Systemic vascular photobiomodulation accelerates the recovery of motor activity in rats following spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) causes the discontinuity of the spinal canal, leading to functional and sensorial losses in areas below the injury, which are often irreversible. Photobiomodulation (PBM) can enhance the neuromuscular repair process, especially in cases of peripheral nerve injuries. However, there is little knowledge regarding the effects of this therapeutic modality on recovery following a SCI, especially the noninvasive systemic form denominated vascular PBM (VPBM). To analyze the effects of VPBM in the immediate, acute and intermediate phases following a compression-induced SCI on morphological aspects of neuromuscular tissue repair, functional recovery and the protein expression of brain-derived neurotrophic factor (BDNF). METHODS: Wistar rats were divided into five groups: control, SCI, SCI + VPBM-Im (immediate administration of VPBM), SCI + VPBM-2h (VPBM administered 2 h after injury) and SCI + VPBM-14d (VPBM administered 14 days after injury). VPBM was administered in the region of the caudal vein/artery with low-level laser (AsGaAl, 780 nm, 80 J/cm², 40 mW for 80 s, totaling an energy of 3.2 J over a single point) for 14 consecutive days. During the analysis periods (1, 3, 7, 14, 21, 28 and 35 days after injury), functioning was evaluated using the Basso-Beattie-Bresnahan (BBB) index. At the end of each experimental period, blood samples were collected for the determination of the concentration of circulating BDNF using ELISA. Muscle tissue and nerve tissue samples were also extracted for morphological and histological analyses using H&E staining. RESULTS: SCI + VPBM-Im and SCI + VPBM-2 h led to the recovery of motor function beginning on the 7th day after injury (p < 0.05), an increase in the cross-sectional area (CSA) of the muscle fibers in the second week (p < 0.05) and an increase in muscle fiber diameter beginning on Day 14 (p < 0.05). Early irradiation had a greater effect on the reduction in the size of the cavity, with stabilization of the cavity found on Day 7 (p < 0.05). Considering the circulating BDNF levels, no changes was found during the experimental periods. CONCLUSION: The present results showed that VPBM was capable of modulating morphological and functional recovery following SCI, especially when administered early. The positive effects on functional recovery were demonstrated by the BBB index; the reestablishment of the structure of the muscle and nerve tissue was demonstrated by the preservation of CSA and diameter of muscle fiber and reduction in the area of the injury (cavity size) respectively. Thus, noninvasive VPBM may be an important component of treatment for spinal cord injuries.

The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.

The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble human lupus nephritis. This study provides evidence for a noncanonical, antigen presentation-independent mechanism of HLA-disease association in SLE and could lay new foundations for our understanding of key molecular mechanisms that trigger and propagate this devastating autoimmune disease.

Efficacy and safety of electrical stimulation in the treatment of neurogenic bladder dysfunction in myelomeningocele-Systematic review of randomized clinical trials.

AIMS: The purpose of this systematic review was to investigate and synthesize the effects (benefits and harms) of electrical stimulation (EE), alone or in association with other interventions, compared with sham and other interventions, for the treatment of neurogenic bladder dysfunction in myelomeningocele. METHODS: This systematic review was conducted following the methodological recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and registered at PROSPERO (CRD42020200425). A search was performed in the following electronic databases: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, LILACS, and PEDro. Randomized clinical trials (RCTs) that assessed any EE in children diagnosed with myelomeningocele and neurogenic bladder and/or urinary incontinence were included and reported. RESULTS: When comparing EE versus sham groups, some estimated effects showed a wide confidence interval, probably due to the small sample size of the included studies. This indicates an imprecision in these findings. Regarding the safety of this intervention and safety of the lower urinary tract, no adverse events resulting from EE were reported. All the included studies have evaluated the efficacy of EE compared with sham, but different EE parameters and electrode positions among studies make it impossible to perform a meta-analysis. CONCLUSIONS: Based on very low certainty evidence, the findings of this systematic review suggested no difference between EE and sham to improve urinary incontinence in children with myelomeningocele. However, the small sample size and the imprecision arising from the wide confidence intervals must be considered. Future RCTs following a rigorous methodology, as recommended by the CONSORT statement, should be conducted to support the use of this intervention in clinical practice.

Effects of Photobiomodulation with Low-level Laser Therapy on Muscle Repair Following a Peripheral Nerve Injury in Wistar Rats.

Peripheral nerve injury (PNI) can lead to sensory and/or motor impairment. As a treatment photobiomodulation (PBM) has demonstrated positive effects in terms of the maintenance of muscle activation and trophism. Wistar rats were divided into five groups: control, injury, injury + PBMn (irradiation over injured nerve), injury + PBMm (irradiation over affected muscle) and injury + PBMnm (irradiation over nerve and muscle). The left sciatic nerve was submitted to a crushing injury. Treatment was administered with low-level laser (780 nm, 0.04 cm2 , 1 W cm-2 , 3.2 J) over the injured nerve and/or the tibialis anterior muscle. The effects of PBM were favorable on muscle morphology and gene expression of calcineurin, myogenin and acetylcholine receptors. PBM led to an acceleration on muscle repair process, and effects were more evident in 2 weeks after PNI. Thus, PBM is indicated for the area over both the injured nerve and the affected muscle.

Correction to: Photobiomodulation versus light-emitting diode (LED) therapy in the treatment of temporomandibular disorder: study protocol for a randomized, controlled clinical trial.

After publication of our article [1] we became aware that several sections of text in our Methods section were copied from a previously published article [2].

Photobiomodulation and different macrophages phenotypes during muscle tissue repair.

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti-inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL-6, TNF-α and TGF-ß mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF-ß mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

Effects of myogenic precursor cells (C2C12) transplantation and low-level laser therapy on muscle repair.

OBJECTIVE: The aim of the present study was to evaluate the effects of myoblast inoculation in combination with photobiomodulation therapy (PBMT) on skeletal muscle tissue following injury. MATERIALS AND METHODS: Sixty-five Wistar rats were divided into five groups: Control-animals not submitted to any procedure; Injury-cryoinjury of the tibialis anterior muscle; HBSS-animals submitted to cryoinjury and intramuscular Hank's Balanced Salt Solution; Injury + Cells-animals submitted to cryoinjury, followed by myogenic precursor cells (C2C12) transplantation; Injury + Cells + LLLT-animals submitted to cryoinjury, followed by myogenic precursor cells (C2C12) transplantation and PBMT (780 nm, 40 mW, 3.2 J in 8 points). The periods analyzed were 1, 3, and 7 days. The tibialis anterior muscle was harvest for histological analysis, collagen analysis, and immunolabeling of macrophages. RESULTS: No differences were found between the HBSS group and injury group. The Injury + Cells group exhibited an increase of inflammatory cells and immature fibers as well as a decrease in the number of macrophages on Day 1. The Injury + Cells + LLLT group exhibited a decrease in myonecrosis and inflammatory infiltrate at 7 days, but an increase in inflammatory infiltrate at 1 and 3 days as well as an increase in blood vessels at 3 and 7 days, an increase in macrophages at 3 days and better collagen organization at 7 days. CONCLUSION: Cell transplantation combined with PBMT led to an increase in the number of blood vessels, a reduction in myonecrosis and total inflammatory cells as well as better organization of collagen fibers during the skeletal muscle repair process. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Photobiomodulation versus light-emitting diode (LED) therapy in the treatment of temporomandibular disorder: study protocol for a randomized, controlled clinical trial.

BACKGROUND: Temporomandibular disorder (TMD) is described as a subgroup of orofacial pain with a set of signs and symptoms that involve the temporomandibular joint, masticatory muscles, ears, and neck. TMD can occur unilaterally or bilaterally and approximately 70% of the population is affected with at least one sign. The disorder progresses with orofacial pain, muscle pain involving the masticatory and cervical muscles, joint noises (clicks and pops), joint block, mandibular dysfunction, and headache. The etiology can be abnormal occlusion and/or posture, trauma involving local tissues, repetitive microtrauma, parafunctional habits, and an increase in emotional stress. Studies have demonstrated that phototherapy is an efficient option for the treatment of TMD, leading to improvements in pain and orofacial function. METHODS: The aim of the proposed study is to compare the effects of two sources of photobiomodulation in individuals with TMD. A randomized, controlled, double-blind, clinical trial is proposed, which will involve 80 individuals aged 18-65 years allocated to either a laser group or light-emitting diode (LED) group submitted to 12 sessions of phototherapy. The Research Diagnostic Criteria for TMDs will be used to evaluate all participants. Pain will be measured using the visual analog scale and maximum vertical mandibular movement will be determined with the aid of digital calipers. DISCUSSION: This study compares the effects of two modalities of laser therapy on the pain and orofacial function of patients with TMD dysfunction. Photobiomodulation and LED therapy are treatment options for reducing the inflammatory process and pain as well as inducing the regeneration of the target tissue. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03257748 . Registered on 8 August 2017.

Correlation between upper limb function and oral health impact in stroke survivors.

[Purpose] The aim of the present study was to evaluate the relationship between upper limb impairment and oral health impact in individuals with hemiparesis stemming from a stroke. [Subjects and Methods] The study subjects were conducted with a sample of 27 stroke survivors with complete or partial hemiparesis with brachial or crural predominance. The 14-item short version of the Oral Health Impact Profile was used to evaluate perceptions of oral health. The Brazilian version of the Stroke Specific Quality of Life Scale was used to evaluate perceptions regarding quality of life. [Results] A statistically significant association was found between the upper extremity function subscale of the SSQOL-Brazil and the impact of oral health evaluated using the OHIP-14, with a strong correlation found for the physical pain subscale, moderate correlations with the functional limitation, psychological discomfort, physical disability, social disability and social handicap subscales as well as a weak correlation with the psychological disability subscale. Analyzing the OHIP-14 scores with regard to the impact of oral health on quality of life, the most frequent classification was weak impact, with small rates of moderate and strong impact. [Conclusion] Compromised upper limb function and self-perceived poor oral health, whether due to cultural resignation or functional disability, exert a negative impact on the quality of life of individuals with hemiparesis stemming from a stroke.

Antimicrobial photodynamic therapy combined with periodontal treatment for metabolic control in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: The relationship between diabetes mellitus (DM) and periodontal disease is bidirectional. DM is a predisposing and modifying factor of periodontitis, which, in turn, worsens glycemic control and increases proteins found in the acute phase of inflammation, such as C-reactive protein. The gold standard for the treatment of periodontal disease is oral hygiene orientation, scaling and planing. Moreover, systemic antibiotic therapy may be employed in some cases. In an effort to minimize the prescription of antibiotics, photodynamic therapy (PDT) has been studied as an antimicrobial technique and has demonstrated promising results. The aim of the proposed study is to determine whether PDT as a complement to periodontal therapy (PT) is helpful in the metabolic control of individuals with type 2 diabetes and the reduction of acute-phase inflammatory markers. METHODS/DESIGN: The patients will be randomized using a proper software program into two groups: 1) PT + placebo PDT or 2) PT + active PDT. All patients will first be examined by a specialist, followed by PT performed by two other healthcare professionals. At the end of each session, PDT (active or placebo) will be administered by a fourth healthcare professional. The following will be the PDT parameters: diode laser (660 nm); power output = 110 mW; exposure time = 90 s per point (9 J/point); and energy density = 22 J/cm(2). The photosensitizer will be methylene blue (50 µg/mL). The patients will be re-evaluated 15, 30, 90 and 180 days after treatment. Serological examinations with complete blood count, fasting glucose, glycated hemoglobin and salivary examinations to screen for tumor necrosis factor alpha, interleukin 1, interleukin 6, ostelocalcin, and osteoprotegerin/RANKL will be performed at each evaluation. The data will be statistically evaluated using the most appropriate tests. DISCUSSION: The results of this study will determine the efficacy of photodynamic therapy as an adjuvant to periodontal treatment in diabetic patients. TRIAL REGISTRATION: The protocol for this trial was registered with Clinical Trials registration number NCT01964833 on 14 October 2013.

Macrophage migration inhibitory factor and oral cancer.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with pro-inflammatory functions and involved in tumorigenesis. The aim of this study was to evaluate the expression and localization of the macrophage MIF in oral squamous carcinoma (OSC). In addition, the relationship between MIF expression and clinicopathological parameters such as survival data, tobacco use, alcohol habits, TNM stage, tumor graduation, and peritumoral inflammatory infiltrate were evaluated. METHODS: Using immunohistochemistry, expression and localization of MIF was detected in 44 specimens of OSC. The absolute number and relative proportions of MIF-positive cells detected were also determined separately for tumor parenchyma vs. stroma. All counts were determined from 10 consecutive high-power fields using an integration graticule. Moreover, some parameters were analyzed separately for lip and intra-oral cancers. RESULTS: Migration inhibitory factor-positive cells were observed in both the tumor parenchyma and in inflammatory cells of all specimens. In contrast, MIF expression was not detected in tumoral nests associated with poorly differentiated tumors. In specimens of lip cancer, a greater number of MIF-positive stromal immune cells were detected than in intra-oral cancer specimens (Mann-Whitney test, P = 0.049). CONCLUSIONS: Oral squamous carcinoma cells consistently express MIF independent of their location. Lip tumors presented more MIF-positive peritumoral inflammatory cells, similar to control, suggesting that immunological differences in leukocyte activation exist between in lip and intra-oral cancers.

Histopathological, cytotoxicity and genotoxicity evaluation of Biosilicate® glass-ceramic scaffolds.

This study evaluated the biocompatibility of Biosilicate® scaffolds by means of histopathological, cytotoxicity, and genotoxicity analysis. The histopathologic analysis of the biomaterial was performed using 65 male rats, distributed into the groups: control and Biosilicate®, evaluated at 7, 15, 30, 45, and 60 days after implantation. The cytotoxicity analysis was performed by the methyl thiazolyl tetrazolium (MTT) assay, with various concentrations of extracts from the biomaterial in culture of osteoblasts and fibroblasts after 24, 72, and 120 h. The genotoxicity analysis (comet assay) was performed in osteoblasts and fibroblasts after contact with the biomaterial during 24, 72, and 96 h. In the histopathology analysis, we observed a foreign body reaction, characterized by the presence of granulation tissue after 7 days of implantation of the biomaterial, and fibrosis connective tissue and multinucleated giant cells for longer periods. In the cytotoxicity analysis, extracts from the biomaterial did not inhibit the proliferation of osteoblasts and fibroblasts, and relatively low concentrations (12.5% and 25%) stimulated the proliferation of both cell types after 72 and 120 h. The analysis of genotoxicity showed that Biosilicate® did not induce DNA damage in both lineages tested in all periods. The results showed that the Biosilicate® scaffolds present in vivo and in vitro biocompatibility.

No effect of low-level lasers on in vitro myoblast culture.

Effects of phototherapy using low-level lasers depend on irradiation parameters and the type of laser used. The aim of the present study was to evaluate the effect of phototherapy on the proliferation of cultured C2C12 myoblasts under different nutritional conditions using low-level GaAlAs and InGaAlP lasers with different parameters and incubation periods. C2C12 cells cultured in regular and nutrient-deficient medium were irradiated with low-level GaAlAs (780 nm) and InGaA1P (660 nm) lasers with energy densities of 3.8, 6.3 and 10 J/cm2, and 3.8, 10 and 17.5 J/cm2, respectively. Cell proliferation was assessed 48 and 72 h after irradiation by MTT assay. There were no significant differences in cell proliferation between laser-treated myoblasts and control cultures for any of the parameters and incubation periods. Further studies are necessary to determine the correct laser parameters for optimizing the biostirhulation of myoblasts.

Healing action of topical chamomile on 5-fluoracil induced oral mucositis in hamster.

BACKGROUND: Oral mucositis is a common complication in the treatment of cancer. Its management and prevention are seen as high priority in cancer patient care. The aim of the present study was to investigate the effect of topical chamomile in the treatment of oral mucositis induced by 5-fluoracil (5-FU) in hamsters. MATERIALS AND METHODS: One hundred five hamsters were randomly separated into three groups (35 animals each): group I--without treatment (control); group II--treatment with chamomile (Ad-Muc®); and group III--treatment with corticoid (betamethasone elixir--Celestone®). The animals received an intraperitoneal injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched and therapy was initiated on day 5. Three animals were sacrificed on days 0, 2, 5, 8, 10, 12, 14, and 16, weighed, and the buccal mucosa removed for clinical and histopathological analysis. RESULTS: The animals that developed mucositis and were treated with chamomile or the corticoid agent weighed significantly less than those in the control group. The group treated with the corticoid agent exhibited a more severe clinical condition, whereas the group treated with chamomile exhibited mild mucositis throughout the experiment. The group treated with chamomile had a 12-fold greater chance of scoring zero (absence of mucositis) than the control group. Analysis of the histopathological results demonstrated that the group treated with chamomile exhibited a lesser degree of mucositis throughout the evaluation period in comparison to the control and corticoid groups. CONCLUSION: Chamomile proved effective in the treatment of oral mucositis in a hamster model. However, well-designed clinical studies are needed to confirm the clinical efficacy of this medicine in humans.