Renal lesions in young rats induced by Salmonella enteritidis endotoxin.

Sepsis in newborns and infants is a major pediatric problem often associated with renal dysfunction. The present report deals with changes in renal tissue induced by Salmonella enteritidis endotoxin in 10- and 28-day-old Sprague-Dawley rats. Our studies revealed a 90% lethality within 24 h of 0.1 mg/kg and 35 mg/kg S. enteritidis endotoxin injection in 10- and 28-day-old rats, respectively. The 10- and 28-day-old animals received a single intraperitoneal injection of the 90% lethality dose and were sacrificed at different intervals for histopathological evaluation of kidneys by light and electron microscopy. The glomeruli showed visceral epithelial and endothelial cell swelling and polymorphonuclear leukocyte and platelet accumulation in the capillary lumina. Cortical and medullary tubules showed edematous separation, mild focal epithelial cell damage and focal intertubular hemorrhage. Renal sections of 28-day-old experimental rats showed increased numbers of polymorphs in the glomerulus and enlarged mesangial matrix. These sections also showed an increase in the number of hemorrhagic foci in 10 x field compared with the 10-day-old experimental rats. Endothelial cells of renal vasculature showed cytoplasmic swelling, vacuolization, autophagic vesicle formation and presence of secondary lysosomes. Changes in the endothelial cells of peritubular microvasculature were extensive, resulting in focal degeneration and partial loss of endothelial lining. These studies show that infant rats are extremely sensitive to S. enteritidis endotoxin requiring 1/350 the dose given to young adults to induce histopathological changes in kidney; the endothelial cells of microvasculature appear to be the primary targets of endotoxic injury irrespective of age.

Microvascular endothelium: a major target site of endotoxin induced injury in 10 day old rat.

We have studied the effects of two endotoxins, S enteritidis and E coli on liver, pancreas, intestine, lung and kidney of 10 day old Sprague Dawley rat at light and electron microscope levels. One group of experimental animals (N = 31) received a single intraperitoneal injection of 0.1 mg/kg of S enteritidis endotoxin. The second experimental group (N = 34) received multiple intraperitoneal injections of 5 to 10 mg/kg of E coli endotoxin at 15 minute intervals over a period of 75 minutes. Within four hours of injections, histopathologic evaluation of all the tissues revealed interstitial edema, widening of blood capillary lumina, accumulation of polymorphonuclear leukocytes and platelets in capillary lumina and marked swelling, vacuolization and focal desquamation of endothelial cells in microvasculature. Hepatocytes showed loss of glycogen, vacuolization and degeneration in the centro-portal region. Islet cells of pancreas also revealed swelling and vacuolization. In the small intestine, hemorrhagic pools of blood were frequently seen in lamina propria and the apical portion of villi showed degeneration and breakdown. Lungs showed focal hemorrhage, collapse of alveolar architecture and swelling of endothelium in larger artereoles. Based on these studies, we suggest that endothelial cells of microvasculature in various tissues of 10 day old rat are extremely sensitive to endotoxins, irrespective of source, and cells derived from reticuloendothelial system may play an important role in the endotoxicosis.

Age related correlation between serum TSH and thyroid C cell hyperplasia in Long-Evans rats.

The purpose of the present investigation was to determine whether there is a correlation between the serum levels of thyroid stimulating hormone (TSH), parafollicular cell (C) population in the thyroid and calcitonin (CT) secretion in aging Long-Evans (L-E) rats. Serum TSH and CT values were determined in 50 male rats at ages 2, 6, 12, 18 and 24 months and 50 female rats at 18, 21 and 24 months. The animals were sacrificed at the end of the experiment to evaluate thyroid C cell pathology. Male rats showed an increase in the serum TSH values at 6 and 12 months of age, a decline at 18 months and a significant increase from 18 to 24 months of age. In female rats, a significant increase in serum TSH concentration was also noted from 18 to 24 months of age. In both sexes, 24 month old animals with thyroid C cell hyperplasia (CH+ group) had a significantly higher level of serum TSH as compared to animals with normal distribution of C cells (CH- group). Concentration of serum CT showed a progressive increase with age in both sexes. Male rats with thyroid C cell pathology had significantly higher levels of serum CT at 24 months of age as compared to rats with normal C cell distribution. In female rats, however, serum CT concentrations in two groups were not statistically significant. We conclude from these studies that in aged L-E rats, serum TSH concentration has an influence on thyroid C cell population.

Age effects on the reactivity of antistreptococcal cell membrane antisera to murine glomerular basement membrane. In vitro versus in vivo analysis.

Antisera to the streptococcal cell membrane (SCM) were evaluated for their reactivity to murine glomerular basement membrane (GBM) in four strains of mice. Animals were studied on a daily basis from birth through 3 months and weekly thereafter through 18 months. Paired animals were compared for in vivo binding of antibody versus an indirect fluorescent antibody technique on fresh kidney sections. The findings demonstrated a granular type GBM staining for all anti-SCM which were positive. Nonspecific background staining accompanied most of the indirect fluorescent antibody sections tested while being totally absent for the direct fluorescent test on tissue from in vivo challenge of the primary antibody. The in vitro testing showed tissue from young mice (0-6 days old) to be most reactive, while the strongest reactivity was seen in the age group of 10-20 days for in vivo testing. These cross-reactive antibodies, i.e., GBM-binding anti-SCM, are best evaluated by in vivo methods where tissue is taken 4 days after antiserum injection. Animals of the age range 6-8 weeks were often negative, indicating that this age range selected for many studies may not be the most favorable one via either in vitro or in vivo studies.

The role of visceral epithelial, endothelial and mesangial cells in the formation and turnover of glomerular basement membrane.

Incorporation of 3H-proline in the mouse kidney was studied by electron microscopic radioautography in a pulse-chase mode to establish the role of visceral epithelial, endothelial, and mesangial elements in the synthesis and turnover of glomerular basement membrane. Visceral epithelial and endothelial cells were found to play a significant role in the formation of glomerular basement membrane components, and turnover time for one of the components was found to be under 2 h. The synthesis of second component is slow and make take 8-24 h. The mesangial cells appear to play a significant role in the reabsorption of the component with a faster turnover rate.