DEVELOPMENT AND VALIDATION OF STABILITY INDICATING HPTLC METHOD FOR ESTIMATION OF SWERTIAMARIN IN BULK AND DOSAGE FORM

Objective: In the present study a novel stability-indicating high-performance thin-layer chromatography (HPTLC) method for quantitative determination of Swertiamarin (SW) in bulk drug and formulation has been developed and validated as per ICH guideline Q2 (R1) for global acceptance of standardized herbal formulations. Methods: HPTLC method is developed and validated using solvent ethyl acetate: ethanol: chloroform (3:2.5:4.5 v/v/v) (Rf of SW 0.65±0.04) in the absorbance mode at 243 nm. Various forced degradation conditions were used to check degradation of drug. Results: The method showed a good linear relationship (r2 = 0.9990) in the concentration range 200-700 ng per spot. It was found to be linear, accurate, precise and specific. Conclusion: It can be applied for quality control as well as for stability testing of different dosage forms containing swertiamarin. The developed method is validated as per ICH guideline Q2(R1) for global acceptance of standardized herbal formulations

Biosynthesis of Vitamin C by Yeast Leads to Increased Stress Resistance

during respiration, or indirectly-caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity

Organelle targeting: third level of drug targeting

Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD) Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptide

Variants of NAT2 polymorphisms: Intra and inter-ethnic differences

N-Acetyltransferase 2 (NAT2) gene is known for its polymorphism. The genetic variations leads to the change in the N-acetylation activity and these differences in the acetylation activity leads to the classification of the population into various groups such as rapid, intermediate and slow acetylators. In the present study, we identified different mutations and alleles by sequencing a stretch of 927 bp which covered exon 2 of NAT2 gene and is reported to have all the allelic variants reported till date. Previously identified mutations and some new allele sub-type were detected for NAT2 gene in the present study. Overall, we were able to classify 94 individuals into two distinct groups as slow and intermediate acetylators based on their genotype. Out of all the reported alleles, NAT2*4, *5, *6, *7 and *12 alleles were found in the studied population (n=94) and two new allele subtype NAT2*5P and NAT2*7C were detected in the studied population which have not been reported earlier. We did not observed any gender differences in the present study based on NAT2 acetylation activity.  Keywords: N-Acetyltransferase 2 (NAT2), polymorphisms, slow acetylators, rapid acetylators.  African Journal of Biotechnology, Vol 13(51) 4639-464

Anti-hyperlipidemic effect of carcia papaya L in sprague dawley rats

No Abstract.Nigerian Journal of Natural Products and Medicine Vol. 10 () 2006: pp.69-7

Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and micro-geographic scales

Objectives CYP2C9, CYP2C19, and CYP2D6 belong to a subfamily of cytochrome P450 (CYP) enzymes, associated mainly with the metabolism of exogenous compounds in the human body. The genes coding for these enzymes are highly polymorphic and thus of major pharmacogenetic importance. By systematically retrieving data from the literature and genotyping new population samples, we aimed at describing the worldwide distribution of genetic variation at these loci. We created a comprehensive resource of frequency data for the most important CYP2C9, CYP2C19, and CYP2D6 genetic variants in 129, 146, and 55 different population samples, respectively. Furthermore, we showed how demographic history can affect pharmacogenetic variation at a micro-geographic scale by analysing regional samples from Finland, which represents a well-known genetic isolate. Methods Data were obtained from the literature from 1991 to 2007 as well as by genotyping new population samples at four CYP2C9, two CYP2C19 and twelve CYP2D6 variable sites affecting enzymatic activity. Results and conclusions Our study shows that: (i) altered activity variants of CYP2C9, CYP2C19, and CYP2D6 occur globally in all geographic regions, reaching extremely high frequencies in some populations; (ii) each of the CYP genes studied shows a distinct geographic pattern of variation; (iii) population substructure can strongly affect the variation seen in 3 pharmacogenetic loci; and (iv) several geographic regions of pharmacogenetic interest are still poorly characterized

Altered composition and secretion of lysosome-derived compartments in Dictyostelium AP-3 mutant cells

Genetic alteration of the adaptor protein (AP)-3 complex is responsible for the type 2 Hermansky-Pudlak syndrome, a lysosomal storage disease similar to the Chediak-Higashi syndrome (CHS). AP-3 presumably participates in the biogenesis of late endosomal compartments and may also be critical for the regulated secretion of lysosomes by specialized cells. Here, Dictyostelium discoideum cells defective for the mu3 subunit of the AP-3 complex were used and their phenotype analyzed. In mu3 mutant cells, endosomal maturation and lysosome secretion were markedly slower than that in wild-type cells. This phenotype is similar to that reported previously in lvsB mutant cells where the ortholog of the LYST gene, involved in CHS, is mutated. Detailed analysis revealed however significant differences between these two isogenic mutant cells: in lvsB mutant cells, the primary defect is an inefficient biogenesis of otherwise normal secretory lysosomes, while in mu3 mutant cells, the biogenesis and also the composition and the fusion properties of secretory lysosomes are affected. These results suggest that in D. discoideum, AP-3 controls both the efficiency and the specificity of postlysosome maturation, which represent two critical elements in the control of lysosome secretion