Goeckerman Regimen Reduces Alarmin Levels and PASI Score in Paediatric Patients with Psoriasis.

BACKGROUND: Psoriasis is a chronic systemic inflammatory disease with (extra-)cutaneous manifestations. Inflammation is associated with cellular stress and tissue damage which lead to the release of alarmins (signals of danger). Goeckerman regimen (GR) is a highly efficacious treatment consisting of the application of pharmaceutical crude tar and UVB light exposure. The reduction of inflammatory processes in the skin is accompanied by changes in the levels of inflammatory markers - alarmins (HMBG-1, S100A7, S1000A8, S100A9, S100A12, IL-17, IL-22, and IL-33). METHODS: The alarmin levels in sera of 19 paediatric patients with psoriasis were determined before and after GR using commercial ELISA kits. The Psoriasis area severity index (PASI) was used to determine the disease severity. RESULTS: GR reduced both PASI and the levels of all measured alarmins. The levels of S100A7, S100A9, IL-22, IL-33, and HMGB-1 were significantly decreased. Positive correlations between IL-22 and PASI, between S100A9 and IL-17, S100A9 and IL-22, and a negative correlation between S100A8 and IL-33 were found. CONCLUSIONS: Goeckerman regimen is a very effective, safe and low-cost therapy. We confirmed, it modulates the immune system reactivity, ameliorates the severity of the disease and reduces the levels of alarmins reflecting the presence and intensity of inflammation.

SAMPA: A free software tool for skin and membrane permeation data analysis.

Skin and membrane permeation experiments comprise an important step in the development of a transdermal or topical formulation or toxicological risk assessment. The standard method for analyzing these data relies on the linear part of a permeation profile. However, it is difficult to objectively determine when the profile becomes linear, or the experiment duration may be insufficient to reach a maximum or steady state. Here, we present a software tool for Skin And Membrane Permeation data Analysis, SAMPA, that is easy to use and overcomes several of these difficulties. The SAMPA method and software have been validated on in vitro and in vivo permeation data on human, pig and rat skin and model stratum corneum lipid membranes using compounds that range from highly lipophilic polycyclic aromatic hydrocarbons to highly hydrophilic antiviral drug, with and without two permeation enhancers. The SAMPA performance was compared with the standard method using a linear part of the permeation profile and a complex mathematical model. SAMPA is a user-friendly, open-source software tool for analyzing the data obtained from skin and membrane permeation experiments. It runs on a Microsoft Windows platform and is freely available as a Supporting file to this article.

Neural stem cells transplanted into intact brains as neurospheres form solid grafts composed of neurons, astrocytes and oligodendrocyte precursors.

Neural stem cells (NSCs) are tissue-specific stem cells with self-renewal potential that can give rise to neurons and glia in vivo and in vitro. The aim of this study was to transplant NSCs as whole neurospheres into intact brain and assess the fate and phenotype of their progeny generated in vivo. We isolated NSCs from E14 foetal rat forebrains and cultured them in basic fibroblast and epidermal growth factor-supplemented serum-free medium in the form of neurospheres in vitro. Neurospheres were transplanted into the intact brains of 2 Wistar rats and after a period of 3 weeks, grafted brains were examined immunohistochemically. Neurospheres formed solid grafts that were found in the lateral ventricle and in the velum interpositum under the hippocampus. The majority of cells in the transplanted tissue were identified as beta-III-tubulin(+), NeuN(+), PanNF(+) and synaptophysin(+) neurons and were accumulated throughout the graft centre. GFAP(+) astrocytes were scattered throughout the entire graft and astrocyte processes delimited the outer and perivascular surfaces. A great number of NG2(+) oligodendrocyte precursors was detected. Nestin(+) endothelial cells were found to line capillaries growing in the transplant. These data indicate that nestin(+) NSCs prevailing in neurospheres differentiate following transplantation into nestin(-) neuronal and glial cells which confirms the multipotency of NSCs. Three weeks posttransplantation neuronal and astrocyte cells reached terminal differentiation (formation of synaptic vesicles and superficial and perivascular limiting membranes) while elements of oligodendroglial cell lineage remained immature. Grafting stem cells as non-dissociated neurospheres provide cells with favourable conditions which facilitate cell survival, proliferation and differentiation. However, in the intact brain, grafted neurosphere cells were not found to integrate with the brain parenchyma and formed a compact structure demarcated from its surroundings.