C.W. Vermeulen

Inactivation of Bladder Tumor Cells and Enzymes by Methylene Blue Plus Light

Using a cystoscopic light source and methylene blue as the sensitizing dye, photoactivation was examined in two types of experiments. In the first, the in vitro study destruction of two enzymes (glucose-6-phosphate dehydrogenase and lactic dehydrogenase) was examined in suspensions of whole and homogenized tumor cells from a transplantable bladder tumor. In the second or in vivo study rats were used to demonstrate that tumor cell suspensions treated with methylene blue plus light, when inoculated into susceptible rats, failed to take and produce new tumors. These experiments suggest a possible therapeutic use in treatment of human bladder tumors, though further study would be required.

Experimental Cytoxan Cystitis and Prevention by Acetylcysteine

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).

Povidone-iodine bladder injury in rats and protection with heparin.

Povidone-iodine (Betadine) has been proposed for clinical use in controlling bacterial infections by intravesical instillation in concentrations ranging from 0.1 to 1 per cent. The effects, however, of povidone-iodine on the urothelium of the bladder have not been well studied. We performed experiments to see if injury to the urothelium occurred from intravesical instillation in female rats. Injury was indeed found with concentrations of 0.3 per cent and 1 per cent povidone-iodine, as judged by the observations of increased bladder weight due to edema, histological examination, in vivo bladder staining, crystal adhesion and bacterial adhesion upon the bladder mucosa after povidone-iodine injury. Further study showed that the urothelium recovered in 6 to 7 days after povidone-iodine injury, while a 3rd experiment demonstrated at least partial protection from bacterial and crystal adhesion to povidone-iodine injured urothelium by immediate treatment with heparin instillation in the bladder.