摘要:

SUMMARY1. The effect on hepatic glutathione was studied in rats pretreated orally with various dosages of paracetamol (acetaminophen) for varying time intervals.2. Paracetamol caused a dose‐dependent depletion of hepatic glutathione, the maximum depletion occurring 3 h after acute dosing, the levels returning to normal by 12 h after low doses (0.1 or 0.25 g/kg, p.o.) and by 72 h after the hghest doses (1 g/kg, p.o.).3. Before returning to normal, the liver glutathione levels became significantly greater than the control values (35–40%) at 24 and 48 h in 0.5 and 1 g/kg paracetamol‐treated rats, respectively, suggesting thereby a ‘glutathione rebound action’ of paracetamol‐pretreatment.4. In contrast with the acutely treated rats, the liver glutathione content remained unchanged when 0–5 g/kg paracetamol was administered twice daily for 7 consecutive days.5. Fasting caused a significant reduction in hepatic glutathione, the glutathione stores were replenished within 6 h after feeding.6. The results suggest that the hepatic glutathione levels are reversibly depleted by single large doses of paracetamol, while the glutathione depletory effect appears to decrease after the repeated administration of this hepa

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02371.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. A series of 1‐(2‐chloroacyl)ureas, related to the sedative‐hypnotic drugs brom‐valetone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1‐(2‐bromoacyl)ureas and two 3‐halo compounds were included for comparison.2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1‐(2‐chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2‐halo, 3‐alkyl substituted compounds.3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity.4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular s

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02372.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. Gavage of rats with β‐aryl derivatives of α‐mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten‐fold increases above normal zinc levels were attained 2–8 h after doses of 50 mg/kg of the phenyl and furan derivatives.2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma.3. Close to 100% of the zinc and of the α‐mercapto‐β‐(2‐furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules.4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein.5. These compounds appear to mobilize zinc from tissue stores and retard zinc cl

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02373.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. Four, six and eight hours after gavage of rats with α‐mercapto‐β‐(2‐furan) acrylic acid (MFA) (25 mg/kg) serum zinc concentration was increased ten‐fold over control levels and a mean molar ratio of 1 albumin:0.4 zinc:0.8 MFA was found for seventeen sera.2. At pH 7.5 a maximum of 1 mole of MFA could be bound per mole of metal‐free bovine serum albumin.3. In the presence of zinc ion, albumin‐zinc‐MFA complexes formed, since for each mole of albumin‐zinc complex an additional mole of MFA could be bound to albumin. Complexes up to a molar stoichiometry of 1 albumin:2 zinc:3 MFA were prepared.4. MFA stabilized the albumin‐zinc complex against dissociation.5. Formation of similar complexesin vivomay account for the markedly delayed clearance of plasma zinc seen in rats administered β‐aryl derivatives o

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02374.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. The amounts by which various weights distended isolated segments from the distal colons of guinea‐pigs were measured.2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect.3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accommodation of the intestine to stretc

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02375.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. In subconstrictor doses, both serotonin and methysergide potentiated the vasoconstrictor responses to histamine in the isolated artery of the rabbit ear.2. In the presence of phentolamine (5 μg/ml) the potentiating actions of serotonin and methysergide were significantly reduced.3. This blocking action of phentolamine could be overcome by increasing the concentration of serotonin or by washing the preparation.4. In arteries taken from rabbits pretreated with reserpine, serotonin still potentiated the response to histamine and phentolamine still blocked this potentiation.5. The concentration of phentolamine required to block potentiation also blocked the direct constrictor response to serotonin. It did, however, produce a significantly greater blockade of the vasoconstrictor response to noradrenaline.6. The results indicate that the action of phentolamine in blocking the vascular potentiation produced by serotonin and methysergide is not due to a blockade of α‐recept

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02376.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

SUMMARY1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force.2. In mammalian heart muscle there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z‐ and I‐lines and increase the cell surface by a factor often.3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane.4. A mechanism is discussed which bases the excitation‐contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the mem

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02377.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1977.tb02378.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY