bluuebunny/crossref_metadata_2025 huggingface dataset:
n‐Butoxyacetic Acid, a Urinary Metabolite from Inhaled n‐Butoxyethanol (Butylcellosolve)
Authors: Jönsson Anna‐Karin , Steen Göran
Published: July 2010

Abstract Male albino rats were exposed to butylcellosolve (n‐butoxyethanol). Collected urine was found to contain a characteristic metabolite, identified as n‐butoxyacetic acid by mass spectrometry. The identity of the compound was confirmed by synthesis.
The Effect of Lithium on the Iodide Concentrating Mechanism in Mouse Salivary Gland
Authors: Lazarus J. H. , Muston H. L.
Published: July 2010

Abstract The iodide concentrating mechanism, measured as the gland to plasma (G/P)125I‐ concentration ratio, was measured in male mouse submandibular glands after the animals had been fed with varying amounts of lithium chloride for intervals ranging from 0 to 8 weeks. After acute exposure (by injection) to lithium the G/P 125I‐ fell compared to control values and was further depressed at high serum lithium values. Chronic exposure to lithium was characterised by an increase in the G/P 125I‐ ratios at therapeutic serum lithium concentrations. It is suggested that lithium has a direct effect on the iodide concentrating mechanism that may be independent of any action of thyroid stimulating hormone during this process. The effect may be important in the formation of lithium induced goitre.
Enhancement of Urine Prostaglandin Excretion by Chlorazanil in Dogs
Authors: Olsen Uffe Bang , Ahnfelt‐Rønne Ian
Published: July 2010

Abstract In conscious dogs chlorazanil (2.5 mg/kg intravenously) markedly enhanced (5‐10 fold) urinary excretion of prostaglandins E2 and F2α. The effect came to a peak at 15‐30 min. following the administration. Chlorazanil did not modify renal blood flow or inulin clearance in non‐pretreated or indomethacin pretreated dogs and the plasma renin activity remained unchanged. A marginal natriuretic and antikaliuretic activity by chlorazanil was similarly observed in non‐pretreated dogs and dogs pretreated with indomethacin. The possible effects of the prostaglandins released by chlorazanil remained obscure. In vitro chlorazanil (10‐4 M) exhibited a moderate inhibition of 15‐OH‐prostaglandin dehydrogenase but an enhanced excretion of 15‐keto‐13, 14‐dihydro PGF2α in vivo suggested that chlorazanil increased renal prostaglandin activity by increased prostaglandin synthesis, probably due to increased precursor availability. This was presumably mediated by some as yet unknown factor since chlorazanil (4 × 10‐5 M) failed to affect the release of precursor and prostaglandins from isolated Krebs‐Henseleit perfused rabbit kidneys.
Metabolism of Zearalenone in Rat Liver
Authors: Kiessling K.‐H. , Pettersson H.
Published: July 2010

Abstract The metabolism of zearalenone in rat liver has been investigated. The studies were performed mainly with liver homogenate, though isolated microsomes and hepatocytes have also been used. Zearalenone was metabolized along two principal pathways, conjugation with glucuronic acid, which was the main route and reduction to an isomer of zearalenol. In no case, however, could all zearalenone metabolized be accounted for as conjugated zearalenone and free and conjugated zearalenol. Therefore another, so far unknown metabolite cannot be excluded. Reduction to zearalenol could be increased three times by the addition of NADH (or NADPH) and is probably catalyzed by a hydroxysteroid dehydrogenase. Some 25–50 per cent of the zearalenol could be conjugated, depending on the incubation conditions. The capacity of hepatocytes to eliminate zearalenone was estimated to be about 100 μg per gram of liver in one hour. With a liver homogenate the highest value obtained was 82 μg.
Bioavailability of Four Different Pharmaceutical Preparations of Carbamazepine
Authors: Pynnönen S. , Mäntylä R. , Iisalo E.
Published: July 2010

Abstract The bioavailabilities of two tablet brands carbamazepine (CBZ) (Tegretol®, A; Neurotol®, B) were compared with two new experimental preparations (C, D). Formulation A showed a more sustained release nature than did the other formulations. The AUCs0→∞ gave no significant differences between treatment A and three other treatments. However, if AUC0→72 was calculated instead of AUC0→∞, the preparation A gave the significantly lower bioavailability than the other compounds. Formulations A and B are marketed as generically equivalent preparations in Finland. However, their pharmacokinetic parameters after a single dose were different.
Effects of Prostaglandins on the Smooth Muscle of the Urinary Tract
Authors: Andersson K–E , Forman A.
Published: July 2010

Abstract A short review is given of the effects of prostaglandins on the smooth muscle of the bladder, urethra and ureter. In several animal species and in man, prostaglandins of the E and F types contract the detrusor. The contractions develop slowly and are not affected by tetrodotoxin, phenoxybenzamine, or atropine, suggesting a direct effect on the smooth muscle cell. However, evidence is also available suggesting a role of the prostaglandins as modulators of transmitter release in the bladder. In animals as well as in man, urethral smooth muscle is contracted by prostaglandin F2α, but relaxed by prostaglandins E1 and E2. The smooth muscle of the ureter seems to react similarly, but published results vary. The detailed mode of action, and the role of prostaglandins in the control of activity in urinary tract smooth muscle remain to be established.
Development of Alcohol Dehydrogenase and Aldehyde Dehydrogenases in the Offspring of Female Rats Chronically Treated with Ethanol
Authors: Sjöblom Mats , Øisund Jan‐Fredrik , Mørland Jørg
Published: July 2010

Abstract The influence of maternal ethanol drinking on the development of alcohol dehydrogenase and aldehyde dehydrogenases in the liver of the offspring was studied in Wistar rats. No statistically significant differences were found between the ethanol group and the control group.
Haematological Anomalies in a Fresh Water Teleost, Colisafasciatus, on Acute Exposure to Cobalt
Authors: Srivastava Anil K. , Agrawal Shanker Ji
Published: July 2010

Abstract Colisa fasciatus, a fresh water teleost, when exposed for 90 hrs to a sublethal concentration of 195 p. p. m. (0.87 of the 96 hrs LC50 value) cobalt chloride elicited leucopenia due to reduction in the number of circulating small lymphocytes. The treatment also caused decline in blood clotting time with a concomitant increase in the abundance of circulating thrombocytes. No differences in total erythrocyte count, haematocrit, erythrocyte sedimentation rate, and haemoglobin values were found between the control and treated fish. The hepatosomatic index of fish increased significantly after exposure to cobalt. Results are discussed in terms of fish's reaction to acute stress.
The Distribution of Soluble Copper‐ and Zinc‐binding Proteins in Goat Liver
Authors: Mjör‐Grimsrud Milica , Søli Nils E. , Sivertsen Tore
Published: July 2010

Abstract The distributions of copper and zinc in the soluble proteins from goat liver after gel filtration were determined. Samples from normal slaughtered animals as well as from experimentally copper‐loaded goats were tested. The copper‐ and zinc‐binding proteins were mainly separated into 3 different fractions. The approximate molecular weights were >65,000, 35,000 and 10,000. Varying amounts of zinc were eluted in a fourth fraction of molecular weight less than 2000. The results indicate that the distribution of copper and zinc among soluble metal‐binding proteins are highly dependent on the total liver zinc concentration. In the majority of samples, with zinc levels within 20 to 45 γg/g wet weight, the dominating copper‐ and zinc‐binding protein fraction was the high‐molecular weight fraction. This did not seem to be influenced by the total liver copper level. In the samples with high total liver zinc levels (>60 pg/g w.w.) there was a shift in protein distribution of both metals toward the low‐molecular weight fractions.
Fluoride and Energy Metabolism in LS Cells
Authors: Holland Roy I. , Hongslo Jan K.
Published: July 2010

Abstract Six mM fluoride had no effect on lactate production in LS cells incubated in Eagle's minimum essential medium. In Krebs‐Ringer phosphate buffer with 10 mM glucose inhibition was found with 3mM fluoride. The fluoride effect was similar in aerobic and anaerobic conditions. Twelve mM fluoride had no inhibitory effect on ATP levels in LS cells.
Urinary Elimination of Nitrazepam and its Main Metabolites
Authors: Kangas L.
Published: July 2010

Abstract Nitrazepam and its main metabolites, 7‐aminonitrazepam and 7‐acetamidonitrazepam, free and conjugated, were determined in the human urine after a single oral dose of 5 mg. The determinations were performed by GLC method using 63Ni‐EC‐detector for unchanged nitrazepam and nitrogen selective detector for the metabolites. Unchanged nitrazepam was poorly eliminated through the kidneys (about 1 per cent of the dose). The interindividual variation of total excreted urinary metabolites was large ranging between 848‐4933 pg (17‐99 per cent of the dose during 7 days). Of this amount conjugated metabolites made up 57 per cent. The urinary half‐lives of free and conjugated 7‐aminonitrazepam were (mean and ranges) 44 (23‐65) and 46 (25‐69) hrs, and of 7‐acetamidonitrazepam 12 (5‐31) and 18 (5‐46) hrs, respectively. The half‐lives of the excreted amounts of the metabolites did not correlate with any pharmacokinetic parameter of unchanged nitrazepam in serum.
Changes in Protein, RNA and DNA Content in Various Rat Organs after Long‐ter m Intake of Ethanol
Authors: Smith‐Kielland Anne , Merland Jørg
Published: July 2010

Abstract Male Wistar rats were given ethanol (approximately 25% of total caloric intake), while two different control groups were pair‐fed isocaloric amounts of lipids or sucrose. After 7‐10 weeks the following organs were studied: liver, cerebrum, heart, diaphragm, kidneys and testes. In fasted, ethanol treated rats there was a reduction in the hepatic concentration of RNA and the cerebral RNA/DNA ratio, when compared to both control groups, while no effects were found with respect to organ weight and amounts of protein, RNA or DNA in heart, diaphragm, kidneys and testes. When fed, ethanol treated animals were compared to both control groups, no effects on organ weight and composition were found in any tissue studied. Several significant differences were registered in the ethanol group as compared to one control group only, as well as between the two control groups. The consumption of ethanol (25% of total calories) thus caused only minor alterations in gross organ composition. These results also indicate the importance of interpreting with care any apparent effect of ethanol ingestion, unless at least two different control groups have been employed.
Reproductive and Teratological Studies with a New Aminoglycoside: Netilmicin (Sch 20569)
Authors: Bamonte F. , Albiero L. , Ongini E.
Published: July 2010

Abstract Reproductive and teratological studies were undertaken with netilmicin (Sch 20569), a new semisynthetic aminoglycoside antibiotic structurally related to sisomicin. The administration of 32 and 80 mg/kg/day, by the intramuscular route, in the rat prior to and during pregnancy and lactation did not affect the fertility of animals, the resorptions rate and the vitality of the litters until the second generation. Also in the rabbit, the dose of 32 mg/kg/day by intramuscular route during pregnancy did not cause any embryotoxic effect. No gross malformations were observed in both species. The minor skeletal malformation, described as “wavy ribs”, was observed at a significant level only in the rat foetuses generated by dams treated with a dose as high as 80 mg/kg/day by the intramuscular route.
Dextran‐induced Lowering of Parameters of the Kallikrein‐kinin System in Rat Plasma: Significance of Monoamine‐depleting Agents
Authors: Briseid Kjell , Berstad Jan
Published: July 2010

Abstract Significant reductions were registered in the plasma levels of prekallikrein proactivator (pro‐PKA), prekallikrein (PK), and high molecular weight kininogen (HMWK) 3‐5 min. after the intravenous injection into rats of serotonin (0.02‐0.20 mg/kg) or noradrenaline (0.02 mg/kg), whereas adrenaline (0.02 mg/kg) showed no effect, and tyramine (3.0 mg/kg) only slightly lowered the parameters mentioned. Pretreatment with reserpine (1.5 mg/kg) injected intraperitoneally 24 hours before dextran (10 mg/100 g) inhibited the dextran‐induced lowering of pro‐PKA and PK, but not the lowering of HMWK, while the effects of serotonin (0.13 mg/kg) were not influenced. After pretreatment of the rats with guanethidine (150 mg and 150 mg/kg respectively 48 hours and 24 hours before dextran) the dextran‐induced reductions in the levels of pro‐PKA and PK took place to the same extent as in control rats. while the lowering of HMWK was abolished. Pretreatment with reserpine protected against dextran‐induced oedemas, whereas pretreatment with guanethidine did not. It is concluded that catecholamines are probably not important in the initial phase of the dextran reaction in the rat, whereas serotonin seems to be an essential factor at this stage, as it is known to be during the fully developed dextran reaction. The results indicate that HMWK is not essential in connection with the early events of the dextran reaction, whereas the parameters pro‐PKA and PK seem to be of primary importance during this phase.
Haematological Effects of Nickel Toxicity on a Fresh Water Teleost, Colisa fasciatus
Authors: Agrawal Shanker J. , Srivastava Anil K. , Chaudhry H. S.
Published: July 2010

Abstract Colisa fasciatius, a freshwater teleost, were exposed for 90 hrs to 45 p.p.m. nickel sulphate under static test conditions. The treatment resulted in leucopenia due to reduction in the number of small lymphocytes and polycythemia with concomitant increases in the haematocrit and haemoglobin values, and in retardation of the erythrocyte sedimentation rate of the moribund fish. No differences in total thrombocyte count, clotting time, and hepatosomatic index were found between the control and the treated fish. Lymphopenia and erythrocytosis may be used in presumptive monitoring nickel toxicity in fish.
Factors Influencing Absorption and Retention of Oral 109Cd in Mice: Age, Pretreatment and Subsequent Treatment with Non‐radioactive Cadmium
Authors: Engström Birgitta , Nordberg Gunnar F.
Published: July 2010

Abstract The influence of age, pretreatment with CdCl2 and long‐term oral treatment with CdSO4 on whole‐body retention, organ distribution and the biological half‐time of 109CdCl2 (given as a single oral dose) was studied in mice in three separate experiments: I) Male CBA‐mice, 1, 3 and 6 months of age, were given a single oral dose of CdCl2 labelled with 109Cd. The whole‐body retention of the radiolabelled cadmium was inversely related to age. This was explained by a significantly higher intestinal absorption of 109Cd in the younger mice, compared to the older. No influence of age on the biological half‐time of 109Cd was observed. II) Three groups of adult of male CBA‐mice were pretreated with 75 mgCd/l (as CdCl2) in the drinking water for 130, 13 or 0 days, respectively, before receiving a single oral dose of CdCl2 labelled with 109Cd. The two pretreated groups showed higher intestinal absorption of radio‐labelled cadmium and a statistically significant longer biological half‐time of 109Cd compared to mice not pretreated with cadmium. The organ retention of radiolabelled cadmium was markedly higher in mice given cadmium in the drinking water compared with those given deionized water. III) Male and female adult CBA‐mice were exposed to a single oral dose of CdCl2 labelled with 109Cd, via stomachtube. and were thereafter given either deionized water (control group) or 50 mgCd/l (as CdCO4) in the drinking water continuously for 18 months. The organ retention of the radiolabelled cadmium was higher in mice exposed to cadmium in the drinking water compared to those given deionized water. Mice exposed to cadmium via the drinking water had a markedly longer biological half‐time of 109Cd compared to non‐Cd‐exposed mice. In all experiments the animals retaining a larger proportion of the cadmium dose showed higher liver: kidney ratios of the radiolabelled cadmium compared to mice retaining less cadmium. The conclusions of the present studies were: Age is of significant importance to the metabolism of cadmium due to the marked raise in intestinal absorption in the youngest age. pretreatment with cadmium caused a higher intestinal absorption of radiolabelled cadmium. A longer biological hall‐time of 109Cd was seen both after pretreatment and subsequent treatment with cadmium.
Inhibitory Effect of Ethanol on 5‐Hydroxytryptamine (Serotonin) Uptake in Human Blood Platelets in Vitro
Authors: Lingjærde Odd
Published: July 2010

Abstract Ethanol in concentrations higher than 10‐2 M (or about 0.5 ‰ W/W) inhibited the uptake of 14C‐5‐hydroxytryptamine (serotonin) in human blood platelets in an artificial, protein‐free medium, by a noncompetitive mechanism. The inhibition was not influenced by the alcohol dehydrogenase inhibitor methylpyrazole (10‐3 M). In concentrations up to 0.1M, ethanol had no effect on 5‐HT efflux from the platelets. At higher concentrations, ethanol increased efflux. Inhibition of 5‐HT uptake was found to increase progressively in the sequence methanol ‐ ethanol ‐ propanol ‐ butanol.
Antagonism of Reserpine‐induced Hypothermia in Mice by Some β‐Adrenoceptor Agonists
Authors: Ross Svante B.
Published: July 2010

Abstract: The reversal of reserpine‐induced hypothermia in mice by three β‐adrenoceptor agonists, terbutaline, salbutamol and clenbuterol, was examined. Terbutaline, 5 and 20 mg/kg intraperitoneally, caused a slight reversal of the hypothermia. Salbutamol, 5 mg/kg intraperitoneally, produced a pronounced and 1 mg/kg a slight reversal. Clenbuterol was very potent in reversing the hypothermic effect of reserpine with significant effect at 0.02 mg/kg intraperitoneally. Propranolol, 2.5 mg/kg intraperitoneally, and the selective β2‐receptor antagonist IPS 339, 5 mg/kg intraperitoneally, almost completely antagonized the effect of clenbuterol, 1 mg/kg intraperitoneally. The β‐receptor antagonist metoprolol at 5 and 25 mg/kg intraperitoneally only partially antagonized the effect of clenbuterol. Since clenbuterol is much more lipophilic than salbutamol and terbutaline, it is suggested that the reserpine reversal produced by clenbuterol is at least partially of central origin and possibly mediated by stimulation of noradrenergic β2 receptors.
Single Dose Pharmacokinetics of Doxepin in Healthy Volunteers
Authors: Virtanen R. , Scheinin M. , Iisalo E.
Published: July 2010

Abstract: The pharmacokinetics of orally administered doxepin (50 mg) was studied in 8 healthy volunteers. Doxepin (DOX) and desmethyldoxepin (DDOX) concentrations in serum (or plasma) and red blood cells (RBCs) were measured by radioimmunoassay. Peak serum concentrations of DOX were observed at 1–2 hours and they ranged between 59.1–107.4 nmol/1. DOX disappearance was biphasic with a mean distribution half‐life of 2.0 hrs and elimination half‐life of 17.9 hrs. The mean total apparent volume of distribution was 22.7 l/kg and plasma clearance 0.93 l/hr/kg. The estimated mean first‐pass metabolism of DOX was 71 % assuming complete absorption. Peak DDOX concentrations were observed at 1–6 hours and they ranged between 35.0–117.8 nmol/1. DDOX elimination was monophasic with a mean apparent half‐life of 28.5 hours. Equilibrium dialysis gave a mean protein binding of 75.5% for DOX and 76.0% for DDOX. A highly time dependent and interindividually variable RBC/plasma concentration ratio was observed for both substances. Initially the plasma concentrations were 3–4 times higher than the respective RBC concentrations, but at later time points more DOX and DDOX could be found from the RBCs than from plasma. The major reason for this seemed to be a slower elimination of both drugs from the erythrocytes than from plasma.
Effect of the Antitumour Agent 5‐(3,3‐Dimethyl‐1‐triazeno imidazole‐4‐carboxamide (DTIC) on Cyclic AMP Levels in Intact MH1C1 Hepatoma Cells
Authors: Haffner Frode , Christoffersen Thoralf
Published: July 2010

Abstract: Addition of the cytostatic agent 5‐(3,3‐dimethyl‐1‐triazeno)‐imidazole‐carboxamide (DTIC, dacarbazin) to MH1C1 hepatoma cells, alone or in combination with adrenaline, was shown to elevate intracellular cyclic AMP. The cyclic AMP level was increased from basal values of about 0.40 to about 0.75 pmol/mg protein 10 min. after DTIC addition. Accumulation of cyclic AMP in response to a supramaximal concentration of adrenaline is amplified in a dose‐dependent way by 0.1–2 mM DTIC. The effect is apparently due to inhibition of cyclic AMP breakdown, since DTIC inhibits the Iow‐Km form of the cyclic AMP phosphodiesterase without significantly affecting the adenylate cyclase activity of MH1C1 homogenates.
Anti‐aggressive Effect of Zimelidine in Isolated Mice
Authors: ögren S.‐O. , Holm Ann‐Charlotte , Renyi Anna L. , Ross S. B.
Published: July 2010

Abstract: The anti‐aggressive actions of zimelidine, a 5‐HT uptake inhibitor, and p‐chloroamphetamine (PCA), a 5‐HT releasing compound, were examined in isolated male mice. Both agents blocked the aggressive behaviour in a dose range in which they produced inhibition of the accumulation of 14C‐5‐HT in brain slices. The time course of the inhibition of both compounds was related to their effects on 5‐HT mechanisms (5‐HT uptake inhibition or 5‐HT release) in the brain. These findings suggest that zimelidine and PCA inhibit aggressive behaviour in mice via enhancement of post‐synaptic activity in certain 5‐HT neuronal pathways. The possible relationship between the role of 5‐HT in the anti‐aggressive effect and in anxiolytic effects is discussed.
Effects of Isoprenaline and l‐Methyl‐3‐isobutylxanthine on Cyclic Nucleotides and Cyclic AMP‐dependent Protein Kinase in Rabbit Colon Smooth Muscle
Authors: Andersson Rolf G. G. , Börjesson Sverker , Nilsson K. B.
Published: July 2010

Abstract From a homogenate of rabbit colon a crude protein kinase was isolated. The phosphorylation of histone by this enzyme was maximal at 20 mM NaF. Higher concentrations inhibited the incorporation of 32P. After chromatography on a DEAE‐cellulose column the crude protein kinase was partly purified. Cyclic AMP and cGMP stimulated the protein kinases eluted at 0.09 M‐NaCl (Type I) and at ∼0.2M‐NaCl (Type II). The main peak was of type II. Mix (l‐methyl‐3‐isobutylxanthine) relaxed the rabbit colon muscle. The increase in the protein kinase activity was closely correlated to the changes of the cAMP level. The cGMP content was also increased. Isoprenaline increased the cAMP level and the protein kinase activity of the colon muscle. Isoprenaline had no effect on the cGMP level. It is suggested that relaxing drugs which increase the cAMP level of rabbit colon muscle may activate protein kinase. This enzyme might be an important factor of the cAMP mediated relaxing mechanism.
Behavioural and Glial Cell Effects of Inhalation Exposure to Styrene Vapour with Special Reference to Interactions of Simultaneous Peroral Ethanol Intake
Authors: Savolainen H. , Helojoki M. , Tengén‐Junnila M.
Published: July 2010

Abstract Male Wistar rats were exposed to 300 p.p.m. of styrene vapour with simultaneous ethanol ingestion for 4 to 17 weeks. The effects on behaviour were analyzed after 4, 9 and 13 weeks of the experiment. The most manifest behavioural effects were found in rats exposed to the combination, and the changes included increased preening time at the 4th week and increased ambulation and rearing at the end of the exposure. The ethanol ingestion affected also the accumulation of the solvent burden by delaying the peak solvent concentration in the perirenal fat to the 8th week of exposure. The fat solvent concentration did not differ from each other in the two groups at the end of the experiment, and they were similar as compared the concentration found in phenobarbital‐pretreated rats exposed for reference. The styrene exposure had almost no effects on cerebral glial cells whereas ethanol induced unexpectedly increased protein destruction in them throughout the experiment. Co‐exposure to ethanol and styrene decreased the magnitude of protein destruction in the glial cells. Withdrawal of the rats after an 8‐week exposure showed that the styrene effects were largely abolished in two weeks of exposure‐free period as analyzed by the determination of brain RNA and acid proteinase activity. Brain RNA was lower than control after two weeks of ethanol deprivation. The present data indicate that marked metabolic interactions between ethanol and styrene take place in agreement with experience on other similar solvent combinations.
On the Role of Cyclic AMP in the Cytotoxic Effect of Fluoride
Authors: Holland Roy I. , Hongslo Jan K. , Christoffersen Thoralf
Published: July 2010

Abstract The possible role of adenosine 3′,5′‐monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl‐cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP‐formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP.
Effect of Selenium on the Contractile Force of Isolated and Perfused Guinea‐pig Heart
Authors: Franconi Flavia , Manghi Nicoletta , Giotti Alberto , Martini Flavio , Dini Germana
Published: July 2010

Abstract Sodium selenite showed a negative inotropic effect on isolated and perfused guinea‐pig heart. The effect was dose‐dependent and was not reversed by a higher calcium concentration or by washing. Electronic microscopy revealed mitochondrial alterations. Pyruvate and lactate 2× 10‐3M seemed able to reverse the negative inotropic effect and mitochondrial alterations induced by sodium selenite.
Effect of Chronic Lead on the Haematology, Blood Glutathione and Bone Marrow Non‐Haeme Iron of Dogs
Authors: Mitema Eric S. , Oehme F. W. , Penumarthy L.
Published: July 2010

Abstract Ten clinically normal male beagle dogs were used in the study. Two dogs served as control, 4 received 2 mg lead/kg daily and 4 received 5 mg lead/kg/daily. Lead was administered for 13 weeks, after which one‐half of each experimental group was treated with calcium ethylene diaminetetraacetate (CaEDTA) for 5 days. All animals were then monitored for another 4 weeks. Blood lead levels, haematology, blood glutathione concentration, and the number of bone marrow cells with stainable iron granules were measured weekly during the 18‐week experimental period. Clinical signs of poisoning were observed only in one dog in the high dose group after 6 weeks. The signs included emaciation, anorexia, muscular weakness, evidence of abdominal pain and depression. These signs were reversed with cessation of lead dosing and CaEDTA treatment. Blood lead levels and the number of marrow cells with non‐haeme iron increased in both lead‐dosed groups; nucleated red blood cells increased only in high lead dosed group. There was a trend for an increased packed cell volume in all groups; however, the high lead dosed group did not increase as fast. No significant changes were observed in blood glutathione concentration and in other haematologic parameters. There were no differences in the parameters studied between the dogs treated with CaEDTA and those not so treated. Blood lead levels and the number of nucleated red blood cells decreased after cessation of lead administration and the number of marrow cells with iron also tended to decrease after lead removal.
A Comparison of the Effects of Intravenous Serotonin and Dextran on the Levels of Factor XII, Prekallikrein and Plasminogen in Rat Plasma
Authors: Berstad Jan
Published: July 2010

Abstract It was previously observed that serotonin injected intravenously into the rat caused significant reductions in the prekallikrein activator (PKA) and the benzoyl arginine ethyl ester (BAEe)‐esterase activities induced in rat plasma by acetone/kaolin activation. In the present work it was demonstrated that serotonin was unable to exert these effects in vitro, in plasma or in whole blood. The assay of PKA and BAEe‐esterase activities after gel filtration on Sephadex G‐100 of acetone‐activated plasma from rats treated with serotonin 0.10 mg/kg revealed reduced fragmentation of factor XII, and reduced levels of kallikrein and of an additional BAEe‐esterase. Serotonin also lowered the plasminogen level. The serotonin‐induced reductions of PKA and BAEe‐esterase were inhibited by pretreatment of the rats with ε‐aminocaproic acid. Evidence was provided that serotonin did not lower the plasma level of factor XII of the coagulation system, but the level of a factor of significance for the activation of factor XII. All the above‐mentioned serotonin effects were fundamentally similar to the corresponding effects caused by dextran. It is concluded that the effects of dextran on the plasma parameters mentioned are mediated by the release of endogenous serotonin.
Glucuronide and Sulphate Binding to Subcellular Fractions of Rat Liver
Authors: Norling Anja , Hänninen Osmo
Published: July 2010

Abstract The binding of glucuronides to various liver subfractions and to bovine serum albumin correlated with their molecular weight. Higher molecular weight glucuronides bound more readily. 4‐Methylumbelliferyl‐glucuronide had some of the characteristics of phenolphthaleinglucuronide. Simple phenolic glucuronides were much less retained by various hepatic fractions. Glucuronides were most effectively bound to mitochondrial subfractions. Sulphates of 4‐nitrophenol and phenolphthalein were bound to the same degree to bovine serum albumin and hepatic cytosol despite their different molecular structures and weights.
The Effect of Antineoplastic Drugs on the Pharmacokinetics of Antipyrine in the Rat
Authors: Høyem‐Johansen T. , Slerdal L. , Høylandskjær A. , Aarbakke J.
Published: July 2010

Abstract: The pharmacokinetics of antipyrine was investigated in individual rats pretreated with cyclophosphamide, 5‐fluorouracil and methotrexate. Before oral dosing a complete emptying of the rat stomach was obtained by 24 hours of fasting and prevention of coprophagy. Antipyrine was given intravenously via a cannula in an inguinal vein and repeated samples of blood were drawn from a cannula in an inguinal artery. Systemic availability of oral antipyrine was studied in rats given the 14C‐labelled drug intravenously and the 3H‐labelled drug orally after pretreatment with cyclophosphamide. The log plasma concentration versus time curve of antipyrine given orally showed a short absorption and distribution phase followed by a linear elimination phase. Peak antipyrine concentrations were reached 3–6 minutes after oral dosing in control rats. The rate of absorption of antipyrine was moderately decreased by methotrexate. All drugs increased the area under the curve (AUC) of antipyrine. The systemic availability of oral antipyrine after cyclophosphamide pretreatment (0.88) was not changed, but the metabolic clearance of the drug was reduced. The apparent elimination rate constant was decreased by methotrexate and the apparent volume of distribution was decreased by cyclophosphamide and 5‐fluorouracil. The results indicate that antineoplastic agents may change drug kinetics in different ways in rats.
Toxicity of Soman after Repetitive Injection of Sublethal Doses in Guinea‐Pig and Mouse
Authors: Sterri Sigrun H. , Lyngaas Synnøve , Fonnum Frode
Published: July 2010

Abstract: Injection of sublethal doses of soman in guinea‐pig and mouse subcutaneously every 3.5, 8, 12 or 24 hours led to cumulative LD50 doses which were markedly higher than the acute one. When animals were exposed every 24 hrs to half LD50 doses of soman, a majority of guinea‐pigs but relatively few mice, survived a total exposure of 5–6 times the acute LD50 dose. Guinea‐pig brain and diaphragm acetylcholinesterase activities declined steadily during the repeated soman exposure. Plasma cholinesterase activity was less than 10% 1 hr after soman injection, but was restored to 40–50% of control within 24 hrs. Liver aliesterase activity was not significantly inhibited by soman, whereas plasma aliesterase activity was 70% inhibited after 1 hr and restored to control level within 24 hrs. TOCP treatment of guinea‐pig led to 3‐fold increase in acute soman toxicity, and reduced their tolerance from more than 6 LD50 to 2.5 LD50 dose of soman. It is concluded that the recovery of plasma aliesterase and cholinesterase play an important part in the observed tolerance towards repeated soman treatment.
The Oral Absorption of Ampicillin, Pivampicillin and Amoxycillin in Infants and Children
Authors: Eriksson Margareta , Bolme Per
Published: July 2010

Abstract: The oral absorption of comparable doses of mixtures of ampicillin, amoxycillin and pivampicillin was studied in 38 children from 6 months to 6 years of age. Plasma concentrations following pivampicillin and amoxycillin were higher than those following the administration of ampicillin. No significant difference was found between amoxycillin and pivampicillin. The oral absorption of pivampicillin mixture was further studied in 12 infants, 0–1 month and 1–5 months of age. The absorption was faster in infants and children more than 6 months of age than in the 1–5 months group. The excretion, indicated by the slope of the plasma concentration curve, was delayed in infants less than one month of age. The oral absorption of amoxycillin and pivampicillin from tablets was also studied in 12 infants and children, 6 months‐6 years of age, in the same doses as when mixtures were studied and was more complete with pivampicillin than with amoxycillin. The absorption of pivampicillin was more complete from tablets than from mixture. Also with amoxycillin there was a trend towards more efficient absorption from tablet than from mixture.
Investigations on the Occurrence of Cytidine 3′,5′ Monophosphate (cCMP) in Tissues
Authors: Wikberg Jarl E. S. , Wingren Gun B.
Published: July 2010

Abstract: A specific and sensitive radioimmunoassay (RIA) for the detection of cCMP was developed. Antibodies were prepared by immunization of rabbits with succinyl cCMP conjugated to human albumin. In the RIA commercially available 3H‐cCMP was used as labeled antigen. Low amounts (0.4–2.6 pmol/g w.wt.) of immunoreactive material could be detected in extracts of brain, heart, ileum, kidney, liver, lung, spleen, testis and uterus from rats, guinea‐pigs and frogs. The immunoassayable material in rat liver was subjected to column chromatography on AG 1‐X8 anion exchange resin. The radioimmunoassayable material isolated from the liver did not cochromatograph with authentic tritiated or unlabeled cCMP. The chromatographic properties of the immunoreactive material did not change in regenerating livers – following partial hepatectomy, or after pronase treatment. However, after treatment with pronase the amount of assayable material, extracted from the rat liver, increased. It is suggested that cCMP – as such – is not present, in detectable amounts, in extracts prepared by commonly used procedures for isolation of cyclic nucleotides. The chemical nature of the cCMP immunoreactive material isolated from rat liver is at present unclear.
Net Sodium and Glucose Transport in the Jejunum, Ileum and Colon of Anaesthetized Rats in Response to Intraluminal Theophylline and Anionic Surfactants
Authors: Sund Reidar Bredo , Olsen Grethe
Published: July 2010

Abstract: Osmotically balanced solutions of sodium chloride and glucose (5–150 mmol/l) were instilled into rats prepared with two tied intestinal loops (jej‐col or il‐col). Luminal accumulation or disappearance of Na and glucose after 15 min. was determined, and the parameters of the linear regression lines of net Na flux (y) with initial Na concentration (x) calculated. Control cation and glucose transport were changed by dioctylsulphosuccinate and dodecylsulphate in the way described by Sund & Matheson (1978). Theophylline (10–25 mmol/l) on the other hand did not alter glucose disappearance, and had a distinctly dissimilar effect on net Na transport compared to the surfactants. This could be described as a parallel displacement of the control regression lines to the right, without improvement in correlation. This effect of theophylline was greatest in the ileum, where mean luminal Na concentration corresponding to zero net transport was raised from about 70 mmol/l under control condition to values above 200 mmol/l. The results are consistent with the view that theophylline mainly affects transcellular and the surfactants mainly paracellular sodium transport, and do not support the theory that the effect of dioctylsulphosuccinate on intestinal transport is related to an activation of the mucosal adenylate cyclase/cAMP system, at least not in short term experiments.
Atropine in Mouse Brain and Plasma Quantified by Mass Fragmentography
Authors: Palmér L. , Edgar J. , Lundgren G. , Karlén B. , Hermansson J.
Published: July 2010

Abstract: A gas chromatography ‐ mass spectrometric method has been developed for the assay of atropine in blood and brain tissue samples of mice. The method is based on the use of deuterium labelled atropine as internal standard and has a sensitivity allowing analyses of small brain structures, e.g. striatum and hippocampus. The method has been used to study the distribution and disposition of atropine in blood and brain of mice. The data obtained in blood can best be fitted by a two compartment open model with the elimination half‐life of about 100 min., which was similar to that in brain. The concentration in brain structures with different cholinergic neuronal density was about the same.
Pharmacological Characterization of the Autonomous Innervation of the Guinea Pig Tracheobronchial Smooth Muscle
Authors: Grundström Nils , Andersson Rolf G. G. , Wikberg Jarl E. S.
Published: July 2010

Abstract: From the trachea, main bronchi and hilus bronchi of guinea pigs, preparations were isolated for registration of mechanical tension on electrical field stimulation and drugs. The trachea contracted on short trains of electrical stimulation. Usually these contractions were followed by a relaxant response. The contractions were abolished while the relaxations were potentiated by atropine. In the main bronchi field stimulation induced a contractile response which was abolished by atropine. In the latter preparation relaxant responses were never observed, even not after atropine. In the trachea and main bronchi neither the α1 blocker prazosin nor the α2 blocker yohimbine affected the contractile or relaxant responses when used in α‐blocking concentrations. The relaxant response in trachea was neither affected by the “P1 blocker” theophylline nor by the “P2 blocker” quinidine but it was partially inhibited by guanethidine or β‐blocking agents. The hilus bronchi contracted on field stimulation as well as by histamine. The contractile response on electrical stimulation was only slightly inhibited by atropine or guanethidine. In all three preparations responses on field stimulation were abolished by tetrodotoxin. It is suggested that in both trachea and main bronchi excitatory cholinergic innervation is present. Further, the trachea but not the main bronchi is innervated by both adrenergic and nonadrenergic inhibitory nerves. The hilus bronchi contains a non‐adrenergic non‐cholinergic excitatory nervous system.
Persistent Organochlorinated Compounds in Norwegian Human Milk in 1979
Authors: Skaare Janneche Utne
Published: July 2010

Abstract: The levels of the persistent organochlorine compounds HCB, sum‐DDT (1.1 DDE+1.1 DDD+DDT), DDE and PCBs were determined in 133 Norwegian human milk samples from 7 cities with various degrees of industrialization. All samples contained organochlorines. No dramatic geographical differences were observed. The average HCB, sum‐DDT, DDE and PCB levels in human milk were 2.1±1.0, 29.8±23.5, 25.8±20.3 and 23.9±13.7 p.p.b. respectively (126±128, 1440±950, 1270±850 and 1210±690 p.p.b. respectively in human milk fat) which are among the lowest reported. The present results were compared to Norwegian results from 1970 and 1976. A slight decrease in the average HCB levels was observed from 1976–1979. The average PCB levels which doubled from 1970–1976 showed no or only a slight increase from 1976–1979. The distinct decrease in average sum‐DDT levels observed from 1970–1976 continued during the period 1976–1979. The present survey demonstrated that human milk is a good indicator substance in monitoring the environment for contamination by organochlorine compounds. The results were evaluated toxicologically by comparison with maximum residue limits and acceptable daily intakes (FAO/WHO 1978). It was concluded that the present levels of organochlorines in Norwegian human milk did not represent any threat to the infants' health.
Toxic Effects of Violamycin BI, Carminomycin and Daunorubicin on the Myocardium of Rabbits
Authors: Kirchner E. , Güttner J. , Fritsch R. S. , Härtl A. , Hoffmann H.
Published: July 2010

Abstract: Cardiac toxicity of the new anthracycline antitumour antibiotics violamycin BI (V) and carminomycin (C) was studied in comparison with daunorubicin (D). Rabbits were intravenously given total doses of 0.1–1.5 mg/kg V or C, and 0.64–18 mg/kg D, respectively, twice weekly for one month. When examined two to six days, two and four weeks, respectively, after the last drug administration the gross findings consisted of hydropericard, hydrothorax and ascites in some animals. Histologically, loss of striation and focal necrosis of cardiac muscle cells and subsequently chronic inflammatory reactions and/or proliferation of mesenchyma cells were mostly found. These alterations were somewhat more pronounced in rabbits treated with V than in animals received D or C. At equitoxic doses of the antibiotics tested the ultrastructural lesions in the myocardial cells were altogether less marked after treatment with D than with C or V.
Genetic Differences in Dimethylnitrosamine Mutagenicity in Vitro Associated with Mouse Hepatic Aryl Hydrocarbon Hydroxylase Activity Induced by 3‐Methylcholanthrene
Authors: Aune Tore , Dybing Erik , Nelson Sidney D. , Thorgeirsson Snorri S.
Published: July 2010

Abstract: The effects of 3‐methylcholanthrene (MC) pretreatment on metabolism and mutagenic activation of dimethylnitrosamine (DMN) were studied with liver subfractions from two strains of mice differing genetically with respect to aromatic hydrocarbon responsiveness. Both mutagenic activation and DMN N‐demethylase activity segregated with aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity as a dominant trait in appropriate crosses between C57BL/6J (Ahb Ahb) and DBA/2J (Ahd Ahd) mice. DMN metabolism and mutagenicity were increased by MC‐pretreatment in responsive Ahb Ahb and Ahb Ahd mice, but not in non‐responsive Ahd Ahd mice. This indicates the involvement of the Ah locus in the genetic regulation of these activities in mice. Deuteration of DMN reduced mutagenicity and DMN N‐demethylase activity by approximately 90 and 50 percent, respectively.
Dose‐related Bronchoconstriction with Methacholine in Rats, as Modified by Terbutaline Alone and in Combination with Theophylline
Authors: Salonen R. O. , Mattila M. J.
Published: July 2010

Abstract: Female Sprague Dawley rats under pentobarbitone anaesthesia, pancuronium relaxation, and artificial ventilation with constant volume, were given methacholine (MeCh) intravenously and the rise in intratracheal pressure indicated bronchoconstriction. Doses of MeCh (2, 3, and 4.5 μg) were given at 2‐min. intervals; another set of MeCh doses (4, 6, and 9 μg) were similarly given 20 min. later. The heights of the peak responses and “response areas” were measured. The sensitivity of the animals to MeCh remained constant throughout the experiment but the intratracheal pressure rose slowly even without MeCh. Terbutaline (20 μg/kg) alone and in combination with theophylline (5 mg/kg) counteracted MeCh bronchoconstriction but not MeCh bradycardia. Theophylline slightly enhanced terbutaline effect. ACh affected the heart rate relatively more than the bronchomotor tone. Rats sensitized with egg albumin showed increased sensitivity to MeCh after the antigen challenge but not without it. The heights of the peak responses proved somewhat more reliable than response areas to assess bronchoconstriction.
Cigarette Smoke Ventilation Decreases the Contractile Responses of Intestinal Smooth Muscle
Authors: Uotila Pekka , Männistö Jussi , Toivonen Hannu
Published: July 2010

Abstract: Hamster stomach strips or isolated rat colons were superfused by the effluent from isolated hamster or rat lungs, respectively. Cigarette smoke ventilation of the lungs caused a decrease in the contractile responses of hamster stomach strips to prostaglandin E2 and of rat colons to angiotensin II, when Krebs buffer was used as perfusion medium. On rat colons, diluted blood was as effective carrier of the inhibitory compounds as was the buffer solution.
The Passage of Flunitrazepam into Cerebrospinal Fluid in Man
Authors: Aaltonne Leena , Kanto Jussi , Iisalo Esko , Koski Kari , Salo Matti , Siirtola Taisto
Published: July 2010

Abstract: The passage of flunitrazepam into cerebrospinal fluid (CSF) was studied in 23 surgical patients (group 1), after a single 0.02 mg/kg intravenous injection, in 9 otherwise healthy patients undergoing neurological examination (group 2), after a single 2 mg oral dose, and in 9 chronically‐ill neurological patients (group 3), after 2 to 4 successive 2 mg oral doses. Flunitrazepam in plasma and the CSF was determined by gas chromatography and its plasma protein binding by equilibrium dialysis. Uptake of flunitrazepam into human CSF was found to be very fast: even 5 min. after intravenous injection the drug level in the CSF was 2.8 % of the corresponding plasma concentration. CSF levels increased up to 77 min. after intravenous injection. In group 2 the mean percentage level in the CSF was 23.5±13.0 (S.D.) and in group 3 it was 16.7±3.1. In group 1,22.9±8.0% of flunitrazepam was not bound to plasma protein, in group 2,12.1±8.3% and, in group 3,30.3±14.1 %. Groups 1 and 2 (P<0.01) and 2 and 3 (P<0.01) differ significantly from each other. In groups 2 and 3 there was no significant correlation between the percentage not bound to protein and CSF levels of flunitrazepam. The uptake of flunitrazepam by CSF provides an explanation for its rapid drug effects. Its binding to plasma protein is affected by disease and, possibly, by other drugs.
Postnatal Development of Renal Function in Piglets: Changes in Excretory Pattern of Sulphachlorpyridazine
Authors: Friis Christian
Published: July 2010

Abstract: The renal excretion of sulphachlorpyridazine (SCP) was measured in 34 unanaesthetized piglets 5–74 days of age. The renal handling of SCP was found to include: glomerular filtration, active tubular secretion and passive reabsorption. During the age period studied the clearance of ultrafiltrable SCP increased several times more than GFR (inulin clearance) indicating that the balance between filtration, secretion and reabsorption is changed during postnatal maturation. The age‐related change in clearance ratio possibly reflects both a greater increase in tubular secretory capacity than in glomerular filtration and a relative decrease in the passive reabsorption.