Methylene blue mediated antimicrobial photodynamic therapy in clinical human studies: The state of the art.

BACKGROUND: The goal of this study was to update the information about aPDT when using methylene blue (MB) for the treatment of human clinical infections of different etiologies, except for dentistry applications, and to also investigate the best parameters of MB to achieve this. METHODS: This study was a systematic literature review performed according to the PRISMA guidelines. A literature search was performed for studies with adult human patients (>18 years-old) published in the English, French, Spanish, Portuguese, and Italian languages when using the electronic databases of MEDLINE, Embase, OpenGrey, and LILACS. RESULTS: 1260 relevant articles were found. After a reading of the titles and the abstracts, only 85 articles were selected for a complete reading. After the complete reading, only 05 studies were selected for data extraction, where the treatments were onychomycosis, oral candidiasis, and infectious diabetic foot ulcers. As for the MB concentrations, 0.0003 to 0.06 molar were used. Pre-irradiation times ranged from 1 to 5 min, while the irradiation times ranged from 8 s to 10 min. As for the light sources, lasers, LED, and lamps were used, with irradiances ranging from 50 to 750 mW/cm2 and radiant exposures from 6 to 18 J/cm2. CONCLUSIONS: For the field of clinical applications of aPDT to develop, studies with a higher level of evidence are needed. For example, future reports should aim at comparing aPDT directly with standard techniques and a placebo aPDT, together with larger samples, and with more objective clinical evaluation methods, in order to provide useful data for the clinically relevant aPDT protocols.

Cholinergic Stimulation Improves Oxidative Stress and Inflammation in Experimental Myocardial Infarction.

We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(-1)·day(-1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1ß, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1ß, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.