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1.
J Biomed Mater Res A ; 103(4): 1577-94, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25044644

ABSTRACT

The rupture of an intracranial aneurysm, which can result in severe mental disabilities or death, affects approximately 30,000 people in the United States annually. The traditional surgical method of treating these arterial malformations involves a full craniotomy procedure, wherein a clip is placed around the aneurysm neck. In recent decades, research and device development have focused on new endovascular treatment methods to occlude the aneurysm void space. These methods, some of which are currently in clinical use, utilize metal, polymeric, or hybrid devices delivered via catheter to the aneurysm site. In this review, we present several such devices, including those that have been approved for clinical use, and some that are currently in development. We present several design requirements for a successful aneurysm filling device and discuss the success or failure of current and past technologies. We also present novel polymeric-based aneurysm filling methods that are currently being tested in animal models that could result in superior healing.


Subject(s)
Biocompatible Materials/pharmacology , Blood Vessel Prosthesis , Intracranial Aneurysm/therapy , Animals , Humans , Prosthesis Design
2.
FEBS J ; 280(15): 3621-31, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23710929

ABSTRACT

The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an oxygen-dependent manner. In skeletal and cardiac muscle, high concentrations of myoglobin (Mb) function as a potent NO scavenger. However, the Mb concentration is very low in vascular smooth muscle, where low concentrations of cytoglobin (Cygb) may play a major role in metabolizing NO. Questions remain regarding how low concentrations of Cygb and Mb differ in terms of NO metabolism, and the basis for their different cellular roles and functions. In this study, electrode techniques were used to perform comparative measurements of the kinetics of NO consumption by Mb and Cygb. UV/Vis spectroscopic methods and computer simulations were performed to study the reaction of Mb and Cygb with ascorbate (Asc) and the underlying mechanism. It was observed that the initial rate of Cygb(3+) reduction by Asc was 415-fold greater than that of Mb(3+). In the low [O2] range (0-50 µM), the Cygb-mediated NO consumption rate is ~ 500 times more sensitive to changes in O2 concentration than that of Mb. The reduction of Cygb(3+) by Asc follows a reversible kinetic model, but that of Mb(3+) is irreversible. A reaction mechanism for Cygb(3+) reduction by Asc is proposed, and the reaction equilibrium constants are determined. Our results suggest that the rapid reduction of Cygb by cellular reductants enables Cygb to efficiently regulate NO metabolism in the vascular wall in an oxygen-dependent manner, but the slow rate of Mb reduction does not show this oxygen dependence.


Subject(s)
Globins/chemistry , Myoglobin/chemistry , Nitric Oxide/chemistry , Oxygen/chemistry , Algorithms , Ascorbic Acid/chemistry , Computer Simulation , Cytoglobin , Humans , Kinetics , Models, Chemical , Oxidants/chemistry , Oxidation-Reduction
3.
Biochemistry ; 51(25): 5072-82, 2012 Jun 26.
Article in English | MEDLINE | ID: mdl-22577939

ABSTRACT

The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an O(2)-dependent manner. This regulates NO levels in the vascular wall; however, the underlying molecular basis of this O(2)-dependent NO consumption remains unclear. While cytoglobin (Cygb) was discovered a decade ago, its physiological function remains uncertain. Cygb is expressed in the vascular wall and can consume NO in an O(2)-dependent manner. Therefore, we characterize the process of the O(2)-dependent consumption of NO by Cygb in the presence of the cellular reductants and reducing systems ascorbate (Asc) and cytochrome P(450) reductase (CPR), measure rate constants of Cygb reduction by Asc and CPR, and propose a reaction mechanism and derive a related kinetic model for this O(2)-dependent NO consumption involving Cygb(Fe(3+)) as the main intermediate reduced back to ferrous Cygb by cellular reductants. This kinetic model expresses the relationship between the rate of O(2)-dependent consumption of NO by Cygb and rate constants of the molecular reactions involved. The predicted rate of O(2)-dependent consumption of NO by Cygb is consistent with experimental results supporting the validity of the kinetic model. Simulations based on this kinetic model suggest that the high efficiency of Cygb in regulating the NO consumption rate is due to the rapid reduction of Cygb by cellular reductants, which greatly increases the rate of consumption of NO at higher O(2) concentrations, and binding of NO to Cygb, which reduces the rate of consumption of NO at lower O(2) concentrations. Thus, the coexistence of Cygb with efficient reductants in tissues allows Cygb to function as an O(2)-dependent regulator of NO decay.


Subject(s)
Globins/chemistry , Globins/physiology , Nitric Oxide/metabolism , Oxygen/physiology , Cytoglobin , Globins/genetics , Humans , Nitric Oxide/chemistry , Nitric Oxide/genetics , Oxygen/chemistry , Plasmids/genetics , Reducing Agents/chemistry , Reducing Agents/metabolism , Spectrophotometry, Ultraviolet
4.
Nitric Oxide ; 23(4): 311-8, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-20854922

ABSTRACT

Carbon fiber microelectrodes and carbon fiber composite minielectrodes (CFM/CFCM) have been generally used for measurements of nitric oxide (NO) concentration in chemical and biological systems. The response time of a CFM/CFCM is usually from milliseconds to seconds depending on the electrode size, the thickness of coating layers on the electrode, and NO diffusion coefficients of the coating layers. As a result, the time course of recoded current changes (I-t curves) by the CFM/CFCM may be different from the actual time course of NO concentration changes (c-t curves) if the half-life of NO decay is close to or shorter than the response time of the electrode used. This adds complexity to the process for determining rate constants of NO decay kinetics from the recorded current curves (I-t curves). By computer simulations based on a mathematical model, an approximation method was developed for determining rate constants of NO decay from the recorded current curves. This method was first tested and valuated using a commercial CFCM in several simple reaction systems with known rate constants. The response time of the CFCM was measured as 4.7±0.7 s (n=5). The determined rate constants of NO volatilization and NO autoxidation in our measurement system at 37 °C are (1.9±0.1)×10(-3) s(-1) (n=4) and (2.0±0.3)×10(3) M(-1) s(-1) (n=7), which are close to the reported rate constants. The method was then applied to determine the rate of NO decay in blood samples from control and smoking exposed mice. It was observed that the NO decay rate in the smoking group is >20% higher than that in control group, and the increased NO decay rate in the smoking group was reversed by 10 µM diphenyleneiodonium chloride (DPI), an inhibitor of flavin enzymes such as leukocyte NADPH oxidase.


Subject(s)
Biosensing Techniques/methods , Carbon/chemistry , Nanocomposites/chemistry , Nitric Oxide/analysis , Nitric Oxide/metabolism , Animals , Carbon Fiber , Computer Simulation , Diffusion , Electrodes , Kinetics , Male , Mice , Mice, Inbred C57BL , Models, Animal , Solutions
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