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INTRODUCTION: Probiotics provide therapeutic benefits not only in the gut but also other mucosal organs, including the lungs. OBJECTIVE AND DESIGN: To evaluate the effects of the probiotic strain L. delbrueckii UFV-H2b20 oral administration in an experimental murine model of A. fumigatus pulmonary infection. BALB/c mice were associated with L. delbrueckii and infected with Aspergillus fumigatus and compared with non-associated group. METHODS: We investigated survival, respiratory mechanics, histopathology, colony forming units, cytokines in bronchoalveolar lavage, IgA in feces, efferocytosis, production of reactive oxygen species and the cell population in the mesenteric lymph nodes. RESULTS: L. delbrueckii induces tolerogenic dendritic cells, IL-10+macrophages and FoxP3+regulatory T cells in mesenteric lymph nodes and increased IgA levels in feces; after infection with A. fumigatus, increased survival and decreased fungal burden. There was decreased lung vascular permeability without changes in the leukocyte profile. There was enhanced neutrophilic response and increased macrophage efferocytosis. L. delbrueckii-treated mice displayed more of FoxP3+Treg cells, TGF-ß and IL-10 levels in lungs, and concomitant decreased IL-1ß, IL-17 A, and CXCL1 production. CONCLUSION: Uur results indicate that L. delbrueckii UFV H2b20 ingestion improves immune responses, controlling pulmonary A. fumigatus infection. L. delbrueckii seems to play a role in pathogenesis control by promoting immune regulation.
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Aspergillus fumigatus , Citocinas , Lactobacillus delbrueckii , Pulmón , Ratones Endogámicos BALB C , Probióticos , Animales , Probióticos/administración & dosificación , Aspergillus fumigatus/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/microbiología , Administración Oral , Lactobacillus delbrueckii/inmunología , Citocinas/inmunología , Citocinas/metabolismo , Ratones , Aspergilosis/inmunología , Aspergilosis/prevención & control , Linfocitos T Reguladores/inmunología , Inmunoglobulina A/inmunología , Femenino , Líquido del Lavado Bronquioalveolar/inmunología , Aspergilosis Pulmonar/inmunología , Heces/microbiología , MasculinoRESUMEN
OBJECTIVE AND DESIGN: The aim of this study was to investigate the effects of ethanol exposure on epigenetic markers in bone marrow (BM) and their impact on inflammatory response during Aspergillus fumigatus infection. RESULTS: Chronic ethanol exposure decreased H3K27me3 enrichment in the Il6 promoter region while increased H3K4me3 enrichment in Tnf. Chimeric mice were generated by transplanting BM from mice exposed to ethanol or water. Infection of ethanol-chimeric mice culminated in higher clinical scores, although there was no effect on mortality. However, previous chronic exposure to ethanol affects persistently the inflammatory response in lung tissue, demonstrated by increased lung damage, neutrophil accumulation and IL-6, TNF and CXCL2 production in ethanol-chimeric mice, resulting in a decreased neutrophil infiltration into the alveolar space. Neutrophil killing and phagocytosis were also significantly lower. Moreover, BM derived macrophages (BMDM) from ethanol-chimeric mice stimulated with A. fumigatus conidia exhibited higher levels of TNF, CXCL2 and IL-6 release and a higher killing activity. The Il6 promoter of BMDM from ethanol-chimeric mice exhibited a reduction in H3K27me3 enrichment, a finding also observed in BM donors exposed to ethanol. CONCLUSIONS: These evidences demonstrate that prior chronic alcohol exposure of bone-marrow modify immune effector cells functions impairing the inflammatory response during A. fumigatus infection. These findings highlight the persistent impact of chronic ethanol exposure on infectious disease outcomes.
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Aspergilosis , Aspergillus fumigatus , Etanol , Histonas , Interleucina-6 , Macrófagos , Neutrófilos , Regiones Promotoras Genéticas , Animales , Interleucina-6/genética , Interleucina-6/metabolismo , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Histonas/metabolismo , Aspergilosis/inmunología , Ratones Endogámicos C57BL , Masculino , Pulmón/inmunología , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Fagocitosis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant socioeconomic and ethno-racial disparities persist in health care access across the region. Breast cancer (BC) incidence and mortality rates in Brazil are comparable to those in other LATAM countries, supporting the relevance of Brazilian data, with Brazil's health care policies and expenditures often serving as models for neighboring countries. We evaluated the impact of mobility on oncological outcomes in LATAM by analyzing studies of patients with BC reporting commuting routes or travel distances to receive treatment or diagnosis. METHODS: We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, LILACS, and Google Scholar databases. Studies eligible for inclusion were randomized controlled trials and observational studies of patients with BC published in English, Portuguese, or Spanish and conducted in LATAM. The primary outcome was the impact of mobility or travel distance on oncological outcomes. Secondary outcomes included factors related to mobility barriers and access to health services. For studies meeting eligibility, relevant data were extracted using standardized forms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Quantitative and qualitative evidence synthesis focused on estimating travel distances based on available data. Heterogeneity across distance traveled or travel time was addressed by converting reported travel time to kilometers traveled and estimating distances for unspecified locations. RESULTS: Of 1142 records identified, 14 were included (12 from Brazil, 1 from Mexico, and 1 from Argentina). Meta-analysis revealed an average travel distance of 77.8 km (95% CI, 49.1-106.48) to access BC-related diagnostic or therapeutic resources. Nonetheless, this average fails to precisely encapsulate the distinct characteristics of each region, where notable variations persist in travel distance, ranging from 88 km in the South to 448 km in the North. CONCLUSION: The influence of mobility and travel distance on access to BC care is multifaceted and should consider the complex interplay of geographic barriers, sociodemographic factors, health system issues, and policy-related challenges. Further research is needed to comprehensively understand the variables impacting access to health services, particularly in LATAM countries, where the challenges women face during treatment remain understudied. TRIAL REGISTRATION: CRD42023446936.
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Neoplasias de la Mama , Accesibilidad a los Servicios de Salud , Viaje , Humanos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/etnología , América Latina , Viaje/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricosRESUMEN
PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.
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Inhibidores de Proteínas Quinasas , Pirazoles , Humanos , Niño , Masculino , Femenino , Adolescente , Pirazoles/uso terapéutico , Preescolar , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Receptor trkA/genética , Receptor trkA/antagonistas & inhibidores , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Lactante , Receptor trkB/genética , Receptor trkC/genética , Ensayos Clínicos como AsuntoRESUMEN
Given the changes in the digestive tract post-bariatric surgery, adapting to a new pattern of eating behavior becomes crucial, with special attention to the specifics of chewing mechanics. This study aimed to investigate the association between self-perception of chewing, chewing behavior, and the presence of gastrointestinal symptoms in preoperative patients undergoing bariatric surgery. Sixty adult candidates for bariatric surgery at a public hospital in Belém (Brazil) were analyzed. Participants predominantly exhibited unilateral chewing patterns (91.6%), a fast chewing rhythm (73.3%), a large food bolus (80%), liquid intake during meals (36.7%), and 41.7% reported that chewing could cause some issue. Significant associations were found between the perception of causing problems and chewing scarcity (p = 0.006), diarrhea (p = 0.004), absence of slow chewing (p = 0.048), and frequent cutting of food with front teeth (p = 0.034). These findings reveal a relationship between the perception of chewing problems and chewing scarcity, presence of diarrhea, and fast chewing.
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Cirugía Bariátrica , Masticación , Autoimagen , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Conducta Alimentaria/psicología , Enfermedades Gastrointestinales/psicología , Enfermedades Gastrointestinales/etiología , Diarrea/etiología , Brasil , Estudios Transversales , Obesidad Mórbida/cirugía , Obesidad Mórbida/psicologíaRESUMEN
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce blood pressure (BP) in patients with hypertension, yet the precise molecular mechanisms remain elusive. SGLT2i inhibits proximal tubule (PT) NHE3-mediated sodium reabsorption in normotensive rodents, yet no hypotensive effect is observed under this scenario. This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-wk-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed higher NKCC2 activity and an abundance of cleaved ENaC α and γ subunits compared with Wistar rats, none of which were affected by EMPA. Another set of male Wistar rats was treated with EMPA, the NCC inhibitor hydrochlorothiazide (HCTZ), and EMPA combined with HCTZ or vehicle for 14 days. In these rats, BP reduction was observed only with combined EMPA and HCTZ treatment, not with either drug alone. These findings suggest that NCC upregulation counteracts EMPA-mediated inhibition of PT NHE3 in male normotensive rats, maintaining their baseline BP. Moreover, the reduction of NHE3 activity without further upregulation of major apical sodium transporters beyond the PT may contribute to the BP-lowering effect of SGLT2i in experimental models and patients with hypertension.NEW & NOTEWORTHY This study suggests that reduced NHE3-mediated sodium reabsorption in the renal proximal tubule may account, at least in part, for the BP-lowering effect of SGLT2 inhibitors in the setting of hypertension. It also demonstrates that chronic treatment with SGLT2 inhibitors upregulates NCC activity, phosphorylation, and expression in the distal tubule of normotensive but not hypertensive rats. SGLT2 inhibitor-mediated upregulation of NCC seems crucial to counteract proximal tubule natriuresis in subjects with normal BP.
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Compuestos de Bencidrilo , Glucósidos , Hipertensión , Ratas Endogámicas SHR , Ratas Wistar , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Intercambiador 3 de Sodio-Hidrógeno , Regulación hacia Arriba , Animales , Masculino , Intercambiador 3 de Sodio-Hidrógeno/metabolismo , Intercambiador 3 de Sodio-Hidrógeno/genética , Intercambiador 3 de Sodio-Hidrógeno/antagonistas & inhibidores , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Hipertensión/fisiopatología , Glucósidos/farmacología , Compuestos de Bencidrilo/farmacología , Regulación hacia Arriba/efectos de los fármacos , Ratas , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Presión Sanguínea/efectos de los fármacos , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Riñón/metabolismo , Riñón/efectos de los fármacosRESUMEN
Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.
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Angiotensina II , Enfermedades Cardiovasculares , Humanos , Dipeptidil Peptidasa 4 , Peptidil-Dipeptidasa A , Receptor de Angiotensina Tipo 1 , Inflamación , Fibrosis , Angiotensina IRESUMEN
Objetivo: Analisar as estratégias de treinamento em segurança do paciente para profissionais de saúde no contexto da atenção primária. Métodos: Trata-se de uma revisão integrativa conduzida nas bases de dados Medical Literature Analysis and Retrieval System Online, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Base de Dados de Enfermagem, Web of Sciencee Scopus, com os descritores "Capacitação Profissional", "Segurança do Paciente" e "Atenção Primária à Saúde". Resultados: Foram identificados 390 estudos nas bases de dados, os quais resultaram em uma amostra final de seis artigos para a composição da revisão. Estes foram publicados entre os anos de 2017 e 2019, desenvolvidos em países da Europa, da América do Norte e Oceania. Conclusão: Descaram-se como estratégias de treinamento os seguintes itens: workshop, implementação de programa de segurança medicamentosa, identificação de fatores-chave para elevação da qualidade, feedback e aprendizagem através de erros. Descritores: Capacitação Profissional; Atenção Primária à Saúde; Segurança do Paciente; Pessoal de Saúde
Objective: To analyze patient safety training strategies for health professionals in the context of primary care.Methods: This is an integrative review conducted in the Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Center on Health Sciences Information, Base de Dados de Enfermagem, Web of Science and Scopus databases, with the descriptors "Professional Training", "Patient Safety" and "Primary Health Care". Results: A total of 390 studies were identified in the databases, which resulted in a final sample of six articles for the composition of the review. These were published between the years 2017 and 2019, developed in countries in Europe, North America and Oceania. Conclusion: The following items were described as training strategies: workshop, implementation of a medication safety program, identification of key factors for quality improvement, feedback and learning through errors.Descriptors:Professional Training; Primary Health Care; Patient Safety; Health Personnel
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Atención Primaria de Salud , Personal de Salud , Capacitación Profesional , Seguridad del PacienteRESUMEN
Many pathogenic organisms need to reach either an intracellular compartment or the cytoplasm of a target cell for their survival, replication or immune system evasion. Intracellular pathogens frequently penetrate into the cell through the endocytic and phagocytic pathways (clathrin-mediated endocytosis, phagocytosis and macropinocytosis) that culminates in fusion with lysosomes. However, several mechanisms are triggered by pathogenic microorganisms - protozoan, bacteria, virus and fungus - to avoid destruction by lysosome fusion, such as rupture of the phagosome and thereby release into the cytoplasm, avoidance of autophagy, delaying in both phagolysosome biogenesis and phagosomal maturation and survival/replication inside the phagolysosome. Here we reviewed the main data dealing with phagosome maturation and evasion from lysosomal killing by different bacteria, protozoa, fungi and virus.
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Lisosomas , Fagocitosis , Lisosomas/microbiología , Fagosomas/metabolismo , Fagosomas/microbiología , Endocitosis , Evasión InmuneRESUMEN
Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.
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Ethanol abuse is a risk factor for the development of pneumonia caused by Streptococcus pneumoniae, a critical pathogen for public health. The aim of this article was to investigate the inflammatory mechanisms involved in pneumococcal pneumonia that may be associated with chronic ethanol exposure. Male C57BL6/J-Unib mice were exposed to 20% (v/v) ethanol for twelve weeks and intranasally infected with 5x104 CFU of S. pneumoniae. Twenty-four hours after infection, lungs, bronchoalveolar lavage and blood samples were obtained to assess the consequences of chronic ethanol exposure during infection. Alcohol-fed mice showed increased production of nitric oxide and CXCL1 in alveoli and plasma during pneumococcal pneumonia. Beside this, ethanol-treated mice exhibited a decrease in leukocyte infiltration into the alveoli and reduced frequency of severe lung inflammation, which was associated with an increase in bacterial load. Curiously, no changes were observed in survival after infection. Taken together, these results demonstrate that chronic ethanol exposure alters the inflammatory response during S. pneumoniae lung infection in mice with a reduction in the inflammatory infiltrate even in the presence of higher levels of the chemoattractant CXCL1.
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Neumonía Neumocócica , Masculino , Ratones , Animales , Neumonía Neumocócica/microbiología , Etanol/efectos adversos , Óxido Nítrico , Líquido del Lavado Bronquioalveolar , Streptococcus pneumoniae , LeucocitosRESUMEN
Introduction: People with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response. Methods: We addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography-coupled mass spectrometry (GC-MS). Results: We identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine. Discussion: Our results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.
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Médula Ósea , Etanol , Ratones , Animales , Ratones Endogámicos C57BL , Etanol/farmacología , Metabolómica/métodos , MetabolomaRESUMEN
AIMS: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. MAIN METHODS: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. KEY FINDINGS: Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. SIGNIFICANCE: Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.
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Dipeptidil Peptidasa 4 , Insuficiencia Cardíaca , Animales , Dipeptidil Peptidasa 4/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Ratas , Ratas Wistar , Sistema Renina-Angiotensina , Valsartán/farmacología , Valsartán/uso terapéutico , Vildagliptina/farmacología , Vildagliptina/uso terapéuticoRESUMEN
Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1ß, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents.
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Aspergilosis , Vesículas Extracelulares , Aspergilosis Pulmonar , Animales , Aspergillus fumigatus , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
RESUMO Objetivo avaliar o conhecimento, a atitude e a prática de universitários intercambistas provenientes do continente africano acerca das Infecções Sexualmente Transmissíveis. Método estudo transversal, realizado de dezembro de 2019 a março de 2020, em universidade pública internacional brasileira localizada no Ceará. A amostra foi constituída por 150 estudantes africanos de diferentes cursos de graduação. Utilizou-se do inquérito de Conhecimento, Atitude e Prática. Resultados os universitários apresentaram conhecimento satisfatório acerca da forma de transmissão das Infecções Sexualmente Transmissíveis, porém, com deficiências a respeito das hepatites virais. Identificou-se associação entre sexo e atitude acerca do uso de preservativo em relação sexual com parceria fixa (p=0,042). No que se refere às práticas, houve associação entre sexo e uso do preservativo na primeira relação sexual (p=0,001), ter mais que um parceiro (p=0,001) e mais que dez parceiros em toda a vida (0,007). No que se relaciona às práticas sexuais nos últimos 12 meses, observou-se associação estatística entre ter relações sexuais com mais de um parceiro sexual e sexo do participante (p=0,001). Conclusão e implicações para a prática enfatiza-se a importância de a universidade pesquisada realizar atividades de educação em saúde que abordem Infecções Sexualmente Transmissíveis, bem como de extensão universitária, que envolvam alunos imigrantes africanos.
RESUMEN Objetivo evaluar el conocimiento, la actitud y la práctica de estudiantes de intercambio del continente africano sobre las Infecciones de Transmisión Sexual. Método estudio transversal, realizado de diciembre de 2019 a marzo de 2020, en una universidad pública internacional brasileña ubicada en Ceará. La muestra estuvo compuesta por 150 estudiantes africanos de diferentes cursos de pregrado. Se utilizó la encuesta de Conocimiento, Actitud y Práctica. Resultados los universitarios mostraron conocimientos satisfactorios sobre la transmisión de Infecciones de Transmisión Sexual, sin embargo, con deficiencias sobre las hepatitis virales. Se identificó asociación entre el sexo y la actitud sobre el uso del preservativo en las relaciones sexuales con pareja estable (p=0,042). En cuanto a las prácticas, hubo asociación entre sexo y uso de preservativo en la primera relación sexual (p=0,001), tener más de una pareja (p=0,001) y tener más de diez parejas en la vida (0,007). En cuanto a las prácticas sexuales en los últimos 12 meses, hubo asociación estadística entre tener sexo con más de una pareja sexual y el género del participante (p=0,001). Conclusión e implicaciones para la práctica se destaca la importancia de que la universidad investigada realice actividades de educación en salud que aborden las Infecciones de Transmisión Sexual, así como actividades de extensión universitaria, involucrando estudiantes inmigrantes africanos.
ABSTRACT Objective to evaluate the knowledge, attitude and practice of university exchange students from the African continent about Sexually Transmitted Infections. Method a cross-sectional study, conducted from December 2019 to March 2020, in a public international Brazilian university located in Ceará. The sample consisted of 150 African students from different undergraduate courses. It was used the survey of Knowledge, Attitude and Practice. Results the students showed satisfactory knowledge about the form of transmission of Sexually Transmitted Infections, however, with deficiencies regarding viral hepatitis. An association between sex and attitude about condom use in sexual intercourse with a fixed partner was identified (p=0.042). Regarding the practices, there was an association between sex and condom use in the first sexual relation (p=0.001), having more than one partner (p=0.001) and more than ten partners in the whole life (0.007). Regarding sexual practices in the last 12 months, there was a statistical association between having sex with more than one sexual partner and the participant's sex (p=0.001). Conclusion and implications for practice the importance of the university researched carrying out health education activities that address Sexually Transmitted Infections, as well as university extension activities that involve African immigrant students, is emphasized.
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Estudiantes , Enfermedades de Transmisión Sexual/prevención & control , Enfermedades de Transmisión Sexual/transmisión , Conocimientos, Actitudes y Práctica en Salud , Población Negra , Salud del Estudiante , Estudios Transversales , África/etnología , Emigrantes e InmigrantesRESUMEN
A presente pesquisa teve como objetivo avaliar o desenvolvimento das competências gerais em cursos de bacharelado em Educação Física, tendo sido estudadas duas Instituições de Ensino Superior do Estado do Paraná. Foi utilizado o instrumento elaborado e validado por De Matia para a avaliação das competências gerais nos cursos da saúde. A amostra total foi de 263 respondentes. Quando comparamos as respostas dos professores à autoavaliação pelos graduandos, observamos escores menores em todas as dimensões estudadas. Os graduandos dos primeiros períodos se avaliam pior do que aqueles em períodos mais avançados do curso. Os professores percebem graduandos do sexo feminino, mais hábeis na postura inovadora e crítica, e os graduandos destacam colegas do sexo feminino como mais hábeis na interação com seus pares e sociedade. Conclui-se que os graduandos envolvidos na pesquisa estão desenvolvendo parcialmente as competências gerais fundamentais para a sua atuação profissional.
This study aimed to evaluate the development of general competences in Physical Education Undergraduate Courses in two Higher Education Institutions in an inland city of the State of Paraná. The instrument developed and validated by De Matia was used to assess general skills in health courses. The total sample consisted of 263 respondents. The comparison of the professors' answers to the students self-evaluation shows lower scores in all the dimensions studied. Undergraduate students of the first terms haver worse self-evaluations when compared to those in more advanced periods of the course. The professors perceive female students as more skilled in their innovative and critical posture, and the students highlight that female students are more skilled in interaction with their peers and society. It is concluded that the undergraduate students involved in the research are partially developing the general basic competences for their professional performance.
Esta investigación tuvo como objetivo evaluar el desarrollo de las competencias generales en los Cursos de Graduación en Educación Física - Bachillerato en instituciones de educación superior públicas y privadas de una ciudad en el interior del estado de Paraná. El instrumento desarrollado y validado por De Matia se utilizó para evaluar las competencias generales en los cursos de salud. La muestra total fue de 263 encuestados. Las respuestas de los maestros en comparación con los estudiantes son más bajas en todas las dimensiones estudiadas. Los graduados de los primeros períodos se evalúan peor que aquellos en períodos más avanzados del curso. Los profesores perciben que las alumnas, son más habilidosas y tienen una postura innovadora y crítica, y los alumnos destacan las alumnas, más capacitadas para interactuar con sus pares y la sociedad. Se concluye que los graduandos involucrados en la investigación, desarrollan parcialmente las competencias generales básicas.
Asunto(s)
Humanos , Educación y Entrenamiento Físico , Estudiantes , Educación Basada en CompetenciasRESUMEN
The angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II) and angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7)) pathways are coexpressed in most tissues. The balance between these pathways determines, at least in part, whether tissue damage will occur in response to pathological stimuli. The present study tested the hypothesis that male sex and high blood pressure are associated with ACE/ACE2 imbalance in the lungs. Experiments were conducted in male and female Wistar rats and spontaneously hypertensive rats (SHRs). Lung ACE and ACE2 gene expression was also evaluated in normotensive and hypertensive humans using the Genotype-Tissue Expression (GTEx) project. Compared with Wistar rats and female SHRs, male SHRs displayed reduced lung ACE2 mRNA, ACE2 protein abundance and ACE2 activity, and increased Ang II concentration. Lung ACE mRNA levels were higher in male SHRs than in Wistar rats, whereas lung ACE protein abundance and activity were similar among the four groups of rats. Lung Ang-(1-7) concentration was higher in female than in male SHRs (89 ± 17 vs. 43 ± 2 pg/g, P<0.05). Lung ACE to ACE2 mRNA expression in hypertensive patients was significantly higher than that in normotensive subjects. Taken together, these results demonstrate that male hypertensive rats display imbalance between the ACE/Ang II and ACE2/Ang-(1-7) pathways in the lungs mainly attributable to ACE2 down-regulation. Further studies should be conducted to investigate whether this imbalance between ACE/ACE2 may promote and accelerate lung injury in respiratory infections, including coronavirus disease 2019 (COVID-19).
Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Pulmón/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Proteína ADAM17/metabolismo , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Animales , Regulación hacia Abajo , Femenino , Masculino , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Caracteres SexualesRESUMEN
This study aimed to investigate the antiproteinuric and hyperkalemic mechanisms activated by dual renin-angiotensin system (RAS) blockade in renovascular hypertensive rats (2-kidney 1-clip model [2K-1C]). Six weeks after clipping the left renal artery or sham operation (2K), rats were treated with losartan, enalapril, or both drugs for two weeks. We found that 2K-1C rats displayed higher tail-cuff blood pressure (BP), increased non-clipped kidney Ang II concentration, and more pronounced urinary albumin excretion than 2K. BP was decreased by the treatment with either enalapril or losartan, and the combination of both drugs promoted an additional antihypertensive effect in 2K-1C rats. Renal Ang II content and albuminuria were reduced by either enalapril or losartan in monotherapy and restored to control levels by dual RAS blockade. Albuminuria in 2K-1C rats was accompanied by downregulation of the glomerular slit protein podocin, reduction of the endocytic receptors megalin and cubilin, and a marked decrease in the expression of the ClC-5 chloride channel, compared to 2K animals. Treatment with losartan and enalapril in monotherapy or combination increased the expression of podocin, cubilin, and ClC-5. However, only the combined therapy normalized podocin, cubilin, and ClC-5 protein abundance in the non-clipped kidney of 2K-1C rats. Renovascular hypertensive 2K-1C rats had a lower concentration of plasma potassium compared to 2K rats. Single RAS blockade normalized potassium plasma concentration, whereas 2K-1C rats treated with dual RAS blockade exhibited hyperkalemia. Hypokalemia in 2K-1C rats was accompanied by an increase in the cleaved activated forms of α-ENaC and γ-ENaC and the expression of ß-ENaC. Combined RAS blockade but not monotherapy significantly reduced the expression of these ENaC subunits in 2K-1C rats. Indeed, double RAS blockade reduced the abundance of cleaved-α-ENaC to levels lower than those of 2K rats. Collectively, these results demonstrate that the antiproteinuric effect of dual RAS blockade in 2K-1C rats is associated with the restored abundance of podocin and cubilin, and ClC-5. Moreover, double RAS blockade-induced hyperkalemia may be due, at least partially, to an exaggerated downregulation of cleaved α-ENaC in the non-clipped kidney of renovascular hypertensive rats.
RESUMEN
Este artigo objetiva estudar os discursos dos primeiros psicanalistas sobre a lesbianidade, a partir de uma análise teórico-documental das Atas da Sociedade Psicanalítica de Viena. Investigando a problemática do desejo lésbico, buscamos contribuir com o reconhecimento dos limites e potencialidades das teorias psicanalíticas sobre o sexual. Para tanto, foram examinadas as duas principais hipóteses sobre o desejo lésbico desenvolvidas nas reuniões da Sociedade Psicanalítica de Viena e discutiu-se a origem das relações entre lesbianidade e masculinidade do ponto de vista psicanalítico, assinalando algumas questões que a lesbianidade pode formular sobre as relações entre a psicanálise e o patriarcado.
The present work aims to research the speeches of the first psychoanalysts on lesbianity, through a theoretical and documentary research of the Minutes of the Vienna Psychoanalytic Society. Investigating the question of the lesbian desire, the article intends to contribute with the acknowledgment of the limits and potentialities of the psychoanalytic sexual theories. To this end, the two main hypotheses about the lesbian desire developed at the meetings of the Vienna Psychoanalytic Society were examined and the origin of the associations between lesbianity and masculinity in the psychoanalytic point of view was discussed, pointing out some questions that lesbianity can formulate about the relations between psychoanalysis and patriarchy.
El presente trabajo objetiva estudiar los discursos de los primeros psicoanalistas sobre la lesbianidad, a través de un análisis teórico y documental de los registros de las Actas de la Sociedad Psicoanalítica de Viena. Investigando el problema del deseo lesbiano, buscamos contribuir con el reconocimiento de los límites y potencialidades de la teoría sexual. Con este fin, se examinaron las dos principales hipótesis sobre el deseo lesbiano desarrolladas en las reuniones de la Sociedad Psicoanalítica de Viena y se discutió el origen de las relaciones entre la lesbianidad y la masculinidad desde el punto de vista psicoanalítico, señalando algunas preguntas que la lesbianidad puede formular sobre las relaciones entre el psicoanálisis y el patriarcado.
Cet article étude les discours des premiers psychanalystes sur la lesbianité, à travers d'une analyse théorique et documentaire des Minutes de la Société psychanalytique de Vienne. En enquêtent sur le problème du désir lesbien, ce travail cherche à contribuer à la reconnaissance des limites et des potentialités de la théorie sexuelle. Pour ce faire, on a examiné les deux hypothèses sur le désir lesbien développées lors des réunions de la Société psychanalytique de Vienne et on a discuté sur l'origine des associations entre lesbianité et masculinité du point de vue psychanalytique, soulignant des questions que la lesbianité peut formuler sur les relations entre psychanalyse et patriarcat.
Asunto(s)
Psicoanálisis , Homosexualidad FemeninaRESUMEN
INTRODUCTION: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. However, the cause of the altered production of peripheral inflammatory mediators is not known. The PI3K/mTOR/GSK3ß pathway is important for different physiological and pharmacological phenomena. Therefore, in the present study, we tested the hypothesis that the PI3K/mTOR/GSK3ß pathway is deregulated in immune cells from patients with epilepsy and contributes to the abnormal production of inflammatory mediators. METHODS: Patients with temporal lobe epilepsy presenting hippocampal sclerosis and controls aged between 18 and 65 years-old were selected for this study. Peripheral blood was collected for the isolation of peripheral mononuclear blood cells (PBMC). Cells were pre-incubated with different PI3K, mTOR and GSK-3 inhibitors for 30â¯min and further stimulated with phytohaemaglutinin (PHA) or vehicle for 24â¯h. The supernatant was used to evaluate the production of IL-1ß, IL-6, IL-10, TNF e IL-12p70. RESULTS: Non-selective inhibition of PI3K, as well as inhibition of PI3Kγ and GSK-3, reduced the levels of TNF and IL-10 in PHA-stimulated cells from TLE individuals. This stimulus increased the production of IL-12p70 only in cells from TLE individuals, while the inhibition of PI3K and mTOR enhanced the production of this cytokine. On the other hand, inhibition of GSK3 reduced the PHA-induced production of IL-12p70. CONCLUSIONS: Herein we demonstrated that the production of cytokines by immune cells from patients with TLE differs from non-epileptic patients. This differential regulation may be associated with the altered activity and responsiveness of intracellular molecules, such as PI3K, mTOR and GSK-3, which, in turn, might contribute to the inflammatory state that exists in epilepsy and its pathogenesis.