ABSTRACT
Apart from chaperoning, disulfide bond formation, and downstream processing, the molecular sequence of proinsulin folding is not completely understood. Proinsulin requires proline isomerization for correct folding. Since FK506-binding protein 2 (FKBP2) is an ER-resident proline isomerase, we hypothesized that FKBP2 contributes to proinsulin folding. We found that FKBP2 co-immunoprecipitated with proinsulin and its chaperone GRP94 and that inhibition of FKBP2 expression increased proinsulin turnover with reduced intracellular proinsulin and insulin levels. This phenotype was accompanied by an increased proinsulin secretion and the formation of proinsulin high-molecular-weight complexes, a sign of proinsulin misfolding. FKBP2 knockout in pancreatic ß-cells increased apoptosis without detectable up-regulation of ER stress response genes. Interestingly, FKBP2 mRNA was overexpressed in ß-cells from pancreatic islets of T2D patients. Based on molecular modeling and an in vitro enzymatic assay, we suggest that proline at position 28 of the proinsulin B-chain (P28) is the substrate of FKBP2's isomerization activity. We propose that this isomerization step catalyzed by FKBP2 is an essential sequence required for correct proinsulin folding.
Subject(s)
Insulin-Secreting Cells , Proinsulin , Proinsulin/metabolism , Protein Folding , Endoplasmic Reticulum/metabolism , Insulin-Secreting Cells/metabolism , Molecular Chaperones/metabolism , Proline/metabolism , Tacrolimus Binding Proteins/genetics , Tacrolimus Binding Proteins/metabolism , Insulin/metabolismABSTRACT
BACKGROUND: Topical drugs are recommended first-line treatment for mild-to-moderate psoriasis. However, patient preferences for the topical drugs differ, since a wide variety of topical drugs and topical drug formulations are available. OBJECTIVES: The aim of this study was to investigate psoriasis patient preferences for topical drugs. METHODS: A systematic literature search was performed for English-language articles in Embase, Medline, PsycINFO, Cinahl, Scopus, and the Cochrane Library. RESULTS: Four surveys, six randomized controlled trials, and two prospective studies of mainly good quality were included. Seven of the studies investigated patient preferences for topical drug formulations, while five studies investigated their preferences for different topical drugs. Overall, patients preferred drugs that are easy to apply, less messy, and have a pleasant scent. CONCLUSION: Psoriasis patient preferences for topical drugs differ. There is no one topical drug or topical drug formulation that suits everyone, which shows the importance of individualized prescriptions for topical drugs that are based on shared decision-making between the prescriber and patient.
Subject(s)
Patient Preference , Psoriasis/drug therapy , Administration, Topical , Humans , Pharmaceutical Preparations/administration & dosage , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Topical medications are first-line treatment for mild-to-moderate psoriasis, but adherence is low, which negatively affects patients' outcomes and quality of life. Nurses can play a central role in patient care, particularly in improving adherence. OBJECTIVES: To explore the experience of dermatology nurses with psoriasis patients' adherence to topical drugs. METHODS: We conducted a semi-structured focus group study with 6 dermatology nurses and 2 dermatology nursing students. Participants were recruited from a dermatology hospital outpatient clinic. Data were analyzed by a systematic text condensation method with a phenomenological-hermeneutic approach. RESULTS: Nurses experienced that factors such as social inequality, patient-centered nursing, and patients' quality of life can have an influence on adherence. CONCLUSION: Optimal adherence to topical treatments is a complex exercise and is influenced by many different factors. Involving nurses when prescribing topical treatments may be beneficial since they are one of the most trustworthy professions and have a holistic view on psoriasis severity, patient preferences, health care resources available and socioeconomic factors.
Subject(s)
Nurses/statistics & numerical data , Patient Compliance , Psoriasis/drug therapy , Quality of Life , Administration, Topical , Adult , Aged , Denmark , Dermatology , Female , Focus Groups , Humans , Male , Middle Aged , Patient Preference , Patient-Centered Care , Pharmaceutical Preparations/administration & dosage , Young AdultABSTRACT
Background: Poor adherence to topical antipsoriatic drugs limits treatment effectiveness.Objective: The aim of this study was to investigate how health care providers may improve psoriasis patients' adherence to topical treatment.Materials and methods: A systematic literature search was performed for English-language articles in Embase, Medline, PsycINFO, Cinahl, Scopus, and the Cochrane Library.Results: Ten studies of varying quality were identified. Two randomized controlled trials (RCTs) testing the adherence-improving potential of interventions by health care providers to support patients showed improvement in adherence to topical treatment. In a prospective study with a pre/postdesign, an individualized, face-to-face consultation reported an improvement in patient-reported adherence to topical treatment over a 9-week period. Based on seven qualitative studies obtaining insights from either patients or health care providers, health care providers may need to address socio-economic factors, health care system factors, and treatment-, patient-, and disease-related factors in interventions that aim to improve the adherence of psoriasis patients to topical antipsoriatic drugs.Conclusion: There is a need to develop better adherence-improving interventions. A good patient-health care provider relationship is considered crucial to adherence and may be an important intervention target. Before interventions to improve adherence to topicals can be recommended for the clinic, the intervention should be tested in high-quality RCTs.
