Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Investigating effects of locally applied boric acid on fracture healing with and without low-level laser therapy.

This study aimed to investigate the effects on fracture healing of locally applied boric acid (BA) with and without low-level laser therapy (LLLT). A unicortical femoral defect was surgically created on the anterolateral surface of proximal femur of each subject. The subjects, totaling 56 Wistar albino rats, were randomly allocated into four groups (n = 14 each): control, LLLT (λ = 905 µm, 10,000 Hz, 25 mW, and peak power 25 W), BA (40 mg/kg), and BA + LLLT groups. On the 30th day, the highest radiological score was recorded for the BA + LLLT group (3.63 [2-4]), followed by the BA (3.38 [2.75-3.75]), control (3 [2-3.25]), and LLLT (2.5 [1.25-3]) groups. On days 15 and 30 post-surgery, malondialdehyde levels were significantly lower among the BA + LLLT group compared to the control group (p < 0.001). On day 30, superoxide dismutase, catalase, and alkaline phosphatase levels were highest in the BA + LLLT group compared to the control group (p < 0.001). When the histopathological, immunofluorescence, and immunohistochemical findings on the 15th and 30th days were compared with the control group, a statistically significant difference was found for the BA and BA + LLLT groups (p ˂ 0.05). This study suggests that locally applied BA with LLLT may accelerate fracture healing.

Photobiomodulation effects in metalloproteinases expression in zymosan-induced arthritis.

Matrix metalloproteinases (MMPs) play a crucial role in the degenerative course of rheumatic disorders. They are responsible for cartilage and other joint-associated tissues breakdown. Amid arthritis treatments, photobiostimulation (PBM), a non-thermal and non-invasive low-power laser application, appears to be an outstanding therapy alternative once it has succeeded in MMPs modulation. Thus, this study aimed to evaluate the PBM effects of low infrared laser (830 nm), testing two different energy densities (3 and 30 Jcm-2) in MMP-2, MMP-9, MMP-13, and MMP-14 as well as the inhibitor TIMP-2 expressions using zymosan-induced arthritis model. C57BL/6 mice were distributed into four groups (n = 8): zymosan-induced arthritis without treatment; zymosan-induced arthritis and dexamethasone-treated; zymosan-induced arthritis and PBM at energy density of 3 Jcm-2 treated; and zymosan-induced arthritis and PBM at energy density of 30 Jcm-2 treated. MMPs and TIMP-2 mRNA relative levels by qRT-PCR and proteins expression by immunohistochemical and Western blotting techniques were performed after PBM treatment in the inflamed joint. Our results demonstrated PBM could modulate both mRNA relative levels and proteins expression of the MMP-2, -9, -13, -14, and TIMP-2 in joint tissues, decreasing MMP-9 protein expression and increasing TIMP-2 protein expression. PBM promotes a better arthritis prognostic, modulating metalloproteinase and its inhibitor, especially MMP-9 and TIMP-2 protein expression that is important inflammatory markers. These findings may also corroborate that PBM may regulate MMPs expression using different pathways.

Photobiomodulation Therapy to Autologous Bone Marrow in Humans Significantly Increases the Concentration of Circulating Stem Cells and Macrophages: A Pilot Study.

Objective: The aim of this study was to examine the effect of photobiomodulation therapy (PBMT) of the bone marrow (BM) on the concentration of stem cells and other cells in the circulating blood (CB) in humans. Background: Circulating stem cells have received increasing attention in recent years due to their potential role in regenerative medicine. Various biological processes have been shown to be affected by PBMT. Methods: The study was conducted on 15 volunteers. Ga-Al-As diode laser 808 nm wavelength was applied to both tibias of each volunteer for PBMT to the BM. The kinetics of concentration of various cells in the CB was followed by comparing blood samples relative to their baseline levels prior to application of PBMT to the BM. CD-34+ cells and macrophages were identified in CB samples using flow cytometry technology. Results: PBMT to the BM caused a significant (p < 0.01) increase in the concentration of CD-34+ cells in the CB from 7.8 ± 3.0% (mean ± SD) of total mononucleated cell to 29.5 ± 10.1% of total commencing at about 2 h post-PBMT. The levels of CD-34+ cells peaked at 2-4 days post-PBMT and then gradually returned to baseline levels. Macrophages in the CB were also significantly (p < 0.01) elevated following PBMT to the BM from 7.8 ± 6.0% (mean ± SD) of the total mononucleated cells to 52.1 ± 7.9% of total. Conclusions: Application of PBMT to the BM in humans can significantly increase the concentration of CD-34+ cells and macrophages in the CB. These cells may consequently home in on the impaired target organs and improve their function, as has been previously shown in experimental animal models. Furthermore, the results may also have clinical relevance in respect to enrichment of CB in cells that may be consequently isolated for cell therapy. Clinical Trial Registration No. is 7/14.

Irradiation with a red light-emitting diode enhances the proliferation of stem cells of apical papilla via the ERK5 signalling pathway.

This Querystudy aimed to investigate the effects of low-energy red light-emitting diode (LED) irradiation on the proliferation of stem cells from apical papilla (SCAPs) and preliminarily elucidated the underlying molecular mechanisms. SCAPs were isolated and identified in vitro. The light source was a 10 W red LED with continuous output and a wavelength of 600-700 nm. SCAPs were irradiated with 0 (control group), 0.5 J/cm2, 1 J/cm2, 3 J/cm2, or 5 J/cm2. Cell Counting Kit-8 (CCK-8) assays were used to analyze cell proliferation rates and determine the most effective concentration of extracellular signal-regulated kinase 5 (ERK5) blocker, BIX02189. A real-time polymerase chain reaction (RT-PCR) was carried out to determine the involvement of the ERK5 signalling pathway and proliferation-associated genes (C-Jun, Jun B, and Cyclin D1). 5-Ethynyl-2'-deoxyuridine (EDU) was used to analyze cell cycle kinetic parameters. CCK-8 assay results suggested that SCAPs in red LED groups exhibited a higher proliferation rate than those in the control group, and 10 µmol/L BIX02189 was the most effective blocker. The RT-PCR results demonstrate that red LEDs upregulated the expression of the ERK5, C-Jun, Jun B, and Cyclin D1 genes, and BIX02189 successfully blocked the ERK5 signalling pathway. The results of EdU staining indicated that red LED promoted DNA synthesis activity and that BIX02189 suppressed cells into S phase. Red LEDs irradiation enhances the proliferation of SCAPs via the ERK5 signalling pathway by upregulating the expression of C-Jun, Jun B, and Cyclin D1.

New perspectives in regenerative medicine and surgery: the bioactive composite therapies (BACTs).

Regenerative medicine and surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival, and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting the effectiveness and outcome of the therapeutic choices. Thus, the authors developed a novel 360° regenerative strategy based on the synergic action of several new components called the bioactive composite therapies (BACTs) to improve grafted cells intake, and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Bioactive composite mixtures (BACMs) are tailor-made bioactive mixtures containing several bioactive components that support cells' survival and induce a regenerative response in vivo by stimulating the recipient site to act as an in situ real bioreactor. Many different tissues have been used in the past for the isolation of cells, molecules, and growth factors, but the adipose tissue and its stromal vascular fraction (SVF) remains the most valuable, abundant, safe, and reliable source of regenerative components and particularly of adipose-derived stems cells (ADSCs). The role of plastic surgeons as the historical experts in all the most advanced techniques for harvesting, manipulating, and grafting adipose tissue is fundamental in this constant process of expansion of regenerative procedures. In this article, we analyze the main causes of cell death and the strategies for preventing it, and we present all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions. The second section of this work is dedicated to the logical and sequential evolution from simple bioactive composite grafts (BACGs) that distinguished our initial approach to regenerative medicine, to BACTs where many other fundamental technical steps are analyzed and integrated for supporting and enhancing the most efficient regenerative activity. Level of Evidence: Not gradable.

Low level laser therapy as adjunctive support in implant dentistry: a reliable option? / Terapia láser de baja potencia como apoyo complementario en la implantología: ¿una opción fiable?

Use of low level laser therapy (LLLT) in bone healing has been studied for years, and its application in implant dentistry is still a controversial topic due to the difficult assessment of its clinical efficacy. We report the application of LLLT as aid in the osseointegration in two patients undergone to implant surgery in the upper jaw. In one hemi-arch the LLLT was applied and the other one was used as control. The assessment of the bone area surrounding the fixtures was performed by means of cone beam compute tomography and the area of bone-implants contact was measured by means of InVesalius® software. The radiological findings support the idea of considering the laser biostimulation as an adjunctive aid in implant surgery.

El uso de la terapia con láser de baja potencia (LLLT) en la reparación ósea se ha estudiado durante años y su aplicación en la implantología sigue siendo un tema controvertido, debido a la difícil evaluación de su eficacia clínica. Reportamos la aplicación de LLLT como ayuda en la osteointegración en dos pacientes sometidos a cirugía de implantes en el maxilar superior. En un hemi-arco se aplicó la LLLT y en el otro se utilizó como control. La evaluación del área ósea que rodea a las fijaciones se realizó mediante tomografía computarizada Cone Beam y el área de contacto hueso-implantes se midió mediante el software InVesalius®. Los hallazgos radiológicos apoyan la idea de considerar la bioestimulación con láser como un coadyuvante en la cirugía de implantes.

Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. RESULTS: Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration. CONCLUSIONS: The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.

Low-level laser and adipose-derived stem cells altered remodelling genes expression and improved collagen reorganization during tendon repair.

OBJECTIVES: The cellular therapy using adipose-derived mesenchymal stem cells (ASCs) aims to improve tendon healing, considering that repaired tendons often result in a less resistant tissue. Our objective was to evaluate the effects of the ASCs combination with a low-level laser (LLL), an effective photobiostimulation for the healing processes. MATERIALS AND METHODS: Rats calcaneal tendons were divided into five groups: normal (NT), transected (T), transected and ASCs (SC) or LLL (L), or with ASCs and LLL (SCL). RESULTS: All treated groups presented higher expression of Dcn and greater organization of collagen fibres. In comparison with T, LLL also up-regulated Gdf5 gene expression, ASCs up-regulated the expression of Tnmd, and the association of LLL and ASCs down-regulated the expression of Scx. No differences were observed for the expression of Il1b, Timp2, Tgfb1, Lox, Mmp2, Mmp8 and Mmp9, neither in the quantification of hydroxyproline, TNF-α, PCNA and in the protein level of Tnmd. A higher amount of IL-10 was detected in SC, L and SCL compared to T, and higher amount of collagen I and III was observed in SC compared to SCL. CONCLUSIONS: Transplanted ASCs migrated to the transected region, and all treatments altered the remodelling genes expression. The LLL was the most effective in the collagen reorganization, followed by its combination with ASCs. Further investigations are needed to elucidate the molecular mechanisms involved in the LLL and ASCs combination during initial phases of tendon repair.

Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.

Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.

Effect of laser on pain relief and wound healing of recurrent aphthous stomatitis: a systematic review.

The aim of this systematic review was to assess a potential benefit of laser use in the treatment of recurrent aphthous stomatitis (RAS). The primary outcome variables were pain relief, duration of wound healing and reduction in episode frequency. A PICO approach was used as a search strategy in Medline, Embase and Cochrane databases. After scanning and excluding titles, abstracts and full texts, 11 studies (ten RCTs and one non-randomised controlled trial) were included. Study selection and data extraction was done by two observers. Study participants varied between 7-90 for the laser and 5-90 for the control groups. Laser treatment included Nd:YAG laser ablation, CO2 laser applied through a transparent gel (non-ablative) and diode laser in a low-level laser treatment (LLLT) mode. Control groups had placebo, no therapy or topical corticosteroid treatment. Significant pain relief immediately after treatment was found in five out of six studies. Pain relief in the days following treatment was recorded in seven studies. The duration of RAS wound healing was also reduced in five studies. However, criteria of evaluation differed between the studies. The episode frequency was not evaluated as only one study addressed this outcome parameter, but did not discriminate between the study (LLLT) and control (corticosteroid) groups. Jadad scores (ranging from 0 to 5) for quality assessment of the included studies range between 0 and 2 (mean = 1.0) for studies analysing pain relief and between 0 and 3 (mean = 1.1) for studies evaluating wound healing. The use of lasers (CO2 laser, Nd:YAG laser and diode laser) to relieve symptoms and promote healing of RAS is a therapeutic option. More studies for laser applications are necessary to demonstrate superiority over topical pharmaceutical treatment and to recommend a specific laser type, wavelength, power output and applied energy (ablative versus photobiomodulation).

Does Low-Level Laser Therapy Enhance the Efficiency of Orthodontic Dental Alignment? Results from a Randomized Pilot Study.

OBJECTIVE: To assess if low-level laser therapy (LLLT) enhances the efficiency of orthodontic dental alignment. BACKGROUND: There is no evidence of the effect of LLLT on the orthodontic treatment time from randomized clinical trials. METHODS: Thirty-six subjects were included in this interventional pilot study and randomly assigned for treatment with fixed appliance and LLLT (test group) or with fixed appliance only (control group). A single monthly administration of LLLT was performed intraorally using a Diode laser (980 nm, 1 W, continuous wave, total energy density = 150 J/cm2; Doctor Smile-Lambda Spa). The date of brackets bonding (T1) and the date of complete resolution of dental crowding (T2) were recorded. The alignment treatment time was defined in days as T2 - T1. The number of monthly scheduled control visits was also recorded. Treatment time duration was assessed in both groups with the log-rank (Mantel-Cox) Test for survival analysis. Mann-Whitney U tests was used to compare the number of control visits from T1 to T2 between the two groups. RESULTS: Patients' age, sex, and amount of crowding were equally distributed between the two groups. The alignment treatment time was significantly shorter (p < 0.001) in the tested group (211.8 days) compared to the control (284.1 days). Consequently, control visits (p < 0.001) were lower in the test group (7 visits, median value) compared to the control group (9.5 visits, median value). CONCLUSIONS: The results of this pilot study suggest that the administration of LLLT might significantly increase the efficiency of orthodontic treatment during dental alignment.

A novel method to promote behavioral improvement and enhance mitochondrial function following an embolic stroke.

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for stroke; tPA increases cerebral reperfusion, blood flow and improved behavior. Novel transcranial laser therapy (TLT) also enhances cerebral blood flow and activates mitochondrial function. Using the rabbit small clot embolic stroke model (RSCEM), we studied the effects of continuous wave TLT (7.5mW/cm(2)) alone or in combination with standardized intravenous (IV) tPA (3.3mg/kg) applied 1h post-embolization on 3 endpoints: 1) behavioral function measured 2 days [effective stroke dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits], 2) intracerebral hemorrhage (ICH) rate, and 3) cortical adenosine-5'-triphosphate (ATP) content was measured 6h following embolization. TLT and tPA significantly (p<0.05) increased P50 values by 95% and 56% (p<0.05), respectively over control. TLT-tPA increased P50 by 136% over control (p<0.05). Embolization reduced cortical ATP content by 39%; decreases that were attenuated by either TLT or tPA treatment (p<0.05). TLT-tPA further enhanced cortical ATP levels 22% above that measured in naïve control. TLT and tPA both effectively and safely, without affecting ICH rate, improved behavioral outcome in embolized rabbits; and there was a trend (p>0.05) for the TLT-tPA combination to further increase P50. TLT and tPA both attenuated stroke-induced ATP deficits, and the combination of tPA and TLT produced an additive effect on ATP levels. This study demonstrates that the combination of TLT-tPA enhances ATP production, and suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex measured using ATP levels as a marker.

808-nm laser therapy with a flat-top handpiece photobiomodulates mitochondria activities of Paramecium primaurelia (Protozoa).

Photobiomodulation is proposed as a non-linear process, and only low-level laser therapy (LLLT) is assumed to stimulate exposed cells, whereas high powered laser and fluences can cause negative effects, exhausting the cell's energy reserve as a consequence of excessive photon-based stimulation. In our work, we investigated and compared the effects of 808-nm diode laser (CW) with a new flat-top handpiece. To this purpose, we tested the photobiomodulation effects of 1 and 3 J/cm(2) fluence, both generated by 100 mW or 1 W of laser power and of 64 J/cm(2) of fluence generated by 100 mW, 1 W, 1.5 W or 2 W, as expressed through oxygen consumption and ATP synthesis of Paramecium. Data collected indicates the incremental consumption of oxygen through irradiation with 3 J/cm(2)-100 mW or 64 J/cm(2)-1 W correlates with an increase in Paramecium ATP synthesis. The Paramecium respiration was inhibited by fluences 64 J/cm(2)-100 mW or 64 J/cm(2)-2 W and was followed by a decrease in the endogenous ATP concentration. The 1 J/cm(2)-100 mW or 1 W and 3 J/cm(2)-1 W did not affect mitochondrial activity. The results show that the fluence of 64 J/cm(2)-1 W more than the 3 J/cm(2)-100 mW causes greater efficiency in Paramecium mitochondria respiratory chain activity. Our results suggest that thanks to flat-top handpiece we used, high fluences by high-powered laser have to be reconsidered as an effective and non-invasive therapy. Possible associated benefits of deeper tissue penetration would increase treatment effectiveness and reduced irradiation time.

An ex vivo study of photobiostimulation in the treatment of skin pathologies.

Photodynamic therapy (PDT) and low level laser therapy (LLLT) may mutually improve the outcomes on the healing process of chronic wounds and other skin pathologies, through processes known to stimulate the proliferation of dermal cellular structures, as well as antimicrobial application. This study proposes the use of nanoemulsion containing aluminium phthalocyanine chloride (ClAlPc) as photosensitizer (PS), to establish the most appropriate protocol for photostimulation in human skin biopsies, associated to type I collagen and elastin production. The combined effect of PS and light (diode laser at 670 nm) at three different doses is compared to the effect of light itself at doses of 70, 140 and 700 mJ c cm-2 , 7 and 14 days after irradiation. Histological analysis reveals the increase in collagen and elastin, higher than 20%, 14 days after treatment with PS and light at 140 mJ c cm-2 . Higher doses of light promote an inhibitory effect, leading to tissue degradation. In addition, the expression levels of the enzymes MMP-2 and MMP-9 (Gelatinases A and B - participant in various processes including tumoral progression and wound healing) are detected by gelatin zymography, reinforcing the efficacy of the combined treatment with PS and light at the intermediate dose.

Prevention of abdominal adhesions and healing skin after peritoniectomy using low level laser.

BACKGROUND: Adhesions commonly occur after abdominal surgery and can cause bowel obstruction, chronic abdominal pain, and infertility. Their prevention remains a challenge. OBJECTIVES: To evaluate the effects of the application of low-level lasers on the prevention of adhesions and scarring of the skin after peritoniectomia. METHOD: Twenty-four New Zealand breed male rabbits, approximately 2 months of age, were randomly divided into 3 groups (n = 8): GC-control group not subjected to laser, GL1-group with laser application at a dose of 0.2 J, and GL2-group with laser application at a dose of 3.6 J. All animals received a longitudinal midline incision and a bilateral resection of the peritoneal fragment, measuring 3 × 1 cm(2) . The animals received a laser treatment of one application every 24 hours, beginning at the time of surgery and lasting for a period of 4 days. After 14 days post-surgery, the animals were killed and adhesion formation was evaluated qualitatively and quantitatively by means of a laparotomy shaped inverted "U", which allowed for the verification of the broad wall of the abdominal cavity and organs. Differences were considered significant at P < 0.05. RESULTS: The adhesion formation was observed in 100% of the rabbits from groups GC and GL1, as compared to 37.5% of the rabbits from group GL2 (P < 0.01). The evaluation of the vascularization and tenacity of adhesions among the groups showed no significant difference. In groups CG and GL1, 72% and 83% of adhesions were verified between visceras, respectively whereas in GL2 occurred among abdominal wall. The tensile strength of the skin between the groups was not significant (P = 0.3106). The resistance of abdominal wall segments without skin he resistance of skin segments between groups GL2 and GC were higher than in GL1 (P = 0.01). CONCLUSION: Low-level LASER is effective in preventing intra-abdominal adhesions in rabbits without compromising strength and healing of the abdominal wall.

The clinical use of regenerative therapy in COPD.

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation.

Introduction to therapeutic lasers in a rehabilitation setting.

Laser therapy, or photobiostimulation, is becoming a popular modality in the animal rehabilitation setting. It is used widely for the treatment of pain reduction, reduction of inflammation, and wound care and healing. Applications in the rehabilitation setting include postoperative cases, osteoarthritis, treatment of pain of a known origin, soft tissue injuries, and wounds.

The energy density of laser light differentially modulates the skin morphological reorganization in a murine model of healing by secondary intention.

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2).