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The degradation of mesoporous silica nanoparticles (MSNs) in the biological milieu due to silica hydrolysis plays a fundamental role for the delivery of encapsulated drugs and therapeutics. However, little is known on the evolution of the pore arrangement in the MSNs in biologically relevant conditions. Small Angle X-ray scattering (SAXS) studies were performed on unmodified and PEGylated MSNs with a MCM-48 pore structure and average sizes of 140 nm, exposed to simulated body fluid solution (SBF) at pH 7.4 for different time intervals from 30 min to 24 h. Experiments were performed with silica concentrations below, at and over 0.14 mg/mL, the saturation concentration of silica in water at physiological temperature. At silica concentrations of 1 mg/mL (oversaturation), unmodified MSNs show variation in interpore distances over 6 h exposure to SBF, remaining constant thereafter. A decrease in radius of gyration is observed over the same time. Mesoporosity and radius of gyration of unmodified MSNs remain then unchanged up to 24 h. PEGylated MSNs at 1 mg/mL concentration show a broader diffraction peak but no change in the position of the peak is observed following 24 h exposure to SBF. PEGylated MSNs at 0.01 mg/mL show no diffraction peaks already after 30 min exposure to SBF, while at 0.14 mg/mL a small diffraction peak is present after 30 min exposure but disappears after 1 h.
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BACKGROUND: Tamoxifen (Tam) is the most frequent treatment for estrogen receptor (ER) positive breast cancer. We recently showed that fibronectin (FN) leads to Tam resistance and selection of breast cancer stem cells. With the aim of developing a nanoformulation that would simultaneously tackle ER and FN/ß1 integrin interactions, we designed polyethylene glycol-polycaprolactone polymersomes polymersomes (PS) that carry Tam and are functionalized with the tumor-penetrating iRGD peptide (iRGD-PS-Tam). RESULTS: Polyethylene glycol-polycaprolactone PS were assembled and loaded with Tam using the hydration film method. The loading of encapsulated Tam, measured by UPLC, was 2.4 ± 0.5 mol Tam/mol polymer. Physicochemical characterization of the PS demonstrated that iRGD functionalization had no effect on morphology, and a minimal effect on the PS size and polydispersity (176 nm and Pdi 0.37 for iRGD-TAM-PS and 171 nm and Pdi 0.36 for TAM-PS). iRGD-PS-Tam were taken up by ER+ breast carcinoma cells in 2D-culture and exhibited increased penetration of 3D-spheroids. Treatment with iRGD-PS-Tam inhibited proliferation and sensitized cells cultured on FN to Tam. Mechanistically, treatment with iRGD-PS-Tam resulted in inhibition ER transcriptional activity as evaluated by a luciferase reporter assay. iRGD-PS-Tam reduced the number of cells with self-renewing capacity, a characteristic of breast cancer stem cells. In vivo, systemic iRGD-PS-Tam showed selective accumulation at the tumor site. CONCLUSIONS: Our study suggests iRGD-guided delivery of PS-Tam as a potential novel therapeutic strategy for the management of breast tumors that express high levels of FN. Future studies in pre-clinical in vivo models are warranted.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Oligopeptídeos/química , Receptores de Estrogênio/metabolismo , Tamoxifeno/administração & dosagem , Animais , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Autorrenovação Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos Nus , Poliésteres/química , Polietilenoglicóis/química , Tamoxifeno/farmacocinética , Tamoxifeno/farmacologia , Ativação Transcricional/efeitos dos fármacosRESUMO
The interaction of polyamine poly(allylamine hydrochloride) with Na3PO4, Na4P2O7, Na5P3O10, Na6P6O18, and (NaPO3)26 salts and the formation of polyamine phosphate nanoparticles (PANs) are studied here. Dynamic light scattering, isothermal titration calorimetry (ITC), electrophoretical mobility measurements, atomic force microscopy, and transmission electron microscopy are used to explore the formation, stability, and pH sensitivity of PANs. An optimal concentration for PAN formation is found for each phosphate salt in terms of the most stable size and lowest polydispersity index of the nanoparticles. The minimal concentration of phosphate ions for PAN formation decreases with the increasing number of phosphate groups per phosphate salt. ITC measurements show that all polyphosphates display a characteristic endothermic peak, which is not present when monophosphates are used for PAN formation. pH stability of PANs depends on the type of phosphate salt. PANs formed with small phosphates show a small window of stability with pH from 8 to 9, while those formed with long phosphates are stable in more acidic pH environments. Our findings open multiple possibilities for fine-tuning the pH sensitivity of PANs by varying phosphate salts for potential applications in drug delivery.
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BACKGROUND: Concomitant cholelithiasis and choledocholithiasis is a disease where incidence increases with age and can have serious complications such as pancreatitis, cholangitis and liver abscesses, but its management is controversial, because there are minimally invasive laparoscopic and endoscopic surgical procedures. OBJECTIVE: To compare the efficiency in the management of cholelithiasis and choledocholithiasis with laparoscopic cholecystectomy with common bile duct exploration vs cholangiopancreatography endoscopic retrograde+laparoscopic cholecystectomy. MATERIAL AND METHOD: Retrospective analysis of a five year observational, cross sectional multicenter study of patients with cholelithiasis and concomitant high risk of choledocholithiasis who were divided into two groups and the efficiency of both procedures was compared. Group 1 underwent laparoscopic cholecystectomy with common bile duct exploration and group 2 underwent cholangiopancreatography endoscopic retrograde+laparoscopic cholecystectomy. RESULTS: 40 patients, 20 were included in each group, we found p=0.10 in terms of operating time; when we compared hospital days we found p=0.63; the success of stone extraction by study group we obtained was p=0.15; the complications presented by group was p=0.1 and the number of hospitalizations by group was p ≤ 0.05 demonstrating statistical significance. CONCLUSIONS: Both approaches have the same efficiency in the management of cholelithiasis and choledocholithiasis in terms of operating time, success in extracting stone, days of hospitalization, postoperative complications and conversion to open surgery. However the laparoscopic approach is favourable because it reduces the number of surgical anaesthetic events and the number of hospital admissions.
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Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia Laparoscópica , Coledocolitíase/cirurgia , Colelitíase/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
El propósito de este trabajo es realizar una revisión bibliográfica acerca de los conocimientos, las actitudesy las prácticas en salud bucal (CAPSB), tres componentes culturales que influyen en la incidencia de afecciones de la cavidad oral. La cultura y sus componentes han pasado por tres fases en su conceptualización: la concreta, la abstracta y la simbólica; esta última es la que se encuentra vigente y sobre la cual otras áreas del conocimiento han trabajado, entre ellas, las ciencias de la salud. La cultura es aprendida, estandarizada y compartida. Los componentes culturales son transmitidos mediante los procesos de socialización (primaria y secundaria) que determinan la manera en la que la salud, y por lo tanto el proceso salud-enfermedad, son comprendidos por los individuos. Los conocimientos son resultado deprocesos sociales y cognitivos que están determinados por las características aceptadas y representativas del grupo social en el que se desarrollan, son la parte cognitiva de la cultura. La concepción que cada ser humano tenga acerca de la salud bucal determinará su actitud. La actitud representa una forma de ser, una posición, inclinación o tendencia, es la variable intermedia entre una situación y la manera encómo se responde a ella. Las prácticas ante el proceso salud-enfermedad son acciones observables en los individuos y están presentes en los niveles individual, familiar y comunitario e impactan en la saludgeneral de las poblaciones. Este trabajo es una aproximación al tema, haciendo un acercamiento al casode la población mexicana.
The aim of this work is to review the literature about the knowledge, attitudes and practices (KAP) about oral health, the three cultural components influencing the incidence of diseases at the oral cavity. The concept of culture and its components has undergone three phases: the concrete phase, the abstract phase and the symbolic phase; the latter is the current one, and the one over which other areas of knowledge have worked, including the health sciences. Culture can be learned, standardized and sha-red. Cultural components are transmitted through the processes of socialization (primary and secondary socialization) and they help determine the way in which health, and therefore the health-disease pro-cess, is understood by individuals. Knowledge is the result of social and cognitive processes determined by the characteristics accepted by and representative of the social group where they develop; they are the cognitive part of culture. The notion that every human being has about oral health will determine his/her attitude towards it. Attitude shows a way of being, a position, an inclination or tendency, it is a variable between situations and how people respond to them. Practices to face the health-disease process are actions that can be observed in individuals. They are present at the individual, family and community levels, and they impact on the overall health of the population. This work is an approach to the theme, while we discuss the Mexican population case.
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Humanos , Características Culturais , Saúde Bucal/educação , Condições Sociais , Literatura de Revisão como Assunto , MéxicoRESUMO
The purpose of this study is to review the prevalence of different uterine defects associated with infertility, recurrent pregnancy loss, and preterm pregnancies. Various infertility etiologies are analyzed, mainly that of uterine basis (adhesions, septa, myomas, polyps, pelvic inflammations or infection, and endometriosis). Importance of surgical techniques with minimal invasion is studied, basically hysteroscopy as a diagnosis and therapeutic method, which is compared with the rest of techniques.
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Histeroscopia , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/terapia , Feminino , Humanos , Infertilidade Feminina/etiologiaRESUMO
La interrupción de la vena cava inferior (VCI), con continuación con el sistema ácigos-hemiácigos, es una entidad poco común, con una incidencia de presentación del 0,6 por ciento. La más frecuente es la ausencia del segmento suprarrenal, que constituye el 90 por ciento de estas anomalías y sólo un 6 por ciento compromete el segmento renal e infrarrenal. Esta entidad puede asociarse a poliesplenia o asplenia y a situs inversus, aunque también puede presentarse aisladamente. Presentamos un paciente de sexo masculino, de 51 años, que presenta interrupción del segmento intrahepático de la VCI, con continuación de las venas ácigos y hemiácigos asociada a poliesplenia
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Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Veia Cava Inferior/anormalidades , Espectroscopia de Ressonância Magnética , Veia Ázigos/anormalidades , Veia Ázigos , Veia Cava Inferior , Veia Cava Inferior , Trombose Venosa/complicações , Trombose Venosa/etiologiaRESUMO
La interrupción de la vena cava inferior (VCI), con continuación con el sistema ácigos-hemiácigos, es una entidad poco común, con una incidencia de presentación del 0,6 por ciento. La más frecuente es la ausencia del segmento suprarrenal, que constituye el 90 por ciento de estas anomalías y sólo un 6 por ciento compromete el segmento renal e infrarrenal. Esta entidad puede asociarse a poliesplenia o asplenia y a situs inversus, aunque también puede presentarse aisladamente. Presentamos un paciente de sexo masculino, de 51 años, que presenta interrupción del segmento intrahepático de la VCI, con continuación de las venas ácigos y hemiácigos asociada a poliesplenia (AU)
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Humanos , Masculino , Pessoa de Meia-Idade , Veia Cava Inferior/anormalidades , Tomografia Computadorizada por Raios X/métodos , Trombose Venosa/complicações , Trombose Venosa/etiologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/diagnóstico por imagem , Espectroscopia de Ressonância Magnética/diagnóstico , Veia Ázigos/anormalidades , Veia Ázigos/diagnóstico por imagemRESUMO
La enfermedad de Crohn es un proceso inflamatorio crónico de causa desconocida, que puede comprometer cualquier zona del tubo digestivo, desde la cavidad oral hasta el ano. Presentamos una paciente de 22 años con enfermedad de Crohn, patología poco frecuente en nuestro medio, con una forma de presentación atípica, donde los métodos de diagnóstico por imágenes asumieron un rol preponderante para arribar al diagnóstico definitivo. Los estudios realizados fueron: ecografía abdominal, TC de abdomen con contraste oral y endovenoso con cortes finos para páncreas, tránsito convencional de intestino delgado, esófago-gastroduodenoscopia y colonoscopia con toma de biopsia
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Humanos , Feminino , Adulto , Doença de Crohn/diagnóstico , Duodenopatias/etiologia , Doença de Crohn , Doença de Crohn , Duodenopatias , Tomografia Computadorizada por Raios XRESUMO
La enfermedad de Crohn es un proceso inflamatorio crónico de causa desconocida, que puede comprometer cualquier zona del tubo digestivo, desde la cavidad oral hasta el ano. Presentamos una paciente de 22 años con enfermedad de Crohn, patología poco frecuente en nuestro medio, con una forma de presentación atípica, donde los métodos de diagnóstico por imágenes asumieron un rol preponderante para arribar al diagnóstico definitivo. Los estudios realizados fueron: ecografía abdominal, TC de abdomen con contraste oral y endovenoso con cortes finos para páncreas, tránsito convencional de intestino delgado, esófago-gastroduodenoscopia y colonoscopia con toma de biopsia (AU)