Identification of (1H)-pyrroles as histone deacetylase inhibitors with antitumoral activity.

Histone deacetylases (HDACs) play a key role in the regulation of gene expression and chromatin structure, and drugs targeting these enzymes might have an important impact in the treatment of human cancer. Herein, we report the characterization of (1H)-pyrroles as a new subfamily of HDAC inhibitors obtained by computational modeling of class-I human HDACs. From a functional standpoint, (1H)-pyrroles are powerful inductors of acetylation of histones H3 and H4, and restore the expression of growth-inhibitory genes. From a cellular view, these compounds cause a marked decrease in the viability of cancer cells in vitro and in vivo, associated with a cell-cycle arrest at G2/M and an inhibition of angiogenesis. Thus, (1H)-pyrroles emerge as a novel group of HDAC inhibitors with promising antitumoral features.

[Influence of postural changes on the variations of blood volume in hemodialysis and reincidence post-dialysis blood volume]. / Influencia de los cambios posturales en las variaciones de la volemia en hemodiálisis y rebote volémico post- diálisis.

The aim of the present work is to study the possible increment of blood volume, in the seated as well as the lying position, and to analyse the influence of changes of posture on the changes of blood volume during the hemodialysis. 17 patients were studied, evaluating the variations of the hematocrit in the extracorporeal circuit on entry into the dialyzer, by means of a photometric system (Crit-Line Instrument, Izasa). Every 15 minutes the values of the hematocrit were taken and heir repercussion in the blood volume in different changes of posture. Initially all of the patients improved their blood volume, both seated and lying down. During the session of hemodialysis and ultrafiltration, with the patient in a seated position, an important drop in the blood volume was noticed; this was the case in the 1st, 2nd and 3rd hours. This drop improved when the patient adopted a lying position and there was a "reincidence of post-dialysis blood volume" at the end. According to these results, the supine posture improves the refill, confirming that the patients position influences the vascular refill.

[Aortic coarctation in the first 3 months of life. Surgical results]. / Coartación de aorta en los primeros 3 meses de vida. Resultados quirúrgicos.

Between January 1973 and September 1989, 51 patients younger than 3 months with coarctation of the aorta underwent surgery. All of them had atrio-ventricular and ventriculo-arterial concordance with well developed ventricular cavities. Thirty-four were male and 17 female. Thirty five had associated anomalies and catheterism was done in 36 before surgical correction. The surgical procedures we used were 19 subclavian plasty (Waldhausen), 13 end-to-end anastomosis, 13 Alvarez technique and three goterex parch. Twelve died (23.5%), three during surgery and the others in a period of 3 to 20 days after surgery. Eight were younger than 17 days, seven had aortic arch hypoplasia associated and six had ventricular septal defect (five with pulmonary hypertension). Other ten developed recoarctation (gradient greater than 20 mmHg) between 10 days and 8 months after first intervention (media = 3 months). Five had previously end-to-end correction (41.6%), two angioplasty with parch (66%), two Alvarez (20%) and one Waldhausen (7%). The correction of the recoarctation required surgery in 4 patients (three with angioplasty with parch and one with end to end correction), and the other six underwent angioplasty with catheter-balloon. None of the 15 patients without previous catheterism died, and neither did those who underwent surgery during the last 4 years. The associated anomalies required a second time surgery. We conclude that morbimortality is related to the aortic arch hypoplasia, pulmonary hypertension and surgery during the first 2 weeks. We recommend surgery without previous catheterism. The recoarctation is more frequent in patients with end to end correction, without an increase of the mortality.

[Dilated myocardiopathy in children]. / Miocardiopatía dilatada en el niño.

Between 1971-1988 we have studied 46 children with dilated cardiomyopathy. Twenty were males and 18 females, with a median age of 17 months (range from 1 day to 11 years). The incidence of 3.4 cases a year during the first nine years dropped to 1.3 cases a year in the following years. Two patients were siblings. Seventeen patients were studied with Eco-Doppler, cardiac catheterization and angiocardiography. The most frequent presentation was heart failure, present in 45 cases (98%). By bidimensional echocardiography it was observed that all patients had a dilated left ventricle, with a left atrial/aorta ratio of 1.5 +/- 0.3; the ejection fraction was diminished in 12 patients (11-36%) and the length of the left ventricle in the long parasternal axis view 4.2 +/- 0.7. All the patients studied had an elevated telediastolic pressure in the left ventricle, four with pulmonary artery pressure of 96 +/- 11 and seven with right atrial pressure of 24 +/- 5. There was mitral insufficiency in 4 patients and tricuspid insufficiency in three. Clinical course was favorable in 18 patients with median age at present of 112 months (range: 11 months to 15 years). The last 6 patients, treated with vasodilators, are living. In conclusion, dilated cardiomyopathy is a moderately frequent disease, with trend to diminish in incidence prognosis improved after treatment with vasodilator was introduced, and easily assessed with non-invasive methods.