Danuta Prokopowicz

Increased Plasma Transforming Growth Factor-β1 Is Associated with Disease Progression in HIV-1-Infected Patients

Transforming growth factor-beta(1) (TGF-beta(1)) is a pleiotropic cytokine with a variety of effects on a wide range of cells in the immune system. Evidence suggests that TGF-beta(1) is also involved in the pathogenesis of human immunodeficiency virus type 1 infections. The aim of this study was to explore possible relationships between circulating TGF-beta(1) and immune as well as clinical HIV infection parameters with special impact on disease progression. TGF-beta(1) concentrations were measured by ELISA in the plasma of 66 patients in different stages of HIV infection and 20 healthy controls. HIV infection resulted in a significant increase of plasma TGF-beta(1) concentration compared to healthy individuals (11.4 +/- 6.8 vs. 6.1 +/- 1.5 ng/mL, p < 0.01). TGF-beta(1) values showed a significant negative correlation with CD4 cells count (r = -0.42, p = 0.001), as well as with CD8 cells count (r = -0.031, p < 0.05). Moreover, patients with the symptomatic phase of HIV infection presented an almost twofold increase of plasma TGF-beta(1) concentration in comparison to asymptomatic patients and healthy individuals. Our results demonstrate the relationship between TGF-beta(1) concentrations and HIV infection advancement with marked elevation in the late stages of the disease. These findings support in vitro observations suggesting an important, immunosuppressive role of TGF-beta(1) in HIV infection pathogenesis.

Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis.

BACKGROUND One of nine types of FABP, intestinal fatty acid binding protein (I-FABP) is primarily limited to the mature enterocytes of the small intestine, with only trace amounts identified in the stomach and large intestine. The aim of this study was to investigate the use of I-FABP as a possible plasma marker of intestinal injury in patients with ulcerative colitis (UC). MATERIAL AND METHODS The study group consisted of 42 patients (11 females and 31 males) with active ulcerative colitis (UC), aged from 24 to 74 years (mean age: 41.8+/-3.5 years). Plasma I-FABP concentrations and hsCRP were compared using endoscopic pictures scored according to the system developed by Meyers et al., and analysed in the context of inflammatory process extension: pancolitis, or distal or left side colitis. RESULTS The mean serum I-FABP concentration /mL), whereas individuals with left-side colitis had a mean I-FABP concentration of 61.8+/-8.5 pg/mL. Significant serum I-FABP elevation was observed in UC patients with a severe form of the disease, in contrast to the serum I-FABP concentration in patients with the mild form (260.5+/-60.6 vs. 61.5+/-7.9 pg/mL). CONCLUSION The elevated serum I-FABP concentration in patients with UC may indicate ileitis. I-FABP may be a useful marker of the extended inflammatory process.

Effects of ulcerative colitis activity on plasma and mucosal prostaglandin E2 concentration

The aim of this study was to determine effects of changes in ulcerative colitis activity on mucosal and plasma PGE2 concentrations measured with an EIA in 49 patients who underwent sigmoidoscopy. The disease was diagnosed in 37 patients. Twelve patients with normal colonic mucosa served as controls. Patients were divided into three groups depending on the changes of endoscopic picture during a three-month follow-up. Some laboratory markers of the disease activity, such as C-reactive protein, albumin, gamma-globulin and hemoglobin concentrations, sedimentation rate, and white blood and platelets counts, were also evaluated. Initial examination revealed a significant, positive correlation of mucosal and plasma PGE2 concentration with endoscopic score. Follow-up of patients without significant progression of mucosal changes revealed constant and close to normal concentration of mucosal PGE2. Plasma PGE2 was higher at the second examination, yet without significant difference. Improvement of endoscopic picture resulted in significant decrease of plasma and mucosal PGE2 concentrations. Worsening of mucosal changes reflected endoscopically was associated with significant increase of PGE2. There were no remarkable changes in the values of analyzed laboratory markers of the disease activity. These results indicate the usefulness of mucosal or plasma PGE2 measurement as a possible prognostic marker in patients with ulcerative colitis.

Immunological response in HIV-positive patients vaccinated against tick-borne encephalitis.

Abstract.Background: Vaccination against infectious diseases is a recommended preventive measure in patients with impaired immunity. The aim of the study was to estimate the immunogenicity of the vaccine against tick-borne encephalitis (TBE) in HIV-infected patients and to determine its safety for this group. Patients and Methods: The TBE vaccine FSME-IMMUN-inject was tested on 29 HIV-positive patients and the response compared to that of 40 healthy controls. The vaccination protocol for the HIV-positive group was modified by the addition of a fourth dose according to a 0/1/2/9-month schedule. Results: No serious adverse reactions were observed in patients with deficient immunity. A better response was obtained in HIV-infected patients with CD4 counts ≥ 500/μl (55% of the patients had levels of IgG antibody > 126 VIEU/μl) than in those with CD4 counts of 200–499/μl (40%). However, the difference did not reach significance. 85% of healthy controls achieved protective antibody titers after a full course of vaccination. Conclusion: The correlation between post-vaccine seroconversion and CD4 lymphocyte count showed that the FSME-IMMUN-inject vaccine can be considered to be a CD4 cell-independent vaccine. The examinations carried out 1 year after the completed vaccination protocol showed maintenance of the anti-TBE response acquired after the third vaccination in healthy subjects and in HIV-infected patients.

Plasma iPGE2 and i6-keto PGF1α in the course of liver cirrhosis

Plasma iPGE2 and i6-keto PGF1α were measured with an EIA assay in twenty patients with alcohol-related liver cirrhosis (ALC group) and 13 patients with hepatitis B virus as an etiologic factor of liver cirrhosis (HLC group). Significant increase of both prostanoids was observed irrespectively of the etiology of liver cirrhosis. Their levels increased depending on the degree of liver insufficiency with the highest values in patients classified as Child-Pugh C class. A significant, positive correlation with Child-Pugh score was found regarding PGE2 (r = 0,657; p < 0,001) as well as 6-keto PGF1α (r = 0, 736; p < 0,001). Correlation (r = 0, 789, p < 0,001) was also observed between levels of both prostaglandins. In conclusion we have shown that plasma iPGE2 and i6-keto PGF1α arise simultaneously with the degree of liver insufficiency, that can be a result of activation of non-parenchymal liver cells accompanying hepatic fibrosis.

Prevalence of antibodies against tick-borne encephalitis among residents of north-eastern Poland.

In 37 out of 613 (6%) residents of north eastern Poland, IgG antibodies to tick-borne encephalitis virus (TBEV) were detected at levels exceeding the diagnostic value of 60 VIEU/ml. The prevalence of the antibodies was not related to sex or place or residence. However, significantly higher antibody levels were found in the group of forest workers than in individuals not professionally connected with forestry.

High prevalence of genotype 4 among hepatitis C virus-infected intravenous drug users in north-eastern Poland.

The aim of this study was to describe the distribution of hepatitis C genotypes among intravenous drug users in north‐eastern Poland. The study group included intravenous drug users recruited at a drug treatment center and a clinic for HIV‐infected patients. HCV infection was confirmed by qualitative nested RT‐PCR to test for the presence of HCV RNA. Genotypes were determined by 5′UTR sequencing and comparing the results with known genotype sequences. Among 111 HCV‐infected and HCV–RNA‐positive intravenous drug users, the most prevalent genotypes were 1 (38.7%), 3 (37.8%), and 4 (23.4%). Most infections with genotype 4 (88.5%) were found among HCV–HIV‐coinfected drug users. The study demonstrated a high prevalence of genotype 4 (23.4%) among HCV‐infected Polish drug users. J. Med. Virol. 80:615–618, 2008.

The possible association between serum cholesterol concentration and decreased bone mineral density as well as intravertebral marrow fat in HIV-1 infected patients

Metabolic and morphologic abnormalities as well as disturbances in bone mineral density (BMD) are prevalent among HIV-infected patients, particularly during highly active antiretroviral treatment (HAART) [1–3]. Hyperlipidaemia may affect up to 60–80% of HIV-infected patients treated with protease inhibitors (PI) and is commonly associated with abnormalities in body composition [1]. Osteoporosis and osteopenia affects at least a half of antiretroviral treated HIV-infected population [2]. Even though the relationship between metabolic and bone alterations has not been clearly established, it has received increased attention in the recent years [4]. In the general population BMD is correlated with serum lipids in one study: negatively for HDL cholesterol and positively for triglycerides and LDL cholesterol [5]. Moreover, data emerging from other clinical studies demonstrate that lipid-lowering agents, mainly statins, enhance bone mineralization and may reduce the risk of osteoporotic fractures in non-HIV infected patients [6]. The mechanism underlying this relationship remains largely unknown. Some authors cite the role of lipid oxidation products in osteoclast differentiation and osteoblast inhibition, which results in the induction of bone resorption [7]. The most commonly used technique to assess BMD is dual-energy X-ray absorptiometry. In the recent years, vertebral marrow fat content as assessed by proton magnetic resonance spectroscopy (1H-MRS) has been recommended as a valuable tool of the evaluation of bone disorders [8]. Schellinger et al. [9] demonstrated a relationship between bone marrow fat content and bone mineral density and suggested that the combination of DEXA and MR spectroscopy may contribute to higher accuracy in estimating bone weakeness. The exact mechanism of this relationship is unclear, though the presence of decreased marrow fat and osteopenia in HIV-infected population has been reported [10]. The aim of our study is to evaluate the relationship between abnormalities in serum lipids and BMD and intravertebral marrow fat content in HIVinfected individuals. We performed a cross-sectional analysis of 55 HIVinfected individuals (39 males, 16 females, aged from 20 to 53 years, median 37) treated in the outpatient Clinic of Infection Correspondence

Increase in expression of monocytic tissue factor (CD142) with monocytes and blood platelet activation in liver cirrhosis.

Tissue factor (TF) is one of the proteins that participate in hemostatic and inflammatory processes. Activated monocytes present in the liver increase expression of TF, and while accumulating in the organ they can intensify inflammation. The aim of the present study was to evaluate the expression of TF on monocytes in advanced liver cirrhosis with regard to other activation markers. The flow cytometric analysis of TF (CD142), CD14, adhesive molecules CD11b and CD11c, costimulatory molecules CD40, CD80 and CD86, and HLA-DR+ on monocytes was carried out in 45 patients with postalcoholic liver cirrhosis (Child Pugh B, 20 patients; Child Pugh C, 25 patients) and in 25 healthy persons. The positive correlation between monocytic TF expression and monocyte [soluble CD14 (sCD14), CD11b, monocyte aggregates] activation, the expression of costimulatory molecules on monocytes (CD40, CD80), blood platelet (soluble P-selectin, microplatelets) activation, the level of tumor necrosis factor-α, biochemical parameters of liver damage (alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, γ-glutamyltransferase, and bilirubin) as well as coagulation disorders were observed in the study. In conclusion, the study revealed that the activation of monocytes and blood platelets is accompanied by the elevation of monocytic TF expression in advanced liver cirrhosis. The monocytic TF is a significant link connecting clotting processes and inflammatory and immunological phenomena in liver cirrhosis.

Transforming Growth Factor-β1 as a Surrogate Marker of Hepatic Dysfunction in Chronic Liver Diseases

Abstract The aim of the study was to evaluate the possible association between plasma concentrations of transforming growth factor-β1 (TGF-β1) and the degree of hepatic dysfunction in patients with chronic liver diseases. TGF-β1 was measured with an enzyme immunoassay in plasma from 21 patients with chronic active hepatitis and 40 patients with liver cirrhosis. Normal values were obtained from a group of 13 healthy volunteers. Results were analysed with respect to aetiology and the degree of liver insufficiency as evaluated by the Child-Pugh classification. The mean plasma concentration of TGF-β1in patients 36.9±2.8 ng/ml) was twice that found in normal volunteers (18.3±1.6 ng/ml). The highest values were observed in patients with alcoholic liver cirrhosis (44.4±4.7 ng/ml). Plasma TGF-β1 showed a statistically significant positive correlation with the degree of liver insufficiency. These results indicate the possible use of plasma TGF-β1 measurement as a good marker of liver function impairment. Further observation of patients involved in this study may help to evaluate its possible prognostic value in chronic liver diseases.