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1.
Bioeng Transl Med ; 9(1): e10607, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38193113

RESUMO

Irreversible electroporation (IRE) has emerged as an appealing non-ionizing, non-thermal ablation therapy, independent of antineoplastic drugs. Limited but successful outcomes in IRE conducted in vivo, in small focal hepatocellular carcinomas (HCC), have been reported. Nonetheless, the electric parameters of IRE are usually delivered in an unplanned manner. This work investigates the integration of computational modeling to hydrogels mimicking the HCC microenvironment, as a powerful framework to: circumvent ethical concerns of in vivo experimentation; safely tune the electric parameters reaching the IRE electric field threshold; and propel the translation of IRE as a routine clinical alternative to the treatment of HCC. Therefore, a parametric study served to evaluate the effects of the pulse amplitude, the number of pulses and electrodes, the treatment time, the hydrogel-tumor size, and the cell type. The ablation extent was surveyed by confocal microscopy and magnetic resonance imaging (MRI) in cylindrical and realistic tumor-shaped hydrogels, respectively. A large ablation (70%-100%) was verified in all constructs.

2.
J Cell Biochem ; 107(4): 803-8, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19452451

RESUMO

Iron is transported across intestinal brush border cells into the circulation in at least two distinct steps. Iron can enter the enterocyte via the apical surface through several paths. However, iron egress from the basolateral side of enterocytes converges on a single export pathway requiring the iron transporter, ferroportin1, and hephaestin, a ferroxidase. Copper deficiency leads to reduced hephaestin protein expression and activity in mouse enterocytes and intestinal cell lines. We tested the effect of copper deficiency on differentiated Caco2 cells grown in transwells and found decreased hephaestin protein expression and activity as well as reduced ferroportin1 protein levels. Furthermore, the decrease in hephaestin levels correlates with a decrease of (55)Fe release from the basolateral side of Caco2 cells. Presence of ceruloplasmin, apo-transferrin or holo-transferrin did not significantly alter the results observed. Repletion of copper in Caco2 cells leads to reconstitution of hephaestin protein expression, activity, and transepithelial iron transport.


Assuntos
Células Epiteliais/metabolismo , Ferro/metabolismo , Proteínas de Membrana/análise , Transporte Biológico , Células CACO-2 , Proteínas de Transporte de Cátions/análise , Diferenciação Celular , Cobre/deficiência , Enterócitos/metabolismo , Humanos , Proteínas de Membrana/metabolismo
3.
J Am Diet Assoc ; 109(5): 830-5, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19394469

RESUMO

OBJECTIVE: Optimal bone mass in early adulthood is achieved through appropriate diet and lifestyle, thereby protecting against osteoporosis and risk of bone fracture in later life. Calcium and vitamin D are essential to build adequate bones, but calcium intakes of many population groups do not meet dietary reference values. In addition, changes in dietary patterns are exacerbating the problem, thereby emphasizing the important role of calcium-rich food products. We have designed a calcium-fortified ice cream formulation that is lower in fat than regular ice cream and could provide a useful source of additional dietary calcium. Calcium absorption from two different ice cream formulations was determined in young adults and compared with milk. SUBJECTS/SETTING: Sixteen healthy volunteers (25 to 45 years of age), recruited from the general public of The Netherlands, participated in a randomized, reference-controlled, double-blind cross-over study in which two test products and milk were consumed with a light standard breakfast on three separate occasions: a standard portion of ice cream (60 g) fortified with milk minerals and containing a low level (3%) of butter fat, ice cream (60 g) fortified with milk minerals and containing a typical level (9%) of coconut oil, and reduced-fat milk (1.7% milk fat) (200 mL). Calcium absorption was measured by the dual-label stable isotope technique. STATISTICAL ANALYSIS: Effects on calcium absorption were evaluated by analysis of variance. RESULTS: Fractional absorption of calcium from the 3% butterfat ice cream, 9% coconut oil ice cream, and milk was 26%+/-8%, 28%+/-5%, and 31%+/-9%, respectively, and did not differ significantly (P=0.159). CONCLUSIONS: Results indicate that calcium bioavailability in the two calcium-fortified ice cream formulations used in this study is as high as milk, indicating that ice cream may be a good vehicle for delivery of calcium.


Assuntos
Conservadores da Densidade Óssea/farmacocinética , Osso e Ossos/efeitos dos fármacos , Cálcio da Dieta/farmacocinética , Alimentos Fortificados , Sorvetes/análise , Adulto , Análise de Variância , Animais , Disponibilidade Biológica , Densidade Óssea , Osso e Ossos/metabolismo , Cálcio/deficiência , Cálcio/metabolismo , Estudos Cross-Over , Gorduras na Dieta/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Absorção Intestinal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Leite/química , Necessidades Nutricionais , Osteoporose/prevenção & controle , Vitamina D/farmacologia
4.
J Biomol Screen ; 10(2): 118-26, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15799955

RESUMO

In this article, the study of 3 different angiotensin II type 1 (AT(1)) receptor binding assays in terms of reproducibility, robustness, and feasibility for high-throughput screening (HTS) is described. The following methods were used: a nonhomogeneous filtration assay in a 96-well format using CHO-AT(1) cell membranes and 2 homogeneous assays, which include the commercially available ScreenReady Target for the AT(1) receptor and the wheat germ agglutinin (WGA) Flashplate, which was coated "in-house" with the CHO-AT(1) cell membranes. Receptors were labeled with [(125)I]-Sar(1)-Ile(8)-angiotensin II, and radioligand binding was displaced using the antagonist losartan and the natural agonist angiotensin II. Reproducible K(d), B(max), and K(i) values and good total binding/nonspecific binding (TB/NSB) ratios were obtained with both the ScreenReady Targets and the filtration assay, whereas the WGA Flashplates showed unacceptably high nonspecific binding and high variation when applied as a homogeneous assay. However, when applied as a heterogeneous assay (i.e., when a wash step at the end of the assay is included), the results were significantly better. Interestingly, ligand affinities were consistently lower in Flashplate-based assays than in the filtration assay. This may be due to the immobilization of the receptors onto the solid surface of the plate, affecting their conformation. In terms of reproducibility, robustness, and feasibility for HTS, the authors conclude that the ScreenReady Target plates are most suitable for AT(1) receptor binding screening.


Assuntos
Filtração/métodos , Receptor Tipo 1 de Angiotensina/metabolismo , Angiotensina II/metabolismo , Animais , Ligação Competitiva , Células CHO , Cricetinae , Filtração/instrumentação , Ligantes , Losartan/metabolismo , Ligação Proteica , Receptor Tipo 1 de Angiotensina/agonistas , Termodinâmica , Aglutininas do Germe de Trigo/metabolismo
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