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1.
Int J Cardiol ; 301: 167-172, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761402

RESUMO

BACKGROUND: In the direct oral anticoagulants (DOACs) era, extended anticoagulation is an attractive strategy after venous thromboembolism (VTE). The role of currently available bleeding risk scores for VTE patients treated with DOACs in clinical practice is undefined. METHODS: Consecutive patients with VTE were included in a prospective multicenter cohort at the initiation of treatment with DOACs. The role of ATRIA, HAS-BLED, Kuijer, ORBIT, RIETE and VTE-BLEED scores in predicting major bleeding (ISTH definition) while on DOAC treatment was assessed. RESULTS: Overall, 1034 patients were included and followed for one year or until the end of treatment or the occurrence of major bleeding. During study period, 26 major bleedings occurred in 25 patients (2.8% patient-year). Anemia, bleeding history and creatinine clearance <60 ml/min were significant predictors of major bleedings. The predictive value of bleeding risk scores was modest. In the 12-month study period, ORBIT (HR intermediate-high vs. low risk patients 3.62, 95% CI 1.65-7.94 and c-statistics 0.645, 95% CI 0.523-0.767) and VTE-BLEED (HR high vs. low 16.11, 95% CI 2.18-119.09 and c-statistics 0.674, 95% CI 0.593-0.755) score significantly predicted major bleeding. The lowest incidence of major bleeding (0.3%) was observed in the low-risk category of VTE-BLEED, while the highest (7.1%) in the high-risk category of ORBIT. CONCLUSIONS: In a real-life cohort of patients with VTE treated with DOACs, the predictive value of currently available bleeding risk scores was modest and not statistically different. Whether these scores can be used for decision making on anticoagulation should be assessed in management studies.


Assuntos
Inibidores do Fator Xa , Hemorragia , Medição de Risco/métodos , Tromboembolia Venosa/tratamento farmacológico , Estudos de Coortes , Duração da Terapia , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Hemorragia/prevenção & controle , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Projetos de Pesquisa , Tromboembolia Venosa/epidemiologia
2.
J Thorac Dis ; 10(7): 4077-4084, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30174851

RESUMO

BACKGROUND: Extra vascular lung water (EVLW) following pulmonary resection increases due to fluid infusion and rises in capillary surface and permeability of the alveolar capillary membranes. EVLW increase clinically correlates to pulmonary oedema and it may generate impairments of gas exchanges and acute lung injury. An early and reliable assessment of postoperative EVLW, especially following major pulmonary resection, is useful in terms of reducing the risk of postoperative complications. The currently used methods, though satisfying these criteria, tend to be invasive and cumbersome and these factors might limit its use. The presence and burden of EVLW has been reported to correlate with sonographic B-line artefacts (BLA) assessed by lung ultrasound (LUS). This observational study investigated if bedside LUS could detect EVLW increases after major pulmonary resection. Due to the clinical association between EVLW increase and impairment of gas exchange, secondary aims of the study included investigating for associations between any observed EVLW increases and both respiratory ratio (PaO2/FiO2) and fluid retention, measured by brain natriuretic peptide (BNP). METHODS: Overall, 74 major pulmonary resection patients underwent bedside LUS before surgery and at postoperative days 1 and 4, in the inviolate hemithorax which were divided into four quadrants. BLA were counted with a four-level method. The respiratory ratio PaO2/FiO2 and fluid retention were both assessed. RESULTS: BLA resulted being increased at postoperative day 1 (OR 9.25; 95% CI, 5.28-16.20; P<0.0001 vs. baseline), and decreased at day 4 (OR 0.50; 95% CI, 0.31-0.80; P=0.004 vs. day 1). Moreover, the BLA increase was associated with both increased BNP (OR 1.005; 95% CI, 1.003-1.008; P<0.0001) and body weight (OR 1.040; 95% CI, 1.008-1.073; P=0.015). Significant inverse correlations were observed between the BLA values and the PaO2/FiO2 respiratory ratios. CONCLUSIONS: Our results suggest that LUS, due to its non-invasiveness, affordability and capacity to detect increases in EVLW, might be useful in better managing postoperative patients.

3.
Islets ; 2(2): 96-103, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21099301

RESUMO

Ex vivo islet cell culture in the presence of stimulating factors prior to transplantation is considered a good strategy in contrast to the short conclusion of islets transplantation. Previously, we demonstrated how T3 can increase b-cell function via specific activation of Akt; therefore we hypothesized that thyroid hormone T3 can be considered a promising candidate for the in vitro expansion of islet cell mass. Rat pancreatic islets have been isolated by the collagenase digestion and cultured in the presence or not of the thyroid hormone T3 10⁻7 M. Islets viability has been evaluated by the use of two different dyes, one cell-permeable green fluorescent dye and propidium iodide, and by the analysis of core cell damage upcoming. Moreover, islets function has been evaluated by insulin secretion. The ability of b-cells to counteract apoptosis induced by streptozotocin has been analyzed by TUNEL assay. We demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented ß-cell vitality with an increase of their functional properties. In addition, a sensible reduction of the core cell damage has been observed in the T3 treated islets, suggesting the preservation of the ß-cells integrity during the culture period. Nonetheless, the insulin secretion is sensibly augmented after T3 stimulation. The strong increment shown in Akt activation suggests the involvement of this pathway in the observed phenomena. In conclusion we indicate T3 as a good factor to improve ex vivo islets cell culture.


Assuntos
Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/fisiologia , Tri-Iodotironina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Citoproteção/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo
4.
Mol Cell Biol ; 29(2): 357-77, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18981221

RESUMO

The mouse aldehyde oxidase AOH2 (aldehyde oxidase homolog 2) is a molybdoflavoenzyme. Harderian glands are the richest source of AOH2, although the protein is detectable also in sebaceous glands, epidermis, and other keratinized epithelia. The levels of AOH2 in the Harderian gland and skin are controlled by genetic background, being maximal in CD1 and C57BL/6 and minimal in DBA/2, CBA, and 129/Sv strains. Testosterone is a negative regulator of AOH2 in Harderian glands. Purified AOH2 oxidizes retinaldehyde into retinoic acid, while it is devoid of pyridoxal-oxidizing activity. Aoh2(-/-) mice, the first aldehyde oxidase knockout animals ever generated, are viable and fertile. The data obtained for this knockout model indicate a significant role of AOH2 in the local synthesis and biodisposition of endogenous retinoids in the Harderian gland and skin. The Harderian gland's transcriptome of knockout mice demonstrates overall downregulation of direct retinoid-dependent genes as well as perturbations in pathways controlling lipid homeostasis and cellular secretion, particularly in sexually immature animals. The skin of knockout mice is characterized by thickening of the epidermis in basal conditions and after UV light exposure. This has correlates in the corresponding transcriptome, which shows enrichment and overall upregulation of genes involved in hypertrophic responses.


Assuntos
Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Epiderme/metabolismo , Flavoproteínas/genética , Flavoproteínas/metabolismo , Glândula de Harder/metabolismo , Tretinoína/metabolismo , Envelhecimento , Aldeído Oxirredutases/isolamento & purificação , Animais , Endocitose/genética , Epiderme/anatomia & histologia , Epiderme/química , Epiderme/patologia , Exocitose/genética , Feminino , Flavoproteínas/isolamento & purificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Glândula de Harder/anatomia & histologia , Glândula de Harder/química , Hipertrofia/metabolismo , Lipídeos/genética , Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Retinaldeído/metabolismo , Glândulas Sebáceas/metabolismo , Caracteres Sexuais , Testosterona/metabolismo
5.
J Lipid Res ; 49(9): 1936-45, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18493032

RESUMO

Nutrition during fetal life is a critical factor contributing to diabetes development in adulthood. The aim of our study was to verify: 1) whether a high-fat (HF) diet in young adult mice induces alterations in beta-cell mass, proliferation, neogenesis, and apoptosis, as well as insulin sensitivity and secretion; 2) whether these alterations may be reversible after HF diet suspension; 3) the effects in a first (F1) and second generation (F2) of mice without direct exposure to a HF diet after birth. Type 2 diabetes developed in adult mice on a HF diet, in F1 mice that were HF diet-exposed during fetal or neonatal life, and in F2 mice whose mothers were HF diet-exposed during their fetal life. beta-cell mass, replication, and neogenesis were high in HF diet-exposed mice and decreased after diet suspension. beta-cell mass and replication remained high in F1 mice and decreased in F2 mice whose mothers were exposed to a HF diet. beta-cell neogenesis was present in adult mice on a HF diet and in F1 mice that were HF diet-exposed during fetal and/or neonatal life. We conclude that a HF diet during fetal life, particularly if combined with the same insult during the suckling period, can induce the type 2 diabetes phenotype, which can be directly transmitted to the progeny even in the absence of additional dietary insults.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Gorduras na Dieta/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Resistência à Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/fisiologia , Camundongos , Pâncreas/embriologia , Gravidez
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