摘要:

SUMMARY1. Isolated blood‐bathed tissues which were superfused with renal venous blood during various manipulations of the visceral organs of dogs showed no detectable pharmacologically active substances, except a noradrenaline‐like substance which was liberated under some conditions of manipulation.2. An acetylcholine‐like substance was liberated into renal venous blood during experimental manipulation of visceral organs in dogs during infusion of physostigmine; the acetylcholine activity was detected with the dorsal muscle of the leech.3. The amount of liberated acetylcholine‐like substance depended on the strength of visceral stimulation as judged by the changes in the hepatic portal venous pressure. Strong reflex stimulation produced the release not only of acetylcholine but also of noradrenaline.4. Physostigmine augmented and prolonged the reflexly induced renal vasodilator and diuretic responses, and these were abolished by atropine. It was suggested that the reflex involves a cholinergic nervous mechanism.5. In some dogs there was a high output of acetylcholine from the kidney during visceral stimulation, and this was accompanied by a decrease in urine flow. The reason was not known.6. Prostaglandin E1administered into the renal artery produced similar vasodilator and diuretic responses to acetylcholine, but the onset of the effects were slower and they persisted longer than those produced by acetyl

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01824.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Regional myocardial blood flow was studied in the anaesthetized, open‐chest dog with a large chronic aorto‐caval fistula, using carbonized microspheres of 7–10 μm diameter. The results from fourteen dogs with fistulae of 4–84 days duration were compared to those from nine normal animals.2. Myocardial blood flow to all areas of both ventricles was increased to between 180 and 250% of the normal despite lower aortic diastolic (coronary diastolic) pressure. Myocardial blood flow in the right ventricle was lower than in the left in both groups of dogs although the increase above normal in dogs with fistulae was relatively greater in the right ventricle. Increased myocardial blood flow is attributed to coronary autoregulation resulting from increased myocardial oxygen consumption due to increase in myocardial tension development.3. Although absolute blood flow to the inner left ventricular wall was markedly increased in all dogs with fistulae, in those with aortic diastolic pressure below 55 mmHg the ratio of flow in the inner to that in the outer free left ventricular wall was significantly less than in those with aortic diastolic pressure above 55 mmHg (P<0·02). Low aortic diastolic pressure and diastolic coronary perfusion pressure probably resulted in relative ischaemia of the inner left ventric

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01825.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The binding of racemic mixtures of warfarin and warfarin‐alcohol to human serum albumin (HSA) is accompanied by an increase in the fluorescence quantum yield of these compounds. This property has been used to measure the characteristics of the binding of warfarin and warfarin‐alcohol to HSA at 22°C and 37°C. Within the limits of the technique, no significant differences between the number of binding sites and strength of binding at the tight site at either temperature were observed.2. The fluorescence of warfarin and warfarin‐alcohol was used to label their binding site on HSA and to study the effects of other drugs on their binding. The results indicate that these two molecules are bound to the same site on HSA.3. The validity of using changes in the fluorescence of warfarin as a measure of its displacement from HSA was investigated. Good correlations were observed between drug‐induced decreases in the fluorescence of bound warfarin and displacement as measured by equilibrium dialysis. The displacement of warfarin, as detected by fluorescence, correlates well with the increase in free warfarin resulting from addition of therapeutic drug concentrations to undiluted human serum.4. The most potent displacing agents, by all the methods used, were iophenoxic acid, phenylbutazone and oxyphenylbutazone. The first of these is no longer used clinically, but the latter two are and have been reported to cause hypoprothromin‐aemia by displacing warfarin from HSA. The present study indicates that changes in the fluorescence of warfarin bound to HSA can be used to measure displacement of bound warfarin and to screen drugs that may cause clinically significant interactions by thi

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01826.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. A comparative cross‐over trial of mefruside and cyclopenthiazide, each drug being given for 6 weeks, was conducted on thirty hypertensive patients with diabetes mellitus or impaired glucose tolerance. Other antihypertensive therapy, any antidiabetic therapy and potassium supplementation were kept constant throughout the trial. Dosages of mefruside and cyclopenthiazide were adjusted to give approximately equal blood pressure levels in the two drug periods.2. There was no significant difference in the following parameters studied during the sixth week of each of the two periods of drug therapy: serum electrolytes, total CO2, chloride, urea, amylase, haemoglobin, erythrocyte sedimentation rate, platelet and white blood cell counts, lying and standing blood pressure and pulse rate, weight, fasting and 2‐h glucose and insulin levels and five‐value glucose and insulin curve areas, fasting calcium and phosphate.3. Serum creatinine and uric acid showed a small but significant fall during mefruside th

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01827.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Administration of 2‐thiophenecarboxylic acid to rats maintained on a low calcium diet resulted in a significant depression in the serum levels of total and ionized calcium and inorganic phosphate.2. The serum magnesium levels were not altered by the dru

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01828.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The substances chromium‐51 (51CrCl3) and phenolsulphonphthalein (phenol red; PR) were compared as non‐absorbable indicators in the human stomach after alteration of ionic permeability by taurocholic acid.2. Control and test solutions containing 10 mmtaurocholic acid and indicators at pH 1 were instilled into the stomach and sampled immediately and after 15 min. The ratios of the initial and final concentrations of the indicators (Ci/Cf) were compared.3. Correlation coefficients of theCi/Cfratios for the two indicators were 0·91 in control studies and 0·75 after taurocholic acid instillation; there was no significant difference between either indicator. During taurocholic acid instillation,Ci/Cfvalues tended to fall compared to controls.4. In a smaller number of subjects in whom polyethylene glycol (PEG) was also measured as a non‐absorbable indicator, results were similar to those obtained with51Cr and PR.5.51Cr, PR and PEG are comparable indicators in the normal human stomach and when it is made abnormal by a lipid‐soluble agent such as unionized taurocholic acid, though the correlation between indicators is reduced in the abnormal stomach.6. No evidence of increased absorption of any indicator was found in spite of the increased ionic permeability produced by tauroch

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01829.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The actions of the new skeletal muscle relaxant chandonium (HS310) on the cardiovascular, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia and on chick and rat isolated skeletal muscle preparations have been described.2. In the cat chandonium exhibited a potent, competitive, non‐depolarizing neuromuscular blocking action that was rapid in onset and of short duration. It possessed a selective atropine‐like action at the cardiac vagus neuro‐effector junction but little or no ganglion blocking activity. Neither adrenergic neurone nor α‐adrenoceptor blocking properties were evident.3. Unlike tubocurarine, chandonium was without effect on the airways system of the anaesthetized cat.4. Chandonium possessed weak anticholinesterase action. It is conceivable that this effect may contribute to its short duration of action.5. The results from these studies suggest that chandonium may have possible clinical applications as a short‐acting muscl

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01830.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. Both a porous silica gel and thin cortical slices of the kidneys of rats showed highly anomalous temperature dependence of selectivity for K+relative to Na+.2. Maxima occurred at about 15°C, 30°C, 45°C and 60°C in the gel, and at about 15°C and 28°C in kidney slices.3. It is suggested that since the anomalies resemble Drost‐Hansen anomalies, they are consistent with the proposal that both in the model silica gel system and in rat kidney slices ion distribution might be determined to some extent by a difference in solvent properties between interfacial and bulk phas

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01831.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The normal levels of 5‐hydroxy‐3‐indoleacetic acid (5HIAA) were determined in the urine of four species of laboratory animals (dog, rabbit, rat and guinea‐pig).2. When 5HIAA excretion was calculated as mg/24 h, the output in the four species was in the order of rabbit>dog>guinea‐pig>rat; but when it was calculated as μg/mg of creatinine, the order was guinea‐pig>rabbit>rat>dog.3. There were significant differences in the excretion of urinary 5HIAA between males and females within two species: r

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01832.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY

摘要:

SUMMARY1. The effects of isoprenaline on the pressure‐flow relationships in the peripheral circulation were studied in five anaesthetized dogs during right heart bypass procedures.2. Isoprenaline (1 μg/kg per min) produced a significant drop in arterial pressure and arterial resistance.3. There was a significant decrease in the resistance to venous return which resulted in a significant increase in venous return.4. The findings suggest that the increase in cardiac output produced by isoprenaline results in large part from dilatation of venous resistance vesse

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1975.tb01833.x

出版商:Blackwell Publishing Ltd    

年代:1975

数据来源: WILEY