The Effects of Vitamin D on the Expression of IL-33 and Its Receptor ST2 in Skin Cells; Potential Implication for Psoriasis

Interleukin 33 (IL-33) belongs to the IL-1 family and is produced constitutively by epithelial and endothelial cells of various organs, such as the skin. It takes part in the maintenance of tissue homeostasis, repair, and immune response, including activation of Th2 lymphocytes. Its involvement in pathogenesis of several inflammatory diseases including psoriasis was also suggested, but this is not fully understood. The aim of the study was to investigate expression of IL-33 and its receptor, ST2, in psoriasis, and the effects of the active form of vitamin D (1,25(OH)2D3) on their expression in skin cells. Here we examined mRNA and protein profiles of IL-33 and ST2 in 18 psoriatic patients and healthy volunteers by qPCR and immunostaining techniques. Potential effects of 1,25(OH)2D3 and its receptor (VDR) on the expression of IL-33 and ST2 were tested in cultured keratinocytes, melanocytes, fibroblasts, and basal cell carcinoma cells. It was shown that 1,25(OH)2D3 effectively stimulated expression of IL-33 and its receptor ST2’s mRNAs in a time-dependent manner, in keratinocytes and to the lesser extends in melanocytes, but not in fibroblasts. Furthermore, the effect of vitamin D on expression of IL-33 and ST2 was VDR-dependent. Finally, we demonstrated that the expression of mRNA for IL-33 was mainly elevated in the psoriatic skin but not in its margin. Interestingly, ST2 mRNA was downregulated in psoriatic lesion compared to both marginal tissue as well as healthy skin. Our data indicated that vitamin D can modulate IL-33 signaling, opening up new perspectives for our understanding of the mechanism of vitamin D action in psoriasis therapy

Mediation in criminal, civil and administrative proceedings

Mediacja w ostatnich latach jest instytucją prawną budzącą niezwykle zainteresowanie wśród teoretyków i praktyków różnych gałęzi prawa. Z jednej bowiem strony mediacja jest traktowana jako jeden z alternatywnych sposobów rozstrzygania konfliktów poza drogą sądową, z drugiej natomiast strony w praktyce niezwykle rzadko sięga się po ten instrument. Postępowanie mediacyjne prowadzi się w sposób bezstronny i poufny, a strony mogą odstąpić od mediacji na każdym etapie postępowania. Mediacja jest uregulowana zarówno w postępowaniu w sprawach o przestępstwa i wykroczenia, jak też w postępowaniu cywilnym i administracyjnym. W każdej z tych procedur dostrzegane są zalety oraz wady mediacji, przy czym należy oczekiwać wzrastającego znaczenia tej instytucji. Warunkiem jest jednak wprowadzenie do mediacji w sprawach karnych przepisów, które pozwolą skutecznie zakończyć postępowanie, jeśli strony pojednają się w drodze mediacji.The purpose of this article is the analysis of the institution of mediation as an alternative dispute resolution method in criminal proceedings, including proceedings in cases of misconduct as well as in civil proceedings and administrative proceedings. Mediation is entirely voluntary and either party may at any time refuse further participation in mediation proceedings. Conduct of mediation proceedings is associated with a number of advantages, especially as I was often mentioned the cost savings and the implementation of the principles of economics. The introduction of this institution was primarily to establish an alternative to prosecution, the way to resolve conflicts. In mediation proceedings the parties are equal partners who have a common aim must be to communicate

Vitamin D in the skin physiology and pathology

Vitamin D plays important, pleiotropic role in the maintenance of global homeostasis. Its influence goes far beyond the regulation of calcium and phosphorus balance, as diverse activities of vitamin D and its natural metabolites assure proper functioning of major human organs, including skin. Recently, we reviewed the current understanding of vitamin D impact on human health from historical perspective (Wierzbicka et al. (2014) The renaissance of vitamin D. Acta Biochim Pol 61: 679-686). This article focuses on its functions in the skin. The skin and its appendages, creates a platform connecting and protecting internal organs against, usually harmful, external environment. It uppermost layer - epidermis in order to maintain a protective barrier undergoes a constant exchange of cornified keratinocytes layer. Its disturbance leads to development of serious skin disorders including psoriasis, vitiligo, atopic dermatitis and skin cancer. All of those dermatopathologies have a huge impact on modern societies, affecting not only the physical, but also mental state of patients as well as their social status. Furthermore, multiple human systemic diseases (autoimmune, blood and digestive diseases) have skin manifestation, thus "condition of the skin" often reflects the condition and pathological changes within the internal organs. In humans, the skin is the natural source of vitamin D, which is produced locally from 7-dehydrocholesterol in photoreaction induced by ultraviolet B (UVB) radiation from the sun. It is also well established, that the process of proliferation and differentiation of keratinocytes is tightly regulated by calcium and the active form of vitamin D (1,25(OH)2D3). Thus, the skin physiology is inseparably connected with vitamin D production and activity. Unfortunately, UVB, which is required for vitamin D production, is also known as the main cause of a skin cancer, including melanoma. Here, we are going to review benefits of vitamin D and its analogues in the maintenance of epidermal barrier and its potential use in the treatment of common skin diseases

The renaissance of vitamin D

There is no doubt that vitamin D plays a crucial role in the maintenance of musculoskeletal system. But the function of this ancient molecule presumably ranges far beyond hormone-like regulation, as it could be generated by simple unicellular organisms. First, we are going to discuss the role of vitamin D as a global regulator of homeostasis from a historical perspective, but later we will focus on current views and its relevance to human physiology and pathology. Three milestones are defining the impact of vitamin D on science and humanity. Firstly, discovery that vitamin D is the cure for rickets, brought us supplementation programs and rapid irradiation of this devastating disease. Secondly, detail description of photoproduction of vitamin D, its subsequent metabolism and interaction with vitamin D receptor VDR, provided mechanistic background for future discoveries. Finally, recent large epidemiological studies provided indirect, but strong evidence that optimal level of vitamin D in serum has beneficial effects on our health and protects us from multiple diseases, including cancer. Furthermore, existence of alternative pathways of vitamin D metabolism and multiple intracellular targets broadens our understanding of its physiological activities and offers new and very promising tools for prophylactics and treatment of many diseases of civilization. Although vitamin D (and its derivatives) should not be regarded as a cure-all for every human disease, its beneficial effects on the human health have to be taken under consideration

Experimental research on the thermal properties of innovative insulation boards made of polyurethane-polyisocyanurate (PUR/PIR)

In this work, the results of investigations of polyurethane materials were presented. Innovative materials based on polyurethane-polyisocyanurate (PUR/PIR) foam were obtained. Different types of additives (flame retardants, aerogels – additives that decrease thermal conductivity) are used in the composition of PUR/PIR foam. Foams are a type of composite composed of two phases: continuous (polyurethane polymers) and dispersed (composed of gases). All samples have been tested for thermal parameters: thermal conductivity, specific heat, and thermal diffusivity. Then they have been compared with each other and with a reference sample (RS) without additives. Based on the research, it was shown that innovative insulation materials were characterized by thermal conductivity λ in the range of 0.0254–0.0294 W/(m · K). The thermal properties of foams depending on the type and chemical composition of the material. Depending on the used substrates, their molar ratio, type, synthesis conditions, modifying agents and catalysts, a different polyurethane material is obtained

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Vitamin D is a precursor for secosteroidal hormones, which demonstrate pleiotropic biological activities, including the regulation of growth and the differentiation of normal and malignant cells. Our previous studies have indicated that the inhibition of melanoma proliferation by a short side-chain, low calcemic analog of vitamin D—21(OH)pD is not fully dependent on the expression of vitamin D receptor (VDR). We have examined the effects of classic vitamin D metabolites, 1,25(OH)2D3 and 25(OH)D3, and two low calcemic vitamin D analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98, A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to 1,25(OH)2D3 and became VDR−/−CYP27B1−/−). All tested compounds efficiently inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b, in which only the short side-chain vitamin D analog—21(OH)pD was effective. Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3 and calcipotriol is explained by a lack of characteristic transcripts for the VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On the other hand, the expression of VDR and its splicing variants and other vitamin D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was detected in WM98 and A375 melanomas with the transcript levels being modulated by vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not to require VDR translocation to the nucleus, which explains the high efficacy of this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR−/−. Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy, although the mechanism of its action remains to be defined

Antiproliferative activity of double point modified analogs of 1,25-dihydroxyvitamin D₂ against human malignant melanoma cell lines

Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs

Evaluation of the Early Results of a Loop Stoma with a Plastic Rod in Comparison to a Loop Stoma Made with a Skin Bridge

Loop stoma allows reducing the percentage of anastomotic leak and re-operation caused by this complication. Our department has performed the loop stoma on a skin bridge since 2011. The aim of the study was to evaluate the early results of treatment after the skin bridge loop stoma creation in comparison with the stoma made on a plastic rod. Both groups had 20 patients. Material and methods. The study involved 40 patients with ileostomy, operated 2010-2013. We evaluated 20 patients with a loop ileostomy on a plastic rod, compared to 20 other patients with a skin bridge ileostomy. The study included 24 men and 16 women. Median age was 68.3. All evaluated patients were previously operated due to rectal cancer. Results. It has been shown that the surgical site infection is more common in the group with a plastic rod (5 vs 1 patient). Inflammation of the skin around the stoma occurred in 18 patients (90%) in the first group, while no such complication was found in patients in the second group. The average number of exchanged ostomy wafers was 2,9 per week in the first group of patients, and 1,1 in the second group (p 0,05). Conclusions. The creation of the skin bridge stoma allows for tight fit of the ostomy appliance immediately after surgery completion. The equipment has stable and long-lasting contact with the skin, no skin inflammatory changes occur. Also the surgical site infection rates are lower in this group of patients. As perioperative patient does not require an increased number of ostomy appliance, the cost of treatment can be considered as an important aspect