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El cuidador familiar (CF) facilita la extensión al hogar de los servicios de salud para el creciente número de adultos mayores (AM). El objetivo del trabajo fue evaluar los efectos de una intervención de masaje terapéutico (MT) aplicado recíprocamente entre AM y CF, para medir cambios en la limitación del movimiento cervical y la percepción de apoyo recibido de parte de cada integrante de la pareja. Al término de la intervención se identificó un aumento significativo en el arco de movimiento del raquis cervical en el AM y CF al comparar las puntuaciones pre-post, sugiriéndose que el MT puede revertir la limitación de movilidad cervical en proveedor y receptor de cuidados, así como favorecer la percepción de apoyo mutuo.

Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning–based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL-3D). Applying the method to pediatric Wilms tumor, we extract molecular, spatial and morphological features of millions of cells and reconstruct the tumor’s spatio-phenotypic patterning. In situ population profiling and pseudotime ordering reveals a highly disorganized spatial pattern in Wilms tumor compared to healthy fetal kidney, yet cellular profiles closely resembling human fetal kidney cells could be observed. In addition, we identify previously unreported tumor-specific populations, uniquely characterized by their spatial embedding or morphological attributes. Our results demonstrate the use of combining mLSR-3D and STAPL-3D to generate a comprehensive cellular map of human tumors. An imaging software for large-scale microscopy data shows how cells are organized in tissues.

La presente obra responde a la necesidad de sustentar legal y científicamente los estudios, dictámenes o informes del área de psicología en el ámbito foren¬se de los casos de violencia familiar y delitos sexuales en cualquiera de sus modalidades. Su finalidad es ofrecer procesos, procedimientos y directrices generales para apoyar a los profesionales en psicología que realicen intervenciones en esta materia, facilitar la evaluación de los daños y la elaboración del informe pericial o dictamen. Las pautas de recomendación presentadas podrán ser aplicadas en personas de diferente edad, sexo, condición social, personas vulnerables e incluso de diversas nacionalidades, y ser consideradas como una directriz en un sentido de transparencia.

Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning-based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL-3D). Applying the method to pediatric Wilms tumor, we extract molecular, spatial and morphological features of millions of cells and reconstruct the tumor's spatio-phenotypic patterning. In situ population profiling and pseudotime ordering reveals a highly disorganized spatial pattern in Wilms tumor compared to healthy fetal kidney, yet cellular profiles closely resembling human fetal kidney cells could be observed. In addition, we identify previously unreported tumor-specific populations, uniquely characterized by their spatial embedding or morphological attributes. Our results demonstrate the use of combining mLSR-3D and STAPL-3D to generate a comprehensive cellular map of human tumors.

Objective: To analyze whether for an equal health problem there are gender differences in the drugs used in an adult population attended in the Health Care Centers of the Valencian Community (Spain). Methods: A cross-sectional analytical study was carried out between February-August 1997. The independent variables were: socio-economic parameters, frequency of visits, and self-perceived or diagnosed health problems, and the dependent one the number of drugs consumed. Results: Of the 812 patients considered, 801 consumed medication. Eighty percent of the health problems for which drugs were used involved 5 apparatuses and systems (mean: 3.3 health problems/patient). The 5 most consumed therapeutic groups accounted for 81% of the total (mean: 4.5 drugs/patient). Significant differences were recorded, with greater female consumption in the central nervous system and genitourinary tract therapeutic groups, and with greater male consumption in relation to the respiratory system and systemic anti-infectious therapy. Drug use increased with age, lowest educational level, lowest professional categories, and with the highest frequency of visits to the physician. Significant differences were also recorded in drug use by occupational status, marital status and family structure. The multivariate analysis showed the number of health problems and the frequency of visits accounted for 82.2% of the variability of the variable «number of drugs consumed». The variability accounted for by gender was explained by the variable health problems, the main factor underlying drug consumption among women and men. Conclusion: The main finding is probably that women do not use larger numbers of drugs than men if health problems and frequency of visits are controlled.

[Background] Episodic ataxia type 1 is a rare autosomal dominant neurological disorder caused by mutations in the KCNA1 gene that encodes the α subunit of voltage-gated potassium channel Kv1.1. The functional consequences of identified mutations on channel function do not fully correlate with the clinical phenotype of patients., [Methods] A clinical and genetic study was performed in a family with 5 patients with episodic ataxia type 1, with concurrent epilepsy in 1 of them. Protein expression, modeling, and electrophysiological analyses were performed to study Kv1.1 function., [Results] Whole-genome linkage and candidate gene analyses revealed the novel heterozygous mutation p.Arg324Thr in the KCNA1 gene. The encoded mutant Kv1.1 channel displays reduced currents and altered activation and inactivation., [Conclusions] Taken together, we provide genetic and functional evidence that mutation p.Arg324Thr in the KCNA1 gene is pathogenic and results in episodic ataxia type 1 through a dominant-negative effect. © 2016 International Parkinson and Movement Disorder Society, This study was supported by grants from the Ministerio de Educacion y Ciencia, Spain (SAF2005-04783, SAF2006-27500-E, and SAF2010-17694) and Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia, Spain (P07-CVI-02790 and P11-CTS-7045).

Póster presentado en el 16th National Congress of the Spanish Society of Neuroscience (SENC 2015), celebrado el Granada del 23 al 25 de septiembre de 2015., Neurexins (NRXN) and neuroligins (NLGN) are synaptic cell-adhesion proteins involved in neurodevelopmental disorders, as autism and intellectual disability. Previously, we have postulated a role of NRNX-NLGN in Alzheimer's disease (AD). Here, we present genetic and functional approaches to identify variants of the NRNX-NLGN pathway in AD patients. Using next-generation sequencing, we have studied a panel of 36 genes of the NRNX-NLGN synaptic pathway in 192 AD patients. Potential causal variants were studied by in silico analysis and validated by Sanger sequencing. Susceptibility variants were analyzed by manual inspection in IGV (Integrative Genomics Viewer). Functional studies of selected variants were performed in N2A and COS cells and cultured hipocampal neurons. To identify susceptibility alleles, we selected SNPs whose allelic frequency differed among the genotyped AD patients and the control databases. These SNPs were then genotyped in a geographically-matched control population. On the other hand, potential causative mutations were selected among novel variants with a predicted pathogenic effect. We present a two base-pair insertion in NLGN1 (p.Thr271fs) in a patient with familial history of AD. The frameshift mutation in NLGN1 predicts a premature STOP codon that truncates the extracellular domain. We generated expression vectors for the p.Thr271fs mutation. In western blot experiments we detected a band of ~130 kD corresponding to wild type NLGN1. In contrast, the p.Thr271fs mutation resulted in truncated proteins of ~30 kDa. Localization studies in COS cells showed that p.Thr271fs NLGN1 failed to reach the plasma membrane and accumulated in the ER. In neurons, NLGN1 induces the formation of glutamatergic synapses. We showed that p.Thr271fs NLGN1 failed to induce the formation of glutamatergic synapses and accumulated in the soma of transfected neurons. Thus, the synaptic activity of NLGN1 was abolished by the AD-associated p.Thr271fs mutation. Our data report the first inactivating mutation in the NLGN1 gene in AD patients and support a role for the NRXN-NLGN pathway in the etiology of AD.

Trabajo presentado en el XL Congreso de la Sociedad Española de Genética, celebrado en Córdoba del 16 al 18 de septiembre de 2015., El trastorno del espectro autista (TEA) es una enfe rmedad del neurodesarrollo que se enmarca dentro de las enfermedades multifactoriales, que re sultan de la contribución conjunta de factores genéticos y ambientales. La elevada hetero geneidad genética del TEA dificulta la interpretación de los hallazgos genéticos. Las neur exinas pertenecen a una familia de proteínas de adhesión presináptica que regulan el f uncionamiento sináptico mediante la unión con sus receptores postsinápticos, entre los que destacan las neuroliguinas. Mediante una aproximación de genes candidatos, en nuestro gr upo hemos identificado mutaciones en el gen NRXN1β en un grupo de pacientes con TEA. El análisis funcional de las mutaciones mostró una reducción en los niveles sinápticos de l as proteínas mutantes. Nuestros resultados, junto con la identificación de variantes raras y CN Vs en la ruta de neurexinas, neuroliguinas y SHANK, sugieren una disfunción de dicha ruta sinápt ica como factor de riesgo para autismo. Dada la naturaleza poligénica del TEA, hemos aborda do la identificación de segundos hits mutacionales mediante el análisis genómico de CNVs y la secuenciación masiva del genoma completo en las familias con mutaciones en NRXN1β. Este abordaje nos permite estudiar nuevos genes con impacto en el desarrollo del TEA j unto con NRXN1β. Por otra parte, mediante abordajes de asociación ge nética y estudio en modelos animales hemos propuesto un papel de neurexinas y neuroligui nas en la enfermedad de Alzheimer (AD). Con el fin de confirmar su papel en AD, lleva mos a cabo la secuenciación masiva de un panel de 36 genes que conforman la ruta sináptica m ediada por neurexinas y neuroliguinas. Hemos identificado una mutación de tipo frameshift en el gen NLGN1 en un paciente con AD y antecedentes familiares de AD. La expresión de la forma mutada de NLGN1 conduce a la acumulación de la proteína en el retículo endoplásm ico, así como a la inhibición de la formación de sinapsis glutamatérgicas por parte de NLGN1 mutante. Estos resultados sugieren un papel novedoso de mutaciones que inhiben la func ión de NLGN1 en AD. Estudios previos de otros grupos habían descrito mutaciones raras de los genes NLGN3 y NLGN4 en TEA, que también resultaban en la inactivación de los alelos mutantes. En conjunto, estas aproximaciones genéticas sugieren que la alteración de la función de neuroliguinas jugaría un papel no sólo en enfermedades del neurodesarrollo, sino también en AD.

ObjetivoConocer la calidad y la relevancia de las reacciones adversas a medicamentos (RAM) publicadas como Cartas al Director en las revistas médicas españolas.DiseñoEstudio descriptivo.ParticipantesCartas al director sobre RAM aparecidas durante 5 años (1994-98).EmplazamientoCuatro revistas españolas (Medicina Clínica, Revista Clínica Española, ATENCIÓN PRIMARIA y Anales de Medicina Interna).Mediciones principalesLas características de los pacientes, de los medicamentos, de las reacciones adversas, el algoritmo de causalidad, los criterios mínimos y la relevancia de la publicación.ResultadosDe 2.244 cartas, 204 (9,1%) se referían a RAM e incluían 235 casos. Los subgrupos terapéuticos más implicados fueron: anticoagulantes y antiplaquetarios, antibióticos y antineoplásicos. El 20,4% de los medicamentos era reciente. Las RAM más frecuentes afectaron al sistema nervioso (13,6%), el hígado (10,2%), la piel y anejos (9,8%), reacciones generales (9,8%) y aparato digestivo (8,1%). El 50,2% fueron moderadas y el 34%, graves/mortales. El valor medio (5,9±2,2) del algoritmo de causalidad fue similar entre revistas; las RAM fueron: 28 (11,9%) definidas, 182 (77%) posibles o probables y 26 (11,1%) improbables o condicionales; el 10,2% eran desconocidas. No se detectaron diferencias en la media (9,5±1,2) de criterios mínimos de publicación. La relevancia de la publicación fue de 3,2±1,6 puntos, superior en Medicina Clínica.ConclusionesLa publicación de RAM supone una parte importante de la sección de Cartas al Director en las revistas estudiadas. La relación de causalidad es aceptable y la calidad documental elevada, con pocas reacciones desconocidas y a medicamentos recientes. La relevancia ha sido escasa, aunque superior en Medicina Clínica.ObjectiveTo assess the quality and relevance of adverse drug reactions (ADRs) published as Letters to the Editor (LE) in Spanish medical journals.DesignObservational study.ParticipantsLE on adverse drug reactions published over 5 years (1994-98).SettingFour Spanish medical journals (Medicina Clínica, Revista Clínica Española, ATENCIÓN PRIMARIA, and Anales de Medicina Interna).Main measurementsPatient characteristics, drugs, ADR, causality algorithm, minimum criteria, and publication relevance.ResultsOut of 2,244 LE, 204 (9.1%) reported ADRs, which included 235 cases. The therapeutic subgroups most commonly implicated were anticoagulants and antiplatelet drugs, antibiotics, and antineoplastic agents; 20.4% of the drugs were recently marketed. ADRs most commonly involved the nervous system (13.6%), liver (10.2%), skin and appendages (9.8%), general reactions (9.8%), and the digestive system (8.1%). The reactions were moderate in 50.2% of cases and severe/fatal in 34%. The mean causality algorithm value (5.9±2.2) was similar among journals. Of the ADRs, 28 (11.9%) were definitive, 182 (77%) possible or probable, and 26 (11.1%) improbable or conditional; 10.2% were unknown. There were no differences in the mean minimum publication criteria (9.5±1.2). Publication relevance was 3.2±1.6 points, and higher in Medicina Clínica.ConclusionsADRs constitute an important part of LE in the journals studied. The causal relationship is acceptable, the documentation quality is high, with few unknown reactions and ADRs to recently marketed drugs. Relevance is generally low, although greater in Medicina Clínica.

Póster presentado en la 5th Spanish Ion Channel Network Meeting (RECI V), celebrada en Barcelona del 4 al 6 de octubre de 2015., Episodic ataxia (EA) is a rare autosomal dominant neurological disorder characterized by brief episodes of cerebellar dysfunction and myokymia or neuromyotonia. We recruited the participation of a family with 5 affected members with a diagnosis of paroxysmal kinesigenic dyskinesia vs episodic ataxia with secondarily generalized epilepsy. The age of onset ranged from 3 to 6 years. The patients had brief episodes (C, p.Arg324Thr. The affected residue is located within the cytoplasmic loop between S4 and S5 of the Kv1.1 channel. The mutation cosegregates with the disease and it is absent from 622 control chromosomes. To study whether the mutation altered the channel biophysical properties, the wild type (WT), heterozygous (WT:R324T) and mutant (R324T) channels were expressed in HEK-293T cells. When compared to the WT channel, the WT:R324T and R324T channels: i) produced significantly smaller currents; ii) activated at more positive potentials (~10 and ~20 mV, respectively) and with significantly slower kinetics; and iii) showed a depolarizing shift (~10 and ~20 mV, respectively) in the voltage dependence of the steady-state inactivation. Taken together, the data reported here support the relevance of the KCNA1 gene in EA and the role of the p.Arg324Thr mutation in the channel kinetics.

Carbonell-Corvillo, Pilar et al.--Trabajo presentado en la LXVII Reunión Anual de la Sociedad Española de Neurología (SEN), celebrada en Valencia del 17 al 21 de noviembre de 2015., [Objetivos] Las enfermedades asociadas a mutaciones en MYH7 presentan una amplia heterogeneidad clínica y genética. Nuestro objetivo es describir el fenotipo clínico y patológico de una nueva mutación en MYH7 (p.R1560P) en dos familias no relacionadas de Andalucía., [Material y métodos] A partir de dos casos índex portadores de la misma mutación y pertenecientes a familias de distintas provincias andaluzas, estudiamos a todos los familiares posibles. Realizamos: cuestionario clínico, exploración física, CK, RM muscular MMII y estudio genético. La biopsia muscular se realizó en los casos índex., [Resultados] La primera familia presentó un fenotipo clínico en general más severo. El inicio más común fue el primer dedo caído, posterior debilidad para la flexión dorsal de pies asociando más tarde debilidad en extensores de dedos de manos y flexores de cuello. Un paciente de 11 años presentó debilidad cervical como único hallazgo. Muchos presentaron pies cavos e hipertrofia de pantorrillas. La segunda familia presentó un fenotipo más leve con primer dedo caído y debilidad de la flexión dorsal de pies con afectación cervical leve. Ninguna familia asoció cardiomiopatía. La CK fue normal. La RM mostró afectación de compartimento anterior de piernas desde fases iniciales y de cuádriceps en los más avanzados. La histopatología mostró inclusiones citoplásmicas (familia 1) y corespseudocores (familia 2)., [Conclusiones] La mutación p.R1560P en el gen MYH7 causa el fenotipo clínico clásico de la miopatía distal de Laing. La debilidad cervical puede ser el síntoma inicial. El estudio de haplotipo permitirá establecer si se trata de una mutación fundadora en la región de Andalucía.

Fundamento El cumplimiento de un tratamiento es necesario para conseguir su efectividad. Se pretende conocer el cumplimiento del tratamiento hormonal sustitutivo (THS) en mujeres menopausicas. Metodo Estudio descriptivo observacional realizado en tres Areas de Salud de la Comunidad Valenciana. Periodo de seguimiento desde 1989 hasta 1999. Se incluyeron mujeres que acudieron a una unidad de menopausia y comenzaron con el THS. La informacion se obtuvo de la historia clinica y de una encuesta telefonica realizada a las pacientes. Se analizaron la edad de la mujer, la edad de inicio y el tipo de la menopausia, la edad de comienzo del THS, el nivel educativo, el motivo de prescripcion, el tiempo de utilizacion, el grado de informacion, los efectos secundarios y las causas de abandono. Se utilizo el metodo de Kaplan-Meier para conocer el cumplimiento y el riesgo proporcional de Cox para conocer las variables que influyen en el cumplimiento. Resultados Se incluyeron 363 mujeres. Existe un 75% de probabilidades de que las mujeres alcancen un tiempo de cumplimiento de 5 anos, la mediana se corresponde con un cumplimiento de 11 anos (intervalo de confianza [IC] del 95%, 9–13). Las mujeres que han padecido efectos secundarios (odds ratio ajustada [ORa], 2,60; IC del 95%, 1,84–3,68) presentan mayor tasa de abandono, mientras que este es menor en las que han tenido beneficios (ORa, 1,77; IC del 95%, 1,22–2,53), aquellas cuya menopausia ha sido quirurgica (ORa, 1,60; IC del 95%, 1,12–2,28) y las que tienen menos de 55 anos al comienzo del THS (ORa, 2,61; IC del 95%, 1,67–4,07). Conclusiones El cumplimiento del THS en mujeres menopausicas es alto y esta condicionado por el hecho de tener beneficios y/o efectos secundarios, por la edad al inicio del tratamiento y el tipo de menopausia.

ObjetivoDada la posibilidad de efectos adversos, interacciones con medicamentos e intoxicaciones por contaminantes entre consumidores de hierbas medicinales (HM), nuestro objetivo es describir el consumo de HM en usuarios de los centros de salud en tratamiento con medicamentos.DiseñoEstudio observacional, transversal.EmplazamientoTrece centros de salud de la Comunidad Valenciana.Pacientes u otros participantesUsuarios, de sexo indistinto, mayores de 14 años, seleccionados para un estudio de utilización de medicamentos para encontrar diferencias entre sexos. Mediciones y resultados principales. Las variables de estudio, edad, sexo, nivel educativo, consumo de medicamentos y uso de HM se recogieron desde la historia clínica, tarjeta de largo tratamiento y encuesta estructurada ad hoc. De los 812 usuarios, 801 consumen medicamentos. Toman HM, 159 (19,6%; IC del 95%, 16,9–22,3); edad media, 55,8 años (DE, 16,5); mujeres, 58,5% (IC del 95%, 50,8–66,1). Consumen HM, 226 (media, 1,42; IC del 95%, 1,32–1,52); los varones consumen más HM (p < 0,05). No existen diferencias de consumo de HM por edad, nivel educativo o número de medicamentos consumidos. Un 42,8% (IC del 95%, 35,1–50,2) de los que consumen HM acudieron a la consulta más de 10 veces en el último año. El 96,9% (IC del 95%, 93,7–98,4) de las HM se consumen por automedicación. Se consumen: «por gusto», 36,7% (IC del 95%, 30,4–43,0); problemas de estómago, 19,5% (IC del 95%, 14,3–24,6); nervios/depresión, 12,8% (IC del 95%, 8,5–17,2); trastornos intestinales, 10,6% (IC del 95%, 6,6–14,6); insomnio, 5,8% (IC del 95%, 3,1–9,6). Un 49,1% (IC del 95%, 42,6–52,6) es HM manufacturadas.ConclusionesUno de cada 5 pacientes en tratamiento con medicamentos consume HM por automedicación. La administración sanitaria y los médicos deberían informar de los riesgos para la salud y las contraindicaciones de estos productos.ObjectiveGiven the possibility of adverse side-effects, interactions with medicines and poisoning by contaminants among herbal medicine consumers (HM), we aimed to describe the consumption of HM by health centre users being treated with medicines.DesignCross-sectional, observational study.SettingThirteen health centres in the Community of Valencia.Patients and others participantsUsers of either sex, over 14, chosen for a study of use of medicines to find differences between the sexes.Measurements and main resultsThe study variables, age, gender, education, consumption of medicines and use of HM, were gathered from the clinical records, the long-treatment card and an ad hoc structured survey. 801 out of 812 users took medicines. 159 took HM (19.6%; 95% CI, 16.9–22.3); average age 55.8 (SD, 16.5); women 58.5% (95% CI, 50.8–66.1). They took 226 HM (mean of 1.42; 95% CI, 1.32–1.52). Men consumed more HM (p < 0.05). There were no differences in consumption of HM for age, educational background or number of medicines taken. 42.8% (95% CI, 35.1–50.2) of those who took HM attended for consultation over 10 times in the previous year. 96.9% (95% CI, 93.7–98.4) of HM were taken by self-medication. They were consumed: «because I like them» by 36.7% (95% CI, 30.4–43.0); stomach problems, 19.5% (95% CI, 14.3–24.6); nerves/depression, 12.8% (95% CI, 8.5–17.2); intestinal disorders, 10.6% (95% CI, 6.6–14.6); insomnia 5.8% (95% CI, 3.1–9.6). 49.1% (95% CI, 42.6–52.6) were manufactured HM.ConclusionsOne of every five patients being treated with medicines is also taking HM by self-medication. The health authorities and doctors should advise of the risks to health and of the counter-indications of these products.

1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.

1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

Las enfermedades cardiovasculares se muestran como la principal causa de muerte en el mundo. Teniendo en cuenta los distintos factores de riesgo y factores protectores de estas enfermedades y, sobre todo, haciendo énfasis en los factores de riesgo de índole psicológica, se plantea un programa de tratamiento psicológico para ver el efecto de este en estas enfermedades. Para ello se seleccionan dos grupos, enfermos cardiovasculares (grupo experimental) y estudiantes universitarios adultos (grupo control), ambas son en población mexicana. Estos grupos se subdividen en un grupo al que se le aplica el tratamiento, y un grupo al que no se le aplica tratamiento, conformando un total de cuatro grupos. Los resultados muestran un efecto favorable del tratamiento psicológico, en los dos grupos que lo reciben, sin embargo los resultados en los enfermos cardiovasculares son más claros.

Póster presentado en el Workshop "Current Trends in Biomedicina", celebrado en Baeza en octubre de 2013., Synaptic circuitry in the brain is formed early during postnatal development and is continuously remodeled in the adult as a consequence of synaptic activity. Defects in synaptic function lie at the molecular basis of several disorders, including autism spectrum disorders (ASD). ASD are characterized by impairments in verbal and non-verbal communication and social interaction, and restricted and stereotyped patterns of behavior, interests and activities. The identification of mutations in neuroligin, neurexin and SHANK genes in patients with ASD has indicated a role of these proteins in autism. Neurexins are presynaptic partners of several postsynaptic proteins, including neuroligins. The characterization of the functional consequences of autism-associated mutations has led us to suggest a role for synaptic deficits of ß-neurexin-1 as a risk factor for autism (1). To analyze the impact of impaired ß-neurexin-1 function in ASD, we have generated a transgenic mouse line that expresses a mutant ß-neurexin-1 protein (HA-ßNrx1¿C) expected to function in a dominant-negative manner. In TRE-ßNrx1¿C mice, the expression of HA-ßNrx1¿C is controlled by the inducible TRE promoter. Here, we show inducible expression of HA-ßNrx1¿C in postnatal forebrain neurons of double transgenic TRE-HA-ßNrx1¿C; CAMKII¿tTA mice. In immunostaining experiments, HA-ßNrx1¿C is expressed in cortex and striatum. In cortical synaptosomes, HA-ßNrx1¿C is localized at presynaptic fractions, indicating incorporation of the mutant ß-neurexin-1 protein at presynaptic terminals in vivo. Moreover, we have evaluated the behavioral phenotype of TRE-HA-ßNrx1¿C; CamKII-tTA mice compared to control littermate mice and how they can be rescued by turning-off the transgene. The generation of a mouse model with inducible expression of a ß-neurexin-1 dominant negative mutant, such as the one described here, may help answering to what extent behavioral defects due to ß-neurexin-1 dysfunction can be rescued by recovering normal ß-neurexin-1 function. 1. Camacho-Garcia et al. Mutations affecting synaptic levels of neurexin-1ß in autism and mental retardation. Neurobiol. Dis.2012 Jul; 47 (1):135-43.

Póster presentado en el Workshop "Current Trends in Biomedicina", celebrado en Baeza en octubre de 2013.

Póster presentado en el 15º Congreso de la Sociedad Española de Neurociencia (SENC 2013) celebrado en Oviedo del 25 al 27 de septiembre de 2013.

UNLABELLED In an attempt to assess the relative toxicity of amoxycillin and amoxycillin-clavulanic acid, we compared the adverse drug reactions reports collected using the spontaneous reporting system of a Regional Drug Surveillance Centre of Spain for both drugs between November 1986 and December 1992. During the 7-year period 1986-92, the 247 reports of amoxycillin-clavulanic acid represent twice the number of reports of amoxycillin alone, and the number of reports related with sales received concerning the association were higher than those concerning amoxycillin alone. The adverse effects classified as severe were quantitatively and qualitatively similar for both drugs and gastrointestinal and skin are the most common system-organ affected by both drugs. With amoxycillin-clavulanic acid there is a higher proportion of stomatological reactions reported and a later onset of adverse drug reactions related with oropharyngeal lesions, and the reaction of the resistance mechanism when compared with the other organs and systems affected. The duration of the adverse drug reactions to amoxycillin-clavulanic acid is longer than for amoxycillin alone. IN CONCLUSION (i) the adverse drug reactions profile of both drugs is different; (ii) the higher reporting rate for amoxycillin-clavulanic acid may be due to more recent marketing; and (iii) amoxycillin-clavulanic acid produces proportionately more gastrointestinal and fewer skin adverse reactions than amoxycillin alone.

Póster presentado en la International Meeting for Autism Research, celebrado en San Sebastián en mayo de 2013., [Background] Synapses are established with precision during brain development and are constantly remodeled as a consequence of synaptic activity in the adult networks. Synaptic dysfunction underlies the molecular basis of several neurodevelopmental disorders, such as autism spectrum disorders (ASD). Trans-synaptic adhesion systems can regulate synaptic function, as they organize pre- and postsynaptic protein complexes. One of these adhesion systems is formed by neurexins and neuroligins. These proteins promote the assembly and maturation of synapses through a bidirectional mechanism. In mammals, neurexins are encoded by three genes with two alternative promoters, which produce the long (alpha-neurexins) and the short (beta-neurexins) isoforms. In addition, alternative splicing in the extracellular domain contributes to generate hundreds of neurexins isoforms. Despite the high heterogeneity of the extracellular region, the cytoplasmic domain is common to all neurexin isoforms and it is thought to regulate intracellular signalling. The relevance of neurexins in neurodevelopmental disorders has been highlighted by the identification of mutations in neurexin genes in ASD. Recently, we have suggested a role for synaptic defects of beta-neurexin-1 as a risk factor for autism and mental retardation., [Objectives] To characterize in cultured neurons the effect of a beta-neurexin-1 dominant negative mutant that lacks the cytoplasmic tail (HA-bNrxDC). To inhibit the function of beta-neurexin-1 in vivo by expressing the HA-bNrxDC mutant. To characterize the behavioral phenotype of a double transgenic mice expressing an inducible form of the HA-bNrx1DC mutant (TRE-HA-bNrx1DC/CamKII-tTA)., [Methods] In vitro studies have been performed in hippocampal neurons at 10-14 DIV isolated from 18-19 embryonic day rat brains. For in vivo studies we have generated a transgenic mouse line that expresses a HA-tagged beta-neurexin-1 mutant lacking the cytoplasmic domain (HA-bNrx1DC) under the control of the inducible TRE promoter. The TRE-HA-bNrx1DC transgenic mice have been crossed with CAMKII ¿tTA animals to direct the expression of the mutant protein to glutamatergic terminals in vivo., [Results] Our in vitro results suggest that HA-bNrx1DC mutant can function as a dominant negative mutant as it can be recruited to the membrane of glutamatergic synapses through interaction with neuroligin-1, but it inhibits intracellular signalling mediated by the cytoplasmic tail. In vivo we show expression of HA-bNrx1DC in the cortex and hippocampal formation by immunolocalization. Moreover, we have evaluated the behavioral consequences of the lack of beta-neurexin-1 function in TRE-HA-bNrx1DC/CamKII-tTA double transgenic mice., [Conclusions] Inducible expression of a beta-neurexin-1 dominant negative mutant might have implications in the study of autism, as it may help answering to what extent synaptic and behavioral defects due to beta-neurexin-1 dysfunction can be rescued by resuming normal beta-neurexin-1 function.

Póster presentado en la 11th International Conference on Alzheimer's & Parkinson's Diseases, celebrada en Florencia del 6 al 10 de marzo de 2013.-- Alzheimers Disease Neuroimaging Inititive, [Objectives] The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD., [Methods] To explore this hypothesis we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1256 SNPs in the NRXN1, NRXN2, NRXN3 and NLGN1 genes (3009 cases and 3006 control individuals) using PLINK software., [Results] We identified a marker in the NRXN3 gene (rs17757879) that showed a consistent protective effect in all GWAS, however the statistical significance obtained did not resist multiple testing corrections (OR=0.851, p=0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A replication study with SNP rs17757879 in a Spanish population (1785 cases and 1634 controls) confirmed this observation (OR=0.752, C.I.=0.570-0.991, p=0.042)., [Conclusions] We conclude that NRXN3 might have a role in susceptibility to AD in males (rs17757879, OR=0.742, 95% C.I.=0.632-0.872, p=0.00028, final meta-analysis).

El CO2 es el gas que más contribuye al Cambio Climático. La oxi-combustión es una tecnología de captura de CO2 muy prometedora, y en ella el combustible se quema con O2 puro en lugar de utilizar aire, junto con parte de los gases de salida que se recirculan para diluir el O2 y controlar la temperatura de la caldera. De esta forma, a la salida se tendrá una corriente muy concentrada en CO2 que puede ser capturado, almacenado o utilizado directamente. En el gas de salida, también pueden aparecer algunos contaminantes, como el SO2 o los NOx entre otros, que si son recirculados, pueden afectar en gran medida al proceso de combustión. En este contexto, el objetivo de este trabajo es el estudio de la influencia del SO2 en el proceso de oxidación de CO en condiciones de oxi-combustión. Los experimentos se realizan en un reactor de flujo pistón a escala de laboratorio. Se pretende estudiar el efecto de la presencia de SO2 analizando la influencia de las variables más importantes del proceso como la temperatura, la estequiometría y las concentraciones de CO2, SO2, CO y NO. Algunos de los experimentos más relevantes se realizan diluidos en N2 en lugar de CO2 para analizar la influencia de la atmósfera de reacción. Los experimentos se simulan utilizando un modelo de reactor de flujo pistón con el software de cinética química Chemkin-Pro. Se utiliza un mecanismo de reacción desarrollado por el propio grupo de investigación, obteniendo una buena correspondencia entre los resultados experimentales y las predicciones del modelo cinético en todos los casos. Se detecta una importante inhibición de la oxidación de CO en atmósfera de CO2 en comparación con el caso de N2, por la competencia entre el CO2 y O2 por radicales H. El efecto inhibidor del CO2 es mayor cuanto mayor es su concentración. A mayor concentración de CO, mayor porcentaje de conversión del mismo para una temperatura dada. El NO en cualquier concentración inhibe la reacción de oxidación en ausencia de SO2, y su efecto inhibidor es mayor cuanto mayor es su concentración. En presencia de SO2, el NO en bajas concentraciones favorece la reacción, mientras que la inhibe con mayores concentraciones. El efecto inhibidor del SO2 en atmósfera de CO2 se debe a que favorece los mecanismos de recombinación de radicales. En condiciones reductoras, la eliminación de radicales se rige por la interconversión: SO2 → HOSO → SO2. El efecto inhibidor del SO2 es menor en atmósfera de CO2 que en N2 a estas estequiometrías. Sin embargo cuando se dan condiciones pobres en combustible, su efecto parece ser similar en ambas atmósferas, con independencia de la concentración de CO2, debido a la importancia cada vez mayor de la reacción de recombinación SO2+O para dar SO3. Se produce una mayor inhibición de la oxidación de CO con un aumento en la concentración de SO2, aunque las diferencias disminuyen a medida que los niveles de concentración de SO2 aumentan. En presencia de NO, el efecto inhibidor del SO2 queda casi anulado.

1 página. IX Jornadas Andaluzas de Salud Investiga. Cádiz 20-22 octubre, 2010., La Discinesia Paroxística Cinesigénica (PKD) es un trastorno del movimiento, caracterizado por movimientos involuntarios episódicos y repentinos, desencadenados por movimientos bruscos. Los distintos tipos de discinesia paroxística muestran un elevado grado de solapa-miento en su presentación clínica. Los estudios genéticos han demostrado, además, la existencia de heterogeneidad genética. En este estudio proponemos identificar los genes causantes de PKD en dos familias independientes.

1 página. IX Jornadas Andaluzas Salud Investiga. Cádiz 20-22 octubre, 2010., El Trastorno del Espectro Autista (TEA) es un conjunto de síndromes del desarrollo que se caracterizan por déficit en la interacción social, comunicación restringida y comportamientos estereotipados. Hasta un 70% de los casos están asociados a retraso mental. La mayor parte de los casos de TEA se enmarcan dentro de las enfermedades complejas, causadas por la combinación de alelos de susceptibilidad y factores ambientales. Se han identificado mutaciones y variaciones estructurales en genes que codifican proteínas sinápticas, como las neurexinas, que podrían incrementar el riesgo a desarrollar la enfermedad. Los objetivos de nuestro estudio son entender el mecanismo de acción de neurexina-1 beta (NRXN1β) en el desarrollo del TEA.

The vascular (blood pressure, heart rate and peripheral blood flow) and uterine (spontaneous motility) responses to intravenous methoxamine were studied in anaesthetized rats pre-treated with diethylstilboestrol. Methoxamine produced an increase (0.5-2 mg/kg) or did not modify (0.01 and 3 mg/kg) spontaneous uterine motility. The alpha 1-agonist also induced a hypertensive effect (0.1-3 mg/kg) accompanied by bradycardia at the highest doses, and a decrease in blood flow significantly greater in intestinal than uterine tissues. These effects were abolished by prazosin. The uterine action of methoxamine in vivo appears to result from the balance between myometrial alpha 1-excitatory effect and vascular alpha 1-vasoconstriction which induced uterine inhibition. The oestrogens appear to protect the alpha 1-mediated vasoconstriction.

1 página., Reply to "Cryptogenic Epileptic Syndromes Related to SCN1A: Twelve Novel Mutations Idenfified"

8 páginas, 1 figura., The porphyrias arise from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Traditionally, the diagnosis of porphyria is made on the basis of clinical symptoms, characteristic biochemical findings, and specific enzyme assays. In some cases however, these diagnostic tools reveal overlapping findings, indicating the existence of dual porphyrias with two enzymes of heme biosynthesis being deficient simultaneously. Recently, it was reported that the so-called Chester porphyria shows features of both variegate porphyria and acute intermittent porphyria. Linkage analysis revealed a novel chromosomal locus on chromosome 11 for the underlying genetic defect in this disease, suggesting that a gene that does not encode one of the enzymes of heme biosynthesis might be involved in the pathogenesis of the porphyrias. After excluding candidate genes within the linkage interval, we identified a nonsense mutation in the porphobilinogen deaminase gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria. However, we could not detect a mutation in the coding or the promotor region of the protoporphyrinogen oxidase gene that is mutated in variegate porphyria. Our results indicate that Chester porphyria is neither a dual porphyria, nor a separate type of porphyria, but rather a variant of acute intermittent porphyria. Further, our findings largely exclude the possibility that a hitherto unknown gene is involved in the pathogenesis of the porphyrias., This study was supported by grants from the “Interdisciplinary Center for Clinical Research in Biomaterials and Tissue-Material-Interaction in Implants” (BMBF project No. 01 KS 9503/9) to JF. PPG was supported by grant No. A/99/02925 from the Deutscher Akademischer Austauschdienst (DAAD). JF was supported by grant No. 01 KX 9820/F from the Bundesministerium für Bildung und Forschung (BMBF).

3 páginas, 1 figura, 1 tabla., Until the 1980s, LI was the term used to describe both LI and NCIE. However, since that time, LI and NCIE have been separated into two distinct clinical disorders.2 Although the classic clinical features of LI and NCIE can be used to distinguish the two disorders, many patients show an intermediate or overlapping phenotype, making the classification of these patients challenging on the basis of clinical findings alone. Patients with LI classically have large, dark plate-like scales involving the entire body surface, toughness of the facial skin leading to ectropion and eclabium, and secondary nail deformity.2 Scarring alopecia is another characteristic of LI, especially at the periphery, because of traction at the hairline. Patients do not usually improve with age although they have a normal life span. In contrast to LI, NCIE is classically characterized by generalized erythema and fine white scales. An affected child is frequently born as a collodion baby.1 Mild ectropion, eclabium or alopecia are common and the palms and soles are hyperkeratotic. In some cases, improvement occurs during childhood and puberty., This study was supported by NIH/NIAMS USPHS grant RO1-AR 47338 (A.M.C.) and the Authority for Research and Development, Hebrew University of Jerusalem (A.Z.).

OBJECTIVE: To describe two cases of stomatitis related to fluoxetine given for the treatment of depression that were detected in the hospital emergency department. DATA SYNTHESIS: Two women developed stomatitis after the intake of fluoxetine for the treatment of depression. One of the patients had six recurrent episodes of stomatitis without suspecting an association with fluoxetine. No other drugs were administered during these episodes. The second patient was treated concurrently with fluoxetine and bentazepam. In both patients the lesion improved upon discontinuation of fluoxetine, even though the second patient continued to take a different benzodiazepine. DISCUSSION: Stomatitis related to fluoxetine has not been previously reported in clinical trials or in the literature. According to the causal algorithm used by the Spanish Drug Surveillance Schemes, the first case constituted a defined adverse reaction and the second was probable. CONCLUSIONS: Our observations suggest that fluoxetine may be considered as a probable cause of stomatitis. The reporting of isolated cases of adverse drug reactions (ADRs) makes it possible to define the toxicity profile of recently marketed drugs such as selective serotonin-reuptake inhibitors, including fluoxetine. Emphasis is placed on the potential role played by emergency departments in detecting ADRs.

An analysis is made of the effect of alternateday dosing of atorvastatin and standard once-daily dosing, based on mean low-density lipoprotein (LDL) reduction from baseline in type 2 diabetics. Forty-four type 2 diabetics were enrolled in the study. In compliance with American Diabetes Association (ADA) and National Cholesterol Education Program Expert Panel (NCEP-III) guidelines, LDL-C

The aim of the present work is to investigate the effects of dopamine on isolated rat colon strips, and whether dopamine receptors are involved in these effects. Experiments on spontaneous motility and under potassium contraction were performed with dopamine and isoprenaline, both in the absence and presence of antagonists (distal colon strips, isotonic recording, Tyrode solution, 31 °C, 1 g of resting tension). At higher concentration (10–4mol/L), dopamine abolished spontaneous motility of the rat colon and this effect was not modified by antagonists. In isolated rat colon strips that were depolarized with potassium, dopamine produced concentration-dependent relaxation, without significant differences in reserpinized rats. Preincubation with sulpiride or Sch 23390, dopamine antagonists, did not modify the effects of dopamine. Propranolol shifted the concentration-response curve to the right, though in a noncompetitive manner. Prazosin and yohimbine (α-antagonists) did not modify the response to dopamine. Isoprenaline produced a concentration-dependent relaxant response to the KCl-induced contraction antagonized by propranolol, but not by prazosin, in a noncompetitive manner. In conclusion, dopamine exhibits a relaxant effect on the isolated rat colon, which is not mediated by specific dopamine receptors or α-adrenoceptors but it may be mediated by atypical β-adrenoceptors. Key words: dopamine, isolated rat colon, dopamine receptors.

To describe patterns observed in the treatment of acute otitis media (AOM) in several locations of five countries.Cross-sectional, descriptive study. Random sample of 12,264 paediatric outpatients seen by paediatricians or general practitioners (GPs). Data on patient demographics, diagnoses and treatment were collected. Diagnoses were coded by ICD-9 and drugs by ATC classification. Patients diagnosed with AOM (ICD-9 codes: 381 and 382) were selected for analysis.Cases of AOM (873) accounted for 7.1% of the sample. There is a clear variation in the percentage of children diagnosed with AOM and treated with antibiotics in the different locations, antibiotic prescriptions being higher in Barcelona (93% of children), and lowest in Smolensk (56.4 % of children were treated without antibiotics). The antibiotics used varied widely: ampicillin use is almost limited to Smolensk (26.7%) and Bratislava (13.8%), whereas amoxicillin plus clavulanic acid is the choice in Toulouse (33.8%), Valencia (30.2%) and Barcelona (28.9%), and cephalosporins are more frequently prescribed in Tenerife (51.7%). Finally, macrolides are used in Barcelona (18.3%), Valencia (17.5%) and Tenerife (13.6%), but not prescribed in Toulouse or Sofia. Prescriptions of anti-inflammatory drugs were only relevant in Valencia (31.7%), Tenerife (27.2%) and Toulouse (17.4%) and of otological preparations in Sofia, where almost each child received ear drops (91.9%). Nasal preparations are commonly used only in Sofia (41.9%), Bratislava (65.5%) and Smolensk (68.6%).Despite the general agreement of most guidelines, wide differences in the treatment of uncomplicated AOM in children are observed. Non-antibiotic therapy for AOM and the use of first-choice antibiotics should be more actively encouraged in the primary care centres. Studies to measure prevailing rates of antibiotic resistance in these populations are needed.

Scarce information about comparative diagnostic and therapeutic patterns in paediatric outpatients of different countries is found in the literature.To describe the similarities and differences observed in diagnosis and therapeutic patterns of paediatric patients of seven locations in different countries.Cross-sectional, prospective, international comparative, descriptive study.A randomly selected sample of 12,264 paediatric outpatients seen in consultation rooms of urban and rural areas and attended by paediatricians or general practitioners of the participating locations. Data on patient demographic information, diagnosis and pharmacological treatment were collected using pre-designed forms. Diagnoses were coded using the ICD-9 and drugs according to the ATC classification.Among the ten most common diagnoses, upper respiratory tract infections are in the first position in all locations; asthma prevalence is highest in Tenerife (8.4%). Tonsillitis, otitis, bronchitis and dermatological affections are the most common diagnoses in all locations. Pneumonia is only reported in Sofia (3.8%) and Smolensk (2.3%). The average number of drugs prescribed per child varied from 1.3 in Barcelona to 2.9 in Smolensk. There are no great differences in the profile of pharmacological groups prescribed, but a considerable range of variations in antibiotic therapy is observed: prescription of cephalosporins is low in Smolensk (0.7%) and higher in the other locations, from 16.5% (Bratislava) to 28% (Tenerife). Macrolides prescriptions range from 12.6% (Toulouse) to 24.7% (Smolensk), except in Sofia where they drop to 5.6%. Trimethoprim and its combinations are used in Smolensk (23.3%), Sofia (11.8%) and Bratislava (8.7%). Check-up consultations are not recorded in Smolensk and Bratislava, whereas in Toulouse these visits account for 16.2% of all consultations and in the other locations the percentage varies from 6.1% (Tenerife) to 1.9% (Sofia). Homeopathic treatments are registered only in Toulouse.Except in asthma prevalence, there are no great differences in diagnostic maps among locations. Significant variations in the number of drugs prescribed per child and antibiotic therapies are observed. Areas for improvement have been identified.

La introduccion de los antimicrobianos en la decada de 1940 represento uno de los mayores avances medicos de todos los tiempos. Sin embargo, las enfermedades infecciosas siguen siendo la causa mas frecuente de consulta en atencion primaria (AP), donde se realiza el 92% de la prescripcion de antibioticos (ATB). Espana es uno de los paises desarrollados con mas consumo de ATB, mayores tasas de resistencia bacteriana (RBA), sobre todo en los patogenos de origen comunitario (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Campylobacter jejuni, Salmonella o Escherichia coli), y exportadora de estas resistencias a nivel mundial1,2. Los datos sobre consumo de ATB en Espana son escalofriantes; fue el segundo pais europeo que mas consumio en el ano 1997 y 20 de cada 1.000 pacientes recibian tratamiento ATB diario en el ano 20003,4. Las infecciones por bacterias resistentes se asocian a una mayor morbilidad, mortalidad, demanda sanitaria, coste del tratamiento y deterioro de la calidad del tratamiento de futuros pacientes1,5. La AP es el nivel asistencial donde mas ATB se consumen; sin embargo, existen grandes diferencias con la asistencia hospitalaria respecto al control de su uso. En el ambito hospitalario existen comisiones asesoras sobre infeccion hospitalaria, listas restringidas, ATB de reserva, guias terapeuticas, la prescripcion se hace por el medico en funcion de las RBA, no existe automedicacion y se controla la evolucion clinica y el cumplimiento del tratamiento a diario. Aspectos que no encontramos en AP, donde hay una oferta de ATB superior a 1.000 especialidades farmaceuticas6,7. Ademas, los cambios acaecidos en la medicina en los ultimos anos, como el uso de protesis, cateteres, tratamientos inmunosupresores cronicos, pacientes con inmunodeficiencias y la hospitalizacion a domicilio, condicionan que las infecciones comunitarias se parezcan cada vez mas a las hospitalarias y sean mas dificiles de tratar. El consumo exagerado de ATB y la aparicion de RBA estan relacionados directamente con la prescripcion medica inadecuada, la dispensacion sin receta por los farmaceuticos y el uso indiscriminado que realizan los pacientes. Otros responsables son los laboratorios farmaceuticos por la presion que realizan sobre la prescripcion y la administracion sanitaria por la falta de una politica de ATB en AP1,7,8. Para mejorar el uso de ATB deberiamos emprender acciones encaminadas a corregir la actuacion de las personas e instituciones implicadas e instaurar politicas de uso racional de ATB en cada area sanitaria1,7-9.

Objective and design: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus.¶Material: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used.¶Treatment: Repetitive responses to histamine (10–6, 10–5, 10–4, 10–3 M), dimaprit and clonidine (10–4 M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/ kg, 24 h before sacrifice) reserpine, 10–7 M propranolol, 10–8 M atropine, and 10–6 M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol.¶Methods: In vitro techniques (de Jalon's solution, 31°C, carbogen, isotonic registration, resting tension 1 g). Levels of cAMP were studied in response to histamine, adrenaline and isoproterenol by radioassay.¶Results: Repeated histamine produced a rapid loss of inhibitory uterine response depending on the number of exposures and increase in concentration. The tachyphylaxis phenomenon is not modified by the different pretreatments used. Dimaprit, but not clonidine or adrenaline, produced tachyphylaxis. The second exposition to 10–3 M histamine produced a 38.8% reduction in cAMP production.¶Conclusion: Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.

68 páginas, 10 figuras. 1º ed., Genetic disease may be caused by defects in one gene (Mendelian or monogenic diseases) or more than one gene (polygenic diseases), but it can also be a result of the interaction of environmental and genetic factors (complex or multifactorial traits) The major Mendelian patterns of inheritance are autosomal recessive (e.g. oculocutaneous albinism), autosomal dominant (e.g. Darier disease), X-linked recessive (e.g. hypohidrotic ectodermal dysplasia), and X-linked dominant (e.g. incontinentia pigmenti). Factors modifying the basic Mendelian pattern of inheritance include incomplete penetrance, age-dependent penetrance, variable expression, de novo mutations, pseudodominant inheritance, genomic imprinting, and mitochondrial inheritance. Chromosomal anomalies can consist of abnormalities in the number (e.g. polyploidy, aneuploidy) or in the structure (e.g. translocations, …)

12 páginas, 2 figuras., We report the clinical and molecular findings in a patient with a mild form of recessive dystrophic epidermolysis bullosa and aortic insufficiency. To our knowledge, this is the first report of association between dystrophic epidermolysis bullosa and abnormalities of the aortic valve. Analysis of the COL7A1 gene has revealed two new mutations, a 20-bp duplication and a splice site mutation., This study was supported by NIH NIAMS R01 AR43602 (A.M.C.).

Genotype-phenotype correlations highlighted the function of ABCA4 in retinitis pigmentosa (RP),cone-rod dystrophy (CRD) and Stargardt/Fundus Flavimaculatus disease (STGD/FFM). Initial screening of ABCA4 variants showed a correlation between the type of mutation and the severity of the disease. In the present study we have undertaken mutational and haplotype analysis of ABCA4 in three mixed pedigrees segregating different retinal dystrophies. In family I, we have shown cosegregation of different ABCA4 alleles with CRD (homozygosity for L1940P) and three subtypes of STGD/FFM. The first, a mild form, consisting on fundus flavimaculatus-like distribution of flecks, but good visual acuity and absence of dark choroid, was found to cosegregate with alleles R1097C and F553L; the second, a conventional Stargardt phenotype was associated to alleles L1940P/R1097C and the third, displaying severely reduced visual acuity and dark choroid (named FFM), was associated to L1940P/F553L. In family II, segregating STGD and RP phenotypes, while the involvement of ABCA4 in STGD seems clear this is not the case for RP. Finally, in family III, also segregating STGD and RP, ABCA4 fails to explain either phenotype. Our data highlight the wide allelic heterogeneity involving this gene and support the genetic variability (beyond ABCA4) of mixed STGD/RP pedigrees.