Pequenos mamíferos do Parque Estadual da Serra do Brigadeiro, Minas Gerais, Sudeste do Brasil: composição de espécies e distribuição altitudinal

The Serra do Brigadeiro State Park represents one of the few remnants of Atlantic forest in a mountainous region of the State of Minas Gerais. The terrestrial small mammal fauna of the park within a 1200- 1800m altitudinal interval was inventoried from 1996 to 2004 to generate estimates about taxonomic composition, richness, abundance, and altitudinal distribution of species. Cytogenetic analyses were carried out for selected species as an additional tool for taxonomic identifications and diversity estimates. A sampling effort of 4620 trapping-nights resulted in 21 species of rodents (families Cricetidae and Echimyidae) and marsupials (family Didelphidae) recorded, of which seven have their karyotypes described. Cumulative curves and non-parametric estimators suggest that the overall inventory is 81% complete and that at least five species are likely to be recorded with additional sampling. Species composition and diversity varied significantly across elevational belts with the lower altitudes characterized by both forest restricted and habitat-generalist species, while the upper altitudes are exclusively characterized by elevationally widespread and habitat-generalist species. Species diversity peaked at middle elevations (1300-1400m) and the putative factors responsible for this pattern are discussed.O Parque Estadual da Serra do Brigadeiro é um dos poucos remanescentes de Mata Atlântica, na Zona da Mata de Minas Gerais, localizado em região montanhosa. No período entre 1996 e 2004, foi empreendido um esforço de captura de 4620 armadilhas-noite, amostrando o intervalo altitudinal 1200-1800m, com o objetivo de inventariar a fauna de pequenos mamiferos terrestres, produzir estimativas sobre a composição taxonômica, riqueza, abundância e distribuição altitudinal das espécies desse grupo no parque. Análises citogenéticas foram realizadas em algumas espécies para auxiliar a identificação taxonômica. Foram registradas 21 espécies de roedores e marsupiais (famílias Cricetidae, Echimyidae e Didelphidae), sete das quais tiveram seus cariótipos descritos. O padrão de diversidade revelado pelas curvas cumulativas de espécie e estimadores não-paramétricos sugere que aproximadamente 81% da riqueza de espécies foi amostrada e que pelo menos cinco espécies possam ser adicionadas à listagem com esforço de captura adicional. A riqueza e composição de espécies variaram significativamente entre as cotas altimétricas, sendo as áreas mais baixas caracterizadas pela presença simultânea de espécies restritas à mata e espécies generalistas, enquanto a comunidade das áreas mais elevadas foi composta exclusivamente por espécies com ampla distribuição altitudinal e generalistas com relação ao hábitat. A maior riqueza de espécies foi detectada nas altitudes intermediárias (1300-1400m), sendo discutidos os fatores possivelmente responsáveis por esse padrão

Brazilian guidelines for the diagnosis of narcolepsy

Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy

Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation

A new series of eight multifunctional thalidomide–donepezil hybrids were synthesized based on the multi target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the N-benzylpiperidine pharmacophore of donepezil and the isoindoline 1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC50 value of 3.15 μM, which was predicted by docking studies as interacting with the enzyme in the same orientation observed in the AChE–donepezil complex and a similar profile of interaction. Additionally, compound 3g significantly decreased iNOS and IL-1β levels by 43% and 39%, respectively, after 24 h of incubation with lipopolysaccharide. In vivo data confirmed the ability of 3g to prevent locomotor impairment and changes in feeding behavior elicited by lipopolysaccharide. Moreover, the PAMPA assay evidenced adequate blood–brain barrier and gastrointestinal tract permeabilities with an Fa value of 69.8%. Altogether, these biological data suggest that compound 3g can treat the inflammatory process and oxidative stress resulting from the overexpression of iNOS and therefore the increase in reactive nitrogen species, and regulate the release of pro-inflammatory cytokines such as IL-1β. In this regard, compound PQM-189 (3g) was revealed to be a promising neuroprotective and anti-neuroinflammatory agent with an innovative thalidomide–donepezil-based hybrid molecular architectur

Amyloid-β Triggers the Release of Neuronal Hexokinase 1 from Mitochondria

Brain accumulation of the amyloid-β peptide (Aβ) and oxidative stress underlie neuronal dysfunction and memory loss in Alzheimer's disease (AD). Hexokinase (HK), a key glycolytic enzyme, plays important pro-survival roles, reducing mitochondrial reactive oxygen species (ROS) generation and preventing apoptosis in neurons and other cell types. Brain isozyme HKI is mainly associated with mitochondria and HK release from mitochondria causes a significant decrease in enzyme activity and triggers oxidative damage. We here investigated the relationship between Aβ-induced oxidative stress and HK activity. We found that Aβ triggered HKI detachment from mitochondria decreasing HKI activity in cortical neurons. Aβ oligomers further impair energy metabolism by decreasing neuronal ATP levels. Aβ-induced HKI cellular redistribution was accompanied by excessive ROS generation and neuronal death. 2-deoxyglucose blocked Aβ-induced oxidative stress and neuronal death. Results suggest that Aβ-induced cellular redistribution and inactivation of neuronal HKI play important roles in oxidative stress and neurodegeneration in AD