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1.
Heredity (Edinb) ; 122(4): 458-467, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30185924

RESUMO

Orchid seeds are presumably dispersed by wind due to their very small size and thus can potentially travel long distances. However, the few related studies indicate that seeds fall close to their mother plants. Because seed dispersal and colonization patterns can have relevant consequences for long-term species persistence, we assessed the fine-scale genetic structure of the epiphytic orchid Epidendrum rhopalostele to provide insight into these patterns. All individuals in the studied population were georeferenced and genotyped with AFLP-markers. Genetic structure was evaluated at two levels (forest and tree) using three approaches: principal coordinates analysis, model-based clustering, and spatial autocorrelation analysis. Results showed two genetic groups, composed of individuals from almost every tree with orchids. Spatial autocorrelation analysis at the forest level found no significant genetic structure when all individuals were considered, but a pattern of genetic patches was revealed when the analysis was performed separately for each group. Genetic patches had an estimated diameter of 4 m and were composed of individuals from more than one tree. A weak genetic structure was detected at the tree level at distances less than 1.5 m. These results suggest that many seeds fall close to the mother plant and become established in the same host tree. Additionally, a sequential colonization process seems to be the predominant mode of expansion, whereby progeny from orchids in one tree colonize neighboring trees. Thus, the existence of two distinct genetic groups and the presence of genetic patches should be considered when seed sampling for ex situ conservation.

2.
Eur J Med Chem ; 148: 372-383, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29471123

RESUMO

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ouro/química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiossemicarbazonas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Citotoxinas , Feminino , Humanos , Células MCF-7 , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiossemicarbazonas/farmacologia
4.
J Inorg Biochem ; 163: 118-130, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27426049

RESUMO

Four novel ligands derived from 2,3-butanedione have been synthesized, two dissymmetric thiosemicarbazone/3-hydroxy-2-naphthohydrazone ligands, H2L1 (bearing 4-isopropyl-3-thiosemicarbazone) and H2L2 (containing 4-cyclohexyl-3-thiosemicarbazone) and the symmetric H2L3, diacetyl bis(3-hydroxy-2-naphthohydrazone), and H2L4, diacetyl bis(4-cyclohexyl-3-thiosemicarbazone). Their reactivity with SnR2Cl2 (R=methyl, n-butyl and phenyl) was explored and the resulting complexes were characterized by elemental analysis, molar conductivity, mass spectrometry, IR, 1H, 13C and 119Sn NMR and seven of them also by single crystal X-ray diffraction. The results showed that the reactivity of the dissymmetric ligands is strongly different and while the cyclohexyl derivative is very stable, with isopropyl easily undergoes a symmetrization reaction to yield the corresponding symmetric ligands. The antimicrobial activity of the ligands and the corresponding diorganotin(IV) complexes was investigated in vitro against seven species of microorganisms and minimum inhibitory concentrations (MICs) were determined. The results showed that the ligand H2L2 and several of its derivatives, together with methyl and phenyl complexes of H2L1, have the ability of inhibiting the growth of tested bacteria and fungi to different extents. Bacillus subtilis and Staphylococcus aureus Gram positive strains were the most sensitive microorganisms.


Assuntos
Anti-Infecciosos , Bacillus subtilis/crescimento & desenvolvimento , Hidrazonas , Staphylococcus aureus/crescimento & desenvolvimento , Tiossemicarbazonas , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia
5.
An. Fac. Cienc. Méd. (Asunción) ; 49(1): 105-118, ene-jun. 2016.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-884917

RESUMO

Este trabajo se realiza en el contexto de un Proyecto de Innovación Curricular (PIC) de la FCM-UNA, basado en un modelo desarrollado por K, Troncoso y sobre la base de las tendencias y lineamientos actuales de la educación superior y la formación profesional universitaria que orienta y guía la construcción, tanto en el diseño como en la instalación y gestión, de currículos universitarios basados en competencias. Considera Hitos, fases, criterios y productos y forma parte de una propuesta metodológica y conceptual que se ha utilizado como marco de referencia y que permite organizar y estructurar la innovación curricular en la carrera de medicina. El hito 1 se refiere al levantamiento de información de las demandas y necesidades de formación a través del análisis de fuentes de investigación, actores claves y diversos marcos de referencia, para organizar y estructurar compromisos formativos para la elaboración y declaración del perfil de egreso. Por lo tanto significa justificar las decisiones tomadas, argumentando desde la lógica de la formación, la racionalidad que se espera modelar y los problemas, situaciones o contexto sobre los que el egresado actuará, utilizando como referencia las respuestas y posición frente al levantamiento de información. Esto responde a exigencias por parte de la sociedad, y así también para poder instalar una propuesta educativa con formación profesional universitaria pertinente. El hito 2 se refiere al análisis y síntesis de la información obtenida de los actores relevantes, de manera a tomar decisiones sobre cuáles son las demandas y necesidades en la formación de los estudiantes de la FCM-UNA. De esta forma ir avanzando hacia la declaración de los compromisos formativos y su representación en el perfil de egreso.


This work is done in the context of Curricular Innovation Project (CIP) of the FCM UNA, based on a model developed by K, Troncoso and based on current trends and guidelines of superior education and degree training that guides the construction, both in the design and installation of university curricula based on competencies. It considers milestones, stages, criteria and products, and forms part of a methodological and conceptual approach which has been used as a reference that allows to organize and structure the curriculum innovation in medical career. Milestone 1 refers to the obtainment of demands and needs of training through the analysis of research sources, stakeholders and various frameworks, to organize and structure training commitments for the development and declaration of the graduate profile. Therefore it means justify the decisions taken, arguing from the logic of training, the rationality that is expected to model and the problems, situation or context on which the graduate will act, using as reference the responses and position on the collection of information This responds to demands from society, and thus also to install an educational proposal with relevant university training. The milestone 2 refers to the analysis and synthesis of information from relevant stakeholders, in order to make decisions about what are the demands and needs in the training of students of the FCM-UNA. Thus moving towards the declaration of training commitments and its representation in the graduate profile.

6.
Prev Med ; 76 Suppl: S94-104, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25625691

RESUMO

OBJECTIVE: To examine evidence on the effectiveness of health-promoting community interventions carried out in primary health care. METHODS: Systematic review of originals and systematic reviews of health-promoting community interventions with the participation of primary health care. A working definition of community activities was used in the inclusion criteria. Databases searched up to 2013: PUBMED, EMBASE, CINHAL, Web of SCIENCE, IBECS, IME, and PSICODOC. No restrictions on year of publication or design. Articles were reviewed by separate researchers to identify risks of bias. RESULTS: Fifty-one articles published between 1966 and 2013 were included: 11 systematic reviews and 40 originals that described 39 community interventions. There is evidence on the effectiveness of community interventions in reducing cardiovascular risk factors, encouraging physical exercise, preventing falls and improving self-care among chronic patients compared with usual individual care. The effectiveness of some interventions increases when the community is involved in their development. Most assessments show positive results despite design limitations. CONCLUSIONS: The community approach may be more effective than the individual in usual preventive interventions in primary care. There is a lack of evidence on many community interventions in primary care and further research is needed.


Assuntos
Serviços de Saúde Comunitária , Promoção da Saúde , Acidentes por Quedas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Exercício Físico , Humanos , Pessoa de Meia-Idade , Atenção Primária à Saúde , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-25240147

RESUMO

Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)-H(7A)-O(2), N(7)-H(7B)-O(3), N(1)-H(1)-N(2), C(5)-H(5)-O(3)-S(1) and N(7)-(H7A)-O(2)-S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37×10(4)M(-1). The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.


Assuntos
Sulfametoxazol/química , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Di-Hidropteroato Sintase/química , Di-Hidropteroato Sintase/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Modelos Químicos , Simulação de Acoplamento Molecular , Streptococcus pneumoniae/enzimologia , Sulfametoxazol/metabolismo , Espectroscopia por Absorção de Raios X
8.
Clin Endocrinol (Oxf) ; 81(6): 883-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24612232

RESUMO

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.


Assuntos
Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Lipodistrofia/induzido quimicamente , Receptores da Somatotropina/antagonistas & inibidores , Adenoma/metabolismo , Adulto , Antineoplásicos/uso terapêutico , Cabergolina , Quimioterapia Combinada , Ergolinas/uso terapêutico , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Estudos Retrospectivos , Espanha , Falha de Tratamento , Resultado do Tratamento
9.
Am J Bot ; 100(12): 2339-48, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24252216

RESUMO

PREMISE OF THE STUDY: The presence of compatible fungi is necessary for epiphytic orchid recruitment. Thus, identifying associated mycorrhizal fungi at the population level is essential for orchid conservation. Recruitment patterns may also be conditioned by factors such as seed dispersal range and specific environmental characteristics. METHODS: In a forest plot, all trees with a diameter at breast height >1 cm and all individuals of the epiphytic orchid Epidendrum rhopalostele were identified and mapped. Additionally, one flowering individual of E. rhopalostele per each host tree was randomly selected for root sampling and DNA extraction. KEY RESULTS: A total of 239 E. rhopalostele individuals were located in 25 of the 714 potential host trees. Light microscopy of sampled roots showed mycorrhizal fungi in 22 of the 25 sampled orchids. Phylogenetic analysis of ITS1-5.8S-ITS2 sequences yielded two Tulasnella clades. In four cases, plants were found to be associated with both clades. The difference between univariate and bivariate K functions was consistent with the random labeling null model at all spatial scales, indicating that trees hosting clades A and B of Tulasnella are not spatially segregated. The analysis of the inhomogenous K function showed that host trees are not clustered, suggesting no limitations to population-scale dispersal. χ(2) analysis of contingency tables showed that E. rhopalostele is more frequent on dead trees than expected. CONCLUSIONS: EPIDENDRUM RHOPALOSTELE establishes mycorrhizal associations with at least two different Tulasnella species. The analysis of the distribution patterns of this orchid suggests a microsite preference for dead trees and no seed dispersal limitation.


Assuntos
Basidiomycota/genética , Ecossistema , Micorrizas , Orchidaceae , Filogenia , Raízes de Plantas/microbiologia , Árvores , Sequência de Bases , Basidiomycota/classificação , DNA Fúngico , DNA Espaçador Ribossômico , Orchidaceae/crescimento & desenvolvimento , Orchidaceae/microbiologia , Dispersão Vegetal , Análise de Sequência de DNA , Especificidade da Espécie , Simbiose
10.
Actas Esp Psiquiatr ; 41(2): 84-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23592068

RESUMO

OBJECTIVES: To determine risk factors associated with presence of depression in young adults 20 to 35. METHODS: Case-control design in 6 health centers. SUBJECTS: Young adult, visited in the past two years in primary health care. CASES: Diagnosis of depression <12 months. CONTROLS: no diagnosis of depression or related treatment. Diagnosis confirmed by CIDI questionnaire. Random selection of controls. MEASUREMENTS: Personal interview. Dependent variable: depressive syndrome present or absent. Independent: demographic, labor, economic, social, health, drug abuse and life events. RESULTS: 95 cases and 93 controls. Response rate 57.7% and 45.0% respectively. Variables associated with depression: being female, being separated/divorced/widow, income <1000 euros/month, difficulties at work, spending free time alone, have problems getting or maintaining relationships, sexual dissatisfaction, worse perceived health status, marijuana use, sedentary lifestyle, having suffered some form of discrimination, child abuse, a family member with serious psychological problems (last year). CONCLUSIONS: The risk factors found are similar to those of other studies with wide age range. Differentiating factors are abuse in childhood, spending time alone, problems with relationships.


Assuntos
Transtorno Depressivo/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
11.
Actas esp. psiquiatr ; 41(2): 84-96, mar.-abr. 2013. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-111609

RESUMO

Objetivos: Determinar factores de riesgo relacionados con presencia de depresión en adultos jóvenes (20-35 años).Material y métodos: Estudio caso-control 6 centros de salud. Sujetos: Adultos jóvenes, visitados en los últimos dos años en Atención primaria. Casos: Diagnóstico de depresión <12 meses. Controles: sin diagnóstico de depresión, o tratamiento relacionado. Diagnóstico confirmado mediante cuestionario CIDI. Selección aleatoria de controles. Mediciones: Entrevista personal. Variable dependiente: síndrome depresivo presente o ausente. Independientes: sociodemográficas, laborales, económicas, relaciones sociales, salud, consumo de drogas, y acontecimientos vitales. Resultados: 95 casos y 93 controles. Tasa de respuesta 57,7% y 45,0% respectivamente. Variables asociadas a depresión: Ser mujer; estar viuda/separada/divorciada; ingresos <1000€/mes; dificultades en el trabajo; pasar el tiempo libre solo; tener problemas para relacionarse o para mantener relaciones cercanas; falta de satisfacción vida sexual; peor percepción estado de salud; consumo de marihuana; sedentarismo; haber sufrido algún tipo de discriminación; maltrato infantil; algún familiar con problema psicológico grave (último año). Conclusiones: Los factores de riesgo encontrados se asemejan a los de otros estudios con rango de edad más amplio. Factores diferenciales son maltrato en la infancia, pasar tiempo solo, problemas para relacionarse (AU)


Objectives: To determine risk factors associated with presence of depression in young adults (20-35 years). Methods: Case-control design in 6 health centers. Subjects: Young adult, visited in the past two years in primary health care. Cases: Diagnosis of depression <12months.Controls: no diagnosis of depression or related treatment. Diagnosis confirmed by CIDI questionnaire. Random selection of controls. Measurements: Personal interview. Dependent variable: depressive syndrome present or absent. Independent: demographic, labor, economic, social, health, drug abuse and life events. Results: 95 cases and 93 controls. Response rate 57.7% and 45.0% respectively. Variables associated with depression: being female, being separated/divorced/widow, income <1000 €/month, difficulties at work, spending free time alone, have problems getting or maintaining relationships, sexual dissatisfaction, worse perceived health status, marijuana use, sedentary lifestyle, having suffered some form of discrimination, child abuse, a family member with serious psychological problems (last year).Conclusions: The risk factors found are similar to those of other studies with wide age range. Differentiating factors are abuse in childhood, spending time alone, problems with relationships (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/terapia , Fatores de Risco , Apoio Social , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/psicologia , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/tendências , Atenção Primária à Saúde , Inquéritos e Questionários , Intervalos de Confiança
12.
Pituitary ; 16(1): 115-21, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22481632

RESUMO

Since 1997 there is an online National Registry of acromegalic patients in Spain (REA). We aimed to study changes in acromegaly treatment and outcomes over the last four decades in Spain. In REA clinical and biochemical data are collected at diagnosis and updated every one to 2 years. We analyzed the first treatment received and the different treatments administered according to decade of diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009. Surgical cure rates according to pretreatment with long-acting somatostatin receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which 698 had accurate follow-up data. Treatment of acromegaly changed over time. Surgery was the main treatment option (83.8 %) and medical treatment was widely used (74.7 %) both maintained over decades, while radiation therapy declined (62.8, 61.6, 42.2 and 11.9 % over decades, p < 0.001). First treatment type also changed: surgery was the first line option up until the last decade in which medical treatment was preferred (p < 0.001). Radiotherapy was barely used as first treatment. Treatment combinations changed over time (p < 0.001). The most common treatment combination (surgery plus medical therapy), was received by 24.4, 16.4, 25.3 and 56.5 % of patients over decades. Medical treatment alone was performed in 7.3, 6, 7.2 and 14.7 % over decades. Type of medical treatment also changed, SRLs becoming the first medical treatment modality in the last decades, whereas dopamine agonist use declined (p < 0.001). Surgical cure rates improved over decades (21, 21, 36 and 38 %, p = 0.002) and were not influenced by SRL pre-surgical use. Acromegaly treatment has changed in Spain in the last four decades. Surgery has been the main treatment option for decades; however, medical therapy has replaced surgery as first line in the last decade and radiotherapy rates have clearly declined. SRLs are the most used medical treatment.


Assuntos
Acromegalia/radioterapia , Acromegalia/cirurgia , Acromegalia/tratamento farmacológico , Adulto , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Software , Espanha
14.
BMC Public Health ; 12: 322, 2012 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-22551017

RESUMO

BACKGROUND: Smoking cessation is beneficial for our health at any point in life, both in healthy people and in people already suffering from a smoking-related disease. Any help to quit smoking can produce considerable benefits for Public Health. The purpose of the present study is to evaluate the efficacy of the CO-oximetry technique together with brief advice in smoking cessation, in terms of reduction of the number of cigarettes or in the variation of the motivation to quit smoking at month 12 compared with brief advice alone. METHODS/DESIGN: Randomised, parallel, single-blind clinical trial in a primary health care setting in Majorca (Spain). Smokers in contemplation or pre-contemplation phase will be included in the study. EXCLUSION CRITERIA: Smokers in preparation phase, subjects with a terminal illness or whose health status does not allow them to understand the study or complete the informed consent, and pregnant or breastfeeding women. The subjects will be randomly assigned to the control group (CG) or the intervention group (IG). The CG will receive brief advice, and the IG will receive brief advice together with a measurement of exhaled CO. There will be follow-up evaluations at 6 and 12 months after inclusion. 471 subjects will be needed per group in order to detect a difference between groups ≥ 5%. PRIMARY OUTCOME: sustained smoking cessation (at 6 and 12 months) confirmed by urine cotinine test. SECONDARY OUTCOMES: point smoking cessation at 6 and 12 months both confirmed by urine cotinine analysis and self-reported, reduction in cigarette consumption, and variation in phase of smoking cessation. DISCUSSION: CO-oximetry is an inexpensive, non-invasive, fast technique that requires little technical training; making it a technique for risk assessment in smokers that can be easily applied in primary care and, if proven effective, could serve as a reinforcement aid in smoking cessation intervention activities. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67499921.


Assuntos
Monóxido de Carbono/análise , Expiração , Atenção Primária à Saúde , Abandono do Hábito de Fumar/métodos , Adolescente , Adulto , Testes Respiratórios , Feminino , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Espanha , Adulto Jovem
18.
Eur J Pharm Sci ; 45(4): 436-41, 2012 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-21896328

RESUMO

The design of long circulating liposomes co-loaded with the glucocorticoid prednisolone phosphate (PLP) and the amphiphilic paramagnetic contrast agent Gd-DOTAMA(C(18))(2) allowed the MRI-guided in vivo visualization of the delivery and biodistribution of PLP, as well as the monitoring of drug efficacy. The performance of this theranostic probe was investigated in a mouse model bearing a melanoma B16 syngeneic tumor. The release kinetics of the drug were evaluated in vitro where it displayed a peculiar behavior characterized by a fast process (completed in few hours) involving only a small portion (<5%) of the drug. Interestingly, the incorporation of the amphiphilic imaging reporter in the liposomal bilayer slightly increased the amount of the fast-release portion (<10%), thus suggesting that it could be attributed to a drug fraction embedded in the liposomal bilayer. In fact, the release of a hydrophilic imaging probe encapsulated in the inner core of the same long circulating liposomes formulated for carrying the drug, displayed different, single-step, kinetics. The in vivo monitoring of the antitumor activity of the nanomedicine revealed that the incorporation of the MRI probe into the liposome bilayer did not significantly affect the drug efficacy. The in vivo experiments also indicated a relevant and fast liposome uptake from macrophage-rich organs like spleen and liver, which reduced the tumor accumulation of the liposomes. The accumulation of the amphipatic MRI label caused the occurrence of a long-term residual T(1) contrast still detectable 1week after injection.


Assuntos
Antineoplásicos/administração & dosagem , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Glucocorticoides/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Prednisolona/análogos & derivados , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Meios de Contraste/química , Gadolínio/química , Glucocorticoides/química , Lipossomos , Imagem por Ressonância Magnética , Magnetismo , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Prednisolona/administração & dosagem , Prednisolona/química , Carga Tumoral/efeitos dos fármacos
19.
J Control Release ; 154(2): 196-202, 2011 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-21621569

RESUMO

This work aims at assessing the in vitro potential of paramagnetic pH sensitive liposomes as imaging tools for visualizing drug-delivery and release processes by Magnetic Resonance Imaging (MRI). pH sensitive liposomes (pSLs) were formulated using the fusogenic phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), the membrane stabilizer D-α-tocopherol-hemisuccinate (THS), and were loaded with several paramagnetic complexes including the clinically approved Gadoteridol (marketed as ProHance™). The proposed formulation allows the fast and full release of Gadoteridol at pH 5.5. The leakage of the imaging reporter from the vesicles was associated with a relaxivity enhancement that allowed its visualization by MRI. It was observed that the release mechanism implies the protonation of the THS basic sites that leads to vesicle aggregation, thus enabling the expression of the fusogenic property of POPE. Attempts for improving the MRI properties of pSLs were pursued through the encapsulation of imaging agents with higher relaxivity than Gadoteridol, but it was observed that the release kinetic can be significantly affected by the probe size. Aiming at preparing stealth pSLs, PEG chains were conjugated to the external surface of the vesicles via cleavable disulphide bridges. Such nanomedicines do not release their content at acidic pH as long as the coating polymer is not removed from the surface. The results obtained suggest that the liposomal formulation investigated in this work has the potential for visualizing drug-delivery and release processes by in vivo MRI preclinical studies.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Imagem por Ressonância Magnética/métodos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Sistemas de Liberação de Medicamentos/normas , Gadolínio , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/farmacocinética , Concentração de Íons de Hidrogênio , Lipossomos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Imagem por Ressonância Magnética/normas
20.
Dalton Trans ; 40(16): 4284-90, 2011 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-21394331

RESUMO

The self-assembly of a carbonylpyridine-based heptadentate ligand with Ln(III) results in the formation of triangular trinuclear europium complexes, which exhibit interesting luminescent properties in the solid state and in solution. With a view to developing multimodal responsive systems, we report here the preparation and characterisation of analogous complexes with Gd(III). The X-ray crystal structure of Gd(3)L2(3) indeed reveals the isostructurality with the Eu(III) complexes. A combination of (1)H NMRD and variable temperature studies yields the parameters elucidating the exchange of coordinated water and relaxivity properties. Conveniently, the competitive spectrophotometric titrations with EDTA and NTA are used to determine the thermodynamic stability constants of the europium complexes in aqueous media. In addition, the exchange reaction with EDTA is monitored with NMR and fluorimetry. The interactions of the Eu(III) trinuclear complex with some potentially interfering ligands are qualitatively investigated by means of luminescence titrations.


Assuntos
Elementos da Série dos Lantanídeos/química , Ácidos Carboxílicos/química , Cristalografia por Raios X , Ácido Edético/química , Espectroscopia de Ressonância Magnética , Magnetismo , Modelos Moleculares , Conformação Molecular , Termodinâmica
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