Derrame pleural e hipertensión pulmonar en un paciente con enfermedad de Parkinson en tratamiento con cabergolina

Cabergoline is a synthetic dopamine agonist used to treat Parkinson disease. The drug occasionally induces pleuropulmonary adverse effects, which manifest as pleural thickening or effusion, interstitial pneumonitis, pulmonary infiltrates, or fibrosis. We report a rare case of pleural effusion and severe pulmonary hypertension in a 79-year-old man with Parkinson disease who had been treated with cabergoline for 1 year. The symptoms disappeared 10 months after the drug was discontinued.     

The Na,K-ATPase alpha4 isoform from humans has distinct enzymatic properties and is important for sperm motility

In the rat, the Na,K-ATPase alpha4 isoform exhibits unique enzymatic characteristics and is important for sperm motility. In this work, we studied expression, localization and function of alpha4 in human spermatozoa. We show two catalytically active Na,K-ATPase alpha polypeptides with different ouabain affinity and identified expression of alpha1, alpha4, beta1 and beta3 isoforms in the gametes. In addition, human sperm presented two Na,K-ATPases composed of alpha4, alpha4beta1 and alpha4beta3. Kinetic analysis of these isozymes produced in insect cells showed that, compared with human alpha1beta1, alpha4beta1 and alpha4beta3 exhibit higher Na(+) and lower K(+) affinity and higher sensitivity to ouabain. These particular enzymatic properties suggested a role for alpha4 in sperm function. Using computer-assisted sperm analysis (CASA), we found that ouabain inhibition of alpha4 significantly decreased percentage sperm motility. In contrast, ouabain did not affect linearity of forward progression, amplitude of lateral head displacement, beat cross frequency and sperm straight-line, curvilinear or average path velocities. This suggests a primary role of alpha4 in flagellar motility. Accordingly, we found alpha4 in the sperm tail, predominating in the mid-piece of the flagellum. Therefore, similar to the rat ortholog, human Na,K-ATPase alpha4 isoform has a distinct activity that is essential for sperm function.     

Soluble sustained release gene delivery system

Delivery of genetic substance to target cells remains an obstacle for efficient utilization of gene therapy approaches. In this study, we describe a formulation of methacrylate acid copolymer carrier of DNA, in which the release rate of the gene can be controlled by pH. Plasmid release was coupled with the polymer's dissolution, which was accelerated in alkali conditions. The released plasmid was intact and bioactive, although alteration from closed circular supercoil to relaxed conformation was observed. Confocal laser scanning microscopy detected the plasmid DNA along the central layers of the polymeric film. Gene delivery systems controlled by the dissolution of the polymeric films offer flexibility in quantity and size of the incorporated DNA, and therefore could have a potential for in vivo use.     

Experimental verification and clinical implementation of a commercial Monte Carlo electron beam dose calculation algorithm

This study describes the modeling and the experimental verification and clinical implementation of the alpha release of Pinnacle3 Monte Carlo (MC) electron beam dose calculation algorithm for patient-specific treatment planning. The MC electron beam modeling was performed for beam energies ranging from 6 to 18 MeV from a Siemens (Primus) linear accelerator using standard-shaped electron applicators and 100 cm source-to-surface distance (SSD). The agreement between MC calculations and measurements was, on average, within 2% and 2 mm for all applicator sizes. However, differences of the order of 3%-4% were noted in the off-axis dose profiles for the largest applicator modeled and for all energies. Output factors were calculated for standard electron cones and square cutouts inserted in the 10 x 10 cm2 applicator for different SSDs and were found to be within 4% of measured data. Experimental verification of the MC electron beam model was carried out using an ionization chamber and film in solid-water slab and anthropomorphic phantoms containing bone and lung materials. Agreement between calculated and measured dose distributions was within +/-3%. Clinical comparison was performed in four patient treatment plans with lesions in highly irregular anatomies, such as the ear, face, and breast, where custom-designed bolus and field shaping blocks were used in the patient treatments. For comparison purposes, treatment planning was also performed using the conventional pencil beam (PB) algorithm with the Pinnacle3 treatment planning system. Differences between MC and PB dose calculations for the patient treatment plans were significant, particularly in anatomies where the target was in close proximity to low density tissues, such as lung and air cavities. Concerning monitor unit calculations, the largest differences obtained between MC and PB algorithms were between 4.0% and 5.0% for two patients treated with oblique beams and involving highly irregular surfaces, i.e., breast and cheek. Clinical results are reported for overall uncertainty values (averaged over voxels with doses >50% dosemax) ranging from 2% to 0.3% and calculations were performed using cubic voxels with side 0.3 cm. Timing values ranged from 2 min to 24.5 h, depending on the field size, beam energy, number, and thickness of computed tomography slices used to define the patient's anatomy for the overall uncertainty values mentioned above.     

Acute coronary syndrome. Physiopathology and genetics

The acute coronary syndrome (ACS) is characterized by a spectrum of arterial diseases that include unstable angina and myocardial infarction. In the last 10 years, ACS has become the cause of up to 29% of deaths in the industrialized countries, becoming the main cause of death, and it will most probably stay that way for the year 2020. The physiopathogenesis of ACS include oxidative, inflammatory, and thrombotic processes. Diverse molecules participate in the processes, increasing of decreasing the damage. The genes that encode these molecules have been associated with the disease. However, in some cases inconsistent results in different populations have been reported. In this review the physiopathogenesis and the role of several candidate genes involved in the pathogenesis of ACS are discussed.     

A standardized technique for performing thromboelastography in rodents

Thromboelastography (TEG), used in liver transplant and cardiac surgery for nearly 50 years, has recently been applied to the trauma setting. Rodents are used widely for shock research, but are known to have differences in their coagulation system compared with humans. Consequently, the appropriate technique for performing TEG requires modification of the standard clinical protocol. Thromboelastography was performed with blood collected from the femoral artery of rodents, and technical modifications were tested to optimize results. Analysis of citrated whole blood using TEG revealed a more rapid onset of coagulation in rats compared with humans. The reference ranges of TEG parameters for Sprague-Dawley rats are detailed. Citrated native whole blood is the optimal TEG method in the assessment of coagulation in rodents. Investigators using TEG for research purposes should establish their own reference ranges to determine normal values for their target population.