scholarly journals Экспериментальные модели сократительной активности миометрия

2020 ◽  
Author(s):  
A.A. Yakovleva ◽  
N.G. Pavlova
Keyword(s):  
In Silico ◽  
Contractile Activity ◽  
Experimental Models ◽  
Pacemaker Activity ◽  
Single View ◽  
Uterine Contractile ◽  
Experimental Approaches

Сократительная деятельность матки до настоящего времени остается актуальным вопросом фундаментальных исследований, поскольку отсутствуют единые представления о биомеханике маточного сокращения, необходимые для профилактики родового и акушерского травматизма. Цель работы - оценка ограничений и возможностей экспериментальных моделей, предназначенных для изучения сократительной активности миометрия. Методика. Основными экспериментальными подходами к изучению сократительной активности матки являлись исследования in vitro, in situ, in vivo, in silico, а также их сочетание. Результаты. В статье рассмотрены исследования, в которых использованы различные сочетания экспериментальных подходов, обсуждаются результаты, полученные при моделировании в экспериментах, обсуждаются результаты изучения синхронизации сокращения отделов матки на различных моделях, а также результаты исследования пейсмейкерной активности миометрия и возможность экстраполяции полученных данных на человека. В связи с активным развитием компьютерных технологий в статье поднимается вопрос об их использовании в моделировании сократительной активности матки человека. Заключение. Делается заключение, что комплексный подход, включающий электромиографические, биохимические и морфологические исследования в хроническом эксперименте, является наиболее адекватным для изучения сократительной активности миометрия и функционального состояния нормально развитых и отставших в развитии плодов, что позволит разработать комплексные методы профилактики родового и акушерского травматизма.Uterine contractile activity remains an important issue of fundamental research as there is no single view of the biomechanics of uterine contraction necessary for the prevention of parturition and obstetric trauma until now. The aim of the review was to assess advantages and limitations of experimental models described in the literature for study uterine contractile activity. At the present time main experimental approaches for study myometrium contractile activity are research in vitro, in situ, in vivo, in silico and the their combinations. The literature presents experimental approaches, different models of uterine contractions synchronization and study of myometrium pacemaker activity. Due to active development of computer technologies there is a need to model human uterine contractile activity with a simplified anatomy. The authors propose that combination of electromyographic, biochemical and morphological methods in chronic experiment is the most correct and appropriate direction for the assessment of the myometrium contractile activity and functional state of normally developed and growth restricted fetuses.

scholarly journals Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses

2013 ◽  
Vol 141 (5) ◽  
pp. 633-647 ◽  
Author(s):  
Eiji Shigetomi ◽  
Eric A. Bushong ◽  
Martin D. Haustein ◽  
Xiaoping Tong ◽  
Olan Jackson-Weaver ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Hippocampal Slices ◽  
Adult Mice ◽  
Neuronal Synapses ◽  
Primary Signal ◽  
Experimental Approaches ◽  
Acute Hippocampal Slices

Intracellular Ca2+ transients are considered a primary signal by which astrocytes interact with neurons and blood vessels. With existing commonly used methods, Ca2+ has been studied only within astrocyte somata and thick branches, leaving the distal fine branchlets and endfeet that are most proximate to neuronal synapses and blood vessels largely unexplored. Here, using cytosolic and membrane-tethered forms of genetically encoded Ca2+ indicators (GECIs; cyto-GCaMP3 and Lck-GCaMP3), we report well-characterized approaches that overcome these limitations. We used in vivo microinjections of adeno-associated viruses to express GECIs in astrocytes and studied Ca2+ signals in acute hippocampal slices in vitro from adult mice (aged ∼P80) two weeks after infection. Our data reveal a sparkling panorama of unexpectedly numerous, frequent, equivalently scaled, and highly localized Ca2+ microdomains within entire astrocyte territories in situ within acute hippocampal slices, consistent with the distribution of perisynaptic branchlets described using electron microscopy. Signals from endfeet were revealed with particular clarity. The tools and experimental approaches we describe in detail allow for the systematic study of Ca2+ signals within entire astrocytes, including within fine perisynaptic branchlets and vessel-associated endfeet, permitting rigorous evaluation of how astrocytes contribute to brain function.

scholarly journals A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene

Cholesterol ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Francisco R. Marín-Martín ◽  
Cristina Soler-Rivas ◽  
Roberto Martín-Hernández ◽  
Arantxa Rodriguez-Casado
Keyword(s):  
In Silico ◽  
Rare Variants ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Experimental Approaches ◽  
And Function

Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2.

The influence of rhein on the absorption of rehmaionoside D: In vivo, in situ, in vitro, and in silico studies

2021 ◽  
pp. 114650
Author(s):  
Hui Yang ◽  
Bingtao Zhai ◽  
Mei Wang ◽  
Yu Fan ◽  
Jing Wang ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Studies

scholarly journals Integrated Strategy From In Vitro, In Situ, In Vivo to In Silico for Predicting Active Constituents and Exploring Molecular Mechanisms of Tongfengding Capsule for Treating Gout by Inhibiting Inflammatory Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenning Yang ◽  
Xiaoquan Jiang ◽  
Jingtong Liu ◽  
Dongying Qi ◽  
Zhiqiang Luo ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
In Silico ◽  
Network Pharmacology ◽  
Intragastric Administration ◽  
Active Constituents ◽  
Integrated Strategy ◽  
Target Network

The study of screening active constituents from traditional Chinese medicine (TCM) is important for explicating the mechanism of action of TCM and further evaluating the safety and efficacy effectively. However, detecting and identifying the active constituents from complicated biological samples still remain a challenge. Here, a practical, quick, and novel integrated strategy from in vitro, in situ, in vivo to in silico for rapidly screening the active constituents was developed. Firstly, the chemical profile of TCM in vitro was identified using UPLC-Q Exactive-Orbitrap HRMS. Secondly, the in situ intestinal perfusion with venous sampling (IPVS) method was used to investigate the intestinal absorption components. Thirdly, after intragastric administration of the TCM extract, the in vivo absorbed prototype components were detected and identified. Finally, the target network pharmacology approach was applied to explore the potential targets and possible mechanisms of the absorbed components from TCM. The reliability and availability of this approach was demonstrated using Tongfengding capsule (TFDC) as an example of herbal medicine. A total of 141 compounds were detected and identified in TFDC, and among them, 64 components were absorbed into the plasma. Then, a total of 35 absorbed bioactive components and 50 related targets shared commonly by compounds and gout were integrated via target network pharmacology analysis. Ultimately, the effects of the absorbed components on metabolism pathways were verified by experiments. These results demonstrated that this original method may provide a practical tool for screening bioactive compounds from TCM treating particular diseases. Furthermore, it also can clarify the potential mechanism of action of TCM and rationalize the application of TFDC as an effective herbal therapy for gout.

Effects of β-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

1987 ◽  
Vol 65 (11) ◽  
pp. 2297-2301 ◽  
Author(s):  
S. J. Lye ◽  
P. Christopher ◽  
R. F. Casper
Keyword(s):  
Contractile Activity ◽  
Vena Cava ◽  
Emg Activity ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Uterine Contractions ◽  
Uterine Contractile ◽  
Differential Increase

Recent studies have reported that β-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether β-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the β-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 μg∙kg−1 min−1; (b) Isop at a dose of 0.08 μg∙kg−1∙min−1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 μg∙kg−1∙min−1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2α or 13,14-dihydro-15-keto-PGF2α (PGFM)) concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 μg∙kg−1∙min−1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2α or PGFM) concentrations. No changes in plasma PGE2, PGF2α, or PGFM occurred during saline infusion. The data suggest that β-adrenergic agonist infusion is associated with a differential increase in plasma PG levels in vivo, but that this effect is probably not related to the failure of Isop (0.16 μg∙kg−1∙min−1) to maintain inhibition of myometrial contractions.

scholarly journals Overview of P-glycoprotein inhibitors: a rational outlook

2012 ◽  
Vol 48 (3) ◽  
pp. 353-367 ◽  
Author(s):  
Kale Mohana Raghava Srivalli ◽  
P. K. Lakshmi
Keyword(s):  
In Silico ◽  
Quantitative Structure Activity Relationship ◽  
Experimental Models ◽  
The Body ◽  
Diverse Range ◽  
Active Efflux ◽  
Chemical Structures ◽  
P Glycoprotein

P-glycoprotein (P-gp), a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC) super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR) analyses in the development of novel rational P-gp inhibitors have also been mentioned.

scholarly journals 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2678 ◽  
Author(s):  
Donato Angelino ◽  
Diogo Carregosa ◽  
Cristina Domenech-Coca ◽  
Monia Savi ◽  
Inês Figueira ◽  
...  
Keyword(s):  
In Silico ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Neuroprotective Effects ◽  
Physical Chemical ◽  
In Silico Study ◽  
Polar Metabolites ◽  
The Brain

Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the “gut-brain axis”.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

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