Actual treatment of attention deficit hyperactivity disorder (ADHD)

El tratamiento del trastorno por défi cit de atención e hiperactividad (TDAH) incluye intervenciones farmacológicas, psicosociales y educativas, y en él se aconseja un diseño personalizado teniendo en cuenta las características del paciente, el tipo de trastorno y la comorbilidad que lo acompaña. Los fármacos de primera línea son el psicoestimulante metilfenidato (MTF) y atomoxetina (ATX), un simpaticomimético de acción central no estimulante. Ambos reducen las manifestaciones clínicas de inquietud, inatención e impulsividad, mejorando la calidad de las relaciones sociales y el rendimiento académico. Metilfenidato bloquea el transportador presináptico de dopamina (DA) y noradrenalina (NA), aumentando la concentración de estos neurotransmisores en el espacio presináptico neuronal. Se presenta en formas de liberación inmediata (LI) (Rubifen® y Medicebran® en preparados de acción prolongada con tecnología OROS® [osmotic controlled-release oral delivery system], Concerta® y Metilfenidato Sandoz®) y en pellets (Medikinet®), que permiten seleccionar adecuadamente la dosis y la pauta posológica. Las formas de LI pueden inducir efecto rebote al provocar un pico plasmático elevado que decae en poco tiempo. Atomoxetina (Strattera®) es un inhibidor muy selectivo y potente del transportador presináptico de NA; aumenta los niveles de NA y DA en la corteza prefrontal, pero no en las regiones corticales relacionadas con el desarrollo de tics o riesgo de abusos de sustancias. Puede ser la alternativa a MTF cuando éste pierde efi cacia o está contraindicado. La efectividad de ambos fármacos debe considerarse a partir de las 2-4 semanas. Sus reacciones adversas son numerosas y con frecuencia causan malestar, lo que difi culta la adherencia. Por ello es necesario el seguimiento de estos pacientes, y el farmacéutico puede ejercer un papel destacado para mejorar el cumplimiento y los efectos de la farmacoterapiaTreatment of attention defi cit hyperactivity disorder (ADHD) includes pharmacological, psychosocial and educational interventions. A custom designed treatment taking into account patient characteristics, type of disorder and comorbidity must be advisable. First election drugs are the psychostimulant methylphenidate (MTF) and the sympathomimetic not stimulant atomoxetine (ATX). These drugs reduce the clinical manifestations of restlessness, inattention and impulsivity, improving the quality of social relationships and academic performance. MTF blocks the presynaptic dopamine (DA) and norepinephrine (NA) transporters increasing the concentration of these neurotransmitters in the presynaptic neuron. Both of them are available in the pharmaceutical forms of immediate release (IR) (Rubifen ® and Medicebran®, prolonged acting preparations with OROS® [osmotic controlled-release oral delivery system] technology, Con certa® and Metilfenidato Sandoz®) and pellets (Medikinet®), allowing a proper selection of dosage pattern. IR pharmaceutical forms can induce rebounding effect by causing high plasma peak that decays quickly. ATX is a highly selective and a potent inhibitor of presynaptic NA transporter, increasing levels of NA and DA in the prefrontal cortex, but not in cortical regions related to the development of tics or risk of substance abuse. It can be an alternative to MTF when this loses effectiveness or is contraindicated. The effectiveness of both drugs must be considered after 2 to 4 weeks of treatment. Their side effects are numerous and often cause discomfort making diffi cult adherence. Therefore it is necessary to monitor these patients playing pharmacist a leading role in improving the performance and the effects of pharmacotherap

Therapeutical interest of statins in the treatment of atherosclerosis

Los inhibidores de la HMG-Co A reductasa o estatinas, son fármacos muy utilizados en el tratamiento de la hipercolesterolemia, ya que consiguen disminuir la concentración plamática de lipoproteína de baja densidad (LDL) regulando la síntesis endógena de colesterol y por tanto, de receptores para LDL. Recientemente se ha comprobado como el tratamiento prolongado con estos fármacos disminuyen la mortalidad y morbilidad cardiovascular. Este fenómeno puede explicarse por los efectos beneficiosos directos de las estatinas en el desarrollo de la placa de ateroma. Las estatinas disminuyen la proliferación y migración de células de musculatura lisa vascular e inducen apoptosis de estas células. También previenen la oxidación de LDL y la formación de células espumosas, reducen la respuesta inflamatoria asociada a la aterosclerosis, normalizan los fenómenos de coagulación y fibrinolisis y por último mejoran significativamente la función endotelial. Todas estas propiedades parecen estar mediadas compuestos isoprenoides intermediarios de la ruta metabólica de la HMG-Co A reductasa, y son indepen- dientes de la concentración de colesterol en el medio. Por tanto, las estatinas también podrían ser utilizadas en enfermedades asociadas a disfunción endotelial indepen- dientemente de las cifras analíticas de LDL, tal y como sucede en la hipertensió

Endothelium modulates contractile response to simvastatin in rat aorta

Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10-5 M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10-5 M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMGCoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10-5 and 10-6 M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+ATPase, cyclopiazonic acid (CPA) (3 x 10-6 M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate

Errores de medicación en farmacias comunitarias: elaboración de un formulario para su detección

INTRODUCCIÓN Desarrollar mecanismos que prevengan errores de medicación o minimicen sus con- secuencias es una tarea que actualmente se desarrolla en todos los niveles asistenciales. Las farmacias comunitarias por su proxi- midad a los pacientes y la formación del farmacéutico representan un punto estraté- gico para llevar a cabo una labor preventiva de errores de medicación. No obstante, es necesario promover y desarrollar herramien- tas que puedan ser integradas en los siste- mas de organización de las farmacias y que garanticen la seguridad del paciente. OBJETIVO Elaborar un Formulario de Recogida de datos para detección de Errores de Me- dicación (FREM) en farmacias comuni- tarias con el objeto de identificar y pre- venir errores de medicación y sus causas, promoviendo a su vez la im- plantación de prácticas seguras en las farmacias comunitarias. MÉTODO Se elaboró un primer formulario basado en la clasificación de Ruiz-Jarabo y se realizó un estudio piloto en tres farmacias comunitarias de Sevilla y una de Málaga durante durante un mes, realizando los titulares de la farmacia la recogida de in- formación sobre los errores de medica- ción. Una vez analizado y consensuado por los investigadores se elaboró el for- mulario definitivo, aplicándolo de nuevo para analizar su efectividad

Endothelium-dependent vasorelaxation induced by L-carnitine in isolated aorta from normotensive and hypertensive rats

The aim of this work was to investigate the mechanism of the vasodilatory effect induced by L- carnitine. Relaxation produced by L-carnitine was studied in rat aortic rings with and without functional endothelium, pre-contracted with phenylephrine by adding cumulative doses of L- carnitine (10-7 to 10-3 M). The relaxation evoked by L-carnitine reached higher values in aortic rings from spontaneously hypertensive rats than those obtained in arteries from normotensive rats; no relaxation was produced in de-endothelialized arteries. However, in the presence of NG-nitro-L- arginine (3¬10-5 M, a nitric oxide synthase inhibitor), Ro 68070 (10-4 M, a thromboxane synthetase inhibitor–thromboxane A2/prostaglandin H2 receptor antagonist) or ICI 192605 (10- M, a thromboxane A2 receptor antagonist) the relaxant response to L-carnitine was signiicantly inhibited. These results show that L-carnitine induced endothelium-dependent relaxation in the rat aorta and the mechanism of this relaxation appeared to be mostly mediated by endothelial production of nitric oxide but also could involve prevention of the action of cyclooxygenase endothelial products acting on the thromboxane A2/prostaglandin H2 receptor

Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats

Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tailcuff method and endothelial function was assessed by carbachol (10-8 to 10-4M -induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-ω-nitroarginine (3 × 10-5M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10-5M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P< 0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10-5M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment

Role of the Intracellular pH in the Metabolic Switch between Oxidative Phosphorylation and AerobicGlycolysis - Relevance to Cancer

Cellular energy in the form of ATP can be produced through oxidative phosphorylation and through glycolysis. Since oxidative phosphorylation requires oxygen and generates ATP more efficiently than glycolysis, it has been assumed for many years that the presence or absence of oxygen determines that cells generate energy through oxidative phosphorylation or through glycolysis. Although cells must activate glycolysis in the absence of oxygen to produce ATP, it is now accepted that they can activate both glycolysis and oxidative phosphorylation in the presence of oxygen. In fact, normal proliferating cells and tumor cells are known to have a high glycolytic activity in the presence of adequate oxygen levels, a phenomenon known as aerobic glycolysis or the Warburg effect. Recent observations have demonstrated that the activation of aerobic glycolysis plays a major role in carcinogenesis and tumor growth. Understanding the mechanisms involved in the metabolic switch between oxidative phosphorylation and aerobic glycolysis may therefore be important for the development of potential preventive and therapeutic interventions. In this article, we discuss the role of the intracellular pH in the metabolic switch between oxidative phosphorylation and aerobic glycolysis. We propose that, in the presence of adequate oxygen levels, the intracellular pH may play a key role in determining the way cells obtain energy, an alkaline pH driving aerobic glycolysis and an acidic pH driving oxidative phosphorylation

Interventions for improving adherence to treatment in patients with multiple pathologies: overview of systematic reviews

Objetivo: Evaluar la evidencia disponible respecto a la eficacia de intervenciones destinadas a mejorar la adherencia al tratamiento que sean aplicables a pacientes pluripatológicos (PP). Diseño: Revisión de revisiones sistemáticas. Fuentes de datos: Se consultaron (septiembre de 2013): Pubmed, EMBASE, the Cochrane Library, CRD y WoS para detectar intervenciones para la mejora de la adherencia en PP, o en su defecto, pacientes con patologías definitorias de pluripatología o polimedicados. Selección de estudios: Se incluyeron revisiones sistemáticas de ensayos clínicos con PP o de características similares. Estas debían comparar la eficacia de cualquier intervención destinada a mejorar el cumplimiento del tratamiento autoadministrado prescrito con la práctica habitual u otra intervención. Extracción de datos: Se extrajo información sobre la población en estudio, la intervención ensayada y la eficacia de la misma en términos de mejora de la adherencia. Resultados: Se recuperaron 566 artículos de los que se seleccionaron 9 revisiones sistemáticas. Ninguna se centraba específicamente en PP. Sí consideraban pacientes con múltiples patologías crónicas, patologías definitorias de pluripatología o polimedicados. La eficacia global de las intervenciones fue modesta, no observándose diferencias relevantes entre las intervenciones de carácter conductual, educativo o combinado. Algunos componentes de estas intervenciones como son el asesoramiento al paciente o las estrategias de simplificación posológica parecen ser herramientas eficaces en la mejora de la adherencia en este grupo poblacional. Conclusiones: Existe una gran heterogeneidad de intervenciones orientadas a la mejora de la adherencia de eficacia modesta, no habiendo sido diseñadas para una población de PP

Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.AMINOVITA, S.L, PRJ201803388Junta de Andalucía 2017/CTS-657, 2019/CTS-657, 2021/CTS-657Universidad de Sevilla VIPPIT-2019-I.5, VIPPIT-2020-I.5, VIPPIT-2021-I.5, VIPPIT-2020-II.