Experimental Planning and Execution

Mullane, Kevin; Curtis, Michael J.; Williams, Michael

doi:10.1016/b978-0-12-804725-5.00002-1

Cited by 2 publications

(2 citation statements)

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“…In this work, a full 2 3 factorial design was applied for the optimization of the extraction method of substances of low polarity from red propolis, aiming to be fast, of low expenditures, and high yield. This model allows a combination of three variables and one central point with three samples and is frequently used in optimization studies [24][25][26][27][28]. However, studies applying factorial design for the analysis of extractive processes of propolis samples using pressurized liquids have not yet been reported in the literature.…”

Section: Resultsmentioning

confidence: 99%

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity

et al. 2020

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Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

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Section: Resultsmentioning

confidence: 99%

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity

et al. 2020

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“…A key concern related to the translational value of the mouse and rat transgenic AD models, in fact for any transgenic model, is the rigor and objectivity with which the behavioral/functional phenotypes have been interrogated, reproduced, and reported. Behavioral studies in animal models have traditionally involved small effect sizes that as a result require experiments that are appropriately and rigorously designed to reduce bias i.e., blinded, randomized and adequately powered with relevant controls and predefined endpoints (Shineman et al., ; Gore & Stanley, ; Egan et al., ; Snyder et al., ; Mullane, Curtis, & Williams, ; Marino, ). Despite this, efficacy outcomes for new AD therapeutics are often reported as significant based on small effect sizes, minimal animal numbers that have not been repeated such that their value is overstated and questionable, reflecting reporting and significance bias (Tsilidis et al., ).…”

Section: Reproducibility Issues With Transgenic Rodent Ad Modelsmentioning

confidence: 99%

Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity

Mullane

Williams

2019

CP Pharmacology

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The only drugs currently approved for the treatment of Alzheimer's Disease (AD) are four acetylcholinesterase inhibitors and the NMDA antagonist memantine. Apart from these drugs, which have minimal to no clinical benefit, the 40‐year search for effective therapeutics to treat AD has resulted in a clinical failure rate of 100% not only for compounds that prevent brain amyloid deposition or remove existing amyloid plaques but also those acting by a variety of other putative disease‐associated mechanisms. This indicates that the preclinical data generated from current AD targets to support the selection, optimization, and translation of new chemical entities (NCEs) and biologics to clinical trials is seriously compromised. While many of these failures reflect flawed hypotheses or a lack of adequate characterization of the preclinical pharmacodynamic and pharmacokinetic (PD/PK) properties of lead NCEs—including their bioavailability and toxicity—the conceptualization, validation, and interrogation of the current animal models of AD represent key limitations. The overwhelming majority of these AD models are transgenic, based on aspects of the amyloid hypothesis and the genetics of the familial form of the disease. As a result, these generally lack construct and predictive validity for the sporadic form of the human disease. The 170 or so transgenic models, perhaps the largest number ever focused on a single disease, use rodents, mainly mice, and in addition to amyloid also address aspects of tau causality with more complex multigene models including other presumed causative factors together with amyloid. This overview discusses the current animal models of AD in the context of both the controversies surrounding the causative role of amyloid in the disease and the need to develop validated models of cognitive function/dysfunction that more appropriately reflect the phenotype(s) of human aged‐related dementias. © 2019 by John Wiley & Sons, Inc.

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Experimental Planning and Execution

Cited by 2 publications

References 183 publications

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity

Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity

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