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Características y valor de las aberraciones cromosómicas inducidas por los tratamientos antitumorales en pacientes pediátricos con cáncer

2013-06-11T15:50:18Z

Title: Características y valor de las aberraciones cromosómicas inducidas por los tratamientos antitumorales en pacientes pediátricos con cáncer Author(s) : Lopez-de-la-Mesa, R. (R.); Sierrasesumaga, L. (Luis); Calasanz, M.J. (María José); Lopez-de-Cerain, A. (Adela); Patiño, A. (Ana) Abstract: Cytogenetic studies were performed on 80 pediatric cancer patients to test the chromosomal damage induced by the chemotherapy treatments. G-banded karyotypes were performed on peripheral blood lymphocytes (PBL) (n = 127) obtained at diagnosis, during treatment, at remission and at relapse. We detected a significant increase in the number of altered karyotypes in the samples during treatment, lowering to similar values to those at diagnosis at two-year remission. Most of the chromosomal aberrations (CA) detected during chemotherapy were unbalanced (75%) and affected most frequently chromosomes 1, 3, 5, 6, 11, 12, 16 and 17. There was also a marked increase of CA in samples at relapse, with similar features (type and distribution) to those detected during treatment. There was an outstanding correlation between the chromosomal breakpoints in our series and fragile sites (58%), oncogene (75%) and tumour suppressor gene (33%) loci described in the literature. The results obtained suggest that the cytostatic drugs induce a transient increase in chromosome fragility that focuses to several cancer-associated breakpoints.

PEGylated-PLGA microparticles containing VEGF for long term drug delivery

2013-06-11T00:50:00Z

Title: PEGylated-PLGA microparticles containing VEGF for long term drug delivery Author(s) : Simon-Yarza, T. (Teresa); Formiga, F.R. (Fabio R.); Tamayo, E. (Esther); Pelacho, B. (Beatriz); Prosper, F. (Felipe); Blanco-Prieto, M.J. (María José) Abstract: The potential of poly(lactic-co-glycolic) acid (PLGA) microparticles as carriers for vascular endothelial growth factor (VEGF) has been demonstrated in a previous study by our group, where we found improved angiogenesis and heart remodeling in a rat myocardial infarction model (Formiga et al., 2010). However, the observed accumulation of macrophages around the injection site suggested that the efficacy of treatment could be reduced due to particle phagocytosis. The aim of the present study was to decrease particle phagocytosis and consequently improve protein delivery using stealth technology. PEGylated microparticles were prepared by the double emulsion solvent evaporation method using TROMS (Total Recirculation One Machine System). Before the uptake studies in monocyte-macrophage cells lines (J774 and Raw 264.7), the characterization of the microparticles developed was carried out in terms of particle size, encapsulation efficiency, protein stability, residual poly(vinyl alcohol) (PVA) and in vitro release. Microparticles of suitable size for intramyocardial injection (5 mu m) were obtained by TROMS by varying the composition of the formulation and TROMS conditions with high encapsulation efficiency (70-90%) and minimal residual PVA content (0.5%). Importantly, the bioactivity of the protein was fully preserved. Moreover, PEGylated microparticles released in phosphate buffer 50% of the entrapped protein within 4 h, reaching a plateau within the first day of the in vitro study. Finally, the use of PLGA microparticles coated with PEG resulted in significantly decreased uptake of the carriers by macrophages, compared with non PEGylated microparticles, as shown by flow cytometry and fluorescence microscopy. On the basis of these results, we concluded that PEGylated microparticles loaded with VEGF could be used for delivering growth factors in the myocardium.

Angiogenic therapy for cardiac repair based on protein delivery systems

2013-06-08T00:39:38Z

Title: Angiogenic therapy for cardiac repair based on protein delivery systems Author(s) : Formiga, F.R. (F.R.); Tamayo, E. (Esther); Simon-Yarza, T. (Teresa); Pelacho, B. (Beatriz); Prosper, F. (Felipe); Blanco-Prieto, M.J. (María José) Abstract: Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Nanoparticules muco-pénétrantes: véhicules pour l’administration orale du paclitaxel

2013-05-27T16:29:43Z

Title: Nanoparticules muco-pénétrantes: véhicules pour l’administration orale du paclitaxel Author(s) : Zabaleta, V. (Virginia); Calleja, P. (Patricia); Espuelas, S. (S.); Corrales, L. (Leticia); Pio, R. (Rubén); Agüeros, M. (Maite); Irache, J.M. (Juan Manuel) Abstract: Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.

Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011

2013-04-17T09:39:42Z

Title: Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011 Author(s) : Martinez-Forero, I. (Iván); Okada, H. (Hideho); Topalian, S.L. (Suzanne L.); Gajewski, T.F. (Thomas F.); Korman, A.J. (Alan J.); Melero, I. (Ignacio) Abstract: Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace.

Obesidad, inflamación e insulino-resistencia: papel de los ligandos del receptor gp 130

2013-03-22T01:50:52Z

Title: Obesidad, inflamación e insulino-resistencia: papel de los ligandos del receptor gp 130 Author(s) : Marcos-Gomez, B. (Beatriz); Bustos, M. (Matilde); Prieto, J. (Jesús); Martinez, J.A. (José Alfredo); Moreno-Aliaga, M.J. (María Jesús) Abstract: Obesity can be considered as a low grade inflammatory disease, characterized by increased plasma levels of proinflammatory cytokines such as tumoral necrosis factor-a (TNF-a), and acute phase reactant proteins like C-reactive protein. In this context, some cytokines of the interleukin-6 (IL-6) family have been involved in the inflammatory processes associated to obesity. In addition to IL-6, the IL-6 cytokine family includes IL-11, ciliary neurotrophic factor (cntf), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF) y Oncostatin M (OsM). These proteins are also known as gp130 cytokines because all of them exert their action via the glycoprotein 130 (gp130) as a common transducer protein within their functional receptor complexes. However, their role in obesity and related disorders is controversial; thus, whereas some studies have described the involvement of gp130 cytokines in the development of obesity and its related cluster of pathophysiologic conditions like insulin-resistance, fatty liver and cardiovascular diseases, other trials have proposed the gp130 receptor ligands as therapeutic targets in the treatment of obesity and its related disorders. In fact, CNTF treatment has demonstrated to be effective in the reduction of body weight, by promoting the inhibition of food intake and the activation of the energy expenditure, together with an improvement of insulin sensitivity. This review analyzes the potential therapeutic role of some of the gp130 ligands in obesity and related diseases.

Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer

2013-02-25T13:38:45Z

Title: Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer Author(s) : Buñuales, M. (María); Garcia-Aragoncillo, E. (Eva); Casado, R. (Raquel); Quetglas, J.I. (José Ignacio); Hervas-Stubbs, S. (Sandra); Bortolanza, S. (Sergia); Benavides-Vallbe, C. (Carolina); Ortiz-de-Solorzano, C. (Carlos); Prieto, J. (Jesús); Hernandez-Alcoceba, R. (Rubén) Abstract: Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors for the delivery of therapeutic genes, with the aim of extending the antitumor effect beyond direct cytolysis. Transgene expression using these vectors is usually intense but short-lived, and repeated administrations are hampered by the rapid appearance of neutralizing antibodies (NAbs). We have studied the performance of monocytes as cell carriers to improve transgene expression in cancer models established in athymic mice and immunocompetent Syrian hamsters. Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were loaded with replication-competent adenovirus-expressing luciferase. Intravenous administration of these cells caused a modest increase in transgene expression in tumor xenografts, but this effect was virtually lost in hamsters. In contrast, intratumoral administration of HM-1 cells allowed repeated cycles of expression and achieved partial protection from NAbs in preimmunized hamsters bearing pancreatic tumors. To explore the therapeutic potential of this approach, HM-1 cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant antitumor effect in the hamster model, and transgene expression was detected following each administration, in contrast with the rapid neutralization of the free virus. We propose monocytes as carriers for multiple intratumoral administrations of armed OAVs.

Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis

2013-02-20T12:40:04Z

Title: Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis Author(s) : Sanchez-Martinez, M. (María); Costa-Martins, R. (Raquel) da; Quincoces, G. (Gemma); Gamazo, C. (Carlos); Caicedo, C. (Carlos); Irache, J.M. (Juan Manuel); Peñuelas, I. (Iván) Abstract: Objetivos: Optimizar el radiomarcaje con 99mTc de nanopartículas de Gantrez® manosiladas y cargadas con el antígeno de Brucella Ovis (Man-NP-HS) y llevar a cabo estudios de biodistribución en ratón tras la administración de las nanopartículas por vía ocular. Metodología: Las Man-NP-HS se obtuvieron por el método de desplazamiento de disolvente. Se purificaron, liofilizaron y caracterizaron. A continuación, se marcaron con 74 MBq de 99mTcO4 - previamente reducido con una disolución ácida de cloruro de estaño, trabajando en ausencia de oxígeno y con un pH final de 4. El rendimiento del marcaje se evaluó mediante TLC. Los estudios de biodistribución se llevaron a cabo en ratones tras la administración oftálmica de la formulación y de un control de 99mTcO4 - libre. Para ello, se sacrificaron los animales a las 2 y a las 24 horas tras la administración ocular y se contaron los órganos en un contador gamma. Resultados: Se obtuvo un rendimiento de marcaje superior al 90%. Los estudios de biodistribución de 99mTc-Man-NP-HS permitieron detectar la actividad concentrada en mucosa nasal y ocular y tracto gastrointestinal tanto a las 2 como a las 24 horas, frente a la biodistribución de 99mTcO4 - libre que permaneció concentrado en la piel alrededor del ojo y en tracto gastrointestinal. Conclusión: Los estudios de biodistribución de 99mTc-Man-NP-HS tras administración oftálmica han permitido demostrar su biodistribución en mucosas y tracto gastrointestinal, característica indispensable como sistema de liberación de antígenos a través de mucosa ocular. Esto, junto con su elevada respuesta inmune, efectiva protección y no virulencia, convierte a estas nanopartículas en una vacuna ideal anti Brucelosis.

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.

2013-01-10T01:57:14Z

Title: Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia. Author(s) : Vilas-Zornoza, A. (Amaya); Aguirre, X. (Xavier); Abizanda, G. (Gloria); Moreno, C. (Cristina); Segura, V. (Víctor); Martino-Rodriguez, A. (Alba) de; San-Jose-Eneriz, E. (Edurne); Miranda, E. (Estibaliz); Martin-Subero, J.I. (José Ignacio); Garate, L. (Leire); Blanco-Prieto, M.J. (María José); Garcia-de-Jalon, J.A. (José A.); Rio, P. (Paula); Rifon, J. (José); Cigudosa, J.C. (Juan Cruz); Martinez-Climent, J.A. (José Angel.); Roman-Gomez, J. (José); Calasanz, M.J. (María José); Ribera, J.M. (José María); Prosper, F. (Felipe) Abstract: Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.

2013-01-10T01:57:14Z

Maintained effectiveness of an electronic alert system to prevent venous thromboembolism among hospitalized patients

2012-12-19T17:56:55Z

Title: Maintained effectiveness of an electronic alert system to prevent venous thromboembolism among hospitalized patients Author(s) : Lecumberri, R. (Ramón); Marques, M. (Margarita); Diaz-Navarlaz, M.T. (María Teresa); Panizo, E. (Elena); Toledo, J. (Jon); Garcia-Mouriz, A. (Alberto); Paramo, J.A. (José Antonio) Abstract: Despite current guidelines, venous thromboembolism (VTE) prophylaxis is underused. Computerized programs to encourage physicians to apply thromboprophylaxis have been shown to be effective in selected populations. Our aim was to analyze the impact of the implementation of a computer-alert system for VTE risk in all hospitalized patients of a teaching hospital. A computer program linked to the clinical record database was developed to assess all hospitalized patients' VTE risk daily. The physician responsible for patients at high risk was alerted, but remained free to order or withhold prophylaxis. Over 19,000 hospitalized, medical and surgical, adult patients between January to June 2005 (pre-intervention phase), January to June 2006 and January to June 2007 (post-intervention phase), were included. During the first semesters of 2006 and 2007, an electronic alert was sent to 32.8% and 32.2% of all hospitalized patients, respectively. Appropriate prophylaxis among alerted patients was ordered in 89.7% (2006) and 88.5% (2007) of surgical patients, and in 49.2% (2006) and 64.4% (2007) of medical patients. A sustained reduction of VTE during hospitalization was achieved, Odds ratio (OR): 0.53, 95% confidence interval (CI) (0.25-1.10) and OR: 0.51, 95%CI (0.24-1.05) during the first semesters of 2006 and 2007 respectively, the impact being significant (p < 0.05) among medical patients in 2007, OR: 0.36, 95%CI (0.12-0.98). The implementation of a computer-alert program helps physicians to assess each patient's thrombotic risk, leading to a better use of thromboprophylaxis, and a reduction in the incidence of VTE among hospitalized patients. For the first time, an intervention aimed to improve VTE prophylaxis shows maintained effectiveness over time.

New therapies for hepatocellular carcinoma

2012-12-20T01:13:48Z

Title: New therapies for hepatocellular carcinoma Author(s) : Avila, M.A. (Matías Antonio); Berasain, C. (Carmen); Sangro, B. (Bruno); Prieto, J. (Jesús) Abstract: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is often diagnosed at an advanced stage when most potentially curative therapies such as resection, transplantation or percutaneous and transarterial interventions are of limited efficacy. The fact that HCC is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy, leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. HCCs are phenotypically and genetically heterogeneous tumors that commonly emerge on a background of chronic liver disease. However, in spite of this heterogeneity recent insights into the biology of HCC suggest that certain signaling pathways and molecular alterations are likely to play essential roles in HCC development by promoting cell growth and survival. The identification of such mechanisms may open new avenues for the prevention and treatment of HCC through the development of targeted therapies. In this review we will describe the new potential therapeutic targets and clinical developments that have emerged from progress in the knowledge of HCC biology, In addition, recent advances in gene therapy and combined cell and gene therapy, together with new radiotherapy techniques and immunotherapy in patients with HCC will be discussed.

S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells

2012-12-20T01:37:35Z

Title: S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells Author(s) : Ansorena, E. (Eduardo); Garcia-Trevijano, E.R. (Elena R.); Martinez-Chantar, M.L. (María L.); Huang, Z.Z. (Zong-Zhi); Chen, L. (Lixin); Mato, J.M. (José M.); Iraburu, M. (María); Lu, S.C. (Shelly C.); Avila, M.A. (Matías A.) Abstract: S-adenosylmethionine (AdoMet) is an essential compound in cellular transmethylation reactions and a precursor of polyamine and glutathione synthesis in the liver. In liver injury, the synthesis of AdoMet is impaired and its availability limited. AdoMet administration attenuates experimental liver damage, improves survival of alcoholic patients with cirrhosis, and prevents experimental hepatocarcinogenesis. Apoptosis contributes to different liver injuries, many of which are protected by AdoMet. The mechanism of AdoMet's hepatoprotective and chemopreventive effects are largely unknown. The effect of AdoMet on okadaic acid (OA)-induced apoptosis was evaluated using primary cultures of rat hepatocytes and human hepatoma cell lines. AdoMet protected rat hepatocytes from OA-induced apoptosis dose dependently. It attenuated mitochondrial cytochrome c release, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. These effects were independent from AdoMet-dependent glutathione synthesis, and mimicked by 5'-methylthioadenosine (MTA), which is derived from AdoMet. Interestingly, AdoMet and MTA did not protect HuH7 cells from OA-induced apoptosis; conversely both compounds behaved as proapoptotic agents. AdoMet's proapoptotic effect was dose dependent and observed also in HepG2 cells. In conclusion, AdoMet exerts opposing effects on apoptosis in normal versus transformed hepatocytes that could be mediated through its conversion to MTA. These effects may participate in the hepatoprotective and chemopreventive properties of this safe and well-tolerated drug.

Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

2012-12-20T01:37:24Z

Title: Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth Author(s) : Andreu-Perez, P. (Pedro); Hernandez-Losa, J. (Javier); Moline, T. (Teresa); Gil, R. (Rosa); Grueso, J. (Judit); Pujol, A. (Anna); Cortes, J. (Javier); Avila, M.A. (Matías Antonio); Recio, J.A. (Juan A.) Abstract: BACKGROUND: Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. METHODS: To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. RESULTS: In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. CONCLUSIONS: MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment.

Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment

2012-12-06T01:48:20Z

Title: Changes in the heart rate variability in patients with obstructive sleep apnea and its response to acute CPAP treatment Author(s) : Kufoy, E. (Ernesto); Palma, J.A. (José A.); Lopez, J. (Jon); Alegre, M. (Manuel); Urrestarazu, E. (Elena); Artieda, J. (Julio); Iriarte, J. (Jorge) Abstract: Obstructive Sleep Apnea (OSA) is a major risk factor for cardiovascular disease. The goal of this study was to demonstrate whether the use of CPAP produces significant changes in the heart rate or in the heart rate variability of patients with OSA in the first night of treatment and whether gender and obesity play a role in these differences. METHODS: Single-center transversal study including patients with severe OSA corrected with CPAP. Only patients with total correction after CPAP were included. Patients underwent two sleep studies on consecutive nights: the first night a basal study, and the second with CPAP. We also analyzed the heart rate changes and their relationship with CPAP treatment, sleep stages, sex and body mass index. Twenty-minute segments of the ECG were selected from the sleep periods of REM, no-REM and awake. Heart rate (HR) and heart rate variability (HRV) were studied by comparing the R-R interval in the different conditions. We also compared samples from the basal study and CPAP nights. RESULTS: 39 patients (15 females, 24 males) were studied. The mean age was 50.67 years old, the mean AHI was 48.54, and mean body mass index was 33.41 kg/m(2) (31.83 males, 35.95 females). Our results showed that HRV (SDNN) decreased after the use of CPAP during the first night of treatment, especially in non-REM sleep. Gender and obesity did not have any influence on our results. CONCLUSIONS: These findings support that cardiac variability improves as an acute effect, independently of gender or weight, in the first night of CPAP use in severe OSA patients, supporting the idea of continuous use and emphasizing that noncompliance of CPAP treatment should be avoided even if it is just once.