Efectividad del tratamiento y seguimiento longitudinal de pacientes con TLP tratados en Hospital de Día / The effectfiveness of the treatment and the longitudinal follow-up of the BPD patients, treated at the Day Hospital / Efectivitat del tractament i seguiment longitudinal de pacients amb TLP tractats en un hospital de dia

El objetivo de este estudio es evaluar la gravedad sintomatologica y el funcionamiento social en una muestra de 35 pacientes que habían sido derivados al Programa TLP (trastorno límite de la personalidad) de un Hospital de Día. La evaluación del cambio clínico, realizada mediante la escala de Impresión Clínica Global (ICG-TLP), puso de manifiesto que los pacientes mejoran tras el tratamiento en ocho de las 10 áreas típicas del trastorno y mantienen esta mejoría a los cinco años de seguimiento, excepto en impulsividad y afectividad. Los resultados muestran que el tratamiento especializado para el TLP en Hospitales de Día es beneficioso para los pacientes que lo sufren

The objective of this study is to evaluate the symptom severity and the social functioning in a sample of 35 patients who had been derived to BPD (borderline personality disorder) (TLP) Programme of a Day Hospital. The evaluation of a clinical change, performed using the Global Clinical Impression scale (ICG-BPD), showed that patients improved after treatment in 8 of the 10 typical areas of the disorder and that they maintained this improvement after five years of follow-up, except in impulsivity and affectivity. The results show that the specialized treatment for BPD in Day Hospitals is beneficial for patients suffering from BPD

L'objectiu d'aquest estudfi és avaluar fla gravetat simptomatològfica i el funcionament social en una mostra de 35 pacients que havien estat derivats afl Programa TLP (trastorn límfit de la personalitat) d'un hospfitafl de dfia. L'avaluacfió defl canvi clínfic, realitzada mitjançant l'escafla d'Impressió Clínica Global (ICG-TLP), posà de manifest que els pacients milloren després del tractament en vufit de fles 10 àrees típiques del trastorn i mantenen aquesta milloria als cinc anys de seguiment, excepte en impulsivitat i afectivitat. Es resultats mostren que el tractament especialitzat pel TLP en hospitals de dia és beneficiós per als pacients que el pateixe

Modulation of sirtuins: new targets for antiageing.

Aging is characterized by a progressive deterioration of physiological functions and metabolic processes. Healthy aging remains one of the ideals of modern society. In aging and in diseases associated with the elderly, such as Alzheimer's or Parkinson's, the loss of cells in vital structures or organs may be related to several factors, among which the production of reactive oxygen species (ROS) by mitochondria is a common denominator, one that leads to DNA damage, apoptosis and death. Although a diet rich in antioxidants seems to offer hope in delaying the onset of unhealthy disorders that accompany aging, no clinical treatment as such has yet been developed and anti-aging drugs are still unavailable. It is well established that reducing food intake (caloric restriction) extends the life-span in a wide range of species. The protein implicated in this protective process is the silent information regulator 2 (SIR2, SIRT1 in mammals), an enzyme that belongs to a nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRs regulate gene silencing, DNA repair, rDNA recombination, and ageing, apart from regulating programmed cell death. In this context, increasing SIRT1 has been found to protect cells against amyloid-beta-induced ROS production and DNA damage, thereby reducing apoptotic death in vitro. Moreover, it has been demonstrated that Alzheimer's and Huntington's disease neurons are rescued by the over-expression of SIRT1, induced by either caloric restriction or administration of resveratrol, a potential activator of this enzyme. The therapeutic use of resveratrol (a polyphenol present in red wines) and other related compounds, which utilize SIRT1 pathway modulators, in treating aging-related brain disorders will be discussed in this review. Provided herein are novel new compound related with resveratrol or sirtinol that are able to modulate sirtuin activity that will be tested to treat and/or prevent a wide variety of diseases including, disorders related to aging or neurodegenerative diseases.

Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

[(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity.

Methylglyoxal (MG) is a reactive alpha-ketoaldehyde physiologically generated as a by-product of glycolysis. MG that is able to form protein adducts resulting in advanced glycation end products accumulates under conditions associated with neurodegeneration such as impaired glucose metabolism or oxidative stress. In the present study, short-term exposure of human neuroblastoma SH-SY5Y cells to MG was associated with an early depolarization of the plasma membrane, glutamate release, and formation of reactive oxygen species. In addition, long-term exposure (24 h) of SH-SY5Y cells to MG caused a decrease in cell viability, intracellular ATP, and rhodamine 123 (Rh-123) fluorescence. ATP depletion and the decrease in Rh-123 fluorescence were prevented by carbonyl scavengers, the nitric oxide synthase inhibitor L-NAME, and N-methyl-d-aspartate (NMDA) receptor antagonists. Furthermore, the MG-induced glutamate release and the loss in cell viability were prevented by NMDA receptor antagonists. Therefore, MG renders cells more vulnerable to excitotoxicity. In conclusion, carbonyl scavengers as well as NMDA receptor antagonists may represent effective therapeutic tools to reduce the risk of pathophysiological changes associated with carbonyl stress in neurodegenerative diseases.