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Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with the major symptoms comprising loss of movement coordination (motor dysfunction) and non-motor dysfunction, including gastrointestinal symptoms. Alterations in the gut microbiota composition have been reported in PD patients vs. controls. However, it is still unclear how these compositional changes contribute to disease etiology and progression. Furthermore, most of the available studies have focused on European, Asian, and North American cohorts, but the microbiomes of PD patients in Latin America have not been characterized. To address this problem, we obtained fecal samples from Colombian participants (n = 25 controls, n = 25 PD idiopathic cases) to characterize the taxonomical community changes during disease via 16S rRNA gene sequencing. An analysis of differential composition, diversity, and personalized computational modeling was carried out, given the fecal bacterial composition and diet of each participant. We found three metabolites that differed in dietary habits between PD patients and controls: carbohydrates, trans fatty acids, and potassium. We identified six genera that changed significantly in their relative abundance between PD patients and controls, belonging to the families Lachnospiraceae, Lactobacillaceae, Verrucomicrobioaceae, Peptostreptococcaceae, and Streptococcaceae. Furthermore, personalized metabolic modeling of the gut microbiome revealed changes in the predicted production of seven metabolites (Indole, tryptophan, fructose, phenylacetic acid, myristic acid, 3-Methyl-2-oxovaleric acid, and N-Acetylneuraminic acid). These metabolites are associated with the metabolism of aromatic amino acids and their consumption in the diet. Therefore, this research suggests that each individual's diet and intestinal composition could affect host metabolism. Furthermore, these findings open the door to the study of microbiome-host interactions and allow us to contribute to personalized medicine.
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Garlic (Allium sativum) possesses healing properties for diseases like systemic arterial hypertension, cancer and diabetes, among others. Its main component, allicin, binds to the Transient Receptor Potential Vanilloid Type 1 (TRPV1). In this study, we investigated TRPV1's involvement in the regulation of various molecules at the systemic and aortic levels in Wistar rats treated with bacterial lipopolysaccharide (LPS) and garlic to activate the receptor. The experimental groups were as follows: 1) Control, 2) LPS, 3) Garlic, and 4) LPS + Garlic. Using Uv-visible spectrophotometry and capillary zone electrophoresis, we measured the levels of nitric oxide (NO), biopterins BH2 and BH4, total antioxidant capacity (TAC) and oxidizing capacity (OXCA). We also analyzed molecules related to vascular homeostasis such as angiotensin Ang 1-7 and Ang II, as well as endothelin ET-1. In addition, we assessed the inflammatory response by determining the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and galectin-3 (GTN-3). For cell damage assessment, we measured levels of malondialdehyde (MDA), malonate (MTO) and 8-hydroxy-2-deoxyguanosine (8HO2dG). The results showed that LPS influenced the NO pathway at both systemic and aortic levels by increasing OXCA and reducing TAC. It also disrupted vascular homeostasis by increasing Ang-II and ET-1, while decreasing Ang1-7 levels. IL-6, TNFα, GTN-3, as well as MDA, MTO, and 8HO2dG were significantly elevated compared to the control group. The expression of iNOS was increased, but TRPV1 remained unaffected by LPS. However, garlic treatment effectively mitigated the effects of LPS and significantly increased TRPV1 expression. Furthermore, LPS caused a significant decrease in calcitonin gene-related peptide (CGRP) in the aorta, which was counteracted by garlic treatment. Overall, TRPV1 appears to play a crucial role in regulating oxidative stress and the molecules involved in damage and inflammation induced by LPS. Thus, studying TRPV1, CGRP, and allicin may offer a potential strategy for mitigating inflammatory and oxidative stress in sepsis.
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The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.
Assuntos
Hibiscus , Síndrome Metabólica , Masculino , Ratos , Animais , Ácido Araquidônico , Ratos Wistar , Ciclo-Oxigenase 2 , Síndrome Metabólica/tratamento farmacológico , Rim/fisiologia , Fosfolipases A2RESUMO
Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.
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Alho , Sulfeto de Hidrogênio , Selênio , Animais , Ratos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Alho/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Lipopolissacarídeos/farmacologia , Estresse Oxidativo , Selênio/farmacologia , Compostos de Sulfidrila/farmacologia , Tiorredoxina Dissulfeto Redutase/metabolismo , Transferases/metabolismoRESUMO
The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here, we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the control of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats perfused according to the Langendorff technique were used to study the effects of an agonist of TRPV1, capsaicin (CS), an antagonist, capsazepine (CZ), and their combination CZ+CS. The hearts were subjected to three conditions: (1) control, (2) ischemia and (3) ischemia-reperfusion. We determined cardiac mechanical activity and the levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue after administration of CS, CZ and CZ+CS. Western blots were used to study the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac mechanical activity and elevating the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.
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Coração/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico/metabolismo , Estresse Oxidativo , Canais de Cátion TRPV/metabolismo , Animais , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
The potential transient vanilloid receptor type 1 (TRPV1) plays important functional roles in the vascular system. In the present study, we explored the role of the TRPV1 in the production of nitric oxide (NO), biopterines (BH4 and BH2), cyclic guanosine monophosphate (cGMP), malondialdehyde (MDA), phosphodiesterase-3 (PDE-3), total antioxidant capacity (TAC), and calcitonin gene-related peptide (CGRP) in the rat aorta. Wistar rats were divided into four groups: (1) control, (2) capsaicin (CS, 20 mg/kg), (3) capsazepine (CZ, 24 mg/kg), and (4) CZ + CS. Treatments were applied daily for 4 days before removing the thoracic aortas for testing of aortic tissue and endothelial cells. TRPV1 activation produced increases in BH4 14%, cGMP 25%, NO 29%, and TAC 59.2% in comparison to the controls. BH2 and MDA increased with CZ. CGRP shows a tendency to decrease with CZ. The analysis by immunocytochemistry confirmed that the TRPV1 is present in aortic endothelial cells. Aortic endothelial cells were obtained from healthy rats and cultured to directly explore the effects of CS and CZ. The activation of the TRPV1 (CS 30 µM) produced increases in BH4 17%, NO 36.6%, TAC 56.3%, and CGRP 65%, when compared to controls. BH2 decreased with CZ + CS. CS effects were diminished by CZ in cells and in the tissue. We conclude that the TRPV1 is a structure present in the membrane of aortic endothelial cells and that it participates in the production of NO. The importance of the TRPV1 should be considered in vascular reactivity studies.
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Aorta/metabolismo , Óxido Nítrico/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Aorta/efeitos dos fármacos , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , GMP Cíclico/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Canais de Cátion TRPV/genéticaRESUMO
The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups: (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.
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Prochilodus magdalenae is a freshwater fish endemic to the Colombian Magdalena-Cauca and Caribbean hydrographic basins. The genetic structure patterns of populations of different members of Prochilodus and the historic restocking of its depleted natural populations suggest that P. magdalenae exhibits genetic stocks that coexist and co-migrate throughout the rivers Magdalena, Cauca, Cesar, Sinú and Atrato. To test this hypothesis and explore the levels of genetic diversity and population demography of 725 samples of P. magdalenae from the studied rivers, we developed a set of 11 species-specific microsatellite loci using next-generation sequencing, bioinformatics, and experimental tests of the levels of diversity of the microsatellite loci. The results evidenced that P. magdalenae exhibits high genetic diversity, significant inbreeding coefficient ranging from 0.162 to 0.202, and signs of erosion of the genetic pool. Additionally, the population genetic structure constitutes a mixture of genetic stocks heterogeneously distributed along the studied rivers, and moreover, a highly divergent genetic stock was detected in Chucurí, Puerto Berrío and Palagua that may result from restocking practices. This study provides molecular tools and a wide framework regarding the genetic diversity and structure of P. magdalenae, which is crucial to complement its baseline information, diagnosis and monitoring of populations, and to support the implementation of adequate regulation, management, and conservation policies.
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INTRODUCCIÓN: La neurofibromatosis tipo 1(NF1) descrita por primera vez por von Recklinghausen en 1884, es una enfermedad de transmisión genética autosómica dominante, causada por un espectro de mutaciones en el gen NF-1, de evolución impredecible, que afecta múltiples órganos y sistemas, como la piel y el sistema nervioso, afectando también el desarrollo infantil y al estado neurocognitivo. Representa para el médico la toma de decisiones de manejo a menudo complejas, que requieren un enfoque multidisciplinario. CASO CLÍNICO: Paciente femenino de 9 años de edad, con antecedente de neurofibromatosis tipo 1. Presenta masa en región cervical anterior, que ocupa además el hemitórax izquierdo, comprimiendo el mediastino anterior, la tráquea del lado izquierdo, el corazón, el pulmón izquierdo; la masa produce sintomatología: disnea, disfagia y dolor, por lo que se programa intervención quirúrgica para exéresis del tumor. Se realizó cervico-esternotomía- toracotomía izquierda, se extirpó masa de 12 x 7 cm, ubicada a nivel de cayado aórtico, íntimamente adherida a la columna vertebral cervico-torácica. EVOLUCIÓN: Durante el acto quirúrgico la paciente tuvo un sangrado cuantioso, proveniente de arteria colateral de carótida común izquierda, por lo que se decidió empaquetar para resolución posterior, 24 horas después se desempaquetó, logrando control del sangrado tras el procedimiento. Los resultados de anatomía patología establecieron que la masa fue un neurofibroma. El seguimiento posterior determinó mejoría de la sintomatología, sin complicaciones quirúrgicas tardías. CONCLUSIÓN: La Neurofibromatosis es una patología congénita, poco frecuente y de complejo manejo. Aunque no existe tratamiento definitivo para la neurofibromatosis tipo 1, se puede realizar un manejo integral para mejorar la calidad de vida del paciente. Los tumores pueden extirparse mediante cirugía, aunque a menudo vuelven a crecer.(au)
BACKGROUND: Neurofibromatosis type 1, first described by von Recklinghausen in 1884, is an autosomal dominant genetically transmitted disease, caused by a spectrum of mutations in the NF-1 gen, with unpredictable evolution, that affects multiple organs and systems, such as the skin and the nervous system, also affecting child development and neurocognitive functions. It often requires complex management decisions from the physician that involve a multidisciplinary approach. CASE REPORTS: 9 year old female patient with a history of type 1 neurofibromatosis. She presented with a mass located in the anterior cervical region, occupying also the left hemithorax, compressing the anterior mediastinum, the trachea from its left side, the heart, and the left lung; the mass produced symptoms: dyspnea, dysphagia and pain, so surgical excision of the mass was scheduled. A left cervical-sternotomy-thoracotomy was performed, a 12 x 7cm mass, located at aortic arch level, closely adhered to the cervical-thoracic spine, was excised. EVOLUTION: During the surgical procedure, the patient had profuse bleeding, coming form the left common carotid colateral artery, so abdominal packing was performed, for later resolution. 24 hours later, bleeding control was achieved after the surgical re-intervention. The pathology lab results established that the mass was in fact a neurofibroma. Subsequent follow-up determined symptoms improvement, without late surgical complications. CONCLUSIONS: Neurofibromatosis is a congenital infrequent, disease, with a complex treatment. Although there is no definitive treatment for type 1 neurofibromatosis, comprehensive management can be achieved to improve the patient's quality of life. Tumors can be surgically removed, although they often grow back.(au)
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Humanos , Masculino , Criança , Toracotomia , Neurofibromatose 1 , Neurofibroma , Procedimentos Cirúrgicos Operatórios , Genética , MétodosRESUMO
The purpose of the present study was to analyze the actions of transient receptor potential vanilloid type 1 (TRPV1) agonist capsaicin (CS) and of its antagonist capsazepine (CZ), on cardiac function as well as endothelial biomarkers and some parameters related with nitric oxide (NO) release in L-NG-nitroarginine methyl ester (L-NAME)-induced hypertensive rats. NO has been implicated in the pathophysiology of systemic arterial hypertension (SAHT). We analyzed the levels of nitric oxide (NO), tetrahydrobiopterin (BH4), malondialdehyde (MDA), total antioxidant capacity (TAC), cyclic guanosin monophosphate (cGMP), phosphodiesterase-3 (PDE-3), and the expression of endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GTPCH-1), protein kinase B (AKT), and TRPV1 in serum and cardiac tissue of normotensive (118±3 mmHg) and hypertensive (H) rats (165 ± 4 mmHg). Cardiac mechanical performance (CMP) was calculated and NO was quantified in the coronary effluent in the Langendorff isolated heart model. In hypertensive rats capsaicin increased the levels of NO, BH4, cGMP, and TAC, and reduced PDE-3 and MDA. Expressions of eNOS, GTPCH-1, and TRPV1 were increased, while AKT was decreased. Capsazepine diminished these effects. In the hypertensive heart, CMP improved with the CS treatment. In conclusion, the activation of TRPV1 in H rats may be an alternative mechanism for the improvement of cardiac function and systemic levels of biomarkers related to the bioavailability of NO.
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Coração/efeitos dos fármacos , Hipertensão/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Biomarcadores/sangue , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Pressão Sanguínea , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Hipertensão/tratamento farmacológico , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase Tipo III , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Resistência VascularRESUMO
Cardiovascular diseases (CVD) constitute one of the most prevalent health problems worldwide, being strongly associated with metabolic syndrome (MS). Oxidative stress (OS) is present in both CVD and MS. Infusions of Hibiscus sabdariffa Linnaeus (HSL) have antioxidant properties and could therefore decrease the presence of OS in these diseases. The aim of this study was to evaluate myocardial protection during ischemia/reperfusion due to the antioxidant effect of HSL infusion (3%) on a MS rat model induced by the administration of 30% sucrose in drinking water. We determined in control, MS, and MS + HSL rat hearts (n = 6 per group) cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and activities of manganese and copper/zinc superoxide dismutases (Mn and Cu/Zn-SOD), peroxidases, glutathione peroxidase (GPx), catalase (CAT), glutathione s-transferase (GST), glutathione reductase (GR), and glutathione (GSH). We also determined lipoperoxidation (LPO), total antioxidant capacity (TAC), and the nitrate/nitrite ratio (NO3 -/NO2 -). The treatment with the HSL infusion restored the CMP (p = 0.01) and CVR (p = 0.04) and increased the Mn- (p = 0.02), Cu/Zn-SOD (p = 0.05), peroxidases (p = 0.04), GST (p = 0.02) activity, GHS (p = 0.02), TAC (p = 0.04), and NO3 -/NO2 - (p = 0.01) and decreased the LPO (p = 0.02) in the heart of MS rats undergoing ischemia/reperfusion. The results suggest that the treatment with an infusion from HSL calices protects the cardiac function from damage by ischemia and reperfusion through the antioxidant activities of the substances it possesses. It favors antioxidant enzymatic activities and nonenzymatic antioxidant capacity.
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Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Hibiscus/química , Síndrome Metabólica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Cardiotônicos/química , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Proteínas Musculares/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , RatosRESUMO
Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.
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Clofibrato/farmacologia , Hipolipemiantes/farmacologia , Inflamação/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Infarto do Miocárdio/metabolismo , PPAR alfa/metabolismo , RoedoresRESUMO
Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.
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Fármacos Cardiovasculares/uso terapêutico , Crataegus/química , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Rosmarinus/química , Angiotensinas/farmacologia , Animais , Biomarcadores/metabolismo , Bradicinina/farmacologia , Fármacos Cardiovasculares/farmacologia , Cromatografia Líquida de Alta Pressão , Testes de Função Cardíaca , Hemodinâmica/efeitos dos fármacos , Masculino , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miocárdio/ultraestrutura , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos Wistar , Vasoconstrição/efeitos dos fármacosRESUMO
ABSTRACT Introduction: Reynolds syndrome (RS) is an autoimmune disorder characterized by overlapping primary biliary cirrhosis (PBC) and limited cutaneous systemic sclerosis (lcSSc). Some published cases do not report pulmonary arterial hypertension (PAH), and diagnoses are usually based on clinical, immunological and histological findings, mainly focused on dermatologic features, on those associated with Sjogren's syndrome, or on an interesting presentation of malignant thymoma; only one case of reported PAH was found, but it was an image report. Case Presentation: This paper reports the case of a 75-year-old woman who presented with some of the features mentioned above, severe PAH, dyspnea for one month and two weeks of purulent expectoration, as well as generalized pruritus, nasal telangiectasias, Raynaud phenomenon, sclerodactyly, and high levels of alkaline phosphatase and transaminases. Pulmonary arterial hypertension was documented through a transthoracic echocardiogram, and inmunoflorecence reported mitochondrial and centromere patterns of antinuclear-antibodies. Consequently, RS was diagnosed and phosphodiesterase type-5 inhibitors were started for PAH treatment resulting in the improvement of dyspnea. Conclusion: Dyspnea could be caused by many conditions, but in the presence of clinical and physical findings, it suggests an autoimmune disorder. Scleroderma should be considered and, additionally, PAH should be investigated since it is present in up to 10% of patients, conferring a worse prognosis. Internists should keep in mind that these disorders may be associated with other autoimmune diseases.
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Humanos , Doença de Raynaud , Esclerodermia Localizada , Hipertensão Pulmonar , Cirrose HepáticaRESUMO
Oophorectomy in adult rats affected cardiac mitochondrial function. Progression of mitochondrial alterations was assessed at one, two and three months after surgery: at one month, very slight changes were observed, which increased at two and three months. Gradual effects included decrease in the rates of oxygen consumption and in respiratory uncoupling in the presence of complex I substrates, as well as compromised Ca2+ buffering ability. Malondialdehyde concentration increased, whereas the ROS-detoxifying enzyme Mn2+ superoxide dismutase (MnSOD) and aconitase lost activity. In the mitochondrial respiratory chain, the concentration and activity of complex I and complex IV decreased. Among other mitochondrial enzymes and transporters, adenine nucleotide carrier and glutaminase decreased. 2-Oxoglutarate dehydrogenase and pyruvate dehydrogenase also decreased. Data strongly suggest that in the female rat heart, estrogen depletion leads to progressive, severe mitochondrial dysfunction.
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Mitocôndrias Cardíacas/metabolismo , Ovariectomia , Fosforilação Oxidativa , Consumo de Oxigênio/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Aconitato Hidratase/metabolismo , Animais , Feminino , Malondialdeído/metabolismo , Ratos , Superóxido Dismutase/metabolismoRESUMO
Abstract: Objective: dental students are particularly affected by stress, which can lead to burnout syndrome by association with other psychological factors. The aim of this study was to analyse the effect of perceived stress, coping strategies, and vocational satisfaction on the severity of burnout in Chilean dental students in the clinical years. Method: The study population was comprised of clinical dental students of five Chilean dental schools. The following variables were considered: age, gender, year of study, burnout, coping strategies, perceived stress, and vocational satisfaction. Statistical analysis included descriptive measures, correlation tests, and stepwise multiple regression analysis. Results: The final sample included 244 students. Three (1.23 percent) students did not have burnout in any of its factors and 38 (15.57 percent) had severe levels in all three factors. There was a statistically significant greater emotional exhaustion in 4th year students. There was a statistically significant correlation of the three factors of burnout with social withdrawal coping strategy, high levels of perceived stress, and low levels of present and future vocational satisfaction. Conclusion: Most students presented moderate and high levels of burnout. This situation is associated with dysfunctional coping strategies, high levels of perceived stress, and low levels of present and future vocational satisfaction.
Resumen: Objetivo: los estudiantes de odontología se ven particularmente afectados por el estrés, que puede conducir al síndrome de burnout por asociación con otros factores psicológicos. El objetivo de este estudio fue analizar el efecto del estrés percibido, las estrategias de afrontamiento y la satisfacción vocacional en la severidad del burnout en los estudiantes de odontología chilenos en los años clínicos. Método: La población estudiada estaba compuesta por estudiantes de odontología en etapa clínica de cinco escuelas dentales chilenas. Se consideraron las siguientes variables: edad, sexo, año de estudio, burnout, estrategias de afrontamiento, estrés percibido y satisfacción vocacional. El análisis estadístico incluyó estadísticas descriptivas, pruebas de correlación y análisis de regresión múltiple. Resultados: La muestra final incluyó a 244 estudiantes. Tres (1.23 por ciento) estudiantes no presentaron burnout en ninguno de sus factores y 38 (15.57 por ciento) tuvieron niveles severos en los tres factores. Hubo un mayor "agotamiento emocional" estadísticamente significativo en los estudiantes de cuarto año. Hubo una correlación estadísticamente significativa de los tres factores de burnout con la estrategia de "retirada social", altos niveles de percepción de estrés y bajos niveles de satisfacción vocacional presente y futura. Conclusión: La mayoría de los estudiantes presentaron niveles moderados y altos de burnout. Esta situación se asocia con estrategias de afrontamiento disfuncionales, altos niveles de estrés percibido y bajos niveles de satisfacción vocacional presente y futura.
Assuntos
Masculino , Feminino , Humanos , Adulto , Adulto Jovem , Esgotamento Profissional/epidemiologia , Estresse Psicológico/epidemiologia , Estudantes de Odontologia/psicologia , Adaptação Psicológica , Esgotamento Profissional/psicologia , Chile , Modelos Logísticos , Saúde Mental , Satisfação Pessoal , Fatores Sexuais , Estresse Psicológico/psicologiaRESUMO
The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats (30% sucrose in drinking water from weaning) plus saline solution (MS + SS), control rats receiving AGE (C + AGE 125 mg/Kg/12 h) and MS rats with AGE (MS + AGE) were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01). Cholesterol was decreased by AGE (p = 0.05). Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05). Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001). Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation) and AGE improved it (p = 0.001). Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001). Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01). In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.
Assuntos
Antioxidantes/administração & dosagem , Alho/química , Testes de Função Cardíaca/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , Modelos Animais de Doenças , Produtos Finais de Glicação Avançada/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Síndrome Metabólica/fisiopatologia , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Triglicerídeos/sangueRESUMO
BACKGROUND: Arterial high blood pressure is a risk factor for target organ damage; the most susceptible organs are the arteries, brain, kidneys, and heart. The damage mechanisms include oxidative stress and renin-angiotensin system (RAS) overactivity. Therefore, our aim was to study whether clofibrate-induced peroxisome proliferator-activated receptor-alpha (PPAR-α) stimulation is able to prevent alterations in cardiac functioning derived from RAS overstimulation in the left ventricle of rats with hypertension secondary to aortic coarctation and to improve antioxidant defenses. METHODS: Male Wistar rats were assigned to Control (Sham)- or aortic coarctation-surgery and further divided to receive (1 or 21 days) vehicle, clofibrate (100mg/kg), captopril (20mg/kg), or clofibrate+captopril. The left ventricle was obtained to measure: angiotensin II and -(1-7), AT1 and AT2 receptors, angiotensin converting enzyme (ACE)-1 and -2, and MAS receptor; the activity and expression of superoxide dismutase, catalase, endothelial nitric oxide synthase, the production of reactive oxygen species (ROS) and peroxidated lipids; as well as ex vivo cardiac functioning. RESULTS: Clofibrate decreased angiotensin II, AT1 receptor and ACE expression, and raised angiotensin-(1-7), AT2 receptor, ACE-2 expression, superoxide dismutase and endothelial nitric oxide synthase participation. These effects promoted lower coronary vascular resistance and improved mechanical work compared to aortic coarctated vehicle-treated rats. CONCLUSIONS: Clofibrate-induced PPAR-α stimulation changes the angiotensin II receptor profile, favors the ACE2/angiotensin-(1-7)/AT2 receptor axis decreasing the vasoconstrictor environment, activates the antioxidant defense, and facilitates endothelial nitric oxide synthase activity favoring vasodilation. This may represent a protection for the stressed heart.
Assuntos
Antioxidantes/farmacologia , Clofibrato/farmacologia , Ventrículos do Coração/fisiopatologia , Hipertensão/fisiopatologia , PPAR alfa/agonistas , Vasodilatação/efeitos dos fármacos , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Coartação Aórtica/complicações , Coartação Aórtica/fisiopatologia , Captopril/farmacologia , Catalase/metabolismo , Sinergismo Farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Abstract: dental students suffer greater stress than the rest of the university population. In general, most health students seek little assistance to help them cope with stress. The aim of this study is to evaluate the use of therapies to manage stress in Chilean clinical dental students. A cross-sectional study was conducted nationwide; this report is a secondary data analysis. The study population was dental students in clinical years (4th and 5th) of 5 Chilean dental schools: Antofagasta, Valparaíso, Viña del Mar, Concepción, and La Frontera. This paper reports the use of therapies for stress management during the past six months considering four options: medical/psychiatric, psychological, self-medication and alternative. Tabulation and analysis were done in STATA 10/SE. Three hundred thirty-seven students were surveyed, 54.01 percent were men and 64.99 percent were in fourth year, with an average age of 22.94 more less 2.04. The 48.07 percent of students have used any of the four types of therapies; women and fourth-year students use more any form of therapy with 53.30 percent (p=.037) and 48.86 percent (p=.694), respectively, than men and fifth year students. About half of the students have used some form of therapy to manage stress in the last six months; of the students that received therapy, the percentage of women was significantly higher.
Resumen: los estudiantes de odontología sufren mayor estrés que el resto de la población universitaria. En general los estudiantes del área de la salud recurren escasamente a ayuda para enfrentar el estrés. El objetivo de este trabajo es evaluar la utilización de terapias para manejar el estrés en estudiantes chilenos de odontología en etapa clínica. Se realizó un estudio de corte transversal con alcance nacional, este corresponde a un análisis secundario de datos. La población en estudio fueron estudiantes de odontología en período de clínica (4to y 5to año), de 5 Universidades: de Antofagasta, de Valparaíso, de Viña del Mar, de Concepción y de La Frontera. Para el presente estudio se reportan la utilización de terapias para manejar el estrés durante los últimos seis meses considerando cuatro opciones: médico/psiquiátrico, psicológico, automedicación y alternativo. La tabulación y análisis se hizo en STATA 10/SE. Se encuestaron 337 alumnos, 54.01 percent correspondió a hombres y el 64.99 percent a cuarto año, con una edad promedio 22.94 más menos 2.04. Un 48.07 percent ha utilizado alguno de los cuatro tipos de terapia consultadas, las mujeres utilizan en mayor proporción alguna forma de terapia con el 53.30 percent (p=.037), así como los alumnos de cuarto año con un 48.86 percent (p=.694), en comparación a los hombres y alumnos de quinto año respectivamente. Aproximadamente la mitad de los estudiantes han utilizado alguna forma de terapia para manejar el estrés en los últimos seis meses, siendo significativamente superior en mujeres.
Assuntos
Humanos , Masculino , Adulto , Feminino , Estresse Psicológico/terapia , Estudantes de Odontologia/psicologia , Chile , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPARα stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.