Sepsis is not only a threat to the health of individual patients but also presents a serious epidemiological problem. Despite intensive research, modern sepsis therapy remains based primarily on antimicrobial treatment and supporting the functions of failing organs. Finding a cure for sepsis represents a great and as yet unfulfilled need in modern medicine. Research results indicate that the activity of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) may play an important role in the inflammatory response and the cellular metabolic disorders found in sepsis. Mechanisms by which PARP-1 may contribute to inflammation and metabolic disorders include effects on the regulation of gene expression, impaired metabolism, cell death, and the release of alarmins. These findings suggest that inhibition of this enzyme may be a promising solution for the treatment of sepsis. In studies using experimental sepsis models, inhibition of PARP-1 has been shown to ameliorate the inflammatory response and increase survival. This action was described, among others, for olaparib, a PARP-1 inhibitor approved for use in oncology. While the results of current research are promising, the use of PARP inhibitors in non-oncological diseases raises some concerns, mainly related to the enzyme’s role in deoxyribonucleic acid (DNA) repair. However, the results of studies on experimental models indicate the effectiveness of even short-term PARP-1 inhibition and do not confirm concerns regarding its impact on the integrity of nuclear DNA. Current research presents PARP inhibition as a potential solution for the treatment of sepsis and indicates the need for further research.
In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.
Introduction : The aim of the study was to develop a Polish version of the Diabetes Quality of Life Brief Clinical Inventory (DQL-BCI) and to perform validating evaluation of selected psychometric aspects. Material and methods : The translation process was performed in accordance with...
This article is devoted to the inquiry of three diseases of the liver: alcoholic liver disease (ALD), primary biliary cirrhosis (PBC), and autoimmune hepatitis (AIH). The aim of the study was to assess the changes in populations of circulating lymphocytes expressing antiapoptotic bcl-2 molecule and proapoptotic Fas (cluster of differentiation 95(CD95)) receptor in patients with ALD, AIH, and PBC. The study population consisted of 110 patients with ALD (n = 50), PBC (n = 30), and AIH (n = 30) and age-matched healthy volunteers (n = 25). Peripheral blood lymphocytes were isolated, stained with monoclonal antibodies against CD4, CD8, and CD19 antigen; intracellular bcl-2; and surface Fas receptor (CD95) antigens, and estimated using the flow cytometric method. Bcl-2 expression was the highest in CD4+ and CD19+ T lymphocytes in ALD; however, only the differences in median/mean fluorescence intensity values of CD4+bcl-2+ lymphocytes between ALD and PBC group and CD19+bcl-2+ between ALD and PBC groups were statistically significant, indicating the different role of B cells in pathology of ALD and PBC. In contrast to that, statistically significant higher percentage of CD4+, CD8+, and CD19+ bearing Fas receptor in all groups of patients with liver diseases in comparison with the control subjects were estimated. The highest expression of Fas in CD4+ lymphocytes in ALD and in CD8+ cells of PBC and AIH groups were detected. Low expression of bcl-2 molecule and high expression of Fas in peripheral blood lymphocytes indicate significant dysregulation of apoptotic mechanisms not only in the liver but also in peripheral blood lymphocytes in all examined groups, especially in ALD group.
19 December 2019 in Annals of Agricultural and Environmental Medicine
Objective: The aim of the study is to compare the hope of rural and urban inhabitants in the terminal stage of a neoplastic disease covered by stationary hospice care. Material and methods: The study was carried out among patients in the terminal phase of a neoplastic disease. They were...