ABSTRACT
New methodological approaches to preclinical study of the efficiency of potential prostatotropic drugs are suggested on the basis of original research and published data. An algorithm is proposed to investigate specific activity and safety of potential drugs for the prevention and treatment of prostate disorders.
Subject(s)
Drug Evaluation, Preclinical/methods , Prostatic Diseases/drug therapy , Animals , Humans , MaleABSTRACT
Methodological approaches to preclinical evaluation of the efficiency of potential dermotropic preparations are proposed on the basis of original investigations and an analysis of published data. At the first stage of the preclinical investigation of preparations for external application, it is necessary to estimate their acute toxicity, allergenic activity, and local irritation effect in addition to studying the specific activity.
Subject(s)
Drug Evaluation, Preclinical/methods , Skin Diseases/drug therapy , Administration, Cutaneous , Animals , HumansABSTRACT
Perisinusoidal fibrosis development in experimental hypervitaminosis A and its combination with preliminary Kupffer cells stimulation with prodigiozan was studied in rat liver using light and electron microscopy. Reticular fibers volume density naturally growing after administration of large dozes of vitamin A, significantly reduces in appropriate terms of experiment after Kupffer cells stimulation with prodigiozan. Two cell type were distinguished in perisinusoidal space: typical fat-accumulating ones and fibroblast-like ones topographically closely connected with reticuline fibres. Endotheliocytes and Kupffer cells acquire dystrophic changes in prodigiozan introduction and hypervitaminosis A combination.
Subject(s)
Anti-Bacterial Agents/pharmacology , Hypervitaminosis A/chemically induced , Kupffer Cells/drug effects , Liver Cirrhosis, Experimental/chemically induced , Liver/drug effects , Prodigiozan/pharmacology , Animals , Diterpenes , Female , Hypervitaminosis A/pathology , Kupffer Cells/pathology , Liver/pathology , Liver Cirrhosis, Experimental/pathology , Microscopy, Electron , Rats , Retinyl Esters , Stimulation, Chemical , Time Factors , Vitamin A/administration & dosage , Vitamin A/analogs & derivativesSubject(s)
Liver/blood supply , Liver/cytology , Animals , Endothelium, Vascular/cytology , Endothelium, Vascular/embryology , Endothelium, Vascular/metabolism , Humans , Kupffer Cells/cytology , Kupffer Cells/metabolism , Liver/embryology , Liver/metabolism , Microcirculation/cytology , Microcirculation/embryology , Microcirculation/metabolismABSTRACT
Differentiation of the hepatic sinusoidal capillary cells has been studied in the embryonal and postnatal periods of the rat ontogenesis. In the embryonal liver cellular elements are differentiated divergently with formation of endotheliocytes, Kupffer cells and fat-accumulating cells. Differentiation of endotheliocytes is accompanied with their flattening, formation of fenestrae and pores in peripheral processes, increasing amount of micro- and macropinocytic vesicles, and also development of intercellular contacts, presented at first as simple, and then as tight junctions. Formation of intercellular clefts occurs by means of parting of simple junctions; this ensures migration of blood cells across the endothelial lining. Kupffer cells develop out of immature macrophagal elements of the perisinusoidal space. During differentiation they migrate into the endothelial lining. Simultaneously in their cytoplasm lysosomes accumulate and acid phosphatase activity increases. The fat-accumulating cells are formed out of poorly differentiating fibroblast-like elements of the perisinusoidal space. Their differentiation is accompanied with a progressive development of the granular endoplasmic reticulum and with accumulation of reticular fibers in the perisinusoidal space, and in cytoplasm--lipid inclusions.
Subject(s)
Animals, Newborn/anatomy & histology , Embryo, Mammalian/cytology , Liver/cytology , Age Factors , Animals , Cell Differentiation , Endothelium/cytology , Endothelium/ultrastructure , Fibroblasts/cytology , Fibroblasts/ultrastructure , Gestational Age , Kupffer Cells/cytology , Kupffer Cells/ultrastructure , Liver/ultrastructure , Microscopy, Electron , RatsABSTRACT
Changes of the fat-storing cells (FSC) in the liver have been studied after oil solution of vitamin A have been injected to intact rats, when Kupffer's cells have been blocked with colloid silver and stimulated with prodigiosan. During these experiments (on the 4th, 7th, 14th days) the amount of FSC does not change, and their size increases. The blockade of Kupffer's cells does not influence the dynamics of the FSC changes, and their stimulation contributes to lipid accumulation in their cytoplasm and to earlier revealing of these elements (on the 2d day of the experiment). In parallel with increasing size of FSC, fatty infiltration of hepatocytes disappears and reticular fibers accumulate in the perisinusoid space. Participation of FSC in lipid metabolism and in synthesis of the III type collagen is proved, as well as existence of intercellular interactions of these elements with endotheliocytes, Kupffer's cells and hepatocytes.