ABSTRACT
BACKGROUND: It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. METHODS: Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. RESULTS: Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. CONCLUSIONS: AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.
Subject(s)
Amantadine/therapeutic use , Dopamine Agonists/therapeutic use , Drug Resistance , Obsessive-Compulsive Disorder/drug therapy , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Aged , Amantadine/adverse effects , Diagnostic and Statistical Manual of Mental Disorders , Dopamine Agonists/adverse effects , Drug Therapy, Combination/adverse effects , Female , Humans , Male , Middle Aged , Patient Dropouts , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/adverse effects , Young AdultABSTRACT
BACKGROUND: We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. METHODS: eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with ß(2)-glycoprotein I (ß(2)-GPI). Autoantibody levels were measured at 1 and 5 months post-immunization. Mice were tested at 4 months post-immunization for behavior and cognitive function in the staircase, elevated plus-maze, and swim T-maze tests. Brains were removed and analyzed by immunohistochemistry for inflammatory markers and neurodegenerative processes. RESULTS: A single immunization with ß(2)-GPI induced significantly higher and longer-lasting immune responses, and this was dependent on the number of FVL alleles. At 1 and 5 months post-immunization, levels of antibodies rose from 1.17 ± 0.07 to 1.62 ± 0.17 (optical density units; ODU) in homozygous FVL mice, compared with stable levels of 0.59 ± 0.17 and 0.48 ± 0.16 ODU in heterozygous FVL mice and a drop from 1.62 ± 0.21 to 0.61 ± 0.13 ODU in wild-type mice. Behavioral and cognitive clinical features of eAPS were also correlated with FVL allele load, as assessed by the elevated plus-maze (altered anxiety), staircase (hyperactivity and higher exploration), and swim T-maze (impaired learning) tests. Histological studies identified significant neurodegenerative changes in both grey and white matter in the eAPS-FVL brains. In spite of the potential interaction of two prothrombotic disease states, there were no ischemic lesions seen in this group. CONCLUSIONS: The results indicate that genetically mediated coagulopathies increase the risk of developing coagulation-targeted autoimmune responses, and suggest the importance of antibody-mediated neurodegenerative processes in the brain in APS.
Subject(s)
Antiphospholipid Syndrome/pathology , Blood Coagulation Disorders, Inherited/complications , Cognitive Dysfunction/chemically induced , Factor V/genetics , Animals , Autoantibodies/blood , Brain/pathology , Disease Models, Animal , Female , Histocytochemistry , Humans , Locomotion , Male , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
A presente pesquisa pretendeu averiguar a influencia de uma manobra militar em diferentes aptidaoes. Para a realiacao da mesma, foi escolhida uma amostra de 46 individuos de uma populacao de 168 alunos do Curso de Formacao de Oficiais da Academia de Policia Militar do Rio Grande do Sul. Nestes, foi aplicada uma testagem antes e depois de uma manobra militar, levantnado-se os dados atraves de um tratamento estatistico que foi a prova de 'T' de Wilcoxon para amostras relacionadas. Tendo como referencia os resultados alcancados atraves deste levantamento, constatamos que a manobra influencia positivo e siginificativamente em divesas aptidoes dos alunos oficiais.
