Setting up an ethics of ecosystem research structure based on the precautionary principle.

Ethical practices in ecological field research differ from those in laboratory research in more than the technical setting and the important distinction between population-level and individual-based concerns. The number of stakeholders affected by the conduct of field research is far larger; private landholders, public water utilities, public land managers, local industries, and communities large and small are only some of those who may be impacted. As research review boards move to establish specific ethical practices for field biologists, the process of identifying appropriate standards will affect the degree to which research will ultimately be disrupted. Standards that lead to research protocols that alienate key interests are not likely to be sustainable. Already, standards that have conflicted with the primary values of a key interest have resulted in disruptions to research and scientific progress. One way to manage this problem of deeply competing interests is to avoid the deepest offenses to any relevant interest group in the design of a proposed study. This is an application of the precautionary principle and is likely to generate a more sustainable balance among competing interests. Unfortunately, this process is also likely to be a never-ending, consensus-seeking process. Fortunately, scientists can have enormous influence on the process if they choose to engage in it early. If scientists use their expertise to function as honest brokers among affected interests, their own interest in scientific research progress is likely to be better met.

A rare incidental finding in a case of painless jaundice.

Portal vein thrombosis secondary to protein C deficiency is a rare finding. Diagnosing a portal vein thrombosis itself is difficult due to nonspecific symptoms such as nausea, vomiting, anorexia, and weight loss. Proving that a protein C deficiency is the cause of a portal vein thrombosis is even more difficult as an extensive and thorough workup is required to rule out malignancies, myeloproliferative disorders, and hypercoaguable states which can all lead to thromboses. Patients require anticoagulation to prevent two dangerous complications of portal vein thrombosis; portal hypertension leading to esophageal varices with massive hemetemesis and extension of thrombus from the portal vein into the mesenteric veins leading to intestinal ischemia and death. In this case report, we present a patient with the complaint of painless jaundice who was found to have an incidental finding of portal vein thrombosis secondary to protein C deficiency. The different etiologies of portal vein thrombosis, along with diagnosis and treatment options will be discussed and highlighted.

Structure-activity relationships in platinum-acridinylthiourea conjugates: effect of the thiourea nonleaving group on drug stability, nucleobase affinity, and in vitro cytotoxicity.

The synthesis, cytotoxicity, and nucleoside binding of some platinum-acridinylthiourea conjugates derived from the prototypical compound [PtCl(en)(ACRAMTU)](NO3)2 ("PT-ACRAMTU"; en=ethane-1,2-diamine, ACRAMTU=1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, protonated form) are reported. To establish structure-activity relationships within this class of compounds, systematic changes were made to the thiourea nonleaving group, which links the intercalator to platinum. Three new derivatives of ACRAMTU, one di-, one tri-, and one tetraalkylated, were generated, where the degree of alkylation indicates the number of alkyl groups attached to the SCN2 framework. Subsequent reaction of the tri- and tetraalkylated derivatives with activated [PtCl2(en)] yielded the corresponding platinum conjugates. The dialkylated thiourea gave an unstable complex, which was not included in the studies. The crystal structure of PT-ACRAMTU x MeOH has been determined. In the solid state, one axial position of the square-planar platinum coordination sphere is partially shielded by the bulky thiourea group, providing a strong rationale for the kinetic inertness of the compound. The cytotoxicity of the prototype, the two new conjugates, and cisplatin was assessed in ovarian (A2780, A2780/CP), lung (NCI-H460), and colon (RKO) cancer cell lines using clonogenic survival assays. The derivatives containing trialkylated thiourea groups showed activity similar or superior to cisplatin, with IC50 values in the low micromolar concentration range. The complex modified with the tetraalkylated (bulkiest) thiourea was significantly less active, possibly due to the greatly decreased rate of binding to nucleobase nitrogen (1H NMR spectroscopy), but was most efficient at overcoming cross resistance to cisplatin in A2780/CP. Possible consequences of the reported structural modifications for the mechanism of action of these agents are discussed.