bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter‐Individual Differences in Metabolism of Drugs: The Role of Genetic Factors
Authors: Evans David Alan Price
Published: July 2010

Abstract: Variability is a frequent finding in pharmacology, and may have a unimodal or polylmodal distribution. Both types of variation are analysable by genetic techniques. Experiments reveal that the variability between persons in their capacity to metabolize drugs is largely genetically determined. Persons who have a greater ability to metabolize a drug may be protected from adverse reactions, but may also not receive therapeutic benefits as compared with those less well endowed, when fixed dosage regimes are utilized.
Effects of Ergot Alkaloids (Hydergine®) on Cerebral Haemodynamics in Man
Authors: Olesen Jes , Skinhøj Erik
Published: July 2010

The intracarotid 133Xe injection method gives a very accurate determination of regional blood flow within the brain and can be used in human subjects when awake. By this method it has been demonstrated that the ergot alkaloid preparation hydergine® has no immediate effect on blood flow through normal cerebral tissue and no direct effect on diseased areas. However, secondary to an ergot initiated decrease in arterial blood pressure, cerebral blood flow is decreased in areas with impaired auto‐regulation. The difference in the blood flow response between diseased and non‐diseased areas illustrates the need for regional measurements in studies of the pharmacology of the cerebral circulation.
Biotransformation of Methyl Mercuric Salts in the Rat with Chronic Administration of Methyl Mercuric Cysteine
Authors: Norseth Tor
Published: July 2010

Biotransformation of methyl mercuric cysteine after repeated injections for 30 days to rats, was followed by the specific determination of inorganic mercury. The rate of biotransformation was found to be dose dependent, low doses releasing relatively more inorganic mercury than high doses. The kidney content of mercury was dependent on the rate of biotransformation, but the brain content was not affected. The significance of biotransformation for the excretion of mercury at different rates dependent on dose, and for the hazards of brain and kidney damage is discussed.
The Herbicide 2, 4‐Dichlorophenoxyacetic Acid II: Triglyceride Accumulation in L Cells
Authors: Kolberg Jan , Helgeland Kristen , Jonsen Jon
Published: July 2010

Abstract: L 929 cells in monolayer cultures exposed to 500 μg/ml of 2,4‐dichlorophenoxyacetic acid have been found to accumulate triglycerides. Labelling experiments were performed with 3H‐palmitate and 14C‐acetate. The incorporation of 3H and 14C into total cell lipids of treated cells was about 3 times that in the control cells. The increase of 3H was mainly recovered in the triglyceride fractions both from whole cells and in isolated cytoplasmic particles. The specific activity of the triglycerides with regard to tritium remained similar, whereas the specific activity with regard to 14C was only one‐fourth in the treated cells as compared to the control cells. This suggested that the fatty acids of the accumulated triglycerides were largely derived from the growth medium.
Postnatal Development of the Effects of Alcohol and of the Induced Tolerance to Alcohol in Mice
Authors: Lagerspetz Kari Y. H.
Published: July 2010

Abstract: The effects of single and repeated intraperitoneally injected doses of ethyl alcohol on selected reflex responses and open field behaviour of mice aged from 2 to 46 days were studied. The effect of alcohol came on very rapidly in the youngest age groups, the maximum effect occurring already 3 minutes after the alcohol injection. The effect was smaller in 20 days old animals than in 8, 14, or 46 days old mice. Significant growth reductions were found in 14 days old mice which had received alcohol daily for 6 days, and in 46 days old mice which had received alcohol daily for 8 or 18 days. Increased tolerance to alcohol was found in 28 days old and in 46 days old animals after 8 daily injections, but not in 20 days old animals after 6 injections or in the younger age groups. The earliest age at which the induced tolerance to alcohol was found to develop corresponds to the age of maturation of the noradrenergic brain mechanisms, as reflected in the attainment of the adult noradrenaline level in the brain.
Effects of Long‐Term Administration of Bendroflumethiazide on Bone Metabolism in the Rat
Authors: Jørgensen F. Schønau , Nielsen S. Pors
Published: July 2010

Abstract: 45Ca was injected subcutaneously in 160 g rats kept in metabolic cages. After an adjustment period of 10 days, bendroflumethiazide was given orally for another 10 days. The concentration of 45Ca and the specific activity in the bones was significantly higher in the thiazide treated animals than in controls. The excretion of hydroxyproline decreased slowly during the thiazide administration period. The results suggest that the breakdown of both bone mineral and bone matrix was reduced during bendroflumethiazide administration. Bone matrix metabolism was not normalized until 7 days after cessation of thiazide administration as judged by the time required for reversion of the hydroxyproline excretion.
The Haemolytic Properties of the Oriental Hornet Venom
Authors: Joshua H. , Ishay J.
Published: July 2010

Abstract: Venom from Vespa orientalis haemolyses erythrocytes of man, guinea pig, rabbit, cat, mouse and rat, but not of sheep, ox, horse and camel. The haemolytic effect was enhanced by the addition of egg yolk phospholipids. Boiling destroyed the haemolytic factor(s), but the haemolytic activity which was demonstrable after addition of phospholipids resisted boiling at pH 3.5. The haemolytic factor(s) could be removed by heparin precipitation and Amberlite adsorption and could be neutralized by rabbit anti wasp venom serum. The haemolytic factors could not be removed by dialysis. Sublytic doses of whole venom caused potassium leakage from susceptible erythrocytes and increased their osmotic fragility. It is suggested that the indirect haemolytic activity of the Oriental hornet's venom is associated with phospholipase activity, while the direct lytic activity is due to basic protein.
Absence of Effects of Methysergide on Connective Tissue in Mice
Authors: Langgård Hans , Ulrich Jergen
Published: July 2010

Abstract: The effects of methysergide on the composition of skin, liver and retro‐peritoneal tissue have been examined in mice. After 14 days of treatment, no changes could be demonstrated in the contents of water, fat, fat‐free solids or hydroxyproline as compared with a control group, nor was the plasma‐hydroxy‐proline level altered.
Phenolic Metabolites in Urine and Faeces from Rats Given Radioactive 14C‐L‐DOPA
Authors: Borud O. , Midtvedt T. , Gjessing L. R.
Published: July 2010

Abstract: Urine and faeces of rats were investigated for phenolic compounds after oral administration of 14C‐L‐DOPA. Germ‐free and conventional rats were used. The urinary radioactive metabolites detected were: 3‐methoxy‐4‐hydroxyphenylethylamine, 3‐methoxy‐4‐hydroxyphenylacetic acid, m‐hydroxyphenylacetic acid, and m‐hydroxyphenylpropionic acid. Conventional rats excreted more radioactive meta‐compounds than the germ‐free rats. The faeces of germ‐free rats contained predominately radioactive 3‐methoxy‐4‐hydroxy‐phenylacetic acid, and faeces of the conventional rats contained predominately m‐ and p‐hydroxyphenylacetic acid.
Components of the Kallikrein‐Kinin System and the Spontaneous Cold Activation of Factor VII in Human Plasma
Authors: Laake Knut , Cjønnaess Halvard , Fagerhol Magne K.
Published: July 2010

Abstract: Samples of plasma with the property of spontaneous activation of factor VII on incubation overnight at 0° were studied with regard to the concentration of prekallikrein, kininogen fractions, and the activity and concentration of proteinase inhibitors. A significantly higher concentration of prekallikrein was observed in the cold activation positive plasmas from pregnant and control subjects. The concentration of kininogen substrate 2, which was increased during pregnancy and treatment with oestrogenic oral contraceptives, was not correlated with the spontaneous cold activation. The rate of inhibition of kinino‐genase activity in normal plasma was very low at 0° as compared with that at 25°, and it is concluded that this may explain the odd temperature dependence of the spontaneous activation of factor VII.
Determination of Furosemide in Blood Plasma and its Binding to Proteins in Normal Plasma and in Plasma from Patients with Acute Renal Failure
Authors: Andreasen Frederik , Jakobsen Preben
Published: July 2010

A modification of the Hajdu & Häussler method (1964) for the determination of furosemide is described. The sensitivity is 10±2 ng/ml. The binding of furosemide to plasma proteins is determined in vitro at room temperature by an ultrafiltration method. At concentrations between 10 and 400 μg/ml, 99‐95% was bound in normal plasma. In therapeutically dialysed plasma from surgical patients with acute renal failure the binding was reduced by 9‐14%. The number of μg of drug bound per mg albumin was also significantly reduced in the patient plasma. A “Kav1 value” for the range 10‐100 μg/ml was approximately 3 × 105 in donor plasma and 2 × 104 in patient plasma. A “kav2 value” (100‐400 μg/ml) was 3 × 104 in donors and 8 × 103 in patients. The kav1 and kav2 values were significantly lower in patient plasma than in donor plasma and also lower in patient plasma than in Ringer solutions to which albumin had been added.
The Effect of Lithium on Blood Pressure and on Plasma Renin Substrate and Renin in Rats
Authors: Kierkegaard‐Hansen Axel
Published: July 2010

For 2 months, two groups of rats were given food containing 0 and 40 mmol lithium/kg dry weight, respectively. Most of the lithium‐treated rats gained weight, although at a lower rate than the control rats. They showed no significant changes in intra‐arterial blood pressure (determined in sodium amytal anaesthesia), plasma renin substrate, or plasma renin. A few lithium‐treated rats lost weight and developed severe lithium intoxication. Their blood pressure was also unchanged, but they showed a fall to zero in plasma renin substrate concentration. In another experiment lasting 9‐18 days, two groups of rats were given food containing 0 and 70 mmol lithium/kg dry weight, respectively. The lithium‐treated rats developed severe lithium intoxication. Their intra‐arterial blood pressure was unchanged; plasma renin substrate showed a pronounced decrease and plasma renin a marked increase. The results do not support previous observations of a lithium‐induced blood pressure increase. They indicate that animals with severe lithium intoxication resemble adrenalectomized animals given an insufficient supply of sodium.
Combined Effects of Diazepam and Ethanol on Mental and Psychomotor Functions
Authors: Mørland J. , Setekleiv J. , Haffner J. F. W. , Strømsæther C. E. , Danielsen A. , Wethe G. Hoist
Published: July 2010

Abstract: The performances of eight healthy young males were tested 1–3 hrs after oral administration of placebo, 10 mg diazepam (mean serum levels 286–281 ng/ml respectively), ethanol (mean serum levels 0.080–0.043), or the same amount of ethanol (mean serum levels 0.081–0.045) combined with 10 mg diazepam (mean serum levels 289–339 ng/ml). Both ethanol and diazepam reduced concentration, efficiency, and attention (Osgood Test). Combined administration augmented this subjective impression, and also reduced motivation. Ethanol significantly (α = 0.05) reduced the score in the Minor Tracing Test, and diazepam significantly reduced the score in the Letter Cancellation, Flicker Fusion Frequency, and Mirror Tracing tests, and in the Clinical Examination. Combined administration of ethanol and diazepam increased the detrimental effects on the tests mentioned above, and also increased the effect on Time Evaluation Ability (not significant) and Complex Coordination (α = 0.04) and Sorting tests (α = 0.055). Generally diazepam slowed the subjects, ethanol speeded them up, but increased their errors, combined administration both slowed them up, and increased their errors.
A Radioimmunoassay for Digoxin in Serum, Urine and Myocardial Tissue
Authors: Brock Axel
Published: July 2010

Abstract: A modified radioimmunoassay for digoxin, suitable for serum, urine and homogenized myocardial tissue, is presented. It includes an initial extraction by dichlormethane after addition of protein (gelatine, 4 g/l). A constant fraction and more than 93 per cent of the digoxin is extracted in this way. The method is suitable for pharmacokinetic studies, since the basis for standardization is aqueous solutions of digoxin, and the interference of proteins in the samples are eliminated. By this means the interference of other digitalis glycosides is reduced, and quenching correction under the final determination of the 3H activity is unnecessary. The precision, including the initial extraction, is 5–7 per cent.
The Effect of Niceritrol (Pentaerythritoltetranicotinate) on Experimental Atherosclerosis in Cholesterol‐fed Rabbits at Different Levels of Plasma Cholesterol
Authors: Brattsand R.
Published: July 2010

The action of the hypolipaemic drug niceritrol (INN) on cholesterol accumulation in the aorta was studied in cholesterol‐fed rabbits at three levels of plasma cholesterol, approximately 100, 500–1000 and 2000 mg/100 ml. This was achieved by feeding diets with three different concentrations of cholesterol. The two higher but not the lowest concentration resulted in a large increase in plasma cholesterol as well as in a moderate lipid infiltration of the aorta. On addition of 0.5–1% niceritrol to the diet there was a significant reduction of plasma cholesterol in all three series. In the series with the lowest plasma cholesterol level the degree of atherosclerotic changes were so slight that the effect of niceritrol could not be evaluated. In the series with plasma cholesterol up to 1000 mg/100 ml niceritrol markedly inhibited the lipid infiltration of the aorta. In the series with the highest plasma cholesterol level niceritrol had no protective effect. The relationship between plasma cholesterol levels and extent of aortic lipid infiltration was studied in a pooled reference material of 154 cholesterol‐fed rabbits. The demonstrated type of relationship could largely explain the difference in the protective action of niceritrol in the three series.
Methyl Mercuric Compounds in Rat Bile
Authors: Refsvik Tor , Norseth Tor
Published: July 2010

Abstract: Methyl mercuric glutathione is the predominant methyl mercuric compound in rat bile following exposure to methyl mercuric chloride. Methyl mercuric chloride also forms methyl mercuric glutathione when added to rat bile in vitro. A small amount of methyl mercuric cysteine is always found in the bile of exposed animals. This amount increases on storage of the bile, and may include most of the metal present. Exchange of the methyl mercuric ion takes place between cysteine and glutathione. Methyl mercuric glutathione releases methyl mercuric cysteine on storage, probably by autolysis, but an action of enzymes cannot be ruled out. Final conclusions cannot be drawn as to which methyl mercuric compound is actually transported from the liver cell to the bile.
In Vitro Studies on the Cytotoxic Action of Different Varieties of Asbestos Dust on Macrophages
Authors: Kaw J. L. , Zaidi S. H.
Published: July 2010

Abstract: The cytotoxic action of a variety of asbestos dusts viz. chrysotile, amosite, anthophyllite, tremolite and actionlite was tested in vitro using alveolar and peritoneal macrophage cell cultures. The release of acid phosphatase and the uptake of the dye erythrosin B were taken as parameters of cytotoxicity. Among the several varieties of asbestos tested for this purpose, chysotile proved to be most cytotoxic for both the alveolar and peritoneal macrophages, although the former were more sensitive. Amosite was only slightly toxic for alveolar macrophages. Anthophyllite, tremolite and actinolite behaved as control inert dusts. Carboxymethylcellulose exhibited an anticytotoxic effect when chrysotile was pretreated with the polymer or when the dust cell interaction was allowed to take place in its presence.
Changes Produced in the Male Genital Organs of Rabbits and Dogs by 2,6‐cis‐Diphenylhexamethylcyclo‐tetrasiloxane (KABI 1774)
Authors: Nicander Lennart
Published: July 2010

Abstract: The drug. 2,6‐cis‐diphenylhexamethylcyclotetrasiloxane, was administered daily per os to rabbits (2 mg/kg body weight in soybean oil) for 2, 5, 10, 15, 20, 25, and 30 days, and to dogs (10 mg/kg and 250 mg/kg) for 40 days. Light and electron microscope studies were made on the testis, epididymis and accessory genital glands. In rabbits, cell death was seen in the epididymis, especially in the middle caput after 2, 5 and 10 days. Longer treatment also caused marked atrophy of the epididymal duct epithelium, and some atrophy of the accessory genital glands. After 15 days, spermatozoa no longer showed the morphological maturation changes that normally take place in the caput epididymidis, and the fine structure of the epididymal epithelium suggested a return to prepuberal conditions. After 20 days, spermatozoa in the the cauda epididymidis were dead. The seminiferous tubules showed arrested spermatogenesis followed by degeneration of all spermatids and many spermatocytes between 15 and 25 days. Some ultrastructural changes of the Leydig cell cytoplasm occurred after 10 days, before spermatogenesis was disturbed.

In dogs, the effect on the seminiferous epithelium varied from arrested spermatogenesis to complete degeneration of most germ cells. The interstitial cells showed atrophy, shrinkage of the nucleus, and marked loss of the specialized cytoplasmic ultrastructure. The epididymis showed some cell death and very marked epithelial atrophy. The prostate gland showed marked epithelial atrophy, with a few areas also displaying epithelial metaplasia.

These observations are compatible with the concept that the cyclotetrasiloxane compound has an antigonadotropic action, but an additional direct antiandrogenic effect on the epididymis may also be involved.
Combined pharmacokinetic and pharmacodynamic studies of metoprolol in the cat and the dog
Authors: Borg Karl Olof , Carlsson Enar , Ek Lars , Johansson Rustan
Published: July 2010

Abstract: The correlation between the plasma concentration of metoprolol and the reduction of the heart rate response to isoprenaline in anaesthetized cats and exercise tachycardia in conscious dogs was studied.

There was a linear relation between the logarithm of the plasma concentration and the pharmacological effect in both species. This relation was independent of the dose level and in the dog it was also found to be independent of the route of administration.

The half‐life of the elimination of metoprolol in plasma was 1.3 hours in the anaesthetized cat and about 1.7 hours in the dog. The ratio between equipotent oral and intravenous doses in the dog was about 3:1 which is in agreement with the bioavailability of metoprolol in this species.
Comparative hemodynamic studies in man of adrenergic β1‐receptor agents without (H 93/26 = metoprolol) or with (H 87/07) intrinsic sympathicomimetic activity
Authors: Stenberg Jesper , Wasir Harbans , Amery Antoony , Sannerstedt Rune , Werkö Lars
Published: July 2010

Abstract: The two new cardioselective β‐adrenergic blocking agents H 93/26 and H 87/07 without and with intrinsic sympathicomimetic activity, respectively, were given intravenously to two groups of young healthy men to study the acute influences on systemic hemodynamics at rest and during standardized physical exercise. The findings indicate that H 93/26 exerts marked negative chronotropic effects both at rest and during physical exercise with only moderate negative inotropic effects resulting in significant reductions in cardiac output with no or only minor changes in stroke volume. In the present doses, a negative chronotropic effect of H 87/07 was, on the contrary, discernible first under strenous physical exercise, the drug exerting no effect on the systemic hemodynamics at rest. It is concluded that the set‐up used for obtaining hemodynamic data at rest and during physical strain could be a suitable and sensitive instrument to differentiate between various types of β‐adrenergic blocking agents.
The Influence of Lithium on Carbohydrate and Lipid Metabolism in the Perfused Rat Liver
Authors: Vendsborg P. B. , Vilstrup H.
Published: July 2010

Abstract Isolated rat liver was perfused with a once‐through technique. Glycogen synthesis was not affected by the presence of lithium (1 or 5 mM) in the perfusion medium. The rate of glycogen breakdown both without and with glucagon stimulation was not affected by lithium (1 mM). The uptake of free fatty acids was stimulated by lithium (5 mM) in the perfusion medium and a trend towards an increase in deposition of triglyceride in the same order of magnitude was seen.
Persistent Organochlorinated Compounds in Human Organs Collected in Denmark 1972–73
Authors: Kraul Inge , Karlog Ole
Published: July 2010

Abstract During the years 1972–73 samples of human abdominal fat, as well as brain and liver tissue were obtained from 82 subjects, and analysed for persistent organochlorinated compounds. Compared with the figures from a similar 8 years old Danish study no downward trend in the content of DDT and its metabolites in the fat tissue was found, while the residue of dieldrin nearly halved during the period. Polychlorinated biphenyls (PCB) were found in a mean concentration of 3.8 mg/kg fat tissue.
Binding of Digitoxin and Digoxin to Normal Human β‐Lipoproteins
Authors: Brock Axel
Published: July 2010

Abstract The binding of digitoxin and digoxin to purified β‐lipoprotein, obtained from pooled normal human serum, was studied under equilibrium conditions. Even with as high concentrations of unbound digitoxin or digoxin as 4 μmol/1 the preparations of β‐lipoproteins, containing cholesterol 1.98–3.95 mmol/1, did not show any signs of saturation. The binding affinity of digitoxin was about ten times as high as that of digoxin. Gel filtration chromatography, performed on native serum after addition of 3H‐digitoxin or 3H‐digoxin, showed a minor fraction of the cardiac glycosides to be associated with the protein fraction of highest molecular weight. This phenomenon disappeared after precipitation of the β‐lipoproteins. In clinical relations the contribution of protein bound digitoxin caused by the lipoprotein interaction is immaterial, in relation to that caused by the albumin interaction.
Effects of a Single Administration of Clozapine on Mouse Brain Catecholamines
Authors: Hyttel John
Published: July 2010

Abstract The effects of clozapine on the accumulation and disappearance of 14C‐labelled catecholamines formed from 14C‐tyrosine, and on the endogenous levels of catecholamines have been studied in mouse brain. Rather low doses of clozapine increased noradrenaline accumulation and disappearance (from 2.5 and 0.16 mg/kg, respectively), whereas dopamine accumulation was only increased from 10 mg/kg and disappearance after 80 mg/kg. However, in the dosage interval of 1.25 to 5 mg/kg dopamine disappearance was decreased. Endogenous noradrenaline levels were decreased from 10 mg/kg in contrast to the dopamine levels which remained unchanged, except in the dosage interval 2.5 to 10 mg/kg, where they were elevated, at the same time at which dopamine disappearance was decreased. It is concluded that clozapine differs biochemically from the typical neuroleptics by changing the metabolism of noradrenaline in doses much lower than those influencing dopamine metabolism. It is suggested that this property together with the ability of clozapine to decrease dopamine disappearance in a certain dose range, could contribute to the unique psychopharmacological action of clozapine.
Oxidative and Conjugative Metabolism of p–Nitroanisole and p–Nitrophenol in Isolated Rat Liver Cells
Authors: Moldéus Peter , Vadi Helena , Berggren Margareta
Published: July 2010

Abstract Isolated rat liver cells were used in the study of p–nitroanisole and p–nitrophenol metabolism. p–Nitroanisole was o–dealkylated to form p–nitrophenol which was subsequently conjugated to form predominantly sulphate esters and β–glucuronides.

1. At low concentrations of p–nitrophenol, sulphate conjugation was predominant but with increasing substrate concentration the glucuronidation activity was increased. At 250 μM p–nitrophenol the major conjugate formed was glucuronide while sulphate conjugation was inhibited.

2. With p–nitroanisole in low concentration, resulting in low oxidation rate, all the p–nitrophenol formed was further conjugated to sulphate esters. With higher phenol production, glucuronide conjugates were also formed.

3. Phenobarbital treatment of the rats increased the rate of p–nitroanisole oxidation by more than four times but had very little effect on the conjugation reactions. In these cells the major conjugate formed was glucuronide.

4. The rate of glucuronidation in the isolated liver cells was higher than in microsomes and responded differently to various inhibitors. Alprenolol, a substrate of the hepatic mono–oxygenase system, had no inhibitory effect on glucuronidation in microsomes in the absence of NADPH. However, low concentrations of alprenolol showed similar inhibitory effects in microsomes in the presence of NADPH as in isolated liver cells.

5. Nitrophenol glucuronide was strongly inhibitory to the glucuronidation in microsomes while almost no inhibition was observed in the isolated liver cells, probably due to poor penetration of the glucuronide through the cell membrane.

6. Rotenone, menadione and ethanol had little effect in microsomes but were potent inhibitors of glucuronidation in the isolated liver cells, most probably by interfering with the synthesis of UDPGlcA.

The effect of ethanol was maximal at as low a concentration as 10 mM and was shown to be due to alcohol dehydrogenase–dependent ethanol oxidation. The inhibition was presumably caused by the the increased cytoplasmic NADH/NAD4 ratio resulting from the metabolism of ethanol.
Effects of Aminooxyacetic Acid and Baclofen on the Catalepsy and on the Increase of Mesolimbic and Striatal Dopamine Turnover Induced by Haloperidol in Rats
Authors: Kääriäinen Ilpo
Published: July 2010

Abstract Effects of aminooxyacetic acid (AOAA) and baclofen on the catalepsy and on the increase of mesolimbic and striatal dopamine turnover induced by haloperidol were studied in rats. AOAA (25 mg/kg intraperitoneally) which increases the cerebral concentration of δ–aminobutyric acid (GABA) and baclofen (10 mg/kg intraperitoneally), a structural analogue of GABA, did not induce catalepsy by themselves but potentiated the catalepsy caused by haloperidol (0.1 mg/kg subcutaneously). AOAA and baclofen did not alter the haloperidol–induced striatal homovanillic acid increase. AOAA and baclofen decelerated the dopamine disappearance caused by α–methyl–p–tyrosine (αMT) both in mesolimbic nuclei and striatum. Haloperidol accelerated the αMT–induced dopamine disappearance in these structures. AOAA and baclofen prevented this stimulatory effect of haloperidol on the dopamine turnover. These results support the earlier suggestions that GABAergic pathways have an inhibitory effect on the mesolimbic and striatal dopaminergic pathways.
Quantitative Gas‐Liquid Chromatographic Determination of Clonidine in Plasma
Authors: Edlund Per‐Olov , Paalzow Lennart K.
Published: July 2010

Abstract A highly sensitive gas‐liquid chromatographic method with electron capture detection of clonidine in plasma is described. The alkaline samples (100–200 μl) are extracted into cyclohexane‐butanol (9:1), re‐extracted into 0.1 N sulphuric acid, made alkaline and back‐extracted into cyclohexane‐butanol. The pentafluorobenzyl derivatives of clonidine and the internal standard 2,‐(2,4‐di‐chlorophenylamino)‐2‐imidazoline are then formed, and excess of reagent is removed by solvent extractions. The minimum detectable quantity (MDQ) of clonidine and the internal standard are 2.5 · 10‐16 mol/sec. (3.3 picogram) and 2.8 · 10‐16 mol/sec. (5.9 picogram), respectively. The smallest amount of clonidine which can be determined in plasma samples with a precision of less than 20 % S. D. is 200 picogram. The time course of clonidine in plasma after intravenous administration of 500 μg/kg to rats revealed that the data best fit a three‐compartment open model.
The Metabolism of Biphenyl. V. Phenolic Metabolites in Some Marine Organisms
Authors: Meyer Trygve , Bakke Torgeir
Published: July 2010

Abstract The phenolic metabolites of biphenyl in the crustacean Cirolana borealis LILJEBORG (ISOPODA), the gastropod Buccinum undatum L and the ophiuroid Ophiocomina nigra ABILDGAARD have been analysed qualitatively and semi‐quantitatively as trimethylsilyl (TMS) ethers by combined gas chromatography/mass spectrometry and gas chromatography, respectively. The findings demonstrate the in vivo metabolic capacity of these organisms to convert biphenyl into its hydroxylated derivatives. Thus, 2‐hydroxybiphenyl is the most prominent metabolite detected in all these experiments, which also showed that minor amounts of the 4‐hydroxy and 4,4′‐dihydroxy metabolites are formed. Metabolites of biphenyl origin are found both in the sea water from the aquaria and in the tissue of the respective marine organisms. The experiments, moreover, indicate a slow metabolism of biphenyl in C. borealis, B. undatum and O. nigra, between which no qualitative metabolic differences are found.
Prostaglandin/Kinin Activity Related to Changed Renal Compliance after Bumetanide in Dogs
Authors: Olsen Uffe Bang
Published: July 2010

Abstract Bumetanide (0.25 mg/kg intravenously) increases kidney volume by 20 % at maximal diuresis in anaesthetized dogs. The kidney expansion is initially accompanied by a 2‐4 fold increase in the subcapsular pressure, which is normalized at a time when kidney volume is still considerably increased. Renal blood flow and urinary kinin excretion are enhanced parallel to kidney volume. Renal prostaglandin E activity decreases. The increase in renal blood flow and urinary kinin excretion are inhibited by indomethacin pretrcatment. The results leads to the conclusion that the kinins mediate the vascular response of bumetanide. The results also suggest that the subcapsular/interstitial pressure might affect the prostaglandin level of activity after bumetanide while factors related to tubular volume activate the kallikrein‐kinin system.
Pharmacology of cis (Z) ‐ Clopenthixol Decanoate, a Depot Neuroleptic
Authors: Pedersen V. , Svendsen O. , Danneskiold‐Samsee P. , Boeck V. , Nielsen I. Mailer
Published: July 2010

Abstract The duration and intensity of the neuroleptic effect of cis(Z)‐clopen‐thixol decanoate in Viscoleo® have been compared with those of cis(Z)‐clopen‐thixol, 2 HCl in aqueous solution in a number of animal experimental models. Cis(Z)‐clopenthixol, 2 HCl had a strong, but short‐lasting neuroleptic effect (apomorphine antagonistic effect in dogs, inhibition of conditioned avoidance response in rats) which was accompanied by marked sedation. In contrast, cis(Z)‐clopenthixol decanoate in oil had an effect which was slower in onset, but of much longer duration and only the highest doses caused a slight sedation. In rats catalepsy could be induced in some animals by high doses of cis(Z)‐clopen‐thixol decanoate whereas cis(Z)‐clopenthixol, 2 HCl at all the doses tested caused catalepsy in all animals. In mice only high doses of cis(Z)‐clopenthixol decanoate in oil caused reduction of spontaneous motor activity and potentiation of barbiturate anaesthesia. The results are discussed with special reference to the clinical use of the depot preparation.
Selenium Content of Tissues in Finnish Infants and Adults with Various Diseases, and Studies on the Effects of Selenium Supplementation in Neuronal Ceroid Lipofuscinosis Patients
Authors: Westermarck Tuomas
Published: July 2010

Abstract A low blood selenium level has previously been observed in healthy inhabitants of Finland (Westermarck et al. 1977). In this study even lower blood selenium values were observed in patients with acrodermatitis entero‐pathica, dystrophia musculorum progressiva (Duchenne), infantile and juvenile type of neuronal ceroid lipofuscinosis (NCL), severe mental retardation caused by various factors, and myocardial infarction. The selenium content of the brain, heart, kidney and liver in patients of different ages was also determined. The highest selenium level was found in the kidney. The mean liver selenium concentrations in stillborn, premature and full‐term neonates were 1.11 ± 0.23 (8), 1.21 ± 0.17 (12) and 0.93 ± 0.16 γg/g dry weight (12) respectively (the number of subjects in parentheses). The selenium values are considerably higher than those in infants of from one to nine months of age and adults, whose liver selenium values were 0.58 ± 0.21 (8) and 0.67 ± 0.08 γg/g dry weight (8) respectively. The vitamin E levels of serum in patients with NCL, as well as in subjects with severe mental retardation (controls), were low compared with values in healthy normal subjects. Sodium selenite supplementation in patients with NCL produced at least a transitory improvement without causing any toxic effects during one year of administration.
Simultaneous Determination of Codeine and Morphine in Biological Samples by Gas Chromatography with Electron Capture Detection
Authors: Dahlström Bengt , Paalzow Lennart , Edlund Per Olov
Published: July 2010

Abstract A sensitive gas chromatographic method for the simultaneous determination of codeine and morphine in plasma and brain samples is described. The method involves solvent extraction of the compounds from plasma, derivatization with pentafluoropropionic anhydride and subsequent separation on a 3 % OV‐17 column. The quantification is performed with electron capture detection. The sensitivity of the method (0.75 ng of morphine and 7.5 ng of codeine in a sample) makes it especially useful for pharmacokinetic investigations. The method was successfully applied to determine the time course of codeine and its metabolite morphine after intravenous administration of codeine to the rat.
Effect of Substance P on Pulmonary Resistance and Dynamic Pulmonary Compliance in the Anaesthetized Cat and Guinea‐pig
Authors: Andersson P. , Persson H.
Published: July 2010

Abstract The effect of substance P, acetylcholine, and histamine on pulmonary resistance (RL) and on pulmonary dynamic compliance (CDYN) was studied in the anaesthetized cat and guinea‐pig. In the anaesthetized guinea‐pig, substance P (0.1‐1.0 üg/kg), acetylcholine (1.0‐10 μg/kg), and histamine (1.0‐10.0 μg/kg) produced a dose‐dependent increase in RL and decrease in CDYN. In the anaesthetized cat, the effect of substance P was weak on both RL and CDYN, whereas histamine (5‐50 μg/kg) produced a dose‐dependent increase in CDYN, but the effect on RL was weak. The effect of acetylcholine was qualitatively the same as in the anaesthetized guina‐pig but about 10 times less effective.
Interactions of Cadmium with Copper, Zinc and Iron in different Organs and Tissues of the Rat
Authors: Julshamn Kåre , Utne Finn , Braekkan Olaf R.
Published: July 2010

Abstract The effect of cadmium on tissue concentrations of iron, zinc and copper was studied in male rats. Two littermate groups were fed a stock diet with or without a supplement of 100 μg cadmium per g. Every three weeks ten animals from each group were sampled and the liver, kidneys, heart, lungs, spleen, testes, muscle, fur, faeces and urine were individually analyzed. Except for the fur, all the other organs showed highly significantly increased levels of cadmium when compared with the control group. The iron levels were significantly depressed in all organs. As the content in the faeces remained unchanged and the urinary excretion showed an increase, it could be concluded that the cadmium supplementation resulted in a depletion of the body stores of iron. The zinc levels showed a significant increase in the liver and testes and a correspondingly significant decrease in the spleen. The levels of copper generally showed no significant changes.
Actions of Fenfluramine on Glucose Uptake in Vitro and in Vivo
Authors: Jørgensen Karin Damm
Published: July 2010

Abstract: Fenfluramine stimulates the glucose uptake of the isolated hemidiaphragm from normal and streptozotocin diabetic rats in the presence of insulin. The drug does not cause an increased storage of glycogen. During hind leg perfusion of the dog fenfluramine stimulated peripheral glucose uptake. No increase in lactate or in free fatty acids release was observed during prolonged infusions of the drug. Fenfluramine caused an improvement of glucose tolerance in normal glucose‐primed rats. A single dose of fenfluramine significantly lowered the blood glucose levels in streptozotocin diabetic rats and in diabetic dogs treated with insulin. Prolonged treatment with fenfluramine of streptozotocin diabetic rats had no significant effect on blood glucose levels. Additional treatment for one week of insulin dependent diabetic dogs with small non‐anorexic doses of fenfluramine resulted in slightly decreased blood glucose levels. The dogs could not be maintained on fenfluramine alone (without insulin).
Selenium Content of Whole Blood and Serum in Adults and Children of Different Ages from Different Parts of Finland
Authors: Westermarck Tuomas , Raunu Paavo , Kirjarinta Mikko , Lappalainen Leo
Published: July 2010

Abstract: A low level of selenium (Se) in the blood and serum of Finns was demonstrated. Inhabitants in the central, eastern and southeastern districts of the country had particularly low levels selenium. However, the Se level of Lapps and the people of the Åland archipelago seemed to be significantly higher than the level of other Finns. In general, the Se levels in the serum were lower than the values for whole blood. Furthermore, the levels were lower in children than in adults. The significance of these findings in the pathogenesis of some human diseases is discussed.
Glucose and Cation Transport in Rat Jejunum, Ileum and Colonin Vivo: Control Experiments, and Effect of Cationic Surfactant
Authors: Sund Reidar Bredo
Published: July 2010

AbstractOsmotically balanced solutions of glucose (0.5–300 mM) and sodium chloride, containing cetrimonium bromide (cetrimide, 0.8–4.1 mM), were instilled into the jejunum, ileum and colon of anaesthetized rats. Net transport of glucose, sodium and potassium was studied by their disappearance from, or accumulation into the intestinal lumen during 15 min incubation. Cetrimide caused the following shifts in normal jejunal and ileal glucose absorption: Atlowluminal glucose levels, absorption was strongly depressed and may be converted to net secretion. Atintermediatelevels, inhibition was less pronounced, and athighluminal glucose levels absorption was enhanced. Similar changes were seen in the colon. Furthermore, cetrimide caused a threefold change in the regression lines relating net sodium fluxes to the initial sodium concentration: The lines became steeper, the correlation was improved and the sodium concentration value corresponding to zero net transport was elevated. Net potassium secretion was increased. — These changes are all consistent with the view that surfactants cause an increase in passive epithelial permeability. Quantitatively, the effect of cetrimide increased with localization in the order colon > ileum >jejunum. Benzalkonium chloride (0.5–1.7 mM) was tested in the ileum only, and caused quite similar effects.
Lithium Effect on Temperature Rhythm in Psychiatric Patients
Authors: Mellerup Erling T. , Widding Alice , Wildschiødtz Gordon , Rafaelsen Ole J.
Published: July 2010

Abstract The diurnal rhythm of oral temperature was studied in 55 lithium treated patients, 51 other psychiatric patients, and 58 healthy subjects. The lithium treated patients had a higher temperature than the normal controls during the 24‐hour period and their temperature maximum was shifted towards an earlier time. When the lithium intake was postponed for 12 hours, temperature temporarily decreased to control values, but returned to the higher level after the lithium dose. The temperature results are discussed in relation to lithium induced changes in electrolyte metabolism.
Excretion of Methyl Mercury in Rat Bile: The Effect of Diethylmaleate, Cyclohexene Oxide and Acrylamide
Authors: Refsvik Tor
Published: July 2010

Abstract Diethylmaleate, cyclohexene oxide and acrylamide administered intraperitoneally to rats, have been shown markedly to inhibit biliary excretion of methyl mercury. Simultaneously the sulphhydryl and sulphide content of the bile decreases. These results probably reflect the conjugation of acrylamide, diethylmaleate and cyclohexene oxide to glutathione in the liver, thereby blocking the biliary excretion of methyl mercury. A high concentration of liver glutathione seems to be a prerequisite for the normal translocation of methyl mercury from liver to bile. These results indicate that methyl mercury is transported from liver to bile as a glutathione complex.
Pharmacological Studies on the Molluscicidal Activity of Phorate on Pila globosa (Gastropoda)
Authors: Singh Onkar , Agarwal R. A.
Published: July 2010

Abstract Amongst heart, rectum and radula protractor muscles of Pila globosa, the heart showed a negative inotropic and negative chronotropic response while the rectum and radula protractor showed a positive tonotropic response to exogenously applied acetylcholine (ACh). The anti‐cholinesterase pesticide phorate substantially increased the response to ACh; at high doses it could also evoke cholinomimetic response from the heart. The anti‐cholinesterase property of phorate gradually increased with an increase in its contact period to the tissue. The extent of alteration in ACh response caused by prior treatment with low and high doses of phorate were very similar, indicating that the efficacy of phorate is by and large time‐dependent rather than dose‐dependent. The effect of phorate remained irreversible even after prolonged washing. The mode of action of phorate has been discussed in the light of the above findings.
Degree of Sedation Obtained with Various Doses of Diazepam and Nitrazepam
Authors: Grundström Ronny , Holmberg Gunnar , Hansen Tage
Published: July 2010

Abstract Using critical flicker fusion (CFF)determination and estimation of drowsiness in eight healthy volunteers the sedative‐hypnotic effects of diazepam and nitrazepam were studied. Three dose levels of each drug were used, so that dose‐effect curves could be produced. The most reliable results were obtained with the CFF method, and significant dose‐effect relations could be demonstrated. The CFF deviation after diazepam initially related well to the concentration in blood serum, but after 4–6 hours the CFF depression vanished rapidly, while the drug concentration remained high. After nitrazepam the signs of drowsiness occurred similarly, while the drug concentration in serum showed on an average a slower rise. The effects began to disappear before the nitrazepam concentration had reached a peak. A rapid tachyphylaxis at the receptor sites seems to be responsible for this incongruity. Nitrazepam exerted significantly stronger sedative effects than diazepam, particularly when the respective serum concentrations were taken into account. This confirms that nitrazepam should be a more efficient sleeping drug, although diazepam also has considerable sedative‐hypnotic action.
Intestinal Secretion of Sulphanilic Acid by the Isolated Mucosa of Guinea Pig Jejunum
Authors: Sund Reidar Bredo , Lauterbach Fritz
Published: July 2010

Abstract Tissue uptake and transepithelial permeation of 35S‐sulphanilic acid were studied in the isolated guinea pig jejunal mucosa. Methoxy‐3H‐inulin added simultaneously served as a marker for the extracellular space and permeability of paracellular shunt pathways in the preparation. The uptake of sulphanilic acid from the blood side exceeded that from the luminal side 4–7 fold. The permeation of the acid was strongly correlated to the permeation of inulin. At 5 μM and 2.5 mM sulphanilic acid under aerobic conditions, the regression lines for the permeation from lumen to blood pass almost through the origin, while the regression lines for the permeation from blood to lumen intersect the ordinate at a positive Y‐value. In anaerobiosis, at 25 mM sulphanilic acid, or with addition of p‐toluene sulphonic acid only one regression line is obtained for the permeation in both directions. It is concluded that besides a permeation of sulphanilic acid across inulin‐ permeable shunt pathways an active transport system exists, which transfers the acid from the blood to the luminal side. This system is saturable, depends on aerobic energy and exhibits mutual inhibition by a structurally related compound. The results are comparable to those previously obtained with cardiac glycosides and quaternary ammonium compounds, in the same preparation. Thus, the intestinal mucosa is able to secrete the same classes of compounds which are secreted by the liver and the kidney.
Effect of Ritodrine on the Bladder Capacity in Unanaesthetized Pigs
Authors: Larsen Jens‐Jørgen , Mortensen Svend
Published: July 2010

Abstract A cystometric investigation was carried out in unanaesthetized pigs. During intravenous infusion of ritodrine (10, 30 and 50 μg/kg/min.) a dose‐dependent and significant increase of the bladder capacity was obtained. A concomitant significant elevation of the heart rate followed the administration of the drug.
The Adrenergic Innervation of the Urinary Bladder in the Cat and Man in the Normal State and After Parasympathetic Denervation
Authors: Dahlström Annica
Published: July 2010

Abstract The adrenergic innervation of the feline and human urinary bladder was studied with the histochemical fluorescence method of Hillarp and Falck. In the normal bladder of both species the trigone area was densely innervated by thick and strongly green‐fluorescent adrenergic terminals while the detrusor muscle contained a sparse innervation of very thin and weakly fluorescent nerve terminals.

After parasympathetic denervation (lower motor neuron lesion in patients) the adrenergic innervation of the detrusor muscle was altered. In the cat, the first signs of altered adrenergic innervation were observed 6 weeks after parasympathetic denervation, when thick, strongly fluorescent adrenergic fibres appeared between and in the smooth muscle bundles. These fibres had the characteristics of growth cones and indicated an outgrowth of new adrenergic fibres into the detrusor muscle. Later on, the muscle bundles were densely innervated by thick and strongly fluorescent terminals, reminiscent of trigone terminals. In the patients with lower motor neuron lesions, thick, strongly fluorescent adrenergic terminals were seen in the detrusor. In both cat and man the appearance of this “new” type of adrenergic nerve terminal in the detrusor muscle coincided with the presence of α‐adrenoceptor function (rather than the normal β‐adrenoceptor activity of the feline and human detrusor).
Adrenergic Innervation and Adrenergic Mechanisms A study of the human urethra
Authors: Ek Anders
Published: July 2010

Abstract Adrenergic nerves studied by a histochemical method were uniformly distributed along the whole extent of the male and female urethra. Corresponding to the adrenergic innervation a preponderance of contraction‐mediating alpha‐adrenoceptors was found in vitro studying urethral strips and in vivo recording the urethral closure pressure profile (UCPP).

Norephedrine significantly reduced incontinence and increased UCPP in stress‐incontinent women.