Effect of Saccharomyces cerevisiae byproducts on milk phagocyte function and milk production in mid-lactation cows / Efeito dos subprodutos de Saccharomyces cerevisiaena função de fagócitos lácteos e na produção de leite de vacas no meio do estágio da lactação

Saccharomyces cerevisiae is a supplement option for ruminants due to its ability to stimulate the immune system and productivity; however, there are few studies that demonstrate the effectiveness of this yeast in dairy cattle, especially regarding its effect on milk phagocyte function. Thus, this study examined the effect of two presentations of autolyzed S. cerevisiae on milk phagocyte function and milk production in healthy Holstein cows from the third to the fifth months of lactation with somatic cell count (SCC) less than 200,000 cells mL-1. Ten animals received cell wall-rich S. cerevisiae autolysate (WC 15 g animal day-1); 8 received the cytoplasm-rich extract (CYT 5 g animal day-1) and 7 received a diet without supplementation (C, control) for 60 days. Weekly oxidative metabolism analysis of milk leukocytes, production and milk constituents was carried out. The oxidative metabolism of milk leukocytes was higher in the WC group than in the C group between D32 and D48 (P≤ 0.05) and in the CYT group than in the C group between D24 and D40 (P≤ 0.05). The production and percentage of milk fat increased in CYT at D48 and D56. It is concluded that the CYT group had a greater effect on productivity, while on immunity the effect was intermediate, compared to the WC group, which was efficient in improving the immunity of the mammary gland.(AU)

Saccharomyces cerevisiae é uma opção de suplemento para ruminantes devido à sua capacidade de estimular o sistema imunológico e a produtividade; entretanto, ainda há poucos estudos que demonstrem a real eficácia das diferentes apresentações desta levedura em bovinos leiteiros, principalmente quanto ao seu efeito sobre a função dos fagócitos lácteos. Assim, o efeito de duas apresentações de S. cerevisiae autolisado na função fagocitária do leite e produção de leite de vacas da raça Holandes saudáveis entre o terceiro e quinto mês de lactação, com CCS inferior a 200.000 células mL-1. Para tanto, 10 animais receberam autolisado de S. cerevisiae ricos em parede celular (WC - 15 g animal dia-1); oito receberam o extrato rico em citoplasma (CYT - 5 g animal dia-1) e 7 receberam dieta sem suplementação (C - controle) por 60 dias. Análises do metabolismo oxidativo de leucócitos lácteos, produção de leite e constituintes do leite foram realizadas semanalmente. O metabolismo oxidativo dos leucócitos lácteos foi maior no grupo WC do que no grupo C entre D32 e D48 (P≤ 0,05) e no grupo CYT do que no grupo C entre D24 e D40 (P≤ 0,05). A produção de leite e a porcentagem de gordura do leite aumentaram no citoplasma (CYT) em D48 e D56. Concluiu-se que o grupo CYT teve um efeito maior na produtividade enquanto que na imunidade o efeito foi intermediário, comparando ao grupo WC que se mostrou eficiente na melhora da imunidade da glândula mamária.(AU)

Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity.

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats

Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Antioxidant activity and hypoglycemic effect assessment of the leaves from Syzygium cumini (L. ) Skeels in Wistar rats

Syzygiumcumini(L.) Skeels wasadaptedto the climatic conditionsandsoil typesin Brazil. Its fruits, leaves andinner barkare usedin folk medicinedue to their highantioxidant, anti-inflammatory, anticarcinogenicandantidiabeticactivities mainlyassociated with the presenceof phenolic compounds. It is estimated thatat least300million peopleworldwide developdiabetesand approximately 11million peopleare carriersof the disease in Brazil.The objectiveof this workwas to evaluate thein vitro antioxidant activity, as well as thehypoglycemic actionofhydroethanolic extract(HEE), the ethyl acetate(EAF) andhydromethanolic(HMF) fractions from leavesofS.cumini(L.) Skeels in rats. All assays werecarried out in three replications. Data wereexpressed as meanSDand significance was evaluated by ANOVAand Bonferronitest (p < 0.05). The results indicatea significant(p < 0.05) total phenolcontent (207 ± 2.3GAE mg g-1) andantioxidant activity(EC50=9.05±0.170 µg mL-1) for EAF. HEE and its fractions showed no significant (p > 0.05) actionto modulateglucosebytheOGTT assayinnondiabetic micecompared to control. Thus the use of the plant against diabetes in individuals is not proven.

Leukocyte telomere length is associated with iron overload in male adults with hereditary hemochromatosis.

BACKGROUND: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality. AIM: To evaluate the relationship between ATL and IO in patients with HH. METHODS: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR. RESULTS: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6-14), without IO: 13 (9-20), and controls: 19 (15-25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05). DISCUSSION: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

Sublethal effects of carbendazim in Jenynsia multidentata detected by a battery of molecular, biochemical and genetic biomarkers.

The fungicide carbendazim (CBM) has been applied all around the world but its potential adverse effects other than its recognized activity as endocrine disruptor in non target organisms have been scarcely studied. The aims of this work were (1) to use a battery of biomarkers that can reflect potential negative effects such as oxidative stress, genotoxicity, neurotoxicity or altered immune response; and (2) to examine biomarkers of detoxification by analyzing the gene expression of cytochrome P4501A1 (CYP1A1) and the multi-xenobiotic resistance protein P-glycoprotein (P-gp) in the freshwater fish Jenynsia multidentata exposed to environmentally relevant concentrations of CBM during 24 h. Fish exposed to 5 µg/L showed inhibition of GST activity and an increase of TBARs contents in gills, the organ of direct contact with waterborne contaminants. Genotoxicity - measured in peripheral blood-was evidenced by the increases of micronuclei frequency when fish were exposed to 5, 10 and 100 µg/L CBM and of nuclear abnormalities (NA) frequency at 0.05, 0.5, 5, 10 and 100 µg/L CBM. The expression inhibition of interleukin (IL-1ß) and tumor necrosis factor a (TNF-α) at 10, and 5 and 10 µg/L CBM, respectively, indicated an altered immune response. The expression of CYP1A1 was down regulated in liver at 10 µg/L and of P-gp at 5 µg/L CBM, indicating a possible slow on CBM metabolization. On the other hand, in gills CYP1A1 decreased at 5 and 10 µg/L while P-gp was induced at 5 and 100 µg/L CBM. Overall, most of these significant effects were detected below 10 µg/L CBM, in a range of realistic concentrations in aquatic ecosystems worldwide.

NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter.

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 µg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion () in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction.

Oxidative stress, inflammation and disease activity biomarkers in lupus nephropathy.

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and ß2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers (P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.

Cholinergic anti-inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model.

Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1ß, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma.

Astrocaryum aculeatum fruit improves inflammation and redox balance in phytohemagglutinin-stimulated macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7 cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (P < 0.05), arrested the cell cycle in G0/G1 phase (P < 0.001), increased antioxidant defenses (P < 0.01), reduced oxidative stress (P < 0.01), and modulated genes related to the inflammatory response (P < 0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.

Evaluating the effects of vanadyl sulfate on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2

Vanadyl sulfate (VS) is an ingredient in some food supplements and experimental drugs. This study was designed to assay the effects of VS on biomarkers of oxidative stress and inflammation in renal tissue of rats with diabetes type 2. 30 male Wistar rats were divided into three equal groups as follow: non-diabetics, non-treated diabetics and VS-treated diabetics. Diabetes type 2 has been induced through high fat diet and fructose in the animals. Diabetic rats were treated with 25 mg/kgBW of VS in water for 12 weeks. At the end of study, glucose and insulin were measured using commercially available kits in serum and biomarkers of oxidative stress and inflammation in renal homogenates of animals were measured by related methods. Compared to controls, glucose and insulin were increased significantly in non-treated diabetic rats (p-value <0.05) that showed the induction of diabetes type 2 in rats. The results showed that in VS-treated diabetic rats compared to the non-treated diabetic group, vanadyl sulfate significantly reduced the glucose and insulin secretion and changed renal inflammatory and oxidative markers, except protein carbonyl so that we couldn't find any significant changes. Our study showed that vanadyl supplementation had positive effects on oxidative stress and inflammation biomarkers in kidney of diabetic rats

Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants.

BACKGROUND: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated. METHODS: A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine. RESULTS: The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05). CONCLUSIONS: Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.

Oxidative stress in endothelial cells induced by the serum of women with different clinical manifestations of the antiphospholipid syndrome / Estrés oxidativo en células endoteliales inducido por el suero de mujeres con diferentes manifestaciones clínicas del síndrome antifosfolípido

Introduction: The antiphospholipid syndrome is characterized by the persistent presence of antiphospholipid antibodies and clinical manifestations of thrombosis or gestational morbidity that are associated with oxidative stress and endothelial dysfunction. Objective: To evaluate markers of oxidative stress in endothelial cells induced by the serum from women with different clinical manifestations of the antiphospholipid syndrome, and to analyze the antioxidant capacity of the sera. Materials and methods: We included 48 women who were classified as follows: presence of antiphospholipid antibodies and clinical criteria of gestational morbidity alone, vascular thrombosis only, and gestational morbidity/vascular thrombosis. Control groups included antiphospholipid antibodies negative women. In an in vitro model of endothelial cells stimulated with sera from women included in the groups, some markers of oxidative stress were determined by flow cytometry. The antioxidant capacity in the sera of these women was analyzed. Results: The sera from the groups of women with antiphospholipid syndrome that presented thrombosis, with or without gestational morbidity, generated a significant increase (p<0.05 and p<0.001) in endothelial oxidative stress markers in contrast to the control of normal human serum. There were no differences in the effect of the sera from the different study groups on endothelial lipid peroxidation. Also, there was also no difference in the antioxidant activity of the sera. Conclusion: Mitochondrial oxidative stress in the endothelium is associated with the presence of thrombosis; instead, its association with gestational morbidity generates intracellular oxidative stress.

Introducción. El síndrome antifosfolípido se caracteriza por la presencia persistente de anticuerpos antifosfolípidos y manifestaciones clínicas de trombosis o morbilidad gestacional, las cuales se asocian con estrés oxidativo y disfunción endotelial. Objetivo. Evaluar los marcadores de estrés oxidativo en células endoteliales, inducidos por el suero de mujeres con diferentes manifestaciones clínicas del síndrome antifosfolípido y analizar la capacidad antioxidante de los sueros. Materiales y métodos. Se incluyeron 48 mujeres que fueron clasificadas así: presencia de anticuerpos antifosfolípidos y criterios clínicos de morbilidad gestacional, trombosis vascular o ambas. Como grupos control se incluyeron mujeres negativas para anticuerpos antifosfolípidos. En un modelo in vitro de células endoteliales estimuladas con los sueros de las mujeres del estudio, se determinaron algunos marcadores de estrés oxidativo por citometría de flujo. También, se analizó la capacidad antioxidante de los sueros incluidos. Resultados. Los sueros de los grupos de mujeres con síndrome antifosfolípido que presentaban trombosis, con morbilidad gestacional o sin ella, generaron un incremento significativo (p<0,05 y p<0,001) en los marcadores de estrés oxidativo endotelial, en contraste con el control de suero humano normal. No se observaron diferencias en el efecto de los sueros de los diferentes grupos de estudio sobre la lipoperoxidación endotelial. Tampoco se encontró diferencia en la actividad antioxidante de los sueros. Conclusión. El estrés oxidativo mitocondrial en el endotelio se asocia con la presencia de trombosis. Sin embargo, cuando esta se asocia con morbilidad gestacional, también se genera estrés oxidativo intracelular.

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease.

Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients' peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro-infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages, diminishing the frequency of IL-1ß- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8+ T cells, improving their functionality. Altogether, these results clearly show that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustain an inflammatory environment in human pathology is key to designing improved therapies.

Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death.

The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3 months after acute ischemic stroke (AIS). We recruited 176 healthy volunteers and 145 AIS patients, categorized as AIS survivors and non-survivors, and measured interleukin (IL)-6, high sensitivity C-reactive protein (hsCRP), ferritin, iron, total serum protein (TSP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), 25 hydroxyvitamin D [25(OH)D], lipid hydroperoxides (CL-LOOH), insulin, glucose and high-density lipoprotein (HDL)-cholesterol. In patients, these biomarkers were measured within 24 h after AIS onset. We also computed two composite scores reflecting inflammatory indices, namely INFLAM index1 (sum of z scores of hsCRP+IL-6 + ferritin+ESR + WBC) and INFLAM index2 (z INFLAM index1 - z 25(OH)D - z iron + z TSP). Three months after AIS, non-survivors (n = 54) showed higher baseline levels of IL-6, hsCRP, ferritin and glucose and lower levels of HDL-cholesterol and 25(OH)D than survivors (n = 91). Non-survivors showed higher baseline ESR and lowered TSP than controls, while survivors occupied an intermediate position. Death after AIS was best predicted by increased IL-6, glucose, ferritin and CL-LOOH and lowered 25(OH)D levels. The area under the receiver operating curves computed on the INFLAM index1 and 2 scores were 0.851 and 0.870, respectively. In conclusion, activation of peripheral immune-inflammatory, oxidative and biochemical pathways is critically associated with mortality after AIS. Our results may contribute to identify new biomarker sets, which may predict post-stroke death, as well as suggest that IL-6 trans-signaling coupled with redox imbalances may be possible new targets in the prevention of short-term outcome AIS death.

HIV-exposed-uninfected infants have increased inflammation and monocyte activation.

BACKGROUND: HIV-exposed-uninfected (HEU) infants have increased infectious morbidity and mortality; little is known about their levels of inflammation and monocyte activation. METHODS: Plasma samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the National Institute of Child Health and Human Development cohorts in Brazil were compared with 88 HIV-unexposed mother-infant pairs. HIV-infected mothers received antiretroviral therapy during pregnancy, their infants received zidovudine prophylaxis and were not breastfed. IL-6, soluble TNFα receptor I (sTNF-RI) and II, soluble CD14, soluble CD163, IFN-γ-induced protein 10 (IP-10), vascular cell adhesion molecule, oxidized LDL, D-dimer and high-sensitivity C-reactive protein were assayed by ELISA at birth and at 6 months. sTNF-RI and IL-6 were considered coprimary endpoints. RESULTS: Among HIV-infected mothers, 79% had HIV-RNA less than 400 copies/ml prior to delivery. Compared with HIV-unexposed, HEU infants had a lower mean gestational age (38.7 vs. 39.3 weeks) and weight (3.1 vs. 3.3 kg); and reached lower weight (5.9 vs. 8.5 kg) and height (53.6 vs. 68.8 cm) at 6 months. With the exception of vascular cell adhesion molecule, inflammatory markers were generally higher (P ≤ 0.005) in HEU at birth, but at 6 months only sTNF-RI and IL-6 remained higher. For HEU pairs, only IP-10 was associated with maternal levels at birth (P < 0.001). In HEU, elevated levels of high-sensitivity C-reactive protein and IP-10 at birth were associated with lower weight at birth (P = 0.04) and at 6 months (P = 0.04). CONCLUSION: HIV-exposed infants have heightened inflammation and monocyte activation at birth, which for some markers persisted to 6 months of life and was not related to maternal inflammatory status. Inflammation may contribute to the increased HEU infectious morbidity and poor growth.

Oxidative stress and fish immune system: phagocytosis and leukocyte respiratory burst activity.

Molecular oxygen is a necessary compound for all aerobic organisms, although oxygen is a potent oxidant, which can cause oxidative stress (OS). OS occurs when there is an imbalance between the production of oxidant and antioxidants components, are result of normal cell metabolism, and many of these compounds play a fundamental role in several metabolic pathways. The organism produces several reactive oxygen species (ROS), but they are balanced by an antioxidant defense system that maintains the levels of these oxidizing compounds at an acceptable level. Many of these components are essential in the organism defense and their byproducts are considered potent bactericides that actively act in the destruction of invading pathogens. Fish immune system is composed of innate and acquired mechanisms of defense. Phagocytosis is an innate process of defense, which interconnects these two systems, since the pathogens processing by professional phagocytes is a fundamental stage for antibodies production. During phagocytosis there is production of ROS and consequent production of free radicals (FR), these compounds lead to the formation of potent bactericides to combat microorganisms. However, it is known that OS limits the immune response, with an impairment in defense compounds in an attempt to decrease the ROS production. Studies of fish FR production are preliminary and should be executed to evaluate the effects of ROS on fish, including their beneficial action against pathogens and its deleterious action on the oxidation of cellular components.

Cytokine modulation, oxidative stress and thymic dysfunctions: Role of age-related changes in the experimental Trypanosoma cruzi infection: Age-related thymic dysfunctions and Trypanosoma cruzi infection.

Aging is linked with a thymic oxidative damage and some infectious diseases such as Chagas' disease may aggravate this process. The aim of this study was to evaluate the production of distinct cytokines as well as the antioxidant/oxidant status of the thymus and thymocytes populations during Trypanosoma cruzi (T. cruzi) infection. Young (5 weeks old) and aged (18 weeks old) male Wistar rats were inoculated with blood trypomastigotes forms of the Y strain of T. cruzi. On the 16th day after T. cruzi infection, increased concentrations of transforming growth factor ß (TGF-ß), interleukin (IL)-12, IL-17 were detected in aged infected subjects as compared to young infected ones. Interestingly, a reduction in the production of tumor necrose factor (TNF)-α was observed in aged infected rats when compared to young infected subjects. Aged-infected rats presented increased O2- levels, compared to young counterparts. Significant raise in the generation of O2- in aged infected animals, as compared to uninfected counterparts was observed. Up-regulated expression of Nox2 in the thymus of young and aged infected animals was observed. An increased SOD2 expression was detected in the thymus of young animals infected with T. cruzi, when compared to uninfected young rats. Aged animals showed reduced thymus weight and the number of thymocytes. Decreased percentages of SPCD4+ and SPCD8+T cells were detected in aged and control groups when compared to young counterparts. In summary, this is the first data to directly examine the influence of aging on age-related dysfunctions during the acute phase of experimental Chagas disease. Concerning to oxidative stress, it is clear from our analysis that aged infected rats suffer a more intense oxidative damage when compared to young and infected ones. Age and infection triggered a dynamic interplay of cytokines, oxidative stress and thymic dysfunctions which led to impaired response from aged and infected rats. Such findings may have significant functional relevance in therapeutic strategies in order to reestablish the thymic immunological function which occurs in aged and T. cruzi infected subjects.