PubMed · 11026239
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M Doi, M Shichiri, Y Hirata. 2000. [Endothelin].. https://pubmed.ncbi.nlm.nih.gov/11026239/
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In summary, regulation of sinusoidal blood flow in normal and injured liver involves structural, cellular, and humoral components. Available data suggest that stellate cells, resident perisinusoidal mesenchymal cells with a histologic orientation in the sinusoid analogous to [figure: see text] vasoregulatory pericytes, modulate sinusoidal blood flow. This regulation by stellate cells is most evident in the context of liver injury but may apply also to the normal liver. The endothelin and NO systems are important in modulating stellate cell contractility, and their degree of equilibrium is significant in determining the level of local intrahepatic resistance, especially in the injured liver. Manipulation of either or both of these systems is feasible and effective in experimental models. Such findings have obvious clinical implications and are expected to set the [figure: see text] stage for novel gene therapy approaches for treatment of patients with portal hypertension.
The review addresses two of vasoactive substances: endothelin and nitric oxide and describes how each of them effects the functions of endothelial cells of kidneys in newborn.
The recently proposed MS-WHIM indices, a set of theoretical descriptors containing information about size, shape and electrostatic distribution of a molecule, have been further investigated. The main objectives of this work were: (i) to confirm the descriptive power of MS-WHIM in modelling specific biological interactions, (ii) to analyse the dependence of MS-WHIM on the type of atomic charges used for computing electrostatic potential and (iii) to compare the performances of MS-WHIM with those provided by other global 3D molecular descriptors. The spatial autocorrelation of atomic and molecular surface properties were selected for comparison purposes. WHIM-based and autocorrelation-based vectors were calculated for two molecular sets from the literature, namely a series of 18 HIV-1 reverse transcriptase inhibitors and a set of 36 sulphonamide endothelin inhibitors. PLS was adopted to derive statistical predictive models that were validated by means of cross-validation. The reported results confirmed that MS-WHIM indices are able to provide meaningful statistical correlations with biological activity. MS-WHIM descriptors are sensitive to the type of partial atomic charges applied and improved models were obtained using more accurate charges. Moreover for both the datasets, MS-WHIM results, in terms of fitting and predictive power of PLS models, were superior to those from autocorrelation. Finally, the strengths/weaknesses of global 3D-QSAR descriptors over local CoMFA-like methods, as well as the main differences between WHIM-based and autocorrelation-based vectors, are discussed.