Dioksini i njihova toksičnost za ljude

The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1. Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants. A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man.Dioksini su skupina kemijskih spojeva koji obuhvaćaju poliklorirane dibenzo-dioksine (PCDD) i poliklorirane dibenzo-furane (PCDF). Najveći toksični potencijal (faktor ekvivalentne toksičnosti) ima 2,3,7,8-TCDD, dok su toksični potencijali drugih PCDD i PCDF određeni u odnosu na njega. Izloženost dioksinima može biti izravna: izloženost dioksinima emitiranim u okoliš kao posljedica nesreće, profesionalna izloženost te neizravna, tzv. pozadinska. Nakon ulaska u ljudski organizam dioksini se djelomično metaboliziraju i eliminiraju, a ostatak se pohranjuje u adipozno tkivo. Postoji određena varijabilnost između ljudi u kapacitetu eliminacije TCDD. Eliminacija TCDD ovisna je o dozi – kod veće izloženosti (izloženost višim koncentracijama) brzina eliminacije je viša nego kod manje izloženosti (izloženost nižim koncentracijama). Enzim P4501A1 najvažniji je u oksigenaciji lipofi lnih supstrata poput dioksina. Kodiran je genom CYP1A1. AhR je stanični receptor koji djeluje kao transkripcijski faktor koji posreduje u njihovu karcinogenom učinku. AhR veže dioksin te se premješta u jezgru gdje zajedno s ARNT (engl. aryl hydrocarbon nuclear translocator) i XRE (engl. xenobiotic responsive element), smještenim u promotorskoj regiji gena za CYP1A1, uzrokuje povećani izražaj CYP1A1. Dioksini su karcinogeni spojevi, ali imaju i nekarcinogene učinke poput ateroskleroze, hipertenzije, dijabetesa, poremećaj živčanog, imunosnog, reproduktivnog i endokrinog sustava, posebice kod kronične izloženosti. Akutna izloženost uzrokuje oštećenja jetre i klorakne. Najosjetljivija skupina izloženosti dioksinu je dojenčad u prenatalnom i postnatalnom razdoblju. U znanstvenoj i stručnoj literaturi dokumentirani su brojni zdravstveni učinci kao posljedice izloženosti dioksinima te ih svi ističu kao jedne od najtoksičnijih kemijskih spojeva

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4

BACKGROUND: Trophoblast expressing paternal HLA-C antigens resemble a semiallograft, and could be rejected by maternal CD4+ T lymphocytes. We examined the possible role in human pregnancy of Th17 cells, known to be involved in allograft rejection and reported for this reason to be responsible for miscarriages. We also studied Th17/Th1 and Th17/Th2 cells never investigated before. We defined for the first time the role of different Th17 subpopulations at the embryo implantation site and the role of HLA-G5, produced by the trophoblast/embryo, on Th17 cell differentiation. METHODS: Cytokine production by CD4+ purified T cell and T clones from decidua of normal pregnancy, unexplained recurrent abortion, and ectopic pregnancy at both embryo implantation site and distant from that site were analyzed for protein and mRNA production. Antigen-specific T cell lines were derived in the presence and in the absence of HLA-G5. RESULTS: We found an associated spontaneous production of IL-17A, IL-17F and IL-4 along with expression of CD161, CCR8 and CCR4 (Th2- and Th17-type markers) in fresh decidua CD4+ T cells during successful pregnancy. There was a prevalence of Th17/Th2 cells (producing IL-17A, IL-17F, IL-22 and IL-4) in the decidua of successful pregnancy, but the exclusive presence of Th17 (producing IL-17A, IL-17F, IL-22) and Th17/Th1 (producing IL-17A, IL-17F, IL-22 and IFN-γ) cells was found in the decidua of unexplained recurrent abortion. More importantly, we observed that Th17/Th2 cells were exclusively present at the embryo implantation site during tubal ectopic pregnancy, and that IL-4, GATA-3, IL-17A, ROR-C mRNA levels increased in tubal biopsies taken from embryo implantation sites, whereas Th17, Th17/Th1 and Th1 cells are exclusively present apart from implantation sites. Moreover, soluble HLA-G5 mediates the development of Th17/Th2 cells by increasing IL-4, IL-17A and IL-17F protein and mRNA production of CD4+ T helper cells. CONCLUSION: No pathogenic role of decidual Th17 cells during pregnancy was observed. Indeed, a beneficial role for these cells was observed when they also produced IL-4. HLA-G5 could be the key feature of the uterine microenvironment responsible for the development of Th17/Th2 cells, which seem to be crucial for successful embryo implantatio

Inventory of current EU paediatric vision and hearing screening programmes

Background: We examined the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes relevant for comparison of screening programmes were derived from literature and used to compile three questionnaires on vision, hearing and public-health screening. Tests used, professions involved, age and frequency of testing seem to influence sensitivity, specificity and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists and audiologists involved in paediatric screening in all EU fullmember, candidate and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% more than once. First measurement of VA varies from three to seven years of age, but is usually before the age of five. At age three and four picture charts, including Lea Hyvarinen are used most, in children over four Tumbling-E and Snellen. As first hearing screening test otoacoustic emission (OAE) is used most in healthy neonates, and auditory brainstem response (ABR) in premature newborns. The majority of hearing testing programmes are staged; children are referred after one to four abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1-4) and funding sources (8)