72 horas do tratamento. Resultados: Os grupos fotoativados apresentaram diferença significativa quanto à deposição colagênica (p<0,05) pela coloração de Tricrômio de Masson, demonstrando evidências de redução do tempo de reparo. Não houve diferença significativa (p> 0,05) pela técnica AgNOR nas regiões organizadoras nucleolares. Conclusões: A Terapia Fotodinâmica e a fotobiomodulação por Laser apresentaram evidência de deposição colagênica já nas primeiras horas do processo de cicatrização, sem necessariamente alterar a duração do ciclo celular local, não exercendo aceleração no processo de proliferação celular nas condições experimentais avaliadas neste estudo.

Objective: To evaluate the tissue effects of a single application of Photodynamic Therapy on lesions induced in experimental models, determining their influence on collagen formation and cell cycle duration. Method: Fifty lesions induced in Mus Musculus mice were randomly treated with 0.01% Methylene Blue mediated Photodynamic Therapy activated by 660 nm Red Laser (G1), Lasertherapy without photosensitizer (G2), 0.01% Methylene Blue (G3), Dermatological Ointment as positive control (G4) and Distilled Water as negative control (G5), being histologically evaluated for collagen deposition and areas of nucleolar organization after 72 hours of treatment. Results: The photoactivated groups showed a significant difference regarding collagen deposition (p<0,05) by the Massons Trichrome Stain, showing evidence of reduced repair time. There was no significant difference (p>0.05) by the AgNOR technique in the nucleolar organizer regions. Conclusions: Photodynamic Therapyand Laser Photobiomodulation showed evidence of collagen deposition in the first hours of the healing process, without necessarily changing the duration of the local cell cycle, not exerting acceleration in the cell proliferation process under the experimental conditions evaluated in this study

Effect of 5-ALA-mediated photodynamic therapy on mast cell and microvessels densities present in oral premalignant lesions induced in rats.

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.

Antimicrobial photodynamic therapy in the treatment of oral candidiasis in HIV-infected patients.

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.

Alterações histológicas provocadas pelas ondas ultrassônicas contínuas de 01 MHz no disco epifisário em tíbia de camundongo / Histological changes caused by continuous ultrasonic waves of 01 MHz on the epiphyseal disk of murine tibia

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...

Análise da expressão de marcadores de morte celular em lesões potencialmente malignas induzidas com 4-NQO e tratadas com terapia fotodinâmica / Analysis of cellular death biomarkers expression in potentially malignant lesions induced with 4-NQO and treated with photodynamic therapy

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.