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Introduction Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE. Methods Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data. Results One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA. Conclusions The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding.

Male mice lacking the androgen receptor (AR) in islet β cells exhibit blunted glucose-stimulated insulin secretion (GSIS) , leading to hypoinsulinemia and hyperglycemia. We showed that dihydrotestosterone (DHT) activation of an extranuclear AR in β cells potentiates GSIS by amplifying the insulinotropic action of GLP-1 in mouse and human islets. To gain information on DHT-stimulated signaling networks promoting GSIS, we combined functional proteomics with highly selective pharmacological inhibitors in male human islets, and islets from genetic mouse models. We found that DHT-stimulated GSIS in human islets involved a signaling cascade including focal adhesion kinases, the nonreceptor tyrosine kinase SRC, phosphoinositide 3-kinase, and the activation of mTOR complex 2. To define the early network of AR interacting proteins, we performed DHT-stimulated AR immunoprecipitation in INS1 832/3 cells followed by mass spectrometry-based proteomics. We will discuss the AR interactome including: 1) adenylate cyclase-modulating G proteins Gαs and Gαi, cAMP-dependent PKA, and the cAMP-dependent protein LASP1 regulating actin-based cytoskeletal activities; 2) Actin cytoskeleton remodeling proteins promoting actin depolymerization, and 3) Vesicular maturation including the lysosomal vacuolar-type ATPase acidifying insulin secretory granules and the prohormone convertase 2 involved in proinsulin processing. Notably, GLP-1 addition to DHT decreased AR interaction with all these proteins and promoted AR interaction with microtubule motor proteins promoting vesicular transport, proteins involved in exocytic vesicle docking to the plasma membrane, as well as small GTPase activating proteins and guanine nucleotide exchange factors involved in actin remodeling, as well as vesicle trafficking. Together these experiments provide novel insights into the architecture of AR action in enhancing GSIS. Disclosure P.Mota de sa: None. M.Qadir: None. M.Blandino-rosano: None. J.Fan: None. W.Xu: None. E.Bernal-mizrachi: None. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical. Funding National Institutes of Health (DK107444 and DK074970) U.S. Department of Veterans Affairs Merit Award (BX003725)

Male mice with elimination of the androgen receptor (AR) in islet β cells (βARKO) exhibit blunted glucose-stimulated insulin secretion (GSIS) , leading to hypoinsulinemia and hyperglycemia. We showed that dihydrotestosterone (DHT) activation of an extranuclear AR in β cells potentiates GSIS by amplifying the insulinotropic action of islet-derived and exogenous GLP-1 via GLP-1R in mouse and human islets. Using electron microscopy, we observe that DHT increases the size of granules and the frequency of multivesicular granules, suggesting that DHT promotes multivesicular exocytosis. Using live β cell models expressing organelle-specific cAMP sensors and novel allosteric inhibitors in human islets, we show that DHT enhances the ability of GLP-1 to produce cAMP at the plasma membrane and endosomes and enhances islet GSIS via the bicarbonate (HCO3 -) sensor, soluble adenylate cyclase (sAC) . The end-products of glucose metabolism in the TCA cycle are CO2 and H2O, which is followed by rapid conversion of CO2 to HCO3 - and H+ by carbonic anhydrase (CA) . Therefore, CO2 production is translated to HCO3 - and specifically sensed by sAC. Bioenergetics analysis of DHT-stimulated respiration in mouse islets using a Seahorse Analyser revealed that DHT decreases glycolytic acidification and increases mitochondrial acidification (H+ efflux rate) , suggesting that DHT increases mitochondrial production of CO2 followed by conversion to HCO3 - and H+, allowing HCO3 - to stimulate sAC. We discuss experiments of single-cell transcriptomics, proteomics and metabolomics dissecting the impact of DHT on human islets glycolysis and mitochondrial CO2 production. Consistent with DHT increasing production of CO2 followed by conversion to HCO3 - by CA and activation of sAC, in cultured human male islets, the CA inhibitor acetazolamide blunted DHT-enhancement of GSIS. Together these experiments provide novel insights into the role of DHT action via an extranuclear AR in enhancing GSIS. Disclosure M.Qadir: None. D.Hodson: Other Relationship; Celtarys Research. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical. W.Xu: None. D.Nasteska: None. M.Bhondeley: None. P.Mota de sa: None. C.R.Evans: None. J.Buck: None. L.Levin: None. C.Burant: None. Funding National Institutes of Health (DK107444 and DK074970) U.S. Department of Veterans Affairs Merit Award (BX003725)

Objectives This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p Conclusions In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)

Testosterone (T) affects β-cell function in men and women. T is a prohormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R) or to the active estrogen 17β-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type 1 isoform (SRD5A1) and aromatase are expressed in male and female β-cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from two out of four male donors. In these donors, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS. In conclusion, male and female human islets convert T into DHT and E2 via the intracrine activities of SRD5A1 and aromatase. This process is necessary for T enhancement of GSIS.

We showed that the gonadal hormones estradiol and testosterone influence islet β-cell function and survival in a sex-specific manner via estrogen and androgen receptors expressed in islet β-cells. The progesterone receptor (PR) is a ligand-activated transcription factor and is believed to be involved in the β-cell adaptation to pregnancy. Leveraging public single-cell RNA-seq datasets we observe PR mRNA expression in α- β- and γ-cells in male and female human pancreatic endocrine cells. Using immunohistochemistry, we observe that, unlike in the uterus where PR is nuclear, PR is localized in the cytoplasm of β-cells in male and female human and mouse islets. We investigated the role of progesterone and PR in β-cell physiology in male and female mice with conditional deletion of PR in β-cells (βPRKO) by crossing PR-Lox/lox and MIP-Cre transgenic mice. Male βPRKO mice exhibited no alteration in glucose homeostasis on normal chow (NC) or following western-diet (WD)-induced insulin resistance and obesity compared to littermate PR-Lox/lox controls. Similarly, NC-fed female βPRKO mice exhibited no abnormality of glucose or insulin homeostasis compared to littermate PR-Lox/lox controls. However, during pregnancy or WD feeding, female βPRKO mice developed enhanced IP-glucose-stimulated insulin secretion, associated with improved IP glucose tolerance compared to littermate PR-Lox/lox controls. These results reveal that PR is a cytosolic receptor in β-cells, and suggest that in conditions of high insulin demand, such as pregnancy and diet-induced insulin resistance, elimination of PR action in β-cells of females improves the ability of β-cells to produce insulin and lowers blood glucose. PR may be involved in the pathogenesis of gestational diabetes. Disclosure P. Mota de sa: None. M. Qadir: None. F. Mauvais-jarvis: None. Funding National Institutes of Health (DK074970, DK107444); U.S. Department of Veterans Affairs (BX003725)

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway has cell-specific functions. Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK-STAT signaling. STAT5 plays a significant role in adipocyte development and function, and bromodomain and extraterminal (BET) proteins may be involved in STAT5 transcriptional activity. We treated 3T3-L1 adipocytes with the BET inhibitor JQ1 and observed that growth hormone (GH)-induced expression of 2 STAT5 target genes from the SOCS family, Socs3 and Cish, were inversely regulated (increased and decreased, respectively) by BET inhibition. Chromatin immunoprecipitation analyses revealed that changes in STAT5 binding did not correlate with gene expression changes. GH promoted the recruitment of the BET protein BRD2 to the Cish, but not Socs3, promoter. JQ1 treatment ablated this effect as well as the GH-induced binding of ribonucleic acid polymerase II (RNA Pol II) to the Cish transcription start site. BRD2 knockdown also suppressed GH induction of Cish, further supporting the role of BRD2 in Cish transcriptional activation. In contrast, JQ1 increased the binding of activated Pol II to the Socs3 coding region, suggesting enhanced messenger RNA (mRNA) elongation. Our finding that JQ1 transiently reduced the interaction between the positive transcription elongation factor (P-TEFb) and its inhibitor hexamethylene bis-acetamide inducible 1 (HEXIM1) is consistent with a previously described off-target effect of JQ1, whereby P-TEFb becomes more available to be recruited by genes that do not depend on BET proteins for activating transcription. These results demonstrate substantially different transcriptional regulation of Socs3 and Cish and suggest distinct roles in adipocytes for these 2 closely related proteins.

A randomized controlled trial was conducted to assess the effects of exercise plus pharmacotherapy on monoamine neurotransmitters (dopamine, noradrenaline, adrenaline, serotonin) and cortisol levels. A total of 26 women with clinical depression were randomly assigned to one of the two groups: aerobic exercise plus pharmacotherapy or only pharmacotherapy. The exercise program consisted of aerobic exercise, 45-50 min/session, three times/week, for 16 weeks. The biological parameters were measured before and after the exercise program. Adding exercise to pharmacotherapy had no additional effects on monoamines and cortisol plasma levels. These data are preliminary outcomes from a small sample and should be replicated.

The main purpose of this pilot study was to investigate the possible influence of genetic polymorphisms of the hOGG1 (Ser326Cys) gene in DNA damage and repair activity by 8-oxoguanine DNA glycosylase 1 (OGG1 enzyme) in response to 16 weeks of combined physical exercise training. Thirty-two healthy Caucasian men (40-74 years old) were enrolled in this study. All the subjects were submitted to a training of 16 weeks of combined physical exercise. The subjects with Ser/Ser genotype were considered as wild-type group (WTG), and Ser/Cys and Cys/Cys genotype were analysed together as mutant group (MG). We used comet assay in conjunction with formamidopyrimidine DNA glycoslyase (FPG) to analyse both strand breaks and FPG-sensitive sites. DNA repair activity were also analysed with the comet assay technique. Our results showed no differences between DNA damage (both strand breaks and FPG-sensitive sites) and repair activity (OGG1) between genotype groups (in the pre-training condition). Regarding the possible influence of genotype in the response to 16 weeks of physical exercise training, the results revealed a decrease in DNA strand breaks in both groups, a decrease in FPG-sensitive sites and an increase in total antioxidant capacity in the WTG, but no changes were found in MG. No significant changes in DNA repair activity was observed in both genotype groups with physical exercise training. This preliminary study suggests the possibility of different responses in DNA damage to the physical exercise training, considering the hOGG1 Ser326Cys polymorphism.

Diabetes mellitus (DM) represents one of the greatest concerns to global health and it is associated with diverse clinical complications, including reproductive dysfunction. Given the multifactorial nature of DM, the mechanisms that underlie reproductive dysfunction remain unclear. Considering that hyperglycemia has been described as a major effector of the disease pathophysiology, we used anin vitroapproach to address the isolated effect of high glucose conditions on human sperm function, thus avoiding otherin vivoconfounding players. We performed a complete and integrated analysis by measuring a variety of important indicators of spermatozoa functionality (such as motility, viability, capacitation status, acrosomal integrity, mitochondrial superoxide production and membrane potential) in human sperm samples after incubation withd- andl-glucose (5, 25, or 50 mM) for 24 and 48 h. No direct effects promoted by 25 or 50 mMd-glucose were found for any of the parameters assessed (P>0.05), except for the acrosome reaction, which was potentiated after 48 h of exposure to 50 mMd-glucose (Pl-glucose drastically increased superoxide production (PPPPPPper sedo not influence human sperm functionin vitro, which stresses the importance of other factors involved in DM pathology. Nevertheless, the absence of metabolizable glucose contributes to a severe impairment of sperm function and thus compromises male fertility.Free Portuguese abstract: A Portuguese translation of this abstract is freely available athttp://www.reproduction-online.org/content/150/1/77/suppl/DC1.

Percutaneous coronary intervention is currently the most common form of revascularization for symptomatic coronary artery disease. In elderly, diabetic and renal patients, there is an increased prevalence of calcified coronary disease. Rotational atherectomy (RA) can be useful in the treatment of these lesions.Plaque removal was initially proposed as an alternative to balloon angioplasty, hence RA required high-velocity protocols with large-sized burrs (over 2.0 mm). With a high incidence of acute complications and disappointing restenosis rates, the use of RA dwindled. However, the advent of drug-eluting stents, which significantly decreased the rate of restenosis, led to the repositioning of RA as an adjunctive technique in the preparation of densely calcified lesions, improving stent delivery and expansion.In recent years, a better understanding of the mechanism of action of RA has changed it from a plaque debulking to a compliance modifying technique. As a result, RA has become less aggressive, using smaller size burrs and lower rotational speeds. This conservative approach has improved immediate results, with increased safety and better long-term outcomes.In this review paper, the technique of RA is explained in the light of current knowledge. Resumo: A angioplastia coronária tornou-se a forma mais habitual de revascularização miocárdica na doença coronária sintomática. Na população mais idosa, nos diabéticos e nos doentes com insuficiência renal crónica, a prevalência de lesões calcificadas tende a aumentar. A aterectomia rotacional (AR) é uma técnica de grande utilidade no tratamento destas situações.Tendo-se considerado inicialmente que a erosão da placa podia constituir uma alternativa à angioplastia de balão, a técnica de aterectomia rotacional utilizava protocolos de alta velocidade com olivas que ultrapassavam os 2,0 mm de diâmetro. A ocorrência de complicações agudas e resultados insuficientes a longo prazo limitaram a sua difusão. O aparecimento dos stents com fármaco com redução significativa das taxas de reestenose, levou ao reposicionamento da aterectomia rotacional como técnica adjuvante na preparação das lesões permitindo uma melhor entrega e expansão dos stents, no contexto de doença aterosclerótica calcificada.Nos últimos anos, tem-se assistido a uma melhor compreensão do mecanismo de acção da aterectomia rotacional que passou de debulking para modificação de compliance da placa. Consequentemente, a técnica tem-se tornado menos agressiva: utilizam-se olivas de menor calibre, com menor velocidade de rotação, alcançando-se elevadas taxas de sucesso e de segurança no procedimento.Neste artigo procuramos reunir o conhecimento atual sobre como executar a técnica de aterectomia rotacional. Keywords: Rotational atherectomy, Rotational atherectomy technique, Percutaneous coronary intervention, Coronary calcification, Palavras-chave: Aterectomia rotacional, Técnica de aterectomia rotacional, Intervenção coronária percutânea, Calcificação coronária

AIMS: Renal dysfunction is a powerful predictor of adverse outcomes in patients hospitalized for acute coronary syndrome. Three new glomerular filtration rate (GFR) estimating equations recently emerged, based on serum creatinine (CKD-EPIcreat), serum cystatin C (CKD-EPIcyst) or a combination of both (CKD-EPIcreat/cyst), and they are currently recommended to confirm the presence of renal dysfunction. Our aim was to analyse the predictive value of these new estimated GFR (eGFR) equations regarding mid-term mortality in patients with acute coronary syndrome, and compare them with the traditional Modification of Diet in Renal Disease (MDRD-4) formula. METHODS AND RESULTS: 801 patients admitted for acute coronary syndrome (age 67.3±13.3 years, 68.5% male) and followed for 23.6±9.8 months were included. For each equation, patient risk stratification was performed based on eGFR values: high-risk group (eGFR

Age-related DNA damage has been regarded as one of the possible explanations of aging, and these age-related changes have been associated with lifestyle variables. Considering this, the purpose of this study was to investigate how age and lifestyle may affect DNA damage, DNA repair capacity and endogenous biomarkers of oxidative stress. Sixty-one healthy men (40 to 89 yrs) were enrolled in this study. The results showed that DNA strand breaks (DNA SBs) and DNA repair capacity were greater in the older group (>=65 yrs) compared to the younger group (

Introduction and Objectives: Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. Methods: Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. Results: Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p

Introduction: Assessment of ischemic and bleeding risk is critical for the management of elderly patients with acute coronary syndromes, but it has been little studied. Objective: This study aims to assess the applicability of the GRACE and CRUSADE scores in patients aged ≥80 years with non-ST-elevation acute coronary syndrome (NSTE-ACS), and to identify the main predictors of in-hospital mortality and major bleeding in this population. Methods: We analyzed 544 patients aged ≥80 years with NSTE-ACS included in the Portuguese Registry on Acute Coronary Syndromes and identified the predictors of in-hospital mortality and major bleeding during hospitalization. Prediction models were created for these endpoints, then compared with the GRACE and CRUSADE scores, and their applicability to the study population was assessed. Results: Use of coronary angiography was associated with reduced risk of in-hospital mortality, without increasing risk of major bleeding (OR 0.2, 95% CI 0.006–0.49, p=0.001). Major bleeding was an independent predictor of in-hospital mortality (OR 10.9, 95% CI 2.36–50.74, p=0.002), and was associated with comorbidities and pharmacological therapy during hospitalization. The GRACE score showed good diagnostic accuracy for in-hospital mortality (AUC 0.75, 95% CI 0.63–0.87, p

Introduction and Objective: Worsening renal function has an unquestionably negative impact on prognosis in patients with acute heart failure (HF). In Portugal there is little information about the importance of this entity in HF patients admitted to hospital. The objective of this work was to assess the prevalence of cardiorenal syndrome and to identify its key predictors and consequences in patients admitted for acute HF. Methods: This was a retrospective study of 155 patients admitted for acute HF. Cardiorenal syndrome was defined as an increase in serum creatinine of ≥26.5 μmol/l. Clinical, laboratory and echocardiographic parameters were analyzed and compared. Mortality was assessed at 30 and 90 days. Results: Cardiorenal syndrome occurred in 46 patients (29.7%), 5.4±4.4 days after admission; 66.7% (n=24) did not recover baseline creatinine levels. The factors associated with cardiorenal syndrome were older age, chronic renal failure, moderate to severe mitral regurgitation, higher admission blood urea nitrogen, creatinine and troponin I, and lower glomerular filtration rate. Patients who developed cardiorenal syndrome had longer hospital stay, were treated with higher daily doses of intravenous furosemide, and more often required inotropic support and renal replacement therapy. They had higher in‐hospital and 30‐day mortality, and multivariate analysis identified cardiorenal syndrome as an independent predictor of in‐hospital mortality. Conclusions: Renal dysfunction is common in acute HF patients, with a negative impact on prognosis, which highlights the importance of preventing kidney damage through the use of new therapeutic strategies and identification of novel biomarkers. Resumo: Introdução e objetivos: O valor prognóstico da deterioração da função renal é indiscutível nos doentes com insuficiência cardíaca aguda. No contexto nacional sabe‐se pouco acerca do peso relativo da síndrome cardiorrenal no internamento destes doentes. Este trabalho pretende avaliar a prevalência, fatores preditores e consequências desta entidade em doentes internados por insuficiência cardíaca aguda. Métodos: Análise retrospetiva de 155 doentes internados por insuficiência cardíaca aguda. Síndrome cardiorrenal definida como um aumento ≥ a 26,5 umol/L na creatinina sérica relativamente ao valor da admissão. Avaliados e comparados dados clínicos, analíticos e ecocardiográficos. Feito seguimento, referente a mortalidade, aos 30 e 90 dias. Resultados: A síndrome cardiorrenal ocorreu em 46 (29,7%) doentes, 5,4±4,4 dias após a admissão; 66,7% (n=24) não recuperaram a função renal basal. Associaram‐se ao desenvolvimento desta entidade: idades mais avançadas; antecedentes de insuficiência renal crónica; insuficiência mitral moderada/grave; níveis na admissão mais elevados de ureia, creatinina e troponina I; e mais baixos de taxa de filtração glomerular. Os doentes com síndrome cardiorrenal tiveram internamentos mais longos; necessitaram de doses diárias máximas de furosemida mais elevadas; mais frequentemente necessitaram de inotrópicos e de terapêutica de substituição renal. A sua mortalidade no internamento e aos 30 dias foi superior, sendo a síndrome cardiorrenal um fator preditor independente de mortalidade intra‐hospitalar. Conclusões: A disfunção renal é comum em doentes com insuficiência cardíaca aguda, com impacto claramente negativo no prognóstico, devendo a prevenção da lesão renal ser um objetivo primário passando por novas estratégias terapêuticas e identificação de novos biomarcadores. Keywords: Acute heart failure, Cardiorenal syndrome, Prognosis, Palavras‐chave: Insuficiência cardíaca aguda, Síndrome cardiorrenal, Prognóstico

In the era of Multislice Computed Tomography (MSCT), few studies have been dedicated to the evaluation of coronary anomalies and variants. We aim to present, describe and assess the prevalence of congenital coronary variants and anomalies (CVA) in the MSCT coronary angiographic studies performed in our department. All the MSCT coronary angiographies performed in our department, between April 1, 2007 and May 31, 2012 were reviewed. Coronary anomalies and variants were characterized and grouped according to their type: origin, course (including myocardial bridging) and distal ending. A total of 663 patients underwent a MSCT coronary evaluation during this period. A total of 84 anomalies and variants were identified in 80 individuals: 12.1% of the population (80/663). The most frequent variant was the myocardial bridging of the anterior descending artery. Four (4.7%) of the anomalies were considered malignant, corresponding to a prevalence of 0.6% (4/663) in the population. Congenital coronary anomalies and variants are relatively common. In our study, the prevalence was 12.1%, myocardial bridging being the most common. This fact may explain the higher prevalence compared to some series based on the cardiac catheterization studies. Few of these anomalies were considered malignant, with prevalence rates similar to those found in the cardiac catheterization studies.

Acute heart failure in patients with severe aortic stenosis and left ventricular systolic dysfunction is well known for its dire prognosis and limited therapeutic options.The authors describe the case of a man admitted for non-ST-elevation myocardial infarction. Diagnostic exams revealed severe aortic stenosis, with good left ventricular systolic function, and two-vessel coronary artery disease. The development of cardiogenic shock with left ventricular systolic dysfunction on day four led to changes in the therapeutic strategy. Percutaneous aortic balloon valvuloplasty coupled with complete myocardial revascularization was performed with a view to future surgical intervention. After discharge, the patient was readmitted with cardiogenic shock after acute pulmonary edema and cardiopulmonary arrest. Ventilator weaning was not possible due to acute heart failure and so it was decided to administer levosimendan, which resulted in substantial clinical and echocardiographic improvement. The patient subsequently underwent successful aortic valve replacement.This case highlights the challenge that characterizes the management of patients with concomitant coronary artery disease, left ventricular systolic dysfunction and severe aortic stenosis. Percutaneous aortic balloon valvuloplasty and levosimendan were safe and effective in the treatment of acute heart failure, acting as a bridge to surgery. Resumo: A insuficiência cardíaca aguda na estenose aórtica grave com compromisso da função sistólica global tem um prognóstico reservado, com opções terapêuticas limitadas.Os autores descrevem o caso clínico de um doente admitido por enfarte agudo do miocárdio sem supradesnivelamento de ST, no qual o estudo complementar revelou estenose aórtica grave, com boa função ventricular esquerda, e doença coronária de 2 vasos. O desenvolvimento de choque cardiogénico, com compromisso grave da função sistólica global, ao quarto dia de internamento, alterou a estratégia terapêutica, optando-se por realizar valvuloplastia aórtica com balão e revascularização miocárdica percutânea completa, com vista a posterior referenciação para cirurgia valvular. Após a alta, apresentou novo quadro de choque cardiogénico em contexto de insuficiência cardíaca aguda e paragem cardiorrespiratória. Por dificuldade na extubação, iniciou perfusão de levosimendan, com franca melhoria clínica e ecocardiográfica. Posteriormente, o doente foi submetido com sucesso a implantação de prótese valvular aórtica.Este caso demonstra o desafio que caracteriza a estabilização e o tratamento destes doentes. A valvuloplastia aórtica com balão e o levosimendan foram eficazes e seguros no tratamento da insuficiência cardíaca aguda e permitiram estabelecer a ponte para a cirurgia. Keywords: Severe aortic stenosis, Cardiogenic shock, Aortic balloon valvuloplasty, Levosimendan, Palavras-chave: Estenose aórtica grave, Choque cardiogénico, Valvuloplastia aórtica com balão, Levosimendan

Oxidative stress has been advanced as one of the major causes of damage to DNA and other macromolecules. Although physical exercise may also increase oxidative stress, an important role has been recognized for regular exercise in improving the overall functionality of the body, as indicated by an increase in maximal aerobic uptake ((V)O2max), and in resistance to cell damage. The aims of this study were 1) to evaluate the association between DNA damage in human lymphocytes and age and 2) to evaluate the association between DNA damage in human lymphocytes and ((V)O2max. The sample was composed of 36 healthy and nonsmoking males, aged from 20 to 84 years. ((V)O2max was evaluated through the Bruce protocol with direct measurement of oxygen consumption. The comet assay was used to evaluate the DNA damage, strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites. We found a positive correlation of age with DNA strand breaks but not with FPG-sensitive sites. ((V)O2max was significantly inversely related with DNA strand breaks, but this relation disappeared when adjusted for age. A significantly positive relation between ((V)O2max and FPG-sensitive sites was verified. In conclusion, our results showed that younger subjects have lower DNA strand breaks and higher (V)O2max compared with older subjects and FPG-sensitive sites are positively related with ((V)O2max, probably as transient damage due to the acute effects of daily physical activity.

On admission, he was hypotensive (85/55 mmHg) and tachypneic (40 bpm); cardiac auscultation revealed arrhythmia, with no murmurs; pulmonary auscultation revealed decreased breath sounds in both bases, and fine crackles in both bases; peripheral edema was also present. ECG showed AF with controlled ventricular response, alterations suggestive of ST-segment elevation in DI and aVL, T-wave inversion in inferior wall, straight ST-T segment in V3 V6, with no dynamic changes in serial electrocardiograms. Chest radiography revealed increased cardiothoracic ratio and effacement of the left costophrenic angle. Blood gas showed hypoxemia with metabolic alkalosis. Laboratory tests showed renal failure (BUN 14.8 mmol/L; creatinine 155 umol/L); hypokalemia (K 2.9 mmol/L); troponin I 0.66 ng/mL; NT-proBNP 4,060 pg/mL; and C-reactive protein 7.6 mg/dL.

Objective: The goal of this study was to verify if 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could have any effect on male germ cells mitochondria and in this way add new insights in how male reproductive alterations observed in other studies occur. Methods: In vivo and in vitro approaches using rat testis and human sperm as models were employed to evaluate TCDD effects on testicular and sperm mitochondria after 24 h of exposure. Results: Testicular mitochondria from TCDD-treated rats presented no differences in the bioenergetic parameters monitored except for a significantly higher electric membrane potential in the presence of ADP, corroborated when TCDD was directly added to testicular mitochondria from untreated rats. Nevertheless, sperm mitochondrial membrane potential, motility, viability, capacitation and acrosomal integrity did not change after TCDD treatment. Moreover, only few sperm cells exposed to TCDD increased their intracellular Ca2+ concentration. Conlusions: TCDD can interact directly with rat testicular mitochondria inducing small changes. This effect, however, does not seem to occur in human sperm or it may be insufficient to induce significant alterations as observed by the maintenance of sperm function. 1. P.C.M., R.S.T. and S.P.P. were supported by Portuguese FCT fellowships (SFRH/BD/23643/2005 and SFRH/BPD/74252/2010, SFRH/ BD/46002/2008 and SFRH/BD/64247/2009, respectively). CNC is supported by PEst-C/SAU/LA0001/2011, FCT. References

Objetivou-se averiguar a eficiência e padrões na resposta superovulatória de caprinos da raça Boer submetidos a produtos com diferentes relações FSH:LH. Foram utilizadas 43 fêmeas caprinas da raça Boer. Em um dia aleatório do ciclo estral, os animais receberam metade de um implante de progesterona (Crestar®). No dia 11, iniciou-se o estímulo à superovulação por meio da utilização do FSH fracionado em seis doses decrescentes administradas a cada 12 horas e os animais foram separados em dois grupos: o grupo I (GI, n=22) recebeu 200mg de FSH (Folltropin®) por via intramuscular (i.m.) nos dias D11 (62,5mg), D12 (35,0mg) e D13 (2,5mg), enquanto o grupo II (GII, n=21) recebeu 300UI de FSH (Pluset®) por via i.m. nos dias D11 (75UI), D12 (50UI) e D13 (25UI). Nas 60 e 72h após o início da superovulação foram retirados os implantes, e aplicaram-se duas doses de 125µg de Cloprostenol (Ciosin®) por via intravulvosubmucosa em todos os animais. Doze, 24 e 36 horas após a remoção dos implantes, as fêmeas foram colocadas com quatro reprodutores para serem cobertas. No D16, os implantes foram reinseridos e, nas 24h antes da coleta dos embriões, retiraram-se os implantes, e administrou-se 125µg de Cloprostenol i.m. a cada animal. Os embriões foram coletados no D21, selecionados e classificados. Os resultados obtidos nesse estudo mostraram que não houve diferença estatística entre os grupos, quanto ao número de estruturas recuperadas, embriões viáveis, embriões degenerados e estruturas não fertilizadas. Portanto, as diferentes relações FSH:LH avaliadas não afetaram a produção e a qualidade de embriões. This study aimed to investigate the efficiency and standards in the superrovulatory response to products with different relationships FSH:LH. It Were used 43 female Boer goats breed. On a random day of the estrous cycle, the animals received half of an implant of progesterone (Crestar®). In the eleventh day, began stimulation to superovulation through the use of FSH fractionated in six decreasing doses administered every 12 hours and the animals were separated into two groups: group I (GI, n=22) received 200mg of FSH (Folltropin®) intramuscularly (i.m) on days D11 (62,5mg), D12 (35,0mg) and D13 (2,5mg), while the group II (GII, n=21) received 300UI FSH (Pluset®) intramuscularly on days D11 (75UI), D12 (50UI) and D13 (25UI). In 60 and 72h after onset of superovulation the implants were removed and applied two doses of 125µg de Cloprostenol (Ciosin®) by intravulvosubmucosal in all animals. Twelve, 24 and 36 hours after removal of the implant, the females were placed with four breeders to be covered. In D16, the implants were reinserted and 24 hours before collection of embryos the implants were withdrawl and administered 125µg de Cloprostenol in each animal intramuscularly. Embryo were collected on D21, selected and classified. The results obtained in this study showed no statistical difference between groups regarding the number of recovered structures, viable embryos, degenerate embryos and unfertilized structures. So, the different relationships FSH:LH evaluated did not affect embryos production and quality.

FUNDAMENTO: A Hipertensão arterial (HA) é uma condição tanto agravante quanto agravada pela Síndrome Metabólica (SM). A menopausa pode tornar o tratamento da hipertensão mais difícil porque é uma condição que favorece a piora nos componentes da SM. Embora existam evidências de que o treinamento com exercícios físicos reduza a pressão arterial, se as condições da menopausa e da SM afetam os benefícios induzidos pelo exercício é algo ainda não evidenciado. OBJETIVO: Comparar os efeitos do treinamento aeróbio na pressão arterial entre mulheres com SM não menopausadas e menopausadas. MÉTODOS: Foram recrutadas 44 mulheres divididas em quatro grupos experimentais: controle não menopausada (CNM: 39,5 ± 1,1 anos, n = 11); controle menopausada (CM: 54,9 ± 1,7 anos, n = 12); aeróbio não menopausada (ANM: 43,1 ± 2,1 anos, n = 11) e aeróbio menopausada (AM: 52,1 ± 1,6 anos, n = 10). Os grupos de exercício realizaram treinamento aeróbio durante três meses, cinco vezes por semana, com intensidade entre 60% e 70% da frequência cardíaca de reserva. A pressão arterial de repouso e a resposta pressórica clínica após 60 minutos de exercício foram medidas antes e após o período treinamento. O teste de ANOVA de dois fatores foi usado, considerando p < 0,05. RESULTADOS: O programa de treinamento resultou em redução da gordura abdominal, glicemia e melhora do VO2 máx. Em comparação aos valores pré-intervenção, Pressão Arterial Sistólica (PAS) e Pressão Arterial Diastólica (PAD) não se alteraram após o treinamento nos grupos CNM, CM, ANM e AM (p > 0,05). CONCLUSÃO: Três meses de treinamento aeróbio melhora componentes da SM, mas não altera a pressão arterial de repouso, nem a resposta pressórica aguda após uma sessão de exercício aeróbio em mulheres com SM. BACKGROUND: Arterial Hypertension (AH) is an aggravating condition for Metabolic Syndrome (MS), as well as being aggravated by it. Menopause can make hypertension treatment more difficult, as it favors the worsening of MS components. Although there is evidence that exercise training reduces blood pressure, whether menopause and SM affect the exercise-induced benefits is yet to be elucidated. OBJECTIVE: To compare the effects of aerobic training on blood pressure in non-menopausal and menopausal women with MS METHODS: A total of 44 women were recruited and divided into four groups: non-menopausal control (NMC: 39.5 ± 3.6 years, n = 11); menopausal control (MC: 54.9 ± 5.9 years, n = 12), non-menopausal aerobics (NMA: 43.1 ± 6.8 years, n = 11) and menopausal aerobics (MA: 52.1 ± 5 years, n = 10). The exercise groups performed aerobic training for three months, five times a week, at an intensity between 60% and 70% of heart rate reserve. The resting blood pressure and blood pressure response after 60 minutes of exercise were measured before and after the training period. The two-way ANOVA test was used, considering a p value < 0.05. RESULTS: The training program resulted in a decrease in abdominal fat, blood glucose and improved VO2 max. Compared to pre-intervention values, Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) did not change after training in NMC, MC, MA and NMA groups (p > 0.05). CONCLUSION: Three months of aerobic training improved MS components, but did not alter resting blood pressure or the BP response after an acute exercise session in women with MS.

Introduction: Device closure of interatrial communications has become a well-established technique to treat left-to-right shunt associated with atrial septal defect (ASD) and to prevent paradoxical embolism in patients with patent foramen ovale (PFO). Guidance by transesophageal echocardiography (TEE) is the standard practice but intracardiac echocardiography (ICE) is a feasible and safe alternative for monitoring these procedures. Objectives: To report our experience in the percutaneous closure of ASD and PFO guided by ICE. Methods: We retrospectively reviewed all patients with ASD or PFO who underwent percutaneous closure guided exclusively by ICE between January 2008 and December 2010. All patients were followed clinically with regular echocardiographic evaluation (at discharge, one month, three, six and twelve months) to exclude residual shunt and device malposition. Results: A total of 127 patients (mean age 46.6±12.2 years; 71% female) underwent transcatheter device closure of ASD or PFO during the study period. Device deployment with ICE monitoring was 100% successful, with a low rate of complications and eliminating the need for additional imaging techniques. Conclusions: ICE provides anatomical detail of ASD/PFO and cardiac structures, facilitating congenital cardiac interventional procedures. It eliminates the major drawbacks associated with TEE and enables the interventional cardiologist to control all aspects of the procedure without relying on additional echocardiographic support. Resumo: Introdução: O encerramento percutâneo (EP) de defeitos do septo interauricular (SIA) é uma técnica comprovadamente eficaz para o tratamento da comunicação interauricular (CIA) e prevenção de embolia paradoxal em doentes com foramen ovale patente (FOP). A monitorização com ecocardiograma transesofágico (ETE) é o método habitualmente utilizado mas o ecocardiograma intracardíaco (EIC) constitui uma alternativa prática e segura para o controlo imagiológico destes procedimentos. Objetivo: Apresentar a experiência de um centro no EP de CIA e FOP guiado exclusivamente por EIC. Métodos: Analisámos retrospetivamente uma série de doentes consecutivos com CIA ou FOP submetidos a EP sob controlo por EIC no período de janeiro de 2008 a dezembro de 2010. Foram todos avaliados clínica, eletro e ecocardiograficamente à data da alta e após o 1.°, 3.°, 6.° e 12.° mês para excluir shunt residual (SR) e malaposição do dispositivo. Resultados: Um total de 127 doentes (46,6±12,2 anos; 71% de mulheres) foi submetido a EP de CIA ou FOP durante o referido período. A utilização do EIC durante o EP permitiu a colocação eficaz dos dispositivos em 100% dos casos, com uma reduzida taxa de complicações, dispensando a utilização adicional de outras técnicas de imagem durante os procedimentos. Conclusão: O EIC fornece informação anatómica detalhada da CIA/FOP e estruturas cardíacas adjacentes, facilitando assim os procedimentos de intervenção. Elimina os inconvenientes do ETE e possibilita ao cardiologista de intervenção controlar os vários aspetos do procedimento sem necessitar de apoio ecocardiográfico adicional. Keywords: Intracardiac echocardiography, Atrial septal defects, Transcatheter device closure, Palavras-chave: Ecocardiograma intracardíaco, Defeitos do septo interauricular, Encerramento percutâneo

Aim Some transoesophageal echocardiogram (TEE) findings are associated with an increased risk of stroke in patients with atrial fibrillation (AF). This study was designed to evaluate and compare the accuracy of CHADS2 and CHA2DS2-VASc in the prediction of these findings and test the additive value of transthoracic echocardiogram (TTE)-derived parameters as a possible refinement for these classifications. Methods and results Cross-sectional study of 405 consecutive patients who underwent TTE and TEE evaluation during AF. Stroke risk assessment was performed using the CHADS2 and CHA2DS2-VASc scores, alone and alongside with the addition of two TTE-derived parameters (left atrium area and left ventricle global systolic function). Comparisons regarding the presence of left atrial appendage thrombi (LAA T), dense spontaneous echo contrast (SEC), and left atrial appendage (LAA) low flow velocities (LFV) were performed using receiver operating characteristic curves. In low-risk patients, as assessed through the CHA2DS2-VASc score and CHADS2 and CHA2DS2-VASc scores plus echo parameters, no high-risk features were found on TEE. In subjects classified as low risk using CHADS2, this figure rose to 10%. No significant differences were found between CHADS2 and CHA2DS2-VASc in the prediction of LAA T, dense SEC, and LAA LFV. The addition of TTE-derived parameters to the previous clinical-risk scores resulted in improved prediction of the TEE endpoints. Conclusion These findings suggest that the use of TTE-derived parameters may be a valuable way of refining the available clinical risk schemes for the detection of surrogate markers of stroke. Follow-up studies using clinical endpoints will be necessary to confirm this hypothesis.

Atherosclerosis is a diffuse arterial disease, discontinuously distributed, that is not always linear in its pathophysiological significance. Starting with a paradigmatic clinical case, we review the hemodynamic techniques that are currently available for the assessment of this condition. We present the case of a male patient with known diffuse atherosclerotic disease, who had previously undergone angioplasty, in which angiography was repeated after acute pulmonary edema, with worsening left ventricular function and local ischemia documented by myocardial scintigraphy. The angiogram showed an intermediate lesion in the left anterior descending artery, not related to the ischemic territory. The significance of the lesion was evaluated anatomically with intravascular ultrasound, and functionally by determining fractional flow reserve with a pressure wire. We review the pathophysiology of the disease and the parameters used for overall evaluation, focusing on catheterization laboratory techniques and their indications and contribution to the diagnosis and treatment of coronary atherosclerosis. Resumo: A aterosclerose é uma doença arterial difusa, com distribuição descontínua, cujo significado fisiopatológico nem sempre é linear. A partir de um caso paradigmático faz-se a revisão das técnicas actualmente disponíveis na sala de hemodinâmica, para este fim. Trata-se de um paciente do sexo masculino, com aterosclerose coronária difusa conhecida, previamente submetido a intervenção percutânea, que realiza coronariografia após descompensação por edema agudo do pulmão, com deterioração da função ventricular esquerda e documentação de isquémia em cintigrafia de perfusão miocárdica. No cateterismo foi observada uma lesão de significado angiográfico intermédio na artéria descendente anterior, em território diferente do documentado por cintigrafia. Procedeu-se primeiro à avaliação do significado da lesão quer anatómico, através de ultrassonografia intravascular, quer funcional, através da determinação da reserva coronária com guia de pressão. Revemos a fisiopatologia desta doença, parâmetros da sua avaliação global, focando estas técnicas per-cateterismo, suas indicações e contribuição no diagnóstico e terapêutica da aterosclerose coronária. Keywords: Atherosclerosis, Pressure, wire, IVUS, Angiography, Palavras-chave: Aterosclerose, Guia de pressão, IVUS, Angiografia

The aim of the present study was to analyze the lifelong differences of femur structure in sedentary and physically active animal models. Thirty male C57BL/6 mice, 2 months old, were either: i) housed in cages with running wheel (AA; n=10), ii) housed in cages without running wheel (AS; n=10), iii) or sacrificed without intervention (Y; n=10). AA and AS animals were sacrificed after 23 months of housing. Right femur structure was analyzed in all animals by histomorphometry. Significant differences in several microarchitectural parameters of cancellous and cortical bone were identified between Y mice and both groups of aged mice, as well as between AA and AS groups. Lifelong physically active mice had significantly higher cancellous bone surface (Cn.BS) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) at both epiphyses when compared to AS animals. No differences were observed between Y and AA groups regarding osteocyte number (N.Ot) despite its significant reduction in AS animals, suggesting that age alone was not a cause for decreases in N.Ot. Our results suggest that the reduced bone quality observed in the elderly is not only a consequence of age but also of lack of physical activity since sedentary behaviour significantly aggravated the degenerative age-related bone differences.

Background : The objective of this study was to analyze the effects of strength training on plasma homocysteine levels and cardiovascular risk factors in patients with type 2 diabetes. Methods : The sample consisted of 14 diabetic women with a mean age of 68 ± 6 years. Biochemical evaluations and anthropometric measurements were taken before and after training. Training sessions lasted 50 min and comprised three sets of 8–12 repetitions each. The established load was 60% of 1 repetition maximum. Results : After the training program, it was observed that the levels of homocysteine (average before 13.4 ± 2.9 and after 12.8 ± 3.3, P = 0.40), very low‑density lipoprotein (LDL) (average before 41.9 ± 17.0 and after 36.2 ± 11.8, P = 0.47), total cholesterol (average before 214.4 ± 60.6 and after 190.2 ± 62.3, P = 0.09), triglycerides (average before 209.3 ± 85.4 and after 181.5 ± 59.2, P = 0.47), and blood glucose (average before 123.5 ± 30.4 and after 110.1 ± 24.7, P = 0.26) showed no signifcant changes, but the LDL (average before 129.1 ± 63.4 and after 95.7 ± 53.3, P = 0.04), high‑density lipoprotein (average before 43.2 ± 12.0 and after 58.2 ± 15.6, P = 0.01), lean mass (average before 41.1 ± 5.7 and after 42.8 ± 5.4, P = 0.008), fat mass (average before 31.4 ± 8.8 and after 29.7 ± 8.5, P = 0.001), and percentage fat (average before 42.6 ± 4.0 and after 40.3 ± 4.6, P = 0.000) showed signifcant changes. Conclusions : This study concluded that strength training does not improve homocysteine levels, but help to improve the lipoprotein profle in type 2 diabetic patients. Keywords : Cholesterol, glucose, hyperhomocysteinemia, obesity, strength exercise

Type-2 diabetic patients constitute a high-risk population for atherosclerosis. Primary prevention, although recommended, is not well funded. Our aim was to evaluate the degree of subclinical atherosclerosis, in asymptomatic diabetic patients, using coronary multi-slice computed tomography (MSCT) angiography.We prospectively studied 71 diabetic patients without any symptoms or documentation of atherosclerotic disease. Coronary MSCT angiography was performed in all patients and coronary artery calcium score (CACS) was evaluated. The number of diseased coronary segments was determined and classified as obstructive or nonobstructive and fibrolipid or calcified lesions. The mean follow-up was 29.5±6.6 months. Major adverse cardiovascular events were registered.The mean age was 59±10 years, 48% were female patients. The duration of diabetes was 12.5±8.7 years. CACS ranged from 0 to 1293 Agatston units (153±269.1). Image quality was generally good, allowing satisfactory evaluation of most of the coronary artery segments. CACS was 0 in 28 patients, but in nine patients MSCT angiography showed fibrolipid plaques. Obstructive coronary artery disease was present in 26.7% of the patients (5.6% with multivessel disease). During the follow-up period, six major adverse cardiovascular events were detected in patients, five of whom had a CACS more than 100 Agatston units.This study shows a high prevalence of silent atherosclerotic lesions in type-2 diabetic patients, reinforcing the importance of risk factor modification even when calcified disease is absent. Coronary MSCT angiography can be performed to identify the atherosclerotic burden and may be an important test in selecting the patients who are benefiting the most from primary prevention.

Background Catechol-O-methyltransferase (COMT) is a catabolic enzyme involved in the degradation of bioactive molecules including the neurotransmitters epinephrine, norepinephrine, and dopamine. Higher COMT activity in depressive patients in comparison to non-depressed individuals has been reported. The effect of aerobic exercise on depressive patients has been studied and a number of researchers and clinicians believe it to be effective in the treatment of depression and to be involved in several molecular underlying mechanisms. However, the effect of physical exercise on this enzyme activity is unknown, and it remains to be elucidated if chronic exercise changes COMT activity. This randomized control trial evaluates the effects of chronic exercise on peripheral COMT (S-COMT) activity in women with depressive disorder. Methods Fourteen women (aged: 51.4±10.5 years) diagnosed with depression (according to International Classification of Diseases-10) were randomized to one of two groups: pharmacotherapy plus physical exercise (n=7) or only pharmacotherapy (n=7). The aerobic exercise program was supervised, lasting between 45–50 min/session, three times/week for 16 weeks. Erythrocyte soluble COMT were assessed prior to and after the exercise program. Results Exercise group when compared to a control group presented a significant decrease (p=0.02, r=−0.535) in S-COMT activity between baseline and post-intervention. Limitations These data are preliminary outcomes from a small sample and should be replicated. Conclusions Chronic exercise therapy combined with pharmacotherapy leads to significant decrease in S-COMT activity. Our results provide evidence that exercise interferes with S-COMT activity, a molecular mechanism involved in depression.

BACKGROUND: Inflammatory bowel disease, comprising Crohn's disease and ulcerative colitis, is a group of debilitating conditions associated with deregulated mucosal immune response. Vitamin D has been implicated in immune response and gastrointestinal function. OBJECTIVES: To investigate the correlation between serum vitamin D levels and disease activity and quality of life in patients with inflammatory bowel disease. METHODS: This cross-sectional study enrolled ambulatory patients with inflammatory bowel disease and assessed clinical disease activity and quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Vitamin D levels were determined via serum 25-hydroxyvitamin D measurement; deficiency was defined as values, Contexto - A doença inflamatória intestinal, que compreende a doença de Crohn e a colite ulcerosa, é um grupo de entidades incapacitantes associada a uma resposta imunitária desregulada. A vitamina D tem sido associada à resposta imune e funções gastrointestinais. Objetivo - Investigar a correlação entre os níveis séricos de vitamina D, a atividade clínica da doença e a qualidade de vida em doentes com doença inflamatória intestinal. Método - Estudo transversal que incluiu doentes em ambulatório com doença inflamatória intestinal avaliando a atividade clínica da doença e a qualidade de vida (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Os níveis séricos de vitamina D foram determinados através dos níveis de 25-hidroxivitamina D; a deficiência de vitamina D foi definida para valores, (undefined), info:eu-repo/semantics/publishedVersion

Minimal hepatic encephalopathy refers to a mild neurocognitive impairment not detectable by clinical examination that can be present in cirrhotic patients.To determine the prevalence of minimal hepatic encephalopathy in a secondary healthcare center in Northern Portugal.A cross-sectional study was conducted. Cirrhotic outpatients were included.overt hepatic encephalopathy, illiteracy, active alcohol consumption, psychotropic drug use and therapy with lactulose. The presence of minimal hepatic encephalopathy was defined as a value ≥ -4 on the Psychometric Hepatic Encephalopathy Score, calculated according to the Portuguese norms. Variables analyzed: etiology and severity of liver disease and venous blood ammonia concentration. p values0.05 were considered significant.From the 102 patients who were evaluated, 41 were included: 31 males, mean age 57 ± 10 years, mean education 5 ± 2 years, 31 in Child-Pugh class A, mean MELD score 6 ± 3. Minimal hepatic encephalopathy was diagnosed in 14 (34%) patients. The presence of minimal hepatic encephalopathy was unrelated to severity of liver disease. Despite being more elevated, the mean venous ammonia concentration in minimal hepatic encephalopathy patients was not statistically different from the mean venous ammonia concentration in non-minimal hepatic encephalopathy patients (48.5 ± 13.3 vs. 45.6 ± 15.6 μmol/L, p = 0.555).The prevalence of minimal hepatic encephalopathy reported is in accordance with the international published data.Minimal hepatic encephalopathy is a frequent condition that is present early in the course of cirrhosis, even in compensated cirrhotic patients. Therefore, this hidden entity should be actively pursued and managed properly.Introdução: A encefalopatia hepática mínima define-se como um défice neurocognitivo ligeiro, não detectável ao exame clínico, que pode estar presente nos doentes cirróticos. Objectivo: Determinar a prevalência da encefalopatia hepática mínima num hospital prestador de cuidados de saúde secundários no Norte de Portugal. Material e Métodos: Realizou-se um estudo transversal em que foram incluídos os doentes cirróticos seguidos na consulta externa. Critérios de exclusão: encefalopatia hepática clínica, iliteracia, consumo activo de álcool e terapêutica com fármacos psicotrópicos ou lactulose. A presença de encefalopatia hepática mínima foi definida como um valor ≥ -4 na Pontuação Psicométrica da Encefalopatia Hepática, calculado de acordo com as normas portuguesas. Analisaram-se as variáveis: etiologia e gravidade da doença hepática e concentração da amónia sanguínea venosa. Considerou-se o valor de p0,05 como significativo. Resultados: Dos 102 doentes avaliados, 41 foram incluídos: 31 homens, idade média de 57 ± 10 anos, escolaridade média de 5 ± 2 anos, 31 Child-Pugh classe A, score MELD médio de 6 ± 3. Foi diagnosticada encefalopatia hepática mínima em 14 (34%) doentes. A presença de encefalopatia hepática mínima não se relacionou com a gravidade da doença hepática. Apesar de mais elevado, o valor médio da concentração da amónia venosa nos doentes com encefalopatia hepática mínima não foi significativamente diferente do valor médio da concentração da amónia venosa nos doentes sem encefalopatia hepática mínima (48,5 ± 13,3 vs. 45,6 ± 15,6 μmol/L, p = 0,555). Discussão: A prevalência da encefalopatia hepática mínima descrita está de acordo com os dados internacionais. Conclusão: A encefalopatia hepática mínima é uma entidade frequente que está presente precocemente na história natural da cirrose, mesmo em doentes compensados. Consequentemente, esta condição escondida deve ser activamente procurada e os doentes devidamente orientados após o diagnóstico.

Tobacco exposure remains the main etiologic factor for lung cancer (LC). Interactions between environment and individual genetic profile are particularly important for this disease. The aim of this study was to evaluate the contribution of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 polymorphisms for the susceptibility to LC in a Portuguese population considering their demographic and clinical characteristics. A total of 200 LC and 247 controls subjects from the Centre of Portugal were studied. Clinical and demographic characteristics were collected from clinical files and by individual questionnaires. Polymorphisms of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 were genotyped using PCR–RFLP, PCR multiplex, ARMS and real time. Gender, family history of cancer, smoke cessation and alcohol consumption were independent risk factors (p

The authors report the case of a patient diagnosed with both hypertrophic cardiomyopathy and aortic stenosis. Due to clinical deterioration, additional investigation was performed, and a high left ventricular outflow tract gradient was identified. Correct identification of the condition causing the symptoms was challenging, and involved several imaging techniques, the contribution of transesophageal echocardiography being crucial. The final diagnosis of severe aortic stenosis led to successful valve replacement surgery. The presence of these two conditions in the same patient has been documented, although it is uncommon. This association poses particular diagnostic and therapeutic challenges, which are discussed in this paper. Resumo: Os autores apresentam o caso de uma doente com os diagnósticos de miocardiopatia hipertrófica e estenose aórtica, na qual foi identificada a presença de um gradiente elevado ao nível do trato de saída do ventrículo esquerdo. O reconhecimento da patologia responsável pela sintomatologia foi desafiante, com envolvimento de várias técnicas de imagem, tendo sido fundamental a contribuição do ecocardiograma transesofágico. O diagnóstico final de estenose aórtica severa conduziu à referenciação para cirurgia de substituição valvular, com sucesso. A presença destas duas patologias em simultâneo num mesmo doente é conhecida, embora incomum. A sua combinação cria importantes desafios diagnósticos e terapêuticos, os quais serão objeto de discussão neste artigo. Keywords: Aortic valve stenosis, Hypertrophic cardiomyopathy, Left ventricular outflow tract obstruction, Echocardiography, Doppler echocardiography, Palavras-chave: Estenose aórtica, Cardiomiopatia hipertrófica, Obstrução do trato de saída do ventrículo esquerdo, Ecocardiografia, Ecocardiografia Doppler

The authors report the case of a 53-year-old man, with a long-standing history of mild mitral stenosis, admitted for worsening fatigue. Transthoracic echocardiography (limited by poor image quality) showed mitral annular calcification, leaflets that were difficult to visualize and an estimated mitral valve area of 1.8 cm2 by the pressure half-time method. However, elevated mean transmitral and right ventricle/right atrium gradients were identified (39 and 117 mmHg, respectively). This puzzling discrepancy in the echocardiographic findings prompted investigation by transesophageal echocardiography, which revealed an echogenic structure adjacent to the mitral annulus, causing severe obstruction (effective orifice area 0.7 cm2). The suspicion of supravalvular mitral ring was confirmed during surgery. Following ring resection and mitral valve replacement there was significant improvement in the patient's clinical condition and normalization of the left atrium/left ventricle gradient.Supravalvular mitral ring is an unusual cause of congenital mitral stenosis, characterized by an abnormal ridge of connective tissue on the atrial side of the mitral valve, which often obstructs mitral valve inflow. Few cases have been reported, most of them in children with concomitant congenital abnormalities. Diagnosis of a supravalvular mitral ring is challenging, since it is very difficult to visualize in most diagnostic tests. It was the combination of clinical and various echocardiographic findings that led us to suspect this very rare condition, enabling appropriate treatment, with excellent long-term results. Resumo: Os autores reportam o caso de um doente de 53 anos, com diagnóstico prévio de estenose mitral ligeira, admitido por agravamento do cansaço. O ecocardiograma (Eco) transtorácico, limitado pela janela acústica, mostrava válvula mitral com ecogenicidade aumentada a nível do anel, deficiente observação dos folhetos e área valvular estimada de 1,8 cm2 por tempo de hemipressão. No entanto, a identificação de elevados gradientes transmitral médio e ventrículo direito/aurícula direita (atingindo respetivamente 39 e 117 mmHg) intrigou os autores. No Eco transesofágico foi observada estrutura hiperecogénica sobre o anel mitral a condicionar obstrução grave (área do orifício efetivo de 0,7 cm2), o que levantou a suspeita de anel supramitral. Esta foi confirmada durante a cirurgia. Após a ressecção do anel e implantação de prótese mecânica, verificou-se uma franca melhoria clínica e normalização do gradiente aurícula esquerda (AE)/ventrículo esquerdo (VE).O anel supramitral é uma causa invulgar de estenose mitral congénita, caracterizado pela presença de uma membrana fibrosa adjacente à face auricular da válvula mitral. Existem poucos casos reportados na literatura, sendo a maioria descritos em idade pediátrica e em associação a outras anomalias congénitas. O diagnóstico é desafiante, dado que o anel raramente é visualizado nos exames complementares. Uma elevada suspeita clínica e a integração dos vários achados ecocardiográficos são aspetos fundamentais para a sua identificação, permitindo o tratamento adequado com bons resultados a longo prazo. Keywords: Supravalvular ring, Supravalvular mitral ring, Mitral stenosis, Congenital mitral stenosis, Supravalvular mitral stenosis, Palavras-chave: Anel supramitral, Anel mitral supravalvular, Estenose mitral, Estenose mitral congénita, Estenose mitral supravalvular

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent.We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 mg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. SPP and GCP are supported by a Portuguese Foundation for Science and Technology (FCT) Ph.D. fellowship (SFRH/BD/64247/ 2009 and SFRH/BD/36938/2007). The present work is supported by FCT grants PTDC-SAU-OSM-64084-2006 and PTDC/QUI-QUI/ 101409/2008 (to PO) and PEst-C/SAU/LA0001/2011 (to CNC) cofunded by FEDER, COMPETE and the Portuguese National Funds.

This study aimed to investigate the role of exercise order on total number of repetitions and to evaluate the possible importance on muscle damage and on rating perceived exertion (RPE). Ten trained participants completed two sequences: sequence A (SEQA) was leg press (LP), leg extension (LE), leg curl (LC), bench press (BP), shoulder press (SP), and triceps extension (TE) and in sequence B (SEQB), the order of execution of the exercises was reversed. Highest creatine kinase (CK) concentrations were observed 24 hours following both sessions, but no differences were found at any time between them, revealing that muscle damage has occurred. There were significant differences between SEQA and SEQB in the total number of repetitions for TE, LE, and LC. Our results suggest that differences in total strength production when exercise order is changed must be explained by some other mechanisms besides muscle damage and RPE.

Type 2 diabetes (T2D) is considered a major risk factor for Alzheimer's disease (AD). To elucidate the links between both pathological conditions, we compared behavioral and cognitive functions, cerebral amyloid-β peptide (Aβ) levels and vasculature integrity of 11-month-old T2D and AD mice. For this purpose, we performed behavioral tests (open field, object recognition, Y-maze, and elevated plus maze tests), ELISA to assess plasma markers of endothelial/vascular dysfunction, spectrophotometric assays to evaluate cerebral vascular permeability and enzymatic activities, and immunohistochemistry for the assessment of Aβ levels. Both T2D and AD showed similar behavioral and cognitive anomalies characterized by increased fear and anxiety and decreased learning and memory abilities. Interestingly, both groups of animals presented increased plasma markers of endothelial/vascular dysfunction and permeability of cerebral vasculature and impaired mitochondrial enzymatic activities. In addition, a significant increase in Aβ levels was observed in the cortex and hippocampus of T2D mice. These results support the notion that T2D predisposes to cerebrovascular alterations, cognitive decline, and development of AD.

Besides known factors that may cause male infertility, systemic diseases such as diabetes mellitus may further exacerbate a decline in male fertility. This metabolic disease, clinically characterised by a hyperglycaemic phenotype, has devastating consequences in terms of human health, with reproductive dysfunction being one of the associated clinical complications. Nonetheless, the mechanisms responsible for such alterations are still poorly understood due to the multiplicity of factors involved in the induced pathophysiological changes. With this in mind, we focused on the main mediator of diabetes-associated alterations and performed an in vitro approach to address the effects of high glucose conditions on spermatogenesis, avoiding other confounding in vivo factors. Mouse (5 days post partum) testis fragments were cultured on agar gel stands at a gas–liquid interface with either 5, 25 or 50 mM D-glucose for 3 weeks. Stereological analysis revealed that high D-glucose levels increased Sertoli cell number (P 0.05), further suggesting altered Sertoli cell maturation. Overall, high D-glucose concentrations may lead to impairment of Sertoli cell function, which, given their significant role in spermatogenic control, may compromise male fertility.

A 77-year-old male patient with a history of bioprosthetic aortic valve replacement and a recently diagnosed urothelial carcinoma was referred to our cardiology outpatient clinic due to dyspnoea on mild exertion. A transthoracic echocardiogram revealed a moderate dilation of the left cardiac chambers, mild dilation of the right atria and pulmonary artery (with a normal-sized right ventricle), moderate pulmonary hypertension and severe left ventricle systolic dysfunction with low cardiac output (3.6 L/min). These findings had not been reported at the time of the cardiac surgery. The patient’s clinical status progressively worsened with respiratory failure requiring supplementary high flow oxygen. A coronary angiography was performed, excluding coronary artery disease and revealing a large coronary fistula arising from the …

The authors present a case of systemic amyloidosis with cardiac involvement. We discuss the need for a high level of suspicion to establish a diagnosis, diagnostic techniques and treatment options. Our patient was a 78-year-old man with chronic renal disease and atrial fibrillation admitted with acute decompensated heart failure of unknown cause. The transthoracic echocardiogram revealed severely impaired left ventricular function with phenotypic overlap between hypertrophic and restrictive cardiomyopathy. After an extensive diagnostic workup, which included an abdominal fat pad biopsy, the final diagnosis was amyloidosis. Resumo: Os autores apresentam um caso de amiloidose sistémica com envolvimento cardíaco e discutem a importância de um elevado índice de suspeição para o diagnóstico, os meios de diagnóstico e as opções terapêuticas à luz do conhecimento atual. Homem de 78 anos, com antecedentes de doença renal crónica e fibrilhação auricular, admitido por insuficiência cardíaca aguda de etiologia desconhecida. O ecocardiograma transtorácico mostrou ventrículo esquerdo não dilatado, com compromisso severo da função sistólica global com overlap fenotípico de miocardiopatia hipertrófica e restritiva. Após estudo complementar alargado, o diagnóstico definitivo de amiloidose foi obtido por biópsia da gordura abdominal. Keywords: Amyloidosis, Hypertrophic cardiomyopathy, Restrictive cardiomyopathy, Heart failure, Palavras-chave: Amiloidose, Miocardiopatia hipertrófica, Miocardiopatia restritiva, Insuficiência cardíaca

Congestive heart failure and left ventricular dysfunction in the setting of severe aortic stenosis are associated with a high mortality rate. Evidence on optimal medical therapy is scanty. Vasodilators were traditionally considered to be contraindicated in severe aortic stenosis, albeit this concept has recently been challenged. The use of levosimendan, which has positive inotropic, vasodilatory and cardioprotective properties seems attractive. We describe a small series of exceedingly ill patients with severe aortic stenosis and left ventricular dysfunction, in different clinical settings (acute heart failure, cardiogenic shock and difficult-to-wean ventilatory support), in which levosimendan was successfully used.

Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by abnormalities of the GLA gene, which encodes the enzyme α-galactosidase A. A deficiency of this enzyme leads to the lysosomal accumulation of glycosphingolipids, which may cause left ventricular hypertrophy that is typically concentric and symmetric.We present the case of a 60-year-old woman with symptoms of dyspnea, atypical chest pain and palpitations, in whom a transthoracic echocardiogram revealed an apical variant of hypertrophic cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative. The patient underwent a screening protocol for Anderson-Fabry disease, using a dried blood spot test, which was standard at our institution for patients with left ventricular hypertrophy. The enzymatic activity assay revealed reduced α-galactosidase A enzymatic activity. Molecular analysis identified a missense point mutation in the GLA gene (p.R118C).This case report shows that Anderson-Fabry disease may cause an apical form of left ventricular hypertrophy. The diagnosis was only achieved because of systematic screening, which highlights the importance of screening for Anderson-Fabry disease in patients with unexplained left ventricular hypertrophy, including those presenting with more unusual patterns, such as apical variants of left ventricular hypertrophy. This case also supports the idea that the missense mutation R118C is indeed a true pathogenic mutation of Anderson-Fabry disease. Resumo: A doença de Anderson-Fabry é uma doença do lisossoma associada ao cromossoma X, causada por alterações no gene GLA que codifica a enzima α-galactosidase A. A deficiência desta enzima leva à acumulação de glicosfingolípidos, podendo causar hipertrofia ventricular esquerda, tipicamente concêntrica e simétrica.Apresentamos o caso de uma mulher de 60 anos com queixas de dispneia, dor torácica atípica e palpitações, que realizou um ecocardiograma transtorácico que mostrou uma variante apical de miocardiopatia hipertrófica. A pesquisa de mutações nos genes das proteínas do sarcómero foi negativa. A doente foi incluída num protocolo de rastreio de doença de Anderson-Fabry, usando o teste da gota de sangue seca, para doentes com miocardiopatia hipertrófica. Foi documentada uma redução da atividade enzimática da enzima α-galactosidase A. A análise molecular identificou uma mutação missense do gene GLA (p.R118C).Este caso clínico mostra que a doença de Anderson-Fabry se pode apresentar com um padrão de hipertrofia ventricular apical. Este diagnóstico apenas foi feito devido ao rastreio sistemático realizado em todos os doentes com hipertrofia ventricular esquerda de causa não esclarecida, incluindo mesmo os doentes com padrões de hipertrofia menos usuais. Este caso clínico também suporta a ideia de que a mutação missense R118C é de facto uma mutação patogénica de doença de Anderson-Fabry. Keywords: Apical hypertrophic cardiomyopathy, Echocardiography, Genetics, Anderson-Fabry disease, Screening, Palavras-chave: Miocardiopatia hipertrófica apical, Ecocardiograma, Genética, Doença de Anderson-Fabry, Rastreio

Since the mechanism(s) underlying menopause-related sarcopenia remain unknown we aimed to investigate the role of physical inactivity in its etiology. Ovariectomized and sham-operated rats were allocated into 2 experimental groups: (1) sedentary-standard housing; and (2) exercise-housed with running wheel. After a 9-month experimental period, soleus muscle structure and biochemical properties were analyzed. No differences existed in muscle fibre size or ultrastructure between sedentary sham and ovariectomized animals housed in standard conditions. In the exercise groups, average daily running distance was 10-fold less in ovariectomized compared to sham-animals. Further, in exercised animals, soleus fibre size was smaller in ovariectomized compared to sham-animals. Nonetheless, compared to both sedentary groups, muscle fibre size was larger in the exercised ovariectomized animals. Our results indicate that ovariectomy-induced sarcopenia is not due to the loss of ovarian hormones per se, but is largely due to physical inactivity.

The loss of genetic diversity due to premature death of valuable individuals is a significant problem in animal conservation programs, including endangered felids. Testis tissue xenografting has emerged as a system to obtain spermatozoa from dead immature animals, however protocols to store this tissue before xenografting are still lacking. This study focused on testis tissue cryopreservation and storage from the domestic cat ( Felis catus ) classified as “pre-pubertal” and “pubertal” according to spermatogenesis development. Grafts from testis tissue cryopreserved with DMSO 1.4M, recovered after 10 weeks xenografting, presented seminiferous tubules with no germ cells. On the contrary, testis tissue from pre-pubertal animals preserved in ice-cold medium for 2 to 5 days presented no loss of viability or spermatogenic potential, while the number of grafts of pubertal cat testis tissue with germ cells after 10 weeks of xenografting decreased with increasing storage time. Nevertheless, even grafts from pre-pubertal cat testis tissue presented lower anti-DDX4 and anti-BOULE staining (proteins necessary for the meiosis completion), when compared with adult cat testis. Finally, a strong correlation found between testis weight and xenograft outcome may help choose good candidates for xenografting.

The release of environmental contaminants can contribute to impaired male fertility. The bioenergetics of isolated liver mitochondria have been used as a toxicological indicator, an inexpensive first line model to screen possible effects of several substances. Here we report the effects of 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethylene (DDE) on the bioenergetical parameters of testicular mitochondria. A significant decrease in repolarization potential (after a phosphorylative cycle), state 3 respiration and uncoupled respiration, with a concomitant increase in lag phase was found, demonstrating a decrease in mitochondrial function. Importantly, there was also a clear increase in maximum potential in DDE-treated testis mitochondria, which was not mirrored by more commonly used liver mitochondria. Indeed, comparative studies showed that testis and liver mitochondria have strikingly different sensitivities and patterns of response to DDE, indicating that testis mitochondria should be used as a primary toxicological model for a proper evaluation of putative effects of environmental toxicants on the bioenergetics of spermatogenesis and male fertility.

Osteocytes are recognized as having a pivotal role in bone tissue homeostasis, and stimuli that increase osteocyte death result in decreased bone tissue quality. Previous in vitro studies have shown that mechanical stimulation prevents osteocyte death; however, in vivo evidence of this protective effect is limited. The aim of this study was to investigate if mechanical stimulation provided by voluntary exercise reduces osteocyte death caused by estrogen deficiency. Thirty-two female Wistar rats (5 months old) were either sacrificed as baseline controls (BSL, n = 7), ovariectomized or sham-operated and housed in cages with a voluntary running wheel (OVXEX, n = 7; SHAMEX, n = 6), or ovariectomized or sham-operated and housed in standard cages of equivalent size (OVXSED, n = 6; SHAMSED, n = 6) and sacrificed at age 14 months. Histomorphometric analysis of femur mid-diaphysis cortical bone revealed a significantly higher osteocyte number (N.Ot) and lower empty lacunae number (N.Lc) in both the OVXEX and SHAMEX groups compared to their SED counterparts. Intracortical porosity (Po.Ar) was also lower in both EX groups compared to their SED counterparts and significantly correlated with N.Lc (r = 0.616; P

The aim of this study was to analyze the influence of aerobic fitness (AF) on age-related lymphocyte DNA damage in humans, giving special attention to the role of the mitochondrial respiratory chain and hydrogen peroxide production. Considering age and AF (as assessed by VO(2)max), 66 males (19-59 years old) were classified as high fitness (HF) or low fitness (LF) and distributed into one of the following groups: young adults (19-29 years old), adults (30-39 years old), and middle-aged adults (over 40 years old). Peripheral lymphocytes obtained at rest were used to assess DNA damage (strand breaks and formamidopyrimidine DNA glycosylase (FPG) sites through the comet assay), activity of mitochondrial complexes I and II (polarographically measured), and the hydrogen peroxide production rate (assayed by fluorescence). Results revealed a significant interaction between age groups and AF for DNA strand breaks (F = 8.415, p = .000), FPG sites (F = 11.766, p = .000), mitochondrial complex I activity (F = 7.555, p = .000), and H(2)O(2) production (F = 7.500, p = .000). Except for mitochondrial complex II activity, the age variation of the remaining parameters was significantly attenuated by HF. Considering each AF level, an increase in DNA strand breaks and FPG sites with age (r = 0.655, p = 0.000, and r = 0.738, p = 0.000, respectively) was only observed in LF. Moreover, decreased mitochondrial complex I activity with age (r = -.470, p = .009) was reported in LF. These results allow the conclusion that high AF seems to play a key role in attenuating the biological aging process.

Diabetes-induced complications are associated with mitochondrial dysfunction and increasing evidence suggests that diabetes has an adverse effect on male reproductive function. The STZ-induced diabetic rat was used as an animal model for the type 1 form of the disease with the aim of determining its effects in spermatogenesis and testicular mitochondrial function. Several aspects of mitochondrial function were measured, including respiratory and electric potential function, as well as mitochondrial calcium loading capacity. Additionally oxidative stress production, antioxidant levels and possible apoptotic alterations were also evaluated. We observed that diabetic animals present alterations in spermatogenesis in both the testis and epidydimus. However, and surprisingly, the overall results in mitochondrial parameters failed to reveal severe testicular mitochondrial dysfunction in diabetic animals, with the exception of a decrease in calcium load. Taken together, results suggest that in animal models that mimic untreated type 1 diabetes the severe effects of the condition on spermatogenesis are not directly mitochondrial-mediated.