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1.
Int J Gynecol Pathol ; 42(3): 270-277, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36508680

RESUMEN

Villoglandular adenocarcinoma of the cervix is a rare histologic entity that typically develops in young women, characterized by an association with oral contraceptives and excellent prognosis, though this point is controversial. These tumors have not been studied in the context of the International Endocervical Adenocarcinoma Criteria and Classification (IECC) or Silva Pattern Classification. We analyzed 31 cases that met strict diagnostic criteria, including being completely excised with negative margins. These were categorized according to IECC and Silva Pattern Classification and the association with various pathologic parameters analyzed. Most patients were young with a mean age of 41.1 (range 25-79). There were 14 (45.2%) pattern A, 11 (35.5%) pattern B, and 6 (19.3%) pattern C cases. Only 1 of 22 patients (4.5%) presented with lymph node metastasis at the time of diagnosis (pattern C, stage IB1) and 3 (9.7%) had lymphovascular invasion (2 pattern C, 1 pattern B). Overall survival was 100%, while recurrence-free survival was 96.2% for the entire cohort with only 1 case (3.2%) recurring 25 mo after surgery (IB2, pattern B). Kaplan Meier analysis (log rank test) revealed no significant correlation for recurrence-free survival at 5 and 10 yr associated with depth of invasion, tumor size, Silva pattern, FIGO stage, lymphovascular invasion, or lymph node metastasis. Cox univariate analysis demonstrated no independent prognostic factors predicting recurrence-free survival. These results indicate that completely excised villoglandular adenocarcinoma generally has an excellent prognosis and when Silva Pattern Classification is applied, those tumors that potentially have a higher chance for adverse outcomes can be identified.


Asunto(s)
Adenocarcinoma , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Infecciones por Papillomavirus/patología , Metástasis Linfática/patología , Cuello del Útero/patología , Pronóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía
2.
J Paediatr Child Health ; 57(5): 653-658, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33301212

RESUMEN

AIM: To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment. METHODS: Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019. RESULTS: We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5). CONCLUSIONS: In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case.


Asunto(s)
Infecciones por Bartonella , Bartonella henselae , Osteomielitis , Adolescente , Animales , Infecciones por Bartonella/diagnóstico , Infecciones por Bartonella/tratamiento farmacológico , Infecciones por Bartonella/epidemiología , Gatos , Niño , Humanos , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/epidemiología , Estudios Retrospectivos
4.
Gastric Cancer ; 19(2): 651-659, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25995035

RESUMEN

BACKGROUND: The T-box transcription factor Brachyury was recently reported to be upregulated and associated with prognosis in solid tumors. Here, we proposed to evaluate the potential use of Brachyury protein expression as a new prognostic biomarker in gastrointestinal stromal tumors (GIST). METHODS: Brachyury protein expression was analyzed by immunohistochemistry in a cohort of 63 bona fide GIST patients. Brachyury expression profiles were correlated with patients' clinicopathological features and prognostic impact. Additionally, an in silico analysis was performed using the Oncomine database to assess Brachyury alterations at DNA and mRNA levels in GISTs. RESULTS: We found that Brachyury was overexpressed in the majority (81.0 %) of primary GISTs. We observed Brachyury staining in the nucleus alone in 4.8 % of cases, 23.8 % depicted only cytoplasm staining, and 52.4 % of cases exhibited both nucleus and cytoplasm immunostaining. The presence of Brachyury was associated with aggressive GIST clinicopathological features. Particularly, Brachyury nuclear (with or without cytoplasm) staining was associated with the presence of metastasis, while cytoplasm sublocalization alone was correlated with poor patient survival. CONCLUSIONS: Herein, we demonstrate that Brachyury is overexpressed in GISTs and is associated with worse outcome, constituting a novel prognostic biomarker and a putative target for GIST treatment.


Asunto(s)
Proteínas Fetales/metabolismo , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Proteínas de Dominio T Box/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Femenino , Tumores del Estroma Gastrointestinal/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Análisis por Matrices de Proteínas
5.
Phys Chem Chem Phys ; 17(18): 12340-9, 2015 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-25898008

RESUMEN

The influence of temperature (20-40 °C) on the acetaminophen adsorption onto activated carbons with different textures was studied. Different temperature dependences, not explained by kinetic effects, were observed for carbons with different micropore size distribution patterns: adsorption capacity increased for pine gasification residues (Pi-fa) derived carbons and decreased for sisal based materials. No significant variation was seen for carbon CP. The species identified by (1)H NMR spectroscopy on the back-extraction solution proved that during the adsorption process exist the conditions required to promote the formation of acetaminophen oligomers which have constrained access to the narrow microporosity. The rotation energy of the dihedral angle between monomers (estimated by electronic DFT methods) showed that conformations in the planar form are less stable than the non-planar conformation (energy barrier of 70 and 23 kJ mol(-1)), but have critical dimensions similar to the monomer and can access most of the micropore volume. The enthalpy change of the overall process showed that the energy gain of the system (endothermic) for Pi-fa samples (≈40 kJ mol(-1)) was enough to allow a change in the dimer, or even a larger oligomer, conformation to the planar form. This will permit adsorption in the narrow micropores, thus explaining the uptake increase with temperature. Non-continuous micropore size distributions centered at pore widths close to the critical dimensions of the planar form seem to be crucial for a positive evolution of the adsorption capacity with temperature.


Asunto(s)
Acetaminofén/aislamiento & purificación , Carbón Orgánico/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Modelos Moleculares , Porosidad , Propiedades de Superficie , Temperatura , Termodinámica , Eliminación de Residuos Líquidos/métodos
6.
Molecules ; 19(1): 550-67, 2014 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-24394438

RESUMEN

The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II) and Ni(II) complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II) complex are consistent with a distorted square pyramidal geometry.


Asunto(s)
Compuestos Aza/química , Compuestos Macrocíclicos/química , Compuestos Aza/síntesis química , Compuestos Aza/farmacología , Quelantes/química , Quelantes/farmacología , Estabilidad de Medicamentos , Compuestos Macrocíclicos/síntesis química , Compuestos Macrocíclicos/farmacología , Metales/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Termodinámica
7.
J Med Chem ; 67(8): 6081-6098, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38401050

RESUMEN

In this work, we investigated the anticancer activity of several novel silver(I) 2,2'-bipyridine complexes containing either triphenylphosphane (PPh3) or 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All compounds were characterized by diverse analytical methods including ESI-MS spectrometry; NMR, UV-vis, and FTIR spectroscopies; and elemental analysis. Moreover, several compounds were also studied by X-ray single-crystal diffraction. Subsequently, the compounds were investigated for their anticancer activity against drug-resistant and -sensitive cancer cells. Noteworthily, neither carboplatin and oxaliplatin resistance nor p53 deletion impacted on their anticancer efficacy. MES-OV cells displayed exceptional hypersensitivity to the dppe-containing drugs. This effect was not based on thioredoxin reductase inhibition, enhanced drug uptake, or apoptosis induction. In contrast, dppe silver drugs induced paraptosis, a novel recently described form of programmed cell death. Together with the good tumor specificity of this compound's class, this work suggests that dppe-containing silver complexes could be interesting drug candidates for the treatment of resistant ovarian cancer.


Asunto(s)
2,2'-Dipiridil , Antineoplásicos , Fosfinas , Plata , Humanos , Fosfinas/química , Fosfinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Plata/química , Plata/farmacología , 2,2'-Dipiridil/química , 2,2'-Dipiridil/farmacología , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Cristalografía por Rayos X , Ligandos , Muerte Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Resistencia a Antineoplásicos/efectos de los fármacos
8.
ChemMedChem ; 18(14): e202300074, 2023 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-37098105

RESUMEN

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4 ], in which PP is a phosphane ligand (triphenylphosphane or 1,2-bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4-(methyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti-trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.


Asunto(s)
Antiinfecciosos , Antineoplásicos , Enfermedad de Chagas , Complejos de Coordinación , Neoplasias Ováricas , Tiosemicarbazonas , Femenino , Masculino , Humanos , Cobre/química , Línea Celular Tumoral , Antiparasitarios/farmacología , Apoptosis , Tiosemicarbazonas/farmacología , Tiosemicarbazonas/química , Ligandos , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química
9.
Rev Port Cardiol ; 31(7-8): 517-20, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22704822

RESUMEN

Fulminant myocarditis associated with influenza A virus is exceedingly rare, with only a few cases reported in the literature. We describe a previously healthy 10-year-old boy, with a three-day history of flu-like symptoms without antiviral treatment. He was hospitalized with dehydration and hypothermia in the context of persistent vomiting, when he suddenly developed heart failure secondary to fulminant myocarditis. Despite aggressive management, including circulatory support and cardiopulmonary resuscitation measures, the patient died of cardiogenic shock. The postmortem histopathology was compatible with a multisystem viral infection with myocarditis and pulmonary involvement, and H1N1v polymerase chain reaction was positive. The prevalence of influenza-associated fulminant myocarditis remains unknown. Findings reported in the literature raise the possibility that the novel H1N1 influenza A virus is more commonly associated with a severe form of myocarditis than previously encountered influenza strains.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Miocarditis/virología , Niño , Resultado Fatal , Humanos , Gripe Humana/epidemiología , Masculino , Pandemias
10.
Clin Cancer Res ; 28(6): 1203-1216, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-34980600

RESUMEN

PURPOSE: Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance. EXPERIMENTAL DESIGN: We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab. RESULTS: In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanistically, PLCγ1 expression was found to bypass cetuximab-dependent EGFR inhibition by activating ERK and AKT pathways. This novel resistance mechanism involves a noncatalytic role of PLCγ1 SH2 tandem domains in the propagation of downstream signaling via SH2-containing protein tyrosine phosphatase 2 (SHP2). Accordingly, SHP2 inhibition sensitizes PLCγ1-resistant cells to cetuximab. CONCLUSIONS: Our discoveries reveal the potential of PLCγ1 as a predictive biomarker for cetuximab responses and suggest an alternative therapeutic approach to circumvent PLCγ1-mediated resistance to cetuximab in patients with RAS WT mCRC. In this way, this work contributes to the development of novel strategies in the medical management and treatment of patients with mCRC.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Neoplasias del Recto , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/farmacología , Cetuximab/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Receptores ErbB/genética , Humanos , Mutación , Fosfolipasa C gamma/genética , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias del Recto/tratamiento farmacológico , Estudios Retrospectivos , Pez Cebra
11.
Dalton Trans ; 49(35): 12273-12286, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32839796

RESUMEN

A new family of eighteen Cu(i) complexes of the general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this series were also characterized by single crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated in breast (MCF7) and prostate (LNCap) human cancer cells and in a normal prostate cell line (RWPE). In general, all compounds showed higher cytotoxicity for the prostate cancer cells than for the breast cells, with IC50 values in the range 0.2-2 µM after 24 h of treatment. The most cytotoxic compound, [Cu(dppe)(2-ap)][BF4] (16), where dppe = 1,2-bis(diphenylphosphano) ethane and 2-ap = 2-acetylpyridine, showed a high level of cellular internalization, generation of intracellular ROS and activation of the cell death mechanism via apoptosis/necrosis. Owing to its high cytotoxic activity for LNCap cells, being 70-fold higher than that for normal prostate cells (RWPE), complex (16) was found to be the most promising for further research in prostate cancer models.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cobre/química , Neoplasias de la Próstata/patología , Apoptosis/efectos de los fármacos , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Células MCF-7 , Masculino , Especies Reactivas de Oxígeno/metabolismo
12.
Sci Rep ; 9(1): 6, 2019 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-30626918

RESUMEN

We evaluated the impact of continued 13-valent pneumococcal conjugate vaccine (PCV13) use in the private market (uptake of 61%) in pediatric invasive pneumococcal disease (pIPD) in Portugal (2012-2015). The most frequently detected serotypes were: 3 (n = 32, 13.8%), 14 (n = 23, 9.9%), 1 (n = 23, 9.9%), 7F (n = 15, 6.4%), 19A (n = 13, 5.6%), 6B and 15B/C (both n = 12, 5.2%), and 24F, 10A and 12B (all with n = 10, 4.3%). Taken together, non-PCV13 serotypes were responsible for 42.2% of pIPD with a known serotype. The use of PCR to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 18.1% (n = 47) of all pIPD. Serotype 3 was mostly detected by PCR (n = 21/32, 65.6%) and resulted from a relevant number of vaccine failures. The incidence of pIPD varied in the different age groups but without a clear trend. There were no obvious declines of the incidence of pIPD due to serotypes included in any of the PCVs, and PCV13 serotypes still accounted for the majority of pIPD (57.8%). Our study indicates that a higher vaccination uptake may be necessary to realize the full benefits of PCVs, even after 15 years of moderate use, and highlights the importance of using molecular methods in pIPD surveillance, since these can lead to substantially increased case ascertainment and identification of particular serotypes as causes of pIPD.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/clasificación , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Portugal/epidemiología , Serogrupo , Serotipificación/métodos , Vacunación , Vacunas Conjugadas/uso terapéutico
13.
Dalton Trans ; 47(23): 7819-7829, 2018 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-29850763

RESUMEN

A family of six phosphane Cu(i) complexes bearing N,N, N,O and N,S bidentate ligands was synthesized. All the compounds were fully characterized by classical analytical and spectroscopic methods, and five of them were also characterized by X-ray diffraction studies. All the compounds exhibit high cytotoxicity against the human breast cancer cell line MCF7 with IC50 values far lower than those found for cisplatin, a current chemotherapeutic in clinical use. Compounds 1[combining low line] and 3[combining low line] induce cell cycle arrest in the G2/M phase and cell death by apoptosis. The cytotoxic and cytostatic effects of these compounds on MCF7 cells suggest that they are suitable for further in vivo studies with breast cancer models.

14.
J Gastrointest Surg ; 11(7): 869-74, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17440788

RESUMEN

The molecular events responsible for the transdifferentiation of epithelial cells of the esophagus to a columnar cell type are not well understood. Cdx2 has been detected in Barrett's esophagus, so we sought evidence of Cdx2 expression during the process of transdifferentiation of the esophageal squamous epithelium into a glandular phenotype. Thirty-two rats underwent an esophago-jejunostomy to produce esophagitis of 20, 25, 30, or 35 weeks of duration. The spectrum of esophageal lesions induced by chronic reflux was examined for expression of Cdx2 and Muc2 by immunohistochemistry. Five animals developed glandular metaplasia and adenosquamous carcinoma, two developed only glandular metaplasia, and two had adenosquamous carcinoma alone. Nuclear Cdx2 expression was detected in 57% (four of seven) and 43% (three of seven) of foci of glandular metaplasia and adenosquamous carcinomas, respectively. Cdx2 staining was detectable in some squamous and some mucus secreting cells. Perinuclear and perivacuolar staining of Muc2 was detected focally in 71% (five of seven) and 57% (four of seven) of areas with glandular metaplasia and adenosquamous carcinoma, respectively. We show that duodenal-content reflux into the esophagus switches on the expression of Cdx2 protein in esophageal keratinocytic cells, promoting a mucinous transdifferentiation process with secretion of intestinal mucin Muc2.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Reflujo Duodenogástrico , Esófago/metabolismo , Proteínas de Homeodominio/biosíntesis , Mucinas/biosíntesis , Transactivadores/biosíntesis , Animales , Biomarcadores de Tumor/análisis , Factor de Transcripción CDX2 , Epitelio/metabolismo , Epitelio/patología , Esófago/patología , Proteínas de Homeodominio/análisis , Masculino , Mucina 2 , Mucinas/análisis , Ratas , Ratas Sprague-Dawley , Transactivadores/análisis
15.
J Inorg Biochem ; 169: 68-78, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28142080

RESUMEN

A new family of copper(I) complexes of general formula [Cu(dppe)(NN)]+ have been synthesized and fully characterized, with dppe=1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2'-bipy=2.2'-bipyridine (1), Me2bpy=4.4'-dimethyl-2,2'-bipyridine (2), dpytz=3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp=2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η5-C5H5)(PPh3)(dpp)]+ (5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(µ-dpp)Ru(η5-C5H5)(PPh3)]2+ (6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 with IC50 values far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC50 values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cobre/química , Rutenio/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Difracción de Rayos X
16.
Braz J Psychiatry ; 37(4): 310-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26692429

RESUMEN

OBJECTIVE: To translate, culturally adapt, and validate a Brazilian Portuguese version of the Yale-Brown Obsessive Compulsive Scale modified for Body Dysmorphic Disorder (BDD-YBOCS). METHODS: Ninety-three patients of both sexes seeking rhinoplasty were consecutively selected at the Plastic Surgery Outpatient Clinic of the Universidade Federal de São Paulo, Brazil, between May 2012 and March 2013. The BDD-YBOCS was translated into Brazilian Portuguese. Thirty patients participated in the cultural adaptation of the scale. The final version was tested for reliability in 20 patients, and for construct validity in 43 patients (correlation of the BDD-YBOCS with the Body Dysmorphic Disorder Examination [BDDE]). RESULTS: Total Cronbach's alpha was 0.918. The BDD-YBOCS had excellent inter-rater (intra-class correlation coefficient [ICC] = 0.934; p < 0.001) and intra-rater reliability (ICC = 0.999; p < 0.001). Significant differences in BDD-YBOCS scores were found between patients with and without BDD symptoms (p < 0.001), and among patients with different levels of BDD severity (p < 0.001). A strong correlation (r = 0.781; p < 0.001) was observed between the BDDE and the BDD-YBOCS. The area under the receiver operating characteristic curve was 0.851, suggesting a very good accuracy for discriminating between presence and absence of BDD symptoms. CONCLUSION: The Brazilian Portuguese version of the BDD-YBOCS is a reliable instrument, showing face, content and construct validity.


Asunto(s)
Trastorno Dismórfico Corporal/diagnóstico , Escalas de Valoración Psiquiátrica/normas , Traducciones , Adulto , Análisis de Varianza , Imagen Corporal , Brasil , Comparación Transcultural , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Trastorno Obsesivo Compulsivo/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto Joven
17.
Hum Mutat ; 24(4): 353-4, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15366000

RESUMEN

Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer. In contrast to the classic dominant condition of familial adenomatous polyposis (FAP) due to germinal mutations in the APC gene, the MYH polyposis is an autosomal recessive disease. The identification of individuals affected by MYH polyposis brings new and important implications for the diagnostic, screening, genetic counseling, follow up and therapeutic options in these patients. In this study, screening for germinal mutations in the MYH gene was performed in 53 Portuguese individuals with multiple colorectal adenomas or classic adenomatous polyposis, in whom no mutation had been identified in the APC gene. The results revealed the presence of biallelic germline MYH mutations in 21 patients. In addition, we here report 3 mutations (c.340T>C [p.Y114H]; c.503G>A [p.R168H]; and c.1186_1187insGG [p.E396fsX437]) which, to our knowledge, have not been previously described.


Asunto(s)
Adenoma/genética , Pólipos del Colon/genética , Neoplasias Colorrectales/genética , ADN Glicosilasas/genética , Mutación de Línea Germinal , Neoplasias Primarias Múltiples/genética , Síndromes Neoplásicos Hereditarios/genética , Adenoma/epidemiología , Adulto , Anciano , Alelos , Sustitución de Aminoácidos , Pólipos del Colon/epidemiología , Neoplasias Colorrectales/epidemiología , Análisis Mutacional de ADN , Reparación del ADN/genética , Femenino , Mutación del Sistema de Lectura , Frecuencia de los Genes , Genes Recesivos , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Neoplasias Primarias Múltiples/epidemiología , Síndromes Neoplásicos Hereditarios/epidemiología , Mutación Puntual , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Portugal/epidemiología
18.
Gene ; 542(2): 217-20, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24656624

RESUMEN

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM# 260920) is a rare recessively-inherited autoinflammatory condition caused by mutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Here we report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non-consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, whereas anakinra showed positive responses only at high doses. The p.R277G mutation here described is a novel missense MVK mutation, and it has been detected in this case with a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.


Asunto(s)
Fiebre/genética , Inmunoglobulina D/genética , Mutación Missense , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Reacción de Fase Aguda/genética , Preescolar , Fiebre/tratamiento farmacológico , Homocigoto , Humanos , Inmunoglobulina D/sangre , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Masculino , Deficiencia de Mevalonato Quinasa/sangre , Deficiencia de Mevalonato Quinasa/genética
19.
Vaccine ; 28(32): 5167-73, 2010 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-20558247

RESUMEN

We characterized 353 isolates responsible for pediatric invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes included in the seven-valent conjugate vaccine (PCV7) accounted for 17% of IPD. Serotypes 1, 7F and 19A were the most frequent causes of IPD and the later consolidated as the most frequent serotype among erythromycin and penicillin non-susceptible isolates. Serotype 1 was associated with older children and empyemas, while serotype 19A was associated with IPD in younger (<2 years) children. The higher valency vaccines PCV10 and PCV13 have a potentially superior coverage, 55% and 83% respectively, but non-vaccine serotypes are emerging as important causes of IPD. A decline of resistance with patient age was noted. Comparing with previous data from Portugal, this study showed a continued decline of PCV7 serotypes and that overall resistance has stabilized following the initial decline of the first post-PCV7 years.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/clasificación , Adolescente , Niño , Preescolar , Farmacorresistencia Bacteriana , Vacuna Neumocócica Conjugada Heptavalente , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Portugal/epidemiología , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Vacunas Conjugadas/administración & dosificación
20.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 37(4): 310-316, Oct.-Dec. 2015. tab, graf
Artículo en Inglés | LILACS | ID: lil-770000

RESUMEN

Objective: To translate, culturally adapt, and validate a Brazilian Portuguese version of the Yale-Brown Obsessive Compulsive Scale modified for Body Dysmorphic Disorder (BDD-YBOCS). Methods: Ninety-three patients of both sexes seeking rhinoplasty were consecutively selected at the Plastic Surgery Outpatient Clinic of the Universidade Federal de São Paulo, Brazil, between May 2012 and March 2013. The BDD-YBOCS was translated into Brazilian Portuguese. Thirty patients participated in the cultural adaptation of the scale. The final version was tested for reliability in 20 patients, and for construct validity in 43 patients (correlation of the BDD-YBOCS with the Body Dysmorphic Disorder Examination [BDDE]). Results: Total Cronbach’s alpha was 0.918. The BDD-YBOCS had excellent inter-rater (intra-class correlation coefficient [ICC] = 0.934; p < 0.001) and intra-rater reliability (ICC = 0.999; p < 0.001). Significant differences in BDD-YBOCS scores were found between patients with and without BDD symptoms (p < 0.001), and among patients with different levels of BDD severity (p < 0.001). A strong correlation (r = 0.781; p < 0.001) was observed between the BDDE and the BDD-YBOCS. The area under the receiver operating characteristic curve was 0.851, suggesting a very good accuracy for discriminating between presence and absence of BDD symptoms. Conclusion: The Brazilian Portuguese version of the BDD-YBOCS is a reliable instrument, showing face, content and construct validity.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Trastorno Dismórfico Corporal/diagnóstico , Escalas de Valoración Psiquiátrica/normas , Traducciones , Análisis de Varianza , Imagen Corporal , Brasil , Comparación Transcultural , Variaciones Dependientes del Observador , Trastorno Obsesivo Compulsivo/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
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