Analysis of Four Genes Involved in the Neurodevelopment Shows Association of rs4307059 Polymorphism in the Cadherin 9/10 Region with Completed Suicide

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide. Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ～550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland. Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049). Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort.     

Polymorphisms in the promotor region of the CRBN gene as a predictive factor for peripheral neuropathy in the course of thalidomide-based chemotherapy in multiple myeloma patients

Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.     

Disorders of serum omega-3 fatty acid composition in dialyzed patients,and their associations with fat mass

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular mortality. Lipid disorders, a constant feature of CKD, might contribute to this state. The aim of this study was to evaluate n-3 polyunsaturated fatty acids (PUFA) composition in CKD patients treated with dialysis, in comparison to the general population and to assess possible associations between the n-3 PUFA profile and anthropometric variables. Thirty-three prevalent dialysis patients were studied and compared with an age- and sex-adjusted control group of 22 patients. Fatty acid composition in serum was analyzed by gas chromatography with a mass spectrometer detector (GC-MS) and anthropometric measures were assessed by bioimpedance spectroscopy. The fatty acid profile of dialyzed patients was characterized by a significantly lower percentage content of n-3 PUFA. For α-linolenic acid (ALA), it was 0.21?±?0.09% in dialysis patients versus 0.33?±?0.11% in the control group (p?p?p?r?=?.48 (p?r?=?.40 (p?相似文献   

Interaction of memantine and ketamine in morphine- and pentazocine-induced antinociception in mice

The interaction between uncompetitive NMDA receptor antagonists (memantine and ketamine), and morphine (mu-opioid receptor agonist) and pentazocine (kappa-opioid receptor agonist) was studied in the writhing test in mice. Memantine and ketamine, administered at subthreshold doses, potentiated antinociceptive effect of the threshold (1 mg/kg) dose of morphine. The effects of the threshold (6 mg/kg) dose of pentazocine were not significantly changed by ketamine, and were significantly enhanced by the higher dose of memantine (15 mg/kg). Simultaneously performed experiments in the chimney test have shown that combination of morphine or pentazocine with an NMDA receptor antagonist did not induce significant alterations in the motor coordination of mice. The obtained results have shown that NMDA receptor antagonists (ketamine, memantine) are able to enhance the antinociceptive activity of opioids (morphine, pentazocine). It is necessary to underline that this effect was more apparent for morphine (mu-opioid receptor agonist) + NMDA antagonists than for pentazocine (kappa-opioid receptor agonist). These results may have some importance for clinical practice.     

Dynamic Analysis of Changes of Protein Levels and Selected Biochemical Indices in Rat Serum in the Course of Experimental Pleurisy

A significant role is played in inflammation by the liver, which, stimulated by inflammatory mediators, synthetizes plasma proteins with various dynamics. The purpose of these studies is to generate a detailed dynamic analysis of changes to concentrations of plasma and serum protein fractions and selected acute-phase proteins as well as nonspecific biochemical indices during the course of an induced pleurisy. The studies were conducted on female inbred Buffalo rats, which were divided into two groups: a control group (C) and an experimental group (IP) in which pleurisy was induced. In the IP group, significant changes in biochemical indices were observed between the 48th and 96th hours of pleurisy. A reduction of albumin, transferrin, urea, and creatinine concentrations was observed, while concentrations of the complement components C3 and C4, haptoglobin, and fibrinogen increased. An early increase of IL-1 was observed, while increases of IL-6 and TNF were noted in the later period. The maximum intensity of the processes described above occurred between the 72nd and 96th hours of pleurisy.     

Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.     

Assessment of the Starch-Amylolytic Complex of Rye Flours by Traditional Methods and Modern One

The properties of the starch-amylolytic complex of commercial low-extract rye flour were determined based on the traditional method, such as falling number and amylograph test as well as differential scanning calorimetry (DSC). The starch, pentosans and protein had a significant effect on the thermal properties of the tested rye flours. Based on the falling number, it was revealed that rye flours were characterized by medium and low alpha-amylase activity. The falling number and amylograph test are not sufficient methods to determine the suitability of currently produced rye flours for bread making. The gelatinization process of the rye flour starch could be evaluated by the DSC test, which, together with the falling number and amylograph test, may allow a better way to evaluate the usefulness of rye flours for bread making. Many significant correlations between parameters determined by DSC endotherm and quality parameters of rye bread, such as volume and crumb hardness, were reported. Breads made from flour with higher enthalpy in DSC were characterized by higher volume and softer crumb.