The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker

Phospholipase A(2) (PLA2) is a key enzyme of the phospholipid metabolism which shows alteration in schizophrenia. Eye movement disturbances occur in a majority of patients with schizophrenia and in a proportion of their first-degree relatives, and they have been suggested as an endophenotypic marker in genetic studies of this illness. Here we report an association between the BAN I polymorphism of the cytosolic PLA2 gene (single nucleotide polymorphism in the first intron of the gene) and the intensity of eye movement disturbances (fixation and smooth pursuit) observed in 126 schizophrenic patients. The mean intensity of both kinds of eye movement disturbances was significantly higher in individuals homozygous for the A2 genotype compared with the remaining phenotypes. There was also a trend for greater A2 allele frequency in schizophrenic patients with a higher degree of eye movement disturbances. The relative frequency of the A2/A2 genotype was higher in patients with a greater degree of eye movement disturbances occurring during both fixation and smooth pursuit tests. Our results correspond to the other studies showing an association between the cPLA2 polymorphism and schizophrenia (predominance of the A2 allele in schizophrenic subjects).     

Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients

Objectives:  The aim of the study was to test a possible association between the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene and performance on a neurocognitive test, the Wisconsin Card Sorting Test (WCST), in bipolar patients.
Methods:  Fifty-four bipolar patients were studied, 18 male and 36 female, aged 18–72 (mean 46 years). The number of perseverative errors (WCST-P), non-perseverative errors (WCST-NP), completed corrected categories (WCST-CC), conceptual level responses (WCST-%CONC) and set to the first category (WCST-1st CAT) were measured in relation to the Val66Met genotypes of BDNF.
Results:  The percentages of subjects with Val/Val, Val/Met and Met/Met genotypes were respectively 81.5, 16.7 and 1.8%. Subjects with Val/Val and Val/Met genotypes did not differ on clinical factors except for the age of onset of the illness, which was earlier in Val/Val than Val/Met genotype (27 years versus 38 years). The performance in all domains of WCST was significantly better in subjects with Val/Val BDNF genotype compared with Val/Met genotype.
Conclusions:  The results suggest a role of BDNF in prefrontal cognitive function in bipolar illness. The tests of prefrontal cognition may be considered as endophenotypic markers in bipolar illness.     

The morphological analysis of vasculature and angiogenic potential in meningiomas: immunoexpression of CD31 and VEGF antibodies

Meningiomas, despite being the mostly well-differentiated tumours, are quite often characterised by invasive growth and recurrences. As this fact may be caused by proangiogenic factors, we have investigated immunoexpression of CD31 and vascular endothelial growth factor (VEGF) in these tumours. The materials included 10 atypical meningiomas (G2), and the following subtypes of benign meningiomas (G1): 21 transitional, 17 meningothelial and 13 fibrous. Paraffin sections were immunostained with CD31 (DAKO) and VEGF (Santa Cruz) antibodies. The highest number of blood vessels was revealed in atypical meningiomas and much lower (statistically significant difference) in benign ones. Diffuse or focal expression of VEGF of various intensity was shown both in atypical and benign types of tumours with no statistically significant differences between both groups of tumours and between subtypes of benign meningiomas.     

Thermal glycation of proteins by D-glucose and D-fructose

The dry thermal glycation method was used to conjugate D-glucose and D-fructose with bovine serum albumin. Reactions were conducted at 50-104 degrees C for 30 min. Depending on temperature, different levels of substitution were achieved. In the case of D-glucose, average substitution levels of up to 53 mol glucose/mol bovine serum albumin were obtained. D-fructose turned out to be less reactive than D-glucose. The pH of the reaction mixture was also found to affect the efficiency of the glycation reaction. The levels of substitution were estimated using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and SDS-polyacrylamide gel electrophoresis. Glycated molecules, and a process of glycation itself are implicated in diabetes complications. Hypothetically bovine spongiform encephelopathy (BSE) was also derived from glycation.     

Immunotherapy in the management of sepsis

This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.     

The role of platelet activating factor (PAF) in physiology and pathology of the central nervous system

This review describes the role of platelet activating factor (PAF) in the central nervous system injury. Cerebral ischaemia, traumatic injury of central nervous system, metabolic, toxic and degenerative neuropathy, and also the increase in Ca2+ concentration in the cell, are strong stimulators of PAF synthesis and its release from cell membranes. Neurons, glial and microglial cells, monocyte cell populations, macrophages and endothelial cells of blood vessels are the targets of platelet activating factor. The release of PAF leads to ischaemia of nervous tissue, acute traumatic or nontraumatic injuries, degenerative and metabolic nervous system disorders in adults. The use of PAF receptor antagonists prevents partially cell injury in central nervous system and leukocyte adhesion to endothelial cells.     

Evaluation of blood flow velocity and cerebrovascular reactivity in patient with posterior circulation stroke

The aim of our study was to determine the type of blood flow disturbances and cerebrovascular reactivity of major anterior and posterior circulation cerebral vessels in patients with posterior stroke (POCI). The examined group consisted of 17 patients, mean age 57 +/- 12 yr, with posterior circulation infarct. Neurological examination, brain CT and Doppler examination including evaluation of BFV and CVR of MCA, PCA and VA was performed in each patient. Doppler examination was done using Pioneer TC 2020 and capnograph Tidal Wave sp Novametrix. RESULTS: BFV of ICA's, MCA's, ACA's and PCA's were diminished while BFV of VA's were significantly diminished in the examined patients compared to healthy controls. CVR of MCA in posterior circulation stroke patients was significantly lower compared to controls. CVR of PCA and VA was significantly lower compared to CVR of MCA in patients with posterior circulation stroke. CONCLUSION: Impairment of CVR, especially in posterior circulation, plays an important role in posterior circulation stroke pathogenesis.     

Lack of association between VNTR polymorphism of DAT gene and schizophrenia

The substantial importance of genetic factors in the etiology of schizophrenia was demonstrated in many studies. The complex model of disease inheritance seems to be the most probable, involving epistatic interaction of many genes. Association studies are based on the analysis of the so-called candidate genes, which are coding for neurotransmitter receptors, neurotransmitter transporters and enzymes involved in their metabolism. In the present work the results of an association study of VNTR polymorphism of dopamine transporter gene (DAT) in schizophrenia are presented. This polymorphism is characterised by a different number of tandem repeats (VNTR) within the 3'-untranslated region of gene. In Caucasians the 40 base pair motif has 3 to 11 repeats, the most common (about 90%) are alleles containing 9 and 10 repeats. In the present study no association between the polymorphism studied and schizophrenia was found.