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Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.
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Purpose of the study: During the early and progressive (late) stages of murine experimental pulmonary tuberculosis, the differential activation of macrophages contributes to disease development by controlling bacterial growth and immune regulation. Mycobacterial proteins P27 and PE_PGRS33 can target the mitochondria of macrophages. This study aims to evaluate the effect of both proteins on macrophage activation during mycobacterial infection. Materials and methods: We assess both proteins for mitochondrial oxygen consumption, and morphological changes, as well as bactericide activity, production of metabolites, cytokines, and activation markers in infected MQs. The cell line MH-S was used for all the experiments. Results: We show that P27 and PE_PGRS33 proteins modified mitochondrial dynamics, oxygen consumption, bacilli growth, cytokine production, and some genes that contribute to macrophage alternative activation and mycobacterial intracellular survival. Conclusions: Our findings showed that these bacterial proteins partially contribute to promoting M2 differentiation by altering mitochondrial metabolic activity.
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Mycobacterium tuberculosis , Tuberculose , Camundongos , Animais , Ativação de Macrófagos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Macrófagos Alveolares/metabolismo , MitocôndriasRESUMO
La Hipertensión Arterial es la enfermedad que se produce cuando las cifras de tensión arterial, medidas como promedio en tres tomas realizadas en condiciones apropiadas, con intervalos de tres a siete días entre cada toma, se encuentran por encima de 140mmHg de tensión arterial sistólica y 90mmHg de tensión arterial diastólica. Tratar la Hipertensión Arterial mediante las diferentes técnicas de la Medicina Natural y Tradicional tiene una gran importancia ya que se evitan de cierto modo los efectos adversos de los fármacos en los pacientes. La presente revisión bibliográfica tuvo como objetivo describir la aplicación de las diferentes técnicas de la Medicina Natural y Tradicional en el tratamiento de la Hipertensión Arterial como enfermedad crónica no trasmisible. Se realizó una exhaustiva revisión documental (bases de datos PubMed, SciELO Regional, Cochrane e infomed), de las cuales se escogieron 11 referencias bibliográficas. Se concluyó que El uso adecuado de estos métodos y técnicas terapéuticas amplía significativamente las posibilidades de los profesionales de la salud cubanos en el tratamiento de los pacientes, a la vez que recurrir a tales recursos contribuye a disminuir el uso de fármacos sintéticos y otros procedimientos más invasivos
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Terapias Complementares , Hipertensão , Bases de Dados Bibliográficas , Cuba , AcupunturaRESUMO
The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.
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Sistema Colinérgico não Neuronal/fisiologia , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/patologia , Acetilcolina/metabolismo , Animais , Colina O-Acetiltransferase/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Inflamação/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Antagonistas Nicotínicos/farmacologia , Sistema Colinérgico não Neuronal/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Regulação para Cima/fisiologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismoRESUMO
Background: individuals with type 2 diabetes show emotional distress as they learn how to cope with the disease. The emotional distress increases the possibility of complications in these patients. The aims of the present study were to evaluate the impact of the emotional distress in the quality of life of individuals with diabetes, and to investigate the demographic and clinical characteristics associated with the emotional distress of living with diabetes in a Mexican population. Methods: a total of 422 Mexican individuals with type 2 diabetes were recruited from the outpatient Diabetes Clinic of the Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa of Villahermosa, Tabasco. Demographic and clinical characteristics along with quality of life (SF-36) were assessed in these individuals. The emotional distress of living with diabetes was measured using the 5-item Problem Areas in Diabetes. Patients were divided according to the presence of high or low distress. Results: we identified that 31.8% (n = 134) of patients presented high diabetes-related emotional distress. We observed that hepatic diseases as comorbidities (p = 0.008) and diagnosis of major depression (p = 0.04) are factors associated with the emotional distress of living with diabetes. These patients showed a reduced quality of life in all dimensions (p < 0.001); the most affected dimensions were physical role (d = 0.37) and general health (d = 0.89) showing lower scores in comparison with patients with low emotional distress. Conclusions: our results suggest that Mexican individuals with type 2 diabetes mellitus show high emotional distress living with the disease and have a decreased quality of life. Therefore, it is necessary to decrease factors associated with the high emotional distress of living with diabetes in patients with type 2 diabetes.
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Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Diabetes Mellitus Tipo 2/psicologia , Nível de Saúde , Angústia Psicológica , Qualidade de Vida/psicologia , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Depression in patients with type 2 diabetes (T2D) is often undiagnosed and remains untreated, leading to poor therapy adherence and ill health-related outcomes. We evaluated the effect of vortioxetine versus sertraline in the treatment of depression, distress and metabolic control in subjects with T2D and depression. METHODS: Participants were selected from the Clinic for Diabetes, diagnosed with depression when the score was ≥14 in the Hamilton Depression Rating Scale, and verified by a psychiatrist in agreement with the DSM-5 instrument (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). The criteria for recruitment also included glycosylated hemoglobin ≥7.5%, 18 to 60 years of age, and written informed consent. Pharmacological treatment for depression was assigned randomly: vortioxetine (10 mg/day) or sertraline (75 mg/day) for 8 weeks. Biochemical parameters, anthropometric measures and depression symptoms were evaluated after antidepressant treatment. This was a randomized singled-blind study. RESULTS: Subjects that met the inclusion criteria were 50, of which only 21 patients with T2D and depression finished the treatment. Vortioxetine and sertraline showed partial remission of depression. Vortioxetine showed a major effect size in glycosylated hemoglobin and a moderate effect size on weight loss, fasting plasma glucose (FPG), cholesterol and triacylglycerol levels. On the other hand, patients treated with sertraline presented a slight increase in body weight, body mass index (BMI), and in all biochemical markers. CONCLUSIONS: Vortioxetine may ameliorate depressive symptoms and metabolic control in patients with T2D and depression. Trial registration number: NCT03978286.
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Objetivo: Evaluar el nivel de autoestima de adolescentes escolarizados en un colegio rural de un corregimiento de Pereira. Métodos: Se convocó a los estudiantes a participar, 292 aceptaron desarrollar la encuesta, mientras 20 se abstuvieron de hacerlo. Resultados: Previo análisis de confiabilidad del test, se encontró que 47,9% de los estudiantes presentaron una baja y muy baja autoestima. Un modelo multivariado reportó que la autoestima se reducía a medida que aumentaba la edad. Conclusiones: La comunidad académica y la familia deben interactuar a favor de un buen nivel de autoestima en los adolescentes
Objective: To assess the level of self-esteem of adolescents in a rural school of a district of Pereira. Methods: Students were called upon to participate, 292 agreed to undergo the test, while 20 abstained. Results: After a previous reliability test analysis, we found that 47.9% of students had low and very low self esteem. A multivariate model reported that self-esteem was reduced as age increased. Conclusions: The academic community and the family must work together in order to improve self-esteem among teenagers in general
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Adolescente , Comportamento do Adolescente , Psiquiatria do Adolescente , Relações Pai-Filho , AutoimagemRESUMO
OBJECTIVE: To assess the level of self-esteem of adolescents in a rural school of a district of Pereira. METHODS: Students were called upon to participate, 292 agreed to undergo the test, while 20 abstained. RESULTS: After a previous reliability test analysis, we found that 47.9% of students had low and very low self esteem. A multivariate model reported that self-esteem was reduced as age increased. CONCLUSIONS: The academic community and the family must work together in order to improve self-esteem among teenagers in general.
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OBJECTIVE: To study the NKX2-1 gene in two half-siblings with elevated thyroid-stimulating hormone (TSH) on state screen, prolonged neonatal respiratory distress despite term gestations, and persistent ataxia, dysarthria, and developmental delay. STUDY DESIGN: We amplified and sequenced DNA samples from blood or buccal swab for subjects and their unaffected siblings. RESULTS: The same mutation that prevents splicing together of exons 2 and 3 of the NKX2-1 gene was present in the affected siblings, their mother, and maternal grandmother but not in their unaffected siblings. The mutation was present in the heterozygous form, thus explaining the disease phenotype. CONCLUSIONS: Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.
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Ataxia/genética , Hipotireoidismo Congênito , Hipotireoidismo/genética , Proteínas Nucleares/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Fatores de Transcrição/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Linhagem , Fator Nuclear 1 de TireoideRESUMO
The comparative effects of dietary level and time of feeding corn (CO) and rose hip (RHO) oils on bile and plasma lipid composition were studied. 48 males Sprague Dawley rats were divided in two groups fed semipurified diets containing CO or RHO as the only lipid source. Groups of 6 rats were fed ad libitum diets containing 5 per cent or 15 per cent vegetable oil during 15 or 60 days. Food intake was not dependent on the type of oil, and was higher in 15 per cent oil diets (p < 0.01), increasing with time of feeding (p < 0.001). Bile flow was similar in all groups. Biliary concentrations of cholesterol, phospholipids and bile acids were affected by the time of feeding (p < 0.001). Plasma total and high density lipoprotein (HDL) cholesterol levels were higher in 15 per cent oil fed rats (p < 0.05). Triglycerides concentrations were similar in all groups. The results indicate that oil concentration and time of feeding were the most important variables affecting the lipid composition of rats, independently of the fatty acid composition of the ingested fats