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Search Results: 1 - 10 of 17296 matches for " Manuel; Puig Domingo "
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Incretin hormones as immunomodulators of atherosclerosis
Nuria Alonso,M. Teresa Julián,Manuel Puig-Domingo,Marta Vives-Pi
Frontiers in Endocrinology , 2012, DOI: 10.3389/fendo.2012.00112
Abstract: Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro- and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide-1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D). GLP-1 based therapies, such as GLP-1 receptor (GLP-1R) agonists and inhibitors of dipeptidyl peptidase-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apoE-/-). These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes.
Diabetes autoinmune del adulto en diabéticos tipo 2: frecuencia y características
Cabrera-Rode,Eduardo; Perich Amador,Pedro; Díaz Horta,Oscar; Molina Matos,Gisela; Suárez Fonseca,Leonel; Tiberti,Claudio; Arranz Calzado,Celeste; Licea Puig,Manuel; Puig Domingo,Manuel; de Leiva,Alberto; Di Mario,Umberto;
Revista Cubana de Endocrinolog?-a , 2001,
Abstract: this paper was aimed at knowing the frequency, clinico-biochemical, immunologic and genetic characteristics of autoimmune diabetes in adults (lada) in 1 000 type 2 diabetic patients aged 35 or over with different times of duration of diabetes. glycemia, anti-pancreatic islet cell antibodies (ica), anti-gad65 antibodies, anti-ica512bdc/ia2 antibodies, anti-microsomal thyroid antibodies (amt), anti-gastric parietal antibodies (agp), antinuclear antibodies (an), microalbuminuria and peptide c during fasting were determined. these patients were surveyed and some clinical characteristics were registered. they were divided into 2 groups according to the presence of ica. all the type 2 + diabetics for anti-islet cell autoantibodies (ica and/or antigad65) were identified as lada. 3.4 % of type 2 ica + were detected. 22.0 % of type 2 ica - diabetics had anti-gad65 antibodies. it was found that type 2 ica + diabetics were younger, that their diabetes was shorter, that they had lower bmi, reduced levels of fasting peptide c, less dm2 history family (parents), lower values of diastolic and systolic arterial pressure, higher presence of anti-gad65 antibodies, amt and agp in comparison with type 2 ica - diabetics. it was observed that type 2 ica+ diabetics (lada) have specific characteristics that make them similar to type 1 diabetics, which would lead to important variations in their treatment and evolution as regards type 2 ica - diabetics. among the cuban type 2 diabetics it was detected a low frequency of ica and a high frequency of gad, which were different to those found in the caucasian populations. the anti-gad65 antibodies were higher than ica to detect lada. the clinical and immunological characteristics of these patients show the slow progression of the autoimmune destruction of b-cells with therapeutic implications.
New Splice Site Acceptor Mutation in AIRE Gene in Autoimmune Polyendocrine Syndrome Type 1
Mireia Mora, Felicia A. Hanzu, Marta Pradas-Juni, Gloria B. Aranda, Irene Halperin, Manuel Puig-Domingo, Sira Aguiló, Eduardo Fernández-Rebollo
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101616
Abstract: Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300) is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison’s disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA) of intron 5 (c.653-1G>A) in two siblings with different clinical outcomes of APS-1. Coding DNA sequencing revealed that this AIRE mutation potentially compromised the recognition of the constitutive SSA of intron 5, splicing upstream onto a nearby cryptic SSA in intron 5. Surprisingly, the use of an alternative SSA entails the uncovering of a cryptic donor splice site in exon 5. This new transcript generates a truncated protein (p.A214fs67X) containing the first 213 amino acids and followed by 68 aberrant amino acids. The mutation affects the proper splicing, not only at the acceptor but also at the donor splice site, highlighting the complexity of recognizing suitable splicing sites and the importance of sequencing the intron-exon junctions for a more precise molecular diagnosis and correct genetic counseling. As both siblings were carrying the same mutation but exhibited a different APS-1 onset, and one of the brothers was not clinically diagnosed, our finding highlights the possibility to suspect mutations in the AIRE gene in cases of childhood chronic candidiasis and/or hypoparathyroidism otherwise unexplained, especially when the phenotype is associated with other autoimmune diseases.
Helicobacter pylori y anticuerpos antiislotes pancreáticos en la diabetes mellitus
Cabrera Rode,Eduardo; Díaz Horta,Oscar; Molina Matos,Gisela; Tiberti,Claudio; Fuentes,Marinela; Perich Amador,Pedro A.; Puig-Domingo,Manel; Vecci,Elio; Paniagua,Manuel; Pi?ol,Felipe; Escobar,María del Pilar; Di Mario,Umberto;
Revista Cubana de Endocrinolog?-a , 2002,
Abstract: 66 ica-positive patients were studied: 21 type 1 diabetics, 24 diabetics initially classified as type 2 and 21 first-degree relatives of type 1 diabetics. they were compared with 101 ica-negative patients: 20 type 2 diabetics, 20 first-degree relatives, 21 children and 40 non-diabetic adult controls to analyze if the immunolgical response to h. pylori is associated with islet cell antibodies (ica). the ica were determined by the indirect immunofluorescence method with prolongued incubation and the levels of antibodies (igg) versus h. pylori (hp) by an elisa using a commercial kit. it was observed a frequency of antibodies (igg) versus h. pylori of 38.0 % (25/66) in ica-positive patients and of 39.6 % (40/101) in ica-negative patients. no correlation was found between the presence of antibodies (igg) versus h.pylori and the ica in the studied groups. there were no differences as regards the presence of igg anitbodies versus h. pylori between diabetes mellitus and the controls (47.7 % [31/65] vs. 40.9 % [ 25/61]). it was observed a high percentage of antibodies (igg) vs. h. pylori in type 1 diabetics (33 %, 7/21) in relation to the controls (14 %, 3/21), but with no significant differences. the frequence of antibodies vs. helicobacter in adult controls is higher than in children (55 %, 22/40 vs. 3/21, p=0.0025). the frequency of antibodies vs. h. pylori is much more elevated in the adult controls may be because of the greater possibility of exposure to reinfections. in spite of these results, we do not exclude the idea that the infection due to h. pylori is related to type i diabetes, since some studies suggest that igg versus h. pylori does not persist for a long time.
Efferocytosis Promotes Suppressive Effects on Dendritic Cells through Prostaglandin E2 Production in the Context of Autoimmunity
Irma Pujol-Autonell, Rosa-Maria Ampudia, Raquel Planas, Silvia Marin-Gallen, Jorge Carrascal, Alex Sanchez, Ana Marin, Manuel Puig-Domingo, Ricardo Pujol-Borrell, Joan Verdaguer, Marta Vives-Pi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063296
Abstract: Introduction Efferocytosis is a crucial process by which apoptotic cells are cleared by phagocytes, maintaining immune tolerance to self in the absence of inflammation. Peripheral tolerance, lost in autoimmune processes, may be restored by the administration of autologous dendritic cells loaded with islet apoptotic cells in experimental type 1 diabetes. Objective To evaluate tolerogenic properties in dendritic cells induced by the clearance of apoptotic islet cells, thus explaining the re-establishment of tolerance in a context of autoimmunity. Methods Bone marrow derived dendritic cells from non-obese diabetic mice, a model of autoimmune diabetes, were generated and pulsed with islet apoptotic cells. The ability of these cells to induce autologous T cell proliferation and to suppress mature dendritic cell function was assessed, together with cytokine production. Microarray experiments were performed using dendritic cells to identify differentially expressed genes after efferocytosis. Results Molecular and functional changes in dendritic cells after the capture of apoptotic cells were observed. 1) Impaired ability of dendritic cells to stimulate autologous T cell proliferation after the capture of apoptotic cells even after proinflammatory stimuli, with a cytokine profile typical for immature dendritic cells. 2) Suppressive ability of mature dendritic cell function. 3) Microarray-based gene expression profiling of dendritic cells showed differential expression of genes involved in antigen processing and presentation after efferocytosis. 4) Prostaglandin E2 increased production was responsible for immunosuppressive mechanism of dendritic cells after the capture of apoptotic cells. Conclusions The tolerogenic behaviour of dendritic cells after islet cells efferocytosis points to a mechanism of silencing potential autoreactive T cells in the microenvironment of autoimmunity. Our results suggest that dendritic cells may be programmed to induce specific immune tolerance using apoptotic cells; this is a viable strategy for a variety of autoimmune diseases.
Análogos de insulina
Licea Puig,Manuel E.;
Revista Cubana de Endocrinolog?-a , 2006,
Abstract: considerable efforts have been made to develop the ideal insulin in the treatment of diabetes mellitus (dm). the recombinant technology of deoxyribonucleic acid (dna) has allowed the development of human insulin; however, this has not totally solved the problems related to immunogenecity, among other problems. therefore, the new technologies are applied to create insulin analogues. it is our purpose to review relevant pharmacological and clinical aspects related to the insulin analogues, as well as their usefulness in the treatment of dm. the insulin analogues result from biochemical modifications of human insulin. these modifications of the insulin molecule alter not only the absorption, but also the beginning and duration of the action, which offer advantages over the conventional insulins. at present, there are three rapid acting insulin analogues: insulin lispro, insulin aspart and glulisine; and three long acting analogues; glargine, detemir and albulin. albulin is the latest long acting analogue reported. at present, it is being subjected to various in vitro and in vivo studies. besides, there have been developed diverse formulations where the rapid acting insulin analogues are premixed with the long acting analogues. the rapid acting insulin analogues have showed a modest global benefit against the conventional insulins in type 1 diabetics. the long acting analogues focus their attention in those persons with dm with nocturnal hypoglycemic episodes. longer term studies are necessary to confirm the safety and benefits of these preparations, as well as to determine their effect on the micro- and macroangiopathic complications of dm.
Análogos de insulina Insulin analogues
Manuel E. Licea Puig
Revista Cubana de Endocrinología , 2006,
Abstract: Se han realizado considerables esfuerzos para desarrollar la insulina, ideal en el tratamiento de la diabetes mellitus (DM). La tecnología recombinante del ácido desoxiribonucleico (ADN) ha permitido el desarrollo de la insulina humana; sin embargo, esta no ha resuelto totalmente los problemas relacionados con la inmunogenicidad, entre otros problemas. Por tanto, las nuevas tecnologías son aplicadas para crear los análogos de insulina. Este trabajo se propone como objetivos revisar aspectos farmacológicos y clínicos relevantes, relacionados con los análogos de insulina, así como su utilidad en el tratamiento de la DM. Los análogos de insulina surgen de modificaciones bioquímicas de la insulina humana. Estas modificaciones de la molécula de insulina alteran tanto la absorción como el inicio y la duración de la acción, lo que ofrece ventajas sobre las insulinas convencionales. En la actualidad se dispone de tres análogos de insulina de acción rápida: la insulina lispro, la aspártica y la glulisina, y de tres análogos de acción prolongada: la insulina glargina, detemir y el albulin. El albulin es el último análogo de acción prolongada comunicado, el cual se está sometiendo actualmente a variados estudios in vitro y en vivo. Además, se han desarrollado diversas formulaciones donde están premezclados los análogos de insulina de acción rápida con análogos de acción prolongada. Los análogos de insulina de acción rápida han demostrado un modesto beneficio global frente a las insulinas convencionales en los diabéticos tipo 1. Los análogos de acción prolongada centran su atención en las personas con DM con episodios hipoglucémicos nocturnos. Se necesitan estudios a más largo plazo para confirmar la seguridad y los beneficios de estos preparados, así como precisar su efecto sobre las complicaciones micro y macroangiopáticas de la DM. Considerable efforts have been made to develop the ideal insulin in the treatment of diabetes mellitus (DM). The recombinant technology of deoxyribonucleic acid (DNA) has allowed the development of human insulin; however, this has not totally solved the problems related to immunogenecity, among other problems. Therefore, the new technologies are applied to create insulin analogues. It is our purpose to review relevant pharmacological and clinical aspects related to the insulin analogues, as well as their usefulness in the treatment of DM. The insulin analogues result from biochemical modifications of human insulin. These modifications of the insulin molecule alter not only the absorption, but also the beginning and duration of the acti
The Truncated Isoform of Somatostatin Receptor5 (sst5TMD4) Is Associated with Poorly Differentiated Thyroid Cancer
Manel Puig-Domingo, Raúl M. Luque, Jordi L. Reverter, Laura M. López-Sánchez, Manuel D. Gahete, Michael D. Culler, Gonzalo Díaz-Soto, Francisco Lome?a, Mattia Squarcia, José Luis Mate, Mireia Mora, Laureano Fernández-Cruz, Oscar Vidal, Antonio Alastrué, Jose Balibrea, Irene Halperin, Dídac Mauricio, Justo P. Casta?o
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085527
Abstract: Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3–6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment.
Dyslipidaemia in HIV-infected women on antiretroviral therapy. Analysis of 922 patients from the Spanish VACH cohort
Vicente Estrada, Paloma Geijo, Manuel Fuentes-Ferrer, María Alcalde, María Rodrigo, María Galindo, Agustín Mu?oz, Pere Domingo, Esteve Ribera, Jaime Cosín, Pompeyo Viciana, Fernando Lozano, Alberto Terrón, Antonio Vergara, Ramón Teira, Josefa Mu?oz-Sánchez, Bernardino Roca, Trinitario Sánchez, José López-Aldeguer, Elisabeth Deig, Francisco Vidal, Enric Pedrol, Manuel Casta?o-Carracedo, Teresa Puig, Myriam Garrido, Ignacio Suárez-Lozano
BMC Women's Health , 2011, DOI: 10.1186/1472-6874-11-36
Abstract: Observational, multicentre, cross-sectional study from the Spanish VACH Cohort. 922 women on stable ART without lipid-lowering treatment were included.Median age was 42 years, median CD4 lymphocyte count was 544 cells/mm3, and 85.6% presented undetectable HIV-1 viral load. Median total cholesterol (TC) was 189 mg/dL (interquartile range, IQR, 165-221), HDL cholesterol 53 mg/dL (IQR, 44-64), LDL cholesterol 108 mg/dL (IQR, 86-134), and triglycerides 116 mg/dL (IQR, 85-163). Mean accumulated time on ART was 116 months; 47.4% were on NNRTI-based regimes, 44.7% on PI, and 6.7% on only-NRTI therapy. 43.8% were also hepatitis C (HCV) coinfected. Patients on PI treatment presented higher TC/HDL ratio than those on NNRTI (p < 0.001). Significantly higher HDL values were observed in NNRTI-treated patients. HCV-coinfected patients presented lower TC/HDL ratio than the non HCV-coinfected. In multivariate analysis, factors independently associated with TC/HDL ratio were age, triglyceride levels and HCV co-infection. PI treatment presented a non-significant association with higher TC/HDL ratio.In HIV-infected women, the NNRTI-based ART is associated with a better lipid profile than the PI-based. Factors unrelated to ART selection may also exert an independent, significant influence on lipids; in particular, age, and triglyceride levels are associated with an increased TC/HDL ratio while HCV co-infection is associated with a reduced TC/HDL ratio.The increase in cardiovascular risk (CVR) observed in HIV-infected patients is a cause for concern. Most clinical studies have detected a relationship between cardiovascular disease and traditional risk factors, among which age, male gender, smoking, hypertension and diabetes are the most important. There is far less information concerning CVR in HIV-infected female patients. For years, some inequalities in female participation in clinical studies have been observed. In HIV infection, women have been under-represented as participants as t
Nueva definición, prevalencia, caracterización y tratamiento de la diabetes autoinmune latente del adulto
Cabrera Rode,Eduardo; Licea Puig,Manuel E;
Revista Cubana de Endocrinolog?-a , 2008,
Abstract: latent autoimmune diabetes of adult is a way of autoimmune diabetes present in some subjects erroneously classified as type 2 diabetics. progression of autoimmune damage of ? cells in this entity is slower than in children presenting with type 1 diabetes. at diagnosis, persons affected by this condition, have a greater preservation of ? cells function than those presenting with the classic type 1 diabetes. their present diagnosis is based on 3 features: age similar o greater than 30 years (however, it may be present in subjects in ages lower than 30 years); presence of at least 1 of the 5 antibodies to pancreatic antigens of islet-cells (anti-islet [ai] auto-antibodies, anti-descarboxylase of glutamic acid [agad], antibodies to phosphatase tyrosine [aia2], and to zinc-cation transporter within ? islet-cells [aznt8]), and the need of insulin requirements, at least 6 months after diagnosis. it is present in 10 % of subjects presenting with type 2 diabetes in 335 years, and in 25 % of those younger than 35 years. some genes of susceptibility for it are described, including genes hla dr3/dr4 and dqb1*0201/dqb1*0302, dqb1*0602, class i mhc related to a chain (mica), as well as class i vntr allele, among others, those similar o different of the classic type 1 diabetes or the type 2. prospective studies on function of ? cells show that subject carriers of it with multiple auto-antibodies associated to type 1 diabetes develops a failure of function above mentioned within the first 5 years of duration of diabetes, while the most of those with on agad or ica develop a failure in this function after 5 years. in these persons may to occur a failure in function of ? cells up to 12 years after diagnosis of disease, although deterioration of ? cells response to i.v. glucose or glucagon, may be detected in some subjects at diagnosis of diabetes. thus, we aren't in presence of a latent disease. there are studies suggesting that insulin-treatment is the more appropriate at diagnosis
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