Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed

A methodology to estimate the potential to move inpatient to one day surgery

BACKGROUND: The proportion of surgery performed as a day case varies greatly between countries. Low rates suggest a large growth potential in many countries. Measuring the potential development of one day surgery should be grounded on a comprehensive list of eligible procedures, based on a priori criteria, independent of local practices. We propose an algorithmic method, using only routinely available hospital data to identify surgical hospitalizations that could have been performed as one day treatment. METHODS: Moving inpatient surgery to one day surgery was considered feasible if at least one surgical intervention was eligible for one day surgery and if none of the following criteria were present: intervention or affection requiring an inpatient stay, patient transferred or died, and length of stay greater than four days. The eligibility of a procedure to be treated as a day case was mainly established on three a priori criteria: surgical access (endoscopic or not), the invasiveness of the procedure and the size of the operated organ. Few overrides of these criteria occurred when procedures were associated with risk of immediate complications, slow physiological recovery or pain treatment requiring hospital infrastructure. The algorithm was applied to a random sample of one million inpatient US stays and more than 600 thousand Swiss inpatient stays, in the year 2002. RESULTS: The validity of our method was demonstrated by the few discrepancies between the a priori criteria based list of eligible procedures, and a state list used for reimbursement purposes, the low proportion of hospitalizations eligible for one day care found in the US sample (4.9 versus 19.4% in the Swiss sample), and the distribution of the elective procedures found eligible in Swiss hospitals, well supported by the literature. There were large variations of the proportion of candidates for one day surgery among elective surgical hospitalizations between Swiss hospitals (3 to 45.3%). CONCLUSION: The proposed approach allows the monitoring of the proportion of inpatient stay candidates for one day surgery. It could be used for infrastructure planning, resources negotiation and the surveillance of appropriate resource utilization

Intestinal glucose transport in carnivorous and herbivorous marine fishes

The influx and transepithelial movements of glucose and their effects on the electrophysiology and Na transport in upper and lower intestines of the herbivorous surgeonfish, Acanthurus mata , and carnivorous eel, Gymnothorax undulatus , were measured. The K t G and J max G of glucose influx into the tissues were higher in the surgeonfish upper intestine than in the surgeonfish lower intestine or in both segments of the eel intestine. A prominent diffusion-like transport component was also measured in all four segments during influx experiments. Net transepithelial glucose fluxes (0.05 mM) were greater in eel intestine than in those of the surgeonfish largely due to an apparent lower apical membrane permeability of the former coincident with reduced backflux of glucose from epithelium to lumen. All four stripped intestinal segments exhibited non-significant (from zero; P >0.05) or small, serosa-negative transepithelial potential differences (-0.1 to -2.2 mV), and low transepithelial resistances (40–88 O cm -2 ). Each tissue displayed significant ( P P >0.05) change the transepithelial resistance, but did induce a significant ( P J net Na with added luminal glucose, these increased net cation fluxes were not quite significant ( P >0.05). It is concluded that coupled Na-glucose transport occurs in these tissues, but that metabolic enhancement of unrelated current-generating mechanisms also takes place and may modify depolarizing effects of organic solute transfer