University Iuliu Hatieganu

Cluj-Napoca, Romania

University Iuliu Hatieganu

Cluj-Napoca, Romania
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Ibrahim K.,University Gr pa | Laurian V.,University Iuliu Hatieganu | Doina L.,University Gr pa | Andreia C.,University Gr pa | And 2 more authors.
Farmacia | Year: 2010

We have analyzed the polyphenols from roots of Glycyrrhiza glabra harvested from Syria. The presence of eighteen polyphenolic compounds was simultaneously assessed through a LC-UV-MS method, before and after hydrolysis. The compounds that we were observed were: p-coumaric acid, ferulic acid, sinapic acid, luteolin and apigenin.

Khalaf I.,University Gr pa | Vlase L.,University Iuliu Hatieganu | Lazar D.,University Gr pa | Corciova A.,University Gr pa | And 2 more authors.
Farmacia | Year: 2010

In this paper we have analyzed the phytoestrogen content of Glycyrrhiza glabra roots harvested from four different locations in Syria. The presence of eight phytoestrogen compounds was simultaneously assessed through a LC-MS method, before and after hydrolysis. All tested extracts contain daidzein, daidzin, genistein, formononetin, ononin and coumestrol.

Friedrich-Rust M.,Goethe University Frankfurt | Lupsor M.,University of Medicine and Pharmacy, Cluj-Napoca | De Knegt R.,Erasmus Medical Center | Dries V.,Institute of Pathology | And 13 more authors.
Ultraschall in der Medizin | Year: 2015

Purpose: The aim of the present prospective European multicenter study was to demonstrate the non-inferiority of point shear wave elastography (pSWE) compared to transient elastography (TE) for the assessment of liver fibrosis in patients with chronic hepatitis C. Materials and Methods: 241 patients with chronic hepatitis C were prospectively enrolled at 7 European study sites and received pSWE, TE and blood tests. Liver biopsy was performed with histological staging by a central pathologist. In addition, for inclusion of cirrhotic patients, a maximum of 10% of patients with overt liver cirrhosis confirmed by imaging methods were allowed by protocol (n=24). Results: Owing to slower than expected recruitment due to a reduction of liver biopsies, the study was closed after 4 years before the target enrollment of 433 patients with 235 patients in the 'intention to diagnose' analysis and 182 patients in the 'per protocol' analysis. Therefore, the non-inferiority margin was enhanced to 0.075 but non-inferiority of pSWE could not be proven. However, Paired comparison of the diagnostic accuracy of pSWE and TE revealed no significant difference between the two methods in the 'intention to diagnose' and 'per protocol' analysis (0.81 vs. 0.85 for F≥2, p=0.15; 0.88 vs. 0.92 for F≥3, p=0.11; 0.89 vs. 0.94 for F=4, p=0.19). Measurement failure was significantly higher for TE than for pSWE (p=0.030). Conclusion: Non-inferiority of pSWE compared to TE could not be shown. However, the diagnostic accuracy of pSWE and TE was comparable for the noninvasive staging of liver fibrosis in patients with chronic hepatitis C. © Georg Thieme Verlag KG.Stuttgart · New York.

Krawczyk M.,Saarland University | Hoblinger A.,University of Bonn | Mihalache F.,Saarland University | Mihalache F.,University Iuliu Hatieganu | And 4 more authors.
Digestive and Liver Disease | Year: 2013

Background: Primary sclerosing cholangitis confers risk of cholangiocarcinoma. Here, we assessed the primary sclerosing cholangitis-associated variant rs3197999 in the MST1 gene, coding for RON receptor tyrosine kinase ligand macrophage stimulating protein, in a large European cholangiocarcinoma cohort. Materials and methods: 223 cholangiocarcinoma patients including three primary sclerosing cholangitis individuals and 355 cancer- and primary sclerosing cholangitis-free controls were genotyped for MST1 rs3197999. Results: The cancer group departed from Hardy-Weinberg equilibrium (p= 0.022) and exhibited a trend for rs3197999 [A] overrepresentation (31% vs. 26%: p= 0.10). Homozygous rs3197999 [AA] carrier status significantly increased overall (OR. = 1.97; p= 0.023) and primary sclerosing cholangitis-unrelated biliary tract cancer risk (OR. = 1.84; p= 0.044), relative to homozygous common allele carriers. The association was most pronounced in patients with extrahepatic tumours. This finding was robust to multivariate analysis (p<. 0.05), validating the [AA] genotype as an independent cholangiocarcinoma risk factor. Conclusions: These results suggest that the [AA] genotype of the common MST1 variant rs3197999 enhances genetic risk of sporadic extrahepatic cholangiocarcinoma irrespective of primary sclerosing cholangitis status, presumably by modulating inflammatory responses and/or altered MSP/RON signalling. © 2013 Editrice Gastroenterologica Italiana S.r.l.

Mihalache F.,Saarland University | Mihalache F.,University Iuliu Hatieganu | Hoblinger A.,University of Bonn | Acalovschi M.,University Iuliu Hatieganu | And 3 more authors.
Hepatobiliary and Pancreatic Diseases International | Year: 2012

BACKGROUND: Micro-RNAs (miRNAs) are small, non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability. A common G/C polymorphism (rs2910164) in the precursor (pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a. We investigated rs2910164 in a large Europeanbased cholangiocarcinoma (CCA) cohort. METHODS: We recruited 182 CCA patients and 350 controls in three academic medical centers. Genotyping for rs2910164 was performed by PCR-based assays with 5'-nuclease and fluorescence detection. Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test; allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage's trend test. Exploratory subgroup analyses included gender, tumor localization (extra- versus intrahepatic CCA) and early-onset CCA. RESULTS: Genotype distributions were consistent with the Hardy-Weinberg equilibrium. No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated. However, there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC, as indicated by an underrepresentation in the CCA group in general (29% vs 35%; P=0.18) and, in particular, for extrahepatic tumor sites (26% vs 35%; OR=0.67; 95% CI, 0.43-1.02; P=0.065). CONCLUSIONS: Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA. However, current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR- 146a species. Given the detected trend towards a potentially protective role of GC heterozygosity, a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further. © 2012, Hepatobiliary Pancreat Dis Int. All rights reserved.

Zimmer V.,Saarland University | Hoblinger A.,University of Bonn | Mihalache F.,University Iuliu Hatieganu | Assmann G.,Saarland University | And 2 more authors.
Oncology Letters | Year: 2012

Aberrant cell cycle control and apoptosis deregulation are involved in biliary carcinogenesis. The tumor suppressor gene p53 and its key negative regulator murine double minute 2 (mdm2) cooperate in modulating these basic cell functions and germline p53 alteration promotes cholangiocarcinoma (CCA) formation in animal models. The potential association between common functional genetic variation in p53 (SNP72 G/C) and mdm2 (SNP309 T/G) and susceptibility to bile duct cancer, however, has not been studied. p53/SNP72 G/C (rs1042522) and mdm2/SNP309 T/G (rs2279744) were genotyped in 182 Caucasian CCA patients and 350 controls using TaqMan assays. Allelic and genotypic differences, including exploratory data analyses (according to gender, tumor localization, early onset and genotypic interactions) were compared in contingency tables using the χ 2 and Fisher's exact tests. The overall comparison of allele and genotype frequencies yielded no significant association between either SNP and CCA susceptibility. Similarly, gender- and localization-specific analyses did not reveal deviations in allelic or genotypic distributions. In carriers of the low-apoptotic p53 genotype CC, the mdm2 SNP309 T allele conferred borderline significant CCA risk [P=0.049; odds ratio (OR), 4.36; 95% CI, 0.92-20.77]. Power analysis confirmed adequate statistical power to exclude major SNP effects (each >97% for OR 1.7). Collectively, the results we obtained from the largest European CCA cohort do not support the hypothesis of a prominent role of common p53 and mdm2 variation in the genetic susceptibility to bile duct cancer. However, epistatic effects may modulate genetic CCA risk in individual subsets.

Krawczyk M.,Saarland University | Mihalache F.,Saarland University | Mihalache F.,University Iuliu Hatieganu | Hoblinger A.,University of Bonn | And 3 more authors.
World Journal of Gastroenterology | Year: 2011

The aim of this study was to investigate an association between the development of cholangiocarcinoma (CCA) and the ABO variant rs505922 (known to increase pancreatic cancer risk) in a large cohort of European individuals with CCA. In total, 180 individuals with CCA and 350 CCA-free controls were included. The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay. Association between this single nucleotide polymorphism (SNP) and CCA was tested in contingency tables. Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant (all P > 0.05). Nevertheless, we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort (P = 0.028) and for patients with intrahepatic (P = 0.037) but not extrahepatic tumor localization (P > 0.05). The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA. However, Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups. © 2011 Baishideng. All rights reserved.

Mihalache F.,Saarland University | Mihalache F.,University Iuliu Hatieganu | Hoblinger A.,University of Bonn | Grunhage F.,Saarland University | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2011

Background Alpha1-antitrypsin (α1AT) deficiency caused by Z allele homozygosity represents a well-established risk factor for hepatocellular carcinoma. Previous studies have also implicated α1AT Z heterozygosity in cholangiocarcinogenesis. Aim To assess the 'common' Z and S alleles as well as the promoter variant rs8004738 for association with cholangiocarcinoma. Methods We genotyped 182 Caucasian patients and 350 controls for rs28929474 (Z), rs17580 (S) and the variant rs8004738. Exploratory analyses were performed in relation to gender and cholangiocarcinoma localisation. Results rs28929474 was significantly enriched in the cholangiocarcinoma group (4.1 vs. 1.7%; OR 2.46, 95% CI 1.14-5.32; Bonferroni corrected pc = 0.036), reinforced by Armitage trend testing (OR 2.53; pc = 0.032). The rs8004738 (promoter) minor allele tended to be overrepresented in Z heterozygotes (30.0 vs. 16.7%: P = 0.13). Exploratory data analyses suggested a high genetic risk for extrahepatic tumour localisation (OR 3.0; pc = 0.016) and potentially female Z allele carriers (OR 3.37; unadjusted P = 0.022, p c = 0.088). Conclusions These data point to a novel role of α1AT Z heterozygosity as a potential genetic susceptibility factor for cholangiocarcinoma formation and suggest a contribution of aberrant α1AT function in biliary carcinogenesis. However, given the overall low rs28929474 minor allele frequency, larger studies are warranted to confirm and extend our findings. © 2010 Blackwell Publishing Ltd.

Parvu M.,Babes - Bolyai University | Toiu A.,University Iuliu Hatieganu | Vlase L.,University Iuliu Hatieganu | Alina Parvu E.,University of Medicine and Pharmacy, Cluj-Napoca
Natural Product Research | Year: 2010

Five Allium species (Allium obliquum L., A. senescens L. subsp. montanum (Fries) Holub, A. schoenoprasum L. subsp. schoenoprasum, A. fistulosum L. and A. ursinum L.) were analysed in order to determine the presence of 19 polyphenolic compounds through an HPLC method coupled with UV and mass spectrometry detection. The pattern of phenol carboxylic acids indicates the presence of p-coumaric and ferulic acids in all species. Isoquercitrin was found in A. obliquum, A. schoenoprasum and A. fistulosum, rutin in A. senescens subsp. montanum and A. schoenoprasum, whereas quercitrin was found only in A. fistulosum, so they represent potential taxonomic markers that differentiate the four plants. Luteolin and apigenin were identified before and after hydrolysis only in A. obliquum. The amounts of all polyphenols were higher in hydrolysed samples, suggesting that these substances are present both as unbonded and bonded glycosides and/or esters. Our study showed large differences between the five Allium species, both qualitative and quantitative. © 2010 Taylor & Francis.

Porfire A.S.,University Iuliu Hatieganu | Zabaleta V.,University of Navarra | Gamazo C.,University of Navarra | Leucuta S.E.,University Iuliu Hatieganu | Irache J.M.,University of Navarra
International Journal of Pharmaceutics | Year: 2010

This work describes the bioadhesive properties of poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN) nanoparticles (NP) associated with various types of dextran (two hydroxyl-functionalized dextrans and one amino-derivative of dextran). The association of dextran to the polymer was performed either prior NP formation or by the attachment of dextran to the surface of the just formed NP. The amount of dextran associated to the nanoparticles was quantified by a HPLC/ELSD method and dextran presence in the nanoparticles was confirmed by IR spectroscopy, 1H NMR and in vitro agglutination assay. The in vivo bioadhesion study has demonstrated significantly higher adhesive interactions with the gastrointestinal tract of rats for all types of dextran associated nanoparticles compared with control nanoparticles. For nanoparticles associated with the aminated-dextran, the curves of bioadhesion were characterized by a maximum of adhesion just after administration followed by a rapid and constant decline with time. On the contrary, nanoparticles associated to conventional dextrans displayed a maximum bioadhesion between 1 and 3h post-administration. These results encourage us for further use of these systems for oral delivery of drugs. © 2009 Elsevier B.V.

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