Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.

Substitution of crude cell wall for neutral detergent fibre in the equations of the Cornell Net Carbohydrate and Protein System that predict carbohydrate fractions: application to sunflower (Helianthus annulus L.)

Prediction of carbohydrate fractions using equations from the Cornell Net Carbohydrate and Protein System (CNCPS) is a valuable tool to assess the nutritional value of forages. In this paper these carbohydrate fractions were predicted using data from three sunflower (Helianthus annuus L.) cultivars, fresh or as silage. The CNCPS equations for fractions B(2) and C include measurement of ash and protein-free neutral detergent fibre (NDF) as one of their components. However, NDF lacks pectin and other non-starch polysaccharides that are found in the cell wall (CW) matrix, so this work compared the use of a crude CW preparation instead of NDF in the CNCPS equations. There were no differences in the estimates of fractions B, and C when CW replaced NDF; however there were differences in fractions A and B2. Some of the CNCPS equations could be simplified when using CW instead of NDF Notably, lignin could be expressed as a proportion of DM, rather than on the basis of ash and protein-free NDF, when predicting CNCPS fraction C. The CNCPS fraction B(1) (starch + pectin) values were lower than pectin determined through wet chemistty. This finding, along with the results obtained by the substitution of CW for NDF in the CNCPS equations, suggests that pectin was not part of fraction B(1) but present in fraction A. We suggest that pectin and other non-starch polysaccharides that are dissolved by the neutral detergent solution be allocated to a specific fraction (B2) and that another fraction (B(3)) be adopted for the digestible cell wall carbohydrates.

Reproductive development and function of female rats exposed to di-eta-butyl-phthalate (DBP) in utero and during lactation

Phthalates are environmental contaminants used in the production of plastics, cosmetics and medical devices. Studies on the effects of phthalates on female reproductive health are particularly sparse and mostly restricted to high-dose exposure in rats. In the present study, pregnant rats were treated with 100 mg/kg-d of di-eta-butyl-phthalate (DBP) or only the vehicle (control group), from GD 12 to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0), and from GD 12 to PND 21 to evaluate reproductive development and function on F1 female offspring. Results showed that all parameters were comparable between groups, although there was a significant increase in the fetal weight after DBP exposure. However, the body weight at birth was normal. Based on these data we can conclude that, in these experimental conditions, DBP did not disturb the reproductive development or function of female rats. (C) 2009 Elsevier Inc. All rights reserved.

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control (C) and Treated (T). The females of the T group received DBP (100 mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial (C=32.86; T=42.04*) and stromal (C=21.61; T=27.88*) compartments were increased, while the luminal compartment was decreased (C=45.54; T=30.08*), *p < 0.05. In T, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Interfacial evaluation of experimentally weakened roots restored with adhesive materials and fibre posts: An SEM analysis

Objectives: To evaluate the bonding interface in experimentally weakened roots reinforced with adhesive restorative materials and quartz fibre posts, varying the light-exposure time of the composite resin used for root reinforcement. Methods: Twelve extracted human maxillary incisors teeth were used. The crowns were removed and the roots were endodontically treated. After post space preparation, the roots were assigned to four groups. The thickness of the root dentine was reduced and adhesively restored with composite resin light-activated through a translucent fibre post for either 40 s (group 1), 80 s (group 2) or 120 s (group 3). In the case of control (group 4), the roots were not weakened. One day after post cementation, the specimens were sectioned transversally in three slices and processed for scanning electron microscopic analysis to observe bonding interface formation, quality of the hybrid layer and density of resin tags using a four-step scale method. Results: Formation of a hybrid layer and resin tags were evident in all groups. There was no statistically (p > 0.05) significant difference between the regions analysed in each group (Friedman test) and between groups in each section depth (Kruskal-Wallis test). Furthermore, comparison of the flared/reinforced groups showed that the different time;; used for composite resin cure did not affect the results significantly (Kruskal-Wallis test, p = 0.2139). Conclusions: Different light-exposure times used for composite resin polymerisation during root canal reinforcement did not affect significantly the formation and quality of the dentine/adhesive/composite resin bonding interface. (C) 2008 Elsevier Ltd. All rights reserved.

Effects of light exposure time on composite resin hardness after root reinforcement using translucent fibre post

Objectives: The purpose of this in vitro study was to evaluate the Vickers hardness (VHN) of a Light Core (Bisco) composite resin after root reinforcement, according to the light exposure time, region of intracanal reinforcement and lateral distance from the light-transmitting fibre post. Methods: Forty-five 17-mm long roots were used. Twenty-four hours after obturation, the root canals were emptied to a depth of 12 mm and the root dentine was artificially flared to produce a 1 mm space between the fibre post and the canal walls. The roots were bulk restored with the composite resin, which was photoactivated through the post for 40 s (G1, control), 80 s (G2) or 120 s (G3). Twenty-four hours after post-cementation, the specimens were sectioned transversely into three slices at depths of 2, 6 and 10 mm, corresponding to the coronal, middle and apical regions of the reinforced root. Composite VHN was measured as the average of three indentations (100 g/15 s) in each region at lateral distances of 50, 200 and 350 mu m from the cement/post-interface. Results: Three-way analysis of variance (alpha = 0.05) indicated that the factors time, region and distance influenced the hardness and that the interaction time x region was statistically significant (p = 0.0193). Tukey`s test showed that the mean VHN values for G1 (76.37 +/- 8.58) and G2 (74.89 +/- 6.28) differed significantly from that for G3 (79.5 +/- 5.18). Conclusions: Composite resin hardness was significantly lower in deeper regions of root reinforcement and in lateral areas distant from the post. Overall, a light exposure time of 120 s provided higher composite hardness than the shorter times (40 and 80 s). (C) 2008 Elsevier Ltd. All rights reserved.

Adaptation to chronic eccentric exercise in humans: the influence of contraction velocity

We compared changes in muscle fibre composition and muscle strength indices following a 10 week isokinetic resistance training programme consisting of fast (3.14 rad(.)s(-1)) or slow (0.52 rad(.)s(-1)) velocity eccentric muscle contractions. A group of 20 non-resistance trained subjects were assigned to a FAST (n = 7), SLOW (n = 6) or non-training CONTROL (n = 7) group. A unilateral training protocol targeted the elbow flexor muscle group and consisted of 24 maximal eccentric isokinetic contractions (four sets of six repetitions) performed three times a week for 10 weeks. Muscle biopsy samples were obtained from the belly of the biceps brachii. Isometric torque and concentric and eccentric torque at 0.52 and 3.14 rad(.)s(-1) were examined at 0, 5 and 10 weeks. After 10 weeks, the FAST group demonstrated significant [mean (SEM)] increases in eccentric [29.6 (6.4)%] and concentric torque [27.4 (7.3) %] at 3.14 rad(.)s(-1), isometric torque [21.3 (4.3)%] and eccentric torque [25.2 (7.2) %] at 0.52 rad(.)s(-1). The percentage of type I fibres in the FAST group decreased from [53.8 (6.6)% to 39.1 (4.4)%] while type lib fibre percentage increased from [5.8 (1.9)% to 12.9 (3.3)%; P < 0.05]. In contrast. the SLOW group did not experience significant changes in muscle fibre type or muscle torque. We conclude that neuromuscular adaptations to eccentric training stimuli may be influenced by differences in the ability to cope with chronic exposure to relatively fast and slow eccentric contraction velocities. Possible mechanisms include greater cumulative damage to contractile tissues or stress induced by slow eccentric muscle contractions.

Modelling the activated sludge flocculation process combining laser light diffraction particle sizing and population balance modelling (PBM)

A technique based on laser light diffraction is shown to be successful in collecting on-line experimental data. Time series of floc size distributions (FSD) under different shear rates (G) and calcium additions were collected. The steady state mass mean diameter decreased with increasing shear rate G and increased when calcium additions exceeded 8 mg/l. A so-called population balance model (PBM) was used to describe the experimental data, This kind of model describes both aggregation and breakage through birth and death terms. A discretised PBM was used since analytical solutions of the integro-partial differential equations are non-existing. Despite the complexity of the model, only 2 parameters need to be estimated: the aggregation rate and the breakage rate. The model seems, however, to lack flexibility. Also, the description of the floc size distribution (FSD) in time is not accurate.

Synthesis and characterization of mono- and bis-ligand zinc(II) and cadmium(II) complexes of the di-2-pyridylketone Schiff base of S-benzyl dithiocarbazate (Hdpksbz) and the X-ray crystal structures of the [Zn(dpksbz)2] and [Cd(dpksbz)NCS]2 complexes

New mono- and bis-chelated zinc(II) and cadmium(II) complexes of formula, [M(dpksbz)NCS] (dpksbz = anionic form of the di-2-pyridylketone Schiff base of S-benzyldithiocarbazate) and [M(dpksbz)(2)] (M = Zn-II, Cd-II) have been prepared and characterized. The structure of the bis-ligand complex, [Zn(dpksbZ)(2)] has been determined by X-ray diffraction. The complex has a distorted octahedral geometry in which the ligands are coordinated to the zinc(II) ion as uninegatively charged tridentate chelates via the thiolate sulfur atoms, the azomethine nitrogen atoms and the pyridine nitrogen atoms. The distortion from a regular octahedral geometry is attributed to the restricted bite angles of the Schiff base ligands. X-ray structural analysis shows that the [Cd(dpksbz)NCS](2) complex is a centrosymmetric dimer in which each of the cadmium(II) ions adopts a five-coordinate, approximately square-pyramidal configuration with the Schiff base acting as a tetradentate chelating agent coordinating a cadmium(II) ion via one of the pyridine nitrogen atoms, the azomethine nitrogen atom and the thiolate sulfur atom; the second pyridine nitrogen atom is coordinated to the other cadmium(II) ion of the dimer. The fifth coordination position around each cadmium(II) is occupied by an N-bonded thiocyanate ligand. (C) 2003 Elsevier Science Ltd. All rights reserved.

Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Sistema integrado de passagens e di??rias: SIPAD

O Sistema Integrado de Passagens e Di??rias (SIPAD), foi concebido no conceito de integra????o de dados e utiliza uma base de dados ??nica que evita o retrabalho e a inconsist??ncia de informa????es. O sistema tem por objetivo tornar mais ??gil, transparente e desburocratizado o processo de solicita????o, gerenciamento e controle de passagens e di??rias no ??mbito do Minist??rio da Sa??de. O SIPAD permite, em tempo real, o atendimento dos pedidos de viagens mediante requisi????es eletr??nicas com alto grau de confiabilidade e seguran??a. O sistema permite ainda o controle f??sico e a gest??o financeira de todos os pedidos de viagem; o c??lculo autom??tico de valores de di??rias inclusive em moeda estrangeira; o acompanhamento de trechos de viagens e conex??es internacionais com indica????o dos aeroportos; o controle e presta????o de contas de viagens; o desconto autom??tico do valor do vale refei????o por UF. A seguran??a do SIPAD ?? garantida por sistema que permite acessos escalonados por n??veis de senha , a partir de perfis previamente definidos. No SIPAD pode-se realizar consultas on line e emiss??o automatizada de relat??rios operacionais e gerenciais com interface gr??fica. Os resultados ap??s a implanta????o , em 01/07/99, j?? causam impactos significativos. A economia estimada para o ano 2000, apenas em uma unidade gestora do Minist??rio, ?? de redu????o de 113.606 folhas de papel; elimina????o de 23.346 etiquetas; elimina????o de 40.468 assinaturas de gestores e ordenadores de despesa; elimina????o de 58.369 procedimentos de carimbo em pap??is; elimina????o de 11.673 registros de controle e 58.459 tramita????es de documentos

Sistema informatizado de controle de di??rias

O projeto consiste na automa????o de todo o processo de elabora????o, c??lculo, concess??o e pagamento de di??rias possibilitando ainda a an??lise da execu????o or??ament??ria e financeira, por meio de um sistema informatizado de controle. Este sistema ?? ??gil e de f??cil opera????o, e confere seguran??a de acesso ??s informa????es. Ele opera em ambiente de rede, de maneira que qualquer setor possa controlar suas di??rias, utilizando-se de um ??nico banco de dados instalado em um computador servidor