Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTB4 Controls Parasite Growth.

5-Lipoxygenase (5-LO) is an enzyme required for the production of leukotrienes and lipoxins and interferes with parasitic infections. In vitro, Toxoplasma gondii inhibits leukotriene B4 (LTB4) production, and mice deficient in 5-LO are highly susceptible to infection. The aim of this study was to investigate the effects of the pharmacological inhibition of the 5-LO pathway and exogenous LTB4 supplementation during experimental toxoplasmosis. For this purpose, susceptible C57BL/6 mice were orally infected with T. gondii and treated with LTB4 or MK886 (a selective leukotriene inhibitor through inhibition of 5-LO-activating protein [FLAP]). The parasitism, histology, and immunological parameters were analyzed. The infection decreased 5-LO expression in the small intestine, and treatment with MK886 reinforced this reduction during infection; in addition, MK886-treated infected mice presented higher intestinal parasitism, which was associated with lower local interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor (TNF) production. In contrast, treatment with LTB4 controlled parasite replication in the small intestine, liver, and lung and decreased pulmonary pathology. Interestingly, treatment with LTB4 also preserved the number of Paneth cells and increased α-defensins expression and IgA levels in the small intestine of infected mice. Altogether, these data demonstrated that T. gondii infection is associated with a decrease in 5-LO expression, and on the other hand, treatment with the 5-LO pathway product LTB4 resulted in better control of parasite growth in the organs, adding to the knowledge about the pathogenesis of T. gondii infection.

Portuguese National Registry on Cardiac Electrophysiology, 2017 and 2018. / Registo Nacional de Eletrofisiologia Cardíaca 2017­2018.

INTRODUCTION: The authors present the results of the national cardiac electrophysiology registry of the Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE) and the Portuguese Institute of Cardiac Rhythm (IPRC) for 2017 and 2018. METHODS: The registry is annual, voluntary, and observational. Data are collected retrospectively. Developments over the years and their implications are analyzed and discussed. RESULTS: In the 22 electrophysiology centers, 3407 ablations were performed in 2017 and 3653 ablations in 2018. Atrial fibrillation (AF) ablation was the most frequently performed procedure: 1017 ablations in 2017 and 1222 procedures in 2018. Of the patients undergoing AF ablation, 63% were male, 60% were between 50 and 69 years old and 74% had paroxysmal AF. Clinically relevant complications were reported in 0.8% of the procedures. In 2017, 216 ventricular tachycardia (VT) ablation procedures were performed in 15 centers. In 2018, 19 centers performed 249 VT ablations. About 45% of VT ablations were performed in patients with structural heart disease. Complications were reported in 3.2% of the procedures, including one death (0.2%). CONCLUSIONS: The national electrophysiology registry showed a sustained increase in the number of catheter ablations. In addition, procedural complexity increased and AF ablation assumed a dominant position among the procedures performed.

The Availability of Iron Is Involved in the Murine Experimental Toxoplasma gondii Infection Outcome.

Iron is an important constituent of our environment, being necessary for both mammalian and pathogenic protozoa survival. Iron-containing proteins exert a wide range of biological processes such as biodegradation and biosynthesis, as well as immune function, fetal development, and physical and mental well-being. This work aimed to investigate the effect of iron deprivation in Toxoplasma gondii infection outcome. C57BL/6 mice were orally infected with T. gondii and treated with an iron chelator, deferoxamine, or supplemented with iron (ferrous sulfate), and the parasitism as well as immunological and histological parameters were analyzed. It was observed that the infection increased iron accumulation in the organs, as well as systemically, and deferoxamine treatment diminished the iron content in serum samples and intestine. The deferoxamine treatment decreased the parasitism and inflammatory alterations in the small intestine and lung. Additionally, they partially preserved the Paneth cells and decreased the intestinal dysbiosis. The ferrous sulfate supplementation, despite not significantly increasing the parasite load in the organs, increased the inflammatory alterations in the liver. Together, our results suggest that iron chelation, which is commonly used to treat iron overload, could be a promising medicine to control T. gondii proliferation, mainly in the small intestine, and consequently inflammation caused by infection.

Hyperbaric oxygenation improves redox control and reduces mortality in the acute phase of myocardial infarction in a rat model.

Among the mechanisms of action of hyperbaric oxygenation (HBO), the chance of reducing injury by interfering with the mechanisms of redox homeostasis in the heart leads to the possibility of extending the period of viability of the myocardium at risk. This would benefit late interventions for reperfusion to the ischemic area. The objective of the present study was to investigate the changes in the redox system associated with HBO therapy maintained during the first hour after coronary occlusion in an acute myocardial infarction (MI) rat model. Surviving male rats (n=105) were randomly assigned to one of three groups: Sham (SH=26), myocardial infarction (MI=45) and infarction+hyperbaric therapy (HBO=34, 1 h at 2.5 atm). After 90 min of coronary occlusion, a sample of the heart was collected for western blot analysis of total protein levels of superoxide dismutase, catalase, peroxiredoxin and 3­nitrotyrosine. Glutathione was measured by enzyme­linked immunosorbent assay (ELISA). The detection of the superoxide radical anion was carried out by oxidation of dihydroethidium analyzed with confocal microscopy. The mortality rate of the MI group was significantly higher than that of the HBO group. No difference was noted in the myocardial infarction size. The oxidized/reduced glutathione ratio and peroxiredoxin were significantly higher in the SH and MI when compared to the HBO group. Superoxide dismutase enzymes and catalase were significantly higher in the HBO group compared to the MI and SH groups. 3­Nitrotyrosine and the superoxide radical were significantly lower in the HBO group compared to these in the MI and SH groups. These data demonstrated that hyperbaric oxygenation therapy decreased mortality by improving redox control in the hearts of rats in the acute phase of myocardial infarction.

Susceptibility of human villous (BeWo) and extravillous (HTR-8/SVneo) trophoblast cells to Toxoplasma gondii infection is modulated by intracellular iron availability.

Congenital toxoplasmosis is a serious health problem that can lead to miscarriage. HTR-8/SVneo is a first trimester extravillous trophoblast, while BeWo is a choriocarcinoma with properties of villous trophoblast cells. In the placenta, iron is taken up from Fe-transferrin through the transferrin receptor being the ion an important nutrient during pregnancy and also for Toxoplasma gondii proliferation. The aim of this study was to evaluate the role of iron in T. gondii proliferation in BeWo and HTR-8/SVneo cells and in human chorionic villous explants. The cells were infected with T. gondii, iron supplemented or deprived by holo-transferrin or deferoxamine, respectively, and parasite proliferation and genes related to iron balance were analyzed. It was verified that the addition of holo-transferrin increased, and DFO decreased the parasite multiplication in both trophoblastic cells, however, in a more expressive manner in HTR-8/SVneo, indicating that the parasite depends on iron storage in trophoblastic cells for its growth. Also, tachyzoites pretread with DFO proliferate normally in trophoblastic cells demonstrating that DFO itself does not interfere with parasite proliferation. Additionally, T. gondii infection induced enhancement in transferrin receptor mRNA expression levels in trophoblastic cells, and the expression was higher in HTR-8/SVneo compared with BeWo. Finally, DFO-treatment was able to reduce the parasite replication in villous explants. Thus, the iron supplementation can be a double-edged sword; in one hand, it could improve the supplement of an essential ion to embryo/fetus development, and on the other hand, could improve the parasite proliferation enhancing the risk of congenital infection.

La dieta en el paciente litiásico: una guía práctica / Diet in the lithiasic patient: A practical guide

La incidencia y prevalencia de la enfermedad litiásica en los países desarrollados ha aumentado en los últimos años. Debido a que la dieta es uno de los factores de riesgo de la urolitiasis, y tanto esta como el estilo de vida han evolucionado en las últimas décadas, dichos cambios podrían explicarnos el aumento en la causística de la litiasis renal. En el presente trabajo analizamos cuál ha sido el proceder del urólogo en cuanto al papel preventivo de la dieta en el paciente litiásico, qué evidencias científicas existen en cuanto a la relación entre dieta y litiasis y, en base a ello, qué recomendaciones generales dietéticas podemos dar actualmente a nuestros pacientes

The incidence and prevalence of lithiasic disease in developed countries has increased over the last years. Being diet one of the risk factors for urolithiasis, and having it evolved in conjunction with lifestyle over the last decades, such changes could explain the increase in lithiasis case-load. In this article, we analyze how the exercise of the urologist has been regarding the preventive role of diet in the lithiasis patient, what are the scientific evidences on the relationship of diet and lithiasis, and, on this base, what general dietetic recommendations we can give currently to our patients

Comment on "Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction".

OBJECTIVES: The objective of this clinical trial was to assess the safety and efficacy of carotid baroreflex activation therapy (BAT) in advanced heart failure (HF). BACKGROUND: Increased sympathetic and decreased parasympathetic activity contribute to HF symptoms and disease progression. BAT results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity. METHODS: Patients with New York Heart Association (NYHA) functional class III HF and ejection fractions < 35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance. RESULTS: One hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event-free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (­17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro-brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08). CONCLUSIONS: BAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro-brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF.

National registry on cardiac electrophysiology (2012).

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implantable cardioverter-defibrillator (ICD) implantations, the authors analyze the number and type of procedures performed during 2012 and compare these data with previous years. In 2012, a total of 2561 diagnostic electrophysiologic studies were performed, which were followed by ablation in 2017 cases, representing a steady situation compared with the previous year. There was a 12% increase in the number of ablation procedures for atrial fibrillation, making it for the first time the most frequent indication for ablation, overtaking atrioventricular nodal reentrant tachycardia. The total number of first ICD implantations was 1048 (around 100 per million population), of which 375 were cardiac resynchronization devices (BiV ICDs). This represents a slight decrease (3.3%) in the total number of new implants, with an increase of 10% in the number of BiV ICDs compared to the previous year. However, there was a considerable increase in the number of ICD generator replacements, resulting in an overall increase of 3.5% in implantations performed in 2012. Some comments are made regarding developments in this activity and its current status, and on some factors that may influence the dynamics of this area of interventional cardiology.

[National registry on cardiac electrophysiology (2010 and 2011)]. / Registo Nacional de Eletrofisiologia Cardíaca (2010 e 2011).

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implant cardioverter-defibrillators (ICDs), the authors analyze the number and type of procedures performed during 2010 and 2011 and compare these data with previous years. In 2011, a total of 2533 diagnostic electrophysiologic procedures were performed, which were followed by ablation in 2013 cases, a steady increase over previous years. The largest share of this increase compared to 2010 was in atrial fibrillation, which is now the second most frequent indication for ablation, after atrioventricular nodal reentrant tachycardia. The total number of ICDs implanted in 2011 was 1084, of which 339 were biventricular (BiV) cardiac resynchronization devices (BiV ICDs). This represents an increase in the total number relative to previous years, 2011 being the first year in which the rate of new ICD implantations in Portugal exceeded 100 per million population. However, compared to 2010, the number of BiV ICDs implanted decreased, despite the recent publication of updated European guidelines on device therapy in heart failure, which clarified and expanded the indications for implantation of these devices. Some comments are made on the current status of cardiac electrophysiology in Portugal and on factors that may influence its development in the coming years.

Effects of acute autonomic modulation on atrial conduction delay and local electrograms duration in paroxysmal atrial fibrillation.

UNLABELLED: Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. AIM: To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). METHODS AND RESULTS: 16P (9 men; 59±14years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58±11years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited - 6; sustained - 3), 68.8% (self-limited - 6; sustained - 5), and 50% (self-limited - 5; sustained - 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively (p=NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600ms, S2). P with PAF have longer IACT (p<0.05), a higher increase in both IACT, interACT (p<0.01) and electrograms duration (p<0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. CONCLUSION: Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration.

Induction of a hyperanxious state by antenatal dexamethasone: a case for less detrimental natural corticosteroids.

BACKGROUND: Synthetic glucocorticoids are commonly prescribed during pregnancy, despite a lack of systematic investigations of their potential impact on the developing brain and neurological and behavioral performance. METHODS: Neuroendocrine parameters and behavior in the adult offspring of pregnant Wistar rats treated antenatally with either dexamethasone (DEX) or corticosterone (CORT) were monitored; DEX (.1 mg/kg and 1 mg/kg) and CORT (25 mg/kg) were given to pregnant rat dams on gestation days 18 and 19. RESULTS: Despite normal basal levels of corticosterone, the adult offspring of mothers given DEX or CORT displayed abnormal responses in the dexamethasone-suppression test. Neither treatment influenced spatial memory performance, but both DEX and CORT facilitated development of depression-like behavior following chronic stress. The latter finding demonstrates that high-dose antenatal corticotherapy can impair the organism's resilience to stress in adulthood. Interestingly, comparison of the progeny of CORT-treated and DEX-treated mothers revealed that the latter were more anxious. CONCLUSIONS: Since DEX and CORT differ in their affinity for glucocorticoid and mineralocorticoid receptors and corticosteroid-binding globulin, our findings emphasize the need to consider the pharmacologic properties of antenatal corticotherapies and demonstrate the potential long-term benefits of ligands that can bind to both receptors.

Tratamento cirúrgico das hérnias inguinais com anestesia local / Surgical treatment of inguinal hernias with local anesthesia

Foi realizado bloqueio regional inguinal por infiltraçäo com lidocaína a 1% em 84 pacientes, para serem submetidos à hernioplastia inguinal pelo método de Bassini modificado. O estudo objetivou avaliar a utilizaçäo da anestesia local no tratamento das hérnias inguinais. Nos 84 pacientes estudados, as hérnias eram pequenas, redutíveis e näo recidivadas. Foram tratados a nível ambulatorial 58 casos e em regime de internaçäo hospitalar 26 casos. Quando a hérnia era a única afecçäo, os pacientes eram operados no centro cirúrgico ambulatorial e recebiam alta duas horas após a intervençäo, os pacientes eram operados no centro cirúrgico ambulatorial e recebiam alta duas horas após a intervençäo cirúrgica. Os pacientes que apresentavam doenças associadas compensadas foram internado e recebiam alta hospitalar no 2§ dia de pós-operatório. Em ambos os grupos, houve boa aceitaçäo da técnica anestésica; a incidência de complicaçöes foi reduzida, sendo a dor local a mais freqüente. Os autores concluem ser a anestesia local procedimento adequado para o tratamento cirúrgico das hérnias inguinais