Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.

Experimental analysis of active-passive vibration control using viscoelastic materials and extension and shear piezoelectric actuators

Hybrid active-passive damping treatments combine the reliability, low cost and robustness of viscoelastic damping treatments and the high-performance, modal selective and adaptive piezoelectric active control. Numerous hybrid damping treatments have been reported in the literature. They differ mainly by the relative positions of viscoelastic treatments, sensors and piezoelectric actuators. In this work we present an experimental analysis of three active-passive damping design configurations applied to a cantilever beam. In particular, two design configurations based on the extension mode of piezoelectric actuators combined with viscoelastic constrained layer damping treatments and one design configuration with shear piezoelectric actuators embedded in a sandwich beam with viscoelastic core are analyzed. For comparison purposes, a purely active design configuration with an extension piezoelectric actuator bonded to an elastic beam is also analyzed. The active-passive damping performance of the four design configurations is compared. Results show that active-passive design configurations provide more reliable and wider-range damping performance than the purely active configuration.

Relationship between surface segregation and rapid propane electrical response in Cd-doped SnO2 nanornaterials

Controlling the surface properties of nanoparticles using ionic dopants prone to be surface segregated has emerged as an interesting tool for obtaining highly selective and sensitive sensors. In this work, the surface segregation of Cd cations on SnO2 nanopowders prepared by the Pechini`s method was studied by infrared spectroscopy, X-ray diffraction, and specific surface area analysis. We observed that the surface chemistry modifications caused by the surface segregation of Cd and the large specific surface area were closely responsible for a rapid and regular electrical response of 5 mol% Cd-doped SnO2 films to 100 ppm propane and NO, diluted in dry air at relatively low temperature (100 degrees C). (c) 2008 Elsevier B.V. All rights reserved.

Forest Policy Reform in Brazil

Rapid deforestation in the Brazilian Amazon, caused by economic, social, and policy factors, has focused global and national attention on protecting this valuable forest resource. In response, Brazil reformed its federal forest laws in 2006, creating new regulatory, development, and incentive policy instruments and institutions. Federal forestry responsibilities are maintained within the ministry of the environment; its regulatory agency responsibilities are divided among three different branches of the agency; many powers are delegated to states and municipalities; and a new private concession system is being developed. These reforms offer promise to improve forest protection and management in Brazil but must overcome significant institutional and social resistance for success.

Micromethod for Quantification of Carbamazepine, Phenobartital and Phenytoin in Human Plasma by HPLC-UV Detection for Therapeutic Drug Monitoring Application

A simple, rapid, selective and sensitive analytical method by HPLC with UV detection was developed for the quantification of carbamazepine, phenobarbital and phenytoin in only 0.2 mL of plasma. A C18 column (150 x 3.9 mm, 4 micra) using a binary mobile phase consisting of water and acetonitrile (70:30, v/v) at a flow rate of 0.5 mL/min were proposed. Validation of the analytical method showed a good linearity (0.3 to 20.0 mg/L for CBZ, 0.9 to 60.0 mg/L for PB and 0.6 to 40.0 mg/L for PHT), high sensitivity (LOQ: 0.3, 0.9 and 0.6 mg/L respectively). The method was applied for drug monitoring of antiepileptic drugs (AED) in 27 patients with epilepsy under polytherapy.

Quantitative Determination of Gemifloxacin Mesylate in Tablets by Capillary Zone Electrophoresis and High Performance Liquid Chromatography

The aim of this study was to develop and validate selective and sensitive methods for quantitative determination of an antibacterial agent, gemifloxacin, in tablets by high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). The HPLC method was carried out on a LiChrospher (R) 100 RP-8e, 5 mu m (125 x 4 mm) column with a mobile phase composed of tetrahydrofuran-water (25:75, v/v) with 0.5 % of triethylamine and pH adjusted to 3.0 with orthophosphoric acid. The CZE method was performed using 50 mM sodium tetraborate buffer (pH 8.6). Samples were injected hydrodynamicaly (0.5 psi, 5 s) and the electrophoretic system was operated under normal polarity, at +20 kV and capillary temperature of 18 degrees C. A fused-silica capillary 40.2 cm (30 cm effective length) x 75 mu m i.d. was used. Both, HPLC and CZE could be interesting and efficient techniques to be applied for quality control in pharmaceutical industries.

Enantioselective analysis of mirtazapine, demethylmirtazapine and 8-hydroxy mirtazapine in human urine after solid-phase microextraction

A selective and reproducible off-line solid-phase microextraction procedure was developed for the simultaneous enantioselective determination of mirtazapine (MRT), demethylmirtazapine and 8-hydroxymirtazapine in human urine. CE was used for optimization of the extraction procedure whereas LC-MS was used for method validation and application. The influence of important factors in the solid-phase microextraction efficiency is discussed, such as the fiber coatings, extraction time, pH, ionic strength, temperature and desorption time. Before extraction, human urine samples were submitted to enzymatic hydrolysis at 37 degrees C for 16 h. Then, the enzyme was precipitated with trichloroacetic acid and the pH was adjusted to 8 with 1 mol/L pH 11 phosphate buffer solution. In the extraction, the analytes were transferred from the aqueous solution to the polydimethylsiloxane-divinylbenzene fiber coating and then desorbed in methanol. The mean recoveries were 5.4, 1.7 and 1.0% for MRT, demethylmirtazapine and 8-hydroxymirtazapine enantiomers, respectively. The method was linear over the concentration range of 62-1250 ng/mL. The within-day and between-day assay precision and accuracy were lower than 15%. The method was successfully employed in a preliminary cumulative urinary excretion study after administration of racemic MRT to a healthy volunteer.

Evaluation of curcumin and cisplatin-induced DNA damage in PC12 cells by the alkaline comet assay

A very appropriate method for antigenotoxicity evaluation of antioxidants is the comet assay, since this analytical method detects initial DNA lesions that are still subject to repair; in other words, lesions that are very associated to damages resulting from the generation and subsequent action of reactive species. However, a solid evaluation should be developed in order to avoid inexact interpretations. In our study, besides the association of curcumin with cisplatin, curcumin and cisplatin agents were also tested separately. Classical genotoxic compounds, when tested by the comet assay, present an increase in the nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA migration. This was an expected effect, as the cross-links between cisplatin and DNA decrease the DNA electrophoretic mobility. A similar effect was observed with the curcumin treatment, which decreased the nucleoid tail. Such effect was not expected and reinforced the necessity of including in the study, separate treatment groups with potentially antigenotoxic substances. The comet assay results have been analyzed using specific software for image analysis, as well as the classical visual analysis, and we have observed that the effect of decrease in DNA electrophoretic mobility was more easily observed when the data were analyzed by the software.

Tetrachromacy, oil droplets and bird plumage colours

There is a growing body of data on avian eyes, including measurements of visual pigment and oil droplet spectral absorption, and of receptor densities and their distributions across the retina. These data are sufficient to predict psychophysical colour discrimination thresholds for light-adapted eyes, and hence provide a basis for relating eye design to visual needs. We examine the advantages of coloured oil droplets, UV vision and tetrachromacy for discriminating a diverse set of avian plumage spectra under natural illumination. Discriminability is enhanced both by tetrachromacy and coloured oil droplets. Oil droplets may also improve colour constancy. Comparison of the performance of a pigeon's eye, where the shortest wavelength receptor peak is at 410 nm, with that of the passerine Leiothrix, where the ultraviolet-sensitive peak is at 365 nm, generally shows a small advantage to the latter, but this advantage depends critically on the noise level in the sensitivity mechanism and on the set of spectra being viewed.

Development and characterization of novel potent and stable inhibitors of endopeptidase EC 3.4.24.15

Solid-phase synthesis was used to prepare a series of modifications to the selective and potent inhibitor of endopeptidase EC 3.4.24.15 (EP24.15), N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), which is degraded at the Ala-Tyr bond, thus severely limiting its utility in vivo. Reducing the amide bond between the Ala and Tyr decreased the potency of the inhibitor to 1/1000. However, the replacement of the second alanine residue immediately adjacent to the tyrosine with alpha-aminoisobutyric acid gave a compound (JA-2) that was equipotent with cFP, with a K-i of 23 nM. Like cFP, JA-2 inhibited the closely related endopeptidase EC 3.4.24.16 1/20 to 1/30 as potently as it did EP24.15, and did not inhibit the other thermolysin-like endopeptidases angiotensin-converting enzyme, endothelin-converting enzyme and neutral endopeptidase. The biological stability of JA-2 was investigated by incubation with a number of membrane and soluble sheep tissue extracts. In contrast with cFP, JA-2 remained intact after 48 h of incubation with all tissues examined. Further modifications to the JA-2 compound failed to improve the potency of this inhibitor. Hence JA-2 is a potent, EP24.15-preferential and biologically stable inhibitor, therefore providing a valuable tool for further assessing the biological functions of EP24.15.

Boston naming test results for healthy older Australians: A longitudinal and cross-sectional study

This study reports on a sample of normal Australian elderly who were assessed for naming ability using the Boston Naming Test (BNT). The study aimed to examine and compare the changes in naming ability, using both longitudinal and cross-sectional analysis, and determine the relationships between naming ability and age, educational level, visual acuity and gender and cultural relevance. Contradictory findings were produced regarding age and were dependent on the research design. Longitudinal analysis showed no age-related change in naming ability in subjects over a four-period. In contrast, cross-sectional analysis showed a weak but significant correlation between age and naming ability. Educational level, visual acuity and gender were unrelated to changes in naming ability over time, and unrelated to naming ability across the cohort of elderly. The Australian elderly performed better on the modified Australian version of the BNT than on the original American version. Thus, clinicians need to be cautious when interpreting the results of the BNT for elderly and for populations outside North America. The results of this study also indicate a need for further longitudinal research of a greater duration to establish age-related decline in naming ability.

Eye design and color signaling in a stomatopod crustacean Gonodactylus smithii

Many species of stomatopod crustaceans have multiple spectral classes of photoreceptors in their retinas. Behavioral evidence also indicates that stomatopods are capable of discriminating objects by their spectral differences alone, Most animals use only two to four different types of photoreceptors in their color vision systems, typically with broad sensitivity functions, but the stomatopods apparently include eight or more narrowband photoreceptor classes for color recognition. It is also known that stomatopods use several colored body regions in social interactions. To examine why stomatopods may be so 'concerned' with color, we measured the absorption spectra of visual pigments and intrarhabdomal filters, and the reflectance spectra from different parts of the bodies of several individuals of the gonodactyloid stomatopod species, Gonodactylus smithii. We then applied a model of multiple dichromatic channels for color encoding to examine whether the finely tuned color vision was specifically co-evolved with their complex color signals. Although the eye design of stomatopods seems suitable for detecting color signals of their own, the detection of color signals from other animals, such as reef fishes, can be enhanced as well. Color vision in G. smithii is therefore not exclusively adapted to detect its own color signals, but the spectral tuning of some photoreceptors (e.g. midband Rows 2 and 3) enhances the contrast of certain color signals to a large enough degree to make co-evolution between color vision and these rather specific color signals likely. Copyright (C) 2000 S. Karger AG, Basel.

Parallel processing and image analysis in the eyes of mantis shrimps

The compound eyes of mantis shrimps, a group of tropical marine crustaceans, incorporate principles of serial and parallel processing of visual information that may be applicable to artificial imaging systems. Their eyes include numerous specializations for analysis of the spectral and polarizational properties of light, and include more photoreceptor classes for analysis of ultraviolet light, color, and polarization than occur in any other known visual system. This is possible because receptors in different regions of the eye are anatomically diverse and incorporate unusual structural features, such as spectral filters, not seen in other compound eyes. Unlike eyes of most other animals, eyes of mantis shrimps must move to acquire some types of visual information and to integrate color and polarization with spatial vision. Information leaving the retina appears to be processed into numerous parallel data streams leading into the central nervous system, greatly reducing the analytical requirements at higher levels. Many of these unusual features of mantis shrimp vision may inspire new sensor designs for machine vision

Attentional modulation of the startle reflex during threat of shock

The present study (N532) investigated attentional modulation of the startle blink reflex at long lead intervals under conditions of differing emotional valence. Participants performed a visual discrimination and counting task while coloured lights indicated whether it was possible for the participant to receive an electrotactile shock (threat of shock) or if no shock would be presented (safe). Latency and magnitude of startle responses to probes during inter-stimulus intervals were facilitated during threat periods relative to safe periods. Startle latency and magnitude modulation were enhanced during attended discrimination and counting task stimuli relative to startle during ignored stimuli. This attention effect did not vary under threat or safe conditions, suggesting that attentional startle modulation is not affected by the emotional valence of the context.

Determination of fluoxetine and norfluoxetine enantiomers in human plasma by polypyrrole-coated capillary in-tube solid-phase microextraction coupled with liquid chromatography-fluorescence detection

A sensitive, selective, and reproducible in-tube polypyrrole-coated capillary (PPY) solid-phase microextraction and liquid chromatographic method for fluoxetine and norfluoxetine enantiomers analysis in plasma samples has been developed, validated, and further applied to the analysis of plasma samples from elderly patients undergoing therapy with antidepressants. Important factors in the optimization of in-tube SPME efficiency are discussed, including the sample draw/eject volume, draw/eject cycle number, draw/eject flow-rate, sample pH, and influence of plasma proteins. Separation of the analytes was achieved with a Chiralcel OD-R column and a mobile phase consisting of potassium hexafluorophosphate 7.5 mM and sodium phosphate 0.25 M solution, pH 3.0, and acetonitrile (75:25, v/v) in the isocratic mode, at a flow rate of 1.0 mL/min. Detection was carried out by fluorescence absorbance at Ex/Em 230/290 nm. The multifunctional porous surface structure of the PPY-coated film provided high precision and accuracy for enantiomers. Compared with other commercial capillaries, PPY-coated capillary showed better extraction efficiency for all the analytes. The quantification limits of the proposed method were 10 ng/mL for R- and S-fluoxetine, and 15 ng/mL for R- and S-norfluoxetine, with a coefficient of variation lower than 13%. The response of the method for enantiomers is linear over a dynamic range, from the limit of quantification to 700ng/mL, with correlation coefficients higher than 0.9940. The in-tube SPME/LC method can therefore be successfully used to analyze plasma samples from ageing patients undergoing therapy with fluoxetine. (C) 2009 Elsevier B.V. All rights reserved.