33 research outputs found
Postsurgical pain related to breast implant: reduction with lipofilling procedure
No full textAfter a review of clinical cases of the Unit of Plastic Surgery of the University of Siena, Italy, we found that 22 patients undergoing lipofilling for breast recontruction needed less pain drugs compared to 18 patients which did not undergo lipofilling. In this work, the postoperative pain was analyzed in two groups of patients: a cohort treated with prosthesis and a cohort treated with prosthesis implant together with a lipofilling procedure
EMLA and Lidocaine Spray: A Comparison for Surgical Debridement in Venous Leg Ulcers
No full textObjective: In this study the author proposes to compare eutectic mixture of local anesthetics (EMLA) and an odontoiatric spray solution of 10% Lidocaine (Ecocain) for surgical debridement in venous leg ulcers. Approach: Fifty patients were recruited and randomly assigned into two groups (A, B). All of them have venous leg ulcer in the medial and/or lateral malleolar region. Group A: topical anesthetic EMLA with film occlusion. Group B: topical anesthesia with Ecocain. The author proceeded to surgical debridement after local anesthesia. A questionnaire and a visual analog scale (VAS) were administered to assess the amount of pain felt during the debridement and during the following 6 h. Results: The analysis of the VAS revealed no major significant differences statistically. The analysis of the questionnaires showed patients treated with Ecocain took more analgesic drugs. Analysis of the timing and quality of procedure showed that Ecocain reduced the timing of debridement and dressing change, improving the outpatient management and patient compliance. Innovations: For rapid debridement, the most appropriate is to use Ecocain. Conclusion: Methods of local anesthesia are multiple and must be identified according to the needs of the patient and the surgeon trying to get the best anesthesia with minimal use of time and resources. © Copyright 2015, Mary Ann Liebert, Inc
Novel potential determinants in endoplasmic reticulum stress, inflammation and insulin resistance: Apo CIII and sAPPβ
No full textDiabetes represents one of the biggest health challenges of the 21st century. Insulin resistance is the primary defect in the most common form of diabetes, type 2 diabetes mellitus (T2D), and is defined as a failure in the capacity of insulin to drive glucose into its target tissues. This condition both predicts and precedes the development of T2D.
Loss of insulin sensitivity in skeletal muscle is the major defect in T2D and is believed to be critical in the pathogenesis of this disease. Elucidating new molecular mechanisms involved in insulin resistance in skeletal muscle may lead to the development of new strategies for the prevention and treatment of T2D.
Insulin resistance develops as the result of the expansion of adipose tissue in obese individuals, which releases increased amounts of fatty acids, hormones, pro-inflammatory cytokines and other factors. Most of these molecules induce the activation of a chronic low-level inflammatory process that contributes to insulin resistance and T2D. The molecular mechanisms by which these molecules induce a low-grade and chronic inflammatory process in obese patients are not completely understood. However, some studies have shown that alterations in the endoplasmic reticulum (ER) might contribute to the development of an inflammatory status and consequently to insulin resistance.
Obesity and insulin resistance are also characterized by the presence of atherogenic dyslipidemia, which refers to elevated levels of triglycerides (TG) and the particles responsible for carrying these lipids in the plasma, the very low-density lipoproteins (VLDL), low levels of high-density lipoproteins (HDL), and increased levels of small, dense low-density lipoproteins (sdLDL). In addition to TG, VLDL also contain apolipoproteins, of which apolipoprotein CIII (Apo CIII) is one of the most abundant. Although plasma levels of VLDL and Apo CIII are increased in diabetic patients, little was known about whether the increase in the levels of these lipoproteins and apolipoproteins contributes to exacerbate insulin resistance and the mechanisms involved.
Recent evidence indicates that subjects suffering T2D are at higher risk of developing Alzheimer’s Disease (AD). In addition, several evidences point out that the converse is also true, since cognitive impairment and Alzheimer’s dementia can induce central and peripheral insulin resistance, thus increasing the risk of T2D.
The β-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) or β-secretase is a key enzyme involved in AD and is responsible for the cleavage of Amyloid Precursor Protein in the amyloidogenic pathway. It has been recently reported that BACE1 is also implicated in glucose metabolism. Thus, BACE1-deficient mice are protected against high fat diet (HFD)-induced glucose intolerance and inhibition of BACE1 activity increases insulin-independent glucose uptake. BACE1 is proteolytically active not only in the brain but also in skeletal muscle, suggesting that this enzyme might be involved in development of systemic insulin resistance. However, little was known about whether BACE1 contributes to ER stress, inflammation and insulin resistance.
In this thesis, we report that the increase in the levels of VLDL can promote ER stress, inflammation, and insulin resistance in skeletal muscle through Apo CIII-mediated activation of the toll-like receptor 2.
Moreover, BACE1 inhibition in myotubes results in an improvement in lipid-induced ER stress, inflammation, and insulin resistance. Further, the product of BACE1 enzymatic activity, soluble amyloid precursor protein β (sAPPβ), mimics the effects of palmitate and induces ER stress, inflammation and insulin resistance.
Overall, these findings suggest that both VLDL-Apo CIII and sAPPβ are new determinants involved in ER stress, inflammation and insulin resistance in skeletal muscle
Filippo Càssola e il circolo Adolfo Omodeo
No full textAppartiene all’eredità intellettuale e materiale di Filippo Càssola anche la creazione di un circolo politico, che egli scelse di chiamare con il nome di Adolfo Omodeo, autore di una storia magistrale del Risorgimento Italiano, ispiratore della vigorosa rinascita culturale dell’Italia antifascista e precoce anticipatore di una comunità europea. Nello spirito di questi ideali, Càssola, autorevole conoscitore delle libertà e dei diritti del mondo antico e moderno, come emerge da tutta la sua prestigiosa produzione scientifica, ispirò molti studiosi e appassionati ad occuparsi di argomenti orientati verso le problematiche civili e politiche più attuali, soprattutto in relazione ai delicati problemi della questione adriatica, del resto non ancora risolti.Belongs to the intellectual heritage and material of Filippo Càssola also the creation of a political circle, that he chose to call with the name “Adolfo Omodeo”, the author of a masterful history of the Italian Risorgimento, the inspirer of vigorous cultural rebirth of the anti-Fascist Italy and early anticipator of a European Community. In the spirit of these ideals, Càssola, authoritative connoisseur of the freedom and rights of the ancient world and modern, as emerges from the whole of its prestigious scientific production, inspired many scholars and enthusiasts to deal with topics oriented toward issues and civil and political more current, especially in relation to the delicate problems of the Questione Adriatica, the rest is not yet solved
Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01
No full textRetinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1. VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.Fil: Pascual-Pasto, Guillem. Hospital Sant Joan de Déu; EspañaFil: Bazan-Peregrino, Miriam. No especifíca;Fil: Olaciregui, Nagore G.. Hospital Sant Joan de Déu; EspañaFil: Restrepo Perdomo, Camilo A.. Hospital Sant Joan de Déu; EspañaFil: Mato Berciano, Ana. No especifíca;Fil: Ottaviani, Daniela. Centre National de la Recherche Scientifique; FranciaFil: Weber, Klaus. No especifíca;Fil: Correa, Genoveva. Hospital Sant Joan de Déu; EspañaFil: Paco, Sonia. Hospital Sant Joan de Déu; EspañaFil: Vila Ubach, Monica. Hospital Sant Joan de Déu; EspañaFil: Cuadrado Vilanova, Maria. Hospital Sant Joan de Déu; EspañaFil: Castillo Ecija, Helena. Hospital Sant Joan de Déu; EspañaFil: Botteri, Gaia. Hospital Sant Joan de Déu; EspañaFil: Garcia Gerique, Laura. Hospital Sant Joan de Déu; EspañaFil: Moreno Gilabert, Helena. Hospital Sant Joan de Déu; EspañaFil: Gimenez Alejandre, Marta. No especifíca;Fil: Alonso Lopez, Patricia. No especifíca;Fil: Farrera Sal, Marti. No especifíca;Fil: Torres Manjon, Silvia. Instituto de Investigación Biomédica de Bellvitge; EspañaFil: Ramos Lozano, Dolores. Instituto de Investigación Biomédica de Bellvitge; EspañaFil: Moreno, Rafael. Instituto de Investigación Biomédica de Bellvitge; EspañaFil: Aerts, Isabelle. Centre National de la Recherche Scientifique; FranciaFil: Doz, François. Universite Paris Descartes; Francia. Centre National de la Recherche Scientifique; FranciaFil: Cassoux, Nathalie. Centre National de la Recherche Scientifique; Francia. Universite Paris Descartes; FranciaFil: Chapeaublanc, Elodie. Centre National de la Recherche Scientifique; FranciaFil: Torrebadell, Montserrat. Hospital Sant Joan de Déu; EspañaFil: Roldan, Monica. Hospital Sant Joan de Déu; EspañaFil: König, Andrés. No especifíca;Fil: Suñol, Mariona. Hospital Sant Joan de Déu; EspañaFil: Claverol, Joana. Hospital Sant Joan de Déu; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Déu; EspañaFil: De Torres, Carmen. Hospital Sant Joan de Déu; EspañaFil: Fu, Ligia. Hospital Escuela Universitario; HondurasFil: Radvanyi, François. Centre National de la Recherche Scientifique; FranciaFil: Munier, Francis L.. Hopital Ophtalmique Jules Gonin; SuizaFil: Catalá-Mora, Jaume. Hospital Sant Joan de Déu; EspañaFil: Mora, Jaume. Hospital Sant Joan de Déu; EspañaFil: Alemany, Ramón. Instituto de Investigación Biomédica de Bellvitge; EspañaFil: Cascalló, Manel. No especifíca;Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Montero Carcaboso, Angel. Hospital Sant Joan de Déu; Españ
PPARβ/δ: A Key Therapeutic Target in Metabolic Disorders
No full textResearch in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic disorders, including obesity, dyslipidaemia, type 2 diabetes mellitus and non-alcoholic fatty liver disease. This review highlights research findings on the PPARβ/δ regulation of energy metabolism and the development of diseases related to altered cellular and body metabolism. It also describes the potential of the pharmacological activation of PPARβ/δ as a treatment for human metabolic disorder
PPARβ/δ: A Key Therapeutic Target in Metabolic Disorders
No full textResearch in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic disorders, including obesity, dyslipidaemia, type 2 diabetes mellitus and non-alcoholic fatty liver disease. This review highlights research findings on the PPARβ/δ regulation of energy metabolism and the development of diseases related to altered cellular and body metabolism. It also describes the potential of the pharmacological activation of PPARβ/δ as a treatment for human metabolic disorders
VLDL and apolipoprotein CIII induce ER stress and inflammation and attenuate insulin signalling via Toll-like receptor 2 in mouse skeletal muscle cells
No full text[Aim/hypothesis] Here, our aim was to examine whether VLDL and apolipoprotein (apo) CIII induce endoplasmic reticulum (ER) stress, inflammation and insulin resistance in skeletal muscle.
[Methods] Studies were conducted in mouse C2C12 myotubes, isolated skeletal muscle and skeletal muscle from transgenic mice overexpressing apoCIII.
[Results] C2C12 myotubes exposed to VLDL showed increased levels of ER stress and inflammatory markers whereas peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and AMP-activated protein kinase (AMPK) levels were reduced and the insulin signalling pathway was attenuated. The effects of VLDL were also observed in isolated skeletal muscle incubated with VLDL. The changes caused by VLDL were dependent on extracellular signal-regulated kinase (ERK) 1/2 since they were prevented by the ERK1/2 inhibitor U0126 or by knockdown of this kinase by siRNA transfection. ApoCIII mimicked the effects of VLDL and its effects were also blocked by ERK1/2 inhibition, suggesting that this apolipoprotein was responsible for the effects of VLDL. Skeletal muscle from transgenic mice overexpressing apoCIII showed increased levels of some ER stress and inflammatory markers and increased phosphorylated ERK1/2 levels, whereas PGC-1α levels were reduced, confirming apoCIII effects in vivo. Finally, incubation of myotubes with a neutralising antibody against Toll-like receptor 2 abolished the effects of apoCIII on ER stress, inflammation and insulin resistance, indicating that the effects of apoCIII were mediated by this receptor.
[Conclusions/interpretation] These results imply that elevated VLDL in diabetic states can contribute to the exacerbation of insulin resistance by activating ERK1/2 through Toll-like receptor 2.This study was partly supported by funds from the Spanish
Ministerio de Economía y Competitividad (SAF2012-30708 and
SAF2015-64146-R to MVC), the Generalitat de Catalunya (2014SGR0013 to MVC), NIH NIDDK (DK101663 to ABK), USDA NIFA
(11874590 to ABK) and USDA NIFA Hatch Formula Funds (2015-
31200-06009 to ABK), an Instituto de Salud Carlos III grant (PI16-
00139 to JCE-G) and European Union ERDF funds. CIBER de
Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is an
Instituto de Salud Carlos III project (Grant CB07/08/0003 to MVC).
GB was supported by an FPI grant from the Spanish Ministerio de
Economía y Competitividad.Peer reviewe
miR-146a targets Fos expression in human cardiac cells.
No full textmiR-146a is a microRNA whose transcript levels are induced in the heart upon activation of NF-κB, a transcription factor induced by pro-inflammatory molecules (such as TNF-α) that is strongly related to the pathogenesis of cardiac disorders. The main goal of this study consisted of studying new roles of miR-146a in cardiac pathological processes caused by the pro-inflammatory cytokine TNF-α. Our results demonstrate that miR-146a transcript levels were sharply increased in cardiac ventricular tissue of transgenic mice with specific overexpression of TNF-α in the heart, and also in a cardiomyocyte cell line of human origin (AC16) exposed to TNF-α. Among all the in silico predicted miR-146a target genes, Fos mRNA and protein levels notably decreased after TNF-α treatment or miR-146a overexpression. These changes correlated with a diminution in the DNA-binding activity of AP-1, the Fos-containing transcription factor complex. Interestingly, AP-1 inhibition was accompanied by a reduction in matrix metalloproteinase (MMP)-9 mRNA levels in human cardiac cells. The specific regulation of this MMP by miR-146a was further confirmed at the secretion and enzymatic activity levels, as well as after anti-miR-mediated miR-146a inhibition. The results reported here demonstrate that Fos is a direct target of miR-146a activity and that downregulation of the Fos-AP-1 pathway by miR-146a has the capacity to inhibit MMP-9 activity. Given that MMP-9 is an AP-1 target gene involved in cardiac remodeling, myocardial dysfunction and progression of heart failure, these findings suggest that miR-146a might be a new and promising therapeutic tool for treating cardiac disorders associated with enhanced inflammation in the heart
The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling
No full textObjective β-secretase/β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPβ (sAPPβ), contribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. Materials/Methods Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1−/−mice and mice treated with sAPPβ and adipose tissue and plasma from obese and type 2 diabetic patients. Results We show that BACE1 inhibition or knockdown attenuates palmitate-induced endoplasmic reticulum (ER) stress, inflammation, and insulin resistance and prevents the reduction in Peroxisome Proliferator-Activated Receptor γ Co-activator 1α (PGC-1α) and fatty acid oxidation caused by palmitate in myotubes. The effects of palmitate on ER stress, inflammation, insulin resistance, PGC-1α down-regulation, and fatty acid oxidation were mimicked by soluble APPβ in vitro. BACE1 expression was increased in subcutaneous adipose tissue of obese and type 2 diabetic patients and this was accompanied by a decrease in PGC-1α mRNA levels and by an increase in sAPPβ plasma levels of obese type 2 diabetic patients compared to obese non-diabetic subjects. Acute sAPPβ administration to mice reduced PGC-1α levels and increased inflammation in skeletal muscle and decreased insulin sensitivity. Conclusions Collectively, these findings indicate that the BACE1 product sAPPβ is a key determinant in ER stress, inflammation and insulin resistance in skeletal muscle and gluconeogenesis in liver.Additional co-authors: Xavier Palomer and Manuel Vázquez-Carrer
