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PL
Włóknienie wątroby jest zło- żonym procesem biochemicznym, w którym uszkodzone obszary tkanki wątrobowej zostają otoczone przez macierz zewnątrzkomórkową z wytworzeniem tkanki bliznowatej. Proces ten rozwija się u pacjentów z przewlekłymi chorobami wątroby i jest uzależniony od rodzaju schorzenia i właściwo- ści osobniczych. Najwcześniej ulegają uszkodzeniu obszary, w których czynnik sprawczy uzyskuje największe stężenie, szczególnie u chorych z chorobą alkoholową i wirusowymi zapaleniami wątroby. Do rozwoju włóknienia dochodzi zwykle po wielu miesiącach lub latach działania czynnika uszkadzającego. Dokładny przedział czasowy, w którym włóknienie staje się nieodwracalne nie jest znany, jakkolwiek pojawiają się kolejne badania dowodzące, że nawet zaawansowane jego stadia mogą ulec regresji. Rozwikłanie mechanizmów molekularnych zaangażowanych w proces włóknienia posiada szereg implikacji klinicznych. Jedną z najistotniejszych jest tworzenie leków opóźniają- cych lub odwracających ten proces. W pracy przedstawiono aktualny stan wiedzy na temat kluczowych mechanizmów leżących u podłoża procesu włóknienia wątroby.
EN
Liver firosis is a complicated biochemical process in which damaged regions of the liver tissue are encapsulated by an extracellular matrix with scar formation. It develops in all patients with chronic liver injury at variable rates depending in part upon the cause of liver disease and in part upon the host factors. This process occurs earliest in regions where injury is most severe, particularly in chronic inflmmatory liver diseases due to alcohol or viral infection. The development of firosis usually requires several months to years of ongoing injury. The exact point in which firosis becomes irreversible is unknown however, increasing evidence suggests that even advanced stages of fibrosis may be reversible. An understanding of the molecular mechanisms involved in firogenesis process has a number of clinical implications. One of the most important is development of therapeutic interventions designed to impede or reverse hepatic firosis. This review discusses the current mechanisms underlying liver firosis.
EN
Metalloproteinases (MMP) are proteolytic enzymes whose activity is determined by the presence of zinc ion in the active site and are a widely distributed family of protease to ensure the preservation of homeostasis in animals. In human body they also play many important functions participating in the process of embryogenesis as well as in the formation of blood cells or bone formation. The main role, as it seemed at the beginning research on this group of enzymes, was to digest the extracellular matrix. However, over the years, it turned out that metalloproteinases are important part in the regulation of cell biology, in particular a tumor cell. Studies have confirmed the participation of metalloproteinases in all stages of the process of carcinogenesis. At the moment, there are numerous reports of available of various MMPs in different tumors. However, two of these MMP–2 and MMP–9 belonging to the gelatinases seem to be the most common. It has been confirmed also that higher levels usually indicate a worse prognosis for the patient. Therefore, they may prove to be a valuable prognostic indication for clinicians. Attention was paid to the potential use of matrix metalloproteinases in targeted therapy. The pharmaceutical industry has long been trying to launch metalloproteinase inhibitors as possible therapeutics in cancer, seeing in them a potential that, however, is limited to the early stages of development. After initial setbacks related primarily to the low selectivity is used at once more modern methods as monoclonal antibodies or liposomal drug delivery system. Thus, giving the possibility of treatment that does not cause so enormous side effects as conventional therapy.
PL
Tętniaki aorty brzusznej (AAA, abdominal aortica neurysm) stanowią jedną z głównych przyczyn wykonywania zabiegów naczyniowych. W procesie destrukcji ściany naczynia i powstania tętniaka istotną rolę spełniają metaloproteinazy. Metaloproteazy macierzy posiadają zdolność trawienia kolagenu, fi bronektyny, elastyny, lamininy. Wzrost aktywności metaloproteinaz powoduje destrukcję macierzy pozakomórkowej. W następstwie oddziaływania ciśnienia tętniczego na osłabioną ścianę aorty brzusznej dochodzi do jej dylatacji i powstania tętniaka. W wielu pracach doświadczalnych i klinicznych wykazano wzrost ekspresji genów dotyczących metaloproteinaz macierzy zewnątrzkomórkowej w ścianie tętniaków aorty brzusznej. Uzyskane wyniki służą do porównania z wynikami ekspresji genów metaloproteinaz w innych tkankach lub zdrowej aorty. Dokładne poznanie roli metaloproteinaz w patogenezie tętniaków aorty brzusznej może zostać wykorzystane w profilaktyce i leczeniu tętniaków aorty.
EN
The abdominal aortic aneurysms (AAA) constitute one of the main reasons for performing a vascular surgery. The metalloproteinases play an important role in the process of the aorta wall destruction and the aneurysm formation. The matrix metalloproteinases posses the ability to digest collagen, elastin, fibronectin and laminin. The increased activity of the matrix metalloproteinases causes the destruction of the extracellular matrix. In consequence of the blood pressure on the damaged wall of the abdominal aorta, it becomes dilated and the formation of the aneurysm occurs. In a series of experimental and clinical works an increased expression of genes for matrix metalloproteinases in the wall of abdominal aortic aneurysms has been demonstrated.. These results are used to compare with the results of metalloproteinase gene expression in other tissues or the healthy aorta. The precise knowledge of the role of MMPs in the pathogenesis of abdominal aortic aneurysms can be used in the prevention and treatment of aortic aneurysms.
EN
Metalloproteinases play an important role in the development and metastasis of many cancers. Their activity is also an important component of tumorgenesis associated processes such as angiogenesis, decreased apoptosis, or unlimited proliferation of pathological cells. In this study we tried to estimate a differences of metalloproteinase activity digesting the gelatin in the sera of patients with chronic lymphocytic leukemia and healthy people, by the zymographic technique. To confirm that the gelatinolytic activity originated from the metalloproteinases their specific inhibitors: phenanthroline and ethylene– diaminetetraacetic acid were used. In patient’s sera a zymographic analysis revealed the presence of additional activity. The first of them are located in a region corresponding to a molecular weight of approximately 240 kDa, probably corresponds to the dimer of proMMP–9. Another two active fractions present in the sera of patients suffering from leukemia corresponded to a molecular weight of about 110 and 130 kDa probably represents a complex of proMMP–9 with lipocain. In a control sera, only one activity could be observed exhibiting a molecular weight of about 110 kDa, which is stronger than corresponding fraction in patient’s sera. The biggest difference between the two investigated sera was gelatynolytic activity located in the region of a molecular weight of about 94 kDa, which probably corresponded to proMMP–9. In some leukemic sera this activity was several times higher compared to the control samples, in which there was a constant and relatively low level of it. Despite significant activity of proMMP–9 in sera of patients with CLL no biologically active equivalent band of molecular weight 84 kDa were detected. The fractions which corresponded to different forms of MMP–2 (72, 64 kDa) were present in the sera of tumor and control, although proMMP–2 was more strongly expressed in the control samples.
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