Mitochondrial respiration as a target for neuroprotection and cognitive enhancement

This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer's disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration.     

Management of visceral vascular anomalies

Vascular malformations affect the viscera less commonly than the head and neck, extremities, and extra-cavitary soft tissues. They present with a wide spectrum of symptoms and findings including pain, respiratory compromise, hemoptysis, chylothorax, ascites, gastrointestinal bleeding, and obstruction. Management options depend upon the subtype of malformation and anatomic extent and may include sclerotherapy, embolization, surgical extirpation, coloanal pull-through, and occasionally more innovative individualized surgical approaches.     

Higher levels of greenness and biodiversity associate with greater subjective wellbeing in adults living in Melbourne,Australia

Natural environments may be important for subjective wellbeing, yet evidence is sparse and measures of nature are unspecific. We used linear regression models to investigate the relationship between greenness, biodiversity and blue space and subjective wellbeing in 4,912 adults living in metropolitan Melbourne, Australia. Greenness (overall, private and public) and biodiversity associated with subjective wellbeing. In particular, we highlight the importance of the private greenness-subjective wellbeing association. Our work has implications for urban policy and planning in the context of increased urban densification.     

Anthraquinones As Pharmacological Tools and Drugs

Anthraquinones (9,10‐dioxoanthracenes) constitute an important class of natural and synthetic compounds with a wide range of applications. Besides their utilization as colorants, anthraquinone derivatives have been used since centuries for medical applications, for example, as laxatives and antimicrobial and antiinflammatory agents. Current therapeutic indications include constipation, arthritis, multiple sclerosis, and cancer. Moreover, biologically active anthraquinones derived from Reactive Blue 2 have been utilized as valuable tool compounds for biochemical and pharmacological studies. They may serve as lead structures for the development of future drugs. However, the presence of the quinone moiety in the structure of anthraquinones raises safety concerns, and anthraquinone laxatives have therefore been under critical reassessment. This review article provides an overview of the chemistry, biology, and toxicology of anthraquinones focusing on their application as drugs.     

Evaluation of photo-activated disinfection effectiveness with methylene blue against Porphyromonas gingivalis involved in endodontic infection: An in vitro study

BackgroundEradication or suppression of microbial pathogens is a major goal in endodontic infection therapy. Sub-lethal doses of photo-activated disinfection (sPAD) as a new treatment method might be able to control the microorganisms involved in endodontic infections normally treated with PAD. This study evaluated the effect of sPAD using methylene blue (MB) in combination with diode laser irradiation on the growth and biofilm formation ability of Porphyromonas gingivalis as an endodontic pathogen.Materials and methodsThe anti-microbial and anti-biofilm potential of sPAD against P. gingivalis were assessed at sub-lethal doses of MB and irradiation by diode laser on colony forming unit and crystal violet assays, respectively.ResultsMB-sPAD using 25 μg/mL at a fluency of 117.18 J/cm² and 50–100 μg/mL at a fluency of 93.75 J/cm² significantly P. gingivalis growth when compared to the control. MB at 100 μg/mL at a fluency of 117.18 J/cm² in MB-mediated PAD showed a significant inhibitory effect on biofilm formation in P. gingivalis compared with MB-sPAD.ConclusionHigh doses of MB-mediated sPAD exhibited anti-microbial and anti-biofilm potential activity, whereas lower doses of MB-mediated sPAD did not display this ability. Therefore, the dose of PAD used in vivo should be taken into account for endodontic treatment.     

Potassium iodide enhances inactivation of Streptococcus mutans biofilm in antimicrobial photodynamic therapy with red laser

ObjectiveTo evaluate the effect of potassium iodide (KI) addition on antimicrobial photodynamic therapy (aPDT) mediated by red laser (λ = 660 nm) and methylene blue in Streptococcus mutans biofilm model.MethodsS. mutans biofilms were cultured in 96-well plates containing BHI broth with 1% sucrose for 18 h, 10% CO₂ and 37 °C and divided in groups (n = 3, in triplicate): C (NaCl 0.9%); CX (0.2% chlorhexidine); P (photosensitizer); KI (10, 25 and 50 mM); PKI (10, 25 and 50 mM); L (L1: 100 J/cm², 9 J; L2: 200 J/cm², 18 J); PL (photosensitizer + L1 or L2); KIL (KI at 10, 25 and 50 mM + L1 or L2); and PKIL (photosensitizer + 10, 25 and 50 mM KI + L1 or L2). Biofilms were submitted to three pre-irradiation (PI) times (5, 10, and 15 min). After the treatments, microbial counting's reduction was analyzed by Kruskal-Wallis and post-hoc Dunn's tests, respectively, and the interaction between light parameters and the PI times by two-way ANOVA (p < 0.05).ResultsThe S. mutans viability significantly reduced in all aPDT groups, in the presence or absence of KI (p < 0.05). For all PI times, PKIL groups (10, 25, and 50 mM) significantly differed from PL groups (p < 0.05) with a reduction of 9.0 logs reached at 50 mM of KI with 15 min of PI, irradiated at 18 J. We found no significant interaction between PI time and irradiation (p > 0.05).ConclusionThe addition of KI to PDT mediated by methylene blue and red laser promoted an additional effect in reducing the microbial viability of S. mutans biofilm.