Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.305
Filtrar
1.
BMC Health Serv Res ; 21(1): 924, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488749

RESUMO

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.


Assuntos
Psoríase , Qualidade de Vida , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica , Humanos , Itália , Estudos Longitudinais , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
2.
Sultan Qaboos Univ Med J ; 21(3): 488-490, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34522419

RESUMO

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system that shares similar immunopathogenic mechanisms with chronic plaque psoriasis, such as the overexpression of the Th17 pathway. We report a 50-year-old male patient with MS and severe chronic plaque psoriasis who presented to Hospital Virgen de la Victoria, Málaga, Spain, in 2019. He was successfully treated with ixekizumab (anti-interleukin [IL]-17A and IL-17A/F monoclonal antibody). The treatment achieved complete skin clearance (i.e. a Psoriasis Area Severity Index 100 response) with no adverse event and no evidence of progression of the neurological disease either.


Assuntos
Fármacos Dermatológicos , Esclerose Múltipla , Psoríase , Anticorpos Monoclonais Humanizados , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
3.
BMJ Open ; 11(9): e047099, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475155

RESUMO

INTRODUCTION: Experimental and clinical data demonstrate that skin diseases like psoriasis are affected by psychological factors and can be modulated by interventions other than conventional drug therapy. The expectation of patients towards the benefit of a forthcoming treatment as well as treatment pre-experiences have been demonstrated as crucial factors mediating placebo responses in inflammatory skin diseases. However, it is unknown whether and to what extent treatment outcomes of psoriasis patients under therapy with monoclonal antibodies like secukinumab can be experimentally modulated at subjective and physiological levels by modifying the expectation of patients via verbal instruction or prior experience. METHODS AND ANALYSIS: Treatment expectations will be modulated in patients with moderate-to-severe psoriasis undergoing treatment with the anti-interleukin-17A monoclonal antibody secukinumab. Patients with a Psoriasis Area and Severity Index (PASI) >12 will be randomly allocated to one of three groups (N=40 each). As a standard schedule, patients in the pharmacological control group (group 1) will be treated weekly with 300 mg secukinumab, while patients in groups 2 and 3 will receive only 75 mg secukinumab (75% dose reduction) during all treatment weeks. In addition to the injections, patients in group 3 will ingest a novel tasting drink, with a cover story explaining that previous studies showed additional beneficial effects of this combination (drug and drink). Patients will be assessed and treated at nine visits over a 16-week period, during which the severity of pain and itch symptoms, skin lesions and quality of life will be analysed with standardised questionnaires and the PASI. ETHICS AND DISSEMINATION: This study was approved by the Ethics committee of the Medical Faculty of the University Duisburg-Essen. Study outcomes will be published in peer-reviewed scientific journals.


Assuntos
Psoríase , Qualidade de Vida , Método Duplo-Cego , Humanos , Motivação , Dor/tratamento farmacológico , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360845

RESUMO

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.


Assuntos
Interleucina-1/imunologia , Interleucinas/uso terapêutico , Psoríase/imunologia , Animais , Humanos , Inflamação , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1/uso terapêutico , Interleucina-33/imunologia , Interleucinas/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Psoríase/tratamento farmacológico , Pele
7.
Front Immunol ; 12: 677957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335579

RESUMO

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Anti-TNF agent was associated with lower rate of hospitalization, as well as lower risks of ventilation, ICU, and death. No significant changes in rates of hospitalization, ventilation, ICU and mortality were observed in patients treated with immunomodulators or biologics apart from anti-TNF agents. The underlying mechanism of these results might be related to pathway of antiviral immune response and cytokine storm induced by SARS-COV-2 infection. Decision on the use of corticosteroids, immunomodulators and biologics should be made after weighing the benefits and potential risks based on individual patients.


Assuntos
Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Psoríase/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2/fisiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , COVID-19/mortalidade , Síndrome da Liberação de Citocina/mortalidade , Hospitalização , Humanos , Imunidade , Doenças Inflamatórias Intestinais/mortalidade , Psoríase/mortalidade , Doenças Reumáticas/mortalidade , Risco , Análise de Sobrevida
8.
S D Med ; 74(8): 363-366, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461001

RESUMO

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.


Assuntos
Artrite Reumatoide , Doença Hepática Induzida por Substâncias e Drogas , Diabetes Mellitus Tipo 2 , Psoríase , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Consenso , Humanos , Metotrexato/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico
9.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445455

RESUMO

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol's effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.


Assuntos
Glicerol/farmacologia , Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , Pele/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Modelos Animais de Doenças , Humanos , Imiquimode/farmacologia , Camundongos , Camundongos Knockout , Fosfolipase D/deficiência , Fosfolipase D/metabolismo , Psoríase/induzido quimicamente , Psoríase/genética , Psoríase/metabolismo
10.
Medicina (Kaunas) ; 57(8)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34441010

RESUMO

Psoriasis is a chronic immunologic disease involving inflammation that can target internal organs, the skin, and joints. The peak incidence occurs between the age of 30 and 40 years, which overlaps with the typical reproductive period of women. Because of comorbidities that can accompany psoriasis, including metabolic syndrome, cardiovascular involvement, and major depressive disorders, the condition is a complex one. The role of hormones during pregnancy in the lesion dynamics of psoriasis is unclear, and it is important to resolve the implications of this pathology during pregnancy are. Furthermore, treating pregnant women who have psoriasis represents a challenge as most drugs generally prescribed for this pathology are contraindicated in pregnancy because of teratogenic effects. This review covers the state of the art in psoriasis associated with pregnancy. Careful pregnancy monitoring in moderate-to-severe psoriasis vulgaris is required given the high risk of related complications in pregnancy, including pregnancy-induced hypertensive disorders, low birth weight for gestational age, and gestational diabetes. Topical corticosteroids are safe during pregnancy but effective only for localised forms of psoriasis. Monoclonal antibodies targeting cytokines specifically upregulated in psoriasis, such as ustekinumab (IL-12/23 inhibitor), secukinumab (IL-17 inhibitor) can be effective for the severe form of psoriasis during pregnancy. A multidisciplinary team must choose optimal treatment, taking into account fetal and maternal risks and benefits.


Assuntos
Transtorno Depressivo Maior , Complicações na Gravidez , Psoríase , Adulto , Anticorpos Monoclonais , Citocinas , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Psoríase/tratamento farmacológico , Psoríase/epidemiologia
11.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207318

RESUMO

Psoriasis (PSO) is a common skin disease that affects about 1%-3% of the general population. It is a great medical, social and economic burden since PSO is associated with many comorbidities, of which the most common are cardiometabolic disorders. Psoriatic patients suffer more frequently from obesity, dyslipidemia, atherosclerosis, and nonalcoholic fatty liver disease. Research shows that lipid expression and metabolism disorders are present more often in such patients. This review focuses on a variety of aberrations in lipids in the skin, blood, and adipose tissue in psoriatic patients and their multifactorial impact on the pathogenesis of psoriasis.


Assuntos
Metabolismo dos Lipídeos , Psoríase/metabolismo , Animais , Humanos , Hipolipemiantes/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/genética , Regulação para Cima
12.
Zhongguo Zhen Jiu ; 41(7): 762-6, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259409

RESUMO

OBJECTIVE: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment. METHODS: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to ashi point (target skin lesions), Zusanli (ST 36), Xuehai (SP 10) and Qihai (CV 6) for 30 min each time, 3 times a week. The control group was treated with calcipotriol ointment (0.25 g each time, once in the morning and evening) on the target skin lesions. Both groups were treated for 8 weeks. The psoriasis area and severity index (PASI) score before and after treatment, main clinical symptoms of TCM score and dermatology life quality index (DLQI) score before and after treatment and 3 and 6 moths follow-up were observed in the two groups; the clinical efficacy after treatment was evaluated and the recurrence rates of the two groups were followed up for 3 and 6 months after treatment. RESULTS: After treatment, the PASI scores in the both groups were lower than before treatment (P<0.01). After treatment and 3 and 6 months follow-up, the main clinical symptoms of TCM scores and DLQI scores of the two groups were lower than those before treatment (P<0.05), and at 3 and 6 months follow-up, those in the observation group were lower than the control group (P<0.01). There was no statistically significant difference between the observation group and the control group in overall effective rate and target skin lesion effective rate (P>0.05). At 3 and 6 months follow-up, the overall recurrence rate and target skin lesion recurrence rate in the observation group were lower than those in the control group (P<0.05). CONCLUSION: Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.


Assuntos
Moxibustão , Psoríase , Pontos de Acupuntura , Humanos , Psoríase/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
13.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 331-337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34281329

RESUMO

Geographic tongue (GT), a form of inverse psoriasis, is frequently linked to plaque psoriasis. The objective of the study is to evaluate IL-17 blocker (secukinumab) effect on GT severity. This reallife, multicenter, retrospective observational pilot study evaluated patients with plaque psoriasis and concomitant GT that started in label treatment with secukinumab. Patients were evaluated twice (T0=baseline and T1=after 16 weeks) by a dentist and a dermatologist collecting data on cutaneous Psoriasis Area Severity Index (PASI) and oral statuses using Hume's classification of the Geographic Tongue Severity Index (GTASI). Twenty-nine psoriatic patients with GT treated with secukinumab were enrolled for the study. Seventeen patients display type I GT, 6 type II and 6 type III with an overall GTASI of 25.52±9.57 at the baseline (T0). No correlation was found between delta GTASI and delta PASI (r=-0.27, p=0.1551). GTASI decrement from T0 to T1 was statistically significant ([95%CI -26.64 to -19.56], t=-13.36, p<0.0001). Secukinumab may enter in GT therapeutic armamentarium as the first biologic IL-17 blocker in patients with concomitant moderate-to-severe plaque psoriasis.


Assuntos
Glossite Migratória Benigna , Psoríase , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Humanos , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Eur J Pharm Sci ; 165: 105956, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314841

RESUMO

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.


Assuntos
Cristais Líquidos , Psoríase , Animais , Hidrogéis , Metotrexato , Camundongos , Psoríase/tratamento farmacológico , Tensoativos , Suínos
15.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201664

RESUMO

The paradigm of psoriasis as a Th17-driven disease has evolved in the last years towards a much deeper knowledge of the complex pathways, mechanisms, cells, and messengers involved, highlighting the crucial role played by the IL-17 family of cytokines. All IL-17 isoforms signal through IL-17R. Five subunits of IL-17R have been described to date, which couple to form a homo- or hetero-receptor complex. Characteristically, IL-17RA is a common subunit in all hetero-receptors. IL-17RA has unique structural-containing a SEFIR/TILL domain-and functional-requiring ACT-1 for signaling-properties, enabling Th17 cells to act as a bridge between innate and adaptive immune cells. In psoriasis, IL-17RA plays a key role in pathogenesis based on: (a) IL-17A, IL-17F, and other IL-17 isoforms are involved in disease development; and (b) IL-17RA is essential for signaling of all IL-17 cytokines but IL-17D, whose receptor has not been identified to date. This article reviews current evidence on the biology and role of the IL-17 family of cytokines and receptors, with focus on IL-17RA, in psoriasis and some related comorbidities, and puts them in context with current and upcoming treatments.


Assuntos
Psoríase/tratamento farmacológico , Psoríase/etiologia , Receptores de Interleucina-17/fisiologia , Anticorpos Monoclonais Humanizados/farmacologia , Humanos , Interleucina-17/imunologia , Interleucina-17/metabolismo , Isoformas de Proteínas
16.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299118

RESUMO

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor expressed in all skin cell types, plays a key role in physiological and pathological processes. Several studies have shown that this receptor is involved in the prevention of inflammatory skin diseases, e.g., psoriasis, atopic dermatitis, representing a potential therapeutic target. We tested the safety profile and the biological activity of NPD-0614-13 and NPD-0614-24, two new synthetic AhR ligands structurally related to the natural agonist FICZ, known to be effective in psoriasis. NPD-0614-13 and NPD-0614-24 did not alter per se the physiological functions of the different skin cell populations involved in the pathogenesis of inflammatory skin diseases. In human primary keratinocytes stimulated with tumor necrosis factor-α or lipopolysaccharide the compounds were able to counteract the altered proliferation and to dampen inflammatory signaling by reducing the activation of p38MAPK, c-Jun, NF-kBp65, and the release of cytokines. Furthermore, the molecules were tested for their beneficial effects in human epidermal and full-thickness reconstituted skin models of psoriasis. NPD-0614-13 and NPD-0614-24 recovered the psoriasis skin phenotype exerting pro-differentiating activity and reducing the expression of pro-inflammatory cytokines and antimicrobial peptides. These data provide a rationale for considering NPD-0614-13 and NPD-0614-24 in the management of psoriasis.


Assuntos
Anti-Inflamatórios/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Catecóis/farmacologia , Diferenciação Celular , Inflamação/tratamento farmacológico , Compostos Organometálicos/farmacologia , Psoríase/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/metabolismo , Pele/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Ligantes , Psoríase/metabolismo , Psoríase/patologia , Pele/metabolismo , Pele/patologia
17.
Nat Commun ; 12(1): 4447, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290243

RESUMO

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1ß, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.


Assuntos
Aminas Biogênicas/farmacologia , Imunomodulação/efeitos dos fármacos , Cinurenina/análogos & derivados , Animais , Aminas Biogênicas/metabolismo , Aminas Biogênicas/uso terapêutico , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Células Endoteliais , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Inflamação , Interferon gama/farmacologia , Cinurenina/metabolismo , Cinurenina/farmacologia , Cinurenina/uso terapêutico , Camundongos , NF-kappa B/metabolismo , Nefrite/tratamento farmacológico , Nefrite/imunologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Triptofano/metabolismo
18.
Biomaterials ; 276: 121027, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293700

RESUMO

Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.


Assuntos
Ácidos Nucleicos Livres , Nanopartículas , Psoríase , Derme , Humanos , Polímeros , Psoríase/tratamento farmacológico , Pele
19.
BMC Res Notes ; 14(1): 253, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193264

RESUMO

OBJECTIVE: Psoriasis is an immune-mediated inflammatory skin disease. It can involve any body skin area, particularly the scalp, lower back, elbows, and knees. There are several topical and systemic therapies for the treatment. Nowadays, herbal medicines are popular treatments for dermatologic conditions. This two-arm parallel, randomized placebo-controlled clinical trial was conducted to examine the hypothesis of the efficacy of Melissa officinalis syrup on patients with mild-to-moderate Plaque psoriasis. RESULT: Among 100 patients, 95 participants completed the trial and five of them withdrew. The mean pruritus intensity and PASI scores decreased significantly in the intervention group compared to the placebo group (P < 0.001). The DLQI score in the intervention group increased post-treatment compared to pre-treatment (P = 0.029); however, there was no significant difference between the intervention and control group at the end of the study (0.065). TRIAL REGISTRATION: The trial was registered in the Iranian registry of clinical trials on November 9th, 2019 ( https://www.irct.ir/trial/43434 ; registration number: IRCT20191104045326N1).


Assuntos
Melissa , Psoríase , Método Duplo-Cego , Humanos , Irã (Geográfico) , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...