Magdalena Rogalska

Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales.

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 (PASI<10), 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 PASI>20. 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.

Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: Possible association with hepatic function impairment

Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

Serum prohepcidin reflects the degree of liver function impairment in liver cirrhosis

Abstract In the past few years the role of hepcidin metabolism disturbances, a recently described key regulator of iron metabolism, has been raised in patients with chronic liver diseases. The aim of this study was to assess the serum concentrations of prohepcidin in liver cirrhosis of various aetiologies and their possible relationship with the disease activity. Prohepcidin was measured in the sera of 70 patients with liver cirrhosis of various aetiologies by an immunoassay technique. The serum concentrations of prohepcidin were compared with the degree of liver insufficiency and biochemical markers of iron metabolism. A significant decrease in serum prohepcidin was observed in patients with liver cirrhosis compared with healthy individuals (52.6±1.9 vs 79.5±9.7 ng ml−1, p<0.01); this was most prominent in patients with hepatitis C virus and alcohol-related liver cirrhosis. The association between serum prohepcidin and the degree of liver dysfunction was observed in alcoholic liver cirrhosis, as illustrated through the inverse correlation with the Child–Pugh score (r= − 0.41, p<0.01). In conclusion, serum prohepcidin concentration is lowered in liver cirrhosis, which at least to some extent, may be a result of impaired liver function.

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype

OBJECTIVES The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

Pigment epithelium-derived factor in ulcerative colitis: possible relationship with disease activity.

OBJECTIVES Pigment epithelium-derived factor (PEDF) is an endogenous most potential angiogenic inhibitor and increased expression of PEDF in intestinal mucosa specimens was shown in the course of ulcerative colitis (UC). The aim of the present study was to evaluate serum concentration of pigment epithelium-derived growth factor, a potent anti-angiogenic factor and its possible association with vascular endothelial growth factor (VEGF) levels and disease activity. METHODS Concentrations of PEDF and VEGF were measured in sera of 33 patients (13 females and 20 males) with active UC. RESULTS There was significant increase of serum PEDF (32.3+/-2.9 vs. 20.6+/-4.7 ng/mL, P<0.05) as well as VEGF (326.4+/-58.1 vs. 110.9+/-15.7 pg/mL, P<0.05) in UC patients compared to healthy controls. Serum PEDF showed strong, positive correlation with endoscopic score (r=0.622, P<0.001), while such association was absent in respect to VEGF (r=0.05, P=0.77). In contrast serum VEGF decreased in severe UC comparing to patients with a mild course of disease, however the difference was not significant (274.9+/-64.9 vs. 360.4+/-103.4 pg/mL, P=0.53). CONCLUSIONS Increase in serum PEDF during UC, especially in severe forms of disease suggests its involvement in UC pathogenesis.

Plasma transforming growth factor β1, metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 in acute viral hepatitis type B

AIM Antiproliferative, pro-apoptotic and immunosuppressive activity effects suggest crucial role of transforming growth factor (TGF)-beta1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-1 in the pathogenesis of acute liver injury that in some patients precede development of chronic liver diseases and fibrogenesis. The aim of this study was to evaluate effect of acute HBV infection on plasma TGF-beta1, MMP-1 and TIMP-1 levels. METHODS TGF-beta1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 39 patients with acute viral hepatitis type B. Baseline measurement was performed within the first week of jaundice and then weekly up to the fourth week of the disease. Results were compared to baseline and normal values and to liver function tests. RESULTS Plasma concentrations of TGF-beta1, TIMP-1 and MMP-1 were significantly elevated in the first week of acute viral B hepatitis in comparison to normal. Analysis of individual values demonstrated significant positive correlation between plasma concentrations of TGF-beta1 and TIMP-1. There was no correlation between MMP-1 and TGF-beta1 or TIMP-1. Significant correlation was demonstrated between both TGF-beta1 and ALT or AST as well as between TIMP-1 and ALT, AST or bilirubin. Elevated baseline levels of both TGF-beta1 and TIMP-1 decreased gradually in consecutive weeks of the disease. TGF-beta1 but not TIMP-1 plasma concentrations were significantly lower in 3rd and 4th week than baseline values. MMP-1 concentration remained on baseline level in the 2nd week of the disease. However in the 3rd week its values increased suddenly but the significant difference in comparison to baseline was observed only in 4th week. CONCLUSIONS These results indicate important role of TGF-beta1, TIMP-1 and MMP-1 in acute viral hepatitis, that seems to be connected first of all with hepatocytes damage. Their role in extracellular matrix metabolism during acute liver injury needs further evaluation.

Time trends in HIV-1 transmitted drug resistance mutation frequency in Poland.

In Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men‐who‐have‐sex‐with‐men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013.