Power Production and Biochemical Markers of Metabolic Stress and Muscle Damage Following a Single Bout of Short-Sprint and Heavy Strength Exercise in Well-Trained Cyclists.

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.

Higher Drop in Speed during a Repeated Sprint Test in Soccer Players Reporting Former Hamstring Strain Injury.

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 (VO2max) 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, VO2max, 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.

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.

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 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.

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.

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 low-level laser therapy (GaAs 904 nm) in skeletal muscle fatigue and biochemical markers of muscle damage in rats.

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.

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.

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 physiologicalfeatures of chronic tendinopathy. Although several studies have shown that low-level laser therapy (LLLT) atcertain parameters has a biostimulatory effect on fibroblast cells, it remains uncertain if LLLT effects depend on thephysiological state. Study Design/Material and Methods: High-metabolic immortal cell culture and primaryhuman 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. Propidiumiodide stain was used for cell-cycle analysis by flow cytometry. Laser irradiation was performed daily onthree consecutive days with a GaAlAs 660-nm laser (mean output: 50mW, spot size 2mm2, power density»2.5W=cm2) and a typical LLLT dose and a high LLLT dose (irradiation times: 60 or 420 s; fluences:150 or1050 J=cm2; energy delivered: 3 or 21 J). Results: Primary fibroblast cell culture from human keloids irradiated with3 J showed significant proliferation by the trypan blue exclusion test ( p<0.05), whereas the 3T3 cell cultureshowed no difference using this method. Propidium iodide staining flow cytometry data showed a significantdecrease in the percentage of cells being in proliferative phases of the cell cycle (S=g2=M) when irradiated with 21 Jin both cell types (hypodiploid cells increased). Conclusions: Our data support the hypothesis that the physiologicalstate of the cells affects the LLLT results, and that high-metabolic rate and short- cell-cycle 3T3 cells are notresponsive to LLLT. In conclusion, LLLT with a dose of 3 J reduced cell death significantly, but did not stimulatecell cycle. A LLLT dose of 21 J had negative effects on the cells, as it increased cell death and inhibited cellproliferation.

Effect of 830 nm low-level laser therapy in exercise-induced skeletal muscle fatigue in humans.

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.

Effect of low level laser therapy on bronchial hyper-responsiveness.

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.

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.

Low-level laser therapy (GaAs lambda = 904 nm) reduces inflammatory cell migration in mice with lipopolysaccharide-induced peritonitis.

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.

Effect of low-level laser (Ga-Al-As 655 nm) on skeletal muscle fatigue induced by electrical stimulation in rats.

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.

Hyperbaric oxygen alone or combined with 5-FU attenuates growth of DMBA-induced rat mammary tumors.

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.

Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme.

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.

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.