Phototherapy Improves Healing of Chronic Venous Ulcers

Objective: We tested the hypothesis that LED phototherapy with combined 660-nm and 890-nm light will promote healing of venous ulcers that failed to respond to other forms of treatment. Background Data: A variety of dressings, growth factors, and adjunct therapies are used to treat venous ulcers, but none seems to yield satisfactory results. Materials and Methods: We used a randomized placebo-controlled double-blind study to compare a total of 20 patients divided with 32 chronic ulcers into three groups. In group 1 the ulcers were cleaned, dressed with 1% silver sulfadiazine (SDZ) cream, and treated with placebo phototherapy (<.03 J/cm(-3)) using a Dynatron Solaris 705 phototherapy research device. In group 2 the ulcers were treated similarly but received real phototherapy (3 J/cm(-2)) instead of placebo. In group 3 (controls), the ulcers were simply cleaned and dressed with SDZ without phototherapy. The ulcers were evaluated with digital photography and computer image analysis over 90 d or until full healing was attained. Results: Ulcers treated with phototherapy healed significantly faster than controls when compared at day 30 (p < 0.01), day 60 (p < 0.05), and day 90 (p < 0.001), and similarly healed faster than the placebo-treated ulcers at days 30 and 90 (p < 0.01), but not at day 60. The beneficial effect of phototherapy was more pronounced when the confounding effect of small-sized ulcers was removed from the analysis. Medium- and large-sized ulcers healed significantly faster with treatment (>= 40% rate of healing per month) than placebo or control ulcers (p < 0.05). Conclusion: Phototherapy promotes healing of chronic venous ulcers, particularly large recalcitrant ulcers that do not respond to conventional treatment.

LED Phototherapy to Prevent Mucositis: A Case Report

Objective: The purpose of this case report was to evaluate the efficacy of phototherapy using light-emitting diodes (LEDs) to prevent oral mucositis in a Hodgkin's disease patient treated with the ABVD ( doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) chemotherapy regimen. Background Data: Mucositis is a common dose-limiting complication of cancer treatment, and if severe it can lead to alterations in treatment planning or suspension of cancer therapy, with serious consequences for tumor response and survival. Therefore, low-power lasers and more recently LEDs, have been used for oral mucositis prevention and management, with good results. Materials and Methods: In this study, a 34-year-old man received intraoral irradiation with an infrared LED array (880 nm, 3.6 J/cm(2), 74 mW) for five consecutive days, starting on chemotherapy day 1. In each chemotherapy cycle, he received the ABVD protocol on days 1 and 15, and received LED treatment for 5 d during each cycle. To analyze the results, the World Health Organization (WHO) scale was used to grade his mucositis, and a visual analogue scale (VAS) was used for pain evaluation, on days 1, 3, 7, 10, and 13 post-chemotherapy. Results: The results showed that the patient did not develop oral mucositis during the five chemotherapy cycles, and he had no pain symptoms. Conclusion: LED therapy was a safe and effective method for preventing oral mucositis in this case report. However, further randomized studies with more patients are needed to prove the efficacy of this method.

LOW-INTENSITY PULSED ULTRASOUND PRODUCED AN INCREASE OF OSTEOGENIC GENES EXPRESSION DURING THE PROCESS OF BONE HEALING IN RATS

The aim of this study was to measure the temporal expression of osteogenic genes during the process of bone healing in low-intensity pulsed ultrasound (LIPUS) treated bone defects by means of histopathologic and real-time polymerase chain reaction (PCR) analysis. Animals were randomly distributed into two groups (n = 30): control group (bone defect without treatment) and LIPUS treated (bone defect treated with LIPUS). On days 7, 13 and 25 postinjury, 10 rats per group were sacrificed. Rats were treated with a 30 mW/cm(2) LIPUS. The results pointed out intense new bone formation surrounded by highly vascularized connective tissue presenting a slight osteogenic activity, with primary bone deposition was observed in the group exposed to LIPUS in the intermediary (13 days) and late stages of repair (25 days) in the treated animals. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) showed an upregulation of bone morphogenetic protein 4 (BMP4), osteocalcin and Runx2 genes 7 days after the surgery. In the intermediary period, there was no increase in the expression. The expression of alkaline phosphatase, BMP4 and Runx2 was significantly increased at the last period. Our results indicate that LIPUS therapy improves bone repair in rats and upregulated osteogenic genes, mainly at the late stages of recovery. (E-mail: a.renno@unifesp.br) (C) 2010 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.

Vibratory noise to the fingertip enhances balance improvement associated with light touch

Light touch of a fingertip on an external stable surface greatly improves the postural stability of standing subjects. The hypothesis of the present work was that a vibrating surface could increase the effectiveness of fingertip signaling to the central nervous system (e.g., by a stochastic resonance mechanism) and hence improve postural stability beyond that achieved by light touch. Subjects stood quietly over a force plate while touching with their right index fingertip a surface that could be either quiescent or randomly vibrated at two low-level noise intensities. The vibratory noise of the contact surface caused a significant decrease in postural sway, as assessed by center of pressure measures in both time and frequency domains. Complementary experiments were designed to test whether postural control improvements were associated with a stochastic resonance mechanism or whether attentional mechanisms could be contributing. A full curve relating body sway parameters and different levels of vibratory noise resulted in a U-like function, suggesting that the improvement in sway relied on a stochastic resonance mechanism. Additionally, no decrease in postural sway was observed when the vibrating contact surface was attached to the subject`s body, suggesting that no attentional mechanisms were involved. These results indicate that sensory cues obtained from the fingertip need not necessarily be associated with static contact surfaces to cause improvement in postural stability. A low-level noisy vibration applied to the contact surface could lead to a better performance of the postural control system.

Comparative study of laser and LED systems of low intensity applied to tendon healing

The aim of this study was to compare the effects of Low-intensity Laser Therapy (LILT) and Light Emitting Diode Therapy (LEDT) of low intensity on the treatment of lesioned Achilles tendon of rats. The experimental model consisted of a partial mechanical lesion on the right Achilles tendon deep portion of 90 rats. One hour after the lesion, the injured animals received applications of laser/LED (685, 830/630, 880 nm), and the same procedure was repeated at 24-h intervals, for 10 days. The healing process and deposition of collagen were evaluated based on a polarization microscopy analysis of the alignment and organization of collagen bundles, through the birefringence (optical retardation-OR). The results showed a real efficiency of treatments based on LEDT and confirmed that LILT seems to be effective on healing process. Although absence of coherence of LED light, tendon healing treatment with this feature was satisfactory and can certainly replace treatments based on laser light applications. Applications of infrared laser at 830 nm and LED 880 nm were more efficient when the aim is a good organization, aggregation, and alignment of the collagen bundles on tendon healing. However, more research is needed for a safety and more efficient determination of a protocol with LED.

Outpatient Radioiodine Therapy for Thyroid Cancer A Safe Nuclear Medicine Procedure

Purposes: To evaluate the dosimetric effect of outpatient radioiodine therapy for thyroid cancer in members of a patient`s family and their living environment, when using iodine-131 doses reaching 7.4 GBq. The following parameters were thus defined: (a) whole-body radiation doses to caregivers, (b) the production of contaminated solid waste, and (c) radiation potential and surface contamination within patients` living quarters. Methods: In total, 100 patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation safety guidelines. Both the caregivers and the radiation dose potentiality inside patients` residences were monitored by using thermoluminescent dosimeters. Surface contamination and contaminated solid wastes were identified and measured with a Geiger-Muller detector. Results: A total of 90 monitored individuals received a mean dose of 0.27 (+/- 0.28) mSv, and the maximum dose registered was 1.6 mSv. The mean value for the potential dose within all living quarters was 0.31(+/- 0.34) mSv, and the mean value per monitored surface was 5.58 Bq/cm(2) for all the 1659 points measured. The overall production of contaminated solid wastes was at a low level, being about 3 times less than the exemption level indicated by the International Atomic Energy Agency. Conclusions: This study indicates that the treatment of thyroid cancer by applying radioiodine activities up to 7.4 GBq, on an outpatient basis, is a safe procedure, especially when supervised by qualified professionals. This alternative therapy should be a topic for careful discussion considering the high potential for reducing costs in healthcare and improving patient acceptance.

Phototherapy Promotes Healing of Chronic Diabetic Leg Ulcers That Failed to Respond to Other Therapies

Objective: We tested the hypothesis that combined 660 and 890 nm LED phototherapy will promote healing of diabetic ulcers that failed to respond to other forms of treatment. Research Design and Methods: A double-blind randomized placebo controlled design was used to study 23 diabetic leg ulcers in two groups of 14 patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine cream and treated with ""placebo"" phototherapy (<1.0 J cm(-2)) twice per week, using a Dynatron Solaris 705 (R) device. Group two ulcers were treated similarly but received 3 J cm(-2) dose. Results: At each of 15,30,45,60,75, and 90 days of healing, mean ulcer granulation and healing rates were significantly higher for group two than the ""placebo"" group (P < 0.02). While ""placebo"" treated ulcers worsened during the initial 30 days, group two ulcers healed rapidly; achieving 56% more granulation and 79.2% faster healing by day 30, and maintaining similarly higher rates of granulation and healing over the ""placebo"" group all through. By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90-100% healing. In contrast, only one ""placebo"" treated ulcer healed fully by day 90; no other ulcer attained >90% healing. Conclusion: Combined 660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers that failed to respond to other forms of treatment. Lasers Surg. Med. 41:433-441, 2009. (C) 2009 Wiley-Liss, Inc.

Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion

Peripheral nerves are structures that, when damaged, can result in significant motor and sensory disabilities. Several studies have used therapeutic resources with the aim of promoting early nerve regeneration, such as the use of low-power laser. However, this laser therapy does not represent a consensus regarding the methodology, thus yielding controversial conclusions. The objective of our study was to investigate, by functional evaluation, the comparative effects of low-power laser (660 nm and 830 nm) on sciatic nerve regeneration following crushing injuries. Twenty-seven Wistar rats subjected to sciatic nerve injury were divided into three groups: group sham, consisting of rats undergoing simulated irradiation; a group consisting of rats subjected to gallium-aluminum-arsenide (GaAlAs) laser at 660 nm (10 J/cm(2), 30 mW and 0.06 cm(2) beam), and another one consisting of rats subjected to GaAlAs laser at 830 nm (10 J/cm(2), 30 mW and 0.116 cm(2)). Laser was applied to the lesion for 21 days. A sciatic functional index (SFI) was used for functional evaluation prior to surgery and on days 7, 14, and 21 after surgery. Differences in SFI were found between group 660 nm and the other ones at the 14th day. One can observe that laser application at 660 nm with the parameters and methods utilised was effective in promoting early functional recovery, as indicated by the SFI, over the period evaluated.

Influence of Photoactivation Protocol and Light Guide Distance on Conversion and Microleakage of Composite Restorations

Purpose: To evaluate the effect of light guide distance and the different photoactivation methods on the degree of conversion (DC) and microleakage of a composite. Methods and Materials: Three photoactivation protocols (600mW/cm(2) x 40 seconds; 400 mW/cm(2) x 60 seconds or 200 mW/cm(2) x 20 seconds, followed by 500 mW/cm(2) X 40 seconds) and three distances from the light source (0, 3 or 7 mm) were tested. Cylindrical specimens (5 nun diameter; 2 mm tall; n=3) were prepared for the DC test (FT-Raman). Class V cavities were made in 90 bovine incisors to conduct the microleakage test. The specimens were conditioned for 15 seconds with phosphoric acid (37%), followed by application of the adhesive system Prime & Bond NT (Dentsply/Caulk). The preparations were restored in bulk. The specimens were stored for 24 hours in distilled water (37 degrees C) before being submitted to the silvernitrate microleakage protocol. The restorations were sectioned and analyzed under 25x magnification. Results: Statistical analyses (two-way ANOVAs and Tukey test, alpha=0.05) found significance only for the factor distance (p=0.015) at the top of the composite for the DC test. Conversion was statistically lower for the 7 mm groups compared to the 0 and 3 mm groups, which were equivalent to each other. At the bottom of the specimens, none of the factors or interactions was significant (p<0.05). The Kruskal-Wallis test showed that, in general, the soft-start method led to lower microleakage scores when compared to the continuous modes, mainly when associated with a distancing of 7 mm (p<0.01). With the exception of specimens irradiated with 400mW/cm(2) that did not demonstrate variations on scores for the distances tested, higher microleakage was observed for shorter distances from the light source. Conclusions: Soft-start methods may reduce microleakage when the light guide distancing provides a low level of irradiance, which also causes a discrete reduction in the DC.

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Photodynamic therapy enhances liposomal doxorubicin distribution in tumors during isolated perfusion of rodent lungs.

BACKGROUND: Photodynamic therapy (PDT) at low drug-light conditions can enhance the transport of intravenously injected macromolecular therapeutics through the tumor vasculature. Here we determined the impact of PDT on the distribution of liposomal doxorubicin (Liporubicin™) administered by isolated lung perfusion (ILP) in sarcomas grown on rodent lungs. METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the left lung of Fischer rats. Treatment schemes consisted in ILP alone (400 μg of Liporubicin), low-dose (0.0625 mg/kg Visudyne®, 10 J/cm(2) and 35 mW/cm(2)) and high-dose left lung PDT (0.125 mg/kg Visudyne, 10 J/cm(2) and 35 mW/cm(2)) followed by ILP (400 μg of Liporubicin). The uptake and distribution of Liporubicin in tumor and lung tissues were determined by high-performance liquid chromatography and fluorescence microscopy in each group. RESULTS: Low-dose PDT significantly improved the distribution of Liporubicin in tumors compared to high-dose PDT (p < 0.05) and ILP alone (p < 0.05). However, both PDT pretreatments did not result in a higher overall drug uptake in tumors or a higher tumor-to-lung drug ratio compared to ILP alone. CONCLUSIONS: Intraoperative low-dose Visudyne-mediated PDT enhances liposomal doxorubicin distribution administered by ILP in sarcomas grown on rodent lungs which is predicted to improve tumor control by ILP.

Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Targeting Adenoviral Gene Therapy Vectors to Head and Neck Squamous Cell Carcinoma and Heart

Gene therapy aims to treat diseases by introducing genetic material to the diseased tissue. For cancer treatment it is important to destroy cancerous cells; this can be achieved by introducing a gene, which induces cell death or by allowing viral vectors to replicate, which also results in destruction of cancerous cells. For cardiac diseases the approach is more like the former, except the gene produces beneficial effects, like angiogenesis. Adenoviruses have many beneficial qualities, which make the virus an interesting gene therapy vector; it can be produced relatively easily, its manipulation is quite easy and it has naturally broad tropism. By removing or replacing certain genes in the adenoviral genome, it can be made non-replicative. In this study, adenoviral receptor expression patterns were characterized in both head and neck squamous cell carcinoma and the human heart. Adenovirus serotype 5 receptor expression in head and neck cancer cell lines was found to be highly variable between cell lines and overall at lower levels, while Ad35 receptor expression was more uniform and at higher levels in all analyzed cell lines. It was also shown that a hybrid virus Ad5/35 is able to infect cells refractory to Ad5, which correlates with receptor expression in these cells. Furthermore, this difference in infection properties extends to cell killing efficiency in case of conditionally replicative viruses. Expression levels of adenoviral receptors CAR, CD46, CD86 and αv-integrins were found to be high both in normal and dilated cardiomyopathy heart tissue. The receptor levels also correlate with transduction efficiency after intracardiac injection. Ad5 showed superior transduction ability compared with Ad5/35, but evoked also a more profound immune reaction when administered this way. Adenoviral gene therapy vectors are the most used delivery vehicles in clinical trials to date. These vectors have proven to be well tolerated and positive results have been obtained when combined with traditional treatments, although poor transduction efficiency has often been reported due to low-level expression of viral receptors on target cells. In spite of this, the results are encouraging and merit for further research.

Effects of low intensity laser in in vitro bacterial culture and in vivo infected wounds

OBJECTIVE: to compare the effects of low intensity laser therapy on in vitro bacterial growth and in vivo in infected wounds, and to analyze the effectiveness of the AsGa Laser technology in in vivo wound infections. METHODS: in vitro: Staphylococcus aureus were incubated on blood agar plates, half of them being irradiated with 904 nm wavelength laser and dose of 3J/cm2 daily for seven days. In vivo: 32 male Wistar rats were divided into control group (uninfected) and Experimental Group (Infected). Half of the animals had their wounds irradiated. RESULTS: in vitro: there was no statistically significant variation between the experimental groups as for the source plates and the derived ones (p>0.05). In vivo: there was a significant increase in the deposition of type I and III collagen in the wounds of the infected and irradiated animals when assessed on the fourth day of the experiment (p=0.034). CONCLUSION: low-intensity Laser Therapy applied with a wavelength of 904nm and dose 3J/cm2 did not alter the in vitro growth of S. aureus in experimental groups; in vivo, however, it showed significant increase in the deposition of type I and III collagen in the wound of infected and irradiated animals on the fourth day of the experiment.