Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents.

A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both and . Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in tests against DNA polymerase with IC values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy--chromen-2-one () and 4-((acetylthio)methyl)-2-oxo--chromen-7-yl acetate () showed the most promising anti-polymerase activity with IC values of 20.

Insights of tricuspid regurgitation mechanisms in patients with right ventricular apical pacing by three-dimensional echocardiography.

Objective: Device lead-induced tricuspid regurgitation (LITR) mechanisms are well-defined by 3D transthoracic echocardiography (3D-TTE). There is a lack of data on the Latin-American population. The objective of this study was to describe the prevalence of several mechanisms and insights in patients with permanent right ventricular (RV) implanted devices by 3D-TTE examination.

Diuretic activity of extracts in Wistar rats.

has been used in central-west region of Argentina in traditional medicine as diuretic plant. The aim of this present study was to evaluate the diuretic activity of in-vivo. We used dried aerial parts, and infusions from these were orally administered to Wistar rats.

Aromaticity at position 39 in α-synuclein: A modulator of amyloid fibril assembly and membrane-bound conformations.

Recent studies revealed that molecular events related with the physiology and pathology of αS might be regulated by specific sequence motifs in the primary sequence of αS. The importance of individual residues in these motifs remains an important open avenue of investigation. In this work, we have addressed the structural details related to the amyloid fibril assembly and lipid-binding features of αS through the design of site-directed mutants at position 39 of the protein and their study by in vitro and in vivo assays.

Left ventricular dyssynchrony as result of right ventricular permanent apical pacing.

La estimulación apical permanente del ventrículo derecho (VD) puede producir asincronía del ventrículo izquierdo (VI) desde los puntos de vista eléctrico y mecánico. Este fenómeno es efecto de una alteración de la activación normal del VI que lleva al deterioro de la función sistólica y la aparición de insuficiencia cardíaca y sus efectos deletéreos relacionados. Para el estudio de la asincronía eléctrica del VI se ha propuesto en fecha reciente el nuevo sistema electrocardiográfico no invasivo Synchromax, que puede cuantificar el grado de asincronía eléctrica que causa una subsecuente asincronía mecánica.

Verbascoside, synthetic derivatives and other glycosides from Argentinian native plant species as potential antitumoral agents.

A phytochemical study was performed on three native plant species from the central-western zone of Argentina: Grisebach Torr. & A. Gray and L.

Metal coordination and peripheral substitution modulate the activity of cyclic tetrapyrroles on αS aggregation: a structural and cell-based study.

The discovery of aggregation inhibitors and the elucidation of their mechanism of action are key in the quest to mitigate the toxic consequences of amyloid formation. We have previously characterized the antiamyloidogenic mechanism of action of sodium phtalocyanine tetrasulfonate ([Na(HPcTS)]) on α-Synuclein (αS), demonstrating that specific aromatic interactions are fundamental for the inhibition of amyloid assembly. Here we studied the influence that metal preferential affinity and peripheral substituents may have on the activity of tetrapyrrolic compounds on αS aggregation.

Interaction of Cu(i) with the Met-X-Met motif of alpha-synuclein: binding ligands, affinity and structural features.

The identity of the Cu(i) binding ligands at Met-X3-Met site of AcαS and its role into the affinity and structural properties of the interaction were elucidated by NMR spectroscopy. We provide evidence that the source of ligands for Cu(i) binding to the Met-X3-Met site comes from the N-terminal acetyl group and the Met-1, Asp-2 and Met-5 residues. From the study of site-directed mutants and synthetic peptide models of αS we demonstrated the critical role played by Met-1 and Met-5 residues on the binding affinity of the Cu(i) complex, acting as the main metal anchoring residues.

Pacemaker-mediated tachycardia with narrow QRS complexes.

Inverted connection of the atrial and ventricular leads is an unusual circumstance during the implantation of a dual-chamber pacemaker. Yet, PMT may present in the absence of complex mechanisms. The detection and termination algorithms used by the device proved to be efficient for the adequate diagnosis and treatment.

DNA Related Enzymes as Molecular Targets for Antiviral and Antitumoral Chemotherapy. A Natural Overview of the Current Perspectives.

Background: The discovery of new chemotherapeutic agents still remains a continuous goal to achieve. DNA polymerases and topoisomerases act in nucleic acids metabolism modulating different processes like replication, mitosis, damage repair, DNA topology and transcription. It has been widely documented that Polymerases serve as molecular targets for antiviral and antitumoral chemotherapy.

Masquerading bundle branch block obscuring the diagnosis of Brugada syndrome: an electrocardiographic and vectorcardiographic study.

We describe the induction of a masquerading bundle branch block in two patients with Brugada syndrome following the administration of Ajmaline. The development of this conduction disturbance prevented the correct electrocardiographic diagnosis. However, the simultaneously obtained vectocardiogram identified both the Brugada pattern and the masquerading bundle branch block.

Cytotoxic and Antitumor Activity of some Coumarin Derivatives.

Several natural and synthetic coumarins were assayed against different cancer cell lines. Four of them have shown cytotoxicity against a panel of three human solid tumor cell lines (HeLa, T-47D, and WiDr) and a clearly activity/hydrophobicity relationship. Compound 13 proved to be the most active product in all cell lines tested, with values of 8.

Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs.

Human Immunodeficiency Virus (HIV) is the viral agent of Acquired Immunodeficiency Syndrome (AIDS), and at present, there is no effective vaccine against HIV. Reverse Transcriptase (RT) is an essential enzyme for retroviral replication, such as HIV as well as for other RNA infectious viruses like Human T lymphocyte virus. Polymerases act in DNA metabolism, modulating different processes like mitosis, damage repair, transcription and replication.

A new iridoid, verbascoside and derivatives with inhibitory activity against Taq DNA polymerase.

DNA polymerases are enzymes that play a crucial role in DNA metabolism such as replication, repair, transcription, recombination, and chromosome segregation during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol, 2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by chemical transformation.

Chemistry and biological activity of coumarins at molecular level.

Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.

The multiple electrocardiographic manifestations of ventricular repolarization memory.

T wave "memory" is a peculiar variety of cardiac remodeling caused by a transient change in the course of ventricular depolarization (due to ventricular pacing, rate-dependent intraventricular block, ventricular preexcitation or tachyarrhythmias with wide QRS complexes). It is usually manifested by inverted T waves that appears when normal ventricular activation is restored. This phenomenon is cumulative and occurs earlier if the ventricular myocardium has previously been exposed to the same conditioning stimuli.

A reappraisal on lidocaine-sensitive repetitive, uniform atrial tachycardia.

Background: Lidocaine sensitive, repetitive atrial tachycardia is an unusual arrhythmia whose electrophysiologic substrate remains undefined. We aimed to analyze the electropharmacologic characteristics of this arrhythmia with emphasis on its cellular substrate and response to drug challenges.

Methods: We retrospectively analyzed a series of 18 patients from an electrocardiographic and electrophysiologic perspective and the response to pharmacological challenge.

Intermittent capture of the right ventricular outflow tract by atrial pacing in a patient with a dual-chamber pacemaker.

We describe a previously unreported phenomenon of intermittent outflow right ventricular tract capture from the atrial lead of a dual-chamber pacemaker. This was more obvious at slower paced atrial rates and disappeared by decreasing the atrial pulses voltage. Electroanatomical mapping showed that the onset of activation was nearly simultaneous at the insertion site of the atrial lead and at an intermediate level of the right ventricular outflow tract.