SYNTHESIS AND CHARACTERIZATION OF SWELLING BEHAVIOR OF PHARMACEUTICAL POLYMERS IN DIFFERENT pH FOR CONTROLLED DRUG DELIVERY SYSTEMS.

The pharmaceutical industry is evaluating modes of delivery for their prized therapeutics at every step of the design cycle. In recent years, pH dependent drug delivery systems have focused much for specific purposes. Synthesis of pH dependent polymer in different monomeric ratio were intended to be used for controlled drug delivery systems. Previously synthesized monomers i.e; ethyl methacrylate (EMA) and acrylic acid (AA)took in different monomeric ratio (in moles) as -  EMA:AA(0.7:0.3), EMA:AA (0.6:0.4), EMA:AA (0.5:0.5),EMA:AA(0.4:0.6) and EMA:AA(0.3:0.7) with solvent Tetrahyrdrofuran(THF) and Azobis-iso butyronitrile (AIBN) initiator, which under goes polymerization .Polymers were prepared by solution polymerization technique and free radical mechanism. Swelling behavior of different polymeric films (polymers) which have obtained from polymerization in different monomeric ratios, studied in different pH buffer solutions. The different pH buffer solutions were  Hydrochloric acid buffer pH 1.2, Hydrochloric acid buffer pH 2.0, Phosphate  buffer pH 6.0,  Phosphate buffer pH 7.4, Phosphate buffer pH 8.0.These different pH buffer solutions were prepared according to Indian Pharmacopoeia 2007.The changes in polymeric films in  phosphate buffer (pH 8.0, pH 7.4) after 15,30, 45,60,75,90,120 minutes were noted. In buffer (pH 6.0,  pH2.0, and pH 1.2) the changes were noted after 1 hour,2hours,2 days,3 days,4 days,5 days,6 days,7 days. Swelling ratio calculated by formula. For microencapsulation paracetamol drug was taken as a model drug.  Emulsification solvent evaporation method have used for micro encapsulation of model drug. The standard calibration curve of paracetamol obtained a straight line. The relation between drug concentration & absorbance measured at 249 nm found linear. The drug was estimated by UV spectrophotometer at 249 nm using a calibration curve based on standard solutions. The percentage of Paracetamol encapsulated with respect to total amount of Paracetamol encapsulation taken loading efficacy. In vitro dissolution release of Paracetamol from micro spheres was evaluated using paddle dissolution apparatus (Lab India Disso 2000 dissolution tester). Dissolution media was 900 ml phosphate buffer (pH 7.4) & to this media the microspheres containing 200 mg of Paracetamol were added. The system was stirred at 500 pm & temp at 37oC± 0.5 oC  samples were drawn at specified time intervals (10 min, 20 min, 30 min, 40 min, 50 min & 60 min) filtered & assayed spectrophotometrically  at 249nm.  For swelling study, all the copolymers in different monomeric ratio did not show good swelling or dissolution characteristic in acidic pH (pH 1.2-pH6.0) ethylmethacrylate : acrylic acid with monomer ratio 3:7 completely dissolved within 2 hours

Increasing the Analytical Sensitivity by Oligonucleotides Modified with Para- and Ortho-Twisted Intercalating Nucleic Acids – TINA

The sensitivity and specificity of clinical diagnostic assays using DNA hybridization techniques are limited by the dissociation of double-stranded DNA (dsDNA) antiparallel duplex helices. This situation can be improved by addition of DNA stabilizing molecules such as nucleic acid intercalators. Here, we report the synthesis of a novel ortho-Twisted Intercalating Nucleic Acid (TINA) amidite utilizing the phosphoramidite approach, and examine the stabilizing effect of ortho- and para-TINA molecules in antiparallel DNA duplex formation. In a thermal stability assay, ortho- and para-TINA molecules increased the melting point (Tm) of Watson-Crick based antiparallel DNA duplexes. The increase in Tm was greatest when the intercalators were placed at the 5′ and 3′ termini (preferable) or, if placed internally, for each half or whole helix turn. Terminally positioned TINA molecules improved analytical sensitivity in a DNA hybridization capture assay targeting the Escherichia coli rrs gene. The corresponding sequence from the Pseudomonas aeruginosa rrs gene was used as cross-reactivity control. At 150 mM ionic strength, analytical sensitivity was improved 27-fold by addition of ortho-TINA molecules and 7-fold by addition of para-TINA molecules (versus the unmodified DNA oligonucleotide), with a 4-fold increase retained at 1 M ionic strength. Both intercalators sustained the discrimination of mismatches in the dsDNA (indicated by ΔTm), unless placed directly adjacent to the mismatch – in which case they partly concealed ΔTm (most pronounced for para-TINA molecules). We anticipate that the presented rules for placement of TINA molecules will be broadly applicable in hybridization capture assays and target amplification systems

Giant Anharmonic Phonon Scattering in PbTe

Understanding the microscopic processes affecting the bulk thermal conductivity is crucial to develop more efficient thermoelectric materials. PbTe is currently one of the leading thermoelectric materials, largely thanks to its low thermal conductivity. However, the origin of this low thermal conductivity in a simple rocksalt structure has so far been elusive. Using a combination of inelastic neutron scattering measurements and first-principles computations of the phonons, we identify a strong anharmonic coupling between the ferroelectric transverse optic (TO) mode and the longitudinal acoustic (LA) modes in PbTe. This interaction extends over a large portion of reciprocal space, and directly affects the heat-carrying LA phonons. The LA-TO anharmonic coupling is likely to play a central role in explaining the low thermal conductivity of PbTe. The present results provide a microscopic picture of why many good thermoelectric materials are found near a lattice instability of the ferroelectric type

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Conventional and Molecular Breeding Approaches for Biofortification of Pearl Millet

Pearl millet [Pennisetum glaucum (L.) R. Br.] is an essential diet of more than 90 million people in the semi-arid tropics of the world where droughts and low fertility of soils cause frequent failures of other crops. It is an important nutri-rich grain cereal in the drier regions of the world grown on 26 mha by millions of farmers (IFAD 1999; Yadav and Rai 2013). This makes pearl millet the sixth most important crop in the world and fourth most important food crop of the India, next to rice, wheat, and maize with annual cultivation over an area of ~8 mha. Pearl millet is also primary food crop in sub-Saharan Africa and is grown on 15 mha (Yadav and Rai 2013). The significant increase in productivity of pearl millet in India is attributed to development and adoption of hybrids of early to medium duration maturity. More than 120 diverse hybrids/varieties have been released till date for various production environments. The heterosis breeding and improved crop management technologies increased productivity substantially achieving higher increased production of 9.80 mt in 2016–2017 from 2.60 mt in 1950–1951 in spite of declined of area under the crop by 20–30% over last two decades (Yadav et al. 2012)