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1.
Biomacromolecules ; 23(5): 2126-2137, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35438963

RESUMEN

We describe the study of a novel aptamer-based candidate for treatment of seropositive rheumatoid arthritis. The candidate is a nanoparticle-formulated cyclic citrullinated peptide aptamer, which targets autoantibodies and/or the immune reactions leading to antibody production. Due to its specificity, the peptide aptamer nanoparticles might not interfere with normal immune functions as seen with other disease-modifying antirheumatic drugs. Over a 3-week course of treatment, joint swelling and arthritis score in collagen-induced rats were significantly decreased compared with animals treated with phosphate-buffered saline, unloaded nanoparticles, or nanoparticles with a noncitrullinated control peptide. The reduction in joint swelling was associated with decreased anticitrullinated peptide autoantibody levels in the blood. Treatment with aptamer nanoparticles also increased interleukin-10 levels. The effect seen with the proposed treatment candidate could be mediated by upregulation of anti-inflammatory mediators and decreased levels of anticitrullinated peptide antibodies.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Péptidos/farmacología , Péptidos/uso terapéutico , Péptidos Cíclicos/uso terapéutico , Ratas
2.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-35163377

RESUMEN

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber-film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.


Asunto(s)
Desamino Arginina Vasopresina/farmacología , Moco/química , Nanofibras/química , Nanotecnología , Adhesividad , Animales , Preparaciones de Acción Retardada/farmacología , Relación Dosis-Respuesta a Droga , Nanofibras/ultraestructura , Saliva , Porcinos
3.
Molecules ; 26(22)2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34833889

RESUMEN

The aim of this study was to investigate binding interactions between ß-lactoglobulin (BLG) and two different mucins, bovine submaxillary mucins (BSM) and porcine gastric mucin (PGM), using intrinsic and extrinsic fluorescence spectroscopies. Intrinsic fluorescence spectra showed an enhanced decrease of fluorescence intensity of BLG at all pH conditions when BLG was mixed with PGM rather than with BSM. We propose that, unlike BSM, the tertiary structure of PGM changes and the hydrophobic regions are exposed at pH 3 due to protonation of negatively charged residues. Results suggest that PGM also facilitated the structural unfolding of BLG and its binding with PGM by a hydrophobic interaction, especially at acidic pH, which was further supported by extrinsic fluorescence spectroscopy. Hydrophobic interaction is suggested as the dominant interaction mechanism between BLG and PGM at pH 3, whereas electrostatic interaction is the dominant one between BLG and BSM.


Asunto(s)
Mucinas Gástricas/metabolismo , Lactoglobulinas/metabolismo , Mucinas/metabolismo , Adsorción , Animales , Bovinos , Mucinas Gástricas/química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Mucosa Intestinal/metabolismo , Lactoglobulinas/química , Mucinas/química , Espectrometría de Fluorescencia/métodos , Glándula Submandibular/metabolismo , Porcinos
4.
Mol Pharm ; 17(11): 4189-4200, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-32885978

RESUMEN

Nicotine replacement therapy (NRT) formulations for oromucosal administration induce a delayed rise in nicotine blood levels as opposed to the immediate nicotine increase obtained from cigarette smoking, this being a shortcoming of the therapy. Here, we demonstrate that α-lactalbumin/polyethylene oxide (ALA/PEO) electrospun nanofibers constitute an efficient oromucosal delivery system for fast-onset nicotine delivery of high relevance for acute dosing NRT applications. In vitro, nicotine-loaded nanofibers showed fast disintegration in water, with a weight loss up to 40% within minutes, and a faster nicotine release (26.1 ± 4.6% after 1 min of incubation) of the loaded nicotine compared to two relevant marketed NRT formulations with a comparable nicotine dose (i.e., 7.9 ± 5.1 and 2.2 ± 0.3% nicotine was released from a lozenge and a sublingual tablet, respectively). Model-fitting of the release data indicated that the release mechanism of nicotine from the hydrophilic nanofibers was possibly governed by more than one type of release phenomena. Remarkably, ex vivo studies using porcine buccal mucosa demonstrated a more efficient permeation of the nicotine released from the nanofibers [flux of 1.06 ± 0.22 nmol/(cm2·min)] compared to when dosing even a ten-fold concentrated nicotine solution [flux of 0.17 ± 0.14 nmol/(cm2·min)]. Moreover, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MS) imaging of ex vivo porcine buccal mucosa exposed to nicotine-loaded nanofibers clearly revealed higher amounts of nicotine throughout the epithelium, as well as in the lamina propria and submucosa of the tissue. Our findings suggest that nicotine-loaded ALA/PEO nanofibers have potential as a mucosal, fast-releasing, and biocompatible delivery system for nicotine, which can overcome the limitations of the currently marketed NRTs.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Lactalbúmina/química , Boca/efectos de los fármacos , Nanofibras/química , Nicotina/administración & dosificación , Nicotina/farmacocinética , Cese del Hábito de Fumar/métodos , Administración Bucal , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Liberación de Fármacos , Células Epiteliales/efectos de los fármacos , Epitelio/efectos de los fármacos , Humanos , Mucosa Bucal/efectos de los fármacos , Porcinos , Distribución Tisular , Dispositivos para Dejar de Fumar Tabaco
5.
Crit Rev Food Sci Nutr ; 60(1): 64-83, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30632771

RESUMEN

Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer that covers epithelial surfaces throughout the body. Mucins, as the major salivary proteins, are also important proteins for the food oral processing and digestion. The interactions of salivary mucins and saliva with several food proteins and food protein emulsions, as well as their functional properties related to the food oral processing were reviewed in this paper. The target food proteins of focus were whey proteins (lactoferrin and beta-lactoglobulin) and non-whey proteins (casein, gelatin, galectin/lectin, and proline-rich proteins). Most of the studies suggest that electrostatic attraction (between positively charged food proteins with negatively charged moieties of mucin mainly on glycosylated region of mucin) is the major mode of interaction between them. On the other hand, casein attracts the salivary proteins only via non-covalent interactions due to its naturally self-assembled micellar structure. Moreover, recent studies related to ß-lactoglobulin (BLG)-mucin interactions have clarified the importance of hydrophobic as well as hydrophilic interactions, such as hydrogen bonding. Furthermore, in vitro studies between protein emulsions and saliva observed a strong aggregating effect of saliva on caseinate and whey proteins as well as on surfactant-stabilized emulsions. Besides, the sign and the density of the charge on the surface of the protein emulsion droplets contribute significantly to the behavior of the emulsion when mixed with saliva. Other studies also suggested that the interactions between saliva and whey proteins depends on the pH in addition to the flow rate of the saliva. Overall, the role of interactions of food proteins and food protein emulsions with mucin/saliva-proteins in the oral perception, as well as the physicochemical and structural changes of proteins were discussed.


Asunto(s)
Proteínas Dietéticas Animales/química , Mucinas/química , Saliva/química , Proteínas y Péptidos Salivales/química , Caseínas , Galectinas , Gelatina , Humanos , Lactoferrina , Lactoglobulinas/química , Proteína de Suero de Leche/química
6.
Molecules ; 25(24)2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339397

RESUMEN

Potato protein particles and fibers were produced using electrohydrodynamic processing (electrospray and electrospinning). The effect of different solvents and protein concentration on the morphology of the potato protein particles and fibers was investigated. Electrosprayed particles with average diameters ranging from 0.3 to 1.4 µm could be obtained using water and mixtures of water: ethanol (9:1) and water:glycerol (9:1). Electrosprayed particles were also obtained using the solvent hexafluoro-2-propanol (HFIP) at a protein concentration of 5% wt/v. For protein concentrations above 10% wt/v, using HFIP, electrospun fibers were produced. The release of vitamin B12, as a model bioactive compound, from potato protein electrospun fibers, was also investigated, demonstrating their potential to be utilized as encapsulation and delivery systems.


Asunto(s)
Hidrodinámica , Proteínas de Plantas/química , Solanum tuberosum/metabolismo , Conductividad Eléctrica , Glicerol/química , Tamaño de la Partícula , Proteínas de Plantas/metabolismo , Solventes/química , Vitamina B 12/química , Vitamina B 12/metabolismo , Agua/química
7.
Bioconjug Chem ; 30(10): 2584-2593, 2019 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-31524379

RESUMEN

Multiple drugs have been proposed for reducing harsh symptoms of human rheumatic diseases. However, a targeted therapy with mild to no side effects is still missing. In this study, we have prepared and tested a series of therapeutic nanoparticles for specific targeting of human neutrophils associated with rheumatoid arthritis. In doing this, a series of citrullinated peptide epitopes derived from human proteins, fibrinogen, vimentin, and histone 3, were screened with regard to specific recognition of neutrophils. The most potent epitope proved to be a mutated fragment of an alpha chain in human fibrinogen. Next, a straightforward synthetic strategy was developed for nanoparticles decorated with this citrullinated peptide epitope and an antisense oligonucleotide targeting disease associated microRNA miR-125b-5p. Our study shows that the nanoparticles specifically recognize neutrophils and knock down miR-125b-5p, with no apparent toxicity to human cells. In contrast to organic dendrimers, chitosan-hyaluronic acid formulations do not activate human innate immune response. Our data proves that the strategy we report herein is effective in developing peptide epitopes for decorating delivery vehicles bearing biological drugs, targeted to a specific cell type.


Asunto(s)
Citrulinación , Epítopos/química , Epítopos/metabolismo , Nanopartículas/química , Nanopartículas/uso terapéutico , Neutrófilos/efectos de los fármacos , Péptidos/química , Secuencia de Aminoácidos , Humanos
8.
Crit Rev Food Sci Nutr ; 59(2): 313-327, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28857615

RESUMEN

Nowadays, there is an aggressive rate in consumption of noodles and pasta products throughout the world. Consumer acceptability and preference of these functional products can be promoted by the discovery of novel knowledge to improve their formulation and quality. The development of fortified-formulations for noodles and pasta products based on microbial transglutaminase (MTGase) can guarantee the shelf life extension with minimum quality losses. The current review focuses on recent trends and future prospects of MTGase utilization in the structural matrix of noodles and pasta products and represents the quality changes of cooking loss, texture, microstructure, color and sensory attributes of the MTGase-incorporated products. Digestibility, nutritional and health aspects of the MTGase-enriched formulations are also reviewed with a vision toward physical functions and safety outcomes of MTGases isolated from new microbial sources. The high potential of MTGase in developing commercial noodles and pasta products is successfully demonstrated. MTGase by modifying the crystallinity or molecular structure via covalent crosslinks between protein molecules strengthens the doughs stability and the textural characteristics of final products with the low- or high-protein flour. Compared with the control samples, the MTGase-supplemented products indicate slower digestion rates and better sensory and cooking properties without any remarkable color instability.


Asunto(s)
Harina , Manipulación de Alimentos/métodos , Transglutaminasas/administración & dosificación , Bacillus/enzimología , Culinaria/métodos , Digestión , Fagopyrum , Manipulación de Alimentos/instrumentación , Alimentos Fortificados , Humanos , Fenómenos Mecánicos , Reología , Sensación , Almidón/metabolismo , Streptomyces/enzimología , Transglutaminasas/metabolismo , Triticum
9.
Int J Mol Sci ; 19(8)2018 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-30072627

RESUMEN

This study aimed to develop hybrid electrospun chitosan⁻phospholipid nanofibers and investigate the effect of phospholipid (P) content and chitosans (Ch) molecular weights (Mw) and degree of acetylation (DA), on the morphological, mechanical and mucoadhesive properties of the nanofibers. Electrospun Ch/P nanofibers exhibited a smooth and uniform surface with average diameters ranging from 300 to 1000 nm, as observed by scanning electron microscopy (SEM). The average diameter of the nanofibers was observed to increase with the increase of the Mw and degree of deacetylation of Ch, and phospholipid content. The elastic and adhesive properties of the nanofibers were determined by atomic force microscopy, and displayed higher values for higher Mw and lower DA Ch used. The elastic modulus of electrospun Ch/P hybrid fibers determined for the different conditions tested was found to be in the range of 500 and 1400 MPa. Furthermore, electrospun Ch/P nanofibers displayed mucoadhesive properties expressed by the work of adhesion calculated after the compression of the nanofibers against a section of pig small intestine. Our results showed that the increase in phospholipid content and DA of Ch decrease the work of adhesion, while the increase of Mw resulted in slightly higher work of adhesion of the nanofibers.


Asunto(s)
Quitosano/química , Nanofibras/química , Fosfolípidos/química , Adhesivos/química , Adhesivos/metabolismo , Animales , Quitosano/metabolismo , Módulo de Elasticidad , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Ensayo de Materiales , Nanofibras/ultraestructura , Fosfolípidos/metabolismo , Porcinos
10.
AAPS PharmSciTech ; 19(8): 3770-3777, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30280354

RESUMEN

Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil-A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a solvent. Three different chitosans designed as HMC+70, HMC+85, and HMC+90 (called as 705010, 855010, and 905010) were tested and its efficacy to be used in oral vaccine delivery applications was investigated. The morphology, size, and zeta potential of the produced particles were investigated, together with the encapsulation efficiency and release of OVA from the three chitosan formulations. Moreover, the mucoadhesion and cytotoxicity of the chitosan microparticles was examined. All the three formulations with OVA and Quil-A were in the micrometer size range and had a positive zeta potential between 46 and 75 mV. Furthermore, all the three formulations displayed encapsulation efficiencies above 80% and the release of OVA over a period of 80 h was observed to be between 38 and 47%. None of the developed formulations exhibited high mucoadhesive properties, either cytotoxicity. The formulation prepared with HMC+70, OVA, and Quil-A had the highest stability within 2 h in buffer solution, as measured by dynamic light scattering. The electrosprayed formulation consisting of HMC+70 with OVA and Quil-A showed to be the most promising as an oral vaccine system.


Asunto(s)
Química Farmacéutica/métodos , Quitosano/síntesis química , Sistemas de Liberación de Medicamentos/métodos , Microesferas , Tamaño de la Partícula , Vacunas/síntesis química , Administración Oral , Animales , Línea Celular , Pollos , Quitosano/administración & dosificación , Composición de Medicamentos , Humanos , Ovalbúmina/administración & dosificación , Ovalbúmina/síntesis química , Saponinas de Quillaja/administración & dosificación , Saponinas de Quillaja/síntesis química , Vacunas/administración & dosificación
11.
Acta Obstet Gynecol Scand ; 96(1): 47-52, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27731893

RESUMEN

INTRODUCTION: The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1-3); peptides believed to influence mucus viscosity. MATERIAL AND METHODS: The study is based on spontaneously shed cervical mucus plugs from 14 women in active labor. The viscoelastic properties; the elastic modulus (G') and the viscous modulus (G") were determined by an oscillatory rheometer. The concentrations of TFF1-3 were measured by an in-house enzyme-linked immunosorbent assay. Associations were analyzed by random-effects generalized least-squares regression analyses. RESULTS: Median (range) concentrations of TFF1, TFF2 and TFF3 were 3.1 (1.2-8.6), 1.1 (<0.006-3.7) and 1000 (170-5300) nmol/g cervical mucus plug, respectively. The TFF3 concentration was associated with G' (regression coefficient 11.7 Pa/Log nm; 95% CI 3.0-20.4, p = 0.009) and G" (regression coefficient 3.2 Pa/Log nm; 95% CI 1.5-5.0, p < 0.001). CONCLUSION: We suggest that TFF3 plays a role in the viscoelastic properties of the cervical mucus plug.


Asunto(s)
Moco del Cuello Uterino/química , Módulo de Elasticidad , Factor Trefoil-3/análisis , Viscosidad , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Embarazo , Adulto Joven
12.
Molecules ; 22(10)2017 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-29039789

RESUMEN

Electrospun phospholipid (asolectin) microfibers were investigated as antioxidants and encapsulation matrices for curcumin and vanillin. These phospholipid microfibers exhibited antioxidant properties which increased after the encapsulation of both curcumin and vanillin. The total antioxidant capacity (TAC) and the total phenolic content (TPC) of curcumin/phospholipid and vanillin/phospholipid microfibers remained stable over time at different temperatures (refrigerated, ambient) and pressures (vacuum, ambient). ¹H-NMR confirmed the chemical stability of both encapsulated curcumin and vanillin within phospholipid fibers. Release studies in aqueous media revealed that the phenolic bioactives were released mainly due to swelling of the phospholipid fiber matrix over time. The above studies confirm the efficacy of electrospun phospholipid microfibers as encapsulation and antioxidant systems.


Asunto(s)
Antioxidantes/administración & dosificación , Antioxidantes/química , Composición de Medicamentos , Fosfatidilcolinas/química , Benzaldehídos/administración & dosificación , Benzaldehídos/química , Curcumina/administración & dosificación , Curcumina/química , Liberación de Fármacos , Microfibrillas/química , Microfibrillas/ultraestructura , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier
13.
J Food Sci Technol ; 54(9): 2670-2683, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28928507

RESUMEN

To effectively promote the industrial utilization of cocoyam (Xanthosoma sagittifolium) roots for enhanced food sustainability and security, there is a need to study their molecular, mechanical and physicochemical properties in detail. The physicochemical and textural characteristics of the red and white varieties of cocoyam roots were thus analysed by low field nuclear magnetic resonance relaxometry, multispectral imaging, uniaxial compression testing, and relevant physicochemical analysis in the current study. Both varieties had similar dry matter content, as well as physical and mechanical properties. However, up to four fast-interacting water populations were observed in the roots, dependent on the root variety and their degree of gelatinization during cooking. Changes in the relaxation parameters indicated weak gelatinization of starch at approximately 80 °C in both varieties. However, shorter relaxation times and a higher proportion of restricted water in the white variety indicated that this variety was slightly more sensitive towards gelatinization. A strong negative correlation existed between dry matter and all multispectral wavelengths >800 nm, suggesting the potential use of that spectral region for rapid analysis of dry matter and water content of the roots. The small, but significant differences in the structural and gelatinization characteristics of the two varieties indicated that they may not be equally suited for further processing, e.g. to flours or starches. Processors thus need to choose their raw materials wisely dependent on the aimed product characteristics. However, the spectroscopic methods applied in the study were shown to be effective in assessing important quality attributes during cooking of the roots.

14.
Mol Pharm ; 13(3): 748-55, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26389817

RESUMEN

Intermolecular interaction phenomena occurring between endogenous compounds, such as proteins and bile salts, and electrospun compounds are so far unreported, despite the exposure of fibers to such biorelevant compounds when applied for biomedical purposes, e.g., tissue engineering, wound healing, and drug delivery. In the present study, we present a systematic investigation of how surfactants and proteins, as physiologically relevant components, interact with insulin-loaded fish sarcoplasmic protein (FSP) electrospun fibers (FSP-Ins fibers) in solution and thereby affect fiber properties such as accessible surface hydrophilicity, physical stability, and release characteristics of an encapsulated drug. Interactions between insulin-loaded protein fibers and five anionic surfactants (sodium taurocholate, sodium taurodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium dodecyl sulfate), a cationic surfactant (benzalkonium chloride), and a neutral surfactant (Triton X-100) were studied. The anionic surfactants increased the insulin release in a concentration-dependent manner, whereas the neutral surfactant had no significant effect on the release. Interestingly, only minute amounts of insulin were released from the fibers when benzalkonium chloride was present. The FSP-Ins fibers appeared dense after incubation with this cationic surfactant, whereas high fiber porosity was observed after incubation with anionic or neutral surfactants. Contact angle measurements and staining with the hydrophobic dye 8-anilino-1-naphthalenesulfonic acid indicated that the FSP-Ins fibers were hydrophobic, and showed that the fiber surface properties were affected differently by the surfactants. Bovine serum albumin also affected insulin release in vitro, indicating that also proteins may affect the fiber performance in an in vivo setting.


Asunto(s)
Electroquímica , Proteínas de Peces/metabolismo , Nanofibras/química , Retículo Sarcoplasmático/metabolismo , Albúmina Sérica Bovina/metabolismo , Tensoactivos/metabolismo , Animales , Materiales Biocompatibles/química , Bovinos , Proteínas de Peces/química , Peces/metabolismo , Ingeniería de Proteínas , Albúmina Sérica Bovina/química , Soluciones , Tensoactivos/química
15.
Endocr Pract ; 20(4): 352-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24246343

RESUMEN

OBJECTIVE: Clinical practice guidelines (CPGs) could have a more consistent and meaningful impact on clinician behavior if they were delivered as electronic algorithms that provide patient-specific advice during patient-physician encounters. We developed a computer-interpretable algorithm for U.S. and European users for the purpose of diagnosis and management of thyroid nodules that is based on the "AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules," a narrative, evidence-based CPG. METHODS: We initially employed the guideline-modeling language GuideLine Interchange Format, version 3, known as GLIF3, which emphasizes the organization of a care algorithm into a flowchart. The flowchart specified the sequence of tasks required to evaluate a patient with a thyroid nodule. PROforma, a second guideline-modeling language, was then employed to work with data that are not necessarily obtained in a rigid flowchart sequence. Tallis-a user-friendly web-based "enactment tool"- was then used as the "execution engine" (computer program). This tool records and displays tasks that are done and prompts users to perform the next indicated steps. The development process was iteratively performed by clinical experts and knowledge engineers. RESULTS: We developed an interactive web-based electronic algorithm that is based on a narrative CPG. This algorithm can be used in a variety of regions, countries, and resource-specific settings. CONCLUSION: Electronic guidelines provide patient-specific decision support that could standardize care and potentially improve the quality of care. The "demonstrator" electronic thyroid nodule guideline that we describe in this report is available at http://demos.deontics.com/trace-review-app (username: reviewer; password: tnodule1). The demonstrator must be more extensively "trialed" before it is recommended for routine use.


Asunto(s)
Guías de Práctica Clínica como Asunto , Nódulo Tiroideo/terapia , Algoritmos , Humanos , Internet , Nódulo Tiroideo/diagnóstico
16.
Acta Obstet Gynecol Scand ; 93(2): 201-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25032247

RESUMEN

OBJECTIVE: To characterize the viscoelastic properties of cervical mucus plugs(CMPs) shed during labor at term. DESIGN: Experimental research. SETTING: Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark. POPULATION/SAMPLE: Spontaneously shed CMPs from 18 healthy women in active labor. METHODS: Viscoelastic properties of CMPs were investigated with a dynamic oscillatory rheometer using frequency and stress sweep experiments within the linear viscoelastic region. MAIN OUTCOME MEASURES: The rheological variables obtained were as follows: elastic modulus (G'), viscous modulus (G″) and tan delta (G″/G'). Random-effects regression was used for statistical analysis. RESULTS: All CMPs showed solid-like viscoelastic behavior.This was substantiated by the elastic modulus which was three to four times greater than the viscous modulus and by tan delta, which was <1 at all frequencies.Mean tan delta at 0.01 Hz was 0.38 (95% CI 0.34-0.43) and 0.27(95% CI 0.23-0.32) at 1 Hz. The elastic modulus could be described by the relation G'(ω) = K(ω)(A) [mean R2 0.95 (95% CI 0.93-0.98)]. Despite relatively large variation in the rheological properties within CMPs, rheological variables obtained from frequency sweeps differed significantly among CMPs (p < 0.05). CONCLUSION: The CMPs are solid-like viscoelastic structures. These rheological characteristics are probably essential for the CMP's ability to form and sustain a plug in the cervical canal during pregnancy, thereby reducing the risk of ascending infections. The technique described here might be used for evaluation of an association between CMP viscoelasticity and preterm delivery.


Asunto(s)
Moco del Cuello Uterino/química , Cuello del Útero/fisiología , Módulo de Elasticidad/fisiología , Trabajo de Parto/fisiología , Adulto , Análisis de Varianza , Elasticidad/fisiología , Femenino , Humanos , Embarazo , Reología
17.
Nanomaterials (Basel) ; 14(6)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38535657

RESUMEN

The encapsulation and the oxidative stability of cod liver fish oil (CLO) within coaxial electrosprayed (ethyl cellulose/CLO) core-(octenyl succinic anhydride, OSA-modified starch) shell, and monoaxial electrosprayed ethyl cellulose/CLO microcapsules were investigated. Core-shell (H-ECLO) and monoaxial (ECLO) electrosprayed microcapsules with an average diameter of 2.8 ± 1.8 µm, and 2.2 ± 1.4 µm, respectively, were produced. Confocal microscopy confirmed not only the core-shell structure of the H-ECLO microcapsules, but also the location of the CLO in the core. However, for the ECLO microcapsules, the CLO was distributed on the microcapsules' surface, as also confirmed by Raman spectroscopy. Atomic force microscopy showed that the average surface adhesion of the H-ECLO microcapsules was significantly lower (5.41 ± 0.31 nN) than ECLO microcapsules (18.18 ± 1.07 nN), while the H-ECLO microcapsules showed a remarkably higher Young's modulus (33.84 ± 4.36 MPa) than the ECLO microcapsules (6.64 ± 0.84 MPa). Differential scanning calorimetry results confirmed that the H-ECLO microcapsules enhanced the oxidative stability of encapsulated CLO by about 15 times, in comparison to non-encapsulated oil, mainly by preventing the presence of the fish oil at the surface of the microcapsules, while ECLO microcapsules enhanced the oxidative stability of CLO about 2.9 times due to the hydrophobic interactions of the oil and ethyl cellulose. Furthermore, the finite element method was also used to evaluate the electric field strength distribution, which was substantially higher in the vicinity of the collector and lower in the proximity of the nozzle when the coaxial electrospray process was employed in comparison to the monoaxial process.

18.
Curr Res Food Sci ; 7: 100620, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37942279

RESUMEN

The effect of the polarity of the direct current electric field on the "organization" of Streptococcus thermophilus (ST44) probiotic cells within electrosprayed maltodextrin microcapsules was investigated. The generated electrostatic forces between the negatively surface-charged probiotic cells and the applied negative polarity on the electrospray nozzle, allowed to control the location of the cells towards the core of the electrosprayed microcapsules. This "organization" of the cells increased the evaporation of the solvent (water) and successively the glass transition temperature (Tg) of the electrosprayed microcapsules. Moreover, the utilization of auxiliary ring-shaped electrodes between the nozzle and the collector, enhanced the electric field strength and contributed further to the increase of the Tg. Numerical simulation, through Finite Element Method (FEM), shed light to the effects of the additional ring-electrode on the electric field strength, potential distribution, and controlled deposition of the capsules on the collector. Furthermore, when the cells were located at the core of the microcapsules their viability was significantly improved for up to 2 weeks of storage at 25 °C and 35% RH, compared to the case where the probiotics were distributed towards the surface. Overall, this study reports a method to manipulate the encapsulation of the surface charged probiotic cells within electrosprayed microcapsules, utilizing the polarity of the electric field and additional ring-electrodes.

19.
Carbohydr Polym ; 303: 120429, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36657829

RESUMEN

Oromucosal administration is an attractive non-invasive route. However, drug absorption is challenged by salivary flow and the mucosa being a significant permeability barrier. The aim of this study was to design and investigate a multi-layered nanofiber-on-foam-on-film (NFF) drug delivery system with unique properties and based on polysaccharides combined as i) mucoadhesive chitosan-based nanofibers, ii) a peptide loaded hydroxypropyl methylcellulose foam, and iii) a saliva-repelling backing film based on ethylcellulose. NFF displays optimal mechanical properties shown by dynamic mechanical analysis, and biocompatibility demonstrated after exposure to a TR146 cell monolayer. Chitosan-based nanofibers provided the NFF with improved mucoadhesion compared to that of the foam alone. After 1 h, >80 % of the peptide desmopressin was released from the NFF. Ex vivo permeation studies across porcine buccal mucosa indicated that NFF improved the permeation of desmopressin compared to a commercial freeze-dried tablet. The findings demonstrate the potential of the NFF as a biocompatible drug delivery system.


Asunto(s)
Quitosano , Nanofibras , Animales , Porcinos , Quitosano/química , Desamino Arginina Vasopresina , Celulosa/química , Sistemas de Liberación de Medicamentos , Mucosa Bucal , Péptidos , Administración Bucal
20.
Pharmaceutics ; 15(11)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38004611

RESUMEN

Vitamin A is an essential micronutrient that is readily oxidized. In this study, the encapsulation of vitamin A palmitate (AP) within a core-shell carbohydrate matrix by co-axial electrospray and its oxidative stability was evaluated. The electrosprayed core-shell microcapsules consisted of a shell of octenyl succinic anhydride (OSA) modified corn starch, maltose (Hi-Cap), and a core of ethyl cellulose-AP (average diameter of about 3.7 µm). The effect of different compounds (digestion-resistant maltodextrin, soy protein hydrolysate, casein protein hydrolysate, and lecithin) added to the base core-shell matrix formulation on the oxidative stability of AP was investigated. The oxidative stability of AP was evaluated using isothermal and non-isothermal differential scanning calorimetry (DSC), and Raman and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy methods. The core-shell carbohydrate matrix minimizes the amount of AP present at the microparticle surface, thus protecting AP from oxidation. Furthermore, the most effective oxidation protection was achieved when casein protein hydrolysate was added to the core of the microcapsule due to hydrophobic and hydrogen bond interactions with AP and by the resistant maltodextrin in the shell, which acted as a filler. The utilization of ethanol as a solvent for the dispersion of the core compounds increased the hydrophobicity of the hydrolyzed proteins and contributed to the enhancement of their antioxidant ability. Both the carbohydrate core-shell microcapsule prepared by co-axial electrospray and the addition of oxidation protection compounds enhance the oxidative stability of the encapsulated AP.

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