Pharmacogenomics: Applications in Drug Discovery and Pharmacotherapy

Pharmacogenomics is the scientific study which explains individual variability of drug targets and to explore the genetic basis for such changes. With the completion of human genomic study, clear relation could now be established between the drug response in relation to a person’s genome. Pharmacogenomics, also known as personalized medicine, uses the person’s genome to determine the dose and dosage regimen, so that therapy could be optimized. As with the techniques like DNA microarray technologies person’s response to a therapy can be predicted and new therapies could be assigned. In the present review, the current technologies, and past significance has been discussed

Receptor Identification: Advances in Ligands and Transmitters Discovery

Receptor identification is an integral part of drug discovery and development. By the beginning of the next millennium, the search for the natural ligands of the orphan G-protein-coupled receptors will lead to the discovery of so many new peptides that it may well double their present number. It has recently become evident that all types of chemical messengers, hormones and transmitters act through membrane receptors which constitute our largest superfamily of proteins, i.e. the G protein-coupled receptors. The development of targeted therapies has revolutionized the treatment of various chronic diseases. Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. These ligands are peptides, lipids or biogenic amines, and act as transmitter molecules. Identification of orphan receptors include screening, binding and reverse engineering that help to find out cysteinyl leukotriene CysLT1 and Cys T2, hepatointestinal leukotriene B4, motilin, Ghrelin, Growth hormone-releasing peptide and growth hormone secretagogue receptor and many more. Techniques involved in screening of receptors include low stringency hybridization followed by PCR-derived approaches helps to discover various orphan g protein couple recptors (oGPCR). The discovery of the oGPCR represents a hallmark in neuroscience research, and the exploitation of its numerous physiological and pathophysiological functions is a promising avenue for therapeutic applications

Traditional and Novel Herbal Drugs Emerging as Potent Novel Combinations for Managing Morbidities by Pharmacological and Mechanistic Studies

Background: Herbal drugs are used in treatment of diseases since decades. Major contributing factor for their use is easy availability, less expensive and more belief of common population because of relatively less side effects compared to allopathic medicines. Medicines of natural origin or functional foods in the prevention of disease are the need of hour. Hence, the present review focused on activity of four drugs viz. Withania somnifera,Allium sativum,Curcuma longa andAzadirachta indica and role in different clinical complications.Methods: A thorough review of all the articles, research as well as reviews available regarding the concerned topic was performed. MEDLINE database was searched and English language articles were preferably selected.Results: Withania somnifera, Allium sativum, Curcuma longa andAzadirachta indicahave shown alleviation in inflammation, diabetes and cancer states. The herbal drugs have shown beneficial effects in the prevention and treatment of these disorders. Conclusion from these facts:Utilizing this concept, it can be assumed that herbal drugs play an intricate role in safeguarding the health of individuals from life-threatening complications. However, validation and reproducibility of results in clinical trails should be there in order to confirm the safety andefficacy of these herbal drugs

A Review on Role of Advanced Glycation End products (AGEs) in Rheumatoid Arthritis

Rheumatoid arthritis (RAa) is a systemic inflammatory connective tissue disease with polyarthritis as a prominent feature; however, extra-articular symptoms and signs are always present. Aadvanced glycation end products with ability of cross-linking of proteins characteristic fluorescence and reaction with AaGEe-specific receptor RAaGEe (receptor for AaGEes). AaGEes action as well as AaGEe formation is directly related to both to inflammation and oxidative stress. RAaGEe is a 35-kDa polypeptide whose gene is located at the junction of the class II and III HLAla regions on chromosome. ligation of RAaGEe has been shown to activate p21ras and mitogen-activated protein (MAaP) kinase, and stimulate nuclear translocation of the transcription factor NF-κB, thereby, resulting in the transcription of target genes thus may induce chronic cellular activation and tissue damage

Sustained Release Solid Dispersions of Pentoxyfylline: Formulation and Optimization

Objective: The purpose of the study is to formulate and optimize sustained release solid dispersions of pentoxyfylline using a combination of eudragit polymers and ethyl cellulose. Methods: Solid dispersions were formulated by solvent evaporation method.Preliminary batches were formulated using various drug to polymer ratio; with eudragit S100 and L100 (1:1 to 1:5 ratio), and with ethyl cellulose(1:1 to 1:3 ratio) and evaluated for solubility analysis. Based on results of preliminary batches, Box Behnken design was further applied and three factors (X1- concentration of Eudragit S100, X2- concentration of Eudragit L100, X3- concentration of Ethyl Cellulose) were selected with three levels (+1, 0, -1). Multiple linear regression was applied to generate polynomial equations and statistical evaluation. Prepared solid dispersions were investigated for sustained release properties via in vitro dissolution studies. Fourier transform infrared spectroscopic analysis (FTIR), X-ray diffraction analysis (X-RD), Differential scanning calorimetry (DSC) studies were carried out to evaluate drug polymer interactions. Scanning Electron Microscopy (SEM) analysis of optimized solid dispersion was carried out to evaluate surface morphology of the particles. Results: Batch F5 showed maximum sustained release (65.46% in 24 h) characteristics out of all solid dispersions. DSC studies indicated drug integrity when mixed with the polymeric carriers. FTIR and X-RD studies also ruled out any drug polymer interaction. A change in crystalline habit was observed in solid dispersion particles (F5 batch) as seen in SEM micrographs. Polynomial mathematical model generated using multiple regression analysis was found to be statistically significant (p<0.05). Conclusion: Release retarding effect was found to be dependent on polymer concentration. Therefore, an optimized combination may lead to better sustaining effect

Prescribing pattern and pharmacoeconomic analysis of antidiabetic drugs

Background: Diabetes Mellitus is a worldwide growing problem causing threat to patient's health because of its association with various complications and comorbidities. It is a chronic disease requiring lifelong medication which further adds to the economic burden. The objective of this study was to evaluate the prescribing pattern and to do pharmacoeconomic analysis of prescribed antidiabetic drugs.Methods: This observational cross sectional study was conducted for 12 months duration in Outpatient Pharmacy of tertiary care hospital. Prescriptions with antidiabetic drugs were captured and evaluation of prescribing pattern along with pharmacoeconomic analysis of antidiabetic drugs was done.Results: A total of 611 prescriptions with antidiabetic drugs were analyzed. There were total 4034 drugs in all prescriptions with a mean of 6.6 drugs per prescription. 4.28% of drugs were prescribed by generic name and 58.9% of prescribed drugs were from essential drug list. Dual drug therapy was prescribed in maximum number of patients (42.2%) followed by monotherapy (28.8%). More commonly prescribed class of antidiabetic drugs was biguanides as monotherapy (n=119) and its combination with sulfonylureas was prescribed maximally among dual drug therapy (n=158). Cost of monthly therapy for antidiabetic drugs prescribed as monotherapy was least with Biguanides (₹ 98.89/ month) whereas combination of biguanides and thiazolidinediones was least expensive among dual drug therapy (₹ 216/ month).Conclusions: Biguanides was the most common prescribed class of antidiabetic drugs among monotherapy and its combination with sulfonylureas was most prescribed as dual drug therapy and both of these therapies were economical

Model free Multiple Heating Rate Degradation Kinetic Studies of Modified Celluloses

Abstract: The present paper depicts about the synthesis of cellulose ethyl ammonium thiophosphate (CEASP) and its metal complexes with Cd, Mo and Ce. CEASP and its metal complexes have been characterized by infrared (IR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDXS) studies. The surface morphology of samples has been premeditated by means of scanning electron microscopy (SEM). The thermal studies of samples have been carried out at multiple heating rates 2, 5, 10 and 20 °C min -1 from ambient to 700 °C in nitrogen atmosphere. Nonisothermal model free kinetic methods have been used to calculate activation energy of samples i.e. Friedman, Ozawa-Flynn-Wall (O-F-W) and modified Coats-Redfern. The activation energy of samples lie in range 72-282 kJ mol -1 . Thermal study shows that initial degradation temperature of CEASP and its metal complexes decreases and there is abrupt increase in char yield of synthesized samples as compared to pure cellulose. These and other related information suggest that such type of derivatisation could be proved a good flame retardant for cellulose

Anti-ulcer activity of the methanolic extract of Nothapodytes foetida in wistar rats

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Finger Millet:A "Certain" Crop for an "Uncertain" Future and a Solution to Food Insecurity and Hidden Hunger under Stressful Environments

Crop growth and productivity has largely been vulnerable to various abiotic and biotic stresses that are only set to be compounded due to global climate change. Therefore developing improved varieties and designing newer approaches for crop improvement against stress tolerance have become a priority now-a-days. However, most of the crop improvement strategies are directed toward staple cereals such as rice, wheat, maize etc., whereas attention on minor cereals such as finger millet [Eleusine coracana (L.) Gaertn.] lags far behind. It is an important staple in several semi-arid and tropical regions of the world with excellent nutraceutical properties as well as ensuring food security in these areas even during harsh environment. This review highlights the importance of finger millet as a model nutraceutical crop. Progress and prospects in genetic manipulation for the development of abiotic and biotic stress tolerant varieties is also discussed. Although limited studies have been conducted for genetic improvement of finger millets, its nutritional significance in providing minerals, calories and protein makes it an ideal model for nutrition-agriculture research. Therefore, improved genetic manipulation of finger millets for resistance to both abiotic and biotic stresses, as well as for enhancing nutrient content will be very effective in millet improvementpublishersversionPeer reviewe

Histone Deacetylase Inhibitors As Potential Therapeutic Agents For Various Disorders

Epigenetic modification acetylation or deacetylation of histone considered as an important element in various disorders. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are the enzymes which catalyse the acetylation and deacetylation of histone respectively. It helps in regulating the condensation of chromatin and transcription of genes. Lysine acetylation and deacetylation present on the nucleosomal array of histone is the key factor for gene expression and regulation in a normal working living cell. Modification in histone protein will lead to the development of cancer and can cause various neurodegenerative disorders. To safeguard the cells or histone proteins from these diseases histone deacetylase inhibitors are used. In this review, the main focus is upon the role of histone deacetylases inhibitors in various diseases