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Made available in DSpace on 2020-12-10T20:04:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-26 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background:Photobiomodulation therapy (PBMT) and creatine (Cr) intake have been used in conjunction with heavy training, but little is known about their possible effects during a long-term training program. Objective:We assessed long-term use of PBMT and Cr in an exercise training program. Methods:Twenty-five male Wistar rats weighing similar to 300 g were randomly allocated to one of five groups: a nontraining control group, a training group, a training group receiving Cr, a training group receiving PBMT, and a training group receiving both PBMT and Cr. The training program consisted of 12 weeks of daily swimming training. PBMT was delivered in six points with a laser device (808 nm, 100 mW, 30 s per point of irradiation, 3 J, 75 J/cm(2)). Results:All training groups showed significantly higher peak force and longer time to 50% decay of force, and lower creatine kinase (CK) levels than the nontraining control group, thus confirming the benefit of the training program. In all outcomes related to muscle performance, the groups receiving PBMT with or without Cr supplement performed significantly better (p < 0.05) peak force and time of force decay during an electrical stimulation protocol than all the other groups. In addition, CK levels were also significantly lower for the PBMT groups than for the other groups. Conclusions:We conclude that PBMT alone or in conjunction with Cr supplement during a 12-week training program resulted in significantly better muscle performance and lower levels of CK, a biochemical marker of muscle damage. Sao Paulo State Univ UNESP, Postgrad Program Movement Sci, Lab Physiol & Sport Performance LAFIDE, Dept Phys Educ, Ave Eng Luiz Edmundo Carrijo Coube, BR-17033360 Bauru, SP, Brazil Univ Brasil, Postgrad Program Biomed Engn, Sao Paulo, SP, Brazil UNESP, Med Sch, Postgrad Program Pathophysiol, Med Clin, Botucatu, SP, Brazil Univ Bergen, Dept Global Publ Hlth & Primary Care, Physiotherapy Res Grp, Bergen, Norway Univ Vale Paraiba UNIVAP, Lab Biophoton & Expt Therapeut, Inst Res & Dev, Sao Jose Dos Campos, SP, Brazil UNINOVE Appl Biophoton Hlth Sci, Sao Paulo, SP, Brazil Sao Paulo State Univ UNESP, Postgrad Program Movement Sci, Lab Physiol & Sport Performance LAFIDE, Dept Phys Educ, Ave Eng Luiz Edmundo Carrijo Coube, BR-17033360 Bauru, SP, Brazil UNESP, Med Sch, Postgrad Program Pathophysiol, Med Clin, Botucatu, SP, Brazil FAPESP: 2017/21724-8 FAPESP: 2019/17445-1

Objective: To evaluate the influence of two different photobiomodulation therapy (PBMT) protocols (red 660 nm vs. infrared 830 nm) combined with a blood flow restriction (BFR) training protocol in ...

Background: Photobiomodulation therapy (PBMT) by lasers or light-emitting diodes (LEDs) has been used in the last two decades to increase muscle performance in humans. The main findings of PBMT on ...

Chitosan-based glycerol-plasticized membranes were prepared aiming to develop low-cost and biocompatible material for wound dressing. They were produced by casting/solvent evaporation, and their formation mechanisms were attributed to intra- and inter-hydrogen bonds between materials. The results show that the glycerol acted as plasticizer and changed the proliferation of fibroblast cells on chitosan membranes. A high increase in the contact angle between water and membrane was observed comparing pure chitosan (more hydrophilic) and chitosan-glycerol (more hydrophobic) membranes. The angle values were found to be ~ 40 and ~ 130 degrees for chitosan and chitosan/glycerol 30% (w/w) membranes, respectively. In comparison with pure chitosan, glycerol-mixed membranes showed lower glass transition temperatures and are less brittle when handling. The antibacterial properties of such membranes against Gram-negative (E. coli) and Gram-positive (S. aureus and B. Cereus) microorganisms were tested, showing efficient growth inhibition. In vitro studies over fibroblast cells using plasticized membranes demonstrated good viability and enhanced cell proliferation in comparison with those composed of pure chitosan. Such results suggest that the as-prepared chitosan-glycerol membrane is a promising material for use as wound dressing in tissue engineering applications.

This systematic review analyzed the light parameters and the effects of photobiomodulation therapy (PBMT) through low-level laser therapy (LLLT) and/or LED (light-emitting diode) on tendon repair of rats submitted to calcaneal injury. This study was conducted in accordance with the guidelines of the Preferred Reporting Items for Meta-Analysis, and PubMed and MEDLINE databases were accessed to search eligible studies published in English. The search terms were as follows: "Achilles tendon" or "Calcaneal tendon" or "tendon injuries" or "soft tissue injuries" and "tendinopathy" or "tendinitis" and "low-level light therapy" or "low-level laser therapy" or "low intensity power therapy" or "light-emitting diode" or photobiomodulation." The SYRCLE (SYstematic Review Center for Laboratory animal Experimentation) risks of bias was used to assess the risk of bias for selected studies. A total of 225 studies were found based on the descriptors used, and only 33 studies were eligible. Light parameters identified per point of irradiation were approximately 60 mW (continuous mode at infrared spectra), 2 W cm-2 , 2 J and 45 J cm-2 . Light parameters at red spectra, continuous versus pulsed mode, and PBMT combined or compared with other therapies such as ultrasound, and studies using unhealthy rats (ovariectomized and/or diabetic models) were also identified and grouped according to these similarities. The main effects found were decreased inflammatory markers and signs of inflammatory process. PBMT (laser/LED) has positive effects in reducing the inflammatory and time for tissue repair in animal models of tendon injury and/or tendinitis using parameters identified.

The aim of this study was to evaluate the acute effects of light-emitting diode therapy (LEDT) on cardiopulmonary adjustments and muscle oxygenation dynamics during transition to moderate exercise, as well as in glucose and lactate levels in patients with type 2 diabetes mellitus (T2DM). Sixteen individuals with T2DM (age 55.1±5.4 years) performed four separate tests receiving LEDT or placebo in random order, at intervals of at least 14 days. A light-emitting diode array (50GaAIAs LEDs, 850nm, 75mW per diode) was used to perform LEDT bilaterally on the quadriceps femoris and triceps surae muscles for 40s at each site. After, a moderate cycling exercise was performed and oxygen uptake, muscular deoxyhemoglobin, heart rate and cardiac output were measured. Lactate and glucose levels were measured before LEDT/placebo and after the exercise. The LEDT decreased the glucose levels after the exercise compared with values before LEDT (173.7±61.0 to 143.5±53.5 mg/dl, P=0.02) and it did not affect the cardiopulmonary and hemodynamic adjustments in exercise, as well as lactate levels in both groups. In conclusion, the LEDT in combination with moderate exercise acutely decreased the glucose levels in men with T2DM.

Made available in DSpace on 2021-06-25T10:21:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-15 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Purpose: The aim of the current study was to investigate the effects of photobiomodulation therapy (PBMT) applied 30 min or 6 h prior to cycling on blood flow velocity and plasma nitrite concentrations at rest, time to exhaustion, cardiorespiratory responses, blood acid-base balance, and K+ and lactate concentrations during exercise. Methods: In a randomized, crossover design, 13 healthy untrained men randomly completed four cycling bouts until exhaustion at the severe-intensity domain (i.e., above respiratory compensation point). Thirty minutes or 6 h prior to the cycling trials, participants were treated with PBMT on the quadriceps, hamstrings, and gastrocnemius muscles of both limbs using a multi-diode array (11 cm × 30 cm with 264 diodes) at doses of 152 J or a sham irradiation (with device turned off, placebo). Blood samples were collected before and 30 min or 6 h after treatments to measure plasmatic nitrite concentrations. Doppler ultrasound exams of the femoral artery were also performed at the same time points. Cardiorespiratory responses, blood acid-base balance, and K+ and lactate concentrations were monitored during exercise sessions. Results: PBMT did not improve the time to exhaustion (p = 0.30). At rest, no differences were found in the peak systolic velocity (p = 0.97) or pulsatility index (p = 0.83) in the femoral artery, and in plasma nitrite concentrations (p = 0.47). During exercise, there were no differences for any cardiorespiratory response monitored (heart rate, p = 0.15; oxygen uptake, p = 0.15; pulmonary ventilation, p = 0.67; carbon dioxide output, p = 0.93; and respiratory exchange ratio, p = 0.32), any blood acid-base balance indicator (pH, p = 0.74; base excess, p = 0.33; bicarbonate concentration, p = 0.54), or K+ (p = 0.22) and lactate (p = 0.55) concentrations. Conclusions: PBMT at 152 J applied 30 min or 6 h before cycling at severe-intensity did not alter resting plasma nitrite and blood flow velocity in the femoral artery, exercise-induced physiological responses, or time to exhaustion in healthy untrained men. Post-Graduate Program in Movement Sciences Laboratory of Physiology and Sport Performance (LAFIDE) Department of Physical Education School of Sciences São Paulo State University – UNESP Post-Graduate Program in Movement Sciences Department of Physical Education School of Sciences São Paulo State University – UNESP Department of Physical Education Federal University of Pernambuco Physical Therapy Department Federal University of Sao Carlos (UFSCar) Post-Graduate Program in Movement Sciences Laboratory of Physiology and Sport Performance (LAFIDE) Department of Physical Education School of Sciences São Paulo State University – UNESP Post-Graduate Program in Movement Sciences Department of Physical Education School of Sciences São Paulo State University – UNESP CAPES: 001 FAPESP: 2017/11255-0 FAPESP: 2017/14187-6 FAPESP: 2017/21724-8

Made available in DSpace on 2021-06-25T10:18:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Objective: To investigate the recovery of male water polo athletes applying full body photobiomodulation therapy (PBMT) regarding inflammation and muscle damage markers, testosterone and cortisol hormonal responses, heart rate variability (HRV), maximal voluntary contraction, and squat jump (SJ) after official water polo matches. Background: PBMT has been applied locally on specific muscle groups to induce faster recovery and improve the performance of athletes and nonathletes. However, many sports modalities require movement of the whole body, and a full body PBMT could be more adequate to irradiate large muscle areas homogeneously and faster. Methods: In a randomized, parallel, and double-blinded design, 13 athletes (whole team) aged 18 years attended the study and were allocated into two groups: PBMT (dose of 6.9 J/cm2, irradiance of 46.17 mW/cm2, 5 min irradiation) and placebo treatment. The study was conducted during the 2019 Brazilian under 20 water polo championship. All athletes were assessed by blood samples and neuromuscular evaluation. Immediately after each match, all athletes received PBMT (effective or placebo). Results: No significant interactions (raw values and percentage related to baseline) were observed for testosterone and cortisol, tumor necrosis factor-alpha, interleukin-6, creatine kinase concentration, maximal isometric voluntary contraction, SJ test, and HRV. Only an isolated interaction (decrease) was found for lactate dehydrogenase (LDH) response after the first match (p = 0.004, post-hoc p = 0.038). Conclusions: The parameters of the full body PBMT of this study did not induce faster recovery of inflammatory, muscle damage (excepting LDH), testosterone, cortisol, HRV, and neuromuscular responses during repeated days of water polo matches. Post-Graduate Program in Movement Sciences Laboratory of Exercise Physiology and Sport Performance (LAFIDE) Department of Physical Education School of Sciences São Paulo State University (Unesp) Post-graduation Program in Biomedical Engineering Universidade Brasil Post-Graduate Program in Movement Sciences Laboratory of Exercise Physiology and Sport Performance (LAFIDE) Department of Physical Education School of Sciences São Paulo State University (Unesp)

The aim of the present study was to analyze the effect of neuromuscular electrical stimulation (NMES) and photobiomodulation (PBMT) on the cardiovascular parameters, hemodynamic function, arterial baroreflex sensitivity (BRS), and autonomic balance (ANS) of rats with heart failure (HF). Male Wistar rats (220–290 g) were organized into five groups: Sham (n = 6), Control-HF (n = 5), NMES-HF (n = 6), PBMT-HF (n = 6), and NMES + PBMT-HF (n = 6). Myocardial infarction (MI) was induced by left coronary artery ligation. Animals were subjected to an eight-week NMES and PBMT protocol. Statistical analysis included the General Linear Model (GLM) followed by a Bonferroni post-hoc test. Rats of the NMES-HF group showed a higher MI area than the Control-HF (P = 0.003), PBMT-HF (P = 0.002), and NMES + PBMT-HF (P = 0.012) groups. NMES-HF and NMES + PBMT-HF showed higher pulmonary congestion (P = 0.004 and P = 0.02) and lower systolic pressure (P = 0.019 and P = 0.002) than the Sham group. NMES + PBMT-HF showed lower mean arterial pressure (P = 0.02) than the Sham group. Control-HF showed a higher heart rate than the NMES-HF and NMES + PBMT-HF (P = 0.017 and P = 0.013) groups. There was no difference in the BRS and ANS variables between groups. In conclusion, eight-week NMES isolated or associated with PBMT protocol reduced basal heart rate, systolic and mean arterial pressure, without influence on baroreflex sensibility and autonomic control, and no effect of PBMT was seen in rats with HF.

Made available in DSpace on 2021-06-25T10:12:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Purpose The purpose of the present study was to investigate the ergogenic effects of two doses of photobiomodulation therapy (PBMT) in comparison to placebo on markers of respiratory and muscle activity, blood acid-base, ion and lactate concentrations, indicators of muscle fatigue (global, central, and peripheral), and time to exhaustion in severe-intensity cycling. Methods Two separate studies were performed, both in a pseudorandomized and balanced, crossover design. In study 1, 14 male recreational cyclists completed three constant-load, severe-intensity cycling bouts that were duration matched. The PBMT (18 × 38 cm array with 200 diodes) treatments occurred before bouts at 260, 130, or 0 J (placebo) doses. EMG activity of selected lower limb musculature was assessed during each bout. Maximal voluntary contractions of knee extension with peripheral nerve stimulations and EMG activity evaluation of vastus lateralis was also performed before and after cycling. In study 2, 13 recreational cyclists performed three bouts of constant-load, severe-intensity cycling until exhaustion, preceded by PBMT as detailed previously. Blood lactate concentrations, respiratory responses, EMG activity, and capillary gasometry aspects were monitored. Results In both studies, there were no interactions effects (time-condition) on the EMG activity, which was displayed as root mean square (P ≥ 0.168) and median frequency (P ≥ 0.055) during cycling. In study 1, there were no interaction effects on the indicators of muscle fatigue after exercise (P ≥ 0.130). In study 2, there were no differences on time to exhaustion (P = 0.353) and no interaction effects among the physiological responses monitored (P ≥ 0.082). Conclusions Based on our findings, the PBMT at 260- and 130-J doses does not have a beneficial effect on muscle fatigue, cycling performance, metabolic parameters, and muscle activity in male recreational cyclists. Laboratory of Physiology and Sport Performance (LAFIDE) São Paulo State University (UNESP) Exercise Physiology Laboratory Department of Kinesiology University of Alabama Biomedical Engineering Postgraduate Program Universidade Brasil Laboratory of Physiology and Sport Performance (LAFIDE) São Paulo State University (UNESP)

Made available in DSpace on 2020-12-12T02:01:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 Photobiomodulation therapy (PBMT) has many effects on the energy metabolism of musculoskeletal tissue, such as increased glycogen and adenosine triphosphate synthesis. In addition, these effects may be due to a systemic blood glucose control. Twenty-four Wistar rats were randomly and equally allocated into four groups: sham, PBMT 10 J/cm2, PBMT 30 J/cm2 and PBMT 60 J/cm2. The animals were fasting for 6 h for blood glucose evaluations during pre-irradiation period, 1 h, 3 h and 6 h after PBMT. Muscle glycogen synthesis was measured 24 h after PBMT. This PBMT used a cluster of 69 LEDs (light-emitting diodes) with 35 red (630 ± 10 nm) and 34 infrared (850 ± 20 nm); 114 mW/cm2 for 90s (10 J/cm2), 270 s (30 J/cm2), 540 s (60 J/cm2) applied on large muscle areas (back and hind legs) of the animals. The 10 J/cm2 group showed lower blood glucose levels and glucose variability over 6 h (5.92 mg/dL) compared to the sham (13.03 mg/dL), 30 J/cm2 (7.77 mg/dL) and 60 J/cm2 (9.07 mg/dL) groups. The PBMT groups had the greatest increase in muscle glycogen (10 J/cm2 > 60 J/cm2 > 30 J/cm2 > sham), characterizing a triphasic dose-response of PBMT. There was a strong negative correlation between blood glucose variability over 6 h and muscle glycogen concentration for 10 J/cm2 group (r = −0.94; p < .001) followed by 30 J/cm2 group (r = −0.84; p < .001) and 60 J/cm2 group(r = −0.73; p < .006). These results suggest that PBMT can play a very important role in the control of blood glucose levels, and its possible mechanism of action is the induction of greater muscle glycogen synthesis independently of physical exercise. Post-Graduation Program in Biomedical Engineering Universidade Brasil Laboratory of Physiology and Human Performance São Paulo State University – UNESP, Bauru Universidade do Sagrado Coração (USC) Bauru Laboratory of Physiology and Human Performance São Paulo State University – UNESP, Bauru

To evaluate the photobiomodulation (PBM) effect on the cardiovascular autonomic control, analyzed by baroreflex sensitivity (sequence method), during constant load exercise and recovery in diabetic men, we evaluated 11 men with type 2 diabetes (DM2) (40–64 years). The constant workload exercise protocol (TECC) was performed on two different days, 14 days apart from each other, to guarantee PBM washout period. After PBM by light-emitting diode (LED) irradiation (150 J or 300 J or placebo), 10 min of rest (REST) was performed. After this period, the volunteer was positioned on a cycloergometer to start the test (1-min rest, 3-min free-load heating, 6-min constant workload–EXERCISE, 6-min free-load cool-down, 1-min rest) followed by a sitting period of 10 min (RECOVERY). The constant workload corresponded to 80%VO2GET (gas exchange threshold) identified by a previous cardiopulmonary exercise test (CPET). PBM was applied in continuous mode, contact technique, bilaterally, on both femoral quadriceps and gastrocnemius muscle groups. The electrocardiogram R-R intervals (BioAmp FE132) and the peripheral pulse pressure signals (Finometer PRO) were collected continuously throughout the protocol. Stable sequences of 256 points were chosen at REST, EXERCISE, and RECOVERY. The baroreflex sensitivity (BRS) was computed in time domain according to the sequence method (αseq). The comparison between therapies (150 J/300 J/placebo) and condition (REST, EXERCISE, and RECOVERY) was performed using the ANOVA two-way repeated measures test. There was no interaction between therapy and conditions during the TECC. There was only the condition effect (p

Photobiomodulation therapy (PBMT) in the infrared spectrum exerts positive effects on glucose metabolism, but the use of PBMT at the red spectrum has not been assessed. Male Swiss albino mice were divided into low-fat control and high-fat diet (HFD) for 12 weeks and were treated with red (630 nm) PBMT or no treatment (Sham) during weeks 9 to 12. PBMT was delivered at 31.19 J/cm2 , 60 J total dose per day for 20 days. In HFD-fed mice, PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia. PBMT also reduced adiposity and inflammatory infiltrate in adipose tissue. Phosphorylation of Akt in epididymal adipose tissue and rectus femoralis muscle was improved by PBMT. In epididymal fat PBMT reversed the reduced phosphorylation of AS160 and the reduced Glut4 content. In addition, PBMT reversed the alterations caused by HFD in rectus femoralis muscle on proteins involved in mitochondrial dynamics and β-oxidation. In conclusion, PBMT at red spectrum improved insulin resistance and glucose metabolism in HFD-fed mice.

To investigate the effects of photobiomodulation applied to respiratory muscles on lung function, thoracoabdominal mobility, respiratory muscle strength, and functional capacity in COPD patients. This is a randomized double-blind crossover clinical trial. Twelve male COPD patients participated in the study. Participants were randomly allocated to receive two photobiomodulation sessions, 1 week apart: (1) an effective photobiomodulation session applied at the main respiratory muscles by means of a cluster with 69 light-emitting diodes (LEDs), containing 35 red (630 ± 10 nm; 10 mW; 0.2 cm2) and 34 near-infrared (830 ± 20 nm; 10 mW; 0.2 cm2) LEDs and (2) a sham photobiomodulation session, following the same procedures without emitting light. The primary outcomes were pulmonary function (spirometric indexes); thoracoabdominal mobility (cirtometry); respiratory muscle strength (maximal respiratory pressures), assessed at three moments: (1) baseline, (2) 1 h after intervention, and (3) 24 h after intervention; and the functional capacity, assessed by the 6-min walk test (6MWT) at baseline and 24 h after intervention. No significant interactions were found for spirometric variables, maximal respiratory pressures, and cirtometry. However, there was a Time × Condition interaction (F = 18.63; p = 0.001; η2p = 0.62) in the walked distance on the 6MWT, with a significant increase after photobiomodulation intervention (p

Exposure of biological tissue to photobiomodulation therapy (PBMT) seems to increase the oxygen availability and mitochondrial electrochemical activity. With the advancement of new technologies, such as near-infrared spectroscopy (NIRS), information can be obtained about the balance between oxygen utilization and delivery by assessing local oxy- ([O2Hb]) and deoxy-myohemoglobin ([HHb]) concentrations, both measured in micromolars (μM). Consequently, NIRS can be used to study (“in vivo”) PBMT effects on the oxidative system, including oxygen availability. Thus, the main objective of the present study was to use NIRS to investigate the acute effects of PBMT by light-emitting diode (LED) on the oxygen delivery and utilization in humans. Twelve healthy young participants were treated with a LED device (850 nm, 50 mW, 2 J) and placebo applied over the proximal third of the flexor carpi ulnaris muscle of the left or right forearm selected in a random order. The LED was applied in direct contact with skin and the device was switched on for 40 s in 4 different interventions (I1, I2, I3 and I4) with a 3-min interval between interventions. The placebo condition was considered as the period before the first PBMT. The NIRS device was used to evaluate the relative changes in [O2Hb] and [HHb] before and after placebo and interventions. We found that PBMT statistically increased the [O2Hb] in 0.39 μM. These results demonstrate the potential of PBMT to increase oxygen availability.

The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks.This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program.Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1β) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy.Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.

6.1 Dose Dependence and Dose Rate Effects: The Biphasic Curve A biphasic response has been demonstrated many times in LLLT research, and the Arndt-Schulz law is frequently quoted as a suitable model to describe the dose-dependent effects of LLLT. The concept of the law dates from the end of the nineteenth century, when H. Schulz published a series of papers that examined the activity of various kinds of poisons (iodine, bromine, mercuric chloride, arsenious acid, etc.) on yeast, showing that almost all of these agents have a slightly stimulatory effect on the yeast metabolism in low doses. He and psychiatrist R. Arndt developed a principle that later became known as the Arndt-Schulz law, stating that weak stimuli slightly accelerate vital activity, stronger stimuli raise it further until a peak is reached, and even stronger stimuli suppress it until a negative response is finally achieved. In 1960, Townsend and Luckey surveyed the field of classic medical pharmacology and published a list of 100 substances capable of causing inhibition at high concentrations and stimulation at low concentrations, and they termed the phenomenon “hormoligosis.” The modern term “hormesis” was first used by Stebbing in 1982 and has been thoroughly reviewed by Calabrese. In the context of LLLT, the increasing “stimulus” may be irradiation time or increased irradiance. This nonlinear effect contradicts the Bunsen-Roscoe rule of reciprocity (originally formulated for the visual detection of light by photoreceptors), which predicts that if the products of the exposure time in seconds and irradiance in mW/cm 2 are equal, i.e., the energy density is the same, then the changes in the biological endpoint will be equal. This inverse linear relationship between irradiance and time has frequently failed in LLLT research.

20.1 Disappointment at Current Lack of Progress Despite the impressive accomplishments that have steadily accumulated since the 1960s that now consist of the publication of thousands of peer-reviewed papers [that can be retrieved by a PubMed search using the MeSH term “LLLT” and a new MeSH term “photobiomodulation therapy” (PBM)] and hundreds of clinical trials, many of which have been high-quality, randomized, and well-controlled, LLLT has still not reached the stage of acceptance by mainstream medicine. There remains considerable skepticism (and sometimes frank disbelief) amongst biomedical scientists, the medical profession, and the public at large. The reasons for this skepticism and disbelief are many and various, and they differ depending on the source. Biomedical scientists often refer to a lack of mechanism and the absence of agreement on dosimetry and parameters. Physicians often claim there is a lack of large clinical trials and not enough systematic reviews. Hospital and insurance administrators cannot agree on coverage and reimbursement. Finally (and regrettably), there has been marketing hype, over-promising, and frank misinformation from some of the companies that make devices (lasers, LED arrays, mixed clusters) that are used in the LLLT industry.

14.1 Photobiomodulation in Tendons Tendons (structures that connect muscles to bones) are composed of a dense connective tissue containing fibroblasts and extracellular matrix, including glycoproteins, elastin, proteoglycans, multiple saccharides, and collagen fibrils, which is the majority component by weight. In normal conditions, type-I collagen provides tensile strength to the tendon, and type-III collagen is distributed among bundles of type-I collagen. The tensile stiffness of collagen fibrils is due to their geometrical configuration, wherein the alignment of the individual fibrils confers resistance to the mechanical tension exerted by the muscle contraction, transmitting the muscle contraction forces to the bone in order to produce the movement of the limb. However, as a result of injuries combined with different kinds of extraneous factors (obesity, trauma, prolonged use of drugs such as antibiotics and corticosteroids, repetitive stress in work activities, and recreational sports activities), tendon tissue can develop a painful condition called tendinopathy that is characterized by an inflammatory process, biochemical changes in the extracellular matrix, and loss of biomechanical properties, such as lower resistance to tensile forces. Classified as a degenerative disease, tendinopathies generally have a poor ability to spontaneously heal, and the chronic conditions can sometimes lead to the complete rupture of the tendons, which requires surgical repair.

b]15.1 Effects of LLLT on Skin 15.1.1 Skin rejuvenation Skin aging is a process that can present itself relatively early on in life, sometimes even as soon as 20 - 30 years of age. Common signs and symptoms associated with skin aging include skin wrinkling, skin dyspigmentation, telangiectasia, and reduced tissue elasticity. At the histological and molecular level, common noticeable features include a reduction in collagen content, fragmentation of collagen fibers, elastotic degeneration of elastic fibers, the appearance of dilated and tortuous dermal vessels, disorientation and atrophy of the epidermis, and up-regulation of matrix metalloproteinases (MMPs), especially MMP-1 and MMP-2. Skin aging can be influenced by both time (normal aging) and environmental factors, but the single most influential factor responsible for accelerated skin aging is believed to be ultraviolet (UV) radiation-induced photodamage.

12.1 Photobiomodulation in Bone Bone tissue comprises different types of cells, such as osteoblasts, osteocytes, and osteoclasts. Osteoblasts are cells responsible for bone matrix synthesis and bone mineralization, and for secreting type-I collagen, proteoglycan, alkaline phosphatase, and osteocalcin. Osteocytes are cells that originate from osteoblasts and became incorporated within the osteoid matrix that is formed and then calcified to become mature bone. These cells are localized deeply within the bone matrix and are well organized. Osteoclasts are the cells responsible for degrading bone and for resorption of mineralized bone during the process of bone remodeling, which is required during repair of bone tissue. In addition, the bone mass (mineralized matrix) is composed of collagen and inorganic components - such as hydroxyapatite, calcium, and phosphate - conferring tensile strength to bones and providing a well-arranged structure that can bear loads and protect against sheer stress. The process of healing bone fractures is formally separated into the following phases: • immediate response to injury, • inflammatory phase, • ossification, and • bone remodeling.

The lymphatic system plays a critical role in the process of reducing inflammation and edema, as well as a major role in the immune response. It moves fluid (lymph) from interstitial spaces in tissues via a network of collecting vessels to the lymph nodes, where it is mostly emptied into the venous system. Some fluid moves further along the lymphatic chain to other lymph nodes and eventually empties into the thoracic duct. PBM reduces swelling, and it seems likely that the lymphatic system is involved, although limited evidence exists to confirm this. A PubMed search for a range of PBM terms (see Chapter 1) AND edema OR oedema OR swelling returns over 50 abstracts. Most of these abstracts are for post-mastectomy lymphedema, post-surgical swelling, acute soft-tissue injury, and arthritic joints. The mechanism by which light affects edema has not been adequately explored, although it makes sense that it should because nitric oxide (NO) modulates lymphatic vessel contraction and subsequent lymph flow, and it has been established that PBM releases stores of NO8–10 and subsequently improves blood flow. As with blood vessels, NO is produced by endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells, which in turn affects the dilation and force of lymph vessel contractions. Small amounts of NO are produced (by eNOS) when lymph vessels are stretched (by movement or a stretch/massage technique), and this leads to alternating periods of diastolic filling and systolic ejection of lymphangions (the tiny functional units of the collecting lymphatic system). Excessive amounts of NO produced by inducible nitric oxide synthase (iNOS) during inflammation can overwhelm the NO gradients produced by eNOS. The suppression of eNOS by iNOS disrupts the contraction/relaxation cycle in favor of excessive contraction and subsequent reduced flow.

Photobiomodulation (PBM) is a simple, efficient and cost-effective treatment for both acute and chronic pain. We previously showed that PBM applied to the mouse head inhibited nociception in the foot. Nevertheless, the optimum parameters, location for irradiation, duration of the effect, and the mechanisms of action remain unclear. In the present study, the pain threshold in the right hind-paw of mice was studied, after PBM (810 nm CW laser, spot size 1 cm(2) or 6 cm(2), 1.2–36 J/cm(2)) applied to various anatomical locations. The pain threshold, measured with von Frey filaments, was increased more than 3-fold by PBM to the lower back (dorsal root ganglion, DRG), as well as to other neural structures along the pathway such as the head, neck and ipsilateral (right) paw. On the other hand, application of PBM to the contralateral (left) paw, abdomen and tail had no effect. The optimal effect occurred 2–3 hours post-PBM and disappeared by 24 hours. Seven daily irradiations showed no development of tolerance. Type 1 metabotropic glutamate receptors decreased, and prostatic acid phosphatase and tubulin-positive varicosities were increased as shown by immunofluorescence of DRG samples. These findings elucidate the mechanisms of PBM for pain and provide insights for clinical practice.

Light-emitting diodes (LEDs) might have a beneficial impact on cytochrome-c oxidase enzyme activity. Thus, it was hypothesized that photobiomodulation by light-emitting diode therapy (LEDT) could influence aerobic metabolism dynamics. Possible LEDT-mediated aerobic improvements were investigated mainly by a precise characterization of the pulmonary O2 uptake dynamics during moderate exercise transitions. Eight healthy young adults were enrolled in this randomized, double-blind, placebo-controlled, crossover study. A multi-diode array of LEDs was used for muscular pre-conditioning 30 min and 6 h before exercise testing. Pulmonary O2 uptake, carbon dioxide output, cardiac output, heart rate, stroke volume, and total arteriovenous oxygen difference dynamics were evaluated by frequency domain analysis. Comparisons revealed no statistical (p > 0.05) differences between LEDT and placebo, suggesting no significant changes in aerobic system dynamics. These results challenge earlier publications that reported changes in pulmonary O2 uptake during incremental exercise until exhaustion after LEDT. Perhaps, increments in peak pulmonary O2 uptake after LEDT may be a consequence of higher exercise tolerance caused by non-aerobic-related factors as opposed to an improved aerobic response.

This study investigated the effects of photobiomodulation by low-laser laser therapy (LLLT) on the activities of citrate synthase (CS) and lactate dehydrogenase (LDH) and the anaerobic threshold (AT) in rats submitted to treadmill exercise. Fifty-four rats were allocated into four groups: rest control (RCG), rest laser (RLG), exercise control (ECG), and exercise laser (ELG). The infrared LLLT was applied daily on the quadriceps, gluteus maximum, soleus, and tibialis anterior muscles. Muscle samples (soleus, tibialis anterior, and cardiac muscles) were removed 48 h after the last exercise session for spectrophotometric analysis of the CS and LDH. The CS activity (μmol/protein) in ELG (16.02 and 0.49) was significantly greater (P

Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice. Male Swiss albino mice received low-fat control diet (n = 16, LFC) or high-fat diet (n = 18, HFD) for 12 weeks. From 9th to 12th week, the mice received PBM therapy (LASER) or Sham (light off) treatment and were allocated into four groups: LFC Sham (n = 8), LFC PBM (n = 8), HFD Sham (n = 9), and HFD PBM (n = 9). The PBM therapy was applied in five locations: to the left and right quadriceps muscle, upper limbs and center of the abdomen, during 40 s at each point, once a day, 5 days a week, for 4 weeks (780 nm, 250 mW/cm2, 10 J/cm2, 0.4 J per site; 2 J total dose per day). Insulin signaling pathway was evaluated in the epididymal adipose tissue. PBM therapy improved glucose tolerance and phosphorylation of Akt (Ser473) and reversed the HFD-induced reduction of GLUT4 content and phosphorylation of AS160 (Ser588). Also, PBM therapy reversed the increased area of epididymal and mesenteric adipocytes. The results showed that chronic PBM therapy improved parameters related to obesity and insulin resistance in HFD-induced obesity in mice.

A von Frey filament (vFF) is a type of aesthesiometer usually made of nylon perpendicularly held in a base. It can be used in paw withdrawal pain threshold assessment, one of the most popular tests for pain evaluation using animal models. For this test, a set of filaments, each able to exert a different force, is applied to the animal paw, from the weakest to the strongest, until the paw is withdrawn.We made 20 low cost vFF using nylon filaments of different lengths and constant diameter glued perpendicularly to the ends of popsicle sticks. They were calibrated using a laboratory balance scale. Building and calibrating took around 4h and confirmed the theoretical prediction that the force exerted is inversely proportional to the length and directly proportional to the width of the filament.The calibration showed that they were precise and accurate. We analyzed the paw withdrawal threshold assessed with the set of home-made vFF and with a high quality commercial set of 5 monofilaments vFF (Stoelting, Wood Dale, USA) in two groups (n=5) of healthy mice.The home-made vFF precisely and accurately measured the hind paw withdrawal threshold (20.3±0.9 g). The commercial vFF have different diameters while our set has the same diameter avoiding the problem of lower sensitivity to larger diameter filaments.Building a set of vFF is easy, cost effective, and depending on the kind of tests, can increase precision and accuracy of animal nociception evaluation.

Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce "killed but metabolically active" microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future.