Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington’s disease knock-in striatal cells

Akt, protein kinase B; ARE, antioxidant response element; Erk, extracellular signal-regulated kinase; CBP, CREB-binding protein; CREB, cAMP response-element (CRE) binding protein; CDK, cyclin-dependent kinase; DHE, dihydroethidium; Drp1, dynamin-related protein 1 or dynamin 1-like (DNM1L); GCL, glutamate-cysteine ligase; GCLc, glutamate-cysteine catalytic subunit; GPx, glutathione peroxidase; GSH, glutathione, reduced form; GSSG, glutathione oxidized form; IGF-1, Insulin-like growth factor 1; IGF1R, insulin-like growth factor 1 receptor; IR, insulin receptor; IRS, insulin receptor substrate; H2DCFDA, 2′,7′-dichlorodihydrofluorescein diacetate; HKII, hexokinase type II; HD, Huntington’s disease; HO-1, heme oxygenase; Hsp60, heat shock 60 kDa protein 1 (chaperonin); mHtt, mutant huntingtin; mtDNA, mitochondrial DNA; MT-COII, mitochondrial-encoded cytochrome c oxidase II; mTOR, mammalian target of rapamycin; NDUFS3, NADH dehydrogenase (ubiquinone) Fe–S protein 3, 30 kDa (NADH-coenzyme Q reductase); NQO1, NAD(P)H dehydrogenase [quinone] 1; Nrf2, nuclear factor (erythroid-derived 2)-like 2; PI-3K, phosphatidylinositol 3-kinase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1α; ROS, reactive oxygen species; SDHA, succinate dehydrogenase complex, subunit A, flavoprotein (Fp); SOD, superoxide dismutase; Tfam, transcription factor A, mitochondrial; TMRM, tetramethylrhodamine methyl ester; Tom20, translocase of outer mitochondrial membrane 20 homolog (yeast); Tom40, translocase of outer mitochondrial membrane 40 homolog (yeast)

Mycobiota and mycotoxins present in finished fish feeds from farms in the Rio de Janeiro State, Brazil

The aim of the present study was to determine species of the fungal genera Aspergillus, Fusarium, and Penicillium and fumonisin B1 (FB1), aflatoxin B1 (AFB1), and ochratoxin A (OTA) contamination from feed intended for fish farms. A total of 60 samples were sampled from tilapia farms in the Rio de Janeiro State, Brazil. The quantitative enumeration of fungi as colony-forming units per gram of feed (CFU/g) was performed using the surface spread method in different culture media. The results were expressed as fungal isolation frequency and relative density. Fungal total counts ranged from <1 × 102 to 4.7 × 104 CFU/g. Fusarium counts were not observed. Among toxigenic genera, Aspergillus (68%) was the most prevalent, followed by Penicillium species (60%). Aspergillus niger aggregate (36%), Aspergillus flavus (35%), and Penicillium citrinum (71%) were the most prevalent species. A high percentage of samples (98%) were contaminated with FB1 levels, while 55% and 3.3% were contaminated with AFB1 and OTA, respectively. The simultaneous occurrence of these mycotoxins emphasizes the need for further research in the area to better assess the risk to the health of fish farms and their implications for the health of consumers of this meat.Fil: Barbosa, Tatiana S.. Universidade Federal Rural do Rio de Janeiro ; BrasilFil: Pereyra, Carina Maricel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soleiro, Carla A.. Universidade Federal Rural do Rio de Janeiro ; Brasil. Conselho Nacional de Desenvolvimiento Científico y Tecnológico; BrasilFil: Dias, Erica O.. Universidade Federal Rural do Rio de Janeiro ; BrasilFil: Oliveira, Aguida A.. Universidade Federal Rural do Rio de Janeiro ; Brasil. Conselho Nacional de Desenvolvimiento Científico y Tecnológico; BrasilFil: Keller, Kelly M.. Universidade Federal Rural do Rio de Janeiro ; Brasil. Conselho Nacional de Desenvolvimiento Científico y Tecnológico; BrasilFil: Silva, Pedro P. O.. Universidade Federal Rural do Rio de Janeiro; BrasilFil: Cavaglieri, Lilia Reneé. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosa, Carlos Alberto da Rocha. Universidade Federal Rural do Rio de Janeiro ; Brasil. Conselho Nacional de Desenvolvimiento Científico y Tecnológico; Brasi

Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease

Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We showed previously that the histone deacetylase inhibitors (HDACIs) trichostatin A and sodium butyrate (SB) ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work, we investigated the effect of HDACIs on the regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3). Exposure to dichloroacetate, an inhibitor of PDKs, increased mitochondrial respiration and decreased production of reactive oxygen species in mutant cells, emphasizing PDH as an interesting therapeutic target in HD. Treatment with SB and sodium phenylbutyrate, another HDACI, recovered cell viability and overall mitochondrial metabolism in mutant cells. Exposure to SB also suppressed hypoxia-inducible factor-1 (HIF-1α) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells. Concordantly, PDK3 knockdown improved mitochondrial function, emphasizing the role of PDK3 inactivation on the positive effects achieved by SB treatment. YAC128 mouse brain presented higher mRNA levels of PDK1-3 and PDH phosphorylation and decreased energy levels that were significantly ameliorated after SB treatment. Furthermore, enhanced motor learning and coordination were observed in SB-treated YAC128 mice. These results suggest that HDACIs, particularly SB, promote the activity of PDH in the HD brain, helping to counteract HD-related deficits in mitochondrial bioenergetics and motor function.SIGNIFICANCE STATEMENT The present work provides a better understanding of mitochondrial dysfunction in Huntington's disease (HD) by showing that the pyruvate dehydrogenase (PDH) complex is a promising therapeutic target. In particular, the histone deacetylase inhibitor sodium butyrate (SB) may indirectly (through reduced hypoxia-inducible factor 1 alpha stabilization) decrease the expression of the most abundant PDH kinase isoforms (e.g., PDK3), ameliorating PDH activity and mitochondrial metabolism and further affecting motor behavior in HD mice, thus constituting a promising agent for HD neuroprotective treatment.FCT, Santa Casa da Misericórdia de Lisboa (SCML), Fundação Luso-Americana para o Desenvolvimento (FLAD) Life Scienc

Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxicity on H9c2 cardiomyoblasts

AbstractThe cardiotoxicity induced by the anti-cancer doxorubicin involves increased oxidative stress, disruption of calcium homeostasis and activation of cardiomyocyte death. Nevertheless, antioxidants and caspase inhibitors often show little efficacy in preventing cell death. We hypothesize that a caspase-independent cell death mechanism with the release of the apoptosis-inducing factor from mitochondria is involved in doxorubicin toxicity. To test the hypothesis, H9c2 cardiomyoblasts were used as model for cardiac cells. Our results demonstrate that z-VAD-fmk, a pan-caspase inhibitor, does not prevent doxorubicin toxicity in this cell line. Doxorubicin treatment results in AIF translocation to the nuclei, as confirmed by Western Blotting of cell fractions and confocal microscopy. Also, doxorubicin treatment of H9c2 cardiomyoblasts resulted in the appearance of 50kbp DNA fragments, a hallmark of apoptosis-inducing factor nuclear effects. Apoptosis-inducing factor knockdown using a small-interfering RNA approach in H9c2 cells resulted in a reduction of doxorubicin toxicity, including decreased p53 activation and poly-ADP-ribose-polymerase cleavage. Among the proteases that could be responsible for apoptosis-inducing factor cleavage, doxorubicin decreased calpain activity but increased cathepsin B activation, with inhibition of the latter partly decreasing doxorubicin toxicity. Altogether, the results support that apoptosis-inducing factor release is involved in doxorubicin-induced H9c2 cell death, which explains the limited ability of caspase inhibitors to prevent toxicity

Morphology of the male genital organs and cloaca of Rhea americana americana

As características morfológicas, macroscópicas e microscópicas, dos órgãos genitais masculinos e da cloaca foram analisados em 23 emas, quatro filhotes (duas semanas), sete jovens (de três a oito meses) e doze adultos (três anos), provenientes da Cooperativa Emas do Brasil, RS, e do CEMAS, Mossoró, RN. Os testículos da ema possuem formato alongado e localizam-se na cavidade celomática, na região intra-abdominal dorsal, com comprimento e larguras médias de 7,6±1,2cm e 2,6± 0,7cm nos adultos; 4,5±1,5cm e 0,9±0,4cm nos jovens; e 0,8±0,3cm, e 0,2±0,1cm nos filhotes. O testículo está envolto pela túnica albugínea e seu parênquima possui túbulos seminíferos irregulares, compostos por epitélio espermatogênico e por células de sustentação, e pelo tecido intersticial, com as células endócrinas intersticiais, tecido conjuntivo frouxo e vasos. Nos adultos observaram-se todas as células da linhagem espermatogênica, enquanto nos jovens com 3 meses, os testículos apresentaram túbulos seminíferos com luz reduzidas, espermatogônias e células de sustentação indiferenciadas. Os ductos eferentes possuem um epitélio cúbico ciliado, enquanto no ducto epididimário o epitélio é columnar. O epidídimo apresentou-se alongado e fusiforme junto a margem medial do testículo. O ducto deferentes apresentou trajeto sinuoso nos adultos, retilíneo nos jovens, convoluto na sua porção média, diminuindo seu formato sigmóide em sua porção caudal, próximo à cloaca. O epitélio é pseudoestratificado e reveste a luz irregular nos adultos e circular nos jovens, mantendo proximidade com o ureter. A cloaca dividiu-se em três segmentos: o coprodeu, o urodeo e o proctodeo. No urodeu os ductos deferentes desembocaram em papilas na parede ventro-lateral, próximo a inserção do falo fibroso. O falo é um órgão fibroso linfático, localizado na parede ventral, no assoalho da cloaca, e apresentou duas porções: uma rígida bifurcada e contorcida, e outra simples espiralada e flexível, a qual normalmente esteve invertida. Em exposição forçada, o falo teve 14 cm de comprimento. De forma geral os órgãos reprodutores das emas compartilharam da morfologia de outras aves, principalmente aquelas descritas para os avestruzes.The rhea (Rhea americana americana) is a bird that belongs to the group of the Ratitas, order Rheiforme and family Rheidae. Macroscopic and microscopic morphology of the male genital organ (testes, epididymis, deferent ducts, and phallus) and the cloaca were analyzed in 23 emas, four chicken (2 weeks old), young (3 to 10 months old), and twelve adult ones (3 years old), from Cooperativa Emas do Brasil, RS and from CEMAS, Mossoró, RN. The testis of rhea had elongated shape and were located inside coelomatic cavity, in dorsal region of abdominal cavity, with medium length and width of 7.6±1.2cm and 2.6±0.7cm at adult animals; 4.5±1.5cm and 0.9±0.4cm at young animals; and 0.8±0.3cm, and 0.2±0.1cm at chicken. The testis were recovered by the tunica albuginea and its parenchyma had seminiferous tubules composed by spermatogenic epithelium and by sustentation cells, and also interstitial tissue, with interstitial endocrine cells, connective tissue and vessels. At the adult animals were observed all the cells from spermatogenic lineage, whilst at the youngs with 3 months the seminiferous tubules had a smale lumen with spermatogonia and undifferentiated sustentacular cells. The efferents ductus were composed by a cubic ciliated epithelium, while the epididimydis duct had a columnar epithelium. The epididymis was elongated and fusiform closely to medial testis board. The deferent duct had sinuous stretch at adult animals, rectilineae at young animal, convolute at its medium portion, decreasing its sigmoid shape at caudal portion, next to cloaca. The epithelium was pseudostratified ciliated, irregular lumen at adult animal, and circular at young animal, closely with urether. The cloaca was divided into three segments: coprodeum, urodeum and proctodeum. At urodeum the deferent ducts discharged into papillas at the ventral side wall, next to fibrous phallus's insertion. The phallus was a lymphatic fibrous organ, located at ventral wall, at the cloaca floor, and was composed by two portions: one rigid forked and twisted, and another simple spiraled and flexible, which normally was inverted. In forced exposition, the phallus had 14 cm in length. In a general way the Rhea genital organs shared the morphology from others birds, mainly those described to the ostrich

Formation and stability of oil-in-water nanoemulsions containing rice bran oil: in vitro and in vivo assessments

<p>Abstract</p> <p>Background</p> <p>Nanoemulsions have practical application in a multitude of commercial areas, such as the chemical, pharmaceutical and cosmetic industries. Cosmetic industries use rice bran oil in sunscreen formulations, anti ageing products and in treatments for skin diseases. The aim of this study was to create rice bran oil nanoemulsions using low energy emulsification methods and to evaluate their physical stability, irritation potential and moisturising activity on volunteers with normal and diseased skin types.</p> <p>Results</p> <p>The nanoemulsion developed by this phase diagram method was composed of 10% rice bran oil, 10% surfactants sorbitan oleate/PEG-30 castor oil, 0.05% antioxidant and 0.50% preservatives formulated in distilled water. The nanoemulsion was stable over the time course of this study. <it>In vitro </it>assays showed that this formulation has a low irritation potential, and when applied to human skin during <it>in vivo </it>studies, the nanoemulsion improved the skin's moisture and maintained normal skin pH values.</p> <p>Conclusion</p> <p>The results of irritation potential studies and <it>in vivo </it>assessments indicate that this nanoemulsion has potential to be a useful tool to treat skin diseases, such as atopic dermatitis and psoriasis.</p

Análise das notificações de eventos adversos em um hospital privado

Introduction: patient safety, in the current context, began to be investigated in the different health fields, aiming to reduce the incidence of damages and adverse events to patients. Objective: to identify and analyze adverse events that compromise patient safety during nursing care in a private hospital. Methods: exploratory, documentary and retrospective research. The instrument of data collection was the report of adverse event notification used by the hospital composed of open and closed questions. Results: the researchers analyzed 262 reports of adverse/incident events that occurred in the period 2015 to 2016. The contributing factors for the occurrence of adverse events were caused by human failure. Of the total number of forms analyzed, 161 (61.83%) reported carelessness and distraction. The omission was highlighted with 11 (4.20%) cases. The lack of attention with the patient led to 116 (44.27%) errors in medication administration, 46 (17.56%) failures during the typing and transcription of the medical prescription and 35 (13.36%) failures in care. Conclusion: the incidents are caused by human factors, with possible reversion. When investigated, they can be minimized, which contributes to quality and safety in patient care.Introducción: La seguridad del paciente, en el contexto actual, pasó a ser investigada en los diversos campos de la salud, con el objetivo de reducir la incidencia de daños y eventos adversos a los pacientes. Objetivo: Identificar y analizar los eventos adversos que comprometen la seguridad del paciente durante la asistencia de enfermería en un hospital privado. Métodos: Investigación exploratoria, documental y retrospectiva. El instrumento de recolección de datos fue el informe de notificación de eventos adversos utilizado por el hospital compuesto por cuestiones abiertas y cerradas. Resultados: Se analizaron 262 informes de notificación de eventos adversos / incidentes que ocurrieron en el período de 2015 a 2016. Se demuestra que los factores contribuyentes para la ocurrencia de los eventos adversos fueron causados por fallo humano. Del total de formularios analizados, 161 (61,83%) indicaron descuido y distracción. La omisión se destacó con 11 (4,20%) casos. La falta de atención con el paciente propició 116 (44,27%) errores en la administración de medicamentos, 46 (17,56%) fallos durante la digitación y transcripción de la prescripción médica y 35 (13,36%) fallos en la asistencia. Conclusión: Se percibe que los incidentes son causados por factores humanos y de posible reversión. Cuando son investigados, pueden ser minimizados, lo que contribuye a la calidad y seguridad en el cuidado al paciente.Introdução: A segurança do paciente, no contexto atual, passou a ser investigada nos diversos campos da saúde, com o objetivo de reduzir a incidência de danos e eventos adversos aos pacientes. Objetivo: Identificar e analisar os eventos adversos que comprometem a segurança do paciente durante a assistência de enfermagem em um hospital privado. Métodos: Pesquisa exploratória, documental e retrospectiva. O instrumento de coleta de dados foi o relatório de notificação de eventos adversos utilizado pelo hospital composto por questões abertas e fechadas. Resultados: Analisaram-se 262 relatórios de notificação de eventos adversos/incidentes que ocorreram no período de 2015 a 2016. Demonstra-se que o fatores contribuintes para a ocorrência dos eventos adversos foram causados por falha humana. Do total de formulários analisados, 161 (61,83%) apontaram descuido e distração. A omissão se destacou com 11 (4,20%) casos. A falta de atenção com o paciente propiciou 116 (44,27%) erros na administração de medicamentos, 46 (17,56%) falhas durante a digitação e transcrição da prescrição médica e 35 (13,36%) falhas na assistência. Conclusão: Percebe-se que os incidentes são causados por fatores humanos e de possível reversão. Quando investigados, podem ser minimizados, o que contribui para a qualidade e segurança no cuidado ao paciente

A Home-Based eHealth Intervention for an Older Adult Population With Food Insecurity: Feasibility and Acceptability Study

Background: Food insecurity is a global public health challenge, affecting predominately the most vulnerable people in society, including older adults. For this population, eHealth interventions represent an opportunity for promoting healthy lifestyle habits, thus mitigating the consequences of food insecurity. However, before their widespread dissemination, it is essential to evaluate the feasibility and acceptability of these interventions among end users. Objective: This study aims to explore the feasibility and acceptability of a home-based eHealth intervention focused on improving dietary and physical activity through an interactive television (TV) app among older adults with food insecurity. Methods: A pilot noncontrolled quasi-experimental study was designed with baseline and 3-month follow-up assessments. Older adult participants with food insecurity were recruited from 17 primary health care centers in Portugal. A home-based intervention program using an interactive TV app aimed at promoting healthy lifestyle behaviors was implemented over 12 weeks. Primary outcomes were feasibility (self-reported use and interest in eHealth) and acceptability (affective attitude, burden, ethicality, perceived effectiveness, and self-efficacy), which were evaluated using a structured questionnaire with a 7-point Likert scale. Secondary outcomes were changes in food insecurity (Household Food Insecurity Scale), quality of life (European Quality of Life Questionnaire with five dimensions and three levels and Functional Assessment of Chronic Illness Therapy-Fatigue), physical function (Health Assessment Questionnaire, Elderly Mobility Scale, grip strength, and regularity of exercise), and nutritional status (adherence to the Mediterranean diet). Results: A sample of 31 older adult individuals with food insecurity was enrolled in the 12-week intervention program with no dropouts. A total of 10 participants self-reported low use of the TV app. After the intervention, participants were significantly more interested in using eHealth to improve food insecurity (baseline median 1.0, IQR 3.0; 3-month median 5.0, IQR 5.0; P=.01) and for other purposes (baseline median 1.0, IQR 2.0; 3-month median 6.0, IQR 2.0; P=.03). High levels of acceptability were found both before and after (median range 7.0-7.0, IQR 2.0-0.0 and 5.0-7.0, IQR 2.0-2.0, respectively) the intervention, with no significant changes for most constructs. Clinically, there was a reduction of 40% in food insecurity (P=.001), decreased fatigue (mean −3.82, SD 8.27; P=.02), and improved physical function (Health Assessment Questionnaire: mean −0.22, SD 0.38; P=.01; Elderly Mobility Scale: mean −1.50, SD 1.08; P=.01; regularity of exercise: baseline 10/31, 32%; 3 months 18/31, 58%; P=.02). No differences were found for the European Quality of Life Questionnaire with five dimensions and three levels, grip strength, or adherence to the Mediterranean diet. Conclusions: The home-based eHealth intervention was feasible and highly acceptable by participants, thus supporting a future full-scale trial. The intervention program not only reduced the proportion of older adults with food insecurity but also improved participants’ fatigue and physical function.publishedVersio

Hydrogel-thickened nanoemulsion with green coffee seed oil for topical delivery of vitamin A

Nanoemulsions are special emulsions that consist in a very small drop with sizes between 20 to 500 nm. When they are intended for topical application, the main problem of nanoemulsions is their low viscosity, which is reflex of the small drop size. It was proposed the attainment of hydrogel-thickned nanoemulsions with vitamin A palmitate (retinyl palmitate) with green coffee seed oil by phase inversion. Hydrogel-thickned nanoemulsions with drops size ranging between 77 to 110 nm were obtained, depending on the polymer used, with increased viscosity. Rheological profile of developed hydrogel-thickned nanoemulsions was determined, showing the influence of the kind of polymer used, here all presented pseudo-plastic behaviour, with different viscosity measurement. The improvement of the viscosity of the systems, associated with the small droplet size, can be very interesting for vitamin A delivery under the skin.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A política interna brasileira de proteção aos refugiados, apátridas e vítimas de tráfico de pessoas: o caso do COMIRAT.

The State Refugee Committees are bodies constituted with the objective of providing humanitarian assistance to migrants, especially regarding the elaboration of a state plan of policies designated to provide care for persons in situations of vulnerability, in order to guarantee the public access to public policies. In this sense, during the Human Mobility Seminar, in October 2012, the State Committee for Refugees of Rio Grande do Sul state (COMIRAT) was established in order to protect of refugees, stateless persons and victims of trafficking in persons, particularly to provide humanitarian assistance to these people. Therefore, this text seeks to point out the fundamental bases that support the construction of COMIRAT and to problematize its points of greatest merit, that is, to extend the discussion about the refuge to also the figure of the stateless person, noting the forms of action of the State in the treatment of migratory flows and the reception of the vulnerable in society.Os Comitês Estaduais de Refugiados são órgãos com o objetivo de dar assistência humanitária para migrantes, especialmente no que tange a elaboração de um plano estadual de políticas de atenção às pessoas em situações de vulnerabilidade, a fim de garantir o acesso desse público à políticas públicas. Nesse sentido, durante o seminário de Mobilidade Humana, em outubro de 2012, foi criado o Comitê Estadual de Refugiados do Estado do Rio Grande do Sul (COMIRAT) para a proteção de refugiados, apátridas e vítimas de tráfico de pessoas, notadamente para prestar assistência humanitária a estas pessoas. Em vista disso, este texto busca apontar as bases fundamentais que sustentam a construção do COMIRAT e problematizar os seus pontos de maior mérito, qual seja, o de ampliar a discussão sobre o refúgio para também a figura do apátrida, notando as formas de atuação do Estado no tratamento dos fluxos migratórios e o acolhimento de vulneráveis na sociedade