Blockage Of Blood Vessels Research Articles

Fluid-Structure Interaction Analysis for Drug Transport in a Curved Stenotic Right Coronary Artery

A blockage of blood vessels resulting from thrombus or plaque deposit causes serious cardiovascular diseases. This study developed a computational model of blood flow and drug transport to investigate the effectiveness of drug delivery to the stenotic sites. A three-dimensional (3D) model of the curved stenotic right coronary artery (RCA) was reconstructed based on the clinical angiogram image. Then, blood flow and drug transport with the flexible RCA wall were simulated using the fluid structure interaction (FSI) analysis and compared with the rigid RCA wall. Results showed that the maximal total displacement and von Mises stress of the flexible RCA model are 2.14 mm and 92.06 kPa. In addition, the effective injecting time point for the best performance of drug delivery was found to be between 0 s and 0.15 s (i.e., the fluid acceleration region) for both rigid and flexible RCA models. However, there was no notable difference in the ratio of particle deposition to the stenotic areas between the rigid and flexible RCA models. This study will be significantly useful to the design of a drug delivery system for the treatment of the stenotic arteries by targeting drugs selectively to the stenotic sites.

Calcium orthophosphates (CaPO4): occurrence and properties

The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates (CaPO4). This type of materials is of the special significance for the human beings because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with CaPO4, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenorthophosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of CaPO4. Similarly, dental caries and osteoporosis might be considered as in vivo dissolution of CaPO4. In addition, natural CaPO4 are the major source of phosphorus, which is used to produce agricultural fertilizers, detergents and various phosphorus-containing chemicals. Thus, there is a great significance of CaPO4 for the humankind and, in this paper, an overview on the current knowledge on this subject is provided.

Infection, vaccination, and childhood arterial ischemic stroke.

A stroke occurs when a blood vessel to the brain is either blocked or ruptured. When blood to part of the brain is blocked, it causes what is called an ischemic stroke. Stroke is much more common in adults and the elderly. This is because fats and cholesterol can build up and block blood vessels as we age. Stroke is much less common in children. Stroke occurs in 11 per 100,000 children under the age of 18 every year.1 Still, it is one of the top 10 causes of death for children.2 We don't routinely expect children to have the major risk factors for atherosclerosis, such as high blood pressure, diabetes, high cholesterol, and smoking. When stroke occurs in children, the causes are much different. Infection has been shown to increase the risk of heart attack and stroke 3-fold among adults.3 Previous studies have suggested that it may also be an important cause of pediatric stroke.

A Case Report of Non-Occlusive Mesenteric Ischemia in a Patient with Multiple Risk Factors

Non-occlusive mesenteric ischemia (NOMI) refers to all types of mesenteric ischemia without any organic blockage of blood vessels. It is usually seen in elderly age group with risk factors of previous myocardial infarction, congestive cardiac failure, aortic insufficiency, renal or liver impairment and post-cardiac surgery. Amongst all the cases of acute mesenteric ischemia, NOMI constitutes 20-30%. The mortality is generally high, at least 50% because it usually presents late and the bowel is already gangrenous. Common presentations include nausea, vomiting and acute abdominal pain. Selective angiography is the gold standard to exclude obstructive mesenteric ischemia, for which the diagnosis of NOMI could be made, but one can use other non-invasive modalities such as CT, MRI or ultrasound. Colonoscopy, lactate, arterial blood gas can be used to investigate for bowel ischemia. In the early stages, there is no need for surgery. Surgical intervention is generally limited unless there is a need to excise away the gangrenous bowel. The only effective treatment is by administering intra-arterial vasodilator therapy and it should be done as early as possible to improve prognosis. We describe a case of large bowel ischemia likely secondary to non-occlusive mesenteric ischemia.

The Challenges and Opportunities Associated with Sickle Cell Disease Prevention, Education, and Management

Sickle cell disease (SCD) is a hereditary blood disorder affecting the shape of the red blood cells that block blood vessels leading to organ damage and frequent erratic painful episodes. SCD is a global public health issue affecting millions of people throughout the world. This article explores (a) what SCD is; (b) the physical and psychosocial impacts of the disease; (c) the challenges and opportunities associated with sickle cell prevention, education, and management; and (d) the implications for social work policy, practice, and research associated with the identified challenges and opportunities.

Pulsation effect on thrombus in a bifurcation pipe by the lattice Boltzmann method

Thrombosis caused by all kinds of cardiovascular diseases, has been influencing people's health. In a blocked blood vessel, pulsation flows have a positive effect on thrombus. Because of the blood viscosity and the inertias of red blood cells and the fluid, the frequency of pulsation flow influences the effect of dredge blood clots. Under the condition of low differential pressure, conduction of the another flow pipe reducing the pressure variation causes the effect of dredging blood clots not to be ideal in the bifurcated pipe model. So we will increase the differential pressure and improve the amplitude of pulsation flow, reduce the influence of the conduction effect of expedite tube, then study the effect of dredge blood clots which is caused by the pulsation flow in the bifurcated pipe. We find that low frequency pulsation flow has a good effect on dredge blood clots for a long time. Relatively, high frequency pulsation flow needs less time, but the effect of dredge blood clots is not obvious if the frequency is higher than a certain value. The friction between cells and the walls of the tube also has an effect on dredge blood clots.

A novel inflammatory role for platelets in sickle cell disease

The severe pain, ischemia and organ damage that characterizes sickle cell disease (SCD) is caused by vaso-occlusion, which is the blockage of blood vessels by heterotypic aggregates of sickled erythrocytes and other cells. Vaso-occlusion is also a vasculopathy involving endothelial cell dysfunction, leukocyte activation, platelet activation and chronic inflammation resulting in the multiple adhesive interactions between cellular elements. Since platelets mediate inflammation as well as thrombosis via release of pro- and anti-inflammatory molecules, we hypothesized that platelets may play an active inflammatory role in SCD by secreting increased amounts of cytokines. Since platelets have been shown to contain mRNA and actively produce proteins, we also hypothesized that SCD platelets may contain increased cytokine mRNA. In this cross-sectional study, we sought to compare both the quantity of cytokines secreted and the cytokine mRNA content, between SCD and control platelets. We measured the secretion of Th1, Th2, and Th17-related cytokines from platelets in a cohort of SCD patients. We simultaneously measured platelet mRNA levels of those cytokines. Platelets from SCD patients secreted increased quantities of IL-1β, sCD40L, and IL-6 compared to controls. Secretion was increased in patients with alloantibodies. Additionally, mRNA of those cytokines was increased in SCD platelets. Platelets from sickle cell patients secrete increased amounts of inflammatory cytokines, and contain increased cytokine mRNA. These findings suggest a novel immunological role for platelets in SCD vasculopathy, in addition to their thrombotic role, and strengthen the rationale for the use of anti-platelet therapy in SCD.

Targeting KLF1 for the Treatment of Sickle Cell Disease Using Antisense Oligonucleotides

Sickle cell anemia (SCD) is a hereditary blood disorder in which red blood cells (RBC) become sickle-shaped and block blood vessels, leading to painful vaso-occlusive episodes. Sickling occurs because of a point-mutation in the β-globin gene of hemoglobin. Fetal hemoglobin (HbF, α2γ2) is the main oxygen transport protein in the fetus during the last months of embryonic development and the first few months of life after birth. HbF has a slightly greater oxygen binding affinity than adult hemoglobin (HbA, α2β2) and inhibits sickling by interfering with the polymerization of hemoglobin S. Higher HbF levels in SCD correlate with better survival and because HbF production can be reactivated pharmacologically in adults, it can be used for the treatment of SCD.Erythroid Kruppel-like factor (KLF1) is an erythroid-specific transcription factor that regulates β-globin expression through direct interaction with its promoter and indirectly regulates γ-globin expression through the regulation of BCL11A. By reducing the expression of KLF1, we can promote production of HbF through the upregulation of γ-globin expression.Since rodents don’t express γ-globin, we have employed both human and engineered mouse cell lines to demonstrate upregulation of γ-globin mRNA expression in vitro. We used MEL-h-b-BAC line#7 cells, a murine erythroleukemic cell line harboring the entire human beta globin locus and expressing mouse KLF1, and treated with antisense oligonucleotides (ASOs) targeting mouse KLF1. After 7 days of free uptake with the ASOs, we observed a 6-fold increase of human γ-globin mRNA expression after achieving 65% mRNA reduction of mouse KLF1 compared to the untreated control. We were also able to demonstrate significant upregulation of human γ-globin protein expression in these cells by western blot. We have shown similar results in a human erythroleukemia cell line, K562, using ASOs targeting human KLF1. K562 cells were electroporated with the KLF1 ASOs and 4 days later, we observed a 5-fold increase of human γ-globin mRNA expression after achieving 40% mRNA reduction of human KLF1 compared to the untreated control. These data indicate that targeting mouse or human KLF1 with ASO treatment can cause an increase in human γ-globin expression in vitrothat is necessary for the upregulation of fetal hemoglobin.We have also shown that we are able to target the bone marrow in both mice and rats through subcutaneous administration of our KLF1 ASOs. In wild type mice, at a dose of 100 mpk/wk for 4 weeks, we observed KLF1 target reduction of 88% and a β-globin reduction of 58% compared to the saline control in whole bone marrow. In Sprague-Dawley rats, at a dose of 50 mpk/wk for 4 weeks, we observed KLF1 target reduction of 83% and a β-globin reduction of 77% compared to the saline control in whole bone marrow. Therefore, we are able to achieve significant β-globin mRNA reduction in the bone marrow in both mice and rats after subcutaneous administration of KLF ASOs. These data indicate that reducing KLF1 with antisense oligonucleotides is a viable option for the treatment of sickle cell anemia. DisclosuresPeralta:Isis Pharmaceuticals, Inc.: Employment. Low:Isis Pharmaceuticals, Inc.: Employment. Booten:Isis Pharmaceuticals, Inc.: Employment. Zhou:Univeristy of Alabama at Birmingham: Employment. Kim:Isis Pharmaceuticals, Inc.: Employment. Freier:Isis Pharmaceuticals, Inc.: Employment. Guo:Isis Pharmaceuticals, Inc.: Employment. Murray:Isis Pharmaceuticals, Inc.: Employment. Townes:University of Alabama at Birmingham: Employment. Hung:Isis Pharmaceuticals, Inc.: Employment.

Worms Inspire New Bioadhesive

Sandcastle worms are pretty good chemists. Without advanced degrees, they have figured out how to biosynthesize glue components they use to build their underwater tubular shelters. Inspired by the worms, Russell J. Stewart of the University of Utah and coworkers are creating similar adhesives that might be used to make in utero surgery safer or to block blood vessels that feed tumors. “It’s a classic example of borrowing successfully from nature,” comments biomedical sealants specialist Jeffrey M. Karp of Brigham & Women’s Hospital, in Boston. When doctors examine or perform surgery on developing fetuses, the amniotic membranes that protect fetuses in the womb can rupture. The membranes often fail to heal, so the procedures carry a significant risk of preterm delivery. Existing medical adhesives fall short in addressing this surgical problem. Some adhesives swell too much when they cure and may cause further damage. Others “are ineffective in the flexible, ...

Hubris and the HHS Mandate

Hubris and the HHS Mandate

Targeting GPVI as a novel antithrombotic strategy.

While platelet activation is essential to maintain blood vessel patency and minimize loss of blood upon injury, untimely or excessive activity can lead to unwanted platelet activation and aggregation. Resultant thrombosis has the potential to block blood vessels, causing myocardial infarction or stroke. To tackle this major cause of mortality, clinical therapies that target platelet responsiveness (antiplatelet therapy) can successfully reduce cardiovascular events, especially in people at higher risk; however, all current antiplatelet therapies carry an increased probability of bleeding. This review will evaluate new and emerging targets for antithrombotics, focusing particularly on platelet glycoprotein VI, as blockade or depletion of this platelet-specific receptor conveys benefits in experimental models of thrombosis and thromboinflammation without causing major bleeding complications.

Oxygen is a critical parameter for chondrogenic differentiation of human umbilical cord blood mesenchymal stem cell in 3D-cultures

Oxygen is a critical parameter for chondrogenic differentiation of human umbilical cord blood mesenchymal stem cell in 3D-cultures

Device Interventions for Stroke Prevention in Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder, with an estimated prevalence of 0.4% to 1% in the general population. In addition, AF is responsible for approximately 15% to 20% of ischemic strokes. Device interventions to prevent strokes in patients with AF are nonsurgical procedures to block blood clots (thrombus) from forming and traveling out of the heart. The “quivering” rather than normal contractions of the upper chambers of the heart (atria) from disorganized electric activity (AF) leads to blood stasis and thrombus formation. A small cul-de-sac called the left atrial appendage (LAA) is especially prone to thrombus formation (Figure 1). In AF patients without valvular heart disease, almost all thrombus originates from the LAA. The thrombus travels to and block major vessels in the body. Blocking blood vessels to the brain leads to strokes and transient ischemic attacks (mini-strokes). Figure 1. Transesophageal echocardiogram image of a thrombus in the left atrial appendage (dotted line). Patients with the following risk factors have a higher stroke risk: heart failure, hypertension, age of 75 years or greater, diabetes mellitus, and prior history of strokes or mini-strokes. These are often combined to form the CHADS2 score. The more risk factors you have, the higher your CHADS2 score and risk of stroke are. Blood-thinning medications (anticoagulants) such as warfarin, dabigatran, rivaroxaban, and apixaban are effective stroke prevention therapies. The risks of bleeding associated with long-term anticoagulation led to the development of permanent treatment options like surgery. Closures by sutures (ligation) and removal (amputation) of the LAA …

Ethno-Pharmacological Survey, In Vitro Anti-Sickling and Free Radical Scavenging Activities of Carapa Procera DC. Stem Bark (Meliaceae)

Drepanocytosis is a genetic and neglected disease, endemic in negroids population. One of the main characteristics of this pathology is the production of a large amount of free radicals, leading to a severe oxidative stress and the consumption of NO by free oxygen radicals, and/or by cell-free plasma heme. The consequences of this defect are hemolytic anemia and tissue damage brought about by the blockage of blood vessels by the sickled cells. The present study evaluated the antisickling and radical scavenging activities of extracts from Carapa procera stem bark using Emmel’s test and the DPPH assay. Carapa procera was selected through an ethno-pharmacological. The results showed that methanolic, ethyl acetate and dichloromethane soluble fractions, anthocyanins and organic acids exhibited a significant antisickling as revealed by the observed normal biconcave form of sickle erythrocyte (normalization rate > 70%) in hypoxic conditions. Methanolic extract exhibited a good radical scavenging activity (ED 50 = 1.698 ± 0.079 µg/mL). The chemical screening performed on the plant revealed the presence of anthocyanins and organic acids which were then extracted. Total anthocyanins and organic acids revealed interesting antisickling and antioxidant properties that could justify the integration of Carapa procera in Congolese pharmacopoeia for the management of sickle cell disease. Bioactive extracts from this plant species could increase nitric oxide by scavenging free oxygen radicals. For the best our knowledge, Carapa procera has not been yet previously reported as antisickling plant in the traditional medicine database of Democratic Republic of the Congo.

Targeting BCL11A and KLF1 For The Treatment Of Sickle Cell Disease and β-Thalassemia In Vitro using Antisense Oligonucleotides

Sickle cell anemia (SCD) is a hereditary blood disorder in which red blood cells (RBC) become sickle-shaped and block blood vessels, leading to painful vaso-occlusive episodes. Sickling occurs because of a point-mutation in the β-globin gene of hemoglobin. Fetal hemoglobin (HbF, α2γ2) is the main oxygen transport protein with greater oxygen binding affinity in the fetus during the last months of embryonic development and the first few months of life after birth. HbF inhibits sickling by interfering with the polymerization of hemoglobin S. Higher HbF levels in SCD correlate with better survival and because HbF production can be reactivated pharmacologically in adults, it can be used for the treatment of SCD as well as β-thalassemia. In β-thalassemia, there is reduced or absent synthesis of the β-globin gene, causing ineffective erythropoiesis.B-cell lymphoma/leukemia 11A (BCL11A) is a transcription factor in the zinc-finger protein family and is expressed in B cells and erythroid cells. BCL11A represses fetal hemoglobin expression by binding to the GGCCCGG motif in the β-globin promoter region. Erythroid Kruppel-like factor (KLF1) is an erythroid-specific transcription factor that regulates β-globin expression through direct interaction with its promoter and indirectly regulates γ-globin expression through the regulation of BCL11A. By reducing the expression of BCL11A and KLF1, we can promote production of HbF through the upregulation of γ-globin expression.To demonstrate upregulation of γ-globin mRNA expression in vitro, we used MEL-h-b-BAC line#7 cells, a murine erythroleukemic cell line harboring the entire human beta globin locus and expressing mouse BCL11A and KLF1 (Tim Townes, Univ. of Alabama at Birmingham). Antisense oligonucleotides (ASOs) targeting mouse BCL11A or mouse KLF1 were added to the cells in a dose-dependent manner. Seven days later, with free uptake of the ASOs into the cells, we observed dose-dependent reduction of mouse BCL11A mRNA (IC50 = 0.7 μM) and mouse KLF1 mRNA (IC50 = 3 μM). Consequently, we observed a 300 +/- 8% upregulation of human γ-globin mRNA expression after achieving ∼90% reduction in BCL11A mRNA expression after ASO treatment compared to the untreated control cells. Similarly, KLF1 ASO treatment caused a 500 +/- 58% up regulation of human γ-globin mRNA expression after achieving ∼80% mRNA reduction in KLF expression. These data indicate that targeting BCL11A and/or KLF1 with ASO treatment can cause an increase in γ-globin expression that is necessary for the upregulation of fetal hemoglobin and may be used for the treatment of sickle-cell anemia and β-thalassemia. Disclosures:Peralta: Isis Pharmaceuticals, Inc.: Employment. Low: Isis Pharmaceuticals, Inc.: Employment. Kim: Isis Pharmaceuticals, Inc.: Employment. Murray: Isis Pharmaceuticals, Inc.: Employment. Guo: Isis Pharmaceuticals, Inc.: Employment. Freier: Isis Pharmaceuticals, Inc.: Employment. Townes: University of Alabama at Birmingham: Employment. Hung: Isis Pharmaceuticals, Inc.: Employment.

Identifying Single S-Nitrosothiol Sites With Cardioprotection

Ischemia/reperfusion injury contributes to heart damage in coronary artery disease through the production by mitochondria of deleterious reactive oxygen species. Nitric oxide bioactivity ameliorates ischemia/reperfusion injury by suppressing reactive oxygen species production. A study recently published in Nature Medicine reports that administration of a mitochondrially targeted S-nitrosothiol, MitoSNO, results in the S-nitrosylation of a critical Cys residue within ND3 of mitochondrial complex I , thereby inhibiting reactive oxygen species production and diminishing ischemia/reperfusion injury. Coronary artery disease, the leading cause of mortality in the United States,1 is caused by the blockage of blood vessels in the heart. The resultant ischemia underlies morbidity ranging from angina to myocardial infarction. However, restoration of blood flow (eg, by angioplasty) can lead to the injurious generation of reactive oxygen species (ROS) in cardiac muscle, which results from uncoupling of electron transport in mitochondria.2 The resultant pathology, known as ischemia/reperfusion (I/R) injury, has been characterized in numerous other organs and tissues as well, including brain, liver, kidney, and endothelium.3,4 Nitric oxide (NO), generated by cardiac-resident NO synthases, is considered to play an important role in amelioration of I/R injury.5 In particular, it has been reported that NO bioactivity mediates the protective effects of myocardial ischemic preconditioning (IPC),6 which refers to the ability of short periods of ischemia followed by reperfusion to confer protection against subsequent I/R injury.7 IPC operates, at least in part, by inhibiting electron transport and thereby suppressing ROS generation on reperfusion, and a well-studied effect of NO in mitochondria is the inhibition of complex I (the first stage in the electron transport chain).8 Complex I is responsible for oxidation of matrix NADH by membrane-bound ubiquinone and is the major entry point for electrons to the respiratory chain and, thus, when active, is a …

Essential thrombocythemia

Essential thrombocythemia is an uncommon disease. It involves an overproduction of megakaryocytes in the marrow. These platelets may not function normally and can cause a blockage in blood vessels and other complications. We report two cases of essential thrombocythemia with different clinical presentations. One with off and on headache and other with stroke, facial palsy and gangrene of hand.

Surgeons implant bioengineered vein in dialysis patient

There can be no doubt that, for the patient receiving haemodialysis, the importance of how venous access is achieved, managed and maintained is paramount. Despite progress having been made in technique and application, the mainstay of current practice continues to be centred on the formation of arteriovenous fistulae. However, this, and the use of various grafts using synthetic materials, remains beset with problems (Fluck and Kumweda, 2011). These centre on issues to do with infection, clotting (when synthetic substitutes are used) and the inherent challenges in harvesting patient’s own veins, which can be further compromised owing to the patient’s age or other associated pathology, such as diabetes mellitus. On 5 June 2013, surgeons at the Duke University Hospital successfully implanted a bioengineered vein into the arm of a patient suffering from endstage kidney disease, in what is the first stage of a US clinical trial. This may well be seen as one of the most significant steps forward in the ongoing management for this group of patients (Duke Health, 2013). Furthermore, and just as exciting, is the potential for future application in patients with blocked blood vessels (e.g. for use in bypass grafting in cardiac patients) and in the promise it holds out for bioengineering with other organs and tissues. The technology that has enabled this new initiative has been slowly developed over 15 years in collaboration between Laura Niklason and Jeffrey Lawson (Duke Health, 2013). This development can be seen as significant for a number of reasons, as Niklason explained:

Investigation of metallic surface area of coronary stents

objectives: Endovascular stents, such as coronary stents, are widely used for the treatment of narrowed or blocked blood vessels caused by plaque formation in the arteries. The narrowing of expanded blood vessels (restenosis) is perhaps the major complication associated with endovascular stent implantation that is believed to be caused by insufficient metallic surface area (MSA) in some stent designs. Our aim was to compare three examination methods which were developed at our department, to measure stent surface areas. methods: The first method was manually performed using rotating equipment under a stereomicroscope. The second method, which has recently been developed, is an automated method using an integrated scanner and a rotating engine. Both methods aimed at converting the cylindrical stent into a flattened two-dimensional image in order to enable the measurement of stent surface area by imaging software. The third method is based on a calculation which uses various stent values such as diameter, length, and strut thickness. Each measurement process was tested on different types of stents. results: Our findings showed that the methods gave similar results. The largest differences between the methods were speed and accuracy. conclusions: The results lead us to propose favouring the automated rotation method. DOI: 10.17489/biohun/2013/1/23

Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Stroke is a leading cause of death worldwide. Ischemic stroke is caused by blockage of blood vessels in the brain leading to tissue death, while intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures, exposing the brain to blood components. Both are associated with glial toxicity and neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), continually sample the environment for signs of injury and infection. Under homeostatic conditions, they have a ramified morphology and phagocytose debris. After stroke, microglia become activated, obtain an amoeboid morphology, and release inflammatory cytokines (the M1 phenotype). However, microglia can also be alternatively activated, performing crucial roles in limiting inflammation and phagocytosing tissue debris (the M2 phenotype). In rodent models, microglial activation occurs very early after stroke and ICH; however, their specific roles in injury and repair remain unclear. This review summarizes the literature on microglial responses after ischemic stroke and ICH, highlighting the mediators of microglial activation and potential therapeutic targets for each condition.