Warfarin toxicity and individual variability-clinical case.

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.

Cytochrome P450 loss-of-function polymorphism genotyping on the Agilent Bioanalyzer and clinical application.

Responses to toxins and drugs, even to standard medical drug treatment regimens, can vary significantly between individuals. Similar dosages can have divergent results due to polymorphisms in the genes that code for the enzymes responsible for the metabolism of drugs. The focus of this report is to describe our exploration of the personalized medicine approach for patient care at Sydney West Area Health Service. We would like to demonstrate the importance of this approach as it is the subject of debate in the medical and scientific community. The critical points in this debate are the cost of testing, laboratory space required and clinical application. We have shown that a simple approach and instruments like the Agilent Bioanalyzer could be cost effective for laboratory operation. The Agilent Bioanalyzer (Agilent Technologies, CA, USA) can be used for proteins, DNA and cell studies. Hence, reduced cost of instruments, laboratory space requirements, maintenance and operational costs are great advantages of this technology, especially for development and research laboratories.

Adsorption of 2-chloropyridine on oxides--an infrared spectroscopic study.

The adsorption of 2-chloropyridine on SiO(2), TiO(2), ZrO(2), SiO(2)-Al(2)O(3) and H-mordenite has been studied by IR spectroscopy. The different modes of interaction with oxide surfaces, i.e. hydrogen-bonding and adsorption at Brønsted or Lewis acid sites, was modelled by ab initio calculations at the B3LYP/DZ+(d) level. Adsorption on SiO(2) results in hydrogen bonding to surface hydroxyl groups, whereas the spectra obtained following adsorption on TiO(2) and ZrO(2) display evidence for electron transfer at Lewis acidic surface sites. Protonation of 2-chloropyridine at Brønsted acidic sites was detected only for adsorption on SiO(2)-Al(2)O(3) and H-mordenite, indicating the presence of Brønsted acidic sites on these oxide surfaces with pK(a) values

IR spectroscopy of N-methylpyrrole adsorbed on oxides--a probe of surface acidity.

IR spectra of N-methylpyrrole (NMP) have been measured following adsorption on, and subsequent desorption from, SiO(2), TiO(2), ZrO(2), SiO(2)-Al(2)O(3), H-mordenite, and sepiolite. Three modes of adsorption have been observed: (i) hydrogen bonding to surface hydroxyl groups, (ii) electron transfer at Lewis acidic surface sites, and (iii) proton transfer at Brønsted acidic surface sites. Protonation of NMP was detected only for adsorption on SiO(2)-Al(2)O(3) and H-mordenite, indicating the presence of Brønsted acidic sites with pK(a) values