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1.
Front Pharmacol ; 14: 1188829, 2023.
Article in English | MEDLINE | ID: mdl-37456758

ABSTRACT

NLRP3 inflammasome has a key role in chronic low-grade metabolic inflammation, and its excessive activation may contribute to the beginning and progression of several diseases, including hepatic insulin resistance (hIR). Thus, this review aims to highlight the role of NLRP3 inflammasome and oxidative stress in the development of hIR and evidence related to phytochemical intervention in this context. In this review, we will address the hIR pathogenesis related to reactive oxygen species (ROS) production mechanisms, involving oxidized mitochondrial DNA (ox-mtDNA) and thioredoxin interacting protein (TXNIP) induction in the NLRP3 inflammasome activation. Moreover, we discuss the inhibitory effect of bioactive compounds on the insulin signaling pathway, and the role of microRNAs (miRNAs) in the phytochemical target mechanism in ameliorating hIR. Although most of the research in the field has been focused on evaluating the inhibitory effect of phytochemicals on the NLRP3 inflammasome pathway, further investigation and clinical studies are required to provide insights into the mechanisms of action, and, thus, encourage the use of these bioactive compounds as an additional therapeutic strategy to improve hIR and correlated conditions.

4.
Enferm. foco (Brasília) ; 14: 1-6, mar. 20, 2023. ilus
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1525291

ABSTRACT

Objetivo: Descrever a atuação da Câmara Técnica de Atenção à Saúde do Conselho Federal de Enfermagem, na elaboração de normas e atualização do conhecimento técnico-científico da profissão. Métodos: Trata-se de um estudo teórico-reflexivo, desenvolvido a partir do conhecimento e das experiências, acadêmicas e profissionais dos autores sobre atuação e contribuição da Câmara Técnica de Atenção à Saúde, na assessoria aos questionamentos dos profissionais de enfermagem, desenvolvendo estudos que possam inferir na mudança comportamental ou evolução das técnicas desenvolvidas pelos profissionais. Resultados: Aponta a atuação da Câmara Técnica de Atenção à Saúde como espaço de discussão, de construção formal e de atualização da ciência enfermagem, frente às realidades vivenciadas pelos profissionais no campo da prática, sobre o seu cenário de exercício profissional de novas condutas, bem como a reflexão sobre possíveis posicionamentos técnicos da profissão. Conclusão: A Câmara Técnica de Atenção à Saúde atua de forma democrática, ética, técnico-científica e legal, apoiando todos os Conselhos Regionais de Enfermagem e profissionais de enfermagem que tenham suas demandas voltadas para a atenção à saúde, oferecendo resultados com qualidade e garantindo provimentos, instruções, elaboração e execução de normativas que tratam de inovação e uniformidade de procedimentos para o exercício da Enfermagem no Brasil. (AU)


Objective: To describe the work of the Federal Nursing Council's Technical Chamber for Health Care in drawing up standards and updating the profession's technical and scientific knowledge. Methods: This is a theoretical-reflective study, based on the authors' academic and professional knowledge and experience of the work and contribution of the Technical Board of Health Care in advising nursing professionals on their questions, developing studies that could lead to behavioral changes or the evolution of techniques developed by professionals. Results: It points to the work of the Technical Chamber for Health Care as a space for discussion, formal construction and updating of nursing science, in the face of the realities experienced by professionals in the field of practice, about their professional practice scenario of new behaviors, as well as reflection on possible technical positions of the profession. Conclusion: The Technical Chamber for Health Care acts in a democratic, ethical, technical-scientific and legal manner, supporting all the Regional Nursing Councils and nursing professionals whose demands are focused on health care, offering quality results and guaranteeing provisions, instructions, preparation and implementation of regulations that deal with innovation and uniformity of procedures for the practice of nursing in Brazil. (AU)


Objetivo: Describir el trabajo de la Cámara Técnica de Cuidados de Salud del Consejo Federal de Enfermería en la elaboración de normas y actualización de los conocimientos técnico-científicos de la profesión. Métodos: Se trata de un estudio teórico-reflexivo, basado en el conocimiento y la experiencia académica y profesional de los autores sobre el trabajo y la contribución de la Cámara Técnica de Cuidados de Salud, en el asesoramiento a los profesionales de enfermería en sus cuestiones, en el desarrollo de estudios que puedan conducir a cambios de comportamiento o en la evolución de las técnicas desarrolladas por los profesionales. Resultados: Se señala el trabajo de la Cámara Técnica para el Cuidado de la Salud como un espacio de discusión, construcción formal y actualización de la ciencia de la enfermería, frente a las realidades vividas por los profesionales en el campo de la práctica, sobre su práctica profesional escenario de nuevos comportamientos, así como la reflexión sobre posibles posiciones técnicas de la profesión. Conclusión: La Cámara Técnica de Atención a la Salud actúa de forma democrática, ética, técnico-científica y jurídica, apoyando a todos los Consejos Regionales de Enfermería y a los profesionales de enfermería cuyas demandas se centran en la atención a la salud, ofreciendo resultados de calidad y garantizando disposiciones, instrucciones, redacción e implementación de reglamentos que se ocupan de la innovación y la uniformidad de los procedimientos para la práctica de la enfermería en Brasil. (AU)


Subject(s)
Professional Practice , Nursing , Delivery of Health Care
5.
Eur Heart J Case Rep ; 7(2): ytad044, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36819889

ABSTRACT

Background: TANGO2-related metabolic encephalopathy and arrhythmia are a rare, newly recognized, and likely under-diagnosed condition. First described in 2016, it is characterized by developmental delay and recurrent metabolic crisis. During these episodes, patients may present QTc prolongation and ventricular arrhythmias. Case summary: A 13-year-old female, with developmental delay, presented with severe rhabdomyolysis and an initially normal electrocardiogram (ECG). Due to the worsening of rhabdomyolysis, QTc prolongation was identified (QTc 570 ms) and oral ß-blocker therapy started. A non-sustained ventricular tachycardia developed, initially managed with magnesium and lidocaine. After a short period, an arrhythmic storm of polymorphic ventricular extrasystoles induced Torsade de Pointes (TdP) was triggered. A temporary percutaneous pacing lead was placed and esmolol infusion started. The electrical instability ran in parallel with the increasing severity of rhabdomyolysis and systolic ventricular function decline. Genetic testing identified a pathogenic variant in homozygosity in the TANGO2 gene. A stable sinus rhythm was achieved with metabolic and serum electrolytes optimization. ECG showed normalization of the QTc interval. Discussion: The full TANGO2-related phenotype emerges over time and the prognosis is linked to the appearance of ECG abnormalities. QT interval prolongation can lead to life-threatening ventricular tachycardias. The arrhythmia mechanism seems to be secondary to metabolite build-up in cardiomyocytes, which can explain the cardiac phenotype during the crisis which subsides after their resolution. In these patients, avoiding bradycardia is fundamental, since long QT-related TdP seems to be triggered by bradycardia and short-long-short ventricular premature beats (VPB). During an acute metabolic crisis, the management of arrhythmias relies on metabolic control.

6.
Cureus ; 15(12): e49779, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38161557

ABSTRACT

Prostate cancer is the second-most common malignancy in males. Despite more frequently metastasizing to the bone, regional lymph nodes, and liver, the brain can also be affected. These metastases can simulate meningiomas, making the diagnosis more difficult. Here, we report the case of a 62-year-old male with a sudden onset of confusion and dysarthria with spontaneous resolution but amnesia for the event. On a neurological exam, the patient had left exophthalmos and palpebral ptosis. He was referred to the emergency room, where he underwent a cranioencephalic CT, which revealed a left anterior temporal lesion with adjacent edema suggestive of meningioma, later confirmed by an MRI. Due to the worsening of the symptoms and an increase in the size of the lesion, total resection was proposed. The anatomopathological study revealed a poorly differentiated carcinoma. To study the primary tumor, a CT of the thorax, abdomen, and pelvis; a spine MRI; and a complementary study with prostate-specific antigen were requested. These studies revealed a prostate adenocarcinoma with brain and bone metastases. After the diagnosis, the patient underwent hormone therapy, chemotherapy, and palliative radiotherapy.

7.
Arch Physiol Biochem ; : 1-15, 2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36328030

ABSTRACT

CONTEXT: The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated. OBJECTIVE: To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks. METHODS: We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120 mg/kg/day or 240 mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1α levels. RESULTS: Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity in vitro. In vivo, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase. CONCLUSIONS: These results suggest that silymarin reduces worsening of NAFLD.

8.
Mol Metab ; 60: 101492, 2022 06.
Article in English | MEDLINE | ID: mdl-35390501

ABSTRACT

OBJECTIVE: Although it is well established that urocortin 2 (Ucn2), a peptide member of the corticotrophin releasing factor (CRF) family, and its specific corticotrophin-releasing factor 2 receptor (CRF2R) are highly expressed in skeletal muscle, the role of this peptide in the regulation of skeletal muscle mass and protein metabolism remains elusive. METHODS: To elucidate the mechanisms how Ucn2 directly controls protein metabolism in skeletal muscles of normal mice, we carried out genetic tools, physiological and molecular analyses of muscles in vivo and in vitro. RESULTS: Here, we demonstrated that Ucn2 overexpression activated cAMP signaling and promoted an expressive muscle hypertrophy associated with higher rates of protein synthesis and activation of Akt/mTOR and ERK1/2 signaling pathways. Furthermore, Ucn2 induced a decrease in mRNA levels of atrogin-1 and in autophagic flux inferred by an increase in the protein content of LC3-I, LC3-II and p62. Accordingly, Ucn2 reduced both the transcriptional activity of FoxO in vivo and the overall protein degradation in vitro through an inhibition of lysosomal proteolytic activity. In addition, we demonstrated that Ucn2 induced a fast-to-slow fiber type shift and improved fatigue muscle resistance, an effect that was completely blocked in muscles co-transfected with mitogen-activated protein kinase phosphatase 1 (MKP-1), but not with dominant-negative Akt mutant (Aktmt). CONCLUSIONS: These data suggest that Ucn2 triggers an anabolic and anti-catabolic response in skeletal muscle of normal mice probably through the activation of cAMP cascade and participation of Akt and ERK1/2 signaling. These findings open new perspectives in the development of therapeutic strategies to cope with the loss of muscle mass.


Subject(s)
Corticotropin-Releasing Hormone/metabolism , Proto-Oncogene Proteins c-akt , Urocortins/metabolism , Adrenocorticotropic Hormone/metabolism , Adrenocorticotropic Hormone/pharmacology , Animals , Hypertrophy/metabolism , Insulin/metabolism , Insulin-Like Growth Factor I/metabolism , Mice , Muscle, Skeletal/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Urocortins/pharmacology
9.
Cardiol Young ; 32(7): 1172-1174, 2022 Jul.
Article in English | MEDLINE | ID: mdl-34866569

ABSTRACT

We report the case of a 14-year-old male presented with raised myocardial injury biomarkers, on the workout, Campylobacter coli was identified on stool culture, treated with antibiotics with total resolution. Cardiac magnetic resonance showed interventricular septum and lateral wall hypokinesia and subepicardial delayed enhancement, with preserved ventricular systolic function. To our knowledge, this is the first report linking Campylobacter coli to myopericarditis in children.


Subject(s)
Campylobacter coli , Myocarditis , Adolescent , Child , Heart , Humans , Magnetic Resonance Imaging , Male , Myocarditis/diagnosis , Systole
10.
Peptides ; 146: 170677, 2021 12.
Article in English | MEDLINE | ID: mdl-34695513

ABSTRACT

Calcitonin Gene-Related Peptide (CGRP) is a potent vasodilator peptide widely distributed in the central nervous system and various peripheral tissues, including cardiac muscle. However, its role in heart protein metabolism remains unknown. We examined the acute effects of CGRP on autophagy and the related signaling pathways in the heart mice and cultured neonatal cardiomyocytes. CGRP (100 µg kg-1; s.c.) or 0.9 % saline was injected in awake male C57B16 mice, and the metabolic profile was determined up to 60 min. In fed mice, CGRP drastically increased glycemia and reduced insulinemia, an effect that was accompanied by reduced cardiac phosphorylation levels of Akt at Ser473 without affecting FoxO. Despite these catabolic effects, CGRP acutely inhibited autophagy as estimated by the decrease in LC3II:LC3I and autophagic flux. In addition, the fasting-induced autophagic flux in mice hearts was entirely abrogated by one single injection of CGRP. In parallel, CGRP stimulated PKA/CREB and mTORC1 signaling and increased the phosphorylation of Unc51-like kinase-1 (ULK1), an essential protein in autophagy initiation. Similar effects were observed in cardiomyocytes, in which CGRP also inhibited autophagic flux and stimulated Akt and FoxO phosphorylation. These findings suggest that CGRP in vivo acutely suppresses autophagy in the heart of fed and fasted mice, most likely through the activation of PKA/mTORC1 signaling but independent of Akt.


Subject(s)
Autophagy/drug effects , Calcitonin Gene-Related Peptide/physiology , Heart/drug effects , Animals , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Mice , Myocytes, Cardiac/drug effects , Rats , Rats, Wistar , Signal Transduction/drug effects
11.
Sci Rep ; 11(1): 15042, 2021 07 22.
Article in English | MEDLINE | ID: mdl-34294826

ABSTRACT

The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. Streptococcus and Prevotella were associated with LC and Haemophilus was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (P value = 0.0068). Our results support the association of Streptoccocus and Prevotella with LC and of Haemophilus with COPD, and advocate for specific CLD signatures.


Subject(s)
Bronchi/microbiology , Lung Diseases/epidemiology , Lung Diseases/etiology , Microbiota , Pulmonary Alveoli/microbiology , Biomarkers , Chronic Disease , Comorbidity , Female , Humans , Lung Diseases/diagnosis , Male , Portugal , Public Health Surveillance , RNA, Ribosomal, 16S
12.
Life Sci ; 278: 119563, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33930364

ABSTRACT

AIM: There is growing evidence about the ability of cyclic adenosine monophosphate (cAMP) signaling and nonselective phosphodiesterase (PDE) inhibitors on mitigate muscle atrophy. PDE4 accounts for the major cAMP hydrolyzing activity in skeletal muscles, therefore advances are necessary about the consequences of treatment with PDE4 inhibitors on protein breakdown in atrophied muscles. We postulated that rolipram (selective PDE4 inhibitor) may activate cAMP downstream effectors, inhibiting proteolytic systems in skeletal muscles of diabetic rats. MAIN METHODS: Streptozotocin-induced diabetic rats were treated with 2 mg/kg rolipram for 3 days. Changes in the levels of components belonging to the proteolytic machineries in soleus and extensor digitorum longus (EDL) muscles were investigated, as well as cAMP effectors. KEY FINDINGS: Treatment of diabetic rats with rolipram decreased the levels of atrogin-1 and MuRF-1 in soleus and EDL, and reduced the activities of calpains and caspase-3; these findings partially explains the low ubiquitin conjugates levels and the decreased proteasome activity. The inhibition of muscle proteolysis may be occurring due to phosphorylation and inhibition of forkhead box O (FoxO) factors, probably as a consequence of the increased cAMP levels, followed by the activation of PKA and Akt effectors. Akt activation may be associated with the increased levels of exchange protein directly activated by cAMP (EPAC). As a result, rolipram treatment spared muscle mass in diabetic rats. SIGNIFICANCE: The antiproteolytic responses associated with PDE4 inhibition may be helpful to motivate future investigations about the repositioning of PDE4 inhibitors for the treatment of muscle wasting conditions.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Diabetes Mellitus, Experimental/metabolism , Muscle, Skeletal/metabolism , Nerve Tissue Proteins/antagonists & inhibitors , Phosphodiesterase 4 Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Animals , Calpain/metabolism , Caspase 3/metabolism , Cyclic AMP/metabolism , Male , Muscular Atrophy/metabolism , Phosphorylation , Proteasome Endopeptidase Complex/metabolism , Rats , Rats, Wistar , Rolipram/pharmacology , Signal Transduction/drug effects
13.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 13: 317-323, jan.-dez. 2021. fig, quad
Article in English, Portuguese | LILACS, BDENF - Nursing | ID: biblio-1151260

ABSTRACT

Objetivo: Compreender as potencialidades e as situações de vulnerabilidades que envolvem os adolescentes quanto às questões de saúde e cidadania. Métodos: Trata-se de um estudo de abordagem qualitativa do tipo pesquisa-ação desenvolvido em uma escola pública da rede estadual de ensino. Participaram 21 adolescentes escolares do primeiro ano do ensino médio, sendo a amostra não probabilística do tipo intencional. Os dados foram coletados mediante a realização de círculos de cultura e analisados por meio da análise de conteúdo. Resultados: O conhecimento foi visto como uma potencialidade para execução de atitudes e práticas adequadas pelos adolescentes, e referenciado como fator positivo para o enfrentamento de situações de vulnerabilidades. Conclusão: Os adolescentes possuem potencialidades que podem ser fortalecidas com a educação em saúde, e as situações de vulnerabilidades existentes em seu cotidiano podem ser enfrentadas com a estimulação do protagonismo desse grupo populacional


Objective: To understand the potentialities and the situations of vulnerabilities that wrap the adolescents as for the questions of health and citizenship. Methods: Inquiry-action is treated as a study of qualitative approach of the type developed in a public school of the state net of teaching. They announced 21 school adolescents of the first year of the secondary education, being the sample not probabilística of the intentional type. The data were collected by means of the realization of circles of culture and analysed through the content analysis. Results: The knowledge was seen as a potentiality for execution of attitudes and practices adapted by the adolescents, and referenciado like positive factor for the enfrentamento of situations of vulnerabilities. Conclusion: The adolescents have potentialities that can be strengthened with the education in health, and the situations of existent vulnerabilities in his daily life can be faced with the stimulation of the protagonismo of this population group


Objetivo: Entender las potencialidades y las situaciones de vulnerabilidades que envuelven a los adolescentes en cuanto a las preguntas de salud y ciudadanía. Método: La acción de la pregunta es tratada como un estudio del enfoque cualitativo del tipo desarrollado en una escuela pública de la red estatal de la enseñanza. Anunciaron a 21 adolescentes escolares del primer año de la educación secundaria, siendo la muestra no probabilística del tipo intencional. Los datos fueron coleccionados por medio de la realización de círculos de la cultura y analizados a través de la análisis de contenido. Resultados: El conocimiento fue visto como una potencialidad para ejecución de actitudes y prácticas adaptadas por los adolescentes y referenciado como el factor positivo para el enfrentamento de situaciones de vulnerabilidades. Conclusión: Los adolescentes tienen potencialidades que pueden ser reforzadas con la educación en la salud, y las situaciones de vulnerabilidades existentes en su vida cotidiana pueden ser enfrentantes con el estímulo del protagonismo de este grupo demográfico


Subject(s)
Humans , Male , Female , Adolescent , Health Education , Adolescent , Community Participation
14.
FASEB J ; 34(9): 12946-12962, 2020 09.
Article in English | MEDLINE | ID: mdl-32772437

ABSTRACT

Although we have shown that catecholamines suppress the activity of the Ubiquitin-Proteasome System (UPS) and atrophy-related genes expression through a cAMP-dependent manner in skeletal muscle from rodents, the underlying mechanisms remain unclear. Here, we report that a single injection of norepinephrine (NE; 1 mg kg-1 ; s.c) attenuated the fasting-induced up-regulation of FoxO-target genes in tibialis anterior (TA) muscles by the stimulation of PKA/CREB and Akt/FoxO1 signaling pathways. In addition, muscle-specific activation of PKA by the overexpression of PKA catalytic subunit (PKAcat) suppressed FoxO reporter activity induced by (1) a wild-type; (2) a non-phosphorylatable; (3) a non-phosphorylatable and non-acetylatable forms of FoxO1 and FoxO3; (4) downregulation of FoxO protein content, and probably by (5) PGC-1α up-regulation. Consistently, the overexpression of the PKAcat inhibitor (PKI) up-regulated FoxO activity and the content of Atrogin-1 and MuRF1, as well as induced muscle fiber atrophy, the latter effect being prevented by the overexpression of a dominant negative (d. n.) form of FoxO (d.n.FoxO). The sustained overexpression of PKAcat induced fiber-type transition toward a smaller, slower, and more oxidative phenotype and improved muscle resistance to fatigue. Taken together, our data provide the first evidence that endogenous PKA activity is required to restrain the basal activity of FoxO and physiologically important to maintain skeletal muscle mass.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Forkhead Box Protein O1/metabolism , Muscle, Skeletal/enzymology , Muscular Atrophy/metabolism , Animals , Cell Line , Forkhead Box Protein O3/metabolism , Male , Mice , Mice, Inbred C57BL , Muscle, Skeletal/pathology , Myoblasts, Skeletal/enzymology , Signal Transduction
15.
J Appl Physiol (1985) ; 128(4): 855-871, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32027543

ABSTRACT

The sympathetic nervous system (SNS) activates cAMP signaling and promotes trophic effects on brown adipose tissue (BAT) through poorly understood mechanisms. Because norepinephrine has been found to induce antiproteolytic effects on muscle and heart, we hypothesized that the SNS could inhibit autophagy in interscapular BAT (IBAT). Here, we describe that selective sympathetic denervation of rat IBAT kept at 25°C induced atrophy, and in parallel dephosphorylated forkhead box class O (FoxO), and increased cathepsin activity, autophagic flux, autophagosome formation, and expression of autophagy-related genes. Conversely, cold stimulus (4°C) for up to 72 h induced thermogenesis and IBAT hypertrophy, an anabolic effect that was associated with inhibition of cathepsin activity, autophagic flux, and autophagosome formation. These effects were abrogated by sympathetic denervation, which also upregulated Gabarapl1 mRNA. In addition, the cold-driven sympathetic activation stimulated the mechanistic target of rapamycin (mTOR) pathway, leading to the enhancement of protein synthesis, evaluated in vivo by puromycin incorporation, and to the inhibitory phosphorylation of Unc51-like kinase-1, a key protein in the initiation of autophagy. This coincided with a higher content of exchange protein-1 directly activated by cAMP (Epac1), a cAMP effector, and phosphorylation of Akt at Thr308, all these effects being abolished by denervation. Systemic treatment with norepinephrine for 72 h mimicked most of the cold effects on IBAT. These data suggest that the noradrenergic sympathetic inputs to IBAT restrain basal autophagy via suppression of FoxO and, in the setting of cold, stimulate protein synthesis via the Epac/Akt/mTOR-dependent pathway and suppress the autophagosome formation, probably through posttranscriptional mechanisms.NEW & NOTEWORTHY The underlying mechanisms related to the anabolic role of sympathetic innervation on brown adipose tissue (BAT) are unclear. We show that sympathetic denervation activates autophagic-lysosomal degradation, leading to a loss of mitochondrial proteins and BAT atrophy. Conversely, cold-driven sympathetic activation suppresses autophagy and stimulates protein synthesis, leading to BAT hypertrophy. Given its high-potential capacity for heat production, understanding the mechanisms that contribute to BAT mass is important to optimize chances of survival for endotherms in cold ambients.


Subject(s)
Adipose Tissue, Brown , Thermogenesis , Animals , Autophagy , Cold Temperature , Lysosomes , Rats , Sympathetic Nervous System
16.
Sci Rep ; 9(1): 12838, 2019 09 06.
Article in English | MEDLINE | ID: mdl-31492894

ABSTRACT

The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities' associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.


Subject(s)
Adenocarcinoma/microbiology , Carcinoma, Squamous Cell/microbiology , Lung Neoplasms/microbiology , Lung/microbiology , Microbiota , Adenocarcinoma/diagnosis , Biodiversity , Biomarkers/metabolism , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Follow-Up Studies , Humans , Lung Neoplasms/diagnosis , Prognosis , Survival Analysis
17.
Rev. bras. promoç. saúde (Impr.) ; 31(2): 1-7, 22/06/2018.
Article in English, Portuguese | LILACS | ID: biblio-906922

ABSTRACT

OBJETIVO: Reconhecer no processo de trabalho dos profissionais da atenção básica, junto a Estratégia Saúde da Família, os domínios de competências em promoção da saúde diante das ações praticadas com base no referencial das Competências em Promoção da Saúde (CompHP). MÉTODOS: Trata-se de estudo descritivo e exploratório de natureza qualitativa, realizado no município de Acopiara, Ceará, Brasil. Participaram do estudo, desenvolvido no período de março a junho de 2016, nove profissionais com atuação definida na Estratégia Saúde da Família. Os dados foram coletados através de entrevista semiestruturada e organizados a partir da técnica da análise temática das falas dos participantes. RESULTADOS: Os profissionais desconhecem o referencial do CompHP, bem como os seus domínios e as competências propostas. Entretanto, evidencia-se que os domínios: de diagnóstico, comunicação, liderança, possibilidade de mudanças e advocacia em saúde são manifestados nas falas dos participantes. Deste modo, os saberes e práticas dos profissionais articulam-se aos domínios de competências do CompHP supracitados. Os domínios não manifestados pelos profissionais foram: parceria, planejamento, implementação e avaliação em saúde. CONCLUSÃO: Observou-se o desconhecimento dos profissionais quanto à existência e proposta no referencial do CompHP, o que revela a necessidade de incluí-los nos momentos formativos, em todo e qualquer nível de formação. (AU)


OBJECTIVE: To recognize in the work process of Primary Health Care professionals, along with the Family Health Strategy, the domains of health promotion competencies in the face of actions carried out on the basis of the Health Promotion Competencies (CompHP) framework. METHODS: This is a qualitative descriptive and exploratory study carried out in the municipality of Acopiara, Ceará, Brazil. The study was carried out from March to June 2016 with nine professionals with a defined role in the Family Health Strategy. The data were collected using a structured interview and organized based on the Thematic Analysis of the participants' statements. RESULTS: The professionals are not aware of the CompHP framework and its domains and proposed competencies. However, it is evident that the needs assessment, communication, leadership, possibility of changes and advocacy for health domains are manifested in the participants' statements. Thus, the professionals' knowledge and practices are linked to the aforementioned domains of CompHP competencies. The domains not manifested by professionals were: partnership, planning, implementation and evaluation in health. CONCLUSION: Professionals are unaware of the existence and purpose of the CompHP framework, which reveals the need to include them in training moments at any and all levels of training. (AU)


OBJETIVO: Reconocer el proceso de trabajo de los profesionales de la atención básica en la Estrategia Salud de la Familia y los dominios de las competencias para la promoción de la salud ante las acciones practicadas basadas en el referencial de las Competencias para la Promoción de la Salud (CompHP). MÉTODOS: Se trata de estudio descriptivo, exploratorio y cualitativo realizado en el municipio de Acopiara, Ceará, Brasil. El estudio ha sido desarrollado en el período entre marzo y junio de 2016 en el cual participaron nueve profesionales con actuación definida en la Estrategia Salud de la Familia. Se recogieron los datos a través de una entrevista semiestructurada y les organizaron a través de la técnica del análisis temático de las hablas de los participantes. RESULTADOS: Los profesionales desconocen el referencial del CompHP así como sus dominios y las competencias propuestas. Sin embargo, se evidencia que los dominios de diagnóstico, comunicación, liderazgo, posibilidades de cambios y abogacía en salud se manifiestan en las hablas de los participantes. Así, los saberes y las prácticas de los profesionales se articulan con los dominios de competencias del CompHP mencionados antes. Los dominios no manifestados por los profesionales fueron la compañía, el planeamiento, la implementación y la evaluación en salud. CONCLUSIÓN: Se observó el desconocimiento de los profesionales respecto la existencia y propuesta en el referencial del CompHP lo que revela la necesidad de incluirlos en los momentos de formación en todo y cualquier nivel de formación. (AU)


Subject(s)
Primary Health Care , Competency-Based Education , Health Promotion
18.
Am J Reprod Immunol ; 79(6): e12838, 2018 06.
Article in English | MEDLINE | ID: mdl-29500854

ABSTRACT

PROBLEM: Sexually transmitted diseases and other infections of male genitourinary tract are thought to negatively impact reproductive health, affecting semen quality. Despite a possible link between bacteria and infertility, few studies attempted to characterize seminal microbiota in healthy and diseased subjects. METHODS OF THE STUDY: A high-throughput sequencing of 16S ribosomal RNA gene was performed in a cohort of infertility-related cases (N = 89) and controls (N = 29) using a pooled sample approach. RESULTS: A global characterization of microbiota was obtained at low cost, without compromising the identification of bacterial taxa. This strategy allowed us to detect changes in the microbiota of infertility-related phenotypes, such as an increment of Proteobacteria in seminal hyperviscosity, and to separate this later group from oligoasthenoteratozoospermia based in bacterial (family/genus) abundances. CONCLUSION: We provide data for a likely contribution of bacteria into seminal hyperviscosity and oligoasthenoteratozoospermia, partially correlated with an increment of Neisseria, Klebsiella, and Pseudomonas pathogens and a reduction in Lactobacillus probiotic agent.


Subject(s)
Bacterial Infections/complications , Infertility, Male/etiology , Infertility, Male/microbiology , Microbiota/genetics , Oligospermia/complications , Semen/microbiology , Bacterial Infections/microbiology , Case-Control Studies , Humans , Male , Oligospermia/epidemiology , Oligospermia/microbiology , Prevalence , RNA, Ribosomal, 16S/genetics
19.
J Appl Physiol (1985) ; 124(3): 704-716, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29357512

ABSTRACT

Advances in the knowledge of the mechanisms controlling protein breakdown in skeletal muscles have allowed the exploration of new options for treating muscle-wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE) inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly via inhibiting protein breakdown. The aim of this study was to explore the mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of atrogin-1 and muscle RING finger-1 were decreased, as were the activities of caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX, which at least partly explains the drop in the ubiquitin conjugate (EDL) levels and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE activity and increased cAMP content in muscles of diabetic rats; moreover, it also increased both the protein levels of exchange protein directly activated by cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle mass was practically prevented in diabetic rats treated with PTX. These findings advance our understanding of the mechanisms underlying the antiproteolytic effects of PTX and suggest the use of PDE inhibitors as a strategy to activate cAMP signaling, which is emerging as a promising target for treating muscle mass loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in addition to ß2AR agonists, phosphodiesterase inhibitors such as pentoxifylline (PTX) can be an interesting option. This study advances the understanding of the mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of diabetic rats, which involve the activation of both exchange protein directly activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and calpain/caspase-3-proteolytic machinery.


Subject(s)
Diabetes Mellitus, Experimental/complications , Muscle, Skeletal/drug effects , Muscular Atrophy/prevention & control , Pentoxifylline/therapeutic use , Phosphodiesterase Inhibitors/therapeutic use , Proteolysis/drug effects , Animals , Blood Glucose/drug effects , Body Weight/drug effects , Cyclic AMP/metabolism , Drug Evaluation, Preclinical , Guanine Nucleotide Exchange Factors/metabolism , Male , Muscle, Skeletal/metabolism , Muscular Atrophy/etiology , Muscular Atrophy/metabolism , Pentoxifylline/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Rats, Wistar , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/blood
20.
Am J Clin Dermatol ; 19(1): 33-50, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28656563

ABSTRACT

Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient's quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign. Several skin-direct therapies are available and may be indicated as monotherapy or adjuvant treatment in order to allow faster tapering and withdrawal of systemic immunosuppression. Treatment of steroid-refractory patients remains a challenge and, to date, no consensus has been reached for one single agent in second-line therapy. This article aims to review skin involvement as well as provide and update discussion on therapeutic options for both acute and chronic cutaneous GVHD.


Subject(s)
Dermatologic Agents/therapeutic use , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Immunosuppression Therapy/methods , Skin Diseases/therapy , Acute Disease/therapy , Administration, Cutaneous , Administration, Intravenous , Administration, Oral , Biomarkers/analysis , Chronic Disease/therapy , Glucocorticoids/therapeutic use , Graft vs Host Disease/diagnosis , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Humans , Quality of Life , Skin/immunology , Skin Diseases/diagnosis , Skin Diseases/immunology , Skin Diseases/mortality
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