摘要:

The abilities of 24 endogenous biochemicals to interfere with gas chromatographic exclusion screening analyses for drugs of direct chloroform extracts obtained from forensic blood specimens were studied. The relative retention onOV‐17 of the 24 endogenous compounds and the direct extract‐abilities of 8 of these were compared with those of 30 directly extractable acidic, phenolic, neutral and basic drugs. On direct extracts of blood, gas chromatographic peaks were obtained with phenylethylamine, 5‐hydroxymethylfurfural, p‐hydroxybenzaldehyde, p‐hydroxybenzoic acid, p‐hydroxyphenylacetic acid and stearic acid. Palmitic acid and p‐hydroxyphenylpropionic acid were not directly extractable, while no gas chromatographic peaks were obtained with three neutral lipids, cholesterol, four cholesterol esters, deoxycholic acid, phosphatidyl‐L‐serine, heparin and L‐glutamine. Tyramine, tryptamine, tristearin and lysolecithin gave gas chromatographic peaks but their direct extractabilities were not determined. Post mortem toxicological cases are described in which apparent barbiturate, tripelennamine, hydroxyglutethimide and desipramine gas chromatographic peaks were probably mimicked by stearic acid, p‐hydroxybenzaldehyde and/or tryptamine; differentiations were effected by selective washing of the chloroform extracts with weak and strong bases, acid, ammoniacal Ag

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00598.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Spontaneous isotonic contractions and electrical activity were obtained from 3 cm sections of rat uteri placed in a 6 ml organ bath. The electrical activity was recorded by means of 2 pairs of platinum wire electrodes, each pair measuring the activity over a 2 to 4 mm uterus section. Uteri were used from 21 pregnant rats (length of pregnancy was 1 to 8 days) and from 4 non‐pregnant rats pre‐treated for 6 or 8 days with 10 mg/kg progesterone subcutaneously. When 0.17 vol % dimethyl sulphoxide (DMSO) was added to the organ bath no or only small changes in the electrical activity and the spontaneous contractions of the myometrium were observed. Administration of progesterone (83 μg per ml organ bath) dissolved in DMSO (50 mg/ml) inhibited the contractions after 10 to 60 seconds, but no or only minor changes were registered in the electrical activity. After DMSO‐progesterone solution had been washed out, the contractions reappeared after 7 to 20 m

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00599.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The mean arterial blood pressure in conscious normotensive Sprague‐Dawley rats was recorded by means of in‐dwelling arterial catheters. Dopamine hydrochloride (DA) was infused intravenously from 0.04 μg/min. up to 0.22 μg/min. The infusions always resulted in a hypertensive reaction. Intravenous injections of DA (1–50 μg/kg) or noradrenaline bitartrate monohydrate (NA) (0.02–0.5 μg/kg) were given before and after phenoxybenzamine (PBZ) (5 mg/kg); protriptyline (PTP) (10 mg/kg) and nialamide (100 mg/kg). The DA injections alone resulted in a pressor action. PBZ blocked or considerably diminished the pressor action of DA. PTP did not result in a clear‐cut augmentation of the blood pressure response to DA like that seen after the various equipotent NA doses tested. Furthermore, there was no prolongation of the duration of the pressor action of DA after PTP, though this was found after NA. Nialamide did not alter the magnitude of the pressor action of DA and NA. However, the hypertensive response of L‐DOPA (25 mg/kg) was markedly augmented by pretreatment with niala

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00600.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The mean arterial blood pressure in conscious rats was recorded by means of in‐dwelling arterial catheters. DL‐5‐hydroxytryptophan (5‐HTP) 200 mg/kg intraperitoneally lowered the blood pressure significantly after 20 min. Following the administration of the peripheral decarboxylase inhibitor L‐α‐hydrazino‐α‐methyl‐β‐(3,4‐dihydroxyphenyl) propionic acid (MK 486) 100 mg/kg intraperitoneally, 5‐HTP 200 mg/kg intraperitoneally caused only a slight lowering of the blood pressure after 1–2 hrs. 5‐HTP 50 mg/kg given intraperitoneally after a combined pretreatment with aMAOinhibitor (nialamide) 100 mg/kg intraperitoneally andMK486 100 mg/kg produced characteristic effects on gross behaviour after 20 min. No significant effects of 5‐HTP on the blood pressure were observed in these experiments. 5‐HTP200 mg/kg intraperitoneally caused a hypothermia which was prevented byMK486 100 mg/kg. After pretreatment with nialamide andMK486 as in the blood pressure experiments, 5‐HTP 50 mg/kg produced an initial hypothermia followed by a pronounced rise in body temperature. 5‐HTP 200 mg/kg intraperitoneally resulted in a marked accumulation of 5‐hydroxytryptamine (5‐HT) in the heart and brain. Pretreatment with MK 486 100 mg/kg prevented the increase in heart 5‐HT but did not change that in the brain. Brain dopamine (DA) but not brain and heart noradrenaline (NA) decreased significantly. 5‐HTP 50 mg/kg after the administration of nialamide and MK 486 increased the brain 5‐HT but caused no change in heart 5‐HT. Nialamide and MK 486 per se increased brain DA and NA significantly; 5‐HTP largely prevented the increase in brain DA but not in brain NA. It is concluded that 5‐HTP has a hypothermic and a hypotensive action due to the effect of 5‐HT on the extracerebral structures, while the hyperthermic effect may have a central nervous origin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00601.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The hydrolysisin vitroof salicylsalicylic acid and acetylsalicylic acid was investigated in human plasma and whole blood. The rate of hydrolysis in plasma as well as in whole blood was considerably greater for acetylsalicylic acid than for salicylsalicylic acid. Acetylsalicylic acid was hydrolyzed much more rapidly in whole blood than in plasma while salicylsalicylic acid tended to hydrolyze more slowly in whole blood than in plasma. These differences may in part explain the differences in biological half‐life between the two drug

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00602.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Drug effects on the size of the exchangeable sulphate pool and the incorporation rate into costal cartilagein vivowere studied by a new double isotope method in growing mice of the N. M. R. I. strain. Adrenalectomy caused a significant decrease both in the size of the sulphate pool and the rate of sul‐phation in cartilage. Hydrocortisone (a water soluble form), acetylsalicylic acid, oxyphenylbutazone and dimethyl‐sulphoxide given in rather high doses had no effect on the sulphate pools or the sulphate incorporation rates. Hydrocortisone‐acetate (in oil or suspension), prednisolone‐acetate and dexamethasone all elicited a dose‐dependent retardation of body growth and a considerable increase in the size both of the total sulphate pool and the pool per g body weight. The sulphation rate of the cartilage samples even at high doses was only moderately depressed by the steroids studied. Only prednisolone elicited a marked inhibition with a dose above 40 μg. Salazopyrin® (4 mg/day × 6) considerably decreased sulphate incorporation without affecting the size of the sulphate pool. Vitamin A caused a marked and dose‐dependent increase in the sulphate pool and a moderate and dose‐independent decrease in the sulphation of cartilage.l‐Thyroxine up to a dose of 1 μg/day depressed sulphate incorporation, but a 10 times higher dose stimulated it. The sulphate pools displayed a graded elevation after increasing

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00603.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The influence of different endocrine conditions and the effects of sex hormones on the sulphate incorporation ratein vivointo costal cartilage were studied in mice by a method which allows a correction of the sulphation rates for alterations in the exchangeable sulphate pools of the animals. Oestrous cycle variations had no measurable effect, but castration of both male and female mice decreased the size of the sulphate pool and sulphation rate of cartilage, while pregnancy had the opposite effect. Testosterone propionate (dose range: 1 μg‐1 mg/day × 6) and ethisterone (dose range: 40 μg‐5 mg/day × 6) stimulated weight gain but had a rather weak effect on the sulphate pools and incorporation rates. Oestradiol benzoate and diethylstilboestrol given to growing mice in doses of 1 μg‐1 mg/day × 6 caused a dose‐dependent growth retardation and a decrease in the size of the total sulphate pool and that per g body weight. The drugs also elicited a graded inhibition of sulphation rate of cartilage in both sexes. Stilboestrol (20 μg/day × 6) also inhibited growth and decreased sulphation rate in 12‐days old suckling mice. Adult male and female animals treated with oestradiol benzoate in the doses described above, displayed only small weight changes but a marked and dose‐dependent decrease in the sulphation rate. Inhibition of sulphate incorporation rate always went together with growth retardation in growing mice but the former effect was produced by lower doses of

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00604.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

By intravenous infusion into rabbits anaesthetized with urethane or barbital the plasma level of a number of drugs was kept constant. The drug concentrations were determined in the vitreous body, aqueous humour, lens, and plasma. The steady state distribution ratios across the blood‐vitreous barrier was found to be: for quinine 1.35, salicylic acid: 0.42 and 1.0 (at plasma concentrations 150 and 900 μmol/l respectively), PAS (p‐aminosalicylic acid): 0.65, salicyluric acid: 0.05, barbital: 0.75. The distribution rate across the blood‐aqueous barrier was found to be for quinine: 0.25, salicylic acid: 0.8 and 1.0 (at plasma concentrations 150 and 900 μmol/l), salicyluric acid: 0.1, barbital: 0.95. The permeability constants for the penetration of the drugs into the vitreous body were calculated, quinine: 2.2 × 10–1, salicylic acid: 1.4 × 10–2, barbital: 1.2 × 10–2, PAS: 8.5 × 10–3, lithium: 6.9 × 10–4, salicyluric acid: 5.3 × 10–5, and into the aqueous humour, quinine, salicylic acid, barbital, and PAS: 1.1 — 1.5 × 10–2, lithium: 6.2 × 10–3, salicyluric acid: 2.9 × 10–4, all per minute. The partly ionized drugs penetrated the vitreous barrier according to the lipid solubility of the unionized form, thus penetration across the aqueous barrier was dependent on both the lipid solubility of the unionized form and the dissociation constant. Li+penetrated into the vitreous body predominantly from the anterior region of the eye and the partly ionized drugs through the whole exchange area. The injection of 25 μl 0.9 % NaCl or liquefaction of the vitreous body with hyaluronidase gave little change in the rate of Li+penetration, while that of PAS was decreased by half. The ratio between the salicyluric acid concentration in the water phase of the lens and the aqueous humour averaged 3.6 (1.1 — 5.6), suggesting that salicyluric acid was transported into th

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00605.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The effects of amphetamine on central and peripheral catecholamines have been studied in guinea pigs, since in this species, unlike several others, amphetamine is not metabolized byp‐hydroxylation. Twenty mg/kg of dl‐amphe‐tamine‐sulphate given intraperitoneally caused a 40 % decrease in brain and heart noradrenaline, a 13 % decrease in brain dopamine and a 60 % decrease in homo‐vanillic acid in the caudate nucleus, four hours after its administration. The changes in tissue catecholamine levels and the increase in motor activity followed the time‐course of the amphetamine concentrations both in the brain and plasma. After chronic administration of amphetamine at 12 hourly intervals for 7 or 18 days, there was a further decrease in brain and heart catecholamine and homovanillic acid levels. A 4‐fold increase in the 3‐O‐methylated metabolites of noradrenaline and dopamine in brain after the administration of amphetamine to guinea pigs pretreated with nialamide and an increase in the urinary excretion of NA (13‐fold) and adrenaline (3‐fold) provided evidence for an amphetamine induced release of central and peripheral catecholamines as has previously been reported in rats and cats. Amphetamine disappeared from brain and plasma with an apparent half‐life of 2.5–3.1 hours. Only amphetamine and hippuric acid were recovered in the urine after the administration of radioactively labelled amphetamine. Nop‐ or βhydroxylated metabolites of amphetamine were present in the brain or heart tissues in the guinea pig. The results show that acute and chronic amphetamine administration causes changes in endogenous catecholamines in guinea pigs similar to those found previously in rats in spite of differences in the metabolism of ampheta

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00606.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Captan was given by gavage in a range of doses once daily for 100 days to young male albino rats. The oral LD50 (100 days) ± S. E. M. or daily dose which killed 50 % of rats over this period was found to be 0.92 ± 0.23 g/kg/day. The oral 100‐day LD50 index, or oral LD50 (100 days) expressed as a percentage of the acute oral LD50 (1 dose) was 7.3 ± 1.9 which indicated that on chronic administration captan was the most toxic of 12 drugs for which published values of the 100‐day LD50 index are available. Signs of toxicity were most evident during the first 3 weeks of daily administration and were due to a severe gastroenteritis, an inflammatory reaction in many organs, and degenerative changes in other

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00607.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY