bluuebunny/crossref_metadata_2025 huggingface dataset:
Subacute and Chronic Trichloroethylene Poisoning: A Neuropathological Study in Rabbits
Authors: Bartonicek V. J. , Brun A.
Published: July 2010

Rabbits were given trichloroethylene parenterally in a subacute trial lasting for 29 days and in a chronic trial lasting from 41 to 247 days. Behaviour, body weight and sedimentation rate were followed. The rabbits were killed at different times during the trial and the brains examined histologically and histochemically for any pathological changes. Moderate changes in the form of diffuse chronic‐ischaemic or toxic nerve cell damage in the majority of the cranial nerve nuclei, in the Gasserian ganglion, the cerebellar cortex were demonstrated as well as increased neuronal acid phosphatase activity. However, no severe neurological disturbances and no changes in the sedimentation rate were noted. The clinically known neurological and/or psychic derangements in humans are discussed in relation to the present pathological findings in rabbits.
Doxycyclinum NFN: A Pharmacological and Bacteriological Investigation
Authors: Nielsen M. Lykkegaard , Laursen H. , Gauguin J. , Rosenkast P.
Published: July 2010

In normal human subjects multiple dose trial with an initial dose of 400 mg doxycycline and subsequent doses of 200 mg every 24 hours gave average minimum serum concentrations of between 1 and 2 μg doxycycline/ml serum. The average urine concentrations varied between 100 and 200 μg doxycycline/ml urine, and 42 per cent of the drug administered was excreted in the urine in an active form. The average renal clearance of doxycycline determined over 96 hours was 28 ml/min. In a single dose trial with 200 mg doxycycline, an 8‐hour renal clearance of doxycycline was found to be 13 per cent of the creatinine clearance, and the serum half‐life period was found to be 11.6 hours. Microbiological assay was used for all determinations of doxycycline in the serum and urine. The in vitro sensitivity of 211 urinary tract pathogens to doxycycline and oxytetra‐cycline was investigated in order to determine the minimum inhibitory concentration (MIC). The strains, which originated from patients with chronic urinary tract infections, were as a whole only slightly sensitive to the two tetracyclines. Compared with oxytetracycline, doxycycline, assessed at the MIC‐level, showed a higher bacteriostatic effect in vitro, especially against gram‐positive strains.
Effect of Carbon Tetrachloride Induced Progressive Liver Damage on the Metabolism of Hexobarbital and Bilirubinin Vivo
Authors: Vorne Martti , Alavaikko Martti
Published: July 2010

Rats were given 2 ml carbon tetrachloride per kg body weight subcutaneously 3 times a week. The development of liver changes was observed from histological specimens, and changes in the functional capacity of the liver were determined by measuring the hexobarbital sleeping time and the retention of bilirubin given to animals after carbon tetrachloride administration for 2, 4, 8, and 16 weeks. The animals receiving carbon tetrachloride gained weight more slowly, and their growth ceased shortly after two months of treatment. The relative liver weights of the rats receiving carbon tetrachloride did not differ from those of the controls after administration for 2 weeks, but after 4 weeks the relative liver weights of those rats receiving carbon tetrachloride were 12%, after 8 weeks 29%, and after 16 weeks 65% greater. It was noted that carbon tetrachloride had induced progressive morphological liver changes. Cirrhosis was apparent after 8 weeks of treatment and after 16 weeks it was severe. After 8 weeks of carbon tetrachloride administration the retention of exogenous bilirubin also increased, being 76% greater than in the controls. After 16 weeks of administration, bilirubin retention was 94% greater than in the controls. The hexobarbital sleeping time increased progressively: after 2 weeks it was twice as long as in the controls, after 4 weeks 2 1/2 times, after 8 weeks more than 3 times, and after 16 weeks approximately 10 times as long as in the controls.
Degradation of DOPA by Intestinal Microorganisms in Vitro
Authors: Bakke Olav M.
Published: July 2010

The degradation of L‐DOPA, 14C‐DL‐DOPA and possible phenolic metabolites in anaerobic incubates of rat caecal contents was studied by gas chromatography, thin‐layer chromatography and radiochromatogram scanning. The main pathway of DOPA metabolism involved degradation to 3,4‐dihydroxyphenylacetic acid which underwent decarboxylation or dehydroxylation to yield 4‐methylcatechol or 3‐hydroxyphenylacetic acid, respectively. The latter compound was decarboxylated to meta‐cresol in a few of the incubates. 3‐Hydroxy‐phenylpropionic acid was an additional metabolite which was apparently further metabolized afterprolonged incubation. The relevance of these findings to DOPA metabolism in the intestinal lumen in vivo is briefly discussed.
Further Studies on the Mode of Action of Amantadine
Authors: Strömberg U. , Svensson T. H.
Published: July 2010

The anti‐Parkinson agent amantadine, when administered to rats and mice, was found to cause increased motor activity in mice, and an increased flexor reflex activity in acutely spinalized rats and rotation to the side of the lesion in unilaterally striatotomized rats. This last‐mentioned effect was inhibited by blockers of the dopamine (DA) receptors in the corpus striatum and by previous depletion of the catecholamines (CA). The drug was found to reduce NA accumulation after L‐DOPA administration to mice pretreated with reserpine and nialamide while the endogenous CA‐levels remained almost unaffected. The CA‐depletion seen after the administration of H 77/77 (4,α‐dimethyl‐metatyramine) was only slightly prevented, indicating that amantadine only to a small extent inhibits the uptake mechanism at the level of the cell membrane. Moreover, studies on brain homogenates revealed, that amantadine probably does not inhibit monoamine oxidase. It is concluded that the anti‐Parkinson effect of amantadine might well be explained by a release of CA in the brain – i.e. particularly of DA in the neostriatum.
Ultrastructural Changes in the Rat Superior Cervical Ganglion Following Prolonged Guanethidine Administration
Authors: Jensen‐Holm Jens , Juul Per
Published: July 2010

The ultrastructure of adult rat sympathetic ganglia after daily guanethidine administration in a dose of 4–40 mg/kg intraperitoneally for 7–14 days was investigated. At 20 mg/kg maximal alterations of the nerve cells were observed, the most prominent feature being a pronounced swelling of the mitochondria which assumed round or irregular shapes. The membranes were preserved but an unfolding of the crests was seen. Irregularization of the endoplasmic reticulum occurred. An increased number of dense bodies was observed. The number and character of the vesicles were probably unchanged. Apart from a peripheral dislocation of the nucleus no other changes were observed in the cell constituents or membranes. The pre‐ and postganglionic nerve fibres, the synaptic vesicles, and synapses were unaffected. A large increase in the number of small cells was observed consisting mainly of lymphocytes. The number of plasma cells was increased. The changes were reversible, partial normalization occurring following discontinuation of medication for 22–56 days. No ultrastructural changes were observed in the nodose and spinal ganglia or in the liver and salivary glands. The ganglionic changes were similar to, but much more pronounced than those following postganglionic axotomy. Guanethidine induced inhibition of oxidative phosphorylation in vitro has been reported by other investigators. On the basis of this report and the present findings a hypothesis for the mechanism of action of prolonged administration of guanethidine is put forward: The structural changes observed following prolonged administration may induce metabolic alterations of the sympathetic ganglion cells impeding the function of the postganglionic neurone without affecting the ganglionic transmission or the survival of the ganglion cells. It cannot be excluded, however, that the ganglionic changes are toxic effects of guanethidine due to the cumulation of guanethidine in the sympathetic neurones.
Developmental Aspects of Pharmacokinetics
Authors: Yaffe Sumner J. , Rane Anders
Published: July 2010

Abstract: The absorption, apparent volumes of distribution, serum concentrations, serum half‐lives, and urinary excretion of several antibiotics were studied in premature infants by means of a micro‐diffusion assay technique. Serum half‐lives of all drugs investigated (except colistin) were markedly prolonged during the first days and weeks of life and approached adult values by three weeks of age. These changes were paralleled by an increase in urinary excretion rate which was independent of birth weight and gestational age. Colistin had a mean serum half‐life in premature infants of 2.4 hours, comparable to that noted in adults and thus is a notable exception. Studies of hepatic microsomal suspensions derived from human foetuses have revealed the presence of the component members of both the NADPH‐ and the NADH‐linked electron transport systems. Exogenous substrates such as aminopyrine and benzpyrene were not significantly metabolized by human foetal liver suspensions but the endogenous compounds, testosterone and laurate, were hydroxylated at substantial rates. The binding of these substrates to cytochrome P‐450 was investigated by studying the spectral changes that occur when they were added to microsomal suspensions. Laurate and testosterone exhibited type I changes, whereas aminopyrine gave rise to a type II spectral change correlating with the low or absent demethylating activity in foetal liver. These findings in the human foetus stand in marked contrast to results obtained in animals and emphasize again the marked species differences which exist in drug metabolism.
Placental Transfer of Ampicillin in Man
Authors: Boréus Lars‐Olof
Published: July 2010

Abstract: A pharmacokinetic analysis of the foetal/maternal distribution of ampicillin was performed in 25 pregnant women undergoing therapeutic abortion in the middle trimester of pregnancy. The drug was given intravenously before the hysterotomy and the plasma levels were followed during the period up to surgery. When the foetus was removed from the uterus a sample of foetal plasma was taken for ampicillin assay. By means of varying the time between injection and surgery, the ratio between foetal and maternal plasma levels could be determined at various times following the intravenous administration. It was found that the two concentrations became equal after 90 minutes and that the ratio was then steadily increasing for at least 200 minutes. If a two‐compartmental pharmacokinetic analysis is made on the basis of the plasma levels in the mother, it shows that a quasi‐equilibrium between the central compartment and the tissue compartment is reached already after about 35 minutes following the intravenous injection. Thus, the distribution of ampicillin to the human foetus through the placenta is slower than the distribution of the drug to the maternal tissues. A placental “barrier”seems to exist in the pharmacokinetic sense.
The Action of Morphine on the Cat Choledochoduodenal Tract
Authors: Persson Carl G. A.
Published: July 2010

The effect of morphine on the cat choledochoduodenal junction was studied by means of differentin vivoandin vitromethods.In vivo:Morphine (1‐100 μg/kg) induced increased duodenal activity and increased resistance to flow through the sphincter of Oddi when given intravenously. Atropine (5 mg/kg intravenously) counteracted the effect of 1 μg/kg morphine intravenously on the choledochoduodenal tract, but was ineffective in preventing the spasm caused by slightly increased doses of morphine. Effective α‐adrenoceptor blockade with dibenzyline (2 mg/kg) did not affect the action of morphine. Morphine (0.001–0.02 μg/kg) consistently produced increased duodenal activity and increased passage pressure through the sphincter when administered i.a. in the pancreatic duodenal artery.In vitro:The isolated sphincter and the isolated duodenum were insensitive to morphine in concentrations up to 80 μg/ml in the bath fluid.In vivomorphine is active locally in the cat choledochoduodenal tract but inactive when added to the bath fluid of the isolated sphincter of Oddi or duodenum. The results support the view that morphine exerts its spasmogenic effect on the sphincter region by the release of some endogenous contracting agent. This agent does not belong to the cholinergic or adrenergic nervous system but may be released from the vascular compartment by morphine.
The Effects of Maternally–administered Morphine on Rat Foetal Development and Resultant Tolerance to the Analgesic Effect of Morphine
Authors: Jóhannesson Torkell , Becker Bernard A.
Published: July 2010

Groups of 6–9 pregnant (sperm = Day 1) Sprague‐Dawley (Simonsen) rats were injected with morphine sulphate, 20 mg/kg subcutaneously, on gestational days 2–5, 7–9 or 11–13. Pups delivered by Caesarian section on gestational day 22 were essentially free of any observable teratogenic changes including bone defects. However, offspring of morphine‐treated rats (20 mg/kg/day subcutaneously on gestational days 17, 18, 19 and 20) which were allowed to litter normally exhibited on day 12–13 a significantly (P < 0.05) decreased response to a nocioceptive (55° surface) stimulus 30 min. following an injection of morphine sulphate 0.45 mg/kg subcutaneously (offspring of morphine‐treated mothers, 16.8 sec. ± 2.3 S.E.M. versus control offspring, 25.2 sec. ± 1.7 S.E.M.). On days 21–22 of age larger doses of morphine were required to elicit an analgesic response in the young. Following an injection of morphine sulphate, 10 mg/kg subcutaneously, the maternal animals also showed significant reduction in reaction time 30 minutes later (treated, 7.6 sec. ± 0.6 S.E.M. versus control, 16.1 sec. ± 0.6 S.E.M.) and 60 minutes later (treated, 7.5 sec. ± 0.9 S.E.M. versus control, 20.8 sec. ± 2.9 S.E.M.) as compared to paired waterinjected control pregnant animals.
Teratological Studies on Thalidomide in Rats
Authors: Jonsson B. Göran
Published: July 2010

Pregnant rats were given 100 mg thalidomide per kg orally during days 7–11 or 10–14 of gestation. The substance was prepared as a 1% suspension by homogenizing in a 0.5% methylcellulose. The foetuses were delivered by Caesarean section and were examined for soft tissue and skeletal malformations. The results indicated a retardation of the development in the group treated during days 7–11. This was based on a lower mean weight per foetus and on a lower degree of ossification in the tail, vertebral column and sternum.
Investigation of Wasp Venom: Antigenic Relationship
Authors: Ishay J. , Fischl J. , Gitter S.
Published: July 2010

Rabbits immunised with venom of Vespa orientalis developed antibodies related to four of the protein fractions of the venom and gave well‐defined precipitin reaction in immuno‐electrophoresis and immuno‐diffusion. Three of the immuno‐proteins present were contained in the same electrophoretic fractions which containing the haemolytic principle of the venom. The fourth was identified as lysozyme. Paravespula germanica venom reacted with the antiserum showing two precipitation bands, indicating partial interspecies cross‐immunity.
In Vitro Studies on the Uptake of 14C‐Labelled Carbamoylcholine in Mouse Kidney*)
Authors: Holm Jan
Published: July 2010

Carbamoylcholine uptake by mouse kidney slices was studied. The slices were incubated in Krebs‐Ringer bicarbonate medium (37°, pH 7.4) containing 14C‐carbamoylcholine, and the 14C‐slice‐to‐medium (S/M) concentration ratio was measured. Carbamoylcholine (2μM) was rapidly accumulated in oxygen‐carbon dioxide (95:5) atmosphere, and a steady state with S/M ratio around 10 was obtained within 1/2 hr. The radioactive material extracted corresponded chromatographically to authentic carbamoylcholine. The S/M ratio was significantly reduced in the presence of metabolic inhibitors or various quaternary and tertiary amines. In nitrogen‐carbon dioxide (95:5) atmosphere the S/M ratio (2μM) reached a constant value around 1 within 1/2 hr. Incubation at 19° markedly depressed the 3 min. S/M ratio, but increased the steady state S/M ratio (1 hr). Under anaerobic conditions carbamoylcholine uptake (mmol/kg tissue; 1 hr incubation) was directly proportional to the external carbamoylcholine concentration. The aerobic uptake consisted of two components: a saturable one (maximum capacity 7 mM/kg; half saturation concentration 700 μM) and another one that increased proportionally with the external concentration. It is concluded that carbamoylcholine is taken up against a concentration gradient by a saturable, energy dependent process which is inhibited by structural analogues.
Adrenoceptors in the Gall bladder
Authors: Persson Carl G. A.
Published: July 2010

Effects of sympathomimetics and sympatholytics were studied on cat gall bladderin vivoand on cat and human gall bladder stripsin vitro.Isoprenaline 0.1‐1 μg/kg and terbutaline 1‐10 μg/kg consistently decreased the intraluminal gall bladder pressurein vivo.Propranolol 1 mg/kg prevented this response. Noradrenaline 1‐10 μg/kg also decreased the gall bladder pressure. Isoprenaline (0.08‐0.24 μg/ml), terbutaline (0.26‐4.4 μg/ml), noradrenaline (0.04‐3.2 μg/ml), adrenaline (0.04‐1.6 μg/ml) and tyramine (0.08‐4 μg/ml) produced the same maximum relaxation in isolated strips from the cat gall bladder. The relaxation was abolished by propranolol 0.1‐1 μg/ml but not by practolol 160 μg/ml. Tyramine 2‐32 μg/ml was without effect on strips from reserpine‐treated cats. After propranolol, noradrenaline and adrenaline consistently produced contraction which was blocked by phenoxybenzamine 0.1 μg/ml. This contraction was much weaker than that produced by acetylcholine 0.08‐0.2 μg/ml and chole‐cystokinin 0.02‐0.3 i.u./ml. Different parts of the gall bladder reacted similarly to α‐ and β‐receptor stimulation. About half of the human gall bladders were relaxed by isoprenaline 0.4‐1 μg/ml and terbutaline 4‐16 μg/ml. Propranolol 5 μg/ml prevented the relaxation. Cat gall bladder contains relaxation mediating β‐receptors possibly of the β2‐type and a small population of contraction mediating α‐receptors. The adrenergic function may be to counteract cholecystokinin. Human gall bladder preparations can also be relaxed by β‐receptor stimulation.
Hexoestrol Analogues as Probes of Oestrogen Receptors II. Importance of Hydrogen‐Bonding Groups for Binding to Uterine Tissue and for Uterotrophic Activity
Authors: Terenius Lars
Published: July 2010

Abstract: Analogues of meso‐hexoestrol with variation in p,p′‐substituents (TERENIUS 1972) were tested with regard to 1) competitive affinity for oestrogen receptors in intact uterine tissue in vitro, 2) uterotrophic and 3) anti‐uterotrophic activities in the mouse. The relative affinities of the analogues for the receptors in the uterine tissue was similar to those determined for the receptor in solution. The SH and NHSO2CH3 analogues were without any activity in all the tests. Two analogues, with H or OCH3 disubstitution were uterotrophic without having receptor affinities. The other analogues (except the p,p′‐NH2‐analogue) were markedly less uterotrophic than expected from their relative receptor affinities. For example, the p‐OH,p′‐NH2‐analogue had 85 % of the receptor affinity of meso‐hexoestrol but only 0.5 % of the uterotrophic potency. On the other hand, when this analogue or meso‐hexoestrol was injected, it was found that the analogue had much less competitive affinity for the uterine receptors and was less efficiently retained than meso‐hexoestrol. No compound was anti‐uterotrophic.
Assay of Preparations of Acetone‐activated Human Plasma Kallikrein by the Effects on Different Kininogen Fractions in Human Citrated Plasma
Authors: Briseid Kjell , Qvigstad Ellen‐Karine
Published: July 2010

Abstract: Prekallikrein in human citrated plasma was activated by incubation with acetone, 17 or 25% (v/v). EDTA‐2Na was added before or after the evaporation of acetone. Determinations of the relative activities of the enzyme preparations were based on the release of kinin from the 3 functional states of kininogen in human citrated EDTA‐plasma as described by BRISEID et al. (1973). Incubations were carried out at 37° or at 0°. The kininogen 1/kininogen 2 activityratios were the same at 37° and 0°, indicating that the kininogenase activities tested were the same. The relative activities of the different kallikrein preparations varied with the type of kininogen used, possibly reflecting the presence of more than one kininogenase. Purification of the kallikrein combined with determinations of kininogen 1/kininogen 2 activity‐ratios must be carried out to solve the problem.
Methaemoglobin Formation by Diamino Metabolites of DNOC and DNBP
Authors: Frøslie Arne
Published: July 2010

Abstract:The diaminophenols DAOC and DABP have been investigated for their methaemoglobin‐forming effect. Both substances were found to be active methaemoglobin inducersin vitroas well asin vivoon goats and pigs. After intra‐peritoneal administration of 33 mg/kg (DAOC), and 43 mg/kg (DABP) of the diaminophenols, the animals died within one hour. Administered in this way DAOC produced a lethal methaemoglobinemia within 15‐20 minutes, while after intraruminal administration the methaemoglobinemia developed less dramatically. At corresponding doses DABP produced almost the same level of methaemoglobinemia in the animals. In a more prolonged experiment haemolysis and acute nephrosis were observed, and haemoconcentration occurred in all the animals. It is concluded that the diaminophenol metabolites are responsible for the methaemoglobin formation following dinitrophenol poisonings in ruminants.
The Irritant Potential of Dilute Solutions of ortho‐Chlorobenzylidene Malononitrile (CS) on the Eye and Tongue
Authors: Ballantyne Bryan , Swanston D. W.
Published: July 2010

Abstract: Median threshold concentrations for the riot control agent o‐chlorobenzylidene malononitrile (CS) to produce blepharospasm were found to be 5.9 × 10−5 M for the rabbit, 2.2 × 10−5 M for the guinea pig and 3.2 × 10−6 M for man. The threshold concentration to produce sensation on the human cornea was 7.3 × 10−7 M. A dose‐response relationship was demonstrated. Extrapolation of log‐probit plots for sensation on the human eye suggest that 2.7 × 10−5 M would be incapacitating. The median threshold concentration of CS required to produce sensation on the human tongue was 6.8 × 10−6 M; a concentration 9.4 times that required to produce eye sensations. A dose‐response relationship on the tongue was demonstrated. The use of irritant tests, species variations in response, and the effects of solvents on the response are discussed.
Trimethoprim in Human Saliva, Bronchial Secretion and Lung Tissue
Authors: Hansen Ib , Nieisen Mogens Lykkegaard , Bertefsen Svend
Published: July 2010

Abstract: Following oral administration of trimethoprim (TMP) in doses varying from 4.0 to 11.2 mg TMP per kg body weight per 24 hours over a period of 1‐5 days, the concentration was determined in lung tissue (obtained by open biopsy), bronchial secretion or saliva, in a total of 51 cases. A microbiological method was used to determine the concentration, using B. pumilus as test organism. The concentrations of TMP found in the lung tissue, bronchial secretion and saliva (6‐13 hours after the last administration of TMP) were at a therapeutically active level (≥ MIC × 5) with regard to the majority of those bacteria usually occurring in respiratory tract infections. In 14 out of 17 patients, TMP was found in the lung tissue in concentrations which were 1 1/2 to 3 1/2 times higher than the corresponding serum concentration. In the other 3 patients, the concentrations found were 4 1/2 times, 7 times and 14 times higher in the lung tissue than in the serum. In the case of bronchial secretion, 6 patients showed a TMP concentration which was 1/2 to 4 times the corresponding serum concentration, while in 14 patients, an examination of the saliva showed a TMP concentration which was 1‐8 1/2 times that of the corresponding serum concentration.
Fatal Digitalis Poisoning
Authors: Steentoft Anni
Published: July 2010

Abstract: Two cases of digitalis poisoning are described. Case 1, a man, aged 40 years, swallowed for suicidal purposes about 50 digitalis tablets, each containing 50 mg standardized digitalis leaf, digitalis purpurea (0.5 i.u.). Death occured about 8 hours after the intake. A quantitative determination of digitalis glycoside in the gastric contents, and in the contents of the small intestine, blood and heart was performed with xanthydrol. Case 2, a child, 11 days old, because of a congenital heart disease was treated with digoxin. 1/2‐1 hour before death the child was given 0.7 mg digoxin intravenously. A quantitative determination of digoxin was performed with xanthydrol in the liver, heart and lung and by the fluorometric method in the liver, heart, kidney, urine and blood.
The Effect of Guanethidine on the Noradrenaline Content of the Adult Rat Superior Cervical Ganglion
Authors: Juul Per , McIsaac Richard L.
Published: July 2010

Abstract:The administration of guanethidine sulphate in doses above 10 mg/kg intraperitoneally for more than a week induced a considerable reduction (up to 80 %) of the noradrenaline content in the adult rat superior cervical ganglion. With 5 mg/kg no changes were observed, even after administration for 4 weeks. Single injections of 5 and 20 mg/kg had no effect on the ganglionic noradrenaline. Following administration for 14 days in a dose of 20 mg/kg, normalization of the ganglionic noradrenaline was complete within 8 days. Following 40 mg/kg For 18 days recovery was only partial ‐ probably due to irreversible degeneration of some ganglion cells. The effect of guanethidine on the noradrenaline content in the superior cervical ganglion is different from its noradrenaline depleting effect in sympathetically innervated peripheral organs and is assumed to be secondary to chromatolytic changes in the ganglionic nerve cells induced by guanethidine, some of these changes being irreversible following high doses for long periods of administration.
Identification Tests for Bases Formed During the Putrefaction of Visceral Material
Authors: Stevens H. M. , Evans P. D.
Published: July 2010

Abstract: Data has been compiled on the general properties of 29 basic compounds which have been reported to occur as putrefaction products of human viscera. The properties include responses to colour tests, behaviour in selected systems of gas, paper, and thin‐layer chromatography, and absorbance in the ultraviolet and infrared range. The relative efficiencies of some acid protein precipitating reagents have been tested with respect to the release of endogenous bases from liver tissues. From this information, together with the development of procedures for extracting the bases from chromatograms, a number of naturally occurring basic compounds have been isolated from human liver tissues and identified.
Study on the Hyaluronic Acid‐Protein Complex, the Molecular Size of Hyaluronic Acid and the Exchangeability of Chloride in Skin of Mice before and after Oestrogen Treatment
Authors: Grosman Nina
Published: July 2010

Abstract: Hyaluronic acid (HA)‐protein complex was extracted with 0.2 M‐NaCl from homogenized skin of the back of mice. The complex was separated from unrelated proteins by ethanol precipitation followed by three times chromatography on CM‐Sephadex columns. The composition of the complex isolated from mice treated with oestradiol differed significantly from the complex of the control mice, the ratio HA/protein was 3.5 times higher in the former than in the latter. The molecular sizes of the HA from the two samples were compared by means of gel filtration on Sepharose 2B column. Apart from a high molecular fraction containing 4 % of the HA from mice treated with oestradiol no difference was found between the elution patterns. The exchangeability of the chloride in the skin of control mice and mice treated with oestradiol was studied by means of the isotope dilution method. No significant difference was found between the two groups of mice.
The Rotacone: A New Apparatus for Measuring Motor Coordination in Mice
Authors: Christensen J. Dencker
Published: July 2010

Abstract: The rotacone is a modified rotarod found suitable for the measurement of drug‐induced changes in motor coordination. On this apparatus mice are forced to walk against increasing surface speed until they drop off the cone. As the test is quick the animals are not exhausted, and there is no problem with mice taking “free rides”. Saline‐treated mice showed a constant performance level in 4 immediately successive trials, whereas animals under the influence of drugs, especially chlordiazepoxide, showed an increase in performance in the 4 trials. After chlorpromazine, meprobamate and chlordiazepoxide there is a graded response with a normal distribution of scores. Pentobarbital gave a response of the all or non type.
A Comparative Study on the Effect of Fluoride, Laurylsulphate and Chlorhexidine on Glucose Utilization in Rat Intestinal Mucosal Cells
Authors: Olsen Ingar , Sögnen Erling
Published: July 2010

Abstract: Suspensions of rat intestinal cells were incubated for 30 min. at 38° with either sodium fluoride, sodium laurylsulphate or chlorhexidine acetate. Except for a slight stimulation with fluoride and laurylsulphate at the lowest concentration tested (0.05 mM), all three compounds progressively suppressed glucose utilization at increasing concentrations. A 50 % inhibition occurred at approximately 3 mM fluoride, 1 mM laurylsulphate and 0.2 mM chlorhexidine. Thus on an equimolar basis fluoride proved to be the least potent inhibitor of mucosal glucose metabolism. The implications of these findings are discussed with regard to the concentrations of these compounds used in oral therapeutics as well as to the amounts that may be swallowed and thereby reach the intestinal epithelium. According to the results from this in vitro system, the amounts of fluoride tested are less likely to affect this essential digestive process than the corresponding quantities of laurylsulphate or chlorhexidine.
Effects of Insulin on Glucose Metabolism in Vascular and Intestinal Smooth Muscle
Authors: Arnqvist Hans J.
Published: July 2010

Abstract:The effect of insulin (0.1 U/ml) on glucose metabolism was studied in bovine mesenteric arteries and rabbit colon smooth muscle. In both tissues the glucose uptake was enhanced by insulin after an incubation period of 180 min. and at a glucose concentration of 5.6 mM. Insulin also augmented the incorporation of glucose‐14C into glycogen as well as the glycogen content and the lactate elimination. Glycogen synthetase I activity was increased by insulin. The total glycogen synthetase, phosphorylaseaor total phosphorylase activities were not affected. The effects of insulin on the glucose metabolism in bovine mesenteric arteries and rabbit colon smooth muscle were qualitatively similar to those in rat skeletal muscle but the effects were less pronounced and appeared later.
Studies on the Interaction of Reserpine, d‐Amphetamine, Apomorphine and 5‐Hydroxytryptophan
Authors: Goetz Christopher , Klawans Harold L.
Published: July 2010

The effect of reserpine on dopamine related d‐amphetamine and apomorphine‐induced stereotyped behaviors and serotonin related myoclonic behaviour was studied. Reserpine pretreatment potentiated amphetamine‐induced stereotyped behaviour, apomorphine‐induced stereotyped behaviour and 5‐hydroxytryptophan‐induced myoclonic behaviour. The possibility that this was related to the influence of reserpine on the behaviourally active monoamine pools was discussed. 5‐Hydroxy‐tryptophan in small amounts was found to inhibit amphetamine‐induced stereotyped behaviour in reserpine pretreated guinea pigs. d‐Amphetamine appeared to potentiate 5‐hydroxytryptophan myoclonic behaviour and this potentiation was further increased by reserpine. 5‐Hydroxytryptophan did not inhibit apomorphine‐induced stereotyped behaviour in reserpinized animals. These results are discussed in relation to the influence of reserpine on the balance of active neurotransmitters within the brain.
Alteration of Electroencephalogram and Evoked Potential in Rats Induced by Organic Mercury
Authors: Lehotzky Kornélia , Mészáros I.
Published: July 2010

An organic mercurial compound, methoxy‐ethyl‐mercury chloride (MEMC) has been studied for its subacute neurotoxic effects by means of EEG and evoked potentials, in male rats. Poisoning by MEMC during four weeks causes characteristic alterations of the electroencephalogram: i.e. increases the α1; β1; β2 frequency, analysed by integration of spectral frequency. The amplitude and duration of the cortical evoked potentials were also changed.
Malathion Induced Biochemical Changes in Rats
Authors: Gupta P. K.
Published: July 2010

Malathion induced changes in blood glucose, plasma electrolytes and glycogen content of different tissues have been investigated. Malathion was administered intra‐peritoneally in dose of 50 mg/100 g body weight to 12 hrs‐fasted rats. A significant increase of blood glucose and plasma sodium was observed during the first 6 hrs of treatment, whereas, the glycogen content of the liver, kidney, heart and spleen showed a marked increase during the next 6 to 24 hrs. No significant change in plasma potassium and brain glycogen content was observed at different time intervals. The possible role of the adrenal medulla in malathion induced biochemical changes is discussed.
Selectivity of Probenecid Congeners for Different Organic Acid Transport Systems in Rabbit Renal Cortex
Authors: Bárány Ernst H.
Published: July 2010

Seventeen probenecid congeners were tested as inhibitors of the simultaneous uptake of labelled o‐iodohippurate and iodipamide into slices of rabbit renal cortex. Compounds with small substituents on the nitrogen were more inhibitory for o‐iodohippurate, while compounds with larger lipophilic substituents were more inhibitory for iodipamide uptake. The results are interpreted in terms of differential inhibition of two transport systems: the classical hippurate or H‐system and the liver‐like L‐system.
A Method for Simultaneous Recording of the Effects of Sympathomimetic Compounds on Respiratory Smooth Muscle, on Slow Skeletal Muscle, and on the Cardiovascular System
Authors: Olsson O. A. Torsten
Published: July 2010

Abstract:Administration of histamine by inhalation to anaesthetized cats restricts the effect of this potent amine to the respiratory system. Tn addition to the relaxing effects from administered sympathomimetic drugs on induced bronchocon‐striction it is also possible to make simultaneous registrations from the soleus muscle and from the cardiovascular system by this method, without any interference from the systemic effect of administered histamine. The activity of iso‐prenaline on respiration and on the contractile response of the soleus muscle is described.
Water Movement in the Vitreous Body, Evaluated Experimentally and Theoretically *
Authors: Bay Michael
Published: July 2010

Abstract: The water movement between plasma and the vitreous body in eyes from guenon monkeys and rabbits was measured under physiological conditions and compared to theoretically calculated values for free water diffusion in a sphere of the same order of magnitude. The results show that a steady‐state is obtained between plasma and the vitreous body after 90 minutes of constant plasma concentration in monkeys as well as in rabbits. In contrast to this, the theoretical calculations show that a steady‐state is not established within 180 minutes if only simple diffusion takes place.
Some Pharmacological Properties of the Combination of Etorphine and Acepromazine (Immobilon®) and the Morphine antagonist, Diprenorphine, in the Dog *
Authors: Hermansen Keld , Larsen Jens‐Jørgen
Published: July 2010

Abstract: The analgesic effect of immobilon® (etorphine 125 μg/ml and acepromazine 500 μg/ml) has been compared with that of its two components and of morphine. The following values were found (ED 50 μg/kg subcutaneously; acetic acid test, mice): immobilon (etorphine 0.3 + acepromazine 1.2); etorphine 1.2; acepromazine 40 and morphine 350. The action of immobilon and of the antagonist, diprenorphine (revivon®) on systolic/diastolic blood pressure, heart rate, ECG, respiration and rectal temperature was checked during clinical neuroleptanalgesia in seven dogs. No effect on the systolic and a slight fall in the diastolic blood pressure were observed. Furthermore a significant bradycardia was noted during the neuroleptanalgesia as well as a significant tachycardia during arousal produced by diprenorphine. The former could readily be antagonized by atropine, and the latter by propranolol. It is concluded that the effect of immobilon®/revivon® on cardiovascular and respiratory parameters does not preclude its clinical use in dogs.
Effect of Prolonged Lithium Ingestion on Glucagon and Parathyroid Hormone Responses in Rats
Authors: Olesen O. Vendelin , Thomsen Klaus
Published: July 2010

Abstract: In the present study the hypothesis is tested that long‐term lithium administration produces a general lowering of hormone responses that are mediated via the adenyl cyclase‐cyclic AMP systems. Rats were given lithium in the food for more than one month before the experiments, and the serum lithium concentration was maintained at a level of 0.7–0.9 mM. Lithium administration did not lower the response to 33 or 100 U/kg b.wt. of parathyroid hormone as measured by the decrease in the urinary excretion of calcium and by an increase in urinary excretion of phosphate and cyclic AMP; on the contrary, the effects of parathyroid hormone were higher in the lithium than in the control group. Lithium did not lower the response to 200 μg/kg b.wt. glucagon as measured by liver glycogen breakdown. The liver glycogen concentration was equal in the lithium and in the control group before the hormone was administered; one hour after its administration the liver glycogen concentration was reduced by about 40 per cent in both groups. Lithium led to a significant increase in the response to glucagon as measured by the increase in the urinary excretion of cyclic AMP. On the basis of the data obtained the hypothesis under investigation must be rejected.
A Gas Chromatographic Method for the Determination of Amitriptyline and Nortriptyline in Human Serum
Authors: Jørgensen Aksel
Published: July 2010

Abstract:Amitriptyline (AMT) and nortriptyline (NT) were extracted from serum with hexane at pH 9. An internal standard was added and extracted with the drugs. During the concentration of the hexane phase nortriptyline was acetylated to improve separation. One fifth of the final hexane phase was injected into a gas chromatograph equipped with a detector, which was selectively sensitive towards nitrogen. The lower limits of detection were 5 ng/ml for AMT and 10–15 ng/ml for NT. A constant relative standard deviation of 7.6% was found in the concentration interval used for the standard curves. No interference appeared from AMT metabolites and some benzoediazepines. The method has been used for the estimation of AMT after a single dose of this drug to two human volunteers and for the estimation of AMT and NT after repeated administration of amitriptyline to patients. After single dose administration NT was not detectable, while the NT concentration was of the same order as the AMT concentration after repeated administration. A great individual variation in the concentrations of the two drugs was seen after repeated administration.
Serotonergic and Antiserotonergic Influences on Apomorphine‐induced Stereotyped Behaviour
Authors: Weiner William J. , Goetz Christopher , Klawans Harold L.
Published: July 2010

Abstract:The possible role of serotonin in modifying apomorphine‐induced stereotyped behaviour was investigated by studying the effects of methysergide and 5‐hydroxytryptophan on the threshold dosage of apomorphine required to induce stereotyped behaviour. The central serotonin antagonist methysergide potentiated apomorphine‐induced stereotyped behaviour, and 5‐hydroxytryptophan, the precursor of serotonin, inhibited apomorphine‐induced stereotyped behaviour. These results suggest that serotonin may play a role in the balance of neurotransmitters within the striatum that influence movements.
Effect of Food and Repeated Injections on Serum Diazepam Levels
Authors: Linnoila M. , Korttila K. , Mattila M. J.
Published: July 2010

Abstract: Diazepam 0.3 mg/kg was administered intravenously three times at intervals of 14 days into seven healthy volunteers. Five hours after injection the subjects ingested either 330 ml of mineral water, mineral water in combination with 2 rusks, or 330 ml of fatty milk with an egg hamburger. Diazepam and N‐ desmethyldiazepam levels were measured in serum samples drawn at 4, 5, 6, 7 and 8 hours after administration of the drug. At the same time the ability to discriminate flickering light was measured, and the feeling of tiredness was recorded. The serum diazepam levels declined regularly as a function of time after mineral water, but both kinds of food significantly elevated the serum diazepam level from the sixth hour onwards. The ability to discriminate flickering light was not modified. Serum N‐desmethyldiazepam levels were significantly elevated after the second and third injections as compared with the first injection. Serum diazepam levels were not lowered. The present findings could be explained by an enterohepatic cycle of diazepam, and suggest that diazepam might induce its own metabolism in man.
Plasma Levels of Nicotinic Acid Compounds in Niceritrol *‐Treated Rabbits
Authors: Brattsand Ralph , Harthon Lennart
Published: July 2010

Abstract: Some pharmacokinetic properties of nicotinic acid (NA) and niceritrol (pentaerythritoltetranicotinate) were investigated in rabbits. Niceritrol released NA at a faster rate on incubation in vitro with plasma or liver homogenate than in a pure buffer solution, indicating that niceritrol was actively hydrolyzed. After administration of niceritrol to rabbits no niceritrol was present in the plasma but metabolites, probably lower esters of niceritrol, free NA and nicotinamide were found. On oral administration of NA in a dose of 16 mg/kg higher maximal plasma levels of free NA (~6 μg/ml) were noted than after adminstration of niceritrol (1.4 μg/ml) in the same dose. A diet producing hyperlipaemia and containing 0.5% niceritrol elevated the levels of free NA in the plasma by about 2 μg/ml. It also reduced the increase in plasma cholesterol. The investigation suggests that the pharmacological and pharmacokinetic properties of niceritrol in the rabbit are similar to those in man.
Anticonvulsant Activity in Mice of Diazepam in an Emulsion Formulation for Intravenous Administration
Authors: Jeppsson Roland , Ljungberg Stellan
Published: July 2010

Abstract: The anticonvulsant activity of diazepam has been investigated in mice using an electrical low voltage square wave technique. Diazepam was administered intravenously using two injection formulations, valium® inj. (Roche) and diazepam emulsion. In the latter formulation the lipophilic drug was dissolved in soya bean oil which was then emulsified to an o/w emulsion. A great difference was found in acute intravenous toxicity (LD50) between the two diazepam formulations. The higher toxicity of valium® inj. could probably be due to the solvents used in this formulation. The anticonvulsant activity was about equal for the two preparations. Thus, no difference was found in duration of anticonvulsant activity at the two dose levels and the slopes of the log. dose‐response curves did not differ.
Function of Erythrocytes in Attaching Selenite‐Se onto Specific Plasma Proteins
Authors: Sandholm Markus
Published: July 2010

Abstract: The binding of 75Se‐selenite onto human plasma proteins was studied in the presence and absence of erythrocytes. The binding proteins were detected by crossed immuno‐electrophoresis followed by autoradiography. Human erythrocytes were shown to metabolize labelled selenite becoming bound to specific plasma proteins. The most heavily labelled proteins were the β‐lipoprotein and an unidentified fraction located electrophoretically between the α1 and α2 globulin fractions.
The Effects of Cyclophosphamide and Azathioprine on Collagen in Skin and Granulation Tissue in Rats, and the Effects of Cyclophosphamide on Collagen in Human Skin
Authors: Hansen T. Mørk , Lorenzen I.
Published: July 2010

Abstract: Granulation tissue was produced in rats by subcutaneous implantation of cellulose sponges. The effect of daily intraperitoneal injections of cyclophosphamide or azathioprine on rat skin and granulation tissue was examined after 14 and 42 days. Skin biopsies from patients with glomerulonephritis were analyzed before and after 42 days of treatment with cyclophosphamide or placebo. In the rats, cytostatic treatment caused an increase in the dry weight of the skin, and azathioprine increased the dry weight and the protein content of the granulomas. The increase in the dry weight was accompanied by a decrease in water percentage. The alpha‐amino nitrogen/OH‐proline ratio in purified acid soluble collagen from skin and granulation tissue increased with the dose and duration of cytostatic treatment. No effect on the aldehyde content was observed. Cyclophosphamide caused a decrease in the alpha/beta ratio in acid soluble collagen from granulation tissue, but not in the collagen from the skin. Salt soluble collagen was increased in the skin after 14 days of cytostatic treatment, but remained unchanged in the granulation tissue. In human skin cyclophosphamide caused no statistically significant changes in the amount of salt soluble or total collagen. It is concluded, that daily treatment of rats with cyclophosphamide or azathioprine from 14 to 42 days seems to inhibit the catabolic processes in the skin and granulation tissue, to decrease the hydroxylation of proline in collagen, and to inhibit the intermolecular cross‐linking in collagen.
Electrophysiological Effect of QX 572, a Lidocaine Derivative, on Isolated Heart Muscle Preparations
Authors: Schipperheijn J. J. , De Klerk G. , Olsson B.
Published: July 2010

Abstract: The effects of N,N‐bis (phenylcarbamoylmethyl) dimethyl ammonium chloride (QX 572), a lidocaine derivative, on isolated rat's heart tissue were studied. At concentration levels usually effective in suppressing arrhythmias (10 mg/l) no effect on normal electrical activity was found. At higher concentrations (20 mg/l) the drug reduced the maximum rising velocity of the intracellular action potential. As a result conduction was slowed down. The onset of action was rapid. The drug could not easily be removed from the preparation by flushing. This is in agreement with the long‐lasting effect after a single dose which is reported in clinical studies. Drug action was independent of potassium concentration. At high concentrations (80 mg/l) contractility was reduced and the duration of the action potential was increased. According to VAUGHAN WILLIAMS'S classification (1970) QX 572 can be considered a pure class I type of drug.