The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- Klíčová slova
- Acetylsalicylic acid, Drug delivery, HPMA, Inflammation, Nanotherapeutics, Salicylic acid hydrazide,
- MeSH
- akrylamidy chemie farmakologie aplikace a dávkování MeSH
- antiflogistika farmakologie aplikace a dávkování chemie MeSH
- Aspirin * aplikace a dávkování farmakologie chemie MeSH
- cyklooxygenasy metabolismus MeSH
- inhibitory cyklooxygenasy farmakologie aplikace a dávkování chemie MeSH
- léky s prodlouženým účinkem * MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery * chemie aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrylamidy MeSH
- antiflogistika MeSH
- Aspirin * MeSH
- cyklooxygenasy MeSH
- inhibitory cyklooxygenasy MeSH
- léky s prodlouženým účinkem * MeSH
- mediátory zánětu MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- polymery * MeSH
The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the calculated disease activity index and by assessment of cytokines and enzymes from the gut tissue - tumor necrosis factor α (TNF-α), transforming growth factor β1, interleukin (IL)-1β, IL-6, IL-10, IL-17, catalase, superoxide dismutase 2, myeloperoxidase (MPO), and matrix metalloproteinase 9. Composites of GPs with incorporated curcumin showed promising results with the capability to lower symptoms of colitis and significantly decrease the production of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and the activity of MPO, as well. The anti-inflammatory effect of the composites was greater than those of pure GPs or curcumin.
- Klíčová slova
- Colitis targeting, Curcumin, Inflammation, Yeast glucan particles, β-Glucan,
- MeSH
- antiflogistika aplikace a dávkování terapeutické užití MeSH
- cytokiny metabolismus MeSH
- glukany aplikace a dávkování terapeutické užití MeSH
- interleukiny metabolismus MeSH
- kolitida chemicky indukované farmakoterapie MeSH
- krysa rodu Rattus MeSH
- kurkumin aplikace a dávkování terapeutické užití MeSH
- nosiče léků terapeutické užití MeSH
- potkani Wistar MeSH
- Saccharomyces cerevisiae metabolismus MeSH
- síran dextranu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- cytokiny MeSH
- glukany MeSH
- interleukiny MeSH
- kurkumin MeSH
- nosiče léků MeSH
- síran dextranu MeSH
BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.
- Klíčová slova
- Adalimumab, CDEIS, IBD, Inflammatory Bowel Diseases,
- MeSH
- adalimumab aplikace a dávkování škodlivé účinky MeSH
- antiflogistika aplikace a dávkování škodlivé účinky MeSH
- azathioprin aplikace a dávkování škodlivé účinky MeSH
- časové faktory MeSH
- Crohnova nemoc diagnóza farmakoterapie imunologie patologie MeSH
- dospělí MeSH
- hospitalizace statistika a číselné údaje MeSH
- indukce remise metody MeSH
- kombinovaná farmakoterapie škodlivé účinky metody MeSH
- lidé MeSH
- mladý dospělý MeSH
- následné studie MeSH
- prednison aplikace a dávkování škodlivé účinky MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa antagonisté a inhibitory imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- adalimumab MeSH
- antiflogistika MeSH
- azathioprin MeSH
- prednison MeSH
- TNF protein, human MeSH Prohlížeč
- TNF-alfa MeSH
OBJECTIVE: To compare the effect of epidural steroid injections (ESI) in patients with discogenic sciatica (Sci) versus patients with lumbar canal stenosis (LSS), not controlled by conservative treatment. MATERIALS AND METHODS: In our study, 80 patients with Sci and 66 with LSS were included. A single ESI (10 mg dexamethasone in 3 cc 0.25% bupivacaine) was applied under fluoroscopic control: one level above the highest stenotic level, in the posterior epidural space, via interlaminar approach in LSS and at the prolapse level, in the anterior epidural space, via transforaminal route in Sci. Pain intensity was assessed by VAS at baseline and on days 1, 15 and 30 after intervention. RESULTS: The procedure was successful in 78 Sci and 63 LSS patients. Patients with Sci responded significantly better. At one month, pain reduction over 50% was achieved in 63% (52.3-73.7% at p = 0.95) of Sci but only in 35% (23.2-46.8%) of LSS (p = 0.03). Return to pre-intervention level happened in 47% (34.7-59.3%) of LSS versus 14% (6.3-21.7%) of Sci patients (p = 0.01). In 5 patients the procedure failed, without resulting morbidity. CONCLUSION: ESI are more effective in patients with Sci than in single level LSS. In multiple level LSS, results are disappointing.
- Klíčová slova
- chronic pain, epidural steroid injections, intervertebral disc disease, low back pain, lumbar spinal stenosis, neuropathic pain, sciatica,
- MeSH
- anestetika lokální aplikace a dávkování MeSH
- antiflogistika aplikace a dávkování MeSH
- bederní obratle MeSH
- bupivakain aplikace a dávkování MeSH
- časové faktory MeSH
- degenerace meziobratlové ploténky komplikace MeSH
- dexamethason aplikace a dávkování MeSH
- dospělí MeSH
- epidurální analgezie MeSH
- fluoroskopie MeSH
- ischialgie farmakoterapie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lumbalgie farmakoterapie etiologie MeSH
- měření bolesti MeSH
- prospektivní studie MeSH
- senioři MeSH
- spinální stenóza komplikace MeSH
- studie případů a kontrol MeSH
- výhřez meziobratlové ploténky komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anestetika lokální MeSH
- antiflogistika MeSH
- bupivakain MeSH
- dexamethason MeSH
Introduction: Depressive symptoms may occur in any phase of schizophrenia and can have far-reaching consequences.Areas covered: The author focuses on recent reviews and meta-analyses dealing with the prevalence, importance, etiopathogenesis, and pharmacotherapy of comorbid depression and schizophrenia. Depressive symptoms in acute episodes may improve in parallel with psychosis due to antipsychotic treatment. Therefore, the first step is to evaluate the current antipsychotic treatment of psychotic symptoms and consider changing the dosage. A second step is switching antipsychotic medications, since there are indications that some medications are slightly more effective in reducing depressive symptoms than others. For persistent depressive episodes, additional therapeutic interventions are indicated. Most guidelines recommend the administration of antidepressants as an add-on treatment with a limited evidence level. Immunotherapeutic strategies could be successful, at least in some schizophrenia patients.Expert opinion: In the near future, precision psychiatry should enable clinicians to recognize specific biotypes with unique biosignatures that will guide accurate and prompt clinical management for individual patients.
- Klíčová slova
- Depression, anti-inflammatory agents, antidepressants, antipsychotics, biomarkers, schizophrenia,
- MeSH
- antidepresiva aplikace a dávkování terapeutické užití MeSH
- antiflogistika aplikace a dávkování terapeutické užití MeSH
- antipsychotika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- deprese komplikace farmakoterapie MeSH
- lidé MeSH
- schizofrenie komplikace farmakoterapie MeSH
- toxické psychózy prevence a kontrola MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antidepresiva MeSH
- antiflogistika MeSH
- antipsychotika MeSH
BACKGROUND: During the coronavirus disease (COVID-19) pandemic, people volunteered for sewing hand-made face masks. However, sewing-machine operating might be associated with high ergonomic risk and a negative impact on musculoskeletal health. OBJECTIVE AND METHODS: This paper describes an ultrasonographic diagnosis of a foot ganglion - after sewing 300 face masks within two months using a foot-operated sewing machine. RESULTS: The patient significantly improved after an ultrasound-guided aspiration and corticosteroid injection. CONCLUSION: In short, we highlight the importance of ultrasound examination in the management of work (overuse)-related disorders in occupational medicine practice.
- Klíčová slova
- Coronavirus, mask, seamstress, sewing machine, ultrasound,
- MeSH
- anestetika lokální aplikace a dávkování MeSH
- antiflogistika aplikace a dávkování MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- cystická ganglia diagnostické zobrazování etiologie MeSH
- dobrovolní pracovníci * MeSH
- drenáž metody MeSH
- intervenční ultrasonografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- masky MeSH
- methylprednisolon acetát aplikace a dávkování MeSH
- nemoci nohy (od hlezna dolů) diagnostické zobrazování etiologie MeSH
- nemoci z povolání diagnostické zobrazování etiologie MeSH
- pandemie MeSH
- poranění nohy (od hlezna dolů) komplikace MeSH
- poranění z opakovaného přetěžování komplikace MeSH
- SARS-CoV-2 MeSH
- textilní průmysl * MeSH
- trimekain aplikace a dávkování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- anestetika lokální MeSH
- antiflogistika MeSH
- methylprednisolon acetát MeSH
- trimekain MeSH
BACKGROUND: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODS: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. RESULTS: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). CONCLUSIONS: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).
- MeSH
- analýza podle původního léčebného záměru MeSH
- angina pectoris epidemiologie MeSH
- antiflogistika aplikace a dávkování škodlivé účinky MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- cévní mozková příhoda epidemiologie MeSH
- dvojitá slepá metoda MeSH
- incidence MeSH
- infarkt myokardu farmakoterapie terapie MeSH
- Kaplanův-Meierův odhad MeSH
- kardiovaskulární nemoci epidemiologie mortalita MeSH
- kolchicin aplikace a dávkování škodlivé účinky MeSH
- koronární angioplastika MeSH
- lidé středního věku MeSH
- lidé MeSH
- proporcionální rizikové modely MeSH
- recidiva MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antiflogistika MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- kolchicin MeSH
Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of dexamethasone in early phase of surfactant-depleted model of acute respiratory distress syndrome (ARDS). In the study, lung-lavaged New Zealand rabbits with respiratory failure (PaO(2)<26.7 kPa in FiO(2) 1.0) were treated with intravenous dexamethasone (DEX): 0.5 mg/kg (DEX-0.5) and 1.0 mg/kg (DEX-1.0), or were untreated (ARDS). Animals without ARDS served as controls. Respiratory parameters, lung edema, leukocyte shifts, markers of inflammation and oxidative damage in the plasma and lung were evaluated. Both doses of DEX improved the lung function vs. untreated animals. DEX-1.0 had faster onset with significant improvement in gas exchange and ventilation efficiency vs. DEX-0.5. DEX-1.0 showed a trend to reduce lung neutrophils, local oxidative damage, and levels of TNFalpha, IL-6, IL-8 more effectively than DEX-0.5 vs. ARDS group. Both dosages of dexamethasone significantly improved the lung function and suppressed inflammation in early phase ARDS, while some additional enhancement was observed for higher dose (1 mg/kg) of DEX.
- MeSH
- antiflogistika aplikace a dávkování MeSH
- bronchoalveolární lavážní tekutina cytologie MeSH
- dexamethason aplikace a dávkování MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- plíce účinky léků MeSH
- počet leukocytů MeSH
- preklinické hodnocení léčiv MeSH
- respirační funkční testy MeSH
- syndrom dechové tísně krev farmakoterapie imunologie MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- dexamethason MeSH
In this study, two extracts from Fatsia japonica-Fatsiphloginum™ (extract of triterpene glycosides containing 45-50 % of fatsiosides (FS)) and purified triterpene-rich extract of saponins with code name PS-551 (PS) were administered in combination with methotrexate (MTX) and in monotherapy to rats suffering adjuvant arthritis (AA). The anti-inflammatory activities of extracts were evaluated as monotherapies in comparison with untreated AA. PS administered in higher dose showed on day 28 effective decrease of hind paw volume (HPV), decreased activity of gamma-glutamyl transferase (GGT) in joints, and also interleukin-17A was decreased significantly on day 14. The higher dose of PS was more effective than both doses of FS. Further, we evaluated the higher doses of PS and FS in combination with MTX. PS improved the effect of MTX in combination more effective than FS (HPV, body weight and activity of GGT in joint). However, FS was more effective in reducing the level of IL-17A on day 14 and activity of GGT in spleen than PS. In conclusion, our study showed that generally FS has higher anti-arthritic activity comparing to PS. Thus, the novel combination of Fatsiphloginum™ and methotrexate could be interesting for future clinical studies in patients suffering auto-immune diseases.
- MeSH
- antiflogistika aplikace a dávkování MeSH
- aralkovité chemie MeSH
- artritida experimentální farmakoterapie MeSH
- gama-glutamyltransferasa metabolismus MeSH
- interleukin-17 krev MeSH
- krysa rodu Rattus MeSH
- methotrexát aplikace a dávkování MeSH
- potkani inbrední LEW MeSH
- rostlinné extrakty terapeutické užití MeSH
- saponiny aplikace a dávkování MeSH
- triterpeny aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- gama-glutamyltransferasa MeSH
- interleukin-17 MeSH
- methotrexát MeSH
- rostlinné extrakty MeSH
- saponiny MeSH
- triterpeny MeSH
Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p < 0.01 vs. T-2 toxin). These changes were completely abolished by the therapeutic use of Lemod-solu® plus Lemod-depo® (p < 0.001 vs. T-2 toxin). Our results show that a significant cardioprotective efficacy of methylprednisolone is mediated by its anti-inflammatory activity.
- Klíčová slova
- Cardiotoxicity, Methylprednisolone, Pathohistology, Rats, T-2 toxin,
- MeSH
- antiflogistika aplikace a dávkování terapeutické užití MeSH
- glykogen metabolismus MeSH
- kardiomyopatie chemicky indukované farmakoterapie MeSH
- léky s prodlouženým účinkem MeSH
- mastocyty účinky léků metabolismus patologie MeSH
- methylprednisolon aplikace a dávkování terapeutické užití MeSH
- myokard metabolismus patologie MeSH
- potkani Wistar MeSH
- T-2 toxin toxicita MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- glykogen MeSH
- léky s prodlouženým účinkem MeSH
- methylprednisolon MeSH
- T-2 toxin MeSH