scholarly journals Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 371 ◽  
Author(s):  
Christin Henein ◽  
Sahar Awwad ◽  
Nkiruka Ibeanu ◽  
Stavros Vlatakis ◽  
Steve Brocchini ◽  
...  
Keyword(s):  
Computational Models ◽  
Sodium Hyaluronate ◽  
Intravitreal Injections ◽  
Surface Tensions ◽  
Medical Specialties ◽  
Dispersion Profile ◽  
Stage Of Development ◽  
Vitreous Substitutes ◽  
The Impact

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes—balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)—using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance.

A Mechanistic Motor-Clutch Model That Explains Cell Shape Dynamics to Cyclic Stretch

2022 ◽  
Author(s):  
Benjamin W. Scandling ◽  
Jia Gou ◽  
Jessica Thomas ◽  
Jacqueline Xuan ◽  
Chuan Xue ◽  
...  
Keyword(s):  
Computational Model ◽  
Computational Models ◽  
The Body ◽  
Cyclic Stretch ◽  
Substrate Stiffness ◽  
Cell Alignment ◽  
Cellular Mechanisms ◽  
Actin Bundles ◽  
The Impact

Many cells in the body experience cyclic mechanical loading, which can impact cellular processes and morphology. In vitro studies often report that cells reorient in response to cyclic stretch of their substrate. To explore cellular mechanisms involved in this reorientation, a computational model was developed by utilizing the previous computational models of the actin-myosin-integrin motor-clutch system developed by others. The computational model predicts that under most conditions, actin bundles align perpendicular to the direction of applied cyclic stretch, but under specific conditions, such as low substrate stiffness, actin bundles align parallel to the direction of stretch. The model also predicts that stretch frequency impacts the rate of reorientation, and that proper myosin function is critical in the reorientation response. These computational predictions are consistent with reports from the literature and new experimental results presented here. The model suggests that the impact of different stretching conditions (stretch type, amplitude, frequency, substrate stiffness, etc.) on the direction of cell alignment can largely be understood by considering their impact on cell-substrate detachment events, specifically whether detachment occurs during stretching or relaxing of the substrate.

scholarly journals Mathematical and computational models for bone tissue engineering in bioreactor systems

2019 ◽  
Vol 10 ◽  
pp. 204173141982792 ◽  
Author(s):  
Iva Burova ◽  
Ivan Wall ◽  
Rebecca J Shipley
Keyword(s):  
Bone Tissue ◽  
Computational Models ◽  
Bone Grafts ◽  
Operating Conditions ◽  
Specific Cell ◽  
Production Models ◽  
Flow Speeds ◽  
Comprehensive Framework ◽  
The Impact

Research into cellular engineered bone grafts offers a promising solution to problems associated with the currently used auto- and allografts. Bioreactor systems can facilitate the development of functional cellular bone grafts by augmenting mass transport through media convection and shear flow-induced mechanical stimulation. Developing successful and reproducible protocols for growing bone tissue in vitro is dependent on tuning the bioreactor operating conditions to the specific cell type and graft design. This process, largely reliant on a trial-and-error approach, is challenging, time-consuming and expensive. Modelling can streamline the process by providing further insight into the effect of the bioreactor environment on the cell culture, and by identifying a beneficial range of operational settings to stimulate tissue production. Models can explore the impact of changing flow speeds, scaffold properties, and nutrient and growth factor concentrations. Aiming to act as an introductory reference for bone tissue engineers looking to direct their experimental work, this article presents a comprehensive framework of mathematical models on various aspects of bioreactor bone cultures and overviews modelling case studies from literature.

364 QUANTIFICATION OF DEVELOPMENTALLY IMPORTANT GENE TRANSCRIPTS EXPRESSED IN EMBRYOS PRODUCED IN VIVO AND IN VITRO USING SEX-SORTED AND NON-SORTED RAM SPERMATOZOA

2010 ◽  
Vol 22 (1) ◽  
pp. 338
Author(s):  
K. H. Beilby ◽  
S. Wilkening ◽  
S. P. de Graaf ◽  
C. Wrenzycki ◽  
C. G. Grupen
Keyword(s):  
Gene Expression ◽  
Epigenetic Modification ◽  
Reproductive Technologies ◽  
Embryo Research ◽  
Cumulative Impact ◽  
Altered Expression ◽  
Stage Of Development ◽  
The Impact

The AI of sex-sorted spermatozoa results in decreased levels of fertility in most species. This is not the case in sheep, where low-doseAI of sex-sorted ram spermatozoa produces similar, if not superior levels of fertility to non-sorted controls (Beilby et al. 2009 Theriogenology, 71, 829-835). In an effort to provide insight into the molecular basis for this difference in fertility between species, the aim of the present study was to examine the impact of sex-sorting technology on ovine embryo gene expression. After semen collection, ejaculates (n = 8) were split and either sex-sorted by flow cytometry and frozen, or diluted and frozen (non-sorted control). Embryos were produced in vivo by inseminating superovulated ewes with either X- or Y-chromosome enriched spermatozoa, or non-sorted control spermatozoa, and collected by flushing uterine horns on Day 6 after AI. Embryos were produced in vitro by using established oocyte in vitro maturation and in vitro fertilization procedures (using X, Y or non-sorted spermatozoa), and cultured in vitro for 6 days. The relative abundance of Glut-3, G6PD, SUV39H1, DnMT3a, and HSP70 was measured in high grade blastocysts (in vivo Day 6: n = 23; in vitro Day 6: n = 21) using quantitative, real-time PCR (iCycler5TM, BioRad, Hercules, CA, USA). Blastocyst cell numbers were quantified to ensure embryos were at a similar stage of development. The sex of all embryos was identified by PCR to allow comparison between treatments. Fold differences in gene expression, acquired through the A ACt method, were calculated and compared by an ANOVA. The expression of HSP70 was up-regulated in in vitro embryos derived from sex-sorted spermatozoa compared to those produced in vivo (P < 0.05). For all other genes examined, there was no effect of sex or sperm treatment on gene expression. Glut-3, G6PD, SUV39H1, andDnMT3a were all up-regulated in in vitro embryos compared with in vivo embryos (P < 0.05). These results suggest that fertilization with sex-sorted ram spermatozoa does not result in aberrant patterns of gene expression in embryos produced in vivo. The data from the present study provide further evidence that in vitro culture induces epigenetic modification within the embryonic genome, when compared to the in vivo physiological standard. It would be of interest to conduct a similar in vivo study in cattle, where sex-sorting technology has not been as biologically successful. The altered expression of HSP70, which is associated with cellular stress, may demonstrate a cumulative impact of in vitro reproductive technologies on the preimplantation embryo. Research supported by XY, Inc.

Multidisciplinary team decision is rare and decreasing in percutaneous vascular interventions despite positive impact on in-hospital outcomes

VASA ◽  
2019 ◽  
Vol 48 (3) ◽  
pp. 262-269 ◽  
Author(s):  
Christian-Alexander Behrendt ◽  
Tilo Kölbel ◽  
Thea Schwaneberg ◽  
Holger Diener ◽  
Ralf Hohnhold ◽  
...  
Keyword(s):  
Multidisciplinary Team ◽  
Positive Impact ◽  
Cross Sectional Study ◽  
Invasive Treatment ◽  
Cross Sectional ◽  
Hospital Outcomes ◽  
Vascular Intervention ◽  
Medical Specialties ◽  
Team Decision ◽  
The Impact

Abstract. Background: Worldwide prevalence of peripheral artery disease (PAD) is increasing and peripheral vascular intervention (PVI) has become the primary invasive treatment. There is evidence that multidisciplinary team decision-making (MTD) has an impact on in-hospital outcomes. This study aims to depict practice patterns and time changes regarding MTD of different medical specialties. Methods: This is a retrospective cross-sectional study design. 20,748 invasive, percutaneous PVI of PAD conducted in the metropolitan area of Hamburg (Germany) were consecutively collected between January 2004 and December 2014. Results: MTD prior to PVI was associated with lower odds of early unsuccessful termination of the procedures (Odds Ratio 0.662, p < 0.001). The proportion of MTD decreased over the study period (30.9 % until 2009 vs. 16.6 % from 2010, p < 0.001) while rates of critical limb-threatening ischemia (34.5 % vs. 42.1 %), patients´ age (70 vs. 72 years), PVI below-the-knee (BTK) (13.2 % vs. 22.4 %), and rates of severe TASC C/D lesions BTK (43.2 % vs. 54.2 %) increased (all p < 0.001). Utilization of MTD was different between medical specialties with lowest frequency in procedures performed by internists when compared to other medical specialties (7.1 % vs. 25.7 %, p < 0.001). Conclusions: MTD prior to PVI is associated with technical success of the procedure. Nonetheless, rates of MTD prior to PVI are decreasing during the study period. Future studies should address the impact of multidisciplinary vascular teams on long-term outcomes.

Problems of Implementation of an Import Substitution Policy in the Oil Industry

2019 ◽  
pp. 50-57
Author(s):  
Yu. V. Vertakova ◽  
A. S. Evtyukhin
Keyword(s):  
Import Substitution ◽  
Oil Industry ◽  
Investment Climate ◽  
Scientific Publications ◽  
Stage Of Development ◽  
Current Economic Situation ◽  
Negative Effect ◽  
Substitution Policy ◽  
Investment Process ◽  
The Impact

The presented study addresses the issues of implementation of an import substitution policy in the Russian oil industry. Support of domestic production is a key objective specified in the message of the President of the Russian Federation in 2019. In light of the current economic situation and considering the importance of the oil industry for the Russian economy, an import substitution policy could help achieve the objective set by the President.Aim. The study aims to identify the problems and ways of implementation of an import substitution policy in the Russian oil industry.Tasks. The authors analyze scientific publications on import substitution and the state of the Russian oil industry at the current stage of development; determine the directions and fundamental trends in the development of the oil industry; identify obstacles that hinder the implementation of an import substitution policy in the oil industry; describe conditions that facilitate the development of the  investment process in the oil industry; propose comprehensive methods and ways to intensify investments and optimize costs for enterprises in the oil industry.Methods. This study uses general scientific methods of cognition, comparative and statistical analysis to identify problems in the implementation of an import substitution policy in the oil industry.Results. Examination of the current state and development prospects of the oil industry allows the authors to identify obstacles to the development of import substitution. The study shows their impact on the potential of import substitution, which has a negative effect on the prospects of intensification of investment processes, and proposes comprehensive methods and mechanisms that could neutralize the impact of the identified obstacles, thus facilitating the formation of a positive investment climate. Conclusions. Investment climate is shown to have a decisive impact on the potential of import substitution in the Russian oil industry, and ways of overcoming negative trends in the development of the oil industry are proposed.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic &#946;-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into &#946;-cells, resulting in enhanced &#946;-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.

The Impact of Antioxidants from the Diet on Breast Cancer Cells Monitored by Raman Microspectroscopy

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Breast Adenocarcinoma ◽  
Coumaric Acid ◽  
Human Breast ◽  
The Impact

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Effects of Transport Medium Composition on in vitro Drug Permeation across Excised Pig Intestinal Tissue

2020 ◽  
Vol 10 ◽  
Author(s):  
Bianca Peterson ◽  
Henrico Heystek ◽  
Josias H. Hamman ◽  
Johan D. Steyn
Keyword(s):  
Medium Composition ◽  
Screening Tests ◽  
Intestinal Tissue ◽  
Predictive Values ◽  
Transport Medium ◽  
Intestinal Fluids ◽  
Lower Permeability ◽  
The Impact ◽  
Simulated Intestinal Fluids

Background:: Knowledge of the permeation characteristics of new chemical entities across biological membranes is essential to drug research and development. Transport medium composition may affect the absorption of compounds during in vitro drug transport testing. To preserve the predictive values of screening tests, the possible influence of transport media on the solubility of model drugs, and on the activities of tight junctions and efflux transporter proteins (e.g. P-glycoprotein) must be known. Objective:: The aim of this study was to compare the impact of different transport media on the bi-directional transport of standard compounds, selected from the four classes of the Biopharmaceutical Classification System (BCS), across excised pig intestinal tissue. Methods:: The Sweetana-Grass diffusion apparatus was used for the transport studies. Krebs-Ringer bicarbonate (KRB) buffer and simulated intestinal fluids in the fed (FeSSIF) and fasted (FaSSIF) states were used as the three transport media, while the chosen compounds were abacavir (BCS class 1), dapsone (BCS class 2), lamivudine (BCS class 3) and furosemide (BCS class 4). Results:: Abacavir exhibited lower permeability in both the simulated intestinal fluids than in the KRB buffer. Dapsone showed similar permeability in all media. Lamivudine exhibited lower permeability in FaSSIF than in the other two media. Furosemide exhibited improved transport with pronounced efflux in FaSSIF. Conclusion:: Different permeation behaviors were observed for the selected drugs in the respective media, which may have resulted from their different physico-chemical properties, as well as from the effects that dissimilar transport media components had on excised pig intestinal tissue.

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