Up-regulation of renal renin-angiotensin system and inflammatory mechanisms in the prenatal programming by low-protein diet: beneficial effect of the post-weaning losartan treatment.

Previous studies have shown that the renin-angiotensin system (RAS) is affected by adverse maternal nutrition during pregnancy. The aim of this study was to investigate the effects of a maternal low-protein diet on proinflammatory cytokines, reactive oxygen species and RAS components in kidney samples isolated from adult male offspring. We hypothesized that post-weaning losartan treatment would have beneficial effects on RAS activity and inflammatory and oxidative stress markers in these animals. Pregnant Sprague-Dawley rats were fed with a control (20% casein) or low-protein diet (LP) (6% casein) throughout gestation. After weaning, the LP pups were randomly assigned to LP and LP-losartan groups (AT1 receptor blockade: 10 mg/kg/day until 20 weeks of age). At 20 weeks of age, blood pressure levels were higher and renal RAS was activated in the LP group. We also observed several adverse effects in the kidneys of the LP group, including a higher number of CD3, CD68 and proliferating cell nuclear antigen-positive cells and higher levels of collagen and reactive oxygen species in the kidney. Further, our results revealed that post-weaning losartan treatment completely abolished immune cell infiltration and intrarenal RAS activation in the kidneys of LP rats. The prevention of augmentation of angiotensin (Ang II) concentration abolished inflammatory and fibrotic events, indicating that Ang II via the AT1 receptor is essential for pathological initiation. Our results suggest that the prenatal programming of hypertension is dependent on the up-regulation of local RAS and presence of immune cells in the kidney.

Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function.

Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms involved are not fully understood. Emerging evidence has suggested the potential role of endothelial progenitor cells (EPCs) in vascular health and repair. Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and EPCs derived from the peripheral blood (PB) and bone marrow (BM) in vitro. Pregnant Wistar rats were fed an ad libitum diet (control group) or 50% of the ad libitum diet (restricted group) throughout gestation. We determined vascular reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male offspring from both groups (aged: 19-20 weeks). Moreover, the amount, functional capacity, and senescence of EPCs were assessed in vitro. Our results indicated that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was similar between both groups; however, IUGR decreased the functional capacity of EPCs from the PB and BM. Furthermore, the senescence process was accelerated in BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the deleterious changes in EPCs from IUGR rats, such as reduced EPC function and accelerated senescence in vitro. These findings may contribute towards elucidating the possible mechanisms involved in endothelial dysfunction induced by fetal programming.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

Dependencia a benzodiacepinas / Dependence on benzodiazepines

Objetivo. Se presenta el caso clínico de una mujer adicta a benzodiacepinas que es ingresada en una Unidad de Hospitalización de Salud Mental con diagnóstico de trastorno depresivo. Material y método. Se estudia el caso clínico de una paciente de 33 años con antecedentes de abuso de sustancias así como los factores de riesgo intercurrentes para abuso de benzodiacepinas. Resultados. Después de describir la historia psiquiátrica y toxicológica de la paciente se realiza el diagnóstico principal y el de otros trastornos comórbidos según criterios DSM-IV-TR; así también, se mencionan las posibilidades de abordaje terapéutico. Conclusiones. La prescripción de benzodiacepinas debe hacerse bajo control y siguiendo las recomendaciones del Ministerio de Sanidad y Consumo para prevenir la dependencia o el consumo inadecuado de estos fármacos. Las estrategias de deshabituación exigen una detallada valoración del paciente para llegar a la recomendación más adecuada y aceptable para cada tipo de paciente AU)

Objective. The case of women addicted to benzodiacepines who is hospitalized in a Mental Health Inpatient Unit and diagnosed as depressive disorder, is presented. Material and methods. The clinical case of a 33-year-old female with personal history of substance abuse and risk factors of benzodiazepines abuse. Results. After describing the clinical and toxicological history of the patient, the main and comorbid diagnosis are done following DSM-IV-TR criteria. Different possibilities for treatment are mentioned. Conclusions. Benzodiazepines prescription must be following Ministry of Health recommendations to prevent drug-addictions and inadequate consumption. Strategies for suppression of the consumption require a precise assessment of the patient to achieve the most adequate recommendation for each patient (AU)

Trastorno bipolar asociado al uso de sustancias adictivas (patología dual). Revisión sistemática de la evidencia científica y consenso entre profesionales expertos / Bipolar disorder associated to substance use disorders (dual diagnosis). Systematic review of the scientific evidence and expert consensus

El presente trabajo está focalizado en la llamada patología dual (PD): trastorno bipolar (TB) asociado a un trastorno por uso de sustancias (TUS). A pesar de que tanto los psiquiatras que tratan a pacientes con TB como los médicos que tratan a los pacientes con TUS encuentran frecuentemente esta asociación, lamentablemente las publicaciones que exploran la PD son escasas. El Grupo Español de Trabajo en Patología Dual en Trastorno Bipolar realizó una revisión del material publicado mediante una búsqueda bibliográfica en Medline y seleccionó los artículos relevantes publicados hasta el momento; a continuación se llevó a cabo un consenso de expertos y finalmente se realizó una encuesta a expertos en PD para responder a las áreas que no estaban suficientemente cubiertas por la evidencia científica o en las cuales no se llegó a un consenso dentro del grupo de trabajo. Se concluye que en las actuales circunstancias el establecimiento de un consenso constituye una herramienta muy útil para complementarla evidencia científica existente (AU)

The present work focuses on the so-called dual diagnosis (DD): bipolar disorder (BD) associated with substance use disorders (SUD). Although the psychiatrists who treat patients with BD and physicians in charge of patients with SUD frequently find this association with DD, unfortunately there are few scientific works that have studied this association. The Spanish Working Groupon Bipolar Disorders in Dual Diagnosis reviewed the published material using a Medline search and selected the most relevant articles. Following this, the Work Group developed an expert consensus in DD and finally, a survey was performed among a group of experts in this disorder to cover the areas that were not fully addressed by the scientific evidence or in those areas in which the Work Group was unable to reach a consensus. We conclude that, in view of the above, establishment of a consensus is a valid tool to complement the current scientific evidence (AU)

Bipolar disorder associated to substance use disorders (dual diagnosis). Systematic review of the scientific evidence and expert consensus.

The present work focuses on the so-called dual diagnosis (DD): bipolar disorder (BD) associated with substance use disorders (SUD). Although the psychiatrists who treat patients with BD and physicians in charge of patients with SUD frequently find this association with DD, unfortunately there are few scientific works that have studied this association. The Spanish Working Group on Bipolar Disorders in Dual Diagnosis reviewed the published material using a Medline search and selected the most relevant articles. Following this, the Work Group developed an expert consensus in DD and finally, a survey was performed among a group of experts in this disorder to cover the areas that were not fully addressed by the scientific evidence or in those areas in which the Work Group was unable to reach a consensus. We conclude that, in view of the above, establishment of a consensus is a valid tool to complement the current scientific evidence.

Trastornos de personalidad y esquizofrenia: ¿comorbilidad o artificio diagnóstico? / Personality disorders and schizophrenia: comorbidity or diagnostic artifact?

Objetivo: Las publicaciones sobre la comorbilidad de los trastornos de personalidad con otras entidades clínicas han proliferado en los últimos años y se ha señalado la alta frecuencia de su presentación. Se ha argumentado que dicha comorbilidad no es real, sino un artificio de los actuales sistemas diagnósticos. La comorbilidad de trastornos de personalidad y esquizofrenia no es una excepción, aunque su frecuencia es menor que en el caso de otros trastornos mentales. Los problemas metodológicos que esta comorbilidad plantea son complejos y ponen en cuestión los fundamentos de los actuales sistemas diagnósticos. El objetivo de este trabajo es plantear las debilidades de estos sistemas diagnósticos, tomando como referencia la aparente comorbilidad de los trastornos de personalidad y la esquizofrenia. Material y método: Se estudia a una población de 60 sujetos diagnosticados de esquizofrenia, siguiendo los criterios de la décima edición de la Clasificación Internacional de Enfermedades (CIE-10). Mediante el instrumento diagnóstico confeccionado por el grupo SECOR, se valoran los criterios diagnósticos de trastornos de personalidad (LIDTP) y los criterios diagnósticos para la esquizofrenia (LIDESQ). Resultados: El 91,6% de los pacientes cumplía criterios para, al menos, 1 trastorno de personalidad, y el 41,7%, entre 3 y 9. Los trastornos más comórbidos eran los pertenecientes al grupo A (esquizotípico, esquizoide y paranoide), como era de esperar. Sin embargo, es sorprendente que un 31,7% de los pacientes esquizofrénicos cumpliese criterios para el trastorno de personalidad ansioso-evitativo y un 26,7% para el de inestabilidad emocional, tipo impulsivo. Conclusiones: La alta comorbilidad de esquizofrenia y trastornos de personalidad es un artificio de los actuales sistemas diagnósticos, que se debe revisar al menos en 3 aspectos: la jerarquización diagnóstica, el solapamiento de los síntomas y la redefinición de los criterios sobre los que se establece el diagnóstico de trastorno de personalidad

Objective: Publications on the comorbidity of personality disorders with other diseases have increased over the last few years, indicating its high frequency. It has been argued that this comorbidity is not real but is rather an artifact of currently used diagnostic criteria. The comorbidity of personality disorders and schizophrenia is not an exception, although its frequency is lower than in the case of other mental disorders. The methodological problems posed by this comorbidity are rather complex, casting doubt on current diagnostic criteria. The aim of this study was to show the weaknesses of these diagnostic systems, taking as a reference the apparent comorbidity of personality disorders and schizophrenia. Material and method: A population of 60 subjects with a diagnosis of schizophrenia following the CIE-10 criteria was studied. Using the diagnostic instrument designed by the SECOR group, the diagnostic criteria for personality disorders (LIDTP) and schizophrenia (LIDESQ) were analyzed. Results: A total of 91.6% of the patients fulfilled the criteria for at least one personality disorder, and 41.7% fulfilled the criteria for between three and nine personality disorders. As expected, the most comorbid disorders belonged to cluster A (schizotypal, schizoid, and paranoid). Surprisingly, however, 31.7% of patients with schizophrenia fulfilled the criteria for anxious/avoidant personality disorder, while 26.7% did so for emotionally unstable personality disorder, impulsive type. Conclusions: The high comorbidity between schizophrenia and personality disorders is an artifact of today's diagnostic criteria, which should be revised in at least three different aspects: diagnostic organization (hierarchical), symptom overlap, and redefinition of the criteria upon which personality disorders are diagnosed

Estado de la asistencia psicogeriátrica en Andalucía / Psychogeriatric care in Andalucia

No disponible

Differential and overlapping expression patterns of X-dll3 and Pax-6 genes suggest distinct roles in olfactory system development of the African clawed frog Xenopus laevis.

In Xenopus laevis, the formation of the adult olfactory epithelium involves embryonic, larval and metamorphic phases. The olfactory epithelium in the principal cavity (PC) develops during embryogenesis from the olfactory placode and is thought to respond to water-borne odorants throughout larval life. During metamorphosis, the PC undergoes major transformations and is exposed to air-borne odorants. Also during metamorphosis, the middle cavity (MC) develops de novo. The olfactory epithelium in the MC has the same characteristics as that in the larval PC and is thought to respond to water-borne odorants. Using in situ hybridization, we analyzed the expression pattern of the homeobox genes X-dll3 and Pax-6 within the developing olfactory system. Early in development, X-dll3 is expressed in both the neuronal and non-neuronal ectoderm of the sense plate and in all cell layers of the olfactory placode and larval PC. Expression becomes restricted to the neurons and basal cells of the PC by mid-metamorphosis. During metamorphosis, X-dll3 is also expressed throughout the developing MC epithelium and becomes restricted to neurons and basal cells at metamorphic climax. This expression pattern suggests that X-dll3 is first involved in the patterning and genesis of all cells forming the olfactory tissue and is then involved in neurogenesis or neuronal maturation in putative water- and air-sensing epithelia. In contrast, Pax-6 expression is restricted to the olfactory placode, larval PC and metamorphic MC, suggesting that Pax-6 is specifically involved in the formation of water-sensing epithelium. The expression patterns suggest that X-dll3 and Pax-6 are both involved in establishing the olfactory placode during embryonic development, but subtle differences in cellular and temporal expression patterns suggest that these genes have distinct functions.

Delirio en el anciano con trastorno mental orgánico: una aproximación nosográfica / Older with delusion and organic-brain disorder: a nosographical aproximation

Los cuadros delirantes que se presentan en el curso de los trastornos orgánico-cerebrales constituyen un tema de interés psiquiátrico tanto por la frecuencia con que se presentan en la clínica, sobre todo gerontopsiquiátrica, como por la dificultad nosológica que entrañan. Desde un punto de vista clásico la proliferación de términos que han ido surgiendo para denominar estos cuadros psicóticos ha sido en no pocos casos motivo de confusión. Desde una perspectiva más actual las denominaciones clásicas (psicosis exógena, psicosis de fundamento corporal conocido, psicosis somatógena o psicosis orgánica/sintomática) engloban el mismo concepto, a saber: aquel grupo de psicosis condicionadas por una enfermedad somática demostrable en la que además de los factores biológicos - que ocupan un primer y preponderante lugar - intervienen también, desde el punto de vista etiopatogénico, los factores psicológicos y ambientales. Uno de los aspectos nucleares de estas psicosis es su planteamiento como entidades nosográficas. La mayoría de los autores actuales están de acuerdo en admitir dos grandes bloques: psicosis agudas y psicosis crónicas, al margen de todo compromiso etiopatogénico. Ocurre igual con los criterios diagnósticos internacionales (DSM-IV y CIE-10) que abordan a estas psicosis desde un planteamiento sindrómico (AU)

Regions of the CD8 molecule involved in the regulation of CD2-mediated activation.

The CD8 molecule regulates T cell activation mediated via the CD3 T cell receptor and the adhesion molecule CD2. CD8 mAbs have been found to inhibit early (Ca2+ rise) as well as late events (cytotoxicity, proliferation, and lymphokine secretion) mediated via the CD2 pathway. A panel of eight anti-human CD8 mAbs was tested for inhibition of CD2-mediated Ca2+ rise in a cytotoxic T cell clone. The inhibition ranged from 5 to 53% independently of mAb isotype and affinity measured by half saturation binding. We then characterized these mAbs for their reactivity toward three mutants of the human CD8 alpha carrying amino acid sequence changes in the surface-exposed loops homologous to the immunoglobulin CDR1, 2, and 3. The mutations included replacement of the human CD8 alpha CDR1- and CDR2-like loops by the homologous mouse sequences and the insertion of a glycine in the middle of the CDR3-like loop. Thus, five mAbs were found to be affected by the mutation in the CDR2-like loop but not by alterations in the other CDR-like loops. Conversely, the other two mAbs (8E1.7 and B9.8) were affected only by mutations in the CDR1- and CDR3-like loops, respectively. Cross-inhibition experiments were essentially in agreement with these results. Interestingly, all the mAbs directed against the CDR2-like loop were potent inhibitors of CD2-mediated Ca2+ rise, with one exception probably due to poor affinity. Thus, in addition to being a site of interaction with major histocompatibility complex Class I as recent data have indicated, this region of the CD8 alpha subunit may play a role in regulating T cell activation.

Regulation of CD2-mediated human T cell activation: anti-CD8 monoclonal antibodies inhibit CD2-mediated rise in intracellular calcium.

The human CD8 glycoprotein regulates the function of cytotoxic T cells activated by antigenic peptide as well as via CD3 or CD2 mAbs. Activation of T cells by CD2 mAbs requires two mAbs directed against distinct CD2 epitopes and induces tyrosine phosphorylation, PI-PLC activity generating the second messengers, IP3 and DAG, and finally lymphokine secretion. We have investigated the role of the CD8 alpha molecule in CD2-mediated activation of human cytotoxic T cell clones and CD8+ resting T cells. CD8 alpha-specific mAb inhibited 60% of the allospecific cytotoxicity of the CD8+ clone against its target cell and 86% of the CD2-redirected killing against the HLA Class I-negative Daudi target cell. In addition, CD8 alpha-specific mAb inhibited CD2-mediated TNF alpha and IL2 secretion by the CD8+ clone. Furthermore, CD8 alpha-specific mAb inhibited the increase in intracellular ionized calcium mediated by CD2 mAbs in the CD8+ clone and in purified T cells. Since the [Ca2+]i recruitment from internal stores induced by CD2 mAbs was inhibited, the inhibitory effect induced by the CD8 alpha-specific mAb probably acts on the PI-PLC activation pathway. This inhibition mechanism involves neither a decrease in affinity of CD2 mAb for its target nor a decrease in CD2 cell surface expression or a rise in cAMP known as an inhibitor of the CD2-mediated PI-PLC activity. These results suggest that the inhibitory mechanism induced by the CD8 mAb may prevent the activation of the PI-PLC activity, probably through the CD8 alpha-associated protein tyrosine kinase p56lck.

Anti-T11.1 and -T11.2 monoclonal antibodies play a different role in CD2-mediated signal transduction.

We comparatively evaluated (Ca2+)i mobilization after triggering with a stimulatory pair of CD2 (CD2.9, anti-T11.1 + CD2.1, anti-T11.2) or CD3 mAbs in the differentiated T-cell line Jurkat, using INDO-1 labeling and cytofluorimetry. The results obtained showed different (Ca2+)i mobilization kinetics following CD2 or CD3 stimulation (the former being slower than the latter), not due to different association kinetics of mAbs. In a nonreciprocal manner, however, preliminary interaction with CD2.1 (anti-T11.2) followed by CD2.9 (anti-T11.1) induces a rapid (Ca2+)i rise, similar to CD3 stimulation, as shown by preincubation experiments. There is no interference between CD2.9 and CD2.1 mAb binding. CD2.1 mAb by itself is unable to induce (Ca2+)i mobilization; in addition, preincubation with CD2.1 mAb did not modify the CD2, CD3, CD45, or CD28 immunoprecipitation patterns. Triggering of the epitope recognized by CD2.1 mAb may favor, possibly via conformational changes of CD2 molecule or (Ca2+)i-unrelated metabolic effect(s), optimal signal transduction.

Signalling through CD28 T-cell activation pathway involves an inositol phospholipid-specific phospholipase C activity.

Stimulation of the human T-cell line, Jurkat, by a monoclonal antibody (mAb) directed against the CD28 molecule leads to sustained increases in intracellular levels of Ca2+ ([Ca2+]i); the initial rise in Ca2+ comes from internal stores, followed by Ca2+ entry into the cells. The CD28 molecule also appears to activate polyphosphoinositide (InsPL)-specific phospholipase C (PLC) activity in Jurkat cells, as demonstrated by PtdInsP2 breakdown, InsP3 and 1,2-diacylglycerol generation and PtdIns resynthesis. We also observed that interleukin-2 (IL2) production induced via CD28 triggering was sensitive to a selective protein kinase C inhibitor. Of the four other anti-CD28 mAbs (CD28.2, CD28.4, CD28.5, CD28.6) tested, only one (CD28.5) was unable to generate any InsPL-specific PLC or IL2 secretion. However, the cross-linking of cell-bound CD28.5 with anti-mouse Ig antibodies led to an increase in [Ca2+]i. CD28-molecule clustering in itself appears to be a sufficient signal for induction of PLC activity.