Abstract Background Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.

ABSTRACT Solitary fibrous tumors of the liver are uncommon benign tumors originating from the submesothelial tissue with non-well-defined malignant potential. Most cases present as asymptomatic, some cases show abdominal bloating and a palpable mass. They may mimic other tumors on imaging tests and surgery is indicated. We report a case of a 70-year-old female patient treated with left lateral liver resection with literature review of the condition.

RESUMEN Los tumores fibrosos solitarios hepáticos, una neoplasia poco frecuente, son tumores benignos del tejido submesotelial, pero con un potencial maligno no definido. Suelen presentarse asintomáticos, pero pueden debutar como una masa abdominal palpable y con síntomas de plenitud. Por imágenes pueden ser confundidos con otros tumores y está indicado el tratamiento quirúrgico. Presentamos el caso de una paciente de 70 años resuelto por hepatectomía lateral izquierda, y realizamos una revisión bibliográfica del tema.

Abstract Background: Spider venom is a potential source of pharmacologically important compounds. Previous studies on spider venoms reported the presence of bioactive molecules that possess cell-modulating activities. Despite these claims, sparse scientific evidence is available on the cytotoxic mechanisms in relation to the components of the spider venom. In this study, we aimed to determine the cytotoxic fractions of the spider venom extracted from Phlogiellus bundokalbo and to ascertain the possible mechanism of toxicity towards human lung adenocarcinoma (A549) cells. Methods: Spider venom was extracted by electrostimulation. Components of the extracted venom were separated by reversed-phase high performance liquid chromatography (RP-HPLC) using a linear gradient of 0.1% trifluoroacetic acid (TFA) in water and 0.1% TFA in 95% acetonitrile (ACN). Cytotoxic activity was evaluated by the MTT assay. Apoptotic or necrotic cell death was assessed by microscopic evaluation in the presence of Hoechst 33342 and Annexin V, Alexa FluorTM 488 conjugate fluorescent stains, and caspase activation assay. Phospholipase A2 (PLA2) activity of the cytotoxic fractions were also measured. Results: We observed and isolated six fractions from the venom of P. bundokalbo collected from Aurora, Zamboanga del Sur. Four of these fractions displayed cytotoxic activities. Fractions AT5-1, AT5-3, and AT5-4 were found to be apoptotic while AT5-6, the least polar among the cytotoxic components, was observed to induce necrosis. PLA2 activity also showed cytotoxicity in all fractions but presented no relationship between specific activity of PLA2 and cytotoxicity. Conclusion: The venom of P. bundokalbo spider, an endemic tarantula species in the Philippines, contains components that were able to induce either apoptosis or necrosis in A549 cells.

O tempo de desenvolvimento é um dos fatores-chave que contribuem para o sucesso do desenvolvimento de novos produtos. Apesar disso, o impacto da incerteza de tempo no desenvolvimento tem sido pouco considerado em modelos de avaliação e valoração deste tipo de projetos. Neste contexto, este trabalho tem como objetivo avaliar projetos de desenvolvimento de novas tecnologias mediante o tempo incerto. Introduzimos um modelo capaz de captar esta fonte de incerteza e desenvolvemos um algoritmo para a valoração do projeto que integra Simulação de Monte Carlo e Programação Dinâmica. A novidade neste trabalho é conseguir integrar meticulosamente o tempo estocástico a uma estrutura formal para tomada de decisão que preserva a propriedade de Markov. O principal ponto para viabilizar este fato é distinção entre o momento de revisão e o tempo estocástico. Ilustramos e discutimos a aplicabilidade deste modelo por meio de um exemplo empírico.

The development time is one of the key factors that contribute to the new product development success. In spite of that, the impact of the time uncertainty on the development has been not fully exploited, as far as decision supporting models to evaluate this kind of projects is concerned. In this context, the objective of the present paper is to evaluate the development process of new technologies under time uncertainty. We introduce a model which captures this source of uncertainty and develop an algorithm to evaluate projects that incorporates Monte Carlo Simulation and Dynamic Programming. The novelty in our approach is to thoroughly blend the stochastic time with a formal approach to the problem, which preserves the Markov property. We base our model on the distinction between the decision epoch and the stochastic time. We discuss and illustrate the applicability of our model through an empirical example.