Meperidine: therapeutic use and toxicity

Meperidine is a synthetic opioid analgesic frequently prescribed in the emergency department. Meperidine is most often administered intramuscularly or intravenously, due to its poor oral bioavailability, and is metabolized extensively by the liver. Analgesic effects usually last 3-4 hours with parenteral administration, and some adverse effects such as nausea may be reduced when meperidine is combined with antiemetic or antihistaminic medications. Although meperidine is often a preferred analgesic by both patients and physicians in the treatment of disorders such as migraine headaches, its analgesic efficacy has rarely proven superior to alternative parenteral pain medications in controlled trials. In addition, meperidine can precipitate monoamine oxidase inhibitor reactions, and during metabolism it is demethylated to normeperidine, a compound with significant central nervous system (CNS) toxicity. Meperidine should be considered a second line agent in the treatment of pain when opioid analgesics are required.     

Intratumoral differences in methotrexate levels within human osteosarcoma xenografts studied by microdialysis

A central tenet in oncology is the assumed relationship between drug concentration and cytotoxicity. Determinations of drug levels in tumor tissues are, however, generally not undertaken. Microdialysis is a method where continuous drug monitoring may be achieved by sampling of low molecular weight substances from the extracellular space. By employing this technique it is possible to observe variable drug levels within tissues, including tumors, over time. Herein, we present results from a nude rat model where subcutaneous human osteosarcoma xenografts were established prior to the administration of the antifolate methotrexate as an intravenous infusion. Significant differences in drug exposure within single tumors were evident. Generally, peak drug concentrations were lower and drug efflux slower from the center of the tumors as compared to the periphery. The use of microdialysis could be an important tool for optimizing current strategies in anticancer chemotherapy.     

Small and large polarons in nickelates, manganites, and cuprates

By comparing the optical conductivities of La_1.67Sr_0.33NiO₄ (LSNO), Sr_1.5La_0.5MnO₄ (SLMO), Nd₂CuO_4-y (NCO), and Nd_1.96Ce_0.04CuO₄ (NCCO), we have identified a peculiar behavior of polarons in this cuprate family. Whereas in LSNO and SLMO small polarons localize into ordered structures below a transition temperature, in these cuprates the polarons appear to be large, and at lowT their binding energy decreases. This reflects an increase of the polaron radius, which may trigger coherent transport.     

Defects of mitochondrial respiratory chain in multiple symmetric lipomatosis

Using lymphocytes from nine unrelated patients with multiple symmetric lipomatosis we investigated a possible defect in the mitochondrial respiratory chain as the biochemical cause for the disease. A significant decrease in oxygen consumption of intact lymphocytes as well as a decreased activity of the individual components of the respiratory chain were detected. These findings are consistent with the recently described deletions and point mutations of mitochondrial DNA in patients suffering from this disease.