A prolina é convertida em glutamato através de dois passos de oxidorredução. Primeiro, prolina é oxidada em D1-pirrolina-5-carboxilato (P5C) que é convertido em glutamato pela TcP5CDH. Neste trabalho demonstrou-se que a enzima TcP5CDH catalisa a oxidação irreversível de gGSA formando glutamato e NADH/NADPH. A TcP5CDH forma um hexâmero que interage com a membrana interna mitocondrial. Os elétrons a partir de NADH abastecem a cadeia transportadora de elétrons para a síntese de ATP. Além disso vimos que a TcP5CDH é regulada positivamente nos estágios infectivos do parasita e, quando esta é induzida pela inserção de uma cópia ectópica, os mutantes apresentam mudanças morfológicas e alterações na expressão da TcGP82. O DSF, reportado como inibidor de aldeído desidrogenasses, interfere na atividade da TcP5CDH, bem como exibiu um efeito tripanocida. Ensaios de RNAi para a TbP5CDH e a análise da expressão desta enzima nas formas do parasita presentes na mosca tsé-tsé também foram discutidos. Os nossos dados reforçam a relevância bioquímica da via prolina-glutamato em T. cruzi, e constituem as primeiras evidências sobre a ocorrência do metabolismo de P5C nessas espécies de tripanossomatídeos. / Proline is converted into glutamate through two oxidorreduction steps. First, prolina is oxidized into D1-pyrroline-5-carboxylate (P5C), which is further converted in glutamate by TcP5CDH. In this work we demonstrate that TcP5CDH catalyzes irreversibly the oxidation of gGSA rendering glutamate and NADH/NADPH. The TcP5CDH undergoes a hexameric conformation interacting with inner mitochondrial membranes. Electrons from NADH fed electron respiratory chain for ATP synthesis. Moreover, we show that TcP5CDH is up regulated in infective stages (M e T). When an additional copy of TcP5CDH was ectopically introduced into parasites, mutant cells exhibited morphological changes and alterations in TcGP82. O DSF, reported as inhibitor of aldehyde dehydrogenases, interferes with TcP5CDH, as well as exhibited a trypanocidal effect. RNAi silencing assays for TbP5CDH and developmental expression of this enzyme throughout main insect stages within tsetse fly were also addressed. Our data support biochemical relevance of proline-glutamate pathway in T. cruzi, and constitute first evidences regarding occurrence of P5C metabolism over these trypanosomatid species.

INTRODUÇÃO: As doenças inflamatórias intestinais têm chamado a atenção da comunidade científica pela multiplicidade de manifestações no trato digestivo, manifestações extra-intestinais e pela sua incidência em ascensão. Existe uma grande prevalência de manifestações extra-intestinais em portadores de doença de Crohn e de retocolite ulcerativa, variando na literatura de 24 a 65%. Estas alterações podem surgir antes dos sintomas intestinais, concomitante ou ulteriormente, podendo ou não ter relação com a atividade da doença intestinal. O conhecimento destas manifestações extra-intestinais assim como seu quadro clínico, evolução e tratamento é importante, devido ao aumento da morbidade e mortalidade desencadeada por elas. OBJETIVO: Objetivou-se neste trabalho determinar a prevalência de manifestações extra-intestinais em retocolite ulcerativa e doença de Crohn, correlacionando com diagnóstico do tipo de doença inflamatória intestinal, extensão, tempo de evolução e aparecimento dos sintomas, sexo e atividade da doença. MÉTODOS: Os pacientes que participaram do estudo estão cadastrados no Ambulatório de Doenças Inflamatórias do Serviço de Cirurgia do Cólon, Reto e Ânus do Departamento de Gastroenterologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo de setembro de 1984 até setembro de 2004. Os dados para a pesquisa foram colhidos retrospectivamente de mil protocolos que foram preenchidos em caráter prospectivo na primeira consulta do doente e atualizados em consultas subsequentes. Foram estudadas as manifestações articulares, dermatológicas, oftalmológicas, urológicas, hepáticas, pulmonares e vasculares. RESULTADOS: Entre os 1.000 pacientes estudados encontrou-se 468 com doença de Crohn (46,8%) e 532 com retocolite ulcerativa (53,2%). Foram encontrados 627 pacientes com pelo menos uma forma de manifestação extra-intestinal(315-59,2% com RCUI e 312-66,7% com doença de Crohn). A média de tempo de duração da doença inflamatória intestinal dos pacientes que tinham manifestações extra-intestinais foi de 10,23 anos, comparado a 7,89 anos daqueles que não possuíam, sendo estatisticamente significativo. Também foi evidenciado que as manifestações extraintestinais surgiram com maior frequencia ulteriormente aos sintomas intestinais da doença. CONCLUSÕES: Na retocolite ulcerativa a maior extensão da doença no cólon foi proporcional a incidência de manifestações extra-intestinais, enquanto na doença de Crohn, quando havia algum acometimento colônico era maior a incidência destas manifestações. Apenas as manifestações urológicas tiveram uma predisposição maior pela doença de Crohn, e nestes, no sexo masculino. As manifestações articulares e dermatológicas foram mais prevalentes no sexo feminino tanto em retocolite ulcerativa quanto na doença de Crohn. Na doença de Crohn também houve maior prevalência de manifestações hepáticas no sexo feminino. As manifestações articulares, dermatológicas e vasculares tiveram uma maior correlação com a atividade da doença intestinal em ambos os grupos. / INTRODUCTION: Intestinal inflammatory diseases have been calling the attention of the scientific community due to the multiplicity of manifestations in the digestive tract, extra-intestinal manifestations and due to its growing incidence. There\'s great prevalence of extra-intestinal manifestations in Crohn\'s disease and ulcerative rectocolitis bearers, varying in literature from 24 to 65%. These alterations may arise before the intestinal symptoms, either at the same time or after, and they may or may not be related to the activity of the intestinal disease. Knowing these extra-intestinal manifestations, as well as their clinical condition, evolution and treatment is important, due to the enhancement in morbidity and mortality aroused by them. AIM: The objective of this paper was to determine the prevalence of extra-intestinal manifestations in ulcerative rectocolitis and Crohn\'s disease, relating it with the diagnosis of the kind of intestinal inflammatory disease, extension, evolution time and the arising of the symptoms, sex and disease activity. METHODS: The patients who took part in the study are registered in the Ambulatory for Inflammatory Diseases of the Anus, Rectum and Colon Surgery Service in the Gastroenterology Service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, from September 1984 until September 2004. The data for the research were retrospectively gotten from one thousand protocols that were filled out in a prospective character during the patient\'s first consultation, and updated during subsequent consultations. Articular, dermatological, ophthalmologic, urologic, hepatic, pulmonary and vascular manifestations were studied. RESULTS: Among the 1,000 patients studied 468 were found to have Crohn\'s disease (46.8%) and 532 had ulcerative rectocolitis (53.2%). 627 patients were found with at least one form of extra-intestinal manifestation (315-59.2% had ulcerative retocolitis and 312-66.7% had Crohn\'s disease). The average duration time of the intestinal inflammatory disease of the patients who had extra-intestinal manifestations was of 10.23 years, compared to 7.89 years of those who had no disease, being statistically significant. It was also evident that the extra-intestinal manifestations came about more frequently subsequently to intestinal symptoms of the disease. CONCLUSIONS: In ulcerative rectocolitis, the greater extension of the disease in the colon was proportional to the incidence of extra-intestinal manifestations, whereas in Crohn\'s disease, when there was some colonic assault, the incidence of these manifestations was greater. Only the urologic manifestations have greater predisposition for Crohn\'s disease and in these ones, in the masculine sex. Articular and dermatological manifestations were more prevalent in the feminine sex both for ulcerative rectocolitis and for Crohn\'s disease. In Crohn\'s disease there was also greater prevalence of hepatic manifestations in the feminine sex. Articular, dermatological and vascular manifestations had greater correlation with the intestinal disease activity in both groups.

A doença de Parkinson (DP) é uma doença neurodegenerativa caracterizada pela progressiva depleção dos neurônios dopaminérgicos da substância negra (pars compacta). A DP não ocasiona apenas uma desordem motora, mas também pode provocar uma disautonomia cardiovascular. A DP com sintomas similares aos que ocorrem em humanos pode ser experimentalmente induzida em ratos e camundongos com a administração das neurotoxinas 1-metil-1-4-fenil-1,2,3,6-tetrahidropirimidina (MPTP), 6-hidroxidopamina (6-OHDA) e rotenona. Mais, na década de 90, camundongos transgênicos que expressam altos níveis de alfa-sinucleína mutante humana têm sido produzidos e utilizados para investigar a possível relação entre a agregação da proteína alfa-sinucleína e a DP, uma vez que em humanos, a alta expressão dessa proteína está relacionada ao desenvolvimento do parkinsonismo associado à desnervação cardíaca simpática. No entanto, a desnervação cardíaca e suas conseqüências no miocárdio na DP não estão claramente caracterizadas, pois na literatura os métodos quantitativos empregados para tal finalidade têm sua confiabilidade e acurácia questionáveis. Desta forma, avaliou-se, no modelo de indução neurotóxico (MPTP), o miocárdio de camundongos C57/BL aplicando-se métodos morfoquantitativos tridimensionais (estereológicos). Neste trabalho, observamos que o volume da parede ventricular, o volume e a densidade de volume do interstício cardíaco foram, respectivamente, 0,8%, 5,3% e 2,4% maior no grupo MPTP. O volume do lúmen ventricular, o volume ventricular, o volume das fibras musculares cardíacas e a sua densidade de volume foram, respectivamente, 11,7%, 0,9%, 2,3% e 1,7% maior no grupo controle. O número total de núcleos de cardiomiócitos foi 14,8% menor no grupo MPTP bem como o número total de cardiomiócitos que foi 19% menor também neste grupo. Houve diferença estatística significativa entre os grupos para o parâmetro número de cardiomiócitos. Não houve, porém, diferença estatística significativa para os outros parâmetros avaliados. / Parkinson´s disease (PD) is a neurodegenerative disorder mostly characterised by a profound reduction of dopamine in the striatum due to a dramatic loss of dopaminergic neurons in the substantia nigra (pars compacta). The disease is not only characterised by a motor disorder but also present cardiovascular dysautonomia. The disease has been chemically induced in rats and mice using neurotoxins such as 1-metyl-1-4-phenyl-1,2,3,6-tetrahydropyrimidina (MPTP), 6-OHDA and rotenone. In the nineties, transgenic α-synuclein mice have recently been used as a model of PD and alpha-synuclein aggregation, because the overexpression of this protein is related to the development of parkinsonism associated to the sympathetic cardiac denervation. Although, the cardiac denervation in PD and its consequences in myocardium is not well defined because the literature reports no reliable quantitative methods. Therefore, the myocardium of the C57/BL mice was investigated in the neurotoxin animal model (MPTP) applying tridimensional morphoquantitative methods (stereological). In this study, we observed an increase of 0,8%, 5,3% and 2,4% in ventricular wall volume, in cardiac interstitial volume and in cardiac interstitial volume density, respectively, in the MPTP group. The lumen ventricular volume, the ventricular volume, the cardiac muscle fibre and their volume density were, respectively, 11,7%, 0,9% , 2,3% and 1,7% larger in control group. The total number of cardiomyocyte nuclei was 14,8% lower in MPTP group as well as the total number of cardiomyocyte that was 19% lower for this group too. Significant difference was observed between the groups to the total number of cardiomyocyte. No significant difference, however, was detected for the others estimated parameters.

Introdução: Aproximadamente 25 a 30% dos pacientes com DC iniciam a doença antes da idade dos 20 anos. O déficit de crescimento é a complicação mais específica da DII pediátrica, causada pela combinação de ingestão calórica inadequada, aumento das perdas calóricas e inflamação ativa persistente da mucosa intestinal. Pacientes com DII comumente sofrem de desnutrição protéico-energética no diagnóstico e com flutuações durante todo o curso da doença. A perda de peso é uma característica comum no paciente com DII recém diagnosticada, particularmente na DC, e acompanha quase todas as recaídas. Aproximadamente 60% das crianças com DC apresentam perda de peso recente no momento do diagnóstico. Objetivos: verificar o estado nutricional de pacientes portadores de DC na adolescência, através da avaliação da composição corporal, dosagem de macro e micronutrientes e consumo alimentar. Casuística e Métodos: vinte e dois pacientes com DC em atividade (leve ou moderada), vinte e nove com DC em remissão e 35 parentes de 1º grau desses pacientes de mesma faixa etária (grupo controle) foram selecionados para participar prospectivamente. Antropometria (peso, estatura e índice de massa corporal (IMC) expressos em z escore, bioimpedância e estágio de Tanner), níveis séricos e a ingestão de macro e micronutrientes foram avaliados. Resultados: os adolescentes com DC em atividade seguidos pelo DC em remissão tiveram menor valor de escore z da estatura/idade e IMC para a idade, da massa magra e do estágio pubertário (p<0,05) do que o grupo controle. Os pacientes com DC apresentaram alterações significativas da qualidade da ingestão alimentar, principalmente calorias, proteínas, fibras e micronutrientes, refletindo nas dosagens séricas principalmente das vitaminas A e E (p<0,05). Conclusão: Adolescentes com DC, mesmo quando na fase de atividade da doença leve e inativa, apresentam riscos nutricionais, reforçando a importância da avaliação nutricional / Introduction: About 25 to 30% of patients with Crohns disease begin before age 20 years. The growth deficit is the most specific complication of pediatric CD, caused by a combination of inadequate energy intake, increased loss of calories and persistent active inflammation of the mucosa intestinal. Patients with IBD often suffer from protein-energy malnutrition in the diagnosis and fluctuations throughout the course of the disease. Weight loss is a common feature in patients with newly diagnosed IBD, particularly in CD, and accompanies almost all relapses. Approximately 60% of children with CD have a recent weight loss at diagnosis Objectives: We aimed to determine the nutritional status of patients with CD in adolescence, through the assessment of body composition, levels of macro and micronutrients and food consumption. Methods: Twenty-two patients with CD activity (mild or moderate), twenty-nine with CD in remission and 35 relatives of a degree of these patients the same age range (control group) were selected to enrolled prospectively . Anthropometry (weight, height and body mass index (BMI) expressed as z score, Tanner stage, and bioimpedance), blood levels and intake of macro and micronutrients were evaluated. Results: Adolescents with CD in activity followed by CD in remission had a lower value of z-score height / age and BMI for age, lean body mass and pubertal stage (p <0.05) than the control group. CD patients showed significant changes in the quality of food intake, especially calories, protein, fiber and micronutrients, mainly reflected in serum levels of vitamins A and E (p <0.05). Conclusion: Adolescents with CD, even when the stage of mild activity and inactive, have nutritional risks, reinforcing the importance of nutritional assessment

A demanda de atenção para manter o equilíbrio postural aumenta com o envelhecimento e pode causar prejuízos na realização concomitante de duas ou mais tarefas. Indivíduos com doença de Alzheimer (DA) possuem menor reserva de atenção e, portanto, apresentam maior dificuldade em realizar uma tarefa motora associada à cognitiva, com conseqüente aumento do risco de quedas e suas conseqüências. O objetivo deste estudo foi verificar o desempenho do equilíbrio durante a realização concomitante de atividades funcionais (dinâmicas e estáticas) e tarefa cognitiva no idoso com DA. Foram avaliados 60 idosos, de ambos os sexos, com idade média de 77 ± 4 anos, divididos em dois grupos: Grupo-DA - indivíduos com DA (n=28) e Grupocontrole - indivíduos sem alteração cognitiva (n=32). O equilíbrio postural foi avaliado na atividade dinâmica através do TUGT e na atividade estática, pela plataforma fixa, Balance Master, NeuroCom. O teste estático foi realizado com os olhos abertos e fechados. Os indivíduos com DA apresentaram pior desempenho no TUGT com e sem a tarefa cognitiva concomitante. No teste estático, o desempenho do Grupo DA foi pior que do Grupo-controle no teste de olhos fechados sem tarefa cognitiva. O equilíbrio do Grupo-DA foi pior que do Grupo-controle nos testes dinâmicos. A DA interfere no desempenho do equilíbrio postural na atividade dinâmica associada à tarefa cognitiva, mas não interfere na atividade estática. A plataforma fixa de avaliação utilizada neste estudo não se mostrou um instrumento sensível para medir as alterações no equilíbrio postural estático causadas pela realização de tarefa cognitiva concomitante nos idosos com DA. / The attentional demand in order to keep the postural balance increases with the aging process and may cause damages in the concomitant performance of two or more tasks. Subjects with Alzheimers disease (AD) have less attentional reserve, and therefore present greater difficulty to perform a motor task associated with a cognitive task, increasing the risk of falls and their consequences. The aim of this study was to verify the balance of elderly people with AD during the concomitant performance of functional activities (dynamic and static) and cognitive tasks. Sixty aged people, male and female, with mean age of 77 ± 4 years, were evaluated; subjects were divided into two groups: AD Group composed by individuals with AD (n=28) and Control Group composed by individuals without cognitive alterations (n=32). The postural balance was evaluated through TUGT in the dynamic activity, and through the stable platform, Balance Master, NeuroCom in the static activity. The static test was done with opened and closed eyes. Patients with AD presented worse performance in the TUGT with and without the concomitant cognitive task. In the static test, the performance of the AD Group was worse than the performance of the Control Group in the test with closed eyes without cognitive task. The balance of the AD Group was worse than the balance of the Control Group during the dynamic tests. The AD interferes in the postural balance performance in the dynamic activity associated with a cognitive task, but it does not interfere in the static activity. The evaluation stable platform used in this study was unable to measure the alterations in static postural balance caused by the concomitant performance of the cognitive task in aged people with AD.

O déficit de controle postural é impactante em indivíduos com doença de Parkinson (DP), nesse sentido, a aprendizagem de tarefas que o envolvam é fundamental para esses indivíduos. Recentemente, estudos têm mostrado que indivíduos com DP são capazes de aprender tarefas com demanda de controle postural, no entanto, o intervalo de retenção destes estudos é muito curto considerando-se uma doença neurodegenerativa. Outra questão que se coloca é, em aprendendo tarefas de demanda de controle postural, poderia haver diminuição da instabilidade postural, porém ainda não existem evidências concretas para responder esse questionamento. Nesse sentido, o objetivo do presente estudo foi investigar a aprendizagem de tarefas que envolvam demanda de controle postural em ambiente de realidade virtual em indivíduos com DP quando comparados com idosos saudáveis em curto e longo prazo, além de verificar seu impacto na cognição e no controle postural dos mesmos. A amostra foi composta por 28 sujeitos, sendo 14, com DP idiopática no grupo experimental (GE) [64.28±6.35 anos; escala de Hoehn e Yahr modificada = 14.28% dos sujeitos 1; 14.28%, 1.5; 7.14%, 2; 21.42%, 2.5; 42.85%, 3; Montreal Cognitive Assessment (MoCA) = 22.42±3.41; e Mini Balance Evaluation Systems Test (MiniBEStest) = 20.78±6.54]. Foram incluídos também 14 idosos saudáveis no grupo controle (GC) [69.71±5.91 anos; MoCA = 23.64±3.17; e MiniBESTest = 27.35±2.67]. Foram realizadas 13 sessões com duração de uma hora, 2x/semana por sete semanas, no período on da medicação para a reposição dopaminérgica, sendo a primeira considerada pré-teste e a última, pós-teste. A prática consistiu em jogar quatro jogos do sistema Kinect, 5 tentativas por jogo. Foram realizados dois testes de retenção, sendo o primeiro após uma semana e o segundo após um mês. A avaliação da cognição, através da MoCA, e do controle postural, através do MiniBESTest, foi realizada antes, imediatamente após e um mês após a fase de aquisição. Indivíduos com DP foram capazes de aprender tarefas com demanda de controle postural, havendo retenção a curto e longo prazo, apesar do desempenho apresentar-se inferior aos idosos neurologicamente saudáveis. Além disso, aprender as tarefas propostas levou a melhora da cognição, especificamente na memória e nos aspectos reativos do controle postural de idosos e indivíduos com DP, além da melhora da estabilidade de marcha somente dos idosos / Postural control deficits are striking in individuals with Parkinson\'s disease (PD), making the learning of postural control tasks crucial for these individuals. Recent studies have shown that PD patients are able to learn tasks with postural control demand; however, the retention interval found in these studies was quite short due to the nature of this neurodegenerative disease. Hence, in the learning process of high demand postural control tasks, is there a decrease in PD patients\' postural instability? Concrete data are needed to answer this question. Therefore, the purpose of this study was to investigate the learning of tasks involving a high demand for postural control in a virtual reality environment in individuals with PD when compared to healthy elderly. The learning process was investigated through both short- and long-term retention. The secondary purpose was to verify the learning process\'s impact on both cognition and postural control. The sample included 28 participants: 14 with idiopathic PD in the Experimental Group (EG) [64.28±6.35 years; Hoehn e Yahr modified scale = 14.28% 1; 14.28%, 1.5; 7.14%, 2; 21.42%, 2.5; 42.85%, 3; Montreal Cognitive Assessment (MoCA) = 22.42±3.41; and Mini Balance Evaluation Systems Test (MiniBEStest) = 20.78±6.54] and fourteen healthy elderly in the Control Group (CG) [69.71±5.91 years; MoCA = 23.64±3.17; e MiniBESTest = 27.35±2.67]. Thirteen one-hour sessions were performed two x/week for seven weeks, which was the on-medication period for dopaminergic replacement. The first session was considered as the pre-test, and the last session was considered as the post-test. The practice consisted of playing four Kinect system games, with five trials per game. Two retention tests were performed, with the first occurring after one week and the second occurring one month after the end of the acquisition phase. The assessment of cognition through MoCA and postural control through MiniBESTest were performed before, immediately after and one month after the acquisition phase. Individuals with PD learned tasks with a high demand for postural control and had both short- and long-term retention, despite their inferior performance compared to the neurologically healthy elderly. In addition, learning the proposed tasks led to an improvement in cognition, specifically in memory, and in the reactive aspects of postural control in the elderly and individuals with PD, as well as gait stability only in the elderly

Introduction The fundamental concept for modern inflammatory bowel disease (IBD) treatment algorithm is an early induction of mucosal healing and its maintenance. Biological therapies are becoming mainstays of IBD therapy. It is however still unclear if there is a difference between Crohn’s disease (CD) and Ulcerative Colitis (UC) in time from diagnosis to stable maintenance treatment when biological treatment is introduced. Aim To investigate the comparative efficacy of biological agents in CD and UC by studying the time course when biological treatment is introduced. Methods Retrospective study of patients suffering from IBD at Falu Hospital, receiving a new start with biologics between 2015-01-01 and 2016-12-31. Remission rate after 3 months of induction therapy was analyzed. Subsequently, when 6 months passed without active disease, it was considered a stable remission. Results Through database extraction 58 patients were identified. A total of 52 % patients fulfilled the criteria for remission. Of patients with CD 49 % got in remission, whereof 33 % had treatment with infliximab, 48 % adalimumab and 19 % vedolizumab. Of patients with UC 60 % got in remission, whereof 33 % had treatment with infliximab and 67 % with adalimumab. Log rank test showed no significant difference in efficacy of biologics in patients suffering from CD or UC in time from diagnosis respective after initiation with biologics to stable maintenance treatment. ConclusionsIn this study patients with CD and UC responded equally to biological treatment.

<p>The present study assessed olfactory and cognitive abilities in two strains of Alzheimer’s disease (AD) model mice and in healthy control mice over a four month time period. To this end an operant conditioning paradigm using an automated olfactometer and a spatial learning test with non-olfactory cues were employed and data on olfactory learning and memory, discrimination, and sensitivity as well as spatial learning and memory were collected. The mice were between 6 to 7 month old at the beginning of the study and 9 to 10 months old at the end of the data collection, that is, in the age range when the animals are supposed to display marked neuroanatomical changes typical of AD. The results demonstrate that there were no systematic differences in olfactory performance and spatial learning and memory abilities of AD model mice and the control mice up to the age they were tested. Further, there was no indication of an age-related decline in performance in any of the mouse strains across the testing period. Several reasons might account for the observed lack of difference in olfactory and cognitive performance between the mouse strains tested here: the AD model mice might not develop amyloid plaques and neurofibrillary tangles at all or they might develop them later than stated by the supplier. Alternatively, the AD model mice may have developed AD-typical neuroanatomical changes but these do not, or not yet, affect their olfactory performance and/or spatial learning and memory capabilities. Ongoing data collection will help to evaluate which of these explanations holds true.</p>

<p>Wilson's disease (WD), bepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene, and is characterised by abnormal metabolism and deposition of copper in the liver, brain and other organs. The main aim of this thesis was to investigate the occurrence of psychopathology, as well as personality traits and neuropsychological function in Swedish patients with treated WD. The research subjects were 29 patients with confirmed WD, investigated at the Department of Internal Medicine at Uppsala University Hospital between 1996 and 2000. </p><p>The treated WD patients showed prominent psychopathology as determined by the Comprehensive Psychopathological Rating Scale. The spectrum of psychopathological symptoms is not typical of classic psychiatric syndromes, and includes symptoms from Anxiety, Depression and Obsessive-Compulsive disorders as well as Negative Symptoms. In self-assessment, the WD patients tended to underestimate the presence of psychopathological symptoms. The treated WD patients differed in their sleep pattern from the control group, as measured with the Uppsala Sleep Inventory. The spectrum of self-reported symptoms suggests an altered REM sleep function. </p><p>The treated WD patients had significant deviations in personality traits, especially in aggressivity-hostility related scales and Psychic anxiety, compared to healthy controls, as measured with the Karolinska Scales of Personality. The deviations were not related to age, age at onset or duration of WD. The treated WD patients displayed a specific profile of moderate neuropsychological impairment, as determined by the Automated Psychological Test battery. Finally, an attempt was made to search for, possible genotype-phenotype relationships in some ATP7B mutations. </p>

<p> <p>&nbsp / </p> </p> <p align="left">This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon&rsquo / s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy.</p>