p53 protein is a sequence-speci®c transcriptional activator which induces the expression of a number of cellular genes involved in dierent metabolic pathways. We report that the computer-selected sequence in human and mouse C-Ha-Ras gene confers to a reporter gene the ability to be directly transactivated by wild-type p53 either over-

ABSTRACT:The role of serum levels on the intracortical accumulation kinetics of gentamicin was evaluated in normal and Enterococcus jaecalis-infected kidn eys using a short term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin achieving individual steady-state serum levels ranging from 0.5 to 20 11g/mL. Pyelonephritis was induced by a direct inoculation of the left kidney with a suspension of E jaecalis. This model resulted in severe infection of the left kidney and mild infection of the right kidney. Gentamicin cortical concentrations were analyzed as a function of serum levels by linear regression (least squares regression analysis). A MINOGLYCOSIDES ARE ESSENTIALLY ELIMINATEDby glomerular filtration and partially reabsorbed and accumulated by proximal tubular cells. Several factors have been recognized which disturb the normal intrarenal pharmacokinetics of gentamicin, eg. impaired renal function ( 1), glomerulonephritis (2). ischemia (3), state of hydration (4), diabetes (5) and renal infection (6).Beauchamp et al (7) and Bergeron et al (6) observed higher intracortical gentamicin concentrations in Escherichia coli-infected kidneys compared to normal kidneys. These changes, observed in the presence of Gram-negative infection, 654-2705. Fax (418) Received for publication February 27, 1990 were more severe than those observed in kidneys infected with Enterococcusjaecalis (8). There has been speculation that endotoxin might have been responsible for the disturbed intrarenal distribution of aminoglycoside in E coli pyelonephritis. In fact., Bergeron and Bergeron (9) showed that endotoxin increases the level of aminoglycoside in the renal parenchyma compared to normal, while the tissue levels of cephalothin were not modified.More recently, Beauchamp et al (10) showed that the intracortical accumulation kinetics of gentamicin was modified in the presence of E coli pyelonephritis. The aim of the present study was to evaluate the effect of E faecalis pyelonephritis on the intracortical accumulation kinetics of gentamicin using a short term infusion model in conscious rats. and 265 g were used. They had free access to food and water throughout the experiment. Two groups of animals were studied: normal (n=22) and pyelonephritic (n=23) rats. Pyelonephritis was induced four days before perfusion . Animals were anesthetized with 350 mg/kg chloral hydrate, and their left sides were shaved. An incision was made at the level of the left kidney and the kidney was exposed and in~ected with 0 . 1 mL of an inoculum containing 10 to 10 8 Ejaecalis (ATCC 23241) . The gentamicin minimal inhibitory and minimal bactericidal concentrations for the strain were 32 and 128~-tg/mL, r espectively. The suspension was injected directly into the medulla through the upper and lower poles of the kidney, as described by Kaye (11). This inoculation produces two kinds of infection: a serious pyelonephritis of the left kidney and a less severe infection of the right kidney due to...