S U M M A R YThe natriuretic peptides (NPs) ANF, BNP, and CNP have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells (SMCs). These properties make NPs relevant to the study of human coronary atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. However, the existence and cytological distribution of NPs and their receptors in human coronary arteries remain undetermined. This has hampered the development of hypotheses regarding the possible role of NPs in human coronary disease. We determined the pattern of expression of NPs and their receptors (NPRs) in human coronary arteries with atherosclerotic lesions classified by standard histopathological criteria as fatty streak/early atherosclerotic lesions, intermediate plaques, or advanced lesions. The investigation was carried out using a combination of immunocytochemistry (ICC), in situ hybridization (ISH), and semiquantitative polymerase chain reaction (PCR). Both by ICC and ISH, ANF was found in the intimal and medial layers of all lesions. BNP was highly expressed in advanced lesions where it was particularly evident by a strong ISH signal but weak ICC staining. CNP was demonstrable in all types of lesions, giving a strong signal by ISH and ICC. This peptide was particularly demonstrable in the endothelium, as well as in the SMCs of the intima, media, and vasa vasorum of the adventitia and in macrophages. By ISH, NPR-A was not detectable in any of the lesions but both NPR-B and NPR-C were found in the intimal and the inner medial layers. By RT-PCR, mRNA levels of all NPs tended to be increased in macroscopically diseased arteries, but only the values for BNP were significantly so. No significant changes in NPR mRNA levels were detected by PCR. In general, the signal intensity given by the NPs and their receptors by ICC or ISH appeared dependent on the type of lesion, being strongest in intermediate plaques and decreasing with increasing severity of the lesion. This study constitutes the first demonstration of NPs and NPR mRNAs in human coronary arteries and supports the existence of an autocrine/paracrine NP system that is actively modulated during the progression of atherosclerotic coronary disease. This suggests that the coronary NP system is involved in the pathobiology of intimal plaque formation in humans and may be involved in vascular remodeling.

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This work reviews the most relevant present-day processing methods used to improve the accuracy of multimodal nonlinear images in the detection of epithelial cancer and the supporting stroma. Special emphasis has been placed on methods of non linear optical (NLO) microscopy image processing such as: second harmonic to autofluorescence ageing index of dermis (SAAID), tumor-associated collagen signatures (TACS), fast Fourier transform (FFT) analysis, and gray level co-occurrence matrix (GLCM)-based methods. These strategies are presented as a set of potential valuable diagnostic tools for early cancer detection. It may be proposed that the combination of NLO microscopy and informatics based image analysis approaches described in this review (all carried out on free software) may represent a powerful tool to investigate collagen organization and remodeling of extracellular matrix in carcinogenesis processes.

Morphogenesis and architecture of a developing epithelium is controlled by both cell shape and contacts, mediated by spatially and temporally regulated cell adhesion molecules. The authors study if E-cadherin functions as a key factor of epithelial adhesion and epidermal architecture in vivo. They apply whole-mount digital deconvolution microscopy to evaluate three-dimensional (3D) E-cadherin expression during skin morphogenesis of Rhinella arenarum and in a cell adhesion alteration model. Results show morphogenetic changes in the 3D E-cadherin spatiotemporal expression pattern correlated with the increase of E-cadherin and in the number of cells with hexagonal geometry. Alterations in junction-protein phosphorylation showed drastic loss of E-cadherin and beta-catenin in cell-cell contacts and the increase of cytoplasm and nuclear beta-catenin in epidermis, suggesting the activation of the beta-catenin signal pathway. Surprisingly, no changes in cell shape and skin architecture were registered, suggesting that epidermal E-cadherin appears to be involved in signaling rather than cell contact maintenance in vivo.

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