PACLITAXEL DISPOSITION STUDIES USING P-GP INHIBTOR & INDUCER BY SINGLE PASS INTESTINAL PERFUSION IN RATS

Objective: The present research work aims to study the intestinal transport of Paclitaxel and to predict its human intestinal permeability and fraction absorbed using SPIP Permeability Coefficient and the effect of P-gp modulators on Paclitaxel were observed in anaesthetized rats. Methods: Jejunal segment was used for performing Single Pass Intestinal Perfusion. The rationale for the selection of jejenum is due to the overexpression of P-glycoprotein when compared with other segments. Drug solution (150µg/ml) in phosphate buffer saline was perfused at a flow rate of 0.2ml/min.Besides,P-gp inhibitor verapamil(200 µg/ml) and inducer Rifampicin (60mg/ml) were coperfused with Paclitaxel to detect its disposition characteristics affected by P-gp .Drug concentrations in samples were analyzed using HPLC. Stability studies were conducted to ensure the loss of Paclitaxel due to absorption. Results: The effective permeability value of Paclitaxel (150µg/ml) in the jejunal segment was found to be lower due to the efflux mediated by P-gp.When coperfused with verapamil its permeability significantly enhanced as it is a P-gp inhibitor and vice versa with Rifampicin which is a P-gp inducer. Subsequently the human intestinal permeability was estimated considering Peff(human) =1.04 Peff(rat)-0.0003. Conclusion: P-Glycoprotein mediated drug resistance is one of the serious limitations of Paclitaxel efficacy and jejunal segment is found to have major MDR expression. The Peff value of Paclitaxel was found to be increased upon the Coperfusion with verapamil and similarly reduced with Rifampicin which are inhibitors & inducers respectively indicating Paclitaxel is efficiently transported by P-gp. Hence, Paclitaxel satisfies all the prerequisites to be a P-gp substrate.   Keywords: Paclitaxel, Intestinal permeability, Single pass intestinal perfusion, P-glycoprotein, RP-HPLC

Stalk Rots

Stalk rots of sorghum are diseases of great destructive potential Rots caused by the fungi Macrophomina phaseolina and Fusarium moniliforme appear to be widely distributed stalk diseases of sorghum. Recently a vascular pathogen, Acremonium strictum that causes leaf and stalk death, has become important on sorghum. Improved high-yielding varieties tend to be highly susceptible to these diseases. Losses vary from season to season and region to region. Grain losses exceeding 15% are not uncommon; as much as 60% can occur. Several fungi and bacteria are often associated in diseased roots and stalks, suggesting that stalk rot diseases are of complex etiology. Etiology and host resistance to charcoal rot, fusarium root and stalk rot, and acremonium wilt are discussed

Structural and Dielectric Characterization of La Modified PZT (52/48) Nano Ceramic Material for Electronic Applications

The objective of the presented work is to investigate the effects of varying concentration of La as hard dopant on structural, morphological and dielectric properties of lead zirconium titanate (PZT). The base material PZT was prepared by sol-gel technique on lab scale to reduce the injection of sintering defects. After addition of varying weight percentage of La, the different composite materials were analyzed under scanning electron microscope to study the structural modifications taking place. X-Ray diffraction patterns were studied in combination with variation of dielectric constant with temperature and frequency. it is observed that a single phase perovskite structure with tetragonal phase is formed for all compositions of PLZT. The dielectric constant of undoped PZT is found to be 11,300 at a temperature of 500OC and frequency of 100Hz. The results further indicate that the dielectric properties of the pure-phase PZT are better than La doped PZT at higher temperature

Crystal and Molecular Docking Studies of 3-[ Bis-(2-Hydroxy-4,4-Dimethyl-6-Oxo-Cyclohex-1-Enyl)-Methyl]Benzonitrilewith Focal Adhesion Kinase Inhibitors

In the present study crystal structure of 3-[Bis-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-methyl]benzonitrile was determined using single crystal X-ray diffraction. Further the structural features was extrapolated to molecular docking studies with focal adhesion kinase (FAK) domain using Autodock to study its anticancerous property. The compound exhibited considerable bacterial inhibition of lower to moderate concentrations. We conclude that these derivatives can be used in medicine and have enormous potential as pharmaceutical agents due to their biological activities. The above titled receptor gain functional and structural insights into their mechanism of inhibition and explore its potential as an anticancer agent

Analysis Of Linear And Planarantenna Arrays

This paper describes the theories and techniques for designing linear and planar Antenna arrays and compares their radiation pattern with conventional arrays. The results of this work are among others, a software that includes the design of linear and planar arrays. Linear arrays cover uniform and non-uniform cases for broadside, endfire, scanning, and Hansen-woodyard radiation patterns. In linear arrays the amplitude and separation can be chosen for any distribution and triangular. Planar uniform arrays have been incorporated in the software for rectangular and circulargeometries and today we are developing non-uniform arrays for the

Crystal and molecular docking studies of 3-​[Bis-​(2-​hydroxy-​4,​4-​dimethyl-​6-​oxo-​cyclohex-​1-​enyl)​-​methyl]​benzonitrile with focal adhesion kinase inhibitors

In the present study crystal structure of 3-​[Bis-​(2-​hydroxy-​4,​4-​dimethyl-​6-​oxo-​cyclohex-​1-​enyl)​-​methyl]​benzonitrile was detd. using single crystal X-​ray diffraction. Further the structural features was extrapolated to mol. docking studies with focal adhesion kinase (FAK) domain using Autodock to study its anticancerous property. The compd. exhibited considerable bacterial inhibition of lower to moderate concns. We conclude that these derivs. can be used in medicine and have enormous potential as pharmaceutical agents due to their biol. activities. The above titled receptor gain functional and structural insights into their mechanism of inhibition and explore its potential as an anticancer agent

Effect of moisture stress, plant population density and pathogen inoculation on charcoal stalk rot of sorghum

The effects of moisture deficit stress, plant population density and pathogen inoculation technique on charcoal stalk rot in the sorghum hybrid CSH 6 were studied in the 1980–81 and 1981–82 post-rainy seasons at three locations in India. Incidence and severity of charcoal rot caused by Macrophomina phaseolina were compared in three plant population densities, subjected to different moisture stress regimes created by withholding irrigation at various plant growth stages. Natural infections were compared to artificial inoculation with M. phaseolina. Combinations of moisture stress, plant population and inoculation treatments were compared to identify the combination most likely to develop maximum disease. Lodging, the first external symptom of charcoal rot, was significantly correlated with other disease symptoms used to measure charcoal rot, such as soft stalk, number of nodes crossed by M. phaseolina infection, root damage and plant senescence. In both seasons the highest incidence of lodging occurred when moisture stress was induced at the ‘flag leaf visible in the whorl’ growth stage. The greatest incidence of the disease was recorded in the highest plant population (266 700 plant ha-) at all three locations. No significant differences were found between artificially and naturally inoculated treatments. The maximum number of lodged plants was found at a density of 266 700 plants ha-1 when moisture stress was induced at the ‘flag leaf visible in the whorl’ growth stage

Transdermal immunization: A recent tool for immunization

Vaccination is one of the most powerful tools available in the ongoing battle against infectious agents. Virtually all recommended immunizations require parenteral administration, and many require a series of injections, therefore, new vaccine delivery methods, specifically alternatives to injections, are being sought. Transdermal immunization (TI) offers a new method for the delivery of vaccines, that relies on the application of antigen with adjuvant onto the outer layer of the skin and subsequent delivery to underlying Langerhans cells that serve as antigen-presenting cells. TI is a needle-free method of vaccine delivery that, will decrease the risk of needle-borne diseases, improve access to vaccination by eliminating the need for trained personnel and sterile equipment, and possibly provide a simple means for multivalent-or multiple boosting immunizations. This review presents various novel approaches for TI that is used alternative to parenteral immunization

Etiology of stalk rot and lodging in grain sorghum

The effects of fungi alone, dmught-stres* alone, and in combination on the development of stalk rot (%lodging)Sorghum were studied in field experiments at ICRISAT Asia Center, Patancheru and at University of Agricultural Sciences, Dharwad in india. Stalk rot and lodging occurred In drought-stressed................