Enhanced biological effect induced by a radioactive C-9-ion beam at the depths around its Bragg peak

To explore the potential of double irradiation source, radioactive C-9-ion beam, in tumor therapy, a comparative study oil the surviving effect of human salivary gland cells at different penetration depths between C-9 and C-12-ion beams has been carried out. The 9C-ion C beam, especially at the distal side of the beam came out more efficient in cell killing at the depths around its Bragg peak than the 12 Bragg peak. Compared to the C-12 beam, an increase in RBE by a factor of up to 2.13 has been observed at the depths distal to the Bragg peak of the 9C beam. The 9C beam showed an enhanced biological effect at the penetration depths around its Bragg peak, corresponding to the stopping region of the incident C-9-ions and where the delayed low-energy particles were emitted. Further analysis revealed that cell lethality by the emitted particles from the stopping C-9-ions is responsible for the excessive biological effect at the penetration depths around the Bragg peak of the C-9 beam

Inhibition of basolateral cAMP permeability in the toad urinary bladder

The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cellThe demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders.Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor