Circulating Endothelial Progenitor Cells in Kidney Transplant Patients

Background: Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs. Methods: We analyzed 52 RTx patients (58613 years; 33 males, mean 6 SD) and 16 age- and gender-matched subjects with normal kidney function (57617; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry. Results: Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1 – a cytokine responsible for EPC mobilization – is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1. Conclusions: We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients.

Исследование изменений твёрдости поверхности при азотировании сталей

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed

The effectiveness of antibacterial therapeutic clothing compared with non-antibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: A randomized controlled, observer-blind pragmatic trial (ABC trial)

BACKGROUND Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation, however its role in the management of AD remains poorly understood. OBJECTIVE To investigate the effectiveness of antibacterial therapeutic clothing plus standard topical treatment in patients with moderate-to-severe AD, compared to standard therapeutic clothing plus standard topical treatment. If effectiveness is demonstrated, the cost-effectiveness will be evaluated. METHODS A pragmatic, double-blinded, multicenter, randomized, controlled, trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1:1:1 to receive standard therapeutic clothing, antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes, topical corticosteroid use, SA colonization, safety, and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed model analyses. RESULTS Between March 16, 2020, and December 20, 2021, 171 patients were enrolled. In the analyses 159 patients were included (n=54 in the standard therapeutic clothing group, n=50 in the chitosan group and n=55 in the silver group). Adherence was high (median: 7 nights/week, IQR: 3-7). Median EASI scores at baseline, 4, 12, 26 and 52 weeks were in the standard therapeutic clothing group 11.8, 4.3, 4.6, 4.2, 3.6 compared to 11.3, 5.0, 3.0, 3.0, 4.4 in the chitosan and 11.6, 5.0, 5.4, 4.6 and 5.8 in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing, chitosan (-0.1, 95%CI: -0.3 to 0.2, p=0.53), and silver group (-0.1, 95%CI: -0.3 to 0.2, p=0.58) were found. However, a small significant (P=0.035) group-by-time interaction effect between the standard and silver group was found, in which the silver group performed worse after 26 weeks. No differences between groups were found in patient-reported outcomes, topical corticosteroid use, SA skin colonization, and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20:Joint results of the ESSCA(A) and the EBSB working groups of the ESCD, and the GEIDAC(C)

Background In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. Objectives To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. Methods Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Espanol de Investigacion en Dermatitis de Contacto y Alergia Cutanea. As patch test outcome, reactions between day (D) 3 and D5 were considered. Results Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. Conclusions Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of theESSCAnetwork, 2015-2018

BACKGROUND Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen

Thermography and thermoregulation of the face

BACKGROUND: Although clinical diagnosis of thermoregulation is gaining in importance there is no consistent evidence on the value of thermography of the facial region. In particular there are no reference values established with standardised methods. METHODS: Skin temperatures were measured in the facial area at 32 fixed measuring sites in 26 health subjects (7–72 years) with the aid of a contact thermograph (Eidatherm). A total of 6 measurements were performed separately for the two sides of the face at intervals of equal lengths (4 hours) over a period of 24 hours. Thermoregulation was triggered by application of a cold stimulus in the region of the ipsilateral ear lobe. RESULTS: Comparison of the sides revealed significant asymmetry of face temperature. The left side of the face showed a temperature that was on the average 0.1°C lower than on the right. No increase in temperature was found following application of the cold stimulus. However, a significant circadian rhythm with mean temperature differences of 0.7°C was observed. CONCLUSION: The results obtained should be seen as an initial basis for compiling an exact thermoprofile of the surface temperature of the facial region that takes into account the circadian rhythm, thus closing gaps in studies on physiological changes in the temperature of the skin of the face

Patch test results with the European baseline series, 2019/20-Joint European results of the ESSCA and the EBS working groups of the ESCD, and the GEIDAC

BACKGROUND Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. OBJECTIVES To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. METHODS Anonymised or pseudonymised individual data, and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. RESULTS In 2019 and 2020, 22581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 (19.2-20.4)% positivity (95% confidence interval)). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43-7.19)% and 6.62 (6.25-7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 (2.16-2.85)% vs. 1.59 (1.33-1.88)); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 (3.16-3.82)%), followed by 2-hydroxyethyl methacrylate (2.32 (2.0-2.68)%). CONCLUSIONS Ongoing surveillance on the prevalence of contact sensitization contributes to an up-to-date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe. This article is protected by copyright. All rights reserved