Acute hemodynamic effect of inhaled iloprost in pulmonary artery hypertension evaluated with echocardiography

Doppler echocardiography is useful in the initial evaluation and long-term follow-up of patients with pulmonary artery hypertension. Aerosolised iloprost has been shown to reduce pulmonary pressure immediately after inhalation. We report the echocardiographic findings in a patient with severe pulmonary hypertension, before and after the inhalation of aerosolized iloprost. These findings illustrate the acute influence of iloprost in right and left ventricular hemodynamics and morphology. These findings were reproduced in subsequent echocardiographic evaluations

8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity

Caffeine is one of the most worldwide consumed methylxanthines. It is well-known for its thermogenic and cell metabolism modulating effects. Based on methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine (PTX) is a novel adenosine antagonist with higher receptor affinity than caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger than those of caffeine. For that purpose, murine 3T3-L1 cells were cultured in the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 μM) for 24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and lactate dehydrogenase (LDH) release. Cell metabolites released to the culture medium were identified and quantified by proton nuclear magnetic resonance (1H NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX displayed no signs of cytotoxicity at all studied concentrations. When compared with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as well as lactate, alanine, and acetate production. Additionally, PTX decreased protein oxidation, thus protecting against oxidative stress-induced damage. These results illustrate that PTX is a stronger and less cytotoxic caffeine substitute with potential applications as metabolic modulator and a good candidate for novel drug design.info:eu-repo/semantics/publishedVersio

Clinical significance of intraventricular gradient during effort in an adolescent karate player

The authors report the case of a 16-year-old boy who practices karate, who underwent medical evaluation because of atypical chest discomfort, related to strenuous effort. The ECG and echocardiogram findings were normal. The young boy did a treadmill stress test which was positive for myocardial ischemia. Late during the investigation, he underwent treadmill stress echocardiography, during which he developed intraventricular gradient of over 130 mmHg with end-systolic peak and systolic anterior movement (SAM) of the mitral valve. These echocardiographic findings were not present at rest and disappeared shortly after termination of exercise. The authors discuss the significance of this event. This leads us to advise withdrawal from participation in competitive sport according to the recomendations of the European Society of Cardiology. A possible role of exercise stress echo for intraventricular pressure gradient assessment in symptomatic athletes with structurally normal hearts is suggested

The usefulness of contrast during exercise echocardiography for the assessment of systolic pulmonary pressure

<p>Abstract</p> <p>Background</p> <p>The systolic pulmonary artery pressure (PAPs) can be accurately estimated, non-invasively, using continuous-wave Doppler (CWD) ultrasound measurement of the peak velocity of a tricuspid regurgitant (TR) jet.</p> <p>However, it is often difficult to obtain adequate tricuspid regurgitation signals for measurement of PAPs, what could lead to its underestimation. Therefore, utilization of air-blood-saline contrast has been implemented for the improvement of Doppler signal in several clinical contexts.</p> <p>It is now recommended in the evaluation of patients with pulmonary hypertension. Physical activity is severely restricted in patients with PAH, being exertional dypnea the most typical symptom. Exercise stress echo-Doppler imaging allows assessment of the response to exercise. It is an excellent screening test for patients with suspected PAH. Our purpose was to evaluate the value and accuracy of agitated saline with blood contrast echocardiography, in the improvement of the Doppler signal, to quantify PAPs during treadmill exercise-echocardiography.</p> <p>Purpose</p> <p>To evaluate the value of contrast echocardiography, using agitated saline with blood, in the improvement of the Doppler signal used to quantify the pulmonary artery systolic pressure during exercise.</p> <p>Methods</p> <p>From a total of 41 patients (pts), we studied 38 pts (93%), 35 women, aged 54 ± 12 years-old. 27 with the diagnosis of systemic sclerosis, 10 with history of pulmonary embolism and one patient with a suspected idiopathic PAH, who were referred to the Unity of Heart Failure and Pulmonary Hypertension for screening of PAH. According to the Unity protocol, a transthoracic echocardiogram was made, in left decubitus (LD), with evaluation of right ventricle-right atria gradient (RV/RAg). A peripheral venous access was obtained, with a 3-way stopcock and the patients were placed in orthostatism (O), with a new evaluation of RV/RAg. Exercise echocardiography (EE) was begun, with evaluation of RV/RAg at peak exercise (P) and afterwards agitated saline (8 cc with 1 cc of air and 1 cc of blood) was injected, followed by a new evaluation of RV/RAg (PC) and then the interruption of the EE. Pulmonary Hypertension was diagnosed when RV/RAg at the end of the exercise was superior to 40 mmHg.</p> <p>Results</p> <p>The quality of Doppler signal was deteriorated in 5 pts, maintained in 6 pts and improved in 26 pts, with the use of contrast. In one patient, an interventricular septal defect was diagnosed. In 6 pts, a Doppler signal was only obtained with the use of contrast. In 15 pts, a RV/RAg superior to 40 mmHg was only obtained with the use of contrast. Of these, 9 have already been submitted to right heart cathetherism, that confirmed the diagnosis of pulmonary hypertension in 5 of them (56%). RV/RAg (P) was 44 ± 11 mmHg and RV/RAg (PC) was 54 ± 11 mmHg, p < 0,001.</p> <p>Conclusion</p> <p>1. The method is applicable in a large number of patients. 2. RV/RA gradients obtained at peak exercise are higher with the use of contrast, and the clinical meaning of this difference should be evaluated in a larger number of pts submitted to right heart cathetherism. The high number of false positives should lead to a higher diagnostic threshold. 3. This method seems to have relevant clinical value in the diagnosis of pulmonary arterial hypertension.</p

Antioxidants and Male Infertility

Oxidative stress has been associated with decreased sperm quality and male infertility [...

Aquaporins and male (in)fertility: Expression and role throughout the male reproductive tract

Aquaporins (AQPs) are a family of transmembrane channel proteins responsible for the transport of water and small uncharged molecules. Thirteen distinct isoforms of AQPs have been identified in mammals (AQP0-12). Throughout the male reproductive tract, AQPs greatly enhance water transport across all biological barriers, providing a constant and expeditious movement of water and playing an active role in the regulation of water and ion homeostasis. This regulation of fluids is particularly important in the male reproductive tract, where proper fluid composition is directly linked with a healthy and competent spermatozoa production. For instance, in the testis, fluid regulation is essential for spermatogenesis and posterior spermatozoa transport into the epididymal ducts, while maintaining proper ionic conditions for their maturation and storage. Alterations in the expression pattern of AQPs or their dysfunction is linked with male subfertility/infertility. Thus, AQPs are important for male reproductive health. In this review, we will discuss the most recent data on the expression and function of the AQPs isoforms in the human, mouse and rat male reproductive tract. In addition, the regulation of AQPs expression and dysfunction linked with male infertility will be discussed

Mitochondrial activation and reactive oxygen-species overproduction during sperm capacitation are independent of glucose stimuli

Spermatozoa capacitation is a complex process that requires specific ionic and energetic conditions to support biochemical alterations leading to motility hyperactivation. However, human sperm capacitation is still poorly understood. Herein, we studied the effects of glucose on human sperm capacitation. Healthy men seminal samples (n = 55) were submitted to a density gradient centrifugation and incubated in capacitating conditions in the absence or presence of increasing glucose concentrations (0, 5.5, 11, and 22 mM). Viability and total motility were accessed. Phosphotyrosine levels were measured. Mitochondrial activity and endogenous ROS production were evaluated. Oxidative stress-induced damage was analyzed. Culture media was collected and analyzed by1H-NMR. Our results show that glucose is essential for human sperm capacitation and motility. Notably, we observed that mitochondrial activity increased even in the absence of glucose. This increased mitochondrial activity was followed by a ROS overproduction, although no oxidative stress-induced damage was detected. Our results show that glucose is essential for capacitation but mitochondrial activation is independent from its stimuli. ROS overproduction may take part on a finely regulated signaling pathway that modulates or even activates capacitation. Taken together, our results constitute a paradigm shift on human sperm capacitation physiology.The work was co-funded by FEDER through the COMPETE/QREN, FSE/POPH to Marco G. Alves (IFCT2015, PTDC/MEC-AND/28691/2017), UMIB (PEst-OE/SAU/UI0215/2019) and QOPNA (UID/QUI/00062/2019); co-funded by the EU Framework Programme for Research and Innovation H2020 (POCI/COMPETE2020). This work was supported by “Fundação para a Ciência e a Tecnologia”—FCT to David F. Carrageta (SFRH/BD/136779/2018) and Bárbara Guerra-Carvalho (PTDC/MEC-AND/28691/2017)