Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

Mass Spectrometric Characterization of a Thermolabile Metabolite of Camazepam

Incubation of camazepam [3-(N,N-dimethyl) carbamoyloxy-7-chloro-1- methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one] with rat liver microsomes and cofactors produced a 3-(N-methyl-N-hydroxymethyl) carbamoyloxy derivative as the most abundant metabolite.This metabolite was thermally unstable and was isolated from a metabolite mixture by normal-phase High-Performance Liquid Chromatography.Its struc- ture was established by chemical ionization and ^(252)Cf plasma desorption time-of-flight mass spectral analyses.

Unitary fermions and Lscher's formula on a crystal

We consider the low-energy particle-particle scattering properties in a periodic simple cubic crystal. In particular, we investigate the relation between the two-body scattering length and the energy shift experienced by the lowest-lying unbound state when this is placed in a periodic finite box. We introduce a continuum model for s-wave contact interactions that respects the symmetry of the Brillouin zone in its regularisation and renormalisation procedures, and corresponds to the nae continuum limit of the Hubbard model. The energy shifts are found to be identical to those obtained in the usual spherically symmetric renormalisation scheme upon resolving an important subtlety regarding the cutoff procedure. We then particularize to the Hubbard model, and find that for large finite lattices the results are identical to those obtained in the continuum limit. The results reported here are valid in the weak,intermediate and unitary limits. These may be used to significantly ease the extraction of scattering information, and therefore effective interactions in condensed matter systems in realistic periodic potentials. This can achieved via exact diagonalisation or Monte Carlo methods, without the need to solve challenging, genuine multichannel collisional problems with very restricted symmetry simplifications.