The "granuloma pouch" model in rats was evaluated on the basis of biochemical, haematological and histological factors. Seven days after formation of the pouch following the intramuscular injection of air and a mixture of 1% croton oil in olive oil as an irritant, the pouch was filled by approximately 5 ml of haemorrhagic exudate. Biochemical assessment of the exudate revealed that its main characteristics were increased lactate dehydrogenase levels as well as increased alpha 2- and gamma-globulin fractions. Histological sections of the surrounding tissue showed a typical granulomatous inflammatory response. The granuloma pouch can therefore be characterized as a local, chronic inflammation caused by the creation of a body cavity. The biochemical data of the pouch exudate were compared with those of human wound fluid obtained after surgery; since the values were in very good agreement, it is assumed that the granuloma pouch model reflects the clinical situation in inflamed wound cavities following the extirpation of organs.
In this paper we have described the microbiology of the granuloma pouch model in rats. We studied the biochemical parameters of pouch exudates infected with Escherichia coli. Data revealed that the inflammatory response increased during the course of infection since lactate dehydrogenase levels as well as alpha 2 and gamma-globulin fractions were increased in comparison to uninfected controls. Infection of the pouches did not spread. We also monitored the growth characteristics of four different E. coli strains. In vitro incubation of these strains in human and rat serum as well as in pouch exudate, and the in vivo growth rate in infected pouches revealed that the degree of serum sensitivity was clearly related to viability in vivo. Serum-resistant strains grew well in pouch exudate, whereas serum-sensitive strains were eliminated from the infected pouches. Since elimination of these strains was dependent on the challenge dose, we concluded that cellular and/or humoral host defense mechanisms became locally exhausted or inactivated. Thus, the granuloma pouch represents a local bacterial infection of a poorly defended, inflamed body cavity.
In order to clarify the etiology of a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidney in male rats, the nephrotoxicity of p-dichlorobenzene (p-DCB) was investigated in a subchronic study. Groups of ten male and ten female Fischer 344 rats were dosed by gavage with 0 (controls), 75, 150, 300 or 600 mg p-DCB/kg/day in corn oil. Half of the animals were sacrificed after 4 weeks and the remainder after 13 weeks. Increased urinary LDH and epithelial cell excretion and exacerbation of hyaline droplet accumulation in the cytoplasm of renal cortical cells were observed in male rats over the entire dose range investigated. Tubular single cell necrosis, dilated tubules with granular cast formation in the outer zone of the medulla, were evident in male rats after 4 and 13 weeks of treatment with doses of 150-600 mg/kg/day. In female rats there was no indication of a nephrotoxic action of p-DCB. The effects on the kidney, both in their morphological characteristics and the fact that they occur exclusively in male animals, correspond to the light hydrocarbon nephropathy observed as a result of short-term treatment with a number of aliphatic and cyclic hydrocarbons. The development of cortical renal tumors seems to be associated with this kind of kidney damage which is unique to male rats. The literature on this subject generally regards these renal effects as not predictive for man.
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