Electron-deficient chlorine covalently immobilised on an amido group of hyaluronic acid (HA) can be potentially exceptional for applications requiring biodegradable and biocompatible polymers with enhanced antibacterial or antiviral activity. This expectation is supported by the assumption that a small amount of HA chloramide (HACl) is formed in the extracellular matrix under inflammatory conditions by a reaction of endogenous HA with hypochlorous acid (HClO) generated by a myeloperoxidase/H2O2/Cl- system. HACl synthesis optimisation showed significant limitations of HClO as an oxidative agent where only lower degrees of substitution (DS) was achieved. Commercially available oxidative agents based on chlorinated isocyanuric acid were successfully tested, producing the HA chain with almost entirely chlorinated amidic groups. The structure of the final HACl was thoroughly studied using advanced 2-dimensional NMR methodologies and LC/MS. Stability of HACl at different temperatures was monitored over 12 months. Preliminary antimicrobial and antiviral tests demonstrated the potential of HACl for applications in biomedicine.
- MeSH
- Anti-Bacterial Agents chemistry pharmacology MeSH
- Antifungal Agents chemistry pharmacology MeSH
- Antiviral Agents chemistry pharmacology MeSH
- Bacteria drug effects MeSH
- Chloramines chemistry pharmacology MeSH
- Halogenation MeSH
- Fungi drug effects MeSH
- Hypochlorous Acid chemistry MeSH
- Hyaluronic Acid chemistry MeSH
- Viruses drug effects MeSH
- Publication type
- Journal Article MeSH
In this study, the effect of chloramine T (Chl-T) on the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione S-transferase (GST); the levels of reduced (GSH) and oxidised glutathione (GSSG) and their ratios; and also membrane lipid peroxidation (LPO) levels in Phanerochaete chrysosporium were investigated in a dose- (0.25-1 mmol/L) and time-dependent (1.5-9 h) manner. The highest SOD activity was observed in 0.5 mmol/L Chl-T at 6th hour as 1.48-fold of its control. The observed highest level in CAT activities was 4.6-fold of control in 0.5 and 0.75 mmol/L at the 6th hour. The GSH levels that were over the control showed decreasing tendency from the beginning of incubation, except 0.25 mmol/L. In contrast with GSH level variations, GSSG levels reached 10.0-fold of its control by showing increasing tendency with the increases in concentration and time. While the GSH/GSSG ratios were over the control at 0.25 mmol/L during all incubation, they fell under the control values at the earlier hours of incubation with the increasing concentrations of Chl-T. Glutathione-related enzymes GSH-Px, GR and GST were also induced with Chl-T treatment, and the highest activities were 3.29-, 7.5- and 6.56-fold of their controls, respectively. On the other hand, the increases in LPO levels with increasing concentration and time up to 5.27-fold of its control showed that the inductions observed in antioxidant system could not prevent the Chl-T-based oxidative stress.
- MeSH
- Antioxidants metabolism MeSH
- Time Factors MeSH
- Chloramines pharmacology MeSH
- Glutathione metabolism MeSH
- Glutathione Peroxidase MeSH
- Glutathione Reductase MeSH
- Glutathione Transferase MeSH
- Catalase metabolism MeSH
- Oxidation-Reduction drug effects MeSH
- Oxidative Stress physiology MeSH
- Oxidants pharmacology MeSH
- Lipid Peroxidation drug effects MeSH
- Phanerochaete drug effects enzymology metabolism MeSH
- Superoxide Dismutase metabolism MeSH
- Tosyl Compounds pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Publication type
- Journal Article MeSH
In this study, cardiac and locomotor activities of signal crayfish Pacifastacus leniusculus were investigated under exposure to a range of natural (i.e., odors of conspecific crayfish, predatory fish, food, and injured conspecific) and one chemical (i.e., disinfectant chloramine-T) stimuli. Crayfish locomotion was simultaneously initiated with an increase in heart rate only when affected by chloramine-T, while locomotor response was delayed in all cases (or was not manifested at all by some specimens) when disturbed by the natural stressors. The heart rate differences measured before and during the stimulation were arranged as follows: odor of conspecific crayfish (9.2 ± 7.1%) < predator (18.4 ± 13%) < food (33.5 ± 15.7%) < chloramine-T (41.1 ± 14.7%) < injured conspecific (51.8 ± 28.4%). Analysis of the peculiarities of crayfish heartbeat under exposure to the tested stimuli revealed complex cardiac responses as was previously observed by an electrocardiography approach, that is, a slowed heart rate followed by a delayed increase. Evaluation of the intrinsic parameters of crayfish bioindicators remains essential due to the possibility of detection of the substantial ethological responses even in motionless animals. The role and appropriateness of signal crayfish as a bioindicator of water quality is discussed; they seem to be an applicable species for this task due to their sufficient sensitivity and broad availability. In addition to providing a better understanding of stereotypic crayfish behaviors induced by common and chemical stressors, the results of this study may serve as reference data for the evaluation of crayfish suitability for water quality tests.
- MeSH
- Chloramines chemistry MeSH
- Disinfectants MeSH
- Water Quality MeSH
- Odorants MeSH
- Seafood MeSH
- Astacoidea chemistry drug effects MeSH
- Heart Rate drug effects MeSH
- Tosyl Compounds chemistry MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Staphylococcus aureus is a common biofilm-forming pathogen. Low doses of disinfectants have previously been reported to promote biofilm formation and to increase virulence. The aim of this study was to use transcriptome sequencing (RNA-seq) analysis to investigate global transcriptional changes in S. aureus in response to sublethal concentrations of the commonly used food industry disinfectants ethanol (EtOH) and chloramine T (ChT) and their combination (EtOH_ChT) in order to better understand the effects of these agents on biofilm formation. Treatment with EtOH and EtOH_ChT resulted in more significantly altered expression profiles than treatment with ChT. Our results revealed that EtOH and EtOH_ChT treatments enhanced the expression of genes responsible for regulation of gene expression (sigB), cell surface factors (clfAB), adhesins (sdrDE), and capsular polysaccharides (cap8EFGL), resulting in more intact biofilm. In addition, in this study we were able to identify the pathways involved in the adaptation of S. aureus to the stress of ChT treatment. Further, EtOH suppressed the effect of ChT on gene expression when these agents were used together at sublethal concentrations. These data show that in the presence of sublethal concentrations of tested disinfectants, S. aureus cells trigger protective mechanisms and try to cope with them.IMPORTANCE So far, the effect of disinfectants is not satisfactorily explained. The presented data will allow a better understanding of the mode of disinfectant action with regard to biofilm formation and the ability of bacteria to survive the treatment. Such an understanding could contribute to the effort to eliminate possible sources of bacteria, making disinfectant application as efficient as possible. Biofilm formation plays significant role in the spread and pathogenesis of bacterial species.
The crayfish play an essential role in the biomonitoring and may reflect ambient water quality through the biochemical, behavioural and physiological reactions. To assess whether narrow-clawed crayfish Astacus leptodactylus can respond by heart rate changes to presence in water of such biocide as chloramine-T, adult males were exposed to its low (2 and 5 mg L(-1)), moderate (10 mg L(-1), commonly used in industry and aquaculture) and exceeded (20 and 50 mg L(-1)) concentrations. In addition, a physical stress test evaluated energy expenditure following the chemical trials. Three key reactions (cardiac initial, first-hour and daily prolonged exposure) were discussed with particular focus on crayfish initial reaction as the most meaningful in on-line water quality biomonitoring. After short-term exposure to both chloramine-T concentrations, crayfish were found to respond rapidly, within 2-5 min. According to heart rate changes, the 1-h exposure did not adversely affect crayfish at either concentration, as well as during daily exposure to 10 mg L(-1). As assessed by the heart rate, the 24-h exposure to 50 mg L(-1) of chloramine-T was toxic for crayfish and led to substantial loss of energy that became apparent during subsequently conducted physical stress. The results supported a hypothesis that crayfish vital functions are connected with environment they inhabit closely enough to serve as biological monitors. Crayfish were tolerant to short-term chloramine-T exposure, while rapid crayfish reaction to an increased chemical level indicated their high sensitivity, an essential attribute of real-time environmental assessment.
- MeSH
- Chloramines toxicity MeSH
- Stress, Physiological MeSH
- Water Quality MeSH
- Environmental Monitoring methods MeSH
- Astacoidea drug effects MeSH
- Heart Rate drug effects MeSH
- Toxicity Tests MeSH
- Tosyl Compounds toxicity MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Úvod: Radioimunoterapie patří mezi rychle se rozvíjející klinické metody. Často je nejvhodnější možností terapie u pacientů s relabujícím lymfomem, případně u starších pacientů. Vývoj nových typů imunokonjugátů patří proto v posledních letech mezi klíčová témata ve vývoji radiofarmak. Metody: Imunoglobulin G M75 byl značen metodou elektrofilní jodace radionuklidem 125I, který je optimální pro vývoj metody značení a také pro stanovení vlastností značeného preparátu (vazebná aktivita, imunospecifita). Výhody 125I jsou zejména jeho dlouhý poločas (59,408 dne) a nízká radiační zátěž. Zachování vazby aktivního místa na antigen bylo testováno metodou ELISA, koncentrace byla stanovena modifikovanou metodou podle Bradfordové. Fyziologická distribuce byla testována na myších CD1-Foxn1nu. Výsledky: Stanovená kumulace značené protilátky v nádorové tkáni byla > 7 % podané radioaktivity, vazebná aktivita protilátky byla první den po značení vyšší než 90 % ve srovnání s vazebnou aktivitou neznačené protilátky. Závěr: Připravený radioimunokonjugát IgG M75 s 125I si zachovává dostatečnou schopnost vazby antigenu, a má proto potenciál v terapii tumorů exprimujících karbonátdehydratasu. Pro použití v radioterapii je třeba otestovat analogický radioimunokonjugát značený radionuklidem 131I.
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- Keywords
- IgG M75 protilátky, CD1-Foxn1nu, radioimunokonjugát, elektrofilní jodace, chloramin-T, chloraminová metoda,
- MeSH
- Chloramines MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Immunoglobulin G immunology MeSH
- Sodium Iodide MeSH
- Carbonic Anhydrases analysis immunology MeSH
- Colorectal Neoplasms radiotherapy MeSH
- Antibodies, Monoclonal * diagnostic use MeSH
- Mice MeSH
- Antibodies, Neoplasm analysis immunology MeSH
- Radioactivity MeSH
- Radiopharmaceuticals * pharmacokinetics chemical synthesis immunology MeSH
- Iodine Radioisotopes * diagnostic use immunology MeSH
- Tissue Distribution * MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Ve 20. století se významně zvýšila expozice sloučeninám chloruu obyvatelstva průmyslově rozvinutých zemí, a to zejména po roce 1960, kdy se začaly budovat veřejné plavecké bazény. Plavci jsou exponováni sloučeninám chloru při vdechování aerosolu těsně nad vodní hladinou. Studie u závodních plavců ukázaly, že chlor v prostředí krytých plaveckých bazénů má škodlivý účinek na dýchací ústrojí, zvyšuje riziko astmatu, bronchiální hyperreaktivity a zánětu průdušek. Recentní práce upozornily na možné nepříznivé účinky chloru na dýchací cesty a zvýšené riziko astmatu také u dětí, které se věnují rekreakčnímu plavání. Jde především o děti s atopií pravidelně navštěvující plavecký bazén v prvních 5 letech života. Teprve dlouhodobé prospektivní studie mohou spolehlivě zjistit, zda skutečně existuje příčinný vztah mezi rekreačním plaváním v bazénech s chlorovanou vodou a astmatem. Trichloramin, který je odpovědný za typický zápach v plaveckých bazénech, byl také označen za příčinu astmatu a dechových obtíží u zaměstnanců plaveckých bazén ů . Bylo zjištěno, že i časté využívání venkovních nekrytých bazénů dezinfikovaných chlorem je spojeno se zvýšeným rizikem astmatu a zánětu průdušek.
Exposure of human population in developed countries to chlorination products has considerably increased during the 20 th century especially after the 1960s with the development of public swimming pools. Swimmers, however, are mainly exposed when they actively inhale aerolised chlorination products in the air just above pool surface. Studies on elite swimmers has shown that the chlorine-laden atmospher e of indoor pools could be detrimental to the lungs, by increasing the risk of asthma, bronchial hyperreactivity and airways inflammation. Recent studies have suggested these adverse effects of pool chlorine on the airways and increased risk of asthma even in children with recreat ional swimming, especially with atopy who regularly attend indoor pools before the age of 5 years. Prospective follow-up studies are needed whe ther or not a cause-effect relationship really exists between recreational swimming and asthma development. Trichloramine, the gas that bui lds up un the air of indoor pools, giving them their distinctive chlorine smell, has been identified as a cause of asthma and respiratory problem s in pool workers. Even frequent attendance of outdoor chlorinated swimming pool is associated with higher risks of asthma and airways inflammatio n.
- MeSH
- Asthma epidemiology chemically induced MeSH
- Chloramines adverse effects MeSH
- Water Purification methods MeSH
- Child MeSH
- Financing, Organized MeSH
- Risk Assessment MeSH
- Humans MeSH
- Swimming Pools MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Case Reports MeSH
Expozice človìka produktùm chlorace bìhem 20. století znaènì stoupala, zvláštì pak od padesátých let, v souvislosti s rozvojem veøejných a rekreaèních koupališś a dalšího rekreaèního využití vody. Pøi návštìvì tìchto zaøízení byla populace v industrializovaných zemích stále více vystavována pùsobení silných oxidantù na bázi chloru, aś už v dùsledku pøímého kontaktu s chlorovanou vodou nebo inhalací oxidantù ve formì plynù (trichloraminu a plynného chloru) èi aerosolù (chlornan/kyselina chlorná a chloraminy). Výskyt respiraèních potíží a alergií u závodních plavcù, kteøí trénují v prostøedí plaveckých bazénù zatíženém chlorem, je rovnìž znám už více než dvacet let. Zvýšenou pozornost však tento problém vyvolal teprve nedávno v souvislosti se zjištìním, že oxidanty na bázi chloru mohou poškodit plicní epitelovou bariéru u rekreaèních plavcù a pøispìt tak ke zvýšení rizika atopických onemocnìní, jako je napøíklad astma nebo senná rýma. Ve studiích zabývajících se profesionální expozicí bylo dále prokázáno, že zamìstnanci bazénù jsou vystaveni vyššímu riziku astmatu a respiraèních potíží, zatímco v ekologických studiích byla zjištìna spojitost mezi prevalencí astmatu èi ekzému u dìtí a poètem bazénù nebo množstvím chloru v pitné vodì. I když jde o zjištìní neèekaná, nejsou ve skuteènosti nijak pøekvapivá. V øadì experimentálních studií bylo prokázáno, že kyselina chlorná a chloraminy patøí mezi oxidanty, které pronikají biologickými membránami a jsou schopné rychle otevøít tìsné spoje mezi epitelovými vrstvami. Vznikla domnìnka, kterou podporují nìkterá epidemiologická a experimentální pozorování, že tyto oxidanty, které mají úzkou spojitost s naším západním stylem života, se mohou uplatnit jako adjuvans pøi vzniku atopických onemocnìní, protože usnadòují transepitelové pronikání alergenù.
Human exposure to chlorination products has considerably increased during the 20th century especially after the 1950s with the development of public and leisure pools and other water recreational areas. When attending these aquatic environments, the populations of industrialized countries have been increasingly exposed to powerful chlorine-based oxidants, either through direct contact with chlorinated water or by inhaling them in the form of gases (trichloramine and chlorine gas) or of aerosols (hypochlorite/hypochlorous acid and chloramines). The existence of respiratory and allergic problems in competitive swimmers training in the chlorine-laden atmosphere of swimming pools has also been known for more than two decades. Serious concern about these chemicals arose, however, only recently when it was found that they could affect the lung epithelial barrier of recreational swimmers and increase the risks of atopic diseases such as asthma or hay fever. Furthermore, studies focusing on occupational exposures have demonstrated an increased risk of asthma and respiratory problems among swimming pool workers while ecological studies have brought to light associations between the prevalence of childhood asthma or eczema and the availability of swimming pools or the chlorine level in drinking water. Albeit unexpected, these findings are not really surprising. A variety of experimental studies have shown that hypochlorous acid and chloramines are membrane permeable oxidants capable of rapidly opening the tight junctions of epithelial layers. This led to the suggestion, supported by some epidemiological and experimental observations, that these oxidants closely linked to our Western lifestyle might act as adjuvant in the development of atopic diseases by facilitating the transepithelial penetration of allergens.
- MeSH
- Allergens MeSH
- Hypersensitivity MeSH
- Biomarkers blood MeSH
- Asthma MeSH
- Chlorine analysis adverse effects MeSH
- Chloramines adverse effects MeSH
- Disinfectants adverse effects MeSH
- Child MeSH
- Adult MeSH
- Risk Assessment MeSH
- Water Pollutants MeSH
- Humans MeSH
- Swimming Pools MeSH
- Environmental Exposure MeSH
- Air Pollution, Indoor analysis adverse effects MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Keywords
- odmořování, otravné látky, chemické zbraně,
- MeSH
- Bentonite administration & dosage chemistry supply & distribution MeSH
- Chemical Warfare Agents adverse effects toxicity MeSH
- Chloramines administration & dosage MeSH
- Decontamination * history methods instrumentation MeSH
- Humans MeSH
- Military Personnel MeSH
- Warfare MeSH
- Mustard Gas history chemistry contraindications adverse effects MeSH
- Check Tag
- Humans MeSH