Endogenní lipidové mediátory vznikající enzymatickou konverzí z ω -3 nenasycených mastných kyselin vykazují velmi silné protizánětové a zánět vstřebávající vlastnosti. Dokáží ovlivnit sílu a délku akutní zánětové odpovědi, stejně jako fázi obnovy tkání po zánětu. Produkty ω -3 mastných kyselin, jako jsou resolviny, maresiny aj., disponují mnoha mechanismy, jak zajistit obnovu tkání i homeostázu. Tyto z ahrnují – omezení prostupu leukocytů , snížení syntézy prozánětových cytokinů a exprese adhezních molekul, zvýšení odstraňování apoptotických buněk a mikrobů makrofágy, podpora tkáňové reparace a hojení. Tyto lipidové mediátory mají znač ný potenciál v léčbě zánětových onemocnění různého původu.

Endogenous lipid mediators with antiinflammatory and resolving activities are derived by enzymatic conversion of ω -3 unsaturated fatty acids. They modulate the magnitude and duration of acute response and the process of recovery from inflammation. Multiple mechanisms p rovided by ω -3 fatty acids derivatives such as resolvins, maresins etc. are involved in restoration and maintenance of homeostasis. These i nclude – li- mitation of leukocyte transmigration, inhibition of proinflammatory cytokine synthesis and adhesive molecule expression, enhanc ed clearance of apoptotic cells and microbial pathogens by macrophages, tissue repair, and wound healing. Th ese lipid mediators have a grea t promising clinical potential in the treatment of the various types of inflammatory diseases.

• Keywords
• EPA, D resolviny RvD1-6, DHA, E resolviny RvE1-3, resolvin, maresin,
• MeSH
• Autoimmune Diseases MeSH
• Diabetes Mellitus MeSH
• Escherichia coli MeSH
• Homeostasis MeSH
• Eicosapentaenoic Acid * analogs & derivatives   therapeutic use   MeSH
• Docosahexaenoic Acids * metabolism   MeSH
• Humans MeSH
• Macrophages enzymology   metabolism   MeSH
• Mice MeSH
• Fatty Acids, Unsaturated * metabolism   MeSH
• Inflammation * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

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.

• Keywords
• resolviny,
• MeSH
• Biotechnology MeSH
• Chronic Periodontitis surgery   MeSH
• Granulation Tissue surgery   MeSH
• Wound Healing MeSH
• Rabbits MeSH
• Lipid Regulating Agents therapeutic use   MeSH
• Humans MeSH
• Lipoxins therapeutic use   MeSH
• Disease Models, Animal MeSH
• Oral Surgical Procedures methods   MeSH
• Inflammation surgery   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Evaluation Study MeSH

• Conspectus
• Stomatologie
• NML Fields
• stomatochirurgie
• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

Acylový zvyšok mastnej kyseliny je hlavnou štrukturálnou zložkou prakticky všetkých lipidov, čím predstavuje jednu zo základných funkčných skupín týchto molekúl. Mastné kyseliny (FAs) sa vzájomne líšia dĺžkou reťazca, počtom násobných väzieb a pozíciou násobnej väzby v reťazci. Podľa počtu násobných väzieb v polynenasýtenej FA (PUFAs) možno rozlíšiť mononenasýtené FAs (MUFAs) a polynenasýtené FAs (PUFAs). V živých bunkách predstavujú PUFAs dominantný substrát pre tvorbu biologicky aktívnych zlúčenín – oktadekanoidov, eikosanoidov a dokosanoidov – klasifikovaných ako oxylipíny alebo PUFAnoidy. Predložená prehľadová práca sa sústreďuje len na skupinu PUFAnoidov, ktorých biologické účinky zahŕňajú “pozitívny efekt” pre bunku. Skupina omega-3 PUFAnoidov pozostáva z lipoxínov, resolvínov a protektínov. Všetky tieto biologicky aktívne lipidy sú prednostne formované metabolickou cestou prostredníctvom LOX. Predstavujú časť bunkových mechanizmov, ktoré prispievajú k odstráneniu zápalových buniek a k obnove integrity tkanív. Nový prístup k protizápalovým modelom je orientovaný na duálnu COX/LOX-inhibíciu a stimuláciu tvorby ochranných eikosanoidov a dokosanoidov, a na ich dôležitý terapeutický potenciál pri riadení molekulárnych mechanizmov v rámci chronických zápalových procesov.

The fatty acyl structure represents the major lipid building block of practically all lipids and therefore is one of the most fundamental categories of these molecules. Fatty acids (FAs) differ particularly in their chain length, number of double bonds and position of the bonds in the chain. The number of double bonds in the unsaturated molecule of FA distinguishes monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs). In the living cell PUFAs represent the dominant substrates for the formation of biologically active compounds – octadecanoids, eicosanoids and docosanoids – classified as oxylipins or as PUFAnoids. The present review focuses only on the groups of PUFAnoids which biological activities comprise a “positive effect” for the cell. This group of omega-3 PUFAnoids consists of lipoxins, resolvins and protectins. All these biologically active lipids are formed mainly in the LOX-pathway. They are part of the cell mechanisms that contribute to the removal of inflammatory cells and restoration of tissue integrity. A new approach to an optimal anti-inflammatory model shows orientation to the dual COX/LOX-inhibition and the stimulation of the protective eicosanoids and docosanoids formation and its considerable therapeutic potential in managing of molecular mechanisms of chronic inflammatory processes.

• Keywords
• resolvins, protectins,
• MeSH
• Biological Transport, Active MeSH
• Chronic Disease drug therapy   MeSH
• Pharmacokinetics MeSH
• Eicosanoids * therapeutic use   MeSH
• Cyclooxygenase 2 Inhibitors metabolism   MeSH
• Lipoxygenase Inhibitors metabolism   MeSH
• Humans MeSH
• Lipoxins * metabolism   MeSH
• Membrane Lipids MeSH
• Fatty Acids, Omega-3 metabolism   MeSH
• Inflammation * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Hojenie je aktívny proces, ktorý stimulujú novoobjavené endogénne lipidové mediátory: lipoxíny, resolvíny a protektíny. Vznikajú z n-3-polynenasýtených mastných kyselín (kyselina eikosapentaénová a dokosahexaénová) a majú výrazné protizápalové, hojivé a antifibrotické účinky. Dôkazy o kľúčovej úlohe endogénnych resolvínov a protektínov pri hojení zápalu otvorili cestu k úplne novej protizápalovej a uzdravujúcej terapii stimuláciou endogénnych mechanizmov hojenia. Táto liečba nemá nepriaznivé nežiaduce účinky inhibítorov COX-2 či biologickej liečby s anti-TNF preparátmi. Na sprístupnení týchto nových lipidových mediátorov pre bežnú terapiu pracuje množstvo laboratórií a viaceré preparáty sú už v klinickom skúšaní. Možno preto očakávať zásadnú revolúciu v liečbe zápalových chorôb, ktoré ešte stále patria k najzávažnejším problémom medicíny.

Resolving of the inflammation is an active process stimulated by new endogenous lipid mediators lipoxins, resolvins and protectins. These mediators are synthesized from n-3-polyunsaturated fatty acids (eicosapentaenic and docohexaenic acid) and have intensive anti-inflammatory, healing and antifibrotic effects. The evidences on key role of the endogenous resolvins and protectins in the healing of the inflammation opened a way to the total new anti-inflammatory and healing therapy by stimulation of the endogenous healing mechanisms. This therapy has not unfavorable side effects of the COX-2 inhibitors or of the biologic therapy with anti-TNF drugs. Many laboratories work on the access of these new lipid mediators for routine management and some drugs are in clinical testing. We can therefore wait substantive revolution in the management of the inflammatory diseases which continually rank to the most important problems of the contemporary medicine.

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 pharmacology   MeSH
• Granulation Tissue MeSH
• Rabbits MeSH
• Lipoxins * MeSH
• Fatty Acids, Omega-3 * pharmacology   MeSH
• Periodontitis * drug therapy   MeSH
• Tuberculin MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

• MeSH
• Atherosclerosis * metabolism   MeSH
• Cardiovascular Diseases * drug therapy   MeSH
• Docosahexaenoic Acids metabolism   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Inflammation Mediators metabolism   MeSH
• Fatty Acids, Omega-3 * metabolism   pharmacology   therapeutic use   MeSH
• Inflammation metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.

• MeSH
• Chronic Pain metabolism   therapy   MeSH
• Fatty Acids, Omega-6 metabolism   MeSH
• Humans MeSH
• Pain Management * MeSH
• Inflammation Mediators metabolism   MeSH
• Fatty Acids, Omega-3 metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

• MeSH
• Macrophage Activation drug effects   MeSH
• Anti-Inflammatory Agents chemistry   therapeutic use   MeSH
• Adipose Tissue, White drug effects   metabolism   MeSH
• 3T3-L1 Cells MeSH
• Diabetes Mellitus, Type 2 immunology   metabolism   MeSH
• Esters chemistry   therapeutic use   MeSH
• Phagocytosis drug effects   MeSH
• Insulin Resistance physiology   MeSH
• Cells, Cultured MeSH
• Linoleic Acid chemistry   MeSH
• Docosahexaenoic Acids chemistry   MeSH
• Humans MeSH
• Lipopolysaccharides pharmacology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Fatty Acids, Unsaturated chemistry   MeSH
• Obesity drug therapy   immunology   metabolism   MeSH
• Adipocytes drug effects   metabolism   MeSH
• Inflammation drug therapy   immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Docosahexaenoic acid (DHA) is an essential fatty acid that is recognized as a beneficial dietary constituent and as a source of the anti-inflammatory specialized proresolving mediators (SPM): resolvins, protectins and maresins. Apart from SPMs, other metabolites of DHA also exert potent biological effects. This article summarizes current knowledge on the metabolic pathways involved in generation of DHA metabolites. Over 70 biologically active metabolites have been described, but are often discussed separately within specific research areas. This review follows DHA metabolism and attempts to integrate the diverse DHA metabolites emphasizing those with identified biological effects. DHA metabolites could be divided into DHA-derived SPMs, DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids. These bioactive metabolites have pleiotropic effects that include augmenting energy expenditure, stimulating lipid catabolism, modulating the immune response, helping to resolve inflammation, and promoting wound healing and tissue regeneration. As a result they have been shown to exert many beneficial actions: neuroprotection, anti-hypertension, anti-hyperalgesia, anti-arrhythmia, anti-tumorigenesis etc. Given the chemical structure of DHA, the number and geometry of double bonds, and the panel of enzymes metabolizing DHA, it is also likely that novel bioactive derivatives will be identified in the future.

• MeSH
• Docosahexaenoic Acids chemistry   metabolism   pharmacology   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Background. This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health. Results. The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders. Conclusion. Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.

• MeSH
• Dietary Fats administration & dosage   MeSH
• Financing, Organized MeSH
• Humans MeSH
• Fatty Acids physiology   chemistry   classification   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH