Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities

Finding a better drug for epilepsy: Preclinical screening strategies and experimental trial design

The anti-epileptic drugs (AEDs) introduced in the last two decades have provided several benefits: they offered new treatment options for symptomatic treatment of seizures, improved ease of use and tolerability, lowered risk for hypersensitivity reactions and detrimental drug-drug interactions. These drugs, however, did not attenuate the problem of drug refractory epilepsy nor proved capable to prevent and/or cure the disease. Thus, new preclinical screening strategies are needed to identify AEDs that target these unmet medical needs. New therapies may derive from novel targets identified on the basis of existing hypotheses for drug refractory epilepsy and the biology of epileptogenesis; from research on genetics, transcriptomics and epigenetics; from mechanisms relevant for other therapy areas. Novel targets should be explored using new preclinical screening strategies and new technologies should be used to develop medium- to high-throughput screening models. In vivo testing of novel drugs should be performed in models mimicking relevant aspects of drug refractory epilepsy and/or epileptogenesis. To minimize the high attrition rate associated with drug development, which mainly arises from a failure to demonstrate sufficient clinical efficacy of new treatments, it is important to define integrated strategies for preclinical screening and experimental trial design. An important tool will be the discovery and implementation of relevant biomarkers, that will facilitate a continuum of proof-of-concept approaches during early clinical testing to rapidly confirm or reject preclinical findings, and thereby lower the risk of the overall development effort. In this review, we overview some of the issues related to these topics and provide examples of new approaches that will hopefully be more successful than those used in the past

Identification of new epilepsy treatments for: issues in preclinical methodology

Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic anti seizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age- or gender specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities

The contribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes no modelo de epilepsia induzido pela pilocarpina

The pilocarpine model of epilepsy in rats is characterised by the occurrence of spontaneous seizures (SRSs) during the chronic period that recur 2-3 times per week during the whole animal life. In a previous study on brain metabolism during the chronic period of the pilocarpine model it was possible to observe that, among several brain structures, the lateral posterior thalamic nuclei (LP) showed a strikingly increased metabolism. Some evidences suggest that the LP can participate in an inhibitory control system involved in the propagation of the seizures. The aim of the present study was to verify the role of LP in the expression and frequency of spontaneous seizures observed in the pilocarpine model. Ten adult male rats presenting SRSs were monitored for behavioural events by video system one month before and one month after LP ibotenic acid lesion. Another group of chronic epileptic rats (n=10) had the anteroventral thalamic nuclei (AV) lesioned by ibotenic acid. After the surgical procedure, the animals were sacrified and the brains were processed for histological analysis by the Nissl method. The LP group seizure frequency was 3.1±1.9 before ibotenic acid injection and showed an increase (16.3±7.2 per week) after LP lesion. No changes in SRSs frequency were observed in the AV group after ibotenic lesion in these nuclei. These results seem to suggest that LP play a role in the seizure circuitry inhibiting the expression of spontaneous seizures in the pilocarpine model.<br>O modelo de epilepsia induzido pela pilocarpina é caracterizado pela ocorrência de crises espontâneas e recorrentes (CERs) durante o período crônico, em uma frequência de 2-3 episódios semanais durante toda a vida do animal. Um estudo prévio do metabolismo cerebral durante o período crônico do modelo da pilocarpina mostra que entre as diferentes estruturas cerebrais,o núcleo talâmico lateral posterior (LP) apresentou um significante aumento em seu metabolismo. Evidências sugerem que o LP pode participar como um sistema de controle inibitório na propagação das crises. O objetivo deste estudo foi verificar o papel do LP na expressão e frequência das CERs no modelo de epilepsia induzido pela pilocarpina. Dez ratos machos adultos da raça Wistar que apresentaram CERs, foram monitorados por um período de dois meses, sendo um mês antes e outro após a lesão do LP com ácido ibotênico, através de um sistema de vídeo para verificar os eventos comportamentais. Outro grupo de animais epilépticos crônicos (n=10) sofreu lesão do núcleo talâmico ântero-ventral (AV) pelo ácido ibotênico. Após esses procedimentos, os animais foram sacrificados e realizada a análise histológica cerebral através do método de Nissl. O grupo LP, o qual apresentava 3,1±1,9 crises por semana antes de sofrer a lesão por ácido ibotênico, apresentou aumento na frequência das CERs de 50,5% após a lesão (16.3±7.2 CERs por semana). Não foi observada alteração na frequência de CERs nos animais pertencentes ao grupo AV. Nossos resultados sugerem que o LP está implicado no mecanismo de controle inibitório das CERs no modelo de epilepsia induzido pela pilocarpina

Statistical voxel-wise analysis of ictal SPECT reveals pattern of abnormal perfusion in patients with temporal lobe epilepsy Análise estatística baseada em voxel do SPECT ictal revela um padrão de alteração perfusional em pacientes com epilepsia de lobo temporal

OBJECTIVE: To investigate the pattern of perfusion abnormalities in ictal and interictal brain perfusion SPECT images (BSI) from patients with temporal lobe epilepsy (TLE). METHOD: It was acquired interictal and ictal BSI from 24 patients with refractory TLE. BSIs were analyzed by visual inspection and statistical parametric mapping (SPM2). Statistical analysis compared the patients group to a control group of 50 volunteers. The images from patients with left-TLE were left-right flipped. RESULTS: It was not observed significant perfusional differences in interictal scans with SPM. Ictal BSI in SPM analysis revealed hyperperfusion within ipsilateral temporal lobe (epileptogenic focus) and also contralateral parieto-occipital region, ipsilateral posterior cingulate gyrus, occipital lobes and ipsilateral basal ganglia. Ictal BSI also showed areas of hypoperfusion. CONCLUSION: In a group analysis of ictal BSI of patients with TLE, voxel-wise analysis detects a network of distant regions of perfusional alteration which may play active role in seizure genesis and propagation.<br>OBJETIVO: Investigar o padrão de anormalidades perfusionais no SPECT de perfusão cerebral (SPC) ictal e interictal na epilepsia de lobo temporal (ELT). MÉTODO: Foram realizados SPCs ictal e interictal de 24 pacientes com ELT que foram analisados visualmente e com o statistical parametric mapping (SPM2). A análise estatística comparou o grupo de pacientes versus um grupo controle de 50 voluntários. RESULTADOS: Na análise do SPM não foram observadas diferenças significativas no grupo de SPC interictal. No grupo de SPC ictal o SPM revelou hiperperfusão no lobo temporal ipsilateral (foco epileptogênico) e também na região parieto-occipital contralateral, porção posterior do cíngulo ipsilateral, lobos occipitais e núcleos da base ipsilateral. O SPC ictal também mostrou áreas de hipoperfusão. CONCLUSÃO: Em uma análise de grupo do SPC ictal de pacientes com ELT, a análise baseada em voxel detecta uma rede de alteração perfusional em regiões distantes que pode ter uma função ativa na origem e propagação das crises

Corpos de inclusão citoplasmática: estudo em diversas doenças e revisão da literatura Inclusion cytoplasmic bodies: a study in several diseases and a literature review

Estudamos 16 casos entre 1400 biópsias musculares que apresentavam vacúolos marginados, cujo aspecto histológico sugeria corpos de inclusão citoplasmáticos. Procuramos correlacionar os dados clínicos, laboratoriais e histopatológicos, a fim de determinar a especificidade dos corpos de inclusão citoplasmáticos para determinadas doenças. A creatinaquinase mostrou-se elevada em 10 casos. A eletromiografia foi anormal em todos os casos. A histoquímica muscular em 5 casos revelou uma miopatia, em 7 padrão misto, em dois desinervação e em 2 casos miopatia inflamatória. A microscopia eletrônica demonstrou a presença de filamentos em 8 casos (nucleares, dispersos no citoplasma ou na região subsarcolemal). Os pacientes foram classificados conforme a história clínica, hereditariedade, dados laboratoriais, eletrofisiológicos, histoquímicos e microscopia eletrônica Encontramos miosite com corpos de inclusão citoplasmática (4 casos), atrofia muscular espinhal juvenil (6 casos), miopatias distais (3 casos), distrofia de cinturas pélvica e escapular (2 casos) e polineuropatia periférica (1 caso). Apresentamos revisão sobre a patogenia, formação e possível etiologia dos vacúolos marginados e sua relação com as diversas entidades em que foram detectados, sugerindo que não são específicos para uma única doença.<br>Among 1400 muscle biopsies, we studied 16 cases with rimmed vacuoles, whose histology suggests cytoplasm inclusion bodies. We tried to correlate the clinical, laboratory and histopatological data in order to verify the specificity of cytoplasm inclusion bodies to certain diseases. The creatinekinase was increased in 10 cases. In all cases electromyography was abnormal. Muscle histochemistry revealed myopathy in 5 cases, mixed pattern in 7, denervation in 2 and in 2 cases, inflammatory myopathy. Electron microscopy showed the presence of filaments in 8 cases (nuclear, disseminated in cytoplasm or in the subsarcolemmal region). The patients were classified according to history, heredity, laboratory, electrophysiologic, histochemistry data and electron microscopy: in myositis with inclusion cytoplasmic bodies (4 cases), juvenile spinal muscular atrophy (6 cases), distal myopathies (3 cases), limb-girdle dystrophy (2 cases) and peripheral neuropathy (1 case). We present a revision on the pathogenesis and possible etiology of rimmed vacuoles and their relationship with several diseases