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1.
Biomed Pharmacother ; 168: 115779, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913737

RESUMO

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.


Assuntos
Artrite Psoriásica , Hepatopatia Gordurosa não Alcoólica , Psoríase , Humanos , Metotrexato/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/complicações , Artrite Psoriásica/epidemiologia , Estudos Retrospectivos , Estudos Longitudinais , Estudos Transversais , Psoríase/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
2.
Actas urol. esp ; 47(7): 462-469, sept. 2023.
Artigo em Espanhol | IBECS | ID: ibc-225299

RESUMO

Objetivo Analizar la situación actual de las mujeres en la especialidad de Urología en España. Material y métodos Estudio descriptivo a partir de los resultados de una encuesta electrónica remitida entre febrero y abril de 2020 a través de la base de datos del grupo de Residentes y Jóvenes Urólogos (RAEU) de la Asociación Española de Urología (AEU). Se analizaron las características demográficas de la encuesta y los resultados de la misma. Resultados Se obtuvieron 257 respuestas, correspondientes a 210 mujeres (81,71%) y 47 hombres (18,29%) procedentes de 111 hospitales en total. Se obtuvieron diferencias estadísticamente significativas (p<0,001), con una mayor proporción de hombres en todas las categorías, excepto en el grupo de adjuntas y adjuntos jóvenes (29-39años; p=0,789) y en el de residentes mujeres frente a residentes hombres (p=0,814). En los hospitales con unidades subespecializadas se encontró un mayor número de hombres en todas, excepto en la unidad de suelo pélvico, en la que no se observó una diferencia estadísticamente significativa (p=0,06). Respecto a cargos de responsabilidad, en solo 7 de 111 hospitales había jefas de servicio. Conclusiones La presencia de las mujeres en la especialidad de Urología es cada vez mayor, debido mayoritariamente a las generaciones más jóvenes. Sin embargo, el acceso de estas mujeres a puestos de relevancia es anecdótica (AU)


Objective To analyze the current state of women in urology in Spain. Material and methods Descriptive study based on the results of an online survey sent between February and April 2020 through the database of the Residents and Young Urologists group (RAEU) of the Spanish Association of Urology (AEU). Demographic characteristics of the survey and its results were analyzed. Results In total, 257 responses were obtained from 210 women (81.71%) and 47 men (18.29%) belonging to 111 hospitals. Statistically significant differences were observed (P<.001) with a higher proportion of men in all categories except for the group of young female and male attendings (29-39 years, P=.789), and the group of female residents against male residents (P=.814). The number of men was higher in hospitals with subspecialty units except for the Pelvic Floor Unit, where no statistically significant difference was observed (P=.06). Regarding positions of responsibility, only 7 out of 111 hospitals had female department chiefs. Conclusions Women's representation in urology is increasing, mainly due to the younger generations. However, the access of these women to relevant positions is anecdotal (AU)


Assuntos
Humanos , Feminino , Médicas/tendências , Urologia/tendências , Inquéritos e Questionários , Espanha
3.
Eur J Intern Med ; 118: 49-58, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37544847

RESUMO

BACKGROUND: The aim of this study was to explore the impact of arthritis on liver function using different approaches in vivo and in vitro. METHODS: A cross-sectional study was performed on 330 non-obese/non-T2DM subjects: 180 RA patients, 50 NAFLD non-RA patients, and 100 healthy donors (HDs). A longitudinal study was conducted on 50 RA patients treated with methotrexate for six months. Clinical and laboratory parameters and markers of liver disease were collected. Mechanistic studies were carried out in both the CIA mouse model and hepatocytes treated with anti-citrullinated protein antibodies (ACPAs). RESULTS: RA patients have an increased risk of suffering from liver disease independent of obesity or T2DM. This risk was associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3. Methotrexate treatment for six months was associated with liver abnormalities in those newly-diagnosed patients having CV risk factors. ACPAs induced a defective hepatocyte function, promoting IR and inflammation. The induction of arthritis in mice caused the infiltration of immune cells in the liver and increased inflammatory, apoptotic, and fibrotic processes. CONCLUSION: RA patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, and the action of ACPAs. This is independent of obesity or diabetes and linked to systemic inflammation, and disease activity levels. The negative effects of methotrexate on liver function could be restricted to the concomitant presence of cardiovascular risk factors.


Assuntos
Artrite Reumatoide , Hepatopatias , Humanos , Animais , Camundongos , Metotrexato/uso terapêutico , Estudos Longitudinais , Estudos Transversais , Peptídeos Cíclicos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos , Inflamação , Obesidade
4.
Actas Urol Esp (Engl Ed) ; 47(7): 462-469, 2023 09.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37442224

RESUMO

OBJECTIVE: To analyze the current state of women in urology in Spain. MATERIAL AND METHODS: Descriptive study based on the results of an online survey sent between February and April 2020 through the database of the Residents and Young Urologists group (RAEU) of the Spanish Association of Urology (AEU). Characteristics of the survey and its results were analyzed. RESULTS: In total, 257 responses were obtained from 210 women (81.71%) and 47 men (18.29%) belonging to 111 hospitals. Statistically significant differences were observed (p < 0.001) with a higher proportion of men in all categories except for the group of young female and male attendings (29-39 years, p = 0.789), and the group of female residents against male residents (p = 0.814). The number of men was higher in hospitals with subspecialty units except for the Pelvic Floor Unit, where no statistically significant difference was observed (p = 0.06). Regarding positions of responsibility, only 7 out of 111 hospitals had female Department Chiefs. CONCLUSIONS: Women's representation in urology is increasing, mainly due to the younger generations. However, the access of these women to relevant positions is anecdotal.


Assuntos
Urologia , Humanos , Masculino , Feminino , Espanha , Urologistas , Inquéritos e Questionários
5.
Br J Cancer ; 127(6): 1142-1152, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35725813

RESUMO

BACKGROUND: Disseminated BRAFV600E melanoma responds to BRAF inhibitors (BRAFi) but easily develops resistance with poor prognosis. Secretome plays a pivotal role during tumour progression causing profound effects on therapeutic efficacy. Secreted M-CSF is involved in both cytotoxicity suppression and tumour progression in melanoma. We aimed to analyse the M-CSF contribution in resistant metastatic melanoma to BRAF-targeted therapies. METHODS: Conditioned media from melanoma cells were analysed by citoarray. Viability and migration/invasion assays were performed with paired melanoma cells and tumour growth in xenografted SCID mice. We evaluated the impact of M-CSF plasma levels with clinical prognosis from 35 metastatic BRAFV600E-mutant melanoma patients. RESULTS: BRAFi-resistant melanoma cells secretome is rich in pro-tumour cytokines. M-CSF secretion is essential to induce a Vemurafenib-resistant phenotype in melanoma cells. Further, we demonstrated that M-CSF mAb in combination with Vemurafenib and autophagy blockers synergistically induce apoptosis, impair migration and reduce tumour growth in BRAFi-resistant melanoma cells. Interestingly, lower M-CSF plasma levels are associated with better prognosis in metastatic melanoma patients. CONCLUSIONS: Secreted M-CSF induces a BRAFi-resistant phenotype and means worse prognosis in BRAFV600E metastatic melanoma patients. These results identify secreted M-CSF as a promising therapeutic target toward BRAFi-resistant melanomas.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Indóis/farmacologia , Indóis/uso terapêutico , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/farmacologia , Fator Estimulador de Colônias de Macrófagos/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Camundongos , Camundongos SCID , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/farmacologia , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico
6.
Biomed Pharmacother ; 149: 112872, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35364381

RESUMO

INTRODUCTION: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3. AIMS: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19. RESULTS: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls. CONCLUSIONS: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients.


Assuntos
Tratamento Farmacológico da COVID-19 , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Cricetinae , Humanos , Lítio , SARS-CoV-2 , Sais
7.
Res Vet Sci ; 139: 177-185, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333252

RESUMO

This work examined the effect of acute nutritional restriction or supplementation one week before male introduction on the reproductive performances of the "male effect" when using photostimulated or control males in goats. On 22 March, 84 anoestrous does were placed with photostimulated bucks or with bucks which had received no treatments. One week before male introduction, the females were provided with different nutritional regimes: Supplemented, restricted or control females. The non-esterified fatty acids (NEFAs) and Insulin Growth Factor-1 (IGF-1) concentrations were measured in the same samples. Fecundity, fertility, prolificacy and productivity were also determined. No interaction between both sources of variation was observed in any of the reproductive variables studied. Treatment of the bucks increased the percentage of females expressing behavioural oestrous associated with ovulation (71% vs 90% for Natural and Photo groups, respectively, P < 0.05). The Supplemented females showed higher ovulation rate than Restricted females (1.77 ± 0.13 vs 1.05 ± 0.05, P < 0.001), fecundity (71% vs 43%, P < 0.05); fertility (76% vs 29%, P < 0.05) and productivity (1.00 ± 0.15 vs 0.29 ± 0.11 kids per female, P < 0.01). In the Supplemented females, the higher reproductive results could be due to the lower NEFAs and higher IGF-1 concentrations at ovulation and at the time of oestrus compared to the Restricted females. Thus, the present experiment results demonstrate that nutrition is an important factor in the response to the "male effect" at Mediterranean latitudes, and its negative effect cannot be counterbalanced by using photostimulated bucks.


Assuntos
Cabras , Ovulação , Fotoperíodo , Animais , Ciclo Estral , Feminino , Masculino , Estado Nutricional , Reprodução , Estações do Ano , Comportamento Sexual Animal
8.
Phys Rev Lett ; 123(17): 171101, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31702251

RESUMO

Superradiance can trigger the formation of an ultralight boson cloud around a spinning black hole. Once formed, the boson cloud is expected to emit a nearly periodic, long-duration, gravitational-wave signal. For boson masses in the range (10^{-13}-10^{-11}) eV, and stellar mass black holes, such signals are potentially detectable by gravitational-wave detectors, like Advanced LIGO and Virgo. In this Letter, we present full band upper limits for a generic all-sky search for periodic gravitational waves in LIGO O2 data, and use them to derive-for the first time-direct constraints on the ultralight scalar boson field mass.

9.
Med. intensiva (Madr., Ed. impr.) ; 43(6): 329-336, ago.-sept. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-183251

RESUMO

Objective: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. Design: A prospective observational study was carried out. Setting: A Paediatric Intensive Care Unit. Patients: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. Interventions: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. Main outcome measures: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. Results: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. Conclusions: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB


Objetivo: Estudiar el valor predictivo de la escala inotrópica (IS) y la escala vasoactiva-inotrópica (VIS) en el síndrome de bajo gasto cardiaco (SBGC) en niños poscirugía de cardiopatías congénitas mediante bypass cardiopulmonar (BCP). Determinar si adrenomedulina (MR-proADM) y troponina cardiaca-I (cTn-I) asociadas con IS y VIS incrementan su capacidad predictora de SBGC. Diseño: Estudio prospectivo y observacional. Ámbito: Cuidados intensivos pediátricos. Pacientes: Ciento diecisiete pacientes pediátricos con cardiopatías congénitas corregidos mediante BCP, clasificados en función de la presencia o no de SBGC. Intervenciones: Los datos analíticos y clínicos se midieron a las 2, 12, 24 y 48h post-BCP. Las principales variables se analizaron mediante regresión logística multivariante, considerando SBGC como variable dependiente. Variables de interés principales: SBGC, IS, VIS, MR-proADM, cTn-I, edad, sexo, BCP, PIM-2 y escala Aristóteles. Resultados: El IS no alcanzó significación estadística en el estudio multivariante; sin embargo, el VIS se asoció independientemente a SBGC. El VIS>15,5 a las 2h del ingreso en CIP, ajustado por edad y tiempo de CEC, muestra alta especificidad (92,87%; IC 95%: 86,75-98,96%) y alto valor predictivo negativo (75,59%; IC 95%: 71,10-88,08) para predecir SBGC a las 48h post-BCP. La capacidad predictora no se incrementa al incorporar cTn-I>14ng/ml a las 2h y ADM>1,5nmol/l a las 24h del postoperatorio. Conclusiones: El VIS a las 2h post-BCP es un predictor independiente precoz de SBGC. Este valor no se incrementa al asociarse biomarcadores cardiacos de LCOS. La escala de VIS fue más útil que la escala de IS en la toma de decisiones terapéuticas tras la cirugía cardiaca


Assuntos
Humanos , Pré-Escolar , Débito Cardíaco , Biomarcadores , Cardiopatias Congênitas/diagnóstico , Adrenomedulina/administração & dosagem , Troponina/administração & dosagem , Valor Preditivo dos Testes , Estudos Prospectivos , Modelos Logísticos , Vasodilatadores/administração & dosagem
10.
Med Intensiva (Engl Ed) ; 43(6): 329-336, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29910113

RESUMO

OBJECTIVE: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. DESIGN: A prospective observational study was carried out. SETTING: A Paediatric Intensive Care Unit. PATIENTS: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. INTERVENTIONS: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. MAIN OUTCOME MEASURES: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. RESULTS: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. CONCLUSIONS: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB.


Assuntos
Adrenomedulina/sangue , Baixo Débito Cardíaco/sangue , Ponte Cardiopulmonar , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Precursores de Proteínas/sangue , Troponina I/sangue , Adolescente , Cardiotônicos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos
11.
J Intern Med ; 284(1): 61-77, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29532531

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.


Assuntos
Artrite Reumatoide/sangue , Glicemia/metabolismo , Inflamação/sangue , Lipídeos/sangue , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Animais , Artrite Experimental/sangue , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Pessoa de Meia-Idade
12.
J Autoimmun ; 82: 31-40, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28465139

RESUMO

OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. RESULTS: NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. CONCLUSIONS: NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.


Assuntos
Artrite Reumatoide/complicações , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Armadilhas Extracelulares/metabolismo , Idoso , Antirreumáticos/uso terapêutico , Aterosclerose/terapia , Biomarcadores , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Peroxidase , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
13.
Sci Rep ; 6: 31375, 2016 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-27502756

RESUMO

MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors. Gene and protein expression of miRNA biogenesis-related molecules were also reduced. Accordingly, more than 75% of identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a and -125a were low, while miR-146a and miR-155 appeared elevated. Altered microRNAs' expression was linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies deregulated microRNAs expression, and decreased miRNA biogenesis-related proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis, significantly altered in neutrophils of APS and SLE patients, is associated to their atherothrombotic status, further modulated by specific autoantibodies.


Assuntos
Síndrome Antifosfolipídica/sangue , Lúpus Eritematoso Sistêmico/sangue , MicroRNAs/sangue , Trombose/sangue , Adulto , Autoanticorpos/sangue , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Biologia Computacional , Epigênese Genética , Feminino , Humanos , Imunoglobulina G/sangue , Inflamação , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Neutrófilos/metabolismo , Estresse Oxidativo , Transfecção
14.
J Parasitol ; 101(6): 711-2, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26301512

RESUMO

Rickettsia massiliae , a member of the spotted fever group of Rickettsia, was first isolated from a Rhipicephalus turanicus tick in France. In the New World, it has been detected in Rhipicephalus sanguineus ticks from different geographical locations in Argentina and the United States, but it has only been isolated in Arizona. The aim of this study was the isolation and genetic characterization of R. massiliae from R. sanguineus ticks collected from dogs in Buenos Aires city, Argentina. In total, 49 R. sanguineus ticks were collected from 10 dogs and grouped into 10 pools of 4-5 specimens. With a PCR assay, which detects a fragment of the Rickettsia genus-specific 23S-5S intergenic space, 1 pool of 5 ticks was found positive. Generated sequences exhibited 100% identity with R. massiliae . A new isolate, named CABA, was obtained from this pool by inoculating it into monolayers of Vero cells. Genotypic characteristics were determined, and results showed that fragments of the 23S-5S intergenic space, ompA, ompB, gltA, htrA, and sca1 genes had great similarity with R. massiliae strain Bar29 (Spain). Although few human cases have been confirmed for this pathogen, its circulation in urban areas is of great importance to public health. This isolation improves knowledge of the circulating pathogen and could improve future diagnostic processes as it allows the production of more specific antigens for serological testing.


Assuntos
Vetores Aracnídeos/microbiologia , Doenças do Cão/parasitologia , Rhipicephalus sanguineus/microbiologia , Infecções por Rickettsia/transmissão , Rickettsia/isolamento & purificação , Infestações por Carrapato/veterinária , Animais , Argentina , Chlorocebus aethiops , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , Doenças do Cão/transmissão , Cães , Genótipo , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Rickettsia/classificação , Rickettsia/genética , Infecções por Rickettsia/microbiologia , Infestações por Carrapato/parasitologia , População Urbana , Células Vero
15.
Actas urol. esp ; 38(4): 257-262, mayo 2014. tab
Artigo em Espanhol | IBECS | ID: ibc-122050

RESUMO

Objetivo: Analizar los resultados de la cirugía retrógrada intrarrenal (CRIR) en pacientes con litiasis ≥ 2 cm tratados en nuestro centro. Material y métodos: Revisión retrospectiva de 106 pacientes con litiasis renales ≥ 2 cm sometidos a RIRS (período comprendido entre enero de 2009 y diciembre de 2011). Los procedimientos se realizaron bajo anestesia general utilizando como fuente de fragmentación el láser Holmium (Litho 30 W Quantasystem) y ureteroscopios flexibles (Storz Flex X2, Olympus P5) a través de vainas de acceso ureteral.Se analizan variables demográficas (edad, antecedentes patológicos, tratamientos antiagregantes o anticoagulantes, tratamiento de litiasis, IMC, ASA), variables de litiasis tratada (tamaño, número, unidades Hounsfield, composición bioquímica) y variables intra y postoperatorias (tiempo quirúrgico, número de pulsos, estancia hospitalaria, complicaciones) con la realización de un análisis descriptivo de las mismas. Para definir nuestros resultados consideramos éxito la ausencia completa de restos litiásicos o residuales < 5 mm en las pruebas de imagen posteriores. Resultados: La media de tamaño de las litiasis tratadas fue de 2,46 cm, siendo la litiasis única en el 87,7% de los casos. La localización más frecuente de la litiasis fue la pelvis renal (44%) seguida del cáliz inferior (39%). La tasa de complicaciones postoperatoria fue del 6,7%, siendo todas de escasa relevancia. El porcentaje de éxito con un único procedimiento fue de un 79,4%, alcanzando el 94,1% con retratamiento. Conclusión: La CRIR es una alternativa válida para el tratamiento de litiasis renales ≥ 2 cm por su alta tasa de éxito y escasas complicaciones si se realiza en centros especializados


Objective: To analyze the results of retrograde intrarenal surgery (RIRS) in patients with ≥2 cm stones treated in our center. Material and methods: A retrospective review of 106 patients with renal calculi underwent RIRS ≥2 cm (period January 2009-December 2011). The procedures were performed under general anesthesia as a source of fragmentation using the holmium laser (30 W Litho Quanta system) and flexible ureteroscopes (X2 Flex Storz, Olympus P5) through ureteral access sheaths. It discusses demographic variables (age, medical history, antiplatelet or anticoagulant treatment, treatment of urolithiasis, BMI, ASA), treated stones variables (size, number, Hounsfield units, biochemical composition) and intra-and postoperative variables (operative time, number of pulses, hospital stay, complications) with the completion of a descriptive analysis of the same. To define our results we consider success to the complete absence of fragments or residual <5 mm posterior imaging tests. Results: The mean stone size was 2.46 cm treated, being the only stone in 87.7% of cases. The most frequent location was the renal pelvis stones (44%) followed by the lower calyx (39%).The postoperative complication rate was 6.7%, with all of little relevance. The success rate with a single procedure was 79.4% to 94.1% with retreatment. Conclusion: RIRS is a valid alternative for the treatment of kidney stones ≥ 2 cm for its high success rate and few complications if performed in specialized centers


Assuntos
Humanos , Nefrolitíase/cirurgia , Litotripsia/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Estudos Retrospectivos , Resultado do Tratamento
16.
Actas urol. esp ; 38(1): 14-20, ene.-feb. 2014. tab
Artigo em Espanhol | IBECS | ID: ibc-118956

RESUMO

Objetivo: Comparar los resultados obtenidos en la nefrolitotomía percutánea tras la introducción del ureteroscopio/nefroscopio flexible (cirugía endoscópica intrarrenal combinada [CEIRC]) con nefrolitomías con solo nefroscopio rígido (nefrolitotomía percutánea estándar [NLPC]). Material y método: Estudio retrospectivo de 171 NLPC en posición de Galdakao realizadas entre enero de 2005 y diciembre de 2011. Comparamos los resultados obtenidos en aquellos procedimientos en los que se realizó CEIRC con aquellos en los solo se utilizó nefroscopio rígido (NLPC). Se estimó el éxito específico y el global, el porcentaje de carga litiásica eliminada, los días de estancia hospitalaria y las complicaciones derivadas. Definimos el éxito por la ausencia completa de litiasis o la presencia de residual < 5 mm. Diferenciamos el éxito específico, el conseguido solo con la cirugía percutánea, y el éxito global, el alcanzado tras una segunda línea de tratamiento. Resultados: En 73 procedimientos (42,4%) se realizó CEIRC con endoscopios flexibles, mientras que 98 (57,6%) fueron NLPC. Ambos grupos fueron comparables en cuanto a parámetros demográficos y características de las litiasis. Las tasas de éxito en el primer procedimiento y de éxito global fueron superiores para el grupo de CEIRC (75,3 vs 40,8% y 93,1 vs 74,5%), siendo las diferencias estadísticamente significativas (p < 0,05). No se encontraron diferencias estadísticamente significativas en cuanto a las complicaciones (28,8 vs 28,3%; p = 0,86) o los días de estancia hospitalaria (4,5 vs 5,0; p = 0,18). Conclusiones: El uso de ureteroscopio/nefroscopio flexible en la NLPC (CEIRC) mejora las tasas de éxito y de eliminación de carga litiásica, permitiendo en la mayoría de casos realizar la cirugía con un acceso único


Objective: To compare the results obtained in percutaneous nephrolithotomy after introduction of flexible ureteroscopy/nephroscopy (endoscopic combined intrarenal surgery - ECIRS) with nephrolitomies with only rigid nephroscopy (standard percutaneous nephrolithotomy; sPCNL). Materials and methods: A retrospective study of 171 sPCNL in Galdakao position performed between January 2005 and December 2011 was conducted. We compared the results obtained in those procedures in which endoscopic combined intrarenal surgery (ECIRS) was performed with those in which only the rigid nephroscopy (sPCNL) was used. Specific and global success, percentage of lithiasic load eliminated, days of hospital stay and complications derived were calculated. We defined success by complete absence of lithiasis or residual presence of <5 mm. We differentiated specific success, that only achieved with percutaneous surgery, from global success, or that achieved after a second line of treatment. Results: In 73 procedures (42.4%) ECIRS was performed with flexible endoscopy while in 98 (57.6%) it was done with sPCNL. Both groups were comparable in regards to demographic parameters and characteristics of the lithiasis. The success rates in the first procedure and global success were superior for the ECIRS group (75.3% vs. 40.8% and 93.1% vs. 74.5%), the differences being statistically significant (P < 0.05). No statistically significant differences were found in regards to the complications (28.8% vs. 28.3%; P = .086) or days of hospital stay (4.5 vs. 5.0; P = 0.18). Conclusions: Use of the flexible ureteroscopy/nephroscopy in sPCNL (ECIRS) improves the success rates and elimination of lithiasic load, making it possible to perform the surgery with a single access in most of the cases


Assuntos
Humanos , Nefrostomia Percutânea , Nefrolitíase/cirurgia , Ureteroscopia/métodos , Posicionamento do Paciente/métodos , Tempo de Internação/estatística & dados numéricos
17.
Actas Urol Esp ; 38(1): 14-20, 2014.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-23911215

RESUMO

OBJECTIVE: To compare the results obtained in percutaneous nephrolithotomy after introduction of flexible ureteroscopy/nephroscopy (endoscopic combined intrarenal surgery - ECIRS) with nephrolitomies with only rigid nephroscopy (standard percutaneous nephrolithotomy; sPCNL). MATERIAL AND METHOD: A retrospective study of 171 sPCNL in Galdakao position performed between January 2005 and December 2011 was conducted. We compared the results obtained in those procedures in which endoscopic combined intrarenal surgery (ECIRS) was performed with those in which only the rigid nephroscopy (sPCNL) was used. Specific and global success, percentage of lithiasic load eliminated, days of hospital stay and complications derived were calculated. We defined success by complete absence of lithiasis or residual presence of<5mm. We differentiated specific success, that only achieved with percutaneous surgery, from global success, or that achieved after a second line of treatment. RESULTS: In 73 procedures (42.4%) ECIRS was performed with flexible endoscopy while in 98 (57.6%) it was done with sPCNL. Both groups were comparable in regards to demographic parameters and characteristics of the lithiasis. The success rates in the first procedure and global success were superior for the ECIRS group (75.3% vs 40.8% and 93.1% vs 74.5%), the differences being statistically significant (P<.05). No statistically significant differences were found in regards to the complications (28.8% vs 28.3% P=.86) or days of hospital stay (4.5 vs 5.0 P=.18). CONCLUSIONS: Use of the flexible ureteroscopy/nephroscopy in sPCNL (ECIRS) improves the success rates and elimination of lithiasic load, making it possible to perform the surgery with a single access in most of the cases.


Assuntos
Nefrostomia Percutânea/métodos , Posicionamento do Paciente , Decúbito Dorsal , Ureteroscópios , Ureteroscopia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrostomia Percutânea/instrumentação , Estudos Retrospectivos
18.
Actas Urol Esp ; 38(4): 257-62, 2014 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24156933

RESUMO

OBJECTIVE: To analyze the results of retrograde intrarenal surgery (RIRS) in patients with ≥2 cm stones treated in our center. MATERIAL AND METHODS: A retrospective review of 106 patients with renal calculi underwent RIRS ≥2 cm (period January 2009-December 2011). The procedures were performed under general anesthesia as a source of fragmentation using the holmium laser (30 W Litho Quantasystem) and flexible ureteroscopes (X2 Flex Storz, Olympus P5) through ureteral access sheaths. It discusses demographic variables (age, medical history, antiplatelet or anticoagulant treatment, treatment of urolithiasis, BMI, ASA), treated stones variables (size, number, Hounsfield units, biochemical composition) and intra-and postoperative variables (operative time, number of pulses, hospital stay, complications) with the completion of a descriptive analysis of the same. To define our results we consider success to the complete absence of fragments or residual <5 mm posterior imaging tests. RESULTS: The mean stone size was 2.46 cm treated, being the only stone in 87.7% of cases. The most frequent location was the renal pelvis stones (44%) followed by the lower calyx (39%). The postoperative complication rate was 6.7%, with all of little relevance. The success rate with a single procedure was 79.4% to 94.1% with retreatment. CONCLUSION: RIRS is a valid alternative for the treatment of kidney stones ≥2 cm for its high success rate and few complications if performed in specialized centers.


Assuntos
Cálculos Renais/cirurgia , Feminino , Humanos , Cálculos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos/métodos
19.
Actas urol. esp ; 37(9): 587-591, oct. 2013. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-116124

RESUMO

Objetivo: La nefrolitotomía percutánea (NLPC) es una técnica con buenos resultados para el tratamiento de la litiasis renal, sin embargo, las complicaciones hemorrágicas derivadas de la misma puedes ser graves si no son diagnosticadas y tratadas eficazmente. El objetivo de este estudio es evaluar las complicaciones hemorrágicas derivadas de la nefrolitotomía percutánea en posición de Galdakao y su manejo terapéutico. Material y métodos: Estudio longitudinal retrospectivo de 172 NLPC realizadas en el Hospital La Ribera entre enero de 2005 y diciembre de 2011, analizando sus complicaciones hemorrágicas y el tratamiento establecido para su resolución. Resultados: Presentaron complicaciones hemorrágicas 20 pacientes (11,6%). El requerimiento transfusional de esta serie fue de 8,1% y la causa más frecuente de transfusión el hematoma perirrenal post-operatorio (7,5%). Hubo 6 lesiones arteriales (3,5%), 5 de ellas tratadas satisfactoriamente con arteriografía y embolización selectiva de la lesión. Conclusiones: Las lesiones arteriales por NLPC son poco frecuentes pero pueden ser graves. La posibilidad de realizar de manera urgente arteriografía y embolización selectiva, ante el diagnóstico de una lesión vascular tras NLPC, permite el tratamiento de la hemorragia de una manera eficaz y segura sin riesgo para la unidad renal afectada (AU)


Objetive: Percutaneous Nephrolithotomy (PCNL) is a technique with good results for the treatment of kidney stones, however, bleeding complications derived can be serious if not diagnosed and treated effectively. The aim of this study is to assess bleeding complications resulting from PCNL in Galdakao position and therapeutic management. Material and methods: Retrospective-longitudinal study of 172 PCNL performed in La Ribera Hospital between January 2005 and December 2011, analyzing their bleeding complications and the treatment provided for resolution. Results: Had bleeding complications 20 patients (11.6%). The need for transfusion in this series was 8.1% and the most common cause of blood transfusion the presence of postoperative retroperitoneal (7.5%). There were 6 arterial injuries (3.5%), 5 of them successfully treated with angiography and arterial selective embolization. Conclusions: The arterial injuries following PCNL are rare but can be serious. The possibility of an urgent arteriography and selective embolization to the diagnosis permits an effective and safe treatment of bleeding without risk to the affected renal unit (AU)


Assuntos
Humanos , Nefrostomia Percutânea/efeitos adversos , Nefrolitíase/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica/métodos , Angiografia , Fatores de Risco , Estudos Retrospectivos
20.
Actas urol. esp ; 37(7): 412-418, jul.-ago. 2013. tab
Artigo em Espanhol | IBECS | ID: ibc-114214

RESUMO

Objetivo: Establecer factores predictivos de complicaciones en nefrolitotomía percutánea (NLPC) utilizando el sistema de Clavien modificado. Material y método: Estudio retrospectivo en el que se incluyen 172 NLPC en posición de Galdakao realizadas en el Hospital La Ribera entre enero de 2005 y diciembre de 2011. Se clasifican las complicaciones derivadas de estos procedimientos utilizando el sistema de Clavien modificado. Se realiza un análisis univariante (test Chi-cuadrado y V de Cramer) y multivariante (regresión logística) de factores predictivos de estas complicaciones (p < 0,05). Resultados: En 49 de los 172 procedimientos se detectaron complicaciones (28,5%). Las complicaciones más frecuentes fueron de grado 1 (9,9%), 12 complicaciones (6,9%) fueron clasificadas como grado 2 por requerir tratamiento médico adicional, 6 como grado 3A (3,5%), 7 como grado 3B (4,1%), 2 como 4A (1,1%), 4 como 4B (2,3%) y una como 5 (0,6%). En el análisis univariante el cultivo de orina positivo previo a la intervención, las litiasis complejas y el tamaño mayor de 40 mm de las mismas mostraron una asociación estadísticamente significativa con la aparición de complicaciones (p < 0,05). El cultivo positivo (OR: 2,96) y las litiasis complejas (OR: 3,03) demostraron ser variables independientes de predicción de complicaciones en el análisis multivariante. Conclusiones: El sistema de Clavien permite utilizar un lenguaje común para clasificar las complicaciones, expresando el grado de las mismas según la complejidad del tratamiento requerido para su resolución. La positividad del urinocultivo preoperatorio y las litiasis complejas demostraron ser factores predictivos de estas complicaciones en nuestra serie (AU)


Objective: Set predictors of complications in percutaneous nephrolithotomy (PCNL) using the modified Clavien system. Material and methods: Retrospective study included 172 PCNL in Galdakao position made in the La Ribera Hospital between January 2005 and December 2011. They classified the complications of these procedures using the modified Clavien system. We performed a univariate analysis (Chi2 Test and Cramer's V) and multivariate (logistic regression) of predictors of these complications (P <0 .05). Results: In 49 of the 172 procedures complications were detected (28.5%).The most frequent complications were grade 1 (9.9%), 12 complications (6.9%) were classified as grade 2 by requiring additional medical treatment, 6 as grade 3A (3.5%), 7 as grade 3B (4.1%), 2 and 4A (1.1%), 4 and 4B (2.3%) and one and 5 (0.6%). In the univariate analysis, positive urine culture before surgery, the stones complex and larger than 40 mm of the same, showed a statistically significant association with the occurrence of complications (P < .05). The positive culture (OR: 2.96) and complex stones (OR: 3.03) proved to be independent variables predicting complications in multivariate analysis. Conclusions: Clavien system allows a common language for classifying complications, expressing the degree of the same as the complexity of treatment required for resolution. The preoperative urine culture positivity and complex stone proved predictors of these complications in our serie (AU)


Assuntos
Humanos , Masculino , Feminino , Nefrostomia Percutânea/classificação , Nefrostomia Percutânea/instrumentação , Nefrostomia Percutânea/métodos , Valor Preditivo dos Testes , Nefropatias/complicações , Nefrostomia Percutânea/efeitos adversos , Nefrostomia Percutânea , Estudos Retrospectivos , Análise Multivariada , Modelos Logísticos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/fisiopatologia , Cálculos da Bexiga Urinária/complicações , Cálculos da Bexiga Urinária/etiologia , Litíase/complicações
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