Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice.

Up-regulation of vascular endothelial growth factor (VEGF) plays a primary role in the pathogenesis of psoriasis. Transgenic mice over-expressing VEGF under the Keratin 14 (K14) promoter develop an inflammatory skin condition with many of the pathobiological features of human psoriasis. In this work, the development of spontaneous psoriatic-like dermatitis in K14-VEGF transgenic mice was monitored from week 6 to week 44 and skin lesions were characterized clinically (application of a clinical score system comparable to the human Psoriasis Area and Severity Index), microscopically (histopathology, leukocyte subset and neoangiogensis) and immunologically (evaluation of local and systemic cytokine/chemokine profiles). Based on PASI score system, three progressive clinical phases were identified: mild acute (8-14 weeks of age), moderate subacute (15-21 weeks of age) and severe chronic-active (22-44 weeks of age) dermatitis. Microscopically, skin lesions consisted of progressive proliferative psoriatic-like dermatitis dominated by dermo-epidermal infiltrates of CD3-positive lymphocytes, an increased number of mast cells and neoangiogenesis. Both local and systemic up-regulation of pro-inflammatory (IL-12, TNF-alpha, IL-6, MCP-1 and IL-8) and regulatory (IL-10) cytokines/chemokines was observed, mainly during the later stages of disease development. The results obtained in this study further confirm the central role of VEGF over-expression in the development of psoriatic-like dermatitis. Similarly to what is reported for human psoriasis, both the local and systemic immunologic profiles observed in K14-VEGF transgenic mice suggest that a combined Th1 and Th17 response may be implicated in lesion development. The identification of three progressive stages of disease, each with peculiar clinicopathological features, renders the K14-VEGF transgenic mouse a valuable model to study novel immunotherapies for psoriasis.

DNA neosynthesis in Auerbach plexus ganglia isolated from the rat hypertrophic gut: an electrophoretic analysis.

We analysed using electrophoresis the total genomic DNA extracted from isolated Auerbach plexus ganglia of the hypertrophic duodenum upstream from a partial experimental stenosis. Results indicated the presence of two extra-bands migrating below the high molecular weight DNA. suggesting that DNA amplification is the basic mechanism of the DNA neosynthesis previously observed in myenteric neurons.

[Hyperplasia of the intestinal smooth muscle tissue proximal to a partial surgical stenosis: an autoradiographic study]. / Iperplasia del tessuto muscolare liscio intestinale a monte di una stenosi chirurgica parziale: uno studio autoradiografico.

Hypertrophy of the smooth muscle wall of the rat small intestine occurs in the loops upstream from a partial surgical stenosis. This phenomenon is due both to cell hypertrophy and cell proliferation (hyperplasia). The thickness of the muscular layers reached its maximum after ten days from the intervention and then was maintained over the following days. Hyperplasia of the smooth muscle tissue has been demonstrated by means of autoradiography after administration of tritiated-thymidine. This investigation revealed the presence of 37%-44.5% of heavily labeled smooth muscle nuclei, index of active DNA neo-synthesis. On the contrary, no labeled nuclei were observed in the downstream tract as well as in the small intestine of the controls. These results, together with those obtained by other researchers, confirms that the smooth muscle tissue can undergo cell proliferation under particular conditions and that this phenomenon is often associated with the hypertrophic process.