Neuroendoscopic techniques in the treatment of arachnoid cysts in children and comparison with other operative methods

Objective: The authors intended to evaluate the application of neuroendoscopic techniques for the treatment of arachnoid cysts in children and compare it with other operative methods. Methods: The analysis covered the results of treatment of 44 children with arachnoid cysts who were subjected to neuroendoscopic procedures and 62 patients who underwent other operations. Results: The neuroendoscopic treatment of arachnoid cysts was very effective because of low rate of reoperative treatment (six out of 44 patients), no need to change the operative method (40 effective out of total 44 operative procedures), and low rate of persistent worsening (none of 44 patients worsened). Conclusions: Summing up all the mentioned aspects of neuroendoscopic techniques, the neuroendoscopic techniques were the most suitable operative procedures in the treatment of arachnoid cysts in the presented group of patients, providing that the connection between the lumen of the arachnoid cyst and the cerebrospinal fluid cisterns was of good quality.     

Mutations in gastrointestinal stromal tumors--a population-based study from Northern Norway

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. This tumor typically expresses KIT, and has KIT or PDGFRA activating mutation. In this study we evaluated 89 GISTs diagnosed in Northern Norway during a 30-year period. KIT exons 8, 9, 11, 13, and 17 were analyzed by PCR amplification and direct sequencing. Subsequently PDGRA exons 12, 14, and 18 were evaluated in KIT wild-type cases. KIT mutations were found in 66 cases (75%), and PDGFRA mutations in 9 cases (10%). Most common were KIT exon 11 mutations, with 58 cases. Tumors with Kit exon 11 point mutations had a significantly better prognosis than those with deletions. There were five KIT exon 9 duplications, three exon 13 point mutations, and one point mutation in exon 17. There were nine PDGFGRA mutations: seven in exon 18 and two in exon 12. All but one PDGFRA mutant GISTs were gastric tumors with epithelioid morphology, and these tumors were on average smaller than those with KIT mutations. KIT and PDGFRA wild type was found in 15% of cases. Analysis of KIT and PDGFRA mutations is of significance for treatment with tyrosine kinase inhibitors, and may also have value when assessing the biological potential of GIST.     

MTHFD 1958G>A and MTR 2756A>G polymorphisms are associated with bipolar disorder and schizophrenia

BACKGROUND: The etiology of bipolar disorder (BD) and schizophrenia is very complex. Polymorphic variants of genes encoding enzymes of the monoaminergic may be involved in development of BD and schizophrenia. Therefore, we examined the prevalence of 1958G>A polymorphism of MTHFD1 gene, encoding trifunctional folate enzyme 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1), and 2756A>G variant of methionine synthase (MTR) gene in patients with BD (n=200), schizophrenia (n=200) and in controls (n=300). OBJECTIVE: We investigated the genotypic and allelic frequencies of MTHFD1 1958G>A (R653Q) and MTR 2756A>G (D919G) gene polymorphisms in a group of bipolar (n=200) and schizophrenic patients (n=200), as well as in controls (n=300). METHODS: The distributon of genotypes in all groups was tested for deviation from Hardy-Weinberg equilibrium (HWE). The Pearson's chi-square (chi) test and Fisher's exact test were applied to assess differences in the genotypic and allelic (respectively) distribution between groups of patients and controls. MAIN RESULTS: We found that MTHFD1 1958AA or 1958AG genotypes constitute risk factors for development of bipolar disorder type I (BDI) or schizophrenia with odds ratios (OR)=1.743 (95% CI=1.211-2.508; P=0.0027; P (corr)=0.0054) and 2.667 (95% CI=1.845-3.854; P=0.0001; P (corr)=0.0002), respectively. In the same groups, the MTR 2756GG or 2756AG genotypes also constitute significant risk factors in occurrence of BDI and schizophrenia with OR=1.621 (95% CI=1.130-2.326; P=0.0086; P (corr)=0.0172) and 1.556 (95% CI=1.085-2.232; P=0.0160; P (corr)=0.032), respectively. Gender classification of patients indicated significant association only of MTHFD1 1958A allele with BDI and schizophrenia in the male patients OR=1.838 (95% CI=1.114-3.031; P=0.0166; P (corr)=0.0332) and OR=3.964 (95% CI=2.358-6.663; P=0.0001 P (corr)=0.0002), respectively. CONCLUSION: Since MTHFD and MTR genes are located in 14q24 and 1q43 loci, our findings support the significance of chromosomes 14q and 1q in etiopathogenesis of bipolar disorder and schizophrenia.     

Biological and Pro-Angiogenic Properties of Genetically Modified Human Primary Myoblasts Overexpressing Placental Growth Factor in In Vitro and In Vivo Studies

Cardiovascular diseases are a growing problem in developing countries; therefore, there is an ongoing intensive search for new approaches to treat these disorders. Currently, cellular therapies are focused on healing the damaged heart by implanting stem cells modified with pro-angiogenic factors. This approach ensures that the introduced cells are capable of fulfilling the complex requirements of the environment, including the replacement of the post-infarction scar with cells that are able to contract and promote the formation of new blood vessels that can supply the ischaemic region with nutrients and oxygen. This study focused on the genetic modification of human skeletal muscle cells (SkMCs). We chose myoblast cells due to their close biological resemblance to cardiomyocytes and the placental growth factor (PlGF) gene due to its pro-angiogenic potential. In our in vitro studies, we transfected SkMCs with the PlGF gene using electroporation, which has previously been proven to be efficient and generate robust overexpression of the PlGF gene and elevate PlGF protein secretion. Moreover, the functionality of the secreted pro-angiogenic proteins was confirmed using an in vitro capillary development assay. We have also examined the influence of PlGF overexpression on VEGF-A and VEGF-B, which are well-known factors described in the literature as the most potent activators of blood vessel formation. We were able to confirm the overexpression of VEGF-A in myoblasts transfected with the PlGF gene. The results obtained in this study were further verified in an animal model. These data were able to confirm the potential therapeutic effects of the applied treatments.

     

Effect of vitamin E and vitamin C supplementation on antioxidative state and renal glomerular basement membrane thickness in diabetic kidney

The aim of this study was to analyze the effect of vitamins C and E on malondialdehyde (MDA) content and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats. Wistar male rats were divided into following groups (12 rats each): the control, diabetic rats, diabetic rats whose drinking water was supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with 200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and 24-hour urinary albumin excretion (UAE) were studied every week (0-12 weeks). After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were measured in the kidney homogenate supernatants. Electron micrographs of glomeruli were scanned and morphometric investigations were performed by means of computer image analysis system to compare GBM thickness. The blood glucose and HbA1C concentrations and UAE in diabetic rats were significantly higher than in the control group. An increase in the MDA level and decrease in the SOD, CAT and GSH-Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks of experiment. Administration of vitamins C and E did not affect body weight, blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM thickness. The results indicate the potential utility of antioxidant vitamins in the protection against the development of diabetic nephropathy.     

Optimization of Dynamic and Buckling Behavior of Thin-Walled Composite Cylinder,Supported by Nature-Inspired Agorithms

The paper presents the optimization of stacking sequence (the lamination angles in subsequent composite layers) of the composite cylinder in order to simultaneously maximize the values of the first natural frequency f1 and the first buckling force Pcr. The optimization problem involves either two objective functions or one which combines both problems using a coefficient whose optimal value is also being searched for. The main idea of the paper is the application of two neural network metamodels which substitute very time- and resource-consuming Finite Element (FE) calculations. The metamodels are created separately through a novel iterative procedure, using examples obtained through Finite Element Method (FEM). The metamodels, once ready, are able to assess the values of f1 and Pcr instantly and thus enable the application of nature-inspired Genetic Algorithm (GA) minimization with reasonable calculation times. Obviously, the maxima of f1 and Pcr may be located in different points of the design parameters (i.e., lamination angles) space, the considered optimization task is to find a solution for which both f1 and Pcr simultaneously reach values as close to their maxima as possible. All the investigated optimization examples are repeated several times and basic statistical analysis of the results is presented.     

Use of natural killer cells as immunotherapy for leukaemia

Natural killer (NK) cells potentially play a significant role in eradicating residual disease following allogeneic haematopoietic cell transplantation, and have been explored as tools for adoptive immunotherapy for chemotherapy-refractory patients. NK cell cytotoxicity is modulated by multiple activating and inhibitory receptors that maintain a balance between self-tolerance and providing surveillance against pathogens and malignant transformation. The functional characteristics of NK cells are dictated by the strength of inhibitory receptor signalling. Major histocompatibility complex (MHC)-specific inhibitory receptor acquisition occurs sequentially during NK cell development, and is determined by the nature of immunological reconstitution after allogeneic haematopoietic cell transplantation. Polymorphisms of inhibitory receptors [killer immunoglobulin-like receptors (KIRs)] and their ligands (MHC) contribute to interindividual variability. As a result, the functional NK cell repertoire of individual donors has variable potential for graft-vs-leukaemia reactions. Models predicting NK cell alloreactivity, including KIR ligand mismatch and missing KIR ligand strategies, are discussed as algorithms for optimal NK cell donor selection. Future modifications to improve NK cell adoptive immunotherapy by means of increasing target recognition and reducing inhibitory signalling are being explored.     

The effect of donor age on the packing susceptibility of erythrocytes

The study of 411 healthy persons indicates that erythrocyte susceptibility to centrifugal packing at 200 g increases with age, evidencing an age-related decrease in red cell deformability. Positive correlations between donor age and blood plasma fibrinogen concentration and erythrocyte sedimentation rate were confirmed. The impairment of red cell deformability may affect the circulatory efficiency in the aged.