Does electrophysical agents work for cellulite treatment? a systematic review of clinical trials.

Cellulite, a perceived alteration in skin topography, is predominantly found in adipose tissue-rich body regions such as the hips, buttocks, thighs, and abdomen. Contrary to common belief, the etiology and pathophysiology of cellulite are not well-established or universally agreed upon. This lack of understanding about the actual etiology of cellulite directly influences the selection of suitable treatments that can address both the aesthetic and inflammatory aspects of the condition. Various treatment methods, including electrophysical agents like electric currents, radiofrequency, ultrasound, and photobiomodulation, have been tested. However, the questionable methodological quality of many studies complicates the determination of effective treatments for cellulite. In this study, we conducted a systematic review of clinical studies that utilized electrophysical agents in cellulite treatment. METHODS: We employed the PICO (population, intervention, control, and outcome) process to develop our search strategy and establish inclusion/exclusion criteria. We searched five databases: Medline, Central, Scopus, Lilacs, and PEDro, for studies conducted between 2001 and July 2021 that involved cellulite treatment with electrophysical agents. To ensure systematicity and guide study selection, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: Our initial search yielded 556 articles: 379 from Medline, 159 from Central, and 18 from Lilacs. After applying our inclusion criteria, only 32 studies remained. Of these, only two (6.2%) were evaluated as having strong and good methodology via the QualSyst tool. CONCLUSIONS: Our findings indicate that the quality of evidence from clinical studies on the use of electrophysical agents for cellulite treatment remains subpar. Further studies with robust experimental designs and more precise assessment techniques are necessary. While our study does not refute the effectiveness of the techniques used for cellulite treatment, it underscores the need for additional well-designed trials.

Effects of photobiomodulation on pain, lactate and muscle performance (ROM, torque, and EMG parameters) of paretic upper limb in patients with post-stroke spastic hemiparesis-a randomized controlled clinical trial.

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.

Transcranial photobiomodulation therapy associated with cardiorespiratory rehabilitation in spastic subjects.

The objective of this study was to evaluate the effects of cardiorespiratory rehabilitation (CR) and transcranial photobiomodulation (tPBM) on exercise tolerance (ET), heart rate variability (HRV), and peripheral muscle activity in individuals with spasticity. Fifteen participants with spasticity were randomly assigned to two groups: the tPBM group (tPBMG) consisted of eight volunteers who underwent tPBM (on mode) and CR, while the control group (CG) consisted of seven volunteers who underwent simulated tPBM (off mode) and CR. The CR program included 12 weeks of treatment, twice a week for one hour, involving aerobic exercises and lower limb strengthening. For tPBM, a cluster with three lasers (λ = 680 nm, 808 nm), with a power of 100 mW/laser and energy of 36 J, applied to the F7, F8, and Fpz points. The following parameters were evaluated after 8 and 12 weeks: ET, HRV, and surface electromyography (EMG) of the rectus femoris muscle during orthostasis (ORT), isometric squatting (ISOM), and isotonic squatting (ISOT). Both groups showed a 40% increase in ET for the CG and a 30% increase for the tPBMG. The CG had more pronounced parasympathetic modulation alterations during post-exercise effort and recovery compared to the tPBMG. The EMG results showed that the tPBMG exhibited progressive improvement in muscle activity during ISOM and ISOT, as well as a decrease in the interlimb difference. In conclusion, both CR and tPBMG demonstrated improvements in ET. However, tPBMG specifically showed promising effects on HRV modulation and peripheral muscle electrical activity, providing additional benefits compared to CR alone.

Improved Spatial Memory And Neuroinflammatory Profile Changes in Aged Rats Submitted to Photobiomodulation Therapy.

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4 months old) and aged (20 months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.

Efficacy of prolonged application of low-level laser therapy combined with exercise in knee osteoarthritis: A randomized controlled double-blind study.

OBJECTIVES: To investigate the effect of prolonged low-level laser therapy application combined with exercise on pain and disability in patients with osteoarthritis of the knee. DESIGN: A randomized controlled trial. SETTING: Special rehabilitation services. SUBJECTS: Forty-three participants with knee osteoarthritis. INTERVENTION: Following initial assessment, participants were randomly allocated to the Laser group (n = 22, 44 knees) and received low-level laser therapy while the Placebo group (n = 21, 42 knees) received placebo therapy three times a week for 3 weeks. Both groups then received low-level laser therapy combined with exercise three times a week for the following 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in knee pain and disability (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscular strength (dynamometer), activity (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and medication intake and relief. RESULTS: Mean (SD) age of participants was 63.02 (9.9) years. Pain scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 9.1 (1.3), 2.6 (2.3), 0.2 (0.9), and 0.2 (0.8) for the Laser group and 9.5 (8.0), 7.7 (5.3), 5.6 (2.4), and 7.4 (5.0) for the Placebo group, respectively. Disability scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 14.9 (4.7), 7.6 (4.8), 3.9 (4.2), and 3.5 (4.1) for the Laser group and 17.8 (14.7), 15.2 (11.5), 11.6 (6.4), and 15.8 (11.9) for the Placebo Group, respectively. CONCLUSION: In participants with osteoarthritis of the knee, the isolated application of low-level laser therapy in the initial 3 weeks and combined with exercises in the final 8 weeks reduced pain, disability, and intake of medication over a 6-month period.

The influence of photobiomodulation on the temperature of the brachial biceps during muscle fatigue protocol.

Physical activity raises body temperature. However, the literature does not contain studies about whether the employment of hotobiomodulation (PMB) could significantly influence body temperature during a muscle fatigue (MF) protocol. Thus, the aim of this study was to evaluate the effects of PMB on the temperature of the biceps brachii muscle during the performance of a muscle fatigue protocol. The study consisted of 14 volunteers who were divided into two groups (placebo group and laser group) and all individuals rotated into all groups (crossover study). To induce muscle fatigue, three maximum voluntary isometric contractions (MVIC) were performed for 50 s with a 50-s interval. During the MVIC, the muscle strength was assessed using surface electromyography and infrared temperature at 0, 5, 10, and 15 min after the tests. The laser group presented a less accentuated decrease in muscle strength, evidencing a lower rate of muscle fatigue (p > 0.05) in relation to the other groups. In the temperature analysis, the control group exhibited the highest average temperature, with a significant difference only for the placebo. The results indicate that the control displayed the greatest physical degeneration and the PMB group had a positive effect on MF attenuation and body thermoregulation.

Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high-performance liquid chromatography coupled to tandem mass spectrometry.

To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (Cmax ), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69-106.16) for Cmax, 97.44% (90% CI = 91.85-103.37%) for area under curve of plasma concentration until the last concentration observed (AUClast ) and 98.30% (90% CI = 92.48-104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC0-inf ). Since the 90% CI for AUClast , AUC0-inf and Cmax ratios were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.

Long-term analyses of spastic muscle behavior in chronic poststroke patients after near-infrared low-level laser therapy (808 nm): a double-blinded placebo-controlled clinical trial.

Stroke results in impairment of basic motor functions, such as muscle weakness in limbs affected by spasticity, leading to peripheral fatigue and impaired functionality. The clinical use of photobiomodulation therapy (PBMT) has provided major advances in the treatment of muscular disorders and prevention of muscle fatigue. The aim of this study was to analyze the effects of two distinct therapies in biceps spasticity of chronic hemiparetic patients. We analyzed range of elbow motion, torque, electromyography, and mean spectral frequency after 10 sessions of PBMT (Laser 100 mW, 808 nm, 159.24 J/cm2/point, 5 J/point); PBMT active or placebo was associated with exoskeleton-assisted functional treatment. A double-blind placebo-controlled sequential clinical trial was conducted with 12 healthy volunteers and 15 poststroke patients who presented upper-limb spasticity. The healthy volunteers performed only the evaluation protocol, and the poststroke volunteers participated in three consecutive phases (PBMT, PBMT + exoskeleton, placebo + PBMT) with a washout period of 4 weeks between each phase. We could observe significant increases in range of elbow motion after PBMT from 57.7 ± 14 to 84.3 ± 27.6 degrees (p < 0.001). The root mean square (RMS) values also increased after PBMT + exoskeleton from 23.2 ± 15 to 34.9 ± 21 µV (p = 0.0178). Our results suggest that the application of PBMT may contribute to an increased range of elbow motion and muscle fiber recruitment, increases in muscle strength, and, hence, to increase signal conduction on spastic muscle fibers in spastic patients.

PBMT and topical diclofenac as single and combined treatment on skeletal muscle injury in diabetic rats: effects on biochemical and functional aspects.

Physical exercise generates several benefits in a short time in patients with diabetes mellitus. However, it can increase the chances of muscle damage, a serious problem for diabetic patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat these injuries, despite the serious adverse effects. In this way, photobiomodulation therapy (PBMT) with low-level laser therapy (LLLT) and/or light emitting diode therapy (LEDT) can be used as an alternative in this case. However, its efficacy in tissue repair of trauma injuries in diabetes mellitus until now is unknown, as well as the combination between PBMT and NSAIDs. The objective of the present study was to evaluate the effects of NSAIDs and PBMT applied alone or combined on functional and biochemical aspects, in an experimental model of muscle injury through controlled trauma in diabetic rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm2; 3 J; 107.1 J/cm2, 30 s), diclofenac sodium for topical use (1 g), or combination of them. Our results demonstrated that PBMT + diclofenac, and PBMT alone reduced the gene expression of cyclooxygenase-2 (COX-2) at all assessed times as compared to the injury and diclofenac groups (p < 0.05 and p < 0.01 respectively). The diclofenac alone showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). Prostaglandin E2 levels in blood plasma demonstrated similar results to COX2. In addition, we observed that PBMT + diclofenac and PBMT alone showed significant improvement compared with injury and diclofenac groups in functional analysis at all time points. The results indicate that PBMT alone or in combination with diclofenac reduces levels of inflammatory markers and improves gait of diabetic rats in the acute phase of muscle injury.

Long-term results of a randomized, controlled, double-blind study of low-level laser therapy before exercises in knee osteoarthritis: laser and exercises in knee osteoarthritis.

OBJECTIVES: To assess the long-term effects of low-level laser therapy (LLLT), in combination with strengthening exercises in patients with osteoarthritis of the knee. DESIGN: Follow-up results at three and six months in a previously published randomized, double-blind, placebo-controlled trial. SETTING: Specialist Rehabilitation Services. SUBJECTS: Forty participants of both genders, aged 50-75 years with knee osteoarthritis grade 2-4 on Kellgren-Lawrence scale. INTERVENTION: The LLLT group received 10 LLLT treatments with invisible infrared laser (904 nm, 3 Joules/point) over three weeks followed by an eight-week supervised strengthening exercise program. The placebo LLLT group received identical treatment, but the infrared laser output was disabled. MAIN MEASURES: Pain on a visual analogue scale, paracetamol consumption, and osteoarthritis severity measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index. RESULTS: The new data obtained during the follow-up period showed that all outcomes remained stable and there were no significant differences between the groups at three and six months. However, daily consumption of rescue analgesics (paracetamol) was significantly lower in the LLLT group throughout the follow-up period, ending at a group difference of 0.45 vs. 3.40 units ( P < 0.001) at six months follow-up. We conclude that within the limitations of this small study, the previously reported improvement after LLLT plus exercise was maintained for a period of six months. CONCLUSION: We find that the immediate post-intervention improvements from LLLT plus strengthening exercises were maintained for six months.

Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers.

Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm2, once a day, with intervals of 24 h, totaling 12 applications. The lesion area analysis revealed averaged improvement of the granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis revealed that IL6 values were not significantly different before and after treatment, TNF gene expression was reduced, and VEFG and TGF-ß gene expression increased after treatment. After LLLT, wounds presented improvement in gross appearance, with increase in factors VEFG and TGF-ß, and reduction of TNF; despite our promising results, they have to be analyzed carefully as this study did not have a control group.

High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue.

It is well established that laser phototherapy (LP) is contraindicated directly over cancer cells, due to its bio modulatory effects in cell and blood vessel proliferation. The aim of the present study was to analyze the influence of typical low-level laser therapy (LLLT) and high intensity laser therapy (HILT) and an in-between dose of 9 J on collagen fibers and blood vessels content in melanoma tumors (B16F10) implanted in mice. Melanoma tumor cells were injected in male Balb C mice which were distributed in four groups: control (no irradiated) or irradiated by 3, 9, or 21 J (150; 450, or 1050 J/cm2). LP was performed in daily sessions for 3 days with a InGaAlP-660 nm (mean output: 50 mW, spot size: 2 mm2). Tumor volume was analyzed using (1) picrosirius staining to quantify collagen fibers content and (2) Verhoeff's method to quantify blood vessels content. Tumor growth outcome measured in the 3-J group was not significantly different from controls. Nine and 21-J groups, presented significant and dose-dependent increases in tumor volume. Quantitative analysis of the intensity of collagen fibers and their organization in stroma and peri-tumoral microenvironment showed significant differences between irradiated and control group. Blood vessels count of 21-J group outnumbered the other groups. High doses (≥ 9 J) of LP showed a dose-dependent tumor growth, different collagen fibers characteristics, and eventually blood vessel growth, while a typical LLLT dose (3 J) appeared harmless on melanoma cell activity.

Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis.

Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E2 and proinflammatory cytokines. The elevation of cytokine levels is closely associated with increased articular tissue degeneration. Thus, the use of combination therapies may presumably be able to enhance the effects on the modulation of inflammatory markers. The present study aimed to evaluate and compare the effects of photobiomodulation therapy (PBMT), physical exercise, and topical nonsteroidal anti-inflammatory drug (NSAID) use on the inflammatory process after they were applied either alone or in different combinations. OA was induced by intra-articular papain injection in the knee of rats. After 21 days, the animals began treatment with a topical NSAID and/or with physical exercise and/or PBMT. Treatments were performed three times a week for eight consecutive weeks, totaling 24 therapy sessions. Analysis of real-time polymerase chain reaction (RT-PCR) gene expression; interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) protein expression; and PGE2 levels by enzyme-linked immunosorbent assay (ELISA) was conducted. Our results showed that PBMT alone and Exerc + PBMT significantly reduced IL-1ß gene expression (p < 0.05) while no treatment changed both IL-6 and TNF-α gene expression. Treatment with NSAID alone, PBMT alone, Exerc + PBMT, and NSAID + PBMT reduced IL-1ß protein expression (p < 0.05). All therapies significantly reduced IL-6 and TNF-α protein expression (p < 0.05) compared with the OA group. Similarly, all therapies, except Exerc, reduced the levels of PGE2 (p < 0.05) compared with the OA group. The results from the present study indicate that treatment with PBMT is more effective in modulating the inflammatory process underlying OA when compared with the other therapies tested.

Effects of low-level laser therapy on performance, inflammatory markers, and muscle damage in young water polo athletes: a double-blind, randomized, placebo-controlled study.

This study aimed to evaluate the effects of 5 days of 810-nm low-level laser therapy (LLLT) intervention on inflammatory and muscle damage markers and performance in young water polo players. Twenty young male water polo players participated in the study, which was designed as a randomized, double-blinded, placebo-controlled trial. Active LLLT or an identical placebo LLLT were delivered to eight points on the adductor muscle region immediately after each training day. Performance was measured by a 200-m maximal swimming (P200) and a 30-s crossbar jump test (30CJ) which was performed every day before training, and blood samples were drawn pre and post the final LLLT intervention to measure interleukins (IL) and muscle damage markers. There was no significant change in the P200 exercise in the LLLT group compared with the placebo group but there was a moderate improvement in the 30CJ (8.7 ± 2.6 %). IL-1ß and tumor necrosis factor-alpha presented increased (P < 0.016) concentration within group 48 h after the last LLLT intervention compared to pre, 0, and 24 h, but did not differ between groups. IL-10 increased over time in the placebo group and reached a moderate effect compared to the LLLT group. The creatine kinase decreased significantly (P = 0.049) over the time within the LLLT treatment group, but there was no significant change in lactate dehydrogenase (P = 0.150). In conclusion, LLLT resulted in a non-significant, but small to moderate effect on inflammatory and muscle damage markers and a moderate effect on performance in water polo players. In addition, the lack of positive results could be due to the small area covered by irradiation and this should be considered in future studies.

The low level laser therapy (LLLT) operating in 660 nm reduce gene expression of inflammatory mediators in the experimental model of collagenase-induced rat tendinitis.

Tendinopathy is a common disease with a variety of treatments and therapies. Laser therapy appears as an alternative treatment. Here, we investigate the effects of laser irradiation in an experimental model of tendinitis induced by collagenase injection on rats' Achilles tendon, verifying its action in important inflammatory markers. Male Wistar rats were used and divided into five groups: control saline (C), non-treated tendinitis (NT) and tendinitis treated with sodium diclofenac (D) or laser (1 J) and (3 J). The tendinitis was induced by collagenase (100 µg/tendon) on the Achilles tendon, which was removed for further analyses. The gene expression for COX-2; TNF-α; IL-6; and IL-10 (RT-PCR) was measured. The laser irradiation (660 nm, 100 mW, 3 J) used in the treatment of the tendinitis induced by collagenase in Achilles tendon in rats was effective in the reduction of important pro-inflammatory markers such as IL-6 and TNF-α, becoming a promising tool for the treatment of tendon diseases.

What is the best treatment to decrease pro-inflammatory cytokine release in acute skeletal muscle injury induced by trauma in rats: low-level laser therapy, diclofenac, or cryotherapy?

Currently, treatment of muscle injuries represents a challenge in clinical practice. In acute phase, the most employed therapies are cryotherapy and nonsteroidal anti-inflammatory drugs. In the last years, low-level laser therapy (LLLT) has becoming a promising therapeutic agent; however, its effects are not fully known. The aim of this study was to analyze the effects of sodium diclofenac (topical application), cryotherapy, and LLLT on pro-inflammatory cytokine levels after a controlled model of muscle injury. For such, we performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg/g of solution), cryotherapy (20 min), or LLLT (904 nm; superpulsed; 700 Hz; 60 mW mean output power; 1.67 W/cm(2); 1, 3, 6 or 9 J; 17, 50, 100 or 150 s). Assessment of interleukin-1ß and interleukin-6 (IL-1ß and IL-6) and tumor necrosis factor-alpha (TNF-α) levels was performed at 6 h after trauma employing enzyme-linked immunosorbent assay method. LLLT with 1 J dose significantly decreased (p < 0.05) IL-1ß, IL-6, and TNF-α levels compared to non-treated injured group as well as diclofenac and cryotherapy groups. On the other hand, treatment with diclofenac and cryotherapy does not decrease pro-inflammatory cytokine levels compared to the non-treated injured group. Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma.

Effects of pre-irradiation of low-level laser therapy with different doses and wavelengths in skeletal muscle performance, fatigue, and skeletal muscle damage induced by tetanic contractions in rats.

This study aimed to evaluate the effects of low-level laser therapy (LLLT) immediately before tetanic contractions in skeletal muscle fatigue development and possible tissue damage. Male Wistar rats were divided into two control groups and nine active LLLT groups receiving one of three different laser doses (1, 3, and 10 J) with three different wavelengths (660, 830, and 905 nm) before six tetanic contractions induced by electrical stimulation. Skeletal muscle fatigue development was defined by the percentage (%) of the initial force of each contraction and time until 50 % decay of initial force, while total work was calculated for all six contractions combined. Blood and muscle samples were taken immediately after the sixth contraction. Several LLLT doses showed some positive effects on peak force and time to decay for one or more contractions, but in terms of total work, only 3 J/660 nm and 1 J/905 nm wavelengths prevented significantly (p < 0.05) the development of skeletal muscle fatigue. All doses with wavelengths of 905 nm but only the dose of 1 J with 660 nm wavelength decreased creatine kinase (CK) activity (p < 0.05). Qualitative assessment of morphology revealed lesser tissue damage in most LLLT-treated groups, with doses of 1-3 J/660 nm and 1, 3, and 10 J/905 nm providing the best results. Optimal doses of LLLT significantly delayed the development skeletal muscle performance and protected skeletal muscle tissue against damage. Our findings also demonstrate that optimal doses are partly wavelength specific and, consequently, must be differentiated to obtain optimal effects on development of skeletal muscle fatigue and tissue preservation. Our findings also lead us to think that the combined use of wavelengths at the same time can represent a therapeutic advantage in clinical settings.

Prevention and treatment of mice paw edema by near-infrared low-level laser therapy on lymph nodes.

Low-level laser therapy (LLLT) has been demonstrated to modulate inflammatory processes and immunological responses. The aim of this work was to investigate the hypothesis that near infrared LLLT (830 nm) over lymph nodes may reduce paw edema and contribute to the modulation of inflammation. The edema was induced by carrageenan inoculation (CGN) into the plantar surface of 100 male mice left hind paw. Animals were divided into five groups: CGN (control), no treatment; Diclo, sodium diclofenac; Paw, LLLT on the paw; Ly, LLLT on the inguinal lymph nodes; and Paw+Ly, LLLT in both paw and lymph nodes, and subdivided according to moment of irradiation: A-1 h and 2 h before CGN, B-1 h and immediately before CGN, C-1 and 2 h after CGN, and D-3.5 and 4.5 h after CGN. The parameters used were: energy=1 J, fluence=35 J/cm(2), power=100 mW during 10 s. Paw volume was measured before and 1 to 6 h after CGN, and myeloperoxidase (MPO) activity was analyzed. Edema prevention was obtained by the irradiation of Paw+Ly at moment A and at Ly at moment B, inhibition of edema formation was achieved by either Paw or Ly at moment C, and edema treatment was obtained by Paw or Ly at moment D (p<0.05). MPO activity was significantly reduced on Paw at moment A, Paw and Ly on C, and in all irradiated groups on B and D. Our results suggest that LLLT was able to produce both anti-inflammatory and pro-inflammatory effects depending on to the site and moment of irradiation.

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart.

BACKGROUND: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. METHODS: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff's preparation. RESULTS: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). CONCLUSIONS: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.

A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.