University Hospital Of Bellvitge
University Hospital Of Bellvitge
Ferrer I.,University Hospital of Bellvitge |
Ferrer I.,University of Barcelona |
Ferrer I.,Hospitalet Of Llobregat |
Ferrer I.,CIBER ISCIII |
And 12 more authors.
Neurobiology of Disease | Year: 2012
Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. This may apply to complex alterations interfering with olfactory and autonomic nervous system functions, emotions, sleep regulation, and behavioral, cognitive and mental performance. Involvement of the cerebral cortex leading to impaired behavior and cognition is related to several convergent altered factors including: a. dopaminergic, noradrenergic, serotoninergic and cholinergic cortical innervation; b. synapses; c. cortical metabolism; d. mitochondrial function and energy production; e. oxidative damage; f. transcription; g. protein expression; h. lipid composition; and i. ubiquitin-proteasome system and autophagy, among others. This complex situation indicates that multiple subcellular failure in selected cell populations is difficult to reconcile with a reductionistic scenario of a single causative cascade of events leading to non-motor symptoms in PD. Furthermore, these alterations may appear at early stages of the disease and may precede the appearance of substantial irreversible cell loss by years. These observations have important implications in the design of therapeutic approaches geared to prevention and treatment of PD. © 2011 Elsevier Inc.
PubMed | University Hospital Of Bellvitge, Institute Investigacion Sanitaria del Hospital Clinico San Carlos, University Pompeu Fabra, Hospital Clinic and Institute dInvestigacio August Pi I Sunyer and 3 more.
Type: Journal Article | Journal: Multiple sclerosis (Houndmills, Basingstoke, England) | Year: 2016
Human cytomegalovirus (HCMV) causes a highly prevalent infection which may have a multifaceted impact on chronic inflammatory disorders. However, its potential influence in multiple sclerosis (MS) remains controversial. The HCMV-host interaction may induce an adaptive reconfiguration of the natural killer (NK) cell compartment, whose hallmark is a persistent expansion of peripheral NKG2C+ NK-cells.The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course.Multicentre analysis of NKG2C expression and genotype according to HCMV serostatus and time of assignment of irreversible disability scores in 246 MS patients prospectively followed up in our institutions.NKG2C expression was unrelated to disease-modifying drugs, remained stable under steady-state conditions, and was higher in HCMV(+) NKG2C(+/+) homozygous individuals. NKG2C+ NK-cell expansion in HCMV(+) patients, as compared to HCMV(+) or HCMV(-) patients with lower NKG2C+ NK-cells proportions, conferred a lower risk of progression in Cox regression analysis (Expanded Disability Status Scale (EDSS)>3.0, hazard ratio (HR)=0.33, 95% confidence interval (CI) 0.15-0.71, p=0.005; EDSS>5.5, HR=0.23, 95% CI 0.07-0.74, p=0.014). Neither HCMV serostatus nor NKG2C genotype appeared to be related to disability progression.HCMV may exert a beneficial influence on MS, decreasing the risk of disability progression in those patients displaying a virus-driven NKG2C+ NK-cell expansion.
PubMed | University of Cologne, University Of Clermont Ferrand, Vilnius University, Fondazione Instituto Of Oncologia Molecolare Ifom and 103 more.
Type: Journal Article | Journal: PloS one | Year: 2015
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
Miranda M.,Rovira i Virgili University |
Miranda M.,CIBER ISCIII |
Escote X.,Rovira i Virgili University |
Escote X.,CIBER ISCIII |
And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010
Context: AQP7 is considered to be the sole adipose glycerol channel, and its regulation is crucial for glycemia control. Objectives: In this work, we aimed to further characterize AQP7 in human adipose tissue in obesity and type 2 diabetes (T2D): 1) to assess AQP7 expression levels in paired abdominal adipose tissue depots (sc and visceral); 2) to relate it with gene expression of genes involved in lipid metabolism; and 3) to confirm that AQP7 is mainly expressed in the adipocytes. Design: We conducted a transversal study of gene expression in paired samples of sc adipose tissue (SAT) and visceral adipose tissue (VAT). Patients: Caucasian lean and obese subjects (n = 62, matched for age and gender) and T2D subjects (n = 11, matched for age, gender, and BMI with their control group) participated in the study. Main Outcome Measure: We measured AQP7 expression levels in paired SAT and VAT. Results: We have proved the presence of AQP7 mRNA and protein in the adipocyte rather than the stromovascular fraction of adipose tissue (P = 0.001) and in mature adipocytes when differentiated in vitro. Increased AQP7 mRNA expression levels in VAT from T2D obese subjects (P < 0.05) were found. AQP7 transcript levels ratio of SAT vs. VAT changed with the presence of obesity and T2D. Interestingly, there were positive associations between AQP7 and both lipogenic and lipolytic genes in a similar manner in both adipose depots. Conclusions: Taken together, these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D. Copyright © 2010 by The Endocrine Society.
Pastor A.,Human Pharmacology and Clinical Neurosciences Research Group |
Pastor A.,IMIM Hospital Del Mar Medical Research Institute |
Farre M.,Human Pharmacology and Clinical Neurosciences Research Group |
Farre M.,IMIM Hospital Del Mar Medical Research Institute |
And 7 more authors.
Journal of Lipid Research | Year: 2014
The analysis of peripheral endocannabinoids (ECs) is a good biomarker of the EC system. Their concentrations, from clinical studies, strongly depend on sample collection and time processing conditions taking place in clinical and laboratory settings. The analysis of 2-monoacylglycerols (MGs) (i.e., 2-arachidonoylglycerol or 2-oleoylglycerol) is a particularly challenging issue because of their ex vivo formation and chemical isomerization that occur after blood sample collection. We provide evidence that their ex vivo formation can be minimized by adding Orlistat, an enzymatic lipase inhibitor, to plasma. Taking into consideration the low cost of Orlistat, we recommend its addition to plasma collecting tubes while maintaining sample cold chain until storage. We have validated a method for the determination of the EC profile of a range of MGs and N-acylethanolamides in plasma that preserves the original isomer ratio of MGs. Nevertheless, the chemical isomerization of 2-MGs can only be avoided by an immediate processing and analysis of samples due to their instability during conservation. We believe that this new methodology can aid in the harmonization of the measurement of ECs and related compounds in clinical samples.-Pastor, A., M. Farré, M. Fitó, F. Fernandez- Aranda, and R. de la Torre. Analysis of ECs and related compounds in plasma: artifactual isomerization and ex vivo enzymatic generation of 2-MGs. J. Lipid Res. 2014. 55: 966-977. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
PubMed | University Hospital of Bellvitge, University of Pavia, University of Barcelona, Igualada General Hospital and Instituto Auxologico Italiano
Type: | Journal: Studies in health technology and informatics | Year: 2016
The objective of this study was to assess the association between external eating style and food craving experienced during exposure to food cues in virtual reality (VR) environments in both clinical and non-clinical samples. According to the externality theory, people with external eating experience higher reactivity when exposed to food cues, which in turn increases the probability of overeating. Forty patients with eating disorders (23 with bulimia nervosa and 17 with binge eating disorder) and 78 undergraduate students were exposed to 10 different food cues in four VR environments (kitchen, dining room, bedroom, and caf). After 30 seconds of exposure to each VR environment, food craving was assessed using a visual analog scale. External, emotional and restrictive eating styles were also assessed using the DEBQ. The results showed a strong association between external eating and cue-elicited food craving. After controlling for the presence of eating disorder diagnosis, external eating was the best predictor of reported food craving. The results lend support to the externality theory but highlight the need for further research in specific patterns of functioning in patients with bulimia nervosa and binge eating disorder.
de Leon-Casasola O.A.,Roswell Park Cancer Institute |
de Leon-Casasola O.A.,State University of New York at Buffalo |
Mayoral V.,University Hospital of Bellvitge
Journal of Pain Research | Year: 2016
Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (#7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. © 2016 de León-Casasola and Mayoral.
Fuentemilla L.,08907 Lhospitalet Of Llobregat |
Fuentemilla L.,University of Barcelona |
Miro J.,08907 Lhospitalet Of Llobregat |
Miro J.,University Hospital of Bellvitge |
And 12 more authors.
Current Biology | Year: 2013
Recent accumulating evidence in animals and humans has shown that memory strengthening occurs, at least partially, during sleep [1, 2] and relies on the covert reactivation of individual memory episodes [3-5]. However, it remains to be determined whether the hippocampus critically promotes memory consolidation via the reactivation of individual memories during sleep. To investigate the hippocampal-dependent nature of this phenomenon in humans, we selected two groups of chronic temporal lobe epileptic (TLE) patients with selective unilateral (TLE+UHS) or bilateral (TLE+BHS) hippocampal sclerosis and a group of matched healthy controls, and we requested them to learn the association of sounds cueing the appearance of words. On the basis of other similar behavioral paradigms in healthy populations [4, 6], sounds that cued only half of the learned memories were presented again during the slow-wave sleep stage (SWS) at night, thus promoting memory reactivation of a select set of encoded episodes. A memory test administered on the subsequent day showed that the strengthening of reactivated memories was observed only in the control subjects and TLE+UHS patients. Importantly, the amount of memory strengthening was predicted by the volume of spared hippocampus. Thus, the greater the structural integrity of the hippocampus, the higher the degree of memory benefit driven by memory reactivation. Finally, sleep-specific neurophysiological responses, such as spindles and slow waves, differed between the sample groups, and the spindle density during SWS predicted the degree of memory benefit observed on day 2. Taken together, these findings demonstrate that the hippocampus plays a crucial role in the consolidation of memories via covert reactivation during sleep. © 2013 Elsevier Ltd. All rights reserved.