Proliferation, cell hyperplasia

Fig. 13.8 Triple staining of a usual ductal hyperplasia for K5 (red), K8/18 (green) and SMA (pink). Note that the proliferating cells are only glandular cells. Myoepithelial cells are seen only in the outer layer (pink) and do not participate in the proliferation process...

If the insult persists, hyperplasia (cell proliferation) proceeds and leads to an abnormal epithelium. Injury produced by chronic exposure to irritants such as SO2, NO2, O3, formaldehyde, and tobacco smoke includes undifferentiated basal cells (hyperplasia), squamous metaplasia, and goblet cell metaplasia. In practice, many irritants produce responses between mild and severe, and various combinations of degeneration, inflammation, and proliferation may be observed. 

Kombrast, D.J., Barfknecht, T.R. Ingram, P. (1984) Effect of di(2-ethylhexyl)phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells. J. Toxicol, environ. Health, 13, 99-116 Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M. Katoh, M. (1998) Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci., 42, 49-56... 

Morishita, R., Gibbons, G.H., Ellison, K.E., et al. (1993). Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc. Natl. Acad. Sci. U.S.A., 90, 8474-8478. 

Application of diglycidyl resorcinol ether caused irritation to the eyes and skin of rabbits. Once-monthly intravenous injection of the compound at doses of 100-200 mg/kg bw produced a progressive lowering of the leukocyte count in monkeys. Hyperkeratosis and basal-cell hyperplasia in the forestomach were observed in rats and mice exposed daily to intragastric doses of 12.5 mg/kg bw and higher for 13 weeks. In a two-year study in rats, dose-related bronchopneumonia occurred, which was not consistent with chemical pneumonitis, but was characterized by polymorphonuclear leukocytes in the alveoli. The compound also inhibited the growth of Walker carcinoma in rats (lARC, 1985). The occurrence of forestomach hyperkeratosis and epithelial cell proliferation was confirmed in a two-week study in rats with doses of 25 mg/kg bw, but not with 12 mg/kg bw (Ghanayem et al., 1986). 

Kurata Y, Kidachi F, Yokoyama M, et al. 1998. Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets Lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol Sci 42 49-56. 

Taken together, the identification of mast cell hyperplasia and mediator release at sites of tissue fibrosis and wound healing, observations in animal models, and study of the actions of mast cell products, has provided much circumstantial evidence that mast cells are involved in tissue remodelling, healing and fibrosis. It is unlikely that mast cells are essential in these responses, but more likely that they augment them. Complex interactions between different connective tissue components, mast cells and other inflammatory cells are likely to operate, and are unlikely to be fully delineated in humans in vivo. It seems reasonable to hypothesize however that initial mast cell mediator release has the potential to activate fibroblasts, which may then promote the recruitment at d proliferation of further mast cells, explaining the mast cell hyperplasia often witnessed at sites of chronic inflammation. 

A classical example is alcoholic cirrhosis, which in the case of chronic alcohol abuse, leads to multiple, polyclonal areas of liver cell hyperplasia and an increased risk for development of hepatocellular neoplasia. In both preneoplasia and certain forms of hyperplasia, the antecedent lesions typically have a higher rate of cell proliferation than the surrounding normal cells and, thus, these cells are at increased risk to sustain additional genetic damage and progress to the next stage in the carcinogenic process. 

M (increased cell proliferating Wilmer et al. 1989 rates in nasal epithelium squamous metaplasia with basal cell hyperplasia In nasal epithelium)... 

Tazarotene (Tazorac) is a third-generation retinoid approved for the treatment of psoriasis and acne vulgaris. This retinoid binds to aU three RARs. In mice, tazarotene blocks ornithine decarboxylase activity, which is associated with cell proliferation and hyperplasia. In cell culmre, it suppresses markers of epidermal inflammation and inhibits comification of the keratinocyte. 

The underlying pathophysiological concepts of treatment by iodine and levothyroxine are different. Iodine aims to reduce cell proliferation and hyperplasia of thy-rocytes, which are regulated by iodine-dependent local growth factors rather than by pituitary-derived TSH. Levothyroxine puts the thyroid to rest by suppressing TSH and reduces cellular hypertrophy due to TSH stimulation (Stubner et al., 1987). A combination of these two agents would therefore, at least in theory, yield additive effects. 

Melamine is not particularly toxic, and its effect in rats is comparable to that of table salt the in rats for ingestion is 3161 mg/kg of body weight, (with other sources showing 6000 mg/kg of body weight), data for humans could not be found. Melamine is excreted from blood plasma with a half-life of 3 h. Large quantities of melamine cause kidney stone formation, inflammation of the irrinary bladder, a type of cell proliferation called hyperplasia, and, in male rats, urinary bladder cancer. A dose of 63 mg/kg of body weight per day (NOAEL, no observed adverse effect level) does not increase the risk of kidney stone in rats. 

In the female Wistar rat, intratracheal instillation of coal dusts of different rank suspended in saline induced a significant Clara cell hyperplasia as compared with TiOa dust (P <0.05) or pure saline (P <0.03) (Albrecht et al. 2000). Proliferation and hyperplasia by coal dust were independent of the quartz content of the dust samples. 

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