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1.
Small ; 19(50): e2303934, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37632323

RESUMEN

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.


Asunto(s)
Neoplasias de la Mama , Nanocáscaras , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/metabolismo , Proteínas Proto-Oncogénicas c-akt , Oro , Receptor ErbB-2/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , ARN Interferente Pequeño , Línea Celular Tumoral
2.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36361892

RESUMEN

Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.


Asunto(s)
Hipertermia Inducida , Nanotubos , Neoplasias , Humanos , Oro , Células HeLa , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Fototerapia
3.
J Environ Manage ; 311: 114839, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35255326

RESUMEN

Rethinking of plastic rigid shampoo bottles based on "Design for the Environment" concepts is proposed. Bottles of most consumed shampoo brands with different capacities were selected. Bottle weight/capacity ratio was assessed and compression mechanical properties were evaluated. Oversizing of bottles and high amounts of material used in caps only for aesthetic purposes was proved. The analysis confirmed the need to change marketing strategies based on aesthetic attractiveness by an ecodesign based on functionality and sustainability aspects. The use of single material for the overall bottle is recommended, and it seems that HDPE is more suitable as it is appropriate to make all bottle parts, is recyclable, and has a low price/performance relationship. From a marketing point of view, a proper ecodesign would lead to a paradigm shift from an aesthetic approach to a sustainable one, in line with the environmental awareness of today's consumer.

4.
J Nanobiotechnology ; 18(1): 85, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32503549

RESUMEN

BACKGROUND: The unique upconversion properties of rare-earth-doped nanoparticles offers exciting opportunities for biomedical applications, in which near-IR remote activation of biological processes is desired, including in vivo bioimaging, optogenetics, and light-based therapies. Tuning of upconversion in purposely designed core-shell nanoparticles gives access to biological windows in biological tissue. In recent years there have been several reports on NIR-excitable upconverting nanoparticles capable of working in biological mixtures and cellular settings. Unfortunately, most of these nanosystems are based on ytterbium's upconversion at 980 nm, concurrent with water's absorption within the first biological window. Thus, methods to produce robust upconverting nanoplatforms that can be efficiently excited with other than 980 nm NIR sources, such as 808 nm and 1064 nm, are required for biomedical applications. RESULTS: Herein, we report a synthetic method to produce aqueous stable upconverting nanoparticles that can be activated with 808 nm excitation sources, thus avoiding unwanted heating processes due to water absorbance at 980 nm. Importantly, these nanoparticles, once transferred to an aqueous environment using an amphiphilic polymer, remain colloidally stable for long periods of time in relevant biological media, while keeping their photoluminescence properties. The selected polymer was covalently modified by click chemistry with two FDA-approved photosensitizers (Rose Bengal and Chlorin e6), which can be efficiently and simultaneously excited by the light emission of our upconverting nanoparticles. Thus, our polymer-functionalization strategy allows producing an 808 nm-activable photodynamic nanoplatform. These upconverting nanocomposites are preferentially stored in acidic lysosomal compartments, which does not negatively affect their performance as photodynamic agents. Upon 808 nm excitation, the production of reactive oxidative species (ROS) and their effect in mitochondrial integrity were demonstrated. CONCLUSIONS: In summary, we have demonstrated the feasibility of using photosensitizer-polymer-modified upconverting nanoplatforms that can be activated by 808 nm light excitation sources for application in photodynamic therapy. Our nanoplatforms remain photoactive after internalization by living cells, allowing for 808 nm-activated ROS generation. The versatility of our polymer-stabilization strategy promises a straightforward access to other derivatizations (for instance, by integrating other photosensitizers or homing ligands), which could synergistically operate as multifunctional photodynamic platforms nanoreactors for in vivo applications.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Polímeros , Química Clic , Estabilidad de Medicamentos , Células HeLa , Humanos , Rayos Infrarrojos , Espacio Intracelular/química , Sustancias Luminiscentes/química , Sustancias Luminiscentes/farmacocinética , Sustancias Luminiscentes/efectos de la radiación , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/efectos de la radiación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacocinética , Fármacos Fotosensibilizantes/efectos de la radiación , Polímeros/química , Polímeros/farmacocinética , Polímeros/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo
5.
Mol Pharm ; 16(8): 3374-3385, 2019 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-31188622

RESUMEN

The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.


Asunto(s)
Portadores de Fármacos/química , Nanopartículas del Metal/química , Neoplasias/terapia , ARN Interferente Pequeño/administración & dosificación , Tratamiento con ARN de Interferencia/métodos , Técnicas de Silenciamiento del Gen , Genes Reporteros/genética , Oro/química , Proteínas Fluorescentes Verdes/genética , Células HeLa , Humanos , Nanotubos/química , Neoplasias/genética , Polilisina/química , Poliestirenos , ARN Interferente Pequeño/genética
6.
J Environ Manage ; 217: 381-390, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29626841

RESUMEN

The aim of this work is to develop compatibilization strategies for High Impact Polystyrene (HIPS)/ Acrylonitrile-Butadiene-Styrene (ABS) blends from WEEE in order to add value to these recycled plastics by improving their mechanical performance. Results from a screening study of HIPS/ABS blends compatibilization by the addition of Styrene-Butadiene Rubber (SBR) are presented. Two different weight proportion of HIPS/ABS physical blends were analyzed, 80/20 and 20/80, with three different concentration of SBR: 2, 10 and 20 wt%. Compatibilization efficiency was analyzed from an accurate thermal and mechanical analysis, by comparing each physical blend and corresponding compatibilized blends with SBR. Results were discussed relating glass transition changes with mechanical performance, both aspects were interpreted in terms of blend morphology. Phase and fillers dispersion and distribution as well as SBR amount and its interaction with each phase were accurate analyzed. Compatibilization of HIPS/ABS blends from WEEE with the addition of SBR is effective in blends with HIPS as main component. With the addition of 2 wt% of SBR, strength and toughness have notably increased respect to the corresponding physical blend, 244% and 186% respectively. From this screening study is possible to infer that SBR is a sustainable and efficient compatibilizer of HIPS rich blends allowing to obtain a final blend that can be used as a replacement material of separated resins from WEEE.


Asunto(s)
Butadienos , Elastómeros , Residuos Electrónicos , Estirenos , Acrilonitrilo , Poliestirenos
7.
J Microencapsul ; 34(3): 231-242, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28449614

RESUMEN

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.


Asunto(s)
Preparaciones de Acción Retardada , Portadores de Fármacos/química , Isotiocianatos/administración & dosificación , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Línea Celular Tumoral , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
8.
Muscle Nerve ; 53(4): 617-25, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26316168

RESUMEN

INTRODUCTION: Numerous rehabilitation treatments have been shown to be useful for peripheral and central restoration after (PNI). METHODS: After sciatic nerve crush, we investigated 4 weeks of endurance training (ET) and balance and coordination training (BCT) with sciatic function index, hind-paw stride length, and spinal cord dorsal horn synaptophysin and neurotrophin-3 immunoreactivity. RESULTS: Our results demonstrated no significant differences between the non-trained (NT), ET, and BCT groups in sciatic functional index, and in stride-length analysis, but the ET showed higher values compared with the NT group. Synaptophysin immunoreactivity was higher in the BCT group compared with the NT group, and neurotrophin-3 immunoreactivity in the BCT group was greater compared with the other groups. CONCLUSION: BCT can positively affect spinal cord plasticity after a (PNI), and these modifications are important in the rehabilitation process.


Asunto(s)
Neurotrofina 3/metabolismo , Condicionamiento Físico Animal/fisiología , Equilibrio Postural/fisiología , Neuropatía Ciática/metabolismo , Médula Espinal/metabolismo , Sinaptofisina/metabolismo , Animales , Vértebras Lumbares , Masculino , Actividad Motora/fisiología , Compresión Nerviosa/métodos , Neurotrofina 3/análisis , Condicionamiento Físico Animal/métodos , Resistencia Física/fisiología , Desempeño Psicomotor/fisiología , Ratas , Ratas Wistar , Médula Espinal/química , Sinaptofisina/análisis
9.
Muscle Nerve ; 51(1): 83-91, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24752648

RESUMEN

INTRODUCTION: Different rehabilitation treatments have proven useful in accelerating regeneration. METHODS: After sciatic nerve crush in rats, we tested balance and coordination training (BCT) and endurance training (ET) through sensorimotor tests and analyzed nerve and muscle morphology. RESULTS: After BCT and ET, rats performed better in sensorimotor tests than did non-trained animals. However, only BCT maintained sensorimotor function during training. Furthermore, BCT and ET produced significantly larger muscle area than in non-trained animals. CONCLUSIONS: These findings indicate that BCT and ET, when initiated in the early phase after sciatic nerve injury, improve morphological properties of the soleus muscle and sciatic nerve, but only the task-oriented BCT maintained sensorimotor function. The success of rehabilitative strategies appears to be highly task-specific, and strategies that stimulate sensory pathways are the most effective in improving balance and/or coordination parameters.


Asunto(s)
Terapia por Ejercicio/métodos , Resistencia Física/fisiología , Equilibrio Postural/fisiología , Desempeño Psicomotor/fisiología , Neuropatía Ciática/fisiopatología , Neuropatía Ciática/rehabilitación , Animales , Modelos Animales de Enfermedad , Locomoción/fisiología , Masculino , Músculo Esquelético/patología , Compresión Nerviosa/métodos , Fibras Nerviosas Mielínicas/patología , Ratas , Ratas Wistar , Recuperación de la Función/fisiología , Neuropatía Ciática/patología
10.
ScientificWorldJournal ; 2015: 258424, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26421310

RESUMEN

This study analyzes the occurrence and distribution of phylogenetic groups of 391 strains of Escherichia coli isolated from poultry, cattle, and water buffalo. The frequency of the phylogroups was A = 19%, B1 = 57%, B2 = 2.3%, C = 4.6%, D = 2.8%, E = 11%, and F = 3.3%. Phylogroups A (P < 0.001) and F (P = 0.018) were associated with E. coli strains isolated from poultry, phylogroups B1 (P < 0.001) and E (P = 0.002) were associated with E. coli isolated from cattle, and phylogroups B2 (P = 0.003) and D (P = 0.017) were associated with E. coli isolated from water buffalo. This report demonstrated that some phylogroups are associated with the host analyzed and the results provide knowledge of the phylogenetic composition of E. coli from domestic animals.


Asunto(s)
Enfermedades de los Bovinos/microbiología , Infecciones por Escherichia coli/veterinaria , Escherichia coli/clasificación , Genes Bacterianos , Filogenia , Enfermedades de las Aves de Corral/microbiología , Animales , Búfalos , Bovinos , Enfermedades de los Bovinos/patología , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/microbiología , Genotipo , Reacción en Cadena de la Polimerasa , Aves de Corral , Enfermedades de las Aves de Corral/patología , Factores de Virulencia/genética
11.
Mem Inst Oswaldo Cruz ; 109(7): 887-98, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25410992

RESUMEN

The role played by different mammal species in the maintenance of Trypanosoma cruzi is not constant and varies in time and place. This study aimed to characterise the importance of domestic, wild and peridomestic hosts in the transmission of T. cruzi in Tauá, state of Ceará, Caatinga area, Brazil, with an emphasis on those environments colonised by Triatoma brasiliensis. Direct parasitological examinations were performed on insects and mammals, serologic tests were performed on household and outdoor mammals and multiplex polymerase chain reaction was used on wild mammals. Cytochrome b was used as a food source for wild insects. The serum prevalence in dogs was 38% (20/53), while in pigs it was 6% (2/34). The percentages of the most abundantly infected wild animals were as follows: Thrichomys laurentius 74% (83/112) and Kerodon rupestris 10% (11/112). Of the 749 triatomines collected in the household research, 49.3% (369/749) were positive for T. brasiliensis, while 6.8% were infected with T. cruzi (25/369). In captured animals, T. brasiliensis shares a natural environment with T. laurentius, K. rupestris, Didelphis albiventris, Monodelphis domestica, Galea spixii, Wiedomys pyrrhorhinos, Conepatus semistriatus and Mus musculus. In animals identified via their food source, T. brasiliensis shares a natural environment with G. spixii, K. rupestris, Capra hircus, Gallus gallus, Tropidurus oreadicus and Tupinambis merianae. The high prevalence of T. cruzi in household and peridomiciliar animals reinforces the narrow relationship between the enzootic cycle and humans in environments with T. brasiliensis and characterises it as ubiquitous.


Asunto(s)
Enfermedad de Chagas/transmisión , Reservorios de Enfermedades/parasitología , Insectos Vectores/fisiología , Triatoma/parasitología , Trypanosoma cruzi/fisiología , Distribución Animal , Animales , Brasil , Gatos , Enfermedad de Chagas/sangre , Pollos/parasitología , Didelphis/parasitología , Perros , Ecosistema , Composición Familiar , Cabras/parasitología , Interacciones Huésped-Parásitos , Lagartos/parasitología , Mephitidae/parasitología , Ratones , Monodelphis/parasitología , Reacción en Cadena de la Polimerasa Multiplex , Roedores/parasitología , Población Rural , Porcinos/parasitología , Triatoma/clasificación
12.
Water Sci Technol ; 69(3): 640-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24552739

RESUMEN

Talc is proposed as a low-cost mineral for wastewater clarification. In this sense, adsorption of methylene blue (MB) from aqueous solutions was studied comparatively by using sepiolite (qualified as very good adsorbent) and two talc samples with different particle size and purity degree. The MB adsorption was assessed by determining remnant dye in the supernatant using UV-vis spectroscopy and by detecting dye adsorbed on mineral samples through thermogravimetric analysis and infrared spectroscopy. Both isothermal curves and kinetic studies demonstrate that talc is a good dye adsorbent. Particularly, with dye concentrations similar to those of textile wastewater, talc was demonstrated to adsorb the same dye content of sepiolite at similar times. Natural talc could be employed as a low-cost alternative in wastewater treatment for the removal of cationic dyes.


Asunto(s)
Azul de Metileno/aislamiento & purificación , Talco/química , Aguas Residuales/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Estudios de Factibilidad , Cinética , Tamaño de la Partícula
13.
Rev Esc Enferm USP ; 48 Spec No: 67-73, 2014 Aug.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-25517837

RESUMEN

A qualitative study was conducted with semi-structured interviews with the aim of understanding the experience of children and adolescents under palliative care when managing pain daily and how they describe the intensity, quality and location of pain. We used Piaget's theory of cognitive development as a theoretical framework and oral history as a methodological framework. We found four themes: describing pain; seeking a life closer to normality, despite pain and disease; using a variety of alternatives for pain control; and living with damaged physical appearance. Although pain is a limiting factor in the lives of children and adolescents, we found that they faced their daily pain and still had a life beyond pain and illness. In addition, we highlight the relevance of nurses' understanding that effective management of pain in children is essential for a normal life and less suffering.

14.
Polymers (Basel) ; 16(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38732764

RESUMEN

A polyethylene (PE) film surface modification method is proposed via benzoic acid (BA) alkylation grafting to improve the surface affinity to polar substances. The procedure involves sequentially spraying AlCl3 and BA onto the heat-softened PE surface. The occurrence of the alkylation reaction was evaluated through comparative chemical, morphological, and thermal analyses. It was demonstrated that the grafting reaction of BA onto the PE film surface took place, limited to the surface layer, while preserving the bulk properties of PE. The reaction resulted in the formation of aluminum benzoate complexes, which improved the surface affinity to polar compounds. The impact of grafting on the surface properties of PE was further assessed by comparing the behavior of PE films treated with BA and untreated PE films when painted with watercolors. The PE film grafted with BA exhibited increased affinity towards watercolors, providing strong evidence of a change in surface polarity from hydrophobic to hydrophilic. These findings indicate that the proposed methodology effectively renders the PE surface paintable, even with non-toxic water-based inks, making it suitable for applications such as packaging.

15.
J Colloid Interface Sci ; 668: 575-586, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691966

RESUMEN

Lanthanide-doped up-converting nanoparticles (UCNPs) have emerged as promising biomedical tools in recent years. Most research efforts were devoted to the synthesis of inorganic cores with the optimal physicochemical properties. However, the careful design of UCNPs with the adequate surface coating to optimize their biological performance still remains a significant challenge. Here, we propose the functionalization of UCNPs with four distinct types of surface coatings, which were compared in terms of the provided colloidal stability and resistance to degradation in different biological-relevant media, including commonly avoided analysis in acidic lysosomal-mimicking fluids. Moreover, the influence of the type of particle surface coating on cell cytotoxicity and endocytosis/exocytosis was also evaluated. The obtained results demonstrated that the functionalization of UCNPs with poly(isobutylene-alt-maleic anhydride) grafted with dodecylamine (PMA-g-dodecyl) constitutes an outstanding strategy for their subsequent biomedical application, whereas poly(ethylene glycol) (PEG) coating, although suitable for colloidal stability purposes, hinders extensive cell internalization. Conversely, surface coating with small ligand were found not to be suitable, leading to large degradation degrees of UCNPs. The analysis of particle' behavior in different biological media and in vitro conditions here performed pretends to help researchers to improve the design and implementation of UCNPs as theranostic nanotools.


Asunto(s)
Endocitosis , Nanopartículas , Propiedades de Superficie , Endocitosis/efectos de los fármacos , Humanos , Nanopartículas/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Polietilenglicoles/química
16.
J Palliat Med ; 27(4): 503-507, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387013

RESUMEN

Background: The pediatric palliative care (PPC) sets up an interdisciplinary approach of chronic complex diseases throughout birth to adolescence. It encompasses countless contrasts in development and diagnosis scopes, which make this area a challenge to nonpediatric practitioners. Objective: We sought to assess the most prevalent diseases in follow-up of the PPC team. Methods: We analyzed the medical records of PPC clinic during the years 2001 and 2021 and the diagnosis of outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC. Results: The most prevalent diseases were epidermolysis bullosa (36.9%), followed by neurological Inherited Errors of Metabolism (IEM) diseases (19.0%), IEM diseases (14.3%), dysmorphological and chromosomal disorders (8.5%), skeletal disorders mainly osteogenesis imperfecta (6.9%), and liver transplantation conditions (5.5%) (p < 0.001). The less frequent conditions were external causes, such as neonatal insults or traffic accidents (2.8%), cancer (1.7%), congenital cardiopathies (1.4%), congenital infectious diseases (1.1%), gastrointestinal and hepatic conditions (0.8%), and rheumatological conditions (0.3%). The patients were older at diagnosis (6.9 years) and at PPC referral (13.2 years) than patients with epidermolysis bullosa and skeletal disorders and dysmorphological and chromosomal disorders were younger on referral. Conclusion: There are a lot of complex chronic conditions which could benefit from palliative care in pediatric setting. However, epidemiological and symptomatological assessment of the health service is necessary to provide an appropriate care to the country's reality.


Asunto(s)
Trastornos de los Cromosomas , Epidermólisis Ampollosa , Recién Nacido , Adolescente , Niño , Humanos , Cuidados Paliativos , Brasil/epidemiología , Hospitales , Enfermedad Crónica
17.
An Bras Dermatol ; 99(3): 350-356, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38368142

RESUMEN

BACKGROUND: Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. OBJECTIVE: To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. METHODS: Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. RESULTS: 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). STUDY LIMITATIONS: Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). CONCLUSION: Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.


Asunto(s)
Epidermólisis Ampollosa , Secuenciación del Exoma , Humanos , Masculino , Femenino , Brasil , Niño , Preescolar , Epidermólisis Ampollosa/genética , Epidermólisis Ampollosa/patología , Adolescente , Colágeno Tipo VII/genética , Biopsia , Adulto Joven , Adulto , Mutación , Lactante , Piel/patología , Persona de Mediana Edad , Queratina-5/genética
18.
JIMD Rep ; 65(3): 182-187, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736637

RESUMEN

The interface between pediatric palliative care (PPC) and inborn metabolic diseases (IMD) remains incipient, though these conditions fill the state of art of complex chronic diseases, eligible to this health approach. We analyzed the medical records of PPC clinic during the years 2001 to 2021 and the IMD outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC and IMD. Among outpatients, 14% were diagnosed with IMD, which were referred to the PPC service earlier compared to Non-IMD cases. The Group 3 (complex molecules) was the most frequent (64.7%), following by Group 1 representing by small molecules (21.6%), the latter having a lower median age at diagnosis when compared to the former (0.7 vs. 5.2 years, p = 0.001). The sphingolipidoses were the pathologies most frequent in our cohort, in line with what was observed in the literature. There were no differences between IMD groups in terms of diagnosis and PPC referral age, however in Non-IMD conditions, the age of diagnosis were earlier than IMD. Nevertheless, IMD group showed lower age of referral to PPC. The IMD comprises large fraction of outpatients in the PPC setting, thus further studies are needed in this field.

19.
Cancers (Basel) ; 16(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275880

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-ß pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.

20.
Front Oncol ; 14: 1376631, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966062

RESUMEN

Introduction: Brazil is a developing and an Upper Middle Income, categorized by the World Bank. Therefore, it is a country that needs a special vision for children with oncological diseases who require Pediatric Palliative Care. This study aimed to understand the specificities of services that provide oncology services in comparison to those that do not provide oncological care. Methods: This is a descriptive, cross-sectional, and online survey study. A questionnaire was created by a multidisciplinary group of leaders from the Brazilian Pediatric Palliative Care Network and then the survey was distributed using a snowball strategy. Results: Of the 90 services that answered the questionnaire, 40 (44.4%) attended oncologic patients. The Southeast represented most of the services (57.57%), followed by the Northeast, with 18.89% (17 services), the South with 12.22% (11 services), and the Center West with 8.89% (8 services). No differences were observed in access to opioid prescriptions between the services. It was observed that those services that attended oncologic patients had a tendency to dedicate more time to Pediatric Palliative Care. Discussion: The distribution of services that cover oncology and those that do not, are similar in the different regions of Brazil. In Brazil, there are difficulties in accessing opioids in pediatrics: access to opioid prescriptions without differences revealed that even pediatric oncologists might have difficulty with this prescription, and this should improve. It is concluded that education in Pediatric Palliative Care is the key to improvements in the area.

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