Peginterferon alfa-2a and peginterferon alfa-2b combined with ribavirin in patients with genotype 1 chronic hepatitis C: results of a prospective single-centre study.

PURPOSE: This prospective, randomized, single-centre study compared peginterferons alfa-2a and alfa-2b, combined with ribavirin, in treating patients infected with hepatitis C virus (HCV) genotype 1. MATERIAL/METHODS: Hundred-and-one patients received 48 weeks of open-label treatment with peginterferon alfa-2a (180 µg/week) and 111 patients received peginterferon alfa-2b (1.5 µg/kg/week). All patients received the same dose of ribavirin 1000/1200 mg/day, depending on weight. The primary efficacy endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) 24 weeks after the end of treatment. RESULTS: Early virologic response (EVR), defined as at least 2 log10 IU/mL reduction of viral load at 12 weeks, was more common in patients treated with peginterferon alfa-2a (88% vs. 74.8%; p=0.04). However, the difference in SVR was not statistically significant (49.5% vs. 44.1%; p=0.43). CONCLUSIONS: Peginterferon alfa-2a treated patients were also more likely to be HCV RNA negative at the end of treatment (67.3% vs. 57.7%), but this difference did not reach statistical significance. Multivariate logistic regression analysis found that SVR was associated with low fibrosis stage (F1-2 by Scheuer; p=0.001) and low serum HCV RNA level (<400,000 IU/L; p=0.023). While both forms of peginterferon showed similar efficacy as measured by SVR, use of peginterferon alfa-2b could lower the number of patients receiving unnecessary treatment beyond 12 weeks.

Identification of GPR39 receptor and ghrelin receptor in thyroid tissues in paediatric patients with immune and non-immune thyroid diseases.

The preproghrelin gene is responsible for generating ghrelin and obestatin, two gastric peptides with opposite effects on food intake. Obestatin suppresses food intake and digestive motility through interaction with GPR39 (GPCR). Ghrelin is supposed to be a link connecting metabolism and energy homeostasis with growth as the result of activation of the growth hormone secretagogue receptor (GHSR).The aim of the current study was to assess the expression of preproghrelin, GPR39 and GHSR in thyroid tissues from patients with Graves' disease (GD; n = 15), non-toxic nodular goiter (NTNG; n = 10) and toxic nodular goiter (TNG; n = 10). GPR39 and GHSR in thyroid tissues were detected by immunohistochemistry and Western blot, revealing higher expression of both proteins in GD patients (+++; ++) in comparison with NTNG (+; +) and TNG (++; +) patients. GPR39 was present in thyroid autoimmune disease, NTNG and TNG at band p51 (kDa). The ghrelin receptor was identified in all study groups at p70. mRNA expression for preproghrelin was found in thyroid tissues from patients with immune and non-immune thyroid diseases. We conclude that the expression of the ghrelin receptor family in thyroid tissues may suggest a role of gastric peptides in thyroid functions. mRNA of preproghrelin expression is a proof of ghrelin gene-derived peptide presence in thyroid tissues.

Asymptomatic and symptomatic glial cysts of the pineal gland.

Glial cysts of the pineal gland are benign and mostly asymptomatic incidental lesions found in the brain MRI or at autopsy examinations. In rare cases pineal cysts become symptomatic and require surgical intervention. Symptomatic glial cysts may be clinically and radiologically indistinguishable from cystic neoplasms of the pineal region; therefore, histopathological diagnosis is critical for further prognosis and therapy in operated patients. In this paper we present detailed histopathological characteristics of symptomatic glial cysts in 2 surgical cases and of asymptomatic cysts of the pineal gland found at random in 3 autopsy cases. Both surgical patients, a 19-year-old girl and a 17-year-old boy, presented with severe headaches, associated with syncope in one case and insomnia in the second one. Preoperative MR imaging suggested tumour of the pineal gland in case no. 2. Histopathological and immunohistochemical examination of the specimens from both surgical and all autopsy cases revealed a characteristic pattern of cystic structures within the pineal gland, surrounded by layers of a dense fibrillar glial tissue and pineal parenchyma, consistent with non-neoplastic glial cysts. Although histopathological findings in asymptomatic and symptomatic cysts are essentially the same, the cyst in surgical case 1 was unilocular and partly lined with ependymal cells, whereas the cysts in other cases were multilocular, comprising cavities of various size, formed in the central part of gliotic tissue or directly within the pineal parenchyma, and lacked ependymal lining. Possible pathophysiological and clinicopathological significance of some morphological variants of pineal glial cysts is discussed.

[Analysis of Fas, FasL and Caspase-8 expression in thyroid gland in young patients with immune and non-immune thyroid diseases]. / Analiza ekspresji czasteczek Fas, FasL oraz kaspazy 8 w tkance gruczolu tarczowego u mlodych pacjentów z chorobami immunologicznymi i nieimmunologicznymi gruczolu tarczowego.

INTRODUCTION: Apoptosis, programmed cell death is a regulating mechanism enabling the removal of superabundantly produced and unnecessary at the certain moment cells. Disturbances of the apoptosis regulation contribute to the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate expression of proapoptotic Fas/FasL and caspase-8 in thyroid tissues in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: Inclusion criteria of Graves' patients were: large goiter, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH < 0.45 microIU/mL for more the 2-3 months from an onset of the disease. Isolated thyrocytes were identified by indirect method: in the first stage mouse monoclonal antibodies (mAbs) anti-TPO were bound to rabbit anti-mouse antibodies IgG (Fab')2 labeled FITC. To obtained cellular suspension mAbs directed against apoptotic Fas/FasL molecules labeled with PE (Phycoerythrin) was added. All investigations were performed on Coulter EPICS XL flow cytometer. Detection of apoptotic proteins was confirmed by Western Blot and immunohistochemistry methods using mAbs in DAB chromogene visuality and marked by Mayer's haematoxylin. Evaluation of caspase-8 expression in thyroid follicular cells was performed by Western Blot test. RESULTS: The analysis of Fas and FasL expression on surface of thyroid follicular cells was higher in patients with Hashimoto's thyroiditis (38%, 26%) in comparison with patients with Graves' disease (18%, 14%). In case of patients with Hashimoto's thyroiditis significantly lower percentage of thyroid tissue infiltrating immune Fas+ (13%) and FasL+ (22%) T cells in comparison with Graves' patients (33%, 43% respectively) was observed . Identification of proapoptotic Fas and FasL molecules in the thyroid follicular cells revealed higher expression of both proteins in patients with GD (++,++) and HT (+++; +++, respectively) in comparison with NTNG patients (+/0; +/0). Caspase-8 expression was detected in band 55 kDa using Western Blot test in patients with thyroid autoimmune diseases. CONCLUSIONS: We conclude that alteration in the expression of proapoptotic proteins in thyroid follicular cells may play a role in pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to increased proliferation of thyroid follicular cells which is responsible for goiter formation.

[Analysis of intracellular proapoptotic (Bax, Bak) and antiapoptotic (Bcl-2, Bcl-XL) proteins expression in thyrocytes from young patients with immune and non-immune thyroid disorders]. / Analiza ekspresji wewnatrzkomórkowych proapoptotycznych (Bax, Bak) i antyapoptotycznych (Bcl-2, Bcl-XL) bialek w tyreocytach u mlodocianych pacjentów ze schorzeniami immunologicznymi i nieimmunologicznymi gruczolu tarczowego.

Apoptosis one of the form of programmed cell death is a physiological occurrence, requisite to the correct function of every organism. This is an active process that proceeds with a participation of the cellular metabolism embracing the activation of genes and the synthesis of proteins. The signal to apoptosis can be started practically in every cell of our organism. Disturbances of the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate the expression of proapoptotic (Bax, Bak) and antiapoptotic (Bcl-2, Bcl-XL) proteins in thyroid tissues from 12 patients with Graves' disease (GD), 10 with non-toxic nodular goitre (NTNG) and 10 with toxic nodular goitre (TNG). Criteria for qualification of Graves' patients: large goitre, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH <0.45 microIU/mL more the 2-3 months from onset of the disease. Detection of apoptotic proteins in thyroid follicular cells was performed by Western Blot. These analysis was confirmed by immunohistochemistry using monoclonal antibodies in DAB chromogene visuality and marked by Mayer's haematoxylin. Identification of antiapoptotic Bcl-2 and Bcl-XL molecules in the thyroid follicular cells revealed a higher expression of both proteins in patients with Graves' disease (+++; ++, respectively) in comparison to patients with NTNG (++/+; +) and TNG (++; +). The detection of proapoptotic molecules showed higher expression of Bak (++/+) and Bax (+) in Graves' thyroid tissues while Bax was in trace amount in NTNG (0/+) and TNG (0/+). We conclude that alteration in the expression of antiapoptotic and proapoptotic proteins on surface of thyroid follicular cells may play a role in the pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to predominance for proliferation of thyroid follicular cells which is responsible for goitre formation.

[Cytofluorometric analysis of chosen markers of apoptosis CD95/CD95L (Fas/FasL) in thyroid tissues from young patients with Graves' disease and Hashimoto's thyroiditis]. / Cytofluorymetryczna analiza wybranych markerów apoptozy Fas/FasL (CD95/CD95L) w tkance gruczolu tarczowego u mlodocianych pacjentów z choroba Gravesa-Basedowa oraz zapaleniem tarczycy typu Hashimoto.

BACKGROUND: Apoptosis, one of the forms of programmed cell death, is a physiologic process of cell death that is central to normal development and occurs in response to a variety of physiologic and pathophysiologic stimuli. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as Hashimoto thyroiditis and Graves disease. The aim of this study was to estimate the expression of chosen apoptotic molecules CD95 (Fas) and CD95L (FasL) on the surface of thyroid follicular cells in application of mouse monoclonal antibodies #64 which recognized B antigen regions of thyroid peroxidase (TPO) and infiltrating inflammatory cells. MATERIAL AND METHODS: The investigation was performed on thyroid cells isolated from surgically treated thyroid tissues of 15 patients with Graves' disease (GD), 15 patients with a nontoxic multinodular goiter (NTMG) and 15 aspirates obtained by FNAB from patients with Hashimoto thyroiditis (HT). The thyrocytes were identified by an indirect method: in the first stage we added mouse monoclonal autoantibodies specific for TPO (mAb #64) regions and in the second stage we conjugated this complex with rabbit anti-mouse antibodies IgG (Fab')2 with FITC. In the next step the cellular suspension was completed with suitably well-chosen two-colour monoclonal antibodies marked (PE or PerCP) (Becton Dickinson) directed against suitable apoptotic (Fas/FasL) molecules. All investigations were performed by flow cytometry using Coulter EPICS XL apparatus. RESULTS: The percentages of thyroid cells were estimated with expression of region B antigenic TPO in reference to individual apoptotic molecules. The analysis of Fas and FasL expression in thyroid tissues revealed significantly increased percentage of intrathyroidal T cells with CD95+ (p<0.005, p<0.001), CD95L+ (p<0.02, p<0.01) and both CD95/CD95L (ns, p<0.05) expression in comparison to percentages of T cells in patients with HT and NTMG. In addition, on the surface of thyroid follicular cells in patients with GD (p<0.01, p<0.01) and NTMG (p<0.001, p<0.004) we observed a lower percentage of thyrocytes with CD95 and CD95L molecules than in cases with HT. The expression of both apoptotic molecules on thyroid cells was higher (18%) in patients with HT in comparison to the percentages of positive cells in patients with GD (p<0.02, p<0.002) and NTMG, 8% and 1%, respectively. CONCLUSIONS: We conclude that alterations in the expression of death receptors and their ligands on the surface of thyroid follicular cells may play a role in the regulation of apoptosis in thyroid autoimmune disorders.

[Study of the efficacy of combined therapy with interferon alfacon-1 and ribavirin for chronic hepatitis C]. / Ocena skutecznosci leczenia skojarzonego interferonem alfacon-1 i rybawiryna pacjentów z przewleklym wirusowym zapaleniem watroby typu c.

The results of combined interferon alfacon-1 and ribavirin therapy of 94 patients with chronic hepatitis C were analyzed. Complete data, including sustained viral response (SVR), were obtained in 88 patients. 46.8% of them achieved SVR. The most important factor influencing SVR, was the presence of HCV RNA in serum at weeks 12 and 24 of therapy. SVR in these cases was achieved in 14.3% and 0%, respectively. Eight patients discontinued therapy due to adverse events. Most frequent were depressive reactions due to interferon (3 cases), and severe anemia due to ribavirin (2 cases). 37% of patients developed thyroiditis, significantly more frequent in women (27 versus 9).