Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

Letters away from the looking glass: Developmental trajectory of mirrored and rotated letter processing within words.

Discrimination of reversible mirrored letters (e.g., d and b) poses a challenge when learning to read as it requires overcoming mirror invariance, an evolutionary-old perceptual tendency of processing mirror images as equivalent. The present study investigated when, in reading development, mirror-image discrimination becomes automatic during visual word recognition. The developmental trajectory of masked priming effects was investigated from 2nd to 6th grade and in adults, by manipulating letter type (nonreversible; reversible) and prime condition (control; identity; mirrored; rotated). Standardized identity priming increased along reading development. Beginning readers showed mirror invariance during reversible and nonreversible letter processing. A mirror cost (slower word recognition in mirrored-letter than identity prime condition) was found by 5th-grade but only for reversible letters. By 6th grade, orthographic processing was no longer captive of mirror invariance. A multiple linear regression showed that letter representations, but not phonological processes or age, were a reliable predictor of the rise of mirror-image discrimination in 2nd-4th-graders. The present results suggest a protracted development of automatic mirror-image discrimination during orthographic processing, contingent upon the quality of abstract letter representations. RESEARCH HIGHLIGHTS: We traced the developmental trajectory of mirrored-letter and rotated-letter priming effects (e.g., ibea and ipea as primes of IDEA) in visual word recognition. Beginning readers (2nd-4th-graders) showed mirror invariance and plane-rotation sensitivity in orthographic processing, thus still being susceptible to the perceptual biases in charge in object recognition. A mirror cost was found in 5th-graders but only for reversible letters; orthographic processing was no longer captive of mirror invariance by 6th-grade. The automation of mirror-image discrimination during orthographic processing depends on the quality of letter representations but not on phonological processes or age.

N2 -fixation can sustain wastewater treatment performance of photogranules under nitrogen-limiting conditions.

Wastewater characteristics can vary significantly, and in some municipal wastewaters the N:P ratio is as low as 5 resulting in nitrogen-limiting conditions. In this study, the microbial community, function, and morphology of photogranules under nitrogen-replete (N+) and limiting (N-) conditions was assessed in sequencing batch reactors. Photogranules under N- condition were nitrogen deprived 2/3 of a batch cycle duration. Surprisingly, this nitrogen limitation had no adverse effect on biomass productivity. Moreover, phosphorus and chemical oxygen demand removal were similar to their removal under N+ conditions. Although performance was similar, the difference in granule morphology was obvious. While N+ photogranules were dense and structurally confined, N- photogranules showed loose structures with occasional voids. Microbial community analysis revealed high abundance of cyanobacteria capable of N2 -fixation. These were higher at N- (38%) than N+ (29%) treatments, showing that photogranules could adjust and maintain treatment performance and high biomass productivity by means of N2 -fixation.

Oral isotretinoin in the treatment of juvenile acne and psychiatric adverse effects - a systematic review.

PURPOSE: Acne vulgaris is a very prevalent dermatological condition, especially among adolescents and young adults up to 25 years old, classifying it as juvenile acne. One of the most effective treatments for severe acne is isotretinoin, a derivative of retinoic acid. Despite its high efficacy, this drug has been linked to several side effects including psychiatric adverse alterations, such as anxiety, depression and even suicide. With this systematic review we aim to determine if it is possible to establish a causal relation between oral isotretinoin in the treatment of juvenile acne and the appearance of psychiatric adverse effects. MATERIALS AND METHODS: We searched two distinct databases, PubMed and Web of Science, and considered the work published between January 2000 and November 2021. RESULTS: Out of the 599 identified articles, we included 19 studies in this systematic review. Globally, the results we found do not support an association between the use of isotretinoin for acne treatment and mental side effects and the safety of this drug appears to be assured. However, the individual characteristics of each adolescent and their environment should be considered; the personal and family history of mental disorders are pointed out as red flags we should look out for when treating these patients. CONCLUSION: Despite this being a highly debated topic, especially among the dermatology community, more studies with larger populations and randomised controlled trials are necessary to increase the strength of the evidence presented.

Localisation of phosphoinositides in the grass endophyte Epichloë festucae and genetic and functional analysis of key components of their biosynthetic pathway in E. festucae symbiosis and Fusarium oxysporum pathogenesis.

Phosphoinositides (PI) are essential components of eukaryotic membranes and function in a large number of signaling processes. While lipid second messengers are well studied in mammals and yeast, their role in filamentous fungi is poorly understood. We used fluorescent PI-binding molecular probes to localize the phosphorylated phosphatidylinositol species PI[3]P, PI[3,5]P2, PI[4]P and PI[4,5]P2 in hyphae of the endophyte Epichloë festucae in axenic culture and during interaction with its grass host Lolium perenne. We also analysed the roles of the phosphatidylinositol-4-phosphate 5-kinase MssD and the predicted phosphatidylinositol-3,4,5-triphosphate 3-phosphatase TepA, a homolog of the mammalian tumour suppressor protein PTEN. Deletion of tepA in E. festucae and in the root-infecting tomato pathogen Fusarium oxysporum had no impact on growth in culture or the host interaction phenotype. However, this mutation did enable the detection of PI[3,4,5]P3 in septa and mycelium of E. festucae and showed that TepA is required for chemotropism in F. oxysporum. The identification of PI[3,4,5]P3 in ΔtepA strains suggests that filamentous fungi are able to generate PI[3,4,5]P3 and that fungal PTEN homologs are functional lipid phosphatases. The F. oxysporum chemotropism defect suggests a conserved role of PTEN homologs in chemotaxis across protists, fungi and mammals.

Dual-specificity protein phosphatase Msg5 controls cell wall integrity and virulence in Fusarium oxysporum.

Mitogen-activated protein kinase (MAPK) cascades are key signaling modules controlling development and virulence in fungal pathogens. Down-regulation of MAPK activity by protein phosphatases provides a critical layer of control during desensitization or adaptation to stimuli. In Saccharomyces cerevisiae, the dual-specificity phosphatase Msg5 dephosphorylates target threonine and tyrosine residues in the two MAPKs Mpk1 and Fus3, which regulate the cell wall integrity (CWI) and pheromone responses, respectively. Here we studied the role of the Msg5 ortholog in Fusarium oxysporum, a soilborne phytopathogen that infects host plants through the roots to cause vascular wilt and plant death. F. oxysporum mutants lacking Msg5 showed constitutively high levels of Mpk1 phosphorylation and increased sensitivity to the cell wall targeting compound Calcofluor White. Moreover, these mutants displayed reduced colony growth and conidiation. Importantly, msg5Δ mutants were impaired in hyphal chemotropism towards host plant roots and in virulence on tomato plants. These results reveal a key role of Msg5 in regulation of the CWI MAPK cascade of F. oxysporum as well as in infection-related signaling of this important fungal pathogen.

Nutrient and pathogen removal from anaerobically treated black water by microalgae.

The demand for systems that efficiently and sustainably recover value-added compounds and materials from waste streams is a major challenge. The use of wastewater as a source for recovery of carbon and nutrients is an attractive and sustainable alternative. In this study, anaerobically treated black water was treated in photobioreactors (PBRs) inoculated with Chlorella sorokiniana, and the process was investigated in terms of phosphorus and nitrogen removal, biomass growth, and the removal of pathogens. The consumption of bicarbonate (alkalinity) and acetate (volatile fatty acids) as carbon sources by microalgae was investigated. The average nutrient removal achieved was 66% for N and 74% for P. A high consumption of alkalinity (83%) and volatile organic acids (76%) was observed, which suggests that these compounds were used as a source of carbon. The biomass production was 73 mg L-1 day-1, with a mean biomass of 0.7 g L-1 at the end of the batch treatment. At the end of the experiments, a log removal/inactivation of 0.51 log for total coliforms and 2.73 log for Escherichia coli (E. coli) was observed. The configuration used, a flat-panel PBR operated in batch mode without CO2 supplementation, is a cost-effective and environmentally sustainable method for recovering of nutrients and production of algal biomass.

NADPH oxidase regulates chemotropic growth of the fungal pathogen Fusarium oxysporum towards the host plant.

Soil-inhabiting fungal pathogens use chemical signals to locate and colonise the host plant. In the vascular wilt fungus Fusarium oxysporum, hyphal chemotropism towards tomato roots is triggered by secreted plant peroxidases (Prx), which catalyse the reductive cleavage of reactive oxygen species (ROS). Here we show that this chemotropic response requires the regulated synthesis of ROS by the conserved fungal NADPH oxidase B (NoxB) complex, and their transformation into hydrogen peroxide (H2 O2 ) by superoxide dismutase (SOD). Deletion of NoxB or the regulatory subunit NoxR, or pharmacological inhibition of SOD, specifically abolished chemotropism of F. oxysporum towards Prx gradients. Addition of isotropic concentrations of H2 O2 rescued chemotropic growth in the noxBΔ and noxRΔ mutants, but not in a mutant lacking the G protein-coupled receptor Ste2. Prx-triggered rapid Nox- and Ste2-dependent phosphorylation of the cell wall integrity mitogen-activated protein kinase (CWI MAPK) Mpk1, an essential component of the chemotropic response. These results suggest that Ste2 and the CWI MAPK cascade function downstream of NoxB in Prx chemosensing. Our findings reveal a new role for Nox enzymes in directed hyphal growth of a filamentous pathogen towards its host and might be of broad interest for chemotropic interactions between plants and root-colonising fungi.

Learning to read facilitates the retrieval of phonological representations in rapid automatized naming: Evidence from unschooled illiterate, ex-illiterate, and schooled literate adults.

Rapid automatized naming (RAN) of visual items is a powerful predictor of reading skills. However, the direction and locus of the association between RAN and reading is still largely unclear. Here, we investigated whether literacy acquisition directly bolsters RAN efficiency for objects, adopting a strong methodological design, by testing three groups of adults matched in age and socioeconomic variables, who differed only in literacy/schooling: unschooled illiterate and ex-illiterate, and schooled literate adults. To investigate in a fine-grained manner whether and how literacy facilitates lexical retrieval, we orthogonally manipulated the word-form frequency (high vs. low) and phonological neighborhood density (dense vs. spare) of the objects' names. We observed that literacy experience enhances the automaticity with which visual stimuli (e.g., objects) can be retrieved and named: relative to readers (ex-illiterate and literate), illiterate adults performed worse on RAN. Crucially, the group difference was exacerbated and significant only for those items that were of low frequency and from sparse neighborhoods. These results thus suggest that, regardless of schooling and age at which literacy was acquired, learning to read facilitates the access to and retrieval of phonological representations, especially of difficult lexical items.

Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline.

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg-1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor ß (ER-ß). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.

Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015.

We characterised Lancefield group B streptococcal (GBS) isolates causing invasive disease among non-pregnant adults in Portugal between 2009 and 2015. All isolates (n = 555) were serotyped, assigned to clonal complexes (CCs) by multilocus sequence typing and characterised by surface protein and pilus island gene profiling. Antimicrobial susceptibility was tested by disk diffusion and resistance genotypes identified by PCR. Overall, serotype Ia was most frequent in the population (31%), followed by serotypes Ib (24%) and V (18%). Serotype Ib increased significantly throughout the study period (p < 0.001) to become the most frequent serotype after 2013. More than 40% of isolates clustered in the CC1/alp3/PI-1+PI-2a genetic lineage, including most isolates of serotypes Ib (n = 110) and V (n = 65). Erythromycin and clindamycin resistance rates were 35% and 34%, respectively, both increasing from 2009 to 2015 (p < 0.010) and associated with CC1 and serotype Ib (p < 0.001). The Ib/CC1 lineage probably resulted from acquisition of the type Ib capsular operon in a single recombination event by a representative of the V/CC1 macrolide-resistant lineage. Expansion of the new serotype Ib/CC1 lineage resulted in increased macrolide resistance in GBS, causing invasive disease among adults in Portugal. The presence of this clone elsewhere may predict more widespread increase in resistance.

Mirrors are hard to break: A critical review and behavioral evidence on mirror-image processing in developmental dyslexia.

The relation between reversal errors (e.g., d for b, Я for R) and developmental dyslexia has been elusive. In this study, we investigated the roles of reading level, visual category, and orientation processing in this relation. Children with developmental dyslexia, chronological-age-matched controls, and reading-level-matched controls performed two "same-different" matching tasks on reversible (e.g., b) and nonreversible (e.g., e) letters and on geometric shapes (e.g., ). In the orientation-based task, orientation processing was explicitly required; in the shape-based task, orientation processing would be automatic inasmuch as it was task irrelevant and would hinder successful performance. Two orientation contrasts were examined: mirror images (e.g., d-b) and plane rotations (e.g., d-p). For the latter, dyslexics behaved as controls; all were worse on shape-based judgments of plane rotation than on identical (e.g., d-d) pairs and were better able to attend to orientation than to shape. In contrast, for mirror images and across visual categories, dyslexics showed an advantage over typical readers on shape-based judgments. Both control groups had worse performance on shape-based judgments of mirror images than of identical pairs and exhibited similar magnitudes of mirror interference. Dyslexic children were the only group whose shape-based judgments were immune to mirror-image differences because they failed to automatize mirror discrimination during visual object processing. This deficit is not a consequence of reading level, is found across visual categories, and is specific to mirror images.

The 1-min Screening Test for Reading Problems in College Students: Psychometric Properties of the 1-min TIL.

Reading is a central cognitive domain, but little research has been devoted to standardized tests for adults. We, thus, examined the psychometric properties of the 1-min version of Teste de Idade de Leitura (Reading Age Test; 1-min TIL), the Portuguese version of Lobrot L3 test, in three experiments with college students: typical readers in Experiment 1A and B, dyslexic readers and chronological age controls in Experiment 2. In Experiment 1A, test-retest reliability and convergent validity were evaluated in 185 students. Reliability was >.70, and phonological decoding underpinned 1-min TIL. In Experiment 1B, internal consistency was assessed by presenting two 45-s versions of the test to 19 students, and performance in these versions was significantly associated (r = .78). In Experiment 2, construct validity, criterion validity and clinical utility of 1-min TIL were investigated. A multiple regression analysis corroborated construct validity; both phonological decoding and listening comprehension were reliable predictors of 1-min TIL scores. Logistic regression and receiver operating characteristics analyses revealed the high accuracy of this test in distinguishing dyslexic from typical readers. Therefore, the 1-min TIL, which assesses reading comprehension and potential reading difficulties in college students, has the necessary psychometric properties to become a useful screening instrument in neuropsychological assessment and research. Copyright © 2017 John Wiley & Sons, Ltd.

Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.

Into the Looking Glass: Literacy Acquisition and Mirror Invariance in Preschool and First-Grade Children.

At what point in reading development does literacy impact object recognition and orientation processing? Is it specific to mirror images? To answer these questions, forty-six 5- to 7-year-old preschoolers and first graders performed two same-different tasks differing in the matching criterion-orientation-based versus shape-based (orientation independent)-on geometric shapes and letters. On orientation-based judgments, first graders outperformed preschoolers who had the strongest difficulty with mirrored pairs. On shape-based judgments, first graders were slower for mirrored than identical pairs, and even slower than preschoolers. This mirror cost emerged with letter knowledge. Only first graders presented worse shape-based judgments for mirrored and rotated pairs of reversible (e.g., b-d; b-q) than nonreversible (e.g., e-ә) letters, indicating readers' difficulty in ignoring orientation contrasts relevant to letters.

Effect of Voriconazole on Candida tropicalis Biofilms: Relation with ERG Genes Expression.

Candida tropicalis has emerged as the third most prevalent fungal pathogens and its ability to form biofilms has been considered one of the most important virulence factors, since biofilms represent high tolerance to antifungal agents. However, the mechanisms of C. tropicalis biofilm resistance to antifungals remain poorly understood. Thus, the main aim of this work was to infer about the effect of voriconazole on the formation and control of C. tropicalis biofilms and disclose its relationship with ERG genes' expression. Planktonic cells tolerance of several C. tropicalis clinical isolates to voriconazole was determined through of antifungal susceptibility test, and the effect of this azole against C. tropicalis biofilm formation and pre-formed biofilms was evaluated by cultivable cells determination and total biomass quantification. ERG genes expression was analyzed by quantitative real-time polymerase chain reaction. This work showed that C. tropicalis resistance to voriconazole is strain dependent and that voriconazole was able to partially control biofilm formation, but was unable to eradicate C. tropicalis pre-formed biofilms. Moreover, C. tropicalis biofilms resistance to voriconazole seems to be associated with alterations of sterol content in the cell membrane, resulting in ERG genes overexpression. Voriconazole is unable to control C. tropicalis biofilms, and the overexpression of ERG genes is a possible mechanism of biofilm resistance.

Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study.

BACKGROUND: We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge. RESULTS: Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2-4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52-.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06-1.56; P = .0109) for being discharged alive. CONCLUSIONS: ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.

Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study.

OBJECTIVES: We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse. METHODS: A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study. Ninety-day mortality was compared between the two groups matched by propensity scores. RESULTS: Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31-1.08, P = 0.0846) for 90 day mortality. CONCLUSIONS: There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.

T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats.

UNLABELLED: Myocardial infarction leads to a reduction in nitric oxide (NO) bioavailability and an increase in reactive oxygen species (ROS) levels. This scenario has been shown to be detrimental to the heart. Recent studies have shown that thyroid hormone (TH) administration presents positive effects after ischaemic injury. Based on this, the aim of this study was to evaluate the effect of TH on NO bioavailability as well as on endothelial nitric oxide synthase (eNOS) expression after myocardial infarction. Male Wistar rats were divided into three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). During 26 days, the AMIT group received T3 and T4 (2 and 8 µg/100 g/day, respectively) by gavage, while SHAM and AMI rats received saline. After this, the rats underwent echocardiographic analysis were sacrificed, and the left ventricle was collected for biochemical and molecular analysis. STATISTICAL ANALYSIS: one-way ANOVA with Student-Newman-Keuls post test. AMI rats presented a 38% increase in ROS levels. TH administration prevented these alterations in AMIT rats. The AMIT group presented an increase in eNOS expression, in NOS activity and in nitrite levels. TH administration also increased PGC-1α expression in the AMIT group. In conclusion, TH effects seem to involve a modulation of eNOS expression and an improvement in NO bioavailability in the infarcted heart.

Aerobic Exercise Promotes a Decrease in Right Ventricle Apoptotic Proteins in Experimental Cor Pulmonale.

Pulmonary arterial hypertension is characterized by progressive increases in resistance and pressure in the pulmonary artery and Cor pulmonale. The effect of exercise on hydrogen peroxide-dependent signaling in the right ventricle (RV) of Cor pulmonale rats was analyzed. Rats were divided into sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM) groups. Rats underwent exercise training (60% of VO2 max) for 5 weeks, with 3 weeks after monocrotaline injection (60 mg/kg intraperitoneally). Pulmonary resistance was enhanced in SM (2.0-fold) compared with SC. Pulmonary artery pressure was increased in SM (2.7-fold) and TM (2.6-fold) compared with their respective controls (SC and TC). RV hypertrophy indexes increased in SM compared with SC. Hydrogen peroxide was higher in SM (1.7-fold) than SC and was reduced by 47% in TM compared with SM. p-Akt was increased in TM (2.98-fold) compared with SM. The Bax/Bcl-2 ratio and caspase 3 were also increased (2.9-fold and 3.9-fold, respectively) in SM compared with SC. Caspase 3 was decreased in TM compared with SM (P < 0.05). Therefore, exercise training promoted a beneficial response by decreasing hydrogen peroxide concentrations, and consequently, apoptotic signaling in RV.