We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did not impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of beta-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.

Aminoglycosides↗

PubMedDate not supplied

Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity.

Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity.

Animals↗

PubMedDate not supplied

Relationship between the bactericidal and bacteriolytic activity of cephalosporins and changes in the cell volumes of Escherichia coli cultures.

The bactericidal effect of cefoxitin and cefotaxime in relation to concentration and exposure time, as demonstrated by the killing curve diagrams of Escherichia coli cultures, was compared with the degree of bacteriolysis and the cell volume increase measured by the coulter counter-channel analyser system. Human plasma ultrafiltrate was used as the growth medium. Cefoxitin has a higher bactericidal activity than cefotaxime. With increasing concentrations the bactericidal efficacy of cefoxitin increases more rapidly in the lower range of concentrations (2-10 mg/l) than in the higher range (10-40 mg/l). In contrast, the bactericidal effect of cefotaxime in the range 0.06-1.2 mg/l is virtually constant and can only be increased by high levels (10-40 mg/l). The morphometric effect of cefoxitin on E. coli cultures, as demonstrated by volume distribution curves, is characterized by intensive and rapidly appearing bacteriolysis 20 min after exposure to the antibiotic without a preceding increase in bacterial cell volume. Higher concentrations result in an earlier onset of bacteriolysis. In contrast, the application of cefotaxime reveals a massive increase in bacterial cell volume (more than five-fold) with a delayed (greater than 2 h) onset of bacteriolysis. High cefotaxime concentrations reduce the extent of bacterial cell volume increase, associated with an earlier and more intensive onset of bacteriolysis. With both cephalosporins, the bacterial cell alterations are particularly dependent on the exposure time. There is evidently a close correlation between bactericidal and bacteriolytic activity. This is valid both for the two cephalosporins and generally for the concentration-activity relationships.

Blood↗

PubMedDate not supplied

[Comparative animal studies on the potential nephrotoxicity of new cephalosporins: EMD 29 645, EMD 29 946, cefuroxine and cefamandole].

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

1,25-Dihydroxycholecalciferol stimulates the expression of intercellular adhesion molecule-1 in renal carcinoma cells.

1,25-Dihydroxycholecalciferol (1,25-D3) is a potent immunomodulatory vitamin modulating major histocompatibility complex class-II expression in monocytes and epithelial cells. However, the impact of 1,25-D3 on the expression of adhesion molecules in epithelial cells has not been investigated. Human renal tubular epithelial and renal carcinoma cells express intercellular adhesion molecule-1 (ICAM-1), a ligand of the leukocyte-function-associated antigen-1 (LFA-1). Therefore, we addressed the question whether 1,25-D3 modulates ICAM-1 expression by renal carcinoma cells. Using an enzyme-linked immunoassay we detected an increase in ICAM-1 expression by a renal carcinoma cell line (ACHN) cultured in the presence of 1,25-D3. Also, in ACHN cells stimulated with gamma-IFN a significant stimulatory effect of 1,25-D3 was evident. ICAM-1 is crucial for the adhesion of LFA-1-expressing lymphocytes and is involved in antigen presentation. In addition, ICAM-1 may be of significance in lymphocyte lysis of tumor cells. Therefore, the impact of 1,25-D3 on ICAM-1 expression by renal and non-renal and non-renal carcinoma cells and renal tubular epithelial cells may be of clinical importance.

Animals↗