Antimicrobial photodynamic therapy with methylene blue and its derivatives in animal studies: Systematic review.

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.

Repercussion of inflammatory bowel disease on lung homeostasis: The role of photobiomodulation.

Inflammatory bowel diseases (IBD) are chronic and multifactorial diseases characterized by dysfunction of the intestinal mucosa and impaired immune response. Data show an important relationship between intestine and respiratory tract. The treatments of IBD are limited. Photobiomodulation (PBM) is an effective anti-inflammatory therapy. Our objective was to evaluate the repercussion of IBD as well as its treatment with PBM on pulmonary homeostasis. Male Wistar rats were submitted to IBD induction by acetic acid and treated or not with PBM. Rats were irradiated with red LED on both right and left sides of the ventral surface and beside the external anal region during 3 consecutive days (wavelenght 660 nm, power 100 mw, total energy 15 J and time of irradiation 150 s per point). Our results showed that IBD altered pulmonary homeostasis, since we observed an increase in the histopathological score, in myeloperoxidase activity (MPO), in mast cell degranulation, and in the release and gene expression of cytokines. We also showed that PBM treatment reduced biomarkers of IBD and reverted all augmented parameters in the lung, restoring its homeostasis. Thus, we confirm experimentally the important gut-lung axis and the role of PBM as a promising therapy.

The supportive use of photobiomodulation on salivary glands: a narrative review and meta-analysis.

PURPOSE: Radiotherapy is one of the main strategies used in the treatment of cancer patients and it can cause early or late xerostomia and/or hyposalivation. Therapeutic management of xerostomia includes oral hygiene, sialogenic agents among others. METHODS: This study reviews the use of extra-oral salivary glands photobiomodulation in treating xerostomia and/or hyposalivation after radiotherapy and performs a meta-analysis of this data. RESULTS: After a broad search of the literature, eight clinical studies were selected. DISCUSSION: In a safe way, the studies found that extra-oral stimulation of the salivary glands has benefits in the hyposalivation and changes in salivary flow resulting from lesions by radiotherapy. A meta-analysis found significant values in pain comparing the pre- and post-treatment moments (MD - 3.02, I2 95%, IC - 5.56; - 0.48) and for stimulated salivary flow at 30 days after the end of radiotherapy (MD 2.90, I2 95%, IC 1.96; 3.84). CONCLUSION: The most promising parameters comprise wavelengths between 630 and 830 nm, radiant exposure from 2 to 10 J/cm2, two-to-three times a week, before the radiotherapy damage, and homogeneously in the glands. Therefore, Light-Emitting Diode (LED) stimulation of larger areas than the punctual stimulation of small millimeters of the Low-Level Laser Therapy (LLLT) appears to be promising.

Application of a physiotherapeutic protocol associated with photobiomodulation for the treatment of leprosy patients.

Leprosy is a chronic infectious disease characterized by acute inflammatory episodes that affect the skin and peripheral nerves and can develop progressive and irreversible disabilities and deformities. In addition, drug therapy and physiotherapy offer resources and techniques capable of mitigating the consequences of neural lesions, but neural lesions can occur before, during, and even after drug treatment. Thus, new treatments are needed. Photobiomodulation (PBM) might be a promissor therapy since it aims to reduce the inflammatory process and restore motor and sensory functions in the affected area. This study aims to compare the evolution of neural status, pain, and functionality in patients with leprosy and neuritis after a physiotherapeutic protocol and PBM treatment. This was a randomized controlled clinical trial that analyzed a group of patients receiving a physiotherapeutic protocol (PPG) and another receiving physiotherapeutic protocol associated with PBM (PLG) (wavelength 904 nm, potency 70 mW, time per point 9 s). Our results showed when evaluating functional capacity limitations with the SALSA scale, the PLG patients improved from moderate to mild limitations. On the other hand, the PPG remained as moderate limitations. Also, the PLG showed a significant reduction in pain on the VAS scale. The neurological assessment showed that PLG improved palpation of the median, radial, and peroneal nerves. In the strength test, PLG patients improved in the 5th finger abduction and ankle dorsiflexion. Assessing sensitivity, it was identified an improvement in PLG for the ulnar nerve and tibial nerve. All those changes were statistically significant when compared to the PPG patients. Finally, the PLG patients improved disabilities, identified by the neurological assessment of the eyes, hands, and feet. In conclusion, this study demonstrated that combining a physiotherapeutic protocol with PBM treatment effectively improved functional status and reduced pain in leprosy patients.

Intravascular laser irradiation of blood (ILIB) used to treat lung diseases: a short critical review.

Intravascular laser irradiation of blood (ILIB) was developed to treat cardiovascular diseases due to its rheological effects. In its original form, ILIB was applied by an intravenous optical fiber, restricting its application. However, this technique was modified to non-invasive irradiation through the radial artery, now called vascular photobiomodulation (VPBM). Many studies have used both, ILIB and VPBM, to treat lung diseases. It is well established that lung diseases affect more than 300 million people worldwide with high morbidity and mortality rates. In this short critical review, we discuss the potential benefits of photobiomodulation to treat lung diseases using these two approaches. The search was performed in the electronic database of MEDLINE (Medical Literature Analysis and Retrieval System Online) via PubMed. The data search was carried out from 1991 to 2017. We selected a total of 10 clinical studies using either ILIB or VPBM, in addition to 2 experimental studies in animals. The respiratory diseases treated in these studies included bronchitis, asthma, pneumonia, and tuberculosis. The results showed overall beneficial effects on lung diseases, characterized by a reduction in the inflammatory cascade and antioxidant effects, improvement of hemodynamic parameters, the efficiency of gas exchange, and reduction of hospitalization periods. In conclusion, all studies showed promising effects of ILIB in both animal and human studies. The studies did not discuss any disadvantages or contraindications. However, further studies are needed in order to understand the dosimetry, and the literature is lacking in randomized, controlled clinical trials. Thus, this review highlights the need for additional studies using this approach.

Comparison between local abdominal and transcutaneous tail vein photobiomodulation in experimental rat model of ulcerative colitis.

Ulcerative colitis (UC) is a chronic autoimmune disease that impacts the quality of life, but current pharmacological treatments are limited. Photobiomodulation (PBM) is a light-based treatment that can be applied either locally or systemically. Here, we compare the effects of local and vascular PBM (VPBM) in an experimental rat model of UC. Male Wistar rats were induced with UC by rectal instillation of acetic acid and treated with either local abdominal PBM or VPBM to the tail vein using a 660-nm LED. The findings indicated that local PBM but not VPBM reduced intestinal histological scores. Both local and VPBM increased mucus production, decreased mast cell degranulation, and modulated TNF-α and IL-1 ß levels in the intestines. Local PBM also affected the expression of the mRNAs for IL-6, TNF-α, and IFN-γ. In conclusion, we suggest that local PBM appears to be more promising than VPBM for treating UC. However, further research is needed to fully understand the mechanisms and to optimize the parameters of PBM for UC treatment.

Effects of photobiomodulation in the experimental acetic acid-induced colitis: comparison between male and female.

Ulcerative colitis (UC) is an important chronic and multifactorial disease, which alters the colon mucosal with a significant impact on life quality affecting both men and women. The difference between genders causes changes in the inflammatory processes, modulating the development of several diseases. The available drugs to treat UC exhibit limited outcomes and side effects; thus, new therapies are needed. Photobiomodulation (PBM) emerges as potential treatment by modulating the inflammatory process without side effects and low costs. The aim of this study was to evaluate the effects of PBM in acetic acid-induced UC comparing the responses between male and females. For this purpose, male and female Wistar rats (36) were submitted to induction of UC by rectal administration of 10% acetic acid (colitis group) and treated or not with PBM (colitis-PBM group) (LED, 660 nm, 100 mW, 150 s) in three points: right side and left of the ventral surface and in the external anal region. Non-manipulated rats were used as control (basal group). We investigated the disease activity index (DAI score), myeloperoxidase enzyme activity (MPO) and release of cytokines in the intestine homogenates, and histological analysis. PBM reduces DAI score, MPO activity, and mast cell degranulation while increased mucous production in both females and males. Moreover, PBM reduced histopathological score as well as the levels of IL-6 and IL-4 in the bowel only in males. We also showed reduced levels of IL-1beta and TNF-alpha after PBM in both males and females, while the levels of IL-10 and IFN-gamma were increased. In conclusion, despite our study has shown some differences between males and females, PBM attenuated the biomarkers of UC in both genders constituting a potential combined treatment that is non-invasive and low cost.

Transcutaneous systemic photobiomodulation reduced lung inflammation in experimental model of asthma by altering the mast cell degranulation and interleukin 10 level.

Asthma is a chronic inflammatory disease characterized by recurrent and reversible episodes of wheezing, dyspnea, chest stiffness, and cough. Its treatment includes several drugs, high cost, and considerable side effects. Photobiomodulation (PBM) emerges as an alternative treatment, showing good results, and it can be applied locally or systemically. Here, we aim to evaluate the effect of transcutaneous systemic photobiomodulation (TSPBM) by red diode light. Therefore, adult rats were sensitized and challenged with ovalbumin (OVA) plus alum for induction of asthma and irradiated or not with TSPBM in the caudal vein (wavelength 660 ± 10 nm; total radiant emission 15 J; area 2.8 cm2; energy density 5.35 J/cm2; irradiance 33.3 mW/cm2; exposure time 150 s). Our investigations prioritized the cell migration into the alveolar space and lung, tracheal responsiveness, release and gene expression of cytokines, mast cell degranulation, and anaphylactic antibodies. Our results showed that TSPBM reduced the cell migration and mast cell degranulation without altering the tracheal responsiveness and ovalbumin antibody titers. Indeed, TSPBM increased the levels of interleukin 10 (IL-10) in the BAL fluid without altering the gene expression of cytokines in the lung tissue. Thus, this study showed that transcutaneous systemic irradiation reduced lung inflammation by altering mast cells degranulation and IL-10 level. Considering that this study is a pioneer in the used of light by the systemic route to treat asthma, the data are interesting and instigate future investigations, mainly in relation to the mechanisms involved and in dosimetry.

Beneficial effects of infrared light-emitting diode in corticosteroid-resistant asthma.

Corticosteroid-resistant asthma (CRA) is a severe form of disease and clinically important, since patients do not respond to mainstay corticosteroid therapies. Thus, new therapies are needed. However, a big limiting factor in the understanding of CRA is the existence of different immunological and inflammatory phenotypes, a fact that makes it difficult to reproduce experimentally. Photobiomodulation (PBM) emerges as an alternative therapy based on earlier studies. This study aims to evaluate the effect of PBM using infrared light-emitting diode (ILED) on the development of corticosteroid-resistant asthma. Therefore, groups of rats were sensitized and challenged with ovalbumin plus Freund's adjuvant for the induction of CRA, and treated or not with ILED directly in the respiratory tract on the skin (wavelength 810 nm; power 100 mW; density energy 5 J/cm; total energy 15 J; time 150 s). Our experimental model was capable to induce neutrophilic asthma. Besides that, the corticosteroid treatment did not reverse the lung cell migration as well as the levels of leukotriene B4, and interleukins 17 and 6. The treatment with ILED reduced the lung cell migration; myeloperoxidase activity; mast cell degranulation; and the levels of leukotriene B4, thromboxane B2, prostaglandin E2, tumoral necrosis factor alpha, and interleukins 17 and 6. Still, ILED increased the level of interleukin 10. In conclusion, we showed promisor effects of ILED when irradiated directly in the respiratory tract as adjuvant treatment of corticosteroid-resistant asthma.

Local (but not systemic) photobiomodulation treatment reduces mast cell degranulation, eicosanoids, and Th2 cytokines in an experimental model of allergic rhinitis.

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, and is a worldwide health problem with a significant impact on the quality of life. The main goal of AR treatment is to relieve symptoms. However, standard treatments have considerable side effects or are not effective. Photobiomodulation (PBM) therapy has emerged as an alternative treatment. Here, we evaluated the effects of transcutaneous systemic (tail) or local (skin over nostrils) PBM using a 660-nm light-emitting diode (LED) array. Adult rats were assigned into 4 groups: basal, as non-manipulated animals; Sham, as rats sensitized with 7 intradermal injections of ovalbumin (OVA) plus alum followed by intranasal instillation with OVA (2%) daily for 7 days; and the LPBM and SPBM groups, in which the animals were treated with PBM (local or systemic) immediately after the last instillation of OVA (1%) daily for 3 days. Our results showed that local PBM treatment reduced mast cell degranulation in the nasopharynx and nostrils; levels of leukotriene B4, thromboxane A2, and interleukin 4 (IL-4) in the nasopharynx; and gene expression of IL-4. Moreover, we showed higher levels and gene expression of IL-10 after local PBM treatment. Systemic PBM treatment did not change any of the evaluated parameters. In conclusion, our data showed that local (but not systemic) treatment with PBM could improve parameters related to AR in an animal model, and should be tested clinically.

Effect of systemic photobiomodulation in the course of acute lung injury in rats.

Acute lung injury (ALI) is a severe, multifactorial lung pathology characterized by diffuse alveolar injury, inflammatory cell infiltration, alveolar epithelial barrier rupture, alveolar edema, and impaired pulmonary gas exchange, with a high rate of mortality; and sepsis is its most common cause. The mechanisms underlying ALI due to systemic inflammation were investigated experimentally by systemic lipopolysaccharide (LPS) administration. Photobiomodulation (PBM) has been showing good results for several inflammatory diseases, but there are not enough studies to support the real benefits of its use, especially systemically. Considering that ALI is a pathology with high morbidity and mortality, we studied the effect of systemic PBM with red light-emitting diode (LED) (wavelength 660 nm; potency 100 mW; energy density 5 J/cm; total energy 15 J; time 150 s) in the management of inflammatory parameters of this disease. For this, 54 male Wistar rats were submitted to ALI by LPS injection (IP) and treated or not with PBM systemically in the tail 2 and 6 h after LPS injection. Data were analyzed by one-way ANOVA followed by Student's Newman-Keuls. Our results point to the beneficial effects of systemic PBM on the LPS-induced ALI, as it reduced the number of neutrophils recruited into the bronchoalveolar lavage, myeloperoxidase activity, and also reduced interleukins (IL) 1ß, IL-6, and IL-17 in the lung. Even considering the promising results, we highlight the importance of further studies to understand the mechanisms involved, and especially the dosimetry, so that in near future, we can apply this knowledge in clinical practice.

Photobiomodulation modulates the resolution of inflammation during acute lung injury induced by sepsis.

Sepsis is a big health problem and one of the most common causes of acute lung injury (ALI) leading to high mortality. Pro-resolving mediators play an important role in abrogating the inflammation and promoting tissue homeostasis restoration. ALI treatment is still a clinical health problem, so new therapies are needed. Here, we evaluated the effect of photobiomodulation treatment on the resolution process of ALI induced by lipopolysaccharide (LPS). Male Balb/c mice were submitted to LPS (ip) or vehicle and irradiated or not with light emitting diode (LED) 2 and 6 h after LPS or vehicle injection, and the parameters were investigated 3 and 7 days after the injections. Our results showed that after 3 days of LED treatment the blood and bronchoalveolar lavage (BAL) cells as well as interleukins (IL) including IL-6 and IL-17 were reduced. No differences were observed in the bone marrow cells, tracheal reactivity, and lipoxin A4 and resolvin E2. Indeed, after 7 days of LED treatment the bone marrow cells, lymphocytes, and lipoxin A4 were increased, while IL-6, IL-17, and IL-10 were decreased. No differences were observed in the blood cells and tracheal reactivity. Thus, our results showed that LED treatment attenuated ALI induced by sepsis by modulating the cell mobilization from their reserve compartments. In addition, we also showed later effects of the LED up to 7 days after the treatment. This study proposes photobiomodulation as therapeutic adjuvant to treat ALI.

Vitamin D treatment abrogates the inflammatory response in paraquat-induced lung fibrosis.

A high incidence of intentional or accidental paraquat (PQ) ingestion is related to irreversible lung fibrosis and no effective therapy is currently available. Vitamin D has emerged with promising results as an immunomodulatory molecule when abrogating the inflammatory responses of lung diseases. Therefore, we have investigated the role of vitamin D treatments on PQ-induced lung fibrosis in male C57/BL6 mice. Lung fibrosis was induced by a single injection of PQ (10 mg/kg; i.p.). The control group received PQ vehicle. Seven days later, after the PQ injection or the vehicle injection, the mice received vitamin D (5 µg/kg, i.p., once a day) or vehicle, for a further 7 days. Twenty-four hours after the last dose of vitamin D or the vehicle, the analysis were performed. The vitamin D treatments reduced the number of leukocytes in their BALF and they decreased the IL-6, IL-17, TGF-beta and MMP-9 levels and the abrogated collagenase deposits in their lung tissues. Conversely, the vitamin D treatments increased the resolvin D levels in their BALF. Moreover, their tracheal contractility was also significantly reduced by the vitamin D treatments. Altogether, the data that was obtained showed a promising use of vitamin D, in treating the lung fibrosis that had been induced by the PQ intoxications. This may improve its prognostic use for a non-invasive and low cost therapy.

Effects of periodontal treatment on exacerbation frequency and lung function in patients with chronic periodontitis: study protocol of a 1-year randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with periodontal disease (PD), and periodontal treatment (PT) has been connected to reduction of lung disease exacerbations. Bronchiectasis has many clinical similarities with COPD but, although it is also a chronic lung disease, to date it has not been studied with relation to PD. The aim of this study is to evaluate whether PT associated with photodynamic therapy (PDT) reduces the number of exacerbations, improves pulmonary function, periodontal clinical parameters and quality of life after 1 year of periodontal treatment follow-up. METHODS: Bronchiectasis patients will undergo medical anamnesis and periodontal examination. Participants with periodontitis will be divided into two groups and PT will be performed as G1 control group (n = 32) - OHO (oral hygiene orientation) + supragingival treatment + simulation of using photodynamic therapy (PDT); G2 experimental (n = 32) - scaling and root planing + PDT + OHO. Lung function will be assessed both at baseline and after 1 year by spirometry, exacerbation history will be analyzed through clinical records monitoring. Three instruments for quality of life assessment will also be applied - Saint George's Respiratory Questionnaire and Impact Profile Analysis Oral health (OHIP-14). It is expected that periodontal treatment can improve the analyzed parameters after 1 year. DISCUSSION: Although only one study evaluates exacerbation in COPD after 1 year of PT, bronchiectasis has not been studied in the dentistry field to date. TRIAL REGISTRATION: NCT02514226. Version #1. This study protocol receives grant from FAPESP (São Paulo Research Foundation) #2015/20535-1. First received: July 22, 2015, 1st version. This protocol has been approved by the Research Ethics Committee of Nove de Julho University.

Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice.

Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm2, irradiance 33.3 mW/cm2, spot size 2.8cm2, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring.

Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150mg/kg, gavage) or vehicle (distilled water, gavage) 1h before FA exposure (0.92mg/m(3), 1h/day, 5days/week), for 21days, and the 30days old offspring were submitted to LPS injection (Salmonella abortus equi, 5mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense.

High dose of formaldehyde exposure during pregnancy increases neutrophils lung influx evoked by ovalbumin in the offspring.

OBJECTIVE: Considering that asthma might have their onset in the intrauterine life and the exposure to FA during pregnancy interferes in the immune system of offspring, here we hypothesized that high dose of FA exposure during pregnancy could to contribute for development and severity of asthma in the offspring. METHODS: Pregnant Wistar rats were submitted to FA inhalation (6.13 mg/m(3), 1 h/day, 5 days/week, for 21 days) or vehicle (distillated water). After 30 days of birth, the offspring was sensitized with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge, the analyses were performed. Non-manipulated rats were used as basal parameters. RESULTS: Our data show that the exposure to high dose of FA during pregnancy predisposes the development of neutrophilic lung inflammation in the offspring, as observed by the profile of cells and cytokines in the lung. CONCLUSION: This study contributes to the understanding of effects of pollution on the development of lung diseases.

Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes.

Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT) has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days) and treated or not with PBMT (1 and 5 h after each FA exposure). Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.

Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring.

Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment.

Photobiomodulation therapy for chronic knee pain in obese patients in pre-rehabilitation for bariatric surgery: randomised, placebo-controlled, double-blinded, clinical trial protocol.

INTRODUCTION: Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain, especially in the knees, which increases significantly and proportionally with weight gain. In patients with severe obesity, with indication for bariatric surgery, the presence of chronic pain disables and often prevents their participation in a pre-surgical rehabilitation programme. As an analgesic therapy, photobiomodulation (PBM) has been studied with safety, efficacy, well-tolerated used and low costs. Thus, this study aims to evaluate the use of PBM for the treatment of chronic knee pain in obese patients undergoing a pre-surgical rehabilitation programme for bariatric surgery. METHODS AND ANALYSES: This is a double-blinded, randomised, placebo-controlled clinical, superiority, trial protocol. The PBM will be applied in bilateral knees and lumbar paraspinal points levels referring to the roots of innervation of the knee. The outcomes evaluated will be pain intensity, functionality, quality of life and clinical signs of neurological sensitization of chronic knee pain pathways. ETHICS AND DISSEMINATION: This protocol has already been approved by the Comitê de Ética em Pesquisa do Hospital das Clínicas da Universidade Federal de Goiás/EBSERH-Ethics Committee and it is following SPIRIT guidelines. The results will be statistically analysed and subsequently published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical Trials Platform (https://clinicaltrials.gov/) with the number NCT05816798.