Photobiomodulation in diabetic wound healing: A review of red and near-infrared wavelength applications.

The development of a painless, non-invasive, and faster way to diabetic wound healing is at the forefront of research. The complexity associated with diabetic wounds makes it a cause for concern amongst diabetic patients and the world at large. Irradiation of cells generates a photobiomodulatory response on cells and tissues, directly causing alteration of cellular processes and inducing diabetic wound repair. Photobiomodulation therapy (PBMT) using red and near-infrared (NIR) wavelengths is being considered as a promising technique for speeding up the rate of diabetic wound healing, eradication of pain and reduction of inflammation through the alteration of diverse cellular and molecular processes. This review presents the extent to which the potential of red and NIR wavelengths have been harnessed in PBMT for diabetic wound healing. Important research challenges and gaps are identified and discussed, and future directions mapped out. This review thus provides useful insights and strategies into improvement of PBMT, including its acceptance within the global medical research community.

Acute application of photobiomodulation does not bring important gains for the muscular performance and functionality of diabetic individuals.

Photobiomodulation therapy (PBMT) has been used to improve the physical performance of individuals with advanced age; however, there are no studies in the literature that support the application of light-emitting diode (LED) therapy for the muscular performance of individuals with diabetes mellitus who show a decline in functionality. The aim of the study was to analyze the acute effects of PBMT on strength and functional performance in type 2 diabetic individuals. Sixty-three volunteers were recruited and randomized into five groups: control (C), sham (S), red LED (R), infrared LED (IR), and red LED + infrared LED (R + IR). On the first day, the volunteers were evaluated using the time up and go (TUG), the 6-min walk test (6MWT), and isokinetic dynamometer of the ankle. In the following 3 days, groups R, IR, R + IR, and S returned for application of PBMT bilaterally, with 180 J of energy on each leg. On the fifth day, a reassessment was performed. There was no statistical difference between groups for the variables of the isokinetic dynamometer, TUG, and 6MWT. Analysis of the size of the clinical effect for the isokinetic variables showed that there was no pattern among the effects observed. There is a moderate effect in favor of R, IR, and R + IR in relation to C for the TUG and a moderate effect of R + IR in relation to C for the 6MWT. The PBMT applied for a short period does not bring important gains for the muscular performance and functionality of diabetic individuals.

Photobiomodulation therapy compensate the impairments of diabetic bone marrow mesenchymal stem cells.

Pathophysiologic conditions associated with diabetes mellitus affect mesenchymal stem cells (MSCs), and this phenomenon may lead to some diabetic secondary complications. The present study was conducted to evaluate the impact of photobiomodulation (PBM) on rat diabetic MSC (DMSC) behavior in vitro. For the purpose of PBM, we used helium-neon laser with a wavelength of 632.8 nm at three different energy densities (0.5, 1, 2 J/cm2) and radiation periodicity of once, twice, and thrice. The survival, proliferation, and apoptosis in the normal MSCs (NMSCs), DMSCs, and diabetic MSCs, which were laser irradiated (DMSCs+L), were assessed using MTT assay, Ki67 immunofluorescence staining, and TUNEL assay, respectively. Our results demonstrated that DMSCs have significantly lower survival (P < 0.05) and proliferation rates (P < 0.001), and dramatically higher population doubling time (PDT, P < 0.001) and apoptosis rates (P < 0.001) as compared to NMSCs. Moreover, PBM with energy density of 1 J/cm2 and the periodicity of 1 or 2 times could improve diabetic MSC capabilities in the term of survival, proliferation, and apoptosis. Considering these findings, it is suggested that PBM could improve the ability of diabetic MSCs in vitro prior to transplantation or may rise their capabilities in their native niche in vivo.

Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers.

Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm2, once a day, with intervals of 24 h, totaling 12 applications. The lesion area analysis revealed averaged improvement of the granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis revealed that IL6 values were not significantly different before and after treatment, TNF gene expression was reduced, and VEFG and TGF-ß gene expression increased after treatment. After LLLT, wounds presented improvement in gross appearance, with increase in factors VEFG and TGF-ß, and reduction of TNF; despite our promising results, they have to be analyzed carefully as this study did not have a control group.

The effect of LED on blood microcirculation during chronic wound healing in diabetic and non-diabetic patients-a prospective, double-blind randomized study.

Chronic wounds, especially in diabetic patients, represent a challenging health issue. Since standard treatment protocols often do not provide satisfactory results, additional treatment methods-like phototherapy using low-level light therapy-are being investigated. The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients. Since a sufficient blood supply is mandatory for wound healing, the evaluation of microcirculation in the healthy skin at a wound's edge was the main outcome measure. Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were randomized to the treated and control groups. The treated group received phototherapy with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks, and the control group received phototherapy with broadband 580-900 nm and power density 0.72 J/cm2. Microcirculation was measured using laser Doppler. A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients (p = 0.040 and p = 0.033), while there was no difference in the control groups. Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group. According to our results, phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients.

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy.

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm2. The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

Low-level Light Therapy for Treatment of Diabetic Foot Ulcer: A Review of Clinical Experiences.

BACKGROUND: Diabetic foot ulcers (DFU) represent a significant complication of diabetes mellitus (DM). DFU affect one in four patients with DM and treatments of DFU are limited and challenging. The management of DFU remains a significant healthcare and socioeconomic burden ($245 billion). There is a wide range of advanced therapies for DFU, but these are costly and have demonstrated only minimal efficacy in limited published studies. An emerging treatment modality to improve DFU and optimize wound healing is the use of low-level light therapy (LLLT). LLLT involves the use of light in the form of low-level or low-power laser or light emitting diodes to alter biochemical pathways, which may result in changes to cell shape, cell migration, and cell signaling.
OBJECTIVE: To review published clinical experiences (case series and case reports) using LLLT for treatment of DFU, and provide evidence-based recommendations and future directions on the potential of LLLT as a therapeutic modality for DFU.
METHODS AND MATERIALS: On January 16, 2016 we searched the published literature using databases: PubMed, EMBASE, CINAHL, and Web of Science with key terms: "diabetic foot" AND ("low level laser therapy" OR "low level light therapy" OR "LLLT" OR "light emitting diode" OR "phototherapy" OR "laser").
RESULTS: After screening of titles, abstracts and/or full-text, 7 original articles were suitable in our review. Our review contains 5 case series and 2 case reports that evaluated LLLT for treatment of DFU, and all reviewed studies have shown positive improvement of DFU using LLLT with no adverse events, albeit with limitations that may be minimized with future RCTs.
CONCLUSIONS: LLLT is an emerging and promising treatment modality to current alternatives that are costly and have shown limited success. Based upon the published evidence, we envision additional research may allow for stronger recommendation with LLLT for treatment of DFU.

J Drugs Dermatol. 2016;15(7):843-848.

Acute chemical toxicity of uranium.

Although human experience with uranium spans more than 200 years, the LD50 for acute intake in humans has not been well established. Large acute doses of uranium can produce death from chemical toxicity in rats, guinea pigs, and other small experimental animals, with variation in sensitivity among species. However, there has never been a death attributable to uranium poisoning in humans, and humans seem to be less sensitive to both acute and chronic toxic effects of uranium than other mammalian species studied. Highly relevant data on uranium toxicity in humans are available from the experience of persons administered large doses of uranium for therapy of diabetes and from acute accidental inhalation intakes. Although the data on which to establish oral and inhalation acute LD50 for uranium in humans are sparse, they are adequate to conclude that the LD50 for oral intake of soluble uranium compounds exceeds several grams of uranium and is at least 1.0 g for inhalation intakes. For intakes of uranium compounds of lesser solubility, acute LD50 values are likely to be significantly greater. It is suggested that 5 g be provisionally considered the acute oral LD50 for uranium in humans. For inhalation intakes of soluble compounds of uranium, 1.0 g of uranium is proposed as the provisional acute inhalation LD50.