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This study is the first to assess redox balance, glutathione metabolism, and oxidative damage to RNA/DNA, proteins, and lipids in the plasma/serum and urine of patients with adrenal masses. The study included 70 patients with adrenal tumors divided into three subgroups: incidentaloma ( n = 30 ), pheochromocytoma ( n = 20 ), and Cushing’s/Conn’s adenoma ( n = 20 ), as well as 60 healthy controls. Blood and urine samples were collected before elective endoscopic adrenalectomy. Antioxidant defense capacity was significantly decreased (serum/plasma: superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), uric acid (UA); urine: SOD, GSH, UA) in patients with adrenal masses. The oxidative damage to proteins (advanced glycation end products (AGE), advanced oxidation protein products (AOPP)) and lipids (lipid hydroperoxides (LOOH), and malondialdehyde (MDA)) was higher in the plasma and urine of these patients. Plasma MDA and DNA/RNA oxidation products, with high sensitivity and specificity, can help to diagnose pheochromocytoma. This biomarker differentiates patients with pheochromocytoma from Cushing’s/Conn’s adenoma as well as from heathy controls. Plasma RNA/DNA oxidation was also positively correlated with urine metanephrine. Oxidative stress can play a crucial role in adrenal tumors. However, further studies are required to clarify the role of redox signaling in adrenal masses.

Background: Psoriasis is an immune-mediated chronic inflammatory disease with cardiometabolic comorbidities. Fatty acid binding protein 5 (FABP5) is elevated in human psoriatic keratinocytes and could be potentially involved in systemic metabolic disturbances. The aim of the study was to evaluate serum FABP5 in psoriatic patients, to assess the relationship between FABP5 and the duration, severity of the disease, inflammatory and metabolic markers and influence of treatment with narrowband - ultraviolet B (NB-UVB). Methods: Seventy four patients with active plaque-type psoriasis and 30 healthy controls were enrolled in the study. Thirty patients were treated with NB-UVB. Patients were divided into subgroups based on their disease severity measured by Psoriasis Area and Severity Index (PASI) and Body Mass Index (BMI). The serum concentrations of FABP5 were measured using commercially available Human FABP5 Enzyme-Linked Immunosorbent Assay kit. Total serum fatty acids content and composition was measured by gas–liquid chromatography. Results: Serum FABP5 levels in psoriatic patients (both obese and non-obese) were higher versus control group (P 20 was higher compared to the mild group (PASI P P P P=0.007). Conclusion: FABP5 is a potential marker of psoriasis, its severity and clinical outcome after therapy with NB-UVB. FABP5 may reflect metabolic disturbances and might be the missing link between psoriasis and metabolic disturbances.

Introduction Psoriasis is a chronic inflammatory disease associated with metabolic disturbances and liver dysfunction. Both serum fatty acids (FA) and ceramides (Cer) have structural functions but also are signal molecules that could be involved in the pathogenesis of liver dysfunction. Aim To assess the concentration of the circulating FA and Cer in correlation with the alanine aminotransferase (ALT) blood level in psoriatic patients. In addition, we have examined the relationship between ALT concentration and severity of the disease and inflammation markers. Material and methods Eighty-five patients with psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 2 groups according to ALT blood levels. Serum concentration of 14 FA and 14 Cer were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile, and inflammatory markers. Results We observed higher PASI score (p = 0.01) and higher C-reactive protein (p = 0.02) concentration in the group of psoriatic patients with high ALT. Serum ALT positively correlated with saturated fatty acids (SFA) (p = 0.01, r = 0.27) and SFA/unsaturated fatty acids (UFA) ratio (p = 0.01, r = 0.26). ALT negatively correlated with UFA level (p = 0.008, r = –0.28). Lignoceric ceramide positively correlated with ALT level (r = 0.22; p = 0.045) in psoriatic patients. Conclusions Patients with severe psoriasis are predisposed to the development of liver dysfunction. We have demonstrated disturbances of serum fatty acid and sphingolipid profile in psoriatic patients, which may trigger liver disease.

Barbara Choromańska,1 Piotr Myśliwiec,1 Tomasz Kozłowski,1 Magdalena Łuba,1 Piotr Wojskowicz,1 Jacek Dadan,1 Hanna Myśliwiec,2 Katarzyna Choromańska,3 Katarzyna Makarewicz,4 Anna Zalewska,5 Mateusz Maciejczyk6 1 1st Department of General and Endocrine Surgery, Medical University of Bialystok, Bialystok, Poland; 2Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland; 3Department of Oral Surgery, Medical University of Gdansk, Gdansk, Poland; 4Regional Centre for Transfusion Medicine in Bialystok, Bialystok, Poland; 5Experimental Dentistry Laboratory, Medical University of Bialystok, Bialystok, Poland; 6Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Mateusz Maciejczyk Email mat.maciejczyk@gmail.comBackground: Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing’s/Conn’s adenoma).Methods: The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05).Results: We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO− and IL-1β depended on cortisol level, while ONOO−, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing’s or Conn’s adenoma.Conclusion: Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.Keywords: adrenal tumors, nitrosative stress, nitric oxide, peroxynitrite, S-nitrosothiols, nitrotyrosine, myeloperoxidase, interleukin 1 beta, tumor necrosis factor, α hypoxia-inducible factor

Introduction Psoriasis is a chronic inflammatory disease associated with metabolic syndrome, including obesity. Ceramides (CER) and sphingosine-1-phosphate (S1P), which belongs to sphingolipids, have both biological and structural functions in the human epidermis. Aim To evaluate serum concentrations of selected CER in psoriatic patients in different weight ranges, the impact of obesity on the concentration of circulating CERs, their association with the course of psoriasis and selected inflammatory markers. Material and methods Eigthy-five patients with active plaque-type psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 3 groups: normal weight, overweight and obese. Serum concentrations of 14 ceramides were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile and inflammatory markers. Results There were no significant differences in total serum CER concentration between psoriatic groups of patients. The S1P concentration was higher in psoriatic patients with normal body weight and overweight than in the control group (p = 0.002 and p = 0.04, respectively). In psoriatic patients with normal body weight, nervonic ceramide (C24:1) correlated with PASI (r = 0.38; p = 0.042) and CRP (C-reactive protein) (r = 0.42; p = 0.023). In overweight patients, the concentration of lignoceric ceramide (C24:0) correlated inversely with the severity of the disease (r = -0.41; p = 0.022) and CRP (r = -0.6; p = 0.0004). Conclusions We have demonstrated an abnormal sphingolipid profile in psoriatic patients in different weight groups. Selected CER might be the biomarkers of psoriasis severity and inflammation, may reflect lipid disturbances and contribute to the development of metabolic syndrome.

Psoriasis is a systemic disease associated with metabolic syndrome and cardiometabolic diseases. Adipocyte fatty acid-binding protein (A-FABP, FABP4) is a relevant mediator of lipid metabolism and several comorbidities development. Aim of the study was to explore the possible role of FABP4 in psoriasis and assess its relationship with disease activity, inflammation or metabolic disturbances, and impact of systemic treatment. Fasting blood samples were obtained from 33 patients with active plaque-type psoriasis before and after 12 weeks of therapy and from 11 healthy volunteers. Serum FABP4 concentrations were analyzed by the enzyme-linked immunosorbent assay (ELISA) and statistically analyzed for their correlations with clinical outcomes and the treatment introduced. Serum FABP4 levels were significantly increased in psoriatics compared to controls (p = 0.03). No relationship between the protein and psoriasis severity expressed through psoriasis area and severity index (PASI) was noted (p = 0.57). FABP4 did not correlate with CRP (p = 0.41), lipid profile, and body mass index (BMI) nor the glucose level or liver enzyme activity. FABP4 significantly correlated with morphotic blood elements. After total therapy, FABP4 did not statistically change (p = 0.07), but significantly decreased after administering acitretin (p = 0.03). FABP4 is a potential marker of psoriasis and clinical outcome after therapy with acitretin. Adipocyte-type FABP may be related to hematological disorders or obesity-mediated comorbidities in psoriasis.

The assessment of total antioxidant activity seems to have a higher diagnostic value than the evaluation of individual antioxidants separately. Therefore, this is the first study to assess the total antioxidant/oxidant status in morbidly obese patients undergoing bariatric surgery. The study involved 60 patients with Class 3 obesity (BMI &gt, 40 kg/m2) divided into two equal subgroups: morbidly obese patients without and with metabolic syndrome. The analyses were performed in plasma samples collected before surgery as well as 1, 3, 6, and 12 months after a laparoscopic sleeve gastrectomy. Total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP), DPPH (2,2&prime, diphenyl-1-picrylhydrazyl) radical assay, and total oxidant status (TOS) were significantly higher before surgery (as compared to the healthy controls, n = 60) and generally decreased after bariatric treatment. Interestingly, all assessed biomarkers correlated positively with uric acid content. However, the total antioxidant/oxidant potential did not differ between obese patients without metabolic syndrome and those with both obesity and metabolic syndrome. Only DPPH differentiated the two subgroups (p &lt, 0.0001, AUC 0.8) with 73% sensitivity and 77% specificity. Plasma TAC correlated positively with body mass index, waist&ndash, hip ratio, serum insulin, and uric acid. Therefore, TAC seems to be the best biomarker to assess the antioxidant status of obese patients.

Psoriasis, affecting 2–4% of the world’s population, is a chronic recurrent inflammatory skin disease. Its multifactorial aetiopathogenesis consists of, for example, abnormal epidermal proliferation, immune disturbances, and genetic, psychosomatic, environmental and hormonal factors. Psoriasis is also considered to be a systemic disorder closely associated with cardiovascular diseases, atherosclerosis, diabetes mellitus, obesity or metabolic syndrome. Lipids have a variety of biological functions. They participate not only in energy storage and expenditure or the formation of cell membranes, but also in inflammatory and metabolic signalling pathways. Disturbances in their homeostasis lead to the development of immunometabolic disorders, including psoriasis. Based on the available literature, this article presents selected molecular and clinical aspects involved in the multidirectional effect of lipids on psoriasis.

Psoriasis is characterized by keratinocyte resistance to apoptosis. We recently demonstrated an increase in serum tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in patients after topical treatment for psoriasis. We decided to verify whether narrowband ultraviolet B (NB-UVB) has a similar effect. Serum concentration of TWEAK was estimated in patients with exacerbated plaque psoriasis treated with NB-UVB. Baseline TWEAK levels were similar in patients with psoriasis and healthy controls, and Psoriasis Area and Severity Index (PASI) correlated inversely with TWEAK levels. Treatment with NB-UVB caused a significant reduction in PASI and concurrent increase in serum TWEAK. This finding may be due to increased expression of TWEAK receptor in psoriatic skin, which has been reported previously, with consequent binding of excess soluble TWEAK during treatment and subsequent release after treatment. Severity of plaque psoriasis and its improvement after NB-UVB treatment may be associated with TWEAK concentrations. The importance of our findings remains to be established.

YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment.A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy.Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p .0001). No significant correlations between investigated protein and metabolic parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found. Significant positive relation with CRP (p = .003) or alanine aminotransferase (p = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level remained unchanged (p = .5) after topical treatment, despite clinical improvement.YKL-40 might be a biomarker of psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.

In this pathbreaking study, we evaluated nitrosative stress in morbidly obese patients with and without metabolic syndrome. 62 women with class 3 obesity (BMI>40 kg/m2) were divided into three subgroups: obese patients (OB), obese patients with hypertension (OB+HYP), and obese patients with metabolic syndrome (OB+MS). In comparison to the lean patients, OB had increased levels of serum myeloperoxidase (MPO), plasma nitric oxide (NO), S-nitrosothiols, and peroxynitrite (ONOO−), as well as nitrotyrosine, while oxidized glutathione (GSSG) rose only in OB+HYP group. Interestingly, ONOO− was significantly higher in OB+HYP and OB+MS as compared to OB group, while MPO only in OB+MS group. OB+MS had greater nitrotyrosine and S-nitrosothiol values than OB+HYP. Moreover, peroxynitrite could differentiate OB from OB+HYP and OB+MS (AUC 0.9292; p<0.0001; 87.5% sensitivity, 90% specificity) as well as between OB and OB+MS group (AUC 0.9125; p<0.0001; 81.25% sensitivity, 83.33%). In conclusion, we showed that MPO activity, NO formation, and nitrosative damage to proteins parallel the progression of metabolic disturbances of obesity. Evaluation of ONOO− concentrations may help predict the development of hypertension and metabolic syndrome in patients with morbid obesity; however, longer-term studies are required for larger numbers of patients.

Psoriasis is characterized by hyperproliferation, deregulated differentiation and impaired apoptosis of keratinocytes. Mechanisms of lipid profile disturbances and metabolic syndrome in the psoriatic patients are still not fully understood. Sphingolipids, namely ceramides (CER) and sphingosine-1-phosphate (S1P) are signal molecules which can regulate cell growth, apoptosis and immune reactions. The aim of the study was to evaluate circulating CER and S1P levels in plaque-type psoriasis and their associations with the disease activity, inflammatory or metabolic markers and the presence of psoriatic comorbidities. Eighty-five patients with exacerbated plaque-type psoriasis and thirty-two healthy controls were enrolled. Serum CER and S1P concentrations before the treatment were examined. General patient characteristics included: PASI (Psoriasis Area and Severity Index), BMI (Body Mass Index), inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidities. Total serum concentration of CER was significantly decreased (p = 0.02) and concomitantly S1P levels significantly increased (p = 0.002) in psoriatic patients compared to the healthy control group. Among patients with psoriasis no significant correlations with the disease activity and inflammation markers were observed and only patients with psoriatic arthritis had significantly higher CER total concentration. Serum sphingolipid disturbances in psoriatic patients were observed. Decreased total CER and increased S1P serum levels may reflect their epidermal altered composition and metabolism. Patients with psoriatic arthritis have higher CER levels than psoriasis with skin involvement only. It might provide additional predictive value for psoriatic arthritis and may convey higher risk of metabolic and cardiovascular disease development in this group of patients.

Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis.The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment.Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment.Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement.Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.

Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid-binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count (p = 0.03) and aspartate aminotransferase (p = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9–30.3) vs. 12.9 (3.5–30.3) ng/ml] (p = 0.96), whereas FABP4 was decreased [27,286 (20,344–32,257) vs. 23,034 (18,320–29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.

TNF-like weak inducer of apoptosis (TWEAK) mediates not only apoptosis, but also inflammation, cell growth and angiogenesis. The role of TWEAK in psoriasis remains unknown. The aim of the study was to assess serum levels of TWEAK in psoriatic patients before and after topical treatment with dithranol in relation to the clinical activity of the disease.Serum samples were collected from 40 patients with plaque type psoriasis before and after topical treatment with dithranol. The concentrations of serum TWEAK were measured by ELISA and next compared with 16 healthy controls. The data were analyzed with respect to Psoriasis Area and Severity Index (PASI).Baseline serum TWEAK concentrations of psoriatic patients (685±166pg/ml) were significantly greater compared to healthy controls (565±110pg/ml). Topical treatment resulted in further increase in serum TWEAK (749±179pg/ml; p0.01). In case of patients with initial serum TWEAK concentrations above the median, PASI after topical treatment was lower compared to the individuals with initial TWEAK below the median.According to the study, serum Tweak was increased in psoriasis patients compared with controls. Moreover, dithranol topical treatment caused further increase in serum TWEAK. Also, a higher effectiveness of topical treatment was observed in case of patients with higher initial TWEAK concentrations. The results suggest a potential role of TWEAK in psoriasis therapy.

Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients.Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment.Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement.Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Objective Accelerated transmembrane transport of long-chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid-binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx-) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome. Methods Lipid content and fatty acid composition in each lipid subclass were estimated by gas liquid chromatography. For total, plasma membrane, and mitochondrial expression of fatty acid transporters, subfractionation with subsequent Western blot technique was used. Results A greater content of triacylglycerol in VAT of participants with obesity (MetSx-) was found. However, only the MetSx+ subjects had increased content of CER in VAT in relation to subcutaneous adipose tissue in MetSx+ and lean individuals. This was accompanied by increased total and membrane expression of FAT/CD36 in VAT in MetSx+ subjects. Accordingly, mitochondrial expression of FAT/CD36 and plasma membrane fatty acid-binding protein was decreased in both groups of subjects with obesity. Conclusions Metabolic syndrome is associated with the accumulation of CER in VAT, possibly related to increased FAT/CD36 protein expression.

Purpose Psoriasis is a chronic, recurrent, inflammatory disease. Recent investigations indicate its autoimmune pathogenesis. Apoptosis plays an important role in the development of many autoimmune diseases. The aim of this study was to evaluate the influence of topical treatment of psoriasis on soluble Fas (sFas) and soluble Fas-ligand (sFasL). Material/methods Serum concentrations of sFas and sFasL were measured using ELISA in 40 psoriatic patients before and after topical treatment with dithranol and compared to the values obtained from 16 healthy subjects. Data were analyzed with respect to severity of psoriasis, duration of the disease and coexisting obesity, diabetes and hypertension. Results We found that serum levels of sFas before (11.9 ± 2.4 ng/mL) and after treatment (12.2 ± 2.5 ng/mL) were significantly higher in patients with psoriasis as compared to the control group (6.4 ± 1.8 ng/mL). Concentrations of sFasL did not differ significantly from healthy subjects, but increased after treatment. The sFas/sFasL ratio was significantly higher in psoriasis (128 ± 47) than in the control group and, even though it tended to decrease after treatment, it still remained higher than in the control group (65 ± 22). Additionally we observed a positive correlation of sFas/sFasL ratio with the age of patients and duration of the disease. Psoriatic patients suffering from hypertension and overweight had significantly higher sFas/sFasL ratio than other psoriatic patients. Conclusions Our data indicate upregulation of the sFas/sFasL system in psoriatic patients. We demonstrate association of sFas/sFasL with commorbidities – components of metabolic syndrome.

Pathogenesis of psoriasis involves epidermal growth factor (EGF) that participates in keratinocyte proliferation, angiogenesis and cell differentiation through binding to soluble epidermal growth factor receptor (sEGFR). It is synthesised by, among others, keratinocytes, especially within psoriatic skin.To evaluate EGF and sEGFR plasma concentrations during topical psoriatic treatment.Blood samples were collected from 51 patients with plaque psoriasis. EGF and sEGFR plasma concentrations were examined with immunoenzymatic method prior and 14 days after topical treatment. The outcomes were analyzed with respect to PASI.Mean EGF concentration was higher in the plasma of psoriatic patients compared to the control group (p = .401) while mean sEGFR concentration was over twofold lower compared to the control group (p .001). After the therapy, an insignificant decrease in EGF plasma concentration (p = .835) and a significant increase in sEGFR concentration (p = .017) compared to initial values were observed. The coefficient of EGF/sEGFR concentration calculated for each individual had similar values before and after the treatment (p = .009), both of which were significantly higher compared to control group (respectively p .001, p .008).Epidermal growth factor and its soluble receptor may be a useful markers in monitoring clinical course of psoriasis and the effectiveness of therapy.

Psoriasis is a chronic inflammatory skin disease that is accompanied by metabolic disturbances and cardio-metabolic disorders. Fatty acids (FAs) might be a link between psoriasis and its comorbidity. The aim of the study was to evaluate serum concentrations of FAs and to investigate their association with the disease activity, markers of inflammation and possible involvement in psoriatic comorbidity: obesity, type 2 diabetes and hypertension. We measured 14 total serum fatty acids content and composition by gas–liquid chromatography and flame-ionization detector after direct in situ transesterification in 85 patients with exacerbated plaque psoriasis and in 32 healthy controls. FAs were grouped according to their biologic properties to saturated FA (SFA), unsaturated FA (UFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA. Generally, patients characteristic included: Psoriasis Area and Severity Index (PASI), Body Mass Index, inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidity. We have observed highly abnormal FAs pattern in psoriatic patients both with and without obesity compared to the control group. We have demonstrated association of PASI with low levels of circulating DHA, n-3 PUFA (p = 0.044 and p = 0.048, respectively) and high percent of MUFA (p = 0.024) in the non-obese psoriatic group. The SFA/UFA ratio increased with the duration of the disease (p = 0.03) in all psoriatic patients. These findings indicate abnormal FAs profile in psoriasis which may reflect metabolic disturbances and might play a role in the psoriatic comorbidity.

Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10-20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.

Psoriasis is a chronic, recurrent, inflammatory disease. Recent investigations indicate an autoimmune pathogenesis of the disease. Apoptosis plays an important role in the regulation of immune mechanisms in many autoimmune diseases. Although CD40, CD40L, and Bcl-2 have already been studied in psoriatic skin lesions, little is known about their circulating forms. The aim of the present study was to evaluate the serum concentrations of Bcl-2, soluble CD40 and CD40L in psoriatic patients. The study was performed using ELISA kits in 39 psoriatic patients before treatment and after two weeks of topical ointment. Data was analyzed with respect to severity of psoriasis, duration of the disease, and coexisting psoriatic arthritis. Our results revealed that serum concentrations of soluble CD40 and CD40L before and after treatment were significantly higher (p < 0.01 and p < 0.001) in patients with psoriasis compared to the control group. Topical treatment of psoriatic lesions with dithranol ointment failed to decrease serum of CD40 and CD40L, which has not been described until now. There was no significant difference in serum Bcl-2 concentration between the compared groups. We did not find significant differences in serum concentrations of Bcl-2, CD40 or CD40L between patients with mild or severe psoriasis, nor any correlation between disease duration and the presence of psoriatic arthritis symptoms. Our data indicates upregulation of the CD40/CD40L system in psoriatic patients despite topical treatment and suggests their possible role in the pathogenesis of psoriasis.

A 60-year-old woman was admitted in October 2000 for disseminated polymorphic papular and vesiculobullous skin lesions with a herpetiform pattern (Fig. 1). The eruption occurred 1 month prior to admission and was accompanied by intense itching and burning. A few vesicles in the oral mucosa appeared 6 months after the onset of the skin lesions. The patient's history was notable for noninsulin-dependent diabetes mellitus since the age of 32 years, complicated by arterial hypertension, neuropathy, and nephropathy with subsequent renal failure. The patient started hemodialysis 20 years after the onset of diabetes and was hemodialyzed three times a week for 4 h (index of dialysis adequacy (Kt/v) ≈ 1.3). She had received insulin since the age of 55 years. Furosemide, started in 1998, was withdrawn in October 2000, a few days after admission. Figure Figure 1 . Papules, blisters, and erosions with a partial herpetiform pattern (popliteal region) Download figure to PowerPoint Histopathologic examination of the skin lesions revealed subepidermal blisters with an infiltrate of polymorphonuclear cells within the tips of dermal papillae (Fig. 2). A diagnosis of linear immunoglobulin A (IgA) bullous dermatosis was confirmed by direct immunofluorescence assay of perilesional skin showing linear IgA (++) and IgG (+) deposits within the basement membrane zone (Fig. 3). No antiepidermal basement membrane zone or antiendomysial IgA antibodies were detected in the patient's serum. Abnormal laboratory values were as follows: hemoglobin concentration, 10.6 g/dL; red blood cell count, 3.1 × 106/µL; platelets, 99.0 × 103/µL; glucose concentration, 228.0 mg/dL; creatinine concentration, 5.3 mg/dL; glycosuria and proteinuria. Figure 2. Histopathology of lesional skin (upper leg): subepidermal blister and infiltrate of polymorphonuclear cells within the dermal papillae (hematoxylin and eosin, × 400) Download figure to PowerPoint Figure 3. Immunopathology of perilesional skin (buttock): linear immunoglobulin A (IgA) deposits within the basement membrane zone. Fluorescein-labeled anti-IgA antibodies (magnification, × 600) Download figure to PowerPoint The administration of dapsone at a daily dose of 100 mg resulted in a rapid improvement of the skin lesions. The dose had to be decreased after 3 weeks, however, because of a worsening of the patient's blood morphology and an increase in the proportion of methemoglobin (MetHb) up to 3%. Erythropoietin at a weekly dose of 6000 U was administered. Treatment with tetracycline (1.5 g/day), followed by prednisone (40 mg/day, gradually tapered) and sulfasalazine (4.5 g/day), did not influence the clinical picture of the skin lesions. Finally, dapsone (50 mg/day), together with prednisone (35 mg every second day), was started. With this treatment regimen, almost complete clearing of the skin lesions was achieved and maintained for 1 year. A few small blisters develop periodically and the concentration of MetHb remains within the normal range.

Aim The aim of this study was to evaluate the effect of psoriasis treatment on plasma concentrations of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with respect to disease severity. Methods MMP-1 and TIMP-1 were measured using an enzyme immunoassay in plasma of 32 patients before and after topical treatment. Data were analysed with respect to baseline values of the Psoriasis Area and Severity Index (PASI). Results Baseline plasma concentrations of both TIMP-1 and MMP-1 (1487 ± 102 and 21.0 ± 2.5 ng/mL, respectively) were significantly higher (P = 0.02 and 0.03, respectively) than normal. Both TIMP-1 and MMP-1 decreased significantly after completion of treatment to values similar to normal (1112 ± 127 and 11.3 ± 1.3 ng/mL, respectively). There was a significant positive correlation (r = 0.522) between baseline PASI and TIMP-1 values. Significant differences were observed between baseline TIMP-1 concentrations in groups with PASI 20. Baseline values (1697 ± 162 ng/mL) in patients with severe course of the disease (PASI > 20) were significantly elevated in comparison to normal values. Treatment caused a decrease in TIMP-1 plasma concentrations in all groups, but a significant difference was noted only in patients with pretreatment PASI > 20. Baseline MMP-1 concentrations exceeded significantly normal values only in patients with PASI