novobiocin and Ascites

We have previously reported that novobiocin potentiates the cytotoxic activity of etoposide (VP-16) and teniposide (VM-26) in a number of experimental tumor cell lines by inhibition of the efflux of the epipodophyllotoxins by an ATP-requiring transporter. In leukemia cells from 12/19 patients and in ovarian carcinoma cells from 2/4 patients, novobiocin, in a concentration range of 150-1000 microM, increased the intracellular accumulation of VP-16 by 30-250% by inhibiting its efflux. Novobiocin did not significantly increase the intracellular concentration of VP-16 in human mononuclear bone marrow cells from two individuals with normal bone marrow, suggesting that it might be possible to selectively modulate the intracellular accumulation of the epipodophyllotoxin in tumor cells relative to normal hematopoietic tissue. Previous findings from our laboratory have provided evidence that the membrane transporter for VP-16 which is inhibited by novobiocin is distinct from the P-glycoprotein. The expression of MRP, measured by immunoblotting, was variable in novobiocin-responsive and non-responsive leukemia cells, indicating that no direct relationship existed between the modulatory activity of novobiocin on the transport of VP-16 and the expression of the MRP gene. The findings indicate that the novobiocin-sensitive VP-16 transporter is (i) present in high frequency in leukemia and ovarian carcinoma cells, and (ii) probably not the P-glycoprotein or MRP.

Topics: Ascites; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Biological Transport; Bone Marrow; Etoposide; Female; Humans; Kinetics; Leukemia; Multidrug Resistance-Associated Proteins; Novobiocin; Ovarian Neoplasms; Tumor Cells, Cultured

Two cases of pseudomembranous colitis are presented. The first patient had been treated with novobiocin-tetracycline and penicillin, and two weeks later developed severe fulminating diarrhea with ascites and bilateral pleural effusions which did not respond to intravenous ACTH. Subsequently she underwent subtotal colectomy and made a rapid and complete recovery. The second patient developed severe diarrhea two weeks after a 10-day course of clindamycin. She was treated with intravenous ACTH, oral Lactobacillus and a fecal enema and made a complete recovery.These cases reconfirm the importance of antibiotics as etiologic agents in this disease. They also stress the classic sigmoidoscopic and histologic findings that should facilitate prompt and rapid diagnosis.

Topics: Adolescent; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Ascites; Biological Products; Clindamycin; Colon; Diarrhea; Enema; Enterocolitis, Pseudomembranous; Female; Humans; Lactobacillus; Middle Aged; Novobiocin; Penicillins; Pleural Effusion; Rectum; Tetracycline

Topics: Aeromonas; Alcoholism; Ascites; Bacteremia; Escherichia coli Infections; Geriatrics; Humans; Intestines; Liver Cirrhosis; Liver Function Tests; Neomycin; Novobiocin; Penicillins; Peritonitis; Sepsis; Streptococcal Infections; Streptomycin; Tetracycline