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Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objectives: Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments., Methods: We determined the effects of current therapy options using a 3D static disease model on human colon carcinoma cell lines (HCT 116) and transforming growth factor-β1 induced epithelial-to-mesenchymal transition (EMT) HCT 116 lines at 37 °C and 42 °C for 30, 60, and 120 min. We determined oxaliplatin's half maximal inhibitory concentrations in a 3D static culture by using viability assay. Clinical practices of HIPEC were applied in the developed model., Results: EMT-induced HCT 116 cells were less sensitive to oxaliplatin treatment compared to non-induced cells. We observed increased cytotoxicity when increasing the temperature from 37 °C to 42 °C and extending the treatment duration from 30 to 120 min. We found that 200 mg/m 2 oxaliplatin administered for 120 min is the most effective HIPEC treatment option within the framework of clinic applications., Conclusions: The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening., Competing Interests: Competing interests: The authors states no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin's cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients.

High-performance liquid chromatography (HPLC)-based analytical assays are used to effectively monitor purity and quantity of plasmid DNA (pDNA) throughout the purification process. However, the phenomenon of physical entrapment of open circular (OC) isoforms pDNA inside narrow channels of chromatographic support decreases its accuracy and precision and the effect increases with pDNA size. The purpose of the study was to develop a chromatographic method for accurate analytical separation between isoforms of <16 kbp pDNA using weak anion exchanging monolithic column with large (6 µm) convective channels. Purified samples of 4.7 and 15.4 kbp large pDNA with known isoform composition were prepared and their isoforms separated in ascending salt gradient. Both OC and supercoiled (SC) isoforms were baseline separated at a flow rate below 0.5 mL min -1 in a guanidinium chloride (GdnCl) gradient with a ≥95% OC pDNA elution recovery. However, these chromatographic conditions increased 2 times the peak width for linear (LIN) pDNA isoform compared to the results using monoliths with 1.4 µm channel size. If other chaotropic agents, such as urea or thiocyanate (SCN), were added to Gdn ions, the elution volume for LIN isoform decreased. Optimization of combined GdnCl/GdnSCN gradient for pDNA elution resulted in a simple and robust chromatographic method, where OC-LIN and LIN-SC pDNA (up to 15 kbp size) were separated with resolution above 1.0 and above 2.0, respectively. The accessibility and general acceptance of anion exchange chromatography for pDNA analytics give the newly developed method a great potential for in-process control monitoring of pDNA production processes., (© 2023 The Authors. Electrophoresis published by Wiley-VCH GmbH.)

Proteolytic activity in the tumour microenvironment is an important factor in cancer development since it can also affect intracellular signalling pathways via positive feedback loops that result in either increased tumour growth or resistance to anticancer mechanisms. In this study, we demonstrated extracellular cathepsin L-mediated cleavage of epidermal growth factor receptor (EGFR) and identified the cleavage site in the extracellular domain after R224. To further evaluate the relevance of this cleavage, we cloned and expressed a truncated version of EGFR, starting at G225, in HeLa cells. We confirmed the constitutive activation of the truncated protein in the absence of ligand binding and determined possible changes in intracellular signalling. Furthermore, we determined the effect of truncated EGFR protein expression on HeLa cell viability and response to the EGFR inhibitors, tyrosine kinase inhibitor (TKI) erlotinib and monoclonal antibody (mAb) cetuximab. Our data reveal the nuclear localization and phosphorylation of EGFR and signal trancducer and activator of transcription 3 (STAT3) in cells that express the truncated EGFR protein and suggest that these phenomena cause resistance to EGFR inhibitors., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Purpose: The aim of this study was to evaluate the prognostic value of PET-derived metabolic features and textural parameters of primary tumors in pediatric sarcoma patients., Methods: The imaging findings of 43 patients (14 girls and 29 boys; age 11.4 ± 4.4 years) who underwent 18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography for primary staging prior to therapy between 2005 and 2020 were retrospectively evaluated. The diagnoses were osteosarcoma in 10, rhabdomyosarcoma in 10, and Ewing sarcoma in 23 patients. PET metabolic data and textural features of primary tumors were obtained. Cox proportional hazards regression models were used to identify predictors for progression-free survival and overall survival. Survival curves were estimated by using the Kaplan-Meier method., Results: Distant metastases were detected in primary staging in 13 patients (30.2%). The median follow-up duration after diagnosis was 28 months (range: 10-171 months). In multivariate Cox regression analysis, the presence of distant metastasis and neighborhood grey-level difference matrix&#95;Contrast (ngldm&#95;Contrast) were found as independent predictors for both progression-free survival and overall survival. Grey-level zone length matrix&#95;Zone-length nonuniformity (glzlm&#95;ZLNU) was also found as an independent predictor for overall survival. The Kaplan-Meier survival analysis showed that higher ngldm&#95;Contrast and glzlm&#95;ZLNU values of primary tumors were significantly associated with shorter progression-free survival and overall survival., Conclusion: In addition to the presence of distant metastasis at initial diagnosis, textural features of primary tumors may be used as prognostic biomarkers to identify patients with worse prognosis in pediatric sarcoma. Higher tumor heterogeneity is significantly associated with shorter progression-free survival and OS., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

It is well known that stem cell transplantation is curative for many diseases; however, graft versus host disease (GVHD), which is a common posttransplant complication, has still a substantial place among the causes of transplant-related morbidity and mortality. The association between ABO incompatibility and GVHD is controversial. There is also limited available data about the association between blood component transfusions during the peritransplant period and GVHD development in the pediatric setting. Hence, we retrospectively evaluated both the impact of ABO-mismatch and transfusions of RBC and platelets between day -7 pre-transplant and +30 post-transplant to the development of acute GVHD (aGVHD). We analyzed 139 allotransplants in 133 patients who were transplanted by myeloablative conditioning. Fifty-one patients out of 133 (36.7 %) were found to have aGVHD within +100 days post-transplantation. Of them 40 patients had grade I-II and 11 patients had grade III-IV aGVHD. Increased risk of aGVHD is associated with ABO minor mismatch (p: 0.030). Nevertheless, there was no association between ABO mismatch and severity of aGVHD. The median number of RBC transfusions in aGVHD patients was higher than the number of transfusions in patients without aGVHD; however, the difference was not statistically significant (p: 0.11). Platelet transfusion numbers were statistically similar between aGVHD patients and the patients without aGVHD (p: 0.79). In conclusion, major and bi-directional ABO-incompatibility between donors and recipients, and RBC and platelet transfusions between day -7 pretransplant and day +30 post-transplant do not contribute to aGVHD development in children undergoing HSCT by myeloablative conditioning, while ABO minor mismatch is associated with the development of aGVHD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A bio-epoxy surface adhesive for adherence of the metal component species to glass substrate with desirable adhesion strength, converted controlled removal upon request, and bio-based resource inclusion was developed. For the development of resin, three different lignin-based aromatic monophenols, guaiacol, cresol, and vanillin, were used in the chemical epoxidation reaction with epichlorohydrin. The forming transformation process was studied by viscoelasticity, in situ FTIR monitoring, and Raman. Unlike other hydroxyl phenyls, guaiacol showed successful epoxide production, and stability at room temperature. Optimization of epoxide synthesis was conducted by varying NaOH concentration or reaction time. The obtained product was characterized by nuclear magnetic resonance and viscosity measurements. For the production of adhesive, environmentally problematic bisphenol A (BPA) epoxy was partially substituted with the environmentally acceptable, optimized guaiacol-based epoxy at 20, 50, and 80 wt.%. Mechanics, rheological properties, and the possibility of adhered phase de-application were assessed on the bio-substitutes and compared to commercially available polyepoxides or polyurethanes. Considering our aim, the sample composed of 80 wt.% bio-based epoxy/20 wt.% BPA thermoset was demonstrated to be the most suitable among those analyzed, as it was characterized by low BPA, desired boundary area and recoverability using a 10 wt.% acetic acid solution under ultrasound.

The elucidation of spontaneous growth of metal whiskers from metal surfaces is still ongoing, with the mainstream research conducted on Sn whiskers. This work reports on the discovery of Pb whisker growth from Bi-Mg-Pb solid pools found in common machinable aluminum alloy. The whiskers and hillocks display unique morphologies and complex growth that have not been documented beforehand. In contrast to typical understanding of whisker growth, the presented Pb whiskers show a clear nanocrystalline induced growth mechanism, which is a novel concept. Furthermore, the investigated whiskers are also found to be completely composed of nanocrystals throughout their entire length. The performed research gives new insight into nucleation and growth of metal whiskers, which raises new theoretical questions and challenges current theories of spontaneous metal whisker growth. Additionally, this work provides the first microscopic confirmation of recrystallization growth theory of whiskers that relates to oriented attachment of nanocrystals formed within an amorphous metallic matrix. The impact of mechanical stress, generated through Bi oxidation within the pools, is theoretically discussed with relation to the observed whisker and hillock growth. The newly discovered nanocrystalline growth provides a new step towards understanding spontaneous metal whisker growth and possibility of developing nanostructures for potential usage in sensing and electronics applications.

Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process that is part of normal embryogenesis and wound healing, and also has a ubiquitous role in various types of carcinoma and glioblastoma. EMT is activated and regulated by specific microenvironmental endogenous triggers and a complex network of signalling pathways. These mostly include epigenetic events that affect protein translation-controlling factors and proteases, altogether orchestrated by the switching on and off of oncogenes and tumour-suppressor genes in cancer cells. The hallmark of cancer-linked EMT is that the process is incomplete, as it is opposed by the reverse process of mesenchymal-to-epithelial transition, which results in a hybrid epithelial/mesenchymal phenotype that shows notable cell plasticity. This is a characteristic of cancer stem cells (CSCs), and it is of the utmost importance in their niche microenvironment, where it governs CSC migratory and invasive properties, thereby creating metastatic CSCs. These cells have high resistance to therapeutic treatments, in particular in glioblastoma., Competing Interests: Declaration of competing interest All authors declare that they have no financial interest and no personal relationship considered potential competing interest., (Copyright © 2020. Published by Elsevier B.V.)

Epidermal growth factor receptor (EGFR) mutations are potential markers driving carcinogenesis, and may alter the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). The frequency of EGFR mutations in patients with NSCLC differs according to sex, smoking habits and regional-based ethnicity differences. The aim of the present study was to determine the frequency of EGFR mutations in Turkish patients with NSCLC to highlight the importance of regional differences, and their associations with patient characteristics. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tumor tissue sections of 409 NSCLC patients. The most common EGFR mutations in exons 18, 19, 20 and 21 were detected using BioFilmChip-based microarray assay. The overall EGFR mutation frequency was 16.6%, and the highest mutation frequencies were observed in exon 19 (6.4%) and exon 21 (7.3%). There was a higher frequency of EGFR mutations in females compared with males and in never-smokers compared with smokers (both P≤0.05). These results were similar to other European population-based studies, but not consistent Middle-Eastern based studies. The present study may contribute to understanding the gradient frequency of EGFR mutation across different ethnicities, and in designing genome wide-based collaborations that may reveal novel decision making and susceptibility mutations in EGFR in patients with NSCLC., (Copyright © 2020, Spandidos Publications.)

Competing Interests: Conflict of interestThe authors have no conflicts of interest.

Background/aim: Natural products are popular insights for researchers to investigate promising anti-cancer agents since some of these substances have lesser adverse effects restricting the treatment than traditional chemotherapeutic agents. A well-known monoterpene Carvacrol, widely consumed in Mediterranean cuisine and lower risks of cancer, has efficient anticancer effects. However, the mechanism of action is yet to be discovered., Materials and Methods: The investigation aims to illuminate a new perceptive in the role of this substance on colorectal cancer treatment, by the means of differences in a well-defined range of soluble factors. Carvacrol effect on both HT-29 and HCT-116 cell lines was evaluated on proliferation and the IC50 values were calculated by the RTCA xCELLigence device. Then MAGPIX assay was performed to obtain the changes in soluble factors of the cell lines., Results: The Multiplexing assay suggests some of these factors were altered in favor of surviving and proliferation in aggressive cell line HCT-116 whereas they were altered against these characters in HT-29, were correlated with the increased IC50 concentration of HCT- 116 in carvacrol treatment., Conclusion: The current study indicates that differences in the levels of these soluble factors could modulate the anticancer effect related to carvacrol., Competing Interests: None declared, (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Purpose: Curcumin is a natural phytopolyphenol compound isolated from the root of turmeric (Curcuma longa) and possesses a wide range of biological properties. The purpose of this study was to evaluate the antiproliferative, wound healing, anti-invasive and anti-migrative effects of curcumin on HCT-116 and LoVo colorectal cancer cell lines., Methods: The antiproliferative activity of 2.5-75 µM curcumin was tested on HCT-116 and LoVo colorectal cell lines and the viability of the cells was tested with WST-1 reagent by using ELISA plate reader at 450 nm. xCELLigence RTCA DP system was used for the detection of anti-invasive and anti-migrative effects of curcumin., Results: The IC50 of curcumin was 10±0.03 for HCT-116 and 20±0.05 µM for LoVo cell lines. The IC50 of curcumin (10µM for HCT-116 and 20 µM for LoVo) showed anti-metastatic activity on these cell lines., Conclusion: This study showed that curcumin could be evaluated as a promising anti-cancer agent for human colorectal cancer.

Aim of the Study: The aim of this study was to investigate the role TNF- α , IL-2, and IL-2RB variants in psoriasis (Ps) and to evaluate the association between these variants and clinical features., Material and Methods: A total of 74 psoriatic patients and 74 healthy individuals were genotyped for these variants by PCR and/or RFLP., Results: The AA genotype of TNF- α (-308) was significantly more common in the patients (p = 0.013). TNF- α (-238) AA genotype was significantly increased in the patients (p = 0.028), while the GG genotype was decreased in the patient group, compared to the controls (p = 0.016). IL-2 (-330) variant GG and TT genotype was more common in the patients (p = 0.037, p = 0.009, respectively), while IL-2 (-330) GT genotype was increased in the control subjects (p = 0.001). IL-2 (-330) GG genotype frequency was significantly decreased (p = 0.021) and the TT genotype frequency was significantly increased among patients with psoriatic arthritis in comparison with Ps patients (p = 0.014). IL-2RB TC genotype frequency was significantly decreased and TT genotype frequency was significantly increased in the patients with positive family history of Ps compared to those who had a negative family history (p = 0.017, p = 0.014, respectively). Also, IL-2RB CC genotype was significantly increased among the patients with late-onset Ps in comparison with the early onset Ps group (p = 0.009). The frequency of IL-2 (-330) TT genotype was significantly higher in mild Ps patients than moderate-severe patients (p = 0.043)., Conclusions: Our data suggest a potential role of these genes as candidate genes for susceptibility to Ps in a Turkish cohort., Competing Interests: The authors declare no conflict of interests.

This study aimed to investigate whether functional variants of endothelial nitric oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA) ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants are responsible for alteration of the NO level in plasma, by reducing/increasing the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell of RA patients. For the control, blood samples obtained from 70 healthy persons were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or PCR technique. The data obtained was compared in itself and response to therapy. We found that "TT genotypic frequency" for the G894T variant was significantly associated with RA with an overall risk of 8.3-fold (p 0.029). No association was identified between intron 4 VNTR A/B variant and RA. At the 6 months, the mean visual analog scale (VAS), health assessment questionnaire (HAQ), and disease activity score for 28 joints (DAS 28) improvement was not significant among groups. Improvement in DAS was significantly better in anti-TNF treatment than disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We report for the first time that variants in the eNOS "TT" genotype might be contributed to the increased risk of RA in the Turkish population. These results imply that functional variants of eNOS gene might have an effect on RA patients and response to anti-TNF treatment. In addition, the results suggest that eNOS variants might be associated and affect host susceptibility and/or response to treatment in Turkish RA patients.

Lentil (Lens culinaris Medik.) is an excellent source of protein and carbohydrates and is also rich in essential trace elements for the human diet. Selenium (Se) is an essential micronutrient for human health and nutrition, providing protection against several diseases and regulating important biological systems. Dietary intake of 55 μg of Se per day is recommended for adults, with inadequate Se intake causing significant health problems. The objective of this study was to identify and map quantitative trait loci (QTL) of genes controlling Se accumulation in lentil seeds using a population of 96 recombinant inbred lines (RILs) developed from the cross "PI 320937" × "Eston" grown in three different environments for two years (2012 and 2013). Se concentration in seed varied between 119 and 883 μg/kg. A linkage map consisting of 1,784 markers (4 SSRs, and 1,780 SNPs) was developed. The map spanned a total length of 4,060.6 cM, consisting of 7 linkage groups (LGs) with an average distance of 2.3 cM between adjacent markers. Four QTL regions and 36 putative QTL markers, with LOD scores ranging from 3.00 to 4.97, distributed across two linkage groups (LG2 and LG5) were associated with seed Se concentration, explaining 6.3-16.9% of the phenotypic variation.

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFα), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFα, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNF α(-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFαgene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNF α(-308) GG genotypes may have roles in myeloma pathogenesis.

DNA repair genes are involved in several diseases such as cancers and autoimmune diseases. Previous studies indicated that a DNA repair system was involved in the development of rheumatoid arthritis (RA). In this study, we aimed to examine whether four polymorphisms in the DNA repair genes (xeroderma pigmentosum complementation group D [XPD], X-ray repair cross-complementing group 1 [XRCC1], and X-ray repair cross-complementing group 4 [XRCC4]) were associated with RA. Sixty-five patients with RA and 70 healthy controls (HCs) were examined for XPD (A-751G), XRCC1 (A399G), and XRCC4 (intron 3 VNTR and G-1394T) polymorphisms. All polymorphisms were genotyped by PCR and/or PCR-RFLP. The association between the polymorphisms and RA was analyzed using the chi-square test and de Finetti program. The intron 3 VNTR polymorphism in the XRCC4 gene showed an association with RA patients. The DI genotype was found lower in RA patients (χ(2)=8.227; p=0.0021), while the II genotype was higher in RA patients (χ(2)=5.285; p=0.010). There were deviations from the Hardy-Weinberg Equilibrium (HWE) in both intron 3 VNTR and G-1394T polymorphisms in the XRCC4 gene and in the polymorphism in the XRCC1 gene, and the observed genotype counts deviated from those expected according to the HWE (p=0.027, 0.004, and 0.002, respectively); however, there was no deviation in the other gene polymorphisms. There is no statistical difference between the RA patients and HCs for XPD (A-751G), XRCC1 (A399G), and XRCC4 (G-1394T) gene polymorphisms (p>0.05). Although XPD (A-751G), XRCC1 (A399G), and XRCC4 (G-1394T) gene polymorphisms have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of RA in Turkish patients. In conclusion, we suggested that the intron 3 VNTR polymorphism in the XRCC4 gene may be associated with the etiopathogenesis of RA as a marker of immune aging.

The aim of this study was to explore the association between polymorphisms of five cytokine genes and clinical parameters in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) treated with imatinib. We analyzed five cytokine genes (interleukin [IL]-6, IL-10, gamma interferon [IFN-γ], transforming growth factor beta-1 [TGF-β1], and tumor necrosis factor-alpha [TNF-α]) in 60 cases with Ph+ CML and 74 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer. All data were analyzed using the de Finetti program and SPSS version 14.0 for Windows. No significant differences were detected between the CML group and healthy controls with respect to the distributions and numbers of genotypes and alleles in TNF-α, TGF-β1, IL-10, and IFN-γ. However, the GG genotype associated with high expression in IL-6 was found to be significantly more frequent in CML as compared to controls (p=0.010). The median follow-up time was 49.3 months (range 6.1-168.4) and the median duration of imatinib treatment was 39.5 months (range 5.2-103.4) for these patients. On multivariateanalysis, only IL-10 GCC/GCC highly produced haplotypes were significantly associated with a shorter event-free survival. The relationship between cytokine genotypes/haplotypes and clinical parameters in CML has not been investigated before. Our results suggest that IL-10 may be a useful marker for CML prognosis and theGG genotype of the IL-6 gene may be associated with susceptibility.

Background: Macrophage migration inhibitory factor and mannose-binding lectin-2 play important roles in the pathogenesis of several acute and chronic inflammatory/autoimmune disorders. The aim of the study was to investigate any possible association between migration inhibitory factor and mannose-binding lectin-2 gene polymorphisms and acute rheumatic fever in children. Material and methods A total of 38 unrelated children with acute rheumatic fever and 40 age- and sex-matched healthy controls were analysed for codon 54 A/B polymorphism in mannose-binding lectin-2 gene and -173 G/C polymorphism in migration inhibitory factor gene by using the polymerase chain reaction method., Results: Frequency of BB genotype of mannose-binding lectin-2 gene was higher in the patient group. Interestingly, children with acute rheumatic fever with AA genotype tended to have chorea compared with children with BB genotype. There was a statistically significant increase in frequency of the migration inhibitory factor -173 CC genotype in patients compared with the control subjects., Conclusion: The present study is the first to investigate the mannose-binding lectin-2 gene polymorphism in children with acute rheumatic fever. BB genotype of mannose-binding lectin-2 (codon 54) and CC genotype of migration inhibitory factor (-173) may have a role in the immunoinflammatory process of acute rheumatic fever.

Purpose: To reveal the possible role of mycoplasmas in the etiopathogenesis of prostate cancer., Methods: In the study, prostate biopsy was performed on 62 patients with an abnormal digital rectal examination and/or elevated PSA. The patients' age was between 62 and 77 (mean 65.4 years) years. Thirty-one patients had adenocarcinoma of the prostate histopathologically (group 1). From these patients, the specimens were divided into two subgroups as specimens with malignant findings (group 1A) and specimens with benign findings (group 1B). The control group consisted of 31 patients with benign prostatic hyperplasia (group 2). In the specimens, the presence of mycoplasma DNA was investigated by the polymerase chain reaction method., Results: The mycoplasma DNA was found to be positive in 11 (35.4 %) patients in group 1A and in 4 (12.9 %) patients in group 1B. There was no mycoplasma DNA in the patients in group 2. The differences between group 1A and group 1B, and between group 1A and group 2 were statistically significant (p values, respectively, 0.006 and 0.0001)., Conclusions: Our data supported the thesis that mycoplasma infections play a role in the etiopathogenesis of the prostate cancer.

The absorption and bioavailability of drugs can be substantially affected by the transit of dosage forms through the gastrointestinal (GI) tract. Gastric emptying is one of the most critical parameters contributing to this inter- and intra-individual GI transit variability. It is especially important for the delayed release dosage forms whose release depends on the local environment and begins when the dosage form passes pylorus and comes into contact with higher pH medium in small intestine. The purpose of our research work was to predict the in vivo dissolution from enteric coated pellets for population and establish a good in vitro/in vivo correlation (IVIVC) with mean in vivo absorption profiles, obtained in a pharmacokinetic study under fasting conditions. The dissolution tests were carried out on a USP 4 - flow-through cell with enteric coated pellets containing an acid-labile drug and formulated as orodispersible tablets. Using several residence times in an acidic medium, we simulated the gastric emptying of the pellets and the exposure of different fractions of the pellets to the gastric medium for different periods of time. The amount of drug released decreased with the increasing time of exposure to the acidic medium due to the drug's degradation. The mean in vivo dissolution profiles, which were predicted on the basis of experimentally determined dissolution profiles and mathematical model of pellets' gastric emptying, gave a very good IVIVC with the mean in vivo absorption profiles., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Unlabelled: Acute rheumatic fever (ARF) is a delayed immunologically mediated sequela of throat infection by group A β-hemolytic streptococci. Inflammatory cytokines may play a pathogenic role in ARF. The objective of this study was to investigate the potential associations between interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and IL-10 gene polymorphisms and childhood ARF. Thirty-eight ARF patients and 40 age- and sex-matched healthy controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874), IL-6 (-174), TNF-α (-308), TGF-β1 (+10, +25), and IL-10 (-1082, -819, -592)]. Cytokine genotyping was performed by polymerase chain reaction sequence-specific primer methods. Patients with ARF had significantly higher frequencies of IFN-γ (+874) polymorphism in both TT genotype (p=0.0002) and T allele (p=0.0004). No statistically significant differences were observed in genotypes, haplotypes, and allele frequencies of IL-6, TNF-α, TGF-β1, and IL-10 genes between ARF and control groups (p>0.05). GG genotype frequency of TNF-α gene (low expression) was higher in patients who had previous ARF history (p=0.006). High expression of TGF-β1 (TT/GG, TC/GG) was more frequent in patients with CRP positivity (p=0.034). IL-6 CC genotype (low expression) frequency was higher in patients with tricuspid valve insufficiency (p=0.002), while IFN-γ TT genotype (high expression) frequency was higher in patients with mitral valve prolapse (p=0.049)., Conclusion: High expression of the IFN-γ gene may carry a higher risk for ARF in Turkish children, while IL-6, TNF-α, and TGF-β1 may have an impact in mediating some clinical and laboratory manifestations of the disease.

Purpose: To investigate the chromosomal aberrations in chronic myelogenous leukemia (CML), particularly in chromosomal regions which carried 67 genes pertaining to oncogenes, transcription factors, signal transduction, tumor suppressors, apoptosis etc, in addition to Philadelphia (Ph+) chromosome by multiplex ligation-dependent probe amplification (MLPA) method and to compare them with clinical parameters., Methods: The aberrations were investigated in 48 CML patients receiving imatinib therapy and a group of 15 healthy controls, by using the MLPA method between 2000 and 2009. The obtained results were compared both between patient and control groups and with clinical parameters., Results: Duplication was detected in the fibroblast growth factor receptor 1 (FGFR1) gene of 2 patients, inosine 5' monophosphate dehydrogenase 1 (IMPDH1) gene of 4, postmeiotic segregation increased S. Cerevisiae 2 (PMS2) gene of 1, nuclear factor kappa beta (NFKB) of 5 and T-cell translocation 2 (LMO2) gene of 1 patient. Univariate analysis showed that splenomegaly, advanced age, Sokal risk score (SRS) and the duplications in IMPDH1 and FGFR1 genes significantly shortened 7-year event-free survival (EFS); multivariate analysis showed that only the duplications in IMPDH1 and FGFR1 genes were the factors that significantly affected EFS. No statistically significant correlations were detected between duplications and other clinical parameters., Conclusion: Duplications in 4 genes (FGFR1, IMPDH1, PMS2, LMO2) in addition to Ph+ chromosome in CML patients were detected for the first time. This study indicates that chromosomes 7 and 8 should be particularly investigated in more detail in addition to the Ph+ chromosome for better determination of disease prognosis and selection of alternative treatments.

Myocardial inflammation is one of the commonest mechanisms in cardiomyopathy (CMP). Mannose binding lectin (MBL) is a key molecule in innate immunity, while macrophage migration inhibitory factor (MIF) is a constitutive element of the host defenses. We investigated the possible association between polymorphisms of MBL2 and MIF genes and CMP in Turkish children. Twenty-children with CMP and 30 healthy controls were analyzed for codon 54 A/B polymorphism in MBL, and -173 G/C polymorphism in MIF genes by using PCR-RFLP methods. No significant difference was found between genotypes and alleles of MBL2 gene codon 54 A/B polymorphism in patients and controls (p>0.05). However, serum uric acid levels was found higher in dilated CMP patients with AA genotype. Frequency of MIF -173 CC genotype was significantly higher in patients (p<0.05), and sodium levels were higher in patients with MIF -173 CC genotype. This study is the first to investigate the MBL and MIF gene polymorphisms in Turkish children with CMP. We conclude that CC genotype of MIF (-173) polymorphism may be a risk factor for CMP patients. However, further studies with larger samples are needed to address the exact role of this polymorphism in CMP.

Aim: To evaluate endothelial nitric oxide synthase (eNOS) gene polymorphisms in preeclampsia with or without eclampsia in a Turkish population., Material and Methods: Fifty-seven preeclamptic and 60 normotensive women were enrolled in the present study. The study focused on two functional variants: a variant in exon 7-G to T conversion at nucleotide position 894 resulting in the replacement of glutamic acid with aspartic acid at codon 298 (Glu298Asp) and a variant variable number of 27 bp tandem repeats in intron 4 (VNTR intron 4). Two polymorphisms in the maternal eNOS gene were characterized by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Preeclamptic pregnant women were evaluated into two subgroups according to the presence of eclampsia., Results: We demonstrated a significant difference in patients with preeclampsia in terms of Glu298Asp/eNOS genotype frequency. G/G homozygotes of Glu298Asp among healthy pregnancies were significantly frequent when T/T homozygotes were significantly frequent among preeclamptic pregnancies. We showed that G/T heterozygotes of Glu298Asp/eNOS gene were significantly frequent among preeclamptic pregnant women who did not develop eclampsia than in preeclamptic pregnant women with eclampsia., Conclusion: Glu298Asp polymorphism in the eNOS gene could be an individual's risk factor and may modulate progression to an eclampsia complication of preeclampsia in the Turkish population., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Objective: This study aims to investigate the association between the polymorphisms in DNA repair genes (XPD, XRCC1, and XRCC4) and clinical parameters in patients with multiple myeloma (MM), their effects on prognosis and their roles in susceptibility to MM., Patients and Methods: Sixty patients, diagnosed with MM and 70 individuals as the healthy control group were included in the study. Gene polymorphisms were detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism method. When the genotype frequencies of XPD (Llys751Gln) and XRCC1 (Arg399Gln) genes were examined in the patient and control groups, no significant difference was detected, while a significant association was found in XRCC4 (VNTR in intron 3 and G-1394T) polymorphisms. A significant association was found in the MM patients group for AA genotype and event-free survival (EFS) in terms of XPD (751) gene polymorphism (P = 0.047). When VNTR intron 3 polymorphism was compared for genotype frequency, DD genotype was found to be significantly low (P = 0.012) in the patient group, whereas GG and TT genotypes were found to be significantly lower in the patient group for the genotype frequency XRCC4 (G-1394T) polymorphism when compared to the control group (P = 0.015, P = 0.010, respectively)., Results: These data provide support for the hypothesis that a common variation in the genes encoding XRCC4 DNA repair proteins may contribute to susceptibility to myeloma. These findings require further validation in independent populations.

Objective: To determine whether endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with an increased risk for Idiopathic Recurrent Miscarriage (IRM) in the Turkish population and to evaluate the association between Nitric Oxide (NO) levels and eNOS gene polymorphisms in women with IRM., Material and Methods: A total of 120 Turkish women were enrolled in this study in four groups. Of these, 30 women were first trimester pregnant who had IRM (Group I). Thirty healthy multipara women were in the first trimester of pregnancy with no history of abortion (Group II). Thirty women were non pregnant with a history of IRM (Group III). The remaining 30 subjects were healthy multipara non-pregnant women with no history of abortion (Group IV). DNA analysis of four groups were performed for the two polymorphisms using the PCR and/or PCR-RFLPs method and NO levels were measured spectrophotometrically., Results: We observed statistically significant decreased NO levels in the pregnant patient group (p=0.001) while elevated NO levels were measured in the non pregnant patient group (p=0.004). We demonstrated that, while there was no significant difference in terms of VNTR 4/eNOS genotype, there was a marginally significant difference in terms of Glu298Asp/eNOS genotype frequency (p=0.055) in patients with IRM in the Turkish population. We observed no association between NO levels and Glu298Asp/eNOS or VNTR 4/eNOS genotypes in any of the groups., Conclusion: The Glu298Asp polymorphism of eNOS could be an intriguing susceptibility factor that modulates an individual's risk of IRM in Turkish population. Further studies to explain the role of the NO pathway in the pathophysiology of IRM are needed.

Objective: To examine MPO gene polymorphisms of women with preeclampsia in Turkish population., Methods: Sixty-one preeclamptic and 61 normotensive women without history of preeclampsia in earlier pregnancies were enrolled in this prospective controlled study. MPO mutations were characterized by PCR-RFLP method., Results: We demonstrated a significant difference in patients with preeclampsia in terms of genotype frequency. Heterozygous carriers of -463A among preeclamptic pregnancies were significantly frequent, whereas rare A/A homozygotes failed to differ from controls., Conclusion: The -463G/A polymorphism of leukocyte MPO could be an intriguing susceptibility factor that modulates an individual's risk of preeclampsia in Turkish population.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies developing against thrombocyte membrane glycoproteins (GPs), such as GPIIa/IIIa and GPIb/IX. Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were investigated in 71 patients with chronic ITP and 71 healthy controls, and they were compared with the clinical parameters. The polymorphisms in the SNPs were investigated with the polymerase chain reaction, polymerase chain reaction with sequence specific primer, and polymerase chain reaction-restriction fragment length polymorphism methods. It was found that the high expression of TNF-alpha (-308) AG phenotype significantly increased in cases with ITP (odds ratio, OR: 0.318, 95% confidence intervals, CI: 0.103-0.987, p < 0.05). TT genotype in TGF-beta 1 (codon 10) significantly decreased in ITP in comparison with the controls (OR: 0.342, 95% CI: 0.149-0.787, p = 0.016). IFN-gamma (+874) TT genotype was detected to be high in cases with ITP (OR: 3.301, 95% CI: 1.400-7.784, p < 0.05), whereas AA genotype was found to be significantly lower (OR: 4.993, 95% CI: 1.586-15.721, p < 0.05). MBL (codon 54) BB genotype (OR: 1.164, 95% CI: 1.059-1.279, p < 0.05) and IL1A A1/A2 genotype (OR: 0.249, 95% CI: 0.076-0.815, p < 0.05) were found to be significantly higher in cases with ITP than in healthy controls. TNF-alpha (-308) AG phenotype was detected to be significantly higher in steroid-refractory and splenectomized cases at the end of the first year than in the steroid-responsive (complete response (CR) and remission (R)) cases (OR: 4.137, 95% CI: 1.156-14.807, p < 0.05). When we compared the cases, from whom we obtained a CR at their first steroid response, with 12 cases, who entered R but from whom we could not obtain any CR, the frequencies of IFN-gamma (+874) AA genotype were found as 12 (20.3%) and 6 (50%) (OR: 0.082, 95% CI: 0.009-0.793, p < 0.05). MBL (codon 54) AB genotype was detected to be significantly higher in CR patients than in R cases (OR: 1.273, 95% CI: 1.110-1.459, p < 0.05). With these findings, it was found that TNF-alpha/AG, TGF-beta 1/TT, IFN-gamma/TT, MBL/BB, and IL-1RA A1/A2 genotypes were detected as the genes of susceptibility to ITP, while TNF-alpha/AG, IFN-gamma/AA, and MBL/AB genotypes might be important in response to steroid treatment.

The aim of this study was to investigate the methylation of the SFRP2, P16, DAPK1, HIC1, and MGMT genes, as well as the mutation of amino acid codons 12 and 13 of the KRAS gene in normal and tumor tissue DNA of patients diagnosed with sporadic colorectal cancer (SCRC). The methylation of gene regions and the KRAS mutations of normal (N) and tumor tissue (T) DNA obtained from 17 patients diagnosed with SCRC and 20 healthy controls were investigated using the polymerase chain reaction and reverse-hybridization methods. There was an Asp mutation in four patients, an Asp and Ser mutations in one patient in codon 12 of the KRAS gene, and an Asp mutation in codon 13 in eight patients. Overall promoter methylation (OPM) in the SFRP2 gene was observed in one N and four T, whereas partial promoter methylation (PPM) was observed in two N and five T. OPM in the P16 gene was present in one T. In the DAPK1 gene, OPM existed in seven T and five N, while PPM was present in two N. In the HIC1 gene, OPM was demonstrated in three T, while PPM was noted in two N; however, no methylation existed in N. In the MGMT gene, OPM occurred in five T and two N, and PPM was present in one T. KRAS mutations in Turkish patients with SCRC are similar to those of other population groups. Methylations in the genes, which underwent methylation analysis, were higher in T in comparison with N, and it has been suggested that significant results would be obtained by making a study with a larger population., (2010 Elsevier Inc. All rights reserved.)

Background: Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC)., Methods: We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR-RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated., Results: In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes., Conclusions: XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.

Objective: The aim of this study was to investigate links among cytokine genetic variants and generalized aggressive periodontitis (GAgP)., Methods: Thirty-five patients with generalized aggressive periodontitis and 85 healthy controls without periodontitis were included in the study. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as clinical parameters. Polymorphisms of IL-6, IL-10, IFN-gamma, TGF-ss1 and TNF-alpha gene were analysed using the polymerase chain reaction sequence-specific primer method (PCR-SSP)., Results: No significant differences were observed for IL-6, IL-10, IFN-gamma, and TGF-ss1 cytokine polymorphisms, from the genotype distribution and allele frequency, between GAgP and healthy control groups. In contrast, significant differences were observed in the TNF-alpha gene polymorphism between GAgP and healthy control groups (P = 0.002)., Conclusion: Our data suggest that TNF-alpha (-308) may be associated with the development of generalized aggressive periodontitis. These results should be replicated in a larger and more diverse population of patients diagnosed with generalized aggressive periodontitis to determine of these findings are generalizable.

Dysregulation in the expression of pro- and anti-inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. Tumour necrosis factor (TNF-alpha), a proinflammatory cytokine is believed to play an important role in MS pathogenesis. The objective of this study is to investigate the association between TNF-alpha promoter region (TNF-alpha-238, -308 and -857) and susceptibility to MS and clinical course of the disease. Eighty-six relapsing remitting MS patients and 150 sex-, age- and ethnic-matched controls were enrolled in the study. Genotyping was performed by PCR-RFLP method. We observed a statistically significant increase in TNF-alpha 857 CC genotype in MS patients than controls (P < 0.001) while TNF-alpha 857 CT genotype showed a significant negative correlation with MS patients (P = 0.033). No differences in the distribution of the TNF-alpha-238 and -308 alleles were observed. None of the three polymorphisms (-238, -308 and -857) did not show relation with disease duration, Expanded Disability Status Scale or age of onset. On the other hand, significant difference of TNF -857 CC genotype was identified with the low disease index (P = 0.025). Although the study group is small, the results indicate that TNF-alpha 857 CC genotype may cause susceptibility to MS in the Turkish population.

Nongestational choriocarcinoma of the ovary is a rare germ cell tumor with a worse prognosis than gestational choriocarcinoma. In this report we present a case of nongestational chroriocarcinoma where the EMA/CO regime was applied. The clinical features, management, and outcome are discussed.

Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes. It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis. The aim of this study was to explore the association between MPO-463G/A gene polymorphism and aggressive periodontitis (AgP) and chronic periodontitis (CP). The study included 147 subjects. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as the clinical parameters. Genomic DNA was obtained from the peripheral blood of 32 subjects with AgP, 25 with CP, and 90 reference controls. We genotyped the MPO-463G/A polymorphism using the PCR-RFLP method. All data were analyzed using SPSS version 13.0 for windows. There were no significant differences between the CP patients and controls regarding MPO-463A/G gene polymorphism either in terms of allele frequency or genotype frequency of MPO-463A/G. However, either in terms of allele frequency or genotype frequency of MPO-463A/G, there were significant differences between the AgP patients and the controls. In conclusion, our data suggest that MPO-463G/A may be associated with increased risk of aggressive periodontitis in Turkish patients.

Elevated levels of macrophage migration inhibitory factor (MIF) have been observed in the cerebrospinal fluid of patients with multiple sclerosis. This study was designed to determine if MIF gene polymorphisms are associated with multiple sclerosis and disease severity. In total, 120 relapsing-remitting patients with multiple sclerosis and 120 control subjects were enrolled in the study. There was a statistically significant increase in the MIF -173 CC genotype in patients with multiple sclerosis compared with the control subjects. The MIF -794 6/7 genotype had a significantly lower progression index compared with MIF -794 6/6. Patients with the MIF -173 CC genotype had a significantly lower age of disease onset compared with those with the MIF -173 CG and MIF -173 GG genotypes. Additionally, patients with the MIF -794 5/6 genotype had a significantly later age of disease onset. This study indicates that the MIF -173 CC genotype may cause susceptibility to multiple sclerosis in the white Turkish population and a younger age of disease onset is associated with this polymorphism.

The aim of this study was to investigate how myeloperoxidase (MPO) G-463A gene polymorphism and enzyme levels varied among patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) and to find the relationship between the MPO gene, enzyme levels, and clinical parameters. We studied the sera from 40 healthy volunteers, patients with CLL (n = 34) and MM (n = 28). In subjects with homozygote GG genotype, MPO levels were higher in the patients with both CLL and MM than in the control group. This difference was statistically significant in patients with CLL. In conclusion, homozygote GG genotype is found to be associated with an increasing amount of serum MPO. In accordance with the results of the study, we assess that the increase in the MPO enzyme level in the patient groups with CLL and MM generated bactericidal effects as well as the increased formation of ROP, thus setting off a pro-cell death pathway and playing a role on the pathogenesis of lymphoproliferative malignancies through this mechanism.

Vitiligo is an acquired depigmentary disorder characterized by white areas of the skin due to loss of epidermal melanocytes. Oxidative stress and free radicals are suggested as important phenomena in the pathogenesis of vitiligo. Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leukocytes and acts as a catalyst in the production of hypochlorous acid, a powerful oxidant. In this study we analysed enzyme activity and gene polymorphism of myeloperoxidase in patients with vitiligo. Fifty-four patients with vitiligo and 58 healthy controls were enrolled to this study. Patient groups were subdivided according to localization of the lesions; generalized, acrofacial and local. Plasma myeloperoxidase enzyme activity was determined with ELISA and G-463A gene (-463) polymorphism with the PCR-RFLP (AciI) method. The plasma MPO level was significantly lower in vitiligo patients than in the healthy controls (p = 0.005), however, it was not significantly different among subtypes of vitiligo (p = 0.8). A significant difference was not observed for G-463A genotype and allele distribution in patients with vitiligo. In conclusion, the present study is the first study investigating MPO G-463A polymorphism and enzyme levels, which warrants further studies with higher patient numbers and broader polymorphism panels.

Background & Objectives: Streptococcus agalactiae (group B streptococcus, GBS) is the predominant bacterial agent responsible for invasive perinatal infection. To obtain reliable data on vaginal and rectal carriage of S. agalactiae in pregnant women in Czech Republic, and to formulate a prevention programme of neonatal GBS disease for the Czech Republic, women at childbirth were screened for vaginal and anorectal carriage of GBS. The isolates were serotyped and tested for susceptibility to antimicrobials including those recommended for intrapartum prophylaxis., Methods: A total of 586 women at childbirth were screened for GBS carriage in vaginal and anorectal regions using the non-enrichment and selective culture media. The isolates were serotyped by precipitation with antisera raised against various serotypes and antigenic extracts prepared according to Lancefield's modification. Mueller Hinton agar with 5 per cent defibrinated sheep blood was used for antimicrobial susceptibility testing. MIC values were evaluated according to the NCCLS criteria., Results: Using selective media, GBS was detected in 172 (29.3%) of 586 women screened, vaginal and anorectal colonization was found in 21.7 and 24.4 per cent of them, respectively, concomitant vaginal and anorectal colonization was recorded in 16.5 per cent of the women studied. Serotypes III (33.2%), Ia (22.0%) and V (13.9%) prevailed among 172 isolates tested. All isolates were susceptible to penicillin, ampicillin and cefotaxime. The rates of GBS resistance to tetracycline, erythromycin and clindamycin were 83.9, 3.8 and 3.2 per cent, respectively., Interpretation & Conclusion: GBS carriage in pregnant women in the Czech Republic is rather high as compared with that reported in literature. The most frequent serotypes III, Ia and V, identified in GBS-colonized pregnant women in the Czech Republic, were among those predominant in the USA and Western Europe. Our findings confirm uniform susceptibility of GBS isolates from pregnant women to penicillin and other beta-lactam antibiotics tested. Resistance to erythromycin remains low in the Czech Republic.