Characterization of dry skin associating with type 2 diabetes mellitus using a KK-Ay/TaJcl mouse model

Purpose: Type 2 diabetes mellitus (DM) induces various dermatological conditions that can affect patient quality of life, including increased susceptibility to skin infections and dry skin. While the mechanisms that underlie the causes of dry skin in type 1?DM have been widely studied, how type 2?DM elicits similar effects is unclear. The purpose of this study was therefore to evaluate skin barrier and hydration function using a KK-A^y/TaJcl mouse model of type 2?DM.

Materials and methods: KK-A^y/TaJcl and control mice were housed separately for 4 weeks and then body weight, water intake, urine production, and blood glucose levels were measured. Skin barrier function was estimated by assessing transepidermal water loss (TEWL) and hydration levels of the stratum corneum. The expression levels of various skin biochemical factors were also examined by western blot, including type 1 collagen, mast cell tryptase, hyaluronic acid binding protein (HABP), and fibroblast protein S100A4.

Results: Compared to control mice, there was a marked increase in body weight, water intake, urine production, and blood glucose levels in the KK-A^y/TaJcl mice over the length of the experiment. Hydration levels in the stratum corneum were lower in KK-A^y/TaJcl mice compared to control mice, although TEWL was not significantly different between groups. We also found that hyaluronic acid binding protein expression was higher in KK-A^y/TaJcl mice, although other biochemical factors were the same.

Conclusions: These findings suggest that hyaluronic acid associates with the dry skin caused by type 2?DM. This contributes to understanding this phenomenon and may lead to better treatment options for patients in the future.     

滚轮微针处理次数对药物皮肤渗透、分布及皮肤刺激性的影响

目的 考察用于皮肤促透研究的滚轮微针处理次数。方法 以维A酸为模型药物,Franz扩散池、组织匀浆法研究裸鼠皮肤的促透效果,用亚甲蓝染色法、激光共聚焦显微镜法等考察裸鼠皮肤的药物分布,经皮水分流失（TEWL）测量法、激光多普勒血流量法评价皮肤刺激性。结果 滚轮微针处理次数为1、3、5、8、10次时,处理次数越多,促透效果越好,皮肤中滞留药量也越高,但是皮肤中滞留药量在处理8次和10次时无显著性差异（P>0.05）。亚甲基蓝染色和激光共聚焦实验均显示处理次数增加,针孔分布均匀度提高;亚甲基蓝染色显示,处理5次以上时,出现部分针眼重叠而皮肤破损现象。在体皮肤内药物吸收实验显示处理1次时,裸鼠皮肤中滞留药量均匀性较差,但是处理3次以上时,皮肤中滞留药量均匀性明显改善。TEWL测量法显示处理5次以下,皮肤屏障功能恢复时间为24 h,处理8次以上为36 h。激光多普勒血流量法显示处理5次以下,皮肤屏障功能恢复时间为1 h,处理8次以上为2 h。结论 滚轮微针处理5次可确保裸鼠皮肤促透研究的安全性和有效性。     

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations

Abstract

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220–350?nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (～13?000 cps). Drugs were localized in stratum corneum?+?epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.     

Short term study of human skin irritation by single application closed patch test: assessment of four multiple emulsion formulations loaded with botanical extracts

Background: Assessment of skin irritation potential is a major concern in safety assessment of cosmetics, when long-term use of these products are expected. Non-invasive bioengineering probes have been used previously to measure skin irritation potential of cosmetic ingredients.

Objectives: Experimentation carried out to weigh up the skin irritation potential of four multiple emulsion formulations via visual and non-invasive measurements. Immediate effects of formulations and comparison of two assessment techniques were also tried to establish.

Methods: Four multiple emulsion formulations one control (without botanical active) and three containing the functional botanical actives plus additives were tested in this study using the following techniques: transepidermal water loss (TEWL), COLIPA visual scoring method (CVSM), Mexameter MPA 5 (Courage + Khazaka, Germany) and capacitance [Corneometer MPA 5 (Courage + Khazaka, Germany)]. Visual examination and non-invasive measurements were performed at baseline and after 24?h. The formulations were applied on the forearm of 12 healthy volunteers of same sexes aged 20–25 years.

Results: We found that none of the formulation produced irritation both on visual and instrumental evaluation. However, formulations MeB and MeC have comparable immediate effects on dryness, erythema, melanin and TEWL. Formulation MeC produced more effective results on different parameters, may be due to synergistic effect of two extracts, while MeA failed to produce any immediate effects on skin parameters. Moreover results of both assessment methods are parallel to each other.

Conclusions: None of the formulation produce irritant effects, barrier impairment effects or immediate effects except for the formulation MeC which produced appreciable results than other formulations but statistically these results were insignificant (p?>?0.05). Based on these results, it could be concluded that formulations may be implied safely as skin rejuvenating candidates.     

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized,split-face,open-label,single-center study

Background: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme.

Objectives: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne.

Materials and methods: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28?days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time.

Results: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p?>?0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p?>?0.05).

Conclusion: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.     

A cross-sectional retrospective assessment of anti-arthritic drugs in patients with arthritis in Korea

SUMMARY

Background: Selective cyclo-oxygenase-2 (COX-2) inhibitors were recently introduced for the treatment of arthritis because of their lower rates of gastrointestinal adverse events compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs).

Objective: To examine the medication usage patterns for both osteoarthritis (OA) and rheumatoid arthritis (RA) in Korea.

Methods: The medical charts of a convenience sample of 402 patients with OA or RA were reviewed by the Arthritis Study Group in 14 hospitals and ten clinics in Korea.

Results: Traditional oral NSAIDs were the most commonly prescribed drugs for OA (68.3%) and RA (65.1%) patients. Two-thirds (66.7%) of the RA patients taking COX-2 inhibitors were prescribed

other arthritis medications concurrently and 85.1% of RA patients taking NSAIDs were prescribed other arthritis medications concurrently. Patients on NSAIDs were almost twice as likely to have a gastroprotective agent (GPA) concurrently compared to COX-2 inhibitor users (OA patients 38.1% vs 21.2%; RA patients 57.9% vs 30.6%). Overall, patients taking COX-2 inhibitors were less likely to take GPAs concurrently compared to patients not taking COX-2 inhibitors (unadjusted OR 0.36; adjusted OR 0.39).

Conclusions: Traditional oral NSAIDs were commonly prescribed to arthritis patients in Korea. In this study, patients taking COX-2 inhibitors were prescribed less adjunctive arthritis treatments and less gastroprotective agents than traditional oral NSAID users.     

Spirodela polyrhiza extract modulates the activation of atopic dermatitis-related ion channels,Orai1 and TRPV3, and inhibits mast cell degranulation

Context: Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash.

Objective: The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated.

Materials and methods: The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100?μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100?μg/mL SH extract.

Results: SH extract (100?μg/mL) significantly inhibited Orai1 activity (63.8?±?0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29?±?0.05% at ?100?mV) compared with the positive control 2-APB (100?μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14?±?0.03, 2.56?±?0.12 and 2.29?±?0.08?mU/mg, respectively).

Conclusion: Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.     

Elevated levels of soluble Endothelial protein C receptor in rheumatoid arthritis and block the therapeutic effect of protein C in collagen-induced arthritis

BackgroundEndothelial protein C receptor (EPCR) is a membranous protein that can be combined with a variety of ligands and plays important roles in anticoagulant and anti-inflammation. Recent reports have shown that surface EPCR expression on T cells is negatively associated with Th17 differentiation and is co-expressed with other immunosuppressive molecules, such as The programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Hence, we hypothesized that EPCR may play a critical role in rheumatoid arthritis (RA) disease progression that is mediated by Th17 differentiation. In order to explore the role of EPCR on RA disease pathogenesis, we detected membranous EPCR (mEPCR) expression in CD4⁺ T cells and soluble EPCR (sEPCR) expression in the sera of RA patients.MethodsThe proportion of CD4⁺/EPCR⁺ T cells in the peripheral blood of RA patients was detected by flow cytometry, and the expression of sEPCR in the sera of RA patients was detected by enzyme-linked immunosorbent assay (ELISA). For in vitro experiments, protein C (PC) and EPCR recombinant proteins were used to block peripheral blood mononuclear cell (PBMC) activation and to detect Th17 differentiation. For in vivo experiments in DBA/1 mice with collagen-induced arthritis (CIA), we administered PC and EPCR recombinant proteins, monitored disease progression, and evaluated the role of EPCR in disease progression.ResultsThe proportion of CD4⁺/EPCR⁺ T cells in the peripheral blood of RA patients was lower than that of osteoarthritis (OA) patients, while the expression level of sEPCR in the sera of RA patients was concomitantly higher than that in OA patients. Subsequent analysis revealed that sEPCR expression was positively correlated with rheumatoid factors (RF) and other inflammatory indicators in RA patients. Further studies confirmed that sEPCR administration alleviated the progression of collagen-induced arthritis and partially blocked the therapeutic effect of PC in CIA mice.ConclusionSoluble EPCR is associated with RA disease progression and induces disease remission in CIA mice by inhibiting Th17 differentiation.     

Transepidermal water loss for probing full-thickness skin barrier function: Correlation with tritiated water flux, sensitivity to punctures and diverse surfactant exposures

Skin barrier function is a key parameter to consider when performing in vitro percutaneous absorption studies. Whilst tritiated water flux measurements were often used to assess skin integrity, recent decades have witnessed the emergence of the more rapid and user-friendly transepidermal water loss (TEWL) approach. Yet to date, the nature of the correlation between TEWL and skin barrier function in vitro has still not been comprehensively established. In this study, a novel TEWL device, operating on a cold-induced vapour sink principle, was used to probe the barrier function of full-thickness porcine skin. The method was sufficiently sensitive to show the influence of punctures on barrier function although the observed non-linear pattern suggested tissue swelling processes and/or capillary action could be occurring. The results of various surfactant application experiments strongly suggested that TEWL was indeed largely predictive of skin sample integrity. A key finding was that basal TEWL was linearly correlated with basal tritiated water flux (r² = 0.80, n = 63). Thus, a dedicated TEWL method can be used as a good alternative to water flux measurements for assessing full-thickness skin barrier function.     

CPT,the main test method of skin neuronal sensitivity

Background: Many scholars concentrate on skin barrier disruption of sensitive skin, but few focus on its increased neuronal sensitivity.

Objective: To study the possibility of using current perception threshold (CPT) measurement for the quantitative evaluation of skin neuronal sensitivity combined with stinging test.

Methods: The amount of 50?μL 10% lactic acid was applied on each side of the nasolabial fold at random. Subjects assessed stinging based on a 4-point scale at 30?s, 2.5?min and 5.0?min. CPT and transepidermal water loss (TEWL) were measured before and after stinging test. Subjects were divided into different groups based on their response to lactic acid.

Results: There was a positive correlation between CPT_before and the sum of clinical scores (CSs). While the beginning time of stinging (BT) was shortened, the CPT_before decreased and TEWL increased.

Conclusion: Different degrees of skin susceptibility can be reflected by BT. CPT can be useful for the quantitative evaluation of skin neuronal sensitivity.     

Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation

Objective: Rheumatoid arthritis (RA) is associated with chronic inflammation. The suppression of inflammation is key to the treatment of RA. Glucocorticoids (GCs) are classical anti-inflammatory drugs with several disadvantages such as poor water solubility and low specificity in the body. These disadvantages are the reasons for the quick elimination and side effects of GCs in vivo. Micelles are ideal carriers for GCs delivery to inflamed synovium. We set out to improve the targeting and pharmacokinetic profiles of GCs by preparing a targeting micelle system.

Methods: In this study, natural chlosterol (CC) and folic acid (FA) were used to fabricate polysialic acid (PSA) micelles for the targeted delivery of Dexamethasone (Dex). The biodistribution and therapeutic efficacy of the resulting micelles were evaluated in vitro and in vivo.

Results: PSA-CC and FA-PSA-CC micelles showed a size below 100?nm and a moderate negative charge. PSA-CC and FA-PSA-CC micelles could also enhance the intracellular uptake of Dex and the suppression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vitro and in vivo. Arthritis mice showed reduced paw thickness and clinical arthritis index using PSA-CC and FA-PSA-CC micelle treatment. Micellized Dex demonstrated a 4?～?5 fold longer elimination half-life and a 2?～?3 folds higher bioavailability than commercial Dex injection. FA modification significantly improved the anti-inflammatory efficacy of PSA-CC micelles.

Conclusion: FA-PSA-CC micelles demonstrated significant advantages in terms of the suppression of inflammation and the treatment of inflammatory arthritis. These reliable and stable micelles possess a high potential to be transferred for clinical use.     

Impact of collagen-induced arthritis on the pharmacokinetic disposition of voriconazole,a widely used antifungal agent: in vitro and in vivo investigations in DBA/1J mice

1. Pharmacokinetics of voriconazole, an anti-fungal agent, was determined in collagen-induced arthritic (CIA) and healthy DBA/1J mice. CIA was confirmed in DBA/1J mice by clinical scoring and histological analysis.

2. In vivo oral pharmacokinetic study (3?mg/kg) and in vitro stability assessment in liver microsomes were performed in CIA vs. healthy DBA/1J mice. Additionally, hepatic portal vein cannulated (HPVC) CIA and healthy mice were used to clarify the role of gut first-pass effect. Voriconazole/N-oxide metabolite was measured in plasma and in vitro samples using liquid chromatography tandem-mass spectrometry method.

3. Voriconazole exposure was reduced in CIA by 27% as compared to healthy mice. Formation of voriconazole N-oxide was higher in CIA mice as evidenced by higher molar C_max ratio (i.e. metabolite/parent) of 2.08 vs. 1.66 in healthy mice. Because voriconazole was stable in microsomes, involvement of presystemic gut metabolism was suspected for decreased voriconazole exposure and formation of higher molar ratio of metabolite. HPVC work revealed higher formation of voriconazole N-oxide in CIA relative to healthy mice resulting in C_max/AUC ratios of 0.41/0.54 and 0.08/0.17, respectively, confirming first-pass effect.

4. The findings may have implications in the clinical therapy of arthritis patients who are concomitantly given voriconazole for the management of fungal infections.

     

Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus

ABSTRACT

Introduction. Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine with upstream regulatory roles in innate and adaptive immunity and is implicated in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several classes of MIF inhibitors such as small molecule inhibitors and peptide inhibitors are in clinical development.

Areas covered. The role of MIF in the pathogenesis of RA and SLE is examined; the authors review the structure, physiology and signaling characteristics of MIF and the related cytokine D-DT/MIF-2. The preclinical and clinical trial data for MIF inhibitors are also reviewed; information was retrieved from PubMed and ClinicalTrials.gov using the keywords MIF, D-DT/MIF-2, CD74, CD44, CXCR2, CXCR4, Jab-1, rheumatoid arthritis, systemic lupus erythematosus, MIF inhibitor, small molecule, anti-MIF, anti-CD74, and peptide inhibitor.

Expert opinion. Studies in mice and in humans demonstrate the therapeutic potential of MIF inhibition for RA and SLE. MIF- directed approaches could be particularly efficacious in patients with high expression MIF genetic polymorphisms. In patients with RA and SLE and high expression MIF alleles, targeted MIF inhibition could be a precision medicine approach to treatment. Anti-MIF pharmacotherapies could also be steroid-sparing in patients with chronic glucocorticoid dependence or refractory autoimmune disease.     

甘草酸铵调控IL-33/ST2通路对特应性皮炎小鼠肥大细胞活化的影响

目的 研究甘草酸铵对特应性皮炎（AD）小鼠IL-33/ST2通路及肥大细胞的活化情况的影响。方法 72只ICR小鼠（雌雄各半）随机均分为对照组、模型组及甘草酸铵低、中、高剂量（25、50、100 mg/kg）和泼尼松龙（阳性药,60 mg/kg）组。除对照组外,以丙酮-DNCB为致敏源构建AD小鼠模型,建模后各组ip相应药物,对照组和模型组ip生理盐水。记录小鼠夜间搔抓次数;甲苯胺蓝患处皮肤组织染色法观察肥大细胞活化情况;ELISA法检测白细胞介素（IL）-33和ST2血清学水平;实时荧光定量PCR（qRT-PCR）和Weston blotting法检测皮肤组织中的IL-33和ST2 mRNA和蛋白水平。结果 与对照组比较,模型组小鼠的搔抓次数显著增多（P<0.05）,肥大细胞密度显著升高（P<0.05）,IL-33和ST2的血清学水平、皮肤组织的转录水平和蛋白表达水平均显著升高（P<0.05）;与模型组比较,泼尼松龙组和甘草酸铵低、中、高剂量组的搔抓次数和肥大细胞密度分别显著减少和降低（P<0.05）,IL-33、ST2的血清学水平、皮肤组织mRNA和蛋白表达均显著降低（P<0.05）。结论 甘草酸铵能够明显抑制AD模型小鼠IL-33和ST2的血清学水平、皮肤组织中的转录水平和蛋白表达,降低了肥大细胞的活化程度,从而减轻AD的瘙痒症状。     

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis.

Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments.

Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment.

Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.     

Use of topical corticosteroids and topical calcineurin inhibitors for the treatment of atopic dermatitis in thin and sensitive skin areas

ABSTRACT

Background: Atopic dermatitis (AD) is a common, chronic skin disorder characterized by itch and dry skin, which can develop into pruritic red plaques that ooze when scratched. AD flares often occur in anatomic areas where the skin is naturally thin (the face, neck, and intertriginous zones). Such regions, especially the face, are also areas of sensitive skin and need special consideration when being treated.

Objective: This article will briefly review the concepts of thin and sensitive skin and discuss the treatment of AD in such areas.

Methods: The MEDLINE database was searched for English-language articles published that contained the text terms atopic dermatitis, sensitive skin, treatment, topical corticosteroids, or topical calcineurin inhibitors. Articles that pertained to the safety and efficacy of various treatments were selected for further review.

Results: Topical corticosteroids (TCSs) are effective for the treatment of AD in thin and sensitive skin areas, but their use is limited due to adverse events, such as skin thinning, and the potential for impairing the skin barrier. Topical calcineurin inhibitors (TCIs) also provide effective AD treatment without impairing the skin barrier or inducing skin thinning. Although TCIs may be associated with a higher incidence of application-site reactions such as pruritus and skin burning, these symptoms are typically transient and mild to moderate in nature.

Limitations: This analysis focused primarily on relatively recent key trials evaluating the treatment of AD in sensitive skin; due to the limited number of controlled trials evaluating TCS agents, consensus statements and comprehensive review articles were used for most of the information pertaining to this therapeutic option.

Conclusions: Although both TCSs and TCIs have a place in a long-term, comprehensive treatment strategy for AD, TCIs may have a particular use in thin and sensitive skin areas.     

In vivo antibacterial activity of Garcinia mangostana pericarp extract against methicillin-resistant Staphylococcus aureus in a mouse superficial skin infection model

Context: Garcinia mangostana Linn. (Guttiferae) (GM) pericarp has been shown to exhibit good in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); however, there is currently no available information regarding its in vivo antibacterial activity.

Objective: To examine in vivo antibacterial activity of G. mangostana extract against MRSA.

Materials and methods: GM pericarp was extracted by ethanol (GM-EtOH) and methanol (GM-MeOH). The crude extracts were examined for in vitro antibacterial activity against MRSA using broth microdilution assay. The in vivo antibacterial activity of 10% GM-EtOH against MRSA was determined in a tape stripping mouse model of superficial skin infection for 9 days by evaluating transepidermal water loss (TEWL) and performing colony counts from cultured swabs.

Results: GM-EtOH showed greater in vitro activity against MRSA than GM-MeOH in broth microdilution assay with minimum inhibitory concentration 17 versus 20?μg/mL and minimum bactericidal concentration 30 versus 35?μg/mL, respectively. The GM-EtOH (13.20?±?0.49%) contained α-mangostin more than the GM-MeOH (9.83?±?0.30%). In the tape stripping mouse model, 10% GM-EtOH reduced the number of MRSA colonies (0–1) recovered from infected wounds (>100 colonies) on the first day of treatment, restored TEWL to normal levels on the fourth day, and had completely healed the wounds by day 9.

Conclusion: GM-EtOH showed promising in vivo antibacterial activity against MRSA in a superficial skin infection model in mice. It is of interest to develop a topical formulation of GM-EtOH to further study its potential as a novel antibacterial agent.     

Psoriatic arthritis: current therapy and future directions

Introduction: Psoriatic arthritis (PsA) once regarded as an auto-inflammatory arthritis that involves the skin is proving to be more complex with a different driver of disease process compared to rheumatoid arthritis. As growing differences emerge between PsA and rheumatoid arthritis so have the experiences and responses to therapeutics used in both disease processes.

Areas covered: This review highlights articles of interest in the past 10 years in the OVID and PubMed database and focuses on major concepts regarding current disease-modifying anti-rheumatic drugs in PsA as well as newer target agents.

Expert opinion: Presently, it is agreed upon that use of tumor necrosis factor inhibitors (TNFi) has greatly changed our ability to manage varying aspects of disease in PsA. However, there remain many unanswered questions in which research in PsA is mirroring RA work, these include: i) the need for outcome measures that are more specific to PsA, ii) the concept of early and treat to target, iii) the role of highly sensitive imaging, and iv) efficacy of combination therapy and further targets in those unable to tolerate or fail TNFi.     

Has dry/cold weather an impact on the skin condition of cleanroom workers?

ABSTRACT

In previous epidemiological studies irritant skin changes were reported significantly more frequently under dry/cold ambient air conditions. The aim of this study was to assess whether a similar effect might be observed in cleanroom workers, occupationally exposed to strictly controlled ambient conditions. This investigation examined 690 employees of a semiconductor production company in Germany, one half in winter (n = 358) and the other half in spring (n = 332). In both waves, both cleanroom workers, who used occlusive gloves predominantly during the entire shift, and employees in the administration, serving as the control group, were included. Ambient outdoor temperature and relative humidity (RH) were measured and absolute humidity (AH) was calculated. Hands were dermatologically examined with quantitative clinical skin score HEROS, supplemented by transepidermal water loss (TEWL) and stratum corneum hydration measurements. Temperature ranged from –5.41 to 6.51°C in winter (RH 71.04–92.38%; AH 2.85–6.7 g/m³) and from 6.35 to 10.26°C in spring (RH 76.17–82.79%; AH 5.66–7.92 g/m³). Regarding HEROS, TEWL, and corneometry, no marked consistent pattern regarding an enhanced or decreased risk of irritant skin changes was found. Work in a strictly controlled environment with prolonged wearing of occlusive gloves, with clean hands and without exposure to additional hazardous substances, did not seem to negatively affect the skin. In this particular setting, meteorological conditions also did not appear to adversely affect the skin. It is conceivable that wearing of gloves and air conditioning in the plant protect skin of the hands from adverse effects due to dry and cold air encountered when not working.     

Increased healthcare resource utilization in higher disease activity levels in initiators of TNF inhibitors among US rheumatoid arthritis patients

Objective: Determine healthcare resource utilization (HCRU) in biologic-naïve initiators of TNF inhibitors (TNFis) associated with their disease activity from a national cohort of rheumatoid arthritis (RA) patients.

Methods: RA patients were identified at their first TNFi initiation (index date) in the Corrona registry. Patients with age of RA onset <18, comorbid psoriasis/psoriatic arthritis, fibromyalgia, or osteoarthritis were excluded. Patients were categorized into disease activity (DA) strata by the lowest level of DA (and sustaining low levels for at least two visits) using the Clinical Disease Activity Index (CDAI) across all visits in Corrona while on a TNFi during 1 year after initiation. Rates of all-cause and RA-related hospitalizations, rheumatologist visits, and joint surgeries while on TNFi therapy were reported and compared across DA levels along with the incidence rate ratio (IRR) adjusted for age, gender, and RA duration using Poisson mixed models.

Results: Of 1931 RA patients: 15% achieved sustained remission, 22% remission, 14% sustained low DA, 23% low DA and 27% moderate/high DA (M/HDA). Those in M/HDA had statistically higher rates of hospitalizations (37.3 per 100 patient years (py), 95% CI: 31.6–43.7 and joint surgeries (20.8 per 100 py, 95% CI: 16.6–25.8) compared to the sustained remission cohort, resulting in respective IRRs of 2.3 (p?<?0.001) and 1.7 (p?=?0.046).

Conclusion: Many biologic naïve RA patients initiating TNFi failed to achieve sustained remission during a 1 year period while remaining on TNFi therapy. Patients in higher DA levels had higher HCRU rates vs. patients in sustained remission, suggesting that achieving treat-to-target goals would reduce health care expenses.