Ajuste del tratamiento farmacológico a las guías de práctica clínica en pacientes octogenarios con infarto agudo de miocardio / Drug treatment adjustment to the clinical guidelines in octagenarians with acute myocardial infarction

Objetivo: Determinar si existe una asociación lineal de la edad y la administración de aspirina ,betabloque antes, inhibidores de la enzima convertidora de la angiotensina y estatinas, en qué medida los pacientes de edad avanzada reciben estos tratamientos y si la edad se asocia de forma independiente a estos tratamientos. Diseño: Estudio de cohortes prospectivo. Ámbito: Unidades Coronarias de 2 hospitales de la Región de Murcia Pacientes: Pacientes consecutivos ingresados con el diagnóstico de infarto agudo de miocardio entre enero de 1998 y enero de 2008.Intervenciones: Ninguna. Variables principales: Las relacionadas con la administración de aspirina, betabloqueantes, inhibidores de la enzima convertidora de la angiotensina y estatinas durante la estancia en la Unidad Coronaria. Resultados: Respecto al resto de pacientes, los octogenarios recibieron en similar proporción inhibidores de la enzima convertidora de la angiotensina (70,8 vs 69,3%, p=0,41) y con menor frecuencia aspirina (90,4 vs 94,6%, p<0,001), betabloqueantes (44,4 vs 69,4%, p<0,001) y estatinas(47,6 vs 64,7%, p<0,001). Solo pudo demostrarse una disminución brusca y significativa en la administración de estatinas a partir de los 80 años. La edad se asoció independientemente con la administración de betabloqueantes (OR 0,59; IC95% 0,47 - 0,73) y estatinas (OR 0,78;IC95% 0,65 - 0,95). La menor administración de estos fármacos también se asoció a una mayor (..) (AU)

Objectives: To determine whether there is a linear association of age and aspirin, beta-blockers, angiotensin-converting enzyme inhibitors and statins; the extent to which elderly patients receive these treatments; and whether age is independently associated with these treatments. Design: A prospective cohort study. Setting: Coronary Unit of two hospitals in the Region of Murcia (Spain).Patients: Consecutive patients admitted with the diagnosis of acute myocardial infarction between January 1998 and January 2008.Interventions: None. Main outcomes: Those related to the administration of aspirin, beta-blockers, angiotens nconverting enzyme inhibitors and statins during stay in the Coronary Care Unit. Results: Regarding the remaining patients, octogenarians received a similar proportion of angiotensin-converting enzyme inhibitors (70.8% vs. 69.3%, p=0.41) and less often aspirin (90.4%vs. 94.6%, p<0.001), beta-blockers (44.4% vs. 69.4%, p<0,001) and statins (47.6% vs. 64.7%,p<0.001). We were only able to demonstrate an abrupt and significant decrease in the use of statins after 80 years of age. Patient age was independently associated with the use of beta blockers (OR 0.59; 95%CI 0.47 - 0.73) and statins (OR 0.78; 95%CI 0.65 - 0.95). The lesser administration of these drugs was also associated with early mortality (OR 0.17, 95%CI 0.09 to0.33 and OR 0.14; 95%CI 0.08 to 0.23, respectively).Conclusions: Octogenarians less often receive aspirin, beta-blockers and statins, though old age was not an independent factor associated with lesser aspirin use (AU)

[Drug treatment adjustment to the clinical guidelines in octagenarians with acute myocardial infarction]. / Ajuste del tratamiento farmacológico a las guías de práctica clínica en pacientes octogenarios con infarto agudo de miocardio.

OBJECTIVES: To determine whether there is a linear association of age and aspirin, betablockers, angiotensin-converting enzyme inhibitors and statins; the extent to which elderly patients receive these treatments; and whether age is independently associated with these treatments. DESIGN: A prospective cohort study. SETTING: Coronary Unit of two hospitals in the Region of Murcia (Spain). PATIENTS: Consecutive patients admitted with the diagnosis of acute myocardial infarction between January 1998 and January 2008. INTERVENTIONS: None. MAIN OUTCOMES: Those related to the administration of aspirin, betablockers, angiotensin-converting enzyme inhibitors and statins during stay in the Coronary Care Unit. RESULTS: Regarding the remaining patients, octogenarians received a similar proportion of angiotensin-converting enzyme inhibitors (70.8% vs. 69.3%, p=0.41) and less often aspirin (90.4% vs. 94.6%, p<0.001), betablockers (44.4% vs. 69.4%, p<0,001) and statins (47.6% vs. 64.7%, p<0.001). We were only able to demonstrate an abrupt and significant decrease in the use of statins after 80 years of age. Patient age was independently associated with the use of betablockers (OR 0.59; 95%CI 0.47 - 0.73) and statins (OR 0.78; 95%CI 0.65 - 0.95). The lesser administration of these drugs was also associated with early mortality (OR 0.17, 95%CI 0.09 to 0.33 and OR 0.14; 95%CI 0.08 to 0.23, respectively). CONCLUSIONS: Octogenarians less often receive aspirin, betablockers and statins, though old age was not an independent factor associated with lesser aspirin use.

Dendrimers as vectors for genetic material delivery to the nervous system.

Transfection of genetic material into primary neuronal cultures remains a challenge because of the intrinsic difficulty in transfecting this type of cell. This review covers the recent developments in the use of dendrimers for siRNA and DNA transfection in both neuronal and glial cells. Crossing the blood brain barrier crossing represents a challenge for the effective use of dendrimer-mediated delivery of therapeutic agents to the central nervous system. We will discuss the effectiveness, both in vitro and in vivo, of various dendrimers in delivering genetic material to neural tissue and its ability to cross the blood-brain barrier. In addition, the use of dendrimers as a potential new therapy in the treatment of glioblastoma will be presented.

Melatonin synthetic analogs as nitric oxide synthase inhibitors.

Nitric oxide (NO), which is produced by oxidation of L-arginine to L-citrulline in a process catalyzed by different isoforms of nitric oxide synthase (NOS), exhibits diverse roles in several physiological processes, including neurotransmission, blood pressure regulation and immunological defense mechanisms. On the other hand, an overproduction of NO is related with several disorders as Alzheimer's disease, Huntington's disease and the amyotrophic lateral sclerosis. Taking melatonin as a model, our research group has designed and synthesized several families of compounds that act as NOS inhibitors, and their effects on the excitability of N-methyl-D-aspartate (NMDA)-dependent neurons in rat striatum, and on the activity on both nNOS and iNOS were evaluated. Structural comparison between the three most representative families of compounds (kynurenines, kynurenamines and 4,5-dihydro-1H-pyrazole derivatives) allows the establishment of structure-activity relationships for the inhibition of nNOS, and a pharmacophore model that fulfills all of the observed SARs were developed. This model could serve as a template for the design of other potential nNOS inhibitors. The last family of compounds, pyrrole derivatives, shows moderate in vitro NOS inhibition, but some of these compounds show good iNOS/nNOS selectivity. Two of these compounds, 5-(2-aminophenyl)-1H-pyrrole-2-carboxylic acid methylamide and cyclopentylamide, have been tested as regulators of the in vivo nNOS and iNOS activity. Both compounds prevented the increment of the inducible NOS activity in both cytosol (iNOS) and mitochondria (i-mtNOS) observed in a MPTP model of Parkinson's disease.

Derivados de 4, 5-DIHIDRO-1H-PIRAZOL como inhibidores selectivos de nNOS: Síntesis y relaciones estructura-actividad / 4, 5-DIHYDRO-1H-PYRAZOLE as nNOS selective inhibitors: Synthesis and structure-activity relationship

INTRODUCCIÓN: La oxido nítrico sintasa (NOS) es la enzima que cataliza la biosíntesis de óxido nítrico (NO) a partir de L-arginina. 1 Hasta el momento, se han descubierto cuatro isoformas:2 nNOS, iNOS, eNOS y mtNOS. El NO es un biomensajero relacionado con importantes funciones fisiológicas. 3Sin embargo, se ha demostrado que una sobreproducción de NO por la nNOS está implicada en procesos neurodegenerativos. 4 Este hecho justifica la necesidad terapéutica de encontrar inhibidores selectivos de la nNOS que permitan luchar contra enfermedades tales como Alzheimer, Parkinson, esclerosis lateral amiotrófica y corea de Huntington. Nuestro grupo de investigación ha sintetizado y evaluado una serie de derivados kinurenínicos 5 1 y kinurenamínicos 6 2 como agentes neuroprotectores que resultaron desprovistos de actividad inhibitoria frente a la enzima kinurenina-3-hidroxilasa (KYN3OH), lo que demuestra que su actividad neuroprotectora se debe a la inhibición de la nNOS. OBJETIVO: Basándonos en estos antecedentes, hemos sintetizado y realizado la evaluación biológica in vitrofrente a las isoformas nNOS e iNOS de una serie de derivados de 4,5-dihidro-1H-pirazol con estructura general 3, con objeto de encontrar inhibidores selectivos de alguna de estas isoformas. METODOLOGÍA: Tomando como referencia los derivados kinurenínicos y kinurenamínicos, hemos sintetizado los análogos rígidos con un resto de 4,5-dihidro-1H-pirazol. Además de la restricción conformacional, se han llevado a cabo otras modificaciones, como la introducción de distintos sustituyentes en el anillo aromático y la modificación del grupo acilo en el anillo de pirazolina(AU)

CONCLUSIÓN /DISCUSIÓN: Todos los compuestos ensayados inhiben nNOS. La inhibición de iNOS es ínfima en la mayoría de los casos, por lo que se pueden considerar selectivos, y no hay inhibición de KYN3OH. Por consiguiente, el potencial neuroprotector de estos derivados se debe únicamente a la inhibición de nNOS(AU)

INTRODUCTION: Nitric Oxide Synthase (NOS) is the enzyme which catalyses the biosynthesis of Nitric Oxide (NO)from L-arginine 1. Four NOS isoforms have been described: 2 nNOS, iNOS, eNOS and mtNOS. NO is a biological messenger involved in several physiologic processes. 3 However, an over production of NO by nNOS produces neurotoxicity which has been associated with various neurological disorders 4.Therefore, it is necessary to found nNOS inhibitors to fight pathologies such as Alzheimer’s disease, Parkinson, amyotrophic lateral sclerosis and Huntington’s disease. In previous papers, our research group have described the synthesis of a series of kynurenine 5 1 and kynurenamine 6 2 derivatives as neuroprotective agents which are not active versus kynurenine-3-hydroxylase (KYN3OH). This fact demonstrates that their neuroprotective activity is only due to then NOS inhibition. 2 3 OBJECTIVE: Basing on these precedents, we have developed and evaluated in vivo, versus nNOS and iNOS, a series of 4,5-dihydro-1H-pyrazole derivatives with general structure 3 in order to find new selective compounds. METHODOLOGY: Taking kynurenine and kynurenamine derivatives as reference, we have synthesized rigid analogous with a ring of 4,5-dihydro-1H-pyrazole . Besides the conformacional restriction, other modification shave been carried out, as the introduction of different substituents in the aromatic ring and the modification of the acyl group in the pyrazoline ring . CONCLUSION /DISCUSION: All compounds inhibit nNOS. In most of cases, the inhibition of iNOS is negligible. Thus, they can be considered selective. On the other hand, there is no KYN3OH inhibition. Consequently, the neuroprotective potential of these derivatives is due only to the inhibition of nNOS(AU)

Structural elucidation of a new delta2-pyrazoline derivatives using 1H and 13C NMR spectroscopy.

This paper describes the unequivocal structural elucidation of a new kind of Delta2-pyrazoline derivatives carried out by means of monodimensional 1H and 13C NMR spectroscopies, bidimensional ones such as HMBC and HMQC experiments, and NOEDIFF effects. Conformational analysis of this molecule agrees very well with the experimentally NOEDIFF effects found.