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STUDY DESIGN: Randomized crossover double-blinded placebo-controlled trial. OBJECTIVE: To investigate if low-level laser therapy (LLLT) can affect biceps muscle performance, fatigue development, and biochemical markers of postexercise recovery. BACKGROUND: Cell and animal studies have suggested that LLLT can reduce oxidative stress and inflammatory responses in muscle tissue. But it remains uncertain whether these findings can translate into humans in sport and exercise situations. METHODS: Nine healthy male volleyball players participated in the study. They received either active LLLT (cluster probe with 5 laser diodes; lambda = 810 nm; 200 mW power output; 30 seconds of irradiation, applied in 2 locations over the biceps of the nondominant arm; 60 J of total energy) or placebo LLLT using an identical cluster probe. The intervention or placebo were applied 3 minutes before the performance of exercise. All subjects performed voluntary elbow flexion repetitions with a workload of 75% of their maximal voluntary contraction force until exhaustion. RESULTS: Active LLLT increased the number of repetitions by 14.5% (mean +/- SD, 39.6 +/- 4.3 versus 34.6 +/- 5.6; P = .037) and the elapsed time before exhaustion by 8.0% (P = .034), when compared to the placebo treatment. The biochemical markers also indicated that recovery may be positively affected by LLLT, as indicated by postexercise blood lactate levels (P<.01), creatine kinase activity (P = .017), and C-reactive protein levels (P = .047), showing a faster recovery with LLLT application prior to the exercise. CONCLUSION: We conclude that pre-exercise irradiation of the biceps with an LLLT dose of 6 J per application location, applied in 2 locations, increased endurance for repeated elbow flexion against resistance and decreased postexercise levels of blood lactate, creatine kinase, and C-reactiveprotein. LEVEL OF EVIDENCE: Performance enhancement, level 1b.J Orthop Sports Phys Ther 2010;40(8):524-532; Epub 12 April 2010. doi:10.2519/jospt.2010.3294. [ABSTRACT FROM AUTHOR]

Background: Low level laser therapy (LLLT) is a modality that has been used by physiotherapists for more than two decades. Clinical use has largely relied on empirical data, but new evidence suggests that LLLT can trigger specific photobiological mechanisms. Objective: To review possible therapeutic windows for LLLT in inflammatory reactions. Methods: Systematic review of LLLT in studies with cell cultures and animals where inflammation is induced. Skin wound studies were excluded unless they measured the influence of drugs on LLLT effects, or made a direct comparison of LLLT and drugs in inflammation. Results: We identified 1 review, 34 cell studies, 54 animal studies and 106 skin incision studies potentially eligible for analysis. Eleven cell studies and 27 animals studies met all our inclusion criteria, and another six animal studies met our inclusion criteria for drug comparisons and LLLT interactions. There is strong evidence of an anti-inflammatory effect from LLLT, which is consistent across all 12 tested laboratory models and phases of inflammation and wavelengths between 633 and 904 nm. The magnitude of the antiinflammatory effect is not significantly different from that of non-steroidal anti-inflammatory drugs (NSAIDs), but it is slightly less than glucocorticoid steroids. There is moderate evidence that concomitant use of glucocorticoid steroid has a negative effect on LLLT mechanisms and should be avoided. Conclusion: Red and near infrared LLLT administered with mean laser output of 2.5-100 mW, irradiation times of 16-600 s and doses of 0.6-9.6 J reduces inflammation significantly, and is equally effective as NSAIDs in animal laboratory studies. Scattered evidence from human studies have found similar antiinflammatory effects of LLLT, suggesting that this mechanism may be responsible for many of the significant effects reported in clinical LLLT studies. [ABSTRACT FROM AUTHOR]

Background: Low level laser therapy (LLLT) has gained increasing popularity in the management of tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action. Objective: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon. Subjects: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms produced by pain inducing activity immediately before the study. Method: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order. Results: Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo LLLT: the mean difference in the change between the groups was 0.40 kg/cm2 (95% confidence interval 0.10 to 0.70). Conclusion: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory component. [ABSTRACT FROM AUTHOR]

Background: Trauma is a major cause of mortality and reduced quality of life. Most trauma-related research originates from trauma centres, and there are limited available data regarding the treatment of trauma patients throughout the Nordic countries. These countries differ from economically similar countries due to their cold climate, mix of rural and urban areas, and the long distances separating many residents from a trauma centre. Research funders and the general public expect trauma research to focus on all links in the treatment chain. Here we conducted a systematic review to assess the amount of trauma-related research from the Nordic countries between January 1995 and April 2018, and the distribution of this research among different countries and different parts of the trauma treatment chain., Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane Library, Web of Science, and Scopus. We included studies concerning the trauma population from Nordic countries, and published between January 1995 and April 2018. Two independent reviewers screened titles and abstracts, and performed data extraction from full-text articles., Results: The literature search yielded 5117 titles and abstracts, of which 844 full-text articles were included in our analysis. During this period, the annual number of publications increased. Publications were equally distributed among Norway, Sweden, and Denmark in terms of numbers; however, Norway had more publications relative to inhabitants. There were fewer overall publications from Finland and Iceland. We identified mostly cohort studies and very few randomized controlled trials. Studies focused on the level of care were predominantly epidemiological studies. Research at the pre-hospital level was three-fold more frequent than research on other elements of the trauma treatment chain., Conclusion: The rate of publications in the field of trauma care in the Nordic countries has increased over recent years. However, several parts of the trauma treatment chain are still unexplored and most of the available studies are observational studies with low research evidence.

The main aim of the present study was to compare skeletal maturity level and physical capacities between male Norwegian soccer players playing at elite, sub-elite and non-elite level. Secondary, we aimed to investigate the association between skeletal maturity level and physical capacities. One hundred and two U14 soccer players (12.8-14.5 years old) recruited from four local clubs, and a regional team were tested for bone age and physical capacities. Bone age was estimated with x-ray of their left hand and used to indicate maturation of the skeleton. Players went through a comprehensive test battery to assess their physical capacities. Between-groups analysis revealed no difference in chronological age, skeletal maturity level, leg strength, body weight, or stature. However, elite players were superior to sub-elite and non-elite players on important functional characteristics as intermittent-endurance capacity (running distance: 1664 m ± 367 vs 1197 m ± 338 vs 693 m ± 235) and running speed (fastest 10 m split time: 1.27 seconds ± 0.06 vs 1.33 seconds ± 0.10 vs 1.39 seconds ± 0.11), in addition to maximal oxygen uptake ( V ˙ O 2 m a x ), standing long jump, and upper body strength (P < .05 for all comparisons). Medium-to-large correlations were found between skeletal maturity level and peak force (r = 695, P < .01), power (r = 684, P < .01), sprint (r = -.471, P<.001), and jump performance (r = .359, P < .01), but no correlation with upper body strength, V ˙ O 2 m a x , or intermittent-endurance capacity. These findings imply that skeletal maturity level does not bias the selection of players, although well-developed physical capacity clearly distinguishes competitive levels. The superior physical performance of the highest-ranked players seems related to an appropriate training environment., (© 2019 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to evaluate the effects of 16 weeks combined aerobic and resistance training, twice a week, on the physical performance in women treated for gynecological cancer., Methods: Sixty women (56.9 ± 13.3 years) who had completed curative treatment for gynecological cancer were divided into two groups: a physical training group (PT) (n = 29) or a control group (C) (n = 31). The PT group performed two sessions of combined aerobic and resistance training weekly for 16 weeks. Peak oxygen consumption (V̇O 2peak ) and one repetition maximum (1RM) of leg press, leg extension, and chest press were measured before group assignment, after 16 weeks and at the 1-year follow-up., Results: A significant increase in V̇O 2peak (ml min -1  kg -1 ) (29.7 ± 8.0 vs. 31.3 ± 8.3, p = .009), leg press (kg) (113.0 ± 27.3 vs. 116.7 ± 29.2, p = .047), leg extension (kg) (44.2 ± 10.1 vs. 48.0 ± 10.6, p < .001), and chest press (kg) (24.5 ± 7.5 vs. 26.9 ± 8.2, p = .001) was seen in the PT group from pre- to post-measurement. The PT group maintained the improved aerobic condition and muscle strength 1 year after the training intervention. In the C group, there were no significant differences between pre- and post-measurements, but a significant decrease (28.2 ± 7.5 vs. 27.0 ± 7.3, p = .040) in the V̇O 2peak from post to 1-year follow-up measurements., Conclusions: Combined aerobic and resistance training twice a week in 16 weeks improves V̇O 2peak and maximal strength in women treated for gynecological cancer. The training effects were sustained after 1 year in the PT group.

Background: The success of implementing damage control resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation; however, none have investigated the effects of blood donation on cognitive performance., Method: We describe a prospective double-blinded, randomized, controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (baseline day), immediately after donation (Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank, where eligibility requirements were met on the testing days, and providing informed consent. Participants were randomized to either the experimental (n = 26) or control group (n = 31). Control group participants underwent a 'mock donation" in which a phlebotomy needle was placed but blood was not withdrawn., Results: In the experimental group, mean ± SEM VO2max declined 6% from 41.35 ± 1.7 mLO2/(min·kg) at baseline to 39.0 ± 1.6 mLO2/(min·kg) on Day 0 and increased to 40.51 ± 1.5 mLO2/(min·kg) on Day 7. Comparable values in the control group were 42.1 ± 1.8 mLO2/(min·kg) at baseline, 41.6 ± 1.8 mLO2/(min·kg)) on Day 1 (1% decline from baseline), and 41.8 ± 1.8 mLO2/(min·kg) on Day 7.Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences (p > 0.05)., Conclusion: Our main findings are that executive cognitive and physical performances were well maintained after whole blood donation in healthy blood donors. The findings inform postdonation guidance on when donors may be required to return to duty., Level of Evidence: Randomized, controlled, double-blinded prospective trial study, level 1.

Purpose: Although strength and sprint training are widely used methods in competitive cycling, no previous studies have compared the acute responses and recovery rates following such sessions among highly trained cyclists. The primary aim of the current study was to compare power production and biochemical markers of metabolic stress and muscle damage following a session of heavy strength (HS) and short-sprint training (SS). Methods: Eleven well-trained male cyclists (18 ± 2 years with maximal oxygen uptake of 67.2 ± 5.0 mL·kg -1 ·min -1 ) completed one HS session and one SS session in a randomized order, separated by 48 h. Power production and biochemical variables were measured at baseline and at different time points during the first 45 h post exercise. Results: Lactate and human growth hormone were higher 5 min, 30 min and 1 h post the SS compared to the HS session (all p ≤ 0.019). Myoglobin was higher following the HS than the SS session 5 min, 30 min and 1 h post exercise (all p ≤ 0.005), while creatine kinase (CK) was higher following the HS session 21 and 45 h post exercise ( p ≤ 0.038). Counter movement jump and power production during 4 sec sprint returned to baseline levels at 23 and 47 h with no difference between the HS and SS session, whereas the delayed muscle soreness score was higher 45 h following the HS compared to the SS session ( p = 0.010). Conclusion: Our findings indicate that SS training provides greater metabolic stress than HS training, whereas HS training leads to more muscle damage compared to that caused by SS training. The ability to produce power remained back to baseline already 23 h after both training sessions, indicating maintained performance levels although higher CK level and muscle soreness were present 45 h post the HS training session.

Aim: Hamstring strain injury is common in soccer. The aim of this study was to evaluate the physical capacity of players who have and have not suffered from hamstring strain injury in a sample of semi-professional and professional Norwegian soccer players in order to evaluate characteristics and to identify possible indications of insufficient rehabilitation. Method: Seventy-five semi-professional and professional soccer players (19 ± 3 years) playing at the second and third level in the Norwegian league participated in the study. All players answered a questionnaire, including one question about hamstring strain injury (yes/no) during the previous 2 years. They also performed a 40 m maximal sprint test, a repeated sprint test (8 × 20 m), a countermovement jump, a maximal oxygen consumption (VO 2max ) test, strength tests and flexibility tests. Independent sample t -tests were used to evaluate differences in the physical capacity of the players who had suffered from hamstring strain injury and those who had not. Mixed between-within subject's analyses of variance was used to compare changes in speed during the repeated sprint test between groups. Results: Players who reported hamstring strain injury during the previous two years (16%) had a significantly higher drop in speed (0.07 vs. 0.02 s, p = 0.007) during the repeated sprint test, compared to players reporting no previous hamstring strain injury. In addition, there was a significant interaction (groups × time) ( F = 3.22, p = 0.002), showing that speed in the two groups changed differently during the repeated sprint test. There were no significant differences in relations to age, weight, height, body fat, linear speed, countermovement jump height, leg strength, VO 2max , or hamstring flexibility between the groups. Conclusion: Soccer players who reported hamstring strain injury during the previous 2 years showed significant higher drop in speed during the repeated sprint test compared to players with no hamstring strain injury. The maximal speed, leg strength, ability to produce maximal power, endurance capacity, and hamstring flexibility was similar for both groups. Thus, a repeated sprint test consisting of 8 × 20 m could be used as a field-based diagnostic tool to identify players in need of reconditioning programs to ensure complete post-injury rehabilitation.

Purpose: The aim of the present study was to investigate effects of low cadence training at moderate intensity on aerobic capacity, cycling performance, gross efficiency, freely chosen cadence, and leg strength in veteran cyclists., Method: Twenty-two well trained veteran cyclists [age: 47 ± 6 years, maximal oxygen consumption (VO2max): 57.9 ± 3.7 ml · kg(-1) · min(-1)] were randomized into two groups, a low cadence training group and a freely chose cadence training group. Respiratory variables, power output, cadence and leg strength were tested before and after a 12 weeks training intervention period. The low cadence training group performed 12 weeks of moderate [73-82% of maximal heart rate (HRmax)] interval training (5 × 6 min) with a cadence of 40 revolutions per min (rpm) two times a week, in addition to their usual training. The freely chosen cadence group added 90 min of training at freely chosen cadence at moderate intensity., Results: No significant effects of the low cadence training on aerobic capacity, cycling performance, power output, cadence, gross efficiency, or leg strength was found. The freely chosen cadence group significantly improved both VO2max (58.9 ± 2.4 vs. 62.2 ± 3.2 ml · kg(-1) · min(-1)), VO2 consumption at lactate threshold (49.4 ± 3.8 vs. 51.8 ± 3.5 ml · kg(-1) · min(-1)) and during the 30 min performance test (52.8 ± 3.0 vs. 54.7 ± 3.5 ml · kg(-1) · min(-1)), and power output at lactate threshold (284 ± 47 vs. 294 ± 48 W) and during the 30 min performance test (284 ± 42 vs. 297 ± 50 W). Moreover, a significant difference was seen when comparing the change in freely chosen cadence from pre- to post between the groups during the 30 min performance test (2.4 ± 5.0 vs. -2.7 ± 6.2)., Conclusion: Twelve weeks of low cadence (40 rpm) interval training at moderate intensity (73-82% of HRmax) twice a week does not improve aerobic capacity, cycling performance or leg strength in highly trained veteran cyclists. However, adding training at same intensity (% of HRmax) and duration (90 min weekly) at freely chosen cadence seems beneficial for performance and physiological adaptations.

Objective: The purpose of this study was to investigate the rat skin penetration abilities of two commercially available low-level laser therapy (LLLT) devices during 150 sec of irradiation., Background Data: Effective LLLT irradiation typically lasts from 20 sec up to a few minutes, but the LLLT time-profiles for skin penetration of light energy have not yet been investigated., Materials and Methods: Sixty-two skin flaps overlaying rat's gastrocnemius muscles were harvested and immediately irradiated with LLLT devices. Irradiation was performed either with a 810 nm, 200 mW continuous wave laser, or with a 904 nm, 60 mW superpulsed laser, and the amount of penetrating light energy was measured by an optical power meter and registered at seven time points (range, 1-150 sec)., Results: With the continuous wave 810 nm laser probe in skin contact, the amount of penetrating light energy was stable at ∼20% (SEM±0.6) of the initial optical output during 150 sec irradiation. However, irradiation with the superpulsed 904 nm, 60 mW laser showed a linear increase in penetrating energy from 38% (SEM±1.4) to 58% (SEM±3.5) during 150 sec of exposure. The skin penetration abilities were significantly different (p<0.01) between the two lasers at all measured time points., Conclusions: LLLT irradiation through rat skin leaves sufficient subdermal light energy to influence pathological processes and tissue repair. The finding that superpulsed 904 nm LLLT light energy penetrates 2-3 easier through the rat skin barrier than 810 nm continuous wave LLLT, corresponds well with results of LLLT dose analyses in systematic reviews of LLLT in musculoskeletal disorders. This may explain why the differentiation between these laser types has been needed in the clinical dosage recommendations of World Association for Laser Therapy.

Objective: To investigate the effect of therapeutic infrared class 3B laser irradiation on skin temperature in healthy participants of differing skin color, age, and gender., Background: Little is known about the potential thermal effects of Low Level Laser Therapy (LLLT) irradiation on human skin., Methods: Skin temperature was measured in 40 healthy volunteers with a thermographic camera at laser irradiated and control (non-irradiated) areas on the skin. Six irradiation doses (2-12 J) were delivered from a 200 mW, 810 nm laser and a 60 mW, 904 nm laser, respectively., Results: Thermal effects of therapeutic LLLT using doses recommended in the World Association for Laser Therapy (WALT) guidelines were insignificant; below 1.5°C in light, medium, and dark skin. When higher irradiation doses were used, the 60 mW, 904 nm laser produced significantly (p < 0.01) higher temperatures in dark skin (5.7, SD ± 1.8°C at 12 J) than in light skin, although no participants requested termination of LLLT. However, irradiation with a 200 mW, 810 nm laser induced three to six times more heat in dark skin than in the other skin color groups. Eight of 13 participants with dark skin asked for LLLT to be stopped because of uncomfortable heating. The maximal increase in skin temperature was 22.3°C., Conclusions: The thermal effects of LLLT at doses recommended by WALT-guidelines for musculoskeletal and inflammatory conditions are negligible (<1.5°C) in light, medium, and dark skin. However, higher LLLT doses delivered with a strong 3B laser (200 mW) are capable of increasing skin temperature significantly and these photothermal effects may exceed the thermal pain threshold for humans with dark skin color.

Background and Objective: Impaired cell metabolism and increased cell death in fibroblast cells are physiological features of chronic tendinopathy. Although several studies have shown that low-level laser therapy (LLLT) at certain parameters has a biostimulatory effect on fibroblast cells, it remains uncertain if LLLT effects depend on the physiological state., Study Design/material and Methods: High-metabolic immortal cell culture and primary human keloid fibroblast cell culture were used in this study. Trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test were used to determine cell viability and proliferation. Propidium iodide stain was used for cell-cycle analysis by flow cytometry. Laser irradiation was performed daily on three consecutive days with a GaAlAs 660-nm laser (mean output: 50 mW, spot size 2 mm(2), power density =2.5 W/cm(2)) and a typical LLLT dose and a high LLLT dose (irradiation times: 60 or 420 s; fluences:150 or 1050 J/cm(2); energy delivered: 3 or 21 J)., Results: Primary fibroblast cell culture from human keloids irradiated with 3 J showed significant proliferation by the trypan blue exclusion test (p < 0.05), whereas the 3T3 cell culture showed no difference using this method. Propidium iodide staining flow cytometry data showed a significant decrease in the percentage of cells being in proliferative phases of the cell cycle (S/g(2)/M) when irradiated with 21 J in both cell types (hypodiploid cells increased)., Conclusions: Our data support the hypothesis that the physiological state of the cells affects the LLLT results, and that high-metabolic rate and short- cell-cycle 3T3 cells are not responsive to LLLT. In conclusion, LLLT with a dose of 3 J reduced cell death significantly, but did not stimulate cell cycle. A LLLT dose of 21 J had negative effects on the cells, as it increased cell death and inhibited cell proliferation.

We wanted to test if pre-exercise muscle irradiation with 904 nm laser affects the development of fatigue, blood lactate levels and creatine kinase (CK) activity in a rat model with tetanic contractions. Thirty male Wistar rats were divided into five groups receiving either one of four different laser doses (0.1, 0.3, 1.0 and 3.0 J) or a no-treatment control group. Laser irradiation was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions with 10 min intervals between them. Contractions were stopped when the muscle force fell to 50% of the peak value for each contraction; blood samples were taken before the first and immediately after the sixth contraction. The relative peak forces for the sixth contraction were significantly better (P < 0.05) in the two laser groups irradiated with highest doses [151.27% (SD +/- 18.82) for 1.0 J, 144.84% (SD +/- 34.47) for 3.0 J and 82.25% (SD +/- 11.69) for the control group]. Similar significant (P < 0.05) increases in mean performed work during the sixth contraction for the 1.0 and 3.0 J groups were also observed. Blood lactate levels were significantly lower (P < 0.05) than the control group in all irradiated groups. All irradiated groups except the 3.0 J group had significantly lower post-exercise CK activity than the control group. We conclude that pre-exercise irradiation with a laser dose of 1.0 J and 904 nm wavelength significantly delays muscle fatigue and decreases post-exercise blood lactate and CK in this rat model.

The objective of this study was to investigate whether low level laser therapy (LLLT) could reduce bronchial hyper-responsiveness (BHR) induced by tumour necrosis factor-alpha (TNF-alpha) modulating the metabolism of inositol phosphate (IP) in bronchial smooth muscle cells (BSMCs). The study was on 28 Wistar rats, randomly divided into four groups. Irradiation (1.3 J/cm(2)) was administered 5 min and 4 h after bronchial smooth muscle (BSM) had been suspended in TNF-alpha baths, and the contractile response-induced calcium ion (Ca(2+)) sensitization was measured. The BSMCs were isolated, and the IP accumulation was measured before and after TNF-alpha immersion in the groups that had been irradiated or not irradiated. BSM segments significantly increased contraction 24 h after TNF-alpha immersion when exposed to carbachol (CCh) as Ca(2+), but it was significantly reduced by 64% and 30%, respectively, after laser treatment. The increase in IP accumulation induced by CCh after TNF-alpha immersion was reduced in the BSMCs by LLLT. The dose of 2.6 J/cm(2) reduced BHR and IP accumulation in the rats' inflammatory BSMCs.

This study aimed to investigate the effect of 830 nm low-level laser therapy (LLLT) on skeletal muscle fatigue. Ten healthy male professional volleyball players entered a crossover randomized double-blinded placebo-controlled trial. Active LLLT (830 nm wavelength, 100 mW output, spot size 0.0028 cm(2), 200 s total irradiation time) or an identical placebo LLLT was delivered to four points on the biceps humeri muscle immediately before exercises. All subjects performed voluntary biceps humeri contractions with a load of 75% of the maximum voluntary contraction (MVC) force until exhaustion. After active LLLT the mean number of repetitions was significantly higher than after placebo irradiation [mean difference 4.5, standard deviation (SD) +/- 6.0, P = 0.042], the blood lactate levels increased after exercises, but there was no significant difference between the treatments. We concluded that 830 nm LLLT can delay the onset of skeletal muscle fatigue in high-intensity exercises, in spite of increased blood lactate levels.

Objective: To investigate if development of skeletal muscle fatigue during repeated voluntary biceps contractions could be attenuated by low-level laser therapy (LLLT)., Background Data: Previous animal studies have indicated that LLLT can reduce oxidative stress and delay the onset of skeletal muscle fatigue., Materials and Methods: Twelve male professional volleyball players were entered into a randomized double-blind placebo-controlled trial, for two sessions (on day 1 and day 8) at a 1-wk interval, with both groups performing as many voluntary biceps contractions as possible, with a load of 75% of the maximal voluntary contraction force (MVC). At the second session on day 8, the groups were either given LLLT (655 nm) of 5 J at an energy density of 500 J/cm2 administered at each of four points along the middle of the biceps muscle belly, or placebo LLLT in the same manner immediately before the exercise session. The number of muscle contractions with 75% of MVC was counted by a blinded observer and blood lactate concentration was measured., Results: Compared to the first session (on day 1), the mean number of repetitions increased significantly by 8.5 repetitions (+/- 1.9) in the active LLLT group at the second session (on day 8), while in the placebo LLLT group the increase was only 2.7 repetitions (+/- 2.9) (p = 0.0001). At the second session, blood lactate levels increased from a pre-exercise mean of 2.4 mmol/L (+/- 0.5 mmol/L), to 3.6 mmol/L (+/- 0.5 mmol/L) in the placebo group, and to 3.8 mmol/L (+/- 0.4 mmol/L) in the active LLLT group after exercise, but this difference between groups was not statistically significant., Conclusion: We conclude that LLLT appears to delay the onset of muscle fatigue and exhaustion by a local mechanism in spite of increased blood lactate levels.

Objective: This study was designed to study the effect of an infrared low-level laser (GaAs lambda = 904 nm, 4 mW) on inflammatory cell migration in lipopolysaccharide (LPS)-induced peritonitis in mice., Background Data: It has been suggested that red wavelengths of low-level laser therapy (LLLT) can exert anti-inflammatory effects, but little is known about the anti-inflammatory effects of infrared lasers. Peritonitis is a potentially life-threatening inflammatory condition that may be suitable for studying anti-inflammatory effects of infrared lasers., Methods: Sixty male mice were randomly divided into five groups, and one group was given an intraperitoneal sterile saline injection. In the remaining four groups, peritonitis was induced by an intraperitoneal LPS injection. Animals in three of the LPS groups were irradiated at a single point over the peritoneum with doses of 3 J/cm(2), 7.5 J/cm(2), and 15 J/cm(2), respectively. The fourth group injected with LPS was an LPS-control group., Results: At 6 hours after injection the groups irradiated with doses of 3 J/cm(2) and 7.5 J/cm(2) had a reduced number of neutrophil cells in the peritoneal cavity compared with the LPS-control group, and there were significant differences between the number of neutrophils in the peritoneal cavity between the LPS-control group and groups irradiated with doses of 3 J/cm(2) (-42%) and 7.5 J/cm(2) (-70%). In the group irradiated with 15 J/cm(2), neutrophil cell counts were lower than, but not significantly different from, LPS controls (-38%; p = 0.07). At 24 hours after injection, both neutrophil and total leukocyte cell counts were lower in all the irradiated groups than in the LPS controls. The 3-J/cm(2) exposure group showed the best results at 24 hours, with reductions of 77% in neutrophil and 49% in leukocyte counts., Conclusion: Low-level laser therapy (904 nm) can reduce inflammatory cell migration in mice with LPS-induced peritonitis in a dose-dependent manner.

Our objective was to investigate if low-level laser therapy (LLLT) could improve respiratory function and inhibit tumor necrosis factor (TNF-alpha) release into the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS injection, and LPS groups receiving either (a) no therapy, (b) four sessions in 24 h with diode Ga-AsI-Al laser of 650 nm and a total dose of 5.2 J/cm2, or (c) an intravenous injection (1.25 mg/kg) of the TNF-alpha inhibitor chlorpromazine (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm muscle from 24.15+/-0.87 N in controls, but the addition of LLLT partly inhibited this reduction (LPS only: 15.01+/-1.1 N vs LPS+LLLT: 18.84+/-0.73 N, P<0.05). In addition, this dose of LLLT and CPZ significantly (P<0.05 and P<0.01, respectively) reduced TNF-alpha concentrations in diaphragm muscle when compared to the untreated control group.

Background and Objective: It is unknown if the decreased ability to relax airway smooth muscles in asthma and other inflammatory airways disorders can be influenced by low level laser therapy (LLLT) irradiation. To investigate if LLLT could reduce impairment in inflamed trachea smooth muscles (TSM) in rats., Study Design/materials and Methods: Controlled rat study where trachea was dissected and mounted in an organ bath apparatus with or without a TNF-alpha solution., Results: Low level laser therapy administered perpendicularly to a point in the middle of the dissected trachea with a wavelength of 655 nm and a dose of 2.6 J/cm(2), partially restored TSM relaxation response to isoproterenol. Tension reduction was 47.0 % (+/-2.85) in the laser-irradiated group compared to 22.0% (+/-2.21) in the control group (P < 0.01). Accumulation of cAMP was almost normalized after LLLT at 22.3 pmol/mg (+/-2.1) compared to 17.6 pmol/mg (+/-2.1) in the non-irradiated control group (P < 0.01)., Conclusion: Low level laser therapy partially restores the normal relaxation response in inflamed TSM and normalizes accumulation of cAMP in the presence of isoproterenol., ((c) 2006 Wiley-Liss, Inc.)

We investigated whether low-level laser therapy (LLLT) can reduce muscular fatigue during tetanic contractions in rats. Thirty-two male Wistar rats were divided into four groups receiving either one of three different LLLT doses (0.5, 1.0, and 2.5 J/cm2) or a no-treatment control group. Electrical stimulation was used to induce six tetanic muscle contractions in the tibial anterior muscle. Contractions were stopped when the muscle force fell to 50% of the initial value for each contraction (T50%). There was no significant difference between the 2.5 J/cm2 laser-irradiated group and the control group in mean T50% values. Laser-irradiated groups (0.5 and 1.0 J/cm2) had significantly longer T50% values than the control group. The relative peak force for the sixth contraction in the laser-irradiated groups were significantly higher at 92.2% (SD 12.6) for 0.5 J/cm2, 83.2% (SD 20.5) for 1.0 J/cm2, and 82.9% (SD 18.3) for 2.5 J/cm2 than for the control group [50% (SD 15)]. Laser groups receiving 0.5 and 1.0 J/cm2 showed significant increases in mean performed work compared with both the control group and their first contraction values. Muscle damage was indirectly measured by creatine kinase levels in plasma. A distinct dose-response pattern was found in which 1.0 and 2.5 J/cm2 LLLT groups had significantly lower creatine kinase levels than the 0.5 J/cm2 LLLT group and the control group. We conclude that LLLT doses of 0.5 and 1.0 J/cm2 can prevent development of muscular fatigue in rats during repeated tetanic contractions.

Docetaxel and prostaglandin E1 (PGE1) increase transcapillary albumin extravasation and reduce interstitial fluid pressure in the skin. In this study the microdialysate concentration (Cm) of 125I-labeled human serum albumin (125I-HSA) and different-sized endogenous plasma proteins (EPP) was compared to evaluate changes in transcapillary extravasation of plasma proteins. 125I-HSA was also used to estimate changes in the specific activity of albumin. Extravasation of 125I-HSA and EPP from plasma to interstitium in the rat skin was compared during continuous administration of docetaxel and PGE1 by using microdialysis in anesthetized rats. Also, 20 ml of Ringer solution (RS) were injected intravenously during 10 min in a separate group. Two hollow plasmapheresis fibers (3 cm, cut off 3,000 kDa), one acting as control, were placed subcutaneously on the back skin and perfused with RS (5 microl/min, 140 min, collected every 10 min). The size of the different EPP was estimated to be 73, 65, 56, 47, and 39 A, separated by a size-exclusion high-performance liquid chromatography column and quantified by UV detection (280 nm). Docetaxel (0.5 mg/ml, n = 5) increased Cm of 125I-HSA and EPP of sizes 73, 65, 56, and 39 A significantly (P < 0.05) compared with control. PGE1 (20 microg/ml, n = 6) increased Cm of 125I-HSA significantly (P < 0.05) but none of the different-sized EPP was increased compared with control. Intravenous RS (20 ml, n = 6) increased Cm of 125I-HSA and increased all the different-sized EPP significantly (P < 0.05) compared with control. Although the microdialysis method is able to monitor qualitative changes in capillary permeability, a quantitative determination of the capillary reflection coefficient or permeability-surface area product was not possible, because steady state between plasma and dialysate was not achieved during the measurement period. The different pattern of extravasation of EPP and 125I-HSA after docetaxel, PGE1, and RS indicates increased interstitial transport rate and/or increased capillary permeability after docetaxel and RS, whereas PGE1 seems to increase transcapillary fluid flux without altering the permeability.

Objective: We designed an animal pleurisy study to assess if the anti-inflammatory effect of photoradiation could be affected by concomitant use of the cortisol antagonist mifepristone., Background Data: Although interactions between photoradiation and pharmacological agents are largely unknown, parallel use of steroids and photoradiation is common in the treatment of inflammatory disorders such as arthritis and tendinitis., Methods: Forty BALB/c male mice were randomly divided in five groups. Inflammation was induced by carrageenan administered by intrathoracic injections. Four groups received carrageenan, and one control group received injections of sterile saline solution. At 1, 2, and 3 h after injections, photoradiation irradiation was performed with a dose of 7.5 J/cm(2). Two of the carrageenan-injected groups were pre-treated with orally administered mifepristone., Results: Total leukocyte cell counts revealed that in carrageenan-induced pleurisy, photoradiation significantly reduced the number of leukocyte cells (p < 0.0001, mean 34.5 [95% CI: 32.8-36.2] versus 87.7 [95% CI: 81.0-94.4]), and that the effect of photoradiation could be totally blocked by adding the cortisol antagonist mifepristone (p < 0.0001, mean 34.5 [95% CI: 32.1-36.9] versus 82.9 [95%CI: 70.5-95.3])., Conclusion: The steroid receptor antagonist mifepristone significantly inhibited the anti-inflammatory effect of photoradiation. Commonly used glucocorticoids are also known to down-regulate steroid receptors, and further clinical studies are necessary to elucidate how this interaction may decrease the effect size of photoradiation over time. For this reason, we also suggest that, until further clinical data can be provided, clinical photoradiation trials should exclude patients who have received steroid therapy within 6 months before recruitment.

Objective: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate acute inflammation and tumor necrosis factor (TNFalpha) levels., Background Data: Drug therapy with TNFalpha-inhibitors has become standard treatment for rheumatoid arthritis, but it is unknown if LLLT can reduce or modulate TNFalpha levels in inflammatory disorders., Methods: Two controlled animal studies were undertaken, with 35 male Wistar rats randomly divided into five groups each. Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes, followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury. The first study served to define the time profile of TNFalpha activity for the first 4 h, while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNFalpha activity was increased. The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser., Results: There was a time-lag before TNFalpha activity increased after BSA injection. TNFalpha levels increased from < or =6.9 (95% confidence interval [CI], 5.6-8.2) units/mL in the first 3 h to 62.1 (95% CI, 60.8-63.4) units/mL (p < 0.001) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm(2) in 42 sec significantly reduced TNFalpha level to 50.2 (95% CI, 49.4-51.0), p < 0.01 units/mL versus control. Chlorpromazine reduced TNFalpha level to 45.3 (95% CI, 44.0-46.6) units/mL, p < 0.001 versus control., Conclusion: LLLT can reduce TNFalpha expression after acute immunocomplex lung injury in rats, but LLLT dose appears to be critical for reducing TNFalpha release.

Objective: To evaluate the effects of dexamethasone (DXM) alone or in combination with 5-fluorouracil (5-FU) on dimethyl-alpha-benzanthracene (DMBA)-induced mammary tumors in rats., Material and Methods: Female Sprague-Dawley rats were divided into 4 groups receiving: 1) saline (controls), 2) DXM (3 mg/kg), 3) 5-FU (1.5 mg/kg) and 4) DXM and 5-FU combined. The drugs were given i.p. every day for 4 days. Interstitial fluid pressure (Pif) and tumor growth were determined in all tumors on days 1, 5 and 7 using the "wick-in-the needle" technique and by external size measurements, respectively. Vessel density and inflammatory cell infiltration of tumor tissue were analyzed by immunohistochemistry., Results: DXM treatment significantly retarded tumor growth and reduced Pif. Treatment with a combination of DXM and 5-FU reduced tumor size significantly more than any of the agents alone (p<0.01-0.001). Enhanced uptake of 5-FU by DXM treatment was demonstrated by microdialysis. There were no differences in the density of CD31-positive vessels after DXM or 5-FU treatment, but inflammatory cell infiltration of tumor tissue was significantly reduced after DXM treatment., Conclusions: Our data suggest that DXM may be beneficial as an adjuvant to chemotherapy in the treatment of mammary cancer by increasing the uptake of 5-FU in the tumor.

Aim: To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF)., Methods: We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats., Results: Platelet activating factor (50 microg mL(-1)) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 A, 56 A and 39 A after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (P(if)) pressure after subcutaneous administration (50 microg mL(-1)). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 microg kg(-1)) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05)., Conclusions: The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers P(if), indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema.

We tested the hypothesis that hyperbaric oxygen (HBO) alone and with chemotherapy (5-FU) attenuates tumor growth of DMBA-induced tumors in rats. Six series were performed: (1) Controls (air and vehicle 0.9% NaCl i.p.), (2) 5-FU (0.2 mg/kg i.p.), (3) HBO (2 bar for 90 min and vehicle), (4) HBO and 5-FU, (5) HBO (11 days) and air (next 12 days), (6) HBO (23 days). All treatments were applied on days 1, 4, 7, 10 (Series 1-4), as well as on days 14, 17 and 23 (Series 5-6). Tumor diameter increased by 76.7 and 41.2% in untreated controls and in the 5-FU group, respectively, after 10 days. Tumor size fell by 17-24.2% in the HBO groups and by 35.5% when combined with 5-FU (P < 0.05 compared to HBO). HBO treatment reduced the total number of blood vessels in the tumors. After completion of HBO treatment tumor size increased, but statistically insignificant, during the next 12 days., (Copyright 2004 Elsevier Ireland Ltd.)

Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P(if)) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2(-/-)). P(if) and PPE were measured after challenge with compound 48/80 (C48/80), and P(if) alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P(if) in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P(if) significantly (P < 0.05) in NDST-2(-/-) mice (-1.67 +/- 0.42 mmHg) compared with vehicle (-0.57 +/- 0.17 mmHg) but the lowering was significantly (P < 0.05) less compared with that of the NDST-2(+/+) mice (-2.31 +/- 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2(+/+) mice, whereas there was no increase in PPE in NDST-2(-/-) mice. Capsaicin, SP, and CGRP lowered P(if) significantly (P < 0.05) compared with vehicle and to the same extent in both NDST-2(+/+) and NDST-2(-/-) mice. We can conclude that although NDST-2(-/-) mice demonstrate an altered response in P(if) after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs.

This study describes the use of microdialysis technique for continuous measurement of plasma protein extravasation (PPE) in rat and mouse skin with drug application either intravenously or via the microdialysis fiber. Hollow plasmapheresis fibers (3-cm length, 0.4-mm diameter, cutoff 3,000 kDa) were placed subcutaneously on the back of anesthetized mice and rats. Intravenous injection of dextran (Macrodex, 60 mg/ml) increased PPE by 355% from baseline within 30 min in rats with ligated kidneys (n = 6; P < 0.05) but not in animals with intact kidneys. Phalloidin (500 microg/kg iv 40 min before dextran, n = 6; P < 0.05) did not change the response to dextran in either group. Animals receiving PGE1, compound 48/80 (mice), paclitaxel, docetaxel, and cremophor EL via the microdialysis fiber were also provided with a control fiber receiving vehicle. Both rats and mice had constant PPE in the control fiber, and there was no change in PPE in the NaCl-treated groups (rats, n = 4; mice, n = 6). Application via the fiber of PGE1 (20 microg/ml), compound 48/80 (mice; 4 mg/ml), and docetaxel (0.5 mg/ml) increased PPE compared with baseline within 60 min by 139% (n = 6; P < 0.05), 273% (n = 6; P < 0.05), and 325% (n = 5; P < 0.05), respectively. Phalloidin alone did not increase PPE (n = 5; P < 0.05). Pretreatment with phalloidin did not inhibit the increase after PGE1 or compound 48/80 but inhibited that after docetaxel (n = 6). Paclitaxel (0.6 mg/ml, n = 5) or vehicle (Cremophor) (n = 5) gave no increase in PPE. The results demonstrate that microdialysis can be used to continuously measure changes in PPE after inflammatory challenges in skin of rats and mice.

Chemotherapy of solid tumors is presently largely ineffective at dosage levels that are compatible with survival of the patient. Here, it is argued that a condition of raised interstitial fluid pressure (IFP) that can be observed in many tumors is a major factor in preventing optimal access of systemically administered chemotherapeutic agents. Using prostaglandin E1-methyl ester (PGE1), which is known transiently to reduce IFP, it was shown that 5-fluorouracil (5-FU) caused significant growth inhibition on two experimental tumors in rats but only after administration of PGE1. Furthermore, timing experiments showed that only in the period in which IFP is reduced did 5-FU have an antitumor effect. These experiments uniquely demonstrate a clear and, according to the starting hypothesis, logical, synergistic effect of PGE1 and 5-FU that offers hope for better treatment of many tumors in which raised IFP is likely to be inhibiting optimal results with water-soluble cancer chemotherapeutic agents.

Interstitial fluid pressure (P(if)) is a key determinant in increasing the transcapillary driving pressure, pulling fluid from the microcirculation into the interstitial space at the onset of acute inflammatory reactions and the oedema formation associated with these. Prostaglandin E1 (PGE1) induces lowering of P(if) in rat skin which increases transcapillary transport of 51Cr-EDTA into the center of a tumor as measured by microdialysis. The aim of this study was twofold: First, to evaluate and develop the microdialysis technique thoroughly with regard to its suitability for investigating transcapillary water transport in rat skin using 51Cr-EDTA as a tracer. Secondly, to evaluate the effect of PGE1 on transcapillary transport of 51Cr-EDTA. This study demonstrates that PGE1 increases transcapillary transport of 51Cr-EDTA into skin interstitium. There were no significant differences between the experimental probe and the control probe when calculations from the entire experiment (90 min) were compared. On the other hand, significant differences were observed by examining the experiment in smaller time intervals. PGE1 increased transcapillary transport of 51Cr-EDTA during the first 15 min when administered through the microdialysis probe. This observation suggests that increased blood flow and/or permeability-surface area product are responsible for raising the transcapillary transport of 51Cr-EDTA, i.e. the transport is diffusion limited. Administration of PGE1 through the probe rather than around the probe resulted in less scatter between experiments than when PGE1 was injected subcutaneously around the probe.