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Psoriasis and metabolic syndrome (MetS) are chronic inflammatory conditions associated with the dysregulation of immune system reactivity. The inflammatory processes of both diseases have not yet been fully characterized, and the evaluation of proteins/markers that could be involved in their pathogenesis is of great importance. We selected four markers: CRP, sCD200R1, CD5L, and sTLR2; in particular, sCDR2001 has not yet been measured in the context of psoriasis and metabolic syndrome. Material and methods: In the study, 64 controls and 43 patients with psoriasis with or without a metabolic syndrome were enrolled. The levels of selected markers were measured using ELISA kits. Results: CRP levels were significantly higher in psoriasis patients, especially in the subgroup of patients with MetS compared to nonMetS patients (p < 0.01). sCD200R1 and sTLR2 were not significantly different between groups and subgroups; however, CD200R1 levels were slightly higher in both control groups compared to both groups of patients. CD5L levels were significantly higher in patients with MetS compared to nonMets patients (p < 0.02). We also evaluated the correlations between parameters in controls and patients’ groups, as well as in subgroups. Correlations between BMI and CRP were found in all groups and subgroups. Other correlations were group- and subgroup-specific. For example, in the patients’ group, CD5L correlated with sCD200R1 (p < 0.05) and in MetS controls, with age (p < 0.03). Conclusion: The results show that the presence of systemic inflammation associated with psoriasis and metabolic syndrome and their combination alters the expression of specific molecules, especially CRP and CD5L, which were significantly increased in patients with psoriasis and a metabolic syndrome compared to controls without metabolic syndromes. Correlations between CRP and BMI in all groups suggest that overweight and obesity increase the intensity of inflammation and potentiate CD5L expression. In contrast, levels of molecules that may limit inflammation were not increased in psoriasis and metabolic syndrome subjects (they were non-significantly lower compared with healthy controls), which may reflect the chronic nature of both diseases and the exhaustion of inhibitory mechanisms.

Polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) represent genotoxic factors that commonly occur in the living and working environment. The dermal form of exposure represents a significant part of the total load of dangerous chemical and physical environmental factors to which an organism is subjected. However, simultaneous dermal exposures to PAHs (pharmaceutical crude coal tar [CCT]) and UV (UVA and UVB) also have therapeutic uses. A typical example is Goeckerman therapy (GT) for psoriasis. The question of the therapeutic efficacy of GT and the related level of genotoxic danger is still under discussion. The aim of the present study was to compare four GT variants (G1-G4) in terms of efficacy and acceptable genotoxic hazard. Efficacy was expressed by the psoriasis area of severity index (PASI) score, genotoxic hazard by chromosomal aberration in peripheral lymphocytes. The lowest risk of genotoxic hazard and the lowest efficiency was observed in G1 variant (3% of the CCT and UVA + UVB). The efficacy of G2 (4% CCT and UVA + UVB), G3 (4% CCT and UVB), and G4 variants (5% CCT and UVA + UVB) was comparable. The highest risk of genotoxic hazard was found in the G3 variant. In the terms of sufficient efficacy and acceptable genotoxic hazard, a combination of 4% or 5% of CCT and UVA and UVB seems to be acceptable (variants G2 and G4).

Background: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological &ldquo, portfolio&rdquo, of both diseases. Material and methods: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. Results: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. Conclusion: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.

BACKGROUND Goeckerman therapy (GT) of psoriasis involves dermal application of crude coal tar containing polycyclic aromatic hydrocarbons (PAHs) and exposure to ultraviolet radiation (UVR). Little is known about GT influence on DNA epigenetics. OBJECTIVE The study aim was to discover epigenetic mechanisms altered by the exposure related to the GT of psoriasis. METHODS Observed group of patients with plaque psoriasis (n = 23) was treated by GT with 3 % CCT. Before and after GT, we analyzed the levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA), p53 protein in serum, 5-methylcytosine (5-mC, global DNA methylation), and methylation in selected CpG sites of p53 gene. RESULTS We found a significant increase in the levels of BPDE-DNA (p < 0.01) and serum levels of p53 protein (p < 0.01) after GT, and an insignificant decrease in the percentage of 5-mC in peripheral blood DNA. Methylation of p53 CpG sites was affected neither by psoriasis nor by GT. The study confirmed good effectiveness of GT (significantly reduced psoriasis area and severity index; p < 0.001). CONCLUSION Our findings indicate that there is a significantly increased genotoxic hazard related to the exposure of PAHs and UV radiation after GT of psoriasis. However, global DNA methylation and p53 gene methylation evade the effect of GT, as they remained unchanged (Tab. 4, Fig. 3, Ref. 50).

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).

Aims: Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. Methods: The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. Results: The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3.4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. Conclusion: The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.

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.

Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman’s rho = 0.420, p = 0.012) and vitamin B12 (rho = −0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09–55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of 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.

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls.

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls.

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

Background Toll-like receptor (TLR) 2 belongs to the large TLR receptor family comprised of at least 10 members with different roles in innate immunity. Psoriasis is recognized as a T-cell driven immune-mediated systemic inflammatory disease with a skin manifestation. An effective therapeutic approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to assess both the kinetics of the expression of TLR2 on blood cells and the concentration of soluble (s)TLR2 in serum of patients with psoriasis and to examine the effect of GT on both TLR2 expression and sTLR2 level. Methods Both membrane and sTLR2 were determined in 20 patients and 20 healthy controls. sTLR2 was evaluated by enzyme-linked immunosorbent assay. Flow cytometry method was used to determine the expression of membrane TLR2 of monocytes and granulocytes. Results The serum level of sTLR2 was significantly lower (P

BACKGROUND Nucleosomes are complexes that are formed during apoptosis. Psoriasis is a chronic skin disease characterized by keratinocyte hyperproliferation and anti-apoptotic features. Presented study was focused to expression of circulating biomarkers of cell death (circulating nucleosomes, CN) during Goeckerman therapy of psoriasis (UV, PAHs). METHODS In a group of patients with psoriasis (19), treated with Goeckerman regimen (GR), we evaluated their level of CN, level of chromosomal aberration in peripheral lymphocytes (CA), level of urinary 1-hydroxypyrene (1-OHP) and their value of Psoriasis Area and Severity Index (PASI). RESULTS Following the treatment, the serum level of CN and urinary level of 1-OHP (p

The Goeckerman regimen (GR) for the treatment of psoriasis comprises dermal application of crude coal tar (polycyclic aromatic hydrocarbons, PAHs) and exposure to ultraviolet radiation (UVR). PAHs and UVR are mutagenic and carcinogenic agents. We evaluated dermal absorption of PAHs as well as the mutagenic and genotoxic effects of GR in 16 children with psoriasis, by determining levels of 1-hydroxypyrene (1-OHP), 1-,2-,3-,4-hydroxyphenanthrene, (1-OHPhe, 2-OHPhe, 3-OHPhe, and 4-OHPhe), urinary mutagenicity (Salmonella mutagenicity assay, Ames test) and numbers of chromosomal aberrations in peripheral lymphocytes (CA), in urine and/or blood, before and after GR. The Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GR. Compared with pre-treatment levels, there were significant increases in urinary concentrations of 1-OHP (p0.001), 1-OHPhe (p0.001), 2-OHPhe (p0.001), 3-OHPhe (p0.001), and 4-OHPhe (p0.01), indicating a high degree of dermal absorption of PAHs. There were also significantly increased numbers of revertants in the Ames test in two different strains (YG1041-S9, p0.01; YG1041+S9, p0.001; TA98+S9, p0.01), which demonstrates urinary mutagenicity. We also found a significant increase in the number of CA (p0.001) and significantly decreased number of CA (p0.01) at 81 days post-treatment, suggesting that GR has a temporary genotoxic effect. The PASI scores were significantly decreased after GR (p0.001), confirming the clinical benefit of GR. In conclusion, our results demonstrate mutagenic and temporary genotoxic effects of GR in the group of 16 treated child patients.

The Goeckerman regimen (GR) represents a local treatment of psoriasis and includes topical dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV-irradiation. The aim of the study was to evaluate contribution of GR to genotoxic risk and cellular stress in pediatric patients who represent a sensitive population subgroup. Genotoxic risk (42 patients) was evaluated by using chromosomal aberrations (CA) in peripheral lymphocytes. Cellular stress (26 patients) was assessed by using heat shock proteins (Hsp70). All indicators were determined in blood samples collected before GR and immediately after GR. Decreasing of psoriasis area and severity index (PASI) score indicated higher likelihood of GR (p < 0.001). Significantly increased CA (p < 0.001) and Hsp70 (p < 0.05) indicated higher genotoxic risk and cellular stress in sensitive pediatric patients, immediately after GR.

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.

Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D).To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs).The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT.Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p0.01). After the therapy, we found an increased level of oxidative stress (p0.05), an increased level of genotoxic damage (ABC; p0.001), a high efficiency of the treatment (p0.001) and an elevated production of 25(OH)D (p0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p0.01), vitD (p0.05) and the PASI score (p0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p0.05) and between genotoxic damage and the PASI score (p0.05).Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

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.

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).

Summary The Goeckerman regimen (GR) is one of the oldest effective treatments for psoriasis. It involves daily dermal application of crude coal tar with dermal exposure to ultraviolet (UV) radiation. A study was carried out to evaluate the genotoxic risk of GR by comparing p53 protein plasma level and chromosomal aberrations (CA) in peripheral lymphocytes in 33 patients with psoriasis, before and after GR. Psoriasis Area and Severity Index (PASI) was used to evaluate the efficacy of GR. PASI significantly decreased after GR (P

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.

Background The Goeckerman regimen (GR) involves the dermal application of a crude coal tar (polycyclic aromatic hydrocarbon, PAH) and exposure to ultraviolet (UV) radiation. Both PAH and UV radiation exhibit immunosuppressive activity. This study describes the changes in the serum levels of the pro-inflammatory cytokine interleukin-12 (IL-12) and the anti-inflammatory cytokine IL-10 in patients with psoriasis (n = 55) treated with GR. Methods The serum levels of IL-12 and IL-10 were compared before and after GR. In addition, the IL-12 and IL-10 levels in psoriatic patients were compared with those in a control group of healthy blood donors (n = 47). The Psoriasis Area and Severity Index (PASI) was used to evaluate the efficacy of GR. Results When compared with the control group, both IL-12 and IL-10 were significantly higher in psoriatic patients in all cases (P

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.

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

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).

Background Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar [polycyclic aromatic hydrocarbons (PAH)] and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. Methods We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Results Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P