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Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation of keratinocytes resistant to apoptosis and inflammation. miR-31 plays pro-proliferative, pro-differentiative and pro-inflammatory roles and modulates apoptosis in psoriatic keratinocytes. Endothelin-1 (ET-1) is produced by psoriatic keratinocytes and suppresses apoptosis. Inflammation increases the production of ET-1, which in turn leads to the chronic stimulation of keratinocyte proliferation. The aim of this study was to identify the putative link between two potential biomarkers (miR-31 and ET-1) in patients with psoriasis. The study design included experimental group (29 patients with psoriasis), and the control group (22 blood donors). The PASI score evaluated the state of the disease (median: 18.6; interquartile range 14.5-20.9). Both, the serum level of ET-1 and the whole blood level of miR-31 were significantly increased (p

Crude coal tar (CCT) contains polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (BaP) is metabolized into a highly reactive metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) that is able to bind to DNA and creates BPDE-DNA adducts. Adducted DNA becomes immunogenic and induces immune response by production of antibodies against BPDE-DNA adducts (Ab-BPDE-DNA). Circulating Ab-BPDE-DNA was proposed as potential biomarker of genotoxic exposure to BaP (PAHs). Goeckerman therapy (GT) of psoriasis uses dermal application of CCT ointment (PAHs). In presented study (children with psoriasis treated by GT; n = 19) the therapy significantly increased the level of Ab-BPDE-DNA (EI = 0.29/0.19–0.34 vs. 0.31/0.25–0.40; median/lower–upper quartile; p < 0.01). The results support the idea of Ab-BPDE-DNA level as a possible tentative indicator of exposure, effects and susceptibility of the organism to the exposure of BaP (PAHs).

Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate – benzo[a]pyrene is metabolized into a highly reactive benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT. For genotyping, droplet digital PCR was applied. The GSTM1 copy number was normalized to β-globin reference gene. In five GSTM1*1/*1 subjects, the GSTM1 to β-globin ratio moved from 0.99 to 1.03 with a median of 1.01. GSTM1*0/*1 heterozygotes (n = 20) contained only one GSTM1 function allele which conditioned the ratio 0.47–0.53 (median 0.50). GSTM1*0/*0 individuals (n = 21) showed no amplification of the null variants because of the large deletion in GSTM1. BPDE-DNA concentrations ranged from 1.8 to 66.3 ng/µg with a median of 12.3 ng/µg. GSTM1*0/*0 and GSTM1*0/*1 genotypes showed non-significantly higher concentrations of BPDE-DNA adducts than the GSTM1*1/*1 one (12.3 and 12.4 vs 7.8 ng/µg). The non-significant relationship between BPDE-DNA adducts and GSTM1 genotypes in psoriatic patients could be associated with relatively low doses of CCT and short-term UV-R exposures used in GT.

Objective: The two main aims of our study were to assess the quality of life (QOL) of patients with moderate or severe psoriasis treated by Goeckerman therapy and to compare QOL of our patients on the date of admission and 1 month after their discharge. Methods: We performed a prospective study on 51 patients treated for chronic plaque psoriasis by Goeckerman regimen (GR). The psoriasis area involvement and severity was measured using the Psoriasis Area and Severity Index (PASI). Patients' health-related QOL was evaluated using Psoriasis Disability Index (PDI). Results: In our study we demonstrated that the QOL of this sample of 51 patients with severe forms of psoriasis was relatively good; an average PDI value on the day of admission was 9.02, which represents a small effect on patient's QOL. We did not find any significant differences in QOL between younger and older respondents or between men and women. Despite good treatment efficiency, we did not find improvement in QOL 1 month after discharge. Conclusions: The QOL of our patients was relatively good. This could be explained by the fact that our patients have been suffering from psoriasis for many years and have probably adapted to their disease. QOL of our patients was not directly dependent on the extent and intensity of skin changes. Further studies on the connection between psoriasis therapy and patients' QOL are still highly needed.

Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6. The range of PASI score in psoriatic patients was 10-34 (median 19). In the patients, we found significantly elevated levels (p

Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI (p<0.05) and diastolic blood pressure (p<0.05) in the psoriatic patients. The values of waist circumference and BMI were significantly higher (p<0.05) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP (p<0.001), Lp-PLA2 (p<0.001), leptin (p<0.01), and resistin (p<0.01) levels in the psoriatic patients. Significantly higher levels of CRP (p<0.01), Lp-PLA2 (p<0.001), leptin (p<0.01), and resistin (p<0.05) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower (p<0.01) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 (p<0.001) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients.

Goeckerman regimen (GR) of psoriasis includes daily dermal application of crude coal tar (CCT) and dermal exposure to UV-A and UV-B radiation. Observed group consisted of 23 patients with psoriasis treated by GR. Therapeutic ointment contained 5% of CCT. The level of psoriasis area and severity index was significantly decreased after GR (P < 0.001) and confirms high efficiency of GR. High levels of selected metabolites of pyrene and phenanthrene indicated high level of dermal penetration. We found significantly increased urinary mutagenicity in samples collected in the middle and in the end of GR (TA98+S9, P < 0.01; YG1041-S9, P < 0.001; YG1041+S9, P < 0.001). Significant increasing of chromosomal aberrations in peripheral lymphocytes (CA) in blood samples collected in the end of GR (P < 0.001) and consecutive decreasing of CA in 78th day after the end of GR has been observed. Almost all results indicated that the patients could be endangered by a peak genotoxic exposure. Nevertheless, the genotoxic effect does not seem to be long lasting. Despite conflicting results from cancer epidemiological studies, it is evident that single GR can contribute to the total load of environmental mutagens in a group of treated patients.

Many of epidemiological studies have certified the relationship between welding and various forms of health damages. In our study we performed an immunological research within a group of twenty men, working in the risky environment of manufacturing of stainless steel constructions (11 welders and 9 grinders, average age was 31 years, 55 % of smokers, average time period in welding occupational exposure was 8 years). The exposed group of men was compared with a group of healthy blood donors, marked as the control group (people with various types of employment, living in same locality as a people from exposed group). People within the control group were not occupationally exposed to harmful chemical compounds (from 30 to 100 men were chosen for the individual immune parameters, average age of the whole group was 38 years, 40 % of smokers). When compared with the control group, the exposed group of welders and grinders showed higher level of C3 complement (p

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

Some specific antibodies indicate the presence of antigenic structures on DNA (DNA adducts) that can play an important role in the process of mutagenesis and/or carcinogenesis. They indicate the presence of increased genotoxic potential (hazard) prior to the formation of disease (primary prevention). The present study was focused on the serum level of benzo[a]pyrene 7,8-diol-9,10-epoxide-DNA adducts antibodies (anti-BPDE-DNA) in psoriatic patients(n=55)dermally exposed to different levels of polycyclic aromatic hydrocarbons (PAHs). The general goal of the study was to contribute to better understanding of the value of the assumed biomarker (anti-BPDE-DNA) for evaluation of the organism's answer to genotoxic exposure to PAHs. Elevated level of exposure to PAHs resulted in the increased level of anti-BPDE-DNA. However, almost all levels of anti-BPDE-DNA ranged within the field of low values. Both variants of GT (CCT-3% and CCT-5%) induced higher expression of anti-BPDE-DNA in the group of nonsmokers. Significant relations between the level of anti-BPDE-DNA and PASI score, total duration of the therapy, or time of UVR exposure were not found. Further studies are needed to reduce interpretation uncertainty of this promising bioindicator.

Background CD163 is the monocyte/macrophage receptor for haptoglobin–haemoglobin complexes. The aim of this study was to assess the kinetics in the expression of CD163 on monocytes and the concentration of soluble sCD163 in serum of psoriatic patients in order to examine the effect of Goeckerman therapy. Methods sCD163 was measured in 71 patients before and after therapy, and in 57 healthy donors. A subgroup of 40 patients and 25 controls was used to assess the expression of membrane CD163. sCD163 was evaluated by ELISA. Flow cytometry method was used to determine the expression of membrane CD163 on monocytes, expressed as mean fluorescence index (MFI). Results Before therapy, the serum level of sCD163 was significantly higher in our patients than in controls ( P = 0.0154). However, we observed a profound decrease in sCD163 in our patients after therapy ( P = 0.0037). Similar to sCD163, pre-treatment expression of CD163 on monocytes was significantly more enhanced in patients than that in controls ( P = 0.0078). There was a trend towards down-regulation of the expression after therapy, nonetheless, the change was not statistically significant compared to the values before therapy ( P = 0.8666). This was also confirmed by comparison with controls which displayed lower expression of CD163 than patients after therapy ( P = 0.0019). The disease activity, expressed as PASI score, was significantly decreased in our patients by GT ( P = 0.0001). Conclusions While sCD163 level in psoriatic patients was diminished after GT therapy, CD163 expression on monocytes was altered only to a minor extent.

Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. Forty otherwise healthy blood donors serve as a control group. The efficacy of GT was delineated by psoriasis area and severity index (PASI). The disease activity was significantly diminished by GT (P < 0.001). The serum levels of both VEGF and bFGF were statistically significantly correlated to PASI value in patients before the treatment by GT. The serum levels of VEGF (329.4 +/- 125.5 microg/ml) and bFGF (10.2 +/- 5.04 pg/ml) in patients before GT were significantly higher than those measured in healthy blood donors (VEGF 236.4 +/- 55.9 pg/ml, bFGF 7.3 +/- 3.7 pg/ ml). The serum levels of both VEGF and bFGF were significantly diminished by GT. The level of VEGF dropped from 329.4 +/- 125.5 pg/ml before GT to 278.5 +/- 109.9 pg/ml after GT (P = 0.0042) and the level of bFGF fell from 10.2 +/- 5.04 to 7.78 +/- 4.5 pg/ml (P = 0.019). Comparing to healthy controls, the serum level of bFGF in psoriasis patients was normalised (P = 0.5723) after GT. In contrast, the serum level of VEGF remained significantly increased in psoriasis patients after GT in comparison with healthy blood donors (P = 0.0319). In conclusion, we found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants, distinguished by genotoxic, hepatotoxic, nephrotoxic and immunotoxic effects. Especially secondary toxicity after bioactivation by microsomal monooxygenases (dependent on cytochromes P450) is characteristic of them. The immunotoxic effect is the result of very global impact on immunological reactivity of an organism and immunosuppression by induction of apoptosis of pre-B lymphocytes represents one of its particular forms. It has been proved that the effect of PAH is caused mostly by the following mechanisms: enzymatic induction by the way of activation of AhR (Aromatic hydrocarbon Receptor); alteration of cellular DNA; development of oxidative stress; increase in the concentration of intercellular calcium and decline of activity of NF-κB (Nuclear Factor – kappa B). Most sensitive to these changes are particularly B-lymphocytic precursors and pre-B lymphocytes. Intensity of entire manifestations is also considerably dependent on the presence and intensity of mechanisms of active or passive resistance of cells.

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density) and CD127low (low molecular density) could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.

Goeckerman’s therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. The aim of this study was to evaluate the influence of Goeckerman’s therapy of psoriasis on the levels of proangiogenic chemokines ENA-78 (CXCL5, Epithelial Cell Derived Neutrophil Attractant- 78), GRO alpha (CXCL1, Growth-Related Oncogene), IL-8 (CXCL8, Interleukin-8), MCP-1 (CCL2, Monocyte Chemotactic (Chemoattractant) Protein 1) and RANTES (CCL5, Regulated on Activation of Normal T Cell Expressed and Secreted) in peripheral blood of 22 children’s patients with psoriasis. 22 otherwise healthy children serve as a control group. The serum levels of chemokines were determined by commercial membrane protein array technique (RayBiotech, USA). Efficacy of Goeckerman’s therapy was delineated by PASI score. Disease activity was significantly diminished by Goeckerman’s therapy (p

Background. Goeckerman’s therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. The aim of study was to evaluate the influence of GT of psoriasis on proinflammatory and angiogenic activities expressed as changes in levels of endoglin (CD105). Methods. Serum levels of a soluble form of endoglin were measured in peripheral blood samples of 38 patients with psoriasis before and after therapy. Sixty three otherwise healthy blood donors serve as a control group. The efficacy of GT was expressed as changes in Psoriasis Area and Severity Index (PASI). Results. PASI score was significantly diminished by GT (p

The welding processes belong among the important sources of occupational pollutions. The welding fumes are ranked, according to the classification of IARC (International Agency for Research on Cancer), into the group of 2B. In our study we have performed the investigation of twenty men (exposed group) working in the stainless steel welding industrial processes (11 welders and 9 grinders, average age was 31 years, 55 % of smokers, average time period of welding occupational exposure was 8 years). The concentrations of chromium (0.557–16.343 mg/m3) and nickel (0.340–10.129 mg/m3) in occupational atmosphere highly exceeded established values of maximum permitted concentrations (0.1 and 1.0 mg/m3, respectively). The concentrations of manganese did not exceed its permitted values. Total concentrations of 12 polycyclic aromatic hydrocarbons (PAH) in occupational atmosphere varied from 300.9 to 961.2 ng/m3. For purposes of biological monitoring, the levels of chromosomal aberrations were determined in the exposed and control group. Healthy blood donors servedas a control group. People from that group were not occupationally exposed to harmful chemical compounds (20 men, average age was 36 years, 40 % of smokers). Increased level of chromosomal aberrations of exposed group brought the evidence about higher genotoxic risk of investigated welding processes.

Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T-cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT, as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001).