Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Manometric study of the lower esophageal sphincter and esophagus in subtotal gastrectomy patients.

There is controversy in the literature regarding the motor function behavior of the lower esophageal sphincter and esophagus following partial gastrectomy. We studied 26 patients with gastric adenocarcinoma of the distal corpus and/or antrum who underwent radical subtotal gastrectomy with Roux-en-Y reconstruction. There were 15 women (57.69%) and 11 men (42.31%) with a mean age of 57.2 years; 21 were White (80.8%) and five were of African descent (19.2%). Before the surgery and 3 months afterwards, every patient underwent manometric and endoscopic examinations. The lower esophageal sphincter showed reductions in mean respiratory pressure (19.41-15.59 mmHg, P= 0.02) and maximum expiratory pressure (8.13-5.54 mmHg, P= 0.02) without significant alteration in diaphragmatic crura pressure (32.92-30.64 mmHg, P= 0.37). An increase in peristaltic wave amplitude (91.43-124.86 mmHg, P < 0.01) and peristaltic wave conduction velocity (3.29 cm/s to 4.23 cm/s; P= 0.024) were detected in esophageal function. The presence of erosive esophagitis decreased from 10 (38.46%) patients to none (P= 0.002). We concluded that following surgery the lower esophageal sphincter function was impaired, through decreased pressure in the esophageal component without alteration in diaphragmatic crura pressure. On the other hand, there was significant increase in peristaltic wave amplitude and velocity, and improvement of the erosive esophagitis. The authors suggest that subtotal gastrectomy, with gastroesophageal junction preservation, and Roux-en-Y reconstruction should be the preferred operation for distal gastric cancer to minimize esophageal dysfunction and gastroesophageal reflux disease.

El papel de los radicales libres en la etiología de la ateroesclerosis / Atherosclerosis and the rol of ROS and RNS

Los mecanismos moleculares que originan la aterosclerosis no están claros, sin embargo se conoce que anormalidades en las señales mediadas por las especies reactivas de oxígeno (ERO) y de nitrógeno (ERN) pueden desencadenar la patogénesis de la enfermedad cuando se asocian con factores de riesgo como hiperlipidemia, hiperglicemia y cambios en las fuerzas hemodinámicas. En esta revisión nos proponemos resaltar los diferentes mecanismos desencadenados por las ERO y ERN que llevan al desarrollo de la aterogénesis incluyendo la regulación de la transcripción de varios genes

Two-dimensional electrophoresis and characterization of antigens from Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is a fungal pathogen of humans. To identify antigens from P. brasiliensis we fractionated a crude preparation of proteins from the fungus and detected the IgG reactive proteins by immunoblot assays of yeast cellular extracts with sera of patients with paracoccidioidomycosis (PCM). We identified and characterized six new antigens by amino acid sequencing and homology search analyses with other proteins deposited in a database. The newly characterized antigens were highly homologous to catalase, fructose-1,6-biphosphate aldolase (aldolase), glyceraldehyde-3-phosphate dehydrogenase, malate dehydrogenase and triosephosphate isomerase from several sources. The characterized antigens presented preferential synthesis in yeast cells, the host fungus phase.

Molecular cloning, characterization and expression of the heat shock protein 60 gene from the human pathogenic fungus Paracoccidioides brasiliensis.

A gene encoding the heat shock protein (HSP) 60 from Paracoccidioides brasiliensis (Pb) was cloned and characterized. The hsp60 gene is composed of three exons divided by two introns. Structural analysis of the promoter detected canonical sequences characteristic of regulatory regions from eukaryotic genes. The deduced amino acid sequence of the Pb hsp60 gene and the respective cloned cDNA consists of 592 residues highly homologous to other fungal HSP60 proteins. The hsp60 gene is present as a single copy in the genome, as shown by Southern blot analysis. The HSP60 protein was isolated from Pb yeast cellular extracts. N-terminal amino acid sequencing of HSP60 confirmed that the cloned hsp60 gene correlated to the predicted protein in Pb. HSP60 expression appeared to be regulated during form transition in Pb, as different levels of expression were detected in in vitro labeling of cells and northern blot analysis. The complete coding region of Pb hsp60 was fused with plasmid pGEX-4T-3 and expressed in Escherichia coli as a glutathione S-transferase-tagged recombinant protein. The protein reacted with a mouse monoclonal antibody raised to a human recombinant HSP60. Western immunoblot experiments demonstrated that the recombinant protein and the native HSP60 were recognized by sera from humans with paracoccidioidomycosis (PCM).

Nontoxic, mutagenic, and clastogenic activities of Mate-Chimarrão (Ilex paraguariensis).

Aqueous extracts of Ilex paraguarariensis (mate-chimarrão), a species that belongs to the Aquifoliaceae family, were analyzed for the presence of genotoxic, mutagenic, and clastogenic activities through bacterial trials based on the induction of the SOS functions, as well as in human lymphocytes in vitro and in mammalian cells in vivo. The extracts of mate-chimarrão were genotoxic, as assessed by lysogenic induction in Escherichia coli, and they also induced mutagenesis in Salmonella typhimurium. They addition of S9 microsomal fraction, catalase, thiourea, or dipyridyl counteracted the genotoxic activity of mate-chimarrão, suggesting that oxygen reactive species play an essential role in the genotoxicity of mate-chimarrão extracts. The extracts were not clastogenic in vivo (bone marrow cells of rats) in our experimental conditions, but we have observed an increased frequency of chromosomal aberrations in mate-chimarrão-treated human peripheral lymphocytes. Our results suggest that a high consumption of mate-chimarrão can potentiate carcinogenesis in the human oropharynx and esophagus.

Plasma cell granuloma of the larynx as a cause of sudden asphyxial death.

A unique case of plasma cell granuloma of the larynx associated with sudden death in a young HIV-positive woman is described. The plasma cell infiltration fulfilled the criteria for plasma cell granuloma, showing characteristic histologic and immunohistochemical features (polyclonality). A review of the most recent literature is provided.

Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms.

Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the Sapindaceae family, were analyzed for the presence of genotoxic activities in bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic induction in Escherichia coli and they were also able to induce mutagenesis in Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting that oxygen reactive species play an essential role in the genotoxicity of aqueous guarana extracts. The genotoxic activity in the extracts was related to the presence of a molecular complex formed by caffeine and a flavonoid (catechin or epicatechin) in the presence of potassium.