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1.
Biomed Pharmacother ; 168: 115791, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924793

RESUMO

Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Humanos , Camundongos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Leucócitos Mononucleares/metabolismo , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Proliferação de Células
2.
Breast ; 69: 342-348, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37011481

RESUMO

PURPOSE: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. METHODS: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. RESULTS: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. CONCLUSION: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Citocromo P-450 CYP2D6/genética , Pontuação de Propensão , Antineoplásicos Hormonais/uso terapêutico , Resultado do Tratamento , Tamoxifeno/uso terapêutico , Genótipo
3.
J Endovasc Ther ; : 15266028221148383, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680500

RESUMO

PURPOSE: Ascending aorta (AAo) acute pathology still has an open-surgery indication with a high mortality rate associated to cardiopulmonary bypass and circulatory arrest. In these cases, the endovascular aortic approach could be an excellent option. The aim of the present study is to detail an optimized technique for the endovascular treatment of AAo diseases, based on thoracic endovascular aortic repair (TEVAR) and transcatheter aortic valve implantation (TAVI) procedures. TECHNIQUE: The procedure implies the usual preparation for TEVAR and TAVI implants. A transient pacemaker lead is necessary to deliver the prosthesis under "rapid pacing." As in the TAVI technique, a final high-support guidewire is placed at the left ventricle. The proximal landing zone is the sinotubular junction (zone 0B). Transesophageal echocardiography is essential to ensure aortic valve function and patency in coronary arteries during the delivery. To assess a potential occlusion of the brachiocephalic artery, a guidewire is positioned in the descending aorta from the axillary artery. Finally, a noncovered stent is implanted to stabilize the AAo prosthesis. CONCLUSION: The technique presented here can standardize a safe and reproducible procedure to endovascular repair of AAo diseases. However, new devices specifically designed for the AAo could facilitate the transcatheter approach. CLINICAL IMPACT: Ascending aorta acute pathology still has an open-surgery indication with high mortality rate associated to cardiopulmonary bypass and circulatory arrest. Moreover, near 30% of patients are not considered suitable for surgery because of age, critical situation or the presence of severe comorbidities. The present study provides a detailed and optimized technique for the endovascular treatment of ascending aorta disease, based on TEVAR and TAVI procedures.

4.
Plant Signal Behav ; 17(1): 2031504, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35105280

RESUMO

For the establishment of the Arbuscular Mycorrhiza (AM) symbiosis it is essential that epidermis and cortical cells from plant roots suffer a strong reorganization to allow the penetration of intracellular fungal hyphae. In the same manner, the new formation of a periarbuscular membrane and a symbiotic interface with specific compositions are required for a functional symbiosis. It is believed that the cytoskeleton of the plant host plays an essential role in these processes, particularly the microtubule (MT) cytoskeleton, as huge modifications have been observed in the MT array of root cells accompanying the establishment of the AM symbiosis. Recent research has established a link between microtubule rearrangements and arbuscule functioning. However, further research is required to elucidate the specific functions of MT cytoskeleton along the different stages of the arbuscule life cycle and to unravel the signals triggering these changes.


Assuntos
Micorrizas , Micorrizas/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Simbiose , Microtúbulos/metabolismo , Regulação da Expressão Gênica de Plantas
5.
Scand J Clin Lab Invest ; 81(4): 282-289, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33974458

RESUMO

BACKGROUND: Early identification of patients with COVID-19 who may develop critical illness is of great importance. METHODS: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in a cohort of 154 cases admitted at Valme and Virgen del Rocio University Hospital. RESULTS: A total of 62 (23.5%) patients developed a critical illness during their hospitalization stay, 21 (8.0%) patients needed invasive ventilation, 34 (12.9%) were admitted at the ICU and the overall mortality was of 14.8% (39 cases). 5 variables were included in the final model: age >59.5 years (OR: 3.11;95%CI 1.39-6.97), abnormal CRP results (OR: 5.76;95%CI 2.32-14.30), abnormal lymphocytes count (OR: 3.252;95%CI 1.56-6.77), abnormal CK results (OR: 3.38;95%CI 1.59-7.20) and abnormal creatinine (OR: 3.30;95%CI 1.42-7.68). The AUC of this model was 0.850 with sensitivity of 65% and specificity of 87% and the IDI and NRI were 0.1744 and 0.2785, respectively. The validation indicated a good discrimination for the external population. CONCLUSIONS: Biomarkers add prognostic information in COVID-19 patients. Our risk-score provides an easy to use tool to identify patients who are likely to develop critical illness during their hospital stay.


Assuntos
Biomarcadores/sangue , COVID-19/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , COVID-19/mortalidade , COVID-19/terapia , Creatina Quinase/sangue , Creatinina/sangue , Estado Terminal , Feminino , Hospitalização , Humanos , Laboratórios , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Adulto Jovem
6.
Breast ; 54: 106-113, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32977298

RESUMO

BACKGROUND: Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients. METHODS: We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age. RESULTS: 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2-28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7-85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity. CONCLUSION: NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Trastuzumab/efeitos adversos , Adulto , Idoso , Biomarcadores Farmacológicos/análise , Neoplasias da Mama/sangue , Cardiotoxicidade/diagnóstico , Diabetes Mellitus/sangue , Monitoramento de Medicamentos , Feminino , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/induzido quimicamente , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
7.
Eur Heart J Acute Cardiovasc Care ; 9(5): 406-418, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32403935

RESUMO

BACKGROUND: The coexistence of other comorbidities confers poor outcomes in patients with acute heart failure. Our aim was to determine the characteristics of patients with acute heart failure and cardiorenal anaemia syndrome and the relationship between renal dysfunction and anaemia, alone or combined as cardiorenal anaemia syndrome, on short-term outcomes. METHODS: We analysed the Epidemiology of Acute Heart Failure in Emergency Departments registry (cohort of patients with acute heart failure in Spanish emergency departments). Renal dysfunction was defined by an estimated glomerular filtration rate <60 ml/min/m2, anaemia by haemoglobin values <12/<13 g/dl in women/men, and cardiorenal anaemia syndrome as the presence of both. Comparisons were made according to cardiorenal-anaemia syndrome positive (CRAS+) with respect to the rest of patients (CRAS-) and according the presence of renal dysfunction (RD+) and anaemia (A+), (alone, RD+/A-, RD-/A+) or in combination (RD+/A+; i.e. CRAS+) with respect to patients without renal dysfunction and anaemia (RD-/A-). The primary outcome was 30-day mortality, and the secondary outcomes were need for admission, prolonged hospitalisation (>10 days), in-hospital mortality during the index event, and reconsultation and the combination of 30-day post-discharge reconsultation/death. These short-term outcomes were compared and adjusted for differences among groups. RESULTS: Of the 13,307 patients analysed, CRAS+ (36.4%) was associated with older age, multiple comorbidities, chronic use of loop diuretics, oedemas and hypotension. The 30-day mortality in CRAS+ was greater than in CRAS- (hazard ratio = 1.46, 95% confidence interval = 1.26-1.68) and RD-/A- (hazard ratio = 1.83, 95% confidence interval = 1.46-2.28) control groups. The mortality level was also higher in RD+/A- (hazard ratio = 1.40, 95% confidence interval = 1.10-1.78) and higher, but not statistically significant, in RD-/A+ (hazard ratio = 1.28, 95% confidence interval = 0.99-1.63) with respect to RD-/A-. All of the secondary outcomes, when related to CRAS- and RD-/A- control groups, were worse for CRAS+ and to a lesser extent, RD+/A-, being more rarely observed in RD-/A+. CONCLUSIONS: Cardiorenal anaemia syndrome in acute heart failure is related to greater mortality and worse short-term outcomes, and the impact of renal dysfunction and anaemia seems to be additive.


Assuntos
Anemia/complicações , Síndrome Cardiorrenal/complicações , Serviço Hospitalar de Emergência/estatística & dados numéricos , Insuficiência Cardíaca/complicações , Sistema de Registros , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Síndrome Cardiorrenal/fisiopatologia , Causas de Morte/tendências , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências
8.
J Vis Exp ; (157)2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32225152

RESUMO

Ralstonia solanacearum is a devastating soil borne vascular pathogen that can infect a large range of plant species, causing an important threat to agriculture. However, the Ralstonia model is considerably underexplored in comparison to other models involving bacterial plant pathogens, such as Pseudomonas syringae in Arabidopsis. Research targeted to understanding the interaction between Ralstonia and crop plants is essential to develop sustainable solutions to fight against bacterial wilt disease but is currently hindered by the lack of straightforward experimental assays to characterize the different components of the interaction in native host plants. In this scenario, we have developed a method to perform genetic analysis of Ralstonia infection of tomato, a natural host of Ralstonia. This method is based on Agrobacterium rhizogenes-mediated transformation of tomato roots, followed by Ralstonia soil-drenching inoculation of the resulting plants, containing transformed roots expressing the construct of interest. The versatility of the root transformation assay allows performing either gene overexpression or gene silencing mediated by RNAi. As a proof of concept, we used this method to show that RNAi-mediated silencing of SlCESA6 in tomato roots conferred resistance to Ralstonia. Here, we describe this method in detail, enabling genetic approaches to understand bacterial wilt disease in a relatively short time and with small requirements of equipment and plant growth space.


Assuntos
Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Ralstonia solanacearum/fisiologia , Solanum lycopersicum/genética , Solanum lycopersicum/microbiologia , Transformação Genética , Agrobacterium/metabolismo , Antibacterianos/farmacologia , Arabidopsis/microbiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Solanum lycopersicum/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Ralstonia solanacearum/efeitos dos fármacos , Ralstonia solanacearum/crescimento & desenvolvimento , Reprodutibilidade dos Testes , Solo , Transformação Genética/efeitos dos fármacos
9.
Clin Res Cardiol ; 109(1): 34-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31037410

RESUMO

OBJECTIVE: To investigate whether patients with an acute heart failure (AHF) episode triggered by infection present different outcomes compared to patients with no trigger and the effects of early antibiotic administration (EAA) and hospitalisation. METHODS: Two groups were made according to the AHF trigger: infection (G1) or none identified (G2). The primary outcome was 13-week (91-days) all-cause mortality, and secondary outcomes were 13-week post-discharge mortality, readmission or combined endpoint. Comparisons are presented as unadjusted and adjusted (MEESSI risk score) hazard ratios (uHR/aHR) for G1 compared to G2 patients, also estimated by weeks. Stratified analysis by EAA (provided/not provided) and patient disposition (discharged/hospitalised) was performed. RESULTS: We included 6727 patients (G1 = 3973; G2 = 2754). The 13-week mortality uHR was 1.11 (0.99-1.25; p = 0.06; with significant increases in the first 3 weeks), and the aHR was 0.91 (0.81-1.02; p = 0.11). There were no differences in unadjusted secondary post-discharge outcomes; however, G1 outcomes significantly improved after adjustment: aHR 0.83 (0.71-0.96; p = 0.01) for mortality, 0.92 (0.84-0.99; p = 0.04) for readmission, and 0.92 (0.85-0.99; p = 0.04) for the combined endpoint. We found a differentiated effect of hospitalisation (p < 0.05 for interaction; better post-discharge readmission and combined outcomes in G1), and a trend (p = 0.06) to lower mortality in G1 patients with EAA. Additionally, there were some differences between groups in baseline and acute episode characteristics. CONCLUSION: AHF triggered by infection is not associated with a higher mid-term mortality and has better post-discharge outcomes; however, the first 3 weeks are an extremely vulnerable period. Since hospitalisation could have a role in limiting adverse post-discharge events, and EAA in reducing mortality, these relationships should be prospectively explored in further studies.


Assuntos
Antibacterianos/administração & dosagem , Insuficiência Cardíaca/etiologia , Hospitalização/estatística & dados numéricos , Infecções/complicações , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Infecções/tratamento farmacológico , Masculino , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Sistema de Registros , Fatores de Tempo
10.
JACC Heart Fail ; 7(10): 834-845, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31521676

RESUMO

OBJECTIVES: This study investigated whether systemic corticosteroids (new onset) administered to patients with acute heart failure (AHF) have any association with outcomes, with differentiated analyses for patients with and without chronic obstructive pulmonary disease (COPD) as a comorbidity. BACKGROUND: Patients with undiagnosed dyspnea frequently receive corticosteroids in emergency departments while determining a final diagnosis, but their effect on the outcomes of patients with AHF without overt COPD exacerbation is unknown. METHODS: We selected patients with AHF from the EAHFE (Epidemiology of Acute Heart Failure in the Emergency Departments) registry, recording key data (new-onset corticosteroid therapy, COPD condition). Patients with and without COPD were analyzed separately. We calculated unadjusted and adjusted ratios for corticosteroid-treated compared with corticosteroid-untreated patients for 2 coprimary endpoints: 90-day all-cause mortality (from index episode) and 90-day post-discharge combined endpoint (all-cause mortality or readmission for AHF), with intermediate time-point estimations. Other secondary endpoints were calculated, and some sensitive and stratified analyses were performed. RESULTS: We analyzed 11,356 patients: 8,635 without COPD (841 corticosteroid-treated, 9.7%) and 2,721 with COPD (753 corticosteroid-treated, 27.7%). There were several differences between treated and untreated patients, essentially because corticosteroid-treated patients were sicker. Although unadjusted outcomes were worse in corticosteroid-treated patients, especially in patients without COPD, these differences disappeared after adjustment: hazard ratios for 90-day mortality (without/with COPD) were 0.91 (95% confidence interval (CI): 0.76 to 1.10)/0.99 (95% CI: 0.78 to 1.26), and 1.09 (95% CI: 0.93 to 1.28)/1.02 (95% CI: 0.86 to 1.21) for the post-discharge combined endpoint. Analyses of intermediate time-point coprimary endpoints and secondary outcomes rendered similar estimations. Sensitivity and stratified analysis did not significantly modify these results. CONCLUSIONS: There is no evidence of harm related to the new onset of systemic corticosteroid therapy during an episode of AHF, either in patients with or without concomitant COPD.


Assuntos
Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Dispneia/terapia , Insuficiência Cardíaca/tratamento farmacológico , Mortalidade Hospitalar , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Diuréticos/uso terapêutico , Dispneia/etiologia , Intervenção Médica Precoce , Serviço Hospitalar de Emergência , Feminino , Insuficiência Cardíaca/complicações , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Mortalidade , Readmissão do Paciente , Prognóstico , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações
11.
Eur J Cardiothorac Surg ; 55(6): 1160-1167, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608571

RESUMO

OBJECTIVES: The decision about whether to use a biological or a mechanical prosthesis for aortic valve replacement remains controversial in patients between 50 and 65 years of age and has yet to be addressed in a Mediterranean population. This research aimed to analyse long-term survival and major morbidity rates (30-day mortality, stroke, any prosthetic reoperation and major bleeding) within this population. METHODS: Our multicentre observational retrospective study included all subjects aged 50-65 years who had a primary isolated aortic valve replacement due to severe aortic stenosis at 7 public hospitals from Andalusia (Spain) between 2000 and 2015. Concomitant surgery, reoperations and endocarditis were the exclusion criteria. A total of 1443 patients were enrolled in the study (272 with biological and 1171 with mechanical valves). Multivariate analyses including a 2:1 propensity score matching (506 mechanical and 257 biological prostheses) were conducted. RESULTS: Bioprostheses were implanted in 18.8% (n = 272): 35% were women; the mean EuroSCORE-I was 3%. The mean follow-up was 8.1 ± 4.9 years in a matched sample: 8.8 ± 4.9 years in those receiving a mechanical vs 7.1 ± 4.5 years in those receiving a biological prosthesis (P = 0.001). In the paired sample, the 15-year survival rate was 73% in those who had a biological vs 76% in those who had a mechanical valve [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.54-1.20; P = 0.159]. No significant differences were observed in patients ≥55 years old (74% of 15-year survival in both groups: HR 0.88, 95% CI 0.56-1.34; P = 0.527). A higher rate of major bleeding was found in patients with a mechanical prosthesis (P = 0.004), whereas reoperation was more frequent among those with a biological prosthesis (P = 0.01). CONCLUSIONS: Long-term survival was comparable in patients above 55 years of age. Mechanical prostheses were associated with more major bleeding and bioprostheses, with more reoperations. A bioprosthesis in patients above 55 years old is a reasonable choice. CLINICAL TRIAL REGISTRATION NUMBER: NCT03239509.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida/tendências
12.
Arch Cardiovasc Dis ; 112(2): 135-143, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30181052

RESUMO

Left superior vena cava draining into the left atrium in the absence of coronary sinus is an anomaly that can appear in heterotaxy syndrome and unroofed coronary sinus syndrome. Regardless of the origin of these syndromes, biventricular repair can be done through rerouting by intracardiac procedures or through disconnection-reconnection of the left superior vena cava to the right atrium or right superior vena cava by extracardiac procedures. Different techniques can be used for this purpose, each of which has its own advantages and limitations. Therefore, appropriate selection is necessary to obtain the best results for each patient, and many factors, such as patient anatomy, age, associated cardiomyopathies, etc., have to be considered. In this review, we focus on heterotaxy and unroofed coronary sinus syndromes, associated cardiomyopathies, the state-of-the-art in their surgical treatment and our results in a sample of 10 patients. Our experience highlights the importance of accurate diagnosis and specific selection of surgical technique for the management of biventricular repair in patients with left superior vena cava draining into the left atrium in the absence of coronary sinus.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Átrios do Coração/cirurgia , Síndrome de Heterotaxia/cirurgia , Veia Cava Superior/cirurgia , Adolescente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Pré-Escolar , Angiografia Coronária , Seio Coronário/anormalidades , Ecocardiografia Doppler em Cores , Feminino , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Síndrome de Heterotaxia/diagnóstico por imagem , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagem
13.
ACS Omega ; 3(9): 11455-11468, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30320262

RESUMO

Saponins are potential wide-spectrum antitumor drugs, and copper(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition is a suitable approach to synthesizing saponin-like compounds by regioselective glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies on the T-84 human colon carcinoma cell line support the role of the hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky nature of the substituents in C28. OA bearing a α-d-mannose moiety at C28 (compound 18) focused our interest because the estimated inhibitory concentration 50 was similar to that reported for ginsenoside Rh2 against colon cancer cells and it inhibits the G1-S phase transition affecting the cell viability and apoptosis. Considering that triterpenoids from natural sources have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling, docking studies were conducted to evaluate whether NF-κB may be a potential target. Results are consistent with the biological study and predict a similar binding mode of MA and compound 18 to the p52 subunit from NF-κB but not for OA. The fact that the binding site is shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one supports the result and points to NF-κB as a potential target of both MA and compound 18.

14.
Plant Methods ; 14: 34, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760765

RESUMO

BACKGROUND: Solanum lycopersicum, an economically important crop grown worldwide, has been used as a model for the study of arbuscular mycorrhizal (AM) symbiosis in non-legume plants for several years and several cDNA array hybridization studies have revealed specific transcriptomic profiles of mycorrhizal tomato roots. However, a method to easily screen candidate genes which could play an important role during tomato mycorrhization is required. RESULTS: We have developed an optimized procedure for composite tomato plant obtaining achieved through Agrobacterium rhizogenes-mediated transformation. This protocol involves the unusual in vitro culture of composite plants between two filter papers placed on the culture media. In addition, we show that DsRed is an appropriate molecular marker for the precise selection of cotransformed tomato hairy roots. S. lycopersicum composite plant hairy roots appear to be colonized by the AM fungus Rhizophagus irregularis in a manner similar to that of normal roots, and a modified construct useful for localizing the expression of promoters putatively associated with mycorrhization was developed and tested. CONCLUSIONS: In this study, we present an easy, fast and low-cost procedure to study AM symbiosis in tomato roots.

15.
J Gastroenterol Hepatol ; 33(4): 792-799, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29156509

RESUMO

Exosomes are extracellular microvesicles released from cells, which are involved in many biological and pathological processes, mainly because of their role in intercellular communication. Exosomes derived from colorectal cancer (CRC) cells are related to oncogenesis, tumor cell survival, chemo-resistance, and metastasis. The role of the exosomes in these processes involves the transfer of proteins, RNAs, or mutant versions of proto-oncogenes to the target cells. In recent years, great efforts have been made to identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis, and treatment response. This review focuses on recent studies on CRC exosomes, considering isolation, cargo, biomarkers, and the effects of exosomes on the development and progression of CRC, including resistance to antitumor therapy.


Assuntos
Neoplasias Colorretais/patologia , Exossomos/fisiologia , Biomarcadores Tumorais , Carcinogênese , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Mutação , Proteínas de Neoplasias/metabolismo , Prognóstico , Transporte Proteico , Proto-Oncogenes/genética , RNA Neoplásico/metabolismo
16.
Front Plant Sci ; 7: 1273, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27602046

RESUMO

Plant hormones have become appropriate candidates for driving functional plant mycorrhization programs, including the processes that regulate the formation of arbuscules in arbuscular mycorrhizal (AM) symbiosis. Here, we examine the role played by ABA/GA interactions regulating the formation of AM in tomato. We report differences in ABA and GA metabolism between control and mycorrhizal roots. Active synthesis and catabolism of ABA occur in AM roots. GAs level increases as a consequence of a symbiosis-induced mechanism that requires functional arbuscules which in turn is dependent on a functional ABA pathway. A negative interaction in their metabolism has been demonstrated. ABA attenuates GA-biosynthetic and increases GA-catabolic gene expression leading to a reduction in bioactive GAs. Vice versa, GA activated ABA catabolism mainly in mycorrhizal roots. The negative impact of GA3 on arbuscule abundance in wild-type plants is partially offset by treatment with ABA and the application of a GA biosynthesis inhibitor rescued the arbuscule abundance in the ABA-deficient sitiens mutant. These findings, coupled with the evidence that ABA application leads to reduce bioactive GA1, support the hypothesis that ABA could act modifying bioactive GA level to regulate AM. Taken together, our results suggest that these hormones perform essential functions and antagonize each other by oppositely regulating AM formation in tomato roots.

17.
Med. clín (Ed. impr.) ; 146(10): 436-439, mayo 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-151749

RESUMO

Fundamento y objetivo: Evaluar si una intervención educativa en mujeres perimenopáusicas con hipertensión, diabetes mellitus y/o dislipidemia sería capaz de mejorar la adherencia a un patrón de dieta mediterráneo y conseguir cambios en parámetros antropométricos. Pacientes: Ensayo clínico aleatorizado de grupos paralelos: 320 mujeres (45-60 años) de 2 servicios de atención primaria urbanos. Variables a estudio: perímetro abdominal y de cadera, índice de masa corporal (IMC), grasa corporal total, visceral y de tronco (medidas con bioimpedancia) y adherencia a dieta mediterránea (cuestionario MEDAS-14). Grupo intervención: 3 talleres interactivos sobre prevención de enfermedad cardiovascular, y grupo control: información por correo. Resultados: Concluyeron el estudio 230 mujeres (113 en el grupo control y 117 en el grupo intervención). Un año después, las diferencias entre grupos fueron significativas en todos los parámetros. En la comparación intragrupos, las mujeres del grupo intervención mantuvieron el IMC y mejoraron la adherencia a la dieta mediterránea. El grupo control aumentó el IMC, el perímetro abdominal y de cadera y los parámetros de grasa (corporal total, visceral y tronco). Conclusiones: Una sencilla intervención educativa en mujeres perimenopáusicas con riesgo cardiovascular puede mejorar sus hábitos saludables (AU)


Background and objective: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. Patients: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. Variables studied: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. Results: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). Conclusions: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Educação em Saúde/métodos , Educação em Saúde/tendências , Educação em Saúde , Mulheres/educação , Menopausa/metabolismo , Menopausa/fisiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea , Antropometria/instrumentação , Antropometria/métodos , Adesão à Medicação , Comportamento Alimentar/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Med Clin (Barc) ; 146(10): 436-9, 2016 May 20.
Artigo em Espanhol | MEDLINE | ID: mdl-26897504

RESUMO

BACKGROUND AND OBJECTIVE: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. PATIENTS: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. VARIABLES STUDIED: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. RESULTS: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). CONCLUSIONS: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Promoção da Saúde/métodos , Educação de Pacientes como Assunto/métodos , Pesos e Medidas Corporais , Doenças Cardiovasculares/etiologia , Complicações do Diabetes/etiologia , Complicações do Diabetes/prevenção & controle , Dislipidemias/complicações , Feminino , Humanos , Hipertensão/complicações , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento
19.
New Phytol ; 205(4): 1431-1436, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25580981

RESUMO

For survival, plants have to efficiently adjust their phenotype to environmental challenges, finely coordinating their responses to balance growth and defence. Such phenotypic plasticity can be modulated by their associated microbiota. The widespread mycorrhizal symbioses modify plant responses to external stimuli, generally improving the resilience of the symbiotic system to environmental stresses. Phytohormones, central regulators of plant development and immunity, are instrumental in orchestrating plant responses to the fluctuating environment, but also in the regulation of mycorrhizal symbioses. Exciting advances in the molecular regulation of phytohormone signalling are providing mechanistic insights into how plants coordinate their responses to environmental cues and mycorrhizal functioning. Here, we summarize how these mechanisms permit the fine-tuning of the symbiosis according to the ever-changing environment.


Assuntos
Meio Ambiente , Micorrizas/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Simbiose/fisiologia , Homeostase/efeitos dos fármacos , Micorrizas/efeitos dos fármacos , Desenvolvimento Vegetal/efeitos dos fármacos , Simbiose/efeitos dos fármacos
20.
Interact Cardiovasc Thorac Surg ; 20(3): 338-44, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25452556

RESUMO

OBJECTIVES: Acute kidney injury (AKI) after cardiac surgery is associated with adverse patient outcome. A new definition and staging system for AKI based on creatinine kinetics (CKs) has been proposed recently. Their proponents hypothesize that early absolute increases in serum creatinine (sCr) after kidney injury are superior to percentage increases, especially in patients with chronic kidney disease (CKD). The aims of our study were to measure agreement between CK definition and the current consensus definition [risk, injury, failure, loss and end-stage renal disease (RIFLE) system], and to compare time to diagnosis and prognostic value between both systems. METHODS: Retrospective cohort study. Agreement on AKI diagnosis by both classifications, time to diagnosis and prognostic value of both systems were compared in cardiac surgeries performed during a 6-year period (2002-2007) in a single centre. RESULTS: We found substantial agreement between both classifications (0.67). More patients were diagnosed with AKI by the CK definition than by RIFLE criteria both globally (28.2 vs 13.9%) and in every category (16.5 vs 8.4% for CK-1 vs RIFLE-R; 8.4 vs 3.6% for CK-2 vs RIFLE-I and 3.2 vs 2.0% for CK-3 vs RIFLE-F). Time to diagnosis was shorter for the CK definition (1.8 vs 2.5 days). Prognostic value in terms of information about in-hospital death and need for renal replacement was comparable between classifications. CONCLUSIONS: In cardiac surgery, the CK definition and classification system showed substantial agreement with the current standard, was more sensitive than RIFLE and detected AKI earlier without loss of prognostic information.


Assuntos
Injúria Renal Aguda/classificação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina/sangue , Complicações Pós-Operatórias , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
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