RESUMEN
Focal atrial tachycardias arising from the atrial appendages and the aortic sinuses of Valsalva are less frequently encountered in clinical practice. This review article describes the clinical presentation, surface P wave morphology, electrophysiologic characteristics and treatment of these arrhythmias. Catheter ablation of these focal tachycardias has a high success rate. It is however important to be aware of specific anatomic considerations in these locations for optimal treatment outcomes with low complication rates.
Asunto(s)
Apéndice Atrial , Seno Aórtico/patología , Seno Aórtico/fisiopatología , Taquicardia/patología , Taquicardia/fisiopatología , Ablación por Catéter , Humanos , Taquicardia/terapia , Taquicardia SupraventricularRESUMEN
Glycogen synthase kinase-3 (GSK-3) protein levels and activity are elevated in skeletal muscle in type 2 diabetes, and inversely correlated with both glycogen synthase activity and insulin-stimulated glucose disposal. To explore this relationship, we have produced transgenic mice that overexpress human GSK-3beta in skeletal muscle. GSK-3beta transgenic mice were heavier, by up to 20% (P < .001), than their age-matched controls due to an increase in fat mass. The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). They were also hyperlipidemic with significantly raised serum cholesterol (+90%), nonesterified fatty acids (NEFAs) (+55%), and triglycerides (+170%). At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. Hepatic glycogen levels were significantly increased 4-fold. Female GSK-3beta transgenic mice did not develop glucose intolerance despite 7-fold overexpression of GSK-3beta protein and a 20% reduction in glycogen synthase activation in skeletal muscle. However, plasma NEFAs and muscle IRS-1 protein levels were unchanged in females. We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance.
Asunto(s)
Intolerancia a la Glucosa/genética , Glucógeno Sintasa Quinasa 3/biosíntesis , Glucógeno Sintasa Quinasa 3/genética , Músculo Esquelético/fisiología , Regiones Promotoras Genéticas/fisiología , Animales , Western Blotting , Composición Corporal/fisiología , Peso Corporal/fisiología , Cartilla de ADN , ADN Complementario/biosíntesis , ADN Complementario/genética , Femenino , Prueba de Tolerancia a la Glucosa , Glucógeno/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Proteínas Sustrato del Receptor de Insulina , Resistencia a la Insulina/genética , Resistencia a la Insulina/fisiología , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/metabolismo , Fenotipo , Fosfoproteínas/biosíntesis , Fosfoproteínas/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Co(II) solution species containing 1 equiv of phenanthroline (phen), 2-methyl-1,10-phenanthroline (MMP), or 2,9-dimethyl-1,10-phenanthroline (DMP) ligand formed inner-sphere surface complexes when grafted on silica. The speciation on the silica surface depended on both the pH of the grafting solution and the steric bulk of the ligand. [Co(DMP)](2+) formed tetrahedral surface adducts exclusively, with a 1:1 ligand-Co ratio. These surface adducts were first detectable at pH values above 5.1. [Co(MMP)](2+) and [Co(phen)](2+) formed exclusively octahedral adducts on the surface with a 1:1 ligand-Co ratio at pH values below 5. The [Co(MMP)](2+) complex formed a tetrahedral adduct initially at pH 6 and increasingly as the pH was raised. The [Co(phen)](2+) complex did not produce a comparable tetrahedral surface species under any conditions. Instead, mixtures of octahedral surface species with both 1:1 and 2:1 ligand-Co ratios began to form at pH values above 6. Taken together, the results indicated that the development of tetrahedral stereochemistry was strongly influenced by steric factors in the presence of a nitrogen-donating ligand. All three phenanthroline derivatives promoted surface binding of the Co(II) ion adducts, so that maximal binding occurred at lower pH values than for binding of [Co(H(2)O)(6)](2+), which formed exclusively tetrahedral adducts.
RESUMEN
[Co(2,9-dimethyl-1,10-phenanthroline)(solvent)4]2+ ([Co(neo)]2+) undergoes a significant decrease in symmetry to form an inner-sphere surface complex when grafted directly on performed silica or introduced during the sol-gel process. The visible and X-ray absorption spectra of the surface adducts are interpreted in terms of a binding mode in which the Co(II) center has a highly distorted pseudo-C2v symmetry. The interaction of [Co(neo)]2+ with the silica surface was analyzed using an acid-base equilibrium relationship. Half-maximal surface binding was observed at pH ca. 6. Linear fits to the pH dependence data are consistent with inner-sphere binding of a single silanol group to the cobalt center. The formation of the surface species in tetramethoxyorthosilicate (TMOS) sol-gels required approximately 2 equiv of hydroxide anion per cobalt center, suggesting a two-proton-dependent binding event to form a species such as [Co(neo)(SiO)2]. Both sol-gel and silica samples showed essentially identical visible and X-ray absorption spectra, indicating formation of very similar surface adducts when the different synthesis procedures were employed. The maximal binding of [Co(neo)]2+ on three silica samples with different pore diameters and surface areas was compared. Increased binding was found to be inversely proportional to surface area and proportional to pore diameter, indicating a preference for less sterically demanding surface sites.