Low-level light therapy of the eye and brain

Abstract: Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain

Prefrontal photobiomodulation produces beneficial mitochondrial and oxygenation effects in older adults with bipolar disorder

There is growing evidence of mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism in bipolar disorder (BD). Older adults with BD exhibit greater decline in PFC-related neurocognitive functions than is expected for age-matched controls, and clinical interventions intended for mood stabilization are not targeted to prevent or ameliorate mitochondrial deficits and neurocognitive decline in this population. Transcranial infrared laser stimulation (TILS) is a non-invasive form of photobiomodulation, in which photons delivered to the PFC photo-oxidize the mitochondrial respiratory enzyme, cytochrome-c-oxidase (CCO), a major intracellular photon acceptor in photobiomodulation. TILS at 1064-nm can significantly upregulate oxidized CCO concentrations to promote differential levels of oxygenated vs. deoxygenated hemoglobin (HbD), an index of cerebral oxygenation. The objective of this controlled study was to use non-invasive broadband near-infrared spectroscopy to assess if TILS to bilateral PFC (Brodmann area 10) produces beneficial effects on mitochondrial oxidative energy metabolism (oxidized CCO) and cerebral oxygenation (HbD) in older (≥50 years old) euthymic adults with BD (N = 15). As compared to sham, TILS to the PFC in adults with BD increased oxidized CCO both during and after TILS, and increased HbD concentrations after TILS. By significantly increasing oxidized CCO and HbD concentrations above sham levels, TILS has the potential ability to stabilize mitochondrial oxidative energy production and prevent oxidative damage in the PFC of adults with BD. In conclusion, TILS was both safe and effective in enhancing metabolic function and subsequent hemodynamic responses in the PFC, which might help alleviate the accelerated neurocognitive decline and dysfunctional mitochondria present in BD

Epilepsia com ponta-onda contínua do sono lento: estudo clínico e eletrencefalográfico

We report four children with epilepsy with continuous spike-waves during slow wave sleep (CSWSS). The main clinical features were partial motor seizures, mental retardation and motor deficit. The EEG findings were characterized by nearly continuous (>85%) diffuse slow spike and wave activity in two patients, and localized to one hemisphere in two other cases during non-REM sleep. The treatment was effective in improving the clinical seizures, but not the EEG pattern. We believe that this epileptic syndrome has been overlooked and routine sleep EEG studies on epileptic children may disclose more cases of CSWSS.Relatamos quatro crianças epilépticas com ponta-onda contínua durante o sono lento (POCSL). Os principais achados clínicos foram crises parciais motoras,retardo mental e déficit motor. Os EEG se caracterizaram por complexos ponta-onda quase contínuos (>85%) difusos em dois pacientes e localizados em um hemisfério nos outros dois casos. O tratamento foi eficaz no controle das crises, mas não em relação ao EEG. Achamos que este quadro tem sido pouco relatado e estudos do sono em crianças epilépticas podem revelar mais casos de POCSL.Escola Paulista de Medicina Head of the EEG SectorEPMUNIFESP, EPM, Head of the EEG SectorEPMSciEL

Different ability of multidrug-resistant and-sensitive counterpart cells to release and capture extracellular vesicles

Cancer multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR is a phenomenon by which tumor cells become resistant to several unrelated drugs. Some studies have previously described the important role of extracellular vesicles (EVs) in the dissemination of a MDR phenotype. EVs’ cargo may include different players of MDR, such as microRNAS and drug-efflux pumps, which may be transferred from donor MDR cells to recipient drug-sensitive counterparts. The present work aimed to: (i) compare the ability of drug-sensitive and their MDR counterpart cells to release and capture EVs and (ii) study and relate those differences with possible distinct fate of the endocytic pathway in these counterpart cells. Our results showed that MDR cells released more EVs than their drug-sensitive counterparts and also that the drug-sensitive cells captured more EVs than their MDR counterparts. This difference in the release and capture of EVs may be associated with differences in the endocytic pathway between drug-sensitive and MDR cells. Importantly, manipulation of the recycling pathway influenced the response of drug-sensitive cells to doxorubicin treatment.This article is a result of the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We thank Spanish MINECO (SAF2015-66312 to JMF) and for the REDIEX (Spanish Excellence Network in Exosomes) and the Severo Ochoa Excellence Accreditation (SEV-2016-0644). The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of DS (SFRH/BD/98054/2013). Cristina P.R. Xavier is supported by FCT and Fundo Social Europeu (FSE), through the post-doc grant SFRH/BPD/122871/2016. The authors also acknowledge the European COST Action-European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD, BM1202) for short-term mission fellowship (ECOST-STSM-BM1202-150317-083396) and Grupo Español de investigacion en Vesiculas Extracelulares for GEIVEX mobility fellowship which allowed the work of DS in CICbioGUNE

Changes in neurosteroidogenesis during demyelination and remyelination in cuprizone-treated mice

Changes of neurosteroids may be involved in the pathophysiology of multiple sclerosis (MS). The present study investigated whether changes of neurosteroidogenesis also occurred in the grey and white matter regions of the brain in mice subjected to cuprizone‐induced demyelination. Accordingly, we compared the expression of neurosteroidogenic proteins, including steroidogenic acute regulatory protein (StAR), voltage‐dependent anion channel (VDAC) and 18 kDa translocator protein (TSPO), as well as neurosteroidogenic enzymes, including the side chain cleavage enzyme (P450scc), 3β‐hydroxysteroid dehydrogenase/isomerase and 5α‐reductase (5α‐R), during the demyelination and remyelination periods. Using immunohistochemistry and a quantitative polymerase chain reaction, we demonstrated a decreased expression of StAR, P450scc and 5α‐R with respect to an increase astrocytic and microglial reaction and elevated levels of tumor necrosis factor (TNF)α during the cuprizone demyelination period in the hippocampus, cortex and corpus callosum. These parameters, as well as the glial reaction, were normalised after 2 weeks of spontaneous remyelination in regions containing grey matter. Conversely, persistent elevated levels of TNFα and low levels of StAR and P450scc were observed during remyelination in corpus callosum white matter. We conclude that neurosteroidogenesis/myelination status and glial reactivity are inversely related in the hippocampus and neocortex. Establishing a cause and effect relationship for the measured variables remains a future challenge for understanding the pathophysiology of MS.Fil: Leicaj, María L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Lima, Analia Ethel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gonzalez Deniselle, Maria Claudia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: De Nicola, Alejandro F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Garay, Laura Ines. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Seleção de primers para o uso de ISSR na análise de diversidade genética em babaçu (Orbignya phalerata mart.).

O babaçu (Orbignya phalerata mart.) e um dos principais produtos extrativistas do Brasil, e a maior fonte mundial de óleo silvestre para uso domestico, tendo utilização industrial em perfumaria, saboaria e lubrificação, contribuindo, de maneira significativa, para a economia dos Estados do Piaui e Maranhao. Dele é feito um aproveitamento de tudo, desde as folhas ate os frutos, tendo um valor alto na industria e comercio sendo hoje uma alternativa para a producao de biodiesel. Este trabalho teve por objetivo selecionar primers para avaliar o potencial do marcador de ISSR (Interrepetições de seqüências simples) para a analise da diversidade genética entre os acessos do banco de germoplasma de babaçu da Embrapa Meio-Norte..

Diffuse light and building history of the galaxy cluster Abell 2667

We have searched for diffuse intracluster light in the galaxy cluster Abell 2667 (z=0.233) from HST images in three filters. We have applied to these images an iterative multi-scale wavelet analysis and reconstruction technique, which allows to subtract stars and galaxies from the original images. We detect a zone of diffuse emission south west of the cluster center (DS1), and a second faint object (ComDif), within DS1. Another diffuse source (DS2) may be detected, at lower confidence level, north east of the center. These sources of diffuse light contribute to 10-15% of the total visible light in the cluster. Whether they are independent entities or are part of the very elliptical external envelope of the central galaxy remains unclear. VLT VIMOS integral field spectroscopy reveals a faint continuum at the positions of DS1 and ComDif but do not allow to compute a redshift. A hierarchical substructure detection method reveals the presence of several galaxy pairs and groups defining a similar direction as the one drawn by the DS1-central galaxy-DS2 axis. The analysis of archive XMM-Newton and Chandra observations shows X-ray emission elongated in the same direction. The X-ray temperature map shows the presence of a cool core, a broad cool zone stretching from north to south and hotter regions towards the north east, south west and north west. This possibly suggests shock fronts along these directions produced by infalling material. These various data are consistent with a picture in which diffuse sources are concentrations of tidal debris and harassed matter expelled from infalling galaxies by tidal stripping and undergoing an accretion process onto the central cluster galaxy; as such, they are expected to be found along the main infall directions.Comment: Accepted for publication in Astronomy and Astrophysic

Histochemical mapping of the duration of action of photobiomodulation on cytochrome c oxidase in the rat brain

IntroductionThis is the first study mapping the duration of action of in vivo photobiomodulation (PBM) on cytochrome-c-oxidase (CCO). In cellular bioenergetics, CCO is the terminal rate-limiting enzyme in the mitochondrial electron transport chain, which catalyzes oxygen utilization for aerobic energy production. PBM using transcranial infrared laser stimulation (TILS) is a promising intervention for non-invasively modulating CCO in the brain. TILS of the human prefrontal cortex directly causes CCO photo-oxidation, which is associated with increased cerebral oxygenation and improved cognition.MethodsThis experiment aimed to map the duration of action of in vivo PBM on CCO activity in discrete neuroanatomic locations within rat brains up to 4 weeks after a single TILS session (50 s, 1064 nm CW, 250 mW/cm2). Control brains from rats treated with a sham session without TILS (laser off) were compared to brains from TILS-treated rats that were collected 1 day, 2 weeks, or 4 weeks post-TILS. Cryostat sections of the 36 collected brains were processed using quantitative enzyme histochemistry and digitally imaged. Densitometric readings of 28 regions of interest were recorded and converted to CCO activity units of oxygen utilization using calibration standards. Data analysis (ANCOVA) compared each laser-treated group to sham with whole-brain average as a covariate.ResultsThe prefrontal infralimbic cortex showed the earliest significant increase in CCO activity between 1-day post-TILS and sham groups, which continued elevated for 2–4 weeks post-TILS. Significant differences in CCO activity between 2-weeks and sham groups were also found in the lateral septum, accumbens core, CA3 of the hippocampus, and the molecular layer of the hippocampus. The medial amygdala showed a significant decrease in CCO activity between 4-weeks and sham. Further analyses showed significant inter-regional CCO activity correlations among the brain regions as the result of TILS, with the most pronounced changes at 4-weeks post-stimulation.DiscussionThe time course of changes in CCO activity and network connectivity suggested that TILS caused different neuroplasticity types of bioenergetic changes at different time scales, depending on brain region and its depth from the cortex. In conclusion, this controlled CCO histochemical study demonstrated a long-lasting duration of action of PBM in the rat brain

Hawking radiation and thermodynamics of dynamical black holes in phantom dominated universe

The thermodynamic properties of dark energy-dominated universe in the presence of a black hole are investigated in the general case of a varying equation-of-state-parameter $w(a)$. We show that all the thermodynamics quantities are regular at the phantom divide crossing, and particularly the temperature and the entropy of the dark fluid are always positive definite. We also study the accretion process of a phantom fluid by black holes and the conditions required for the validity of the generalized second law of thermodynamics. As a results we obtain a strictly negative chemical potential and an equation-of-state parameter $w<-5/3.$Comment: 22 pages,3 figure