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1.
Immunity ; 52(1): 17-35, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31940268

RESUMEN

Cancer immunotherapy is a validated and critically important approach for treating patients with cancer. Given the vast research and clinical investigation efforts dedicated to advancing both endogenous and synthetic immunotherapy approaches, there is a need to focus on crucial questions and define roadblocks to the basic understanding and clinical progress. Here, we define ten key challenges facing cancer immunotherapy, which range from lack of confidence in translating pre-clinical findings to identifying optimal combinations of immune-based therapies for any given patient. Addressing these challenges will require the combined efforts of basic researchers and clinicians, and the focusing of resources to accelerate understanding of the complex interactions between cancer and the immune system and the development of improved treatment options for patients with cancer.


Asunto(s)
Inmunoterapia/métodos , Neoplasias/terapia , Humanos , Modelos Biológicos , Neoplasias/genética , Neoplasias/inmunología , Microambiente Tumoral/inmunología
2.
Adv Exp Med Biol ; 1232: 299-306, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31893424

RESUMEN

Hypoxic ischemic encephalopathy (HIE) is a significant cause of death and neurological disability in newborns. Therapeutic hypothermia at 33.5 °C is one of the most common treatments in HIE and generally improves outcome; however 45-55% of injuries still result in death or severe neurodevelopmental disability. We have developed a systems biology model of cerebral oxygen transport and metabolism to model the impact of hypothermia on the piglet brain (the neonatal preclinical animal model) tissue physiology. This computational model is an extension of the BrainSignals model of the adult brain. The model predicts that during hypothermia there is a 5.1% decrease in cerebral metabolism, 1.1% decrease in blood flow and 2.3% increase in cerebral tissue oxygenation saturation. The model can be used to simulate effects of hypothermia on the brain and to help interpret bedside recordings.


Asunto(s)
Circulación Cerebrovascular , Cerebro , Hipotermia , Modelos Biológicos , Animales , Animales Recién Nacidos , Circulación Cerebrovascular/fisiología , Cerebro/metabolismo , Simulación por Computador , Humanos , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Porcinos
3.
Hautarzt ; 71(2): 91-100, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-31965205

RESUMEN

The skin is a complex organ that performs a number of vital functions, including forming a physical barrier that protects our body from the penetration of pathogens and irritants and from excessive transepidermal water loss. In addition to its passive properties, the skin is also actively involved in the immune process. A complex structure of different cell types and structures allows the skin to fulfil these functions. In vitro research often faces the problem that simple 2D cell cultures are not able to adequately map these functions. Here 3D skin models offer a possible solution. In recent years, there has been significant development in this field; the reproducibility of the method as well as the physiological structure and tissue architecture of the 3D skin models have been improved. Depending on the research question, protocols for 3D skin models have been published, ranging from simple multilayer epidermis models to highly complex vascularized 3D full skin models.


Asunto(s)
Técnicas de Cultivo de Célula , Dermatología , Modelos Biológicos , Técnicas de Cultivo de Célula/métodos , Epidermis , Humanos , Reproducibilidad de los Resultados , Piel
4.
Nat Commun ; 11(1): 539, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988277

RESUMEN

In the Caenorhabditis elegans zygote, PAR protein patterns, driven by mutual anatagonism, determine the anterior-posterior axis and facilitate the redistribution of proteins for the first cell division. Yet, the factors that determine the selection of the polarity axis remain unclear. We present a reaction-diffusion model in realistic cell geometry, based on biomolecular reactions and accounting for the coupling between membrane and cytosolic dynamics. We find that the kinetics of the phosphorylation-dephosphorylation cycle of PARs and the diffusive protein fluxes from the cytosol towards the membrane are crucial for the robust selection of the anterior-posterior axis for polarisation. The local ratio of membrane surface to cytosolic volume is the main geometric cue that initiates pattern formation, while the choice of the long-axis for polarisation is largely determined by the length of the aPAR-pPAR interface, and mediated by processes that minimise the diffusive fluxes of PAR proteins between cytosol and membrane.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Polaridad Celular , Animales , División Celular Asimétrica , Caenorhabditis elegans/citología , Caenorhabditis elegans/embriología , Biología Computacional , Citosol/metabolismo , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Desarrollo Embrionario , Cinética , Modelos Biológicos , Fosforilación , Transducción de Señal , Termodinámica
5.
Bull Entomol Res ; 110(1): 44-56, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31190649

RESUMEN

Environmental temperature is an important driver of the population dynamics of tsetse (Glossina spp) because the fly's immature stages are particularly vulnerable to temperatures (T) outside the range T = 16-32°C. Laboratory experiments carried out 50 years ago provide extensive measures of temperature-dependent rates of development, fat consumption and mortality in tsetse pupae. We improve on the models originally fitted to these data, providing better parameter estimates for use in population modelling. A composite function accurately models rates of pupal development for T = 8-32°C. Pupal duration can be estimated by summing the temperature-dependent daily percentage of development completed. Fat consumption is modelled as a logistic function of temperature; the total fat consumed during pupal development takes a minimum for T ≈ 25°C. Pupae experiencing constant temperatures <16°C exhaust their fat reserves before they complete development. At high temperatures, direct effects kill the pupae before fat stores are exhausted. The relationship between pupal mortality and temperature is well described by the sum of two exponential functions. Summing daily mortality rates over the whole pupal period does not reliably predict overall mortality. Mortality is more strongly correlated with the mean temperature experienced over pupal life or, for T ≤ 30°C, the fat consumption during this period. The new results will be particularly useful in the construction of various models for tsetse population dynamics, and will have particular relevance for agent-based models where the lives of individual tsetse are simulated using a daily time step.


Asunto(s)
Modelos Biológicos , Pupa/crecimiento & desarrollo , Moscas Tse-Tse/crecimiento & desarrollo , Animales , Femenino , Metabolismo de los Lípidos , Masculino , Mortalidad , Pupa/metabolismo , Temperatura Ambiental , Moscas Tse-Tse/metabolismo
6.
Forensic Sci Int ; 306: 110060, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31785511

RESUMEN

In order to investigate potential causal relations between the shaking of infants and injuries, biomechanical studies compare brain and skull dynamic behavior during shaking to injury thresholds. However, performing shaking tolerance research on infants, either in vivo or ex vivo, is extremely difficult, if not impossible. Therefore, infant injury thresholds are usually estimated by scaling or extrapolating adult or animal data obtained from crash tests or whiplash experiments. However, it is doubtful whether such data accurately matches the biomechanics of shaking in an infant. Hence some thresholds may be inappropriate to be used for the assessment of inflicted head injury by shaking trauma in infants. A systematic literature review was conducted to 1) provide an overview of existing thresholds for head- and neck injuries related to violent shaking, and 2) to identify and discuss which thresholds have been used or could be used for the assessment of inflicted head injury by shaking trauma in infants. Key findings: The majority of studies establishing or proposing injury thresholds were found to be based on loading cycle durations and loading cycle repetitions that did not resemble those occurring during shaking, or had experimental conditions that were insufficiently documented in order to evaluate the applicability of such thresholds. Injury thresholds that were applied in studies aimed at assessing whether an injury could occur under certain shaking conditions were all based on experiments that did not properly replicate the loading characteristics of shaking. Somewhat validated threshold scaling methods only exist for scaling concussive injury thresholds from adult primate to adult human. Scaling methods that have been used for scaling other injuries, or for scaling adult injury thresholds to infants were not validated. There is a clear and urgent need for new injury thresholds established by accurately replicating the loading characteristics of shaking.


Asunto(s)
Fenómenos Biomecánicos/fisiología , Síndrome del Bebé Sacudido/fisiopatología , Aceleración , Animales , Lesión Axonal Difusa/fisiopatología , Medicina Legal/métodos , Traumatismos Cerrados de la Cabeza/fisiopatología , Humanos , Lactante , Hemorragias Intracraneales/fisiopatología , Modelos Biológicos , Traumatismos del Cuello/fisiopatología , Hemorragia Retiniana/fisiopatología
7.
J Agric Food Chem ; 68(2): 574-583, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31820633

RESUMEN

Food structure is a key determinant for the release of phenolic compounds during gastric and intestinal digestion. We evaluated the bioaccessibility of polyphenols from apple tissue during gastric digestion in vitro from bio-mechanical perspectives including the effects of gastric juice and mucin on the apple tissue matrix under simulated stomach peristalsis. The gastric model system was effective in releasing polyphenols because of simultaneous compression and extrusion, with 3 times higher release from coarse than from fine particles. However, bioaccessibility of polyphenols was reduced up to 44% in the presence of both cell walls and gastric mucin. Most individual phenolic molecules were gradually released and were stable in the gastric environment, except for procyanidin B2. The study suggests that the bioaccessibility of polyphenols from apples in the upper digestive tract is dependent on mechanical disintegration and the residual matrix present in the swallowed bolus.


Asunto(s)
Digestión , Malus/metabolismo , Polifenoles/metabolismo , Estómago/fisiología , Disponibilidad Biológica , Pared Celular/química , Pared Celular/metabolismo , Frutas/química , Frutas/metabolismo , Humanos , Malus/química , Modelos Biológicos , Polifenoles/química
8.
J Chem Theory Comput ; 16(1): 700-710, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31769987

RESUMEN

Two permeation mechanisms, namely the water-chain-assisted mechanism and the dehydration mechanism, have been proposed for ions through lipid membranes. In previous studies, multiple reaction coordinates and potential of mean force calculations have been applied in studying such complex transmembrane processes of ions. To reduce the expensive computational cost, we develop two new reaction coordinates in our recent work and in this work to study the two permeation mechanisms. An intrinsically one-dimensional free energy calculation method developed in our recent work is successfully employed in these studies: First, one-dimensional umbrella samplings are performed using the two reaction coordinates. Then, bin segmentations are performed along the transition paths in multidimensional phase spaces. Finally, the weighted least-square analysis method (Welsam) is used for free energy analysis. Based on the new reaction coordinates and the one-dimensional free energy calculation method, we systematically study the two transmembrane permeation mechanisms of sodium ion and chloride ion through lipid bilayers with different thicknesses. Our results suggest that the water-chain-assisted mechanism is dominant for cations, whereas the dehydration mechanism is competitive for anions through thick membranes, which is consistent with previous experimental results.


Asunto(s)
Iones/metabolismo , Membrana Dobles de Lípidos/metabolismo , Termodinámica , Agua/metabolismo , Algoritmos , Permeabilidad de la Membrana Celular , Simulación por Computador , Transporte Iónico , Modelos Biológicos , Modelos Moleculares
9.
Ecol Lett ; 23(2): 274-282, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31755216

RESUMEN

The coexistence of many species within ecological communities poses a long-standing theoretical puzzle. Modern coexistence theory (MCT) and related techniques explore this phenomenon by examining the chance of a species population growing from rarity in the presence of all other species. The mean growth rate when rare, E [ r ] , is used in MCT as a metric that measures persistence properties (like invasibility or time to extinction) of a population. Here we critique this reliance on E [ r ] and show that it fails to capture the effect of temporal random abundance variations on persistence properties. The problem becomes particularly severe when an increase in the amplitude of stochastic temporal environmental variations leads to an increase in E [ r ] , since at the same time it enhances random abundance fluctuations and the two effects are inherently intertwined. In this case, the chance of invasion and the mean extinction time of a population may even go down as E [ r ] increases.


Asunto(s)
Modelos Biológicos , Dinámica Poblacional
10.
Toxicol Lett ; 320: 46-51, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31812603

RESUMEN

Pterostilbene (PT) is a natural stilbene common in small berries and food supplements, possessing numerous pharmacological activities. However, whether PT can affect the activities of UDP-glucuronosyltransferases (UGT) enzymes remains unclear. The aim of the present study was to investigate the effect of PT on UGT activities and to quantitatively evaluate the food-drug interaction potential due to UGT inhibition. Our data indicated that PT exhibited potent inhibition against HLM, UGT1A6, UGT1A9, UGT2B7, and UGT2B15, moderate inhibition against UGT1A1, UGT1A3, UGT1A8, and UGT2B4, negligible inhibition against UGT1A4, UGT1A7, UGT1A10, and UGT2B17. Further kinetic investigation demonstrated that PT exerted potent noncompetitive inhibition 4-MU glucuronidation by UGT1A9, with IC50 and Ki values of 0.92 µM and 0.52 ± 0.04 µM, respectively. Quantitative prediction study suggested that coadministration of PT supplements at 100 mg/day or higher doses may result in at least a 50% increase in the AUC of drugs predominantly cleared by UGT1A9. Thus, the coadministration of PT supplements and drugs primarily cleared by UGT1A9 may result in potential drug interaction, and precautions should be taken when coadministration of PT supplements and drugs metabolized by UGT1A9.


Asunto(s)
Suplementos Dietéticos/efectos adversos , Inhibidores Enzimáticos/toxicidad , Interacciones Alimento-Droga , Glucuronosiltransferasa/antagonistas & inhibidores , Estilbenos/toxicidad , Glucurónidos/metabolismo , Glucuronosiltransferasa/metabolismo , Humanos , Cinética , Tasa de Depuración Metabólica , Fase II de la Desintoxicación Metabólica , Modelos Biológicos , Medición de Riesgo , Estilbenos/farmacocinética
11.
J Agric Food Chem ; 68(1): 358-368, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31815446

RESUMEN

Nanoscale chitosan materials exhibit size-specific properties that make them useful in agri-food and biomedical applications. Chitosan nanoparticles (Chnps) are being explored as nanocarrier platforms to increase oral bioavailability of drugs and nutraceuticals, but little is known of their fate and transformations in the gastrointestinal tract (GIT) or of their potential toxicity. Here, the GIT fate and cytotoxicity of Chnps, soluble starch-coated Chnps (SS-Chnps), and bulk chitosan powder (Chp), were assessed using a 3-phase simulated digestion and an in vitro cellular small intestinal epithelium model. Physico-chemical characterization revealed dissolution of Chp, but not of Chnps or SS-Chnps, during the gastric phase of digestion, stability of the starch coating of SS-Chnps in the oral and gastric phases, and agglomeration of all materials during the small intestinal phase. A slight but significant (10%, p < 0.01) increase in cytotoxicity (LDH release) was observed with exposure to digested Chnps but not Chp or SS-Chnps.


Asunto(s)
Quitosano/química , Quitosano/metabolismo , Epitelio/metabolismo , Intestino Delgado/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Disponibilidad Biológica , Células CACO-2 , Quitosano/toxicidad , Tracto Gastrointestinal/metabolismo , Humanos , Cinética , Modelos Biológicos , Nanopartículas/toxicidad , Tamaño de la Partícula
12.
Toxicol Lett ; 319: 95-101, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31678400

RESUMEN

Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species.


Asunto(s)
Animales Domésticos/metabolismo , Bovinos/metabolismo , Farmacocinética , Oveja Doméstica/metabolismo , Porcinos/metabolismo , Animales , Peso Corporal/fisiología , Bovinos/anatomía & histología , Modelos Biológicos , Tamaño de los Órganos/fisiología , Flujo Sanguíneo Regional/fisiología , Oveja Doméstica/anatomía & histología , Especificidad de la Especie , Porcinos/anatomía & histología
14.
Plant Dis ; 104(1): 147-153, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31729931

RESUMEN

Pseudothecia development stages of Venturia inaequalis (apple scab) were investigated in two climatically different regions in the Western Cape of South Africa. The aim was to determine the pseudothecial density (PD; pseudothecia per fertile lesion [p/f]) and ascal density (AD; asci per pseudothecium [a/p]) that contributes to defining the potential ascospore dose in a common prediction model of the apple scab infection risk. The PD and AD were compared between Elgin (EL), now considered a warm winter apple-growing region because of climate warming, and Koue Bokkeveld (KB), a cold winter region. In 2012 and 2013, scabbed apple leaves were collected during leaf-drop in KB and EL and overwintered either in their region of origin or in the other region. PD was significantly higher in scabbed leaves collected and overwintered in KB (mean, 24.11 p/f) than in leaves collected in KB and overwintered in EL (mean, 17.11 p/f; P < 0.001). PD of scabbed leaves collected and overwintered in EL (mean, 15.27 p/f) or collected in EL and overwintered in KB (mean, 16.07 p/f) did not differ significantly. Ascal density did not differ significantly in any treatment or season. We concluded that the significantly higher PD of scabbed leaves collected from the cooler region of KB and overwintered in KB compared with scabbed leaves collected in EL or KB and overwintered in EL could be caused by adaptations of V. inaequalis populations to the respective climates. This implied long-term effects of climate warming on apple scab epidemiology and management.


Asunto(s)
Ascomicetos , Modelos Biológicos , Enfermedades de las Plantas , Temperatura Ambiental , Ascomicetos/fisiología , Malus/microbiología , Enfermedades de las Plantas/microbiología , Hojas de la Planta/microbiología , Sudáfrica
15.
Plant Dis ; 104(1): 44-51, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31730412

RESUMEN

Stripe rust, caused by Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst), is an important disease of wheat. In China, Pst management has focused on the Gansu region where the pathogen can complete its annual cycle, including oversummering and overwintering. From this region, Pst inoculum is dispersed to the southern Yangtze River region in the late autumn/early winter and then to the main wheat production regions in the following spring. We used historical weather data (1995 to 2016) and field stripe rust assessment data (8 years) in the spring to evaluate the performance of a published model for predicting the potential of Pst overwintering in the Gansu region. Both predicted and observed values of rust overwintering in the Gansu region varied greatly between years and between sites within a single year, indicating the value of predicting rust overwintering for disease management. The model predictions fitted with observed values satisfactorily. All high incidences of rust in the spring were observed in the fields of the monitoring sites where the high potential of overwintering was predicted. Conversely, the predicted rust overwintering potential was also close to zero in the fields where rust was not observed in the spring. There were many false-positive predictions, which may be attributable to the absence of rust in autumn seedlings. This model can be used to target rust management in the spring and its effectiveness will be further improved if autumn rust assessment can be carried out.


Asunto(s)
Basidiomycota , Modelos Biológicos , Estaciones del Año , Triticum , Basidiomycota/fisiología , China , Enfermedades de las Plantas/microbiología , Triticum/microbiología
16.
Ecol Lett ; 23(2): 242-253, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31742858

RESUMEN

Dispersal evolution impacts the fluxes of individuals and hence, connectivity in metapopulations. Connectivity is therefore decoupled from the structural connectedness of the patches within the spatial network. Because of demographic feedbacks, local selection also drives the evolution of other life history traits. We investigated how different levels of connectedness affect trait evolution in experimental metapopulations of the two-spotted spider mite. We separated local- and metapopulation-level selection and linked trait divergence to population dynamics. With lower connectedness, an increased starvation resistance and delayed dispersal evolved. Reproductive performance evolved locally by transgenerational plasticity or epigenetic processes. Costs of dispersal, but also changes in local densities and temporal fluctuations herein are found to be putative drivers. In addition to dispersal, demographic traits are able to evolve in response to metapopulation connectedness at both the local and metapopulation level by genetic and/or non-genetic inheritance. These trait changes impact the persistence of spatially structured populations.


Asunto(s)
Ecosistema , Modelos Biológicos , Demografía , Dinámica Poblacional
17.
World Neurosurg ; 133: e666-e682, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31568908

RESUMEN

BACKGROUND: Giant aneurysms at carotid arteries are typically treated with flow diverter (FD) stents in the clinic. Although the goal of an FD stent is to direct most of the blood flow into the main artery, not much is known regarding the effects of wire number an FD possesses on the hemodynamics inside the aneurysm. METHODS: In this study, 48-, 72-, and 96-wire FD stents were separately implanted into the site of aneurysm of a 45-year-old woman to evaluate the effects of the FD's number of wires on fluid flow behavior in the aneurysm sac. Time evolution of both finite-time Lyapunov exponent (FTLE) and hyperbolic time fields in the aneurysm sac were calculated by using computational fluid dynamics along with Lagrangian coherent structure (LCS) methods. RESULTS: The computations reveal that a 48-wire FD stent allows a large amount of blood to enter inside the aneurysm sac revealing scattered nonstagnant flow zones formation. Besides, time-dependent results of LCS analysis show that most of the blood flow is diverted into the main artery when 72- and 96-wire number Surpass brand FD stents are separately implanted into the site of the aneurysm, yielding a small amount of blood flow to penetrate into the aneurysm sac. CONCLUSIONS: Furthermore, FTLE and hyperbolic time field plots are in good agreement with the patient's digital subtraction angiography image captured 3.5 minutes after 72-wire Surpass brand FD stent implantation.


Asunto(s)
Procedimientos Endovasculares/instrumentación , Hemodinámica/fisiología , Aneurisma Intracraneal/cirugía , Modelos Biológicos , Stents , Angiografía de Substracción Digital , Simulación por Computador , Femenino , Humanos , Hidrodinámica , Persona de Mediana Edad
18.
J Forensic Sci ; 65(1): 255-258, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31411743

RESUMEN

The horizontal displacement of the human body resulting from fatal fall from a height is an important variable commonly used to inversely determine the cause or identify other forensic aspects of the fall. When examining the horizontal displacement, the wind effect is generally ignored. This technical note reports analytical modeling of the falling process, utilizing previous measurements of wind force acting on the human body, for determining the functional relationship between the wind speed and the horizontal displacement in the falling process. The result reveals that it does not take extremely rare wind conditions to cause a considerable shift of the human body, highlighting the importance to consider wind as a factor in investigations of fatal falls.


Asunto(s)
Accidentes por Caídas , Ciencias Forenses/métodos , Modelos Biológicos , Modelos Estadísticos , Viento , Fenómenos Biofísicos , Estatura , Índice de Masa Corporal , Femenino , Humanos , Masculino
19.
J Agric Food Chem ; 68(1): 97-105, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31830779

RESUMEN

The oral delivery efficiency of aged citrus peel extract containing polymethoxyflavones and 5-demethylated polymethoxyflavones (PMFs) in three different systems, including a pure oil phase, a Tween 80-stabilized nanoemulsion, and a milled-cellulose-particles-stabilized Pickering emulsion, was investigated using two typical in vitro digestion models. The digestion profiles and release of PMFs in these emulsions and bulk oil in the human upper gastrointestinal (GI) tract were evaluated using the pH-stat lipolysis model and TNO's gastrointestinal model (TIM-1). Compared to the bulk oil sample, the bioaccessibilities of PMFs in the nanoemulsion and Pickering emulsion were both increased by around 14 fold when the pH-stat lipolysis model was used. However, the results from the TIM-1 system indicated that the bioaccessibilities of PMFs in the nanoemulsion and Pickering emulsion were around two and four times that in bulk oil, respectively. The results from this work would provide valuable information for the rational design and evaluation of lipid-based delivery systems for lipophilic bioactive compounds.


Asunto(s)
Citrus/metabolismo , Composición de Medicamentos/métodos , Lípidos/química , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Citrus/química , Digestión , Emulsiones/química , Flavonas/química , Flavonas/metabolismo , Frutas/química , Frutas/metabolismo , Tracto Gastrointestinal , Humanos , Modelos Biológicos , Tamaño de la Partícula
20.
Int J Clin Pharmacol Ther ; 58(1): 1-9, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31319907

RESUMEN

OBJECTIVE: To establish a population pharmacokinetic (PopPK) model of cyclosporine A (CsA) in Chinese patients with nephrotic syndrome (NS) and to use the model to guide the adjustment of individualized dosage regimens. MATERIALS AND METHODS: 216 CsA therapeutic drug monitoring (TDM) concentration observations were collected from 127 Chinese patients with NS. The basic model was developed as a one-compartment PK model with first-order absorption and linear elimination. The first-order conditional estimation (FOCE) method was applied to establish the final model with covariates using NONMEM software. The final model was evaluated through internal validation including goodness-of-fit analysis and bootstrap method as well as external validation using 39 additional PK observations from 35 patients with NS. RESULTS: A PopPK model of CsA was established in Chinese NS patients with influence of body weight on clearance. The internal and external validation results showed that the final model was stable. CONCLUSION: The established population model adequately characterized the PK of CsA in Chinese patients and could support individualized medication during treatment of NS with CsA.


Asunto(s)
Ciclosporina/farmacocinética , Inmunosupresores/farmacocinética , Síndrome Nefrótico/tratamiento farmacológico , Grupo de Ascendencia Continental Asiática , China , Humanos , Modelos Biológicos , Programas Informáticos
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