Wrodzone i nabyte mechanizmy odporności komórkowej w patogenezie przewlekłych nieswoistych zapaleń jelit

Inflammatory bowel disease (IBD) is a group of chronic autoimmune conditions that include Crohn’s disease (CD) and ulcerative colitis (UC). The exact aetiology of IBD has not been fully elucidated yet, although it appears that the main pathogenic factor is abnormal response of the immune system against host microflora in genetically susceptible patients. Immunological processes underlying development of IBD include interactions between the cells of both innate and adaptive immune response. Novel advances in immunology demonstrate the role of imbalance between proinflammatory and regulatory mechanisms in the chronic inflammatory conditions. Recently described innate lymphoid cells and new subclasses of T helper cell (Th) and regulatory T cells (Treg) have joined the classical components of the immune system such as T cells, B cells, dendritic cells and macrophages. This review provides an over view of the most impor tant cellular components of the innate and the adaptive immune response involved in the pathogenesis of IBD. It also presents the role of interactions between cells of both systems, highlighting the role of IL-22, IL-23 and IL-17, in the development and progression of IBD. Described dependencies may contribute to the discovery of new treatment for this group of diseases.Przewlekłe nieswoiste zapalenia jelit (PNZJ; IBD) stanowią grupę autoimmunologicznych schorzeń obejmujących dwie główne jednostki kliniczne: chorobę Leśniowskiego-Crohna (CD) i wrzodziejące zapalenie jelita grubego (UC). Etiologia tych chorób nie została jeszcze w pełni wyjaśniona, jednak wydaje się, że główną przyczyną jest nadmierna aktywacja układu odpornościowego skierowana przeciwko antygenom naturalnej flory bakteryjnej jelit u osób predysponowanych genetycznie. Procesy immunologiczne leżące u podstaw patomechanizmów PNZJ obejmują interakcje pomiędzy komórkami zarówno odpowiedzi wrodzonej, jak i nabytej. W ostatnich latach do klasycznych elementów układu immunolo­gicznego, takich jak limfocyty T i B, komórki dendrytyczne i makrofagi, dołączyły tak zwane wrodzone komórki limfoidalne (ILC) oraz nowe podklasy limfocytów pomocniczych (Th) oraz regulatorowych (Treg). Niniejsza praca stanowi przegląd najistotniejszych elementów komórkowych wrodzonych i nabytych mechanizmów układu odpornościowego zaangażowanych w rozwój PNZJ. Wspomniane również zostały najważniejsze interakcje pomiędzy komórkami obu układów, ze szczególnym uwzględnieniem roli interleukin IL-22, IL-23 i IL-17 w etiologii PNZJ. Opisane patomechanizmy PNZJ mogą przyczynić się do odkrycia nowych możliwości leczenia tej grupy chorób

Analiza rozwoju wybranych inwestycji celu publicznego w gminie Zbuczyn ze szczególnym uwzględnieniem potrzeb młodzieży

Rozwój inwestycji celu publicznego ma wpływ na jakość życia mieszkańców terenów wiejskich. Zwiększa atrakcyjność obszaru, co przekłada się na wzrost poziomu zadowolenia mieszkańców, a w dalszej perspektywie w prowadzi do wzrostu liczby mieszkańców. Celem naszych badań była analiza potrzeb rozwoju inwestycji celu publicznego na przykładzie gminy wiejskiej. Do badań wybrano następujące obiekty celu publicznego: świetlice wiejskie, biblioteki, boiska sportowe oraz place zabaw. Obszarem badań objęto gminę Zbuczyn, położoną w województwie mazowieckim, w powiecie siedleckim, która zajmuje obszar 210,8 km2. Na podstawie informacji uzyskanych z urzędu gminy, analizy dokumentów planistycznych oraz wizji lokalnej wykonano mapę przestrzennego rozmieszczenia wybranych obiektów celu publicznego. Analizę potrzeb rozwoju wykonano na podstawie przeprowadzonej ankiety wśród mieszkańców gminy. Badania ankietowe przeprowadzono jesienią 2017 r. na 227-osobowej grupie. Ze względu na charakter analizowanych obiektów ankieta skierowana była głównie do osób młodych (65% ankietowanych poniżej 18. roku życia). Gmina Zbuczyn ma dobrą bazę obiektów celu publicznego, którą zna i z której korzysta aż 77% ankietowanych. Z badań ankietowych wynika, że frekwencja korzystania z tych obiektów wzrasta w miarę zmniejszania się odległości do określonych obiektów. Według mieszkańców odległość powyżej 5 km jest już dystansem, który w znacznym stopniu ogranicza dostęp do danego obiektu. Mieszkańcy odczuwają brak głównie obiektów sportu, turystyki i rekreacji, np. pływalni, lodowisk, siłowni plenerowych itp. Przy podejmowaniu decyzji o rozwoju wspomnianych obiektów gmina powinna brać pod uwagę ich przestrzenne rozmieszczenie na terenie gminie, jak również zachęcać mieszkańców do większego zaangażowania się w proces planistyczny

An evaluation of the impact of rehabilitation on the quality of life in patients after cerebral stroke

Cerebral stroke is the third most frequent cause of death in the human population, and one of leading causes of long-lasting disability. Medical rehabilitation has proven to be an indispensable element in stroke management. The aim of this study is to evaluate the quality of life in patients after a cerebral stroke, before and after rehabilitation. This analysis was based on data obtained from an empirical study conducted on 70 people after a stroke. The research was performed with the use of an original survey questionnaire. Due to their conditions, respondents perceived varying degrees and extents of changes in their organisms and environments pertaining to their physical, psychological, social, and professional spheres of life. In the vast majority of the patients, applied rehabilitation had a positive influence on their quality of life. There was an improvement in their physical and psychological conditions, as well as in various other aspects of life, while the intensity of emerging disorders decreased

Choroba Alexandra w badaniu rezonansu magnetycznego i spektroskopii protonowej HMRS : opis trzech przypadków

Background: Alexander's disease is a rare genetic leukodystrophy connected with mutation of the GFAP gene. Infantile, juvenile, and adult subtypes are described. Case reports: We analyzed MR images in three and HMRS in two cases of Alexander's disease. The examinations were performed with a 1.5T scanner in the SE, FSE, and FLAIR sequences in T1,T2 W I before and after gadolinium injection. Single voxel HMRS was performed. M RI showed extensive abnormal signal in the white matter of the frontal lobes, in external capsules, basal ganglia, posterior limbs of the internal capsules, and the hilus of dentate nuclei. Focal contrast enhancement was seen near the frontal horns. HMRS revealed increased Cho/Cr and mI/Cr ratios and decreased NAA/Cr ratio. The presence of lactate was also observed. Conclusions: MR is useful in imaging typical forms of Alexander's disease. Genetic investigation is necessary for definitive diagnosis. HMRS demonstrates metabolic abnormalities of white matter

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Mitochondrial protein associated neurodegeneration – Case report

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders with a progressive extrapyramidal syndrome and excessive iron deposition in the brain, particularly in the globus pallidus and substantia nigra. We present the case of a 31-year-old woman with mitochondrial protein associated neurodegeneration (MPAN). MPAN is a new identified subtype of NBIA, caused by mutations in C19orf12 gene. The typical features are speech and gait disturbances, dystonia, parkinsonism and pyramidal signs. Common are psychiatric symptoms such as impulsive or compulsive behavior, depression and emotional lability. In almost all cases, the optic atrophy has been noted and about 50% of cases have had a motor axonal neuropathy. In the MRI on T2- and T2*-weighted images, there are hypointense lesions in the globus palidus and substantia nigra corresponding to iron accumulation