Inhibitory Janusových kináz (JAK) patří k novějším terapeutickým modalitám v léčbě zánětlivých revmatických onemocnění. Našly si své místo v terapii u nemocných s refrakterním onemocněním, u kterých došlo k selhání nejen konvenčních chorobu modifikujících léků, ale i biologik. Nitrobuněčná signalizace prostřednictvím JAK je aktivována navázáním celé řady cytokinů na odpovídající buněčné receptory a dochází k aktivaci transkripčních proteinů (signal transducer and activator of transcription protein, STAT) a v konečné fázi dochází k transkripci genů zapojených do imunitní odpovědi. Filgotinib je inhibitor JAK s pětinásobně vyšší selektivitu pro JAK1 než pro JAK2, JAK3 a TYK2. V současné době je schválen v České republice pro terapii revmatoidní artritidy a ulcerózní kolitidy.
Janus kinase (JAK) inhibition is a newer therapeutic approach for treating autoimmune inflammatory rheumatic diseases. It has found its place in the therapy of patients with refractory disease, in whom not only conventional disease-modifying drugs have failed, but also biologics. JAKs activate intracellular signaling by binding to cellular receptors and activating signal transducers and activator of transcription (STAT) proteins, which ultimately lead to the transcription of genes involved in the immune response. Filgotinib is a JAK inhibitor with fivefold higher selectivity for JAK1 than for JAK2, JAK3, and TYK2. It is currently approved in the Czech Republic for the treatment of rheumatoid arthritis and ulcerative colitis.
BACKGROUND: Rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) are autoimmune illnesses characterised by chronic inflammation demonstrating differential associations with psychiatric conditions. OBJECTIVE: In this matched-cohort study, we aimed to investigate whether the associations between these inflammatory illnesses and mental disorders are predominantly the consequence of the burden of the former or whether common causes might underpin the susceptibility to both. METHODS: Using Czech national inpatient care data, we identified individuals with RA or axSpA during the years 1999-2012. We investigated the occurrence of psychiatric outcomes up to 2017 using stratified Cox proportional hazards models. In evidence triangulation, we assessed the potential moderation by age at inflammatory illness, the associations relative to counterparts with other similarly burdensome chronic illnesses and the temporal ordering of conditions. FINDINGS: Both RA and axSpA were associated with mood and anxiety disorders and behavioural syndromes. In evidence triangulation, the associations with depression showed a decreasing age-at-inflammatory-illness gradient in RA; the association between RA and depression was stronger than that between other chronic illnesses and depression; and excluding prevalent depression attenuated the RA-depression association. RA showed consistent inverse associations with schizophrenia and Alzheimer's disease. CONCLUSIONS: Common aetiologies might be involved in increasing the risk of developing both RA and depression. The consistent inverse associations between RA and schizophrenia and between RA and Alzheimer's disease suggest that at least part of these associations might also be a consequence of shared aetiologies as well as potential medication effects. CLINICAL IMPLICATIONS: People with autoimmune arthritides are more likely to experience mood and anxiety disorders, even relative to counterparts with other similarly burdensome chronic illnesses.
- MeSH
- dospělí MeSH
- duševní poruchy * epidemiologie imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida * epidemiologie imunologie psychologie komplikace MeSH
- senioři MeSH
- spondylartritida imunologie epidemiologie psychologie MeSH
- zánět epidemiologie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Monascus pigments having yellow, orange, and red colors are widely studied for their potential beneficial properties. Many different biological activities have been reported regarding Monascus pigments and their derivatives, but the usual method is to test complex extracts from the mycelium of the fungus or from a fungus-fermented substrate. However, this review is mainly concerned with the biological activities of purified Monascus pigments. Both yellow (ankaflavin, monascin) and red (rubropunctamine, monascorubramine) Monascus pigments are proven antioxidants if used in concentrations of 10 μg/mL or higher. Antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi has been observed with all Monascus pigments. However, the best antimicrobials are red Monascus pigments, and their amino acid derivatives (l-cysteine derivatives have MIC 4 μg/mL against Enterococcus faecalis). Yellow monaphilones and orange monaphilols seem to have the highest anti-inflammatory activity (IC50 1.7 μM of monaphilol D) and, together with red Monascus pigment derivatives, have mild antiobesity and antidiabetic activities. Further, monascin and ankaflavin in daily doses of 0.5 and 0.08 mg, respectively, lowered serum blood levels of low-density lipoprotein cholesterol complexes in rats on a high-fat diet. Orange Monascus pigments, rubropunctatin and monaphilols A and C, exhibit cytotoxic and antitumor activities (IC50 8-10 μM).
- MeSH
- antibakteriální látky farmakologie chemie izolace a purifikace MeSH
- antiflogistika farmakologie chemie izolace a purifikace MeSH
- antiinfekční látky farmakologie chemie izolace a purifikace MeSH
- antioxidancia farmakologie chemie izolace a purifikace MeSH
- biologické pigmenty * farmakologie chemie izolace a purifikace MeSH
- flaviny farmakologie chemie MeSH
- grampozitivní bakterie účinky léků MeSH
- heterocyklické sloučeniny tricyklické MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Monascus * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.
- Publikační typ
- časopisecké články MeSH
Úvod: Revmatoidní artritida (RA) je zatížena řadou komorbidit. Duševní onemocnění mohou vést k vyšším dopadům RA na život nemocného. Cílem naší studie bylo zkoumat výskyt psychiatrické komorbidity a její dopady na RA v rámci terciárního revmatologického centra v České republice. Metody: Jedná se o průřezovou studii terciárního centra, zavzati byli pacienti s RA trvající 2–15 let, s detailní charakteristikou onemocnění včetně aktivity (Disease Activity Score – DAS-28) a zdraví jedinci jako kontrolní skupina. Psychické zdraví bylo hodnoceno pomocí Mini mezinárodního europsychiatrického interview (M.I.N.I.), Beckova inventáře deprese (BDI-II) a úzkosti (BAI). Další dotazníková šetření spočívala v kvalitě života (5DEQ), funkčních schopnostech (HAQ) a sociodemografických údajích. Výsledky: Nemocní s RA se významně liší od kontrol jak v přítomnosti jakéhokoliv psychického onemocnění (PO) z testovaných M.I.N.I. modulů (24,78 % vs. 6,67 %, p < 0,001), zejména velké depresivní epizody a suicidality, tak i dosažení hranic pro depresi (18,59 % vs. 3,8 %) a anxietu (38,93 % vs. 13,08 %; obojí p < 0,0001) pomocí sebehodnotících dotazníků. Pacienti s RA a PO jsou ve střední aktivitě onemocnění (DAS28 3,40 ± 1,39) na rozdíl od M.I.N.I. negativních (2,79 ± 1,07, p < 0,05). Obdobný nález stran aktivity RA lze pozorovat u nemocných se současnou depresí a anxietou dle Beckových dotazníků. Tito lidé mají navíc významně nižší kvalitu života (5DEQ 0,56 ± 0,25 vs. 0,76 ± 0,17, p < 0,01 a 0,59 ± 0,07 a 0,80 ± 0,11, p < 0,001) a horší funkční schopnosti (HAQ1,68 ± 0,96 vs. 0,38 ± 0,40 a 1,28 ± 0,93 vs. 0,25 ± 0,42, obojí p < 0,0001). Závěr: Studie jako první mapuje vztah duševního zdraví u revmatoidní artritidy v České republice. Klinická data ukazují, že pacienti se současnou psychiatrickou komorbiditou Adresa pro korespondenci: MUDr. Markéta Hušáková Revmatologický ústav Praha Na Slupi 4 128 00 Praha 2 e-mail: husakova@revma.cz Autoři prohlašují, že nejsou v konfliktu zájmů. Do redakce doručeno: 29. 1. 2025 Práce vznikla s podporou výzkumnému projektu AZV NU21-09-00297 a je součástí výzkumného záměru RÚ 00023728.
Introduction: Rheumatoid arthritis (RA) is associated with multiple comorbidities. Mental health disorders can exacerbate the impact of RA on patients’ lives. The aim of our study was to investigate the prevalence of psychiatric comorbidities and their effects on RA in a tertiary rheumatology center in the Czech Republic. Methods: This is a cross-sectional study conducted at a tertiary center, including patients with RA with disease duration of 2–15 years, with a detailed characterization of disease activity (Disease Activity Score – DAS-28). A control group of healthy individuals was also included. Mental health was assessed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Beck Depression Inventory (BDI-II), and the Beck Anxiety Inventory (BAI). Additional questionnaires evaluated quality of life (5DEQ), functional abilities (HAQ), and sociodemographic characteristics. Results: RA patients significantly differed from controls in the presence of any psychiatric disorder (PD) in the M.I.N.I. modules (24.78% vs. 6.67%, p < 0.001), particularly major depressive episodes and suicidality. They also had a higher prevalence of depression (18.59% vs. 3.8%) and anxiety (38.93% vs. 13.08%; p < 0.0001 in both) based on self-reported questionnaires. RA patients with a positive M.I.N.I. screening had a moderate disease activity (DAS28 3.40 ± 1.39) compared to M.I.N.I.-negative patients (2.79 ± 1.07, p < 0.05). A similar pattern was observed in patients with concurrent depression and anxiety according to the Beck inventories. These individuals also had significantly lower quality of life (5DEQ 0.56 ± 0.25 vs. 0.76 ± 0.17, p < 0.01 and 0.59 ± 0.07 vs. 0.80 ± 0.11, p < 0.001) and worse functional abilities (HAQ 1.68 ± 0.96 vs. 0.38 ± 0.40 and 1.28 ± 0.93 vs. 0.25 ± 0.42; p < 0.0001 in both). Conclusion: This is the first study to examine the relationship between mental health and rheumatoid arthritis in the Czech Republic. Clinical data indicate that RA patients with concurrent psychiatric comorbidities experience higher disease activity, poorer quality of life, and reduced functional abilities.
- MeSH
- deprese diagnóza epidemiologie etiologie MeSH
- duševní zdraví * statistika a číselné údaje MeSH
- kvalita života psychologie MeSH
- lidé MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- revmatoidní artritida * diagnóza psychologie MeSH
- úzkost diagnóza epidemiologie etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The fungus Monascus is a well-known source of secondary metabolites with interesting pharmaceutical and nutraceutical applications. In particular, Monascus pigments possess a wide range of biological activities (e.g. antimicrobial, antioxidant, anti-inflammatory or antitumoral). To broaden the scope of their possible application, this study focused on testing Monascus pigment extracts as potential photosensitizing agents efficient in antimicrobial photodynamic therapy (aPDT) against bacteria. For this purpose, eight different extracts of secondary metabolites from the liquid- and solid-state fermentation of Monascus purpureus DBM 4360 and Monascus sp. DBM 4361 were tested against Gram-positive and Gram-negative model bacteria, Bacillus subtilis and Escherichia coli and further screened for ESKAPE pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. To the bacterial culture, increasing concentration of extracts was added and it was found that all extracts showed varying antimicrobial activity against Gram-positive bacteria in dark, which was further increased after irradiation. Gram-negative bacteria were tolerant to the extracts' exposure in the dark but sensitivity to almost all extracts that occurred after irradiation. The Monascus sp. DBM 4361 extracts seemed to be the best potential candidate for aPDT against Gram-positive bacteria, being efficient at low doses, i.e. the lowest total concentration of Monascus pigments exhibiting aPDT effect was 3.92 ± 1.36 mg/L for E. coli. Our results indicate that Monascus spp., forming monascuspiloin as the major yellow pigment and not-forming mycotoxin citrinin, is a promising source of antimicrobials and photoantimicrobials.
- MeSH
- antibakteriální látky * farmakologie chemie MeSH
- biologické pigmenty farmakologie MeSH
- biologické přípravky farmakologie chemie MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky farmakologie chemie MeSH
- grampozitivní bakterie účinky léků účinky záření MeSH
- komplexní směsi farmakologie chemie MeSH
- mikrobiální testy citlivosti * MeSH
- Monascus * chemie metabolismus MeSH
- mycelium * chemie účinky záření účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
- MeSH
- analgetika terapeutické užití MeSH
- ankylózující spondylitida * farmakoterapie MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- antirevmatika * terapeutické užití MeSH
- lidé MeSH
- spondylartritida * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antikoagulancia farmakologie terapeutické užití MeSH
- dabigatran * farmakologie terapeutické užití MeSH
- inhibitory koagulačních faktorů MeSH
- lidé MeSH
- parciální tromboplastinový čas MeSH
- rivaroxaban * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
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