ISOLATION AND CHARACTERISATION OF RAPAMYCIN, TEMSIROLIMUS REGIO ISOMER (MONOESTER) AND TEMSIROLIMUS DIESTER IN TEMSIROLIMUS DRUG

Objective: Separation and identification of the process impurities in the manufacture of temsirolimus drug viz., rapamycin, temsirolimus regioisomer (monoester) (TS monoester), and temsirolimus diester (TS diester). Methods: During the process development of temsirolimus (TS), three process impurities-rapamycin, temsirolimus regioisomer (monoester) and temsirolimus diester-were detected by high-performance liquid chromatography (HPLC). Impurities were isolated by medium pressure liquid Chromatography (MPLC) and characterized by ESI-MS/MS, 1H NMR, FT-IR spectral data. Results: These impurities are characterised with the help of ESI MS/MS, 1H NMR, and FT-IR data. The impurities are identified and characterised as the process impurities. One of them is the starting material i.e. rapamycin and the other two are formed during the manufacture of the drug. This method offers advantages over using photodiode-array UV detection (LC-PDA) for the determination of peak purity, viz. components with similar UV spectra can be distinguished. Conclusion: The structures of these impurities were characterized as rapamycin, TS Monoester, and TS Diester. Out of these process impurities, rapamycin has been previously identified while the other two are previously unreported

Evaluation of Anti-Inflammatory Properties of Isoorientin Isolated from Tubers of Pueraria tuberosa

Inflammation is the major causative factor of different diseases such as cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Anti-inflammatory drugs are often the first step of treatment in many of these diseases. The present study is aimed at evaluating the anti-inflammatory properties of isoorientin, a selective cyclooxygenase-2 (COX-2) inhibitor isolated from the tubers of Pueraria tuberosa, in vitro on mouse macrophage cell line (RAW 264.7) and in vivo on mouse paw edema and air pouch models of inflammation. Isoorientin reduced inflammation in RAW 264.7 cell line in vitro and carrageenan induced inflammatory animal model systems in vivo. Cellular infiltration into pouch tissue was reduced in isoorientin treated mice compared to carrageenan treated mice. Isoorientin treated RAW 264.7 cells and animals showed reduced expression of inflammatory proteins like COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-lipoxygenase (5-LOX), and interleukin 1-β (IL-1-β) both in vitro and in vivo. The antioxidant enzyme levels of catalase and GST were markedly increased in isoorientin treated mice compared to carrageenan treated mice. These results suggest that isoorientin, a selective inhibitor of COX-2, not only exerts anti-inflammatory effects in LPS induced RAW cells and carrageenan induced inflammatory model systems but also exhibits potent antioxidant properties

Unsteady flow of a nanofluid over a sphere with nonlinear Boussinesq approximation

A theoretical study is presented of transient mixed convection boundary layer flow of a nanofluid in the forward stagnation region of a heated sphere which is rotating with time dependent angular velocity. The effect of the non-linear Boussinesq approximation is taken into account. The nanofluid is treated as a two-component mixture i.e. nano-particles distributed homogenously in a base fluid (water or gas). The effects of the Brownian motion and thermophoresis are included for the nanofluid and constant wall temperature is imposed at the sphere surface. The first and second laws of thermodynamics are employed in order to study thermophysics as well as heat and mass transfer phenomena. By introducing appropriate similarity variables the governing equations are transformed into a system of dimensionless, nonlinear, coupled, ordinary differential equations which are solved numerically by applying the second-order accurate implicit finite difference Keller box method. The reliability and efficiency of the obtained numerical results are validated via comparison with the previously published results for special cases. The effects of various parameters on primary and secondary velocities, temperature, nanofluid volume fraction (concentration), primary and secondary shear stress functions, Nusselt number function (wall heat transfer rate) and Sherwood number function (wall nanoparticle mass transfer rate) are visualized. Furthermore the influence of non-linear temperature parameter, Brinkman parameter (ratio of Brinkman number to dimensionless temperature ratio), local Reynolds number and unsteadiness parameter on entropy generation number is computed. A strong elevation in entropy generation number is computed with both increasing Brinkman parameter and unsteadiness parameter. Primary and secondary surface shear stresses, Nusselt number and Sherwood number also increase with unsteadiness and rotation parameters. Primary shear stress is boosted with increasing mixed convection parameter and Brownian motion effect whereas secondary shear stress is depressed. Temperatures are suppressed with increasing nonlinear temperature parameter whereas nano-particle concentrations are elevated. Increasing thermophoresis parameter enhances both temperatures and nano-particle concentration values. The simulations find applications in rotating chemical engineering mixing systems and nano-coating transport phenomena

Entropy analysis on convective film flow of power-law fluid with nanoparticles along an inclined plate

Entropy generation in a two-dimensional steady laminar thin film convection flow of a non-Newtonian nanofluid (Ostwald-de-Waele-type power-law fluid with embedded nanoparticles) along an inclined plate is examined theoretically. A revised Buongiorno model is adopted for nanoscale effects, which includes the effects of the Brownian motion and thermophoresis. The nanofluid particle fraction on the boundary is passively rather than actively controlled. A convective boundary condition is employed. The local nonsimilarity method is used to solve the dimensionless nonlinear system of governing equations. Validation with earlier published results is included. A decrease in entropy generation is induced due to fluid friction associated with an increasing value of the rheological power-law index. The Brownian motion of nanoparticles enhances thermal convection via the enhanced transport of heat in microconvection surrounding individual nanoparticles. A higher convective parameter implies more intense convective heating of the plate, which increases the temperature gradient. An increase in the thermophoresis parameter decreases the nanoparticle volume fraction near the wall and increases it further from the wall. Entropy generation is also reduced with enhancement of the thermophoresis effect throughout the boundary layer

Radiation and chemical reaction effects on MHD flow along a moving vertical porous plate

This paper presents an analysis of the effects of magnetohydrodynamic force and buoyancy on convective heat and mass transfer flow past a moving vertical porous plate in the presence of thermal radiation and chemical reaction. The governing partial differential equations are reduced to a system of self-similar equations using the similarity transformations. The resultant equations are then solved numerically using the fourth order Runge-Kutta method along with the shooting technique. The results are obtained for the velocity, temperature, concentration, skin-friction, Nusselt number and Sherwood number. The effects of various parameters on flow variables are illustrated graphically, and the physical aspects of the problem are discussed

Studies on stress- strain behaviour of fibre reinforced self-compacting concrete in confined state

In the present study, the stress-stain behaviour of self-compacting concrete (SCC) and fibre reinforced self-compacting concrete (FRSCC) were taken up. The stress-strain behaviour was studied for the SCC and FRSCC mixes in unconfined and confined states. The confinement was given in the form of steel hoops in the cylinders, 3 hoops (0.8%), 4 hoops (1.1%), 5 hoops (1.3%) and 6 hoops (1.6%). The addition of fibres along with confinement of FRSCC with steel hoops enhanced the compressive strength, indicating further confinement effect in the FRSCC. It is observed that the addition of fibres is helpful in lower confinements only. Beyond 1.1% confinement, the addition of any type of fibres doesn’t show any effect on compressive strengths. From the stress-strain behaviour of all types of FRSCC, it is concluded that the ultimate load-carrying capacity and strains at peak stresses are more in SFRSCC and HFRSCC for mixes up to 1.1% confinement. The addition of fibres to SCC has increased the ductility in both confined and unconfined state

Flexural behaviour of hybrid fibre reinforced concrete beams made with various packing factors and fine to total aggregate ratio

The objective of this study is to investigate the flexural behavior of M30 grade PSCC, GFRSCC, SFRSCC and HFRSCC beams made with PF=1.12 and s/a=0.53 and PF=1.14 and s/a=0.57 to understand the effect of copper slag as partial replacement of fine aggregate on its deflection characteristics and cracking behaviour. The yield and ultimate load taken by HFRSCC beams made with optimum PF and s/a ratios are higher than the conventional RCC beam elements. The deflections at centre at failure in HFRSCC beams made with optimum PF and s/a ratios were more than that of conventional beams. This shows improvement in ductility of HFRSCC beams. First crack formation was delayed in M30 grade HFRSCC beams due to dense micro structure with low pore fraction and reduced pore size due to which fatigue strength is increased which in turn increases the time taken for first crack occurrence and thereby increasing the load carrying capacity. The deflection at the mid span decreased in HFRSCC beams which shows that the flexural stiffness of the elements increases thereby reducing the structural member’s deformability, increasing strength and hence controlling deflection

Entropy Generation Analysis in Nonlinear Convection Flow of Thermally Stratified Fluid in Saturated Porous Medium With Convective Boundary Condition

This article emphasizes the significance of entropy generation analysis and nonlinear temperature density relation on thermally stratified viscous fluid flow over a vertical plate embedded in a porous medium with a thermal dispersion effect. In addition, the convective surface boundary condition is taken into an account. By using the suitable transformations, the governing flow equations in dimensional form are converted into set of nondimensional partial differential equations. Then the local similarity and nonsimilarity procedures are applied to transform the set of nondimensional partial differential equations into set of ordinary differential equations and then the resulting system of equations are solved by Chebyshev spectral collocation method along with the successive linearization. The effect of pertinent parameters, namely, Biot number, mixed convection parameter, and thermal dispersion on velocity, temperature, entropy generation rate, and heat transfer rate are displayed graphically and the salient features are explored in detail

High-throughput screening assays for cyclooxygenase-2 and 5-lipoxygenase, the targets for inflammatory disorders

256-261High-throughput screening (HTS) involves testing of compound libraries against validated drug targets using quantitative bioassays to identify ‘hit’ molecules that modulate the activity of target, which forms the starting point of a drug discovery effort. Eicosanoids formed via cyclooxygenase (COX) and lipoxygenase (LOX) pathways are major players in various inflammatory disorders. As the conventional non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit both the constitutive (COX-1) and the inducible (COX-2) isoforms have gastric and renal side effects and the recently developed COX-2 selective anti-inflammatory drugs (COXIBs) have cardiac side effects, efforts are being made to develop more potent and safer anti-inflammatory drugs. Current assay methods for these enzymes, such as oxygraphic, radioisotopic, spectrophotometric etc. are not compatible for screening of large number of compounds as in drug discovery programs. In the present study, HTS-compatible assays for COX-1, COX-2 and 5-LOX were developed for screening of compound libraries with the view to identify potential anti-inflammatory drug candidates. A spectrophotometric assay involving co-oxidation of tetramethyl-p-phenylene diamine (TMPD) during the reduction of prostaglandin G2 (PGG2) to PGH2 was adopted and standardized for screening of compounds against COX-1 and COX-2. Similarly, the HTS-compatible FOX (ferrous oxidation-xylenol orange) based spectrophotometric assay involving the formation of Fe3+/xylenol orange complex showing absorption in the visible range was developed for screening of compounds against 5-LOX