Regulation of activity of the yeast TATA-binding protein through intra-molecular interactions

Dimerization is proposed to be a regulatory mechanism for TATA-binding protein (TBP) activity bothin vitro andin vivo. The reversible dimer-monomer transition of TBP is influenced by the buffer conditionsin vitro. Usingin vitro chemical cross-linking, we found yeast TBP (yTBP) to be largely monomeric in the presence of the divalent cation Mg2+, even at high salt concentrations. Apparent molecular mass of yTBP at high salt with Mg2+, run through a gel filtration column, was close to that of monomeric yTBP. Lowering the monovalent ionic concentration in the absence of Mg2+, resulted in dimerization of TBP. Effect of Mg2+ was seen at two different levels: at higher TBP concentrations, it suppressed the TBP dimerization and at lower TBP levels, it helped keep TBP monomers in active conformation (competent for binding TATA box), resulting in enhanced TBP-TATA complex formation in the presence of increasing Mg2+. At both the levels, activity of the full-length TBP in the presence of Mg2+ was like that reported for the truncated C-terminal domain of TBP from which the N-terminus is removed. Therefore for full-length TBP, intra-molecular interactions can regulate its activity via a similar mechanism

The transcriptional activator GAL4-VP16 regulates the intra-molecular interactions of the TATA-binding protein

Binding characteristics of yeast TATA-binding protein (yTBP) over five oligomers having different TATA variants and lacking a UASGal, showed that TATA-binding protein (TBP)-TATA complex gets stabilized in the presence of the acidic activator GAL4-VP16. Activator also greatly suppressed the non-specific TBP-DNA complex formation. The effects were more pronounced over weaker TATA boxes. Activator also reduced the TBP dimer levels bothin vitro andin vivo, suggesting the dimer may be a direct target of transcriptional activators. The transcriptional activator facilitated the dimer to monomer transition and activated monomers further to help TBP bind even the weaker TATA boxes stably. The overall stimulatory effect of the GAL4-VP16 on the TBP-TATA complex formation resembles the known effects of removal of the N-terminus of TBP on its activity, suggesting that the activator directly targets the N-terminus of TBP and facilitates its binding to the TATA box

GC-MS Analysis of Methanol and Ethyl Acetate Extract of fruits of Sphaeranthus indicus

Introduction: To identify the various phytoconstituents present in the plant Sphaeranthus indicus by using gas chromatography and mass spectrometry. Meth­ods: The fruits of Sphaeranthus indicus were extracted with Different solvents of increasing polarity. The methanol and ethylacetate extract were subjected to GCMS analysis to detect the phytoconstituents. Results: Totally 26 compounds were identified. Among these 13 constituents in methanol extract and 13 constituents in ethylacetate extract were identified during the GC-MS analysis. Stigmasterol and lupeol which were identified in the plant is considered to have antiarthritic properties. Keywords: Sphaeranthus indicus, Gas chromatography, Mass spectrometry

DESIGN & DEVELOPMENT OF SOLID SELF MICRO-EMULSIFYING OSMOTIC DRUG DELIVERY SYSTEM FOR ISRADIPINE

Objective: The objective of the study was to design and develop self-microemulsifying osmotic pump tablet Isradipine, a BCS Class IV antihypertensive agent for improved solubility and obtain controlled release characteristics. Material & Methods: Methodology for undertaken project involved pre-formulation studies, comprising of analytical method adoption and drug: excipient compatibility studies. Further steps involve formulation and characterization of liquid SMEDDS of Isradipine. Developed SMEDDS was incorporated into selected adsorbent and compressed with osmotic agents, a binder and lubricant into tablet. Tablets were film coated with semi-permeable membrane and drilled with orifice. Final formulation was optimized for various formulation components and evaluated on various dimensions, among dissolution profiling and stability studies. Results and Discussion: Solubility studies in oils, surfactants and co-surfactants were carried out and SMEDDS formulation was finalized as Isradipine (11.63%), Gelucire 50/13 (34.88%), Lutrol F127 (30.23%) and Transcutol P (23.26%). Neusilin US 2 was selected as adsorbent in 1:1 ratio based on excellent adsorption and huge surface area. Final optimized formulation of tablet comprises of core tablet and functional coatings of cellulose acetate (60%) and PEG 400 (40%) with 5% film coating build up. Developed formulation was optimized for various formulation components and evaluated for release kinetics and accelerated stability study. Conclusion: The developed novel SME-OPT of Isradipine will be a promising template for formulating controlled release dosage form of BCS Class II and IV bioactive agents. The technology used for the preparation of SME-OPT is relatively simple manufacturing technology which can be easily adopted in industrial units on a commercial scale

REVIEW OF RECENT STUDIES ON STATISTICAL OPTIMIZATION IN DRUG DELIVERY TECHNOLOGIES

Statistical modeling and experimental design are essential tools in field of drug delivery during product development and can be divided into formula and process optimization. Experimental design allows efficient experimentation in which all or a large subset of factors are together varied over a set of experiments, in contrast to the traditional approach of varying only one variable at time (OVAT). Good estimates for the required composition, geometry, dimensions and preparation procedure of various types of delivery systems will be available, taking into account the desired administration route, drug dose and release profile. Thus, the number of required experimental studies during product development can be significantly reduced, saving time and reducing costs. The present review discusses types of designs and methodologies used recently in academic as well as industrial research for optimization of novel drug delivery systems

Complex Dynamics and Synchronization of Delayed-Feedback Nonlinear Oscillators

We describe a flexible and modular delayed-feedback nonlinear oscillator that is capable of generating a wide range of dynamical behaviours, from periodic oscillations to high-dimensional chaos. The oscillator uses electrooptic modulation and fibre-optic transmission, with feedback and filtering implemented through real-time digital-signal processing. We consider two such oscillators that are coupled to one another, and we identify the conditions under which they will synchronize. By examining the rates of divergence or convergence between two coupled oscillators, we quantify the maximum Lyapunov exponents or transverse Lyapunov exponents of the system, and we present an experimental method to determine these rates that does not require a mathematical model of the system. Finally, we demonstrate a new adaptive control method that keeps two oscillators synchronized even when the coupling between them is changing unpredictably.Comment: 24 pages, 13 figures. To appear in Phil. Trans. R. Soc. A (special theme issue to accompany 2009 International Workshop on Delayed Complex Systems

Design development and optimization of immediate release tablet of valsartan

The objective of the present study was to prepare immediate release tablets (IRTs) of valsartan by direct compression method. Two types of superdisintegrants i.e. sodium starch glycolate (SSG) and Ac-Di-sol were used in the formulation of tablets. Twelve preliminary trial batches were prepared by varying the concentration of superdisintegrants. It was found that formulation containing Ac-Di-Sol disintegrated in less time as compared to formulation containing sodium starch glycolate. Values of friability was found to be more in case of formulation containing Ac-Di-Sol. Attempts were also made to prepare the tablets containing superdisintegrants in combination and these resulted in the formulation with improved values of disintegration time and friability. On the basis of preliminary studies optimization of IRT was done employing 32 full factorial design using design expert 7. The optimized batch of IRTs showed friability and disintegration time values of 0.82 ± 0.07 and 29 ± 1 respectively. The percent release was also found to be 94.73 ± 4.97% in 5 min. Keywords: Immediate release tablets, Valsartan, Hypertension, Sodium starch glycolate, Ac-Di-Sol, 32 full factorial desig

Design, development and optimization of immediate release tablet of deflazacort

The objective of the present study was to prepare immediate release tablets (IRTs) of deflazacort by direct compression method. Two types of superdisintegrants i.e. sodium starch glycolate (SSG) and Ac-Di-sol were used in the formulation of tablets. Twelve preliminary batches were prepared by varying the concentration of superdisintegrants. It was found that formulation containing Ac-Di-Sol disintegrated in less time as compared to formulation containing sodium starch glycolate. Values of friability was found to be more in case of formulation containing Ac-Di-Sol. Attempts were also made to prepare the tablets containing superdisintegrants in combination and these resulted in the formulation with improved values of disintegration time and friability. On the basis of preliminary studies optimization of IRT was done employing 32 full factorial design using design expert 7. The optimized batch of IRTs showed friability and disintegration time values of 0.598 and 64.17±3.50 respectively. It was also found that 96.26±1.82% of drug was released within 5 min. Keywords: Immediate release tablets, deflazacort, Rheumatoid arthritis, Sodium starch glycolate, Ac-Di-Sol, 32 full factorial desig

Evidence-based national vaccine policy

India has over a century old tradition of development and production of vaccines. The Government rightly adopted self-sufficiency in vaccine production and self-reliance in vaccine technology as its policy objectives in 1986. However, in the absence of a full-fledged vaccine policy, there have been concerns related to demand and supply, manufacture vs. import, role of public and private sectors, choice of vaccines, new and combination vaccines, universal vs. selective vaccination, routine immunization vs. special drives, cost-benefit aspects, regulatory issues, logistics etc. The need for a comprehensive and evidence based vaccine policy that enables informed decisions on all these aspects from the public health point of view brought together doctors, scientists, policy analysts, lawyers and civil society representatives to formulate this policy paper for the consideration of the Government. This paper evolved out of the first ever ICMR-NISTADS national brainstorming workshop on vaccine policy held during 4-5 June, 2009 in New Delhi, and subsequent discussions over email for several weeks, before being adopted unanimously in the present form