摘要:

The nature of the impaired cardiac performance seen in septic shock, acute myocarditis, dilated cardiomyo‐pathy, heart transplant rejection and immunotherapy cardiomyopathy is not well understood. The current treatment options for these conditions are limited by a lack of understanding of the underlying pathogenesis, and the management of patients with these conditions is centred on the consequences of the myocardial damage rather than the causes. However, recent research has opened new doors to the comprehension of the cellular mechanisms underlying these myocardial disorders, which may lead to more specific treatment. In this review, we present evidence for the hypothesis that myocardial production of nitric oxide (NO) is a final common pathway of several different immunological challenges and accounts for, at least in part, the negative inotropism associated with these heart muscle disorder

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01517.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Nitric oxide has been reported to affect both adhesion and respiratory burst of neutrophils. This indicates a possible role of nitric oxide in regulation of acute inflammatory responses. Release of oxygen metabolites from neutrophils can be measured using luminol‐enhanced chemiluminescence and this method can detect both extracellularly and intracellu‐larly released oxygen metabolites. Neutrophils treated with nitroprusside and activated with FMLP, type I collagen or PMA decreased their extracellular release of oxygen metabolites, while their intracellular release was almost unaffected. The effect of nitroprusside was mediated by nitric oxide since treatment with cyanide had the opposite effect. N‐ethylmaleimide treatment decreased both extra‐ and intracellular release of oxygen metabolites. This indicates that nitric oxide affects membrane‐bound NADPH‐oxidase either indirectly or directly, and not a cytosol factor of the oxidase as earlier shown for N‐ethylmaleimide. In conclusion, extracellular nitric oxide attenuates extracellularly released oxygen metabolites from activated neutrophils in an inflamma

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01518.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.This paper assesses alterations in collagen metabolism following thrombolytic therapy of acute myocardial infarction with tissue‐plasminogen activator. Sequential serum measurements of the amino‐terminal propeptide of type III procollagen (S‐PIIINP) and the carboxyterminal propeptide of type I collagen (S‐PICP) in patients suspected of acute myocardial infarction randomized to tissue‐plasminogen activator or placebo were used. S‐PIIINP increased at 3h in patients with acute myocardial infarction treated with tissue‐plasminogen activator (P<0.05). S‐PIIINP was higher in patients treated with tissue‐plasminogen activator compared with placebo‐treated patients at 3 and 6 h (P<0.05). S‐PICP decreased independently of therapy and diagnosis. Tissue‐plasminogen activator, therefore, induces breakdown of collagen, some of which is located in the wall of atheromatous arteries. Vascular patency following thrombolytic therapy may partly be mediated by breakdown of thrombogenic collagen in the vessel wall. The findings may suggest a role for S‐PIIINP as a non‐invasive indicator

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01519.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.This study examined the ability of nitrova‐sodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin‐induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity (P<0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively (P<0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% (P<0.001). Isosorbide dinitrate treatment for 1 month in non‐diabetic and diabetic rats significantly increased blood flow (P<0.01). When between‐group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non‐diabetic and diabetic rats, respectively (P<0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium‐derived nitric oxide releas

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01520.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The activation of the respiratory burst by complement factor 5a (C5a), platelet‐activating factor (PAF), formyl‐Met‐Leu‐Phe (fMLP) and neutrophil‐activating peptide IL‐8 was explored in eosinophils from patients with the hypereosinophilic syndrome. The amplitude of the response increased with increasing concentrations of C5a and PAF, but the time for its induction was unaffected by the amount of stimulus applied. Respiratory burst activity resulting from phorbol 12‐myristate, 13‐acetate (PMA)‐mediated activation of protein kinase C (PKC) produced longer onset times, which shortened with increasing PMA concentrations. Total inhibition of the C5a‐ and PMA‐mediated burst could be achieved with the PKC inhibitor staurosporine at concentrations of 100 and 5 nM, respectively. Calcium depletion abolished agonist‐induced rises in cytosolic free calcium ([Ca2+]i) and respiratory burst activity, but not PMA‐mediated NADPH‐oxidase activation. While PMA reduced elevations in [Ca2+]i, it restored the burst response to agonists in Ca2+‐depleted eosinophils. These results agree with the agonist‐induced activation of the NADPH‐oxidase via PKC, but suggest a parallel, Ca2+‐, phospholipase C‐ and PKC‐independent signal transduction pathway. Data obtained withB. pertussistoxin showed that the respiratory burst in eosinophils is blocked by ADP‐ribosylation of Gi‐proteins, but that in the presence of PMA portions

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01521.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.In this study, the composition and the role of membrane glycoproteins in phagocytosis were determined in G6PD deficient RBCs. G6PD deficient RBCs were recognized and significantly phagocytosed by murine macrophages, without pre‐exposure to oxidantsin vivo. Phagocytosis was partially (60%) inhibited by incubating macrophages with either galactose or mannose, or by incubating RBCs with β‐galactosidase, indicating the involvement of lectin‐like receptors in the recognition of G6PD deficient RBCs. Membrane glycoproteins on G6PD deficient cells were detected by binding of Con A to both intact RBCs and to purified membrane proteins. The results demonstrated modifications in the glycoprotein pattern of G6PD deficient RBCs compared to untreated controls. These included reduction in the amounts of several high molecular weight glycoproteins and appearance of lower molecular weight bands. These results suggest that G6PD deficient RBCs undergo glycoprotein modifications, which may lead to premature removal from circulation, even in non‐acute h

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01522.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Acute reduction of salt intake causes an increase in serum lipid and insulin levels in healthy volunteers and patients with essential hypertension, suggesting induction of insulin resistance by salt restriction. Direct measurements of insulin sensitivity using the euglycaemic clamp showed no significant change after 7 days of salt restriction. Our previous study showed a time dependent course of dyslipidae‐mia after institution of a low salt diet. We therefore assessed insulin sensitivity (M‐value) under euglycaemic conditions (clamp technique) at discrete time points using a parallel group design. Two groups of healthy males were examined on high (200 mmold‐1) and low (20 mmold‐1) salt intake. One group (n— 7, 25 ± 3 years, BMI 22.4 ±2.1 kg m‐2) received high and low salt diet in random order each for 7 days. The other group (n= 7, 26 ± 3 years, 22.1 ± 1.9 kg m‐2) received the respective diet in random order for 3 days. A significantly (P<0.01) different mean M‐value was noted in the group receiving the diets for 3 days, i.e. after low salt intake it was 7.4 ± 1.2mg kg‐1min‐1and after high salt intake 8.6± 1.1 mg kg‐1min‐1. In contrast, the mean M‐value was similar after low and high salt periods in the group of individuals who had been studied after 7 days on either salt take (7.8 ± 1.8 on low salt vs. 7.6 ± 1.3 mg kg‐1min‐1on high salt). There were no differences in baseline mean serum glucose and potassium levels on either salt intake, whereas baseline mean serum insulin concentrations were significantly (P<0.05) higher on low salt intake as compared with high salt intake in the group on diets for 3 days and for 7 days, respectively. Mean plasma renin activity, angiotensin II and nor‐adrenaline levels were higher after low salt than after high salt intake in both groups of volunteers. The data suggest that modulation of dietary salt intake can influence insulin sensitivity in healthy volunteers. The change in insulin sensitivity is, however, an evanescent phenomenon as previously also shown for dyslipidaemia. Extrapolations from acute effects of severe salt restriction on glucose and lipid metabolism to long‐term consequences of moderate low salt diet in the therapy of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01523.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The vascular responses to 17β‐oestradiol were examined in 23 postmenopausal women (59 ± 7 years [mean ± SD]) using a placebo‐controlled double‐blind crossover design. All women received 1 mg 17β‐oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60–80 min after application of verum or placebo as well as 10–30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4±4.1% of basal,P<0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 ± 2.1%). The blood flow rate increased significantly after oestradiol application (+30 ± 28%,P<0.05 vs. basal and P), but not after placebo (+11 ±21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17β‐oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases i

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01524.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.This study aims to understand the behaviour and clinical value of total serum calcium in untreated primary hyperparathyroidism, to identify the significant relationship between pre‐operative total serum calcium and the risk of death after surgery, and to consider the issue of when to operate. The risk of death after surgery was studied as dependent on pre‐operative serum calcium levels in a series of 896 patients followed up for mean 12.9 years (SD 6.1) after surgery. The predictive power of pre‐operative peak calcium levels was stronger than that of mean calcium levels. It was found that an increase of peak serum calcium from 2.60 mmolL‐1to 2.90 in one patient meant a death risk increase, with 38% still 5 years after surgery. The marginal risk increase per mmolL‐1was found to be higher below the peak serum calcium level of 2.90 mmolL‐1than above that level. The variation of total serum calcium before surgery was found to be substantial and the occurrence of transient high serum calcium levels was not unusual. Therefore, conservative surveillance with yearly total serum calcium estimations seems insufficient. Rather, early surgery, when serum calcium levels are not more than moderately increased, appears to be the most favourable

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01525.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.δ‐Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured δ‐aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [x(SD)] did not differ between groups A and B [0.51 (0.21) and 0.43 (019) μmol L‐1, respectively] while those of group C [2.28 (0.56) μmol L‐1were significantly higher (P<0.001) as compared to the controls. δ‐Aminolae‐vulinic acid dehydratase activity [x(SD)] was significantly increased [3599 (1909) μmol L‐1h‐1] in group B and decreased in group C [1052 (532) μmol L‐1h‐1] as compared to the controls [2034 (446) μmol L‐1h‐1] (P<0.001). There was a significantly negative correlation of logarithm of δ‐aminolaevulinic acid dehydratase with lead in both groups B (P<0.05) and C (P<0.001) but not in group A (P= 0.1). δ‐Amino‐laevulinic acid dehydratase activity had a high specificity (100%) but a low sensitivity (37%) as an index of toxic lead exposure. According to our data the value of δ‐aminolaevulinic acid dehydratase measurement in the diagnosis of lead intoxication is doubtful in cases with low blood lead levels, while in the presence of iron deficiency its reliability is further reduced, since low blood lead levels may be falsely predicted. δ‐Amino‐laevulinic acid dehydratase activity should be restricted only to monitori

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01526.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY