Paclitaxel is used for the treatment of several types of cancers. However, one of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy. In this study we examined the engagement of antioxidative signal pathway of the dorsal root ganglion (DRG) in mechanical and thermal hypersensitivity evoked by paclitaxel. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western blot analysis and ELISA were used to examine expression of Nrf2-antioxidant response element (ARE) and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our results show that paclitaxel increased mechanical and thermal sensitivity as compared with vehicle control animals. Paclitaxel also impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress, namely 8-isoprostaglandin F2alpha and 8-hydroxy-2'-deoxyguanosine. Systemic administration of SOD mimetic using tempol, antioxidant vitamin C or blocking oxidative pathway using NADPH oxidase inhibitor (GKT137831) attenuated mechanical and thermal hypersensitivity induced by paclitaxel. This inhibitory effect was accompanied with decreases of proinflammatory cytokines (PICs) such as IL-1beta, IL-6 and TNF-alpha in the DRG. In conclusion, the data revealed impairment of Nrf2-ARE and heightened oxidative and PIC signals in the DRG of paclitaxel rats, leading to neuropathic pain. Balancing of reactive oxygen species by supplying antioxidants and/or inhibiting NADPH oxidase appears significant to yield beneficial effects in neuropathic pain conditions after chemotherapeutic paclitaxel.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- antitumorózní látky fytogenní toxicita MeSH
- krysa rodu rattus MeSH
- měření bolesti účinky léků metody MeSH
- neuralgie chemicky indukované farmakoterapie metabolismus MeSH
- nocicepce účinky léků fyziologie MeSH
- paclitaxel toxicita MeSH
- potkani Sprague-Dawley MeSH
- signální transdukce účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Common variable immunodeficiency (CVID), the most frequent symptomatic immunoglobulin primary immunodeficiency, is associated with chronic T cell activation and reduced frequency of CD4(+) T cells. The underlying cause of immune activation in CVID is unknown. Microbial translocation indicated by elevated serum levels of lipopolysaccharide and soluble CD14 (sCD14) has been linked previously to systemic immune activation in human immunodeficiency virus/acquired immune deficiency syndrome (HIV-1/AIDS), alcoholic cirrhosis and other conditions. To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of immune cell populations and serum levels of sCD14, soluble CD25 (sCD25), lipopolysaccharide and markers of liver function in 35 patients with CVID, 53 patients with selective immunoglobulin (Ig)A deficiency (IgAD) and 63 control healthy subjects. In CVID subjects, the concentration of serum sCD14 was increased significantly and correlated with the level of sCD25, C-reactive protein and the extent of T cell activation. Importantly, no increase in serum lipopolysaccharide concentration was observed in patients with CVID or IgAD. Collectively, the data presented suggest that chronic T cell activation in CVID is associated with elevated levels of sCD14 and sCD25, but not with systemic endotoxaemia, and suggest involvement of lipopolysaccharide-independent mechanisms of induction of sCD14 production.
- MeSH
- aktivace lymfocytů MeSH
- antigeny CD14 krev imunologie MeSH
- B-lymfocyty imunologie MeSH
- běžná variabilní imunodeficience krev imunologie MeSH
- bronchiektazie krev MeSH
- C-reaktivní protein imunologie metabolismus MeSH
- deficience IgA krev imunologie MeSH
- dospělí MeSH
- endotoxemie krev imunologie MeSH
- granulom krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidy krev imunologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoci jater krev MeSH
- receptor interleukinu-2 - alfa-podjednotka krev imunologie MeSH
- senioři MeSH
- splenomegalie krev MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
PCR and SYBR Green I real-time PCR techniques were applied to the rapid detection of Vibrio metschnikovii by designing primers based on infC (initiation factor 3) gene sequence. The specificity, sensitivity, and practical applications of the methods have been also analyzed. The methods showed high detecting specificity with no cross amplifications of other closely related and nonrelated species; they provide a simple and rapid tool for V. metschnikovii detection with high sensitivity and specificity.
- MeSH
- bakteriologické techniky metody MeSH
- barvení a značení metody MeSH
- časové faktory MeSH
- DNA primery genetika MeSH
- hodnotící studie jako téma MeSH
- mikrobiologie vody MeSH
- organické látky metabolismus MeSH
- polymerázová řetězová reakce metody MeSH
- prokaryotický iniciační faktor 3 genetika MeSH
- senzitivita a specificita MeSH
- Vibrio izolace a purifikace MeSH
The crystal structure of an efficient Diels-Alder antibody catalyst at 1.9 angstrom resolution reveals almost perfect shape complementarity with its transition state analog. Comparison with highly related progesterone and Diels-Alderase antibodies that arose from the same primordial germ line template shows the relatively subtle mutational steps that were able to evolve both structural complementarity and catalytic efficiency.
- MeSH
- chemické jevy MeSH
- chemie fyzikální MeSH
- genetické matrice MeSH
- hapteny chemie metabolismus MeSH
- imunoglobuliny - Fab fragmenty chemie metabolismus MeSH
- katalytické protilátky chemie genetika metabolismus MeSH
- katalýza MeSH
- konformace proteinů MeSH
- krystalografie rentgenová MeSH
- ligandy MeSH
- molekulární evoluce * MeSH
- molekulární modely MeSH
- mutace MeSH
- progesteron imunologie MeSH
- rozpustnost MeSH
- teplota MeSH
- vazebná místa protilátek MeSH
- vodíková vazba MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
