Incapacity for work and disability pensions in persons with mental disorders

The number of people suffering from mental disorders and receiving disability pensions is still increasing in Europe. Young persons in their working-age are receiving disability pensions more and more often. Among those who are incapable to work (due to both mental and somatic disorders), persons on benefits due to mental disorders are usually younger. The number of disability pensions depends on the sort of mental disorder. Persons suffering from affective and anxiety disorders are the most common group receiving benefits. An increase in the number of disability payments among people with several mental disorders or both, mental and somatic diseases is observed. Furthermore, research data shows Poland as the country with high costs relevant disability payments. Disability pensions assignment for persons suffering from mental disorders, as well as incapacity for work, is discussed in this article. The reason for a still increasing number of disability payments is explained, the characteristics of persons applying for disability pensions is introduced and the mental impaired persons' incapacity for work is described.     

Different vulnerability of fibrinogen subunits to oxidative/nitrative modifications induced by peroxynitrite: functional consequences

Based on previous studies suggesting that fibrinogen (Fg) might be a potential target for peroxynitrite (PN) action in plasma, we investigated the effects of PN on structure and hemostatic function of Fg in vitro. Using fluorescence and spectrophotometric methods, we estimated that about 0.5, 2 and 8 tyrosine residues per molecule were nitrated following the reaction of Fg at concentration 5.88 muM with 10, 100 and 1000 muM PN, respectively. At the same molar ratios of Fg to PN, about 0.01, 0.19 and 0.34 of tyrosine residues per molecule were oxidized to dityrosine and the amount of carbonyl groups in Fg increased 1.3-, 2,3- and 3.6-fold when compared to control Fg. SDS-PAGE analysis of PN-modified Fg suggests that inter- and intramolecular dityrosine cross-links occur between A alpha chains of Fg. Vulnerability of Fg subunits to oxidative/nitrative modifications induced by PN was different. Within the Fg molecule, mainly alpha C domains as well as D domains (contrary to E domain) undergo the majority of the modifications. Low extent of nitration and oxidation of Fg molecule (induced by 10 microM PN) did not affect its clotting activity and susceptibility to degradation by plasmin. Modification of Fg induced by higher PN concentrations decreased these properties.     

The myelin-associated glycoprotein inhibitor BENZ induces outgrowth and survival of rat dorsal root ganglion cell cultures

The novel myelin-associated glycoprotein (MAG) inhibitor BENZ binds to the N-acetylneuraminic acid (Neu5Ac) portion of the N-terminal Ig-like domain of MAG. Treatment of rat dorsal root ganglion (DRG) cell cultures with BENZ-induced outgrowth of neurofilament 200-positive neurites improved survival of neurons and increased the number of GFAP-positive cells, as determined by fluorescence and confocal laser microscopy and by Western immunoblotting. Furthermore, treatment of DRG cell cultures with BENZ repressed gene and protein expression of the small GTPase RhoA but induced expression of Rho GTP-activating proteins 5 and 24, likely to counteract protein kinase A activity. Specifically, expression of inhibitors of neurite outgrowth, for example, Rock2 and PAK4, was repressed, but cofilin 1, a promoter of axonal growth, was induced. We propose that the MAG inhibitor BENZ abrogates the RhoA-ROCK-cofilin pathway to promote neurite outgrowth. Our findings require confirmation by in vivo animal studies.     

Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry

Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of freated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits.     

Improved cognitive function in schizophrenia after one year of cognitive training and vocational services

A year-long program of Neurocognitive Enhancement Therapy (NET) was used to remediate cognitive deficits in people with schizophrenia who were participating in a vocational program. Seventy-two stable outpatients with schizophrenia or schizoaffective disorder, recruited from an urban community mental health center were randomly assigned to a twelve-month vocational program (VOC) or NET+VOC. The vocational program had characteristics of individual placement and support (IPS) programs but also included transitional funding. NET included computer-based cognitive training exercises, a social information processing group and a work feedback group. Sixty-two participants completed a neuropsychological test battery before and after treatment. After one year of treatment, participants receiving NET+VOC had significantly greater improvements on measures of executive function and working memory than did participants in the VOC only condition. Augmenting vocational services with a multifaceted cognitive remediation program may improve cognition in participants with schizophrenia or schizoaffective disorder.     

Screening of amide analogues of Trichostatin A in cultures of primary rat hepatocytes: search for potent and safe HDAC inhibitors

Summary  The vast majority of preclinical studies of HDAC inhibitors (HDAC-I) focus on the drug–target (cancer) cell interaction, whereas little attention is paid to the effects on non-target healthy cells, which could provide decisive information to eliminate potential cytotoxic compounds at a very early stage during drug development. In the current study we used cultures of primary rat hepatocytes as a read out system to select for the most potent HDAC-I in the group of structural analogues of an archetypal HDAC-I, namely Trichostatin A. This kind of approach allowed selecting compounds with high biological activity and with no apparent toxicity towards cultured hepatocytes. Joanna Fraczek and Sarah Deleu contributed equally to this article. T. Vanhaecke is a postdoctoral research fellow of the Fund for Scientific Research Flanders (FWO-Vlaanderen, Belgium)