To examine whether exposure to sodium salicylate disrupts expression of vesicular glutamate transporter 3 (VGLUT3) and whether the alteration in expression corresponds to increased risk for tinnitus. Rats were treated with saline (control) or sodium salicylate (treated) Rats were examined for tinnitus by monitoring gap-pre-pulse inhibition of the acoustic startle reflex (GPIAS). Auditory brainstem response (ABR) was applied to evaluate hearing function after treatment. Rats were sacrificed after injection to obtain the cochlea, cochlear nucleus (CN), and inferior colliculus (IC) for examination of VGLUT3 expression. No significant differences in hearing thresholds between groups were identified (p>0.05). Tinnitus in sodium salicylate-treated rats was confirmed by GPIAS. VGLUT3 encoded by solute carrier family 17 members 8 (SLC17a8) expression was significantly increased in inner hair cells (IHCs) of the cochlea in treated animals, compared with controls (p<0.01). No significant differences in VGLUT3 expression between groups were found for the cochlear nucleus (CN) or IC (p>0.05). Exposure to sodium salicylate may disrupt SLC17a8 expression in IHCs, leading to alterations that correspond to tinnitus in rats. However, the CN and IC are unaffected by exposure to sodium salicylate, suggesting that enhancement of VGLUT3 expression in IHCs may contribute to the pathogenesis of tinnitus.
- MeSH
- antiflogistika nesteroidní škodlivé účinky MeSH
- colliculus inferior účinky léků metabolismus MeSH
- nucleus cochlearis účinky léků metabolismus MeSH
- potkani Wistar MeSH
- salicylan sodný škodlivé účinky MeSH
- sluchový práh účinky léků MeSH
- tinnitus chemicky indukované MeSH
- vezikulární transportní proteiny pro glutamát metabolismus MeSH
- vnitřní vláskové buňky účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hypersensitive pain response is observed in patients with Parkinson's disease (PD). However, the signal pathways leading to hyperalgesia still need to be clarified. Chronic oxidative stress is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role NADPH oxidase (NOX) of the PAG in regulating exaggerated pain evoked by PD. PD was induced by central microinjection of 6-hydroxydopamine to lesion the left medial forebrain bundle of rats. Then, Western Blot analysis and ELISA were used to determine NOXs and products of oxidative stress (i.e., 8-isoprostaglandin F2alpha and 8-hydroxy-2'-deoxyguanosine). Pain responses to mechanical and thermal stimulation were further examined in control rats and PD rats. In results, among the NOXs, protein expression of NOX4 in the PAG of PD rats was significantly upregulated, thereby the products of oxidative stress were increased. Blocking NOX4 pathway in the PAG attenuated mechanical and thermal pain responses in PD rats and this was accompanied with decreasing production of oxidative stress. In addition, inhibition of NOX4 largely restored the impaired GABA within the PAG. Stimulation of GABA receptors in the PAG of PD rats also blunted pain responses. In conclusions, NOX4 activation of oxidative stress in the PAG of PD rats is likely to impair the descending inhibitory GABAergic pathways in regulating pain transmission and thereby plays a role in the development of pain hypersensitivity in PD. Inhibition of NOX4 has beneficial effects on the exaggerated pain evoked by PD.
- MeSH
- bolest farmakoterapie etiologie metabolismus patologie MeSH
- fasciculus telencephali medialis účinky léků metabolismus MeSH
- GABA metabolismus MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- NADPH-oxidasa 4 antagonisté a inhibitory MeSH
- Parkinsonova nemoc enzymologie metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- práh bolesti účinky léků fyziologie MeSH
- pyrazolony farmakologie MeSH
- pyridony farmakologie MeSH
- signální transdukce účinky léků MeSH
- substantia grisea centralis účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Circulating miRNAs have been proposed as the effective diagnostic biomarkers for muscular fibrosis-associated diseases. However, circulating biomarkers for early diagnosis of contracture muscles are limited in gluteal muscle contracture (GMC) patients. Here we sought to explore the abnormally expressed miRNAs in plasma and contraction bands of GMC patients. The results showed miR-29a-3p expression in plasma and contraction bands tissue was significantly reduced in GMC patients compared with normal control. Cell viability and levels of proliferation-associated protein cyclin D1 and cyclin-dependent-kinase 2 (CDK2) were powerfully inhibited by miR-29a mimics and enhanced by miR-29a inhibitor compared with negative control. Furthermore, miR-29a mimics effectively impeded, while miR-29a inhibitor enhanced the expression of collagen I and collagen III, followed by the secretion of transforming growth factor beta1 (TGF-beta1), TGF-beta3 and connective tissue growth factor (CTGF) in primary human contraction bands (CB) fibroblasts. The miR-29a-3p negatively regulated the expression of TGF-beta1 through binding to the 3´ UTR region of SERPINH1 (encoding heat shock protein HSP47), but had no effect on Smad2 activity. The miR-29a-3p was inversely correlated with HSP47 in contraction bands tissue from GMC patients. Collectively, miR-29a was notably depressed and regulated cell viability and fibrosis by directly targeting HSP47 in GMC, which suggest that circulating miR-29a might be a potential biomarker for early diagnosis and provides a novel therapeutic target for GMC.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- fibroblasty metabolismus patologie MeSH
- fibróza genetika patologie prevence a kontrola MeSH
- hýždě patologie MeSH
- kontraktura genetika patologie prevence a kontrola MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- proteiny tepelného šoku HSP47 genetika metabolismus MeSH
- studie případů a kontrol MeSH
- svaly metabolismus patologie MeSH
- transformující růstový faktor beta1 genetika metabolismus MeSH
- viabilita buněk fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.
- MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- antiuratika terapeutické užití MeSH
- delfská metoda MeSH
- direktivní poradenství MeSH
- dna (nemoc) krev farmakoterapie terapie MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- interleukin-1 antagonisté a inhibitory MeSH
- kyselina močová krev MeSH
- lidé MeSH
- medicína založená na důkazech MeSH
- syndrom vzplanutí nemoci MeSH
- vzdělávání pacientů jako téma MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- směrnice pro lékařskou praxi MeSH
- Klíčová slova
- infiltrace makrofágy,
- MeSH
- biopsie statistika a číselné údaje MeSH
- exprese genu MeSH
- fibróza * etiologie MeSH
- interferon gama MeSH
- klinické laboratorní techniky metody MeSH
- ledviny patologie MeSH
- lidé MeSH
- makrofágy * MeSH
- metabolické sítě a dráhy MeSH
- nemoc štěpu proti hostiteli etiologie patologie MeSH
- transplantace ledvin statistika a číselné údaje MeSH
- transplantáty patologie statistika a číselné údaje MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Austrálie MeSH
The iol cluster (consisting of genes involved in myo-inositol utilization) was investigated in Lactobacillus casei strains isolated from koumiss. Ten strains were tested for the presence of iol cluster by PCR screening; three strains encoded this cluster. Full-sequencing procedure was conducted; the iol cluster was identical to that of L. casei BL23 (GenBank access. no. FM177140) except for an upstream transposase. The iol cluster is not a common feature for L. casei strains isolated from koumiss.
- MeSH
- bakteriologické techniky metody MeSH
- financování organizované MeSH
- koně MeSH
- Lactobacillus casei genetika izolace a purifikace MeSH
- mléko mikrobiologie MeSH
- molekulární sekvence - údaje MeSH
- multigenová rodina MeSH
- plošný screening metody MeSH
- polymerázová řetězová reakce MeSH
- sekvenční analýza DNA MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
We studied hsBAFF activity in in vitro mouse splenic B cells. hsBAFF effects on intracellular free Ca2+ concentration ([Ca2+]i) were assayed, using a laser scanning confocal microscope with fluorescent probe, Fluo-3/AM. We showed that treatment of B cells with 0.5-5 µg/ml hsBAFF resulted in significantly higher [Ca2+]i levels in a dose-dependent fashion at 12 and 24 h, respectively (p<0.05 or p<0.01 vs. control). Furthermore, we noticed that 2.5 µg/ml hsBAFF-treated cells were significantly resistant to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca2+-ATPase inhibitor (p<0.05 hsBAFF plus Tg group vs. Tg group). Thus hsBAFF may promote B cell survival by direct upregulation of [Ca2+]i physiological homeostasis contributing to prevention of [Ca2+]i dysfunction. Using immunocytochemistry and Western blot analysis, we found that the activation of ERK1/2 due to hsBAFF was triggered by a [Ca2+]i-dependent pathway, leading to elevation of B cell proliferation. This is supported by the findings that intracellular Ca2+ chelator BAPTA/AM attenuated phosphorylated ERK1/2 expression and cell proliferation in hsBAFF-stimulated B cells. hsBAFF-stimulated B cell proliferation was obviously reduced by mitogen extracellular kinase 1/2 (MEK1/2, upstream of ERK1/2) inhibitor U0126. Taken together, the main finding of this study is that hsBAFF elicits higher but homeostatic [Ca2+]i levels, which regulates ERK1/2 activity and cell proliferation in in vitro B cells
- MeSH
- B-lymfocyty enzymologie MeSH
- butadieny farmakologie MeSH
- časové faktory MeSH
- chelátory farmakologie MeSH
- EGTA analogy a deriváty farmakologie MeSH
- faktor aktivující B-buňky metabolismus MeSH
- financování organizované MeSH
- fosforylace MeSH
- homeostáza MeSH
- inhibitory enzymů farmakologie MeSH
- inhibitory proteinkinas farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mitogenem aktivovaná proteinkinasa 1 metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 metabolismus MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nitrily farmakologie MeSH
- proliferace buněk MeSH
- sarkoplazmatická Ca2+-ATPáza antagonisté a inhibitory metabolismus MeSH
- thapsigargin farmakologie MeSH
- vápník metabolismus MeSH
- viabilita buněk MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- fosfoproteiny MeSH
- lidé MeSH
- membránové proteiny imunologie metabolismus MeSH
- proteiny imunologie metabolismus MeSH
- receptory imunologické imunologie MeSH
- signální transdukce fyziologie MeSH
- transportní proteiny imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
