Effects of cellular radioresponse on therapeutic helium-, carbon-, oxygen-, and neon-ion beams: a simulation study.

Objective. Helium, oxygen, and neon ions in addition to carbon ions will be used for hypofractionated multi-ion therapy to maximize the therapeutic effectiveness of charged-particle therapy. To use new ions in cancer treatments based on the dose-fractionation protocols established in carbon-ion therapy, this study examined the cell-line-specific radioresponse to therapeutic helium-, oxygen-, and neon-ion beams within wide dose ranges.Approach. Response of cells to ions was described by the stochastic microdosimetric kinetic model. First, simulations were made for the irradiation of one-field spread-out Bragg peak beams in water with helium, carbon, oxygen, and neon ions to achieve uniform survival fractions at 37%, 10%, and 1% for human salivary gland tumor (HSG) cells, the reference cell line for the Japanese relative biological effectiveness weighted dose system, within the target region defined at depths from 90 to 150 mm. The HSG cells were then replaced by other cell lines with different radioresponses to evaluate differences in the biological dose distributions of each ion beam with respect to those of carbon-ion beams.Main results. For oxygen- and neon-ion beams, the biological dose distributions within the target region were almost equivalent to those of carbon-ion beams, differing by less than 5% in most cases. In contrast, for helium-ion beams, the biological dose distributions within the target region were largely different from those of carbon-ion beams, more than 10% in several cases.Significance.From the standpoint of tumor control evaluated by the clonogenic cell survival, this study suggests that the dose-fractionation protocols established in carbon-ion therapy could be reasonably applied to oxygen- and neon-ion beams while some modifications in dose prescription would be needed when the protocols are applied to helium-ion beams. This study bridges the gap between carbon-ion therapy and hypofractionated multi-ion therapy.

Creation, evolution, and future challenges of ion beam therapy from a medical physicist's viewpoint (Part 3): Chapter 3. Clinical research, Chapter 4. Future challenges, Chapter 5. Discussion, and Conclusion.

Clinical studies of ion beam therapy have been performed at the Lawrence Berkeley Laboratory (LBL), National Institute of Radiological Sciences (NIRS), Gesellschaft für Schwerionenforschung (GSI), and Deutsches Krebsforschungszentrum (DKFZ), in addition to the development of equipment, biophysical models, and treatment planning systems. Although cancers, including brain tumors and pancreatic cancer, have been treated with the Bevalac's neon-ion beam at the LBL (where the first clinical research was conducted), insufficient results were obtained owing to the limited availability of neon-ion beams and immaturity of related technologies. However, the 184-Inch Cyclotron's helium-ion beam yielded promising results for chordomas and chondrosarcomas at the base of the skull. Using carbon-ion beams, NIRS has conducted clinical trials for the treatment of common cancers for which radiotherapy is indicated. Because better results than X-ray therapy results have been obtained for lung, liver, pancreas, and prostate cancers, as well as pelvic recurrences of rectal cancer, the Japanese government recently approved the use of public medical insurance for carbon-ion radiotherapy, except for lung cancer. GSI obtained better results than LBL for bone and soft tissue tumors, owing to dose enhancement enabled by scanning irradiation. In addition, DKFZ compared treatment results of proton and carbon-ion radiotherapy for these tumors. This article summarizes a series of articles (Parts 1-3) and describes future issues of immune ion beam therapy and linear energy transfer optimization.

Stopping-power ratio of body tissues with updated effective energies and elemental I values for treatment planning of proton therapy and ion beam therapy with helium, carbon, oxygen, and neon ions.

The stopping-power ratio (SPR) of body tissues relative to water depends on the particle energy and mean excitation energy (I value) of the tissues. Effective energies to minimize the range error in proton therapy and ion beam therapy with helium, carbon, oxygen, and neon ions and elemental I values have been updated in recent studies. We investigated the effects of these updates on SPR estimation for computed tomography-based treatment planning. The updates led to an increase of up to 0.5% in the SPRs of soft tissues, whereas they led to a decrease of up to 1.9% in the SPRs of bone tissues compared with the current clinical settings. For 44 proton beams planned for 15 randomly sampled patients, the mean water-equivalent target depth change was - 0.2 mm with a standard deviation of 0.2 mm. The maximum change was - 0.6 mm, which we consider to be insignificant in clinical practice.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON).

PURPOSE: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD. METHODS: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed. CONCLUSION: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.

Adaptation of stochastic microdosimetric kinetic model to hypoxia for hypo-fractionated multi-ion therapy treatment planning.

For hypo-fractionated multi-ion therapy (HFMIT), the stochastic microdosimetric kinetic (SMK) model had been developed to estimate the biological effectiveness of radiation beams with wide linear energy transfer (LET) and dose ranges. The HFMIT will be applied to radioresistant tumors with oxygen-deficient regions. The response of cells to radiation is strongly dependent on the oxygen condition in addition to radiation type, LET and absorbed dose. This study presents an adaptation of the SMK model to account for oxygen-pressure dependent cell responses, and develops the oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model. In the model, following assumptions were made: the numbers of radiation-induced sublethal lesions (double-strand breaks) are reduced due to lack of oxygen, and the numbers of oxygen-mediated lesions are reduced for radiation with high LET. The model parameters were determined by fitting survival data under aerobic and anoxic conditions for human salivary gland tumor cells and V79 cells exposed to helium-, carbon-, and neon-ion beams over the LET range of 18.5-654.0 keVµm-1. The OSMK model provided good agreement with the experimental survival data of the cells with determination coefficients >0.9. In terms of oxygen enhancement ratio, the OSMK model reproduced the experimental data behavior, including slight dependence on particle type at the same LET. The OSMK model was then implemented into the in-house treatment planning software for the HFMIT to validate its applicability in clinical practice. A treatment plan with helium- and neon-ion beams was made for a pancreatic cancer case assuming an oxygen-deficient region within the tumor. The biological optimization based on the OSMK model preferentially placed the neon-ion beam to the hypoxic region, while it placed both helium- and neon-ion beams to the surrounding normoxic region. The OSMK model offered the accuracy and usability required for hypoxia-based biological optimization in HFMIT treatment planning.

Application of lung substitute material as ripple filter for multi-ion therapy with helium-, carbon-, oxygen-, and neon-ion beams.

A development project for hypo-fractionated multi-ion therapy has been initiated at the National Institute of Radiological Sciences in Japan. In the treatment, helium, carbon, oxygen, and neon ions will be used as primary beams with pencil beam scanning. A ripple filter (RiFi), consisting of a thin plastic or aluminum plate with a fine periodic ridge and groove structure, has been used to broaden the Bragg peak of heavy-ion beams in the beam direction. To sufficiently broaden the Bragg peak of helium-, carbon-, oxygen-, and neon-ion beams with suppressed lateral scattering and surface dose inhomogeneity, in this study, we tested a plate made of a lung substitute material, Gammex LN300, as the RiFi. The planar integrated dose distribution of a 183.5 MeV u-1neon-ion beam was measured behind a 3 cm thick LN300 plate in water. The Bragg peak of the pristine beam was broadened following the normal distribution with the standard deviationσvalue of 1.29 mm, while the range of the beam was reduced by 8.8 mm by the plate. To verify the LN300 performance as the RiFi in multi-ion therapy, we measured the pencil beam data of helium-, carbon-, oxygen- and neon-ion beams penetrating the 3 cm thick LN300 plate. The data were then modeled and used in a treatment planning system to achieve a uniform 10% survival of human undifferentiated carcinoma cells within a cuboid target by the beam for each of the different ion species. The measured survival fractions were reasonably reproduced by the planned ones for all the ion species. No surface dose inhomogeneity was observed for any ion species even when the plate was placed close to the phantom surface. The plate made of lung substitute material, Gammex LN300, is applicable as the RiFi in multi-ion therapy with helium-, carbon-, oxygen- and neon-ion beams.

Estimating the biological effects of helium, carbon, oxygen, and neon ion beams using 3D silicon microdosimeters.

In this study, the survival fraction (SF) and relative biological effectiveness (RBE) of pancreatic cancer cells exposed to spread-out Bragg peak helium, carbon, oxygen, and neon ion beams are estimated from the measured microdosimetric spectra using a microdosimeter and the application of the microdosimetric kinetic (MK) model. To measure the microdosimetric spectra, a 3D mushroom silicon-on-insulator microdosimeter connected to low noise readout electronics (MicroPlus probe) was used. The parameters of the MK model were determined for pancreatic cancer cells such that the calculated SFs reproduced previously reported in vitro SF data. For a cuboid target of 10 × 10 × 6 cm3, treatment plans of helium, carbon, oxygen, and neon ion beams were designed using in-house treatment planning software (TPS) to achieve a 10% SF of pancreatic cancer cells throughout the target. The physical doses and microdosimetric spectra of the planned fields were measured at different depths in polymethyl methacrylate phantoms. The biological effects, such as SF, RBE, and RBE-weighted dose at different depths along the fields were predicted from the measurements. The predicted SFs at the target region were generally in good agreement with the planned SF from the TPS in most cases.

The 20th Gray lecture 2019: health and heavy ions.

OBJECTIVE: Particle radiobiology has contributed new understanding of radiation safety and underlying mechanisms of action to radiation oncology for the treatment of cancer, and to planning of radiation protection for space travel. This manuscript will highlight the significance of precise physical and biologically effective dosimetry to this translational research for the benefit of human health.This review provides a brief snapshot of the evolving scientific basis for, and the complex current global status, and remaining challenges of hadron therapy for the treatment of cancer. The need for particle radiobiology for risk planning in return missions to the Moon, and exploratory deep-space missions to Mars and beyond are also discussed. METHODS: Key lessons learned are summarized from an impressive collective literature published by an international cadre of multidisciplinary experts in particle physics, radiation chemistry, medical physics of imaging and treatment planning, molecular, cellular, tissue radiobiology, biology of microgravity and other stressors, theoretical modeling of biophysical data, and clinical results with accelerator-produced particle beams. RESULTS: Research pioneers, many of whom were Nobel laureates, led the world in the discovery of ionizing radiations originating from the Earth and the Cosmos. Six radiation pioneers led the way to hadron therapy and the study of charged particles encountered in outer space travel. Worldwide about 250,000 patients have been treated for cancer, or other lesions such as arteriovenous malformations in the brain between 1954 and 2019 with charged particle radiotherapy, also known as hadron therapy. The majority of these patients (213,000) were treated with proton beams, but approximately 32,000 were treated with carbon ion radiotherapy. There are 3500 patients who have been treated with helium, pions, neon or other ions. There are currently 82 facilities operating to provide ion beam clinical treatments. Of these, only 13 facilities located in Asia and Europe are providing carbon ion beams for preclinical, clinical, and space research. There are also numerous particle physics accelerators worldwide capable of producing ion beams for research, but not currently focused on treating patients with ion beam therapy but are potentially available for preclinical and space research. Approximately, more than 550 individuals have traveled into Lower Earth Orbit (LEO) and beyond and returned to Earth. CONCLUSION: Charged particle therapy with controlled beams of protons and carbon ions have significantly impacted targeted cancer therapy, eradicated tumors while sparing normal tissue toxicities, and reduced human suffering. These modalities still require further optimization and technical refinements to reduce cost but should be made available to everyone in need worldwide. The exploration of our Universe in space travel poses the potential risk of exposure to uncontrolled charged particles. However, approaches to shield and provide countermeasures to these potential radiation hazards in LEO have allowed an amazing number of discoveries currently without significant life-threatening medical consequences. More basic research with components of the Galactic Cosmic Radiation field are still required to assure safety involving space radiations and combined stressors with microgravity for exploratory deep space travel. ADVANCES IN KNOWLEDGE: The collective knowledge garnered from the wealth of available published evidence obtained prior to particle radiation therapy, or to space flight, and the additional data gleaned from implementing both endeavors has provided many opportunities for heavy ions to promote human health.

Experimental validation of stochastic microdosimetric kinetic model for multi-ion therapy treatment planning with helium-, carbon-, oxygen-, and neon-ion beams.

The National Institute of Radiological Sciences (NIRS) has initiated a development project for hypo-fractionated multi-ion therapy. In the treatment, heavy ions up to neon ions will be used as a primary beam, which is a high linear energy transfer (LET) radiation. The fractionated dose of the treatment will be 10 Gy or more. The microdosimetric kinetic (MK) model overestimates the biological effectiveness of high-LET and high-dose radiations. To address this issue, the stochastic microdosimetric kinetic (SMK) model has been developed as an extension of the MK model. By taking the stochastic nature of domain-specific and cell nucleus-specific energies into account, the SMK model could estimate the biological effectiveness of radiations with wide LET and dose ranges. Previously, the accuracy of the SMK model was examined by comparison of estimated and reported survival fractions of human cells exposed to pristine helium-, carbon-, and neon-ion beams. In this study, we verified the SMK model in treatment planning of scanned helium-, carbon-, oxygen-, and neon-ion beams as well as their combinations through the irradiations of human undifferentiated carcinoma and human pancreatic cancer cells. Treatment plans were made with the ion-species beams to achieve a uniform 10% survival of the cells within a cuboid target. The planned survival fractions were reasonably reproduced by the measured survival fractions in the whole region from the plateau to the fragment tail for all planned irradiations. The SMK model offers the accuracy and simplicity required in hypo-fractionated multi-ion therapy treatment planning.

Nuclear-interaction correction for patient dose calculations in treatment planning of helium-, carbon-, oxygen-, and neon-ion beams.

In charged-particle therapy treatment planning, the patient is conventionally modeled as variable-density water, i.e. stopping effective density ρ S, and the planar integrated dose distribution measured in water (PID) is applied for patient dose calculation based on path length scaling with the ρ S. This approximation assures the range accuracy of charged-particle beams. However, it causes dose calculation errors due to water nonequivalence of body tissues in nuclear interactions originating from compositional differences. We had previously proposed and validated a PID correction method for the errors in carbon-ion radiotherapy. In the present study, we verify the PID correction method for helium-, oxygen-, and neon-ion beams. The one-to-one relationships between ρ S and the nuclear effective density ρ N of body tissues were constructed for helium-, carbon-, oxygen-, and neon-ion beams, and were used to correct the PIDs to account for the dose calculation errors in patient. The correction method was tested for non-water materials with un-scanned and scanned ion beams. In un-scanned beams penetrating the materials, the dose calculation errors of up to 5.9% were observed at the Bragg peak region, while they were reduced to ⩽0.9% by the PID correction method. In scanned beams penetrating olive oil, the dose calculation errors of up to 2.7% averaged over the spread-out Bragg peak were observed, while they were reduced to ⩽0.4% by the correction method. To investigate the influence of water nonequivalence of body tissues on tumor dose, we carried out a treatment planning study for prostate and uterine cases. The tumor over-doses of 0.9%, 1.8%, 2.0%, and 2.2% were observed in the uterine case for the helium-, carbon-, oxygen-, and neon-ion beams, respectively. These dose errors could be diminished by the PID correction method. The present results verify that the PID correction method is simple, practical, and accurate for treatment planning of these four ion species.

Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study.

PURPOSE: This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well-established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue. METHODS: The gate/geant4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 µm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions in a water phantom were scored considering two minibeams center-to-center distances: 1400 and 3500 µm. Peak and valley doses, peak-to-valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions. RESULTS: Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center-to-center distance leads to a minimized contribution of heavier secondary fragments in valleys. CONCLUSIONS: The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of neon and heavier ions for the treatment of radioresistant tumors, while preserving normal tissues. The authors' results support the further exploration of this avenue. Next steps include the realization of biological experiment to confirm the shifting of normal tissue complication probability curves.

Optimizing SHIELD-HIT for carbon ion treatment.

The SHIELD-HIT Monte Carlo transport code has been widely used in particle therapy, but has previously shown some discrepancies, when compared with experimental data. In this work, the inelastic nuclear cross sections of SHIELD-HIT are calibrated to experimental data for carbon ions. In addition, the models for nuclear fragmentation were adjusted to experiments, for the partial charge-changing cross section of carbon ions in water. Comparison with fragmentation yield experiments for carbon and neon primaries were made for validation. For carbon primaries, excellent agreement between simulation and experiment was observed, with only minor discrepancies. For neon primaries, the agreement was also good, but larger discrepancies were observed, which require further investigation. In conclusion, the current version SHIELD-HIT10A is well suited for simulating problems arising in particle therapy for clinical ion beams.

Optimizing normal tissue sparing in ion therapy using calculated isoeffective dose for ion selection.

PURPOSE: To investigate how the selection of ion type affects the calculated isoeffective dose to the surrounding normal tissue as a function of both normal tissue and target tissue α/ß ratios. METHODS AND MATERIALS: A microdosimetric biologic dose model was incorporated into a Geant4 simulation of parallel opposed beams of protons, helium, lithium, beryllium, carbon, and neon ions. The beams were constructed to give a homogeneous isoeffective dose to a volume in the center of a water phantom for target tissues covering a range of cobalt equivalent α/ß ratios of 1-20 Gy. Concomitant normal tissue isoeffective doses in the plateau of the ion beam were then compared for different ions across the range of normal tissue and target tissue radiosensitivities for a fixed isoeffective dose to the target tissue. RESULTS: The ion type yielding the optimal normal tissue sparing was highly dependent on the α/ß ratio of both the normal and the target tissue. For carbon ions, the calculated isoeffective dose to normal tissue at a 5-cm depth varied by almost a factor of 5, depending on the α/ß ratios of the normal and target tissue. This ranges from a factor of 2 less than the isoeffective dose of a similar proton treatment to a factor of 2 greater. CONCLUSIONS: No single ion is optimal for all treatment scenarios. The heavier ions are superior in cases in which the α/ß ratio of the target tissue is low and the α/ß ratio of normal tissue is high, and protons are superior in the opposite circumstances. Lithium and beryllium appear to offer dose advantages similar to carbon, with a considerably lower normal tissue dose when the α/ß ratio in the target tissue is high and the α/ß ratio in the normal tissue is low.

Láser helio-neón combinado con clorhexidina al 0, 2 por ciento. Efectos clínicos y microbiológicos en el tratamiento de la gingivitis crónica / Helium-neon laser combined with 0.2 per cent chlorhexidine. Clinical and microbiological effects in the treatment of chronic gingivitis

La gingivitis crónica constituye una de las formas más frecuentes de enfermedad periodontal, caracterizada por la inflamación crónica de la encías, tumefacción, enrojecimiento y sangramiento. Su principal factor de riesgo lo constituye la microbiota del surco gingival, que resulta necesario, pero no suficiente para desencadenarla. Se realizó un ensayo clínico-terapéutico fase II, controlado, aleatorizado y a simple ciegas, para evaluar los efectos clínicos y microbiológicos del tratamiento combinado de la radiación láser helio-neón (He-Ne) con la clorhexidina al 0,2 por ciento. Todos los pacientes recibieron tratamiento inicial; al mes de finalizado este, se distribuyeron aleatoriamente en 2 grupos: un grupo estudio que recibió la combinación láser-neón y clorhexidina al 0,2 por ciento y otro grupo control que solo recibió clorhexidina al 0,2 por ciento. Se realizó una evaluación a los 15, 30 y 45 días, con criterios de eficacia clínicos y microbiológicos. Los resultados clínicos fueron satisfactorios en el grupo estudio con predominio de los morfotipos I, caracterizados por cocos gramnegativos y positivos, compatibles con un periodonto sano. Los eventos adversos detectados con esta terapéutica fueron mínimos, todos relacionados con la somnolencia(AU)

Chronic gingivitis is one of the most common periodontal diseases that is characterized by chronic inflammation, tumefaction, redness and bleeding. The main risk factor is gingival sulcus microbiota that is essential but not enough to unleash it. A phase II controlled randomized blind clinical/therapeutical assay was conducted to evaluate the clinical and microbiological effects of the combined treatment based on helium-neon laser (He-Ne) with 0.2 per cent chlorhexidine. All the patients were initially treated; after a month, they were randomly distributed into two groups, that is, the study group received a helium-neon laser plus 0.2 per cent chlorhexidine combination and the control group was treated with 0.2 per cent chlorhexidine only. They were evaluated at 15th, 30th and 45th days by using clinical and microbiological efficacy criteria. The clinical results were satisfactory in the study group where morphotypes I, characterized by Gram-negative and Gram-positive cocci and compatible with a healthy periodontium, prevailed . Adverse events were minimal, all of them related to somnolence(AU)

Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs.

We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm(2))-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 +/- 20 vs 63 +/- 8 mm(2)). The basal cellularity values on day 1 were: C = 763 +/- 47, L = 1116 +/- 85, D = 376 +/- 24, D + L = 698 +/- 31, X = 453 +/- 29, X + L = 639 +/- 32 U/mm(2). These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs

We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²)-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm²). The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

Transmissão do laser de baixa potência através de filmes plásticos de PVC / Transmission of low-power laser through PVC plastic film

O laser de baixa potência é utilizado na fisioterapia na cicatrização de lesões, para acelerar a reparação tecidual. Um filme de PVC na ponteira do equipamento é comumente usado na prática clínica para evitar a contaminação da lesão pelo equipamento, principalmente em mucosas e áreas cruentas...

Low-intensity laser application is used in physical therapy in view of accelerating wound repair processes. In clinical practice, a PVC film is commonly used covering the lasers pen's tip to avoid contamination of the wound by the equipment, mainly on mucosa and cruent...

Effects of helium-neon laser on the mucopolysaccharide induction in experimental osteoarthritic cartilage.

OBJECTIVE: To investigate the effects of mucopolysaccharide induction after treatment by low power laser for experimental osteoarthritis (OA). METHODS: Seventy-two rats with three different degrees of papain induced OA over right knee joints were collected for helium-neon (He-Ne) laser treatment. The severity of induced arthritis was measured by 99mTc bone scan and classified into three groups (I-III) by their radioactivity ratios (right to left knee joints). The rats in each group were further divided into study subgroups (Is, IIs, and IIIs) and control subgroups (Ic, IIc, and IIIc) randomly. The arthritic knees in study subgroups received He-Ne laser treatment, and those in controls received sham laser treatment. The changes of arthritic severity after treatment and follow-up 2 months later were measured. The histopathological changes were evaluated through light microscope after disarticulation of sections (H.E. stain), and the changes of mucopolysaccharide density in cartilage matrix were measured by Optimas scanner analyzer after Alcian blue (AB) stain. The densities of mucopolysaccharide induced after treatment in arthritic cartilage were compared and correlated with their histopathological changes. RESULTS: The density of mucopolysaccharide rose at the initial stage of induced arthritis, and decreased progressively in later stages. The densities of mucopolysaccharide in treated rats increased upon complete laser treatment more than those of the controls, which is closely related with the improvement in histopathological findings, but conversely with the changes in arthritic severity. CONCLUSION: He-Ne laser treatment will enhance the biosynthesis of arthritic cartilage, and results in the improvement of arthritic histopathological changes.

Helium-neon laser in viability of random skin flap in rats.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the role of helium-neon (He-Ne) laser random skin flap viability in rats. STUDY DESIGN/MATERIALS AND METHODS: Experimentally controlled randomized study. Forty-eight Wistar-EPM rats were used, weighed, and divided into 4 groups with 12 rats each. The random skin flap was performed measuring 10 x 4 cm, with a plastic sheet interposed between the flap and the donor site. The Group 1 (control) underwent sham irradiation with He-Ne laser. The Group 2 was submitted to laser irradiation, using the punctual contact technique on the skin flap surface. The Group 3 was submitted to laser irradiation surrounding the skin flap, and the Group 4 was submitted to laser irradiation both on the skin flap surface and around it. The experimental groups were submitted to He-Ne laser irradiation with 3 J/cm(2) energy density immediately after the surgery and for the four subsequent days. The percentage of necrotic area of the four groups was calculated at the 7th post-operative day, through a paper-template method. RESULTS: Group 1 reached an average necrotic area of 48.86%; Group 2, 38.67%; Group 3, 35.34%; and Group 4, 22.61%. After the statistic analysis, results showed that all experimental groups reached statistically significant values when compared to the control group, and Group 4 was the best one, when compared to all groups of this study (P<0.001). CONCLUSION: The He-Ne laser irradiation was efficient to increase random skin flap viability in rats.

[The French project ETOILE: review of clinical data for light ion hadrontherapy]. / Le projet français ETOILE : données médicales actuelles de l'hadronthérapie par ions légers.

The Lawrence Berkeley Laboratory was the pioneer in light ions hadrontherapy with almost 2500 patients treated between 1957 and 1993 with Helium and Neon. The NIRS (National Institute For Radiological Science, Chiba, Japan) was the first dedicated medical centre for cancer with more than 1200 patients exclusively treated with carbon ion from 1994. A three-year 70 to 100% local control was reported for radio-resistant cancers, supporting the use of high LET particles. Hypo-fractionation was particularly explored for lung cancers and hepatocarcinoma (4 sessions only). Dose escalation studies demonstrated a tumour dose-effect and permitted to precise dose constraints for healthy tissues especially for the rectum. More than 140 patients were treated with carbon ion exclusively or associated with photons since 1997 in the GSI laboratory Gesellschaft Für Schwerionenforschung, Darmstadt, Germany). A very high local control was also obtained for radioresistant cancer of the base of the skull. Preliminary clinical data seem to confirm the expected therapeutic gain with light ions, due to their ballistic and radio-biological properties, and justify the European projects for the construction of dedicated medical facilities for cancers. The French "Etoile" project will be integrated in the European hadrontherapy network "Enlight", with the objectives to coordinate technologic, medical and economic features.