Paracoccidioides brasifiensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P brasiliensis killing by human PMNs, and that H2O2 and Superoxide anion participate as effectors molecules in this process.

Potentially modifiable predictors of mortality in patients treated with long-term oxygen therapy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Gender and Health Status Response to Long-Term Oxygen Therapy in COPD Patients

Introduction: The association of gender with health status (HS) response to long-term oxygen therapy (LTOT) in very severe COPD is unclear. The aims of this study were: (1) to compare dyspnea perception and HS between male and female with very severe COPD at baseline and (2) to provide a prospective assessment of HS response to LTOT, according to gender.Patients and methods: Hypoxemic COPD (n =97, age: 65.5 +/- 9.6 years, 53% males) were enrolled in a prospective longitudinal study over 12 months or until death. St. George's Respiratory Questionnaire (SGRQ) and baseline dyspnea index (BDI) were assessed.Results: At baseline, HS impairment and dyspnea sensation were similar between genders. After 12 months of LTOT, women presented improvement in symptom (64.1 +/- 120.6 versus 40.6 +/- 122.9; P < 0.0001) and total SGRQ scores. Men also showed improvement in symptoms after 12 months (62.7 +/- 23.3 versus 49.6 +/- 22.8; P < 0.0005); however, they presented deterioration of activity, impact and total scores during the study period, with markedly decline of activity domain (68.5 +/- 20.0 versus 75.9 +/- 16.9; P = 0.008). BDI did not show significant difference by gender over the study period.Conclusions: Our results show that the HS course in very severe COPD patients differs according to gender, as females show greater response longitudinally to LTOT. (C) 2010 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

Predictors of first-year survival in patients with advanced COPD treated using long-term oxygen therapy

Little evidence-based guidance is available to aid clinicians in determining short-term prognoses in very severe COPD patients. Therefore, the present study was designed to provide a prospective assessment (1) of the mortality rates and (2) whether the baseline measurements may be determinants of 1-year mortality in hypoxemic COPD patients receiving long-term oxygen therapy (LTOT).Seventy-eight clinically stable patients with advanced COPD treated using LTOT were enrolled in a prospective cohort study. Outcome variable: first-year mortality. Baseline measurements: categorical variables: age (<60 or >= 60 years); gender; body mass index (<20 or >= 20 kg/m(2)); fat-free mass (FFM) index (<16 [men] and <15kg/m(2) [women]; baseline dyspnea index (BDI) (<= 3 or >3); and corticosteroid use. Continuous variables: smoking history; lung function; FFM; fat mass; hemoglobin; hematocrit; arterial blood gases; forearm muscle strength; St. George's Respiratory Questionnaire (SGRQ); and comorbidity score. By the end of 1-year of follow-up, 12 patients (15.4%) had died. Kaplan-Meier curves showed that BDI <= 3 was the only variable associated with higher mortality. Cox proportional hazards analysis revealed that tower PaO2 and SPO2, higher PaCO2 and SGRQ scores were associated with reduced survival. In the multivariate analysis, BDI remained predictive of mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.31-0.81), as did PaO2 (HR, 0.49; 95% CI, 0.26-0.95). These data suggest that readily available parameters as dyspnea intensity and hypoxemia severity may be useful in predicting first-year survival rates in advanced COPD patients receiving LTOT (C) 2007 Elsevier Ltd. All rights reserved.

The importance of knowing the home conditions of patients receiving long-term oxygen therapy

Purpose: Long-term oxygen therapy (LTOT) is one of the main treatments for patients with chronic obstructive pulmonary disease. Patients receiving LTOT may have less than optimal home conditions and this may interfere with treatment. The objective of this study was, through home visits, to identify the characteristics of patients receiving LTOT and to develop knowledge regarding the home environments of these patients.Methods: Ninety-seven patients with a mean age of 69 plus or minus 10.5 years were evaluated. This study was a cross-sectional descriptive analysis. Data were collected during an initial home visit, using a questionnaire standardized for the study. The results were analyzed retrospectively.Results: Seventy-five percent of the patients had chronic obstructive pulmonary disease, and 11% were active smokers. The patients' mean pulse oximetry values were 85.9% plus or minus 4.7% on room air and 92% plus or minus 3.9% on the prescribed flow of oxygen. Most of the patients did not use the treatment as prescribed and most used a humidifier. The extension hose had a mean length of 5 plus or minus 3.9 m (range, 1.5-16 m). In the year prior to the visit, 26% of the patients received emergency medical care because of respiratory problems. Few patients reported engaging in leisure activities.Conclusion: The home visit allowed us to identify problems and interventions that could improve the way LTOT is used. The most common interventions related to smoking cessation, concentrator maintenance and cleaning, use of a humidifier, and adjustments of the length of the connector hose. Therefore, the home visit is a very important tool in providing comprehensive care to patients receiving LTOT, especially those who show lack of adequate progress and those who show uncertainty about the treatment method.

Increased Reactive Oxygen Species and Tumor Necrosis Factor-Alpha Production by Monocytes are Associated with Elevated Levels of Uric Acid in Pre-Eclamptic Women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis

Background: Improved pregnancy, implantation, and birth rates have been reported after the use of reduced O2 concentration during embryo culture, mainly due to a reduction of the cumulative detrimental effects of reactive oxygen species. However, some studies have failed to report any positive effects. The objective of this meta-analysis was to evaluate the effect of a low-O2 environment on IVF/intracytoplasmic sperm injection (ICSI) outcomes.Methods: All available published and ongoing randomised trials that compared the effects of low (similar to 5%; OC similar to 5) and atmospheric (similar to 20%; OC similar to 20) oxygen concentrations on IVF/ICSI outcomes were included. Search strategies included online surveys of databases from 1980 to 2011. The outcomes measured were fertilisation rate, implantation rate and ongoing pregnancy rates. The fixed effects model was used to calculate the odds ratio.Results: Seven studies were included in this analysis. The pooled fertilisation rate did not differ significantly (P = 0.54) between the group of oocytes cultured at low O2 tension and the group at atmospheric O2 tension. Concerning all cycles, the implantation (P = 0.06) and ongoing pregnancy (P = 0.051) rates were not significantly different between the group receiving transferred sets containing only OC similar to 5 embryos and the group receiving transferred sets with only OC similar to 20 embryos. In a meta-analysis performed for only those trials in which embryos were transferred on day 2/3, implantation (P = 0.63) and ongoing pregnancy (P = 0.19) rates were not significantly different between the groups. In contrast, when a meta-analysis was performed using only trials in which embryos were transferred on days 5 and 6 (at the blastocyst stage), the group with transferred sets of only OC similar to 5 embryos showed a statistically significantly higher implantation rate (P = 0.006) than the group receiving transferred sets with only OC similar to 20 embryos, although the ongoing pregnancy (P = 0.19) rates were not significantly different between the groups.Conclusions: Despite some promising results, it seems too early to conclude that low O2 culture has an effect on IVF outcome. Additional randomised controlled trials are necessary before evidence-based recommendations can be provided. It should be emphasised that the present meta-analysis does not provide any evidence that low oxygen concentration is unnecessary.

Hyperbaric oxygen therapy treatment for the fixation of implant prosthesis in oncology patients irradiated

doi: 10.1111/j.1741-2358.2012.00636.x Hyperbaric oxygen therapy treatment for the fixation of implant prosthesis in oncology patients irradiated Objectives: This study aimed to present a clinical report of an irradiated oncologic patient who underwent hyperbaric oxygen therapy to be rehabilitated with implant-supported prosthesis. Materials and Methods: A 67-year-old man was admitted at Oral Oncology Center (FOA-UNESP) presenting a lesion on the mouth floor. After clinical evaluation, incisional biopsy and histopathological exam, a grade II squamous cell carcinoma was diagnosed. The patient was subjected to surgery to remove the lesion and partial glossectomy. Afterwards, the radiotherapy, in the left/right cervicofacial area of the supraclavicular fossa, was conducted. After 3 years of the surgery, the patient was submitted to hyperbaric oxygen therapy. Then, four implants were installed in patients mandible. Five months later, an upper conventional complete denture and lower full-arch implant-supported prosthesis were fabricated. Conclusion: The treatment resulted in several benefits such as improving his chewing efficiency, swallowing and speech, less denture trauma on the mucosa and improving his self-esteem.

Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata

The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the cardiovascular reflexes within the brainstem. It is well-known that one of the mechanisms by which angiotensin II exerts its effect is via the activation of pathways that generate reactive oxygen species (ROS). In the central nervous system, ROS are reported to be involved in several pathological diseases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.

Dihydrolipoyl dehydrogenase as a source of reactive oxygen species inhibited by caloric restriction and involved in Saccharomyces cerevisiae aging

Replicative life span in Saccharomyces cerevisiae is increased by glucose (G1c) limitation [ calorie restriction (CR)] and by augmented NAD(+). Increased survival promoted by CR was attributed previously to the NAD(+)-dependent histone deacetylase activity of sirtuin family protein Sir2p but not to changes in redox state. Here we show that strains defective in NAD(+) synthesis and salvage pathways (pnc1 Delta, npt1 Delta, and bna6 Delta) exhibit decreased oxygen consumption and increased mitochondrial H2O2 release, reversed over time by CR. These null mutant strains also present decreased chronological longevity in a manner rescued by CR. Furthermore, we observed that changes in mitochondrial H2O2 release alter cellular redox state, as attested by measurements of total, oxidized, and reduced glutathione. Surprisingly, our results indicate that matrix-soluble dihydrolipoyl-dehydrogenases are an important source of CR-preventable mitochondrial reactive oxygen species (ROS). Indeed, deletion of the LPD1 gene prevented oxidative stress in npt1 Delta and bna6 Delta mutants. Furthermore, pyruvate and alpha-ketoglutarate, substrates for dihydrolipoyl dehydrogenase-containing enzymes, promoted pronounced reactive oxygen release in permeabilized wild-type mitochondria. Altogether, these results substantiate the concept that mitochondrial ROS can be limited by caloric restriction and play an important role in S. cerevisiae senescence. Furthermore, these findings uncover dihydrolipoyl dehydrogenase as an important and novel source of ROS leading to life span limitation.

Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae

Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

Production of reactive oxygen (H2O2) and nitrogen (NO) intermediates and TNF-α in mice genetically selected for high (H) and low (L) antibody response and experimentally infected with Leptospira serovar pomona

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Heat budgets, thermal structure and dissolved oxygen in Brazilian reservoirs

A comparison of the thermal regime and oxygen distribution patterns of some Brazilian reservoirs was made. A strong latitudinal dependence of surface temperature, annual mean and annual range was found. Except for Tucurui Reservoir, a reservoir of the Equatorial zone, the lowest surface temperature of the year in the other compared reservoirs was observed from June to August while the highest extended from October to February. The decreasing trend of annual mean temperatures and thermal ranges was due to the increasing seasonal variability of insolation with the latitude. A positive relationship between the increase on thermal surface-bottom differences and the depth of water column was found for reservoirs of similar latitudes. A long thermal stratification (around four months) was evidenced in the lacustrine zone of reservoirs with a residence time higher than 40 days. Low fluctuation (<2%) of the annual variability of heat contents was observed for the Tucurui Reservoir, while in das Garcas Reservoir a manmade lake located in the frontier between tropical and temperate regions, the annual coefficient of variation attained 13%. Concerning the heat budgets, the value for the Tucurui Reservoir was two times higher than in das Garcas Reservoir. Both the morphometric and climatological factors affected the heat contents of the two compared reservoirs. In deep eutrophic reservoirs, a significant reduction on the oxygen concentrations in the hypolimnetic zone was frequently observed. In some oligotrophic stratified reservoirs, a decrease on oxygen with depth occurred when the temperature of the hypolimnion was higher than 20 degrees C and caused a biochemical oxygen demand. In das Garcas Reservoir, the actual oxygen deficits ranged from 0.40 to 1.52 mg.O-2.cm(-2) and appear to be linked to oxygen consumption after the senescence of Microcystis aeruginosa populations in the spring. But, other factors such as the allochthonous loads of organic matter also had an important role on the oxygen balance of das Garcas Reservoir.