Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies.

This work aimed to analyse the pharmacogenetic information in the Spanish Drug Regulatory Agency (AEMPS) Summary of Products Characteristics (SmPC), evaluating the presence of pharmacogenetic biomarkers, as well as the associated recommendations. A total of 55.4% of the 1891 drug labels reviewed included information on pharmacogenetic biomarker(s). Pharmacogenomic information appears most frequently in the "antineoplastic and immunomodulating agents", "nervous system", and "cardiovascular system" Anatomical Therapeutic Chemical groups. A total of 509 different pharmacogenetic biomarkers were found, of which CYP450 enzymes accounted for almost 34% of the total drug-biomarker associations evaluated. A total of 3679 drug-biomarker pairs were identified, 102 of which were at the 1A level (PharmGKB® classification system), and 33.33% of these drug-pharmacogenetic biomarker pairs were assigned to "actionable PGx", 12.75% to "informative PGx", 4.9% to "testing recommended", and 4.9% to "testing required". The rate of coincidence in the assigned PGx level of recommendation between the AEMPS and regulatory agencies included in the PharmGKB® Drug Label Annotations database (i.e., the FDA, EMA, SWISS Medic, PMDA, and HCSC) ranged from 45% to 65%, being 'actionable level' the most frequent. On the other hand, discrepancies between agencies did not exceed 35%. This study highlights the presence of relevant pharmacogenetic information on Spanish drug labels, which would help avoid interactions, toxicity, or lack of treatment efficacy.

Persistence of SARS-CoV-2 total immunoglobulins in a series of convalescent plasma and blood donors.

BACKGROUND: The vast majority of COVID-19 cases both symptomatic and asymptomatic develop immunity after COVID-19 contagion. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The aim of this study was to determine how long total anti-SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting. MATERIAL AND METHODS: A series of 2421 donations either of SARS-CoV-2 convalescent plasma or whole blood from 1107 repeat donors from January 2020 to March 2021 was analysed. An automated chemiluminescence immunoassay for total antibodies recognizing the nucleocapsid protein of SARS-CoV-2 in human serum and plasma was performed. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings. Blood donation is allowed after a minimum of one-month post symptom's relapse. Donors were 69.7% males and their average age was 46. The 250 donors who had later donations after a positive one underwent further analysis. Both qualitative (positivity) and quantitative (rise or decline of optical density regarding consecutive donations) outcomes were evaluated. RESULTS AND DISCUSSION: In 97.6% of donors with follow-up, anti-SARS-CoV-2 protein N total antibodies remained positive at the end of a follow-up period of 12.4 weeks median time (1-46, SD = 9.65) after the first positive determination. The blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils would help predict future waning or decay of antibodies. Most recovered donors maintain their total anti-SARS-CoV-2 N protein antibodies for at least 16 weeks (at least one month must have been awaited from infection resolution to blood donation). The 10 individuals that could be followed up longer than 40 weeks (approximately 44 weeks after symptom's relapse) were all still positive.

Epithelial component and intraepithelial lymphocytes of conjunctiva-associated lymphoid tissue in healthy children.

Conjunctiva-associated lymphoid tissue (CALT) plays a key role in protecting the eye surface by initiating and regulating immune responses. The aim of this study was to investigate in healthy children the proportion of intraepithelial lymphocytes (IELs), the degree of viability and/or apoptosis and cell proliferation in three different topographic areas of the conjunctiva. Superior tarsal, superior bulbar, and inferior tarsal-bulbarfornix conjunctival cells were collected by brush cytology (BC) from 24 healthy paediatric subjects (13 boys and 11 girls, mean age 6±2 years) who were to undergo strabismus correction surgery under general anaesthesia. Subsequently, these cells were analysed phenotypically and functionally by flow cytometry (FC). Flow cytometry analysis showed that not all the cells obtained by BC were of the epithelial lineage, but that there was a population of CD45+ cells (IELs) regularly present in the conjunctiva of healthy children. These IELs were mostly T-lymphocytes (CD3+) and B-lymphocytes (CD19+), with higher levels of T-lymphocytes (CD3+) in the upper areas than in the inferior tarsal-bulbar-fornix, where the highest levels of B-lymphocytes (CD19+) were found. In the apoptosis assay, two groups of cell populations were differentiated by cell size and complexity (cytoplasmic granularity), with more complex cells predominating in the upper areas of the conjunctiva and less complex cells being more abundant in the inferior tarsal-bulbar-fornix. Finally, the proliferative capacity of the conjunctival epithelium was significantly higher in the upper tarsal zone than in the rest of the zones analysed. These results suggest that the epithelial component and the IELs of CALT are also regularly present in the conjunctiva of the healthy child, varying in phenotype, viability and cell proliferation according to the different conjunctival regions analysed, which could lead us to believe that each conjunctival zone plays a different, specific role in the regulation of the immune response at the ocular level.

Prospective study of sexual function and analysis of risk factors after rectal cancer surgery.

AIM: The aim of this study was to assess the evolution of sexual function over time after rectal cancer surgery and to identify risk factors that may have an impact on the deterioration of postoperative function. METHOD: This was a prospective cohort study of sexual function after rectal cancer surgery using the International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI) preoperatively and at 6 and 12 months after surgery. Predictive factors of worsening were identified by univariate and multivariate analysis. RESULTS: One hundred and one patients were included (56 men and 45 women). In men, the average IIEF showed decreased erectile function and intercourse satisfaction at 6 months (respectively 21.58 ± 7.18 to 16.60 ± 7.96, p = 0.002 and 10.87 ± 2.94, to 8.09 ± 4.45, p = 0.002) with recovery at 1 year. As a percentage, erectile dysfunction increased from the preoperative value to 6 months (64.5% vs 87.1%, p = 0.022) and was observed in 72% at 1 year. Patients with moderate to severe dysfunction increased from 22% preoperatively to 58% (p = 0.009) at 6 months and 44% at 1 year (p < 0.0001). Neoadjuvant chemoradiotherapy (OR 5.4, 95% CI 0.9-29.6; p = 0.041) and erectile worsening at 6 months (OR 20, 95% CI 1.6-238; p = 0.004) were independent factors for worse function at 6 or 12 months, respectively. No significant worsening of the FSFI was found, although there was an improvement in lubrication and orgasm. CONCLUSION: Temporary deterioration of erectile function in men is common at 6 months after surgery and chemoradiotherapy is the only predictive factor. Furthermore, patients who remain dysfunctional show an increase in the severity of symptoms in relation to the preoperative period.

Mannheimia haemolytica and Bibersteinia trehalosi Serotypes Isolated from Merino Breed Lambs in Extremadura (Southwestern Spain).

Pneumonia caused by Mannheimia haemolytica is an important disease in ruminants. Because of its economic significance, several methods have been developed to study the pathogenicity and epidemiology of M. haemolytica. In this study, bacterial isolates of M. haemolytica and Bibersteinia trehalosi identified from the lungs of sheep were serotyped by means of indirect haemagglutination. Of the 598 lungs studied, 34 isolates were identified and serotyped. In decreasing order, M. haemolytica serotypes were: not typable (50 %), A1 (17.65 %), A7 (11.76 %), A6 (5.88 %), and A12, A2, A5 and A9 (each representing 2.94 %). The only B. trehalosi serotype was T4 (2.94 %). Serotypes A1, A6 and A7 of M. haemolytica were the most commonly isolated from pneumonic sheep producing greater changes in the lungs and having important implications for sheep production.

Angioedema hereditario por déficit del inhibidor de la esterasa C1 / No disponible

No disponible

Efficacy of a brief multifactorial adherence-based intervention in reducing blood pressure: a randomized clinical trial.

BACKGROUND: Lowering blood pressure (BP) by antihypertensive (AHT) drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to AHT medications reduces their effectiveness and increases the risk of adverse events. OBJECTIVE: To evaluate the effectiveness of a multifactorial adherence-based intervention in a primary care setting in lowering BP. METHODS/DESIGN: Multicenter parallel randomized controlled trial. Thirty two nurses in 28 primary care centers of three Spanish regions. Patients aged 18-80 years, taking AHT drugs with uncontrolled BP (n=221) were randomized to a control group (usual care) or a multifactorial adherence-based intervention including nurse-led motivational interviews, pill reminders, family support, BP self-recording, and simplification of the dosing regimen by a pharmacist. MAIN OUTCOME MEASURES: The primary outcome was 12-month blinded measure of systolic BP (mean of three measurements). The secondary outcomes were 12-month diastolic BP and proportion of patients with adequately controlled BP. RESULTS: One hundred and fourteen patients were allocated to the intervention group and 109 to the control group. At 12 months, 212 (89%) participants completed the study. The systolic BP in the intervention group was 151.3 versus 153.7 in the control group (P=0.294). The diastolic BP did not differ between groups (83.4 versus 83.6). Of the patients in the control group, 9.2% achieved BP control versus a 15.8% in the intervention group. The relative risk for achieving BP control was 1.72 (95% confidence interval: 0.83-3.56). CONCLUSION: A multifactorial intervention based on improving adherence in patients with uncontrolled hypertension failed to find evidence of effectiveness in lowering systolic BP. TRIAL REGISTRATION: ISRCTN21229328.

Producción de fosfolipasa y proteinasa en cepas de Malassezia pachydermatis aisladas de perros con otitis y sin otitis / Phospholipase and proteinase production by Malassezia pachydermatis isolated in dogs with and without otitis

Antecedentes. Malassezia pachydermatis forma parte de la microbiota cutánea de perros y gatos. M. pachydermatis se ha asociado frecuentemente a otitis externa y dermatitis seborreicas, sobre todo en el perro, y con menor frecuencia en el gato. M. pachydermatis podría actuar como patógeno cuando existen alteraciones en los mecanismos físicos, químicos o inmunológicos de la piel. Se han identificado diversos factores de virulencia como la capacidad de producir estearasas, lipasas, lipooxigenasas, proteinasas, condroitinsulfatasas e hialuronidasas. Objetivos. Se ha estudiado la actividad fosfolipasa medida a pH 6,3 y la actividad proteinasa medida a pH 6,3 y pH 6,8 (pH de oídos de perros con otitis) de cepas de M. pachydermatis aisladas de perros con otitis y sin otitis. Métodos. Se ha estudiado la actividad fosfolipasa mediante un método semicuantitativo con yema de huevo y la actividad proteinasa mediante un método semicuantitativo con agar albúmina sérica bovina. Se ha realizado el estudio en 96 aislamientos de M. pachydermatis, 43 de ellos aislados de perros sin sintomatología clínica de otitis y 52 aislados de perros con otitis. Resultados. Se observó que el 75,8% de los aislamientos presentaron actividad fosfolipasa a pH 6,3 y el 81% presentaron actividad proteinasa medida a pH 6,3, y el 97,9% a pH 6,8. Se detectó una mayor actividad fosfolipasa en cepas aisladas de perros con otitis. Con respecto a la actividad proteinasa, esta fue mayor a pH 6,8. Conclusiones. Estos hallazgos sugieren que la actividad fosfolipasa podría jugar un papel importante en la invasión de los tejidos del hospedador, por lo menos en la otitis crónica canina. Con respecto a la actividad proteinasa, estos hallazgos podrían ayudar a mejorar la terapéutica de la otitis cuando está implicada M. pachydermatis en el proceso, ajustando a pH bajos los tratamientos aplicados (AU)

[Phospholipase and proteinase production by Malassezia pachydermatis isolated in dogs with and without otitis]. / Producción de fosfolipasa y proteinasa en cepas de Malassezia pachydermatis aisladas de perros con otitis y sin otitis.

BACKGROUND: Malassezia pachydermatis is part of the skin microbiota of dogs and cats. M. pachydermatis has been associated with external otitis and seborrhoeic dermatitis, reported more often in dogs than in cats. When the physical, chemical or immunological mechanisms of the skin are altered, M. pachydermatis could act as a pathogen. Thus, several virulence factors, such as the ability to produce esterase, lipase, lipoxygenase, protease, chondroitin sulphatase, and hyaluronidase, have been studied. AIMS: In the present study, we aim to identify the phospholipase activity measured at pH 6.3, and the proteinase activity measured at pH 6.3 and pH 6.8 (pH from ears of dogs with external otitis) of M. pachydermatis strains isolated from dogs with and without external otitis. METHODS: The phospholipase activity was measured using a semi-quantitative method with egg yolk, and the proteinase activity with a semi-quantitative method using bovine serum albumin agar. The study was performed on 96 isolates of M. pachydermatis, 43 isolated from dogs without clinical symptoms of otitis, and 52 isolated from dogs with otitis. RESULTS: In our study, 75.8% of the isolates showed phospholipase activity at pH 6.3, and 81 and 97.9% of them showed proteinase activity measured at pH 6.3 and 6.8, respectively. A higher phospholipase activity was detected in strains isolated from dogs with otitis. The proteinase activity was increased at a pH of 6.8 (97.9%) in comparison to a pH of 6.3 (81%). CONCLUSIONS: Our results suggest that the phospholipase activity may play an important role in the invasion of host tissues in chronic canine otitis cases. The proteinase activity results obtained in this study suggest that a reduction in the pH of the treatment may improve its efficacy in the resolution of M. pachydermatis otitis.

Association between shared epitope and anti-citrullinated peptide antibodies in rheumatoid arthritis: A systematic review and meta-analysis

The group of major histocompatibility complex (MHC) alleles known as shared epitope (SE)is to date the strongest rheumatoid arthritis (RA) genetic risk factor. Many studies have shown that the measurement of anti-citrullinated peptides antibodies would be useful in the diagnosis and follow-up of RA. Our aim is to determine the magnitude of the association between the possession of SE alleles and serum positive titres of antibodies against citrullinated peptides. Our selection criteria included case–control or cohort studies, where data involving antibodies against citrullinated peptides and SE in RA patients were available. No date or language restrictions were imposed. Bibliographical databases MEDLINE, Cochrane Database of Systematic Reviews and EMBASE were searched for pertinent literature. Two reviewers independently identified relevant citations and extracted data. Data extraction was then checked by two different reviewers. Five published and one unpublished (own data) studies were included in the final metaanalysis. Overall, 2700 European descent RA patients were included in this meta-analysis. A significant association between SE and positive titres of serum antibodies against citrullinated peptides [OR(95% CI) = 3.19 (2.21–4.60)] was found. Positive titres for antibodies against citrullinated peptides are threefold more frequent in RA patients who carry SE alleles than in those patients lacking them (AU)

El grupo de alelos del complejo mayor de histocompatibilidad (MHC) conocidos como epí-topo compartido (EC) es a día de hoy el más fuerte los factores de riesgo genético a artritisreumatoide (AR). Diferentes estudios han puesto de manifiesto que la presencia de autoanticuerpos contra péptidos citrulinados sería útil en el diagnóstico y seguimiento de la artritisreumatoide. Nuestro objetivo es determinar la magnitud de la asociación entre la posesión de alelos del SE y la presencia de títulos positivos de anticuerpos contra péptidos citrulinados. Nuestros criterios de selección incluyeron estudios de cohortes y caso-control en los que hubiera datos disponibles acerca de los anticuerpos contra péptidos citrulinados y el epítopo compartido en artritis reumatoide. No se hicieron restricciones de fecha ni de idioma. Se realizaron búsquedas en las bases de datos bibliográficas MEDLINE, Cochrane Database of Systematic Reviews y EMBASE. Dos revisores identificaron de manera independiente lascitas relevantes y extrajeron los datos. La extracción de datos fue comprobada posteriormente por dos revisores diferentes de los anteriores. En el meta-análisis definitivo se incluyeron cinco estudios publicados y uno no publicado(datos propios). En total se incluyeron 2700 casos de RA de ascendencia europea en el metaanálisis. Se encontró una asociación significativa entre los títulos de anticuerpos positivos y el hecho de ser portador de alelos del epítopo compartido [OR(95% CI) = 3.19 (2.21–4.60)]. Los títulos positivos de anticuerpos contra péptidos citrulinados son tres veces más frecuentes en pacientes de AR portadores de alelos del EC que en los no portadores (AU)

Procedimiento de validación de magnitudes bioquímicas en un gasómetro. Aplicación al alcance flexible en la Norma ISO 15189 / Validation procedure of biochemical parameters in a gasometer. Application to the flexible scope in the standard ISO 15189

Objetivos. Diseñar un procedimiento de validación de 4 magnitudes bioquímicas en un gasómetro frente a un analizador acreditado que sea sencillo, consistente y aceptable según la Norma ISO 15189:2007 y que pueda servir como método de acreditación flexible. Métodos. Medición secuencial en los analizadores Dimension RxL y GEM 4000 de glucosa, sodio (Na+), potasio (K+) y lactato en 91 muestras de plasma (heparina de litio) de pacientes entre marzo y junio de 2009 (EP-9). Se chequearon outliers y error sistemático. Los pares de resultados se estudiaron mediante análisis de regresión lineal y gráficos de Bland-Altman. Métodos. El criterio de aceptación fue obtener un error sistemático inferior a las especificaciones de calidad definidas en el laboratorio acreditado. Resultados y discusión. Los resultados de glucosa y K+ fueron aceptables según el procedimiento 6.1 de la guía EP-9, mientras que Na+ fue aceptable según el procedimiento 6.2. En cuanto a lactato, se detectó un error sistemático superior a la especificación del laboratorio. Conclusiones. Se han validado los métodos de determinación de glucosa, Na+ y K+ en un gasómetro GEM 4000 mediante la aplicación de la norma EP-9 con respecto a los del Dimension RxL (métodos de referencia). El lactato no se pudo validar porque el error sistemático superó la especificación del laboratorio. Conclusiones. Este procedimiento se propone como herramienta de validación de métodos para laboratorios acreditados con alcance flexible según la Norma UNE EN ISO 15189 (AU)

Objectives. Designing a 4 biochemical parameters validation procedure in a gasometer versus an accredited analyzer. This procedure is simple, robust and acceptable according to the standard ISO 15189: 2007 and that can serve as flexible accreditation method. Methods. Sequential measurement in Dimension RxL and GEM 4000 analysers of glucose, Na+, K+ and lactate in 91 patients plasma samples (Lithium heparin) between March and June 2009 (EP-9). Checked outliers and bias results pairs were studied using linear regression analysis and Bland-Altman graphics. Methods. The acceptance criterion was to get a bias lower than quality specifications defined in the accredited laboratory. Results and discussion. The results of glucose and K+ were acceptable, following the procedure 6.1 of EP9 guideline, while for Na+ it was acceptable by the procedure 6.2. For lactate, a superior to the specification of the lab bias was detected. Conclusions. Measuring methods of glucose, sodium and potassium in a GEM 4000 gasometer applying standard EP9 versus Dimension RxL as reference methods have been validated. Lactate could not be validated because the bias exceeded the specification of the laboratory. Conclusions. This procedure is intended as validation tool of methods for laboratories accredited with flexible scope according to UNE EN ISO 15189 standard (AU)

Impact of sulfur starvation on cysteine biosynthesis in T-DNA mutants deficient for compartment-specific serine-acetyltransferase.

Sulfur plays a pivotal role in the cellular metabolism of many organisms. In plants, the uptake and assimilation of sulfate is strongly regulated at the transcriptional level. Regulatory factors are the demand of reduced sulfur in organic or non-organic form and the level of O-acetylserine (OAS), the carbon precursor for cysteine biosynthesis. In plants, cysteine is synthesized by action of the cysteine-synthase complex (CSC) containing serine acetyltransferase (SAT) and O-acetylserine-(thiol)-lyase (OASTL). Both enzymes are located in plastids, mitochondria and the cytosol. The function of the compartmentation of the CSC to regulate sulfate uptake and assimilation is still not clearly resolved. To address this question, we analyzed Arabidopsis thaliana mutants for the plastidic and cytosolic SAT isoenzymes under sulfur starvation conditions. In addition, subcellular metabolite analysis by non-aqueous fractionation revealed distinct changes in subcellular metabolite distribution upon short-term sulfur starvation. Metabolite and transcript analyses of SERAT1.1 and SERAT2.1 mutants [previously analyzed in Krueger et al. (Plant Cell Environ 32:349-367, 2009)] grown under sulfur starvation conditions indicate that both isoenzymes do not contribute directly to the transcriptional regulation of genes involved in sulfate uptake and assimilation. Here, we summarize the current knowledge about the regulation of cysteine biosynthesis and the contribution of the different compartments to this metabolic process. We relate hypotheses and views of the regulation of cysteine biosynthesis with our results of applying sulfur starvation to mutants impaired in compartment-specific cysteine biosynthetic enzymes.

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis.

Therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) are limited due to lack of effective treatments. Thus, there is a need to thoroughly characterize the pathways of molecular pathogenesis and to identify potential targets for therapy in MTC. Since epidermal growth factor receptor (EGFR) seems to play a crucial role for RET activation, a key feature of MTCs, and several promising EGFR/vascular endothelial growth factor receptor 2 (VEGFR2)-targeted drugs have been developed, the present study was designed to investigate whether these proteins are altered in MTCs. We used a well-characterized series of 153 MTCs to evaluate EGFR activation by sequencing and FISH analysis, and to perform EGFR and VEGFR2 immunohistochemistry. EGFR tyrosine kinase domain mutations were not a feature of MTCs; however, EGFR polysomy and a strong EGFR expression were detected in 15 and 13% of the tumors respectively. Interestingly, EGFR was significantly overexpressed in metastases compared with primary tumors (35 vs 9%, P=0.002). We also studied whether specific RET mutations were associated with EGFR status, and found a decrease in EGFR polysomies (P=0.006) and a tendency towards lower EGFR expression for the most aggressive RET mutations (918, 883). Concerning VEGFR2, metastasis showed a higher expression than primary tumors (P=2.8 x 10(-8)). In this first study investigating the relationship between EGFR, RET, and VEGFR2 in a large MTC series, we found an activation of EGFR and VEGFR2 in metastasis, using both independent and matched primary/metastasis samples. This suggests that some MTC patients may benefit from existing anti-EGFR/VEFGR2 therapies, although additional preclinical and clinical evidence is needed.

Calidad de vida y trasplante renal en mayores de 65 años / Quality of life and kidney transplants in over-65s

La calidad de vida se define como “la percepción personal de un individuo de su situación de vida, dentro del contexto cultural y de valores en el que vive, y en relación con sus objetivos, expectativas, valores e intereses”. El objetivo de este trabajo es conocer la calidad de vida de los pacientes trasplantados renales mayores de 65 años. Estudio cualitativo, descriptivo y retrospectivo. La muestra abarcó un total de 31 pacientes mayores de 65 años que fueron trasplantados en nuestro centro desde julio de 2003 hasta julio de 2006. El instrumento de recogida de información fue doble: una encuesta de 11 ítems y el cuestionario SF-36.El aspecto peor valorado por los encuestados (51,6 puntos) se refería a la capacidad de realizar un esfuerzo físico intenso. Sin embargo, actividades de menor intensidad recibieron una puntuación más elevada (88,7 puntos). Los pacientes mayores de 65 años que han recibido un trasplante renal, perciben una mejoría importante en su calidad de vida respecto al período anterior. Esto se refleja en una ampliación del abanico de actividades a realizer (AU)

Quality of life is defined as “the personal perception of an individual of his or her life situation, within the cultural context and the context of the values in which he or she lives, and in relation to his orher goals, expectations, values and interests”. The aim of this study is to determine the quality of life of patients over 65 years of age who have undergone kidney transplants. A qualitative, descriptive and retrospective study. The sample encompassed a total of 31 patients aged over 65 who received kidney transplants at our centre between July 2003 and July 2006. The instrument used to compile the information was in two parts: a survey of 11 items and questionnaire SF-36.The aspect that received the lowest rating from the patients surveyed (51.6 points) related to the capacity for intense physical efforts. However, activities of lower intensity received a higher score (88.7 points). Patients aged over 65 who have received a kidney transplant perceive an important improvement in their quality of life compared to the period prior to the transplant. This is reflected in an extension of the range of activities they can carry out (AU)

Intervención farmacéutica en el seguimiento de la terapia antirretroviral / Pharmaceutical intervention in the follow-up of antiretroviral therapy

La eficacia y el alto coste de la terapia antirretroviral exigen un estrechoseguimiento para lograr su máxima efectividad y eficiencia, siendofundamental el papel del farmacéutico para alcanzarla mediante laindividualización de los tratamientos. El objetivo de este estudio ha sidoconseguir un adecuado control clínico del paciente VIH+ a través deluso correcto de los medicamentos antirretrovirales prescritos. Para ellose ha puesto en marcha un Programa de Atención Farmacéutica paralos pacientes externos VIH+ en tratamiento antirretroviral en un hospitaluniversitario. Después de un año y medio de iniciarlo se han realizadoun total de 853 entrevistas en 386 pacientes VIH+ (79,6% del total),consiguiéndose un aumento del 9% en la proporción de pacientes conadherencia óptima. A su vez, se han detectado 1.060 acontecimientosadversos por medicamentos y 513 problemas relacionados con la medicación.En función de ello, se han realizado 1.401 intervenciones en 365pacientes.El grado de aceptación de los pacientes al servicio de atención farmacéuticaha alcanzado una puntuación media de 3,27 (escala 0-4).El número de pacientes cuyas concentraciones plasmáticas de fármacosantirretrovirales se han monitorizado es de 381, con un totalde 849 determinaciones. Sólo el 39% de ellas se encontraba dentro delos márgenes terapéuticos aceptados para estos fármacos. Basándoseen la información farmacocinética, los clínicos han realizado el ajusteposológico en 16 pacientes.La experiencia obtenida desde la implantación del programa de seguimientoha puesto de manifiesto su utilidad para la optimizaciónde los tratamientos con fármacos antirretrovirales(AU)

Pharmaceutical intervention in the follow-up of antiretroviraltherapy.The elevated cost of antiretroviral treatment demands close follow-upto achieve the effectiveness and efficacy of the treatments implemented,the role of pharmacists in achieving such goals is crucial in the sense thatthey are mainly involved in directing antiretroviral treatments aimed atgenerating maximum benefit with the available resources. The aim of thepresent study was to achieve an appropriate clinical control of HIV+ patientsthrough the correct use of the antiretroviral drugs prescribed.The study was carried out for external HIV-patients with antiretroviraltreatment in a university hospital. One and a half years after implementinga Pharmaceutical Care Program, a total of 853 interviewswere obtained from 386 HIV+ patients (79.6% of the total), achievinga 9% increase in optimal adherence. In turn, we observed 1060 adversedrugs events and 513 drug related problems. In consequence, weperformed 1401 interventions in 365 patients. The degree of patientacceptance of the program had a mean score of 3.7 (scale 0-4).The number of patients whose antiretroviral plasma concentrationswere monitored was 381, with a total of 849 determinations.Only 39% of them were within the therapeutic range established forthese drugs. Based on pharmacokinetic information, the cliniciansperformed a dosage adjustment in 16 patients.The experience gained since the implementation of the HIV+ patientfollow-up program has proved to be useful for the optimisationof treatments using antiretroviral drugs(AU)

Analysis of cytosolic and plastidic serine acetyltransferase mutants and subcellular metabolite distributions suggests interplay of the cellular compartments for cysteine biosynthesis in Arabidopsis.

In plants, the enzymes for cysteine synthesis serine acetyltransferase (SAT) and O-acetylserine-(thiol)-lyase (OASTL) are present in the cytosol, plastids and mitochondria. However, it is still not clearly resolved to what extent the different compartments are involved in cysteine biosynthesis and how compartmentation influences the regulation of this biosynthetic pathway. To address these questions, we analysed Arabidopsis thaliana T-DNA insertion mutants for cytosolic and plastidic SAT isoforms. In addition, the subcellular distribution of enzyme activities and metabolite concentrations implicated in cysteine and glutathione biosynthesis were revealed by non-aqueous fractionation (NAF). We demonstrate that cytosolic SERAT1.1 and plastidic SERAT2.1 do not contribute to cysteine biosynthesis to a major extent, but may function to overcome transport limitations of O-acetylserine (OAS) from mitochondria. Substantiated by predominantly cytosolic cysteine pools, considerable amounts of sulphide and presence of OAS in the cytosol, our results suggest that the cytosol is the principal site for cysteine biosynthesis. Subcellular metabolite analysis further indicated efficient transport of cysteine, gamma-glutamylcysteine and glutathione between the compartments. With respect to regulation of cysteine biosynthesis, estimation of subcellular OAS and sulphide concentrations established that OAS is limiting for cysteine biosynthesis and that SAT is mainly present bound in the cysteine-synthase complex.

[Influence of mutations of proteinase-activated receptors F2R/PAR1 and F2RL1/PAR2 on inflammatory bowel disease]. / Influencia de las mutaciones de los receptores activados por proteinasa F2R/PAR1 y F2RL1/PAR2 en la enfermedad inflamatoria intestinal.

BACKGROUND AND OBJECTIVE: Inflammatory bowel disease (IBD) is a polygenic complex trait. The expression and presence in biopsiae from IBD patients points to a putative role of these genes in genetic susceptibility to IBD. This is the first association study on these genes in relation with IBD. PATIENTS AND METHOD: Two polymorphisms were analyzed within F2R/PAR1 and another one mapping to F2RL1/PAR2 in 778 healthy controls and 943 IBD cases (Crohn's disease and ulcerative colitis patients from 2 cohorts from Madrid and Granada). RESULTS: No significant differences in the distribution of the PARs' polymorphisms were found. CONCLUSIONS: There is no evidence of association of the analyzed polymorphisms with IBD risk.