Digestibilnost alergoida polena pelina u simuliranim uslovima gastrointestinalnog trakta

Chemically modified allergens (allergoids) have found use in both traditional and novel forms of immunotherapy of allergic disorders. Novel forms of immunotherapy include local allergen delivery, via the gastrointestinal tract. This study conveys the gastrointestinal stability of three types of mugwort pollen allergoids under simulated conditions of the gut. Allergoids of the pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, succinic and maleic anhydride. Gastrointestinal tract conditions (saliva, and gastric fluid) were simulated in accordance with the EU Pharmacopoeia. The biochemical and immunochemical properties of the derivatives following exposure to different conditions were monitored by determining the number of residual amino groups with 2,4,6-trinitrobenzenesulfonic acid, SDS PAGE, immunoblotting and inhibition of mugwort-specific IgE. Exposure to saliva fluid for 2 min did not influence the biochemical and immunochemical properties of the derivatives. In the very acidic conditions of the simulated gastric fluid, the degree of demaleylation and desuccinylation, even after 4 h exposure, was low, ranging from 10 to 30 %. The digestion patterns with pepsin proceeded rapidly in both the unmodified and modified samples. In all four cases, a highly resistant IgE-binding protein the Mwof which was about 28-35 kD, was present. Within the physiological conditions, no new IgE binding epitopes were revealed, as demonstrated by immunoblot and CAP inhibition of the mugwort specific IgE binding. An important conclusion of this study is the stability of the modified derivatives in the gastrointestinal tract of patients, within physiological conditions. The means that they are suitable for use in much higher concentrations in local forms of immunotherapy than unmodified ones.U ovom radu su prikazani rezultati ispitivanja stabilnosti tri tipa alergoida polena pelina u simuliranom želudačnom soku. Koristeći kalijum-cijanat anhidrid ćilibarne i anhidrid maleinske kiseline, napravljeni su alergoidi polena pelina (Artemisia vulgaris). Saliva i želudačni sok su simulirani na osnovu evropske farmakopeje. Biohemijske i imunohemijske osobine derivata posle izlaganja različitim uslovima, praćene su: određivanjem broja slobodnih amino grupa u reakciji sa TNBS, SDS PAG elektroforezom, imunoblotom i određivanjem pelin-specifičnog imunoglobulina E (IgE). Izlaganje salivi u trajanju od 2 minuta ne utiče na biohemijske i imunohemijske osobine derivata. U kiseloj sredini želudačnog soka ne dolazi do značajnog demaleilovawa i desukcinilovanja. Čak i posle četvoročasovnog izlaganja, taj procenat je u opsegu 10-30 %. Alergoidi pelina se trenutno digestuju pepsinom, sa izuzetkom visoko rezistentne proteinske trake molekulske mase 28-35 kD, koja odgovara važnom IgE-vezujućem proteinu polena pelina. Imunoblotom i CAP-inhibicijom je pokazano da, u okviru fizioloških uslova, ne dolazi do stvaranja novih IgE-vezujućih epitopa. Hemijska stabilnost modifikovanih derivata u simuliranim uslovima želudačnog soka omogućuje da se tokom imunoterapije mogu primenjivati veće doze alergoida nego nemodifikovanog ekstrakta polena pelina

Prohibition of discrimination in practice of the European Court of Human Rights

Zabrana diskriminacije predstavlja jedno od temeljnih ljudskih prava, koje je zajamčeno Europskom konvencijom za zaštitu ljudskih prava i temeljnih sloboda. Europska konvencija za zaštitu ljudskih prava i temeljnih sloboda potpisana je u Rimu 4. studenog 1950., a 3 rujna 1953. stupila je na snagu i ona predstavlja jedan od najučinkovitijih mehanizama za zaštitu ljudskih prava i temeljnih sloboda. Njezinoj učinkovitosti najviše pridonosi Europski sud za ljudska prava kao i veliki broj država potpisnica na čije pravne poretke konvencija ima vrlo veliki i važan utjecaj.The prohibition of discrimination is one the fundamental human rights guaranteed by the European Convention for the Protection of Human Rights and Fundamental Freedoms. The European Convention for the Protection of Human Rights and Fundamental Freedoms was signed in Rome on 4 November 1950, and 3 September 1953 came into force and it is one of the most effective mechanisms for the protection of human rights and fundamental freedoms. Its effectiveness is best attributed to the European Court of Human Rights as well as to a large number of signatory states on whose legal arrangements the convention has a very large and important impact

Prohibition of discrimination in practice of the European Court of Human Rights

Zabrana diskriminacije predstavlja jedno od temeljnih ljudskih prava, koje je zajamčeno Europskom konvencijom za zaštitu ljudskih prava i temeljnih sloboda. Europska konvencija za zaštitu ljudskih prava i temeljnih sloboda potpisana je u Rimu 4. studenog 1950., a 3 rujna 1953. stupila je na snagu i ona predstavlja jedan od najučinkovitijih mehanizama za zaštitu ljudskih prava i temeljnih sloboda. Njezinoj učinkovitosti najviše pridonosi Europski sud za ljudska prava kao i veliki broj država potpisnica na čije pravne poretke konvencija ima vrlo veliki i važan utjecaj.The prohibition of discrimination is one the fundamental human rights guaranteed by the European Convention for the Protection of Human Rights and Fundamental Freedoms. The European Convention for the Protection of Human Rights and Fundamental Freedoms was signed in Rome on 4 November 1950, and 3 September 1953 came into force and it is one of the most effective mechanisms for the protection of human rights and fundamental freedoms. Its effectiveness is best attributed to the European Court of Human Rights as well as to a large number of signatory states on whose legal arrangements the convention has a very large and important impact

The North Shore of Staten Island: Community Driven Solutions to Improve Child and Family Well-Being

Citizens' Committee for Children of New York (CCC) has worked over the last year to gather quantitative and qualitative data about the North Shore of Staten Island to provide a comprehensive assessment of the needs of children and families in the area, as well as the resources available to them. CCC's model for community-based research utilizes existing government data on child and family well-being and complements it by mapping community assets and elevating the voices of service providers and community members through a participatory research process. This work builds on our experience maintaining the nation's most comprehensive municipal-level database illustrating the well-being of children and families in New York City, Keeping Track Online.In this report, we highlight both welcomed and worrisome trends districtwide and across the seven neighborhoods that make up the North Shore—Grymes Hill-Park Hill, Mariner's Harbor, Port Richmond, Stapleton, St. George-New Brighton, West Brighton, and Westerleigh—and compare these outcomes against borough and citywide averages.In order to address the challenges faced by children and families on the North Shore—and in Staten Island broadly—residents and service providers have come together to engage in efforts to improve outcomes across the range of issues impacting child and family well-being. This includes several collective impact initiatives, a term describing a systematic approach to collaboration among organizations aligned by a common agenda, shared measurement systems, mutually reinforcing activities, continuous communication, and support from a backbone organization tasked with coordinating the partnership.CCC's data collection and participatory research process are designed to inform and support efforts in the community to improve well-being for children and families. We believe that reliable data is a foundational element of effective advocacy, and that community engagement elevating the voices and concerns of residents is essential in identifying the challenges that need to be addressed. We are hopeful this report will be a useful tool as residents and service providers continue working to improve outcomes for children and families on the North Shore

Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma

Background: The p27(KIP1) gene, whose protein product is a negative regulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans, This study was undertaken to identify and to assess potential alterations of p27(KIP1) gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer, Methods: We analyzed 130 prostate carcinomas from primary and metastatic sites, as well as prostate samples from normal subjects and from patients with BPH. Immunohistochemistry and in situ hybridization were used to determine the levels of expression and the microanatomical localization of p27 protein and messenger RNA (mRNA), respectively. Immunoblotting and immunodepletion assays mere performed on a subset of the prostate tumors. associations between alterations in p27(KIP1) expression and clinicopathologic variables were evaluated with a nonparametric test. The Kaplan-Meier method and the logrank test were used to compare disease-relapse-free survival. Prostate tissues of p27(KIP1) null (i.e., knock-out) and wild-type mice were also evaluated, Results: Normal human prostate tissue exhibited abundant amounts of p27 protein and high levels of p27(KIP1) mRNA in both epithelial cells and stromal cells. However, p27 protein and p27(KIP1) mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions, Furthermore, p27(KIP1) null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27(KIP1) mRNA but either high or low to undetectable levels of p27 protein, Primary prostate carcinomas expressing lower levels of p27 protein appeared to be biologically more aggressive (two-sided P = .019 [Cox regression analysis]). Conclusions/Implications: On the basis of these results, we infer that loss of p27(KIP1) expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer

Artemisia vulgaris pollen allergoids digestibility in the simulated conditions of the gastrointestinal tract

Chemically modified allergens (allergoids) have found use in both traditional and novel forms of immunotherapy of allergic disorders. Novel forms of immunotherapy include local allergen delivery, via the gastrointestinal tract. This study conveys the gastrointestinal stability of three types ofmugwort pollen allergoids under simulated conditions of the gut. Allergoids of the pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, succinic and maleic anhydride. Gastrointestinal tract conditions (saliva, and gastric fluid) were simulated in accordance with the EU Pharmacopoeia. The biochemical and immunochemical properties of the derivatives following exposure to different conditions were monitored by determining the number of residual amino groups with 2,4,6-trinitrobenzenesulfonic acid, SDS PAGE, immunoblotting and inhibition of mugwort-specific IgE. Exposure to saliva fluid for 2 min did not influence the biochemical and immunochemical properties of the derivatives. In the very acidic conditions of the simulated gastric fluid, the degree of demaleylation and desuccinylation, even after 4 h exposure, was low, ranging from 10 to 30 %. The digestion patterns with pepsin proceeded rapidly in both the unmodified and modified samples. In all four cases, a highly resistant IgE-binding protein theMwof which was about 28 – 35 kD, was present. Within the physiological conditions, no new IgE binding epitopes were revealed, as demonstrated by immunoblot and CAP inhibition of the mugwort specific IgE binding. An important conclusion of this study is the stability of the modified derivatives in the gastrointestinal tract of patients, within physiological conditions. The means that they are suitable for use inmuch higher concentrations in local forms of immunotherapy than unmodified ones

Remodeling of the Methylation Landscape in Breast Cancer Metastasis

<div><p>The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI)-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.</p></div