Biomedical subjects

Gabriella Pár

Publications and source records attributed to Gabriella Pár.

6 recordsLinked to original sources

PubMed2006

[Immunology of HCV infection: the causes of impaired cellular immune response and the effect of antiviral treatment].

BACKGROUND: The outcome of HCV infection and the response to antiviral treatment depend on both viral and host factors. Host immune response contributes not only to viral control, clinical recovery and protective immunity, but also to chronic hepatitis and liver cirrhosis. Establishing immunological status and identifying pretreatment immunological factors associated with better response to therapy might be of importance in the understanding of the successful immune response and in the future of combination therapy to HCV infection. AIMS: The authors delivered a review on the immunology of HCV infection and characterized the cause of impaired cellular immune response in chronic HCV infection. Natural killer (NK) cell activity, perforin and the inhibitory CD81 HCV co-receptor expression, and Th1/Th2 cytokine production of the monocytes and lymphocytes have been investigated. PATIENTS AND METHODS: 42 patients with chronic hepatitis C, out of them 25 being on interferon (PEG-IFN) + ribavirin (RBV) therapy, 12 sustained virological responders, 26 HCV carriers with normal transaminase values and 22 healthy controls were studied. NK cell activity, perforin and CD81 expression, the IFNgamma, TNFalpha, IL-2 (Th1) and IL-4, IL-6, IL-10 (Th2) production of LPS stimulated monocytes and PMA + ionomycine stimulated lymphocytes were measured by flow-cytometry. RESULTS: In patients with chronic hepatitis C we demonstrated decreased NK cell activity associated with increased CD81 expression. The perforin expression of lymphocytes was also impaired in HCV patients. The pretreatment capacity of the macrophages to produce TNFalpha was predictive for sustained virological response. This increased TNFalpha production of the monocytes counteracted the observed impaired Th1 type cytokine production of the lymphocytes. IL-10 and IL-4 production showed positive correlation with HCV RNA levels, and negative correlation with histological activity index was noted. PEG-IFN + RBV treatment increased NK activity, perforin expression, Th1 type cytokine production of thr lymphocytes and downregulated CD81 expression inducing effective cellular immune response against HCV. The author's results provide further data to understand the causes of impaired cellular immune response in chronic HCV hepatitis and may be useful in the developement of immunotherapy as an adjunctive treatment to cure patients with chronic hepatitis C.

Adult↗

PubMed2005

Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary.

AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers. METHODS: The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used. RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer. CONCLUSION: Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

Adult↗

PubMed2005

[Safety of pegylated interferon in patients with hepatitis C virus induced cirrhosis].

OBJECTIVES: The authors described their experience with the therapy with pegylated interferon and its safety in patients with hepatitis C virus (HCV) induced liver cirrhosis treated at First Department of Medicine, Medical School, University of Pécs and at Tawam Hospital, Al Ain, United Arab Emirates. PATIENTS AND METHODS: Twenty four (12 male, 12 female, average: 55.66 +/- 7. 02 years) anti-HCV and/or HCV-RNA PCR positive cirrhotic patients were examined. Liver cirrhosis was diagnosed by abdominal ultrasound and/or histological examination of liver biopsy. RESULTS: Different genotypes of HCV were detected: genotype 1 in 7 cases, genotype 2 in 1 person, genotype 3 in 3 cases. Genotype 4 was detected in 10 patients, all of them were treated out of Hungary. Thirteen of 24 patients were not treated earlier, 6 persons were non-responders to previous interferon monotherapy, pegylated interferon was administered to 5 patients because of relapse. Biochemical parameters showed improvement in 16 cases (16/24, 66.66%), but did not in 5 patients. Until now, virological response was achieved in 13 patients (13/24, 54.16%), while three patients remained HCV-PCR positive. Temporary dose reduction was needed in 13/24 cases (54.16%). Withdrawal of therapy became necessary in only 2 patients due to severe neutropenia, thrombocytopenia and/or signs of decompensation. CONCLUSIONS: Pegylated interferon treatment is well tolerated by patients with compensated liver cirrhosis (Child-Pough stage A). Frequent side-effects (half of all cases) were usually mild or moderate requiring discontinuation only in 2 of 24 patients. The incidence of neutropenia and thrombocytopenia emphasizes the need of frequent blood cell count tests and patients follow up.

Antiviral Agents↗

PubMed2005

[Liver fibrosis: pathophysiology, diagnosis and treatment].

The extracellular matrix deposition in the liver parenchyma is a major component of cirrhosis. A great deal of knowledge has been gathered in the past two decades regarding the regulation and dynamics of fibrogenesis, and based on these advances, a review is delivered on the pathophysiology, diagnosis and therapy of liver fibrosis. The key event in fibrogenesis is the activation of hepatic stellate cells, and in its mechanism, inflammation, oxidative stress, steatosis, cytokines, growth factors, enzymes and enzyme inhibitors play a pivotal role. The phenotypic response of activated stellate cells comprises proliferation, fibrogenesis, contractility, loss of vitamin A and matrix degradation. In the diagnosis of liver fibrosis, besides liver biopsy--as "golden standard"--recently non-invasive methods, such as imaging techniques, and mainly serum fibrosis markers and indices have widely been studied. Experimental and clinical data have proved the reversibility of fibrosis, and suggested that an effective antifibrotic treatment in the future may serve even for the prevention of cirrhosis.

Biomarkers↗

PubMed2003

Impaired reproduction of histamine deficient (histidine-decarboxylase knockout) mice is caused predominantly by a decreased male mating behavior.

PROBLEM: Histamine induces a Th2 shift. As successful allopregnancy is characterized by a peripheral Th2 dominance, we investigated the role of histamine in reproduction. METHOD OF STUDY: HDC knockout (HDC-/-) or wild-type (HDC+/+) mice kept on histamine-deficient or normal diet were mated. Appearance of vaginal plugs indicated day 0.5 of pregnancy. On day 10.5 uteri were inspected. Splenic IFN-gamma production and cytotoxic activity were determined. RESULTS: In HDC+/+ or HDC-/- females on normal diet, plugs appeared between 3 and 6 days. In 80% of the (HDC-/-)/(HDC-/-) matings on histamine-deficient diet, no vaginal plugs were observed for more than 1 month. After replacing males with the wild type, plugs appeared within 3 days. In HDC-/- mice, litter size was lower than in HDC+/+ animals. Cytotoxicity and IFN-gamma production were significantly increased in non-pregnant histamine-deficient mice, but not in pregnant mice. CONCLUSION: Histamine affects male mating behavior, but is not indispensable for successful pregnancy.

Animals↗

PubMed2002

Decrease in CD3-negative-CD8dim(+) and Vdelta2/Vgamma9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection.

BACKGROUND/AIMS: As chronic hepatitis C virus (HCV) infection is associated with impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and perforin expression of peripheral blood lymphocytes, as well as the effect of interferon-alpha2b (IFN-alpha2b) therapy. METHODS: Thirty-three patients had chronic hepatitis C, and of them 12 had been on IFN-alpha2b treatment. Eleven individuals had been treated earlier with IFN-alpha2b and completely cured, and eight were HCV carriers with persistently normal serum alanine aminotransferase. Three-colour flow cytometry was used to measure the percentage of CD3(+/-)CD8+, CD3+CD4+, gammadeltaTcR+, Vdelta2 TcR+, Vgamma9 TcR+, Vdelta1 TcR+, CD3-CD16+, CD3-CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by single cell cytotoxic and flow cytometric assay. RESULTS: Patients with chronic hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3-negative-CD8dim-positive (NK subtype) and Vgamma9/Vdelta2 TcR+ as well as perforin-positive T lymphocytes, compared to controls and to those who were cured from HCV infection. IFN-alpha2b increased NK cell cytotoxicity and the percentage of perforin-positive lymphocytes. CONCLUSIONS: Our findings suggest that in chronic HCV infection a decreased percentage of CD3(-)CD8+, Vgamma9/Vdelta2 TcR+ and perforin-positive T cells and simultaneous decreased peripheral NK activity may contribute to the impaired cellular immune response and the chronicity of the disease.

Adult↗