Multiple metabolic signals in the CeA regulate feeding: The role of AMPK.

BACKGROUND: The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and controls energy balance. Recently, a cluster of neurons was identified as responsive to the orexigenic effect of ghrelin and fasting. However, the signaling pathway by which ghrelin and fasting induce feeding is unknown. AMP-activated protein kinase (AMPK) is a cellular energy sensor, and its Thr172 phosphorylation (AMPKThr172) in the mediobasal hypothalamus regulates food intake. However, whether the expression and activation of AMPK in CeA could be one of the intracellular signaling activated in response to ghrelin and fasting eliciting food intake is unknown. AIM: To evaluate the activation of AMPK into CeA in response to ghrelin, fasting, and 2-deoxy-D-glucose (2DG) and whether feeding accompanied these changes. In addition, to investigate whether the inhibition of AMPK into CeA could decrease food intake. METHODS: On a chow diet, eight-week-old Wistar male rats were stereotaxically implanted with a cannula in the CeA to inject several modulators of AMPKα1/2Thr172 phosphorylation, and we performed physiological and molecular assays. KEY FINDINGS: Fasting increased, and refeeding reduced AMPKThr172 in the CeA. Intra-CeA glucose injection decreased feeding, whereas injection of 2DG, a glucoprivation inductor, in the CeA, increased food intake and blood glucose, despite faint increases in AMPKThr172. Intra-CeA ghrelin injection increased food intake and AMPKThr172. To further confirm the role of AMPK in the CeA, chronic injection of Melanotan II (MTII) in CeA reduced body mass and food intake over seven days together with a slight decrease in AMPKThr172. SIGNIFICANCE: Our findings identified that AMPK might be part of the signaling machinery in the CeA, which responds to nutrients and hormones contributing to feeding control. The results can contribute to understanding the pathophysiological mechanisms of altered feeding behavior/consumption, such as binge eating of caloric-dense, palatable food.

Efeito antifúngico da vitrocerâmica derivada do biovidro 45S5 dopada com prata para modificação de superfície de resina acrílica de uso odontológico / Antifungal effect of glass-ceramic derived from 45S5 bioglass with silver for surface modification of acrylic resin for dental use

O objetivo do estudo foi sintetizar e caracterizar a resina acrílica de PMMA recoberta com vitrocerâmica derivada do biovidro 45S5 dopado com prata para uso odontológico. A vitrocerâmica foi sintetizada, dopada com prata, incorporada ao glaze e aplicado sobre a superfície de corpos de prova de PMMA com dimensões de 9 mm de diâmetro por 2 mm de espessura. O material foi caracterizado morfologica por Microscopia eletrônica de varredura (MEV-FEG) e química por Difratometria de raios X (DRX), Espectroscopia de raios x por Dispersão de energia (EDS), Espectroscopia de infravermelho por transformada de Fourier (FTIR) e os seus efeitos sobre a formação de biofilmes de Candida albicans foram avaliados, assim como a sua citotoxicidade para células de queratinócitos orais de linhagem NOK. Os resultados foram analisados estatisticamente por testes apropriados (One-way ANOVA e Tukey), adotando-se o nível de significância de 5%. A vitrocerâmica apresentou efeito antifúngico sobre Candida albicans, no entanto, esta propriedade não é mantida quando incorporada ao glaze para modificação de superfície do PMMA (AU)

The aim of the study was to synthesize and characterize PMMA acrylic resin coated with 45S5 bioactive glass-derived vitroceramic doped with silver for dental use. The vitroceramic was synthesized, silver-doped, incorporated into the glaze, and applied onto the surface of PMMA test specimens measuring 9 mm in diameter by 2 mm in thickness. The material was morphologically characterized by Scanning Electron Microscopy (SEM-FEG). and chemically characterized by X-ray Diffraction (XRD), Energy-Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and. Its effects on Candida albicans biofilm formation were evaluated, as well as its cytotoxicity to oral keratinocyte cells of NOK lineage. The results were statistically analyzed using appropriate tests (One-way ANOVA and Tukey), adopting a significance level of 5%. The vitroceramic showed antifungal effect against Candida albicans; however, this property is not maintained when incorporated into the glaze for PMMA surface modification(AU)

Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota.

Introduction: The timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition. Methods: Unexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders. Results: PM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring's gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders. Discussion: Our data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.

Obesity increases blood-brain barrier permeability and aggravates the mouse model of multiple sclerosis.

Obesity-induced insulin resistance (OIR) has been associated with an increased prevalence of neurodegenerative disorders such as multiple sclerosis. Obesity results in increased blood-brain barrier (BBB) permeability, specifically in the hypothalamic regions associated with the control of caloric intake. In obesity, the chronic state of low-grade inflammation has been implicated in several chronic autoimmune inflammatory disorders. However, the mechanisms that connect the inflammatory profile of obesity with the severity of experimental autoimmune encephalomyelitis (EAE) are poorly defined. In this study, we show that obese mice are more susceptible to EAE, presenting a worse clinical score with more severe pathological changes in the spinal cord when compared with control mice. Analysis of immune infiltrates at the peak of the disease shows that high-fat diet (HFD)- and control (chow)-fed groups do not present any difference in innate or adaptive immune cell compartments, indicating the increased severity occurs prior to disease onset. In the setting of worsening EAE in HFD-fed mice, we observed spinal cord lesions in myelinated regions and (blood brain barrier) BBB disruption. We also found higher levels of pro-inflammatory monocytes, macrophages, and IFN-γ+CD4+ T cells in the HFD-fed group compared to chow-fed animals. Altogether, our results indicate that OIR promotes BBB disruption, allowing the infiltration of monocytes/macrophages and activation of resident microglia, ultimately promoting CNS inflammation and exacerbation of EAE.

Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies.

RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses.

Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury.

Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation.

Aplicação e segurança da aromaterapia durante o tratamento oncológico: scoping review / Application and safety of aromatherapy during cancer treatment: scoping review

Resumo: Pesquisa desenvolvida em programa de mestrado acadêmico em enfermagem, da Universidade Federal do Paraná, na Linha de Pesquisa Tecnologia e Inovação para Cuidar em Saúde e Enfermagem. A iniciativa partiu da realidade de que as doenças crônicas como o câncer, apresentam projeções de incidência crescente para os próximos triênios, segundo o Instituto Nacional do Câncer. Na trajetória do tratamento, devem ser disponibilizadas informações pertinentes incluindo as práticas integrativas e complementares, baseadas em evidências para guiar os familiares, profissionais de saúde, e especialmente a equipe de enfermagem. Esta pesquisa inova ao atender a necessidade em reunir e dispor sistematicamente, as características relacionadas aos métodos de escolha, aplicação e segurança da aromaterapia para indivíduos em tratamento oncológico. Objetivo foi mapear as evidências, dos últimos 20 anos, relativas à aromaterapia durante o tratamento oncológico para adultos com câncer, quanto a sua aplicação e medidas de segurança. O método adotado foi a Scoping Review, segundo as diretrizes JBI®. Incluídos 296 estudos, publicados entre Setembro / 2021 a Outubro / 2022, resgatados nas bases de dados: Cochrane Library; EMBASE; CINAHL; PubMed; Scopus; LILACS e Web of Science. E, 328 evidências em literatura cinzenta disponíveis na Open Acess Theses and Dissertations, TROVE Austrália e ProQuest. Os critérios de inclusão foram estudos com adultos (> 18 anos), diagnosticados com câncer, submetidos à alguma modalidade de tratamento neoadjuvante ou adjuvante, como cirurgia, quimioterapia, radioterapia, imunoterapia ou hormonioterapia; e, que recebiam, de forma complementar, a aromaterapia inalatória ou tópica em cenário hospitalar, ou ambulatorial. A triagem e seleção dos estudos se deu por dois revisores independentes, com auxílio online do Rayyan. Excluídos estudos: conduzidos em cuidados paliativos; com população com diagnóstico de metástase; com gestantes; e, que incluíssem outra modalidade de prática complementar - isolada ou em associação à aromaterapia -; e, experimentos in vitro. A amostra final foi de 25 estudos. As pesquisas foram predominantes em países orientais, publicadas em revistas dos Estados Unidos da América; o método prevalente foi de Ensaio Clínico Randomizado, com média amostral de 103 participantes. O diagnóstico recordista foi de câncer de mama, e a utilização da aromaterapia ocorreu, mais frequentemente, na forma inalatória, utilizando os óleos essenciais de Lavanda (Lavandula angustifólia) e Menta (Menta x piperita), para redução da ansiedade, náusea ou vômitos induzidos pela quimioterapia. Para a segurança na aplicação da aromaterapia enfatizaram-se os cuidados com a seleção dos participantes, o armazenamento e a garantia de qualidade dos óleos essenciais utilizados. Nenhum efeito colateral grave ou toxicidade foram reportados pelas pesquisas e, concluiu-se que seu uso apresenta potencial benefício para manejo de sintomas físicos, emocionais e psicológicos, para adultos com câncer, durante o tratamento oncológico. A execução do estudo favoreceu a apropriação das evidências para desenvolvimento de novas pesquisas clínicas, o que potencialmente pode resultar em oferta de uma assistência complementar, centrada no indivíduo, versátil e segura para manejo de sintomas provocados pelo uso da quimioterapia, radioterapia, imunoterapia ou hormonioterapia por meio da aromaterapia. Sugere-se novos estudos clínicos, com maior rigor metodológico quanto aos dados de aplicação e segurança da aromaterapia.

Abstract: Research developed in the academic master's program in nursing, at the Federal University of Paraná, in the Technology and Innovation Research Line for Health Care and Nursing. The initiative was based on the fact that chronic diseases such as cancer are projected to increase in incidence over the next three years, according to the National Cancer Institute. In the course of treatment, relevant information should be made available, including integrative and complementary practices, based on evidence to guide family members, health professionals, and especially the nursing team. This research innovates by meeting the need to systematically gather and arrange the characteristics related to the methods of choice, application and safety of aromatherapy for individuals undergoing cancer treatment. The objective was to map the evidence, from the last 20 years, regarding aromatherapy during oncological treatment for adults with cancer, regarding its application and safety measures. The method adopted was the Scoping Review, according to the JBI® guidelines. Included 296 studies, published between September/2021 to October/2022, retrieved from the databases: Cochrane Library; BASE; CINAHL; PubMed; Scopus; LILACS and Web of Science. And, 328 gray literature evidence available from Open Access Theses and Dissertations, TROVE Australia, and ProQuest. Inclusion criteria were studies with adults (> 18 years old), diagnosed with cancer, undergoing some form of neoadjuvant or adjuvant treatment, such as surgery, chemotherapy, radiotherapy, immunotherapy or hormone therapy; and, who received, in a complementary way, inhaled or topical aromatherapy in a hospital or outpatient setting. The screening and selection of studies was carried out by two independent reviewers, with online help from Rayyan. Excluded studies: conducted in palliative care; with population diagnosed with metastasis; with pregnant women; and, which included another modality of complementary practice - alone or in association with aromatherapy -; and, in vitro experiments. The final sample consisted of 25 studies. The surveys were predominant in eastern countries, published in journals in the United States of America; the prevalent method was the Randomized Clinical Trial, with a sample mean of 103 participants. The record-breaking diagnosis was breast cancer, and the use of aromatherapy occurred, more frequently, in the inhaled form, using the essential oils of Lavender (Lavandula angustifolia) and Peppermint (Menta x piperita), to reduce anxiety, nausea or induced vomiting. by chemotherapy. For safety in the application of aromatherapy, care was taken with the selection of participants, storage and quality assurance of the essential oils used. No serious side effects or toxicity were reported by research, and it was concluded that its use has potential benefit for managing physical, emotional and psychological symptoms for adults with cancer during cancer treatment. The execution of the study favored the appropriation of evidence for the development of new clinical research, which can potentially result in the provision of complementary, individual-centered, versatile and safe assistance for the management of symptoms caused by the use of chemotherapy, radiotherapy, immunotherapy or hormone therapy through aromatherapy. New clinical studies are suggested, with greater methodological rigor regarding data on the application and safety of aromatherapy.

Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity.

Obesity is a major concern for global health care systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production of cytokines, glycolytic rates, and morphological and functional changes in the mitochondria through an mTORC2-dependent, mTORC1-independent mechanism. Leptin also boosts the effects of IL-4 in macrophages, leading to increased oxygen consumption, expression of macrophage markers associated with a tissue repair phenotype, and wound healing. In vivo, hyperleptinemia caused by diet-induced obesity increases the inflammatory response by macrophages. Deletion of leptin receptor and subsequently of leptin signaling in myeloid cells (ObR-/-) is sufficient to improve insulin resistance in obese mice and decrease systemic inflammation. Our results indicate that leptin acts as a systemic nutritional checkpoint to regulate macrophage fitness and contributes to obesity-induced inflammation and insulin resistance. Thus, specific interventions aimed at downstream modulators of leptin signaling may represent new therapeutic targets to treat obesity-induced systemic inflammation.

Immunometabolic regulation of adipose tissue resident immune cells.

Adipose tissue (AT) performs immunoregulatory functions beyond fat storage. In addition to adipocytes, AT has a diverse spectrum of resident and infiltrating immune cells in health and disease. Immune cells contribute to the homeostatic function of AT by adapting their metabolism in accordance with the microenvironment. However, how the metabolic reprogramming of immune cells affects their inflammatory profile and the subsequent implication for adipocyte function is not completely elucidated. Here, we discuss the available data on metabolic regulatory processes implicated in the control of adipose tissue-resident immune cells and their crosstalk with adipocytes.

Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.

A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 µm (PM2.5) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding. Compared to the filtered air group (FA), one-day-exposure-PM2.5 did not affect adiposity. However, five-days-exposure-PM2.5 increased hypothalamic microglia density, toll-like-receptor-4 (Tlr4), and the inhibitor-NF-kappa-B-kinase-epsilon (Ikbke) expression. Concurrently, fat mass, food intake (FI), and ucp1 expression in brown adipose tissue were also increased. Besides, decreased hypothalamic STAT3-phosphorylation and Pomc expression were found after twelve-weeks-exposure-PM2.5. These were accompanied by increased FI and lower energy expenditure (EE), leading to obesity, along with increased leptin and insulin levels and HOMA. Mechanistically, the deletion of Tlr4 or knockdown of the Ikbke gene in the hypothalamus was sufficient to reverse the metabolic outcomes of twelve-weeks-exposure-PM2.5. These data demonstrated that short-term exposure-PM2.5 increases hypothalamic inflammation, similar to a HFD. Long-term exposure-PM2.5 is even worse, leading to leptin resistance, hyperphagia, and decreased EE. These effects are most likely due to chronic hypothalamic inflammation, which is regulated by Tlr4 and Ikbke signaling.

Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

OBJECTIVE: Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. RESULTS: Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. CONCLUSIONS: Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders.

A regulação da proteína quinase ativada pelo AMP (AMPK) no CeA e os efeitos sobre o controle da ingestão alimentar e gasto energético / Regulation of AMP-activated protein kinase (AMPK) in the CeA and the effects on food intake control and energy expenditure

Resumo: A AMP-activated protein kinase (AMPK) regula o balanço energético por ações no hipotálamo. Sua ativação está ligada ao aumento da ingestão alimentar e sua inibição leva a redução da ingestão alimentar. Recentes evidências demonstram que outras regiões do sistema nervoso podem contribuir para o controle da ingestão alimentar. O núcleo central da amígdala (CeA) é parte integrante do sistema dopaminérgico de recompensa e juntamente com o hipotálamo participa do controle da homeostase energética. Na amígdala vias moleculares como a via da insulina participam do controle da ingestão alimentar, contudo ainda não foi avaliado se a AMPK poderia contribuir com esse controle. Em vista disso, o presente estudo avaliou a possível fosforilação da AMPK no CeA e sua participação no controle da ingestão alimentar em resposta a diversas situações. A AMPK estava expressa no CeA. O jejum aumentou a fosforilação em treonina da AMPK?1/2Thr172 e a realimentação reduziu essa fosforilação. A injeção de glicose no CeA diminuiu a fosforilação em AMPK?1/2Thr172, ao passo que, a injeção de 2DG aumentou essa fosforilação, assim como a ingestão alimentar. A injeção de grelina no CeA aumentou a ingestão alimentar e a fosforilação em AMPK?1/2Thr172. Esse resultado foi acompanhado pelo aumento da expressão gênica do NPY e redução de ocitocina. Em contrapartida, a insulina reduziu a fosforilação em AMPK?1/2Thr172 no CeA. A ativação farmacológica da AMPK no CeA, com AICAR, aumentou a ingestão como esperado. A infusão crônica de MTII reduziu a massa corporal, a ingestão e a fosforilação em AMPK?1/2Thr172 no CeA. O tratamento por 14 dias com siRNA-AMPK?2 no CeA, inibiu a expressão gênica da AMPK e reduziu a massa corporal. Essa redução foi acompanhada de aumento na expressão gênica de UCP1 no tecido adiposo marrom sem alteração na ingestão alimentar. Em adição, houve redução na expressão gênica de NPY e aumento de ocitocina no CeA. Esses resultados sugerem que a ativação da AMPK no CeA, participa do controle da homeostase energética por modular a ingestão alimentar em reposta a ação de nutrientes e hormônios como grelina e insulina(AU)

Abstract: AMP-activated protein kinase (AMPK) is a cellular energy sensor that regulates energy balance at cellular and whole body nivel. Several studies demonstrate that hypothalamic AMPK participates in the control of food intake in response to nutrients and hormones such as insulin and ghrelin. Increased AMPK activity in hypothalamus is associated with enhance in food intake and its inhibition leads to reduced food intake. Recent evidence demonstrates that other regions from central nervous system may contribute to control energy metabolism and food intake. The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and jointly with the hypothalamus participates in control of food intake. In amygdala molecular pathways such as insulin pathway participate in the control of food intake, however other cellular pathways, such as AMPK may contribute to this control. In this sense, the present study investigated AMPK activation in CeA and its participation in food intake control. Fasting increased phosphorylation in Thr172 of AMPK?1/2 and refeeding reduced this phosphorylation. Injection of glucose in CeA decreased the phosphorylation in Thr172 of AMPK?1/2, whereas 2DG injection increased this phosphorylation as well as food intake. Ghrelin injection in CeA increased food intake and Thr172 phosphorylation of AMPK?1/2. In adiction, NPY gene expression was increased and oxytocin gene expression was lower. In contrast, insulin reduced Thr172 phosphorylation of AMPK?1/2 in CeA. As expected, AMPK pharmacological activation in CeA with AICAR increased food intake. Chronic injection of MTII in CeA reduced body mass, food intake and phosphorylation in Thr172 of AMPK?1/2. Further, knocking down Alpha 1/2 AMPK in the CeA for 14 days was sufficient to decrease body mass without altering food intake. AMPK?2 and NPY gene expression in CeA was reduced and oxytocin gene expression in CeA and UCP-1 in BAT was increased. These results suggest that once active in CeA, AMPK participates in control of energy homeostasis by modulating food intake in response to nutrients and hormones such as ghrelin and insulin(AU)

[Quality of life domains affected in women with breast cancer]. / Os domínios afetados na qualidade de vida de mulheres com neoplasia mamária.

OBJECTIVE: This study aimed to investigate the quality of life of women suffering from breast cancer undergoing chemotherapy in public and private health care systems. METHOD: It is an observational, prospective study with 64 women suffering from breast cancer. Data was collected with two instruments: Quality of Life Questionnaire C30 and Breast Cancer Module BR23. By applying Mann Whitney and Friedman's statistical tests, p values < 0.05 were considered statistically significant. RESULTS: The significant results in public health care systems were: physical functions, pain symptom, body image, systemic effects and outlook for the future. In private health care systems, the results were sexual, social functions and body image. Women's quality of life was harmed by chemotherapy in both institutions. CONCLUSION: The quality of life of women has been harmed as a result of the chemotherapy treatment in both institutions, but in different domains, indicating the type of nursing care that should be provided according to the characteristics of each group.

Quality of life domains affected in women with breast cancer / Los dominios afectados en la calidad de vida de mujeres con neoplasia mamaria / Os domínios afetados na qualidade de vida de mulheres com neoplasia mamária

OBJECTIVE: This study aimed to investigate the quality of life of women suffering from breast cancer undergoing chemotherapy in public and private health care systems. METHOD: It is an observational, prospective study with 64 women suffering from breast cancer. Data was collected with two instruments: Quality of Life Questionnaire C30 and Breast Cancer Module BR23. By applying Mann Whitney and Friedman's statistical tests, p values < 0.05 were considered statistically significant. RESULTS: The significant results in public health care systems were: physical functions, pain symptom, body image, systemic effects and outlook for the future. In private health care systems, the results were sexual, social functions and body image. Women's quality of life was harmed by chemotherapy in both institutions. CONCLUSION: The quality of life of women has been harmed as a result of the chemotherapy treatment in both institutions, but in different domains, indicating the type of nursing care that should be provided according to the characteristics of each group. .

OBJETIVO: Se objetivó investigar la calidad de vida de las mujeres con neoplasia mamaria sometidas a quimioterapia, en el seguro médico público y privado. MÉTODO: Se trata de un estudio observacional, de cohorte, prospectivo, realizado con 64 mujeres con neoplasia mamaria. Los datos fueron recolectados mediante dos instrumentos Quality of Life Questionnaire C30 y Breast Cancer Module BR23. Para el análisis los datos se utilizaron pruebas estadísticas de Mann Whitney y Friedman, con valores estadísticamente significativas para p <005. RESULTADOS: Fueron verificadas diferencias estadísticamente significativas en el seguro médico público: la función física, síntoma dolor, la imagen corporal, los efectos sistémicos en las perspectivas de futuro, en el seguro médico privado fueron la función sexual, la imagen social y el cuerpo. CONCLUSIÓN: La calidad de vida de las mujeres se ha visto comprometida como consecuencia de la quimioterapia en ambas instituciones, pero en diferentes dominios que subsidia la atención de enfermería dirigida según las características de cada grupo. .

OBJETIVO: O objetivo deste estudo foi investigar a qualidade de vida das mulheres com neoplasia mamária submetidas à quimioterapia nos convênios público e privado. MÉTODO: Trata-se de estudo observacional, de coorte prospectivo, realizado com 64 mulheres portadoras de neoplasia mamária. Os dados foram coletados com a utilização dos instrumentos Quality of Life Questionnaire C30 e Breast Cancer Module BR23. Para análise dos dados, foram utilizados os testes estatísticos de Mann Whitney e Friedman, com valores estatisticamente significantes para p<005. RESULTADOS: Os resultados significantes no convênio público foram: função física, dor, imagem corporal, efeitos sistêmicos e perspectivas futuras. No convênio privado, foram: função sexual, social e imagem corporal. CONCLUSÃO: A qualidade de vida das mulheres foi comprometida em decorrência do tratamento quimioterápico em ambas as instituições, porém em domínios diferentes, o que subsidia um cuidado de enfermagem direcionado de acordo com as características de cada grupo. .

IKKε is key to induction of insulin resistance in the hypothalamus, and its inhibition reverses obesity.

IKK epsilon (IKKε) is induced by the activation of nuclear factor-κB (NF-κB). Whole-body IKKε knockout mice on a high-fat diet (HFD) were protected from insulin resistance and showed altered energy balance. We demonstrate that IKKε is expressed in neurons and is upregulated in the hypothalamus of obese mice, contributing to insulin and leptin resistance. Blocking IKKε in the hypothalamus of obese mice with CAYMAN10576 or small interfering RNA decreased NF-κB activation in this tissue, relieving the inflammatory environment. Inhibition of IKKε activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus. These improvements were independent of body weight and food intake. Increased insulin and leptin action/signaling in the hypothalamus may contribute to a decrease in adiposity and hypophagia and an enhancement of energy expenditure accompanied by lower NPY and increased POMC mRNA levels. Improvement of hypothalamic insulin action decreases fasting glycemia, glycemia after pyruvate injection, and PEPCK protein expression in the liver of HFD-fed and db/db mice, suggesting a reduction in hepatic glucose production. We suggest that IKKε may be a key inflammatory mediator in the hypothalamus of obese mice, and its hypothalamic inhibition improves energy and glucose metabolism.

Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats.

Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala.

A refletindo sobre a vida e a morte / Reflecting on life and death

O presente artigo tem como objetivo refletir sobre a vida e a morte. Levanta questões sobre as diferenças entre estes dois conceitos e amplia a discussão para uma visão mais abrangente destes fenômenos, baseada na abordagem reichiana e na de outros autores. Ao aplicarmos o enfoque proposto por Reich do princípio do funcionamento comum, podemos lançar um olhar que vá além da simples dicotomia vida X morte, buscando a unidade subjacente, o entrelaçamento e a interdependência entre os dois. (AU)

The present article aims at reflecting on life and death. It raises questions about the differences between these two concepts and broadens the discussion to a wider view about these phenomena, based on the approach developed by Wilhelm Reich and other authors. By applying the concept proposed by Reich of the common functioning principle to life and death, we can look farther than a simple dichotomy, searching for the underlying unity, intertwining and interdependence between both. (AU)

Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles.

This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA-STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.

Novel vesicular and particulate drug delivery systems for topical treatment of acne.

BACKGROUND: The efficacy of the antiacne topical drugs is well established. The local side effects, however, mainly cutaneous irritation, erythema, dryness, peeling and scaling, remain major problems. Novel vesicular and particulate drug delivery systems have been proposed to reduce the side effects of drugs commonly used in the topical treatment of acne. OBJECTIVE: This review focuses on the development and evaluation of antiacne drug-loaded vesicular and particulate delivery systems (liposomes, polymeric microspheres and solid lipid nanoparticles) for topical treatment, their advantages and challenges. METHODS: All the literature available was reviewed to highlight the potential of these novel systems for the topical treatment of acne. CONCLUSION: The encapsulation of antiacne drugs in vesicular and particulate delivery systems represents an innovative alternative to minimize side effects, while preserving their efficacy. This can be obtained by the capacity of these systems to provide controlled release or to improve the drug penetration into skin or even into the pilosebaceous unit.

Development of a new solid lipid nanoparticle formulation containing retinoic acid for topical treatment of acne.

The development of solid lipid nanoparticles (SLN) containing all-trans retinoic acid (RA) is an interesting approach to topical treatment of acne. SLN has potential for controlled release and follicular penetration, which can reduce adverse effects in comparison with conventional formulations. However, the encapsulation efficiency (EE) of RA in SLN is usually low, unless a high surfactant/lipid ratio is used. The aim of this work was to develop SLN with high EE using a low surfactant/lipid ratio. Different formulations of RA-loaded SLN were prepared using glyceryl behenate as lipid matrix. The particle size, EE, zeta potential and differential scanning calorimetry (DSC) were investigated. High EE in SLN was obtained with addition of amines. These results indicate that the utilization of amines is an interesting approach to improve the EE of RA in SLN using a low surfactant/lipid ratio.