N-acetylcysteine modulates effect of the iron isomaltoside on peritoneal mesothelial cells.

Intravenous (i.v.) iron supplementation is used in patients on chronic peritoneal dialysis (pd). Iron induced intraperitoneal inflammation observed in our previous studies with iron sucrose may deteriorate the function of the peritoneum as the dialysis membrane. We evaluated effect iron compound, iron-isomaltoside-100 (IIS) on the peritoneal mesothelial cells (MC). We studied the effect of iv treatment with IIS ± N-acetylcysteine (NAC) on the dialysate parameters and function of MC. In 7 uremic pd patients IIS 200 mg was infused i.v. ± NAC 600 mg. Afterward, a 4 hours exchange was performed with Dianeal 1.5%. As a control dialysate exchange preceding IIS treatment was used. Inflammatory parameters of the drained dialysates as well as the dialysates and IIS effects on MC were evaluated in ex vivo experiments. Intravenous infusion of IIS resulted in an increase of the dialysate Fe (+147%, P < 0.01). Concentrations of the dialysates inflammatory mediators were increased: interleukin-6 (IL-6) +39%, P < 0.02, monocyte chemoattractant protein-1(MCP1) +50%, P < 0.02, and hyaluronan (HA) +64%, P < 0.02. Simultaneous i.v. infusion of NAC prevented increase of the dialysate inflammatory mediators. Dialysates collected after IIS treatment induced oxidative stress in MC (+29%, P < 0.05) and stimulated IL-6 synthesis (+64%, P < 0.05) in MC; no such effect was seen in dialysates obtained after simultaneous IIS and NAC i.v. treatment. IIS used as the additive to culture medium stimulated synthesis in MC of IL6 (+76%, P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (28%, P < 0.001) whereas synthesis of tissue plasminogen activator (t-PA) was reduced (-16%, P < 0.001). These changes were prevented in the presence of NAC 1 mmol/L. Intravenous administration of IIS results in the mild stimulation of intraperitoneal inflammation. IIS changes MC phenotype to the inflammatory one with reduced fibrinolytic activity. These effects are prevented by NAC.

The synthesis and SAR of rhodanines as novel class C beta-lactamase inhibitors.

Beta-lactam antibiotics such as the cephalosporins and penicillins have diminished clinical effectiveness due to the hydrolytic activity of diverse beta-lactamases, especially those in molecular classes A and C. A structure activity relationship (SAR) study of a high-throughput screening lead resulted in the discovery of a potent and selective non-beta-lactam inhibitor of class C beta-lactamases.

31P nuclear magnetic resonance studies of growth inhibition and dexamethasone resistance in human leukemic cells.

31P Nuclear magnetic resonance spectra of perchloric acid extracts from wild-type human leukemic CEM-C7 cells and the dexamethasone-resistant CEM-C1 mutant reveal significant differences in concentrations of phospholipid precursors and ATP+, which indicate metabolic differences between these two cell lines. At high cell concentrations the CEM-C7 cells are growth inhibited, which is reflected by low phospholipid precursor levels, indicative of low phospholipid turnover. The CEM-C1 mutant does not exhibit this growth inhibition and has constant phospholipid precursor levels over the same cell concentration range. Dexamethasone causes phospholipid precursor and ATP levels in CEM-C7 to drop after 48 h, but spectra obtained for CEM-C1 cells continue to show high cell viability up to 72 h.

Treatment of patients with metastatic osteogenic sarcoma: a report from the Children's Cancer Study Group.

Fifty-three patients with metastatic osteogenic sarcoma were treated with vincristine, high-dose methotrexate with citrovorum factor rescue, and cisplatin. Metastases were surgically removed in most patients, either prior to chemotherapy or following initial response to therapy. Among 29 previously treated patients, responses to initial chemotherapy included two complete remissions, six partial remissions, and eight patients with stable disease. Twenty-three patients were disease-free, six for greater than 12 months. Toxicity was moderate, but usually reversible. There were two toxic deaths and one unexplained death 48 hours following a dose of cisplatin.