Increased glucose uptake as a principal energy source is a requirement for the continued survival of tumour cells. Facilitative glucose transporter-1 (GLUT1) and -3 (GLUT3) have been previously shown to be present and regulated in breast cancer cells and are associated with poor patient prognosis. In cancer cells, the cAMP secondary messenger pathway is known to potentiate described glucose transporter activators and regulate cell fate. However, no regulation of the glucose transporters in breast cancer cells by cAMP has previously been examined. Herein, we determined in the well-characterized breast cancer cell line ZR-75, if the cAMP analogue 8-br-cAMP was capable of regulating GLUT1 and GLUT3 expression and thus glucose uptake. We demonstrated that 8-br-cAMP transiently up-regulates GLUT3 mRNA levels. The use of actinomycin-D and the cloning of 1,200 bp upstream of the human GLUT3 promoter demonstrated that this regulation was transcriptional. Immunocytochemistry and Western blotting confirmed that the increase in mRNA was reflected by an increase in protein levels. No notable regulation of GLUT1 in the presence of 8-br-cAMP was detected. Finally, we determined using the non-metabolizable glucose analogue 2-DOG if this up-regulation in GLUT3 increased glucose uptake. We observed the presence of two uptake components, one corresponding to the Km of GLUT1/4 and the other to GLUT3. A doubling in the uptake velocity was observed only at the Km corresponding to GLUT3. In conclusion, we demonstrate and characterize for the first time, an up-regulation of GLUT3 mRNA, protein and glucose uptake by the cAMP pathway in breast cancer cells.

We studied prospectively the perioperative changes of renal function in nine children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and (131)I-hippuran clearances before CPB, during hypo and normothermic CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for tubular cellular damage. Plasma and urine creatinine and electrolytes were measured. Free water, osmolal and creatinine clearances, as well as fractional excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were calculated. GFR was normal before and after surgery. ERPF was low before and after surgery; it increased significantly immediately after CPB. Filtration fraction (FF) was abnormally elevated before and after surgery; however, a significant decrease during normothermic CPB and sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also increased in this period, but not significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were normal in all patients pre- and postoperatively. We conclude that there is no evidence of clinically significant deterioration of renal function in children undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm cellular tubular damage. There was no tubular dysfunction at that time.

Various drugs with a triptan-like chemical structure interact with cellular components of the innate immune system, resulting in an apparent indirect inhibition of NKC activity and direct inhibition of neutrophils pMMP-9 secretion. These results suggest that they may play a positive role in decreasing the severity of inflammatory processes. Whether this effect is part of triptans antimigraine mechanism of action, or just an added beneficial effect of their use for the reversal treatment of migraine headaches remains to be explored.

Renal function during cardiac surgery with extracorporeal circulationBackground: Patients with valvular heart disease are at high risk of acute renal failure after surgery with extracorporeal circulation. Aim: To describe changes in renal function parameters during surgery with extracorporeal circulation in patients with valvular heart disease and compare them with those found in patients undergoing elective coronary surgery. Material and Methods: Two groups of patients were studied. Group 1 was composed by twelve patients undergoing elective coronary surgery and group 2 was composed by eleven patients undergoing surgery for heart valve replacement. Glomerular filtration rate and effective renal plasma flow were estimated from inulin and the 131 I-hippuran clearance respectively, at five different times, during surgery and the postoperative period. Sodium filtration fraction and fractional excretion were calculated. Alpha and pi-glutathione stransferase in urine were measured as markers of tubular damage in the pre and postoperative periods. Results: Effective renal plasma flow was reduced in both groups before induction of anesthesia, did not change during surgery and decreased significantly in patients with valvular disease in the postoperative period. Glomerular filtration rates were normal during all the study period. There was a non significant reduction of filtration fraction during extracorporeal circulation. Alpha and pi glutathione s-transferases were normal and did not change. Fractional excretion of sodium increased significantly postoperatively. Conclusions: In patients with valvular disease undergoing surgery with extracorporeal circulation, renal function does not deteriorate. No significant difference was found when compared with patients undergoing coronary surgery. No evidence of functional and cellular renal disfunction or damage was found in both study groups (