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1.
Sensors (Basel) ; 22(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36433470

RESUMO

In this paper, we present an analysis of important aspects that arise during the development of neural network applications. Our aim is to determine if the choice of library can impact the system's overall performance, either during training or design, and to extract a set of criteria that could be used to highlight the advantages and disadvantages of each library under consideration. To do so, we first extracted the previously mentioned aspects by comparing two of the most popular neural network libraries-PyTorch and TensorFlow-and then we performed an analysis on the obtained results, with the intent of determining if our initial hypothesis was correct. In the end, the results of the analysis are gathered, and an overall picture of what tasks are better suited for what library is presented.


Assuntos
Redes Neurais de Computação
2.
J Vis Exp ; (179)2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35156664

RESUMO

DILI is a major cause of attrition in drug development with over 1000 FDA-approved drugs known to potentially cause DILI in humans. Unfortunately, DILI is often not detected until drugs have reached clinical stages, risking patients' safety and leading to substantial losses for the pharma industry. Taking into account that standard 2D models have limitations in detecting DILI it is essential to develop in vitro models that are more predictive to improve data translatability. To understand causality and mechanistic aspects of DILI in detail, a human liver MPS consisting of human primary liver parenchymal and non-parenchymal cells (NPCs) and cultured in 3D microtissues on an engineered scaffold under perfusion has been developed. Cryopreserved primary human hepatocytes (PHHs) and Kupffer cells (HKCs) were cocultured as microtissues in the MPS platform for up to two weeks, and each compound of interest was repeatably dosed onto liver microtissues at seven test concentrations for up to four days. Functional liver-specific endpoints were analyzed (including clinical biomarkers such as alanine aminotransferase, ALT) to evaluate liver function. Acute and chronic exposure to compounds of various DILI severities can be assessed by comparing responses to single and multi-dosed microtissues. The methodology has been validated with a broad set of severe and mildly hepatotoxic compounds. Here we show the data for pioglitazone and troglitazone, well-known hepatotoxic compounds withdrawn from the market for causing liver failures. Overall, it has been shown that the liver MPS model can be a useful tool to assess DILI and its association with changes in hepatic function. The model can additionally be used to assess how novel compounds behave in distinct patient subsets and how toxicity profiles may be affected by liver disease states (e.g., viral hepatitis, fatty liver disease).


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Alanina Transaminase , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatócitos , Humanos , Células de Kupffer , Fígado
3.
Clin Cosmet Investig Dermatol ; 11: 461-465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349343

RESUMO

INTRODUCTION: Emollient therapy is the mainstay for treating skin conditions such as atopic dermatitis and psoriasis. New emollients have been introduced recently and are assumed to be therapeutically interchangeable with the innovator products because, superficially, they appear to have similar compositions. This study compares a) the ex vivo human skin occlusion performance and b) the visual and microscopic properties of Isomol gel (IMG) and Doublebase gel (DBG). MATERIALS AND METHODS: Occlusion was measured gravimetrically by reduction in cumulative 48-hour evaporative weight loss from ex vivo human skin samples following single applications of the two test emollients and Vaseline®. Skin samples from a single donor were mounted in Franz diffusion cells and then the emollients were spread over the skin surface with an applied dose of approximately 2 mg/cm2. The assemblies (four replicates per treatment) were then accurately weighed at baseline (T0) and again after 5-, 24-, and 48-hour postapplication. The quality of the two emollient gel formulations was compared by visual examination of their film-forming characteristics and by microstructural examination using environmental scanning electron microscopy (ESEM). RESULTS: Occlusivity of the DBG emollient gel formulation was comparable with Vaseline and substantially better than IMG, with the DBG-treated skin samples losing less than half as much weight as the IMG-treated skin samples over 48 hours and at a much slower rate during the first 5 hours. The film-forming characteristics and microstructure of the gels were also very different. Whereas DBG maintained a smooth, uniform film over 24 hours, the IMG formulation phase-separated. ESEM results showed that the DBG emulsion has a stable structural matrix with uniform oil droplets, whereas for IMG the emulsion system is inhomogeneous with the oil phase coalescing into larger irregular shaped rafts. CONCLUSIONS: We have demonstrated substantial performance differences between two prescribed emollient gels.

4.
Discoveries (Craiova) ; 4(3): e66, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32309585

RESUMO

Myocardial infarction represents the most investigated pathology. Heart tissues are histologically assayed on a routine base in clinical laboratories. However, the lack of a standard operation procedure for e.g. calculating the size of the infarcted area of myocardium, may lead to an increased errors' interval, with little correlation between results of a same tissue and/or with other pathophysiological parameters. This creates a clear barrier for further development of novel therapeutic strategies. In the present study, we present the robust applicability of a novel methodology such as: advanced modular automated calculation of (i) the size of infarcted heart of mice, (ii) the net collagen content present in the scar, and (iii) the interstitial fibrosis in remote, which are simultaneously performed. The new approach of defining the infarct size, one of the important predictor of every cardiac therapeutic intervention, will create a positive impact in the research accuracy. Additionally, it will be expected that the readily assembled reports of simultaneously computed parameters and its user-friendly operation allow an efficient and effective estimation of measurements.

5.
J Mater Sci Mater Med ; 21(4): 1241-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19924518

RESUMO

The aim of this paper is theophylline (THP) inclusion into xanthan-chitosan polyionic complex (Xa-CS) and the study of its in vitro and in vivo kinetic release. Xa-CS hydrogel was obtained by ionic complexation between two oppositely charged polysaccharides. THP was loaded into the Xa-CS matrix by diffusion of the drug solution. The obtained samples were characterized by FTIR spectroscopy, SEM microscopy and study of the swelling behavior. THP in vitro release experiments were carried out in conditions mimicking the gastrointestinal environment. The chosen drug dose for in vivo study was 15 mg THP/Kg body weight of THP powder or an equivalent dose in complex form. THP serum concentrations were determined by an HPLC assay. The THP peak serum concentration (C(max)) was 7.18 microg/ml for free THP and AUC(0-48) was 25.76 microg h/ml, while in the case of Xa-CS-THP, C(max) was of 5.72 microg/ml and AUC(0-48) = 45.72 microg h/ml. The in vivo study regarding the behaviour of the obtained formulation, showed an increase bioavailability of THP compared to the raw drug, suggesting the possible application of the complex Xa-CS as an oral controlled drug delivery system in the management of chronic pulmonary obstructive disease.


Assuntos
Quitosana/química , Portadores de Fármacos/síntese química , Hidrogéis/síntese química , Polissacarídeos Bacterianos/química , Teofilina/administração & dosagem , Administração Oral , Animais , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Composição de Medicamentos , Hidrogéis/química , Hidrogéis/farmacocinética , Teste de Materiais , Tamanho da Partícula , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Teofilina/farmacocinética , Molhabilidade
6.
J Mater Sci Mater Med ; 20(5): 1095-102, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19160025

RESUMO

Chitosan, a natural polycationic polysaccharide, was coupled with two polyanionic polymers: Na-alginate and carboxymethylcellulose (CMC) and with tannic acid (TA) obtaining three species of self-assembled complexes: chitosan/alginate/TA (sample 1), chitosan/TA (sample 2) and chitosan/CMC/TA (sample 3). The microparticle formation was achieved by dropwise addition of one solution into other by using a coaxial airflow sprayer. These systems were characterized with regard to particle size distribution, thermal stability, tannic acid entrapment efficiency. Sample 2 showed quite a different behavior compared to the other two samples; the particle diameter is located in the nanometric region, the quantity of incorporated tannic acid is higher than in the other two samples and the material shows better thermal stability. The release of tannic acid from these complexes was studied in water (pH = 5.89), phosphates buffer (pH = 7.04) and acetate buffer (pH = 4.11). These studies revealed two distinct periods in tannic acid delivery process: an initial period, varying between 4 and 10 h, characterized by a high release rate with a delivered tannic acid amount of approximately 80% of the incorporated polyphenol and a second period, which starts after 20 to 30 h of delivery and it ends after approximately 120 h, when the release process takes place with low and constant rate and the kinetic curve is linear--characteristic for a zero order kinetic.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Portadores de Fármacos/química , Taninos/administração & dosagem , Alginatos/química , Preparações de Ação Retardada , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Teste de Materiais , Microesferas , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
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