Medicinal Chemistry

TLRs are important innate immune receptors. It has been found that vanadium can affect the immune function in broilers. However, vanadium action in the regulation of TLRs is unknown. A total of 420 one-day-old avian broilers were divided into six groups, and fed on a corn-soybean basal diet as control diet (vanadium 0.073 mg/kg) or the same diet supplemented with vanadium at the doses of 5, 15, 30, 45 and 60 mg/kg in the form of ammonium metavanadate. TLR4 and TLR7 mRNA expression in lymphoid organs of each group were studied by real time RT-PCR form. The results indicated that the TLR4 and TLR7 mRNA expression in thymus and TLR4 mRNA expression in bursa were down-regulated in the 60 mg/kg group. The TLR7 mRNA expression in bursa was down-regulated in 30 mg/kg, 45 mg/kg and 60 mg/kg groups, and up-regulated in the 5 mg/kg group. Also, the TLR4 and TLR7 mRNA expression in spleen was down-regulated in the 45 mg/kg and 60 mg/kg groups, and up-regulated in the 5 mg/kg group. The abovementioned results showed that dietary vanadium in excess of 30 mg/kg could down-regulate the TLR4 and TLR7 mRNA expression in lymphoid organs, which finally impaired innate immunity in broilers.

Introduction: Dissolution is an example of in-vitro test which can be used to identify formulations that may present potential bioequivalence problems. It is defined as the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. It is considered one of the most important tools to predict the in-vivo bioavailability and in some cases replacing clinical studies to determine bioequivalence. Aim: To compare the differences in the dissolution behaviour between two anticancer formulations, Xeloda® 500 mg (reference product) and Capeda 500 mg (test product). Methods: Four replicates for each batch of the tested medicines were carried out using a PT-DT70 dissolution tester (Pharma Test) to detect any differences in their dissolution behaviour. Samples at nine time intervals were tested according to the US Pharmacopeia with the rate of dissolution determined by ultra-violet spectrophotometery. Results: All the tested medicines complied with the pharmacopoeial specifications, the EMA and the FDA guidance for industry when achieved 85% dissolution in 60 minutes. However, Capeda 500 mg (test product) showed slower, different and incomplete dissolution rate compared to Xeloda® 500 mg (reference product) at both 60 and 120 minutes. Other visual differences in the weight, size, clarity of solution, presence of un-dissolved residue and particles during the dissolution test were also detected. Conclusion: Results in this study clearly raise a question about the interchangeability between Xeloda® 500 mg and its Intended copy Capeda 500 mg. Awareness of these scientific concerns should be considered when a clinical choice between these two drugs is required. Differences between the innovator and copy medicines with regard to pharmacokinetics, clinical efficacy and safety may exist. Thereby, patients’ monitoring after performing drug substitution of these two medicines is strongly recommended.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the world. An important implication of this disease is the progression of the disease to a more complicated condition called non-alcoholic steatohepatitis (NASH) and the wide variety of clinical presentations. Over the past 5 years, remarkable progresses have been made in understanding the genetic basis for the disease. Recent clinical trials in pharmacotherapy for the disease have been encouraging as well. It is anticipated that the integration of the wide spectrum information retrieved from genomics, transcriptomics and proteomics studies conducted in NAFLD and NASH will mediate a better understanding of the disease pathogenesis and facilitate the postulation of disease pathobiology pathways. Genetic and biological markers identified from the omics studies may hold promise for diagnosis, personalized treatment, early prevention and new drug development.