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Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
Published on: December 14, 2015
Physiology and pathology of skin after burns and derangement of gene expression
1Burn Medicine Clinic, 3rd Medical Faculty of the Charles University and Faculty Hospital of Královské Vinohrady, Prague, Czech Republic.
Abstract:
Temperature and time are two basic factors influencing the effect of heat on the human organism. The degree of resulting damage also depends on the anatomical organization of the skin and hypodermis. Sweat glands and the vascular supply, with blood flowing in corium and hypodermis, act as an effective thermo-regulators for the deeper structures. Under each fully developed necrosis there is a problematic transient area, also known as a zone of blood stasis, which corresponds to the partial damage caused by heat conducted into deeper structures. In this area during the first 3 days cells are selected according to the resistance to the thermal trauma. The basis genetic information of cells is very resistant, but disorders develop on the genetic expression level. Cells--mainly fibroblasts--which survive the first selection are damaged by the thermal injury to varying degrees and often cause other complications. During synthesis of transcripts of RNA from DNA chains an excessive amount of transcripts can develop, subjecting the receptor to information about the loss of skin firmness in defective feedback to the CNS, blocked by fixed trauma emotion. The status is accompanied by swelling, lymphatic stasis, capillary stasis, changes of the local pH and others. During repair facilitated by inflammatory process, excessive amount of collagen is created, as has repeatedly been proved in experiments. The problem can be partially solved by early compression, which limits the amount of impulses about insufficient firmness of the skin, and improves the circulation, while reducing edema, normalizes pH and optimizes production of transcripts. RNA polymerase lacks the ability to correct perfectly and in fact frequently makes mistakes, even under completely normal physiological conditions. If the pH is wrong, it can make even more mistakes and produce pathological collagen in excessive amounts. RNA is not intended to preserve information permanently, and after a certain time it degrades. The onset of this degradation is determined by the cell as well as the amount of created proteins. If RNA is not degraded on time, overproduction of protein and collagen is a natural consequence of the developed defect. Messenger RNA (mRNA) directs the creation of proteins. In case that it is not properly cut in the cellular nucleus, qualitative and quantitative errors in transcription into the protein develop. The non-information RNA takes an enzyme part and plays a role during the transfer of RNA into the protein. It does not have the correction ability. Transfer tRNA chooses appropriately amino acids and places them into the growing protein chain. At the same time, it can make errors and interchange amino acids.
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