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INTRODUCTION: Respiratory syncytial virus (RSV) causes an acute respiratory illness similar to influenza, although there are few data comparing both of them in adults. The existence of clinical differences between these two infections could have implications for their management. MATERIALS AND METHODS: Retrospective observational cohort study including 63 adults with positive PCR for RSV and 221 for influenza during winter 2018-2019. Epidemiological, clinical characteristics and outcomes were contrasted between both groups. RESULTS: Compared to influenza, RSV-positive patients presented a higher association with active neoplasia (OR=2.9; 95% CI: 1.2-6.9), dependence for basic activities of daily living (OR=3.4; 95% CI: 1.4-8.2) and immunosuppression due to chronic glucocorticoid administration (OR=7.6; 95% CI: 1.6-36.1). At diagnosis, fever was less common (OR=0.3; 95% CI: 0.2-0.7), and C-reactive protein level ≥100mg/l was more frequent (OR=2.1; 95% CI: 1.0-4.5). They developed bacterial co-infection by Staphylococcus aureus in a higher proportion (OR=8.3; 95% CI: 1.5-46.9) and presented a greater need for admission to the intensive care unit (OR=5.4; 95% CI: 1.4-19.2). CONCLUSION: RSV is an important cause of respiratory illness in adults during the influenza season. It especially affects vulnerable patients with chronic underlying diseases, and has a higher morbidity than influenza. For all these reasons, specific detection, prevention and treatment of RSV is necessary in order to reduce the consumption of health care resources due to RSV disease in adults.
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Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Humanos , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Influenza Humana/diagnóstico , Estudos Retrospectivos , Atividades Cotidianas , Doença CrônicaRESUMO
This article aims to make visible a common non-oncologic pain condition in cancer patients. Myofascial pain syndrome can generate an increase in the symptomatic burden of the oncologic patient, increase the demand for opioid medication, and decrease the quality of life. We consider that health professionals involved in the care of cancer patients in its different stages should be aware of it, diagnose it, and treat it early to avoid processes of pain chronification, peripheral tissue modification, and deterioration of the functional condition of patients with oncologic diseases.
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Síndromes da Dor Miofascial , Neoplasias , Humanos , Qualidade de Vida , Síndromes da Dor Miofascial/diagnóstico , Síndromes da Dor Miofascial/terapia , Oncologia , Dor , Neoplasias/complicaçõesRESUMO
Dendrimers are multifunctional molecules with well-defined size and structure due to the step-by-step synthetic procedures required in their preparation. Dendritic constructs based on carbosilane scaffolds present carbon-carbon and carbon-silicon bonds, which results in stable, lipophilic, inert, and flexible structures. These properties are highly appreciated in different areas, including the pharmaceutical field, as they can increase the interaction with cell membranes and improve the therapeutic action. This article summarizes the most recent advances in the pharmaceutical applications of carbosilane dendritic molecules, from therapeutics to diagnostics and prevention tools. Dendrimers decorated with cationic, anionic, or other moieties, including metallodendrimers; supramolecular assemblies; dendronized nanoparticles and surfaces; as well as dendritic networks like hydrogels are described. The collected examples confirm the potential of carbosilane dendrimers and dendritic materials as antiviral or antibacterial agents; in therapy against cancer, neurodegenerative disease, or oxidative stress; or many other biomedical applications. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Dendrímeros , Nanoestruturas , Doenças Neurodegenerativas , Humanos , Preparações FarmacêuticasRESUMO
Resumen OBJETIVO: Estimar la cantidad de pacientes con irregularidades menstruales que se embarazaron luego de una cirugía bariátrica (manga gástrica) y describir los desenlaces de los embarazos. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos de pacientes obesas y con irregularidades menstruales intervenidas mediante cirugía bariátrica (manga gástrica). Se operaron entre el 1 de junio de 2014 y el 31 de diciembre de 2019 en el Centro Médico Imbanaco Cali, Colombia. RESULTADOS: De 1418 cirugías bariátricas, tipo manga gástrica, 117 pacientes cumplieron con los criterios de inclusión, 80 de ellas se localizaron telefónicamente y aceptaron incluirse al estudio. Luego de la manga gástrica, el 86.25% (n = 69) de las pacientes logró la regularización de sus ciclos menstruales. Además, el 31% (n = 25) consiguió el embarazo, 80% (n = 20) de ellas tenían la intención de buscar el embarazo. Los desenlaces de esos embarazos fueron favorables, con partos a término, con adecuado peso y talla al nacer. CONCLUSIONES: Después de la cirugía bariátrica, tipo manga gástrica, en mujeres con irregularidades menstruales, 25 de las 80 pacientes se embarazaron y los desenlaces obstétricos fueron satisfactorios. Sin duda, hacen falta más estudios prospectivos para poder afirmar, con una mejor representación estadística, las repercusiones de la disminución del peso corporal en la tasa de fertilidad.
Abstract OBJECTIVE: To estimate the number of patients with menstrual irregularities who became pregnant after bariatric surgery (gastric sleeve) and to describe the pregnancy outcomes. MATERIALS AND METHODS: Retrospective study of a series of cases of obese patients with menstrual irregularities who underwent bariatric surgery (gastric sleeve). They were operated between June 1, 2014 and December 31, 2019 at the Imbanaco Cali Medical Center, Colombia. RESULTS: Of 1418 bariatric surgeries, gastric sleeve type, 117 patients met the inclusion criteria, 80 of them were located by telephone and agreed to be included in the study. After gastric sleeve, 86.25% (n = 69) of the patients achieved regularization of their menstrual cycles. In addition, 31% (n = 25) achieved pregnancy, 80% (n = 20) of them intended to seek pregnancy. The outcomes of these pregnancies were favorable, with full-term deliveries, with adequate weight and height at birth. CONCLUSIONS: After bariatric surgery, gastric sleeve type, in women with menstrual irregularities, 25 of the 80 patients became pregnant and the obstetric outcomes were satisfactory. Undoubtedly, more prospective studies are needed to be able to affirm, with a better statistical representation, the repercussions of the decrease in body weight on the fertility rate.
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Enzyme immobilization is a powerful strategy for enzyme stabilization and recyclability. Materials covered with multipoint molecules are very attractive for this goal, since the number of active moieties to attach the enzyme increases with respect to monofunctional linkers. This work evaluates different dendrimers supported on silica to immobilize a protease enzyme, Alcalase. Five different dendrimers were employed: two carbosilane (CBS) dendrimers of different generations (SiO2-G0Si-NH2 and SiO2-G1Si-NH2), a CBS dendrimer with a polyphenoxo core (SiO2-G1O3-NH2), and two commercial polyamidoamine (PAMAM) dendrimers of different generations (SiO2-G0PAMAM-NH2 and SiO2-G1PAMAM-NH2). The results were compared with a silica support modified with a monofunctional molecule (2-aminoethanethiol). The effect of the dendrimer generation, the immobilization conditions (immobilization time, Alcalase/SiO2 ratio, and presence of Ca2+ ions), and the digestion conditions (temperature, time, amount of support, and stirring speed) on Alcalase activity has been evaluated. Enzyme immobilization and its activity were highly affected by the kind of dendrimer and its generation, observing the most favorable behavior with SiO2-G0PAMAM-NH2. The enzyme immobilized on this support was used in two consecutive digestions and, unlike CBS supports, it did not retain peptides released in the digestion.
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Dendrímeros , Dendrímeros/química , Dióxido de Silício/química , Enzimas Imobilizadas/químicaRESUMO
Current therapies against prostate cancer (PCa) disease, such as surgery, radiotherapy, or in last term chemical castration by androgen deprivation, have led to significant reduction of the incidence of PCa throughout the world. Worse prognosis is found in those patients which exhibit castration resistance, relapsing into the disease with even greater aggressiveness. Hypoxia cancer cell adaption has been observed to be closely connected to fatal prognostic tumor features. Therefore, hypoxia adaptive mechanisms of cancer cells have attracted large interest as a relevant biological target for treatment-resistant patients. Dendrimers have been established as a promising nanotechnological tool owing to their beneficial physicochemical features such as multivalency and monodispersity. Herein, we have completed a thorough study to better understand the effect within the cell of the already published ruthenium(II)-N-heterocyclic carbene metallodendrimer (G2Ru) that was able to drastically reduce HIF-1α stabilization and exhibited antiproliferative capability against androgen-sensitive (LNCaP) and androgen-resistant prostate cancer cells (LNFLU) in vitro. G2Ru, as well as its cationic imidazolium precursor (G2P), displayed scavenging properties against intracellular and externally stimulated ROS levels, which would presumably hinder the stabilization of HIF-1α by prolyl hydroxylase (PHD) inhibition. Furthermore, these dendrimers have shown considerably beneficial properties against tumor progression capability in terms of apoptosis, cell cycle, CSCs expression, and epithelial phenotype promotion. Taken all together, in this study we could demonstrate the extraordinary anticancer properties of NHC-based carbosilane dendrimers against androgen-resistant prostate cancer cells in vitro.
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Androgênios , Neoplasias da Próstata , Humanos , Masculino , Androgênios/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Fator A de Crescimento do Endotélio Vascular , Antagonistas de Androgênios , Linhagem Celular Tumoral , Transdução de Sinais , Ciclo Celular , HipóxiaRESUMO
Introducción: Los profesionales del área de la salud tienen un riesgo incrementado de contraer la infección por el virus de hepatitis B (VHB). Objetivo: Evaluar anticuerpos contra el antígeno de superficie de la hepatitis B, en los residentes de pediatría del Hospital Central de Maracay en el período junio-agosto de 2021. Materiales y métodos: Estudio clínico epidemiológico, no experimental y de corte transversal, en el que se tomó muestra sanguínea a 54 médicos residentes para la determinación de anticuerpos contra el antígeno de superficie del VHB (Anti-HBs). Resultados: El promedio de edad fue 27,48 años con una desviación estándar de 1,6. El 83,33 % pertenecían al sexo femenino, 51,85.% cursaban el 1er año del posgrado, 33,33 % con esquema de vacunación documentado, de estos, 66,67.% completaron el esquema y 77,78 % cumplidos en la adultez. Con respecto al tiempo de la última dosis, el 66,67 % hasta 10 años. Se detectaron niveles de Anti-HBs mayores de 10 mUl/mL en el 94,44 %, con mayor prevalencia de niveles protectores a favor del sexo femenino. Se evidenció una correlación lineal positiva entre los niveles de Anti-HBs y el tiempo desde la última dosis de la vacuna contra la hepatitis B. Conclusiones: Aunque existe una debilidad en los médicos residentes en cuanto a la tenencia y cumplimiento del esquema de inmunización, la mayoría de ellos mostraron niveles protectores de anti-HBs. A mayor tiempo transcurrido desde la última dosis de la vacuna hay un descenso en los niveles de anti-HBs lo que justifica dosis de refuerzo a los 10 años.
Introduction: Health professionals have an increased risk of contracting hepatitis B virus infection (HBV). Objective: To evaluate antibodies against hepatitis B surface antigen in residents of pediatrics of the Central Hospital of Maracay in the period June-August. 2021. Materials and methods: Clinical epidemiological, nonexperimental and cross-sectional study, in which blood samples were taken from fifty-four medical residents for the determination of antibodies against the HBV surface antigen. Results: The average age was 27.48 years with a standard deviation of 1.6. 83.33 % were female, 51.85 % were in the first year of postgraduate studies, 33.33 % had a documented vaccination schedule, of these, 66.67 % completed the schedule and 77.78 % completed it in adulthood. Regarding the time of the last dose, for 66.67 % of the study population, it was up to 10 years ago. Anti-HBs levels greater than 10mUl/ml were detected in 94.44 %, with a higher prevalence of protective levels in favor of the female sex. A positive linear correlation between the levels of Anti-HBs and the time since the last dose of the hepatitis B vaccine was evidenced. Conclusions: Although there is a weakness in the resident doctors in terms of possession and compliance with the immunization schedule, the most of them showed protective levels of anti-HBs. The longer the time elapsed since the last dose of the vaccine, there is a decrease in anti-HBs levels, which justifies a booster dose at 10 years.
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Reactive oxygen species (ROS) play a critical role in different human pathophysiological processes. ROS, together with nitrogen reactive species, generated as by-products of cellular metabolism or external factors, affects intracellular redox homeostasis. Redox-active groups found in proteins and other compounds such as polyphenols are involved in maintaining intracellular redox homeostasis. In this work, a new family of heterofunctional first-generation carbosilane dendrons functionalised with different polyphenols at the focal point and dimethylammonium groups at the periphery has been obtained through two synthetic strategies: reductive amination and straightforward amidation reaction. Their antioxidant activity has been evaluated through two spectrophotometric methods: ferric reducing antioxidant power (FRAP) assay and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay to establish a correlation between the number of hydroxyl groups and the antioxidant activity.
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Background: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem. Methods: Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy). Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer. Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.
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Carcinoma , Rosa Bengala , Humanos , Rosa Bengala/química , Rosa Bengala/farmacologia , Silanos/farmacologia , Triazinas/farmacologiaRESUMO
Cancer is one of the most important problems of modern medicine. At the present time, gene therapy has been developed against cancer, which includes the delivery of anticancer small interfering RNAs (siRNAs) directed at cancer proteins. The prospect of creating drugs based on RNA interference implies the use of delivery systems. Metal nanoparticles are the most studied objects for medicine, including their application as non-viral vectors. We have synthesized gold nanoparticles (AuNPs) modified with cationic carbosilane dendrons of 1-3 generations, with a positive charge on the surface, gold nanoparticles can effectively bind small interfering RNAs. Using a photometric viability test and flow cytometry, we assessed the ability of dendronized gold nanoparticles in delivering siRNAs to tumor cells. The efficiency of the complexes in initiating apoptosis was measured and, also, the overall effect of proapoptotic siRNA on cells. AuNP15 has both the highest efficacy and toxicity. The delivery efficiency in suspension cell lines was 50-60%. Complexes with targeted siRNA decreased cell viability by 20% compared to control and initiated apoptosis.
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Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APDDD (-61 [-148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p < 0.001), but not in APDWD (81 [-8, 176], 81 [-4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.
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Modelos Biológicos , Monitorização Fisiológica , Diálise Peritoneal , Peritônio/patologia , Água , Adulto , Idoso , Automação , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Numérica Assistida por Computador , Ultrafiltração , Adulto JovemRESUMO
With the purpose of obtaining a new dendritic system against cancer, this paper is focused on the synthesis of spherical carbosilane metallodendrimers of different generations holding Ru(II) N-heterocyclic carbene (NHC) on the periphery from the imidazolium precursors. Both imidazolium salt dendrimers and their metallodendrimers counterparts showed promising anticancer activity, similar to cisplatin, mainly at high generations. In addition, both families of second and third generations were able to form dendriplexes with anticancer small interfering RNA (siRNA), protecting the cargo against RNAse and being able to internalize it in HEPG2 (human liver cancer) tumour cells. The characterization and effectiveness of the dendriplexes were evaluated by various analytical techniques such as zeta potential, electrophoresis and circular dichroism, the stability of the system and the protective nature of the dendrimer estimated using RNAse and the internalization of dendriplexes by confocal microscopy. The major advantage observed with the ruthenium metallodendrimers with respect to the imidazolium salts precursors was in cellular uptake, where the internalization of Mcl-1-FITC siRNA (myeloid cell leukaemia-1 fluorescein labelled siRNA) proceeded more efficiently. Therefore, we propose here that both imidazolium and Ru metallodendrimers are interesting candidates in cancer due to their double action, as anticancer per se and as carrier for anticancer siRNA, providing in this way a combined action.
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Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Dendrímeros/farmacologia , Portadores de Fármacos/farmacologia , Compostos Organometálicos/farmacologia , RNA Interferente Pequeno/farmacologia , Antineoplásicos/síntese química , Complexos de Coordenação/síntese química , Dendrímeros/síntese química , Portadores de Fármacos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Imidazóis/síntese química , Imidazóis/farmacologia , Compostos Organometálicos/síntese química , Rutênio/químicaRESUMO
Salmorejo is a traditional Spanish food made of raw tomatoes, bread, garlic, and virgin olive oil. The food industry aims to satisfy consumer demand for ready-to-eat salmorejo while trying to maintain characteristics of the homemade product. In this work, we have assessed physical-chemical and color parameters, radical scavenging activity, and total polyphenol, lycopene, and ß-carotene contents of raw and pasteurized commercial salmorejo, as well as homemade (raw) salmorejo samples. Our results showed that heat treatment had a significant influence on color parameters of salmorejo, with pasteurized samples being less red and exhibiting an increase in the degree of browning. Pasteurized samples also showed the highest radical scavenging activity when expressing the results per dry weight. However, when water content was considered, radical scavenging activity was superior in homemade samples when analyzing non-polar molecules extracted with acetone. Results were similar for polyphenol content. It was also observed that heat treatment affected lycopene but not ß-carotene content. When acquiring commercial salmorejo at the supermarket, consumers have the option to choose between already prepared pasteurized or raw salmorejo. According to the results obtained in this work, physicochemical and functional properties of commercial raw salmorejo were comparable to a larger extent than pasteurized salmorejo compared to those exhibited by homemade salmorejo samples.
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Objetivo: Determinar la asociación entre las condiciones laborales y el acceso al equipo de protección personal (EPP) en profesionales de la salud de la ciudad de Lima-Perú. Métodos: Estudio descriptivo, transversal y analítico. La muestra fue de 323 encuestados virtualmente en la ciudad de Lima, que cumplieron los criterios de selección, captados entre el 09/07/2020 al 09/08/2020. El instrumento de recolección de datos fue validado por juicio de expertos con un puntaje >80% (validez de contenido). Se realizó un análisis con el modelo lineal generalizado de familia Poisson, función de enlace log, modelos robustos con ajuste. Se consideró un valor estadísticamente significativo de p<0,05. Resultados: El 52% de los profesionales de la salud (PS) trabajaron más de 12 horas y solo el 55% recibieron un EPP por día de trabajo. El 50,9% del PS casi nunca recibió una mascarilla. En el análisis multivariado el PS con edades <26 años (p=0,00) y de 26 a 55 años (p=0,00) recibieron un EPP incompleto. Los PS que no tenían un vínculo laboral con la institución (p=0,006) y los que trabajaban en áreas de poco contacto con pacientes COVID-19 (p=0,022) recibieron una mascarilla en pocas oportunidades. Conclusión: Los profesionales de la salud menores de 56 años recibieron con poca frecuencia un EPP. Cuando trabajan sin un vínculo laboral y pertenecen a áreas de poco contacto con pacientes COVID-19, reciben algunas veces una mascarilla.
Objective: To determine the association between working conditions and access to personal protective equipment (PPE) in health personnel in the city of Lima-Perú. Methods: Descriptive, cross-sectional and analytical study. The sample was of 323 respondents virtually in the city of Lima, who met the selection criteria, captured between 07/09/2020 to 08/09/2020. The data collection instrument was validated by expert judgment with a score> 80% (content validity). An analysis was carried out with the generalized linear model of the poisson family, log link function, robust models with fit. A statistically significant value of p <0.05 was considered. Results: 52% of health personnels (HP) worked more than 12 hours and only 55% received one PPE per work day. 50.9% of the HCP almost never received a mask. In the multivariate analysis, the SP with ages <26 years (p=0.00) and from 26 to 55 years (p=0.00) received an incomplete PPE. HP who did not have an employment relationship with the institution (p=0.006) and those who worked in areas with little contact with COVID-19 patients (p=0.022) received a mask on few occasions. Conclusion: Health personnels under 56 years of age rarely received PPE. When they work without an employment relationship and belonged to areas with little contact with COVID-19 patients, they sometimes received a mask.
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Antibodies are macromolecules that specifically recognize their target, making them good candidates to be employed in various therapies. The possibility of attaching a drug to an immunoglobulin makes it possible to release it specifically into the affected tissue as long as it overexpresses the target. However, chemical coupling could affect the functionality (specificity and affinity) of the antibody. It has been observed that the use of intermediaries, such as dendrimers, could resolve this issue. Because carbosilane dendrimers have aroused great interest in the field of biomedicine, this report describes the synthesis of an anionic carbosilane dendrimer with a fluorochrome on its surface that then forms a conjugate with an antibody. It has been used as immunoglobulin and infliximab, whose target is TNF-α, which is a cytokine that is overexpressed in the inflamed area or even in the blood of patients with autoimmune diseases, such as rheumatoid arthritis. In addition, the integrity and functionality of the antibody has been studied to see if they have been affected after the chemical coupling process.
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Artrite Reumatoide/tratamento farmacológico , Dendrímeros/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Infliximab/uso terapêutico , Nanomedicina Teranóstica , Dendrímeros/síntese química , Infliximab/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Resumen Introducción: Las personas con diálisis de mantenimiento se consideran una población en alto riesgo de infección por SARS-CoV-2, complicaciones y muerte. La periodicidad de la diálisis, la organización y la demanda en las unidades de diálisis y las limitaciones de alfabetización en salud poblacional limitan el cumplimiento del aislamiento y el distanciamiento social. Objetivo: Desarrollar, mediante un consenso de expertos, recomendaciones informadas en evidencia para la prevención, el diagnóstico y el manejo de la infección por SARS-CoV-2/COVID-19 en pacientes con enfermedad renal crónica. Materiales y métodos: Se realizó una revisión rápida de literatura en Pubmed, Embase y sociedades científicas. La calidad de evidencia fue evaluada según el tipo de estudio incluido. El acuerdo se definió para cada recomendación con umbral de al menos 70% de aprobación. La fuerza de las recomendaciones fue graduada como fuerte o débil. Resultados: El colectivo fue consultado entre el 17 y 19 de mayo de 2020. Se obtuvo respuesta de 44 expertos clínicos que declararon conflicto de interés previo a la consulta. El acuerdo de las recomendaciones estuvo entre 70,5 y 100%. Se presentan las recomendaciones de un colectivo experto para la prevención, el diagnóstico y el manejo de infección por SARS-CoV-2/COVID-19 en pacientes con enfermedad renal crónica. Conclusión: Debido a la reciente aparición de la infección por SARS-CoV-2 y las incertidumbres respecto a la prevención, el diagnóstico y el manejo, las recomendaciones presentadas se conciben como un estándar colombiano que permita garantizar un cuidado centrado en las personas con enfermedad renal crónica y la protección de los profesionales de la salud.
Abstract Introduction: People with chronic dialysis are considered a population at high risk of SARS CoV2 infection and its derived complications and death. The need to go to strict dialysis schedules, the high demand in the kidney facilities and the difficulties derived from the time and space organization in the rooms in the face to the pandemic added to the difficult learning, teaching and adapting new protocols manifest the needed of standard recommendation according to this problem in people who couldn't have an ideal isolation. Objective: Develop through an expert consensus, evidence-informed recommendations for the prevention, diagnosis, and management of SARS-CoV-2/COVID-19 infection in patients with chronic kidney disease on Dialysis. Materials and methods: We carried out a quick literature review, PubMed, Embase and scientific societies were consulted. The quality of the evidence was considered according to the type of study included. The agreement threshold defined for each recommendation was > 70% approval among experts. The strength of the recommendations was rated as strong or weak. Results: Between May 17 and 19, 2020, was conformed a team of 44 clinical experts who declared their interest conflict prior to the consultation. The agreement of the recommendations was between 70.5% and 100%. The recommendations were separated in prevention, early identification, and diagnostic, isolation in hemodialysis facilities and peritoneal dialysis, and team protection. Ethical considerations also were included. Conclusion: Due to the recent appearance of SARS-CoV-2 infection and the uncertainties regarding prevention, diagnosis and management, the recommendations presented are conceived as a Colombian standard that allows guaranteeing focused care for people with chronic kidney disease and the protection of health team.
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Humanos , Masculino , Feminino , Insuficiência Renal Crônica , COVID-19 , Pacientes , Diálise Renal , Colômbia , DiagnósticoRESUMO
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer.
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Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species-triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.
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A family of heterofunctional Schiff base carbosilane metallodendrons with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) at the focal point and dimethylamino groups on the periphery are described. The new systems have proved their ability to interact with biological molecules such as Human Serum Albumin (HSA) without affecting its secondary structure and erythrocytes membranes, causing haemolysis in a dose and generation dependent way. The combination of two active functional groups in one single dendritic platform has shown a cooperative effect in the viability of HeLa and PC-3 cells, with the second generation derivative standing out as the most promising with the lowest IC50. Experiments focused on advanced prostate cancer have shown an antimetastasic activity for those metallodendrons, hindering the adhesion of cells in one of the main targets of metastasis, bones, and inhibiting cell migration. Finally, the second generation metallodendron with one single metal centre and four dimethylamino groups on the dendritic wedge, was selected for an ex vivo experiment in nude mice with advanced prostate cancer inhibiting the tumour growth in a 40% compared to control mice.