C-reactive protein, chemerin, fetuin-A and osteopontin as predictors of cardiovascular risks in persons with psoriasis vulgaris.

The study aimed to contribute to understanding the role of CRP, chemerin, fetuin-A and osteopontin and to assess their suitability as biomarkers of early stages of cardiovascular diseases in psoriasis vulgaris. Serum levels measured in 28 patients and 22 controls. Patients: increased levels of CRP (p<0.001), chemerin (p<0.05), osteopontin (p<0.05) and decreased levels of fetuin-A (p<0.05), significant relationships between CRP and fetuin-A (rho=0.530, p<0.01), CRP and chemerin (rho=0.543, p<0.01), CRP and age (rho=0.590, p<0.001), osteopontin and fetuin-A (r=-0.415, p<0.05), chemerin and PASI score (rho=-0.424, p<0.05). We confirmed specific roles of the biomarkers in psoriasis. CRP, fetuin-A and osteopontin could be considered appropriate markers for the detection of early stages of cardiovascular diseases.

Variation of selected genotoxic and epigenetic markers due to therapeutic exposure to PAHs and ultraviolet radiation.

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).

Serum Levels of Aryl Hydrocarbon Receptor, Cytochromes P450 1A1 and 1B1 in Patients with Exacerbated Psoriasis Vulgaris.

The aryl hydrocarbon receptor (AhR) is highly expressed in psoriasis skin lesions. The aim of this study was to investigate serum concentrations of AhR, cytochromes P450 (CYP) 1A1 and 1B1 in patients with exacerbated psoriasis vulgaris treated with combined therapy of ultraviolet radiation (UVR) and crude coal tar. The analyses were performed by using enzyme-linked immunosorbent assays. Before the treatment, the patients had significantly higher serum levels of AhR and CYP1A1 than healthy controls. AhR median noticeably decreased after the therapy; nevertheless, it remained significantly higher compared to the controls. CYP1A1 levels measured before and after the therapy did not differ significantly. Serum CYP1A1 positively correlated with AhR values before and after the treatment. The serum values of CYP1B1 were very low and we did not see any differences between the study group and the control group. The study demonstrated that serum levels of AhR and CYP1A1 could indicate their immunopathological and metabolic roles in exacerbated psoriasis.

Roles of miR-31 and endothelin-1 in psoriasis vulgaris: pathophysiological functions and potential biomarkers.

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<0.001 and p<0.05, respectively) in patients compared to the controls. However, a significant negative relationship between ET-1 and miR-31 was observed (Spearman's rho=-037, p=0.05). It is possible that a negative feedback loop will be present between miR-31 and ET-1. Our results indicate that miR-31 and ET-1, potential biomarkers of the disease, play significant roles in the pathophysiology of psoriasis.

Elevated levels of circulating biomarkers of cell death (nucleosomes) in the patients with plaque psoriasis treated with the Goeckerman regimen.

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<0.05) were significantly increased (p<0.01). We found significant correlation between CN and urinary level of 1-OHP after GR (r=0.57; p<0.05). Immediately after the treatment we found significantly increased total numbers of abnormal chromosomes (ABB; p<0.01) and structurally abnormal chromosomes (SAB; p<0.05). CONCLUSIONS: We found slightly (but statistically significant) elevated level of circulating biomarkers of cell death (nucleosomes) in patients with plaque psoriasis treated with GR (PAHs, UV radiation). We suppose that elevated level of CN is a result of combination of the positive effects of GR and its weak genotoxic effect (mainly PAHs). Conclusions are supported by significant correlation between CN and urinary level of 1-OHP after GR and significantly elevated level of CA after GR (Tab. 2, Fig. 1, Ref. 28).

Expression of soluble sCD163 in serum of psoriatic patients is modulated by Goeckerman therapy

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, CD163expression on monocytes was altered only to a minor extent (AU)

Expression of soluble sCD163 in serum of psoriatic patients is modulated by Goeckerman therapy.

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.

Plasma levels of p53 protein and chromosomal aberrations in patients with psoriasis treated with the Goeckerman regimen.

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 < 0.001), confirming the excellent efficacy of the treatment, However, significant increases in level of p53 protein (P < 0.05) and CA (P < 0.001) after treatment indicates that this method carries an increased genotoxic risk in patients with psoriasis.

Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy.

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.

Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8.

Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation. When compared with the control group (healthy blood donors), the patients before GT had significantly increased serum levels of sE-selectin (p<0.001), sP-selectin (p<0.001), sICAM-1 (p<0.001) and IL-8 (p<0.001). Significantly decreased serum levels of sE-selectin (p<0.05) and significantly increased serum levels of IL-8 (p<0.05) were found after GT therapy. Serum levels of sICAM significantly correlated with the disease activity and with serum levels of sE-selectin. The level of PASI score (Psoriasis Area and Severity Index) significantly decreased after GT (p<0.001) and confirms the high efficiency GT. These findings confirmed that pro-inflammatory chemokine (IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1) play an important role in the development and regulation of inflammation in psoriasis. Determination of sE-selectin and sICAM seems to be a promising marker of psoriasis's activity. Chemokine pathway (IL-8) and TNF-alpha activity seem to be modulated by Goeckerman's therapy (polycyclic aromatic hydrocarbons).

Cytogenetic and immunological changes after dermal exposure to polycyclic aromatic hydrocarbons and UV radiation.

Goeckerman's therapy (GT), which combines exposure to coal tar (polycyclic aromatic hydrocarbons - PAHs) and UV radiation (UV) is often used as the first option for treatment of psoriasis. However, PAHs and UV represent mutagenic, carcinogenic and immunotoxic agents. Therefore GT can represent a health risk for the patients. The group under observation consisted of thirty patients undergoing GT. Before and after the treatment, blood samples were collected and chromosomal aberrations and selected immunological markers were determined. The relationships between chromosomal aberrations and immunological markers and the extent (duration) of exposure to GT were evaluated. The Psoriasis Area and Severity Index (PASI) score confirmed the high efficacy of GT. However, significantly elevated levels of chromosomal aberrations of peripheral lymphocytes were also found after the therapy (p<0.001). The levels of chromosomal abnormalities correlated to the extent and the total duration of exposure to PAHs (r = 0.682, p<0.01 and r = 0.605, p<0.05). After the therapy, significantly decreased levels of IgE, IgM isotypes of immunoglobulin, alpha(2)-macroglobulin and transferrin together with beta(2)-microglobulin were found. From the immunological markers listed above only the decreased level of alpha(2)-macroglobulin correlated to the extent of exposure to PAHs (r = -0.568, p<0.05). No correlation was found between chromosomal aberrations, significantly changed immunological markers and the duration of UV exposure. Our study revealed that GT has a significant impact on both genetic and immunological parameters of psoriatic patients. The results indicate that GT could increase genotoxic risk and modulates immunity of treated patients.

Possible genotoxic risk of combined exposure to pharmaceutical coal tar and UV-B radiation.

Goeckerman's therapy of psoriasis combines exposure to pharmaceutical coal tar and UV-B radiation. In the pilot study (15 patients had been diagnosed with psoriasis, the average time period in hospital therapy was 24 days, the average age of the patients was 29 years, 47% of them were smokers) a level of genotoxic risk from therapy was evaluated by using chromosomal aberration of peripheral lymphocytes. The study suggested the presence of an increased genotoxic risk from the therapy. The PASI scores (Psoriasis Area and Severity Index) were monitored.

[New findings in monitoring health status of welders and grinders of stainless steel]. / Novejsí zkusenosti se sledováním zdravotního stavu svárecu a brusicu nerezových ocelí.

During the occupational preventive care check up we investigated a group of 20 stainless steel welders and grinders in the factory producing technology for chemical industry. Results have been compared with 21 healthy persons--blood donors. In the group exposed there have not been discovered any marked deviations in either their health status, or in the CBC and biochemical screening results, though there had been found substantially increased chromium and nickel concentrations, mainly in grinders. Also the levels of polycyclic aromatic hydrocarbons were in some cases even higher than on the busy city crossing. The chromosome aberrations investigations proved to be very sensitive and confirmed that employees of the followed up factory are exposed to an increased genotoxic risk.

Monitoring of occupational exposure in manufacturing of stainless steel constructions. Part I: Chromium, iron, manganese, molybdenum, nickel and vanadium in the workplace air of stainless steel welders.

Exposure to workplace airborne pollutants was examined in a group of 20 workers dealing mainly with welding, polishing, drilling and assembling of stainless steel constructions. Airborne particulate matter (APM) collected using both personal and stationary samplers was analyzed by instrumental neutron activation analysis (INAA). Quality assurance procedures of both sampling and analytical stages are described. Of the elements determined, results are presented for chromium, iron, manganese, molybdenum, nickel and vanadium. The median values of element concentrations exceeded the maximum admissible limits for workplace pollutants only for chromium, while for nickel the limit was exceeded in several individual cases. Sampling of hair, nails, blood, urine and saliva to be used for biological monitoring of the exposed and control groups is also described.

[Polycyclic aromatic hydrocarbons. II. Toxic effects]. / Polycyklické aromatické uhlovodíky. II. Toxické úcinky.

Polycyclic aromatic hydrocarbons (PAH) represent dangerous environmental pollutants. Many of them have toxic and carcinogenic potential. Presented work summarizes most of available data on the absorption, metabolism and elimination of PAH. The second part of article contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. In the third part of article, the populations with higher susceptibility to exposure to PAH are described and the influences of chemical interaction of PAH to biological effects are mentioned.

[Polycyclic aromatic hydrocarbons. Biological indicators of exposure and possibilities of prevention]. / Polycyklické aromatické uhlovodíky. III. Biologické ukazatele expozice a moznosti prevence.

Polycyclic aromatic hydrocarbons (PAH) represent an extensive group of ubiquitous environmental pollutants disposing of a considerable toxic and carcinogenic potential. According to the IARC data (International Agency for Research on Cancer), PAH represent the largest group of chemical carcinogens produced during combustion, pyrolysis and pyrosynthesis of organic matter. PAH can be identified in atmosphere, water, soil, food and other materials which are in daily contact which the general population. Presented work summarizes most of available data on the biological markers used to identify or quantify the exposure to PAH and on the biological markers used to characterize the effects caused by PAH. The digest of possibilities of reduction toxic effects of PAH concludes the work.

[Effect of polycyclic aromatic hydrocarbons on the immune system]. / Vliv polycyklických aromatických uhlovodíku na imunitní systém.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous compounds in our environment. They are formed during incomplete burning of coal, oil, gas, wood, garbage or other organic substances such as tobacco and charbroiled meat. PAHs enter the environment mostly as releases to air from volcanoes, forest fires, residential wood and coal burning and exhaust from automobiles and trucks. There are more than 100 different PAHs. Some of them have danger toxic properties including mutagenic and carcinogenic potential. Since 1993 PAHs are classified as the compounds which can cause immunosuppression. They reduce the body resistance against infection and cancer diseases. Immunosuppressive, carcinogenic and hypersensitivity effects of some PAHs representatives were described well in experimental studies. On the other hand, only sporadic information about immunological changes after long-term occupational exposure to PAHs were found from existing human epidemiological database. In addition, these studies usually did not cover the complex immunological profile represented by cellular and humoral activity.

[Health status of persons occupationally exposed to chromium, nickel, manganese and polycyclic aromatic hydrocarbons]. / Zdravotní stav osob profesionálne exponovaných chromu, niklu, manganu a polycyklickým aromatickým uhlovodíkum.

Occupational environment monitoring and biological-medical monitoring of persons professionally exposed to welding fumes have been performed. Chromium, manganese and polycyclic aromatic hydrocarbons in welding fumes represents an important health risk. Pollutant concentrations found in metal welding fumes represented only fractions of those acceptable ones. Polycyclic aromatic hydrocarbons have been reached the concentration found in a busy road crossing in Hradec Králové (compared with these as in Czech Republic no maximum acceptable levels for PAHs having been declared). Family, personal and occupational history have been taken. Health state including total haematological count, biochemical and cytogenetical changes of 19 stainless steel welders were checked-up. The level of mercapturates in urine were examined as well. The data were statistically compared with those of non exposed (control group). No changes witnessing the above mentioned risk factors influence on the haematological, biochemical and cytogenetical findings were ever proved. In conclusion, our results did not confirm an increased professional risk in this group of welders.

[Biological monitoring of occupational exposure in welders of stainless steel. Immunologic methods]. / Biologické monitorování pracovní expozice u svárecu nerezových ocelí. Imunologické metody.

Biological monitoring of occupational exposure to toxic compounds enables an early detection of adverse health effects. Apart from the standard biological monitoring methods of occupational exposure represented by metabolites and enzymes activities analysis also immunological detection methods seem to be promising. The changes of immunological system are demonstrable extraordinary sensitive markers of load of organism. The process of welding belongs between important sources of pollution of working environment with heavy metals and other harmful compounds including polycyclic aromatic hydrocarbons. According to IARC classification the welding fumes are included into group 2B and are supposed as possible human carcinogens. Numbers of different epidemiological studies have proved relationship between welding and serious health disorders namely malignancies. We recorded a number of changes in immunological parameters when compared with those in control group in our study. The results of analysis were statistically evaluated. The statistically significant reduction of number of phagocytosis capable cells was found in the group of welders when compared with the control group. The levels of neopterin, beta-2-microglobulin and IL-1 beta have indirectly monitored cell component of immunological response. In the case of these markers a statistically significant increases were found in the group of welders. We found statistically significant IgM decrease and statistically significant IgA increase in humoral responses with the same group when compared with control group.

[Effect of acute exposure to SO2 on cellular defense mechanisms in the lung (pilot study)]. / Ucinek akutní expozice SO2 na celulární obranné mechanismy plic (pilotní studie).

Sulphur dioxide is one of the most important and most frequent atmospheric pollutant of our environmental setting. In presented pilot-study we describe the influence of acute exposure to sulphur dioxide on alveolar macrophages of guinea pigs. The alveolar macrophages represent the main part of mononuclear phagocytic system, which is responsible for the defence of respiratory tract against foreign compounds. The experimental animals were exposed over three hours to sulphur dioxide with the concentration of about 400 ppm. After exposure we did not find significant changes in phagocytic activity of alveolar macrophages.