The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100

Summary Serum lipid concentrations of patients with familial defective apolipoprotein B-100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apopolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n=36) were compared with those of a normolipidemic control group (n=272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 ± 53.7 for E3/2 genotype (n = 3), 234.2±48.3 for E3/3 genotype (n=20), and 252.4±73.8 for E4/3 genotype (n=13). Means of triglycerides (mg/dl) were 121.0±21.2, 114.8± 60.7, and 110.0 ± 62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was –6.0% for allele e2 and +3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and –3.6% for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike.Abbreviations FDB familial defective apolipoprotein B-100 - apo apolipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein - HDL high-density lipoprotein - PCR polymerase chain reaction Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Estimation of IgG-antiglobulins in sera of patients with rheumatoid arthritis and chronic liver disorders

Summary Antiglobulin factors of the IgG class were measured in human sera by a modified immunoadsorbent-technique involving absorption to and elution from insoluble preparations of horse IgG. 32 mg of horse IgG insolubilized with bisdiazotized benzidine were used for quantitative immunoadsorption of IgG antiglobulins from 100 µl serum. Different IgG-antiglobulin concentrations could be obtained in two control groups differing in age. Elevated IgG-antiglobulins levels were found both in seropositive (mean value 23.21±7.08 µg/ml serum) and seronegative (mean value 20.06±8.39 µg/ml serum) RA patients. High values of IgG-antiglobulins were found in chronic liver disorders, particularly in the group of CAH patients (mean value 25.10±6.1 µg/ml serum).This work was supported by the Deutsche Forschungsgemeinschaft, SFB 54, Project G3     

Spider monkeys (Ateles sp.) as animal models for atherosclerosis research

Spider monkeys (Ateles sp.) were evaluated for their usefulness in research on atherosclerosis. These animals became only slightly hypercholesterolemic (increase from control serum cholesterol concentrations of about 200 mg/100 ml to about 290 mg/100 ml) when fed diets containing 1 mg of cholesterol/kcal (diets shown previously to produce marked hypercholesterolemia in most species of nonhuman primates).Both control and experimental monkeys had aortic fatty streaks and occasional lesions of the major branches of the coronary arteries. Cholesterol feeding for up to 48 months exacrebated the lesions only slightly.Biochemically, the atherosclerotic lesions of spider monkeys, as compared with other primates, have relatively less cholesterol ester and markedly more phospholipid.     

Diffusion of Nutrients in a Biphasic Medium for the Cultivation of Trypanosomes

Summary 1. Studies on uninoculated, biphasic media, containing 10% defibrinated rabbit blood in an agar base with Locke's solution as an overlay, have shown that diffusion of nutrients from the agar base into the overlay requires about 24–48 hr for equilibration.2. Large molecules as well as nominally insoluble molecules will diffuse into the overlay and become available as nutrients.3. The incorporation of blood into the molten agar base does not inactivate all enzymes and several active enzymes have been observed in equilibrated overlay solutions.4. After a five day equilibration period, we have observed the following concentrations in the overlay: amino acids, 6.0 ± 1.3 mM; glucose, 146 ± 3 mg/100 ml; cholesterol, 24.8 ± 0.4 mg/100 ml; total protein, 1.50 ± 0.04 g/100 ml; albumin, 0.18 ± 0.01 g/100 ml; alkaline phosphatase, 11.5 ± 1.1 mU/ml; lactic dehydrogenase, 358 ± 20 mU/ml; and aspartic amino transferase, 4.0 ± 1.2 mU/ml.     

加味二至丸通过抑制铁死亡减轻高脂血症小鼠肝脏脂质沉积

目的:观察加味二至丸对高脂血症模型小鼠肝脏脂质沉积及铁死亡相关蛋白表达的影响.方法:30只ApoE?/?小鼠随机分为模型组、辛伐他汀组和加味二至丸组,每组10只,另取10只相同背景的C57BL/6J小鼠作为正常对照组.模型组及各治疗组均给予高脂饲料喂养,正常对照组给予普通饲料喂养.造模12周后按分组分别给予相应的药物灌...     

Changes in lipid metabolism in women with age-related macular degeneration

Abstract Age-related macular degeneration (AMD) is one of the leading causes of visual loss among people aged 65 and older. At present the origin of AMD still remains unknown. The objective was to evaluate the chosen lipid and lipoprotein concentrations in blood of patients with AMD. Sixty women aged 55–71 (mean age 65.1±5.7) were treated in the outpatient ophthalmological clinic for more than two years because of AMD. We evaluated total serum cholesterol (TCH), triglycerides (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) by direct spectrophotometry (Human and Randox standard kits, USA). We found a significant increase of TCH, LDL and TG (224.36±41.67 mg/dl, 159.02±39.66 mg/dl and 120.92±42.64 mg/dl), and a significant decrease of HDL (38.68±6.36 mg/dl) in the AMD patients when compared with the control group. We have not found a significant difference in the average TG level between the studied groups. The concentration of Apo B was markedly increased (164.66±46.46 mg/dl) and Apo AI concentration was markedly decreased (128.9±17.01 mg/dl) in the AMD patients when compared with the control group. There was no significant difference in the concentration of the Lp(a) between the two groups. The results of our present study could point to the fact that changes in the lipid metabolism could be one of the very important risk factors involved in the pathogenesis of AMD.The results of this study have been presented as a poster presentation at the XIII Congress of the European Society of Ophthalmology 3–7 June 2001, Istanbul, Turkey     

Effects of a surfactant on thromboatherosclerosis and cholesterol atherosclerosis

The objective was to study the effect of the surfactant polymer 30-oxyethylated t-octyl phenol formaldehyde tetramer on the severity and lipid accumulation of experimental cholesterol atherosclerosis in the arch and thoracic aorta induced by feeding 0.5 gm cholesterol per day, in comparison with its effect on fibrofatty type atherosclerosis developing from organized white mural thrombus in the abdominal aorta of the same rabbits. Cholesterol atherosclerosis at 12 weeks measured as percentage intimal area in the arch 74 ± 28 S.D.%, thoracic aorta 48 ± 22% was markedly reduced in severity in rabbits fed the same cholesterol diet and treated with the surfactant: arch 9 ± 21% (P < 0.001) and thoracic 3 ± 4% (P < 0.001). Cholesterol + cholesterol ester18 mg/100 mg dry aortic tissue in the control group was markedly reduced in the surfactant group to 5 mg/100 mg dry tissue. Severity of fibrofatty type lesions expressed in terms of weight were the same in both groups. Cholesterol + cholesterol ester 20 mg/100 mg fibrofatty lesions in the cholesterol group was not significantly different in the surfactant group where 21 mg cholesterol + cholesterol ester/100 mg tissue was found. It is concluded that this surfactant markedly reduces the severity and the lipid accumulation in fatty streak type cholesterol atherosclerosis but does not modify lipid accumulation in fibrofatty lesions developing from thrombus. This surfactant may be a useful agent to differentiate pathways of lipid accumulation in these two different types of lesions.     

Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis

Summary The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851±361 ng/ml in group A versus 840±348 ng/ml in group B; after the 5th infusion it was 2,005±588 ng/ml in group A versus 2,463±1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582±308 ng/ml in group A versus 379±170 ng/ml in group B;P<0.05) and in the elimination half life (8.5±2.6 h in group A versus 6.1±1.1 h in group B;P<0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.     

Airway responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo

BACKGROUND: Chronic exposure to fenoterol (FEN), a beta(2)-adrenergic receptor (beta(2)-AR) agonist, was shown to induce both airway hyperresponsiveness and airway remodeling in experimental animals. OBJECTIVE: We wanted to know the effects of chronic exposure to procaterol (PRO), a beta(2)-AR agonist, on airway function and structure, because this agent is widely used as a bronchodilator in Japan. For comparison, the effects of FEN were also examined. METHODS: Aerosolized PRO (0.1 or 1 mg/ml), FEN (1 mg/ml) or vehicle (0.9% NaCl) was given to guinea pigs 3 times a day for 6 weeks. Sublaryngeal deposition of these agents was calculated using radioisotopes. At 72 h after the last inhalation of PRO, FEN or vehicle, the dose-response relationship between lung resistance (R(L)) and intravenously administered acetylcholine (ACh) was measured. After measuring R(L), histological changes in noncartilaginous airway dimensions were evaluated. RESULTS: The amount of sublaryngeal deposition of 0.1 mg/ml PRO in the present study was speculated to be 100 times larger than that of therapeutic dose. ACh concentrations causing 2-fold, 10-fold and maximal increases in R(L) were not different in 4 groups tested. In the smaller membranous airways (<0.4 mm in diameter), but not the larger ones, thickening of adventitial areas was significantly greater in animals treated with beta(2)-AR agonists than in control animals (23 and 25, and 96% higher in animals treated with 0.1 and 1 mg/ml PRO or 1 mg/ml FEN, respectively). The degree of the increase was significantly less in PRO-treated animals than in FEN-treated animals (p < 0.01). CONCLUSION: Our results did not provide any evidence that regular inhalation of PRO at the therapeutic dose might induce bronchial hyperresponsiveness. In addition, huge amounts of PRO only caused a mild thickening of the adventitial areas, suggesting that PRO may be a weak inducer of airway remodeling compared with FEN.     

Pancreatic blood flow in hemorrhagic shock

Pancreatic blood flow rates were determined using a¹³³Xe washout technique in a total of 40 dogs, 14 of which were used as a control group and the remaining 26 as the experimental group. The initial pancreatic blood flow rates of control group and of the experimental group were 85.1±10.1 ml/100g/min of pancreas/min and 81.1±5.4 ml/100g/min respectively. These values were not significantly different from each other (P>0.05). In the control group the blood flow was determined 3 times at 30 min intervals. These mean values were 73.0±9.4, 74.6±8.7, and 79.4 ±10.4 ml/100g/min respectively (P>0.05). The dogs in the experimental group were bled and the peripheral arterial blood pressure was reduced stepwise to 80, 50, and 30 mm Hg. At each level a 30 min of stabilization period the pancreatic blood flow rates were 49.8±3.7, 29.3±2.3 and 20.2±2.3 ml/100g/min respectively. These mean values were very significantly reduced compared to those of the control group, at 30 min (P<0.02), at 60 and 90 min (P>0.001). They were also very significantly different from their own initial values (P<0.001). the metabolic consequences of this reduction in pancreatic blood flow are discussed.This study was supported in part by grants No. 264 and 315 of Turkish Scientific and Technical Research Council     

The inhibitory effect of apolipoproteins in HDL on experimental atherosclerosis in rabbits

The main apolipoproteins in HDL are known to be apo A1, A2, and A4. Apolipoprotein (mainly apo A1) were isolated and purified from about 100 liters of rabbit's serum for the purpose of studying their inhibitory effect on the development of atheromatous plaques in rabbits. Data indicated that lipid content in aortic intima: lipid deposition in intima morphologically; area of atheromatous lesion involved and the severity of atheromatous lesions obtained were much lower in animals of the experimental group after intravenous administration of apolipoproteins isolated from HDL for 8 to 12 weeks than those in animals of the cholesterol control groups in two successive experiments. In accordance with data obtained from epidemiological and experimental surveys. HDL level was known to be correlated reversely with the incidence of atherosclerosis. Data of these experiments confirmed that apolipoproteins (mainly apoA1) in HDL are the main factors of this inhibitory effect. This result provides a scientific basis for the measurement of preparation of certain apolipoproteins (apo A1 and possibly A1) by high bio-technology for prevention and treatment of atherosclerosis in the near future.     

Seasonal changes of blood serum biochemistry in relation to sexual maturation of female common carp (Cyprinus carpio)

In this study, biochemical parameters in the blood serum of the common carp were investigated. To establish baseline blood serum biochemistry values, blood samples were collected from ten common carp per season for three seasons (autumn, winter, and spring). The results showed that protein, cholesterol, and 17β-estradiol increased significantly (p?<?0.05) during the experimental period from autumn to spring. Total lipid, triglyceride, and 17α-hydroxyprogesterone indicated no significant differences during the three seasons (p?>?0.05). A Pearson analysis revealed that there was no significant correlation between the studied parameters except for protein and cholesterol. The mean contents of protein, total lipid, triglyceride, cholesterol, 17β-estradiol, and 17α-hydroxyprogesterone obtained were 3.29?g/dl, 615.7?mg/dl, 101.1?mg/dl, 162.9?mg/dl, 46.6?ng/ml, and 0.67?ng/ml, respectively. GSI measurements increased from autumn to spring. Histological measurements detected ovary progression of the common carp from sexual stage III to V, during autumn to spring. These results suggest that sexual maturation can affect biochemical variations of fish blood serum.     

The effects of wild pistachio oil on serum leptin, thyroid hormones, and lipid profile in female rats with experimental hypothyroidism

The aim of this study was to determine the administrative effects of wild pistachio oil in the diet on serum leptin, thyroid hormones, and lipid profile in female rats with experimentally induced hypothyroidism. Thirty healthy adult female Sprague–Dawley rats were selected and randomly allocated into five equal groups (n?=?6/group). Blood samples were taken from the heart of each animal into Vacutainers before administration of propyl thiouracil (PTU) or wild pistachio oil. Female rats in the control group were fed a stock diet with fresh water. During the 30-day experimental period, all animals in the experimental groups had PTU (500?mg/l) added to their drinking water to induce hypothyroidism. Rats in experimental group 1 had PTU only, but experimental groups 2, 3, and 4 also had 5%, 10%, and 20% of wild pistachio oil in the diet, respectively. Following drug and oil administration, the rats were anaesthetized with ether and 2?ml of blood was taken from the heart at three different time points (days?10, 20, and 30). Determination of the serum concentration of thyroid hormones (T3, T4, fT3, and fT4), leptin, and serum lipid profile (cholesterol, triglyceride, LDL, and HDL) was carried out by standard routine procedures. In the present study, a significant decrease in the level of leptin was observed upon treatment with PTU. Although we observed an obvious decline in the serum leptin concentration of PTU-treated rats in the three experimental groups that received wild pistachio oil, the rate of decline decreased. During the present study, a significant increase in the serum concentration of total cholesterol, triglyceride, HDL, and LDL of hypothyroid rats was observed. Although we observed a marked overall increase in serum lipid profile concentration of the rats treated with PTU, in the three experimental groups that received wild pistachio oil, the increased rates of the lipid profiles were decreased due to unsaturated fatty acids. In conclusion, our results showed that wild pistachio oil can modulate hypothyroidism and its effects on serum lipid profile and leptin concentration.     

The effects of a hydroalcoholic extract of silymarin on serum lipids profiles in streptozotocin induced diabetic rats

Diabetes mellitus is a metabolic disease resulting from defects in insulin secretion, insulin action, or both. Diabetes produces disturbances in lipid profile and increased incidence of atherosclerosis. Lipid abnormalitiesare defined by increases in triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-c), low-density lipoprotein cholesterol (LDL-c), and decreases in high-density lipoprotein cholesterol (HDL-c). Silymarin is a natural hepato-protector extracted from Silybum marianum. It is possible that that Silymarin might be able to modulate metabolic changes in the liver and pancreas. In the present study, fifty adult male Wistar rats were used in five groups: group I—control (0.9 % NaCl), group II—diabetic control (0.9%NaCl), group III—diabetic receiving 100 mg/kg silymarin, group IV—diabetic receiving 125 mg/kg, silymarin, and group V—diabetic receiving 250 mg/kg silymarin. All groups were dosed for 14 days via oral gavage. Diabetes was induced by single injection of streptozotocin in rats (45 mg/kg b.w., ip.). Fasting glucose level and weight were measured before injection, 3 days after injection, and on days 7 and 14 of treatment. At the end of day 14, blood samples were collected via a heart puncture after animals had been anaesthetized with ether. Lipid profile of the serum samples were analysed (TC, TG, HDL-c, LDL-c). The results showed that hydroalcoholic extract of silymarin increased the average weight and decreased glucose level in this period, and TC, TG, LDL-c and VLDL-c level experienceda dose dependent reduction; the level of HDL-c increased in a dose-dependent manner at the end of 14 days (P?<?0/05). The results of the present study demonstrate that hydroalcoholic extract of silymarin has an overall beneficial effect on weight, glucose level and lipid profile in an experimental model.     

Redistribution of cardiac output after hypothalamic lesions and hemorrhage

Summary The effects of ablation of the anteroventral portion of the third cerebral ventricle (AV3V) on cardiac output and distribution of regional blood flows were determined in conscious rats using 15 m radiolabelled microspheres before, and 2 min and 15 min after hemorrhage (n=11 for each group). Prior to hemorrhage, cerebral blood flow was significantly greater (216±30 ml/min/100 g), and cerebral vascular resistance was lower (0.60±0.09 mm Hg/ml/min/ 100 g) in rats with AV3V lesions than in controloperated animals (132 ±16 ml/min/100 g; 0.92+0.1 mm Hg/ml/min/100 g, respectively), while mean arterial blood pressure, cardiac output, and regional blood flow to other organs were similar. Less blood was withdrawn from animals with AV3V lesions (4.4 ±0.6 ml) than from control-operated rats (6.0±0.5 ml) to reduce blood pressure to approximately 65 mm Hg. Hemorrhage decreased cerebral vascular resistance in control-operated animals (0.52±0.07 mm Hg/ml/min/100 g), but not in rats with AV3V lesions (0.48±0.1 mm Hg/ml/min/100 g). Cardiac output and regional blood flow to other organs were similar between rats with AV3V lesions and controloperated animals following hemorrhage. These data demonstrate that electrolytic ablation of the AV3V region results in a selective increase in cerebral blood flow and decreased cerebral vascular resistance, but does not alter the reflex changes in regional blood flow evoked by hemorrhage.     

Morphological effects of moderate diet and clofibrate on swine atherosclerosis

Early proliferative coronary atherosclerosis was produced in swine by feeding them a high-fat, high-cholesterol diet for 17 months, at which time one group of animals was killed (reference group), while the remainder was transferred for 12 months to a moderate diet that resulted in serum cholesterol levels of about 190 mg/100 ml. The moderate diet only did not decrease the size of coronary lesions, but prevented their progression. The addition of clofibrate therapy caused regression that involved a significant decrease in size, gross sudanophilia, and extent of calcification and the disappearance of foam-cell lesions. Resultant serum cholesterol levels appear to be more important than the amount of dietary cholesterol in the progression, prevention, and regression of swine coronary atherosclerosis.     

Encapsulated native and glucagon-like peptide-1 transfected human mesenchymal stem cells in a transgenic mouse model of Alzheimer's disease

Encapsulated human mesenchymal stem cells(MSC) are studied in a double transgenic mouse model of Alzheimer's disease (AD) after intraventricular implantation at 3 months of age. Abeta 40/42 deposition, and glial (GFAP) and microglial (CD11b) immunoreactivity were investigated 2 months after transplantation of either native MSC or MSC transfected with glucagon-like peptide-1 (GLP-1). CD11b immunostaining in the frontal lobes was significantly decreased in the GLP-1 MSC group compared to the untreated controls. Also, the plaque associated GFAP immunoreactivity was only observed in one of four animals in the GLP-1 MSC group. Abeta 40 whole brain ELISA was decreased in the MSC group: 86.06 ± 5.2 pg/ml (untreated control) vs. 78.67 ± 11.2 pg/ml (GLP-1 MSC group) vs.70.9 ± 11.1 pg/ml (MSC group, p < 0.05). Intraventricular transplantation of native and GLP-1 transfected MSC has been shown effective. Decreased amyloid deposition or suppression of glial and microglial responses were observed. However, encapsulation of MSC may alter their biological activity.     

Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

Summary There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease.Abbreviation NSAIDs nonsteriodal anti-inflammatory drugs Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday     

The effect of acute saline volume expansion on renal Na−K-ATPase

To examine the role of Na-K-ATPase in the natriuresis that occurs after acute extracellular volume expansion, we performed acute clearance experiments and in vitro analysis of renal microsomal ATPase activity in rats receiving intravenous 0.9% sodium chloride (0.1 ml/100g bw/min). Despite increased absolute reabsorption of filtered sodium (196±8.1 vs. 165±11.4 uEq/min, p<0.05), renal medullary microsomal Na-K-ATPase activity was decreased from 134±5.9 to 110±6.3 pmol Pi/mg protein/hour (p<0.02). No changes occurred in cortical or papillary regions and Mg-ATPase was unaffected. Similar results were obtained after adding 4 mEq/l potassium chloride to the infusion to prevent any fall in serum K⁺. These data suggest that a considerable percentage of sodium reabsorption is suppressed in acutely volume expanded animals and it is proposed that this is mediated by inhibition of medullary Na-K-ATPase.     

Thrombolytic therapy with urokinase reduces increased circulating endothelial adhesion molecules in acute myocardial infarction

The aim was to investigate circulating E-selectin and Intercellular Adhesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study was carried out in 80 patients, 40 hospitalized for acute myocardial infarction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patients at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI+urokinase) or conventional therapy (AMI+nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules. The CK was determined by means of a Hitachi 901 automatic analyser using an enzymatic method (reagents Boheringer-Biochemia, Germany). Soluble E-selectin (sE-selectin) and soluble ICAM-1 (sICAM-1) were measured in the serum using a specific immunoassay (British Biotechnology Products). The serum levels of Tumor Necrosis Factor (TNF-) were evaluated using an immunoenzymatic assay to quantitate the serum levels of the cytokine British Biotechnology Products). Patients with acute myocardial infarction (AMI) had increased serum levels of soluble E-selectin (sE-selectin; AMI+urokinase= 312±20 ng/ml; AMI+nitroglycerin=334±15 ng/ml) and soluble ICAM-1 (sICAM-1; AMI+urokinase= 629±30ng/ml; AMI+nitroglycerin=655±25 ng/ml) compared to both patients with chronic angina (sE-selectin =67±10 ng/ml; sICAM-1=230±20 ng/ml) and healthy control subjects (sE-selectin=53±15 ng/ml; sICAM-1 200±16 ng/ml). Furthermore patients with acute myocardial infarction also had increased serum levels of Tumor Necrosis Factor (TNF-=309±10 pg/ml; control subjects=13±5 pg/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus for 5 minutes, followed by an infusion of an additional 1,000,000 IU for the following two hours) succeeded in producing reperfusion and reduced the serum levels of sE-selectin (52±13 ng/ml) and sICAM-1 (202±31 ng/ml). In contrast patients not eligible for thrombolytic therapy and therefore treated with conventional therapy (a continuous i.v. infusion of nitroglycerin at the dose of 50 mg/die) did not show any significant reduction in both sE-selectin and sICAM-1 throughout the study. Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.accepted by I. Ahnfelt-Rønne