scholarly journals Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

2021 ◽  
Author(s):  
Mariko Seishima ◽  
Yasuko Yamamoto ◽  
Masashi Sakurai ◽  
Rika Sakai ◽  
Kento Fujii ◽  
...  
Keyword(s):  
High Performance ◽  
Severity Index ◽  
Skin Lesions ◽  
Kynurenine Pathway ◽  
Psoriasis Area Severity Index ◽  
Systemic Inflammatory Disease ◽  
Cytokine Levels ◽  
Uninvolved Skin ◽  
Psoriasis Therapy ◽  
Hydroxyanthranilic Acid

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

Preliminary Validation of the Severity of Nail Psoriasis Score (SNAPS) for the Assessment of Nail Psoriasis in Patients With Psoriatic Arthritis

2021 ◽  
pp. 247553032110114
Author(s):  
Anna Antony ◽  
Sadaf Saeed ◽  
Darren Hart ◽  
Preeti Nair ◽  
Charlotte Cavill ◽  
...  
Keyword(s):  
Severity Index ◽  
Routine Care ◽  
Measurement Properties ◽  
Strong Correlations ◽  
Nail Dystrophy ◽  
Psoriasis Area Severity Index ◽  
Nail Psoriasis ◽  
Outcome Instrument ◽  
Preliminary Validation

Background: Psoriatic nail dystrophy is infrequently assessed in routine care and observational cohorts due to the lack of a feasible validated outcome measure. Objective: To assess the measurement properties of the “Severity of NAil Psoriasis Score” (SNAPS) in PsA. Methods: Nail photography was performed on prospectively recruited patients at baseline and 6 months. The modified Nail Psoriasis Severity Index (mNAPSI) and Physician Nail Visual Acuity Scale (PhNVAS) were comparator instruments for construct validity. Reliability and feasibility were assessed using intra-class correlations (ICCs) and timed scoring. Responsiveness was assessed by correlating the changes in SNAPS, mNAPSI and PhNVAS. Retrospective data from the Bath PsA database was further utilized to assess responsiveness. Results: 21 patients participated in the prospective validation at baseline. Inter- and intra-rater reliability of SNAPS were 0.94 and 0.93-0.96 (p ≤ 0.005). Mean times required to score SNAPS and mNAPSI were 59 and 136 seconds. There were strong correlations between SNAPS and mNAPSI (r = 0.95, p < 0.001) and PhNVAS (r = 0.77, p < 0.001) at baseline. There was a significant reduction in the mNAPSI and SNAPS (p < 0.005) at 6 months and a strong correlation between the change in SNAPS and mNAPSI (rho = 0.838, p < 0.001). Historical data from 57 patients commenced on Etanercept were evaluated. Mean SNAPS reduced from 3.6 to 2.0 at 3 months and 1.2 at 6 months (p < 0.05). Change in SNAPS correlated with changes in Psoriasis Area Severity Index and Dermatology Quality of Life at 3 and 6 months (r≥0.510; p ≤ 0.003). Conclusion: SNAPS is a feasible, reliable and responsive outcome instrument for psoriatic nail dystrophy.

Identifying Top Predictors of Change in Noncalcified Coronary Burden in Psoriasis by Machine Learning Over 1-Year

2021 ◽  
pp. 247553032110007
Author(s):  
Eric Munger ◽  
Amit K. Dey ◽  
Justin Rodante ◽  
Martin P. Playford ◽  
Alexander V. Sorokin ◽  
...  
Keyword(s):  
Machine Learning ◽  
Blood Pressure ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Severity Index ◽  
Blood Cell Count ◽  
Psoriasis Area Severity Index ◽  
Severity Index Score

Background: Psoriasis is associated with accelerated non-calcified coronary plaque burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that worsened NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that improved NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.

scholarly journals The difference of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Bing Wang ◽  
Hui Deng ◽  
Yao Hu ◽  
Ling Han ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Inflammatory Marker ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Severity Index ◽  
Lipid Profiles ◽  
Apolipoprotein A1 ◽  
Concomitant Disease ◽  
Psoriasis Area Severity Index ◽  
Male Patients ◽  
The Difference

Abstract Background Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. Objective To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). Methods In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. Results Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. Conclusion PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. Trial registration ChiCTR2000036192

scholarly journals Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Amira Ben Afia ◽  
Èlia Vila ◽  
Karina S. MacDowell ◽  
Aida Ormazabal ◽  
Juan C. Leza ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
High Performance ◽  
Interaction Analysis ◽  
Kynurenine Pathway ◽  
Psychotic Symptoms ◽  
Post Mortem ◽  
Control Subjects ◽  
Network Interaction ◽  
Hydroxyindoleacetic Acid ◽  
Cortical Circuit

Abstract Background The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

scholarly journals Prospective, Comparative Clinical Pilot Study of Cold Atmospheric Plasma Device in the Treatment of Atopic Dermatitis

2021 ◽  
Author(s):  
Young Jae Kim ◽  
Dong Jun Lim ◽  
Mi Young Lee ◽  
Woo Jin Lee ◽  
Sung Eun Chang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Pilot Study ◽  
Severity Index ◽  
Skin Lesions ◽  
Treated Group ◽  
Atmospheric Plasma ◽  
Clinical Severity ◽  
Control Treatment ◽  
Cold Atmospheric Plasma ◽  
Plasma Device

Abstract Introduction: Cold atmospheric plasma generates free radicals through the ionization of air at room temperature. Its effect and safety profile in patients with atopic dermatitis have not been evaluated prospectively.Objective: We aimed to investigate the effect and safety of cold atmospheric plasma in patients with atopic dermatitis with a prospective pilot study.Methods: Cold atmospheric plasma treatment or sham control treatment were applied respectively in randomly assigned and symmetric skin lesions. Three treatment sessions were performed at weeks 0, 1, and 2. Clinical severity indices were assessed at weeks 0, 1, 2, and 4 after treatment. Additionally, the microbial characteristics of the lesions before and after treatments were analyzed.Results: We included 22 patients with mild to moderate atopic dermatitis presented with symmetric lesions. We found that cold atmospheric plasma can alleviate the clinical severity of atopic dermatitis. Modified atopic dermatitis antecubital severity and eczema area and severity index score were significantly decreased in the treated group. Furthermore, scoring of atopic dermatitis score and pruritic visual analog scales significantly improved. In microbiome analysis revealed significantly reduced proportion of Staphylococcus aureus in the treated group.Conclusion: Cold atmospheric plasma can significantly improve mild and moderate atopic dermatitis without safety issues.

scholarly journals Cytokine levels in persistent skin lesions of adult-onset Still disease

2018 ◽  
Vol 79 (5) ◽  
pp. 947-949 ◽  
Author(s):  
Elina Zuelgaray ◽  
Maxime Battistella ◽  
Marie-Dominique Vignon-Pennamen ◽  
Sophie Ly Ka So ◽  
Michel Rybojad ◽  
...  
Keyword(s):  
Skin Lesions ◽  
Adult Onset ◽  
Cytokine Levels ◽  
Still Disease

scholarly journals Therapeutic Efficacies of Artemisia capillaris Extract Cream Formulation in Imiquimod-Induced Psoriasis Models

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Song Yi Lee ◽  
Suyeong Nam ◽  
Sungyun Kim ◽  
Ja Seong Koo ◽  
In Kee Hong ◽  
...  
Keyword(s):  
Skin Lesions ◽  
The Other ◽  
Epidermal Thickness ◽  
Artemisia Capillaris ◽  
Cream Formulation ◽  
Cumulative Score ◽  
Intracellular Adhesion Molecule ◽  
Psoriasis Therapy ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining

A cream formulation containing Artemisia capillaris (AC) extract (ACE) was developed for psoriasis therapy. Although ACE can be dissolved in organic solvents, its topical application is restricted because of toxicities. Therefore, a cream formulation was developed for the convenient and safe local application of ACE on skin lesions. The antipsoriatic properties of the ACE cream were evaluated using an imiquimod- (IMQ-) induced psoriasis-like mouse model. In psoriasis-like mouse models, the cumulative score (redness, thickness, and scaling) of the IMQ + ACE cream group was significantly lower than those of the other groups on day 4 (p < 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that the epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other experimental groups (p < 0.05). The expression level of intracellular adhesion molecule-1 (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment.

scholarly journals Cost-effectiveness analysis of ixekizumab versus secukinumab in patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis in Spain

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e032552 ◽  
Author(s):  
Bernd Schweikert ◽  
Chiara Malmberg ◽  
Mercedes Núñez ◽  
Tatiana Dilla ◽  
Christophe Sapin ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Cost Effectiveness ◽  
Maintenance Therapy ◽  
Induction Period ◽  
Severity Index ◽  
Cost Effectiveness Analysis ◽  
Severe Psoriasis ◽  
Base Case ◽  
Psoriasis Area Severity Index ◽  
Effectiveness Analysis

ObjectiveTo conduct a cost-effectiveness analysis from the perspective of the Spanish National Health System (NHS) comparing ixekizumab versus secukinumab.DesignA Markov model with a lifetime horizon and monthly cycles was developed based on the York model. Four health states were included: a biological disease-modifying antirheumatic drug (bDMARD) induction period of 12 or 16 weeks, maintenance therapy, best supportive care (BSC) and death. Treatment response was assessed based on both Psoriatic Arthritis Response Criteria (PsARC) and ≥90% improvement in the Psoriasis Area Severity Index score (PASI90). At the end of the induction period, responders transitioned to maintenance therapy. Non-responders and patients who discontinued maintenance therapy transitioned to BSC. Clinical efficacy data were derived from a network meta-analysis. Health utilities were generated by applying a regression analysis to Psoriasis Area Severity Index and Health Assessment Questionnaire‒Disability Index scores collected in the ixekizumab SPIRIT studies. Results were subject to extensive sensitivity and scenario analysis.SettingSpanish NHS.ParticipantsA hypothetical cohort of bDMARD-naïve patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis was modelled.InterventionsIxekizumab and secukinumab.ResultsIxekizumab performed favourably over secukinumab in the base-case analysis, although cost savings and quality-adjusted life-year (QALY) gains were modest. Total costs were €153 901 compared with €156 559 for secukinumab (difference −€2658). Total QALYs were 9.175 vs 9.082 (difference 0.093). Base-case results were most sensitive to the annual bDMARD discontinuation rate and the modification of PsARC and PASI90 response to ixekizumab or secukinumab.ConclusionIxekizumab provided more QALYs at a lower cost than secukinumab, with differences being on a relatively small scale. Sensitivity analysis showed that base-case results were generally robust to changes in most input parameters.Trial registration numberSPIRIT-P1: NCT01695239; Post-results, SPIRIT-P2: NCT02349295; Post-results.

scholarly journals Monitoring and characterization of vibration and shock conditions aboard high-performance marine craft

2018 ◽  
Vol 233 (4) ◽  
pp. 1068-1081
Author(s):  
Manudul Pahansen de Alwis ◽  
Karl Garme
Keyword(s):  
Real Time ◽  
High Speed ◽  
High Performance ◽  
Severity Index ◽  
Irregular Waves ◽  
Vibration Exposure ◽  
Data Set ◽  
Real Time Analysis ◽  
Impact Acceleration ◽  
The Impact

The stochastic environmental conditions together with craft design and operational characteristics make it difficult to predict the vibration environments aboard high-performance marine craft, particularly the risk of impact acceleration events and the shock component of the exposure often being associated with structural failure and human injuries. The different timescales and the magnitudes involved complicate the real-time analysis of vibration and shock conditions aboard these craft. The article introduces a new measure, severity index, indicating the risk of severe impact acceleration, and proposes a method for real-time feedback on the severity of impact exposure together with accumulated vibration exposure. The method analyzes the immediate 60 s of vibration exposure history and computes the severity of impact exposure as for the present state based on severity index. The severity index probes the characteristic of the present acceleration stochastic process, that is, the risk of an upcoming heavy impact, and serves as an alert to the crew. The accumulated vibration exposure, important for mapping and logging the crew exposure, is determined by the ISO 2631:1997 vibration dose value. The severity due to the impact and accumulated vibration exposure is communicated to the crew every second as a color-coded indicator: green, yellow and red, representing low, medium and high, based on defined impact and dose limits. The severity index and feedback method are developed and validated by a data set of 27 three-hour simulations of a planning craft in irregular waves and verified for its feasibility in real-world applications by full-scale acceleration data recorded aboard high-speed planing craft in operation.

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