Toxin
Dotaz
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23 sv.
- MeSH
- biologické toxiny MeSH
- Publikační typ
- periodika MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- toxikologie
Cieľ práce: Od roku 1980 sa stali infekcie kmeňmi Escherichia coli produkujúcimi shiga toxíny (STEČ) veľmi sledovanými nielen mikrobiológmi ale aj širokou verejnosťou. STEČ sú asociované so závažným a často aj fatálne prebiehajúcim hemolyticko-uremickým syndrómom. Najdôležitejšiu úlohu v patogeneze tohoto ochorenia zohráva uvoľnenie shiga toxínov (Stx) do cirkulácie po prieniku cez črevnú stenu. STEČ získa najčastejšie pacient požitím kontaminovanej potravy. Autori opisujú rodinný výskyt hemolyticko-uremického syndrómu (HUS) spôsobeného kmeňom E. coli O157. Zo štrnástich členov rodiny, bola u deviatich členov detekovaná E. coli O157 v stolici, v troch prípadoch došlo k rozvoju HUS. Materiál a metódy: Bolo vyšetřených 69 vzoriek: 54 stolíc, 1 vzorka kozího mUeka a kozího trusu, 1 vzorka domácky vyrobenej detskej výživy, 7 vzoriek nepasterizovaného kravského mheka a 5 vzoriek kravského trusu. Na izoláciu STEČ a detekciu vybraných faktorov virulencie bola použitá selektívna kultivácia, imunomagnetická separácia, latexová aglutinácia a multiplexná PCR. Výsledky: Izolovali sme 14 kmeňov E. coli O157, ktoré nefermentovali sorbitol. Izolovali sme ich od pacientov s HUS (n = 3), s hemoragickou kolitidou (HC) (n = 2), od asymptomatických nosičov (n = 4), z kravského trusu (n = 4) a z kravského mlieka (n = 1). Všetky izolované kmene mali gén pre shiga toxin 2, intimín a enterohemolyzín. U vrtkých kmeňov sme dokázali produkciu Stx2. Záver. Autori detekovali prvýkrát na Slovensku STEČ produkujúce Stx2, ktoré vyvolali HUS. Autorom sa podarilo dokázať aj zdroj infekcie, kterým bolo kontaminované nepasterizované mlieko použité pri príprave pudingu.
Purpose of the study. Since 1980 both microbiologists and the general public are paying increasingly more attention to infections by the serotypes of Escherichia coli that produce shiga toxins (STEC). STECs are associated with the serious and often fatal haemolytic uraemic syndrome. Crucial in the pathogenesis of this disease is the release, through the intestinal wall, of shiga toxins (Stx) into blood circulation. The most frequent source of STECs is contaminated food. The authors describe the family incidence of the haemolytic uraemic syndrome (HUS) caused by the E. coli serotype O157. E. coli O157 was detected in the faeces of nine out of fourteen family members. HUS developed in three cases. Material and methods: 69 samples were analysed: 54 faeces samples, 1 sample of goat's milk and of goat's dung, 1 sample of home-made baby food, 7 samples of non-pasteurized cow's milk and 7 samples of cow's dung. Selective cultivation, immunomagnetic separation, latex agglutination and multiplex PCR were used to isolate STECs and to detect selected virulence factors. Results: We isolated 14 E. coli serotypes O157 that did not ferment sorbitol. They were isolated from patients presenting HUS (n = 3) and haemorrhagic colitis (HC) (n = 2), from asymptomatic carriers (n = 4), from cow's dung (n = 4) and from cow's milk (n = 1). All the isolated serotypes presented a gene for shiga toxin 2, intimin and enterohaemolysin. In all serotypes we demonstrated the production ofStx2. Conclusions: The authors detected, for the first time in Slovakia, STECs producing Stx2 that cause HUS. They succeeded in tracing the source of the infection -contaminated non-pasteurized milk used to make a pudding.
- MeSH
- bakteriologické techniky metody MeSH
- Escherichia coli O157 patogenita MeSH
- finanční podpora výzkumu jako téma MeSH
- hemolyticko-uremický syndrom diagnóza patologie MeSH
- imunologické techniky metody MeSH
- infekce vyvolané Escherichia coli diagnóza patologie MeSH
- lidé MeSH
- shiga toxin 2 MeSH
- zdraví rodiny MeSH
- Check Tag
- lidé MeSH
Ricín je mimoriadne toxický lektín typu RIP II. Jeho jedovatosť je možné zneužiť na teroristickéúčely, pričom nie je zatiaľ známy efektívny protijed. Mechanizmus toxického pôsobenia je zároveňštudovaný s cieľom prípravy selektívnych imunotoxínov, ktoré by sa dali použiť pri liečbe rôznychtypov rakoviny či HIV infekcie. Napriek sľubným in vitro výsledkom, nepriaznivé vedľajšie účinkyv pokusoch in vivo zatiaľ obmedzujú ich použitie v reálnej terapii.
Ricin is a very toxic RIP II type lectin.As no effective antidote is known, its toxicity could be misusedin terrorist actions. The mechanism of the toxic action is currently studied for the preparation ofselective immunotoxins, which could be used in the therapy of various cancer diseases or HIVinfection. There are promising in vitro results, but some adverse in vivo effects limit the use of thesepreparations in real therapy.
- MeSH
- biologické toxiny chemie škodlivé účinky MeSH
- lidé MeSH
- monoklonální protilátky farmakologie chemie terapeutické užití MeSH
- otrava etiologie terapie MeSH
- ricin chemie škodlivé účinky MeSH
- ricinový olej chemie terapeutické užití toxicita MeSH
- Ricinus MeSH
- vztahy mezi strukturou a aktivitou terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
V této práci jsme se zaměřili na výskyt a na metody detekce a stanovení T-2 toxinu, který patří mezi nejtoxičtější fusariové toxiny. Vzhledem ke svým fyzikálně-chemickým vlastnostem a vysoké toxicitě je T-2 toxin též klasifikován jako potenciálně zneužitelný pro vojenské operace a bioterorismus.
The paper is focused on the occurrence and methods for the detection of T-2 toxin, one of the most toxic trichothecene Fusarium mycotoxin. Due to its physical-chemical properties and high toxicity, T-2 toxin is classified as a potential biological warfare agent.
- MeSH
- bioterorismus prevence a kontrola MeSH
- chromatografie metody využití MeSH
- ELISA využití MeSH
- Fusarium izolace a purifikace růst a vývoj MeSH
- lidé MeSH
- mykotoxiny izolace a purifikace škodlivé účinky toxicita MeSH
- nemoci přenášené potravou prevence a kontrola MeSH
- potravinářský průmysl MeSH
- T-2 toxin izolace a purifikace škodlivé účinky toxicita MeSH
- toxikologie metody MeSH
- trichotheceny izolace a purifikace škodlivé účinky toxicita MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- BEAUFOUR (IBSEN),
- MeSH
- botulotoxiny typu A aplikace a dávkování terapeutické užití MeSH
- dítě MeSH
- dolní končetina MeSH
- lidé MeSH
- mozková obrna MeSH
- spasmus diagnóza etiologie farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- klinické zkoušky MeSH
- srovnávací studie MeSH
Lateral epicondylitis is a common disease in orthopaedic practice. Although the majority of cases do not become chronic, patients who do not respond to the initial treatment may suffer from pain in the long term and effective treatment is challenging. The off-label use of botulinum toxin is one of the common potential indications for the substance in orthopaedics and traumatology. In a literature review of 2000 - 2019, eight EBM ≥ level 3 studies evaluating the use of botulinum toxin in lateral epicondylitis were found. Five of these studies evaluated botulinum toxin versus placebo in chronic cases; two other studies compared botulinum toxin with corticosteroids in acute cases and classic Hohmann surgery in chronic cases; the eighth study compared botulinum toxin in two different injection sites and corticosteroids by classic injection. Our findings suggest that the use of this substance may be a treatment option in refractory chronic cases before surgery is indicated. The working group on botulinum toxin in O & T of the International Musculoskeletal Pain Society (IMPS/IGOST) introduced an alternative injection schedule, which combines findings from the recent clinical literature with practical experience in order to reduce the risk of side effects while ensuring treatment effectiveness. Using 2 simple tests of function and, if necessary, sonographic verification, 2 separate injection sites in the extensor carpi radialis or the extensor digitorum can be identified by palpation. The tendon level on the lateral epicondyle acts as the third injection site. With optimal use of the ampoule content, the 3 injection sites can be infiltrated individually, depending on the muscle status. On the one hand, this enables treatment to take place after a dual therapy approach and, on the other hand, the risk of overdose in a muscle with subsequent unnecessary muscle weakening can be reduced.
- MeSH
- bolest MeSH
- botulotoxiny typu A * MeSH
- lidé MeSH
- měření bolesti MeSH
- šlachy MeSH
- tenisový loket * diagnóza farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Monocytes arriving at the site of infection differentiate into functional effector macrophages to replenish the resident sentinel cells. Bordetella pertussis, the pertussis agent, secretes an adenylate cyclase toxin-hemolysin (CyaA) that binds myeloid phagocytes through complement receptor 3 (CD11b/CD18) and swiftly delivers its adenylyl cyclase enzyme domain into phagocytes. This ablates the bactericidal capacities of phagocytes through massive and unregulated conversion of cytosolic ATP into the key signaling molecule cAMP. We show that exposure of primary human monocytes to as low a concentration as 22.5 pM CyaA, or a low (2:1) multiplicity of infection by CyaA-producing B. pertussis bacteria, blocks macrophage colony-stimulating factor (M-CSF)-driven differentiation of monocytes. CyaA-induced cAMP signaling mediated through the activity of protein kinase A (PKA) efficiently blocked expression of macrophage markers, and the monocytes exposed to 22.5 pM CyaA failed to acquire the characteristic intracellular complexity of mature macrophage cells. Neither M-CSF-induced endoplasmic reticulum (ER) expansion nor accumulation of Golgi bodies, mitochondria, or lysosomes was observed in toxin-exposed monocytes, which remained small and poorly phagocytic and lacked pseudopodia. Exposure to 22.5 pM CyaA toxin provoked loss of macrophage marker expression on in vitro differentiated macrophages, as well as on primary human alveolar macrophages, which appeared to dedifferentiate into monocyte-like cells with upregulated CD14 levels. This is the first report that terminally differentiated tissue-resident macrophage cells can be dedifferentiated in vitro The results suggest that blocking of monocyte-to-macrophage transition and/or dedifferentiation of the sentinel cells of innate immunity through cAMP-elevating toxin action may represent a novel immune evasion strategy of bacterial pathogens.IMPORTANCE Macrophages are key sentinel cells of the immune system, and, as such, they are targeted by the toxins produced by the pertussis agent Bordetella pertussis The adenylate cyclase toxin (CyaA) mediates immune evasion of B. pertussis by suspending the bactericidal activities of myeloid phagocytes. We reveal a novel mechanism of potential subversion of host immunity, where CyaA at very low (22 pM) concentrations could inhibit maturation of human monocyte precursors into the more phagocytic macrophage cells. Furthermore, exposure to low CyaA amounts has been shown to trigger dedifferentiation of mature primary human alveolar macrophages back into monocyte-like cells. This unprecedented capacity is likely to promote survival of the pathogen in the airways, both by preventing maturation of monocytes attracted to the site of infection into phagocytic macrophages and by dedifferentiation of the already airway-resident sentinel cells.
- MeSH
- adenylátcyklasový toxin škodlivé účinky metabolismus MeSH
- alveolární makrofágy účinky léků metabolismus MeSH
- Bordetella pertussis chemie MeSH
- buněčná diferenciace účinky léků MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- monocyty účinky léků metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Myeloid phagocytes have evolved to rapidly recognize invading pathogens and clear them through opsonophagocytic killing. The adenylate cyclase toxin (CyaA) of Bordetella pertussis and the edema toxin (ET) of Bacillus anthracis are both calmodulin-activated toxins with adenylyl cyclase activity that invade host cells and massively increase the cellular concentrations of a key second messenger molecule, 3',5'-cyclic adenosine monophosphate (cAMP). However, the two toxins differ in the kinetics and mode of cell entry and generate different cAMP concentration gradients within the cell. While CyaA rapidly penetrates cells directly across their plasma membrane, the cellular entry of ET depends on receptor-mediated endocytosis and translocation of the enzymatic subunit across the endosomal membrane. We show that CyaA-generated membrane-proximal cAMP gradient strongly inhibits the activation and phosphorylation of Syk, Vav, and Pyk2, thus inhibiting opsonophagocytosis. By contrast, at similar overall cellular cAMP levels, the ET-generated perinuclear cAMP gradient poorly inhibits the activation and phosphorylation of these signaling proteins. Hence, differences in spatiotemporal distribution of cAMP produced by the two adenylyl cyclase toxins differentially affect the opsonophagocytic signaling in myeloid phagocytes.
- MeSH
- adenylátcyklasový toxin toxicita MeSH
- AMP cyklický metabolismus MeSH
- antigeny bakteriální toxicita MeSH
- bakteriální toxiny toxicita MeSH
- časoprostorová analýza MeSH
- fagocytóza účinky léků MeSH
- fagocyty účinky léků metabolismus MeSH
- fosforylace účinky léků MeSH
- lidé MeSH
- mikrofilamenta účinky léků MeSH
- opsoniny farmakologie MeSH
- receptory imunologické metabolismus MeSH
- signální transdukce účinky léků MeSH
- THP-1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
