Qualitative environmental risk assessment of photolytic transformation products of iodinated X-ray contrast agent diatrizoic acid.

Recent studies have confirmed that the aquatic ecosystem is being polluted with an unknown cocktail of pharmaceuticals, their metabolites and/or their transformation products (TPs). Although individual chemicals are typically present at low concentrations, they can interact with each other resulting in additive or potentially even synergistic mixture effects. Therefore it is necessary to assess the environmental risk caused by these chemicals. Data on exposure is required for quantitative risk assessment of TPs and/or metabolites. Such data are mostly missing because of the non-availability of TPs and very often metabolites for experimental testing. This study demonstrates the application of different in silico tools for qualitative risk assessment using the example of photodegradation TPs (photo-TPs) of diatrizoic acid (DIAT), which itself is not readily biodegradable. Its photolytic transformation was studied and the photodegradation pathway was established. The aerobic biodegradability of photo-TPs under the conditions of an aquatic environment was assessed using standardized OECD tests. The qualitative risk assessment of DIAT and selected photo-TPs was performed by the PBT approach (i.e. Persistence, Bioaccumulation and Toxicity), using experimental biodegradation test assays, applying different QSAR models with several different toxicological endpoints and in silico read-across approaches. The qualitative risk assessment pointed out that the photo-TPs were less persistent compared to DIAT and none of them possessed any bioaccumulation threat. However, a few photo-TPs were predicted to be active for mutagenicity and genotoxicity, which indicate the need for further testing to confirm these predictions. The present study demonstrates that in silico qualitative risk assessment analysis can increase the knowledge space about the environmental fate of TPs.

Histopaque provides optimal mouse islet purification kinetics: comparison study with Ficoll, iodixanol and dextran.

Islet transplantation has become a very promising treatment for type 1 diabetes. To facilitate further clinical improvements in this exciting field, rodent islets are used to evaluate new strategies and modifications. One method to purify islets is on a density gradient, although the optimal gradient component can be debated. N=6 separate mouse islet isolations were used and the resulting islets were separated and purified on either a Ficoll, Histopaque, Dextran or Iodixanol gradient. Islets were assessed for recovery, viability, purity and in vitro functionality. Aliquots were transplanted into diabetic mice to assess in vivo functionality and survival. There was no difference in the number of islets recovered across groups nor in the size of recovered islets. Use of a Ficoll or Histopaque gradient led to the most pure and viable islets in comparison to Dextran and Iodixanol. Functionally, islets isolated on a Ficoll gradient had the highest glucose-stimulated insulin release in vitro while performing equally to Histopaque and Dextran gradients in vivo. Using a Ficoll gradient, however, comes at a higher monetary cost. We recommend using a Histopaque gradient, which led to the isolation of viable and functional islets with a reduced cost as compared to a Ficoll gradient.

Comparative tolerability of contrast media used for coronary interventions.

Radiographic contrast media (CM) are necessary to provide x-ray absorption of the bloodstream; all other observed effects need to be regarded as adverse. Four types of CM are currently used in diagnostic and interventional cardiology: ionic high-osmolar CM (HOCM), either ionic or non-ionic low-osmolar CM (LOCM), and non-ionic iso-osmolar CM (IOCM). Focusing on the potential cardiovascular effects caused by the CM, there is a clear difference between HOCM and the LOCM or IOCM. HOCM have a poorer profile due to a higher incidence of hypotension and electrophysiological effects. To prevent contrast-induced nephropathy, HOCM should be avoided and patients should receive the minimal dose of LOCM or IOCM with intravenous hydration before and after the procedure. Clinical hyperthyroidism has been detected after CM use, but the condition appears, ultimately, to be self-limited and to occur mainly in elderly patients. When assessing the need for a CM in terms of improved patient safety, preventing serious complications should be the major factor determining the choice. CM should not be selected on the basis of minor adverse effects since these are, ultimately, of low clinical relevance. Thrombotic events, in contrast, carry a high clinical relevance and we consider that these should be the main issue governing current choice. Ionic LOCM appear to have better profile than other CM with respect to interaction with platelet function and coagulation. In relation to thrombotic events in randomised clinical studies, ionic CM have been associated, mainly, with favourable and some neutral results compared with non-ionic agents. Only one trial indicated a more pronounced antithrombotic effect of the non-ionic IOCM relative to the ionic LOCM. The antithrombotic advantages of ionic over non-ionic LOCM are, in part, balanced by a greater frequency of minor adverse effects such as nausea, vomiting or cutaneous rashes. A matter of concern is the delayed adverse effects observed with non-ionic IOCM. However, severe and life-threatening reactions are exceptional and there are probably no significant differences between IOCM and LOCM whether ionic or non-ionic. However, in patients with known allergies, non-ionic CM are to be recommended. On the basis of the available pre-clinical and clinical data, the ionic LOCM or the non-ionic IOCM are the agents to be recommended in percutaneous coronary interventions because of their antithrombotic advantages over non-ionic LOCM.