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Detection of oxidized phospholipid-protein adducts using anti-15-hydroperoxyeicosatetraenoic acid-modified protein antibody: contribution of esterified fatty acid-protein adduct to oxidative modification of LDL.

The reaction of lipid hydroperoxide with protein was investigated using an antibody, which was prepared using 15-hydroperoxyeicosatetraenoic acid (15-HPETE)-modified keyhole limpet hemocyanin as an immunogen. The obtained antibody recognized not only 15-HPETE-modified bovine serum albumin (BSA) but also 13-hydroperoxyoctadecadienoic acid (13-HPODE)-modified BSA. Glutaroyl-BSA adduct, which was prepared by the reaction of glutaric anhydride with protein, was also recognized by the antibody. The results revealed that the carboxyl terminus of lipid moiety in adducts was required for an appearance of the antigenicity. The cross-reactivity of phosphatidylcholine hydroperoxide-modified BSA (PCAOOH-BSA) with the antibody was examined. The antibody could not recognize the intact PCAOOH-BSA, whereas alkaline-treated modified BSA revealed the antigenicity. Furthermore, stearic acid at the 1 position in the phospholipid was liberated from the PCAOOH-BSA following treatment with 0.25 N NaOH. The result showed that the phospholipid moiety could be covalently bound to the protein molecule. The formation of esterified fatty acid-protein adduct during oxidation was confirmed using low-density lipoprotein (LDL). During oxidation of LDL by copper ion or 2,2'-azo-bis(2-amidinopropane)dihydrochloride, the formation of antigenic materials was observed in a time- or dose-dependent fashion. The antigenicity was significantly enhanced by the alkaline treatment on the oxidized LDL, suggesting that considerable amounts of oxidized esterified fatty acids can covalently react with apoprotein B-100 in oxidatively modified LDL.

Amidines↗

Determination of diethylpyrocarbonate-modified amino acid residues in alpha 1-acid glycoprotein by high-performance liquid chromatography electrospray ionization-mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry.

The chemical modification reagent diethylpyrocarbonate (DEPC) was used to modify alpha 1-acid glycoprotein (orosomucoid, OMD) under various conditions. The extents of DEPC modification of the histidine and tyrosine residues were followed by UV spectrophotometry. The resulting modified OMD was analyzed using enzyme digestion, reverse-phase HPLC, electrospray ionization-mass spectrometry (ESI/MS), and matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF/MS). The inherent problem of instability of DEPC-modified histidine residues was overcome by adjusting the time scale of the postreaction processing of modified OMD. There were observed differences in reactivity of histidine 97 and histidine 100 that were consistent throughout the pH range 6-8. Furthermore, several lysine residues were modified and the amount of modification increased over the pH range 6-8. These experiments show that HPLC-ESI/MS and MALDI-TOF/MS analysis coupled with enzyme digestion provide the necessary information to describe the reaction of DEPC with OMD. In addition, the results provide the carbethoxy-histidine stability and histidine reactivity information of DEPC-modified OMD necessary for the design of experiments to characterize the drug binding properties of OMD.

Amino Acid Sequence↗

Malondialdehyde-modified HDL leads to accumulation of cholesterol in rat liver endothelial cells.

In order to study in vivo the effect of modified high density lipoprotein (HDL) on the movement of free cholesterol to liver cells and bile, we injected i.v. into rats, native or malondialdehyde modified HDL labelled with [14C]cholesterol. Bile analysis indicated that the contribution of labelled cholesterol to bile acid secretion was diminished in the group receiving MDA-modified HDL when compared to control group. On the other hand, the liver analysis revealed higher radioactivity in the treated group. A separation of liver cells into parenchymal, endothelial, and kupffer at 90 min after the injection of MDA-modified HDL or native HDL indicated that the endothelial cell uptake of labelled free cholesterol from MDA-modified HDL was 2.6-fold higher than for native HDL. It is suggested that liver endothelial cells may be involved in the protection against atherogenoic oxidized lipoprotein. However, with regard to our finding, the uptake of cholesterol from modified HDL was detrimental to bile acid secretion.

Animals↗

Thermodynamics of Chromium(VI) Anionic Species Sorption onto Surfactant-Modified Montmorillonite Clay.

Batch sorption experiments performed on Cr(VI) species sorption showed a significantly enhanced removal of inorganic hexavalent chromium anionic species from aqueous solution by montmorillonite clays modified with quaternary amine, hexadecyltrimethylammonium (HDTMA) bromide. Unmodified clay had no affinity for chromium(VI) species. The sorption of Cr(VI) species has been carried out as a function of pH, contact time, adsorbate concentration (4.14x10(-5) to 8.62x10(-3) M), and temperature (5-45 degrees C). The surfactant-modified clay surface was stable when exposed to extremes in pH. The optimum pH for maximum sorption of Cr(VI) species was found to be at pH 1 and was constant between pH 2 and pH 6. The sorption data obtained was well described by DKR and Langmuir sorption isotherms. Sorption energy (E) for (i) surfactant sorption by montmorillonite clay and (ii) sorption of chromium(VI) species by surfactant modified clay have been computed from the DKR equation. Sorption energy evaluated for the sorption of both surfactant and Cr(VI) species showed that an ion-exchange mechanism was operative. The mechanism of retention appears to be replacement of counterion of the surfactant by Cr(VI) anionic species. Adsorbent capacity for the sorption of Cr(VI) species has been evaluated from the Langmuir sorption isotherm data. Thermodynamic parameters (Delta H degrees, Delta S degrees and Delta G degrees ) for surfactant sorption on montmorillonite clay and Cr(VI) sorption by modified clay have been evaluated. The specific rate constant for sorption of Cr(VI) species on modified montmorillonite was rapid during the first 10 min and equilibrium was found to be attained within 30 min. The sorption of Cr(VI) species onto modified montmorillonite clay followed first-order rate kinetics. Copyright 2000 Academic Press.

Journal Article↗

Modified axonemes and ciliary membranes in three polychaete species.

In living Ophryotrocha puerilis, Polyophthalmus pictus and Dinophilus gyrociliatus no modified cilia are present. Treatment with hyper- and hypotonic magnesium chloride solutions leads to the formation of either cilia with dilated tips or discocilia (paddle cilia). Discocilia show axoneme loops within distal swellings of the ciliary membranes. Both types of modified cilia regain their normal appearance if they are allowed to recover in seawater. The total number of discocilia and the diameter of the loops are inversely related to the osmolarity of the magnesium chloride solution used. Even isotonic solutions of magnesium chloride, which are usually used to anaesthetize marine worms, readily induce modified cilia. This indicates that the effect is not merely due to osmotic conditions. Glutaraldehyde and osmium tetroxide may act in the same way to induce modified cilia, a fact which may account for the numerous TEM and SEM documentations of modified cilia in various marine invertebrates. Which cilia in a particular species are modified varies from one specimen to another.

Animals↗

Interaction of 4-aminopyridine with normal and chloramine-T-modified K channels of neuroblastoma cells.

The steady-state effects and rate of action of 4-aminopyridine (4-AP) on normal and chloramine-T (CL-T)-modified voltage-dependent potassium (K) currents were studied in neuroblastoma cells with the whole-cell voltage-clamp current recording technique. 4-AP apparently slows both the activation and inactivation of the normal current but does not modify the time course of the CL-T-modified current. These differential effects of 4-AP are interpreted as resulting from the existence of two types of K channels with different 4-AP sensitivities under normal conditions and similar 4-AP sensitivities after CL-T, which furthermore slows their inactivation [8, 9]. While the onset of 4-AP action on the normal current is delayed and can be described by the difference of two exponentials, the onset of 4-AP action on CL-T-modified current starts immediately after the external application of the drug and can be described by the sum of two exponentials. The 4-AP-induced block of the normal current exhibits use-dependent features and is relieved by long conditioning depolarizations. In contrast, the block of the CL-T-modified current is not use-dependent. At high 4-AP concentrations (1-10 mM), the steady-state block of the normal current reaches a saturating value of 95%, while the steady-state block of the CL-T-modified current and the "unblocked" normal current only reaches a saturating value of 35%. The results suggest that CL-T inhibits a channel or membrane constituent which contributes to the inactivation of channels and increases their apparent affinity for 4-AP when they are in closed or open states.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

Identification of a locus modifying the electrophoretic mobility of malate dehydrogenase isozymes in incense-cedar (Calocedrus decurrens), and its implications for population studies.

Using megagametophyte (maternal haploid) and embryo (diploid) tissues of incense-cedar seeds, the expression of one of three malate dehydrogenase (MDH) loci was found to be influenced by a second, unlinked, modifier locus. Whereas alleles of the affected structural locus are codominant, the modifier alleles show dominance. The action of the modifier, limited to 1 of 28 structural loci examined, results in a shift of electrophoretic mobility detectable in conventional starch gels. Both the structural and the modifier MDH loci are polymorphic in all populations surveyed. Studies of genetic variation in natural populations made without rigorous genetic analysis may not detect such modification. By misinterpreting the genetic basis of enzyme phenotypes, such undetected modification can result in overestimates of genetic diversity in natural populations and can cause an apparent excess of homozygotes relative to expectations. These effects on allele and genotype frequency estimates are dependent on the levels of polymorphism at both the structural and the modifier loci. Using procedures common to many surveys of electrophoretic variation, the frequency of a recessive modifier allele could be as high as 0.3 before being detected.

Electrophoresis↗

Differential effect of food on kinetics of bromocriptine in a modified release capsule and a conventional formulation.

The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolactin over 36 h, in all subjects, both fasted and after a meal.

Adult↗

Pharmacokinetics of low-dose oral modified release, soluble and intravenous aspirin in man, and effects on platelet function.

The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng.ml-1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, microgram.h.ml-1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h-1 after intravenous injection to 1.88 h-1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effect of chemical modifiers of amino acid residues on proton conduction by the H+-ATPase of mitochondria.

The effect of chemical modifiers of amino acid residues on the proton conductivity of H+-ATPase in "inside out" submitochondrial particles has been studied. Treatment of submitochondrial particles prepared in the presence of EDTA (ESMP) with the arginine modifiers, phenylglyoxal or butanedione, or the tyrosine modifier, tetranitromethane, caused inhibition of the ATPase activity. Phenylglyoxal and tetranitromethane also caused inhibition of the anaerobic release of respiratory delta micro H+ in ESMP as well as in particles deprived of F1 (USMP). Butanedione treatment caused, on the contrary, acceleration of anaerobic proton release in both particles. The inhibition of proton release caused by phenylglyoxal and tetranitromethane exhibition in USMP a sigmoidal titration curve. The same inhibitory pattern was observed with oligomycin and with N,N'-dicyclohexylcarbodiimide. In ESMP, relaxation of delta micro H+ exhibited two first-order phases, both an expression of the H+ conductivity of the ATPase complex. The rapid phase results from transient enhancement of H+ conduction caused by respiratory delta micro H+ itself. Oligomycin, N,N'-dicyclohexylcarbodiimide, and tetranitromethane inhibited both phases of H+ release, and butanedione accelerated both. Phenylglyoxal inhibited principally the slow phase of H+ conduction. In USMP, H+ release followed simple first-order kinetics. Oligomycin depressed H+ release, enhanced respiratory delta micro H+, and restored the biphasicity of H+ release. Phenylglyoxal and tetranitromethane inhibited H+ release in USMP without modifying its first-order kinetics. Butanedione treatment caused biphasicity of H+ release from USMP, introducing a very rapid phase of H+ release. Addition of soluble F1 to USMP also restored biphasicity of H+ release. A mechanism of proton conduction by Fo is discussed based on involvement of tyrosine or other hydroxyl residues, in series with the DCCD-reactive acid residue. There are apparently two functionally different species of arginine or other basic residues: those modified by phenylglyoxal, which facilitate H+ conduction, and those modified by butanedione, which retard H+ diffusion.

Adenosine Triphosphatases↗

Modifier effects on supercritical CO2 extraction efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves.

The effects of modifiers such as methanol, water, diethylamine in methanol (10 v/v %), and diethylamine in water (10 v/v %) were investigated at three different concentrations (1, 5, and 10 v/v %) of the modifiers in supercritical CO2 (SC-CO2) in order to enhance the supercritical fluid extraction (SFE) efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves. Among the modifiers employed, methanol basified with diethylamine was found to greatly enhance the extraction efficiency relative to any other modifiers employed. The results suggest that cephalotaxine in plant matrices may be readily changed from SC-CO2-insoluble salt to SC-CO2-soluble free base by basified modifiers. In addition, SC-CO2 modified with basified methanol could enhance the extraction efficiency of cephalotaxine more than 30% when compared to the conventional organic solvent extraction.

Antineoplastic Agents, Phytogenic↗

The emerging role of leukotriene modifiers in allergic rhinitis.

Leukotriene modifiers have been shown to be efficacious in the treatment of asthma. Because of this success, and the fact that leukotrienes can be recovered not only from bronchoalveolar lavage fluid but also nasal lavage fluid, some researchers have suggested that these medications may also be useful for treating allergic rhinitis. Because the upper and lower airways are linked physically, there has been an assumption that therapy for upper and lower airway disease should be similar. This critical appraisal examines available data both supporting and refuting the emerging role of leukotriene modifiers in the treatment of allergic rhinitis. Although many studies have shown an improvement in nasal symptoms when comparing a leukotriene modifier with placebo, few studies have conclusively shown that a leukotriene modifier is any more effective in treating allergic rhinitis than an antihistamine. Results from several reported studies suggest that the addition of a leukotriene antagonist to an antihistamine is no more efficacious than antihistamine alone. However, many of these studies were small and/or primarily designed to examine the asthmatic response, with nasal symptoms being a lesser endpoint. To better understand how, where, and when leukotriene modifiers should be used in the armamentarium of therapies for allergic rhinitis, larger clinical investigations designed specifically to study allergic rhinitis need to be undertaken. We conclude that currently, the data do not support widespread use of a leukotriene modifier with or without an antihistamine in place of an intranasal corticosteroid with or without an antihistamine in the treatment of allergic rhinitis.

Histamine H1 Antagonists↗

Direct determination of selenium in urine samples by electrothermal atomic absorption spectrometry using a Zr plus Rh-treated graphite tube and co-injection of Rh as chemical modifier.

Different chemical modifiers for use with electrothermal atomic absorption spectrometry (ET AAS) were investigated in relation to determining the selenium in human urine samples. The samples were diluted in a solution containing 1% v/v HNO3 and 0.02% m/v cetyltrimethylammonium chloride (CTAC). Studying the modifiers showed that the use of either Ru or Ir as the permanent modifier gave low sensitivity to Se and the peak shape was very noisy, while Zr or Rh gave no peak at all. The same occurred when Zr was used in solution. For mixtures of permanent modifiers, Ir plus Rh or Zr plus Rh gave very low sensitivity, Zr plus Rh with co-injection of Ir in solution was also not efficient, Zr plus Rh in solution gave good sensitivity, but the best results were obtained with a mixture of Zr and Rh as the permanent modifier and co-injection of Rh in solution. Using this last modifier, the following dilutions with the HNO3 and CTAC were studied: 1:1, 1:2, 1:3 and 1:4. The best dilution was 1:1, which promoted good sensitivity and a more defined peak shape and made it possible to correct for the background using a deuterium arc lamp. Under these conditions, a characteristic mass of 26+/-0.2 pg was obtained for Se in aqueous solution. Six certified urine samples were analyzed using matrix matching calibration and the measured concentrations were in agreement with the certified values, according to a t-test at the 95% confidence level. Recovery tests were carried out and the recoveries were in the range 100-103%, with relative standard deviation better than 9%. The limit of detection (LOD, 3 sd, n = 10) was 3.0 microg L(-1) in the sample. The treated graphite tube could be used for at least 600 atomization cycles without significant alteration of the analytical signal.

Electrochemistry↗

Soil-modified carbon paste electrode: a useful tool in environmental assessment of heavy metal ion binding interactions.

Carbon paste electrodes (CPEs) modified with different soils in their native form were prepared to create a soil-like solid phase suitable for application in studies of heavy metal ion uptake and binding interactions. The preparation of CPEs modified with five different soils was examined and their heavy metal ion uptake behavior investigated using a model Cu(II) aqueous solution. Metal ions were accumulated under open circuit conditions and were determined after a medium exchange using differential pulse anodic stripping voltammetry, applying preelectrolysis at -0.7 V. The soil-modified CPE accumulation behavior, including the linearity of the current response versus Cu(II) concentration, the influence of the pH on the solution, and the uptake kinetics, was thoroughly investigated. The correlation between the soil-modified CPE uptake capability and the standard soil parameters, such as ion exchange capacity, soil pH, organic matter and clay content, were evaluated for all five examined soils. The influence of selected endogenous cations (K(I), Ca(II), Fe(III)) on the transfer of Cu(II) ions from a solution to the simulated soil solid phase was examined and is discussed. Preliminary examinations of the soil-modified CPE uptake behavior with some exogenous heavy metal ions of strong environmental interest (Pb(II), Hg(II), Cd(II) and Ag(I)) are also presented. This work demonstrates some attractive possibilities for the application of a soil-modified CPE in studying soil-heavy metal ion binding interactions, with a further potential use as a new environmental sensor appropriate for fist on-site testing of polluted soils.

Journal Article↗

Vaccination with IL-18 gene-modified, superantigen-coated tumor cells elicits potent antitumor immune response.

OBJECTIVE: To investigate the induction of antitumor immune response by vaccination with interleukin-18 (IL-18) gene-modified, C215Fab-SEA-coated tumor cells. MATERIALS: A B16-C215 cell clone stably expressing C215 antigen was established by transfecting the gene-encoding C215 antigen into B16 melanoma cells. The manipulated tumor cell vaccine was prepared with B16-C215 cells genetically modified with the IL-18 gene, coated with the fusion protein of SEA and the Fab region of C215 mAb (C215Fab-SEA) which specifically binds to the C215 antigen and then irradiated. C57BL/6 mice were vaccinated with IL-18 gene-modified, C215Fab-SEA-coated B16-C215 cells followed by tumor challenge. Tumor growth and survival time were observed. The expansion of CD4+, CD8+ cells in lymphocytes derived from draining lymph node was detected by FACS. Induction of CTL activity by vaccination was measured by 51Cr release assay. RESULTS: IL-18 gene-modified, C215Fab-SEA-coated B16-C215 cell vaccine effectively stimulated lymphocyte proliferation and CD4+, CD8+ cell expansion in vitro. It was more immunogenic than B16-C215 cells genetically modified with IL-18 gene alone or B16-C215 cells coated with C215Fab-SEA alone. Immunization of the mice with the manipulated vaccine elicited protective immunity against the following tumor challenge of parental B16-C215 and wild-type B16 cells. Significant expansion of CD4+, CD8+ T cells was observed in the draining lymph node of the immunized mice when compared with that in unvaccinated mice. Higher CTL activity was induced in vaccinated mice than that in unvaccinated mice. CONCLUSION: Vaccination with IL-18 gene-modified, C215Fab-SEA-coated tumor cells elicited potent antitumor response through induction of tumor-specific immune response.

Animals↗

Effect of modified Fenton's reaction on microbial activity and removal of PAHs in creosote oil contaminated soil.

This study describes the removal of polycyclic aromatic hydrocarbons (PAHs) from creosote oil contaminated soil by modified Fenton's reaction in laboratory-scale column experiments and subsequent aerobic biodegradation of PAHs by indigenous bacteria during incubation of the soil. The effect of hydrogen peroxide addition for 4 and 10 days and saturation of soil with H(2)O(2) on was studied. In both experiments the H(2)O(2) dosage was 0.4 g H(2)O(2)/g soil. In completely H(2)O(2)-saturated soil the removal of PAHs (44% within 4 days) by modified Fenton reaction was uniform over the entire soil column. In non-uniformly saturated soil, PAH removal was higher in completely saturated soil (52% in 10 days) compared to partially saturated soil, with only 25% in 10 days. The effect of the modified Fenton's reaction on the microbial activity in the soil was assessed based on toxicity tests towards Vibrio fischeri, enumeration of viable and dead cells, microbial extracellular enzyme activity, and oxygen consumption and carbon dioxide production during soil incubation. During the laboratory-scale column experiments, the toxicity of column leachate towards Vibrio fischeri increased as a result of the modified Fenton's reaction. The activities of the microbial extracellular enzymes acetate- and acidic phosphomono-esterase were lower in the incubated modified Fenton's treated soil compared to extracellular enzyme activities in untreated soil. Abundance of viable cells was lower in incubated modified Fenton treated soil than in untreated soil. Incubation of soil in serum bottles at 20 degrees C resulted in consumption of oxygen and formation of carbon dioxide, indicating aerobic biodegradation of organic compounds. In untreated soil 20-30% of the PAHs were biodegraded during 2 months of incubation. Incubation of chemically treated soil slightly increased PAH-removal compared to PAH-removal in untreated soil.

Aliivibrio fischeri↗

Ultrafiltration and modified ultrafiltration in pediatric open heart operations.

The capillary leak associated with cardiopulmonary bypass results in an increase in content of water in the tissues measurable by an increase in total body water after cardiac operation. Following work by Magilligan in the 1970s, ultrafiltration was introduced during bypass as a means of hemoconcentrating patients and potentially removing water from the tissues. Conventional methods proved inconsistent; thus, we modified the technique to ultrafilter the patients immediately after cessation of bypass. Modified ultrafiltration takes 10 minutes and results in an elevation of the on-bypass hematocrit to about 35% or 40%. In pilot studies comparing bypass in absence of ultrafiltration with conventional ultrafiltration and modified ultrafiltration, only the modified technique was seen reliably to reduce the elevation in total body water to only 4%, within a narrow range. Subsequent prospective studies confirmed the reduction in accumulation of total body water and also demonstrated a reduction in blood loss and in requirements for blood transfusion. Systolic blood pressure was observed to increase uniformly in all patients undergoing modified ultrafiltration. This effect was investigated and found to be associated with a marked increase in cardiac index, no change in systemic vascular resistance, a decrease in heart rate, and a marked decrease in pulmonary vascular resistance. Recently, we have demonstrated an increase in contractility and a decrease in myocardial wall volume. The modified technique of ultrafiltration has been employed successfully in more than 400 patients in our institution, and represents an excellent option for perioperative management of both accumulation of fluid in the tissues and hemodynamics after hypothermic bypass.

Adolescent↗

Effective 30-hour preservation of canine lungs with modified ET-Kyoto solution.

BACKGROUND: With the aim of developing a preservation solution that can preserve donor lungs reliably for a long time, we prepared a modified ET-Kyoto solution by adding N-acetylcysteine, nitroglycerin, and dibutyryl adenosine 3', 5'-cyclic phosphate to the previously reported ET-Kyoto solution, which contains trehalose, gluconate, and hydroxyethyl starch. In this study, we examined the efficacy of modified ET-Kyoto solution in 30-hour lung preservation. METHODS: Twenty five pairs of adult mongrel dogs were divided into four groups. Donor lungs were flushed with modified ET-Kyoto solution (n = 9), with ET-Kyoto solution (n = 6), with University of Wisconsin solution group (n = 6), or with ET-Kyoto solution plus the solvents of nitroglycerin (ethanol and propylene glycol) (n = 4), then stored at 4 degrees C for 30 hours. All animals were treated with prostaglandin E1. Left lungs were transplanted and reperfused for 6 hours. RESULTS: With respect to arterial oxygen tension, peak inspiratory pressure, and wet-to-dry lung weight ratio, modified ET-Kyoto solution was significantly superior to ET-Kyoto solution. The modified ET-Kyoto solution was significantly superior to University of Wisconsin solution with respect to survival rate, arterial oxygen tension, and wet-to-dry lung weight ratio. Ultrastructural findings supported these results. CONCLUSIONS: These results suggest that modified ET-Kyoto solution is superior to University of Wisconsin solution for 30-hour lung preservation.

Acetylcysteine↗