bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Pyrithioxine, EMD 17246 and Diethanolamine‐Rutin on Acute Alcoholic Intoxication in Rats
Authors: Hillbom M. E. , Linkola J. , Nikander P. , Wallgren H.
Published: July 2010

Abstract: The effects of pyrithioxine, EMD 17246 (a derivative of pyrithioxine) and a mixture of diethanolamine and rutin on acute alcoholic intoxication were tested in male Wistar rats. A standardized tilting plane test and sleeping‐time measurements were carried out. Neither pyrithioxine nor diethanolamine 4‐ rutin counteracted the depressant effect of ethanol. Administration of a single dose of diethanolamine + rutin per os two hours before testing did not markedly affect motor co‐ordination during inebriation. On the other hand motor capability was slightly better in animals pretreated orally with pyrithioxine (0.1 g/kg/ day) for one week than in control animals. Following acute oral administration of 0.005 g pyrithioxine/kg body weight there was also slightly improved performance, but larger doses (0.1 and 2.0 g/kg) made this rather worse. An injection of pyrithioxine (0.025 g/kg) or EMD 17246 (0.025 g/kg) given intra‐peritoneally together with ethanol improved motor co‐ordination. Blood ethanol concentrations were not significantly affected by pre‐treatments with the drugs. The results suggest that pyrithioxine and EMD 17246 slightly protect rats against acute alcoholic intoxication, but the effect appears to be dependent on dose level and mode of administration.
The Ultrastructure of Livers from Chickens Embryogenically Injected with DDT
Authors: Svendsen Ove
Published: July 2010

Abstract:DDT (1,1,1‐trichloro‐2,2‐bis(p‐chlorophenyl)ethane) embryogenically injected into eggs causes hepatic fine structural changes in one to three days old chickens as compared with appropriate controls. The most striking changes are proliferation of agranular endoplasmic reticulum with concomitant vesiculation of rough endoplasmic reticulum and prolongation and accentuation of the presence of mitochondrial myeloid bodies. The proliferation of agranular endoplasmic reticulum supports the finding that DDT increases the activity of drug metabolizing enzymes in hepatocytes from similarly treated chickens. Mitochondrial myeloid bodies in embryonic chicken hepatocytes reported in the literature are only visible after double fixation in glutaraldehyde and osmium tetroxide and disappear after the 17th day of embryonic development. In this study they were found in one to three days old chickens but were larger and more numerous in the treated chickens, suggesting that the normal occurrence of myeloid bodies in embryonic chicken livers is morphologically an expression of cellular immaturity, which can be prolongated or reinduced by DDT.
Biological Availability and in Vitro Release from Oral Oxytetracycline and Tetracycline Preparations
Authors: Bergan Tom , Øydvin Bjørg , Lunde Inga
Published: July 2010

Abstract: The in vitro dissolution rates of 7 oxytetracycline and 2 tetracycline preparations and the absorption characteristics as obtained by a randomized, cross‐over study on 10 healthy volunteers, were studied. It was found that a. Two oxytetracycline preparations (nos. 1 and 7) were inferior to the others in terms of mean serum levels and in producing non‐detectable or insufficient serum concentrations in 2 and 3 persons respectively. b. The bio‐availability of the 5 other oxytetracycline preparations were of the same order (statistically not significantly different) although one preparation (no. 3) exhibited higher mean serum levels, c. The area under the serum concentration curves were proportional to and correlated with the amounts of oxytetracycline and tetracycline recovered in the urine during the period of study, d. The rate of dissolution was related to the absorption characteristics cfr. the preparations 1 and 3. No correlation could be demonstrated between the results of the dissolution tests and the results of the absorption study for preparation 7. e. The tetracycline preparations gave serum concentrations above those of mast oxytetracyclines. f. The oxytetracycline and tetracycline preparations tested showed marked variation in the biological availability of active ingredients.
Fate of Methylatropine in the Puppy
Authors: Winbladh B.
Published: July 2010

Abstract:The fate of tritium labelled methylatropine was investigated in newborn, 3 and 6 weeks and 3 months old dogs and compared with data for adult dogs. After intravenous injection the half‐life of plasma radioactivity was 165‐225 minutes in the three oldest groups. After subcutaneous injection the corresponding figure was 110‐155 min. and there were no consistent differences in the plasma half‐lives and concentrations between the different age groups. The urinary excretion of radioactivity in four hrs was the same after subcutaneous and intravenous injection and varied between 40 and 70 per cent of the injected amount independantly of the age of the dog. The fraction of unchanged drug in the urine collected between 2‐4 hrs after injection was 50‐100 per cent and there were no significant age differences in the fraction or pattern of metabolites. At 2 and 4 hrs after injection the concentration of radioactivity in the liver, and kidney in the newborn dog was about half of that of the adult and 6 weeks old dogs respectively, while the bile concentrations were 3‐15 times higher in the older dogs than in the newborn. The brain and cerebrospinal fluid concentrations at 2 and 4 hrs after injection were not significantly different between the newborn, 6 weeks old and adult animals.
Organ Bath with Controlled Pco2
Authors: Gøttsche Helge , Holm‐Jensen Ib
Published: July 2010

Abstract: Two simple arrangements are described by means of which the Pco2 and Po2 of physiological salt solutions placed in open vessels can easily be adjusted and maintained at known and constant levels during biological experiments on immersed living tissue. The characteristic feature of the proposed arrangements is that a certain fraction of the area of the free surface of the fluid, under standardized stirring conditions, is exposed to an atmosphere with known and constant concentrations of CO2 and O2. The constancy of the Pco2 and the Po2 in the fluid is practically uninfluenced by the additional stirring caused by the biological experiments for which the bath is used.
Tolerance Development with Chlordiazepoxide in Relation to the Plasma Levels of the Parent Compound and its Main Metabolites in Mice
Authors: Christensen J. Dencker
Published: July 2010

Abstract:A single pretreatment with chlordiazepoxide, HCl (50 or 165 mg/kg) to male mice produced tolerance to the compound 24 hours later as measured by the performance on a modified rotarod (the rotacone). The plasma levels of chlordiazepoxide and the major metabolites 7‐chloro‐2‐amino‐5‐phenyl‐3H‐1,4‐benzodiazepine‐4‐oxide (D‐M) and 7‐chloro‐1,3‐dihydro‐5‐phenyl‐2H‐1,4‐benzo‐diazepine2‐one‐4‐oxide (“lactam”) were determined in mice acutely and repeatedly treated with chlordiazepoxide. Although a single pretreatment of chlordiazepoxide, HCl increases the rate of metabolism other factors must be involved to explain the tolerance developed. Mice treated twice with chlordiazepoxide, HCl 165 mg/kg had significantly higher plasma levels of the compound and its metabolites 10 and 30 minutes after the second injection (given 24 hours after the first injection) as compared with mice receiving 50 mglkg chlordiazepoxide, HCl acutely, while the performance on the rotacone was similar in the two groups. Chlordiazepoxide had the most potent effect in the rotacone test, D‐M and “lactam” were about equipotent.
Temperature‐Dependent Sensitivity of Adrenoreceptors in the Toad's Heart
Authors: Harri Mikko N. E.
Published: July 2010

Abstract:A decrease of the experimental temperature from 25° to 12° resulted in a 10.2 × increase in the sensitivity of the toad's heart to the positive chronotropic effect of adrenaline, measured as ED50 ratios, and in a 4.9 × increase of the sensitivity to the α‐adrenergic drug, phenylephrine. In contrast, the sensitivity to the β‐adrenergic drug, isoprenaline, did not change significantly with temperature alteration. Acclimatization of the animals to 25° increased the sensitivity of the heart to adrenaline by 2.2 × compared wih the 10° maintained toads. The blocking capacity of the β‐adrenergic blocking agent, propranolol, was decreased with cold. The most pronounced decrease was seen in the blocking capacity to the effect of isoprenaline. On the other hand, the blocking capacity of the α‐adrenergic blocking agent, phenoxybenzamine, was decreased with warmth. In this case the most marked decrease was observable during antagonism between phenoxybenzamine and phenylephrine.
Uptake of Piribenzil by Rat Liver Slices
Authors: Ryrfeldt Åke
Published: July 2010

Abstract: The uptake of 3H‐piribenzil (2‐hydroxymethyl)‐1,1‐dimethylpiperidinium (‐3H) benzilate, an anticholinergic agent, into rat liver slices was found to be concentration and time dependent. At a medium concentration of 10−5 M the slice to medium (S/M) ratio was about 4 after 60 minutes incubation. The uptake was decreased by metabolic inhibitors (iodoacetic acid and 2,4‐dinitrophenol) and by incubation in N2‐atmosphere. Structurally similar compounds (cations) also decreased the uptake of piribenzil but organic anions did not influence the uptake process. Chromatographic studies revealed unchanged piribenzil in the slices. Binding of piribenzil to liver homogenate occurred. Moreover efflux of piribenzil from liver slices was decreased by iodoacetic acid. These in vitro experiments may reflect processes responsible for the biliary excretion of organic cations.
The Comparative Pharmacology of Flupenthixol and some Reference Neuroleptics
Authors: Nielsen I. Møller , Pedersen V. , Nymark M. , Franck K. F. , Boeck V. , Fjalland B. , Christensen A. V.
Published: July 2010

Abstract:Flupenthixol, a thioxanthene derivative may exist in two isomeric forms, α and β. Flupenthixol contains 45‐55 % α‐flupenthixol. The pharmacological effects of flupenthixol, α‐ and β‐flupenthixol have been compared with those of clopenthixol, chlorprothixene, fluphenazine, perphenazine, chlorpromazine and haloperidol. In most pharmacological screening tests α‐flupenthixol was equipotent with fluphenazine. β‐Flupenthixol showed very low pharmacological activity. As expected the potency of flupenthixol was about one half that of α‐flupenthixol. Flupenthixol was considerably more potent than clopenthixol and chlorprothixene in the inhibition of conditioned avoidance response. The influence on temperature regulation and the peripheral α‐adrenolytic effect was considerably weaker than that of chlorprothixene.
Thein VivoEffect of Tropolone on Noradrenaline Metabolism and Catechol‐O‐Methyl Transferase Activity in Tissues of the Rat
Authors: Broch O. J.
Published: July 2010

Abstract:Tropolone (100 mg/kg intraperitoneally) was given to rats and the catechol‐O‐methyl transferase (COMT) activity and tropolone concentrations were measured in the submaxillary gland and in the liver and the concentrations of noradrenaline (NA) and normetanephrine (NM) and the accumulation of metabolites from14C‐tyrosine were measured in the brain and in the submaxillary gland. The maximal tropolone concentrations were found after 0.5 hr and were 50 % higher in the liver than in the gland. After 2.5 hrs it was reduced to 70 % (liver) and 25 % (gland). Tropolone caused a slight reduction of 15 % in the COMT activity when measuredin vitrobut a rapid fall of 40‐60 % was found in the NM concentrations. After 24 hrs the NM concentration was normal in the brain but still maximally reduced in the gland. A parallel decrease of the NA content was found in the brain but not in the gland. The studies of metabolites from14C‐tyrosine indicated a reduced synthesis of NA from tropolone with no change in the NM fraction. No significant traces of acidic or neutral metabolites from NA were found but there was evidence of the formation of transaminated products, the most prominent of which wasp‐hydroxy‐phenyllactic acid. Two large radioactive metabolites could not be identified. The results indicate that the measurement of COMTin vimmay not be an adequate measure of the enzyme inhibitionin vivo. The enzyme‐tropolone complex is probably easily released by thein vitroprocedures.
Relationship of Uptake of Sodium and45Calcium to ATP‐Induced Histamine Release from Rat Mast Cells
Authors: Dahlquist Rune
Published: July 2010

Histamine release from isolated rat mast cells induced by extracellular adenosine 5′‐triphosphate (ATP) in the presence of calcium was preceded by the uptake of sodium and45Ca in the cells. In contrast, the release induced by compound 48/80, n‐decylamine and chlorpromazine was not preceded by uptake of45Ca. Histamine release and45Ca uptake by ATP were completely inhibited byp‐hydroxymercuribenzoate and incubation at 0°, whereas sodium uptake was partly reduced. In the presence of 2.5 mM‐CaCl2, ATP activated the uptake of45Ca whereas, as previously reported, no sodium uptake or histamine release occurred. All three effects of ATP were inhibited by MgCl2. Thus, under conditions where the uptake of either sodium or45Ca was inhibited, no histamine release was induced by extracellular ATP.

Antimycin A did not inhibit ATP‐induced increase in membrane permeability for sodium and calcium but completely blocked the histamine release. It is concluded that for histamine release to be induced by extracellular ATP from rat mast cells, an increased cell membrane permeability for sodium and calcium is necessary but not in itself sufficient since the release reaction is also dependent on the metabolic state of the cells.
A Comparative Study on Drug Hydroxylation and Glucuronidation in Liver Microsomes of Phenobarbital and 3‐Methylcholanthrene Treated Rats
Authors: Vainio H. , Hänninen O.
Published: July 2010

The treatment of hepatic microsomes with phospholipase A or phospholipase C decreased the drug hydroxylase activity. The exception was the aryl hydrocarbon hydroxylase in hepatic microsomes from 3‐methylcholanthrene pre‐treated rats. Its specific activity remained unchanged after phospholipase A digestion. In hepatic microsomes from phenobarbital pretreated rats the aryl hydrocarbon hydroxylase was not significantly increased and after phospholipase A or phospholipase C digestion, it decreased in both treated and control rats. The phenobarbital or 3‐methylcholanthrene inducedp‐nitroanisole 0‐demethylase activity in liver microsomes decreased in a manner corresponding to the decrease in cytochrome P‐450 (P‐448) concentrations. The treatment of hepatic microsomes with phospholipase A or phospholipase C activated the membrane‐bound UDP glucuronosyltransferase both in control and drug‐treated rats. Phospholipase A increased the measurable UDP glucuronosyltransferase activity particularly in hepatic microsomes from 3‐methylcholanthrene pretreated rats. However, digestion with trypsin was necessary in order to detect the induction in UDP glucuronosyltransferase after phenobarbital pretreatment of rats. Other agents studied, such as phospholipase A or C, digitonin, cetylpyridinium chloride, or NaSCN, were unable to do this. Digestion with trypsin released considerable amounts of UDP glucuronosyltransferase activity into 27,000 g supernatant, especially from phenobarbital microsomes, whereas phospholipase A was more active in releasing UDP glucuronosyltransferase into 27,000 g supernatant from hepatic microsomes of 3‐methylcholanthrene pretreated rats. Membrane perturbating agents seem to differ in their action towards the hepatic microsomal membranes obtained from rats treated with phenobarbital or 3‐methylcholanthrene.
Withdrawal in the Rat after Long‐term Forced Oral Barbital Administration
Authors: Wahlström Göran
Published: July 2010

In 5 experiments a barbital solution was the sole drinking source for male rats. On an average 200 mg/kg/day was consumed. There was no increase in dosage during treatments between 12 and 42 weeks. A positive correlation between the dose of barbital consumed and a pre‐experimental hexobarbital threshold developed during the treatment (fig. 5). After the end of the barbital treatment the animals showed a loss of weight and an increased water consumption. Tolerance recorded as an increase in the hexobarbital threshold had a first maximum 3 days after the end of the barbital treatment. After prolonged barbital treatment a second maximum was seen approximately 3 weeks later. Using the duration of barbital treatment as an independent variable, none of these changes in the abstinence period after barbital treatment showed a tendency towards a steady state (fig. 6).
Effects of Water Deprivation in Rats with Polydipsia and Polyuria Due to Long‐term Administration of Lithium
Authors: Christensen Sten
Published: July 2010

Wistar rats with Li‐induced polydipsia and polyuria (group 3) were deprived of water in order to examine their maximal urinary concentrating ability. For comparison, water deprivation was also achieved in rats with “polydipsia” induced by replacing the drinking water with 5 % glucose (group 1) and in rats with hereditary hypothalamic diabetes insipidus (group 2). The animals were totally deprived of water either for 72 hours or until 20 % loss of body weight had been obtained. Body weight, urine flow and urine osmolality were recorded every 6 hour, and serum osmolality at maximal dehydration. The urine osmolality was initially less than 250 mosm/kg in all groups. Maximal urine osmolality recorded during water deprivation was (1) 2732±100, (2) 1067±84, and (3) 1200±216 (S.D.) mosm/kg. Under the same conditions normal Wistar rats concentrated the urine to 3529±170mosm/kg. Terminal serum osmolality was (1) 310±1, (2) 346±9, and (3) 390 ±31 mosm/kg as compared to 307±2 mosm/kg in normal Wistar rats. During water deprivation, the urine flow was diminished more rapidly and to a lower level in group (1) than in groups (2) and (3). The results indicate that rats with Li‐induced polydipsia and polyuria exhibit marked impairment of the renal concentrating ability. Nothing in the results suggests Li‐polyuria to be secondary to a primary polydipsic action of the lithium ion.
The Relationship between Myocardial Content of Digoxin and Increase in Myocardial Contractility
Authors: Videbæk Jørgen , Brock Axel
Published: July 2010

The effect of digoxin on the contractility of the nonfailing heart was studied in anaesthetized dogs receiving continuous infusion of digoxin 0.8 jig/kg/ min. The contractility, described by Vce5was increased to 30 % above control levels after infusion of 35 μg/kg of digoxin. From this point only an insignificant increase in contractility was obtained following futher infusion of digoxin. The myocardial content of digoxin, measured by a radio immuno method, was proportional to the cummulated dose and calculated to be about 140 ng/g tissue, when the maximal increase in contractility was achieved. The content of digoxin in the myocardium of 275 ng/g tissue was not associated with dysrhythmias.
Absorption, Distribution and Excretion of Alprenolol in Man, Dog and Rat
Authors: Bodin N. ‐O. , Borg K. O. , Johansson R. , Obianwu H. , Svensson R.
Published: July 2010

The plasma levels of unchanged alprenolol and its radioactive metabolites were determined in four healthy male volunteers after intravenous and oral administration of 3H‐alprenolol. The mean plasma half‐life was 2.28 hrs and the apparent volume of distribution 2.99 l/kg as determined from the intravenous experiment. In the rat the tissue distribution was studied after intravenous and oral administration by determination of unchanged drug and its radioactive metabolites, in eight different tissues. A high degree of extra‐vascular distribution of the drug was observed, with especially high amounts of unchanged alprenolol in the lung after intravenous administration. In the rat, dog and man the urinary excretion of total radioactivity after intravenous and oral administration of3H‐alprenolol was studied. It was concluded that the drug was completely absorbed after oral administration. In man, the drug was almost completely excreted in the urine within 48 hrs mainly as metabolites. In the rat and dog a considerable amount of the drug was excreted in the faeces. From studies in the rat and dog it was demonstrated that this was due to biliary excretion of the drug.
Effects of Phenobarbital and Ethanol on Rat Liver Aldehyde Dehydrogenases
Authors: Tottmar S. O. C. , Kiessling K.‐H. , Forsling M.
Published: July 2010

The aldehyde dehydrogenases and the drug‐metabolizing system (the mixed function oxidase) were studied in Wistar rats treated with ethanol and phenobarbital. Phenobarbital treatment had no effect on the microsomal aldehyde dehydrogenase activity, whereas the mitochondrial aldehyde dehydro‐genase activity was slightly decreased and the activities of ethylmorphine demethylase, NADPH‐cytochromecreductase and the concentration of cytochrome P‐450 were increased two to threefold. Ethanol treatment caused no changes in the activities of the aldehyde dehydrogenases, and the drug metabolizing system was only slightly affected. Very little aldehyde dehydrogenase activity was found in the cytosol from livers of either control, ethanol‐treated or phenobarbital‐treated rats. The results are discussed with particular reference to the oxidation of acetaldehyde and other aldehydes during ethanol metabolism.
Effect of Acute Ethanol Administration on Tryptophan Oxygenase Activity in Rat Liver
Authors: Mørland Jørg
Published: July 2010

Ethanol was given as short‐term treatment to intact animals in the following ways: Orally in mixture with sucrose as drinking fluidad libitumfor one or 18‐21 hrs, or intraperitoneally (i.p.) as a single dose (2.5 or 3.3 g/kg rat). Ethanol was also added to perfusates (final concentration 0.2 %) of isolated livers. Short‐term ethanol treatment (in vivo) was also given to animals which had been pretreated with ethanol for 3‐4 weeks.

I.p. injection of ethanol caused a significant rise in tryptophan oxygenase (TO)‐activity (337 %) and plasma corticosterone (approximately 400 %), while consumption of ethanol only slightly increased the enzyme activity without any significant effects on steroid hormone concentration. The administration of cycloheximide (1.5 mg/kg) abolished the increase in TO‐activity normally found after i.p. injection of ethanol. Ethanol did not affect the basal TO‐activity in the perfused liver, but slightly increased the effect of dexamethasone induction. TO degradation measured after administration of cycloheximide (20 μg/ml) was unchanged by ethanol in the perfused liver. An i.p. injection of ethanol increased the TO‐activity (268 %) in ethanol‐pretreated rats, but to a smaller extent than in normal animals. The TO‐activity measured after consumption in ethanol‐pretreated rats was significantly reduced. It was concluded that the acute stimulatory effect of ethanol on TO‐activity was due to the rise in plasma corticosterone which induced enzyme synthesis. Long‐term consumption of ethanol was accompanied by reduced basal TO synthesis as well as by reduced enzyme induction after acute ethanol treatment.
The Pharmacokinetics of Propylthiouracil
Authors: Kampmann J. , Skovsted L.
Published: July 2010

The half‐life of propylthiouracil was determined in 7 normal subjects after intravenous injection of 400 mg of the drug. An average value of 77 ± 17 minutes (mean ± S. D.) was found. As the concentration of the drug in the blood declined by a rapid phase followed by a more slow phase a two‐compartment model was used for further calculations, and the rate constants between the 2 compartments and the overall elimination constant have been calculated. The same dose of propylthiouracil was later administeredper osto the same 7 persons and the plasma concentration was followed to non‐measurable values. An average maximum concentration of 9.1 ± 2.5 μg/ml was obtained after a period of 57 ± 22 minutes. The area under the “peroral” curve has been calculated in per cent of the area under the “intravenous” curve. An average value of 77 ± 13 % was found expressing the bioavailability of the drug after oral administration.
Interpretation of Post Mortem Serum Levels of Cardiac Glycosides after Suspected Overdosage
Authors: Moffat A. C.
Published: July 2010

Post mortem serum concentrations of cardiac glycosides have been measured in 13 patients who had suddenly died from suspected overdosage of cardiac glycosides. With digoxin, the highest level observed was 71 ng/ml after an intramuscular injection to an infant, whilst levels of 7.2 to 24 ng/ml were found after oral administration to adults. These levels are much higher than the mean therapeutic levels, which were 1.34 ng/ml for optimally digitalised patients and 3.11 ng/ml for those showing evidence of toxicity, although some overlap did occur. Other cardiac glycosides (digitoxin, lanatoside C and deslanoside) showed a similar relationship between concentrations found during therapy and after overdosage.
Effects of Social Stress on the Turnover of Brain Catecholamines and 5 ‐ Hydroxytryptamine in Mice
Authors: Modigh K.
Published: July 2010

Abstract:Male mice were isolated or housed in groups for 10 to 11 weeks. Some of the isolated mice were then brought together in groups of 20. These latter animals began to fight almost immediately. The turnover of brain DA, NA and 5‐HT was estimated in such isolated, grouped and fighting animals by measuring the rate of depletion of these monoamines after inhibition of their biosynthesis. The animals were given α‐propyl dopacetamide (H 22/54), 500mg/kg intraperitoneally, an inhibitor of tyrosine‐ and tryptophan‐hydroxylase, or the methylester HCl of α‐methyl‐tyrosine (H 44/68), 250 mg/kg intraperitoneally, an inhibitor of tyrosine‐hydroxylase. The H 22/54 induced depletion of NA was similar in the isolated and grouped animals but was accelerated in the fighting animals. The rate of depletion of DA or 5‐HT, after H 22/54, did not differ significantly among the isolated, grouped or fighting animals. The H 44/68 induced depletion of NA in the grouped animals was faster than that in isolated animals, while the NA depletion in the fighting animals was faster than that in grouped animals. The H 44/68 induced depletion of DA was more rapid in the fighting than in the isolated animals.
The Effect of NH4Cl on Polyuria and Polydipsia during Prolonged Lithium Administration in the Rat
Authors: Smith Donald F.
Published: July 2010

Abstract:Polyuria and polydipsia developed in rats given water to drink and fed a diet containing lithium which maintained their serum lithium level between 0.45 and 0.65 meq./l for two weeks. Polyuria and polydipsia were completely prevented and partially cured in rats given the lithium‐containing diet and solutions of NH4Cl. Polyuria and polydipsia were partially prevented but not cured in rats given water and fed a diet containing lithium and NH4Cl. The possible mechanisms responsible for the effects of NH4Cl on polyuria and polydipsia in the rats given lithium are discussed.
Renal and Hepatic Toxicity of Methoxyflurane in Combination with Tetracycline or Oxytetracycline Treatment in Rats
Authors: Rosenberg Per H. , Wahlström Torsten
Published: July 2010

Abstract: Methoxyflurane and tetracyclines may cause dose‐related renal dysfunction. In the present study rats were treated with oxytetracycline (37.5 and 75 mg/kg/day) or tetracycline (75 mg/kg/day) intraperitoneally for four days and one methoxyflurane anaesthesia (1 % for 45 minutes) was given on the second day. The combined treatment as well as methoxyflurane anaesthesia alone, caused polyuria, elevated urinary fluoride excretion, increased serum uric acid concentration and SGPT activity. The histological examination showed shrinkage of glomeruli and tubular protein deposits in the kidneys and marked fat infiltration in the liver of rats treated with the antibiotics and methoxyflurane, while the anaesthetic seemed to cause only slight fatty changes in the liver. A probable renal tubular lesion caused by methoxyflurane, or its metabolites, was indicated by the polyuric effect, the lack of response to injected vasopressin and the uric acid retention while the tetracyclines probably added to the toxic effect mainly through their anti‐anabolic action. Oxytetracycline, in combination with one halothanc anaesthesia, did not seem to cause hepatotoxicity in the rats.
Effects of Verapamil and Propranolol on Contractility, Frequency, Coronary Flow and Oxygen Consumption in the Isolated Rabbit Heart
Authors: Magnussen I. , Kudsk F. Nielsen
Published: July 2010

Abstract:The effects of verapamil and propranolol on contractility, frequency, coronary flow and myocardial oxygen consumption were compared in isolated rabbit hearts, which were retrogradely perfused in a re‐circulatory system. Cumulative concentrations of verapamil ranging from 0.01–0.2 μg/ml had a progressive coronary vasodilatatory effect accompanied by a very pronounced inhibition of contractility and a reduction in cardiac efficiency. Heart rate was not significantly changed. Propranolol produced a decrease in coronary flow, but lower concentrations from 0.05 up to about 1 μg/ml caused an improvement in cardiac efficiency and a less pronounced inhibition of contractility. A negative chronotropic effect was observed. Both agents caused an increase in the ratio of coronary venous oxygen content to myocardial oxygen consumption.
The Spasmolytic Effect of Terbutaline on Histamine Induced Bronchoconstriction in Phenobarbital Treated Guinea‐pigs
Authors: Olsson O. A. Torsten
Published: July 2010

Abstract:Guinea‐pigs injected with phenobarbital subcutaneously or given the drug in the drinking water for 6–10 days were significantly more sensitive to inhaled histamine than corresponding control groups. Despite this induced hypersensitivity, the phenobarbital pretreatment did not diminish the protecting activity of terbuline against the histamine bronchospasm.
Binding of Cadmium and Mercury in the Rat Bile: Studies Using Gel Filtration
Authors: Havrdová Jana , Cikrt Miroslav , Tichy Milon
Published: July 2010

Abstract: Bile components Cd2+ and Hg2+ binding was followed up by the chromatographic fractionation on Sephadex G‐100 of bile from rats that were given CdCl2 or HgCl2 intravenously. Mercury was bound with the high molecular weight fraction while cadmium was bound with both the high (> 100,000) and the low molecular weight fraction. The change in bile composition after CdCl2 or HgCl2 administration was observed; a new fraction containing yellow pigments of low molecular weight and virtually no proteins was identified.
The Effect of Dialysis on the Protein Binding of Drugs in the Plasma of Patients with Acute Renal Failure
Authors: Andreasen Frederik
Published: July 2010

Abstract:The protein‐bound fraction of acetylsalicylic acid, salicylic acid, phenylbutazone, diphenylhydantoin, sulphadiazine and thiopental was found to be increased in blood plasma afterin vitrodialysis of plasma from blood donors and also in the plasma of surgical patients suffering from acute renal failure. The concentrations of the drugs ranged from 50 to 600 μg/ml. The increments (in μg drug bound/mg albumin) were significantly larger in the patient‐plasmas than in the donor plasmas for diphenylhydantoin, phenylbutazone and sulphadiazine. The albumin‐bound fraction of all the six drugs was significantly greater when human serum albumin and the drug were dissolved in patient‐plasma ultrafiltrate which had previously been dialysed against a Ringer‐solution, than when albumin and the drug were dissolved in undialysed patient plasma ultrafiltrate. For ultrafiltrate prepared from donor plasma only acetylsalicylic acid showed significantly increased binding in dialysed ultrafiltrate. The increments (in μg drug bound/mg albumin) were significantly greater in the patient ultrafiltrates than in the donor ultrafiltrates for thiopental, salicylic acid, phenylbutazone and sulphadiazine. The drug‐binding capacity of the protein in dialysed patient plasma for four of the drugs was significantly lower than the drug‐binding capacity of albumin added in the same concentration to the dialysed plasma ultrafiltrate. For two drugs, diphenylhydantoin and thiopental, the differences in the same direction were not statistically significant. In donor plasma, the binding to genuine plasma protein was not different from the binding to added albumin.
Inhibitory Action of Exogenous Adenosine‐5′‐triphosphate on Glycolysis in Isolated Rat Mast Cells: Significance for Histamine Release
Authors: Peterson Curt , Diamant Bertil
Published: July 2010

Abstract:Histamine release and lactate content were concomitantly determined in samples of isolated rat mast cells. Histamine release induced by exogenous ATP or compound 48/80 was inhibited by antimycin A (0.2 μM). Glucose (0.60 mM) restored the release induced by compound 48/80 but not that induced by ATP. ATP but not compound 48/80 inhibited the accumulation of lactate in suspensions of mast cells containing glucose (0.60 mM). ATP induced inhibition of lactate accumulation and release of histamine within the same concentration range. However, the time courses for the two processes were different. Antimycin A (0.2 μM) enhanced the accumulation of lactate, an effect which was counteracted by ATP. 0.05 mM ATP or more reduced the lactate accumulation to the same values as those found in the absence of antimycin A. The inhibitory action of ATP on glycolysis may explain the observed inability of glycolytic substrates to restore the ATP‐induced histamine release blocked by inhibitors of oxidative metabolism.
Inhibitory Action of Antimycin A on Histamine Release from Isolated Rat Mast Cells
Authors: Peterson Curt
Published: July 2010

Abstract:Pretreatment of isolated rat mast cells with antimycin A (0.03 μM or more) inhibited histamine release induced by subsequent exposure to compound 48/80 or exogenous ATP. When the mast cells were simultaneously exposed to antimycin A (0.1 μM) and the releasing agents, compound 48/80, but not ATP, released histamine. In contrast, exogenous ATP, but not compound 48/80, induced histamine release from cells which after pretreatment with antimycin A were diluted to an ineffective concentration of the inhibitor with a solution containing the releasing agent. The different effects of antimycin A on histamine release induced by compound 48/80 and exogenous ATP can be explained by the difference in the time courses between the release reactions. The ATP content in mast cells was gradually reduced during treatment with antimycin A (0.2 μM) so that after 3 min. only about 30 % of the original content remained. Concomitantly, the ability of the cells to release histamine when exposed to compound 48/80 decreased. This suggests that histamine release induced by compound 48/80 is dependent on the ATP content in the cells at the time of exposure to the releasing agent.
Histamine Release Induced by Compound 48/80 from Isolated Rat Mast Cells: Dependence on Endogenous ATP
Authors: Peterson Curt
Published: July 2010

Abstract:Antimycin A (0.2 μM) reduced the ATP content in isolated rat mast cells to 25–30 % of the original value. Pyruvate (4.9 mM) did not restore the ATP content in antimycin A‐treated cells, indicating a complete block of oxidative ATP production. 82–97 % of the glucose which disappeared from suspensions of mast cells in the presence of antimycin A was recovered as lactate. Therefore, the rate of lactate accumulation in suspensions of antimycin A‐treated cells was used as a measure of the cellular ATP production rate. Maximal accumulation occurred with 1.1 mM glucose. Incubation with glucose (0.51 mM) for 2.5 min. completely restored the ability of mast cells pretreated with antimycin A to release histamine when exposed to compound 48/80. Concomitantly, the ATP content in the cells was restored to a steady‐state level of about 75 % of the original value. 0.29 mM glucose partially restored the histamine release as well as the ATP level whereas 0.13 mM glucose did not affect either of these parameters. The turnover time of ATP at steady‐state was about 30 sec. with all three concentrations of glucose, which indicates that the rate of ATP utilization by the cells is directly proportional to the ATP content. The present study supports the view that histamine release induced by compound 48/80 is dependent on the ATP content in the mast cells at the time of exposure to compound 48/80.
Interaction of ATP and Calcium on the Rat Mast Cell: Effect on Histamine Release
Authors: Dahlquist Rune , Diamant Bertil
Published: July 2010

Abstract:Histamine release from rat mast cells was induced by the simultaneous presence of ATP and calcium in the incubation medium. The minimum concentration of calculated free ATP necessary for histamine release was 1–2 μM. The amount of histamine released as well as the rate of the release increased when the concentration of free ATP was raised. The gradual inhibition of the release observed with increasing concentrations of CaCl2and MgCl2could be ascribed to decreasing concentrations of free ATP by the formation of CaATP and MgATP complexes. By pretreating the cells with ATP before the addition of CaCl2less free ATP was required during the calcium‐dependent secretory phase. It is concluded that free ATP and free calcium (or/and possibly CaATP complex) interact on the rat mast cells since the lowering of the concentration of one factor could, within certain limits, be compensated for by increasing concentrations of the other with regard to the magnitude of the secretory response of the mast cells.
The Formationin Vivoof 3,4‐Dihydroxyphenylalanine (DOPA) from 3‐Hydroxy‐DL‐phenylalanine (m‐Tyrosine)
Authors: Hollunger Gunnar , Persson Sven‐Åke
Published: July 2010

Abstract:The formation of 3,4‐DOPA from m‐tyrosinein vivois demonstrated. The kinetic aspects of DOPA accumulation in the brain after central and peripheral inhibition of the 1‐aromatic amino acid decarboxylase are considered. It is concluded that the excess DOPA accumulation after administration of m‐tyrosine is due to the uptake from the blood of DOPA generated in the liver. This exogenous DOPA is shown to be much less exposed to brain decarboxylase than DOPA generated in the brain. The possibility that the pharmacological effects of m‐tyrosine can at least partly be explained by dopamine generation from DOPA is discussed.
Reduced Concentrations of Plasma Diazepam in Chronic Alcoholic Patients Following an Oral Administration of Diazepam
Authors: Sellman R. , Pekkarinen A. , Kangas L. , Raijola E.
Published: July 2010

Abstract:Diazepam (tensopam®) 10 mg was given orally to 12 chronic alcoholic patients, at the beginning of the alcohol‐free period and to 14 controls. Diazepam in the plasma was determined gaschromatographically with a63Ni‐EC detector. During the absorption phase the plasma levels of diazepam were reduced to 44% at 2 hours (P < 0.01) and 32% at 3.5 hours (P < 0.001) in alcoholic patients compared with respective values of normal subjects. The reduced values, found in the alcoholic patients, may be due to disturbances in the gastro‐intestinal absorption of diazepam, or to processes involving the portal vein or liver. Some alcoholic patients received a simultaneous treatment with neuroleptic or hypnotic drugs.
Inhibition of the Uptake of3H‐Dopamine and14C‐5‐Hydroxytryptamine in Mouse Striatum Slices
Authors: Ross Svante B. , Rényi Anna L.
Published: July 2010

Abstract:The inhibitory activities of a number of compounds on the simultaneous uptake of3H‐dopamine (3H‐DA) and14C‐5‐hydroxytryptamine (14C‐5‐HT) in the same slices of the mouse striatum were examined. Experiments with inactive DA and 5‐HT demonstrated that the uptake of the two amines occurs at different sites.In vitro(+)‐amphetamine was 2.7 times more potent than the (‐)‐isomer whereasin vivothis difference was about 6 times. (+)‐Amphetamine was also significantly more active than the (‐)‐enantiomer on the3H‐DA uptake in striatal slices from the rat. The methylester group in cocaine is essential for the inhibitory activity of cocaine, which had similar potencies on the two uptake mechanisms. Benztropine was much more active on the3H‐DA uptake than on the14C‐5‐HT uptake.In vivothe amphetamine derivatives including prolintane and methylphenidate were the most active compounds on the3H‐DA uptake, but the 4‐substituted amphetamines were more active on the14C‐5‐HT uptake. Among other compounds benztropine was as active as (+)‐amphetamine on the3H‐DA uptake. None of the compounds tested seem to be useful as model compounds for the selective inhibition of the DA uptake, since they have other pharmacological effects at lower doses.
Determination of Prekininogenase in Rat Plasma
Authors: Arntzen Finn Cato , Briseid Kjell , Qvigstad Ellen‐Karine
Published: July 2010

Abstract:Prekininogenases in rat citrated plasma were activated with acetone (20% v/v). EDTA was addedafterthe evaporation of acetone to increase the activity of the enzyme preparation. The preparation was tested for kininogenolytic activity (release of kinin in 60$dG‐heated human citrated EDTA‐plasma), esterolytic activity (hydrolysis of benzoyl arginine ethyl ester or tosyl arginine ethyl ester) and caseinolytic activity. The decrease in urokinase activable caseinolytic activity together with the development of spontaneous caseinolytic activity which could be inhibited by lima bean trypsin inhibitor, and also experiments on the hydrolysis of lysine ethyl ester, suggested the presence of plasmin in the enzyme preparation. When enzyme preparations were prepared from plasma of rats pretreated with carrageenin, ellagic acid or serotonin, significant reductions in the above mentioned activities were observed. A good correlation was obtained between the two acyl‐arginine esterase assays, while no such correlation was obtained between the kininogenase and the esterase assays. This fact probably reflects differences in the relative amounts of kallikrein and plasmin present.
Effect of Potassium on Lithium‐induced Growth Retardation and Polyuria in Rats
Authors: Olesen O. Vendelin , Jensen Jørgen , Thomsen Klaus
Published: July 2010

Abstract: The effect of potassium on lithium‐induced growth retardation and polyuria was examined in rats given food containing 100 mmol/kg of lithium and 600 mmol/kg of sodium. The increase of the potassium content of the food from 100 to 700 mmol/kg led to a statistically significant increase of the weight gain and diminished the polyuria with unaltered serum lithium concentration; in control rats the high electrolyte content had a slightly decreasing effect on normal weight gain. At 9 weeks the lithium treated rats and the control rats weighed almost the same. At a lower level of sodium in the food (350 mmol/kg) addition of extra potassium had no effect on the weight gain of the rats given lithium, but the polyuria was reduced to the same level as that in the experiment with the high sodium diet. Addition of sodium to the food in place of potassium also led to increased weight gain and diminished polyuria, but the effect of sodium was less than the effect of potassium and could be accounted for by a sodium‐induced lowering of the serum lithium concentration. Lithium administration led to a shift of the urine pH in an alkaline direction; this effect was counteracted by potassium in all three experiments. It is concluded that potassium counteracts lithium‐induced growth retardation and polyuria in rats; the effects are not mediated via a reduction of the serum lithium concentration.
Effect of Ethanol Dependence and Withdrawal on the Catecholamines in Rat Brain and Heart
Authors: Abtee Liisa , Svartström‐Fraser Margareta
Published: July 2010

Abstract:To study whether ethanol dependence is accompanied by changes in the brain monoamines, male Sprague‐Dawley rats were intubated intragastrically with 10% (w/v) ethanol solution 3 times daily (daily dose 8–11 g/kg) for 7–10 days. Control rats were intubated with similar volumes of tap water. The rats were killed 4–6 hrs (intoxicated group) or 16–18 hrs (withdrawal group) after the last administration of ethanol. At this time the withdrawn rats showed a stiff tail, spastic rigidity, piloerection, tremor, hyperexcitability, stereotyped head movements as well as convulsions. The dopamine and homovanillic acid concentrations as well as the disappearance rate of dopamine after synthesis blockade (α‐methyl‐p‐tyrosine 250 mg/kg intraperitoneally 3 hrs) were similar in the brain of control, ethanol intoxicated and withdrawn rats. Chronic ethanol administration did not alter the concentration of noradrenaline in the brain or the heart of the rats. However, the disappearance rate of noradrenaline after synthesis blockade was accelerated by about 30–50% in the brain and heart of rats withdrawn from ethanol. Moreover, the concentration of noradrenaline was decreased by 40–60% in the brain and heart of rats which died in withdrawal convulsions. The experiments suggest that the noradrenergic mechanisms but not the dopaminergic mechanisms may be associated with the occurrence of withdrawal symptoms.
A Simple Method for Determining Diazepam and Its Major Metabolites in Biological Fluids: Application in Bioavailability Studies
Authors: Arnold Elisabeth
Published: July 2010

Abstract:A simple gas chromatographic analytical method for determining diazepam and its major metabolites in the blood, urine, and muscle homogenate is described. Its applicability is illustrated by bioavailability studies, on man and on animals. The human studies revealed equivalence between two marketed brands of diazepam tablets and a slight difference between two brands of suppositories. The animal experiments showed agreement ofin vivoproperties of two different formulations of a diazepam injection fluid.
Placental and Foetal Metabolism of Acetaldehyde in Rat II. Studies on Metabolism of Acetaldehyde in the Isolated Placenta and Foetus
Authors: Sippel H. W. , Kesäniemi Y. A.
Published: July 2010

Abstract: The aldehyde‐oxidizing capacity of placenta and foetal liver from the rat was studied using acetaldehyde as substrate. In the placenta the activity was approximately 8 % and in foetal liver 49 % of that found in the liver of adult animal. The placenta seems to prevent most of the acetaldehyde found in maternal blood during ethanol oxidation from entering the foetal circulation.
Indomethacin Inhibition of Bumetanide Diuresis in Dogs
Authors: Olsen Uffe Bang
Published: July 2010

Abstract:Clearance experiments in conscious, trained, intact dogs and also a one minute urine collection in conscious, ureterostomized dogs show that indomethacin pretreatment significantly alters the renal haemodynamic end excretional effects of bumetanide. The haemodynamic parameters (inulin and PAH clearance) are significantly reduced during the time interval 10–40 minutes after bumetanide administration in indomethacin pretreated dogs. In the same conditions urine volume, and sodium and chloride excretion are reduced while potassium excretion is less influenced. Indomethacin pretreatment does not affect the abolition of the cortico‐medullary electrolyte gradient caused by bumetanide administration. The results support evidence for an important role of prostaglandins in the diuretic effect of bumetanide.