Pharmacokinetic assessment of teratologically effective concentrations of an endogenous retinoic acid metabolite

Retinoic acid is a natural vitamin A derivative that undergoes oxidative metabolism in the body to yield several metabolites, which apparently represent the products of a detoxification pathway. To assess if such metabolic conversions diminished teratogenic potency, one of the major metabolites (4-oxo-all-trans-retinoic acid) was tested for its teratogenic activity in pregnant ICR mice and further investigated for its pharmacokinetic features to determine if it accumulated in the embryo in concentrations sufficient to elicit a teratogenic response. Administration of single oral doses (10, 25, 50, or 100 mg/kg) of the compound to ICR mice on day 11 of gestation (plug day = day 0) produced dose-dependent frequencies of serious fetal anomalies of the type usually associated with the use of retinoic acid and other retinoids. The metabolite was equivalent in teratogenic potency to retinoic acid, and, in the instance of cleft palate frequency, it was even more active. Concentrations of 4-oxo-all-trans-retinoic acid and its 13-cis isomer were measured in the maternal plasma and whole embryos at 30 min to 10 hr after administration of the lowest (10 mg/kg) and the highest (100 mg/kg) teratogenic dose of 4-oxo-all-trans-retinoic acid by means of high-performance liquid chromatography methodology. Distribution of the compound in the maternal system and transfer to the embryo occurred rapidly with either dose. Peak concentration in the maternal plasma and the embryo persisted for 3-4 hr after the higher dose but not with the lower dose; however, elimination kinetics for the two dose levels were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nucleotide sequence of psbQ gene for 16-kDa protein of oxygen-evolving complex from Arabidopsis thaliana and regulation of its expression.

The psbQ gene encoding a 16-kDa polypeptide of the oxygen-evolving complex of photosystem II has been isolated from Arabidopsis thaliana and characterized. The gene consists of a 28 nucleotide long leader sequence, two introns and three exons encoding a 223-amino-acid precursor polypeptide. The first 75 amino acids act as a transit peptide for the translocation of the polypeptide into the thylakoid lumen. Expression studies show that the gene is light-inducible and expresses only in green tissues with high steady-state mRNA levels in leaves. Using this gene as a probe, restriction fragment length polymorphism between two ecotypes, Columbia and Estland, has also been detected.     

Peripartum Cardiomyopathy Presenting With Ventricular Tachycardia: A Rare Presentation

A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia.     

Current status of regulating biotechnology-derived animals in Canada: animal health and food safety considerations

Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are 'novel' organisms for which there is limited information. The issues associated with the regulation of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. It is a challenge for the developers to prove the safety of the products of biotechnology-derived animals and also for regulators to regulate this increasingly powerful technology with limited background information. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those posing an unacceptable risk. Regulatory initiatives for biotechnology-derived animals and their products should be able to ensure high standards for human and animal health, a sound scientific basis for evaluation; transparency and public involvement, and maintenance of genetic diversity. This review proposes a regulatory regime that is based on scientific risk based assessment and approval of products or by-products of biotechnology-derived animals and its application in context to Canadian regulations.     

Nutritional metabonomics: applications and perspectives

Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well-determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level.