摘要:

AbstractIntravenous injections of the quaternary dipyridylium salt paraquat (14C–labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat–containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non–metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge–transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected.In vitrothe uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte–ghosts than in the non–haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood–stream and make them permeable to paraquat, possibly, as judged from thein vitroexperiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03199.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effects of timolol and bendroflumethiazide, either alone or combined in a fixed ratio of 4:1, on blood pressure, plasma renin activity, and plasma potassium concentration, have been investigated in normotensive and renal hypertensive dogs, and in normotensive and spontaneously hypertensive rats. In addition, the urinary kallikrein excretion has been measured in normotensive and hypertensive rats. When administered to hypertensive dogs and rats, the drug combination significantly reduced the blood pressure. Marginal reductions were observed in normotensive animals or after the administration of the single drugs. The thiazide–induced hypokalemia and hyperreninaemia were almost completely antagonised by the concomitant administration of timolol in both animal species. A highly significant elevation of urinary kallikrein excretion was also observed in rats treated with the drug combination. A less marked increase of kallikrein excretion was noted in the bendroflumethiazide treated rats. The possibility that renal haemodynamic changes, in addition to the inhibition of the increase in plasma renin, play a role in the observed antihypertensive effects is discusse

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03200.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractFour daily doses of pyrazole (50 mg/kg), caused a reduction in rat brain noradrenaline (NA) of over 20% when determined 24 hrs after the final injection. Neither 4–methylpyrazole (10–50 mg/kg), nor 4–iodopyrazole (10–50 mg/kg) had any effect. In mice treated similarly, pyrazole (50–400 mg/kg) caused a dose–dependent decrease in brain NA. Neither 4–methylpyrazole, 4–bromopyrazole nor 4–iodopyrazole caused any significant change in the levels. However if the brain NA levels were examined 6 hrs after a single dose, then in addition to pyrazole, 4–methylpyrazole showed a dose–dependent ability to lower brain NA. 4–bromopyrazole and 4–iodopyrazole, given acutely, caused a dose–dependent decrease in rectal temperature and exploratory behaviour. 4–methylpyrazole, in high doses (200–400 mg/kg) showed similar properties but they did not correlate with the decrease in brain NA. Pyrazole, after acute treatment, showed little ability to change rectal temperature or exploratory behaviour. It is concluded that the NA–depleting effect of pyrazole is not related to inhibition of alcohol dehydrogenase, since other 4–substituted pyrazoles which are more potent inhibitors of the enzyme have lit

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03201.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractOrange RN (monosodium salt of l–phenylazo–2–naphthol–6–sulphonic acid) was administered to female pigs either by intraveneous injection or by stomach tube. After intravenous injection of Orange RN, 7.8 mg/kg, the following metabolites were indentified in 24–hour urines: Orange RN (31 %), l–(4–hydroxyphenylazo)–2–naphthol–6–sulphonic acid (3 %), p–aminophenol and o–aminophenol (34 % and 4 % of the theoretical yield, respectively). l–Amino–2–naphthol–6–sulphonic acid was present, but not determined. When the urine collection was extended to 72 hours the excretion of p–aminophenol accounted for the remainder of the phenylazo moiety. The excretion pattern for p–aminophenol suggests that Orange RN is partly excreted in the bile and thereafter undergoes azo reduction in the gut. After administration of Orange RN, 78 mg/kg, by stomach tube the following metabolites were identified in the urine: Total coloured metabolites (Orange RN and l–(4–hydroxyphenylazo)–2–naphthol–6–sulphonic acid) (0.4 % of the theoretical yield), p–aminophenol and o–aminophenol (52 % and 6 % of the theoretical yield, respectively) and aniline (0.3 % of the theoretical yield). 1–Amino

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03202.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effects of aminooxyacetic acid (AOAA) and baclofen on the catalepsy, striatal homovanillic acid (HVA) increase and antinociception caused by methadone were studied in rats. Antinociceptive responses were tested by the electric foot–shock method. A new type of stimulator unit which delivered nearly constant current over a wide range of output voltage and which was noiseless was designed and its construction is described. AOAA (25 mg/kg) which increases the cerebral concentration of δ–aminobutyric acid (GABA) and baclofen (10 mg/kg), a structural analogue of GABA, did not change the catalepsy induced by methadone (5 mg/kg). AOAA (25 and 50 mg/kg) alone did not alter the striatal HVA content and had no effect on the methadone– induced HVA increase. Baclofen (10 mg/kg) increased the striatal HVA content by 19% (P<0.01) and reduced the methadone–induced HVA increase by 36 % (P<0.01). AOAA (25 mg/kg) and baclofen (5 mg/kg) had no antinociceptive effect but they increased significantly the antinociception caused by methadone (2 and 5 mg/kg). These results suggest that narcotic analgesics might cause catalepsy and increase striatal dopamine turnover by some other mechanism than neuroleptics. The results support the suggestion that GABA might be involved in pain me

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03203.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractIn this work the concentration of chlorinated hydrocarbons (PCB and DDT) was analyzed from 73 autopsy samples. Half of the material came from the coastal area of the Gulf of Bothnia and the other half from Central Finland. The correlation of the concentration of the drug to age, sex and the locality was studied as well as the occupation of the dead subjects.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03204.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractMicrosomes were prepared from the liver, kidney and lung of phenobarbital or 20–methylcholanthrene treated and control rats with the conventional ultracentrifugation and calcium aggregation methods. The two methods were compared as to the yield of microsomal protein, amount of cytochrome P–450/448 and activity of UDPglucuronosyltransferase, benzopyrene hydroxylase and p–nitroanisole O–demethylase. The absolute amount of cytochrome P–450/448 (nmol/g wet weight), as well as the enzymatic activities dependent on it (nmol produced/g wet weight) did not differ significantly in any tissue of either treated or control animals nor did that of UDPglucuronosyltransferase. However, the ultracentrifugation method resulted in a slightly smaller yield of the hepatic microsomal protein and a correspondingly higher yield of cytochrome P–450/448 per mg protein as well as higher specific enzymatic activities of both the consecutive drug biotransformation reactions studied. The specific activity of UDPglucuronosyltransferase in digitonin treated microsomes was twice as high in the conventional microsomes as in the calcium aggregated microsomes; no differences was found in the trypsin treated microsomes. The specific activity of the hepatic benzpyrene hydroxylase of the benzpyrene treated animals in the calcium harvested microsomes was 55 per cent of that in the ultra–centrifugat

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03205.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractLevels of DNA, RNA, DNase, RNase and manganese in different regions of rat brain were studied after daily administration of manganese chloride (8 mg MnCl24H2O/kg intraperitonealy) for a period of 120 days. DNA and RNA contents decreased significantly in cerebrum, cerebellum and rest of the brain regions after manganese treatment. A decrease in the DNase and an increase in the RNase activity was observed in the cerebellum and rest of brain region of the manganese treated animals. The manganese content increased significantly in all the regions of the brain, the maximum concentration being in the rest of brain portion. The presence of excess manganese in brain presumably leads to alterations in the functional activity of lysosomal enzymes. The decrease in the levels of nucleic acids is perhaps a consequence of the degenerating and dead neurones.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03206.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03207.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03208.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY