Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland

Hepatitis B virus (HBV) infection is one of the major global epidemiological problems. The aim of our study was to determine the distribution of HBV genotypes in Poland since the data concerning the spread of HBV viruses in the central-eastern region of Europe is still very limited. HBV DNA was extracted from 58 serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were performed. The HBV virus from 43 serum samples from hepatitis B infected patients was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most prevalent subtype in the Amerindians. Our results coincide with the general European HBV prevalence. However, HBV genotype F, which is not a common genotype in European countries, was detected and so was relatively high occurrence of genotype D, which may reflect historical and ethnical migration events in Poland in the past.     

10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.     

Application of Statistical Methods to Accurately Assess the Effect of Gamma Aluminum Oxide Nanopowder on the Hardness of Composite Materials with Polyester–Glass Recyclate

Polymer composites are materials that are used in many industries. Their wide application has a direct impact on the amount of post-production and post-consumer waste. The global problem with recycling, especially of fiber-reinforced polymeric materials, has prompted research into methods of their use. Previous research on composite materials with polyester–glass recyclate showed a decrease in mechanical properties. The construction material should have the highest mechanical properties. Based on the literature, it was found that the use of nanoadditives may have a positive effect on the parameters of the materials. The use of gamma aluminum nanopowder, in a small amount can significantly increase the mechanical properties of composites with polyester–glass recyclate, and thus can affect the application of these materials to structural elements. The article is devoted to the research on the hardness of composite materials with polyester–glass recyclate and gamma aluminum nanopowder. The main goal is to investigate the possibility of using a nanoadditive as a material, increasing the mechanical properties of composites with polyester–glass recyclate, so as to create a recycled material with the highest possible strength parameters. Hardness tests were performed using the Barcol method. For each composite material, 30 measurements were made in order to subject the results to a statistical analysis. Using parametric statistical tests it was shown that the obtained hardness values at the assumed level of statistical significance p_v = 0.05 for comparisons for the samples of the reference material (B0) do not differ by chance, while for the comparisons in the configurations of the reference material (B0) with the modified materials, (R10, A2, R10A2) they do not differ by accident. Studies have shown that the addition of 2% gamma aluminum nanopowder slightly lowers the hardness of a pure polyester–glass composite, but the same additive allows the hardness of composite materials to be increased with the addition of glass recyclate. This is of particular importance for the development of the optimal composition of polyester–glass composites with the addition of recyclate, which will have good strength properties and at the same time enable the reuse of composite waste.     

Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer

The RAD51 protein and its paralog, XRCC3, play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination. Since DSBs may contribute to the pathogenesis of breast cancer and variability in DNA repair genes may be linked with some cancers, we performed a case-control study (135 cases and 175 controls) to check the association between the genotypes of the Thr241Met polymorphism of the XRCC3 gene and the 135G>C polymorphism of the RAD51 gene and breast cancer occurrence and progression. Genotypes were determined in peripheral blood lymphocytes by RFLP-PCR. We did not find any association between either polymorphism singly and breast cancer occurrence. Both polymorphisms were not related to tumor size, estrogen and progesterone receptors status, cancer type and grade. However, the Thr241Met genotype of the XRCC3 polymorphism slightly increased the risk of local metastasis in breast cancer patients (OR 2.56, 95% CI 1.27-5.17). The combined Thr241Met/135G>C genotype decreased the risk of breast cancer occurrence (OR 0.22, 95% CI 0.08-0.59). Our results suggest that the variability of the DNA homologous recombination repair genes RAD51 and XRCC3 may play a role in breast cancer occurrence and progression, but this role may be underlined by a mutual interaction between these genes.     

A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo

Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the Western world. However, immediate reinfection of the grafted donor liver by circulating virus is inevitable and liver disease progresses much faster than the original disease. Standard antiviral therapy is not well tolerated and usually ineffective in liver transplant patients, whereas anti-HCV immunotherapy is hampered by the extreme genetic diversity of the virus and its ability to spread by way of cell-cell contacts. We generated a human monoclonal antibody against scavenger receptor class B type I (SR-BI), monoclonal antibody (mAb)16-71, which can efficiently prevent infection of Huh-7.5 hepatoma cells and primary hepatocytes by cell-culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16-71 in "human liver urokinase-type plasminogen activator, severe combined immune deficiency (uPA-SCID) mice" (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before viral inoculation completely protected all chimeric mice from infection with serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals) suppressed the rapid viral spread observed in untreated control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise of the viral load was observed. CONCLUSION: Using in vitro cell culture and human liver-chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR-BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy.     

Mucinous cystadenocarcinomas of the pancreas

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic characteristics, diagnosis and treatment of mucinous cystadenocarcinomas (MCACs) of the pancreas. METHODOLOGY: This is a retrospective review of 6 patients who underwent curative resection for MCACs of the pancreas in the Department of General Endocrine and Transplantation Surgery, Medical University of Gdańsk from 1994-2004. Clinical presentation, radiological evaluation and surgical procedures were analyzed. RESULTS: There were 4 women and 2 men. Median age was 59 years. Patients complained of abdominal pain, nausea, vomiting and weigh loss, 2 of them had jaundice and 1 gastrointestinal (GI) bleeding. Ultrasonography and computed tomography showed cystic lesions. Solid component was found in 3 cases. Three endoscopic retrograde cholangiopancreatographys (ERCPs) were unhelpful in differentiating between malignant tumor and benign lesion. All patients underwent resection. In 3 cases Whipple resection, in 1 case Traverso - Longmire resection and in 2 cases distal pancreatectomy was performed. Histopathologically, all tumors were mucinous cystadenocarcinomas. CONCLUSIONS: Diagnostic accuracy for cystic pancreatic neoplasm is still limited. Surgical resection is recommended in all cystic tumors that are not clearly defined.     

CD28, CTLA-4 and CCL5 gene polymorphisms in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction caused by infiltrating leukocytes including T cells. An important role in T cell co-stimulation is played by the CD28, as a stimulatory signal transducer and the inhibitory CTLA-4. CCL5 is produced by circulating T cells and plays an active role in the chemotactic activity of T cells in RA. The aim of this study was to examine the associations between polymorphisms within CD28, CTLA-4, and CCL5 genes and RA. We examined 422 patients (340 female, 82 male, mean age 57.5 ± 12.5 years) with rheumatoid arthritis and 338 healthy subjects (261 female, 77 male). Disease activity was determined on the basis of DAS28 score. The patients with DAS28 of ≤2.5 were classified as subjects in remission of disease symptoms; the patients who had DAS28 of >2.5 were classified as subjects with active form of RA. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. A statistically significant difference was observed in the distribution of CTLA4 exon 1 +49A>G rs231775 genotypes between patients with DAS28 ≤ 2.5 and DAS28 > 2.5 where the increased frequency of AA genotype among patients with DAS28 > 2.5 was revealed (OR 1.55; 95% CI 1.01–2.38). The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population. Our results indicate a possible association between CTLA-4 exon 1 +49A>G rs231775 gene polymorphism and RA activity.     

Flow-mediated dilation and gender in patients with coronary artery disease: arterial size influences gender differences in flow-mediated dilation

BACKGROUND: The risk of atherosclerosis and its complications differs between male and female subjects. This is probably associated with gender differences in endothelial function as reflected by endothelium-dependent vasodilation. The aim of the study was to compare flow-mediated dilatation (FMD) in males and females with coronary artery disease (CAD), and to determine factors that might potentially influence FMD. METHODS: Ninety-six patients with stable CAD (CCS II-III): 76 males (mean age: 57.7 +/- 10 years) and 20 postmenopausal females (mean age: 60.1 +/- 10 years) were included into the study. Clinical data, pharmacotherapy, concomitant diseases, and FMD were all assessed. FMD was measured with high-resolution ultrasound as the percent change of brachial artery diameter (BAd) after a 3-minute occlusion (%FMD), and following the administration of 0.4 mg sublingual nitroglycerin (%NTG-MD). RESULTS: The percentage of FMD was significantly decreased (P < 0.05), and BAd was significantly larger (P < 0.001) in males as compared to females. Clinical data, pharmacotherapy, and concomitant diseases were comparable in the study groups.In all subjects examined, %FMD was related to BAd (r =-0.415, P < 0.001) and the percentage of ejection fraction (EF%) (r = 0.325, P < 0.01) in the univariate analysis, and to BAd only (r =-0.343, P < 0.01) in the multivariate analysis. The percentage of nitroglycerine-mediated vasodilatation (NTG-MD) correlated negatively with BAd (r =-0.430, P < 0.001), and positively with EF% (r = 0.334, P < 0.01) in the univariate analysis, and with BAd (r =-0.288, P < 0.05) in the multivariate analysis. Index %FMD x BAd was comparable for male and female subjects. CONCLUSIONS: Males and postmenopausal females with CAD show differences in endothelium-dependent vasodilatation that seem to secondarily result from differences in the BAd. Objective comparison of %FMD is only possible between patients with the same brachial artery size.     

Kynurenic acid and zaprinast diminished CXCL17-evoked pain-related behaviour and enhanced morphine analgesia in a mouse neuropathic pain model

Background

The G protein-coupled receptor 35 (GPR35), is considered important for nociceptive transmission, as suggested by accumulating evidence. This receptor was discovered in 1998; however, a lack of pharmacological tools prevented a complete understanding of its function and how to exploit it therapeutically. We studied the influence of CXCL17, kynurenic acid and zaprinast on nociceptive transmission in naïve and neuropathic mice. Additionally, we investigated the influence of kynurenic acid and zaprinast on morphine effectiveness in neuropathic pain.