Reatividade e tolerância ao calor de fêmeas ovinas de diferentes grupos genéticos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização de segurança e tecnológica de bactérias acidoláticas termofílicas autóctones e aplicação em queijo parmesão

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Is cardiac tissue more susceptible than lung to oxidative effects induced by chronic nasotropic instillation of residual oil fly ash (ROFA)?

The current study aimed to determine the role of oxidants in cardiac and pulmonary toxicities induced by chronic exposure to ROFA. Eighty Wistar rats were divided into four groups: G1 (10 mu L Saline), G2 (ROFA 50 mu g/10 mu L), G3 (ROFA 250 mu g/10 mu L) and G4 (ROFA 500 mu g/10 mu L). Rats received ROFA by nasotropic instillation for 90 days. After that, they were euthanized and bronchoalveolar lavage (BAL) was performed for total count of leukocytes, protein and lactate dehydrogenase (LDH) determinations. Lungs and heart were removed to measure lipid peroxidation (MDA), catalase (CAT) and superoxide dismutase (SOD) activity. BAL presented an increase in leukocytes count in G4 in comparison to the Saline group (p = 0.019). In lung, MDA level was not modified by ROFA, while CAT was higher in G4 when compared to all other groups (p = 0.013). In heart, G4 presented an increase in MDA (p = 0.016) and CAT (p = 0.027) levels in comparison to G1. The present study demonstrated cardiopulmonary oxidative changes after a chronic ROFA exposure. More specifically, the heart tissue seems to be more susceptible to oxidative effects of long-term exposure to ROFA than the lung.

Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Modulation of Lung Allergic Response by Renal Ischemia and Reperfusion Injury

The Th1/Th2 balance represents an important factor in the pathogenesis of renal ischemia-reperfusion injury (IRI). In addition, IRI causes a systemic inflammation that can affect other tissues, such as the lungs. To investigate the ability of renal IRI to modulate pulmonary function in a specific model of allergic inflammation, C57Bl/6 mice were immunized with ovalbumin/albumen on days 0 and 7 and challenged with an ovalbumin (OA) aerosol on days 14 and 21. After 24 h of the second antigen challenge, the animals were subjected to 45 minutes of ischemia. After 24 h of reperfusion, the bronchoalveolar lavage (BAL) fluid, blood and lung tissue were collected for analysis. Serum creatinine levels increased in both allergic and non-immunized animals subjected to IRI. However, BAL analysis showed a reduction in the total cells (46%) and neutrophils (58%) compared with control allergic animals not submitted to IRI. In addition, OA challenge induced the phosphorylation of ERK and Akt and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung homogenates. After renal IRI, the phosphorylation of ERK and expression of COX-2 and iNOS were markedly reduced; however, there was no difference in the phosphorylation of Akt between sham and ischemic OA-challenged animals. Mucus production was also reduced in allergic mice after renal IRI. IL-4, IL-5 and IL-13 were markedly down-regulated in immunized/challenged mice subjected to IRI. These results suggest that renal IRI can modulate lung allergic inflammation, probably by altering the Th1/Th2 balance and, at least in part, by changing cellular signal transduction factors. Copyright (C) 2012 S. Karger AG, Basel

BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2 weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease.

Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke

It has recently been suggested that regular exercise reduces lung function decline and risk of chronic obstructive pulmonary disease (COPD) among active smokers; however, the mechanisms involved in this effect remain poorly understood. The present study evaluated the effects of regular exercise training in an experimental mouse model of chronic cigarette smoke exposure. Male C57BL/6 mice were divided into four groups (control, exercise, smoke and smoke+exercise). For 24 weeks, we measured respiratory mechanics, mean linear intercept, inflammatory cells and reactive oxygen species (ROS) in bronchoalveolar lavage (BAL) fluid, collagen deposition in alveolar walls, and the expression of antioxidant enzymes, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase (TIMP) 1, interleukin (IL)-10 and 8-isoprostane in alveolar walls. Exercise attenuated the decrease in pulmonary elastance (p<0.01) and the increase in mean linear intercept (p=0.003) induced by cigarette smoke exposure. Exercise substantially inhibited the increase in ROS in BAL fluid and 8-isoprostane expression in lung tissue induced by cigarette smoke. In addition, exercise significantly inhibited the decreases in IL-10, TIMP1 and CuZn superoxide dismutase induced by exposure to cigarette smoke. Exercise also increased the number of cells expressing glutathione peroxidase. Our results suggest that regular aerobic physical training of moderate intensity attenuates the development of pulmonary disease induced by cigarette smoke exposure.

Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice

Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25mg/kg) and AMPH (2.0mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801+AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice.

Metformin attenuates the exacerbation of the allergic eosinophilic inflammation in high fat-diet-induced obesity in mice

A positive relationship between obesity and asthma has been well documented. The AMP-activated protein kinase (AMPK) activator metformin reverses obesity-associated insulin resistance (IR) and inhibits different types of inflammatory responses. This study aimed to evaluate the effects of metformin on the exacerbation of allergic eosinophilic inflammation in obese mice. Male C57BL6/J mice were fed for 10 weeks with high-fat diet (HFD) to induce obesity. The cell infiltration and inflammatory markers in bronchoalveolar lavage (BAL) fluid and lung tissue were evaluated at 48 h after ovalbumin (OVA) challenge. HFD obese mice displayed peripheral IR that was fully reversed by metformin (300 mg/kg/day, two weeks). OVA-challenge resulted in higher influx of total cell and eosinophils in lung tissue of obese mice compared with lean group. As opposed, the cell number in BAL fluid of obese mice was reduced compared with lean group. Metformin significantly reduced the tissue eosinophil infiltration and prevented the reduction of cell counts in BAL fluid. In obese mice, greater levels of eotaxin, TNF-α and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin. In addition, metformin nearly abrogated the binding of NF-κB subunit p65 to the iNOS promoter gene in lung tissue of obese mice. Lower levels of phosphorylated AMPK and its downstream target acetyl CoA carboxylase (ACC) were found in lung tissue of obese mice, which were restored by metformin. In separate experiments, the selective iNOS inhibitor aminoguanidine (20 mg/kg, 3 weeks) and the anti-TNF-α mAb (2 mg/kg) significantly attenuated the aggravation of eosinophilic inflammation in obese mice. In conclusion, metformin inhibits the TNF-α-induced inflammatory signaling and NF-κB-mediated iNOS expression in lung tissue of obese mice. Metformin may be a good pharmacological strategy to control the asthma exacerbation in obese individuals.

Cuantificación de la recarga natural al acuífero del norte de Gran Canaria mediante el balance diario de agua en el suelo

[ES]La recarga al acuífero noreste de Gran Canaria ha sido calculada dentro del proyecto REDESAC mediante la realización de un balance diario de agua en el suelo. Para llevarlo a cabo ha sido necesario adaptar los datos de partida existentes referentes a la pluviometría, la evapotranspiración (ET0 y ETP) y los parámetros del suelo. La zona se ha dividido en subzonas según la situación de las estaciones pluviométricas y atendiendo a las características climáticas. Los cálculos realizados mediante la utilización del código Easy-Bal han arrojado una recarga de unos 15±4 hm3/a, lo que supone el 13±4% de la precipitación, la mayor parte de la misma concentrada en las zonas altas y de medianías

El corte de Puerto Real y el problema del límite plio-pleistoceno en la Bahía de Cádiz

[ES] Alrededor de la Bahía de Cádiz, los depósitos marinos de la regresión del Plioceno superior, forman una orla más o menos continua que se extiende hasta las proximidades de Chipioja al N., hasta Chiclana al S., constituyendo la Sierra de San Cristóbal el límite más oriental de la misma. Una cantera situada a 1,5 km al NE. de Puerto Real (lat. 36' 32' 15", long. 2' 28' 40". H.M.T.N. 1 : 50.000 núm. 1062), ofrece un amplio corte donde es posible observar los tramos marinos y salobres regresivos, así como los depósitos cuaternarios, continentales, más antiguos observados en el litoral gaditano. Se realiza un estudio detallado de dicho corte, y se discute el problema del límite Plio-Pleistoceno en dicho sector.

Modelling coupled physical-biogeochemical processes in ice-covered oceans

The last decades have seen a large effort of the scientific community to study and understand the physics of sea ice. We currently have a wide - even though still not exhaustive - knowledge of the sea ice dynamics and thermodynamics and of their temporal and spatial variability. Sea ice biogeochemistry is instead largely unknown. Sea ice algae production may account for up to 25% of overall primary production in ice-covered waters of the Southern Ocean. However, the influence of physical factors, such as the location of ice formation, the role of snow cover and light availability on sea ice primary production is poorly understood. There are only sparse localized observations and little knowledge of the functioning of sea ice biogeochemistry at larger scales. Modelling becomes then an auxiliary tool to help qualifying and quantifying the role of sea ice biogeochemistry in the ocean dynamics. In this thesis, a novel approach is used for the modelling and coupling of sea ice biogeochemistry - and in particular its primary production - to sea ice physics. Previous attempts were based on the coupling of rather complex sea ice physical models to empirical or relatively simple biological or biogeochemical models. The focus is moved here to a more biologically-oriented point of view. A simple, however comprehensive, physical model of the sea ice thermodynamics (ESIM) was developed and coupled to a novel sea ice implementation (BFM-SI) of the Biogeochemical Flux Model (BFM). The BFM is a comprehensive model, largely used and validated in the open ocean environment and in regional seas. The physical model has been developed having in mind the biogeochemical properties of sea ice and the physical inputs required to model sea ice biogeochemistry. The central concept of the coupling is the modelling of the Biologically-Active-Layer (BAL), which is the time-varying fraction of sea ice that is continuously connected to the ocean via brines pockets and channels and it acts as rich habitat for many microorganisms. The physical model provides the key physical properties of the BAL (e.g., brines volume, temperature and salinity), and the BFM-SI simulates the physiological and ecological response of the biological community to the physical enviroment. The new biogeochemical model is also coupled to the pelagic BFM through the exchange of organic and inorganic matter at the boundaries between the two systems . This is done by computing the entrapment of matter and gases when sea ice grows and release to the ocean when sea ice melts to ensure mass conservation. The model was tested in different ice-covered regions of the world ocean to test the generality of the parameterizations. The focus was particularly on the regions of landfast ice, where primary production is generally large. The implementation of the BFM in sea ice and the coupling structure in General Circulation Models will add a new component to the latters (and in general to Earth System Models), which will be able to provide adequate estimate of the role and importance of sea ice biogeochemistry in the global carbon cycle.

Accretion disk winds in active galactic nuclei: an X-ray view

This Thesis focuses on the X-ray study of the inner regions of Active Galactic Nuclei, in particular on the formation of high velocity winds by the accretion disk itself. Constraining AGN winds physical parameters is of paramount importance both for understanding the physics of the accretion/ejection flow onto supermassive black holes, and for quantifying the amount of feedback between the SMBH and its environment across the cosmic time. The sources selected for the present study are BAL, mini-BAL, and NAL QSOs, known to host high-velocity winds associated to the AGN nuclear regions. Observationally, a three-fold strategy has been adopted: - substantial samples of distant sources have been analyzed through spectral, photometric, and statistical techniques, to gain insights into their mean properties as a population; - a moderately sized sample of bright sources has been studied through detailed X-ray spectral analysis, to give a first flavor of the general spectral properties of these sources, also from a temporally resolved point of view; - the best nearby candidate has been thoroughly studied using the most sophisticated spectral analysis techniques applied to a large dataset with a high S/N ratio, to understand the details of the physics of its accretion/ejection flow. There are three main channels through which this Thesis has been developed: - [Archival Studies]: the XMM-Newton public archival data has been extensively used to analyze both a large sample of distant BAL QSOs, and several individual bright sources, either BAL, mini-BAL, or NAL QSOs. - [New Observational Campaign]: I proposed and was awarded with new X-ray pointings of the mini-BAL QSOs PG 1126-041 and PG 1351+640 during the XMM-Newton AO-7 and AO-8. These produced the biggest X-ray observational campaign ever made on a mini-BAL QSO (PG 1126-041), including the longest exposure so far. Thanks to the exceptional dataset, a whealth of informations have been obtained on both the intrinsic continuum and on the complex reprocessing media that happen to be in the inner regions of this AGN. Furthermore, the temporally resolved X-ray spectral analysis field has been finally opened for mini-BAL QSOs. - [Theoretical Studies]: some issues about the connection between theories and observations of AGN accretion disk winds have been investigated, through theoretical arguments and synthetic absorption line profiles studies.