Oxidative stress in rheumatoid arthritis: what the future might hold regarding novel biomarkers and add-on therapies

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction-self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?-represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis

Physical exercise on inflammatory markers in type 2 diabetes patients: a systematic review of randomized controlled trials

Background. Type 2 diabetes mellitus (T2DM) is a serious disease associated with high morbidity and mortality. Scientific findings showed that physical exercise is an option for treatment of these patients. This study's objective is to investigate the effects of supervised aerobic and/or resistance physical training on inflammatory markers in subjects with T2DM. Methods. A systematic review was conducted on four databases, MEDLINE, CENTRAL, LILACS, and Scopus, and manual search from 21 to 30 November 2016. Randomized clinical trials involving individuals diagnosed with T2DM, who have undergone supervised training protocols, were selected in this study. Results. Eleven studies were included. Studies that evaluated control group versus aerobic exercise reported controversial results about the effectiveness of physical training in modifying C-reactive protein (CRP) and cytokine levels. The only variable analyzed by the six studies in comparison to the control group versus resistance exercise was CRP. This protein showed no significant difference between groups. Between the two modes of exercise (aerobic and resistance), only one study demonstrated that aerobic exercise was more effective in reducing CRP. Conclusion. The evidence was insufficient to prove that aerobic or resistance exercise improves systemic levels of inflammatory markers in patients with T2DM

Oxidative status imbalance in patients with metabolic syndrome: Role of the myeloperoxidase/hydrogen peroxide axis

The present study evaluated the cardiometabolic and redox balance profiles in patients with Metabolic Syndrome compared to apparently healthy individuals, and the participation of the myeloperoxidase/hydrogen peroxide axis in systemic lipid peroxidation. Twenty-four patients with Metabolic Syndrome and eighteen controls underwent a full clinical assessment. Venous blood samples were collected for general biochemical dosages, as well as for the oxidative stress analyses (superoxide dismutase, catalase, and arginase activities; and lipid peroxidation, myeloperoxidase activity, nitrite, and hydrogen peroxide concentrations in plasma). Arterial stiffness was assessed by radial artery applanation tonometry. Plasma lipid peroxidation, erythrocyte superoxide dismutase activity, myeloperoxidase activity, and hydrogen peroxide concentrations were shown to be increased in Metabolic Syndrome patients, without significant differences for the other enzymes, plasma nitrite concentrations, and arterial stiffness. Linear regression analysis revealed a positive and significant correlation between lipid peroxidation and myeloperoxidase and also between this enzyme and hydrogen peroxide. In contrast, such correlation was not observed between lipid peroxidation and hydrogen peroxide. In summary, Metabolic Syndrome patients exhibited evident systemic redox imbalance compared to controls, with the possible participation of the myeloperoxidase/hydrogen peroxide axis as a contributor in lipid peroxidation

3-amino-1,2,4-triazole induces quick and strong fat loss in mice with high fat-induced metabolic syndrome

BACKGROUND: Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS. METHODS: Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg(-1)·24 h(-1)) for 12 weeks. RESULTS: The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels. CONCLUSIONS: In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status

Characterising pressure and bruising in apple fruit

A large percentage of apples are wasted each year due to damage such as bruising. The apple journey from orchard to supermarket is very complex and apples are subjected to a variety of static and dynamic loads that could result in this damage occurring. The aim of this work was to use a novel ultrasonic technique to study apple contact areas and stresses under static loading that may occur, for example, in bulk storage bins used during harvesting. These results were used to identify load thresholds above which unacceptable damage occurs. They were also used to validate output from a finite element model, which will ultimately be developed into a packaging design tool to help reduce the likelihood of apple damage occurring

Genetic deletion of ACE2 induces vascular dysfunction in C57BL/6 mice: role of nitric oxide imbalance and oxidative stress

Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance

INFECCION FILARIAL DE APROCTELLA STODDARDI CRAM, 1931 (NEMATODA: ONCHOCERCIDAE) EN PASSERIFORMES DE AREAS PERIURBANAS, ESTADO DE PARÁ. BRASIL

Reports of filarial nematodes in wild birds are scarce in South America, particularly in the Amazon region. We analyzed the organs in the thoracic and abdominal cavities of 34 wild birds belonging to 12 different species of the order Passeriformes in the Periurban areas of Para State. Adult filariae was observed in 3/34 (9%) birds, located in the abdominal cavity of hosts. The morphological and morphometric characteristics of the filarial nematodes were consistent with the taxonomic classification of Aproctella stoddardi Cram, 1931, making this the first report of this species in the Amazon region in northern Brazil. Due to the observed migration of other genera of filariae, Aproctella Cram, 1931 may have the ability to infection at other sites, such as the liver, heart, lung, and brain. In addition, it is necessary to expand the records of the presence of filariae in birds of the region to elucidate the factors that influence this infection.Reportes de nematodos filarias en aves silvestres son escasos en América del Sur, principalmente en la región amazónica. Fueron analizados los órganos de las cavidades torácica y abdominal de 34 aves silvestres pertenecientes a 12 especies diferentes de aves Passeriformes en áreas periurbanas del Estado de Pará. Filarias adultas fueron observadas en 3/34 (9%) aves, localizadas en la cavidad abdominal de los huéspedes Las características morfológicas y morfométricas de los nematodos fueron compatibles con la clasificación taxonómica de Aproctella stoddardi Cram, 1931, siendo este el primer relato de esta especie en la amazónica en el norte de Brasil. Debido a la migración observada de otros géneros de filarias, Aproctella Cram, 1931 puede tener la capacidad de infección en otros sitios, como hígado, corazón, pulmón y cerebro. Además, es necesario ampliar los registros de filarias en aves de la región para elucidar los factores que influencian esta infección

Ablation of angiotensin (1-7) receptor Mas in C57Bl/6 mice causes endothelial dysfunction

The Mas gene codes for an angiotensin (1-7) receptor. There is accumulating evidence that Mas is involved in vascular homeostasis. We have recently backcrossed Mas-knockout mice to two different genetic backgrounds, C57Bl/6 and FVB/N. FVB/NMas-deficient mice exhibited elevation in blood pressure (BP) and impaired endothelial function. In the present study, we aimed to address the question whether this phenotype is strain-specific. Therefore, we evaluated endothelial function in C57Bl/6Mas-deficient mice. Similar to FVB/NMas-knockout animals, Mas-deficiency in C57Bl/6 mice leads to endothelial dysfunction evaluated by the acute BP effect of acetylcholine administration. Measurements of nitric oxide (NO) and reactive oxygen species (ROS) and the systems involved in their metabolism revealed an imbalance between these vasoactive factors in C57Bl/6Mas-knockout mice, which may explain the impairment of endothelial function in these animals. However, endothelial dysfunction was less prominent in Mas-deficient mice on a C57Bl/6 background compared to FVB/N. Moreover, C57Bl/6Mas-deficient mice remained normotensive while FVB/N-based animals exhibited elevated BP. The impairment of endothelium-dependent vasodilatory response to acetylcholine in two different mouse strains with Mas deficiency indicates a key role of Mas in endothelial function by its effects on the generation and metabolism of NO and ROS

Atypical Glandular Cells And Adenocarcinoma In Situ According To The Bethesda 2001 Classification: Cytohistological Correlation And Clinical Implications

Background: The objective of this study was to evaluate the correlation between the 2001 Bethesda classification of endocervical glandular abnormalities and histological diagnosis. Study design: A series of 155 women with endocervical glandular abnormalities on cervical smears were included: 91 with atypical glandular cells (AGC) not otherwise specified (NOS), 15 with AGC-favor neoplastic (FN); 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) as combined diagnosis and 14 with adenocarcinoma in situ (AIS). Results: Histological outcome of squamous neoplasias (CIN 2 or worse) and adenocarcinoma were significantly associated with AGC-FN and AIS, taking as reference AGC-NOS, and more associated with AIS than AGC-FN. Similar associations were observed for histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present, but no association was observed with only for adenocarcinoma histological outcome. Conclusions: AGC-NOS, AGC-FN and AIS cytological diagnosis represent a progressively increasing association with neoplastic diagnosis, due to progressively increasing association with adenocarcinoma. Histological outcome of squamous neoplasia is frequent but does not differ with these cytological interpretations. The presence of HSIL associated with AGC represents greater probability of squamous neoplasia but not adenocarcinoma. © 2007 Elsevier Ireland Ltd. 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