A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium/glucose cotransporters

Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes. The pharmacokinetic profile, metabolites of the PRZ, and efficacy of metabolites towards SGLTs are unknown. Therefore, the present study on the characterization of hitherto unknown in vivo metabolites of PRZ and pharmacokinetic profiling using liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) and accurate mass measurements is undertaken. Plasma, urine, and feces samples were collected after oral administration of PRZ to Sprague–Dawley rats to identify in vivo metabolites. Furthermore, in silico efficacy of the identified metabolites was evaluated by docking study. PRZ at an intraperitoneal dose of 400 mg/kg showed maximum concentration in the blood to 439.32 ± 8.84 ng/mL at 1 h, while phloretin showed 14.38 ± 0.33 ng/mL at 6 h. The pharmacokinetic profile of PRZ showed that the maximum concentration lies between 1 and 2 h after dosing. Decreased blood glucose levels and maximum excretion of glucose in the urine were observed when the PRZ and metabolites were observed in plasma. The identification and characterization of PRZ metabolites by LC/ESI/MS/MS further revealed that the phase I metabolites of PRZ are hydroxy (mono-, di-, and tri-) and reduction. Phase II metabolites are O-methylated, O-acetylated, O-sulfated, and glucuronide metabolites of PRZ. Further docking study revealed that the metabolites diglucuronide metabolite of mono-hydroxylated PRZ and mono-glucuronidation of PRZ could be considered novel inhibitors of SGLT1 and SGLT2, respectively, which show better binding affinities than their parent compound PRZ and the known inhibitors.     

Determination of electron affinity of carbonyl radicals by means of negative ion mass spectrometry

Appearance energies of [M-H](-) ions from carbonyl compounds R-CO-R' (R,R' = H, CH(3), NH(2), OH) have been measured by means of negative ion mass spectrometry in resonant electron capture mode. Values of electron affinity of the corresponding radicals, CH(2)&dbond;C(X)O, NH&dbond;C(X)O and O&dbond;C(X)O, have been determined. Copyright 1999 John Wiley & Sons, Ltd.     

Transmission properties of a double-periodic quasi-crystal containing single-negative materials

The transmission properties of a double-periodic quasi-crystal containing single-negative materials are investigated with the transfer matrix method and effective medium theory. It is shown that the double-periodic quasi-crystal has a single-negative band gap between the zeros of average permittivity and average permeability of the effective medium. These zeros are affected only by the filling factor of the structure, and are independent from the order of the double-periodic quasi-crystal. Moreover, we show that the periodic structure created by repeating the double-periodic quasi-crystal has some omnidirectional band gaps at the single-negative frequency region. The number of such omnidirectional band gap increases by increasing the order of double-periodic quasi-crystal. Then, the structure can be used as a multichannel filter.     

Band structure of two-dimensional square lattice photonic crystals of circular dispersive metamaterial rods

By virtue of the efficiency of the Dirichlet-to-Neumann map method, the details of the band structure of a two-dimensional square lattice photonic crystal composed of dispersive metamaterial circular rods in air background has been studied. We show that there are two flat bands at the band structure of the system for both H-polarization and E-polarization. These flat bands are created around the magnetic resonance frequency, surface plasmon frequency and magnetic surface plasmon frequency. We realized that the modes with frequencies lying above the resonance frequency behave like resonant cavity modes created in a single metallic cylindrical waveguide. While, due to the relatively large and imaginary refractive index of the metamaterial rods at the frequencies lying below the resonance frequency, the modes are localized modes with negligible penetration into the rods. Moreover, the modes are localized at the interface of the cylindrical metamaterial rods and the air background for the frequencies around the surface plasmon frequency and the magnetic surface plasmon frequency.     

Disentanglement of atom-photon via quantum interference in driven three-level atoms

In this paper, the effect of quantum interference on the entanglement of a driven V-type three-level atom and its spontaneous emission field was investigated by using the quantum entropy. The results indicate that, in the absence of quantum interference the atom and its spontaneous emission field are always entangled at the steady-state. But, in the presence of full quantum interference their steady-state entanglement depends on the atomic parameters. Specifically, with appropriate atomic parameters they can be entangled or disentangled at the steady-state. We realized that the steady-state entanglement is due to completely destructive nature of quantum interference. On the contrary, the steady-state disentanglement is due to instructive nature of quantum interference.