scholarly journals Detection of small molecule concentration gradients in ocular tissues and humours

2019 ◽  
Vol 55 (4) ◽  
pp. e4460 ◽  
Author(s):  
Berin A. Boughton ◽  
Oliver R.B. Thomas ◽  
Nicholas J. Demarais ◽  
Dennis Trede ◽  
Stephen E. Swearer ◽  
...  
Keyword(s):  
Small Molecule ◽  
Concentration Gradients ◽  
Ocular Tissues ◽  
Molecule Concentration

scholarly journals Microfluidic Multi-Drug and Multi-Dose Functional Profiling Towards Personalized Clinical Predictions in Pediatric Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2960-2960
Author(s):  
Evelyn Kendall Williams ◽  
Dan Y. Zhang ◽  
Ryan J Summers ◽  
Jamie Oakley ◽  
Christopher C. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Viability ◽  
Small Molecule ◽  
Vehicle Control ◽  
Drug Combinations ◽  
Concentration Gradients ◽  
Combination Drug ◽  
Patient Sample ◽  
Small Molecule Drugs ◽  
Functional Screens

Abstract Treatment of pediatric acute lymphoblastic leukemia (ALL) has seen dramatic improvements over the last several decades, leading to survival rates of over 90% for specific groups. However, for patients with relapsed/refractory disease, achieving complete remission remains a significant challenge. To further improve treatment outcomes for these patients, improved functional screens are needed to better match high risk leukemia patients with novel therapeutic strategies. Current functional screens are limited by the large patient samples required, particularly for combination drug screening and evaluation of higher order drug interactions. To that end, this work aims to develop a microfluidic multi-drug and multi-dose chemosensitivity assay to directly test candidate combinations of therapeutics in patient derived ALL cells. This will allow for analysis of response to combinations of 3 small molecule drugs while minimizing required patient sample and reducing experimental workload. Once validated, this assay can be used to identify biomarkers of response to novel combination regimens in pediatric ALL, and ultimately, could be used to prospectively guide therapy in newly diagnosed patients. Specifically, this is accomplished by generating stable, overlapping concentration gradients of small molecule drugs across 3D cultures of leukemia cells with and without human bone marrow derived mesenchymal stem cells (Fig 1A). We have demonstrated the ability to generate and maintain these gradients over 48 hours, and have shown that experimentally generated concentration gradients closely match steady state computational fluid dynamics (CFD) model predictions (Fig 1B). Moreover, exposing a T-ALL cell line (Jurkats) to a single gradient of cytarabine results in a gradient in cell viability. In drug treated devices, increasing drug dose led to decreasing averaged viability, while no appreciable difference was seen in vehicle control devices (Fig 1C). A commonly used 3 drug combination, Daunorubicin, Vincristine, and Prednisolone, was then used to validate the utility of the device for evaluating multi-dose drug combinations. Here, Jurkats were exposed to superimposed concentration gradients of Daunorubicin, Vincristine, and Prednisolone for 48 hours, after which cell viability as a function of concentration was examined. Specifically, a ternary contour map of the average viability across the device was generated, clearly depicting the range of response across the device (Fig 2B). Previous results have demonstrated Jurkats' sensitivity to Daunorubicin as well as Vincristine and relative resistance to Prednisolone, and these results are closely recapitulated in the device. Previous reports in literature have also demonstrated potential for antagonism between anthracyclines and vinca alkaloids, specifically between Doxorubicin and Vincristine in Jurkats (Ehrhardt, 2011). Our results also suggest that some amount of antagonism may exist between Daunorubicin and Vincristine in Jurkats at these concentration ranges tested, evidenced by the high average viability in regions of high vincristine concentrations and mid-range daunorubicin concentrations. Finally, we then used this system to evaluate response to drug combinations in a test patient sample. Specifically, combinations of Vincristine, Prednisolone, and Daunorubicin, as well as combinations of Nelarabine, Etoposide, and Cytoxan were evaluated in a standard risk B-ALL bone marrow aspirate sample. Drug treated devices resulted in significantly reduced viability relative to the vehicle control, with a differential in response observed between the 2 combinations tested (Fig 3A). Moreover, at these drug concentration ranges, it appears that combinations of Etoposide and Ara-G are particularly ineffective relative to other combinations in this sample (Fig 3B). Future studies will work to improve the baseline viability of banked samples in the device, and include testing of fresh leukemia samples as well. We are also working to develop methods to use data collected from these devices to identify synergistic or antagonistic drug combinations, and in the future, can correlate this with clinical outcome metrics as well as biomarkers of response. Tissue samples were provided by the Children's Healthcare of Atlanta Pediatric Bio-Repository. Other investigators may have received specimens from the same subjects. Figure 1 Figure 1. Disclosures Lam: Sanguina, Inc.: Current holder of individual stocks in a privately-held company.

On the structural organization of biological pumps and channels

1984 ◽  
Vol 42 ◽  
pp. 138-141
Author(s):  
G. Zampighi ◽  
M. Kreman
Keyword(s):  
Active Transport ◽  
Transport System ◽  
Plasma Membranes ◽  
Transport Proteins ◽  
Molecular Organization ◽  
Passive Transport ◽  
Concentration Gradients ◽  
Cell Functions ◽  
Natural Concentration ◽  
Active Transport System

The plasma membranes of most animal cells contain transport proteins which function to provide passageways for the transported species across essentially impermeable lipid bilayers. The channel is a passive transport system which allows the movement of ions and low molecular weight molecules along their concentration gradients. The pump is an active transport system and can translocate cations against their natural concentration gradients. The actions and interplay of these two kinds of transport proteins control crucial cell functions such as active transport, excitability and cell communication. In this paper, we will describe and compare several features of the molecular organization of pumps and channels. As an example of an active transport system, we will discuss the structure of the sodium and potassium ion-activated triphosphatase [(Na+ +K+)-ATPase] and as an example of a passive transport system, the communicating channel of gap junctions and lens junctions.

A privileged ternary blend enabling non-fullerene organic photovoltaics with over 14% efficiency

2020 ◽  
Vol 8 (43) ◽  
pp. 15135-15141
Author(s):  
Jing Yan ◽  
Yuan-Qiu-Qiang Yi ◽  
Jianqi Zhang ◽  
Huanran Feng ◽  
Yanfeng Ma ◽  
...  
Keyword(s):  
Small Molecule ◽  
Organic Photovoltaics ◽  
Power Conversion ◽  
Ternary Blend ◽  
Conversion Efficiencies

Two non-fullerene small molecule acceptors, NT-4F and NT-4Cl, were designed and synthesized. Power conversion efficiencies of 11.44% and 14.55% were achieved for NT-4Cl-based binary and ternary devices, respectively.

Development of small-molecule-based probes for the vitamin D receptor

2020 ◽  
Author(s):  
Tania Mutchie ◽  
Alexander Arnold
Keyword(s):  
Vitamin D ◽  
Small Molecule ◽  
Vitamin D Receptor

The small-molecule antibiotics pipeline: 2014–2018

2019 ◽  
Vol 18 (10) ◽  
pp. 739-739 ◽  
Author(s):  
Cara Lepore ◽  
Lynn Silver ◽  
Ursula Theuretzbacher ◽  
Joe Thomas ◽  
David Visi
Keyword(s):  
Small Molecule

Anisotropic forces in small molecule crystals

1985 ◽  
Vol 82 ◽  
pp. 91-97 ◽  
Author(s):  
H. Bonadeo ◽  
E. Burgos
Keyword(s):  
Small Molecule

P157 FBXO3-FBXL2 AXIS MODULATORS AS A NOVEL CLASS OF ORAL SMALL MOLECULE COMPOUNDS FOR THE TREATMENT OF CROHN’S DISEASE

2020 ◽  
Vol 158 (3) ◽  
pp. S9-S10
Author(s):  
Franca Angeli ◽  
Russell Wyborski ◽  
Bill Chen ◽  
Rama Mallampalli ◽  
Michael Lark
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Small Molecule

Targeting the p53 tumor suppressor activity in glioblastomas using small molecule MDM2-inhibitor

2011 ◽  
Vol 42 (01) ◽  
Author(s):  
P. Monfared ◽  
T. Viel ◽  
G. Schneider ◽  
Y. Waerzeggers ◽  
S. Rapic ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Small Molecule ◽  
Suppressor Activity ◽  
P53 Tumor Suppressor ◽  
Tumor Suppressor Activity ◽  
Mdm2 Inhibitor

TO ANALYZE THE EFFECT OF DAMAGE TO OTHER OCULAR TISSUES ON VISUAL OUTCOME AFTER TRAUMATIC CATARACT SURGERY.

2019 ◽  
Vol 3 (9) ◽  
Author(s):  
Dr. Mita V. Joshi ◽  
Dr. Sudhir Mahashabde
Keyword(s):  
Visual Outcome ◽  
Corneal Opacity ◽  
Research Centre ◽  
Traumatic Cataract ◽  
Visual Axis ◽  
College Hospital ◽  
Ocular Tissues ◽  
Department Of Ophthalmology ◽  
Ocular Injuries ◽  
Final Visual Outcome

All patient coming to Index Medical College Hospital & Research Centre, Indore operated in Department of Ophthalmology for traumatic cataract due to various injuries Result: Of the 37 patients, 19 patients (51%) showed corneal/ corneal sclera injury. 10 cases had injury to iris in the form of spincter tear, traumatic mydriasis, iris incarceration, floppy iris, posterior and anterior synechiae. Subluxation of lens was seen in 2 cases and Dislocation of lens was in 1 cases. 3 cases had corneal opacity. Old retinal detachment was seen in 1 (3%) case. Out of 30 cases who had associated ocular injuries, 3 cases had vision of HM, 07 cases had vision of CF-ctf – CF-3’, 01 cases had vision of 5/60, 07 cases had vision of 6/60-6/36, 03 cases had vision of 6/24-6/18, 09 cases had vision of 6/12-6/6. Out of 7 cases without associated in injury, 2 cases had vision of 6/24-6/18, 05 cases had vision of 6/12-6/6. Conclusion: Corneal scarring obstructing the visual axis as well as by inducing irregular astigmatism formed an important cause of poor visual outcome in significant number of cases. Irreversible posterior segment damage lead to impaired vision case. The final visual outcome showed good result however the final visual outcome depends upon the extent of associated ocular injuries. Effective Intervention and management are the key points in preventing monocular blindness due to traumatic cataract. Keywords: Ocular, Tissues, Traumatic, Cataract & Surgery.

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