Vegard Vereide Iversen

A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations

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.

Effects of Low-Level Laser Therapy (LLLT) in the Development of Exercise-Induced Skeletal Muscle Fatigue and Changes in Biochemical Markers Related to Postexercise Recovery

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.

Effect of 655-nm Low-Level Laser Therapy on Exercise-Induced Skeletal Muscle Fatigue in Humans

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.

Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy

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.

Low-level laser irradiation (InGaAlP-660 nm) increases fibroblast cell proliferation and reduces cell death in a dose-dependent manner.

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.

The Thermal Effects of Therapeutic Lasers with 810 and 904 nm Wavelengths on Human Skin

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.

Skin Penetration Time-Profiles for Continuous 810 nm and Superpulsed 904 nm Lasers in a Rat Model

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 rats 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.

The anti-inflammatory mechanism of low level laser therapy and its relevance for clinical use in physiotherapy

Abstract 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.

High‐dose, short‐term, anti‐inflammatory treatment with dexamethasone reduces growth and augments the effects of 5‐fluorouracil on dimethyl‐α‐benzanthracene‐induced mammary tumors in rats

Objective. To evaluate the effects of dexamethasone (DXM) alone or in combination with 5‐fluorouracil (5‐FU) on dimethyl‐α‐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.

Low cadence interval training at moderate intensity does not improve cycling performance in highly trained veteran cyclists.

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.