Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin

Thyrotropin releasing hormone [L-proglutamyl-L-histidyl-L-proline amide (TRH)], a tripeptide with molecular weight of 362 and a pKa of 6.2, was used as a model peptide for in vitro passive and iontophoretic diffusion cell studies using excised dorsal nude mouse skin. The results indicate that both the charged and uncharged TRH fluxes across the excised tissue were greater than those obtained by passive diffusion alone. The steady-state flux of both the uncharged and charged TRH was directly proportional to the applied current density, with flux being greater for the uncharged TRH. Additional studies on the transport of methylene blue indicate that transport may be occurring through pores, and that positive ions are preferentially passed through the skin. These results imply that the steady-state flux of TRH is primarily due to a direct, electrically induced ion motion and convection. A practical implication of these results is that it may be possible to enhance and control the transdermal delivery of peptides.     

A case of abdominal pregnancy at term with a live child

The authors report a new case of abdominal pregnancy with living baby. The analysis of this observation permits to present then the clinical and paraclinical characteristics of this exceptional localization of pregnancy and emphasize the surgical principles involved with its treatment, around the time of the term delivery.     

The surgical risk of colectomy in patients with cirrhosis

The records of 54 patients with documented cirrhosis who underwent colectomy between January 1970 and January 1984 were studied to assess the operative risk and to determine the preoperative predictive risk factors. In-hospital mortality was 24 percent (13 patients), and postoperative complications occurred in 48 percent (26 patients). The risk of surgical intervention was significantly increased if encephalopathy, ascites, anemia, or hypoalbuminemia was present before operation. A simple operative risk index involving the presence of encephalopathy and ascites and the levels of hemoglobin and albumin is proposed to help distinguish a low-risk subgroup in whom postoperative mortality was 12.8 percent from a high-risk subgroup in whom postoperative mortality was 53.3 percent.     

Mechanism of multidrug resistance in relation to passive membrane permeation.

Passive uptake of drugs into cells is described in terms of the following steps: (1) massive immediate binding of the drugs to the outer leaflet of the plasma membrane resulting in practical equilibrium between extremely high drug concentrations at the cell surface compared to the drug concentration in the medium. (2) Due to their amphipathic nature, anticancer drugs are practically excluded from the lipid core of the membrane. They cross the lipid core by distinct flip-flop events that occur in the case of doxorubicin and daunorubicin after an average period of 0.7 and 0.15 min, respectively. (3) The drug reaching the inner leaflet of the plasma membrane is in practical equilibrium with the drug present in the cytoplasm. (4) Almost all the amounts of anticancer drugs present in the cells are bound by molecular sinks, such as DNA or cytoskeleton elements. The resistance afforded to multidrug resistant (MDR) cells by extrusion pumps, such as P-glycoprotein, is negatively correlated with the affinity of the drugs to the membranes and with their flip-flop rates across membranes. Binding rates of the drugs to membranes and intracellular sinks have no effect on drug concentration in the cytoplasm once equilibrium is reached between the passive uptake of drugs and their active extrusion.