RESUMEN
The organizing of magnetic skyrmions shows several forms similar to atomic arrays of solid states. Using Lorentz transmission electron microscopy, we report the first direct observation of a stable liquid-crystalline structure of skyrmions in chiral magnet Co_{8.5}Zn_{7.5}Mn_{4}(110) thin film, caused by magnetic anisotropy and chiral surface twist. Elongated skyrmions are oriented and periodically arranged only in the ⟨110⟩ directions, whereas they exhibit short-range order along the ⟨001⟩ directions, indicating a smectic skyrmion state. In addition, skyrmions possess anisotropic interaction with an opposite sign depending on the crystal orientation, in contrast to existing isotropic interaction.
RESUMEN
The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM). As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice. These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 2/enzimología , Animales , Western Blotting , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/análisis , Humanos , Insulina/administración & dosificación , Intestino Delgado/enzimología , Intestino Delgado/ultraestructura , Cinética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Ratones Obesos , Microsomas/enzimología , Microsomas Hepáticos/enzimología , Triazolam/administración & dosificación , Triazolam/metabolismo , Triazolam/farmacocinéticaRESUMEN
To investigate the pharmacokinetic characteristics in TSOD (Tsumura, Suzuki, obese, diabetes) mice, a model of type 2 diabetes and obesity, the expressions of major hepatic CYP enzymes in TSOD and TSNO (Tsumura, Suzuki, non-obesity; control) mice were compared. The 7-month-old TSOD mice, which represented severe obesity/diabetes-related pathophysiology, showed higher expressions of Cyp2c and Cyp3a compared with TSNO mice, while those of Cyp1a and Cyp2e were lower. Cyp3a metabolic activity was also higher in TSOD mice. In the 7-month-old liver, pregnane X receptor (PXR) (nuclear receptor) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) (cofactor) mRNA expression were higher in TSOD mice, possibly playing a role in the altered expression of Cyp3a. This specifically altered CYP expression in TSOD mice suggests that the biotransformation of drugs metabolized by these CYP enzymes differs from that in normal animals. Based on these findings, further investigation on the relationship between altered CYP expression and pathophysiology may be useful in elucidating changes in pharmacokinetics in obese/diabetic patients.
Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/enzimología , Obesidad/complicaciones , Obesidad/enzimología , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Dexametasona/farmacología , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Gluconeogénesis/efectos de los fármacos , Gluconeogénesis/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Obesidad/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Tiempo , Triazolam/metabolismo , Triazolam/farmacocinéticaRESUMEN
In order to determine the effects of intestinal flora on the expression of cytochrome P450 (CYP), the mRNA expression of CYP was compared between specific pathogen-free (SPF) and germ-free (GF) mice. Most of the major CYP isozymes showed higher expression in the livers of SPF mice compared with GF mice. Nuclear factors such as pregnane X receptor (PXR) and constitutive androstane receptor (CAR), as well as transporters and conjugation enzymes involved in the detoxification of lithocholic acid (LCA), also showed higher expression in SPF mice. The findings suggest that in the livers of SPF mice, LCA produced by intestinal flora increases the expression of CYPs via activation of PXR and CAR. Drugs such as antibiotics, some diseases and ageing, etc. are known to alter intestinal flora. The present findings suggest that such changes also affect CYP and are one of the factors responsible for individual differences in pharmacokinetics.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Intestinos/microbiología , Hígado/metabolismo , ARN Mensajero/metabolismo , Animales , Bacterias/química , Western Blotting , Cromatografía Líquida de Alta Presión , Receptor de Androstano Constitutivo , Citocromo P-450 CYP3A , Cartilla de ADN/genética , Vida Libre de Gérmenes , Isoenzimas/metabolismo , Cinética , Ácido Litocólico/farmacología , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptor X de Pregnano , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Esteroides/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Organismos Libres de Patógenos Específicos , Factores de Transcripción/metabolismoRESUMEN
The physical picture of higher-order Laue zone (HOLZ) line contrast in a large-angle convergent-beam electron diffraction pattern around a dislocation, which is used for determining the Burgers vector, was examined. To evaluate the analytical expression of diffracted wave amplitude, we introduced an approximate form of the atomic displacement field of a dislocation. We showed that the four features of the HOLZ line contrast, that is, splitting, fading, bending and periodical contrast can be explained by analysis of the atomic displacement field. The localized lattice plane bending around a dislocation core made a HOLZ line split, fade and bend. However, we found that the periodical contrast of a HOLZ line was produced by the change of phase difference of the atomic displacement field between the crystals above and below the slip plane across the dislocation line.
RESUMEN
We have established a (110) cross-sectional high-resolution transmission electron microscopy (HREM) method to observe atomic structures of semiconductor hetero-interfaces. We show theoretically that the semiconductors in a hetero-structure exhibit strong contrast for an EM specimen thickness near their extinction distances, allowing atomic-scale observations of the interfacial structures between them. Furthermore, to obtain a clear HREM image, an EM specimen preparation technique is developed in which chemical etching is used to remove ion milling artifacts. This HREM method allows edge-on imaging of interfaces formed along the (110) direction; observations of atomic steps at AlAs/GaAs interfaces and a chemically ordered structure at Si/Ge interfaces are demonstrated.