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Objectives: The purpose of this study is to understand how patient safety professionals from healthcare facilities and patient safety organizations develop patient safety interventions and the resources used to support intervention development., Methods: Semistructured interviews were conducted with patient safety professionals at nine healthcare facilities and nine patient safety organizations. Interview data were qualitatively analyzed, and findings were organized by the following: patient safety solutions and interventions, use of external databases, and evaluation of patient safety solutions., Results: Development of patient safety interventions across healthcare facilities and patient safety organizations was similar and included literature searches, internal brainstorming, and interviews. Nearly all patient safety professionals at healthcare facilities reported contacting colleagues at other healthcare facilities to learn about similar safety issues and potential interventions. Additionally, less than half of patient safety professionals at healthcare facilities and patient safety organizations interviewed report data to publicly available patient safety databases. Finally, most patient safety professionals at healthcare facilities and patient safety organizations stated that they evaluate the effectiveness of patient safety interventions; however, they mentioned methods that may be less rigorous including audits, self-reporting, and subjective judgment., Conclusions: Patient safety professionals often utilize similar methods and resources to develop and evaluate patient safety interventions; however, many of these efforts are not coordinated across healthcare organizations and could benefit from working collectively in a systematic fashion. Additionally, healthcare facilities and patient safety organizations face similar challenges and there are several opportunities for optimization on a national level that may improve patient safety., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors disclose no conflict of interest.

This study assessed the effects of hydroxytyrosol (HT) on 8- to 20-day-old broilers challenged with lipopolysaccharide (LPS); 180 Cobb500™ male chicks were randomly assigned to 3 treatment groups, each comprising 10 replicates with 6 birds per replicate. Treatments included a control diet (CON), CON with LPS administration, and CON + LPS supplemented with 10 mg of HT/kg of feed. LPS was administered intraperitoneally on days 14, 16, 18, and 20. Body weight (BW), body weight gain (BWG), and the feed conversion ratio (FCR) were measured. On day 20, ten birds per treatment were slaughtered for analysis. Bursa, spleen, and liver were collected, and their respective relative weight was determined. The jejunum was destined for morphological analyses of villus height (VH), crypt depth (CD), and their ratio (VH:CD), and for mRNA expression of nuclear factor kappa B (NF-κB), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and interleukins 10 (IL-10), 1 beta (IL-1β), and 8 (IL-8). HT improved BW, BWG, and FCR, and reduced crypt depth (CD) while increasing the VH:CD ratio in the jejunum. Moreover, HT downregulated mRNA expression of CAT, GPx, IL-10, and IL-1β. In conclusion, HT enhances broiler growth performance, mitigates jejunal mucosa damage from LPS, and modulates antioxidant and immune responses.

This study investigated the effect of the serine protease on metabolizable energy and amino acids' digestibility of different soybean meal for broilers. A total of 684 broilers chickens form 14 to 23 d age were distributed with nineteen treatments, six replicates, and six birds per replicate. Nine samples of soybean meal from different regions in Brazil were used, with some samples supplemented with the protease enzyme and others without addition. Apparent and corrected-for-nitrogen-balance metabolizable energy were evaluated, as well as the coefficients of amino acid digestibility. All collected data were submitted to ANOVA at a significance level of 5% and Tukey's test was applied. The results showed that the addition of the protease enzyme significantly increased the values of AME and AMEn in all soybean meal samples. The soybean meal of different origins has significant variations in AME and AMEn. The addition of the protease improved the digestibility of essential amino acids compared to soybean meal without enzyme addition. These results indicate that supplementation with serine protease can improve the metabolizable energy and amino acid digestibility of soybean meal from different regions in the diet of broilers, potentially being an effective strategy to enhance nutrient utilization and animal performance.

Diatoms are important primary producers in the world's oceans, yet their growth is constrained in large regions by low bioavailable iron (Fe). Low-Fe stress-induced limitation of primary production is due to requirements for Fe in components of essential metabolic pathways including photosynthesis and other chloroplast plastid functions. Studies have shown that under low-Fe stress, diatoms alter plastid-specific processes, including components of electron transport. These physiological changes suggest changes of protein content and in protein abundances within the diatom plastid. While in silico predictions provide putative information on plastid-localized proteins, knowledge of diatom plastid proteins remains limited in comparison to well-studied model photosynthetic organisms. To address this, we employed shotgun proteomics to investigate the proteome of subcellular plastid-enriched fractions from Thalassiosira pseudonana to gain a better understanding of how the plastid proteome is remodeled in response to Fe limitation. Using mass spectrometry-based peptide identification and quantification, we analyzed T. pseudonana grown under Fe-replete and -limiting conditions. Through these analyses, we inferred the relative quantities of each protein, revealing that Fe limitation regulates major metabolic pathways in the plastid, including the Calvin cycle. Additionally, we observed changes in the expression of light-harvesting proteins. In silico localization predictions of proteins identified in this plastid-enriched proteome allowed for an in-depth comparison of theoretical versus observed plastid-localization, providing evidence for the potential of additional protein import pathways into the diatom plastid., (© 2023 The Authors. Journal of Phycology published by Wiley Periodicals LLC on behalf of Phycological Society of America.)

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

Communicating physiological information via the tactile modality is shown as a promising means to address data overload faced by anesthesia providers. However, it is important to ensure that the tactile parameters which represent information are intuitive. There is currently no consensus on which tactile parameters should be used to present information within anesthesia. The two studies presented here evaluate: (a) a set of 24 tactile cues manipulating intensity, temporal, and spatial tactile parameters in a usability study and (b) a prototype tactile display based on the usability study's findings in a single and dual-task scenario. Findings of the usability study show intensity and temporal were rated most urgent and had the most potential to represent changes in physiological measures. This was confirmed in the follow up study as increases/decreases in intensity were shown to represent increases/decreases in a physiological measure and using different spatial locations to represent physiological measures resulted in greater than 95% response accuracy. Response times and accuracy were not adversely affected while performing a secondary task. The findings contribute to a better understanding of how to map tactile parameters to physiological information and demonstrate the effectiveness of end-user feedback in tactile display design to develop intuitive alerts.

Infections related to non-tuberculous mycobacteria (NTM) have recently increased worldwide. The transmission of these microorganisms from the environment has been suggested as the main source for human infections. To elucidate the epidemiological aspects and distribution of these pathogens, many studies have evaluated several decontamination methods and protocols to properly isolate NTM from environmental samples, mainly from water. However, no satisfactory strategy has been found for isolation of most of the NTM species harboring different phenotypic characteristics. Here, we evaluated the susceptibility of 23 NTM strains presenting variable growth rate and pigmentation patterns to eight different methods: oxalic acid (2.5% and 5%), cetylpyridinium chloride (CPC) (0.0025% and 0.005%), sodium hydroxide (NaOH) (2% and 4%), and sodium dodecyl sulfate (SDS) plus NaOH (SDS 1.5%-NaOH 0.5% and SDS 3%-NaOH 1%). It was found that the viability of NTM exposed to different decontamination methods varies according to their phenotypic characteristics and two methods (SDS 1.5% plus NaOH 0.5% and CPC 0.0025%) were necessary for effective isolation of all of the species tested. These findings supply important insights for future studies on the environmental occurrence of mycobacteria and improving the sensibility of traditional strategies.

Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed. In this context, thiourea derivatives have a wide range of biological activities, including anti-TB. This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea as a pharmacophore group., Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of fifty-nine benzoylthioureas derivatives., Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship study of this series of compounds has been performed., Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1 and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the para-position in benzene ring plays an important role in the antitubercular activity of Series A. These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2 and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general, Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles., Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the first line anti-TB drug ethambutol and 0.65 times less active than isoxyl., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study describes and illustrates the morphology of the second juvenile stage of the blue-fingered burrowing crayfish Parastacus caeruleodactylus. One female carrying 20 juveniles was collected in January 2019 from a swamp forest in the municipality of Dom Pedro de Alcântara, state of Rio Grande do Sul, southern Brazil. Juveniles were dissected and the appendages were mounted in slides. The general morphology and the pattern of attachment of the second juvenile stage of P. caeruleodactylus correspond to that reported for other parastacids. The main differences among the co-generic species are related to the number of articles in the flagella of the antennae, the number of spines in the antennal scale, the number of setae in the articles of the appendages, the number of teeth in the mandible molar and incisor processes, the absence of segmentation in the exopod flagellum of the maxillipeds and the number of teeth in the crista dentata of the ischium of maxilliped 3.

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. In this work, we synthesized two series of new acylhydrazides and evaluated their activity against different strains of Mtb. Derivatives of isoniazid (INH) showed important anti-Mtb activity, some being more potent than all anti-TB drugs of first choice. Moreover, three compounds proved to be more potent than INH against resistant Mtb. The Ames test showed favorable results for two of these substances compared to INH, one of which presented expressly lower toxicity to HepG2 cells than that of INH. This result shows that this compound has the potential to overcome one of the main adverse effects of this drug., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The phylum Actinobacteria, which comprises a great variety of Gram-positive bacteria with a high G+C content in their genomes, is known for its large production of bioactive compounds, including those with antimicrobial activity. Among the antimicrobials, bacteriocins, ribosomally synthesized peptides, represent an important arsenal of potential new drugs to face the increasing prevalence of resistance to antibiotics among microbial pathogens. The actinobacterial bacteriocins form a heterogeneous group of substances that is difficult to adapt to most proposed classification schemes. However, recent updates have accommodated efficiently the diversity of bacteriocins produced by this phylum. Among the bacteriocins, the lantibiotics represent a source of new antimicrobials to control infections caused mainly by Gram-positive bacteria and with a low propensity for resistance development. Moreover, some of these compounds have additional biological properties, exhibiting activity against viruses and tumour cells and having also potential to be used in blood pressure or inflammation control and in pain relief. Thus, lantibiotics already described in Actinobacteria exhibit potential practical applications in medical settings, food industry and agriculture, with examples at different stages of pre-clinical and clinical trials.

Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

This work demonstrates the use of a new additional constraint for the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) algorithm called "area correlation constraint", introduced to build calibration models for Excitation Emission Matrix (EEM) data. We propose the application of area correlation constraint MCR-ALS for the quantification of cholesterol using a simulated data set and an experimental data system (cholesterol in a ternary mixture). This new constraint includes pseudo-univariate local regressions using the area of resolved profiles against reference values during the alternating least squares optimization, to provide directly accurate quantifications of a specific analyte in concentration units. In the two datasets investigated in this work, the new constraint retrieved correctly the analyte and interference spectral profiles and performed accurate estimations of cholesterol concentrations in test samples. This the first study using the proposed area constraint using EEM measurements. This new constraint approach emerges as a new possibility to be tested in general cases of second-order multivariate calibration data in the presence of unknown interferents or in more involved higher order calibration cases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Two new species of Parastacus Huxley, 1879 are described from material collected in the state of Rio Grande do Sul, southern Brazil: Parastacus fluviatilis sp. nov. from highland streams and Parastacus caeruleodactylus sp. nov. from wetlands. Parastacus fluviatilis sp. nov. is distinguished mainly by large chelipeds with dense setae cover on the cutting edge of fingers, telson subtriangular with two lateral blunt spines and strongly concave ventral surface of lateral process of thoracic sternites 6 and 7. Parastacus caeruleodactylus sp. nov. is distinguished mainly by blue cheliped fingers and a large gap between them, reduced abdomen, dorsal and ventral margins of dactylus, propodus and carpus of second pair of pereiopods with tufts of long setae and mid-dorsal carina of exopod of uropods unarmed. According to IUCN Red List criteria both species are considered endangered. Habitat characterization and a method for defining the shape of second abdominal pleura are also provided.

The aim of this study was to evaluate the potential of the successive projection algorithm for interval selection in partial least squares (iSPA-PLS) together with near-infrared reflectance spectroscopy (NIRS) as a feasible method to determine the total anthocyanin content (TAC) of intact jaboticaba fruit [Myrciaria jaboticaba (Vell.) O. Berg]. A total of 579 jaboticaba fruit were collected in three different harvests in three separate years (2011 and 2013). The correlation coefficients between the predicted and measured TAC were between 0.65 and 0.89, the RMSEPs were 7.55 g kg(-1) and 9.35 g kg(-1) (good accuracy) for prediction set, respectively. The RPD ratios for TAC were in the range of 2.57-3.19 with iSPA-PLS, which showed better predictive performance (acceptable precision). These results suggest that the NIR spectroscopy and wavelength selection (iSPA-PLS) algorithm can be used to determine the TAC of intact jaboticaba fruit., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background/objectives: We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy are unknown and should be established to determine the optimal time window for drug treatment., Methods: Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H₂O₂ release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats., Results: We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H₂O₂ release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24h after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats., Conclusion: Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to evaluate the potential of near-infrared reflectance spectroscopy (NIR) as a rapid and non-destructive method to determine soluble solid content (SSC) in intact jaboticaba [Myrciaria jaboticaba (Vell.) O. Berg] fruit. Multivariate calibration techniques were compared with pre-processed data and variable selection algorithms, such as partial least squares (PLS), interval partial least squares (iPLS), a genetic algorithm (GA), a successive projections algorithm (SPA) and nonlinear techniques (BP-ANN, back propagation of artificial neural networks; LS-SVM, least squares support vector machine) were applied to building the calibration models. The PLS model produced prediction accuracy (R(2)=0.71, RMSEP=1.33 °Brix, and RPD=1.65) while the BP-ANN model (R(2)=0.68, RMSEM=1.20 °Brix, and RPD=1.83) and LS-SVM models achieved lower performance metrics (R(2)=0.44, RMSEP=1.89 °Brix, and RPD=1.16). This study was the first attempt to use NIR spectroscopy as a non-destructive method to determine SSC jaboticaba fruit., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model., Methods and Results: We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca(2+)-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load., Conclusions: Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Worldwide, nontuberculous mycobacteria (NTM) have become emergent pathogens of pulmonary infections in cystic fibrosis (CF) patients, with an estimated prevalence ranging from 5 to 20%. This work investigated the presence of NTM in sputum samples of 129 CF patients (2 to 18 years old) submitted to longitudinal clinical supervision at a regional reference center in Rio de Janeiro, Brazil. From June 2009 to March 2012, 36 NTM isolates recovered from 10 (7.75%) out of 129 children were obtained. Molecular identification of NTM was performed by using PCR restriction analysis targeting the hsp65 gene (PRA-hsp65) and sequencing of the rpoB gene, and susceptibility tests were performed that followed Clinical and Laboratory Standards Institute recommendations. For evaluating the genotypic diversity, pulsed-field gel electrophoresis (PFGE) and/or enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) was performed. The species identified were Mycobacterium abscessus subsp. bolletii (n = 24), M. abscessus subsp. abscessus (n = 6), Mycobacterium fortuitum (n = 3), Mycobacterium marseillense (n = 2), and Mycobacterium timonense (n = 1). Most of the isolates presented resistance to five or more of the antimicrobials tested. Typing profiles were mainly patient specific. The PFGE profiles indicated the presence of two clonal groups for M. abscessus subsp. abscessus and five clonal groups for M. abscesssus subsp. bolletii, with just one clone detected in two patients. Given the observed multidrug resistance patterns and the possibility of transmission between patients, we suggest the implementation of continuous and routine investigation of NTM infection or colonization in CF patients, including countries with a high burden of tuberculosis disease., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

A method for rapid, inexpensive and sensitive simultaneous analysis of glucose, creatinine, triglycerides, total cholesterol and total protein is needed to analyze blood. The proposed method is based on the production of a specific color after reaction. The method was adapted to a 64-microwell plate format, and it uses the transparency scanner feature of a commercially available desktop scanner. Each microwell plate had an 8×8 array of flat-bottomed 250μL microwells, and these microwells were used to simultaneously house the solutions for clinical assay. The scanned image was saved in TIFF format in a portable computer and then processed using a Graphic User Interface (GUI) designed in our laboratory to obtain analytical curves and to automate the mathematics and statistics calculations. This automation improved the analytical frequency of the method. The results showed that it is possible to measure a few microliters of solution with exactitude and precision better than 5.30%. The measured concentration ranges of glucose, triglycerides, creatinine, total cholesterol and total protein were 0.781 to 100, 1.56 to 200, 0.031 to 4.0, 1.56 to 200mg dL(-1) and 0.031 to 4.0g dL(-1), respectively. The limits of detection were 16.2, 51.7, 0.12, 41.5mg dL(-1) and 0.62g dL(-1) for glucose, triglycerides, creatinine, total cholesterol and total protein, respectively. The recoveries were from 98.7% to 101.3% for total cholesterol, 98.7% to 124.9% for triglycerides, 54.2% to 98.3% for total protein, 89.6% to 101% for glucose and 65.7% to 115.4% for creatinine. The results provided by the scanner were compared with those obtained with a commercial photometer and did not show significant differences at a confidence level of 95%. Good results were obtained for the correlation coefficient and Root Mean Square Error of Prediction (RMSEP) values for the five parameters, especially the total cholesterol and creatinine. The RMSEP values for glucose, creatinine, triglyceride, total cholesterol and total protein were 8.05, 0.28, 7.69, 1.41mg dL(-1) and 2.2g dL(-1), respectively., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study describes two applications of a variant of the multivariate curve resolution alternating least squares (MCR-ALS) method with a correlation constraint. The first application describes the use of MCR-ALS for the determination of biodiesel concentrations in biodiesel blends using near infrared (NIR) spectroscopic data. In the second application, the proposed method allowed the determination of the synthetic antioxidant N,N'-Di-sec-butyl-p-phenylenediamine (PDA) present in biodiesel mixtures from different vegetable sources using UV-visible spectroscopy. Well established multivariate regression algorithm, partial least squares (PLS), were calculated for comparison of the quantification performance in the models developed in both applications. The correlation constraint has been adapted to handle the presence of batch-to-batch matrix effects due to ageing effects, which might occur when different groups of samples were used to build a calibration model in the first application. Different data set configurations and diverse modes of application of the correlation constraint are explored and guidelines are given to cope with different type of analytical problems, such as the correction of matrix effects among biodiesel samples, where MCR-ALS outperformed PLS reducing the relative error of prediction RE (%) from 9.82% to 4.85% in the first application, or the determination of minor compound with overlapped weak spectroscopic signals, where MCR-ALS gave higher (RE (%)=3.16%) for prediction of PDA compared to PLS (RE (%)=1.99%), but with the advantage of recovering the related pure spectral profile of analytes and interferences. The obtained results show the potential of the MCR-ALS method with correlation constraint to be adapted to diverse data set configurations and analytical problems related to the determination of biodiesel mixtures and added compounds therein., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Excitation emission matrix (EEM) fluorescence spectroscopy combined with the OPLS method has been investigated as a promising tool to discriminate between normal and cancer cell lines in two datasets: (i) using several types of normal and cancer cells (including 3T3, ARPE, HEK, HepG2, HeLa, HT-29 and 786-0 cells); (ii) considering the expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in suspensions of HEK and 786-0 cell lines. Partial Least Squares-Discriminant Analysis (PLS-DA) using the score matrix from PARAFAC (Parallel Factor Analysis), UPLS-DA (Unfolded Partial Least Squares with Discriminant Analysis) and orthogonal projection to latent structures (OPLS) were used as the bases for the discrimination models. UPLS-DA presented relevant performance for cancer cells in both datasets, with 100% and 66.7% correct prediction for first and second cases, respectively, and poor discrimination relative to normal cells in the first dataset (25%). By using the OPLS, we achieved 75% correct prediction for normal cells and maintained 100% concordance for cancer objects. On applying OPLS to the second dataset, we obtained 100% correct prediction in both classes (normal and cancer) for calibration and prediction sets. These results suggest that EEM fluorescence spectroscopy combined with chemometrics could be used as a clinical tool for cancer cell detection based on intrinsic biomolecular signatures.

Objectives: To evaluate oxidative damage through the thiobarbituric acid-reactive species (TBARS) and protein carbonyl groups; antioxidant enzymatic system - superoxide dismutase (SOD) and catalase (CAT); and energetic metabolism in the brain of spontaneously hypertensive adult rats (SHR) after both acute and chronic treatment with methylphenidate hydrochloride (MPH)., Methods: Adult (60 days old) SHRs were treated during 28 days (chronic treatment), or 1 day (acute treatment). The rats received one i.p. injection per day of either saline or MPH (2 mg/kg). Two hours after the last injection, oxidative damage parameters and energetic metabolism in the cerebellum, prefrontal cortex, hippocampus, striatum and cortex were evaluated., Results: We observed that both acute and/or chronic treatment increased TBARS and carbonyl groups, and decreased SOD and CAT activities in many of the brain structures evaluated. Regarding the energetic metabolism evaluation, the acute and chronic treatment altered the energetic metabolism in many of the brain structures evaluated., Conclusion: We observed that both acute and chronic use of methylphenidate hydrochloride (MPH) in adult spontaneously hypertensive rats (SHRs) was associated with increased oxidative stress and energetic metabolism alterations. These data also reinforce the importance of the SHR animal model in further studies regarding MPH.

Staphylococcus aureus is one of the leading causes of bacteremia, with high levels of accompanying morbidity and mortality. Current gold standard for the detection of S. aureus is very time-consuming, typically taking 24h or longer. We set out to determine whether Fourier-transform infrared spectroscopy (FT-IR) combined with variable selection techniques, such as, genetic algorithm-linear discriminant analysis (GA-LDA) and successive projection algorithm-linear discriminant analysis (SPA-LDA) could be applied to detect this pathogen of bloodstream infection in samples based on the unique spectral "fingerprints" of their biochemical composition. Thirty real blood samples from healthy volunteers were contaminated with five different concentrations (10(7) until 10(3) CFU/mL) of microorganism and it analyzed by IR spectroscopy. The resulting GA-LDA model successfully classified all test samples with respect to their concentration in contaminated blood using only 18 wavenumbers. Discriminant functions revealed that GA-LDA clearly segregated different microorganism concentrations and the variable selected confirmed the chemical entities associated with the microorganism. The current study indicates that IR spectroscopy with feature selection techniques have the potential to provide one rapid approach for whole-organism fingerprint diagnostic microbial directly in blood culture., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Reactive oxygen and nitrogen species regulate a wide array of signaling pathways that governs cardiovascular physiology. However, oxidant stress resulting from disrupted redox signaling has an adverse impact on the pathogenesis and progression of cardiovascular diseases. In this review, we address how redox signaling and oxidant stress affect the pathophysiology of cardiovascular diseases such as ischemia-reperfusion injury, hypertension and heart failure. We also summarize the benefits of exercise training in tackling the hyperactivation of cellular oxidases and mitochondrial dysfunction seen in cardiovascular diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Investigations on biodegradation of textile effluent by filamentous fungi strains Curvularia lunata URM 6179 and Phanerochaete chrysosporium URM 6181 were performed in static bioreactors under aerated and non-aerated conditions. Spectrophotometric, HPLC/UV and LC-MS/MS analysis were performed as for to confirm, respectively, decolourisation, biodegradation and identity of compounds in the effluent. Enzymatic assays revealed higher production of enzymes laccase (Lac), lignin peroxidase (LiP) and manganese-dependent peroxidase (MnP) by P. chrysosporium URM 6181 in aerated bioreactor (2020; 39 and 392 U/l, respectively). Both strains decolourised completely the effluent after ten days and biodegradation of the most predominant indigo dye was superior in aerated bioreactor (96%). Effluent treated by P. chrysosporium URM 6181 accumulated a mutagenic metabolite derived from indigo. The C. lunata URM 6179 strain, showed to be more successful for assure the environmental quality of treated effluent. These systems were found very effective for efficient fungal treatment of textile effluent., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study shows the application and usefulness of near infrared (NIR) transflectance spectra measurements in the identification and classification of Escherichia coli and Salmonella Enteritidis from commercial fruit pulp (pineapple). Principal component analysis (PCA), soft independent modeling of class analogy (SIMCA) analysis and partial least-squares discriminant analysis (PLS-DA) were used in the analysis. It was not possible to obtain total separation between the samples using PCA and SIMCA. PLS-DA presented good performance achieving prediction ability of 87.5% for E. coli and 88.3% for S. Enteritidis, respectively. For the best models, the sensitivity and specificity was 0.87 and 0.83 for PLS-DA with second derivative spectra. These results suggest that NIR spectroscopy and PLS-DA can be used to discriminate and detect bacteria in fruit pulp for modeling linear class boundaries., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate near-infrared reflectance spectroscopy (NIR), and multivariate calibration potential as a rapid method to determinate anthocyanin content in intact fruit (açaí and palmitero-juçara). Several multivariate calibration techniques, including partial least squares (PLS), interval partial least squares, genetic algorithm, successive projections algorithm, and net analyte signal were compared and validated by establishing figures of merit. Suitable results were obtained with the PLS model (four latent variables and 5-point smoothing) with a detection limit of 6.2 g kg(-1), limit of quantification of 20.7 g kg(-1), accuracy estimated as root mean square error of prediction of 4.8 g kg(-1), mean selectivity of 0.79 g kg(-1), sensitivity of 5.04×10(-3) g kg(-1), precision of 27.8 g kg(-1), and signal-to-noise ratio of 1.04×10(-3) g kg(-1). These results suggest NIR spectroscopy and multivariate calibration can be effectively used to determine anthocyanin content in intact açaí and palmitero-juçara fruit., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The quantitative analysis of glucose, triglycerides and high-density lipoprotein (HDL) in rat plasma without sample pre-treatment using direct near-infrared spectroscopy was studied. Comparison was made of several multivariate calibration techniques and algorithms for data pre-processing and variable selection, including partial least squares (PLS), interval partial least squares (iPLS), genetic algorithm (GA) and successive projections algorithm (SPA). Variable selection yielded good results for the correlation coefficient and Root Mean Square Error of Prediction (RMSEP) values for the three parameters, especially triglycerides. The RMSEP values for glucose, triglycerides and HDL produced by the PLS model were 6.08, 16.07 and 2.03 mg dl(-1), respectively. F tests and t-tests were performed to compare the results of the models with each other and with a reference method. These results suggests that the PLS method can be used to simultaneously determine the concentrations of glucose, triglycerides and HDL in complicated biological fluids with NIR spectroscopy, offering an alternative analysis in animals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study describes a method for non-destructive detection of adulterated glibenclamide tablets. This method uses near infrared spectroscopy (NIRS) and fluorescence spectroscopy along with chemometric tools such as Soft Independent Modeling of Class Analogy (SIMCA), Partial Least Squares-Discriminant Analysis (PLS-DA) and Unfolded Partial Least Squares with Discriminant Analysis (UPLS-DA). Both brand name (Daonil) and generic glibenclamide tablets were used for analysis. The levels of glibenclamide in each type of tablet were evaluated by derivative spectrophotometry in the ultraviolet region. The results obtained from the NIR and fluorescence spectroscopy along with those obtained from multivariate data classification show that this combined technique is an effective way to detect adulteration in drugs for the treatment of diabetes. In the future, this method may be extended to detect different types of counterfeit medications., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This work utilized the near-infrared spectroscopy (NIRS) and multivariate calibration to measure the percentage drug dissolution of four active pharmaceutical ingredients (APIs) (isoniazid, rifampicin, pyrazinamide and ethambutol) in finished pharmaceutical products produced in the Federal University of Rio Grande do Norte (Brazil). The conventional analytical method employed in quality control tests of the dissolution by the pharmaceutical industry is high-performance liquid chromatography (HPLC). The NIRS is a reliable method that offers important advantages for the large-scale production of tablets and for non-destructive analysis. NIR spectra of 38 samples (in triplicate) were measured using a Bomen FT-NIR 160 MB in the range 1100-2500nm. Each spectrum was the average of 50 scans obtained in the diffuse reflectance mode. The dissolution test, which was initially carried out in 900mL of 0.1N hydrochloric acid at 37±0.5°C, was used to determine the percentage a drug that dissolved from each tablet measured at the same time interval (45min) at pH 6.8. The measurement of the four API was performed by HPLC (Shimadzu, Japan) in the gradiente mode. The influence of various spectral pretreatments (Savitzky-Golay smoothing, Multiplicative Scatter Correction (MSC), and Savitzky-Golay derivatives) and multivariate analysis using the partial least squares (PLS) regression algorithm was calculated by the Unscrambler 9.8 (Camo) software. The correlation coefficient (R(2)) for the HPLC determination versus predicted values (NIRS) ranged from 0.88 to 0.98. The root-mean-square error of prediction (RMSEP) obtained from PLS models were 9.99%, 8.63%, 8.57% and 9.97% for isoniazid, rifampicin, ethambutol and pyrazinamide, respectively, indicating that the NIR method is an effective and non-destructive tool for measurement of drug dissolution from tablets., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) were reported in many Brazilian states (2032 notified cases) from 2004 to 2010. Most of the confirmed cases were mainly associated with Mycobacterium massiliense (recently renamed as Mycobacterium abscessus subsp. bolletii) BRA100 clone, recovered from patients who had undergone invasive procedures in which medical instruments had not been properly sterilized and/or disinfected. Since quinolones have been an option for the treatment of general RGM infections and have been suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro activities of all generations of quinolones for clinical and reference RGM by broth microdilution, and analysed the peptide sequences of the quinolone resistance determining regions (QRDRs) of GyrA and GyrB after DNA sequencing followed by amino acid translation. Fifty-four isolates of M. abscessus subsp. bolletii, including clone BRA100, recovered in different states of Brazil, and 19 reference strains of RGM species were characterized. All 54 M. abscessus subsp. bolletii isolates were resistant to all generations of quinolones and showed the same amino acids in the QRDRs, including the Ala-83 in GyrA, and Arg-447 and Asp-464 in GyrB, described as being responsible for an intrinsic low level of resistance to quinolones in mycobacteria. However, other RGM species showed distinct susceptibilities to this class of antimicrobials and patterns of mutations contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones.

Objective: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle., Method: Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection., Results: The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test., Conclusion: Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.

Methylphenidate (MPH) is a very effective treatment option for children and adolescents with attention-deficit/hyperactivity disorder. Nevertheless, there have been inconsistent reports regarding the effects of MPH on learning and memory. The aim of this study was to evaluate whether the treatment with MPH during the morning differs from that during the night on learning and memory (short and long term) in young and adult male Wistar rats. The animals received once daily intraperitoneal injection of either MPH (2 mg/kg) or saline (0.9%) for 28 days (either in the morning or at night). The animals underwent two behavioral tasks to evaluate learning and memory: inhibitory avoidance task and continuous multiple trials step-down inhibitory avoidance (CMIA). Young rats treated in the morning showed significant impaired long-term memory for inhibitory avoidance training and facilitated acquisition in the CMIA. Adult rats treated in the night showed impaired long-term retention in the CMIA. We observed similar performances in both tests for young rats treated at night or adult rats treated in the morning. Our results suggest that age and time of treatment can alter the MPH effects in learning and memory.

Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.

In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.

An epidemic of infections after video-assisted surgery (1,051 possible cases) caused by rapidly growing mycobacteria (RGM) and involving 63 hospitals in the state of Rio de Janeiro, Brazil, occurred between August 2006 and July 2007. One hundred ninety-seven cases were confirmed by positive acid-fast staining and/or culture techniques. Thirty-eight hospitals had cases confirmed by mycobacterial culture, with a total of 148 available isolates recovered from 146 patients. Most (n = 144; 97.2%) isolates presented a PRA-hsp65 restriction pattern suggestive of Mycobacterium bolletii or Mycobacterium massiliense. Seventy-four of these isolates were further identified by hsp65 or rpoB partial sequencing, confirming the species identification as M. massiliense. Epidemic isolates showed susceptibility to amikacin (MIC at which 90% of the tested isolates are inhibited [MIC(90)], 8 microg/ml) and clarithromycin (MIC(90), 0.25 microg/ml) but resistance to ciprofloxacin (MIC(90), >or=32 microg/ml), cefoxitin (MIC(90), 128 microg/ml), and doxycycline (MIC(90), >or=64 microg/ml). Representative epidemic M. massiliense isolates that were randomly selected, including at least one isolate from each hospital where confirmed cases were detected, belonged to a single clone, as indicated by the analysis of pulsed-field gel electrophoresis (PFGE) patterns. They also had the same PFGE pattern as that previously observed in two outbreaks that occurred in other Brazilian cities; we designated this clone BRA100. All five BRA100 M. massiliense isolates tested presented consistent tolerance to 2% glutaraldehyde. This is the largest epidemic of postsurgical infections caused by RGM reported in the literature to date in Brazil.

Dopamine may alter the phosphorylation state of DARPP-32 that plays a central role in the dopaminergic neurons biology. Studies have shown that DARPP-32/protein phosphatase 1 cascade is a major target for psychostimulants drugs. Methylphenidate is a psychostimulant that acts blocking the dopamine transporter has been used as an effective treatment for Attention Deficit Hyperactivity Disorder. We investigated if methylphenidate could alter DARPP-32 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. Our results showed that methylphenidate treatment is able to alter DARPP-32 expression in rat brain. Acute methylphenidate treatment has reduced hippocampal DARPP-32 protein levels in old rats, while chronic methylphenidate treatment has decreased them in old rat hippocampus and young rat cerebellum. It was found an increased cortical expression after chronic methylphenidate administration in old rats. Our results provide the first experimental demonstration that methylphenidate induces changes in total DARPP-32 expression that are posology- and age-related in some rat brain areas, although further studies are needed to shed more light on the mechanisms behind these findings.

Aims: The high prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) and the increased therapeutic use of methylphenidate (MPH) raise some concerns regarding its long-term side effects and safety profile. Considering that MPH effects on brain metabolism are poorly known and that creatine kinase (CK) plays an important role in cell energy homeostasis, we evaluated CK activity in the brain of young and adult rats following acute (one injection) or chronic (28 days) administration of MPH., Main Methods: MPH was acutely or chronically administered to young and adult rats. For acute administration, a single injection of MPH was given to rats on postnatal day (PD) 25 or PD 60, in the young and adult groups, respectively. For chronic administration, MPH injections were given to young rats starting at PD 25 once daily for 28 days (last injection at PD 53). In adult rats, the same regimen was performed starting at PD 60 (last injection at PD 88). CK activity was measured in brain homogenates., Key Findings: Our results showed that MPH acute administration increased the enzyme in prefrontal cortex, hippocampus, striatum and cerebral cortex, but not cerebellum of young and adult rats. Chronic administration of MPH also increased CK activity in these brain regions, as well as the cerebellum, in young and adult rats. The highest dose (10.0 mg/kg) presented more pronouncing effects., Significance: The present findings suggest that acute or chronic exposure to MPH increased CK activity, an enzyme involved in energy homeostasis, in the brain of young and adult rats.

Methylphenidate has been used as an effective treatment for attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) blocks dopamine and norepinephrine transporters causing an increase in extracellular levels. The use of psychomotor stimulants continues to rise due to both the treatment of ADHD and illicit abuse. Methylphenidate sensitization mechanism has still poor knowledge. Neuronal calcium sensor 1 was identified as a dopaminergic receptor interacting protein. When expressed in mammalian cells, neuronal calcium sensor 1 attenuates dopamine-induced D2 receptor internalization by a mechanism that involves a reduction in D2 receptor phosphorylation. Neuronal calcium sensor 1 appears to play a pivotal role in regulating D2 receptor function, it will be important to determine if there are alterations in neuronal calcium sensor 1 in neuropathologies associated with deregulation in dopaminergic signaling. Then, we investigated if methylphenidate could alter neuronal calcium sensor 1 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. These regions were chosen because some are located in brain circuits related with attention deficit hyperactivity disorder. Our results showed changes in neuronal calcium sensor 1 expression in hippocampus, prefrontal cortex and cerebellum mainly in adult rats. The demonstration that methylphenidate induces changes in neuronal calcium sensor 1 levels in rat brain may help to understand sensitization mechanisms as well as methylphenidate therapeutic effects to improve attention deficit hyperactivity disorder symptoms.

Methylphenidate (MPH) is psychostimulants used to treat Attention-Deficit/Hyperactivity Disorder and can lead to a long-lasting neurochemical and behavioral adaptations in experimental animals. In the present study, the cerebral antioxidant enzymatic system, superoxide dismutase (SOD) and catalase (CAT) was evaluated at in different age following MPH (1, 2 or 10 mg/kg MPH, i.p.) treatment in young rats. In the acute treatment the SOD activity decreased in the cerebral prefrontal cortex with opposite effect in the cerebral cortex; and the CAT activity decreased in hippocampus. In the chronic treatment the SOD activity increased in the hippocampus and cerebral cortex and decreased in the striatum. The observed changes on the enzyme activities in rat brain were dependent on the structure brain region and duration of treatment with MPH. Probably, the activity of enzymes was not be enough to prevent MPH-induced oxidative damage in specific regions from brain, such as observed for us in another recent study.

Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D(2) dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic (28 days) HAL, clozapine (CLO), olanzapine (OLZ) or aripiprazole (ARI) administration. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg), CLO (25 mg/kg), OLZ (2.5, 5 or 10 mg/kg) or ARI (2, 10 or 20 mg/kg); control animals received vehicle (Tween 1% solution). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the prefrontal cortex, hippocampus, striatum and cerebral cortex. The results showed that TBARS were increased in the striatum after HAL treatment. On the other hand, TBARS were diminished in the prefrontal cortex by OLZ and ARI. Our results also showed that all drugs tested in this work decreased TBARS levels in the cerebral cortex. In hippocampus, TBARS levels were not altered by any drug. Protein carbonyl content after HAL and CLO treatment was increased in the hippocampus. Moreover, OLZ and ARI did not alter protein carbonyl content when compared to control group. ARI chronic administration (20 mg/kg) also increased mitochondrial superoxide in the prefrontal cortex and striatum. ARI did not alter mitochondrial superoxide in the hippocampus and cerebral cortex. Moreover, HAL, OLZ and CLO did not cause significant alterations in mitochondrial superoxide in rat brain. Our findings demonstrate that OLZ and ARI do not induce oxidative damage in rat brain as observed after HAL and CLO treatment.

Background: Methylphenidate (MPH) is a widely prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). Recently, some studies have addressed the genotoxic potential of the MPH, but the results have been contradictory. Hence, the present study aimed to investigate the index of cerebral and peripheral DNA damage in young and adult rats after acute and chronic MPH exposure., Methods: We used (1) single cell gel electrophoresis (Comet assay) to measure early DNA damage in hippocampus, striatum and total blood, and (2) micronucleus test in total blood samples., Results: Our results showed that MPH increased the peripheral index of early DNA damage in young and adult rats, which was more pronounced with chronic treatment and in the striatum compared to the hippocampus. Neither acute nor chronic MPH treatment increased micronucleus frequency in young or in adult rats. Peripheral DNA damage was positively correlated with striatal DNA damage., Conclusion: These results suggest that MPH may induce central and peripheral early DNA damage, but this early damage may be repaired.

Malathion [S-(1,2-dicarbethoxy) ethyl-0,0-dimethyl-phosphorodithioate] is an organophosphorus compound that is widely used as pesticide especially in developing countries. This pesticide affects the central nervous system by inhibiting acetylcholinesterase, leading to an increase of acetylcholine in the synaptic cleft, and subsequent activation of cholinergic muscarinic and nicotinic receptors. In humans, intoxication with organophosphates causes a wide range of neurological symptoms, including memory deficits. The present study was aimed to investigate the effects of the acute (1 h prior the test) and subacute (once a day for 28 days) exposure to malathion at doses of 25, 50, 100 and 150 mg/kg in rats tested in the step-down inhibitory avoidance task, open-field habituation and elevated plus-maze tests. Interestingly, the acute and subacute treatment with malathion impaired aversive-memory in the step-down inhibitory avoidance task, but did not alter the animal performance in the elevated plus-maze and in the habituation to the open-field tests, and neither modified spontaneous locomotion. The activity of acetylcholinesterase enzyme was significantly reduced after subacute, but not acute, treatment with malathion (25, 100 and 150 mg/kg). Our results suggest that malathion impairs aversive-memory retention but not non-associative memory, without affecting anxiety-related behaviors. These findings support the view that the inhibition of acetylcholinesterase enzyme is not correlated with cognitive deficits observed in acute and subacute malathion-treated rats.