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2.
Am Heart J ; 187: 10-18, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28454793

RESUMEN

BACKGROUND: Radiation exposure is an important issue for interventional cardiologists that is often underevaluated. Our aim was to evaluate determinants of operator radiation exposure during percutaneous coronary procedures. METHODS: The RADIANT (NCT01974453) is a prospective, single-center observational study involving 4 expert operators and 2 fellows performing percutaneous coronary procedures. The operator radiation dose was evaluated using dedicated electronic dosimeters in 2,028 procedures: 1,897 transradial access (TRA; 1,120 right and 777 left TRA) and 131 transfemoral access (TFA). RESULTS: In the whole population, operator radiation dose at the thorax did not differ between TFA (9µSv [interquartile range 5-18µSv]) and TRA (9µSv [4-21µSv]), but after propensity score matching analysis, TFA showed lower dose (9µSv [5-18µSv]) compared with TRA (17µSv [9-28µSv], P<.001). In the whole transradial group, left TRA (5µSv [2-12µSv]) was associated with significant lower operator dose compared with right TRA (13µSv [6-26µSv], P<.001).The use of adjunctive protective pelvic drapes was significantly associated with lower radiation doses compared with procedures performed without drapes (P<.001). Among the operators, an inverse relation between height and dose was observed. Finally, left projections and the use of angiographic systems not dedicated for coronary and high frame rates were all associated with a significant higher operator radiation exposure. CONCLUSIONS: In a high-volume center for transradial procedures, TFA is associated with lower operator radiation dose compared with TRA. The use of adjunctive anti-rx drapes seems a valuable tool to reduce the higher operator radiation exposure associated with TRA.


Asunto(s)
Angiografía Coronaria/métodos , Intervención Coronaria Percutánea/métodos , Exposición a la Radiación , Protección Radiológica , Adulto , Cardiólogos , Angiografía Coronaria/efectos adversos , Femenino , Arteria Femoral , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arteria Radial
3.
Pharmacoepidemiol Drug Saf ; 26(1): 91-96, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27859873

RESUMEN

PURPOSE: The purpose of the study is to analyze the impact of an intervention to disseminate safety alerts on the utilization of Aliskiren added to angiotensin converting enzyme inhibitor (ACEI) or an angiotensin-receptor blocker (ARB). METHODS: Quasi-experimental design (non-randomized intervention) comparing the utilization of Aliskiren + ACEI or ARB in a primary care area-intervention (PCA-I) with a primary care area-control (PCA-C) following a safety alert. All physicians were provided with a list of diabetic patients (DM) on Aliskiren + ACEI or ARB. Physicians in the PCA-I received also a non-DM patients list, a report with recommendations and information on the utilization of Aliskiren + ACEI or ARB in their area. Information was obtained from electronic medical records, period from May 2010 to December 2012. Interrupted time series analysis were used to assess the effect of the intervention on the number of patients on Aliskiren + ACEI or ARB. RESULTS: The number of DM receiving Aliskiren + ACEI or ARB at the time of the alert (23 December 2011) was 106 in the PCA-I (91 non-DM) and 45 in the PCA-C (25 non-DM). After the alert, a decreased in the number of patients on Aliskiren + ACEI or ARB was noted at both PCAs, although the average of daily treatments ended was significantly higher in the PCA-I, both in the DM group (slope after alert: -0.81, 95%CI -0.91 to -0.71 vs. -0.30, 95%CI -0.37 to -0.22) as well as in the non-DM group (-0.56, 95%CI -0.67 to -0.45 vs. -0.10 95%CI -0.17 to -0.04). CONCLUSIONS: The prescription of Aliskiren + ACEI or ARB decreased at both PCAs, albeit such decreased was more significant at the PCA-I. The intervention led to a more expeditious implementation of the safety alert recommendations. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Amidas/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Fumaratos/administración & dosificación , Amidas/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Registros Electrónicos de Salud , Fumaratos/efectos adversos , Humanos , Análisis de Series de Tiempo Interrumpido , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud
4.
Catheter Cardiovasc Interv ; 87(5): 868-74, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26269451

RESUMEN

OBJECTIVES: The aim of this prospective study was to evaluate muscle force of the hand, thumb, and forefinger in patients with prolonged radial occlusion after transradial percutaneous coronary procedures. BACKGROUND: There are no data on hand strength and function in patients with prolonged radial occlusion after percutaneous coronary procedures. METHODS: Elective patients with chronic stable angina undergoing percutaneous coronary procedures were evaluated the day before the procedure for radial artery patency, Allen test, hand grip, and thumb and forefinger pinch tests. The same measures were performed the day after the procedure and at follow-up. At follow-up, patients were divided in two groups according to the radial patency (group 1) or occlusion (group 2). RESULTS: Of the 99 patients included in the study, 90 patients had a patent radial artery (group 1), and nine (9.1%) patients had an occluded artery (group 2). At baseline, there were no significant differences in hand grip test between the two groups (42 ± 11 kg in group 1 and 41 ± 17 kg in group 2, P = 0.74). In both groups, after the procedure, the hand grip test values was significantly reduced compared with baseline values (40 ± 11 kg in group 1, P < 0.0001 and 37 ± 17 kg in group 2, P = 0.007). Finally, at follow-up, in both groups, the hand grip test values returned to baseline values. Thumb and forefinger pinch tests did not show significant differences after the procedure and at follow-up, compared with baseline. CONCLUSIONS: Radial artery occlusion after percutaneous coronary procedures was not associated with a reduction in hand and finger strength.


Asunto(s)
Angina Estable/terapia , Arteriopatías Oclusivas/etiología , Cateterismo Cardíaco/efectos adversos , Fuerza Muscular , Músculo Esquelético/irrigación sanguínea , Intervención Coronaria Percutánea/efectos adversos , Arteria Radial , Anciano , Angina Estable/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/fisiopatología , Cateterismo Cardíaco/métodos , Enfermedad Crónica , Constricción Patológica , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Punciones , Arteria Radial/diagnóstico por imagen , Arteria Radial/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular
5.
Biomed Pharmacother ; 177: 116991, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906021

RESUMEN

Macropinocytosis is a cellular process that enables cells to engulf extracellular material, such as nutrients, growth factors, and even whole cells. It is involved in several physiological functions as well as pathological conditions. In cancer cells, macropinocytosis plays a crucial role in promoting tumor growth and survival under nutrient-limited conditions. In particular KRAS mutations have been identified as main drivers of macropinocytosis in pancreatic, breast, and non-small cell lung cancers. We performed a high-content screening to identify inhibitors of macropinocytosis in pancreatic ductal adenocarcinoma (PDAC)-derived cells, aiming to prevent nutrient scavenging of PDAC tumors. The screening campaign was conducted in a well-known pancreatic KRAS-mutated cell line (MIAPaCa-2) cultured under nutrient deprivation and using FITC-dextran to precisely quantify macropinocytosis. We assembled a collection of 3584 small molecules, including drugs approved by the Food and Drug Administration (FDA), drug-like molecules against molecular targets, kinase-targeted compounds, and molecules designed to hamper protein-protein interactions. We identified 28 molecules that inhibited macropinocytosis, with potency ranging from 0.4 to 29.9 µM (EC50). A few of them interfered with other endocytic pathways, while 11 compounds did not and were therefore considered specific "bona fide" macropinocytosis inhibitors and further characterized. Four compounds (Ivermectin, Tyrphostin A9, LY2090314, and Pyrvinium Pamoate) selectively hampered nutrient scavenging in KRAS-mutated cancer cells. Their ability to impair albumin-dependent proliferation was replicated both in different 2D cell culture systems and 3D organotypic models. These findings provide a new set of compounds specifically targeting macropinocytosis, which could have therapeutic applications in cancer and infectious diseases.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pinocitosis , Pinocitosis/efectos de los fármacos , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Mutación
6.
Proc Natl Acad Sci U S A ; 106(49): 20782-7, 2009 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-19926856

RESUMEN

Unlike other neuronal counterparts, primary synaptic proteins are not known to be involved in vascular physiology. Here, we demonstrate that neurexins and neuroligins, which constitute large and complex families of fundamental players in synaptic activity, are produced and processed by endothelial and vascular smooth muscle cells throughout the vasculature. Moreover, they are dynamically regulated during vessel remodeling and form endogenous complexes in large vessels as well as in the brain. We used the chicken chorioallantoic membrane as a system to pursue functional studies and demonstrate that a monoclonal recombinant antibody against beta-neurexin inhibits angiogenesis, whereas exogenous neuroligin has a role in promoting angiogenesis. Finally, as an insight into the mechanism of action of beta-neurexin, we show that the anti-beta-neurexin antibody influences vessel tone in isolated chicken arteries. Our finding strongly supports the idea that even the most complex and plastic events taking place in the nervous system (i.e., synaptic activity) share molecular cues with the vascular system.


Asunto(s)
Arterias/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Sinapsis/metabolismo , Animales , Anticuerpos/farmacología , Arterias/citología , Arterias/efectos de los fármacos , Pollos , Membrana Corioalantoides/citología , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/metabolismo , Humanos , Técnicas In Vitro , Ratones , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Sinapsis/efectos de los fármacos
7.
Minerva Cardioangiol ; 68(6): 592-598, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32326678

RESUMEN

In the cardiology community, the use of transradial access for percutaneous coronary procedures is progressively increasing all around the world overtaking the use of transfemoral access. The advantages of the transradial access are based on a significant reduction in bleeding and vascular events compared to the femoral access and on a reduction in mortality in the setting of acute coronary syndromes. However, in recent years a slight but significant increase in radiation exposure for patients and operators associated with the radial approach has been detected, increasing concerns about possible long term increased stochastic risk. In particular interventional cardiologists are among physicians performing interventional procedures using X-rays, those exposed to the highest radiation dose during their activity and this exposure is not without possible long-term clinical consequences in term of deterministic and stochastic effects. All the operators should be aware of these risks and manage to reduce their radiation exposure. In this review we analysed the differences in term of radiation exposure comparing the radial and the femoral access for percutaneous coronary procedures. Then, we discussed the possible clinical consequences of these differences and finally we showed the available tools aimed to reduce the operator radiation exposure. In particular the use of adjunctive protective drapes placed on the patient might reduce operator radiation exposure in up to 81% of the dose.


Asunto(s)
Exposición Profesional , Intervención Coronaria Percutánea , Exposición a la Radiación , Angiografía Coronaria , Arteria Femoral , Humanos , Arteria Radial , Dosis de Radiación
8.
Mol Autism ; 11(1): 88, 2020 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-33208191

RESUMEN

BACKGROUND: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26-28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams-Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms. In the above-indicated interval at 7q11.23, defined as WBS critical region, several genes, such as GTF2I, BAZ1B, CLIP2 and EIF4H, emerged as critical for their role in the pathogenesis of WBS and 7Dup both from mouse models and human studies. METHODS: We performed a high-throughput screening of 1478 compounds, including central nervous system agents, epigenetic modulators and experimental substances, on patient-derived cortical glutamatergic neurons differentiated from our cohort of induced pluripotent stem cell lines (iPSCs), monitoring the transcriptional modulation of WBS interval genes, with a special focus on GTF2I, in light of its overriding pathogenic role. The hits identified were validated by measuring gene expression by qRT-PCR and the results were confirmed by western blotting. RESULTS: We identified and selected three histone deacetylase inhibitors (HDACi) that decreased the abnormal expression level of GTF2I in 7Dup cortical glutamatergic neurons differentiated from four genetically different iPSC lines. We confirmed this effect also at the protein level. LIMITATIONS: In this study, we did not address the molecular mechanisms whereby HDAC inhibitors act on GTF2I. The lead compounds identified will now need to be advanced to further testing in additional models, including patient-derived brain organoids and mouse models recapitulating the gene imbalances of the 7q11.23 microduplication, in order to validate their efficacy in rescuing phenotypes across multiple functional layers within a translational pipeline towards clinical use. CONCLUSIONS: These results represent a unique opportunity for the development of a specific class of compounds for treating 7Dup and other forms of intellectual disability and autism.


Asunto(s)
Trastorno del Espectro Autista/patología , Corteza Cerebral/patología , Duplicación Cromosómica/genética , Cromosomas Humanos Par 7/genética , Ensayos Analíticos de Alto Rendimiento , Inhibidores de Histona Desacetilasas/farmacología , Neuronas/patología , Factores de Transcripción TFII/genética , Trastorno del Espectro Autista/genética , Cromosomas Humanos Par 7/metabolismo , Variaciones en el Número de Copia de ADN/genética , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción TFII/metabolismo , Transcripción Genética/efectos de los fármacos
9.
ACS Med Chem Lett ; 11(5): 754-759, 2020 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-32435381

RESUMEN

Lysine-specific demethylase 1 (LSD1 or KDM1A) is a FAD-dependent enzyme that acts as a transcription corepressor or coactivator by regulating the methylation status of histone H3 lysines K4 and K9, respectively. KDM1A represents an attractive target for cancer therapy. While, in the past, the main medicinal chemistry strategy toward KDM1A inhibition was based on the optimization of ligands that irreversibly bind the FAD cofactor within the enzyme catalytic site, we and others have also identified reversible inhibitors. Herein we reported the discovery of 5-imidazolylthieno[3,2-b]pyrroles, a new series of KDM1A inhibitors endowed with picomolar inhibitory potency, active in cells and efficacious after oral administration in murine leukemia models.

10.
Gastroenterology ; 135(1): 173-84, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18514073

RESUMEN

BACKGROUND & AIMS: Junctional adhesion molecule-A (JAM-A) is localized at the tight junctions and controls leukocyte migration into the tissues. However, its functional role in inflammatory bowel disease (IBD) is unexplored. METHODS: Control, Crohn's disease (CD), and ulcerative colitis (UC) tissue specimens were studied for JAM-A expression, as well as the colon of mice given dextran sodium sulfate (DSS). Wild-type and JAM-A(-/-), Tie-2-Cre-JAM-A(-/-) (endothelial/hematopoietic-specific JAM inactivation) mice were studied for susceptibility to DSS. Disease activity and colonic inflammation were assessed using a disease activity index histology and endoscopy, and mucosal cytokines were measured by enzyme-linked immunosorbent assay. JAM-A function was investigated by RNA silencing in epithelial cells, and apoptosis was measured. RESULTS: In both CD and UC, as well as in experimental colitis, there is a loss of epithelial but not endothelial JAM-A expression. Deletion of JAM-A results in a dramatic increase in susceptibility to DSS colitis, as assessed by weight loss, disease activity index, histologic and endoscopic severity, and strikingly high mortality rates. This is not caused by the absence of JAM-A in the endothelial or hematopoietic compartments because Tie-2-Cre-JAM-A(-/-) mice are no more susceptible to DSS colitis than wild-type animals. JAM-A(-/-) mice displayed increased intestinal permeability and inflammatory cytokine production, and marked epithelial apoptosis. Silencing of JAM-A in intestinal epithelial cells resulted in increased permeability in vitro. CONCLUSIONS: Our results show a nonredundant and novel role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function.


Asunto(s)
Moléculas de Adhesión Celular/inmunología , Moléculas de Adhesión Celular/metabolismo , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Homeostasis/inmunología , Inmunoglobulinas/inmunología , Inmunoglobulinas/metabolismo , Animales , Apoptosis , Moléculas de Adhesión Celular/genética , Movimiento Celular/inmunología , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/inmunología , Eliminación de Gen , Humanos , Inmunoglobulinas/genética , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Leucocitos/citología , Leucocitos/inmunología , Masculino , Ratones , Ratones Mutantes , Permeabilidad , Interferencia de ARN , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo
11.
Circ Cardiovasc Interv ; 12(2): e007586, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30732471

RESUMEN

BACKGROUND: Different tools and devices are effective to reduce operator radiation exposure at thorax level during percutaneous coronary procedures, but the operator radiation dose received at pelvic region still remains high. Our aim was to evaluate the efficacy of under-the-table adjunctive shields to reduce operator radiation exposure during percutaneous coronary procedures Methods and Results: The EXTRA-RAD study (Extended Protective Shield Under Table to Reduce Operator Radiation Dose in Percutaneous Coronary Procedures) is a prospective, single-center, randomized study. Patients who underwent transradial coronary procedures were randomized into 2 groups: group 1 (standard arrangement) and group 2 (adjunctive anti-rx shield under the angiographic table). In group 2, a further randomization was performed to compare 2 different under-the-table shields (a small curtain and a drape). A total of 205 procedures (122 diagnostic coronary angiographies and 83 percutaneous coronary interventions) performed in 157 patients by 4 different operators were included without significant differences in clinical and procedural characteristics between groups. The use of adjunctive shields was associated with lower radiation dose compared with no shield at pelvic region (42 µSv [14-98] in group 1, 13 µSv [5-27] in group 2; P<0.0001) and also at thorax level (4 µSv [1-13] in group 1, 2 µSv [1-4] in group 2; P=0.001). The reduction in dose was observed in all the operators. No significant differences were observed in pelvic dose using the 2 different shields ( P=0.183). CONCLUSIONS: The use of adjunctive anti-rx shields under the angiographic table during transradial coronary procedures is associated with a significant lower radiation dose to operators at pelvic and thorax level. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03259126.


Asunto(s)
Angiografía Coronaria , Exposición Profesional/prevención & control , Salud Laboral , Mesas de Operaciones , Intervención Coronaria Percutánea , Dosis de Radiación , Exposición a la Radiación/prevención & control , Protección Radiológica/instrumentación , Radiografía Intervencional , Paños Quirúrgicos , Anciano , Angiografía Coronaria/efectos adversos , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Exposición a la Radiación/efectos adversos , Radiografía Intervencional/efectos adversos , Medición de Riesgo , Factores de Riesgo , Ciudad de Roma
12.
Cardiovasc Revasc Med ; 19(7 Pt A): 755-758, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29691182

RESUMEN

BACKGROUND: The use of adjunctive protective drapes placed on the patient protects the operating physician from scatter radiation during percutaneous coronary procedures (PCP). No data are available on the effect of these drapes for staff members' radio-protection. PURPOSE: To evaluate staff radiation exposure during PCP and the effect of adjunctive protective drapes on dose reduction. METHODS: The RADIANT study (NCT01974453) is a prospective, observational study evaluating operator radiation exposure during PCP using electronic dosimeter. In a sub-group of procedures all the staff members (II operator, nurse circulator and technologist) were also equipped with a dedicated electronic dosimeter. RESULTS: From a total of 2028 procedures included in the RADIANT study, staff members' doses were available for 122 procedures (67 coronarography and 55 percutaneous coronary interventions). Median fluoroscopy time was 306 s (Interquartile range 155-526 s) and the dose area product (DAP) was 18.0 Gy*cm2 (10-35.5 Gy*cm2). The radiation exposure was highest for the operating physician (6.7 µSv) and progressively lower for the nurse circulator (1.8 µSv), the II operator (1 µSv) and the technologist (0.7 µSv, p < 0.001). Protective pelvic drapes were used in 43 procedures and associated with a lower radiation exposure for all staff members (14 µSv vs 2.2 µSv for operating physician, p < 0.001, 1.7 µSv vs 0.49 µSv for II operator, p < 0.001, 2.16 µSv vs 0.93 µSv for nurse circulator, p = 0.02 and 0.85 µSv vs 0.39 µSv for technologist, p = 0.01). CONCLUSIONS: The use of adjunctive protective drapes is effective in reducing radiation protection for all staff members during PCP.


Asunto(s)
Personal de Salud , Exposición Profesional/prevención & control , Salud Laboral , Intervención Coronaria Percutánea , Dosis de Radiación , Exposición a la Radiación/prevención & control , Protección Radiológica/instrumentación , Radiografía Intervencional , Paños Quirúrgicos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personal de Enfermería , Exposición Profesional/efectos adversos , Auxiliares de Cirugía , Intervención Coronaria Percutánea/efectos adversos , Médicos , Estudios Prospectivos , Factores Protectores , Exposición a la Radiación/efectos adversos , Radiografía Intervencional/efectos adversos , Medición de Riesgo , Factores de Riesgo , Dispersión de Radiación , Factores de Tiempo
13.
J Clin Invest ; 114(5): 729-38, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15343392

RESUMEN

Junctional adhesion molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. In the present work, we found that DCs also express JAM-A. To evaluate the biological relevance of this observation, Jam-A(-/-) mice were generated and the functional behavior of DCs in vitro and in vivo was studied. In vitro, Jam-A(-/-) DCs showed a selective increase in random motility and in the capacity to transmigrate across lymphatic endothelial cells. In vivo, Jam-A(-/-) mice showed enhanced DC migration to lymph nodes, which was not observed in mice with endothelium-restricted deficiency of the protein. Furthermore, increased DC migration to lymph nodes was associated with enhanced contact hypersensitivity (CHS). Adoptive transfer experiments showed that JAM-A-deficient DCs elicited increased CHS in Jam-A(+/+) mice, further supporting the concept of a DC-specific effect. Thus, we identified here a novel, non-redundant role of JAM-A in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity.


Asunto(s)
Moléculas de Adhesión Celular/deficiencia , Movimiento Celular/inmunología , Células Dendríticas/inmunología , Dermatitis por Contacto/inmunología , Ganglios Linfáticos/inmunología , Animales , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Movimiento Celular/genética , Dermatitis por Contacto/genética , Células Endoteliales , Técnica del Anticuerpo Fluorescente , Moléculas de Adhesión de Unión , Ratones , Ratones Noqueados
14.
EuroIntervention ; 12(18): e2253-e2261, 2017 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-28044985

RESUMEN

AIMS: The aim of this study was to compare different radiation protection drapes in terms of radiation dose absorbed by operators during right or left transradial procedures. METHODS AND RESULTS: Patients who underwent transradial coronary procedures were randomised initially into four groups: Group 1 (no drapes), Group 2 (drape on patient's arm), Group 3 (pelvic drape), Group 4 (combined arm and pelvic drapes). Subsequently, each group was further randomised to right or left radial access. The primary endpoint was the operator radiation dose at the thorax. A total of 452 procedures were included. The use of drapes was associated with a lower radiation dose compared to no drapes (8.6 µSv [4.1-17.9] Group 1, 5.8 µSv [3.4-13] Group 2, 3.6 µSv [2.1-6.9] Group 3, 3.7 µSv [1.9-10.3] Group 4, p<0.001). Among radiation protection drapes groups the radiation dose was significantly lower in Groups 3 and 4 compared to Group 2 (p<0.008). Compared to Group 1, the dose in Group 2 was significantly lower only in right radial procedures (p<0.008) whereas in Groups 3 and 4 the dose was significantly lower in both radial accesses (p<0.008). CONCLUSIONS: The use of radiation protection drapes during transradial coronary procedures is associated with a significantly lower radiation dose to operators, with the pelvic drape more effective than the use of a single arm drape.


Asunto(s)
Exposición Profesional/prevención & control , Intervención Coronaria Percutánea , Dosis de Radiación , Protección Radiológica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arteria Radial
15.
Am J Cardiol ; 120(4): 563-568, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28651849

RESUMEN

Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100 µg) or high-dose IC adenosine (≥100 µg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80 µg) and 5 studies high-dose boluses (120 to 600 µg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p = 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p = 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifying hemodynamically significant coronary stenosis and is better tolerated by the patients.


Asunto(s)
Adenosina/administración & dosificación , Enfermedad de la Arteria Coronaria/diagnóstico , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/fisiopatología , Reserva del Flujo Fraccional Miocárdico/fisiología , Vasodilatación/fisiología , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Infusiones Intraarteriales , Infusiones Intravenosas , Índice de Severidad de la Enfermedad , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación
16.
Future Med Chem ; 9(11): 1161-1174, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28722470

RESUMEN

BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor. MATERIAL & METHODS: The KDM1A inhibitors 5a-w were synthesized and tested in vitro and in vivo. The biochemical potency was determined, modulation of target in cells was demonstrated on KDM1A-dependent genes and the anti-clonogenic activity was performed in murine acute promyelocytic Leukemia (APL) blasts. An in vivo efficacy experiment was conducted using an established murine promyelocytic leukemia model. RESULTS: We report a new series of tranylcypromine derivatives substituted on the cyclopropyl moiety, endowed with high potency in both biochemical and cellular assays. CONCLUSION: The most interesting derivative (5a) significantly improved survival rate after oral administration in a murine model of promyelocitic leukemia.


Asunto(s)
Antineoplásicos/síntesis química , Histona Demetilasas/antagonistas & inhibidores , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tranilcipromina/análogos & derivados , Tranilcipromina/síntesis química , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular , Humanos , Leucemia Promielocítica Aguda/patología , Ratones , Relación Estructura-Actividad , Tranilcipromina/farmacocinética , Tranilcipromina/farmacología
18.
CES med ; 35(1): 16-25, ene.-abr. 2021. tab
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1345579

RESUMEN

Resumen Introducción: el tamoxifeno ha sido el medicamento de primera línea para el tratamiento del cáncer de mama; sin embargo, se han evidenciado serios eventos adversos con su uso. El objetivo de este trabajo fue determinar la hiperplasia endometrial asociada al uso de tamoxifeno en mujeres con cáncer de mama en una institución oncológica de la ciudad de Barranquilla- Colombia. Metodología: estudio de casos y controles retrospectivo. Se incluyeron 202 pacientes con cáncer de mamá tratadas entre 2012 y 2017. Fueron evaluadas variables antropométricas, sociodemográficas, personales, clínicas y patológicas. Se estimaron los Odds Ratios (OR) crudos y ajustados. Resultados: 68 participantes fueron diagnosticadas con hiperplasia endometrial secundaria al tratamiento antineoplásico. De éstas, 59 (86,7 %) usaron tamoxifeno, la mayoría (37,2 %) por un lapso de 6-11 meses. El análisis bivariado mostró asociación entre la hiperplasia endometrial y uso del tamoxifeno con un OR de 3,9 (IC95 %: 1,8-8,5) y 2,9 (IC95 %: 1,18-7,5) en los análisis crudos y ajustados, respectivamente. Conclusión: el uso de tamoxifeno se asocia con la presencia de hiperplasia endometrial.


Abstract Introduction: tamoxifen has been the first line drug for the treatment of breast cancer; however, serious adverse events have been evidenced with its use. The aim of this study was to determine endometrial hyperplasia associated with the use of tamoxifen in women with breast cancer in an oncological institution in the city of Barranquilla, Colombia. Methodology: retrospective case-control study. A total of 202 patients with breast cancer treated between 2012 and 2017 were included. Anthropometric, sociodemographic, personal, clinical and pathological variables were evaluated. Crude and adjusted Odds ratios (OR) were estimated. Results: 68 participants were diagnosed with endometrial hyperplasia secondary to antineoplastic treatment. Of these, 59 (86.7 %) used tamoxifen, the most of them (37.2 %) for a period of 6-11 months. Bivariate analysis showed an association between endometrial hyperplasia and tamoxifen use with an OR of 3.9 (95%CI: 1.8-8.5) and 2.9 (95%CI: 1.18-7.5) in the crude and adjusted analyses, respectively. Conclusion: tamoxifen use is associated with the presence of endometrial hyperplasia.

19.
Cardiovasc Revasc Med ; 16(1): 15-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25576274

RESUMEN

OBJECTIVES: The aim of this study was to compare radiation exposure, assessed by dose-area product (DAP), in right trans-radial approach (RR) versus left trans-radial approach (LR) for coronary procedures. BACKGROUND: In LR the catheter course is more similar to trans-femoral approach, thus allowing an easier negotiation of coronary ostia which, in turn, might translate into reduced fluoroscopy time (FT) and radiation exposure as compared to RR. METHODS: We retrospectively selected diagnostic and interventional procedures (PCI) performed by RR or LR at our center from May 2009 to May 2014. We only included in the analysis the procedures in which DAP values were available. RESULTS: We analyzed 1464 procedures, 1175 of which performed by RR (80.3%) and 289 by LR (19.7%). Median DAP values were significantly higher in RR as compared to LR for diagnostic and interventional procedures (4482 vs. 3540 cGy.cm(2) and 11523 vs. 10086 cGy.cm(2), respectively; p < 0.05). No significant differences were observed in FT and in contrast volume (CV). In the propensity-matched cohort, consisting of 269 procedures for each group, no significant differences between LR and RR were observed in median DAP values for both diagnostic and interventional procedures (3990 vs. 3542 cGy.cm(2) and 9964 vs. 10216 cGy.cm(2), respectively; p = ns); FT and CV were also similar. At multiple linear regression analysis laterality of trans-radial approach was not associated with DAP. CONCLUSIONS: In an experienced trans-radial center LR is not associated with a reduction in radiation exposure, FT or CV as compared to RR.


Asunto(s)
Cateterismo Cardíaco/métodos , Angiografía Coronaria/métodos , Seguridad del Paciente , Intervención Coronaria Percutánea/métodos , Arteria Radial/diagnóstico por imagen , Dosis de Radiación , Radiografía Intervencional/métodos , Anciano , Anciano de 80 o más Años , Cateterismo Cardíaco/efectos adversos , Distribución de Chi-Cuadrado , Angiografía Coronaria/efectos adversos , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Puntaje de Propensión , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Protección Radiológica , Radiografía Intervencional/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Ciudad de Roma , Factores de Tiempo
20.
Cardiovasc Revasc Med ; 16(7): 386-90, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26235976

RESUMEN

BACKGROUND: Previous studies showed a possible lower radiation dose absorbed by operators comparing LRA and RRA for percutaneous coronary procedures. The reasons of this lower radiation dose are not well known. The aim of this study was to evaluate the radiation dose absorbed by operators comparing left with right radial access (LRA and RRA respectively) during a simulated diagnostic coronary angiography using a phantom. METHODS: A coronary angiography examination was simulated on a phantom by 5 operators using eight projections with 5 seconds fluoroscopy each. Each operator was equipped with 4 electronic dosimeters placed at thorax, at left wrist, at left head and at hip level. Radiation doses were expressed in picosievert and normalized by dose area product. RESULTS: LRA compared to RRA was associated with a significant lower operator dose at wrist (36pSv/cGYcm(2) [IQR 18-59pSv/cGYcm(2)] and 48pSv/cGYcm(2) [IQR 22-148pSv/cGYcm(2)] respectively, p=0.01) and thorax (3pSv/cGYcm(2) [IQR 2-5pSv/cGYcm(2)] and 10pSv/cGYcm(2) [6-23pSv/cGYcm(2)] respectively, p<0.001) but with a significant higher radiation dose at hip level (102pSv/cGYcm(2) [IQR 44-199pSv/cGYcm(2)] and 67pSv/cGYcm(2) [IQR 39-132pSv/cGYcm(2)] respectively, p=0.02). Conversely the radiation dose at left side of the head did not show significant differences between the two approaches. CONCLUSIONS: In this phantom study simulating a diagnostic coronarography the use of LRA compared to RRA was associated with a significant lower radiation dose at wrist and thorax but with an increased dose at hip level. SUMMARY: To evaluate the radiation dose absorbed by operators comparing left with right radial access (LRA and RRA respectively) we simulated a diagnostic coronary angiography using a dedicated phantom. Operators were equipped with dedicated electronic dosimeters at wrist, hip, head and thorax level. LRA compared to RRA was associated with a significant lower operator dose at wrist and thorax but with a significant higher radiation dose at hip level whereas the radiation dose at left side of the head did not show significant differences between the two approaches.


Asunto(s)
Cateterismo Periférico/métodos , Angiografía Coronaria/instrumentación , Angiografía Coronaria/métodos , Exposición Profesional , Salud Laboral , Fantasmas de Imagen , Arteria Radial/diagnóstico por imagen , Dosis de Radiación , Exposición a la Radiación , Angiografía Coronaria/efectos adversos , Humanos , Exposición Profesional/efectos adversos , Exposición a la Radiación/efectos adversos , Monitoreo de Radiación , Medición de Riesgo , Factores de Riesgo
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