In Vitro Ketamine CYP3A Mediated Metabolism Study using Mammalian Liver S9 Fractions, cDNA Expressed Enzymes and Liquid Chromatography Tandem Mass Spectrometry

Ketamine is widely used in medicine in combination with several benzodiazepines including midazolam. The objectives of this study were to develop a novel HPLC-MS/SRM method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well-known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 x 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μM. The precision (%CV) and accuracy (%NOM) observed were ranging from 3.9–7.8 and 95.9.2–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentration and Km values of 18.4 μM, 13.8 μM and 30.8 μM for rat, dog and human liver S9 fractions were observed respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T1/2 = 159.4 min) compared with rat (T1/2 = 12.6 min) and dog (T1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC50 and Ki values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed the formation of norketamine is mediated by CYP3A but results suggest an important contribution from others isoenzymes, most likely CYP2C particularly in rat.

Emission spectral studies of phthalocyanines in borate glass matrix

Cochin University of Science & Technology

Topological Invariants in Hydrodynamics and Hydromagnetics

In this thesis we are studying possible invariants in hydrodynamics and hydromagnetics. The concept of flux preservation and line preservation of vector fields, especially vorticity vector fields, have been studied from the very beginning of the study of fluid mechanics by Helmholtz and others. In ideal magnetohydrodynamic flows the magnetic fields satisfy the same conservation laws as that of vorticity field in ideal hydrodynamic flows. Apart from these there are many other fields also in ideal hydrodynamic and magnetohydrodynamic flows which preserves flux across a surface or whose vector lines are preserved. A general study using this analogy had not been made for a long time. Moreover there are other physical quantities which are also invariant under the flow, such as Ertel invariant. Using the calculus of differential forms Tur and Yanovsky classified the possible invariants in hydrodynamics. This mathematical abstraction of physical quantities to topological objects is needed for an elegant and complete analysis of invariants.Many authors used a four dimensional space-time manifold for analysing fluid flows. We have also used such a space-time manifold in obtaining invariants in the usual three dimensional flows.In chapter one we have discussed the invariants related to vorticity field using vorticity field two form w2 in E4. Corresponding to the invariance of four form w2 ^ w2 we have got the invariance of the quantity E. w. We have shown that in an isentropic flow this quantity is an invariant over an arbitrary volume.In chapter three we have extended this method to any divergence-free frozen-in field. In a four dimensional space-time manifold we have defined a closed differential two form and its potential one from corresponding to such a frozen-in field. Using this potential one form w1 , it is possible to define the forms dw1 , w1 ^ dw1 and dw1 ^ dw1 . Corresponding to the invariance of the four form we have got an additional invariant in the usual hydrodynamic flows, which can not be obtained by considering three dimensional space.In chapter four we have classified the possible integral invariants associated with the physical quantities which can be expressed using one form or two form in a three dimensional flow. After deriving some general results which hold for an arbitrary dimensional manifold we have illustrated them in the context of flows in three dimensional Euclidean space JR3. If the Lie derivative of a differential p-form w is not vanishing,then the surface integral of w over all p-surfaces need not be constant of flow. Even then there exist some special p-surfaces over which the integral is a constant of motion, if the Lie derivative of w satisfies certain conditions. Such surfaces can be utilised for investigating the qualitative properties of a flow in the absence of invariance over all p-surfaces. We have also discussed the conditions for line preservation and surface preservation of vector fields. We see that the surface preservation need not imply the line preservation. We have given some examples which illustrate the above results. The study given in this thesis is a continuation of that started by Vedan et.el. As mentioned earlier, they have used a four dimensional space-time manifold to obtain invariants of flow from variational formulation and application of Noether's theorem. This was from the point of view of hydrodynamic stability studies using Arnold's method. The use of a four dimensional manifold has great significance in the study of knots and links. In the context of hydrodynamics, helicity is a measure of knottedness of vortex lines. We are interested in the use of differential forms in E4 in the study of vortex knots and links. The knowledge of surface invariants given in chapter 4 may also be utilised for the analysis of vortex and magnetic reconnections.

Chaotic dynamics of electric-field domains in periodically driven superlattices

Self-sustained time-dependent current oscillations under dc voltage bias have been observed in recent experiments on n-doped semiconductor superlattices with sequential resonant tunneling. The current oscillations are caused by the motion and recycling of the domain wall separating low- and high-electric-field regions of the superlattice, as the analysis of a discrete drift model shows and experimental evidence supports. Numerical simulation shows that different nonlinear dynamical regimes of the domain wall appear when an external microwave signal is superimposed on the dc bias and its driving frequency and driving amplitude vary. On the frequency-amplitude parameter plane, there are regions of entrainment and quasiperiodicity forming Arnold tongues. Chaos is demonstrated to appear at the boundaries of the tongues and in the regions where they overlap. Coexistence of up to four electric-field domains randomly nucleated in space is detected under ac+dc driving.

Quadrupole moments of radium isotopes from the 7p^2P_3/2 hyperfine structure in Ra II

The hyperfine structure and isotope shift of ^{221- 226}Ra and ^{212, 214}Ra have been measured in the ionic (Ra 11) transition 7s^2 S_{1/2} - 7p ^2 P_{3/2} (\lamda = 381.4 nm). The method of on-line collinear fast-beam laser spectroscopy has been applied using frequency-doubling of cw dye laser radiation in an external ring cavity. The magnetic hyperfine fields are compared with semi-empirical and ab initio calculations. The analysis of the quadrupole splitting by the same method yields the following, improved values of spectroscopic quadrupole moments: Q_s(^221 Ra)= 1.978(7)b, Q_s (^223 Ra)= 1.254(3)b and the reanalyzed values Q_s(^209 Ra) = 0.40(2)b, Q_s(^211 Ra) = 0.48(2)b, Q_s(^227 Ra)= 1.58(3)b, Q_s (^229 Ra) = 3.09(4)b with an additional scaling uncertainty of ±5%. Furthermore, the J-dependence of the isotope shift is analyzed in both Ra II transitions connecting the 7s^2 S_{1/2} ground state with the first excited doublet 7p^ P_{1/2} and 7p^ P_{3/2}.

Relativity and screening effects in heavy-ion collisions

Diatomic correlation diagrams are the main basis for the description of heavy-ion collisions. We have constructed the first realistic relativistic many-electron correlation diagrams based on nonrelativistic self-consistent-field, Hartree-Fock calculations of diatomic molecules plus relativistic corrections. We discuss the relativistic influences as well as the many-electron screening effects in the I-Au system with a combined charge of Z = 132 as an example.