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1.
Heliyon ; 10(2): e24284, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293450

RESUMO

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient. The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

2.
ChemMedChem ; 16(14): 2217-2222, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33843142

RESUMO

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (ß-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.


Assuntos
Amidas/farmacologia , Fármacos Anti-HIV/farmacologia , Glicerol/farmacologia , Inibidores da Fusão de HIV/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Polímeros/farmacologia , beta-Ciclodextrinas/farmacologia , Amidas/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Relação Dose-Resposta a Droga , Glicerol/química , Inibidores da Fusão de HIV/síntese química , Inibidores da Fusão de HIV/química , Transcriptase Reversa do HIV/metabolismo , HIV-1/metabolismo , Humanos , Estrutura Molecular , Polímeros/química , Relação Estrutura-Atividade , beta-Ciclodextrinas/química
3.
Rev. Fund. Educ. Méd. (Ed. impr.) ; 23(6): 331-333, dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-198789

RESUMO

INTRODUCCIÓN: El abandono escolar representa desde hace años uno de los grandes problemas a los que se enfrenta la educación en México, principalmente a nivel superior y en licenciaturas de alta exigencia académica como es el caso de medicina. SUJETOS Y MÉTODOS: Se realizó un análisis cuantitativo de tres promociones de la licenciatura de médico cirujano de la Universidad Nacional Autónoma de México con el fin de comparar el abandono escolar según sexo y promoción. RESULTADOS: Se observó que el primer año de la licenciatura de médico cirujano es donde se presenta un mayor porcentaje de abandono escolar (77%), con un predominio de población femenina y abandono definitivo. CONCLUSIÓN: Se estudió el comportamiento estudiantil de la licenciatura de Médico Cirujano para replantear métodos y estrategias institucionales en términos de abandono escolar


INTRODUCTION: For years, school dropout has represented one of the greatest problems that education in Mexico faces, mainly at the higher level and in highly demanding academic degrees such as Medicine. SUBJECTS AND METHODS: We carried out a quantitative analysis of three generations enrolled in Medicine Bachelor of the UNAM's School of Medicine in order to compare school dropouts by sex and generation. RESULTS: It was observed that the Medicine Bachelor's first year is where the highest percentage of school dropouts (77%) occurs, with a predominance of female population and definitive dropout. CONCLUSION: Medicine Bachelor's student behavior was studied to rethink institutional methods and strategies focused on scholar dropout


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Evasão Escolar/educação , Evasão Escolar/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Educação Médica , Estudos de Coortes , Evasão Escolar/psicologia , 28599
4.
Clin Sci (Lond) ; 134(7): 751-763, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32227160

RESUMO

The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin-haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.


Assuntos
Corticosteroides/farmacologia , Dexametasona/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Humanos , Ferro/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Transdução de Sinais , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo
5.
RSC Adv ; 10(34): 20083-20088, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35520432

RESUMO

The anionic carbosilane (CBS) dendrimer with sulfonate groups G2-S16 is a promising compound for the preparation of a microbicide gel to prevent HIV infection. However, until now its synthesis required aggressive conditions. Hence, a reliable synthetic procedure is very important to face GMP conditions and clinical trials. In this study, G2-S16 has been prepared by a new approach that involves the addition of an amine-terminated dendrimer to ethenesulfonyl fluoride (C2H3SO3F, ESF) and then transformation to the sulfonate dendrimer by treatment with a base. This strategy also makes feasible the synthesis of a labelled sulfonate dendrimer (G2-S16-FITC) to be used as a molecular probe for in vivo experiments. Interestingly, G2-S16-FITC enters into human peripheral blood mononuclear cells (PBMCs).

6.
Future Med Chem ; 11(23): 3005-3013, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31710246

RESUMO

Aim: To research the synergistic activity of G2-S16 dendrimer and dapivirine (DPV) antiretroviral as microbicide candidate to prevent HIV-1 infection. Materials & methods: We assess the toxicity of DPV on cell lines by MTT assay, the anti-HIV-1 activity of G2-S16 and DPV alone or combined at several fixed ratios. Finally, their ability to inhibit the bacterial growth in vitro was assayed. The analysis of combinatorial effects and the effective concentrations were performed with CalcuSyn software. Conclusion: Our results represent the first proof-of-concept study of G2-S16/DPV combination to develop a safe microbicide.


Assuntos
Fármacos Anti-HIV/farmacologia , Dendrímeros/farmacologia , Células Epiteliais/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Pirimidinas/farmacologia , Silanos/farmacologia , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/toxicidade , Bactérias Anaeróbias/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Dendrímeros/administração & dosagem , Dendrímeros/toxicidade , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células Epiteliais/virologia , Infecções por HIV/prevenção & controle , Humanos , Testes de Sensibilidade Microbiana , Polieletrólitos , Polímeros , Pirimidinas/administração & dosagem , Pirimidinas/toxicidade , Silanos/administração & dosagem , Silanos/toxicidade , Células Vero
7.
J Diabetes Res ; 2019: 6271591, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485453

RESUMO

PURPOSE: To explore the factors involved in adherence to self-care behaviors in patients with type 1 diabetes. MATERIALS AND METHODS: Patients with type 1 diabetes (age range: 14-71 years) were invited to participate at seven Spanish hospitals. They completed a dossier which recorded sociodemographic and clinical variables and also measured personality variables, emotional state, beliefs, and concerns regarding the illness, by means of questionnaires. RESULTS: A total of 428 patients with type 1 diabetes were included (58% women, age 36 (11.8) years, diabetes duration 18.3 (10.2) years, HbA1c 7.9 +/-1.3%). A total of 60.1% of patients found it difficult to follow the treatment recommendations for the care of their disease. The reasons given were mood (25.2%), lack of motivation (13.4%), work (12%), and economic difficulties (3.8%). Other personal reasons were reported by 5.7%. Motivation, training in diabetes management, importance the patient attributed to the disease, and self-efficacy were the variables that predicted adherence to self-care behaviors, together accounting for 32% of its variance. Anxiety and depression were highly prevalent in this study population (57.1% and 23.1%, respectively) and were associated with lower adherence. CONCLUSION: In the present study assessing patients with type 1 diabetes, motivation, training in diabetes management, beliefs regarding the disease, and self-efficacy were the main contributors to adherence to self-care behaviors. On the other hand, anxiety and depression were highly prevalent and associated with lower adherence. Thus, supplementing therapeutic education with strategies designed to raise levels of motivation, discussion of beliefs about the disease, and encouragement of self-efficacy might be a useful way to increase patient involvement in self-care.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Cooperação do Paciente/psicologia , Autocuidado/psicologia , Adulto , Ansiedade/complicações , Ansiedade/epidemiologia , Depressão/complicações , Depressão/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Emoções , Feminino , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Motivação/fisiologia , Cooperação do Paciente/estatística & dados numéricos , Autocuidado/estatística & dados numéricos , Autoeficácia , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Adulto Jovem
8.
An Real Acad Farm ; 85(3): 248-259, jul.-sept. 2019. graf, ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-184874

RESUMO

El objetivo de este trabajo fue estudiar la influencia de la divisibilidad en comprimidos de prednisona 30 mg. La división de comprimidos se utiliza a menudo en la práctica farmacéutica para ajustar las dosis administradas. La prednisona es un corticoesteroide (glucocorticoide) utilizado en el tratamiento de sustitución en la insuficiencia adrenal incluyendo entre otras la enfermedad de Addison. Como medicamento de referencia se utilizó Dacortin 30 mg, el cual se comparó con dos medicamentos genéricos. Se estudiaron diferentes características farmacotécnicas para evaluar la calidad de los comprimidos estudiados, tales como la disgregación y la resistencia a la rotura. Atendiendo al estudio de fraccionamiento de comprimidos, se determinó la diferencia sobre el peso teórico esperado (pérdida de masa media tras el fraccionamiento de cada marca comercial). La liberación del principio activo se estudió mediante el ensayo de velocidad de disolución en fracciones de comprimidos. Los resultados de las tres presentaciones comerciales fueron estudiados y analizados estadísticamente con un nivel de confianza de un 95 %


The objective of this work was to study the influence of the division in prednisone tablets 30 mg. The division of tablets is often used in pharmaceutical practice to adjust the administered doses. Prednisone is a corticosteroid (glucocorticoid) used in the substitution treatment in adrenal insufficiency including, among others, Addison's disease. As a reference drug, Dacortin 30 mg was used, and compared with two generic drugs. Different pharmacotechnic characteristics were studied to evaluate the quality of the tablets studied, such as disintegration, and the resistance to crushing. Based on the study of tablet fractionation, the difference over the expected theoretical weight was determined (loss of average mass after the fractionation of each trademark). The release of the active substance was carried out with dissolution rate study in fractions of tablets. The results of the three commercial formulations were studied and statistically analyzed with a confidence level of 95 %


Assuntos
Prednisona/química , Comprimidos/química , Medicamentos Fracionados , Medicamentos Genéricos/química , Prednisona/síntese química , Medicamentos Genéricos/síntese química , Comercialização de Medicamentos , Microscopia Eletrônica de Varredura/métodos , Fotomicrografia
9.
Nanoscale ; 11(19): 9679-9690, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31066407

RESUMO

Acquired immune deficiency syndrome (AIDS) due to human immunodeficiency virus type-1 (HIV-1) represents one of the most important sexually transmitted infections (STI) worldwide. Great international efforts have been made to stop new infections but, to date, several compounds failed as microbicides at different stages of clinical trials. The quest to design new molecules that could prevent these infections is essential. In this work, we synthesized the first, second and third generations of anionic dendrimers having carboxylate and sulfonate terminal groups, respectively named G1C, G2C, G3C and G1S, G2S, and G3S, starting from a family of poly(alkylideneamine) dendrimers with nitrile termini. The anionic terminal groups of these dendrimers were expected to prompt them to act against HIV-1 infection. All dendrimers were fully characterized by 1H- and 13C-NMR, FTIR, MS and zeta potential techniques. Importantly, they were able to remain stable in the solid state and aqueous solutions at least for one and a half years. Screening of these six new dendrimers was then performed to shed light on their potential anti-HIV-1 activity and their mechanism of action. Results showed that the dendrimers were cytocompatible and that G1C and G1S dendrimers had important activity against R5-HIV-1NLAD8 and X4-HIV-1NL4.3 isolates by acting directly on viral particles and blocking their entry in host cells. Additionally, G1C and G1S dendrimers maintained their inhibitory effect at different pH values. Through a vaginal irritation assay carried out in BALB/c mice, the safety of these new dendrimers for topical application was also shown. Taken together, our results clearly show that G1C and G1S dendrimers are strong candidates for developing an effective microbicide to prevent HIV-1 new infections.


Assuntos
Anti-Infecciosos/química , Dendrímeros/química , Animais , Ânions/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Ácidos Carboxílicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/farmacologia , Dendrímeros/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , HIV-1/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ácidos Sulfônicos/química , Vagina/efeitos dos fármacos , Vagina/patologia , Internalização do Vírus/efeitos dos fármacos
10.
Vasc Health Risk Manag ; 15: 57-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936712

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) with no evidence of relevant stenosis of the coronary artery, known as myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA), has a prevalence of up to 14%. The various causes of MINOCA lead to damage of the myocardium, and there are marked differences in diagnoses, prognoses, and treatments. Although the number of patients affected is considerable owing to the high prevalence of acute coronary syndrome (ACS), the causes of MINOCA have received little attention with the result that some patients may not receive appropriate treatment. Awareness of this disease among clinicians has started only to improve since the beginning of the current century. The aim of this study was to develop a score that enables patients with MINOCA to be distinguished from patients with MI with coronary artery disease (MI-CAD) and thus to facilitate appropriate diagnosis and therapy. PATIENTS AND METHODS: A multicenter observational cohort study was designed. All patients aged ≥18 years from the ARIAM-SEMICYUC (Analysis of Delay in AMI-Spanish Society of Intensive Care Medicine and Coronary Unit) registry, diagnosed with AMI, and admitted to critical care units or coronary care units (CCUs) were included. Patients were classified into two groups: MINOCA, comprising patients with no significant lesions on angiography, and MI-CAD, comprising patients with lesions of the coronary artery tree. RESULTS: A score based on standard variables to assess the probability of MINOCA on admission was designed, showing a maximum value corresponding to a 40% probability of MINOCA. The discriminative power of the model was 0.756 (P-value for the Hosmer-Lemeshow test was >0.05). At 30-day follow-up, the mortality rate was higher for MI-CAD patients. CONCLUSION: Patients with MINOCA constitute a population that differs from other patients with AMI. Their differential characteristics require a certain diagnostic effort to align therapy with the disease causing the ischemic event. This score could prove useful in establishing additional diagnostic procedures.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Técnicas de Apoio para a Decisão , Infarto do Miocárdio/diagnóstico , Fatores Etários , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Estenose Coronária/sangue , Estenose Coronária/epidemiologia , Estenose Coronária/terapia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Troponina/sangue , Regulação para Cima
11.
J Cell Physiol ; 234(5): 5880-5887, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29323711

RESUMO

Since the success of combined antiretroviral therapy, HIV-1-infected individuals are now living much longer. This increased life expectancy is accompanied by a higher prevalence of HIV-1 associated neurocognitive disorders. Rising too is the incidence in these patients of pathological hallmarks of Alzheimer's disease such as increased deposition of amyloid beta protein (Aß). Although neurons are major sources of Aß in the brain, astrocytes are the most numerous glial cells, therefore, even a small level of astrocytic Aß metabolism could make a significant contribution to brain pathology. Neprilysin (NEP) is a decisive/crucial regulator of Aß levels. We evaluated the effects of HIV-1 on Aß deposition and the expression and activity of NEP in primary human astrocytes. Specifically, no differences in intracellular amyloid deposits were found between infected and control cells. However, primary cultures of infected astrocytes showed more extracellular Aß levels compared to controls. This was accompanied by reduced expression of NEP and to a significant decrease in its activity. These results indicate that the presence of HIV-1 in the brain could contribute to the increase in the total burden of cerebral Aß.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Astrócitos/enzimologia , Encéfalo/enzimologia , Infecções por HIV/enzimologia , HIV-1/patogenicidade , Neprilisina/metabolismo , Fragmentos de Peptídeos/metabolismo , Astrócitos/patologia , Astrócitos/virologia , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Infecções por HIV/patologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Cultura Primária de Células , Regulação para Cima
12.
An. pediatr. (2003. Ed. impr.) ; 89(5): 314.e1-314.e6, nov. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-177123

RESUMO

La investigación clínica es la piedra angular para el desarrollo de la Medicina, y, en el ámbito de la Pediatría, supone un reto adicional debido a las peculiaridades que diferencian a los niños de los adultos. A pesar del enorme impacto de la salud infantil en el resto de la vida, nuestra sociedad aún no está suficientemente concienciada sobre la importancia de la investigación pediátrica, que, en general, se encuentra también muy alejada del día a día de quienes nos dedicamos a esta profesión. Desde la Asociación Española de Pediatría (AEP) se ha creado una plataforma específica de investigación -INVEST-AEP- para dar respuesta específica a los retos de la investigación en el seno de nuestra sociedad. En este artículo se retrata el escenario actual de la investigación pediátrica en España y se objetivan las metas alcanzadas en los últimos años, gracias al esfuerzo de los pediatras investigadores. Además, se realiza un análisis en profundidad sobre las barreras cotidianas que dificultan el desarrollo amplio y competitivo de la investigación pediátrica, como la falta de incentivación y ausencia de formación específica de pre y posgrado, la elevada carga asistencial o la falta de infraestructuras y financiación específicas. Definimos la misión, visión y valores de INVEST-AEP para tratar de diseñar una "hoja de ruta" para la investigación pediátrica española de los próximos años


Research is the cornerstone of medical progress. Paediatric research has its own nuances and represents an additional challenge due to the intrinsic characteristics of the paediatric population compared with adults. Despite the tremendous importance of childhood health and its impact during adulthood, society is still not convinced about the importance of conducting research in paediatrics. This also applies to paediatricians themselves, who think about research as a discipline that does not directly involve them. The Spanish Academy of Paediatrics has developed a specific research platform- INVEST-AEP- to try to help and answer the challenges associated with paediatric research in the society This article reflects the current status of paediatric research in Spain, and the goals achieved over the last few years due to the effort of paediatric researchers. In addition, a deeper analysis is provided as regards: a) the barriers that represent a hurdle for the development of broad and competitive paediatric research in our day to day work; b) the limited incentives and specific pre- and post-doctoral training; c) the high clinical burden for paediatricians or; d) the lack of specific infrastructure and dedicated funding for paediatrics. The mission, vision and values of INVEST-AEP are to develop an accessible roadmap for the development and implementation of paediatric research in Spain for the next few years


Assuntos
Pesquisa , Pediatria , Prioridades em Saúde , Sociedades Médicas/normas , Espanha
13.
An Pediatr (Engl Ed) ; 89(5): 314.e1-314.e6, 2018 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-30309723

RESUMO

Research is the cornerstone of medical progress. Paediatric research has its own nuances and represents an additional challenge due to the intrinsic characteristics of the paediatric population compared with adults. Despite the tremendous importance of childhood health and its impact during adulthood, society is still not convinced about the importance of conducting research in paediatrics. This also applies to paediatricians themselves, who think about research as a discipline that does not directly involve them. The Spanish Academy of Paediatrics has developed a specific research platform- INVEST-AEP- to try to help and answer the challenges associated with paediatric research in the society This article reflects the current status of paediatric research in Spain, and the goals achieved over the last few years due to the effort of paediatric researchers. In addition, a deeper analysis is provided as regards: a) the barriers that represent a hurdle for the development of broad and competitive paediatric research in our day to day work; b) the limited incentives and specific pre- and post-doctoral training; c) the high clinical burden for paediatricians or; d) the lack of specific infrastructure and dedicated funding for paediatrics. The mission, vision and values of INVEST-AEP are to develop an accessible roadmap for the development and implementation of paediatric research in Spain for the next few years.


Assuntos
Pesquisa Biomédica , Pediatria , Espanha
14.
Bioconjug Chem ; 29(5): 1584-1594, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29570280

RESUMO

Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.


Assuntos
Fármacos Anti-HIV/farmacologia , Dendrímeros/farmacologia , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Silanos/farmacologia , Internalização do Vírus/efeitos dos fármacos , Ânions/química , Ânions/farmacologia , Fármacos Anti-HIV/química , Antígenos CD4/metabolismo , Linhagem Celular , Dendrímeros/química , Infecções por HIV/metabolismo , HIV-1/fisiologia , Humanos , Modelos Moleculares , Silanos/química
15.
Colloids Surf B Biointerfaces ; 162: 380-388, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29241096

RESUMO

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe2R]+, R=Me, (CH2)2OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G1O3(NMe2(CH2)2OH))6]6+; the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation.


Assuntos
Dendrímeros/química , Técnicas de Transferência de Genes , RNA Interferente Pequeno/química , Silanos/química , Produtos do Gene nef do Vírus da Imunodeficiência Humana/química , Dendrímeros/metabolismo , Estabilidade de Medicamentos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Leucócitos Mononucleares/citologia , Conformação Molecular , Simulação de Dinâmica Molecular , Tamanho da Partícula , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Silanos/metabolismo , Eletricidade Estática , Termodinâmica , Produtos do Gene nef do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo
18.
Front Psychol ; 8: 904, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28620331

RESUMO

This study describes the development of a new questionnaire to measure health-related quality of life (HRQoL) in patients with type 1 diabetes (the ViDa1 questionnaire) and provides information on its psychometric properties. For its development, open interviews with patients took place and topics relevant to patients' HRQoL were identified and items were generated. Qualitative analysis of items, expert review, and refinement of the questionnaire followed. A pilot study (N = 150) was conducted to explore the underlying structure of the 40-item ViDa1 questionnaire. A Principal Component Analysis (PCA) was performed and six of the items that did not load on any of the factors were eliminated. The results supported a four-dimensional structure for ViDa1, the dimensions being Interference of diabetes in everyday life, Self-care, Well-being, and Worry about the disease. Subsequently, the PCA was repeated in a larger sample (N = 578) with the reduced 34-item version of the questionnaire, and a Confirmatory Factor Analysis (CFA) was performed (N = 428). Overall fit indices obtained presented adequate values which supported the four-factor model initially proposed [([Formula: see text] 2601.93) (p < 0.001); Root Mean Square Error of Approximation = 0.060 (CI = 0.056 -0.064)]. As regards reliability, the four dimensions of the ViDa1 demonstrated good internal consistency, with Cronbach's alphas ranging between 0.71 and 0.86. Evidence of convergent-discriminant validity in the form of high correlations with another specific HRQoL questionnaire for diabetes and low correlations with other constructs such as self-efficacy, anxiety, and depression were presented. The ViDa1 also discriminated between different aspects of clinical interest such as type of insulin treatment, presence of chronic complications, and glycemic control, temporal stability, and sensitivity to change after an intervention. In conclusion, the ViDa1 questionnaire presents adequate psychometric properties and may represent a good alternative for the evaluation of HRQoL in type 1 diabetes.

19.
Eur J Pharmacol ; 811: 155-163, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28577966

RESUMO

Amyloid fibrils, which are present in semen, were considered to be a cause of topical vaginal gel ineffectiveness in vivo after microbicides failed as HIV-1 prophylaxis. Therefore, it was necessary to determine whether a dendrimer was suitable for further evaluation in an in vitro model of semen-enhanced viral infection (SEVI). We demonstrated that SEVI in TZM.bl cell cultures increased the infectivity of R5-HIV-1NL(AD8), pTHRO.c and pCH058.c isolates, causing higher IC50 values for two polyanionic carbosilane dendrimers, G2-STE16 and G3-S16. However, both dendrimers maintained protection rates of 90% at non-toxic concentrations. When dendrimers were combined with Tenofovir/Maraviroc (TDF/MVC), the anti-HIV-1 effect remained at a minimum IC50 increase between 1- and 7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC50 values were slightly influenced by the presence of semen. In brief, dendrimers combined with antiretrovirals showed a synergistic effect. This result plays a crucial role in new microbicide formulations, as it overcomes the negative effects of amyloid fibrils.


Assuntos
Dendrímeros/química , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Sêmen/virologia , Silanos/química , Silanos/farmacologia , Amiloide/metabolismo , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Humanos , Sêmen/metabolismo
20.
Thromb Haemost ; 117(6): 1141-1149, 2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28276569

RESUMO

Acute coronary syndrome (ACS) is nowadays one of the leading causes of morbid-mortality in HIV-infected population, but innate and adaptive immune mechanisms preceding this event are unknown. In this work we comprehensively and longitudinally observed, by multiparametric flow cytometry and following a case-control design, increased CCR5+CD8+ T-cells levels and monocytes expressing activation and adhesion markers in HIV-infected patients who are going to suffer ACS. In addition, we found direct associations between activated CD8+ T-cells and myeloid cells that were only statistically significant in the group of patients with ACS and in the follow up time point just before the ACS. Our data highlight the important role of CCR5 in the onset of ACS and suggest this receptor as a marker of cardiovascular risk and potential therapeutic target to prevent the development of such non-AIDS-related event in HIV-infected patients.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/diagnóstico , HIV/fisiologia , Monócitos/imunologia , Receptores CCR5/metabolismo , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/imunologia , Adulto , Antirretrovirais/uso terapêutico , Estudos de Casos e Controles , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Prognóstico , Risco , Carga Viral
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