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Biomedical subjects

B Asztalos

Publications and source records attributed to B Asztalos.

At least 19 recordsLinked to original sources

Differential response to low-fat diet between low and normal HDL-cholesterol subjects.

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (</=35 mg/dL). A low-fat diet is generally recommended to patients with coronary heart disease. A low-fat diet decreases both low density (LDL) and high density lipoproteins (HDL). We have shown that on an Average American Diet, subjects with different HDL-cholesterol (HDL-C) levels have different HDL subpopulation profiles. In low HDL-C subjects (</=35 mg/dL), the apoA-I-only subpopulation alpha(1) is significantly decreased compared to individuals with normal HDL-C levels (>35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and alpha(1) concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only alpha(1) subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C.

Adult↗

Flow visualization analysis for evaluation of shear and recirculation in a new closed-type, monopivot centrifugal blood pump.

Flow visualization has great potential in analyzing flow patterns of centrifugal blood pumps to locate possible hemolysis and thrombus formation sites. This study focused on the said phenomena thought to correlate with areas of high shear velocity and stagnation and analyzed a new closed-type centrifugal blood pump. As a result of analyzing the flow of inlet and front gap of the impeller, flow in the front gap was approximately 30% of the external flow. Visualization in the back gap showed sufficient exchange also. Analysis in the volute area and around the washout holes revealed high shear locations and quantified the highest shear velocity. Maximum shear on the volute wall was found to be 9,000-19,000 s-1 and was located in the 0.2-mm vicinity of the wall. Based on these results, previous hemolysis tests, and small pump size, one concludes that the analyzed closed-type centrifugal pump has a relatively smooth flow suitable for a totally implantable artificial heart.

Algorithms↗

Flow visualization study to improve hemocompatibility of a centrifugal blood pump.

A correlation study was conducted among quantitative flow visualization analysis, computational fluid dynamic analysis, and hemolysis tests regarding the flow in a centrifugal blood pump to prevent hemolysis. Particular attention was paid to the effect of the impeller/casing gap widths on the flow in the volute and in the outlet. Flow vector maps were obtained for 250% scaled-up models with various geometries, using an argon ion laser light sheet, a high speed video camera, and particle tracking velocimetry. In terms of the results, in the small radial gap model, high shear occurred near the inside wall of the outlet and stagnation near the outside wall of the outlet whereas the standard model maintained smooth flow and low shear. The small radial gap model showed a lower head and greater hemolysis than the standard model. This head decrease could be partly restored by relocating the outlet position; however, the hemolysis level hardly decreased. From these results, it was found that the small radial gap itself is important. It was also confirmed by detailed flow visualization and simple laminar shear analysis near the wall that the small radial gap caused a wider high shear layer (110-120 microm) than the standard model (approximately 80 microm). In the small radial gap model, the high shear layer in the outlet (approximately 50 microm) is much narrower than that in the volute. Flow visualization together with the aid of computational fluid dynamic analysis would be useful to eliminate the causes of hemolysis.

Blood Flow Velocity↗

Development of design methods for a centrifugal blood pump with a fluid dynamic approach: results in hemolysis tests.

The purpose of this study was to examine the relationship between local flow conditions and the hemolysis level by integrating hemolysis tests, flow visualization, and computational fluid dynamics to establish practical design criteria for centrifugal blood pumps with lower levels of hemolysis. The Nikkiso centrifugal blood pump was used as a standard model, and pumps with different values of 3 geometrical parameters were tested. The studied parameters were the radial gap between the outer edge of the impeller vane and the casing wall, the position of the outlet port, and the discharge angle of the impeller vane. The effect of a narrow radial gap on hemolysis was consistent with no evidence that the outlet port position or the vane discharge angle affected blood trauma in so far as the Nikkiso centrifugal blood pump was concerned. The radial gap should be considered as a design parameter of a centrifugal blood pump to reduce blood trauma.

Animals↗

Computational fluid dynamics analysis to establish the design process of a centrifugal blood pump: second report.

To establish an efficient design process for centrifugal blood pumps, the results of computational fluid dynamics (CFD) analysis were compared to the results of flow visualization tests and hemolysis tests, using the Nikkiso centrifugal blood pump. CFD analysis revealed that the radial gap greatly affected the shear stress in the outlet diffuser. The hemolysis study also indicated a similar tendency. To see the flow behind the impeller, we conducted a comparative study between models with and without washout holes using the CFD technique. CFD analysis indicated that flow and pressure distributions behind the impeller were different between both models, and a particle was observed to remain longer behind the impeller in the model without washout holes. In the future, CFD analysis could be a useful tool for developing blood pumps in comparison to flow visualization tests and hemolysis tests.

Computer Simulation↗

Flow visualization as a complementary tool to hemolysis testing in the development of centrifugal blood pumps.

With a 250% scaled-up pump model, high speed video camera, and argon ion laser light sheet, flow patterns related to hemolysis were visualized and analyzed with 4 frame particle tracking software. Different flow patterns and shear distributions were clarified by flow visualization for pumps modified to have different hemolysis levels. A combination of in vitro hemolysis tests, flow visualization, and CFD analysis suggested a close relationship between hemolysis and high shear caused by small impeller/casing gaps. Because arbitrary cross sections can be illuminated by laser light sheet, flow visualization is a useful tool in finding locations related to hemolysis in the design process of rotary blood pumps.

Biomechanical Phenomena↗

Development of design methods of a centrifugal blood pump with in vitro tests, flow visualization, and computational fluid dynamics: results in hemolysis tests.

There are few established engineering guidelines aimed at reducing hemolysis for the design of centrifugal blood pumps. In this study, a fluid dynamic approach was applied to investigate hemolysis in centrifugal pumps. Three different strategies were integrated to examine the relationship between hemolysis and flow patterns. Hemolytic performances were evaluated in in vitro tests and compared with the flow patterns analyzed by flow visualization and computational fluid dynamic (CFD). Then our group tried to establish engineering guidelines to reduce hemolysis in the development of centrifugal blood pumps. The commercially available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the dimensions of 2 types of gaps between the impeller and the casing, the axial and the radial gap, were varied. Four impellers with different vane outlet angles were also prepared and tested. Representative results of the hemolysis tests were as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100 L, respectively. The backward type vane and the standard one resulted in NIH values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that small gaps led to more hemolysis and that the backward type vane caused more hemolysis. Therefore, the design parameters of centrifugal blood pumps could affect their hemolytic performances. In flow visualization tests, vortices around the impeller outer tip and tongue region were observed, and their patterns varied with the dimensions of the gaps. CFD analysis also predicted high shear stress consistent with the results of the hemolysis tests. Further investigation of the regional flow patterns is needed to discuss the cause of the hemolysis in centrifugal blood pumps.

Animals↗

Washout hole flow measurement for the development of a centrifugal blood pump.

Washout holes in the impeller of a centrifugal blood pump reduce thrombus formation in areas where blood is apt to stagnate, especially in the back gap of the impeller. In this study, flow through the washout holes is quantified by pressure measurement and flow visualization with a 300% scaled-up model to understand the force driving flow through the washout holes and the flow itself. When external circuit resistance is constant, pressure distribution normalized by the square of the tip speed is constant and independent of the impeller rotational speed. The ratio of the flow rate through the washout holes to the flow rate of the external circuit is also constant. When the external circuit resistance increases, the pressure difference at the washout holes between the front and back gap of the impeller increases and generates a greater flow rate through the washout holes.

Biomechanical Phenomena↗

Characterization of phospholipids in pre-alpha HDL: selective phospholipid efflux with apolipoprotein A-I.

Previously, we have shown that lipid-free apoA-I, when incubated with fibroblasts, will produce lipoproteins of pre-alpha mobility (Asztalos, B. F., et al. 1997. Arterioscler. Thromb. Vasc. Biol. 17: 1630-1636). In order to understand the nature of these pre-alpha particles, we further characterized their lipid content. The pre-alpha particles are high density lipoproteins, having a median density of 1.08 g/ml. They have a surface charge of -18.45 mV. The phospholipid composition of these particles showed that they have 4% each of phosphatidyl ethanolamine and inositol; 69% phosphatidyl choline and 18% sphingomyelin. This phospholipid composition is different from those of plasma HDL (81% phosphatidyl choline, 13% sphingomyelin), plasma membrane on the fibroblasts, and whole fibroblast phospholipid. To demonstrate that the pre-alpha mobility resides in the lipids, lipids from pre-alpha lipoproteins were reconstituted with lipid-free apoA-I. The resultant particles retained their pre-alpha mobility. We conclude that apoA-I may react with specific regions of plasma membrane to acquire this unusual lipid composition and that pre-alpha mobility is caused in part by the unusual phospholipid composition.

Apolipoprotein A-I↗

Quantitative visualization of flow through a centrifugal blood pump: effect of washout holes.

To clarify the effect of washout holes on the flow in a centrifugal blood pump to prevent blood stagnation, a quantitative flow visualization technique was applied to compare flows in models with and without washout holes. A scaled-up model of a prototype pump and a high speed video camera were used for the flow visualization, and images were processed by particle tracking velocimetry. Particular attention was paid to the flow through the gaps behind and in front of the impeller. The results showed that in the gap behind the impeller, washout holes caused not only an inward flow, but also an increase in the tangential velocities. In the gap in front of the impeller, washout holes caused an outward flow and a decrease in the tangential velocities. Head flow characteristics were little affected by the washout holes in this initial design for which the flow through the washout holes was set to be approximately 10% of the flow in the external circuit. These results suggest that the flow through washout holes is significant in the prevention of blood stagnation in 2 ways. First, the inward radial velocity behind the impeller and outward velocity in front of the impeller result in fluid exchange, and second, a tangential velocity increase reduces fluid stagnation behind the impeller.

Blood Flow Velocity↗

Role of free apolipoprotein A-I in cholesterol efflux. Formation of pre-alpha-migrating high-density lipoprotein particles.

This article characterizes products formed by the interaction of purified apolipoprotein (apo) A-I and human fibroblasts. Fibroblasts were incubated with different concentrations of purified apoA-I (1 to 30 micrograms/mL) in tissue culture medium for different periods of time (0 to 24 hours). The medium was then characterized by one- (agarose) and two-dimensional (agarose: polyacrylamide nondenaturing gradient gel) electrophoresis. At any given concentration of apoA-I, the rate of cellular cholesterol efflux appeared linear over 24 hours. Incubating purified apoA-I with fibroblasts for 4 hours, we detected five pre-alpha lipoproteins with particle sizes between 114 and 684 kDa. Formation of pre-alpha lipoproteins was concentration-dependent. At low concentrations (below 5 micrograms/mL apoA-I), all purified apoA-I (with pre-beta mobility) was converted to pre-alpha lipoproteins. At higher concentrations (greater than 5 micrograms/mL apoA-I), more apoA-I remained with pre-beta mobility. The pre-alpha lipoproteins were characterized by colocalization of apoA-I particles with 14C-cholesterol and 32P-phospholipids. Results showed that the pre-alpha particle of lowest molecular weight contained phospholipid and apoA-I but no cholesterol. The remaining pre-alpha particles contained all three substances. When pre-alpha particles were subjected to ultracentrifugation, all particles floated at d < 1.21 g/mL with some of the smallest phospholipid apoA-I only particles being present in the d > 1.21 g/mL fraction. Based on these results, we postulated that in the first stages of reverse cholesterol transport, pre-alpha lipoproteins are formed by the interaction of lipid free apoA-I and peripheral cells.

Apolipoprotein A-I↗

Lipid composition of HDL subfractions in dog plasma and lymph.

We report the lipid composition of dog plasma and peripheral lymph lipoproteins as separated into pre-beta, alpha, and pre-alpha fractions by agarose gel electrophoresis. Plasma lipoproteins with alpha mobility have a composition different from that of plasma lipoproteins with pre-alpha mobility, having 9% versus 11% free cholesterol, 21% versus 17% cholesterol ester, 1% versus 16% triacylglycerol, and 69% versus 56% phospholipid. On the other hand, lymph alpha and pre-alpha lipoproteins have compositions that are quite similar (9% versus 7% free cholesterol, 17% versus 17% cholesterol ester, 2% versus 4% triacylglycerol, and 71% versus 71% phospholipid). The lipid compositions of plasma and lymph alpha lipoproteins are quite similar (9% versus 9% free cholesterol, 21% versus 17% cholesterol ester, 1% versus 2% triacylglycerol, and 70% versus 72% phospholipid). The lipid compositions of plasma and lymph pre-alpha lipoproteins are different (11% versus 7% free cholesterol, 17% versus 17% cholesterol ester, 16% versus 4% triacylglycerol, and 56% versus 71% phospholipid). Peripheral lymph lipoproteins with pre-beta mobility contained 15% cholesterol, 13% cholesterol ester, 10% triacylglycerol, and 61% phospholipid. Compared with plasma, peripheral lymph lipoproteins are free cholesterol-enriched in all fractions. Calculated stoichiometric ratios of lipid to apoA-I per particle, alpha lipoproteins have two molecules of apoA-I per particle, and pre-alpha lipoproteins have four molecules of apoA-I per particle.

Animals↗

The effect of pesticides on carp (Cyprinus carpio L). Acetylcholinesterase and its biochemical characterization.

The activity and molecular forms of acetylcholinesterase (AChE) were characterized in tissues of the carp (Cyprinus carpio). Tissue AChE activity was determined in response to specific inhibitors (ethopropazine, BW 284 C51) or pesticides (CuSO4, paraquat (PQ), methidathion (MD)). The highest AChE activity was found in the serum (878 +/- 100 U/liter), followed by the brain (113 +/- 12 U/liter), heart (89 +/- 6 U/liter), and trunk muscle (35 +/- 5 U/liter). Experiments with specific choline esterase inhibitors revealed a very low amount of pseudocholinesterase in all tissues studied. The ratio of the membrane-bound to the cytoplasmic-free AChE molecular forms was increased in the order of brain, trunk muscle, and heart. In sera of fish treated with MD (2 ppm) there was an 80% inhibition of AChE lasting for 2 weeks. Treatment with CuSO4 or PQ (both 5 ppm) led to a 50% decrease in the serum AChE activity followed by a transient increase over the control level. After 2 weeks of chronic treatment, AChE activity in fish exposed to CuSO4 returned to the control level, whereas in fish treated with PQ an elevated level (130% when compared to the control level) of enzyme activity was found. Our present experimental data indicate that pesticides occurring in natural waters not only inhibit AChE activity in fish but may influence the resynthesis of the enzyme as well.

Acetylcholinesterase↗

Comparison of effects of paraquat and methidation on enzyme activity and tissue necrosis of carp, following exposure to the pesticides singly or in combination.

Under aquarium conditions, treatment with the herbicide paraquat (PQ) and with the insecticide methidation (MD) caused cell damage and stress in carp (Cyprinus carpio L.), as shown by increases in glutamate-dehydrogenase (GIDH, EC 1.4.1.2), glutamate-oxalacetate transaminase (GOT, EC 2.6.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) activities and in blood sugar levels. PQ proved synergistic with MD in certain cases as regards the harmful effect exerted. On combined treatment, dilated extracellular spaces were visible by light microscope in the liver, while electronmicroscopic studies revealed signs indicative of cell autolysis in the same organ.

Journal Article↗

The effect of an organophosphorus pesticide on the enzymes of carp (Cyprinus carpio L.).

1. The effect of 1.5, 2.0 and 5.0 ppm methidation was studied on the ASAT, ALAT, LDH and AChE enzymes, as well as the blood sugar and adrenaline levels in carp. 2. According to our studies methidation implies a potential hazard on the normal biochemical processes of fishes: causing tissue necrosis indicated by the increase ASAT, ALAT and LDH activities, inducing continual stress effect reflected by the increased blood sugar and adrenaline levels, inhibiting AChE activity in the various organs, the consequence under acute effects being fish kill.

Acetylcholinesterase↗