ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01730.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Potential antioxidant properties of aminophylline and theophylline were investigated. We have found that these drugs, though ineffective against superoxide anion and hydrogen peroxide, are scavengers of hydroxyl radical (OH·). Indeed, second‐order rate constants (k) of aminophylline and theophylline with OH· are about 1.9 times 1010mol‐1s‐1and 4.5 times 109mol‐1s‐1, respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to this marked OH· scavenging activity, since it is characterized by a high k value, i.e. about 8 times 109mol‐1s‐1. However, when using therapeutically relevant concentrations of the methylxanthines (9 and 13 μmL‐1), significant antioxidant effects against OH·‐induced oxidant injury are evident only with aminophylline. Although all three substances can apparently bind and inactivate iron, only aminophylline is effective at 9 and 13 μgmL‐1; also this action is favoured by ethylenediamine. Moreover, therapeutic concentrations of aminophylline, but not of theophylline, are capable of antagonizing hypochlorous acid (HOC1); this effect is entirely due to the presence of ethylenediamine. Oxidant species, such as OH· and HOC1, have been implicated in the pathophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidant properties, which are partly or totally attributable to ethylenediamine, depending on the chemical identity of the prooxidant antagonized (e.g. iron/OH· or HOC1). Aminophylline antioxidant capacity should be taken into account when investigating the lung epithelial lining fluid antioxidant capacity and oxidati

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01731.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.There is growing evidence that the amyloid β‐peptide (β1_40) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta1_40has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether β1‐40(or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2h and 4h at 37°C together with 6μmolL‐1of β1‐40or of fragments β1_28and β25‐35, resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05μmolL‐1). Moreover, β1_40and its two fragments induced a significant alteration of45Ca permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of β1_40and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca2+‐ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanis

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01732.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Isolated human mononuclear and polymorphonuclear phagocytes were stimulated in the presence and absence of serotonin (5‐HT), the major secretory product of activated platelets, and the release of reactive oxygen metabolites during the respiratory burst was assessed by luminol‐enhanced chemilumi‐nescence. In the presence of 5‐HT, a dose‐dependent suppression of the chemiluminescence signal occurred, irrespective of the stimulus used to elicit the respiratory burst. A similar suppression of luminol‐enhanced chemiluminescence was also seen in a radical generating cell free system. 5‐HT was found to be oxidized by the reactive oxygen species released by stimulated phagocytes. This oxidation is prevented in the presence of other antioxidants. The major 5‐HT oxidation product was isolated by gel chromatography and identified by mass‐spectrometry as a 5‐HT dimer, probably 5,5′‐dihydroxy‐4,4′‐bitryptamine. It is concluded that the 5‐HT released from activated thrombocytes at sites of inflammation and endothelial cell damage acts as a true scavenger of reactive oxygen species generated during the respiratory burst of stimulated phagocytes and may thus modulate various aspects of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01733.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.To evaluate serum apo AI, apo B, Lp(a) and the ratio of unesterified cholesterol to total cholesterol as markers of hepatic synthetic capacity after orthotopic liver transplantation, serial measurements of these variables were performed on post‐transplant days 1, 3, 5, 7, 10 and 14 in 70 patients. Liver function was assessed by a quantitative dynamic test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX). Patients were divided into two groups on the basis of clinical and laboratory findings, those with evidence (n= 46) and those without evidence (n= 24) of hepatic dysfunction. Apo AI levels fell in both groups to day 5, but then began to increase in the group with good hepatic function, a highly significant (P&0001) positive correlation being found with the results of the MEGX test on post‐transplant days 7, 10 and 14. The ratio of unesterified cholesterol to total cholesterol rose in both groups from days 1 to 7 and then began to fall in the group without hepatic dysfunction; a highly significant (P<0.001) negative correlation was observed with the results of the MEGX test on days 10 and 14. Apo B levels rose in both groups from days 1 to 10, with no significant differences between the two groups; no correlation was observed with the results of the MEGX test on any study day. In contrast, serum Lp(a) concentrations fell in both groups to day 5, but then began to increase in patients with good hepatic function; a highly significant (P<0001) positive correlation with the results of the MEGX test was recorded on post‐transplant day 14. We conclude that serial measurements of serum apo AI, Lp(a) and the ratio of unesterified cholesterol to total cholesterol are of value in monitoring the restoration of hepatic synthetic capacity in patients after orthotopic liver transplant

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01734.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Twenty‐one patients with non‐insulin‐dependent diabetes in poor metabolic control were subjected to intensified therapy, in most cases with insulin, to investigate whether it is possible to slow down the accumulation of advanced glycosylation end products of collagen by improving glycaemic control. Fasting and mean daily blood glucose, serum fructo‐samine and glycohaemoglobin levels, as well as glycation of collagen were measured before and after 1.5 years of intensified therapy. All these parameters except for fructosamine correlated significantly with fasting blood glucose and glycohaemoglobin when measured before the insulin therapy was started, when the patients had had poor but stable metabolic control for a long period of time. After 1.5 years of intensified therapy the level of glycation of collagen did not significantly correlate with the fasting blood glucose or glycohaemoglobin levels, suggesting that the non‐enzymatic glycosylation of collagen reflects a longer period of metabolic control of diabetes than the glycohaemoglobin level. Intensified treatment improved previously poor metabolic control in patients with non‐insulin‐dependent diabetes, and this improvement was reflected in a decrease in fasting and mean daily blood glucose levels, serum fructosamine and glycohaemoglobin concentrations, and in the level of early products of glycation of collagen. The average content of advanced glycosylation end products of collagen, assayed in terms of collagen‐linked fluorescence did not decrease. However, they accumulated more slowly in the patient tercile with the greatest decrease in the level of fasting blood glucose than in the tercile with the smallest decrease, and even a decrease in fluorescence was observed in the patients with the greatest improvement in the metabolic control. Our findings suggest that the improvement of metabolic control in non‐insulin‐dependent diabetes is reflected in a slower accumulation of advanced glycosylation end products in collagen. If the slower accumulation of advanced glycosylation end products in collagen is translated into a slower development of the long‐term complications of diabetes

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01735.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Intravenous magnesium lowers mortality in patients with suspected myocardial infarction. We tested the hypothesis that the protective effect may be due to a direct, local influence of magnesium on myocardial reperfusion injury in a dog model of ischaemia/reperfusion. Ten anaesthetized open chest dogs underwent 1 h of left anterior descending artery (LAD) occlusion and 6 h of reperfusion. The animals received intracoronary (i.c.) magnesium aspartate (Mg,n= 5) or vehicle infusion (n= 5) for the first hour of reperfusion. Mg infusion was adapted to actual LAD flow (ultrasonic flow probe) to increase regional plasma concentration by 4 mmol L‐1. Regional myocardial function was measured as percent systolic wall thickening (sWTh, sonomicrometry). Intracoronary Mg increased LAD flow during application (at 15min reperfusion; Mg, 194±44 (mean±SD); control, 116±41 mLmin‐1100g‐1,P<0.01). sWTh decreased during coronary occlusion from 14.3 ± 7.1 % to ‐ 4.7 ± 2.7% in the control group and from 14.8±2.5% to ‐4.1 ±3.1% in the Mg group. Throughout the reperfusion period wall function remained depressed in both groups to a similar degree (control, ‐ 3.5 ± 1.8%; Mg, ‐ 3.0 ± 1.9% at 6 h reperfusion). Global haemodynamics were not different. Infarct size after 6h reperfusion (TTC staining) was similar in both groups (Mg, 20.6±5.0; control, 24.4±8.7% of area at risk). Regional magnesium application (i.e.) to post‐ischaemic reperfused myocardium had no influence on infarct size or post‐ischaemic regional wall function in this model. The beneficial action of systemic Mg in patients with myocardial infarction is probably not due to an early direct protective effect on isc

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01736.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The authors consider two groups of patients with overt sporadic porphyria cutanea tarda (PCT) from different continents, with the aim of evaluating the possible impairment of the liposoluble antioxida‐tive system, given the possible synergic effect of porphyrins and iron in promoting oxidative cellular damage. Twenty‐three Italian outpatients with overt sporadic PCT and 11 outpatients with PCT from Buenos Aires (Argentina) were matched with 60 patients with liver cirrhosis and 52 healthy Italian controls. Serum levels of alpha‐ and beta‐carotene, cryptoxanthin, zeaxanthin, lutein, lycopene, retinol and alpha‐tocopherol were detected by a high‐performance liquid chromatographic technique devised in our laboratory, which afforded an accurate and simultaneous resolution of all these compounds. The results point to a significant reduction in plasma levels of alpha‐ and beta‐carotene in both the PCT populations with respect not only to controls, but also to the cirrhotic population, which had more severe liver damage. Moreover, other carotenoids with proven antioxidative properties, like cryptoxanthin and lycopene, are greatly reduced in our PCT populations. This confirms the suggested synergic effect of iron and porphyrins in the oxidative intracellular damage with consequent depletion of antioxidative liposo

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01737.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Microvascular research is seriously hampered by the great temporal and spatial variability of the measured skin blood flow and variation in sympathetic vasomotor reflexes within and between persons. Therefore skin vasomotor reflexes were studied before and after ulnar nerve blockade within the same person, resulting in a temporal complete denervation of the fifth finger and partial denervation of the fourth finger. Skin temperature and laser Doppler flux (LDF) were registrated to measure predominantly arteriove‐nous shuntflow. Measurements were performed on the palmar tip of the second and fifth finger in nine healthy volunteers, at baseline, and during a sympathetic reflex test (i.e. inspiratory gasp) and postural response test. Beat‐to‐beat digital blood pressure was recorded from the third and fourth finger by a Finapres device. Baseline capillary blood cell velocity (CBV) was measured at the nailfold of the second and the fifth finger. After ulnar blockade baseline skin temperature, LDF and CBV increased significantly, with respectively (mean±SE) 3.2±0.9d̀C, 20.9 ±5.9 relative perfusion units and 0.79 ±0.40 mm‐1s. The percentage LDF decrease of the fifth finger during inspiratory gasp was 48.2 ±5.3% before and 31 ±0.9% after blockade. The postural response test showed a decrease in LDF of the fifth finger with no significant difference before and after blockade, respectively 12.3± 14.7% and 8.0±2.7%, while no difference was found in the increase in digital blood pressure in the denervated fourth finger compared to both the same finger before blockade and to the third non‐blocked finger. It is concluded that ulnar nerve blockade enables the study of sympathetic skin vasomotor reflexes by comparison of a denervated and a non‐denervated vascular bed within the same person. After ulnar blockade arteriovenous shunt flow as well as nutritional capillary blood flow increased significantly. Postural vasoconstrictor response is not abolished by ulnar blockade, suggesting that local regulatory mechanism

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01738.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Erythrocyte aggregation and sedimentation is determined by the concentration of high molecular plasma proteins such as fibrinogen and immuno‐globulins. The role of albumin, the most abundant plasma protein, is controversial. We analysed the influence of human albumin (0–80 gL‐1) on sedimentation behaviour of erythrocytes suspended (haematocrit 35%) in fibrinogen‐enriched normal plasma, plasma from patients with hypoalbuminae‐mia, solutions of dextran 70 in buffer, and mixtures of fibrinogen, immunoglobulins and albumin in buffer. Sedimentation was measured by the Westergren method, viscometry was performed at low and high shear rate. The addition of albumin to normal plasma, hypoalbuminaemic plasma, or dextran solutions in buffer decreased the erythrocyte sedimentation rate. In contrast, in a mixture of fibrinogen and immunoglobulins in buffer, albumin increased erythrocyte sedimentation. When either fibrinogen or immunoglobulins were omitted, or fibrinogen was replaced by dextran, albumin did not increase sedimentation, which indicates that increased sedimentation was due to an interaction of all three compounds. The viscosity of erythrocyte suspensions was increased by albumin. It is concluded that the influence of albumin on erythrocyte aggregation is complex and depends on the technique used; low shear viscosity is increased, but erythrocyte sedimentation, i.e. under no flow conditions, is decreased. The inhibitory action of albumin on the erythrocyte sedimentation rate has clinical implications and must be known by physicians. It may help to interpret sedimentation rates more correctly and prevent misinterpreting presumed therapeutic successes or

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01739.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY