摘要:

Summary—Aspirin‐like drugs mainly include paracetamol, salicylates and other non‐steroidal anti‐inflammatory drugs, and metamizole. Their analgesic effect is classically ascribed to a peripheral site of action, within the pain‐processing site. There is, however, convincing evidence that a central component contributes to the overall analgesia provided by these agents. Experimental and clinical studies referring to this challenging proposal are reviewed here. The exact site and mode of action of aspirin‐like drugs within the central nervous system remains controversial. It is likely that supraspinal mechanisms play an important role. Some experiments lend support to the involvement of monoaminergic control systems. Other data indicate that these drugs act centrally through the inhibition of cyclo‐oxygenase activity. The interactions between prostaglandins and various neurotransmitters suggest that both mechanisms

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00258.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—Restenosis after coronary angioplasty, the main limitation of interventional cardiology, remains an unsolved issue. The failure to‐date of all pharmacological attemps at prevention has prompted the development of alternative strategies. A mechanistic approach to the problem of restenosis is based on the assumption that creating a more satisfactory acute angioplasty result would reduce the development of restenosis. With the exception of coronary stenting, however, none of the new angioplasty devices have convincingly reached this goal. Furthermore, recent advances in the field of vascular biology have opened new avenues for a molecular approach of restenosis. Better understanding of the pathophysiology of restenosis, in conjunction with high‐pace development of catheter, polymer, and virus technologies, provide opportunities to deliver agents — drugs, genes, or antisense oligonucleotides — locally, at the site of angioplasty to interfere specifically with the restenosis process. Some of these molecular strategies are currently being investigated in animal models. Clinical application of a molecular approach to prevent restenosis, however, will require close collaboration between physicians, molecular biologists, and bio

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00259.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—The effect of SR 49059, a new potent non‐peptide vasopressin (AVP) V1areceptor antagonist, was investigated on AVP‐induced electrocardiogram modifications. A high intravenous dose of AVP (0.5 IU or 1.23 μg/animal) produced an important transientt‐wave elevation (from 4.7 ± 0.2 to 8.9 ± 0.7 mm) and heart rate decrease (from 199 ± 5 to 99 ± 6 bpm) in conscious rabbits. Thet‐wave increase was a significant index of coronary vasoconstriction‐induced cardiac ischemia. SR 49059 had potent protective effects in this model both by intravenous (0.125 to 0.5 mg/kg) and oral (2.5 to 10 mg/kg) routes. After a 30‐min pre‐treatment, SR 49059 showed dose‐dependent protection ont‐wave elevation and heart rate decrease with ED50's of 95 (95% CL: 168‐22) and 30 (95% CL:54‐6) μg/kg iv, respectively. Complete blockade occurred with doses of 2 mg/kg iv and upwards. By the oral route, SR 49059 was rapidly absorbed and a dose of 10 mg/kg displayed a protective effect lasting more than 6 hours on both electrocardiogram parameters. Moreover, SR 49059 exerted a high stereospecific inhibitory effect since its enantiomer was totally inactive at 0.5 mg/kg iv, suggesting that protection occurred by interaction with vascular AVP V1areceptors. Thus, SR 49059 is the first specific non‐peptide V1aantagonist with long‐lasting oral activity on AVP‐induced coronary vasoconstriction and bradycardia. With this original profile, SR 49059 could be a promising therapeutical antivasospastic agent for pre

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00260.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—The influence of vascular endothelium on angiotensin II‐induced contraction and the underlying mechanisms in the rabbit renal artery were investigated. In endothelium‐intact preparations, angiotensin II (3–100 nM) caused a concentration‐dependent increase in tension by maximally (Emax) 0.74 ± 0.05 g. Removal of the endothelium significantly enhanced the angiotensin II‐induced contractions (Emax: 3.91 ± 0.19 g). Indomethacin (10 μM) did not influence the angiotensin II‐induced contractions. Methylene blue (10 μM) and NG‐methyl‐1‐arginine (L‐NMMA, 5 μM) significantly enhanced angiotensin II‐induced contractions by 418 ± 29% and 200 ± 14%, respectively, in endothelium intact preparations, but not in those devoid of endothelium. L‐arginine (1 mM), but not D‐arginine, reversed the L‐NMMA‐induced enhancement of the angiotensin II‐induced contraction. The present results suggest that angiotensin II‐induced contractions in rabbit renal artery are largely subject to the influence of the endothelium. The endothelium‐derived relaxant factor (EDRF), rather than cyclo‐oxygenase products, appears to be involved in mediating the inhibitory effects of the endothelium. Nitric oxide (NO) derived from endothelium may play a major role in inhibiting angiotens

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00261.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—Objective: to examine the effect of losartan on short‐term variability of blood pressure (BP) in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats.Design and methods: variability of BP was characterized during baseline condition and 20 minutes after blocking the renin‐angiotensin system (RAS) with the ATI receptor antagonist losartan (10 mg/kg, iv). A Fast Fourier Transform algorithm was used for analysis.Results: under baseline conditions, SHR exhibited enhanced variability of BP compared to WKY, reflected by increased standard deviation (SD) of systolic BP (SBP). On the other hand, the mid frequency (0.2–0.6 Hz, MF) and the low frequency (0.02–0.2 Hz, LF) components of SBP were exaggerated. Enhanced MF area probably reflected a hyperactivity of the sympathetic nervous system in SHR. After a single injection of losartan, the mean BP was lowered in SHR by 13 ± 5 mmHg, mean ± SEM,P<0.05). In WKY, losartan solely decreased the LF component of BP. In SHR, losartan increased the MF component of BP.Conclusion: losartan resulted in differential effects on BP variability in the two strains. In WKY, the RAS contributed to the genesis of LF fluctuations. In SHR, the increase in the MF component of BP after losartan probably indicated a reflex sympathetic activation triggered by v

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00262.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level,in vitroexperiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25‐week‐old SHR and age‐matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D100) were determined and vessels were set up to a normalized internal diameter (0.9 D100). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro‐L‐arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L‐arginine (100 μM) but not D‐arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5‐HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA‐precontracted MRA and 5HT‐precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine‐induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30‐min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO‐like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium‐derived relaxing factor‐nitric oxide (EDRF‐NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence o

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00263.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—As feto‐placental vessels in humans are not innervated, regulation of vascular tone in the fetal extracorporeal circulation most likely depends on either circulating hormones or local paracrine mechanisms. However, the latter have not yet been fully investigated. The aim of our study was to characterize vasomotor behaviour of resistance stem villi arteries when challenged with various constrictor and dilator agents, with special emphasis on the physiological importance of endothelium. The latter is poorly characterized in this particular vascular bed in humans. Villous stem arterial rings (internal diameter 182 ± 6 μm) were isolated under microscopy from term human placentae obtained after cesarean section. The vessels were mounted as ring preparations in an isometric myograph for tension measurements. Endothelium was removed from some of the rings by gentle insertion of a knotted human hair into the vascular lumen. Of the three vasoconstrictors tested, endothelin‐1 (ET‐1) showed the greatest potency, being 1,000 times more potent than serotonin and phenylephrine. The classical endothelium‐dependent vasodilators, acetylcholine, adenosine diphosphate (ADP) and histamine, caused dose‐dependent relaxation of the rings; an effect which was completely abolished by the removal of endothelium. Pre‐treatment with the nitric oxide (NO) synthase inhibitor, Nω‐nitro‐L‐arginine, also markedly reduced the endotheliumdependent relaxant responses to ADP. By contrast, the vasodilatory response to sodium nitroprusside was not affected by endothelial removal. We conclude that i) ET‐1 is a potent vasoconstrictor of the human placental vascular bed and ii) placental villous endothelial cells synthesize and release relaxing factor(s) wh

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00264.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—The aim of this study was to document the accuracy of magnetic resonance imaging (MRI) during fluoroquinolone‐ associated Achilles tendinitis. Fourteen Achilles tendons were examined by MRI (T1 and T2 or T2*‐weighted sequences) in nine patients with typical tendinopathy (13 cases of tendinitis and 1 rupture) during fluoroquinolone therapy. Tendinous involvement was classified according to the prominence of intra‐ or peritendinous changes. The most typical feature was the presence of intratendinous changes, longitudinal or transversal, detected on T1 or T2‐weighted sequences. Peritendinitis was most visible in two cases and nodular involvement in three cases. It was concluded that MRI appears a helpful and accurate method in identifying and classifying such iatrogenic tendinitis. In addition, MRI indicates orthopedic management when detecting risk o

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00265.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary—The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one‐compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (Cs= 0.96 ± 0.33), and either the total volume of distribution (Vd= 23.9 ± 7.0 I) or the volume of distribution relative to body weight (Vs= 0.36 ± 0.10 1·kg−1. The volume of distribution was increased with respect to the usual value of 0.25 1·kg−1. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of Csand Vswere used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg·1−1for peaks and 0.5 mg·1−1for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of amin

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00266.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1995.tb00267.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY