bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Plasma Membrane Ca++‐Mg++Activated Adenosine Triphosphatase of Rat Mast Cells on Histamine Release
Authors: Chakravarty Nirmal
Published: July 2010

Abstract:The role of a Ca++‐Mg++activated ATPase, demonstrated on the outer surface of rat peritoneal mast cells, on histamine release induced by antigen (anaphylactic reaction), compound 48/80 and ionophore A23187 has been studied. A high level of the enzyme activity is retained at the optimal pH for histamine release induced by the three releasing agents. The effect of fourteen inhibitors of ATPase has been studied, viz. quinidine, fluoride, platinum salt, suramin, ethacrynic acid, ethyl alcohol, N‐ethylmaleimide, Mn++, Ni++, ADP, AMP and the flavones: kaempferol, quercetin, morin. All the inhibitors, which caused varying degrees of inhibition of ATPase, also inhibited histamine release. The inhibition of the enzyme was competitive with ADP, AMP, ethacrynic acid, suramin and morin and non‐competitive with the others. The degree of inhibition of ATPase and of histamine release tended to be similar with six inhibitors. With the others the extent of the inhibition of the release and of the enzyme varied. But a marked inhibition of the enzyme was always associated with a pronounced inhibition of histamine release. ATP in lower concentrations (10–20 μM) has been shown to potentiate histamine release induced by all the three releasers, possibly through its utilization by plasma membrane ATPase. The observations agree with the hypothesis that plasma membrane ATPase participates in the histamine release process.
Comparison of p‐ṕ‐DDE and o‐ṕ‐DDE on Eggshell Thickness and Ca Binding Activity of Shell Gland in Ducks
Authors: Lundholm C. E.
Published: July 2010

Abstract: One of the main ecotoxicological effects of DDT and its stable metabolite DDE is to reduce the reproductive success in several species of birds by decreasing the thickness of the eggshell. In two different strains of ducks (Anas platyrhynchos var.) addition of 40 mg/kg dry weight of p‐ṕ‐DDE to the diet for 45 days produced a significant and long‐lasting reduction of the shell thickness, measured as eggshell index. The reduction was more marked in Indian Runner Ducks (IRD; 30±3%) than in a SwedishXRouen breed (SR; 10±2%. The p‐ṕ‐DDE residues in the egg yolk + egg white were almost similar in the two strains; 38±2 and 51±6 p.p.m. (wet weight) respectively. In the IRD 40 mg/kg of o‐ṕ‐DDE in the diet for 45 days was much less potent in reducing the eggshell index (8 ±3%) than thep‐pisomer; the amount of residue of the o‐ṕ isomer in the eggs (2.2±0.1 p.p.m.) was also smaller. A homogenate of the shell gland from the SR breed accumulated 45Ca2+ in the presence of ATP. The accumulation was inhibited about 50% by 5 mM sodium azide and 100% by 3 mM mersalyl. p‐ṕ‐ and o‐ṕ‐DDE in the incubation medium both reduced the Ca2+ binding, in a similar and dose‐dependent manner. The threshold concentration was about 20 p.p.m.; 40 p.p.m. reduced the accumulation by about 40%. DDE may reduce eggshell thickness by inhibiting the Ca binding to the membranes of the cells of the eggshell gland.
Polyamine Metabolism in Mouse Kidney after Administration of Mercuric Chloride
Authors: Cameron Robert , Persson Lo , Rosengren Elsa
Published: July 2010

Abstract:Testosterone administration to gonadectomized male mice, besides giving rise to a distinct hypertrophy of the kidneys, results in a large increase in renal ornithine decarboxylase activity and accumulation of polyamines. Experiments were performed to examine the effects of localized renal injury caused by mercuric chloride administration on the polyamine metabolism in the testosterone stimulated mouse kidney. A single injection of mercuric chloride resulted in severe damage of tubular epithelium primarily in the proximal convolutions situated in the cortex and outer medullary stripe. Although the injection of mercuric chloride to testosterone treated mice decreased the stimulation of ornithine decarboxylase activity it did not prevent the increase in the concentration of putrescine. The levels of spermidine as well as of RN A were elevated. These results may indicate early reperative growth following mercuric chloride administration. The observations are discussed in relation to the effects of 1,3‐diaminopropane, another nephrotoxic agent on renal growth and polyamine metabolism.
Histamine H2 Receptor‐Mediated Cyclic AMP Formation in Human Platelets
Authors: Klysner R. , Geisler A. , Hansen K. W. , Skov P. Stahl , Norn S.
Published: July 2010

Abstract: The influence of histamine on the level of cyclic AMP was studied in human platelets. A dose‐related accumulation of cyclic AMP was obtained, culminating at about 10 μM of histamine. The response was blocked by the H2 antagonist cimetidine, but neither by H1 antagonists nor by α‐ or β‐adrenergic antagonists. The results suggest that histamine causes an accumulation of cyclic AMP in human platelets by stimulation of H2 receptors. Cyclic AMP accumulation is supposed to be associated with a depression of the platelet function, and a reduced platelet release reaction was actually demonstrated by our results.
Effects of β‐Adrenergic Agonists on Rat Uterine Motility and cAMP Levelin Vivo
Authors: Johansson Solveig R. M. , Andersson Rolf G. G.
Published: July 2010

Abstract:Intravenous injection of isoprenaline and salbutamol into rats caused an inhibition of the spontaneous contractions of uterus and increased the uterine cAMP level in a dose‐dependent manner. The effects of isoprenaline (0.036 nmol/kg) were diminished or completely prevented by propranolol (0.07–7 μmol/kg). Intravenous infusion of the β‐adrenergic agonists during one hour increased the uterine cAMP level. The highest level of cAMP measured was at 3 min. after start of infusion, thereafter it declined first rather fast but later more slowly. This time pattern of cAMP was very similar to what was seen during incubation of uterine tissue with isoprenalinein vitro. Pretreatment with isoprenaline three times daily 4–7 days before the experiments, decreased both the degree of inhibition and the increase of cAMP in uterus caused by an intravenous injection of isoprenaline. A slight effect on the cAMP rise was detectable after one day of pretreatment, and it seemed to have reached its maximal effect after 4 days, since no further decline in the cAMP response was seen when the pretreatment was prolonged. A desensibilization to P‐adrenergic agonists was thus seen in uterus after excessive stimulation of isoprenalinein vivo.
Renal Prostaglandins and Sodium Balance in the Rabbit: Lack of Effect of Aspirin‐like Drugs
Authors: Davila Tatjana , Davila Dusan , Oliw Ernst , Änggård Erik
Published: July 2010

AbstractUrinary prostaglandin E2(PGE2) and PGF2excretion was previously found to be inversely related to sodium intake in the rabbit. Renal prostaglandin (PG) synthesis might therefore be involved in the renal handling of sodium. This possibility was tested by studying sodium excretion during inhibition of renal PG synthesis with four different nonsteroidal anti‐inflammatory drugs in unanaesthetized, female rabbits. The rabbits n = 5–6) were kept in metabolic cages and chronically maintained on different sodium containing diets. On a medium salt diet (0.4% NaCl), neither treatment with indomethacin (1.5 mg/kg×2 or 3 mg/kg×2) nor diclofenac (1.5 mg/kg × 2) for three days changed the urinary excretion of sodium and water although the mean excretion of immunoreactive PGE2(iPGE2) and iPGF2were reduced by between 43–78%. On a very low salt diet (0.05% NaCl), two days treatment with aspirin (30 mg/kg ×2), diclofenac (3 mg/kg× 2), indomethacin (3.5 mg/kg×2) or naproxen (10 mg/kg×2) did not alter sodium excretion in any significant direction. The mean urinary PGE2and PGF2excretion was reduced by 35–63% and 63–85%, respectively. These results do not support a major role of PGs in the chronic regulation of sodium balance in the rabbit. The possible influence of mineralocorticoids on renal PG synthesis was studied by administration of aldosterone (100 μg/kg×2) fortwo days to rabbits on a high salt diet (2% NaCl) and cancrenoate (10 mg/kg×2), an aldosterone antagonist, to rabbits on the very low salt diet. However, neither drug significantly changed the urinary excretion of PGF2α, indicating that renal PG synthesis is not influenced by mineralocorticoids in the rabbit
The Binding of Aprindine to Serum Proteins with Statistical Considerations Concerning the Analysis of Binding Data
Authors: Andreasen F. , Husted S. , Jakobsen P. , Jensen E. B.
Published: July 2010

Abstract The binding of the potent, basic antiarrhythmic agent aprindine to serum proteins was studied in solutions of human serum albumin (HSA, lyophilized, 98% pure, KABI) and in human sera. The percentual binding in serum (90.9–96.7%) was considerably higher than in HSA solutions. The binding in serum decreased from 95–97% to 91–93% as the aprindine concentration was raised from 4 to 15 μg/ml. The serum binding differed significantly in sera from three normal individuals. By plotting as a function of bound drug and performing statistical analysis of the curves a striking difference between the number of primary binding sites in serum and in HSA solution was found (N1 for the HSA solution was 0.0016 and for one serum it was 0.020 “per albumin molecule”.) The association constants for the primary binding sites (K1) were 4.3×106M‐1 for serum and 2.1×106M‐1 for the HSA solution. Furthermore, the analysis indicated that considerably less than one secondary binding site was present for each albumin molecule in the HSA solution. Therefore, no binding of aprindine to albumin molecules has been demonstrated and it is concluded that the entire binding of aprindine in serum as well as in 98% HSA solutions may be due to the presence of acid protein molecules. In particular, low percentual binding in HSA solutions in spite of the high association constant can be explained by a very low concentration of the binding proteins. The addition of propranolol or phenprocoumon did not cause any displacement of aprindine. In the appendix statistical problems in the analysis of the binding curves are elucidated. The experimental variance and the statistical acceptability of the binding model are discussed.
The Effect of Lithium on the Incorporation of32P‐Orthophosphate into Synaptosomal Phospholipids from Rat Brain
Authors: Edelfors Sven
Published: July 2010

AbstractRats were treated with lithium added to the diet for five weeks (40 mmol LiCl/kg diet). The mean plasma lithium concentration was 0.48 mmol/l plasma, and the blood was drawn at 8 a.m. The brains were removed and synaptosomes were prepared according to the method of Gray & Whittaker (1962) and Bradford (1972). The synaptosomes were incubated for 120 min. with32P‐orthophosphate, either in a lithium‐containing medium or in a lithium‐free medium. The32P‐incorporation was lower in the synaptosomes from lithium‐treated rats than the32P‐incorporation in synaptosomes from control rats regardless of the medium chosen. The results indicate that lithium treatmentin vivodecreases the32P‐incorporation into synaptosomal phospholipids and that the effect remains after the removal of the lithium ion.
Effects of Low Protein Consumption on the Renal Clearance of 2,4‐Dichlorophenoxyacetic Acid (2,4‐D) in Goats
Authors: Örberg Jan
Published: July 2010

Effects of low protein consumption on the renal excretion of 2,4‐dichlorophenoxyacetic acid (2,4‐D) in four female goats were studied by means of clearance methods. During periods of low protein consumption the 2,4‐D clearance values are lower than during periods of normal protein consumption. The average reduction of 2.4‐D clearance varies between 20 and 50 per cent.
Potassium‐Induced Renal Loss of Sodium in Lithium‐Treated Rats
Authors: Olesen Ole Vendelin , Thomsen Klaus
Published: July 2010

AbstractA high intake of potassium prevents lithuim‐induced renal water and sodium losing conditions. In order to investigate a probable curative effect of potassium against these conditions Wistar rats were given lithium by the food (80 mmol/kg). The animals had access to water and a 0.46 M NaCl solution. The potassium content of the food was 100 mmol/kg during the pretreatment period of about 4 weeks, then 500 mmol of KCl per kg food was added. Potassium administration did not significantly influence the intake of water but led to a temporary rise of the intake of 0.46 M NaCl. The intake rose from 100 μmol to 500 μmol/hr/100g body weight in the course of 2–3 days and then gradually declined during three weeks. The increase of the sodium intake was not superfluous but due to a renal loss of sodium. If the animals were not allowed to replace the lost sodium by drinking more NaCl solution, plasma renin rose, body weight, lithium clearance, and water intake fell. It is concluded that a high potassium intake was unable to cure lithium‐induced water and sodium losing conditions in rats. Prolonged lithium administration interferes with the mechanism for selective renal excretion of potassium. A high potassium intake resulted in a temporary renal loss of sodium.
Imipramine Cardiotoxicity: An Electrocardiographic and Haemodynamic Study in Rabbits
Authors: Müller Jørn , Schulze Svend
Published: July 2010

AbstractThe purpose of the present study was to investigate the cardiotoxicity of the tricyclic antidepressant imipramine. The experiments were carried out in rabbits during continous intravenous infusion of imipramine, and electrocardiographic and haemodynamic changes were observed. The blood flows were measured using the radioactive microsphere method based upon the principles of Fick and Stewart Hamilton. It was found that the decrease in heart rate and the changes in heart rhythm were always preceded by a fall in arterial blood pressure and cardiac contractility, expressed by a fall in dp/dtmax. On the basis of the results it is concluded that a direct depressing action on the myocardium is of importance in the development of cardiac complications, although both a depressing influence on cardiac conduction, an anticholinergic effect, and an influence on adrenergic factors may also contribute. The possibility of positive correlations between the changes in plasma‐ imipramine concentration and the changes in the dp/dtmaxand the QRS complex cannot be excluded.
A Radioimmunoassay for cyclic AMP (cAMP) Obtained by Acetylation of Both Unlabeled and Labeled (3H‐cAMP) Ligand, or of Unlabeled Ligand only
Authors: Skomedal T. , Grynne B. , Osnes J. B. , Sjetnan A. E. , Øye I.
Published: July 2010

Abstract A sensitive radioimmunoassay (limit of detection 7± 1 fmol per tube) for cyclic AMP (cAMP) based on acetylation of both 3H‐cAMP and unlabeled ligand was developed. Rabbit anti‐cAMP antibodies had an apparent Ka for the acetylated ligand of 2× 1010 l/mol. When the unlabeled ligand only was acetylated an increased sensitivity was obtained without loss of specificity.
The Pharmacokinetics of Dihydroergotamine in the Beagle Dog after a Single Intravenous Injection and after a Continuous Intravenous Infusion
Authors: Kanto J. , Allonen H. , Kleimola T. , Mäntylä R.
Published: July 2010

Abstract The pharmacokinetics of dihydroergotamine (DHE) was studied in 6 beagles after a single 2.0 mg intravenous dose and after a continuous intravenous infusion (dose 2.0 mg, infusion time 51 min. = 2.8–3.5 μg/min./kg). The concentrations of DHE in the plasma during 6 hours were determined by a radioimmunoassay. The mean α‐phase T1/2 was 0.92 min. and 5.93 min., the mean β‐phase T1/2 was 104.42 min. and 115.79 min., and the mean plasma clearance value 202.88 ml/min. and 234.79 ml/min. after a single intravenous injection and a continuous infusion administration, respectively. Similarly, the Vdc — values were 0.12 l/kg and 0.38 l/kg and the Vdβ — values 3.41 l/kg and 4.31 l/kg. Only the α‐phase T1/2 and the Vdc‐values differed significantly from each other. The simulated concentrations of DHE in the peripheral compartment increased rapidly explaining its fast effect on the vasculature in clinical use.
Placental Transmission and Foetal Distribution of H‐Ouabain
Authors: Saarikoski Seppo
Published: July 2010

AbstractPlacental transfer and foetal distribution of3H‐ouabain were studied in eight pregnant women undergoing legal termination of pregnancy during the first half of gestation. The3H activity in maternal and foetal plasma, in foetal tissues and amniotic fluid was estimated using the oxidation method. The intactness of the labelled drug was determined by thin‐layer chromatography.3H‐ouabain rapidly disappeared from the maternal blood‐stream, and a measurable amount of3H activity was already present in the umbilical blood of the foetus two min. after the administration of the drug into the maternal blood. The foetal plasma3H values were lower than the maternal values during the time interval 2 to 120 min. after injection, and the foetal3H plasma concentrations approximated the maternal values five hours after drug administration. The3H concentrations found in the amniotic fluid were lower than those in the corresponding maternal or foetal plasma samples. The distribution of ouabain in the foetal tissues was relatively uniform, with the highest3H concentrations foundin the heart and placenta, the lowest in the brain. The results suggest that the human foetal heart has some capacity to bind ouabain even during the first half of gestation.
Comparative Ototoxic Effects of RU 25434, Amikacin and Neomycin in Guinea‐pigs
Authors: N'guyen P. , Dumont C. , Boissier J. R.
Published: July 2010

Abstract The ototoxic effects of RU 25434, a new semi‐synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new‐born guinea‐pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new‐born guinea‐pigs seems to be particularly suitable for this type of study because of their apparent sensitivity to ototoxicity.
Contralateral Circling Behaviour Induced by Intranigral Injection of Taurine in Rats
Authors: Kaakkola Seppo , Kääriäinen Ilpo
Published: July 2010

Abstract A study was made of the effect of unilateral injection of taurine into the substantia nigra on the behaviour of rats. Taurine (10–200 μg) induced a dose‐dependent contralateral circling behaviour. The maximum intensity of circling after doses of 100–200 μg of taurine was reached within 10 min. and the circling lasted for about 4–5 hrs. There was neither ipsilateral circling nor stereotyped behaviour. Intranigral injection of isethionic acid, a metabolite of taurine, induced weak ipsilateral circling of short duration. Pretreatment with bicuculline (3 mg/kg intraperitoneally) or strychnine (0.25 mg/kg intraperitoneally) significantly inhibited the taurine‐induced circling. A dose of 1 mg/kg but not of 0.5 mg/kg of haloperidol (subcutaneously) significantly decreased the intensity of the taurine‐induced circling. Pretreatment with atropine (10 mg/kg intraperitoneally) had no significant effect on the circling behaviour. Besides the dopaminergic nigrostriatal pathway, the non‐dopaminergic nigral output pathways also seem to be involved in the taurine‐induced circling behaviour. The results show that taurine may play some role in the function of the substantia nigra.
Elimination Pattern and Tissue Distribution of Intravenous Iron‐poly (sorbitol‐gluconic acid) Complex in the Rat
Authors: Lake‐Bakaar Desmond M.
Published: July 2010

AbstractThe elimination pattern and tissue distribution in rats of intravenous [14C‐gluconic acid]‐poly(sorbitol‐gluconic acid) and59Fe‐iron‐poly(sorbitol‐gIuconic acid) complex, glusoferron (Ferastral®) have been examined. Twenty‐four hours after injection of 20 or 200 mg/kg of [14C‐gluconic acid]‐poly(sorbitol‐gluconic acid), 5%‐6% of the injected dose of radiolabel was eliminated as14CO2and about 85% in the urine and faeces. Administration of59Fe‐iron‐poly(sorbitol‐gluconic acid) complex (10 and 100 mg of iron/kg) resulted in a urinary and faecal excretion of about 18 % and 40% of the given dose, respectively, during the first 4 days. Biliary excretion was low. The mean molecular weight of the biliary product after the iron complex was lower than that of the parent compound. Radiocarbon in tissues after 24 hours was negligible. Liver and bones accounted for most of the retained radioiron following 100 mg of iron/kg body weight of the59Fe‐iron complex with maximum levels of 27% and 12% of the injected dose, respectively, 4 days after dosing. Red cell incorporation of59Fe attained a level of 16% at the end of 28 days.
The Distribution of Chlorpromazine between Plasma and Erythrocytes
Authors: Lund Alf
Published: July 2010

Abstract: Chlorpromazine is found to be taken up by the erythrocytes in a dissociable binding similar to that of the plasma protein binding so that an equilibrium is attained between these binding sites. The plasma/cell ratio is on an average 2 but is subject to large interindividual variations. This ratio is only moderately influenced by the presence of other drugs and anticoagulants in the blood. The consequences of the cell binding of drugs for the analytical result when using plasma or whole blood and the evaluation of blood concentrations of their relation to the therapeutic effect are discussed.
Dialysability of Benzodiazepines by Haemodialysis and Controlled Sequential Ultrafiltration (CSU) in Vitro
Authors: Balogh A. , Fünfstück R. , Demme U. , Kangas L. , Sperschneider H. , Traeger A. , Stein G. , Pekkarinen A.
Published: July 2010

Abstract: The efficacy of haemodialysis and controlled sequential ultrafiltration (CSU) for the elimination of three hypnotic and 6 benzodiazepine drugs was compared in vitro. In comparison to haemodialysis the efficacy of ultrafiltration by CSU was poor, as the mean per cent of CSU/haemodialysis (mg/hr) for 5 benzodiazepines was only 0.6–4.0% and for three hypnotics, phenobarbital 3.4%, pyrithyldione 8.2% and glutethimide 2.5% of the haemodialysis values. In haemodialysis in vitro phenobarbital, pyrithyldione, glutethimide and chlordiazepoxide were significantly and markedly more dialysable than 5 other benzodiazepines. The mean clearance of six benzodiazepine derivatives was about 2 to 3 times higher at blood flow rates of 200 ml/min. than 100 ml/min. In CSU experiments in vitro it was possible to remove approximately (as the mean percent of the initial dose) only the amount of five benzodiazepines corresponding to the per cent of the protein unbound fraction in the plasma (correlation r=0.975, P<0.01). Only low amounts of three hypnotics, especially glutethimide, were removed by CSU in vitro.
Antacids and Sotalol Absorption
Authors: Kahela P. , Anttila M. , Sundqvist H.
Published: July 2010

Abstract: The effect of concurrent administration of antacids on the relative bioavailability of sotalol has been examined in five healthy volunteers. Each subject received an oral 160 mg dose after an overnight fast in four different experimental schedules. Venous blood samples were drawn 1,2,3,4,5,6,7,8,12,24, and 32 hrs after the drug administration, and sotalol concentrations were determined fluorometrically. The results show that concurrent administration of calcium carbonate or aluminium hydroxide with sotalol has negligible pharmacokinetic consequences. The adsorption of sotalol onto magnesium hydroxide leads to somewhat decreased biovailability but in long term use the phenomenon is not likely to be of clinical importance.
Effect of Prenalterol, a β‐1‐Adrenoceptor Agonist, on Renin Secretion Rate in the Anaesthetized Dog
Authors: Kopp Ulla , Aurell Mattias , Svensson Lennart , Åblad Bengt
Published: July 2010

Abstract:The effects of the β‐1‐adrenoceptor agonist, prenalterol, 20 μg/kg intravenously on renin secretion rate (RSR), renal haemodynamics and sodium excretion were examined in anaesthetized dogs with innervated or denervated kidneys. In dogs with innervated kidneys, prenalterol increased RSR from 1.1±0.2 to 7.9±0.1 unitsXmin.−1Xg−1(P<0.01). Prenalterol did not affect mean arterial pressure, renal blood blow, glomerular filtration rate or sodium excretion. Heart rate was increased by 53±17 beats/min. (P<0.01). The increase in RSR produced by prenalterol was independent of intact renal innervation as RSR increased to the same extent in dogs with denervated kidneys. Pretreatment with the β‐1‐adrenoceptor antagonist, metoprolol 0.5 mg/kg intravenously, abolished the increase in RSR produced by prenalterol. These findings suggest that prenalterol directly activates renal β‐1‐adrenoceptors to increase RSR.
Methyl Mercury Decomposition in Mice Treated with Antibiotics
Authors: Seko Yoshiyuki , Miura Teiji , Takahashi Masako , Koyama Tohru
Published: July 2010

Abstract: The role of intestinal flora in the decomposition and faecal excretion of methyl mercury was studied in mice treated with antibiotics. The antibiotics, neomycin sulfate and chloramphenicol, were given to mice in drinking water for six days before intraperitoneal administration of methyl mercuric chloride (MMC), and intestinal microorganisms were thereby reduced. Inorganic and organic mercury were determined separately for faeces, intestinal contents and organs. On the fourth day after the mercury administration, the percentage ratios of inorganic mercury to total mercury in the contents of the caecum and large intestine were less in the mice treated with antibiotics, at 37% and 39%, respectively, than in the control mice (66% and 65%, respectively). Administration of the antibiotics reduced the excretion of inorganic mercury in the faeces to 26% of that of control mice and also reduced the excretion of total mercury to 60%. Reduction of intestinal microorganisms by the antibiotics was assumed to have caused the reduced decomposition of methyl mercury in the caecal contents and the reduced excretion of total mercury in the faeces.
Effect of Furosemide on Parathyroid Hormone Stimulated Guinea Pig Renal Adenylate Cyclase and Thyrotrophin and Fluoride Stimulated Human Thyroid Adenylate Cyclase
Authors: Thode J. , Børresen T. , Beck K. , Madsen S. Nistrup
Published: July 2010

Abstract: The effect of furosemide 8×10−4 mol/l and 8×10−5 mol/l on parathyroid hormone stimulated adenylate cyclase was studied in renal tissue slices from guinea pigs. Furosemide caused a dose‐dependent inhibition of the effect of parathyroid hormone on production of cyclic AMP, without having any significant effect on the basal cyclic AMP production. Furosemide in similar concentrations did not inhibit the stimulatory effect of thyrotrophin and fluoride in human thyroid homogenates suggesting that furosemide is not an universal inhibitor of adenylate cyclase and that the inhibition is not caused by a direct action of furosemide on the adenylate cyclase enzyme. Furosemide did not interfere with binding of cyclic AMP to cyclic AMP binding protein kinase from rabbit muscle. The results indicate that furosemide exerts an inhibitory influence either upon binding of parathyroid hormone to renal receptors or upon transmission of impulse from receptor to adenylate cyclase. The inhibitory influence of furosemide on parathyroid hormone action in kidney could explain the value of furosemide in the acute treatment of hypercalcaemia, but also suggest that chronic treatment with furosemide might interfere with normal calcium metabolism.
Zinc Concentrations in Human Plasma and in Rat Plasma and Tissues during Lithium Administration
Authors: Schou Mogens , Holt Elisabeth
Published: July 2010

Abstract: Zinc concentrations, determined with atomic absorption spectrophotometry, did not differ significantly in plasma from manic‐depressive patients about to start lithium treatment and in patients having been in lithium treatment for six months or 1‐2 years. Plasma zinc concentrations and zinc concentrations in liver, muscle, kidney, bone, and skin did not differ in control rats and rats given lithium with the food for four weeks.
Xylene and Alcohol Involvement of the Human Equilibrium System
Authors: Savolainen Kai , Riihimäki Vesa
Published: July 2010

Abstract: Ten healthy male subjects were exposed at weekly intervals to m‐xylene concentrations of 6 μmol/1 (145 p.p.m.) and 11.5 μmol/1 (290 p.p.m.) for 4 hrs alone and in combination with the prior ingestion of single doses of alcohol (0.8 g/kg). Alcohol alone was ingested at two dose levels, 0.4 and 0.8 g/kg. Body sway was recorded with a strain gauge transducer platform with the subjects' eyes closed and open, and the eyes closed/open ratio, indicating the grade of visual compensation for body balance, was calculated. The variation observed in the eyes closed/open ratio in different experimental situations was due to changes with the eyes closed rather than to differences with the eyes open. Alcohol or a xylene concentration of 6 μmol/1, as well as their combination, had little if any effect on this ratio. Exposure to a xylene concentration of 11.5 μmol/1 tended to decrease the eyes closed/open ratio, possibly due to functional tolerance or adaptation. Interestingly, alcohol with a xylene concentration of 11.5 μmol/1 significantly increased the ratio, a finding suggesting an unexpected combined effect of xylene and alcohol, possibly of metabolic origin, on the human equilibrium system. The possible mechanism of this action remains to be elucidated.
Enterohepatic Circulation, Urinary Excretion and Laxative Action of Some Bisacodyl Derivatives after Intragastric Administration in the Rat
Authors: Sund Reidar Bredo , Songedal Karl , Harestad Toril , Salvesen Bjarne , Kristiansen Sidsel
Published: July 2010

Abstract: Bisacodyl (BIS), the parent diphenol (DES) and its sulphuric acid di‐ester (picosulphate = PICO) were given by stomach tube to fasted rats at a dose of 3.1 μmol/100 g rat. Bile was sampled in the periods 0–6, 6–12 and 12–18 hrs after drug administration, and assayed for total diphenol (= free + conjugated) by HPLC. Mean fractions (% of dose±S.E.M.) excreted in 5 rats per compound and period were: BIS 74.0±4.7, 51.9±7.9 and 30.8±2.5; DES 41.2±4.3, 46.8±4.7 and 25.1±2.5; PICO 9.0±0.9, 26.0±5.4 and 19.6±3.1. Only minor amounts were excreted as free diphenol. Urine samples taken by bladder puncture and assayed as above furthermore showed that the renal excretion of total diphenol was insignificant compared to the amounts excreted in bile. Practically no diphenol was present in urine 0–6 hrs after the administration of PICO. In experiments with BIS and DES at 0.85 μmol/100 g, total diphenol excreted in bile during 0–6 hrs was: BIS 67.1±2.6 (n = 5); DES: 55.4±3.0 (5). ‐ The latency time for laxative effect was studied in groups of 10 unfasted rats per compound. Cumulative time response curves showed that PICO caused diarrhoea more promptly at 0.85 μmol/100 g than either BIS or DES. In most rats, this delayed action of BIS and DES persisted also at 1.7 μmol/100 g. At 3.1 μmol/100 g, however, the majority of the rats reacted as promptly to these two compounds as to PICO. These results are discussed in relation to the biliary excretion experiments, and interpreted in terms of the relative importance at the different dose levels of: 1. The enterohepatic recirculated fraction, and 2. The non‐absorbed fraction, which passes directly to the large intestine. For PICO, the latter fraction is the single determinant of the effect, which is triggered when the di‐ester is being hydrolyzed to active diphenol in this part of the GI‐tract.
Uptake and Egress of Cadmium in Cultures of Cadmium‐resistant and the Corresponding “Wild‐Type” Cells
Authors: Bakka Arne , Rugstad Hans Erik
Published: July 2010

Abstract: Development of resistance against the highly toxic Cd++ ion has been described earlier both in animals, cell cultures and in bacteria. In this paper we have tested if decreased intracellular concentration of Cd plays a role in resistance to Cd in three mammalian cell cultures. The cells originated from different tissue and from two different species. Cd‐resistant and corresponding “wild‐type” strains were used. The results from all three lines show essentially the same, namely that there is no significant difference in Cd content between the Cd‐resistant and the non‐resistant cells. The resistant cells from all three lines grow continuously with a cellular Cd‐content which is several times higher than that killing all cells of the non‐resistant “wild‐type”.
Influence of Chelating Agents on Toxicity and Distribution of Cadmium among Proteins of Mouse Liver and Kidney Following Oral or Subcutaneous Exposure
Authors: Engström Birgitta
Published: July 2010

Abstract: Acute toxicity and organ distribution of cadmium was investigated in mice exposed to 1) single subcutaneous doses of 109Cd‐labelled cadmium (3.2 mg (0.028 mmol)/kg b.wt.) alone or in combination with nitrilotriacetic acid, NTA (32 mg (0.167 mmol)/kg b.wt.) or sodium tripolyphosphate, STPP (32 mg (0.087 mmol)/kg b.wt.) and 2) single oral doses of cadmium (60 mg (0.53 mmol)/kg b.wt.) alone or together with NTA (600 mg (3.14 mmol)/kg b.wt.) or STPP (600 mg (1.63 mmol)/kg b.wt.) Whole‐body retention of radiolabelled cadmium as well as mortality was registered in all groups during 20–21 days. Five hours after exposure, 3–4 mice in each group were killed and cadmium distribution among proteins in liver and kidney studied by gel chromatography on a G‐75 Sephadex column. Organ concentration of cadmium was also determined at sacrifice of all other mice after an observation time of 20–21 days. A markedly increased mortality was observed during the first 24 hours after subcutaneous exposure to Cd+NTA (70%) or Cd + STPP (40%) compared to Cd alone (0%). On the contrary, no mortality was seen after oral exposure to Cd + STPP while oral exposure to Cd alone or with NTA resulted in a mortality of about 45% during the same observation time. Five hours after subcutaneous exposure, liver cadmium concentrations were equal in all mice and bound mainly to a low molecular weight protein (probably metallothionein). In kidney, concentrations were about twice as high in mice given Cd + NTA or Cd + STPP compared to mice given Cd alone. More cadmium was transferred to the kidneys in the presence of chelating agents. This was further supported by the decreased liver/kidney cadmium concentration ratio between 5 hours and 21 days. The increased mortality in mice given Cd + NTA or Cd + STPP may be due to an initially high accumulation of cadmium in liver, which may exceed the upper limit for metallothionein synthesis, whereby toxic damage of the hepatic cells and leakage of cadmium from the liver would occur. Five hours after oral exposure, cadmium retention in organs of mice given Cd+STPP was 4–6 times lower than in mice given Cd alone, while mice given Cd+NTA had slightly higher organ concentrations. The binding of more cadmium to metallothionein in liver of Cd + STPP‐exposed mice 5 hours after exposure, may be due to the lower accumulation of cadmium in these mice compared to those given Cd alone or Cd+NTA, where cadmium was bound mainly to high molecular proteins in the liver. After 20 days, mice given Cd+STPP has slightly higher body and organ retention of cadmium compared to mice given Cd alone. This may be due to a binding of cadmium to metallothione in these mice which is known to prolong the retention time of cadmium in tissue.
Effect of Nicotinic and Muscarinic Drugs on Amphetamine‐ and Apomorphine‐induced Circling Behaviour in Rats
Authors: Kaakkola Seppo
Published: July 2010

Abstract: The effect of drugs modulating the activity of nicotinic or muscarinic cholinergic receptors on the circling behaviour induced by amphetamine and apomorphine in rats with unilateral 6‐hydroxydopamine lesion of nigrostriatal dopaminergic pathway was studied. Nicotine (0.2 mg/kg subcutaneously) significantly increased amphetamine‐induced circling behaviour and tended to inhibit apomorphine‐induced circling behaviour. Mecamylamine and pempidine (both 2 mg/kg intraperitoneally) slightly but significantly depressed the intensity of circling behaviour induced by amphetamine, but failed to modify that induced by apomorphine. Pilocarpine (10 mg/kg intraperitoneally) clearly inhibited both amphetamine‐ and apomorphine‐induced circling behaviour. Unlike pilocarpine, atropine (10 mg/kg intraperitoneally) significantly increased the intensity of the circling behaviour induced by amphetamine and also to some extent that induced by apomorphine. Neither hexamethonium (5 mg/kg intraperitoneally) nor methylatropine (1 mg/kg subcutaneously) modified the circling behaviour induced by either amphetamine or apomorphine. The results show that stimulation of central nicotinic and muscarinic receptors may have some opposite effects on the dopamine‐dependent circling behaviour. The presynaptic nicotinic cholinergic receptors on the terminals of the nigrostriatal dopaminergic neurones, stimulation of which may increase the release of dopamine, might be involved in the action of nicotinic drugs. The muscarinic cholinergic receptors in the striatum and/or in the substantia nigra might be involved in the action of muscarinic drugs.
Cigarette Smoke Inhibits Contractile Responses of Rat Isolated Colon to Angiotensin II
Authors: Toivonen Hannu , Nienstedt Walter , Uotila Pekka
Published: July 2010

Abstract:The contractile response of isolated superfused rat colons to angiotensin II was inhibited almost totally when cigarette smoke was in contact with the serosal surface of the colon. Filtration of visible particles from the smoke diminished but did not abolish this inhibitory action. An inhibitory factor was also retained by the filter papers. One inhibitor, which was dissolved in Krebs buffer, behaved like nicotine. Carbon monoxide and dioxide were effective inhibitors but only at higher concentrations than they are present in cigarette smoke. Removal of carbon dioxide from cigarette smoke did not abolish the inhibitory action. Neither of the gases nor nicotine alone could fully mimic the action of cigarette smoke. It is possible that the inhibitory action of cigarette smoke was due to combined action of these compounds. It is, however, also possible, that cigarette smoke contains still other inhibitory compounds. Cigarette smoke probably had its effect directly on the smooth muscle cells, but activation of inhibitory nerves could not be excluded.
Effects of Cyclophosphamide on the Formation and Solubility of Collagen
Authors: Wie Henrik , Beck Eva Imislund
Published: July 2010

Abstract: The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesis.
Effect of D‐Penicillamine on Collagen, Glycosaminoglycans, DNA and RNA of Granulation Tissue and Connective Tissue of Skin, Bone and Aorta in Rats
Authors: Junker Peter , HeliN Grethe , Lorenzen Ib
Published: July 2010

Abstract: Granulation tissue was produced by subcutaneous implantation of viscose‐cellulose sponges on rats. The effect of D‐penicillamine 500 mg/kg/day for 10 days on granulation tissue and the connective tissue of skin, bone and aorta was studied by comparison of treated animals with operated and unoperated controls. In addition, the effect of sponge implantation on intact tissues was studied by comparison between the control groups. The amount of granulation tissue was not affected by D‐penicillamine, and the granuloma‐DNA content even increased. D‐penicillamine increased the amount of salt soluble collagen in all tissues consistent with an inhibition of collagen crosslinking as reflected by increased aldehyde content and α/β chain ratio in soluble skin collagen. Skin appeared to be most sensitive. The content of free hydroxyproline and RNA and the RNA/DNA ratio in skin decreased suggesting a decreased collagen biosynthesis. The hydroxylation of proline and lysine was not affected by the treatment. The water percentage of aorta increased during D‐penicillamine treatment, and the 35S‐sulphate uptake in the sulphated glycosaminoglycans was stimulated in all tissues, in granulation tissue mainly in the chondroitin‐4/6‐sulphate fraction. No quantitative glycosaminoglycan changes occurred in granulation tissue. Sponge implantation caused an increase in the amount of salt soluble skin collagen without any change in α/β chain ratio and aldehyde content of purified, soluble collagen. D‐penicillamine plus operation reduced the collagen content of aorta. The effects of D‐penicillamine on connective tissue compounds may be of importance for its antirheumatic efficacy, but the accompanying effect on normal tissues may imply side effects.
Regio‐Selectivity of Purified Forms of Rabbit Liver Microsomal Cytochrome P‐450 in the Metabolism of Benzo(a)pyrene, n‐Hexane and 7‐Ethoxyresorufin
Authors: Nilsen Odd G. , Toftgård Rune , Eng Lars , Gustafsson Jan‐åke
Published: July 2010

Abstract:The specificity of electrophoretically homogeneous preparations of rabbit liver microsomal cytochrome P‐450lm2–4towards oxygenation of n‐hexane, 7‐ethoxyresorufin and benzo(a)pyrene was examined using a reconstituted system consisting of cytochrome P‐450, NADPH‐cytochrome P‐450 reductase and dilauroylphosphatidylcholine. Epoxide hydrase was included when benzo(a)pyrene was used as substrate. Cytochrome P‐450lm2was most active in n‐hexane and benzo(a)pyrene oxygenation especially with regard to the formation of 2‐hexanol, B(a)P‐4,5‐dihydrodiol and B(a)P‐phenol metabolites. 7‐Ethoxyresorufin was, however, a very poor substrate for cytochrome P‐450lm2. Cytochrome P‐450lm3had less activity towards the investigated substrates while cytochrome P‐450lm4preferentially formed 2‐ and 3‐hexanol, resorufin and B(a)P‐9,10‐dihydrodiol. Cytochrome P‐450lm4isolated after pretreatment with 3‐methylcholanthrene or pheno‐barbital showed roughly the same characteristics except in the formation of 1‐hexanol where cytochrome P‐450lm4isolated after phenobarbital treatment was the most effective. The formation of B(a)P‐4,5‐ and −9,10‐dihydrodiols was greatly increased by incorporation of epoxide hydrase. Our results indicate a certain specificity of the different forms of cytochrome P‐450 in the liver microsomes although some overlap in activities was observed.
Pharmacological and Toxicological Properties of 4‐Hydroxypyrazole, a Metabolite of Pyrazole
Authors: MacDonald Ewen , Ihalainen Erkki , Pispa Jaakko P.
Published: July 2010

Abstract:The effects of 4‐hydroxypyrazole (4‐HP), a principal metabolite of pyrazole, were studied in mice. The compound was toxic, much more so than pyrazole with an LD50 of 1.1 mmol/kg (92 mg/kg) and doses greater than 1.5 mmol/kg (126 mg/kg) were almost invariably fatal. Toxicity seemed to be centred on the liver with microscopic evidence of centrolobular necrosis apparent. Mouse liver catalase was almost totally inhibited 1 hour after administration of 1 mmol/kg of 4‐HP. Tryptophan pyrrolase was also inhibited. 4‐HP seemed to penetrate into the brain as judged by inhibition of brain catalase activity. A slight increase in brain serotonin concentration was found but 4‐HP hadno effect in the doses used(l.5 mmol/kgor4× 1.0 mmol/kg)on brain or heart noradrenaline. We conclude that the pyrazole‐induced decrease in brain noradrenaline is not mediated via 4‐HP. Furthermore, simultaneous treatment with methanol and pyrazole, which prevents the formation of 4‐HP, did not prevent the decrease in brain noradrenaline levels. Since methanol prevented the pyrazole‐induced decrease in brain catalase activity, we can also rule out the possibility that the decrease in brain noradrenaline is secondary to pyrazole‐induced inhibition of brain catalase. It is concluded that though 4‐HP is an active metabolite of pyrazole, causing, in particular, the hepatotoxicity of the parent molecule, it is not responsible for all the varied biological effects of pyrazole.
Relationship between Plasma, Dentin and Bone Fluoride Concentrations in Rats following Long‐term Fluoride Administration
Authors: Ekstrand J. , Lange A. , Ekberg O. , Hammarström L.
Published: July 2010

Abstract: A detailed knowledge of fluoride (F) pharmakokinetics is necessary if its pharmacologic and toxicologic effects are to be adequately understood. In the present study plasma F concentrations have been analysed using repeated blood samples taken from the ethmoidal sinus of rats given 25,50,100 and 150 p.p.m. F in drinking water ad libitum for 79 days. A close relationship between the F‐concentration in the drinking water and plasma F concentrations was found. When the administration of F was stopped, a rapid decline in plasma F concentration was noted during 48 hrs in all groups. The plasma F concentrations in the 25 p.p.m. group returned to preexperimental levels but remained elevated in the other groups. The F concentrations of dentin and bone were determined and calculated on a dry fat free basis. The results show that there was a close relationship between plasma, bone and dentin concentrations.
Metrifonate and Dichlorvos: Cytogenetic Investigations
Authors: Moutschen‐Dahmen Jean , Moutschen‐Dahmen Madeleine , Degraeve Noël
Published: July 2010

Abstract Contradictory results are found in the literature about the cytogenetical effects of dichlorvos and metrifonate in mammals whereas their chromosome breaking ability was demonstrated in plant and Drosophila cells. They were tested on both in vitro and in vivo cells for chromosome breakage. Dominant lethal mutations were also investigated in mouse as well as epidemiological studies in man. In our experiments on mouse bone marrow and testis, one acute dose was injected respectively: 10 mg/kg for dichlorvos and 100 mg/kg for metrifonate. These experiments failed to reveal any clastogenic effect in these test systems as well as in chronic treatments respectively 2 p.p.m./5 days a week for 7 weeks for dichlorvos and 0.5 p.p.m. 5 days a week for 7 weeks for metrifonate. In an investigation of dominant lethal mutations, dichlorvos did not enhance the frequency of dead embryos but the frequency of pre‐implantation losses was significantly increased in two specific periods of the seven investigated. In the same test, metrifonate did not produce any effect. These data are compared with those obtained with trimethylphosphate and MMS taken as positive controls. These results will serve to reevaluate the cytogenetical risks of dichlorvos and metrifonate.
Reduced Decomposition and Faecal Excretion of Methyl Mercury in Caecum‐Resected Mice
Authors: Seko Voshiyuki , Miura Teiji , Takahashi Masako
Published: July 2010

Abstract: Decomposition and faecal excretion of methyl mercury in caecum‐resected mice was investigated in order to elucidate the role of the caecum in metabolizing methyl mercury. During a four‐day period after methyl mercury administration, the caecum‐resected mice excreted less inorganic mercury in the faeces than did sham‐operated control mice (3.4% and 11.5% of the administered dose, respectively). Furthermore, the amount of total mercury excreted in the faeces was also smaller in the caecum‐resected mice than in the control mice (9.3% and 19.3%, respectively). These data indicate that the caecum is important in the decomposition and faecal excretion of methyl mercury in mice.