Ion-pairing high-performance liquid chromatography–ultraviolet (HPLC–UV) methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid (EDTA) in Abilifys (a small molecule drug with aripiprazole as the active pharmaceutical ingredient) oral solution and die-thylenetriaminepentaacetic acid (DTPA) in Yervoys (a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient) intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions (Cu2 t , Fe3 t ) which generate highly stable metallocom-plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in-volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de-termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids (APCAs) including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.

<p>OBJECTIVETo characterize the profiles of chromosome imbalance in esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the high incidence area in Henan.p><p>METHODSChromosomal aberrations of 37 samples of SCC and 30 GCA were analyzed by comparative genomic hybridization comparative genomic hybridization (CGH).p><p>RESULTSIt was found that the most frequently detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and 7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%), and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p (57%), and followed by 19p, 1p and 4p.p><p>CONCLUSIONThe present findings demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance in GCA, which provide important theoretic information for identifying and cloning novel SCC/GCA-related genes.p>
Adenocarcinoma ; genetics ; Carcinoma, Squamous Cell ; epidemiology ; genetics ; Cardia ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 20 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; genetics ; Esophageal Neoplasms ; epidemiology ; genetics ; Gene Amplification ; Gene Deletion ; Humans ; Nucleic Acid Hybridization ; methods ; Stomach Neoplasms ; epidemiology ; genetics

Objective: To isolate and screen Actinomycetes from Lagos Lagoon soil sediments for production of bioactive metabolites. Methods: Sediment samples were collected from four different locations of Lagos Lagoon and were dried for 2 weeks after which the Actinomycetes were isolated by serial dilution using the spread plate method on starch casein and Kuster's agar supplemented with 80 μg/ mL cycloheximide to prevent fungal growth. The plates were incubated at 28 °C for 1-2 weeks. Isolates were selected based on their colonial characteristics as well as their Gram's reaction and subcultured using the same media for isolation until pure cultures were obtained and incubated at 28 °C for 3 d. Thereafter, they were inoculated into starch casein and Kuster's broth media and incubated for 8 d. The secondary metabolites were screened for antimicrobial activity against the following microorganisms: methicillin resistant Staphylococcus aureus, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 29522, Pseudomonas aeruginosa ATCC 27853, Candida albicans and Enterococcus faecalis ATCC 29212. Coagulasenegative staphylococci isolated from HIV patients were also used (Staphylococcus warneri, Staphylococcus xylosus and Staphylococcus epidermidis). The antimicrobial metabolites of the Actinomycetes isolates were identified using gas chromatography (GC). Results: Crude extracts of isolates showed antimicrobial activity against some of the test organisms. The GC data analysis showed the antibiotic profile of these isolates. Conclusions: Analysis of the crude extracts of the isolates using GC method, revealed the presence of antibiotics including an anticholinergic hyoscyamine among other conclusions.

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.