Zapobieganie marginalizacji społecznej głównym zadaniem Siemachy

"W debacie poświęconej przekształceniom i procesom, jakie zachodzą w nowoczesnym czy ponowoczesnym świecie, często pojawiają się głosy dotyczące kondycji rodziny i wyzwań, jakie przed nią stoją w związku z radykalnie zmieniającymi się uwarunkowaniami kulturowymi, społecznymi czy gospodarczymi (Słany 2005, 2002, Giddens 2001). Sytuacja rodziny bywa różnie określana i oceniana: niektórzy mówią o kryzysie rodziny, inni zaś tylko o zmianach w jej funkcjach i formach (Marody i Giza-Poleszczuk 2004)."(...

Problemy ludzi przewlekle chorych w opiniach osób udzielających im pomocy w środowisku zamieszkania

"Jednym z uderzających paradoksów współczesności jest dostrzegalny - mimo niezaprzeczalnych postępów medycyny - wzrost odsetka osób niepełnosprawnych w poszczególnych społeczeństwach. Do zwiększenia ich udziału przyczynia się niewątpliwie, szczególnie w krajach wysoko rozwiniętych, nasilający się proces demograficznego starzenia się populacji, bowiem w wieku senioralnym, przede wszystkim w późniejszych jego fazach, następuje wyraźny przyrost osób o ograniczonej sprawności. Istotne znaczenie ma też obniżanie się śmiertelności z powodu różnych chorób, dawniej nieuchronnie prowadzących do rychłego zgonu, a dziś opanowanych na tyle, że cierpiące na nie osoby udaje się utrzymać przy życiu, choć często w stanie niepełnej sprawności."(...

Aspartic proteases and major cell wall components in Candida albicans trigger the release of neutrophil extracellular traps

Neutrophils use different mechanisms to cope with pathogens that invade the host organism. The most intriguing of these responses is a release of neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins with antimicrobial activity. An important potential target of NETs is Candida albicans—an opportunistic fungal pathogen that employs morphological and phenotype switches and biofilm formation during contact with neutrophils, accompanied by changes in epitope exposition that mask the pathogen from host recognition. These processes differ depending on infection conditions and are thus influenced by the surrounding environment. In the current study, we compared the NET release by neutrophils upon contact with purified main candidal cell surface components. We show here for the first time that in addition to the main cell wall-building polysaccharides (mannans and β-glucans), secreted aspartic proteases (Saps) trigger NETs with variable intensities. The most efficient NET-releasing response is with Sap4 and Sap6, which are known to be secreted by fungal hyphae. This involves mixed, ROS-dependent and ROS-independent signaling pathways, mainly through interactions with the CD11b receptor. In comparison, upon contact with the cell wall-bound Sap9 and Sap10, neutrophils responded via a ROS-dependent mechanism using CD16 and CD18 receptors for protease recognition. In addition to the Saps tested, the actuation of selected mediating kinases (Src, Syk, PI3K, and ERK) was also investigated. β-Glucans were found to trigger a ROS-dependent process of NET production with engagement of Dectin-1 as well as CD11b and CD18 receptors. Mannans were observed to be recognized by TLRs, CD14, and Dectin-1 receptors and triggered NET release mainly via a ROS-independent pathway. Our results thus strongly suggest that neutrophils activate NET production in response to different candidal components that are presented locally at low concentrations at the initial stages of infection. However, NET release seemed to be blocked by increasing numbers of fungal cells

Kinetic and thermodynamic characterization of the interactions between the components of human plasma kinin-forming system and isolated and purified cell wall proteins of Candida albicans

Cell wall proteins of Candida albicans, besides their best known role in the adhesion of this fungal pathogen to host's tissues, also bind some soluble proteins, present in body fluids and involved in maintaining the biochemical homeostasis of the human organism. In particular, three plasma factors - high-molecular-mass kininogen (HK), factor XII (FXII) and prekallikrein (PPK) - have been shown to adhere to candidal cells. These proteins are involved in the surface-contact-catalyzed production of bradykinin-related peptides (kinins) that contribute to inflammatory states associated with microbial infections. We recently identified several proteins, associated with the candidal cell walls, and probably involved in the binding of HK. In our present study, a list of potential FXII- and PPK-binding proteins was proposed, using an affinity selection (on agarose-coupled FXII or PPK) from a whole mixture of β-1,3-glucanase-extrated cell wall-associated proteins and the mass-spectrometry protein identification. Five of these fungal proteins, including agglutinin-like sequence protein 3 (Als3), triosephosphate isomerase 1 (Tpi1), enolase 1 (Eno1), phosphoglycerate mutase 1 (Gpm1) and glucose-6-phosphate isomerase 1 (Gpi1), were purified and characterized in terms of affinities to the human contact factors, using the surface plasmon resonance measurements. Except Gpm1 that bound only PPK, and Als3 that exhibited an affinity to HK and FXII, the other isolated proteins interacted with all three contact factors. The determined dissociation constants for the identified protein complexes were of 10-7 M order, and the association rate constants were in a range of 104-105 M-1s-1. The identified fungal pathogen-host protein interactions are potential targets for novel anticandidal therapeutic approaches

Starość zależna: opieka i pomoc społeczna: perspektywa gerontologii społecznej

Praca recenzowana / peer-reviewed pape

Zagrożenia współczesnej rodziny: wieloaspektowość pomocy instytucjonalno-prawnej

Z wprowadzenia: "Zebrane w niniejszym tomie artykuły nie stanowią monolitycznej całości. Ukazują raczej różnorodność problemów, a ich autorzy sygnalizują konieczność dokładniejszej analizy obszarów zagrożeń stojących przed rodziną, a także sformułowania zadań instytucji powołanych do niesienia pomocy rodzinie w zwalczaniu tych zagrożeń."(...

Characterization of the interactions between human high-molecular-mass kininogen and cell wall proteins of pathogenic yeasts Candida tropicalis

Candida tropicalis is one of the most frequent causes of serious disseminated candidiasis in human patients infected by non-albicans Candida species, but still relatively little is known about its virulence mechanisms. In our current study, the interactions between the cell surface of this species and a multifunctional human protein - high-molecular-mass kininogen (HK), an important component of the plasma contact system involved in the development of the inflammatory state - were characterized at the molecular level. The quick release of biologically active kinins from candidal cell wall-adsorbed HK was presented and the HK-binding ability was assigned to several cell wall-associated proteins. The predicted hyphally regulated cell wall protein (Hyr) and some housekeeping enzymes exposed at the cell surface (known as "moonlighting proteins") were found to be the major HK binders. Accordingly, after purification of selected proteins, the dissociation constants of the complexes of HK with Hyr, enolase, and phosphoglycerate mutase were determined using surface plasmon resonance measurements, yielding the values of 2.20 × 10-7 M, 1.42 × 10-7 M, and 5.81 × 10-7 M, respectively. Therefore, in this work, for the first time, the interactions between C. tropicalis cell wall proteins and HK were characterized in molecular terms. Our findings may be useful for designing more effective prevention and treatment approaches against infections caused by this dangerous fungal pathogen

Proteinous components of Neutrophil extracellular traps are arrested by the cell wall proteins of Candida albicans during fungal infection, and can be used in the host invasion

One of defense mechanisms of the human immune system to counteract infection by the opportunistic fungal pathogen Candida albicans is the recruitment of neutrophils to the site of invasion, and the subsequent production of neutrophil extracellular traps (NETs) that efficiently capture and kill the invader cells. In the current study, we demonstrate that within these structures composed of chromatin and proteins, the latter play a pivotal role in the entrapment of the fungal pathogen. The proteinous components of NETs, such as the granular enzymes elastase, myeloperoxidase and lactotransferrin, as well as histones and cathelicidin-derived peptide LL-37, are involved in contact with the surface of C. albicans cells. The fungal partners in these interactions are a typical adhesin of the agglutinin-like sequence protein family Als3, and several atypical surface-exposed proteins of cytoplasmic origin, including enolase, triosephosphate isomerase and phosphoglycerate mutase. Importantly, the adhesion of both the elastase itself and the mixture of proteins originating from NETs on the C. albicans cell surface considerably increased the pathogen potency of human epithelial cell destruction compared with fungal cells without human proteins attached. Such an implementation of adsorbed NET-derived proteins by invading C. albicans cells might alter the effectiveness of the fungal pathogen entrapment and affect the further host colonization