Augmentation of sickling process due to turbulent blood flow

1976 ◽  
Vol 40 (1) ◽  
pp. 60-66 ◽  
Author(s):  
P. D. Stein ◽  
H. N. Sabbah ◽  
A. K. Mandal
Keyword(s):  
Blood Flow ◽  
Turbulent Flow ◽  
Sickle Cell ◽  
Sol Gel ◽  
Control Sample ◽  
Mechanical Stresses ◽  
Hydrodynamic Stresses ◽  
Sickle Cell Crises ◽  
Hot Film

The purpose of this study was to determine if the fluid mechanical stresses associated with turbulent blood flow can contribute to the sickling process. Blood from seven patients with sickle cell disease was subjected to intermediate and high levels of turbulent flow in vitro. Turbulence was quantitated by hot film anemometry. Control samples showed 20 +/- 3% sickled cells. Cells subjected to intermediate levels of turbulent flow showed 26 +/- 4% sickling (P less than 0.01); and blood subjected to high intensities of turbulence showed 31 +/- 4% sickling (P less than 0.01). A quantitative count by electronmicroscopy, performed in one patient, showed polymerization of the hemoglobin indicative of sickling in more cells subjected to turbulence than in the control sample. A turbulence-reducing agent, polyethylene oxide, diminished the augmentation of the sickling process as it reduced turbulence at comparable Reynolds numbers. These results support the hypothesis that a deleterious effect upon hemoglobin SS erythrocytes may occur due to the mechanical stresses of turbulent flow. The agitation associated with turbulent flow presumably modifies the stabilizing factors of the intracellular colloidal solution of hemoglobin, thereby contributing to sol-gel transformation. Such hydrodynamic stresses may supplement the previously described factors which contribute to sickle cell crises.

In-Vitro Evaluation of Hot-Film Anemometry Using a Sensor-Tipped Coronary Guide-wire

2007 ◽  
Author(s):  
Maartje C. F. Geven ◽  
Arjen Van Der Horst ◽  
Marcel C. M. Rutten ◽  
Wilbert Aarnoudse ◽  
Nico H. J. Pijls ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Arteries ◽  
Functional Significance ◽  
Guide Wire ◽  
Coronary Angiogram ◽  
Arterial Tree ◽  
In Vitro Evaluation ◽  
Coronary Catheterization ◽  
Hot Film

During coronary catheterization, the epicardial coronary arteries are visually assessed for stenoses on the coronary angiogram. However, the functional significance of disease in the coronary arterial tree, the increased resistance to blood flow, may easily be over- or underestimated by using a 2D projection.

Peg-Cohb Mediated Carbon Monoxide and Oxygen Transfer to Hypoxic Red Blood Cells Prevent, Slow, and/or Reverse Sickling in Vitro.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 967-967
Author(s):  
Peter Buontempo ◽  
Rick Yglesias ◽  
Yuli Chen ◽  
Catherine Buontempo ◽  
Ronald G. Jubin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sickle Cell ◽  
Cell Morphology ◽  
Oxygen Transfer ◽  
Blood Cells ◽  
Normal Cell ◽  
Cell Disease ◽  
Normal Blood Flow ◽  
O2 Transfer

Abstract Background: In Sickle Cell disease (SCD), a single amino acid substitution in the beta globin chain converts HbA to sickle genotype HbS. This genetic change promotes HbS polymerization upon deoxygenation that can promote occlusion of small blood vessels that is often associated with increased blood viscosity, and circulatory inflammation. PEGylated-carboxyhemoglobin (PEG-COHb; SANGUINATE) was designed as a novel therapeutic agent to initially release carbon monoxide (CO) and then transfer oxygen (O2) to hypoxic tissue and cells. Delivery of either CO and/or O2 to hypoxic, sickled red blood cells (RBCs) should return cells to a more normal cell morphology and help re-establish normal blood flow and rheology. PEG-COHb was shown to mediate transfer of either a CO or O2/CO mixture and restore normal morphology to hypoxic, sickled RBCs in vitro. Studies are now focused on the potential therapeutic implications of delaying or slowing sickling, which should maintain normal blood flow through hypoxic microvasculature. Unsickling is expected to be expedited by O2 transfer by PEG-COHb. To examine these potential therapeutic effects, current in vitro studies examined the effects of time and dose of PEG-COHb to not only reverse, but also prevent or delay sickling by transferring CO as well as expedite atmospheric O2 transfer to the sickled RBCs. Methods: Reversal of sickling studies were conducted by deoxygenating RBCs from healthy (control) and SCD volunteers in followed by treatment with either PEG-COHb, fully oxygenated PEG-Hb (PEG-O2Hb) or PEG-BSA for 2 hours. For prevention of sickling studies, fully oxygenated RBC suspensions were treated with increasing amounts of PEG-COHb and then subjected to hypoxia for 3 hours. Time-dose effects were quantified by area under the curve (AUC) analysis. O2 transfer studies were conducted by treating hypoxic, sickled RBCs to increasing concentrations of PEG-COHb and raising the pO2 from 3.8mm to 40mm. In all studies, the fractions of CO-Hb, O2-Hb and reduced Hb were determined by co-oximetry and sickled RBCs were quantified by imaging flow cytometry of fixed RBC specimens. Results: PEG-COHb-mediated delivery of either CO or O2 can unsickle hypoxic SCD RBCs. Controls exhibited gas exchange similar to SCD RBCs. Interestingly, sickle reversion time-course studies showed differential kinetics between the CO and O2 capacity to cause unsickling. AUC analysis at 20 minutes demonstrated that both CO and O2 reversed sickling by 41% and 42%, respectively. PEG-O2Hb was able to exert substantial unsickling by 5 minutes, where PEG-COHb showed a delayed, more pronounced effect, peaking approximately 20 to 40 minutes post-treatment. When fully oxygenated SCD RBCs were pretreated with PEG-COHb prior to oxygenation, sickling was inhibited with an IC50 of 2.5±0.6 mg per mL in deoxygenated saline (PBS). In addition, treatment concentrations below IC50 values had increased time-dose AUC values indicating that although, not completly inhibited, sickling was delayed. Oxygen transfer facilitation studies indicated that PEG-COHb increased the rate of unsickling as measured by AUC by 50% and 15% at 4 and 2 mg per mL, respectively. These levels are within the expected therapeutic dosage of SANGUINATE. Summary: RBCs from patients with SCD undergo a conformational shift upon deoxygenation resulting in HbS polymerization and morphological changes of the RBCs. The occlusive and fragile properties of sickled RBCs are responsible for the development of the numerous comorbidities associated with SCD. It is only when the fraction of oxygenated or carboxylated HbS reaches a sufficient level that reversion to normal cell morphology occurs which promotes vascular perfusion. These experiments showed a concentration and time-dependent effect of PEG-COHb ability to deliver both O2 and CO to sickled RBC. These data suggested that PEG-COHb is a promising gas transfer agent that has the potential to improve sickle cell morphology by reversing sickling; the underlying pathology of sickle cell disease co-morbidities. Disclosures Buontempo: Prolong Pharmaceuticals: Employment. Yglesias:Prolong Pharmaceuticals: Employment. Chen:Prolong Pharmaceuticals: Employment. Buontempo:Prolong Pharmaceuticals: Employment. Jubin:Prolong Pharmaceuticals: Employment. Abuchowski:Prolong Pharmaceuticals: Employment.

scholarly journals GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1779-1786 ◽  
Author(s):  
Jungshan Chang ◽  
John T. Patton ◽  
Arun Sarkar ◽  
Beat Ernst ◽  
John L. Magnani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sickle Cell ◽  
Leukocyte Adhesion ◽  
Blood Rheology ◽  
Leading Edge ◽  
Polymorphonuclear Neutrophils ◽  
In Vitro Assays ◽  
Critical Reduction ◽  
Vascular Occlusions

Abstract Leukocyte adhesion in the microvasculature influences blood rheology and plays a key role in vaso-occlusive manifestations of sickle cell disease. Notably, polymorphonuclear neutrophils (PMNs) can capture circulating sickle red blood cells (sRBCs) in inflamed venules, leading to critical reduction in blood flow and vaso-occlusion. Recent studies have suggested that E-selectin expression by endothelial cells plays a key role by sending activating signals that lead to the activation of Mac-1 at the leading edge of PMNs, thereby allowing RBC capture. Thus, the inhibition of E-selectin may represent a valuable target in this disease. Here, we have tested the biologic properties of a novel synthetic pan-selectin inhibitor, GMI-1070, with in vitro assays and in a humanized model of sickle cell vaso-occlusion analyzed by intravital microscopy. We have found that GMI-1070 predominantly inhibited E-selectin–mediated adhesion and dramatically inhibited sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival. These results suggest that GMI-1070 may represent a valuable novel therapeutic intervention for acute sickle cell crises that should be further evaluated in a clinical trial.

Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Activation ◽  
In Vivo Studies ◽  
Blood Flow Response ◽  
Flow Response

The Mesothelial Cell as a Non-Thrombogenic Surface

1984 ◽  
Vol 52 (02) ◽  
pp. 102-104 ◽  
Author(s):  
L J Nicholson ◽  
J M F Clarke ◽  
R M Pittilo ◽  
S J Machin ◽  
N Woolf
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Blood Flow ◽  
Cell Surface ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Plastic Film ◽  
In Vitro System ◽  
Scanning Electron

SummaryA technique for harvesting mesothelial cells is described. This entails collagenase digestion of omentum after which the cells can be cultured. The technique has been developed using the rat, but has also been successfully applied to human tissue. Cultured rat mesothelial cells obtained in this way have been examined by scanning electron microscopy. Rat mesothelial cells grown on plastic film have been exposed to blood in an in vitro system using a Baumgartner chamber and have been demonstrated to support blood flow. No adhering platelets were observed on the mesothelial cell surface. Fibroblasts similarily exposed to blood as a control were washed off the plastic.

Tantalum Oxide Nanoparticles as Versatile Contrast Agents for X-ray Computed Tomography

2020 ◽  
Author(s):  
Shatadru Chakravarty ◽  
Jeremy Hix ◽  
Kaitlyn Wieweora ◽  
Maximilian Volk ◽  
Elizabeth Kenyon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Sol Gel ◽  
Tantalum Oxide ◽  
High Signal ◽  
Drug Delivery Vehicles ◽  
X Ray Computed

Here we describe the synthesis, characterization and in vitro and in vivo performance of a series of tantalum oxide (TaOx) based nanoparticles (NPs) for computed tomography (CT). Five distinct versions of 9-12 nm diameter silane coated TaOx nanocrystals (NCs) were fabricated by a sol-gel method with varying degrees of hydrophilicity and with or without fluorescence, with the highest reported Ta content to date (78%). Highly hydrophilic NCs were left bare and were evaluated in vivo in mice for micro-CT of full body vasculature, where following intravenous injection, TaOx NCs demonstrate high CT contrast, circulation in blood for ~ 3 h, and eventual accumulation in RES organs; and following injection locally in the mammary gland, where the full ductal tree structure can be clearly delineated. Partially hydrophilic NCs were encapsulated within mesoporous silica nanoparticles (MSNPs; TaOx@MSNPs) and hydrophobic NCs were encapsulated within poly(lactic-co-glycolic acid) (PLGA; TaOx@PLGA) NPs, serving as potential CT-imagable drug delivery vehicles. Bolus intramuscular injections of TaOx@PLGA NPs and TaOx@MSNPs to mimic the accumulation of NPs at a tumor site produce high signal enhancement in mice. In vitro studies on bare NCs and formuated NPs demonstrate high cytocompatibility and low dissolution of TaOx. This work solidifies that TaOx-based NPs are versatile contrast agents for CT.

PDO Rotonda’s Red Eggplant Extract: In vitro Determination of Biological Properties and Minerals Bioaccessibility

2020 ◽  
Vol 16 (1) ◽  
pp. 65-74
Author(s):  
Ortensia Ilaria Parisi ◽  
Mariarosa Ruffo ◽  
Fabio Amone ◽  
Rocco Malivindi ◽  
Domenico Gorgoglione ◽  
...  
Keyword(s):  
Control Sample ◽  
Specific Area ◽  
Biological Properties ◽  
Ammonium Molybdate ◽  
Antihypertensive Activity ◽  
Protected Designation Of Origin ◽  
The Family ◽  
Oil Red O Staining

Background: The Rotonda’s Red Eggplant belongs to the family of Solanum aethiopicum and it is cultivated in a specific area of Potenza (Basilicata, South of Italy) including villages of Rotonda, Viggianello, Castelluccio Superiore and Castelluccio Inferiore. The Red Eggplant cultivated in this area has gained the PDO, “Protected Designation of Origin”. Objective: The aim of this research was to evaluate the use of PDO Rotonda’s Red Eggplant extract as a possible nutraceutical supplement. The antioxidant, antihypertensive, hypoglycemic, and hypolipidemic properties were in vitro evaluated. Methods: The antioxidant activity was investigated by evaluating the scavenging properties against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and by performing the Ammonium Molybdate and Folin-Ciocalteu assay. The hypoglycemic and antihypertensive activity was studied by evaluating the α-Amylase, α-Glucosidase and Angiotensin Converting Enzyme, respectively, inhibiting activity. In order to evaluate the hypolipidemic activity, the pancreatic lipase inhibiting property was determined and Oil Red O staining assay was performed. Finally, to evaluate the possible use of this extract as a minerals supplement, Selenium, Potassium and Chrome bioaccessibility was studied. Results: The obtained results underline the good antioxidant, hypoglycemic, antihypertensive and hypolipidemic in vitro properties of the PDO Rotonda’s Red Eggplant extract. Moreover, the obtained data show a higher minerals bioaccessibility and this higher value could be ascribable to the natural phytocomplex of PDO Rotonda’s Red Eggplant, which increases the minerals bioaccessibility if compare it with a control sample. Conclusion: The obtained results show that PDO Rotonda’s Red Eggplant extract, might be used as a possible nutraceutical supplement, along with traditional therapies, both for its biological properties and for its minerals bioaccessibility value.

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