[Efficacy and safety of intramuscular imipenem/cilastatin (IPM/CS) for complicated urinary tract infections].

An intramuscular preparation of imipenem/cilastatin (IPM/CS, 500 mg/500 mg) was administered to 59 patients with complicated urinary tract infections (UTI; cystitis and pyelonephritis) to evaluate its efficacy and safety. The obtained results are summarized as follows: In patients with cystitis, evaluations based on daily frequencies of administration were also performed. 1) According to the treating doctors, the drug showed an overall efficacy rate of 80% (45/56 patients). The efficacy rate was 89% in patients with cystitis treated by a u.i.d. regimen. Among patients treated by a b.i.d. regimen, the efficacy rate was 67% for cystitis cases and 84% for pyelonephritis cases. 2) When clinical efficacy was assessed according to the criteria for UTI drug efficacy evaluation, the drug was 'markedly effective' in 14 patients, 'effective' in 23, and ineffective in 11 patients, for an efficacy rate of 77% (37/48 patients). 3) The microbiological eradication rate was 88% (59/67 strains). The rate was 95% (20/21 strains) for Gram-positive bacteria and 85% (39/46 strains) for Gram-negative bacteria. The efficacy for Enterobacter faecalis and Pseudomonas aeruginosa was 100% and 73%, respectively. 4) As side effects, pain at the injection site was reported by one patient and abnormal laboratory test values were observed in 2 patients. All of these reactions were mild and resolved shortly after the completion of treatment. Based on these findings, it is concluded that this intramuscular preparation of IPM/CS is effective for treating complicated urinary tract infections.

Human simple renal cyst fluid contains a cyst formation-promoting activity for Madin-Darby canine kidney cells cultured in collagen gel.

Simple renal cysts are commonly observed in the elderly, but few examinations have been performed to study the mechanism of this disease. We have previously shown that simple renal cyst fluid contains some growth factors, including epidermal growth factor (EGF; less than 54 pg mL-1) and insulin-like growth factor I (IGF-I; 30-2070 pg mL-1) (M. Taide et al. Clin Chim Acta, 1993; 217:199-203). In this report, the biological significance of growth factors or of human simple renal cyst fluid on the formation of renal epithelial cyst was determined using Madin-Darby canine kidney (MDCK) cells cultured in collagen gel. Both EGF (200 pg mL-1 or more) and IGF-I (100 pg mL-1 or more) were found to stimulate cyst formation in MDCK cells. Additionally, 12/21 human simple renal cyst fluid samples were found to be capable of stimulating cyst formation in MDCK cells. This activity was due to a heat- and acid-labile protein and not inhibited by the anti-IGF-I neutralizing antibody. These results indicate that in some instances simple renal cyst fluid would thus appear to contain specific activity for cyst formation, which may affect cyst formation in vivo.

Peritubular endothelial cell proliferation in mice during compensatory renal growth after unilateral nephrectomy.

The proliferation of peritubular endothelial cells during compensatory renal growth (CRG) following unilateral nephrectomy in mice was investigated using a labeling index. The labeling index of peritubular endothelial cells increased 6 h after uninephrectomy and decreased to the normal level within 72 h. Immunohistochemical study revealed that c-myc protein was expressed in the nuclei of both cortical tubular cells and peritubular endothelial cells. Furthermore, intravenous injection of anti-basic fibroblast growth factor (bFGF) neutralizing antibody just after uninephrectomy led to significant inhibition of proliferation of peritubular endothelial cells, but not tubular cells. These results indicate that peritubular endothelial cells proliferate transiently during CRG and that bFGF plays an important role for the growth regulation of that cell in the kidney.

Transforming growth factor-beta in rat kidney during compensatory renal growth.

Transforming growth factor-beta (TGF-beta) inhibits the DNA synthesis and stimulates the alkaline phosphatase activity of cultured renal cortical tubular cells. When unilateral nephrectomy was performed, TGF-beta activity content gradually decreased in the remaining kidney. An immunohistochemical study of the remaining kidney after uninephrectomy, however, showed that the expression of TGF-beta increased by the third day after uninephrectomy in the proximal tubular cells and an autoradiographic study revealed that TGF-beta expressing tubular cells were different from proliferating cells during compensatory renal growth. These results indicate that the total renal TGF-beta content decreases after uninephrectomy, while the expression of TGF-beta in the proximal tubular cells may increase and act as a brake for compensatory renal hyperplasia.

Transforming growth factor-beta-like activity is secreted by rabbit renal cortical tubular cells in primary culture.

The activity of an autocrine growth factor in a medium conditioned by cultured rabbit renal cortical tubular cells was investigated. Little stimulatory growth activity for tubular cells was observed in the conditioned medium, and inhibitory activity was seen only in acidified conditioned medium. This factor stimulated the colony formation of NRK 49F cells in soft agar only with epidermal growth factor and inhibited the DNA synthesis of primary cultured rat hepatocytes, and its molecular weight was about 25 kDa. The factor was neutralized by the specific antibody to transforming growth factor (TGF)-beta 1. These results indicate that renal tubular epithelial cells can produce latent TGF-beta in primary culture.

Gene expression and immunohistochemical localization of basic fibroblast growth factor in renal cell carcinoma.

Renal cell carcinoma is known as a neoplastic condition of renal tubular cells and usually shows a hypervascular tumor in angiographic examination. We examined the presence of basic fibroblast growth factor (bFGF) in human renal cell carcinoma. To determine if alterations in bFGF gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from 6 patients were analyzed for bFGF mRNA content by Northern blot hybridization. In 4 out of 6 patients, tumor tissue expressed bFGF mRNA 2 to 4 times greater than corresponding normal tissue. Two patients showed minimal elevation of tumor bFGF mRNA. The localization of bFGF in the renal cell carcinoma tissue was also examined using immunohistochemical staining, and it was found that bFGF was positively stained at the nuclei of tumor cells and the cell surface. These results suggest that increased expression of bFGF may be associated with neoplastic growth in renal tubular epithelial cells and neovascularization.

Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells.

The effects of various cytokines including interleukin-1 beta, -2, and -6, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor on the DNA synthesis of cultured rabbit renal cortical tubular cells were investigated. Among these cytokines, it was found that only interleukin-1 beta could stimulate the DNA synthesis of cultured renal tubular cells, while interleukin-6 mildly suppressed the DNA synthesis of such cells. Interleukin-1 beta and -6 are produced by mesangial cells. The above results suggest that these cytokines may regulate the growth of tubular cells via the urinary flow in the nephron.

Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse.

A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor was established for measurement of the content of epidermal growth factor in the remaining kidney after uninephrectomy. In 5-week-old male mice, the renal epidermal growth factor content before uninephrectomy was 355 +/- 97 ng/g wet tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter it gradually decreased. In 15-week-old mature male mice, the renal epidermal growth factor content increased 1.7-fold on the first day after uninephrectomy. Immunohistochemical analysis showed that epidermal growth factor was present in the distal tubular cells and that the staining intensity was increased on the first day after uninephrectomy. During the course of compensatory renal growth, no significant alteration of epidermal growth factor content was observed in plasma or in the submaxillary gland. Our data suggest that the increase in renal epidermal growth factor content after uninephrectomy is due to an increased production of epidermal growth factor in the kidney itself. The significance of this phenomenon is discussed.

The effect of transforming growth factor-beta on the alkaline phosphatase activity in rabbit renal cortical tubular cell cultures.

The effect of various growth regulators including epidermal growth factor and transforming growth factor-beta on the alkaline phosphatase activity of rabbit renal cortical tubular cells has been investigated in a serum-free culture. As a result, it was found that transforming growth factor-beta, known to be a growth inhibitor of renal tubular cells, increased the alkaline phosphatase activity of the tubular cells dose-dependently and that cycloheximide blocked any increase in the activity of this factor. In contrast, epidermal growth factor decreased the alkaline phosphatase activity in the tubular cells.