We hypothesized that one mechanism underlying advanced periodontal disease in diabetes may involve oxidant stress in the gingiva, induced by the effects of Advanced Glycation Endproducts (AGEs), the irreversible products of non-enzymatic glycation and oxidation of proteins and lipids which accumulate in diabetic plasma and tissue. Infusion of AGE albumin, a prototypic ligand, into mice resulted in increased generation of thiobarbituric acid reactive substances (TBARS) compared with infusion of non-glycated albumin in the gingiva, as well as in the lung, kidney and brain. Pretreatment of the animals with the antioxidants probucol or N-acetylcysteine (NAC) prevented the generation of TBARS in the gingiva. Affinity-purified antibody to AGEs demonstrated increased immunoreactivity for AGEs in the vasculature and connective tissues of the gingiva in streptozotocin-induced diabetic mice compared to non-diabetic controls. Increased immunoreactivity for AGEs was also demonstrated in the gingiva of diabetic humans compared with non-diabetic individuals via immunohistochemistry and ELISA. Consistent with these data, immunohistochemistry for heme oxygenase-1, a marker of enhanced oxidant stress, was increased in the gingival vasculature of diabetic mice and humans compared with non-diabetic controls. These data suggest that AGEs present in diabetic gingiva may be associated with a state of enhanced oxidant stress, a potential mechanism for accelerated tissue injury.

Confluent cultures of normal diploid WI-38 human embryonic lung fibroblasts released somatomedin (SM)-like activity into their incubation medium during culture in serum-free medium. This postculture medium (conditioned medium) stimulated cell division in these same cultured WI-38 fibroblasts and 35SO4 uptake by hypophysectomized rat cartilage in vitro. The conditioned medium also contained immunoreactive SM (IRSM) activity which yielded parallel dose-response curves to human serum in a RIA for SM. The IRSM activity measured in conditioned medium was not the artifactual result of effects of possible SM-binding proteins or proteolytic enzymes in conditioned medium. These studies suggest that cultured WI-38 fibroblasts produce and release SM-like activity which has SM-like biological activity and is immunoreactive with a basic SM purified from human plasma Cohn fraction and having similarity with SM-C and insulin-like growth factor-I. Human GH appears to stimulate production and release of IRSM activity by these cells.

The effects of ACTH and 8-Br-CAMP on growth and replication of a functional mouse adrenal tumor cell line (Y-1) were investigated. ACTH and 8-BrcAMP both inhibited DNA synthesis and replication when added to randomly growing cell cultures. ACTH addition and serum deprivation each arrested cells in GI; an additional point of arrest in G P occurred with 8-BrcAMP. Cells

Dead and dying cells were localized by light microscopy in the mucosal epithelium of the intestine of an outbred strain (CD1) and an inbred strain (B10A) of mice by vital staining with the dye, trypan blue. In whole mounts of the intestinal wall, trails, or variable-sized clusters of blue-stained cells were seen throughout the course of infection and in mice given a range of inoculum levels. In CD1 mice, irregular trails of dead cells were seen in the intestine floor and clusters of them along the villi. In B10A mice, dead cells were seen only as trails or clusters in the intestinal floor. The results suggest that worms move through the epithelium only in the intestinal floor. Cells killed by this activity may be sloughed from the epithelium more rapidly by B10A mice than by CD1 mice where the dead cells migrate up villi before being sloughed.

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