Contrasting pharmacodynamic requirements of disease models revealed through characterization of a novel and selective M1 agonist

SUMMARYChagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinicalin vivoevidence on the applicability of plant-based products in the treatment ofTrypanosoma cruziandTrypanosoma bruceiinfections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species. The disease models and treatments were highly variable. Most studies used native (n= 36, 54·54%) or exotic (n= 30, 45·46%) plants with ethnodirected indication (n= 45, 68·18%) for trypanosomiasis treatment. Complete phytochemical screening and toxicity assays were reported in only 15 (22·73%) and 32 (48·49%) studies, respectively. The currently available preclinical evidence is at high risk of bias. The absence of or incomplete characterization of animal models, treatment protocols, and phytochemical/toxicity analyses impaired the internal validity of the individual studies. Contradictory results of a same plant species compromise the external validity of the evidence, making it difficult determine the effectiveness, safety and biotechnological potential of plant-derived products in the development of new anti-infective agents to treatT. cruziandT. bruceiinfections.

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Micro-CT for Characterization of Murine CV Disease Models

JACC Cardiovascular Imaging ◽

10.1016/j.jcmg.2010.01.012 ◽

2010 ◽

Vol 3 (7) ◽

pp. 783-785 ◽

Cited By ~ 4

Author(s):

Ahmad Y. Sheikh ◽

Koen E.A. van der Bogt ◽

Timothy C. Doyle ◽

Maryam K. Sheikh ◽

Katherine J. Ransohoff ◽

...

Keyword(s):

Disease Models ◽

Micro Ct ◽

Cv Disease

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Transmission Electron Microscopy of the Retina: A Method for Sample Preparation and Evaluation

Toxicologic Pathology ◽

10.1177/0192623320954124 ◽

2020 ◽

pp. 019262332095412

Author(s):

Christopher M. Hayden ◽

Emily K. Meseck

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Sample Preparation ◽

Clinical Examination ◽

Spherical Shape ◽

Disease Models ◽

Posterior Aspect ◽

Orientation Imaging ◽

Transmission Electron

Ultrastructural pathology is critical in the morphologic evaluation and characterization of subcellular structures in nonclinical toxicity and efficacy studies. In murine models of ophthalmologic disease, clinical examination is typically paired with other techniques like electroretinography (ERG) and/or optical coherence tomography (OCT) to more fully characterize a finding. High-quality transmission electron microscopy (TEM) can provide a critical, image-based link between these approaches, providing greater confidence in interpretation of ERG or OCT results. In addition to characterization of disease models, TEM can provide detailed visualization of retinal changes identified by clinical examination or light microscopy in nonclinical toxicity studies. The spherical shape of the eye presents unique challenges for trimming, orientation, imaging, and evaluation by TEM. The varied components of the eye require specialized approaches for embedding to facilitate successful sectioning. Controlling for the orientation of the retina is critical to consistent evaluation, driving the need for an improved method of embedding this unique and complex organ. The authors describe a method of sample preparation resulting in optimal orientation of the posterior aspect of murine eyes (rat and mouse) for TEM of the neural retina, Bruch’s membrane and/or choroid, with examples from mouse ophthalmic disease models.

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Morphological Characterization of Mycobacteriophage R1

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051281 ◽

1974 ◽

Vol 32 ◽

pp. 254-255

Author(s):

B. L. Soloff ◽

T. A. Rado

Keyword(s):

Carbon Source ◽

Stationary Phase ◽

Growth Phase ◽

Minimal Medium ◽

Morphological Characterization ◽

Logarithmic Growth Phase ◽

Complete Lysis ◽

Lysogenic Culture ◽

Logarithmic Growth

Mycobacteriophage R1 was originally isolated from a lysogenic culture of M. butyricum. The virus was propagated on a leucine-requiring derivative of M. smegmatis, 607 leu−, isolated by nitrosoguanidine mutagenesis of typestrain ATCC 607. Growth was accomplished in a minimal medium containing glycerol and glucose as carbon source and enriched by the addition of 80 μg/ ml L-leucine. Bacteria in early logarithmic growth phase were infected with virus at a multiplicity of 5, and incubated with aeration for 8 hours. The partially lysed suspension was diluted 1:10 in growth medium and incubated for a further 8 hours. This permitted stationary phase cells to re-enter logarithmic growth and resulted in complete lysis of the culture.

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AEM analysis of crystallization in Ti-based amorphous alloys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075142 ◽

1983 ◽

Vol 41 ◽

pp. 270-271

Author(s):

A.R. Pelton ◽

A.F. Marshall ◽

Y.S. Lee

Keyword(s):

Magnetic Properties ◽

Amorphous Alloys ◽

Amorphous Materials ◽

Isothermal Annealing ◽

Amorphous Matrix ◽

Nucleation And Growth ◽

Current Interest ◽

Amorphous Films ◽

Electrical And Magnetic Properties

Amorphous materials are of current interest due to their desirable mechanical, electrical and magnetic properties. Furthermore, crystallizing amorphous alloys provides an avenue for discerning sequential and competitive phases thus allowing access to otherwise inaccessible crystalline structures. Previous studies have shown the benefits of using AEM to determine crystal structures and compositions of partially crystallized alloys. The present paper will discuss the AEM characterization of crystallized Cu-Ti and Ni-Ti amorphous films.Cu60Ti40: The amorphous alloy Cu60Ti40, when continuously heated, forms a simple intermediate, macrocrystalline phase which then transforms to the ordered, equilibrium Cu3Ti2 phase. However, contrary to what one would expect from kinetic considerations, isothermal annealing below the isochronal crystallization temperature results in direct nucleation and growth of Cu3Ti2 from the amorphous matrix.

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