A second-generation series of biscyclometalated 2-(5-aryl-thienyl)-benzimidazole and -benzothiazole Ir(III) dppz complexes [Ir(C^N)2(dppz)]+, Ir1-Ir4, were rationally designed and synthesized, where the aryl group attached to the thienyl ring was p-CF3C6H4 or p-Me2NC6H4. These new Ir(III) complexes were assessed as photosensitizers to explore the structure-activity correlations for their potential use in biocompatible anticancer photodynamic therapy. When irradiated with blue light, the complexes exhibited high selective potency across several cancer cell lines predisposed to photodynamic therapy; the benzothiazole derivatives (Ir1 and Ir2) were the best performers, Ir2 being also activatable with green or red light. Notably, when irradiated, the complexes induced leakage of lysosomal content into the cytoplasm of HeLa cancer cells and induced oncosis-like cell death. The capability of the new Ir complexes to photoinduce cell death in 3D HeLa spheroids has also been demonstrated. The investigated Ir complexes can also catalytically photo-oxidate NADH and photogenerate 1O2 and/or •OH in cell-free media.
- MeSH
- antitumorózní látky * farmakologie MeSH
- benzothiazoly MeSH
- fotosenzibilizující látky farmakologie terapeutické užití MeSH
- fototoxická dermatitida * farmakoterapie MeSH
- iridium farmakologie MeSH
- komplexní sloučeniny * farmakologie MeSH
- lidé MeSH
- lyzozomy MeSH
- nádorové buněčné linie MeSH
- nádory * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.
- MeSH
- atopická dermatitida * farmakoterapie MeSH
- humanizované monoklonální protilátky * MeSH
- kontrolní skupiny MeSH
- leukocyty MeSH
- lidé MeSH
- pyl MeSH
- roční období MeSH
- T-lymfocyty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- atopická dermatitida * MeSH
- B-lymfocyty MeSH
- humanizované monoklonální protilátky MeSH
- lidé MeSH
- roční období MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.
- MeSH
- atopická dermatitida * diagnóza farmakoterapie MeSH
- cíle MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- kohortové studie MeSH
- kvalita života MeSH
- lidé MeSH
- monoklonální protilátky škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Atopická dermatitida (AD) je chronické imunitně zprostředkované zánětlivé kožní onemocnění charakterizované intenzivním pruritem a snížením kvality života pacientů. Většina nemocných s AD si přeje dosáhnout co nejrychlejšího a co nejvýraznějšího zmírnění (ideálně vymizení) projevů onemocnění včetně pruritu, u mnoha pacientů však je kontrola onemocnění suboptimální. Upadacitinib je selektivní inhibitor JAK1, který se vyznačuje vysokou a setrvalou účinností stran objektivních i subjektivních projevů AD a zároveň rychlým nástupem působení. Má tak potenciál splnit očekávání a preference pacientů týkající se léčby AD.
Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by intense pruritus and reduced quality of life. Most patients with AD desire to achieve the most rapid and significant relief (ideally resolution) of symptoms, including pruritus, but in many patients, the disease control is suboptimal. Upadacitinib is a selective JAK1 inhibitor with high and sustained efficacy against both objective and subjective symptoms of AD, as well as rapid onset of action. Thus, it has a potential to meet patients’ expectations and preferences for AD treatment.
- Klíčová slova
- upadacitinib,
- MeSH
- atopická dermatitida * farmakoterapie MeSH
- heterocyklické sloučeniny tricyklické aplikace a dávkování terapeutické užití MeSH
- inhibitory Janus kinas * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- pruritus farmakoterapie MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
Chronický pruritus představuje symptom výrazně snižující kvalitu života pacientů s řadou kožních a systémových onemocnění. O chronickém pruritu hovoříme v případě, že svědění trvá více než 6 týdnů. Modelovým onemocněním s výskytem chronického pruritu je atopická dermatitida. Dlouhodobě byly v terapii chronického pruritu užívány pouze vysoké denní dávky antihistaminik, topické kortikosteroidy a UVB terapie, účinek těchto modalit však nebyl dostatečný. Díky poznání patofyziologického podkladu chronického pruritu však máme k dispozici účinnou cílenou terapii. Svou účinnost v rámci klinických studií a praxe prokazuje monoklonální protilátka dupilumab (anti-IL-4/IL-13), a potom zejména selektivní inhibitory JAK1, které jsou indikovány pro léčbu středně těžké až těžké atopické dermatitidy. Inhibitory JAK1 abrocitinib a upadacitinib vykazují vyšší účinnost při potlačení chronického pruritu a rychlejší nástup účinku v porovnání s dupilumabem. Nově zaváděná terapie přináší klinický prospěch při vysoké bezpečnosti takové léčby. V případě abrocitinibu probíhají klinické studie v rámci indikace prurigo nodularis a idiopatický chronický pruritus.
Chronic pruritus is a clinical symptom that compromises the quality of life in patients with various skin and systemic diseases. Chronic pruritus is a sign of itching lasting more than six weeks. A typical disease connected with chronic pruritus is atopic dermatitis. High daily doses of antihistamines, topical steroids and UVB therapy were therapeutical options for chronic pruritus for decades. However, the clinical effect was poor. Due to intensive research, the pathophysiology of chronic pruritus was described recently. We can design new drugs targeted to the crucial stones of chronic pruritus cascade. The first one was dupilumab - an anti-IL4/IL13 monoclonal antibody. Selective JAK1 inhibitors have been discovered lately. Clinicians use those molecules in the treatment of moderate to severe atopic dermatitis. JAK1 inhibitors abrocitinib and upadacitinib have shown better antipruritic effects compared with dupilumab. Clinical effect was evident in 4 days after the first dose. Abrocitinib is a phase II study also in other indications – prurigo nodularis and idiopathic prurigo. Novel therapies in atopic dermatitis are effective, well-tolerated, and safe therapeutical options.