Abstract Background-Pulmonary arterial hypertension (PAH) increases afterload in the right ventricle (RV), inducing adverse ventricular remodelling. Objective- This study explored the protective effects of thyroid hormones and grape juice on serum biomarkers and proteins related to intermediary metabolism in the RV in a model of PAH. Methods- PAH was induced in Wistar rats via the administration of monocrotaline (60 mg/kg i.p.) and they were subsequently treated with organic grape juice (GJ) and thyroid hormones (TH), administered separately or in combination. Results: The RV systolic diameter significantly increased (20%) in the PAH group compared to the control group (P = 0.002). Total CK, LDH, and ALT levels were reduced (~50%) (P<0.001) in the PAH+TH+GJ group as compared to PAH group. Glucose, albumin, triglyceride, and total cholesterol levels were reduced (~50%) (P<0.001) in the PAH group; however, these parameters returned to baseline in the PAH+GJ group. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein expression increased two-fold (P<0.001) and PDH protein levels were reduced (~25%) in the PAH+TH+GJ group compared to the PAH group (P<0.001). Conclusion: The data suggest that serum biomarkers can help in the evaluation of this disease, and that this therapeutic approach can attenuate maladaptive remodelling in the PAH model. BackgroundPulmonary Background Pulmonary (PAH RV, , (RV) Objective Methods 60 (6 mgkg mg kg i.p. ip i p GJ (GJ TH, TH (TH) combination Results 20% 20 (20% P 0.002. 0002 0.002 . 0 002 0.002) CK LDH ~50% 50 (~50% P<0.001 P0001 001 (P<0.001 PAHTHGJ Glucose albumin triglyceride however PAHGJ proliferatoractivated proliferator activated 1alpha alpha 1 PGC1α PGCα PGC 1α α (PGC-1α twofold two fold ~25% 25 (~25% P<0.001. Conclusion disease (RV 6 ( i.p (TH 2 (20 000 0.00 00 ~50 5 (~50 P<0.00 P000 (P<0.00 ~25 (~25 (2 0.0 ~5 (~5 P<0.0 P00 (P<0.0 ~2 (~2 0. ~ (~ P<0. P0 (P<0. P<0 (P<0 P< (P<

Abstract Background Adverse remodeling of lung vessels elevates pulmonary pressure and provokes pulmonary arterial hypertension (PAH). PAH results in increased right ventricle (RV) afterload, causing ventricular hypertrophy and the onset of heart failure. There is no specific treatment for maladaptive RV remodeling secondary to PAH. Objectives This study aims to explore two therapeutic approaches, grape juice (GJ) and thyroid hormones (TH), on PAH-induced oxidative stress and cardiac functional changes. Methods Parameters of echocardiography related to lung vessel resistance (AT/ET ratio), RV contractility (TAPSE), and RV diastolic function (E/A peaks ratio) were evaluated. Also, total ROS, lipid peroxidation, antioxidant enzymes, calcium handling proteins, pro-oxidant and antioxidant protein expression were measured. Values of p<0.05 were considered statistically significant. Results Both GJ and TH treatments demonstrated reductions in pulmonary resistance (~22%) and improvements in TAPSE (inotropism ~11%) and AT/ET ratio (~26%) (p<0.05). There were no changes amongst groups regarding the E/A peak ratio. Although ROS and TBARS were not statistically significant, GJ and TH treatments decreased xanthine oxidase (~49%) levels and normalized HSP70 and calcium handling protein expression (p<0.05). However, only TH treatment ameliorated diastolic function (~50%) and augmented NRF2 immunocontent (~48%) (p<0.05). Conclusions To the best of our knowledge, this study stands as a pioneer in showing that TH administered together with GJ promoted functional and biochemical improvements in a PAH model. Moreover, our data suggest that GJ and TH treatments were cardioprotective, combined or not, and exhibited their beneficial effects by modulating oxidative stress and calcium-handling proteins. . (PAH) (RV afterload failure approaches (GJ TH, , (TH) PAHinduced induced ATET AT ET ratio, TAPSE, (TAPSE) EA E A evaluated Also peroxidation enzymes proteins prooxidant pro oxidant measured p005 p 0 05 p<0.0 significant ~22% 22 (~22% inotropism ~11% 11 ~26% 26 (~26% p<0.05. (p<0.05) ~49% 49 (~49% HSP HSP7 However ~50% 50 (~50% NRF ~48% 48 (~48% knowledge model Moreover cardioprotective calciumhandling (PAH (TH (TAPSE p00 p<0. ~22 2 (~22 ~11 1 ~26 (~26 (p<0.05 ~49 4 (~49 ~50 5 (~50 ~48 (~48 p0 p<0 ~2 (~2 ~1 (p<0.0 ~4 (~4 ~5 (~5 p< ~ (~ (p<0. ( (p<0 (p< (p

Resumo Fundamento A remodelação adversa dos vasos pulmonares eleva a pressão pulmonar e provoca hipertensão arterial pulmonar (HAP). A HAP resulta em aumento da pós-carga do ventrículo direito (VD), causando hipertrofia ventricular e consequente insuficiência cardíaca. Não existe um tratamento específico para o remodelamento desadaptativo do VD secundário à HAP. Objetivos Este estudo tem como objetivo explorar duas abordagens terapêuticas, o suco de uva (SU) e os hormônios tireoidianos (HT), no tratamento do estresse oxidativo induzido pela HAP e nas alterações funcionais cardíacas. Métodos Parâmetros ecocardiográficos relacionados à resistência dos vasos pulmonares (relação TA/TE), contratilidade do VD (ESPAT) e função diastólica do VD (relação dos picos E/A) foram avaliados. Além disso, foram medidos ROS totais, peroxidação lipídica, enzimas antioxidantes, proteínas de manipulação de cálcio, expressão de proteínas pró-oxidantes e antioxidantes. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados Ambos os tratamentos, com SU e HT, demonstraram uma redução na resistência pulmonar (~22%), além de melhorias na ESPAT (inotropismo ~11%) e na relação TA/TE (~26%) (p<0,05). Não houve alterações entre os grupos na relação do pico de E/A. Embora ROS e TBARS não tenham sido estatisticamente significativos, os tratamentos com SU e HT diminuíram os níveis de xantina oxidase (~49%) e normalizaram a expressão de HSP70 e proteínas de manipulação de cálcio (p<0,05). No entanto, apenas o tratamento com HT melhorou a função diastólica (~50%) e aumentou o imunoconteúdo de NRF2 (~48%) (p<0,05). Conclusões Até onde sabemos, este estudo é pioneiro ao mostrar que o HT administrado em conjunto com o SU promoveu melhorias funcionais e bioquímicas em um modelo de HAP. Além disso, nossos dados sugerem que os tratamentos com SU e HT se mostraram cardioprotetores, sejam combinados ou não, e exibiram seus benefícios ao modular o estresse oxidativo e as proteínas de manipulação do cálcio. . (HAP) póscarga pós carga VD, , (VD) cardíaca terapêuticas (SU (HT) cardíacas TA/TE, TATE TA TE TA/TE) (ESPAT E/A EA E avaliados disso totais lipídica antioxidantes próoxidantes pró oxidantes p005 p 0 05 p<0,0 significativos ~22%, 22 ~22% (~22%) inotropismo ~11% 11 ~26% 26 (~26% p<0,05. (p<0,05) ~49% 49 (~49% HSP HSP7 entanto ~50% 50 (~50% NRF ~48% 48 (~48% sabemos cardioprotetores (HAP (VD (HT p00 p<0, 2 ~22 (~22% ~11 1 ~26 (~26 (p<0,05 ~49 4 (~49 ~50 5 (~50 ~48 (~48 p0 p<0 ~2 (~22 ~1 (~2 (p<0,0 ~4 (~4 ~5 (~5 p< ~ (~ (p<0, ( (p<0 (p< (p

ABSTRACT Objective Hyperthyroidism causes many injuries in its target organs and the consequences are reflected systemically. As systemic alterations in hyperthyroidism at earlier stages have received partial attention, this study aimed to investigate systemic redox and inflammatory status at an early stage of T4-induced hyperthyroidism. Materials and methods Male Wistar rats were assigned to control and hyperthyroid groups (n = 7/group). The hyperthyroid group received L-thyroxine (12 mg/L) in their drinking water for 14 days whereas control group received only the vehicle. Body weight was measured on the 1st and 14th day of the protocol. On the 14th day, animals were anaesthetized. Blood was then collected from the retro-orbital venous plexus and then the animals were euthanised. The blood was separated into plasma and erythrocytes. Plasma was used to measure ROS levels, sulfhydryl compounds, IL-10, TNF-α and LDH levels; erythrocytes were used for the analysis of thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes (total G6PD, G6PD and 6PGD). Results Hyperthyroid animals presented body weight gain and final body weight reduction, which was associated with increased ROS levels and decreased sulfhydryl content in plasma. Thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes levels in erythrocytes, as well as IL-10, TNF-α and LDH plasma levels were unaltered. Conclusion Taken together, our results suggest an impairment in corporal mass associated with systemic oxidative stress at this stage of hyperthyroidism. Meanwhile, the pentose cycle was not influenced and systemic inflammation and tissue damage seem to be absent at this stage of hyperthyroidism.

Resumo Neste trabalho, estudou-se a degradação da matéria orgânica presente no efluente de laticínio sintético por ozonização combinada (ozônio (O3)/peróxido de hidrogênio (H2O2)) e a ozonização catalítica (ozônio (O3)/manganês (Mn2+)) associada com o processo de flotação por ar disperso para obter o ponto ótimo de tratamento. Foi avaliado o efeito dos fatores independentes concentração de O3, pH e concentração de H2O2 e Mn2+. Para o tratamento flotação/O3/H2O2 os parâmetros significativos (p ≤ 0,05) do modelo foram: concentração de O3 (efeito linear e quadrático), concentração de H2O2 (efeito linear e quadrático), valores de pH (linear e quadrático) e interação concentração de O3 versus pH. Para a ozonização catalítica, observou-se que houve diferença significativa no tratamento apenas para o efeito linear da concentração de O3. De acordo com a função de desejabilidade, concluiu-se que a condição ótima para o tratamento de flotação/O3/H2O2 pode ser obtida em meio ácido utilizando concentrações de O3 superiores a 42,9 mg L-1 associada com concentrações de H2O2 mais elevadas que 1071,5 mg L-1. No entanto, em valores de pH maiores do que 9,0, a utilização de O3 pode ser negligenciada quando se usam concentrações mais elevadas do que 1071,5 mg L-1 de H2O2. Observou-se também que a flotação/ozonização catalisada pela adição do metal Mn2+ não afetou o tratamento, obtendo-se como condição ótima de 53,8 mg L-1 O3 e pH 3,6.

Abstract This work investigated the degradation of organic matter present in synthetic dairy wastewater by the combination of ozonation (ozone (O3)/hydrogen peroxide (H2O2)) and catalytic ozonation (ozone (O3)/manganese (Mn2+)) associated with dispersed air flotation process. The effect of independent factors such as O3 concentration, pH and H2O2 and Mn2+ concentration was evaluated. For the flotation/O3/H2O2 treatment, the significant variables (p ≤ 0.05) were: O3 concentration (linear and quadratic effect), H2O2 concentration linear and quadratic effect, pH values (linear and quadratic effect) and interaction O3 concentration versus pH. For catalytic ozonation, it was observed that the significant variable was the linear effect of O3 concentration. According to the desirability function, it was concluded that the optimal condition for the treatment of flotation/O3/H2O2 can be obtained in acidic solution using O3 concentrations greater than 42.9 mg L-1 combined with higher concentrations of H2O2 to 1071.5 mg L-1. On other hand, at pH values higher than 9.0, the addition of O3 may be neglected when using higher concentrations than 1071.5 mg L-1 of H2O2. For flotation/ozonation catalyzed by Mn2+, it was observed that metal addition did not affect treatment, resulting in an optimum condition: 53.8 mg L-1 of O3 and pH 3.6.

Abstract Introduction: Oxidative stress seems to be a role in the atherosclerosis process, but research in human beings is scarce. Objective: To evaluate the role of oxidative stress on human aortas of patients submitted to surgical treatment for advanced aortoiliac occlusive disease. Methods: Twenty-six patients were divided into three groups: control group (n=10) formed by cadaveric organ donors; severe aortoiliac stenosis group (patients with severe aortoiliac stenosis; n=9); and total aortoiliac occlusion group (patients with chronic total aortoiliac occlusion; n=7). We evaluated the reactive oxygen species concentration, nicotinamide adenine dinucleotide phosphate-oxidase, superoxide dismutase and catalase activities as well as nitrite levels in samples of aortas harvested during aortofemoral bypass for treatment of advanced aortoiliac occlusive disease. Results: We observed a higher level of reactive oxygen species in total aortoiliac occlusion group (48.3±9.56 pmol/mg protein) when compared to severe aortoiliac stenosis (33.5±7.4 pmol/mg protein) and control (4.91±0.8 pmol/mg protein) groups (P<0.05). Nicotinamide adenine dinucleotide phosphate oxidase activity was also higher in total aortoiliac occlusion group when compared to the control group (3.81±1.7 versus 1.05±0.31 µmol/min.mg protein; P<0.05). Furthermore, superoxide dismutase and catalase activities were significantly higher in the severe aortoiliac stenosis and total aortoiliac occlusion groups when compared to the control cases (P<0.05). Nitrite concentration was smaller in the severe aortoiliac stenosis group in comparing to the other groups. Conclusion: Our results indicated an increase of reactive oxygen species levels and nicotinamide adenine dinucleotide phosphate-oxidase activity in human aortic samples of patients with advanced aortoiliac occlusive disease. The increase of antioxidant enzymes activities may be due to a compensative phenomenon to reactive oxygen species production mediated by nicotinamide adenine dinucleotide phosphate oxidase. This preliminary study offers us a more comprehensive knowledge about the role of oxidative stress in advanced aortoiliac occlusive disease in human beings.

ABSTRACT PURPOSE: To evaluated the role of oxidative stress on aging process in patients submitted to carotid endarterectomy. METHODS: Twenty patients were divided into two groups: older group (≥ 70 years old); and the younger group (< 70 years old). We evaluated the reactive oxygen species (ROS) concentration, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, superoxide dismutase (SOD) and catalase (CAT) activities as so as nitrite levels in fragments of carotid arteries harvested during carotid endarterectomy for treatment of high grade carotid stenosis. RESULTS: We observed a higher levels of ROS and NADPH oxidase activity in the older group (p<0.05). Furthermore, the nitrite concentration was lower in the older group (14.55 ± 5.61 x 10-3 versus 26.42 ± 8.14 x 10-3 µM; p=0.0123). However, the activities of antioxidant enzymes (CAT and SOD) were similar in both the groups. CONCLUSIONS : Arterial aging is associated with increased concentrations of oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity as so as nitrite reduction in human carotid artery specimens. Maybe therapies that block NADPH oxidase activity and enhance nitrite stores would be a good strategy to reduce the effect of oxidative stress in arterial aging.