[Correlation between nephrotoxic potential and renal accumulation of aminoglycosides].
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Amikacin↗
Biomedical subjects
K Sack
Publications and source records attributed to K Sack.
Tamm-Horsfall protein inhibits binding of S- and P-fimbriated Escherichia coli to human renal tubular epithelial cells.
Escherichia coli is the predominant pathogen in urinary tract infections. Fimbriae are one of the major virulence factors of these bacteria, since these protein appendices contribute towards bacterial adhesion to epithelial cells. In clinical E. coli isolates from urinary tract infections, P fimbriae are more frequently present than S fimbriae. However, these two types of fimbriae mediate adhesion to cultured tubular epithelial cells equally well. Tamm-Horsfall protein, which is the most abundant protein in normal human urine, inhibits hemagglutination by E. coli expressing S fimbriae, but does not interfere with hemagglutination by P-fimbriated E. coli. Therefore, it has been speculated that Tamm-Horsfall protein may serve as a clearance factor for S-fimbriated E. coli in human urine. In our experiments, adherence of purified S fimbriae and of S-fimbriated E. coli to tubular epithelial cells was inhibited by Tamm-Horsfall protein, but the protein also decreased binding of P-fimbriated E. coli to approximately the same degree. We found less adherence of both types of fimbriae to a Madin-Darby canine kidney cell line expressing soluble and membrane-bound Tamm-Horsfall protein as compared with the control cell line. In conclusion, our in vitro data suggest that urinary Tamm-Horsfall protein may serve as a clearance factor for E. coli expressing both S and P fimbriae. In the light of these findings, the low clinical relevance of S-fimbriated E. coli for urinary tract infections may be readily explained; however, the predominance of P fimbriae remains unresolved.
Adjuvants, Immunologic↗
Pentoxifylline, cyclosporine A and taurolidine inhibit endotoxin-stimulated tumor necrosis factor-alpha production in rat mesangial cell cultures.
Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the pathogenesis of glomerular disease. Intrinsic glomerular cells as well as extraglomerular cells have been found as a source of TNF-alpha. Rat glomerular mesangial cells produce TNF-alpha after stimulation with bacterial lipopolysaccharide (0.1, 1.0 and 10 microg/ml) over different times (4, 8, 16 and 24 h). We show that lipopolysaccharide-induced production of TNF-alpha in rat mesangial cell cultures is inhibited by pentoxifylline (50 mg/ml), cyclosporine A (0.1 microg/ml) and taurolidine (100 mg/ml). Inhibition of this production seems to be a promising treatment option for renal disease. Already pentoxifylline and cyclosporine A have been shown to improve different glomerular pathologies. Their in vitro effect on TNF-alpha production shown here might influence this.
Animals↗
Serum erythropoietin and creatinine concentrations as predictive factors for response to recombinant human erythropoietin treatment in anaemic tumour patients on chemotherapy.
Recent studies have shown that recombinant human erythropoietin (rHuEPO) is effective in correcting anaemia in about 50% of tumour patients. Predictive parameters for the response to rHuEPO still need to be established. In the present prospective study, rHuEPO therapy was scheduled in 22 patients with solid tumours for 12 weeks (3x10,000 U rHuEPO/week s.c.). If response was not achieved within 4 weeks, the dose was increased to 3x20,000 U rHuEPO/week. All patients received combined chemotherapy (ifosfamide, carboplatin, etoposide) before and during rHuEPO therapy. 10 of the 22 patients responded to rHuEPO and did no longer need blood transfusions. In 8 of the 10 responders and in 2 of the 12 non-responders serum creatinine concentration was increased before rHuEPO therapy was started. In addition, the endogenous serum EPO concentrations were significantly lower in the responders versus the non-responders. We conclude that rHuEPO is primarily effective in patients with chemotherapy-induced renal impairment. The rate of the response to rHuEPO is high when the baseline serum EPO level is <75 U/l and the serum creatinine concentration is greater than normal (or the estimated creatinine clearance <60 ml/min).
Adult↗