Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Chronic periodontitis (CP), an infectious disease of the supporting structures of teeth which may lead to their elimination, effects about half of the adult population. Connection to systemic diseases such as cardiovascular diseases, diabetes mellitus, low birth weight and others has been shown in several studies. Resolvins and lipoxins are low-weight lipid mediators which terminate the inflammatory response. During healing of periodontal defects granulation tissue (GT) was traditionally removed during surgical procedure. If exposed to optimal environment GT could change to a functional tissue. By using biotechnology granulation tissue modified by resolvins and lipoxins represents an innovative approach to the treatment of CP. In the experimental part, effectiveness of the termination of periodontal inflammation on the animal model will be accessed. If positive results would be achieved, clinical part of the project will follow with the aim to analyze the techniques and procedures in correlation to standard treatment of CP.
Chronická parodontitida (CP), zánětlivé onemocnění závěsného aparátu zubů, které může vést k jejich ztrátě, postihuje přibližně polovinu populace. Řada studií prokázala souvislost CP s některými systémovými chorobami, např. kardiovaskulárními onemocněními, diabetem mellitem, nízkou porodní váhou novorozenců a dalšími. Na ukončení zánětu se podílí řada mediátorů, mezi jinými také lipidové mediátory resolviny a lipoxiny. Během hojení tkání parodontu dochází k tvorbě granulační tkáně (GT), která je při chirurgickém zákroku běžně odstraněna. Pokud by se však GT nacházela ve vhodných podmínkách, je schopna se přeměnit na funkční tkáň. Pomocí biotechnologií připravení a využití resolvinů a lipoxinů při modifikaci granulační tkáně a následné chirurgické léčbě by mohlo představovat inovativní přístup k terapii CP. V experimentální části bude na animálním modelu ověřena efektivnost použitého postupu při hojení parodontálního zánětu. V navazující klinické části budou při pozitivních výsledcích předchozích experimentů použité techniky a postupy analyzovány ve vztahu ke standardní léčbě CP.
- Klíčová slova
- resolviny,
- MeSH
- biotechnologie MeSH
- chronická parodontitida chirurgie MeSH
- granulační tkáň chirurgie MeSH
- hojení ran MeSH
- králíci MeSH
- látky regulující metabolismus lipidů terapeutické užití MeSH
- lidé MeSH
- lipoxiny terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- stomatochirurgické výkony metody MeSH
- zánět chirurgie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- hodnotící studie MeSH
- Konspekt
- Stomatologie
- NLK Obory
- stomatochirurgie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
AIMS: Granulation tissue (GT) and specialized pro-resolving mediators such as lipoxins and resolvins are key elements in the successful resolution of periodontitis. Aspirin-triggered lipoxins and resolvins are even more powerful than their natural analogues. Their biosynthesis can be accelerated by omega-3 fatty acids. The aim of this study was to evaluate the use of GT enriched by aspirin and omega-3 fatty acids during the surgical treatment of periodontitis in an experimental animal model (rabbit). METHODS: In each of 24 rabbits, two experimental periodontal defects were created. In total, 47 defects were treated with open-flap debridement and one of three procedures: (1) GT extracted and soaked with aspirin and omega-3 fatty acids (ASA+OMEGA3 group); (2) GT soaked with saline (PLACEBO group); or (3) GT left untreated (CONTROL group). Then, the GT was replaced in situ. Primary evaluated criteria were the probing pocket depth (PPD) and the clinical attachment level (CAL). Necropsies were harvested 2, 6, and 12 weeks after surgery. The samples were used for histological and molecular biological assessment. RESULTS: A trend of greater PPD and CAL in the ASA+OMEGA3 group was observed at 6 weeks. However, there was no significant difference between them. During the observation period, tissue levels of FGF-7, IL-1β and TIMP-1 showed a statistically significant decrease (P<0.05). For the other variables, the ASA+OMEGA3 group was comparable with the PLACEBO and CONTROL groups. CONCLUSION: This experiment did not demonstrate the superiority of the proposed approach. However, the enriched granulation tissue did not impair healing outcomes.
- MeSH
- Aspirin farmakologie MeSH
- granulační tkáň MeSH
- králíci MeSH
- kyseliny mastné omega-3 * farmakologie MeSH
- lipoxiny * MeSH
- parodontitida * farmakoterapie MeSH
- tuberkulin MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The effect of venlafaxine, a pharmaceutical commonly found in aquatic environment, was analyzed on non-target organism, Danio rerio (Hamilton, 1822). D. rerio embryos were treated by two different concentrations of venlafaxine: either concentration relevant in aquatic environment (0.3 μg/L) or concentration that was two orders of magnitude higher (30 μg/L) for the evaluation of dose-dependent effect. Time-dependent effect was rated at 24, 96, and 144 h post-fertilization (hpf). For gene expression, genes representing one of the phases of xenobiotic biotransformation (0 to III) were selected. The results of this study showed that the effect of venlafaxine on the zebrafish embryos is the most evident at hatching (96 hpf). At this time, the results showed a downregulation of gene expression in each phase of biotransformation and in both tested concentrations. In contrast, an upregulation of most of the genes was observed 144 hpf for both tested venlafaxine concentrations. The study shows that venlafaxine can affect the gene expression of biotransformation enzymes in D. rerio embryos even in the environmentally relevant concentration and thus disrupt the process of biotransformation. Moreover, the pxr regulation of genes seems to be disrupted after venlafaxine exposure in dose- and time-dependent manner.
- MeSH
- antidepresiva farmakologie MeSH
- biotransformace MeSH
- chemické látky znečišťující vodu farmakologie MeSH
- dánio pruhované * MeSH
- embryo nesavčí účinky léků enzymologie MeSH
- regulace genové exprese enzymů * MeSH
- venlafaxin hydrochlorid farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Deoxynivalenol (DON) is a mycotoxin frequently found in cereals, and pigs are one of the most sensitive farm species to DON. The aim of this study was to determine the effects of DON in very low doses on peripheral blood mononuclear cells (PBMC) and on particular lymphocyte subpopulations. The cells were exposed to 1, 10 and 100 ng/mL of DON and lymphocyte viability, proliferation, and cytokine (Interleukin (IL)-1β, IL-2, IL-8, IL-17, Interferon (IFN) γ and tumor necrosis factor (TNF) α production were studied. Cells exposed to DON for 5 days in concentrations of 1 and 10 ng/mL showed higher viability compared to control cells. After 18 h of DON (100 ng/mL) exposure, a significantly lower proliferation after mitogen stimulation was observed. In contrast, an increase of spontaneous proliferation induced by DON (100 ng/mL) was detected. After DON exposure, the expression of cytokine genes decreased, with the exception of IL-1β and IL-8, which increased after 18 h exposure to 100 ng/mL of DON. Among lymphocyte subpopulations, helper T-cells and γδ T-cells exhibiting lower production of IL-17, IFNγ and TNFα were most affected by DON exposure (10 ng/mL). These findings show that subclinical doses of DON lead to changes in immune response.
- MeSH
- cytokiny biosyntéza genetika MeSH
- exprese genu účinky léků MeSH
- kultivované buňky MeSH
- leukocyty mononukleární účinky léků imunologie MeSH
- podskupiny lymfocytů účinky léků imunologie MeSH
- prasata MeSH
- proliferace buněk účinky léků MeSH
- trichotheceny toxicita MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Different approaches to enhance healing of hard or soft tissues include the use of cytokines and growth factors to modify cellular behaviour. Numerous growth factors are found in autologous blood concentrates - platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). Enamel matrix derivative (EMD) may improve tissue healing via amelogenins. Bilayered collagen matrix (CM) is used for soft tissue augmentation. The aim of the present study was to assess potential benefits of PRP, PRF and EMD in combination with bilayered collagen matrix or CM alone in treatment of oral mucosal defects in rabbits. Twenty-seven New Zealand white rabbits were included in this randomized controlled trial. Artificial oral mucosal defects were treated with one of these five approaches: PRP+CM, PRF+CM, EMD+CM, CM alone, or left untreated as a negative control - CO. The animals were euthanized 1 day, 7 days, or 28 days after surgery and necropsies were harvested. Histological and molecular biological analyses were performed. All defects were healed by day 28. No differences between PRP+CM, PRF+CM, CM alone and CO groups were recorded at any time point. Slower angiogenesis and a higher presence of inflammatory infiltrate were observed in the EMD+CM group 28 days after surgery. Molecular biological analyses did not reveal any statistically significant changes. In conclusion, no improvement in mucosal healing of wounds covered with a collagen membrane and PRP, PRF, or EMD was observed, compared with CM alone or untreated controls.
- Publikační typ
- abstrakt z konference MeSH
