New Perspectives about Drug Candidates Targeting HTLV-1 and Related Diseases.

Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases.

Growth and Nutritional Biomarkers in Brazilian Infants with Cow's Milk Allergy at Diagnosis and 18-Month Follow-Up: A Prospective Cohort Study.

Purpose: This study aimed to describe the growth, body protein status, and micronutrient biomarkers of Brazilian infants with cow's milk allergy (CMPA) at baseline and at 18 months of follow-up in comparison with their healthy peers. Methods: Thirty infants with CMPA younger than six months of age were included in this longitudinal study, and their nutritional status was compared with that of 24 non-allergic age-matched children. Anthropometric measurements were used to assess growth, and blood and urine samples were analyzed for protein and micronutrient status. Mixed linear models adjusted for birth weight, socioeconomic status, infant feeding at baseline, weight-for-age, C-reactive protein, serum albumin, micronutrient dietary supplementation, and salt consumption were employed to evaluate the evolution of nutritional parameters throughout the follow-up period. Results: Overall, the mean age of the children at enrolment was 2.9 (standard deviation 1.7) months, and 29 children (53.7%) were male. Infants with CMPA showed a higher prevalence of functional iron depletion (transferrin saturation <20) (p=0.027), lower serum ferritin (p=0.009), and lower urinary iodine (p=0.034) levels than non-allergic children at baseline. Patients with CMPA showed a higher increment in weight-for-age and length-for-age over time than those in the control group (p<0.01). Mixed linear analyses showed a significantly lower increase in serum vitamin B12 (s-B12) (p=0.001) and urinary iodine (p<0.001) concentrations over time compared to the control group. Conclusion: Infants with CMPA on a cow's milk elimination diet had a higher weight and length at 18 months of follow-up but showed signs of inadequate iron, iodine, and B-12 vitamin status.

Programa Condicionamento Vocal e Respiratório (CVR II): nova proposta para profissionais da voz / Vocal and Respiratory Conditioning Program (CVR II): new proposal for voice professionals / Programa de Acondicionamiento Vocal y Respiratorio (CVR II): nueva propuesta para profesionales de la voz

Proposta recente de apresentação de Programa de Condicionamento Vocal e Respiratório (CVR I) incentivou a continuidade (CVR II), considerando novas estratégias de treinamento muscular vocal e respiratório que pudessem contribuir para melhor desempenho de profissionais da voz. Para a condução da ação, mais uma vez, houve a participação integrada de fonoaudiólogos e fisioterapeutas e, no papel de participantes, profissionais da voz. Planejada para dez encontros, em que dois deles (início e fim) foram destinados à coleta de dados, a proposta teve como objetivo aumentar ainda mais a resistência vocal e respiratória dos participantes, promovendo melhor rendimento profissional. Exercícios de trato vocal semiocluído e respiratórios foram realizados com o uso dos incentivadores denominados New Shaker® e Respiron Athletic 2®. Trata-se de mais uma experiência relatada na direção de convocar outros profissionais a colocarem em prática ações para o condicionamento vocal e respiratório de profissionais da voz. O uso de incentivadores respiratórios e a parceria com a Fisioterapia são apresentados e recomendados para melhor entendimento e consequente atendimento das questões da voz e da respiração. (AU)

This is a continuation (VRC II) of a recent proposal to present a Vocal and Respiratory Conditioning (VRC I) Program using new vocal and respiratory muscle training strategies aimed at contributing to a better performance of voice professionals. Once again, the initiative included the integrated participation of speech-language pathologists and physiotherapists, as well as voice professionals as participants. Ten meetings were planned in the initial proposal, with the first and last meeting focused on data collection, the proposal aimed to further increase the vocal and respiratory resistance of the participants, promoting better professional performance. Semi-occluded vocal tract and respiratory exercises were performed with using the New Shaker® and Respiron Athletic 2® boosters. This is an experience reported in order to encourage other professionals to put into practice actions for vocal and respiratory conditioning. The use of respiratory boosters and the partnership with Physiotherapy are recommended, aiming at a better understanding and consequent care of voice and breathing issues in voice professionals. (AU)

Una propuesta reciente de presentar un Programa de Acondicionamiento Vocal y Respiratório (CVR I) fomentó la continuidad (CVR II), considerando nuevas estratégias para el entrenamiento de los músculos vocales y respiratórios que podrían contribuir a un major desempeño de los profesionales de la voz. Para conducir la acción, una vez más, se contó con la participación integrada de fonoaudiológos y kinesiológos, y en el papel de participantes, profesionales de la voz. Planificada para diez encuentros, en los que dos de ellos (inicio y final) están destinados a la recolección de datos, la propuesta tiene como objetivo aumentar aún más la resistência vocal y respiratoria de los participantes, promoviendo un mejor desempeño profesional. Se realizaron ejercicios de tracto vocal y respiratorio semiocluidos con el uso de incentivos denominados New Shaker® y Respiron Athletic 2®. Esta es una experiencia más reportada en la dirección de invitar a otros profesionales a poner en práctica acciones para el acondicionamiento vocal y respiratório de los profesionales de la voz. Se presenta y recomienda el uso de soportes respiratórios y la asociación con Kinesiología para una mejor comprensión y consecuente atención de problemas de voz y respiración. (AU)

Relatos da pandemia: ser mulher e mãe em tempos de covid-19 / Pandemic reports: being a woman and mother in covid-19 times / Relatos de la pandemia: ser mujer y madre en tiempos del covid-19

Partindo da pergunta "Como tem sido ser mulher e mãe em tempos de pandemia?", o presente estudo convidou mulheres que são mães, em redes sociais virtuais, a partilhar um relato de suas experiências com a readaptação parental em função do distanciamento social causado pela pandemia de covid-19. O objetivo foi refletir sobre a experiência de ser mulher e mãe em tempos de covid-19 e distanciamento social, apontando algumas ressonâncias do cenário pandêmico na subjetividade dessas mulheres. O estudo teve como base o referencial psicanalítico, tanto na construção da pesquisa e análise dos relatos quanto na sua discussão. A análise dos cerca de 340 relatos coletados, os quais variaram de uma breve frase a longos parágrafos, apontou para uma série de questionamentos, pontos de análise e reflexões. A pandemia, e o decorrente distanciamento social, parece ter colocado uma lente de aumento sobre as angústias das mulheres que são mães, evidenciando sentimentos e sofrimentos sempre presentes. Destacaram-se, nos relatos, a sobrecarga das mulheres com as tarefas de cuidado dos filhos e da casa, a culpa, a solidão, a exaustão, e o sentimento de que não havia espaço nesse contexto para "ser mulher", sendo isso entendido especialmente a questões estéticas e de vaidade.(AU)

Starting from the question "How does it feel to be a woman and a mother in pandemic times?", this study invited women who are mothers, in virtual social networks, to share their experiences regarding parental adaptations due to social distancing caused by the COVID-19 pandemic. The objective was to reflect on the experience of being a woman and a mother in the context of COVID-19 and of social distancing, pointing out some resonances of the pandemic scenario in the subjectivity of these women. The study was based on the psychoanalytical framework, both in the construction of the research and analysis of the reports and in their discussion. The analysis of about 340 collected reports, which ranged from a brief sentence to long paragraphs, pointed to a series of questions, analysis topics, and reflections. The pandemic, and the resulting social distancing, seems to have placed a magnifying glass over the anguish of women who are mothers, showing ever-present feelings and suffering. The reports highlighted women's overload with child and house care tasks, the guilt, loneliness, exhaustion, and the feeling that there was no space in this context to "be a woman," and it extends to aesthetic and vanity related questions especially.(AU)

A partir de la pregunta "¿cómo te sientes siendo mujer y madre en tiempos de pandemia?", este estudio invitó por las redes sociales a mujeres que son madres a compartir un relato de sus experiencias sobre la readaptación parental en función del distanciamiento social causado por la pandemia del covid-19. Su objetivo fue reflexionar sobre la experiencia de ser mujer y madre en tiempos del covid-19 y el distanciamiento social, señalando algunas resonancias del escenario pandémico en la subjetividad de estas mujeres. Este estudio se basó en el marco psicoanalítico, tanto en la construcción de la investigación y análisis de los informes como en su discusión. El análisis de los casi 340 relatos, que variaron de una pequeña frase a largos párrafos, generó en las investigadoras una serie de cuestionamientos y reflexiones. La pandemia y el consecuente distanciamiento social parece haber agrandado las angustias de las mujeres que son madres, evidenciando sentimientos y sufrimientos siempre presentes. En los relatos destacan la sobrecarga de las mujeres con las tareas de cuidado de los hijos y del hogar, la culpa, la soledad, el cansancio, así como el sentimiento de que no hay espacio em este contexto para "ser mujer", relacionado principalmente a cuestiones estéticas y de vanidad.(AU)

Prevalence of intestinal parasitic infections versus knowledge, attitudes and practices of male residents in Brazilian urban slums: a cross-sectional study.

Intestinal parasitic infections (IPIs) are neglected diseases caused by helminths and protozoa, with the relationships between parasite, host and environment having the potential to produce high morbidity and incapacity to work and mortality in vulnerable areas. This study assessed the prevalence of IPIs concerning socio-environmental conditions and analyzed the knowledge, attitudes and practices related to these diseases among men living in the slums of Rio de Janeiro city, Rio de Janeiro State, Brazil. A cross-sectional study was conducted in an agglomeration of urban slums between 2018 and 2019, with men aged between 20 and 59 years. A socioeconomic status questionnaire and an IPIs knowledge, attitudes and practices questionnaire (KAPQ) were applied. Coproparasitological diagnoses (n=454) were performed using four methods and samples of water for household consumption (n=392) were subjected to microbiological and physicochemical analysis. A total of 624 participants were enrolled. About 40% of the households had "water unsuitable for consumption". Only one Major Area, MA 3 was not statistically significant for IPIs (AOR=0.75; 95% CI: 0.30-1.88; p=0.55). The overall prevalence of IPIs was 23.8%. Endolimax nana (n=65, 14.3%) and hookworm (n=8, 1.7%) were the most frequently identified parasites. The analysis of the frequency of responses to the KAPQ has shown that men reported to seeking medical care if they were suspicious of IPIs, and around 35% would self-medicate. The results have shown the need to adopt integrated health education practices targeting male residents in urban slums to qualify the care with water for human consumption and promote self-care about IPIs. The household can be considered strategic for Primary Health Care activities for men.

Production of new lipase from Preussia africana and partial characterization.

The present work aims to study the production of a new extracellular lipase from the endophytic fungus Preussia africana isolated from red lapacho tree (Handroanthus impetiginosus). Tests were carried out in order to evaluate the influence of different inducing oils (sunflower, cotton, corn, palm kernel, canola and linseed) and carbon/nitrogen ratio (C/N of 11.73, 8.63 and 7.05) on submerged fermentation aiming at optimal production of a single extracellular lipase. Results show that an optimal lipase production of 14.5 kDa has been attained after 48 h of fermentation when sunflower oil was used in the C/N ratio of 8.63 in the fermentation medium. The produced lipase showed greater activity for oils that had higher percentage of unsaturated fatty acids in their composition. Characterization was performed using a two-factor central composite rotatable design (CCRD), and the pH 6 was found to be optimal (around 28 U/mL). The temperature range studied (from 20 to 54 °C) showed no difference for the lipase catalytic activity. This is an advantage, especially when aiming at its application in reactions of industrial interest.

Prevalence of intestinal parasitic infections versus knowledge, attitudes and practices of male residents in Brazilian urban slums: a cross-sectional study

ABSTRACT Intestinal parasitic infections (IPIs) are neglected diseases caused by helminths and protozoa, with the relationships between parasite, host and environment having the potential to produce high morbidity and incapacity to work and mortality in vulnerable areas. This study assessed the prevalence of IPIs concerning socio-environmental conditions and analyzed the knowledge, attitudes and practices related to these diseases among men living in the slums of Rio de Janeiro city, Rio de Janeiro State, Brazil. A cross-sectional study was conducted in an agglomeration of urban slums between 2018 and 2019, with men aged between 20 and 59 years. A socioeconomic status questionnaire and an IPIs knowledge, attitudes and practices questionnaire (KAPQ) were applied. Coproparasitological diagnoses (n=454) were performed using four methods and samples of water for household consumption (n=392) were subjected to microbiological and physicochemical analysis. A total of 624 participants were enrolled. About 40% of the households had "water unsuitable for consumption". Only one Major Area, MA 3 was not statistically significant for IPIs (AOR=0.75; 95% CI: 0.30-1.88; p=0.55). The overall prevalence of IPIs was 23.8%. Endolimax nana (n=65, 14.3%) and hookworm (n=8, 1.7%) were the most frequently identified parasites. The analysis of the frequency of responses to the KAPQ has shown that men reported to seeking medical care if they were suspicious of IPIs, and around 35% would self-medicate. The results have shown the need to adopt integrated health education practices targeting male residents in urban slums to qualify the care with water for human consumption and promote self-care about IPIs. The household can be considered strategic for Primary Health Care activities for men.

Transcutaneous electrical nerve stimulation in speech therapy rehabilitation of voice and swallowing function in adults-a systematic review.

INTRODUCTION: In recent years, a number of clinical trials have been published comparing transcutaneous electrical nerve stimulation (TENS) and traditional speech therapy treatment of voice and swallowing functions, but results have been conflicting. OBJECTIVE: Assess the methodological quality of studies and determine whether TENS is an efficient therapeutic strategy for speech therapy treatment of healthy adults or those with dysphonia and/or dysphagia. METHODS: The databases used were Medical Literature Analysis and Retrieval System Online (MedLine), Biblioteca Virtual em Saúde (BVS), Cochrane Library and Web of Science (ISI Web of Knowledge). The study was conducted between May 2018 and January 2019, in line with Cochrane Handbook guidelines, and included studies on the use of TENS in healthy adults or those with compromised voice and/or swallowing function. RESULTS: After the search and extraction of studies, the following were identified: TENS + VOICE: 7 articles; TENS + SWALLOWING: 5 articles. The studies exhibited medium quality and are heterogeneous, making it difficult to determine their effectiveness and the parameters to be used in future research. There were no statistically significant differences between the use of TENS alone or associated with another therapeutic technique for voice. For swallowing function, one study proved better results in cases of associated techniques - TENS + traditional therapy. DISCUSSION: Speech therapy should increase the number of studies published and improve their methodological quality, reassessing methodological criteria. Current clinical practice is not grounded in evidence-based science. CLINICAL MESSAGE: the studies analyzed exhibited medium methodological quality; there are variations in the time, number and periodicity of the therapeutic sessions for TENS; there were no statistically significant differences between the use of TENS alone or associated with another therapeutic technique in voice; there were statistically significant differences between the use of TENS associated with traditional therapeutic in swallowing function.

Programa Condicionamento Vocal e Respiratório (CVR): proposta de intervenção para profissionais da voz / Vocal and Respiratory Conditioning (VRC) Program: intervention proposal for voice professional / Programa de Condicionamiento Vocal y Respiratorio (CVR): propuesta de intervención para profesionales de la voz

Programas de intervenção para profissionais da voz podem englobar estratégias de treinamento muscular vocal e respiratório. Neste tipo de abordagem, a integração de ações fonoaudiológicas e fisioterapêuticas tem produzido resultados positivos. A presente comunicação tem como objetivo apresentar uma proposta de intervenção fonoaudiológica e fisioterapêutica denominada Condicionamento Vocal e Respiratório (CVR), desenvolvida com profissionais da voz. Composta por oito encontros semanais, ela teve como objetivo aumentar a resistência vocal e respiratória dos participantes, promovendo melhor desempenho profissional. Para a fonação, foram indicados exercícios de trato vocal semiocluído com a utilização de canudos comerciais e de silicone; para a respiração, foram realizados exercícios com um incentivador a fluxo (Respiron Classic®).

Intervention program for voice professionals may cover strategies for vocal and respiratory muscle training. The integration of speech-language pathology and physiotherapeutic interventions in these approaches has resulted in positive outcomes. This communication aims to introduce a proposal for speech-language pathology and physiotherapy intervention called Vocal and Respiratory Conditioning (VRC). Developed with voice professionals and consisting of eight weekly meetings, this proposal aimed to increase the vocal and respiratory endurance of the participants, promoting better professional performance. On the one hand, semi-occluded vocal tract exercises using commercial and silicone straws were indicated for phonation; on the other hand, exercises with a flow stimulator (Respiron®) were performed for breathing.

Los programas de intervención para profesionales de la voz pueden incluir estrategias de entrenamiento de los músculos vocales y respiratorios. En este tipo de abordaje, la integración de las acciones de fonoaudiología y fisioterapia ha producido resultados positivos. Esta comunicación tiene como objetivo presentar una propuesta de intervención fonoaudiológica y fisioterapeutica denominada Condicionamiento Vocal y Respiratorio (CVR), desarrollada con profesionales de la voz. Compuesto por ocho reuniones semanales, tuvo como objetivo aumentar la resistencia vocal y respiratoria de los participantes, promoviendo un mejor desempeño profesional. Para la fonación, se indicaron ejercicios de vías vocales semicerrados utilizando canutos comerciales y de silicona; para la respiración, los ejercicios se realizaron con un estimulador de flujo (Respiron Classic®).

Extra virgin olive oil and flaxseed oil have no preventive effects on DSS-induced acute ulcerative colitis.

OBJECTIVES: The aim of this study was to evaluate the preventive effects of extra virgin olive oil (EVOO) or flaxseed oil (FO) on dextran sodium sulfate (DSS)-induced acute ulcerative colitis in female mice. METHODS: Eighty C57BL/6J mice of 8-weeks-old were divided in four groups: Control (SO), 10%EVOO, 10%FO and 5%EVOO+5%FO. The oils were given through the AIN-93M diet. After 30 days, animals were divided in four more groups, in which half received 3%DSS in water for 5 days. Body weight loss, bleeding and stool consistency were verified for the Disease Activity Index (DAI). Animals were euthanized and their colon and spleen weighted and measured. Histopathological analysis, the concentrations of TNF-α, IL-1ß, and IL-10 and the iNOS expression were evaluated in the colon samples. RESULTS: Animals that received DSS presented with elevated disease activity index values; increased colon weight-to-length ratio; augmented leukocyte infiltration into the lamina propria and submucosa; and increased production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and greater inducible nitric oxide synthase expression in the distal colon. Individually or in combination, the oils were not able to reverse or mitigate any of the DSS-induced symptoms or damage. Additionally, the group of animals treated with DSS and supplemented with FO displayed increased spleen weight-to-body weight ratio, and the group that received a combination of EVOO and FO presented increased TNF-α levels compared with the respective control group. CONCLUSION: Consumption of large amounts of EVOO and FO as a treatment for or prevention against ulcerative colitis could potentially elicit unwanted adverse effects.

Prosopis juliflora as a new cosmetic ingredient: Development and clinical evaluation of a bioactive moisturizing and anti-aging innovative solid core.

Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an α-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an α-glucan as a cosmetic ingredient.

Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats.

Deficiency of hepatic enzyme tyrosine aminotransferase characterizes the innate error of autosomal recessive disease Tyrosinemia Type II. Patients may develop neurological and developmental difficulties due to high levels of the amino acid tyrosine in the body. Mechanisms underlying the neurological dysfunction in patients are poorly known. Importantly, Tyrosinemia patients have deficient Omega-3 fatty acids (n-3 PUFA). Here, we investigated the possible neuroprotective effect of the treatment with n-3 PUFA in the alterations caused by chronic administration of L-tyrosine on important parameters of energetic metabolism and oxidative stress in the hippocampus, striatum and cerebral cortex of developing rats. Chronic administration of L-tyrosine causes a decrease in the citrate synthase (CS) activity in the hippocampus and cerebral cortex, as well as in the succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) activities, and an increase in the α-ketoglutarate dehydrogenase activity in the hippocampus. Moreover, in the striatum, L-tyrosine administration caused a decrease in the activities of CS, SDH, creatine kinase, and complexes I, II-III and IV of the mitochondrial respiratory chain. We also observed that the high levels of L-tyrosine are related to oxidative stress in the brain. Notably, supplementation of n-3 PUFA prevented the majority of the modifications caused by the chronic administration of L-tyrosine in the cerebral enzyme activities, as well as ameliorated the oxidative stress in the brain regions of rats. These results indicate a possible neuroprotective and antioxidant role for n-3 PUFA and may represent a new therapeutic approach and potential adjuvant therapy to Tyrosinemia Type II individuals.

Immobilization of Aspergillus ficuum tannase in calcium alginate beads and its application in the treatment of boldo (Peumus boldus) tea.

Tannase (tannin acyl hydrolase, E.C. 3.1.1.20) is an enzyme that catalyzes the hydrolysis of ester and depside linkages in hydrolysable tannins such as tannic acid, releasing gallic acid and glucose. It has several commercial applications in food industry, among which are gallic acid production, reduction of tannin content in fruit juices, and preparation of instantaneous tea. In this study we immobilized Aspergillus ficuum tannase in calcium alginate beads and then used it to treat boldo (Peumus boldus) tea. Such a technique allowed entrapping tannase with a 75% efficiency and appreciably increasing its thermal and pH stability compared with the free enzyme. Storage stability and reuse of the immobilized enzyme were very promising, in that about 60% of starting enzyme activity was retained after bead storage for 90 days at 4 °C or after six cycles of use. Boldo tea treatment with immobilized tannase for 120 min at 40 °C led to 31 and 60% removals of tannins and epigallocatechin gallate, an increase of about two orders of magnitude in gallic acid content, 56 and 109% increases in total flavonoids and epigallocatechin contents, a 42.8% increase in antioxidant activity and significant enhancements of tea color, clarity and pH.

Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: Reversal by cannabidiol.

Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.

Role of antioxidant treatment on DNA and lipid damage in the brain of rats subjected to a chemically induced chronic model of tyrosinemia type II.

Tyrosine levels are abnormally elevated in tissues and body fluids of patients with inborn errors of tyrosine metabolism. Tyrosinemia type II, which is caused by tyrosine aminotransferase deficiency, provokes eyes, skin, and central nervous system disturbances in affected patients. However, the mechanisms of brain damage are still poorly known. Considering that studies have demonstrated that oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia, in the present study we investigated the effects of antioxidant treatment (NAC and DFX) on DNA damage and oxidative stress markers induced by chronic administration of L-tyrosine in cerebral cortex, hippocampus, and striatum of rats. The results showed elevated levels of DNA migration, and thus DNA damage, after chronic administration of L-tyrosine in all the analyzed brain areas, and that the antioxidant treatment was able to prevent DNA damage in cerebral cortex and hippocampus. However, the co-administration of NAC plus DFX did not prevent the DNA damage in the striatum. Moreover, we found a significant increase in thiobarbituric acid-reactive substances (TBA-RS) and DCFH oxidation in cerebral cortex, as well as an increase in nitrate/nitrite levels in the hippocampus and striatum. Additionally, the antioxidant treatment was able to prevent the increase in TBA-RS levels and in nitrate/nitrite levels, but not the DCFH oxidation. In conclusion, our findings suggest that reactive oxygen and nitrogen species and oxidative stress can play a role in DNA damage in this disorder. Moreover, NAC/DFX supplementation to tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the current treatment of this disease.

Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.

Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.

Effects of Acerola (Malpighia emarginata DC.) Juice Intake on Brain Energy Metabolism of Mice Fed a Cafeteria Diet.

Obesity is a multifactorial disease that comes from an imbalance between food intake and energy expenditure. Moreover, studies have shown a relationship between mitochondrial dysfunction and obesity. In the present study, we investigated the effect of acerola juices (unripe, ripe, and industrial) and its main pharmacologically active components (vitamin C and rutin) on the activity of enzymes of energy metabolism in the brain of mice fed a palatable cafeteria diet. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into six subgroups, each of which received a different supplement for one further month (water, unripe, ripe or industrial acerola juices, vitamin C, or rutin) by gavage. Our results demonstrated that CAF diet inhibited the activity of citrate synthase in the prefrontal cortex, hippocampus, and hypothalamus. Moreover, CAF diet decreased the complex I activity in the hypothalamus, complex II in the prefrontal cortex, complex II-III in the hypothalamus, and complex IV in the posterior cortex and striatum. The activity of succinate dehydrogenase and creatine kinase was not altered by the CAF diet. However, unripe acerola juice reversed the inhibition of the citrate synthase activity in the prefrontal cortex and hypothalamus. Ripe acerola juice reversed the inhibition of citrate synthase in the hypothalamus. The industrial acerola juice reversed the inhibition of complex I activity in the hypothalamus. The other changes were not reversed by any of the tested substances. In conclusion, we suggest that alterations in energy metabolism caused by obesity can be partially reversed by ripe, unripe, and industrial acerola juice.

Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

Studies have shown that oxidative stress is involved in the pathophysiology of bipolar disorder (BD). It is suggested that omega-3 (ω3) fatty acids are fundamental to maintaining the functional integrity of the central nervous system. The animal model used in this study displayed fenproporex-induced hyperactivity, a symptom similar to manic BD. Our results showed that the administration of fenproporex, in the prevent treatment protocol, increased lipid peroxidation in the prefrontal cortex (143%), hippocampus (58%) and striatum (181%), and ω3 fatty acids alone prevented this change in the prefrontal cortex and hippocampus, whereas the co-administration of ω3 fatty acids with VPA prevented the lipoperoxidation in all analyzed brain areas, and the co-administration of ω3 fatty acids with Li prevented this increase only in the prefrontal cortex and striatum. Moreover, superoxide dismutase (SOD) activity was decreased in the striatum (54%) in the prevention treatment, and the administration of ω3 fatty acids alone or in combination with Li and VPA partially prevented this inhibition. On the other hand, in the reversal treatment protocol, the administration of fenproporex increased carbonyl content in the prefrontal cortex (25%), hippocampus (114%) and striatum (91%), and in prefrontal coxter the administration of ω3 fatty acids alone or in combination with Li and VPA reversed this change, whereas in the hippocampus and striatum only ω3 fatty acids alone or in combination with VPA reversed this effect. Additionally, the administration of fenproporex resulted in a marked increase of TBARS in the hippocampus and striatum, and ω3 fatty acids alone or in combination with Li and VPA reversed this change. Finally, fenproporex administration decreased SOD activity in the prefrontal cortex (85%), hippocampus (52%) and striatum (76%), and the ω3 fatty acids in combination with VPA reversed this change in the prefrontal cortex and striatum, while the co-administration of ω3 fatty acids with Li reversed this inhibition in the hippocampus and striatum. In conclusion, our results support other studies showing the importance of ω3 fatty acids in the brain and the potential for these fatty acids to aid in the treatment of BD.

Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L.-tyrosine.

Tyrosinemia type II is a rare autosomal recessive disease caused by deficiency of hepatic tyrosine aminotransferase and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that high concentrations of tyrosine provoke mitochondrial dysfunction and oxidative stress, in the present study we investigated the in vivo influence of antioxidants (N-acetylcysteine, NAC; and deferoxamine, DFX) administration on the inhibitory effects on parameters of energy metabolism in cerebral cortex, hippocampus and striatum of rats, provoked by chronic administration of L.-tyrosine. Our results showed that chronic administration of L.-tyrosine results in a marked decrease in the activity of citrate synthase in all the analyzed structures and succinate dehydrogenase activities in hippocampus and striatum, and that antioxidants administration can prevent this inhibition in hippocampus and striatum. Moreover, chronic administration of L.-tyrosine inhibited the activity of complex I, II-III and IV in the striatum, which can be prevented by antioxidant treatment. However, the co-administration of NAC plus DFX could not prevent the inhibition of creatine kinase activity in the striatum. In conclusion, the present study demonstrates that the administration of antioxidants NAC and DFX attenuates the L.-tyrosine effects on enzymes of the Krebs cycle and the mitochondrial respiratory chain, suggesting that impairment of energy metabolism can be involved with oxidative stress. These results also indicate a possible neuroprotective role for NAC and DFX as a potential adjuvant therapy to the patients with Tyrosinemia type II.

Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex.

Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.