摘要:

Uptake and biotransformation of radioactive choline (3H‐Ch) have been studied in P2 fractions from different brain regions of mice treated with different doses of sodium pentobarbital (45–120 mg/kg intraperitoneally) or saline. Sodium dependent uptake (SDU) has been measured as the difference between results of incubations with Na+in the incubation medium and when the sodium salts were replaced by Trisphosphate and sucrose. The uptake of radioactivity increased during the incubation with3H‐Ch but the proportion of3H‐ACh was the same at all time points. The proportion of3H‐ACh to3H‐Ch in the P2 pellet was 86, 81 and 69 per cent in hippocampus, striatum and cortex, respectively. Omission of sodium ions in the incubation medium reduced uptake of3H‐Ch by about 90 per cent at 1 μM Ch in the incubation medium and the proportion of3H‐ACh to3H‐Ch was only 10 to 20 per cent while the proportion of3H‐PhCh increased from insignificant amounts to between 20 to 30 per cent. There were quantitative regional differences in SDU, a two times greater uptake was obtained in the striatum compared with cortex and hippocampus. Apparent Kmand Vmaxwere 0.9 × 106M and 71 pmol/mg, respectively, for the cortex of untreated animals. The contribution of endogenous Ch from the P2 fraction to the incubation medium gave a final concentration of 0.5 μM Ch in the standard uptake experiments. The3H‐Ch uptake was significantly reduced in P2 fraction from cortex and hippocampus prepared from mice anaesthetized with sodium pentobarbital while the uptake in P2 fractions from the striatum was unaffected. Sodium pentobarbital treatment did not affect the proportion

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01275.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The serum concentrations of theophylline, total free fatty acids (FFA) and subgroups were studied in ten healthy volunteers treated with sustained release theophylline twice daily during 9 days. Analyses were performed before and on day 1, 4 and 9 of treatment. Mean theophylline serum levels within the therapeutic range were obtained during the study, ranging from 62 ± 7 to 82 ± 10 umol/1. The mean serum concentrations of total FFA and subgroups increased significantly during treatment, showing the highest levels on day 4. Comparing fasting total FFA concentrations, an increase of 123% and 48% from pretreatment levels were found on day 4 and 9, respectively. The subgroups were influenced to a different degree by theophylline intake. Arachidonic acid (20:4) was not increased, while among the others, saturated FFA increased less than the unsaturate

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01276.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effects of chronic salt loading on central adrenergic mechanisms were evaluated in spontaneously hypertensive rats maintained on tap water or 1.2% sodium chloride drinking water for 4 weeks. Basal blood pressure was increased by 10% in the high salt group. Central catecholamines were measured spectrofluorimetrically after cation exchange chromatography. Endogenous levels of noradrenaline (NA) were not influenced by salt loading but the NA turnover (disappearance of NA following synthesis inhibition by α‐methyltyrosine) was increased in the hemisperes. Central α2‐adrenoceptor sensitivity was assessed as the clonidine‐induced reduction in blood pressure and as the clonidine‐induced deceleration of NA turnover and locus coeruleus (LC) NA cell firing rate (single unit recording). The results were slightly disparate but the unchanged sensitivity of Clonidine to reduce LC NA cell firing suggests that there were no alterations in central α‐adrenoceptor sensitivity following a salt load. There were also no changes in α‐adrenoceptor function, which was assessed semiquantitatively as the clonidine‐induced increase in flexor reflex activity in spinalized rats. In salt loaded rats there was an enhanced blood pressure and heart rate reduction following ganglionic blockade which may be interpreted as an increased basal sympathetic tone. In the periphery the pressor responses to phenylephrine were increased whereas the chronotropic response to isoprenaline was unchanged. In conclusion, in the spontaneously hypertensive rat on a high salt intake the aggravated development of hypertension was not associated with major changes in central α1and α2‐adrenoceptor mediated functions or in neuronal activity of brain stem NA neurons. There were indications of an increased basal sympathetic tone and increased blood pressure response

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01277.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effect of retinylacetate (RA) was investigated on rat liver guanylate cyclase stimulated by nitroprusside (NP). The stimulated enzyme seemed to adhere to Michaëlis‐Menten kinetics with an apparent Kmfor MnGTP of 0.10 mM and a Vmax, of 410 pmol cGMP/min. × mg prot. RA (0.1–1mM) dose‐dependently inhibited the enzyme stimulated by NP (0.1–10 mM). In the presence of 1 mM RA the activity was only 10% of the control activity. The inhibitory action of RA seemed to be non‐competitive since it depressed Vmaxwithout affecting the Kmfor MnGTP. In contrast, however, RA was instead found to stimulate the enzyme when low concentrations of NP (0.01–0.1 mM) were used. The concentration‐activity curve for NP was bell‐shaped showing an optimum at 0.5 mM. The inhibition induced by RA could not be surmounted by increasing the NP concentration indicating that RA did not compete with NP. A bell‐shaped activity curve was also seen when the enzyme activity was measured in the presence of increasing Mn2+concentrations and during these conditions RA also caused inhibition. In the presence of the sulphydryl reductant dithiothreitol (DTT), the NP concentration needed for optimal enzyme activation was about 100‐fold less than in the absence of DTT. The maximal enzyme activity was also slightly increased. In the presence of DTT, RA was much less effective to induce inhibition of the stimulated enzyme, than when DTT was absent. (In the presence of DTT 1 mM RA caused only 30% inhibition compared to 90% inhibition in its absence). These results suggest that sulphydryl groups are of crucial importance in regulating guanylate cyclase activity and that the inhibitory effect of RA on the enzyme might be dependent on the interaction with th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01278.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The enantiomers of clenbuterol, a β2‐selective adrenoceptor agonist with partial agonistic activity, were examined with respect to their ability to reactin vitroon adrenoceptors in the trachea (mostly β2), the soleus muscle (β2) and in the papillary muscle of the left ventricle (β1) from the guinea‐pig. (—)‐Clenbuterol relaxed the carbachol contracted trachea and depressed the subtetanic contractions of the soleus muscle in a concentration‐dependent manner. (+)‐Clenbuterol was at least 1,000 times less potent in this respect. Both isomers inhibited competitively the effect of isoprenaline on the trachea, the (—)‐isomer being about 100 times more active than the (+)‐isomer. None of the isomers showed any detectable positive inotropic effect on the papillary muscle but both inhibited competitively the response to isoprenaline. Also in this respect (—)‐clenbuterol was more potent than (+)‐clenbuterol. It is concluded that the β2‐agonistic as well as the β1‐antagonistic effect of clenbuterol resides in the (—)‐isomer and that the (+)‐isomer does not seem to contribute to the pharmacological e

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01279.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The solubility of 2,2′,4,4′,5,5‐hexachlorobiphenyl (HCB) in heparinized blood from guinea‐pig, heparinized plasma from mouse and in solutions of Intralipid®, bovine serum albumin (BSA) and in gammaglobulin was examined by studying the equilibrium between HCB adsorbed to a test tube wall and HCB in the aqueous phase. After 24 hours of incubation at 37° the highest concentration of HCB was found in the Intralipid® solution, the lowest one in the gammaglobulin solution. Blood and plasma were able to dissolve equivalent concentration of HCB. One conclusion of these experiments is that the largest part of HCB in blood is bound to albumin. The explanation of different patterns of uptake to solutions of Intralipid and BSA is

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01280.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Many organic solvents are lipophilic and concentrate in lipid rich tissues e.g. nervous tissue, where they are known to induce toxic effects in humans, especially in the central nervous system. Changes in the presynaptic neurotransmitter metabolism may play a role in these effects. The platelet is proposed as an alternative human model for this complex in the investigation of such changes, especially regarding 5‐hydroxytryptamine (5‐HT). The platelet 5‐HT concentration was measured in platelets isolated from exposed persons with diagnosed neurointoxication caused by exposure to organic solvents and compared to controls. No difference in the concentration was found. Instead of using the platelet 5‐HT concentration in the prediction of neurotoxic effects, the platelet 5‐HT uptake rate may be an alternative parameter. A specific and sensitive double isotope derivative technique for 5‐HT measurements is described. A solvent induced reduction in the number of platelets/ml platelet rich plasma was found and i

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01281.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

One prepubertal gilt, fed 192 μg zearalenone/kg body weight/day for 4 days, showed plasma concentrations of α‐zearalenol 3–4 times higher than of the parent compound during the treatment. Zearalenone and α‐zearalenol could be traced in plasma until the 5th day and in urine until the 4th day of the posttreatment period. A maximum circulating amount of zearalenone plus α‐zearalenol, 10.4 ng/ml plasma, was found on the 4th day of treatment followed by an urinary excretion of 305 ng/ml urine. All zearalenone and α‐zearalenol in plasma and urine were bound to glucuronic acid. On the second day of treatment the animal showed oedema and reddening of the vulva which became more pronounced during the treatment. Hormone analysis, however, showed that the animal had no oestrus cycle during the 3 week exper

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01282.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

A new method is introduced to recognize the acute pulmonary effect of airborne contaminants in guinea pigs. The method avoids anaesthesia and invasive techniques and requires minimal restraint of the animal. To recognize the acute pulmonary effect, the inspiratory volume of the animal was increased by continuous inhalation of a mixture containing 10% CO2in 18% O2and 72% N2. Once a plateau increase in inspiratory volume was reached, the aerosol to be studied was added to this mixture and its effect in reducing inspiratory volume measured. By exposing the animals to different exposure concentrations of carbamylcholine, serotonin and propranolol aerosols, concentration‐response relationships were obtained which permitted comparison of their potency. Comparisons were also made with histamine and sulfuric acid aerosols previously studie

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01283.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

In adult rats, the intracerebroventricular injection of α‐difluoromethylornithine (DFMO), a polyamine antimetabolite which specifically inhibits ornithine‐decarboxylase, induces a typical convulsive syndrome (ED50= 100 μg/rat) and death (LD50 = 300 μg/rat). Histological lesions are seen only with the highest doses and are essentially restricted to the Ammon's horn neurones. Since DFMO is currently undergoing clinical trials for use in cancer chemotherapy, including brain tumours, its CNS toxicity should be carefully cons

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01284.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY