bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does the Freezer Burn Our Food?
Authors: Schmidt Shelly J. , Lee Joo Won
Published: March 2009

ABSTRACT:  Freezer burn is a common problem that significantly affects the color, texture, and flavor of frozen foods. Food science students should be able to clearly explain the causes and consequences of freezer burn. However, it is difficult to find a modern, detailed, accurate, yet concise, explanation of the mechanism and factors influencing the rate of freezer burn, suitable for classroom use. Thus, the purpose of this article is to provide students and instructors alike with such an explanation, replete with visual explanations, including 2 short animations. The animations, in QuickTime format, are available as supporting information and can be downloaded for free educational use.
Phylogeny and Systematic Position of Zosterodasys (Ciliophora, Synhymeniida): A Combined Analysis of Ciliate Relationships Using Morphological and Molecular Data
Authors: KIVIMAKI K. LINDHOLM , BOWDITCH BRUNELLA M. , RIORDAN GAVIN P. , LIPSCOMB DIANA L.
Published: March 2009

ABSTRACT. The Synhymeniida is characterized both by a band of somatic dikinetids, the synhymenium, extending across the surface of the cell and by a ventral cell mouth lacking specialized feeding cilia but subtended by a well‐developed cyrtos. The synhymeniids have been hypothesized to be members of the class Nassophorea but our previous ultrastructural study of the synhymeniid genus Zosterodasys did not show any clear synapomorphies that would permit definitive placement in the Nassophorea or as a sister taxon to any of the other ciliate groups possessing a cyrtos. In the present study, simultaneous analysis of morphological and small subunit rDNA molecular data indicates that the Synhymeniida are sister to the class Phyllopharyngea and that this clade is, in turn, sister to the remaining Nassophorea, although this result is sensitive to dataset inclusion and alignment parameters. While this suggests that taxa with a ventral cyrtos might be united into a named taxon (e.g. resurrecting the Hypostomata), additional data are needed to reach a definitive conclusion.
Atypical neurofibroma of the skin and subcutaneous tissue: clinicopathologic analysis of 11 cases
Authors: Jokinen Chris H. , Argenyi Zsolt B.
Published: March 2009

Background: Neurofibroma (NF) is a relatively common cutaneous tumor, which typically presents little diagnostic difficulty. Occasionally, however, pleomorphic cells may be present in NF raising consideration of other neoplasms like malignant peripheral nerve sheath tumor (MPNST).

Methods: This study examines the clinicopathologic and immunohistochemical features of 11 dermal and subcutaneous ‘atypical’ NF.

Results: 9/11 (82%) atypical NF were from females, aged 8–70 years. One patient had neurofibromatosis‐1. Most presented on the extremities or trunk. The atypical cells had large hyperchromatic, irregular nuclei, and were arranged in a distinct lamellar or fibrillar pattern. Some tumors were hypercellular, but marked density characteristic of MPNST was not observed. All were nonplexiform. Mitoses were mostly absent. The pleomorphic cells expressed S‐100 protein. All were negative for p53. MIB‐1 was negative in 7/10 (70%) and stained only rare cells in 3 (30%). Epithelial membrane antigen (EMA) and p16 expression were variable. Of six patients with available follow‐up, no tumor recurred and none developed malignancy (range 6–63, mean 33 months).

Conclusions: Superficial atypical NF, while morphologically unusual, has no apparent association with neurofibromatosis‐1 or short‐term risk of recurrence or malignant transformation. Awareness of this variant is important in order to avoid misdiagnosis of a more aggressive neoplasm.
Biochemical and Functional Evidence for Nerve Sprouting in the Decentralized, Hypertrophied Rat Urinary Bladder
Authors: Ekström Jörgen , Malmberg Lars , Wallin Åsa
Published: March 2009

Abstract: The preganglionic nerves of the rat urinary bladder were cut. The decentralized bladders gained markedly in weight. Both one and four weeks post‐operatively, transmural nerve stimulation evoked contractile responses of the muscle strips of the decentralized bladders, that were of the same magnitude as those of the control bladders. However, four weeks post‐operatively, the atropine resistant fraction of the response was decreased; consequently, the atropine sensitive (cholinergic) fraction was increased. The activity of the acetylcholine synthesizing enzyme, choline acetyltransferase, was increased at the late time of observation. The present biochemical and functional findings may suggest outgrowth of branches from the decentralized post‐ganglionic cholinergic nerves.
Kinetic Models for Insulin Disappearance from Plasma in Type I Diabetic Patients
Authors: Thorsteinsson Birger , Fugleberg Steen , Feldt‐Rasmussen1 Bo , Ellemann Karsten , Andersen Ole Ortved , Binder Christian
Published: March 2009

Abstract: We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long‐term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non‐saturable (first order equation) or saturable (Michaëlis‐Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0‐23.7) ml.kg1‐.min.−1 versus 25.0 (18.6‐47.1) ml.kg−1.min.−1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.
Effects of Diazepam on Blood Choline and Acetylcholine Turnover in Brain of Mice
Authors: Lundgren G. , Nordgren I. , Karlén B. , Jacobsson G.
Published: March 2009

Abstract: The effect of diazepam on the acetylcholine (ACh) synthesizing system has been studied in mouse brain in vivo. ACh and choline (Ch) were analyzed by gas chromatography ‐ mass spectrometry using deuterated internal standards. Turnover of ACh was studied by following the incorporation of Ch into ACh after an intravenous injection of [2H6]‐Ch. The mice were killed by focussed microwave irradiation on the head. Diazepam was found to increase the endogenous level of Ch, while the concentration of [2H6]‐Ch was only half of that of the controls. The incorporation of [2H6]‐Ch into [2H6]‐ACh was decreased, while the endogenous level of ACh was slightly increased. The turnover rate of ACh was decreased, consistent with a decrease in neuronal excitability induced by diazepam. The elevated endogenous Ch‐level and the lower concentration of [2H6]‐Ch in the brain, might be explained by an effect of diazepam on the Ch‐transport across the blood‐brain barrier. This theory is supported by experiments where levels of endogenous and [2H6]‐labelled Ch were analyzed in blood following an intravenous injection of [2H6]‐Ch. The [2H6]‐Ch was found to be eliminated faster in blood from diazepam treated mice. The increased blood level of endogenous Ch, induced by the [2H6]‐Ch injection also returned more rapidly to normal in these animals. This is consistent with peripheral Ch beeing eliminated faster when the central Ch supply is decreased.
Effect of Cadmium on Lipid Metabolism of Brain: In Vivo Incorporation of Labelled Acetate into Lipids
Authors: Gulati S. , Gill K. D. , Nath R.
Published: March 2009

Abstract: The effect of early postnatal cadmium exposure on the in vivo incorporation of (1‐14C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd‐exposed animals compared to controls.
β1‐ and β2‐Adrenoceptor Affinity and Stimulatory Effects of (S)‐Pindolol and Iodinated (S)‐Pindolol
Authors: Abrahamsson Tommy , Nerme Viveca
Published: March 2009

Abstract:The β1‐ and β2‐adrenoceptor affinity and stimulatory effects of iodinated (S)‐pindolol (IPIN) and (S)‐pindolol were investigatedin vitrousing β‐adrenoceptor binding technique and isolated right atrium (rate increase, β1) and uterus (relaxation, β2) of the rat. IPIN had a higher affinity towards β‐adrenoceptors compared to (S)‐pindolol, with some β2‐adrenoceptor selectivity. In the rat uterus, IPIN produced only marginal stimulatory effects, while (S)‐pindolol caused a concentration‐dependent relaxation with a maximal effect that was 55% of that generated by isoprenaline. In the right atrium IPIN caused an increase in the atrial rate similar to that caused by (S)‐pindolol. The concentration of IPIN required in the right atrium for a half‐maximal response (pD2= 7.81) was markedly greater than that required for occupation of half the β‐adrenoceptor population (pKB= 9.81). The β1‐selective blocker metoprolol antagonized the effect of (S)‐pindolol and IPIN on the atrial rate but a greater concentration of metoprolol (5 × 10−6M compared with 5 × 10−7M) was required to antagonize the effect of IPIN significantly. It is concluded that iodination of (S)‐pindolol increased its affinity and decreased its efficacy towards β‐adrenoceptors.
Effects of Cadmium on Preimplantation and Early Postimplantation Mouse Embryos in Vitro with Special Reference to their Trophoblastic Invasiveness
Authors: Yu H. S. , Chan S. T. H.
Published: March 2009

Abstract: Cadmium chloride, at concentrations of 0.5 or 1 μg/ml medium, did not affect the trophoblastic invasiveness of mouse embryos treated for 24 hours at 4‐cell and morula stages. At higher concentrations of 5 or 10 μg/ml medium, most treated embryos in vitro underwent degeneration while a few survivors formed trophoblastic outgrowths with variable areas. Cadmium chloride, at a low concentration of 0.5 μg/ml medium presented continuously to blastocysts after attachment in vitro, has significantly retarded the trophoblastic outgrowth areas and reduced the number of trophoblastic giant‐cell nuclei, though the spreading blastocysts appeared morphologically normal. At higher concentrations of 1 or 5 μg/ml medium, cytoplasmic disintegration and detachment of trophoblasts were observed. It is suggested that cadmium may interfere with the cell division and/or the transformation of trophectoderm cells into giant cells, resulting in the retardation of the trophoblastic outgrowths.
Further Evaluation of the Kinetics of White Spirit in Human Volunteers
Authors: Pedersen Lisbet Milling , Rasmussen Seren , Cohr Carl‐Heinz
Published: March 2009

Abstract: This paper gives supplementary informations on the kinetics of aliphatic white spirit in humans. Eight volunteers were exposed to 600 mg/m3 (100 p.p.m.) white spirit during 3 hrs. Calculated pulmonary uptake (dose) was 392±38 mg, residence time 47.5 hrs, volume of distribution 749 1, and total body clearance 263 ml/min. Then 7 volunteers were exposed to 600 mg/m3 white spirit 6 hrs daily in 5 consecutive days. Calculated pulmonary uptake was 3464±329 mg. A mathematic model is presented which uses the blood concentrations to calculate the tissue concentrations during repeated doses administered over an extended period. By means of this model and the measured concentrations in blood and fat, the partition coefficient fat: blood for white spirit was calculated to 47. Estimated redistribution phase of white spirit in adipose tissue was approximately 20 hrs for the first 5 exposures, and half‐life in adipose tissue after redistribution 46‐48 hrs. During exposure to 600 mg/m3 white spirit 6 hrs daily, 5 days a week, calculated maximum steady state concentrations were 55 mg/kg fat and 5 mg/kg brain, minimum steady state concentrations 35 mg/kg fat and 0.6 mg/kg brain. These values for half‐life and steady‐state concentrations are considered more correct than our previously reported values, which did not take into account the existence of a redistribution phase.
Han/Wistar Rats are Exceptionally Resistant to TCDD. I
Authors: Pohjanvirta Raimo , Tuomisto Jouko , Vartiainen Terttu , Rozman Karl
Published: March 2009

Abstract:Adult male Han/Wistar rats were administered 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) intraperitoneally at doses ranging from 125 to 1400 μg/kg and monitored for 39 to 48 days. Two rats succumbed in the course of the experiment: one in the group receiving 625 and one dosed 1000 μg/kg. Body weights of the animals decreased by 20 to 30% during the first 10 to 14 days and became stable thereafter. Feed consumption decreased to 1/3‐1/2 of control levels by Day 4 (calculated per metabolic body mass) and returned gradually to starting values by about 4 weeks after dosing. Water intake displayed a triphasic pattern: at first it was slightly increased (Days 1 to 3), then reduced (on Days 4 to 12) and finally increased again throughout the remainder of the test period. The absolute and/or relative weights of thymus, testicles, ventral prostate and interscapular brown fat were significantly decreased at termination. These results indicate that the LD50‐value for TCDD in the male, adult Han/Wistar rat is substantially above 1400 μg/kg, and that suppression of appetite is the principal phenomenon responsible for TCDD‐induced body weight reduction.
Cefotaxime Disposition Pharmacokinetics during Peritoneal Dialysis
Authors: Overgaard S. , Løkkegaard N. , Scrøder S. , Fugleberg S. , Nielsen‐Kudsk F.
Published: March 2009

Abstract: The pharmacokinetics of cefotaxime and its main metabolite des‐acetyl‐cefotaxime were studied after a single 1000 mg intravenous dose in 8 patients with end stage renal disease during peritoneal dialysis. Pharmacokinetic parameters were determined by iterative non‐linear least squares regression analysis of plasma and dialysis fluid drug concentration curves. Biological half‐life of cefotaxime ranged from 2.3 to 8.2 hours and total plasma clearance from 11 to 103 ml/min. (0.11 to 1.7 ml/min./kg b.wt). Only 1.4% to 4.2% of the intravenous dose of cefotaxime was distributed to the dialysis fluid. We conclude that the dosage of cefotaxime to uraemic patients adjusted to the renal function needs no further adjustment during peritoneal dialysis.
Can Blood Pressure Reduction Induced by Slow Calcium Channel Blockade (Verapamil) be Reversed by Calcium Infusion?
Authors: Midtbø Kjell , Hals Ottar
Published: March 2009

Abstract:The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31‐63 years, with mild and moderate essential hypertension, being on long‐term treatment with the slow calcium channel blocker verapamil. The calcium load induced a signifiant (P<0.001) increase in mean serum ionized calcium (from 1.240.01 to 1.40±0.2 mmol/1). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verapamil.
Effect of Chlorpromazine on the Metabolism of3H‐Noradrenaline Released from Rabbit Aorta
Authors: Nedergaard Ove A. , Abrahamsen Jan
Published: March 2009

Abstract:The effect of chlorpromazine on the metabolism of3H‐noradrenaline (3H‐NA) released spontaneously or by electrical‐field stimulation was studied on the rabbit isolated aorta preloaded with3H‐NA. Chlorpromazine (10−6M) neither altered the spontaneous outflow of total tritium nor had any major effect on the distribution of the3H‐outflow on3H‐NA and its3H‐metabolites. Chlorpromazine (10−6M) altered the distribution in stimulation‐evoked3H‐overflow. Thus,3H‐NA and3H‐NMN were increased,3H‐DOPEG was markedly decreased and3H‐DOMA and3H‐OMDA were unchanged. It is concluded that chlorpromazine is an inhibitor of uptake‐1.
Allyl Alcohol Liver Injury: Suppression by Ethanol and Relation to Transient Glutathione Depletion
Authors: Penttilä Kai E. , Mäkinen Judith , Lindros Kai O.
Published: March 2009

Abstract:Rats metabolized a sublethal gastric dose (0.73 mmol/kg) of allyl alcohol (AlOH) within 10‐15 min. Oxidation of AlOH to acrolein was accompanied by an equally rapid, but only transient depletion of hepatic reduced glutathione (GSH). GSH was restored to levels above normal within 5 hrs. Simultaneously, AlOH provoked marked elevation of alanine aminotransferase, γ‐glutamyl transpeptidase, and glutamate dehydrogenase activities in plasma and formation of lesions mainly in the periportal regions of the liver. Inhibition of alcohol dehydrogenase by 4‐methyl pyrazole completely counteracted these effects. On the other hand, attempts to potentiate the toxicity of acrolein by the aldehyde dehydrogenase inhibitor cyanamide enhanced only the release of alanine aminotransferase. Co‐administration of ethanol (3 g/kg) inhibited the rate of AlOH oxidation by more than 90%. Although with ethanol GSH remained depleted for several hours, the release of enzymes was markedly suppressed and the histologic changes completely prevented. These results indicate that the rapid rate of acrolein formation, rather than persistently lowered GSH content, is crucial in the hepatotoxicity of AlOH. They also suggest, that oxidation of acrolein via aldehyde dehydrogenase does not represent a major pathway for its detoxicationin vivo.
Effects of Cadmium on Superoxide Dismutase and Lipid Peroxidation in Liver and Kidney of Growing Rats:In VivoandIn VitroStudies
Authors: Hussain T. , Shukla Girja S. , Chandra S. V.
Published: March 2009

Abstract:Intraperitoneal administration of cadmium acetate (Cd2+, 0.4 mg/kg) to rats daily for 30 days was found to inhibit the activity of superoxide dismutase (SOD), to increase the endogenous levels of lipid peroxides and lipid peroxidation in the liver and the kidney tissues. Addition of varying concentrations of Cd2+(10‐100 μM)in vitroalso inhibited SOD in both the tissues. It appears that the inhibition of SOD could be due to direct interaction of Cd2+with the enzyme molecule. Lipid peroxidation reaction was also increased after addition of Cd2+to fresh homogenate of these tissues, however, it did not produce any effect in heated homogenates inin vitroexperiments. It indicated that Cd‐induced elevation in lipid peroxidation may not be only due to the possibility of higher level of superoxide radicals resulting from inhibited superoxide dismutase but could also be as a result of direct action of Cd2+on the peroxidation reaction. Thus, the possibility of involvement of free radical damage to the membrane structures in Cd toxicity has been demonstrated in these experiments.
Acute Comparison of Clovoxamine and Mianserin, Alone and in Combination with Ethanol, on Human Psychomotor Performance
Authors: Strömberg C. , Mattila M. J.
Published: March 2009

Abstract:Objective and subjective effects on human performance of clovoxamine and mianserin were measured in 12 student volunteers who participated in 12 test sessions and received single doses of clovoxamine 50 mg, 100 mg and 150 mg, mianserin 20 mg, and placebo in a double‐blind and cross‐over manner. Each test drug was given twice, both in combination with alcohol 0.8 g/kg and with a non‐alcoholic drink. The tests included tracking, body balance, flicker fusion, horizontal nystagmus, digit symbol substitution, recall memory, and subjective assessments on visual analogue scales. Mianserin and alcohol impaired objective performance in most tests, and their combination showed at least an additive effect. Alcohol counteracted rather than increased mianserin‐induced subjective sedation. Clovoxamine neither differed significantly from placebo nor increased alcohol effects. On the contrary, clovoxamine 150 mg reduced significantly alcohol‐induced body sway. No evidence of pharmacokinetic interactions were found between the study drugs and alcohol.
Methyl Mercury Decreases the Eggshell Thickness and Inhibits the Ca2+ Uptake in a Homogenate of the Eggshell Gland Mucosa and its Subcellular Fractions from the Domestic Fowl
Authors: Lundholm C. E.
Published: March 2009

Abstract: In the domestic fowl 20 mg of methyl mercuric chloride (MeHg) in a single oral dose given a day before egg‐laying reduced the eggshell index by 35% and decreased the Ca content of the eggshell by 31% compared with those in the eggs laid on the previous days. The plasma concentration of Ca was reduced by MeHg by 50% in comparison with controls. The Ca concentration in the shell gland mucosa was not decreased by MeHg in relation to the control value. The rate of ATP‐dependent Ca2+ binding by the homogenate of the mucosa was reduced by 33% by MeHg in relation to the control rate. The activity of Ca2+‐Mg2+‐ATPase was not changed.
Antagonist Effects of the Enantiomers of 3‐PPP towards α1‐Adrenoceptors Coupled to Inositol Phospholipid Breakdown in the Rat Cerebral Cortex
Authors: Fowler Christopher J. , Thorell Gun
Published: March 2009

Abstract:The effects of the two enantiomers of 3‐PPP upon α1‐adrenergic and muscarinic receptors coupled to the inositol phospholipid (PI) breakdown response have been investigated. 3‐PPP(‐) and 3‐PPP(+) were found to antagonize the noradrenaline (10 μM) ‐ stimulated PI breakdown in rat cerebral cortical miniprisms with IC50 values of 18 and 61 μM, respectively. The dopamine receptor antagonists haloperidol and raclopride were also antagonists, with IC50 values of 0.4 and 25 μM, respectively. 3‐PPP(‐) and raclopride were found further to act as competitive antagonists, with pA2values of 6.03 and 5.44, respectively. 3‐PPP(‐), 3‐PPP(+) and haloperidol also antagonized the muscarinic receptor‐mediated carbachol (50 μM) ‐ stimulated PI breakdown in cortical miniprisms, albeit at high concentrations (IC50 values of 91, 170 and 28 μM, respectively) whereas raclopride produced only 24% inhibition at the highest concentration tested (100 μM).
Tremorigenic Effect and Inhibition of Tryptamine and Serotonin Receptor Binding by β‐Carbolines
Authors: Airaksinen M. M. , Lecklin A. , Saano V. , Tuomisto L. , Gynther J.
Published: March 2009

Abstract:The abilities of some naturally occurring β‐carbolines (BCs), dihydro‐BCs and tetrahydro‐BCs to inhibit the specific binding of3H‐tryptamine (TA),3H‐serotonin (5‐HT) and3H‐ketanserine to rat brain membranes and to induce tremor in mice were studied. These compounds, particularly DHBCs and BCs, showed higher affinity for TA binding sites than to 5‐HT1or 5‐HT2binding sites inhibiting the former at nanomolar and the two latter ones at micromolar or high micromolar concentrations. The Kivalues for norharmane, harmaline and harmine (17, 18 and 74 nM, respectively) for TA sites indicate the highest affinity so far described for natural β‐carbolines to any receptor sites and thus may indicate their major site of action. Among the BC derivatives studied, the before mentioned harmala alkaloids were the most potent inducers of tremor in mice, although the orders of the tremorogenic potency and the binding to TA site did not correlate. It is suggested that especially the tremorigenic effect of BC derivatives is partly based on the binding to specific tryptamine receptors.
Studies on the Mechanism of Acetamide Hepatocarcinogenicity
Authors: Dybing Erik , Søderlund Erik J. , Gordon W. Perry , Holme Jørn A. , Christensen Terje , Becher Georg , Rivedal Edgar , Thorgeirsson Snorri S.
Published: March 2009

Abstract:The hepatocarcinogen acetamide, in single doses of 100 and 400 mg/kg b.wt., was shown to act as an initiator in a dose‐dependent fashion in rat liver using the Solt‐Farber method. Acetamide and its putative metabolite N‐hydroxy‐acetamide did not cause liver necrosis in single dose experiments. Acetamide showed no evidence for genotoxicity in tests for mutations inSalmonella typhimurium, for DNA damage in rat hepatoma cells or for DNA repair in isolated rat hepatocytes. In contrast, N‐hydroxy‐acetamide displayed genotoxic activity in all 3 test systems. Neither acetamide nor N‐hydroxy‐acetamide induced transformation of primary Syrian hamster embryo cells or gave evidence of inhibition of metabolic cooperation in V79 cells. Radiolabeled acetamide and N‐hydroxy‐acetamide were not bound covalently to proteins in the presence of various metabolic activation systems (microsomes plus NADPH or xanthine/xanthine oxidase, cytosol or cytosol plus acetyl CoA or proline plus ATP). N‐Hydroxy‐acetamide was cytotoxic to monolayers of isolated hepatocytes at concentrations above 2.5 mM. This cytotoxicity was increased after diethyl maleate treatment, but N‐hydroxy‐acetamide did not deplete cellular glutathione. A HPLC system was developed for the separation and quantification of acetamide, N‐hydroxy‐acetamide and acetic acid. No significant excretion of N‐hydroxy‐acetamide or acetic acid in the urine could be demonstrated after treatment of rats with 100 or 1,000 mg/kg b.wt. of acetamide. The underlying mechanism for the observed initiating effect of acetamide is obscure.
Effects of Lithium on Calmodulin‐stimulated Adenylate Cyclase Activity in Cortical Membranes from Rat Brain
Authors: Mørk Arne , Geisler Arne
Published: March 2009

Abstract:The influence of lithium on calmodulin‐stimulated adenylate cyclase activity has been studiedin vitroand after chronic treatment. Chronic lithium treatment decreased calcium‐calmodulin‐stimulated adenylate cyclase activity in rat cortical membranes, while no effect was observed on GTP‐stimulated activity. Lithiumin vitroinhibited adenylate cyclase activity stimulated by isoprenaline, GTP or calcium‐calmodulin. Calcium‐calmodulin‐stimulated activity was more sensitive to lithium (2 mM) than isoprenaline‐ and GTP‐stimulated activities (5 mM) and activities by these agents combined. Lithium had no effect on the unstimulated enzyme activity. The inhibitory effect of lithiumin vitroon calcium‐calmodulin‐stimulated adenylate cyclase activity was antagonized by magnesium. The inhibition induced by lithiumin vitroon the GTP‐stimulated adenylate cyclase activity was increased by substituting manganese for magnesium in the assay media. Furthermore, the manganese‐stimulated activity was also reduced by lithium. The latter effect was not observed in calmodulin‐depleted membranes, but the inhibitory effect of lithium could be restored by addition of exogenous calmodulin. The present results suggest that lithium might influence the interaction of calmodulin with the enzyme and/or interfere with the divalent cation site(s) on the adenylate cyclase system.
Barbiturate and Ethanol Sleeping Times and Pharmacokinetics of Propranolol in Mice after Intravenous Administration of Haem Arginate
Authors: Tokola Olavi
Published: March 2009

Abstract:Haem arginate is a new haem compound recently introduced for treatment of porphyrias. Previously haematin has been reported to increase certain hydroxylase activities in extrahepatic tissues, but even in therapeutic doses it impairs the microsomal foreign substance metabolism in the liver. Haem arginate at a dose equivalent to haem 10 mg/kg (threefold therapeutic dose) did not prolong the hexobarbital sleeping time of mice, 20 mg/kg did prolong the hexobarbital and possibly also the ethanol sleeping time. Haem arginate administered in high doses prior to oral propranolol did not alter the bioavailability of the latter. With regard to drug interactions haem arginate may be safer than haematin.
A Method Using L‐Hyoscyamine for the Study of Muscarinic Acetylcholine Receptor Binding in Vivo
Authors: Palmér L. , Lundgren G. , Karlén B.
Published: March 2009

Abstract:Studies of muscarinic receptor concentration and comparative binding assays of agonists and antagonists are presently donein vitroby incubation and measurement of the binding to tissue homogenates of the radiolabeled potent antagonists3H‐scopolamine or3H‐quinuclidinyl benzilate. We have developed a technique based on gas chromatography ‐ mass spectrometry that allows studies of the muscarinic receptor concentration to be performedin vivounder physiologic conditions. By injecting the optical antipodes of atropine, D‐ and L‐hyoscyamine separately in mice and following their kinetics in different parts of the brain it was possible to separate the specific receptor binding of the active antipode L‐hyoscyamine from that of the inactive antipode D‐hyoscyamine, representing unspecific binding. Two hrs after the administration of L‐hyoscyamine, 2 mg/kg intravenously, its concentration in brain was found to represent “maximum” specific binding. The physiological significance of specifically bound L‐hyoscyamine was tested on its blocking effect on oxotremorine induced tremor.
Chelation in Metal Intoxication XXIV: Influence of Various Components of Vitamin B Complex on the Therapeutic Efficacy of Disodium Calcium Versenate in Lead Intoxication
Authors: Tandon S. K. , Flora S. J. S. , Singh S.
Published: March 2009

Abstract: The supplementation of vitamin‐B complex reduces lead intoxication. With a view to identify the components of vitamin‐B complex responsible for such protection, riboflavin, calcium pentothenate, pyridoxine, nicotinamide, folic acid and cyanocobalamine were investigated for their ability, and their influence on the efficacy of disodium calcium versenate (Na2CaEDTA), to enhance the urinary excretion of lead, mobilize tissue lead and restore lead induced biological alterations in lead intoxicated rats. Folic acid and pyridoxine besides thiamine may be the responsible factors in prophylaxis of lead poisoning by vitamin B complex or in enhancing the antidotal properties of Na2CaEDTA.
Acute Effects of Nomifensine onin VivoUptake and Metabolism of Dopamine, Noradrenaline and Serotonin in the Rat Brain
Authors: Broch Ole Jacob
Published: March 2009

Abstract:Nomifensine, in contrast to all other antidepressants, inhibits the neuronal uptake of dopamine. The effect of this drug (10 mg/kg intraperitoneally) on the metabolism of dopamine, serotonin and noradrenaline was studied in the rat brain. After 1.5 hours, nomifensine increased the concentrations of homovanillic acid (HVA) in corpus striatum and total (free and conjugated) 3‐methoxy, 4‐hydroxyphenylglycol (MOPEG) in mesencephalon, but had no effect on the 5‐hydroxyindoleacetic acid (5‐HIAA) in pons/medulla oblongata and mesencephalon. The effect was identical with that of desipramine (25 mg/kg) on MOPEG and of imipramine (25 mg/kg) on 5‐HIAA. Two methods ordinarily used for estimating turnover rates of monoamines were compared: accumulation of acid metabolites after probenecid (measuring efflux of metabolites from the brain) and accumulation of monoamine precursors after decarboxylase inhibition (measuring amine synthesis). The efflux was reduced for 5‐HIAA and MOPEG but increased for HVA after nomifensine. Imipramine had the same effect on 5‐HIAA and desipramine on MOPEG. Desipramine decreased the efflux of HVA from corpus striatum. In contrast, nomifensine did not change the synthesis of noradrenaline and serotonin significantly. Imipramine reduced the synthesis of serotonin in pons/medulla oblongata. In corpus striatum nomifensine, unlike imipramine, increased the concentration of 5‐HIAA and synthesis of serotonin in spite of a decrease in efflux, probably because of a secondary effect from the dopaminergic action. The conclusion was made that there were more than one compartment of monoamine metabolites. The antidepressants could to some extent lead to a shift in the metabolism to sites more distant to the transport mechanism.
Similar Effects of Acetylsalicylic Acid and Morphine on Immediate Responses to Acute Noxious Stimulation
Authors: Hunskaar Steinar
Published: March 2009

Abstract: The formalin and writhing tests in mice were employed to investigate a possible delay in the onset of antinociceptive action of acetylsalicylic acid (ASA). Drugs were given 30 min. before the noxious stimulation by either formalin or acetic acid. In the formalin test, the difference between the drug treated groups and the control group reached statistical significance within 30 sec. of noxious stimulation. ASA (400 mg/kg intraperitoneally) and morphine (5 mg/kg intraperitoneally) treated groups were not significantly different in any of the ten periods (30 sec. each) that were analysed during the first 5 min. In the writhing test, the number of writhings in response to intraperitoneal injection of acetic acid was counted during the first 20 min. The difference between the drug treated groups and the control group reached statistical significance after 3 min. both for ASA (400 mg/kg subcutaneously) and morphine (2 mg/kg subcutaneously) and no significant differences between the drug treated groups were found in any of the one min. periods that were analysed. Thus no delay of onset in the action of ASA compared to morphine could be demonstrated, and ASA seems to be antinociceptive also in acute non‐inflammatory pain. Actions apart from inhibition of the synthesis of prostaglandins are suggested for this effect of ASA.
Haemodynamic Effects of Disopyramide Using a New Model of Intravenous Administration
Authors: Bonde Jan , Pedersen Lars E. , Angelo Helle R. , Svendsen Tage L. , Trap‐Jensen Jens , Graudal Niels A. , Kampmann Jens P.
Published: March 2009

Abstract:Intravenous treatment with disopyramide is usually performed by administration of a bolus injection of 150 mg given over 5 min. followed by a continuous infusion of 18‐24 mg hour‐1. A decrease in cardiac output is associated with this rapid bolus injection. Seven patients with ischaemic heart disease entered an open randomised cross‐over trial to elucidate if an extension of the bolus injection time to 20 min. resulted in a smaller decrease in cardiac output. Cardiac index decreased significantly (P< 0.001) in both situations, with maximum decrease observed at time 5 and 20 min., respectively (equivalent to the ending of the administration of 150 mg disopyramide). The decrease in Cardiac index (mean ± S.E.M.) was identical in the two situations (2.56 ± 0.23 to 1.78 ± 0.21 1/min. × m2(30%) and 2.66 ± 0.17 to 1.94 ± 0.19 1/min. × m2(27%)), respectively. Blood pressure was unchanged, while heart‐rate (P < 0.025) and preejection period index (P< 0.005) increased significantly and to the same extent in the two situations. Significant correlations between the log free and log total serum concentration of disopyramide and the relative change in preejection period index of r = 0.840 (P<0.01) and 0.919 (P<0.01), respectively, were observed giving disopyramide over 5 min. A significant anticlockwise hysteresis was observed extending the time of administration to 20 min. As no haemodynamic advantages are achieved by the slower way of administration we would still recommend the bolus injection to be given over 5 min.
The Effect of Mercury Chloride and Methyl Mercury on Brain Microsomal Na+‐K+‐ATPase after Partial Delipidisation with Lubrol®
Authors: Magour S. , Mäser H. , Greim H.
Published: March 2009

Abstract: The microsomal Na+‐K+‐ATPase of rat brain was inhibited by mercury chloride and methyl mercury. The IC50 was 6.5 × 10‐7 M for mercury chloride and 3.5 × 10‐6 M for methyl mercury. The inhibition was of a non‐competetive type with respect to ATP. The non‐ionic detergent Lubrol$rG potentiated the inhibitory effect of both mercurials. It is concluded that Lubrol$rG removes the bulk lipids present outside the catalytic center of the enzyme. Consequently, the enzyme will become more sensitive to the inhibition by both mercurials.
Distribution of Microcystis aeruginosa Peptide Toxin and Interactions with Hepatic Microsomes in Mice
Authors: Brooks W. P. , Codd G. A.
Published: March 2009

Abstract: Purified 14C‐labelled peptide toxin from the cyanobacterium Microcystis aeruginosa was administered intraperitoneally to mice and the distribution of label determined between the major organs. Seventy per cent of the label was localized in the liver after 1 min.; this value increasing to almost 90 per cent after 3 hours. Label associated with the lungs and other individual organs varied between 10 and 1 per cent of the 14C recovered throughout. Three microsomal enzyme inducers, β‐naphthoflavone, 3‐methylcholanthrene and phenobarbital, afforded protection against liver damage and extended survival if given to mice before the administration of an LD50 dose of toxin. Toxin‐dependent changes in liver cytochrome levels were also reduced by the enzyme inducers.
A Comparative Study of the Pharmacodynamics and Pharmacokinetics of Nicardipine and Nitrendipine in the Isolated Rabbit Heart
Authors: Nielsen‐Kudsk F. , Askholt J.
Published: March 2009

Abstract: The myocardial pharmacodynamic effects of the two dihydropyridine calcium‐antagonists nicardipine and nitrendipine were comparatively studied in the isolated, spontaneously beating and retrogradely perfused rabbit heart at stepwise increased drug concentrations within the range 0.5‐260 ng·ml‐1 (1.1‐721 nM). Both drugs produced a progressive and very pronounced inhibition of myocardial contractility as measured by both contraction amplitude and contraction velocity. The corresponding Emax‐values were about 100% and IC50‐values about 10 and 65 nM, respectively. Myocardial oxygen consumption did not decrease at the lower concentrations of neither nicardipine nor nitrendipine but were at the higher levels inhibited significantly with Emax‐values of about 68 and 78% and IC50‐values about 21 and 136 nM, respectively. Coronary flow‐rate increased at the lower concentrations of the drugs to about 125 and 118% and then decreased to 80 and 77%, respectively. Both drugs, but especially nitrendipine, showed a marked negative chronotropic effect (Emax 33 and 56% and IC50 6 and 81 nM, respectively). The frequency‐corrected QT‐intervals were progressively decreased by the drugs. Myocardial accumulation and disposition pharmacokinetics of nicardipine, nitrendipine and nimodipine were also studied. The terminal half‐lives for the drugs were about 56, 16 and 29 min., respectively. Apparent relative volumes of drug distribution in the myocardium which equals the average concentration ratio for the drugs between this tissue and the perfusion liquid at kinetic steady‐states were about 290, 61 and 177 ml·g‐1, respectively. Although nicardipine and nitrendipine accumulated slowly at different rates in the rabbit heart both drugs produced a faster progressing and very marked negative inotropic effect and a less than proportional reduction in oxygen consumption accompanied by an only initial increase in coronary flow‐rate.
Gastrointestinal Transit Rate‐related Absorption of Emepronium: A Study in Mice
Authors: Hallén Bengt , Sundwall Anders
Published: March 2009

Abstract:The gastrointestinal (GI) absorption in mice of the anticholinergic quaternary ammonium compound emepronium, assessed by the urinary excretion of radioactivity and unchanged drug, increased from 1% to 7% and from 0.5% to 5%, respectively, in the dose range 0.1 to 40 mg/kg, whereafter a plateau was reached. Changes in the metabolism were evident at doses exceeding 80 mg/kg when 80% of the radioactivity was excreted as unchanged emepronium, as compared to 50% at lower doses. No dose‐dependent urinary excretion of radioactivity was detected following intravenous injection. The increase in the fraction of the dose excreted in the urine after oral administration therefore cannot be easily explained by a dose‐dependent metabolism or renal excretion. However, a relationship was seen between the reduced gastrointestinal motility, produced by increasing doses of the drug, and the increased bioavailability. Atropine sulphate given subcutaneously (1–50 mg/kg) more than doubled the urinary recovery of a small pharmacologically inactive oral dose of emepronium (5 mg/kg) and thus confirmed the transit rate‐dependent absorption of emepronium. The superimposed effect of the pharmacological action on the GI transit rate, derived from the inherent property of an anticholinergic drug, may be of special significance for a drug with a low degree of absorption and a high variability, such as has been observed in clinical trials with the quaternary drug emepronium (Cetiprin®).
Interactions between Morphine‐like Analgesics and Anticonvulsant Drugs
Authors: Frey Hans‐Hasso
Published: March 2009

Abstract:The effect of pretreatment with morphine‐like analgesics on the anticonvulsant effect of phenytoin and phenobarbital against electroconvulsions and of phenobarbital and ethosuximide against pentetrazole‐induced convulsions was studied in mice. High doses of morphine (4 mg/kg subcutaneously), fentanyl (100 μg/kg subcutaneously), pethidine and pentazocine (4 and 8 mg/kg subcutaneously) increased the anti‐electroshock effect of phenytoin; that of phenobarbital was likewise increased by morphine (2 and 4 mg/kg), fentanyl (25–100 μg/kg) and pentazocine (2–8 mg/kg), whereas pethidine had no corresponding effect. There was no consistent effect of pretreatment with the analgesics studied on the anticonvulsant effects of phenobarbital and ethosuximide in the pentetrazole seizure threshold test.
Neuroleptic Malignant Syndrome during Perphenazine Treatment
Authors: Nielsen Dorthe , Aunsholt Niels Aage , Andersen Per Thorgaard
Published: March 2009

Abstract: A 50‐year old woman developed symptoms of a neuroleptic malignant syndrome with myoglobinuric renal failure during treatment with perphenazine. After discontinuation of perphenazine and repetitive haemodialysis, the patient recovered. Clinical characteristics of the syndrome, differential diagnosis and various therapeutic possibilities are shortly reviewed.
Metabolic Alkalosis Following Administration of an Organophosphorus Compound, O,S,S‐Trimethyl Phosphorodithioate
Authors: Nemery B.
Published: March 2009

Abstract: The oral administration of a single dose of O,S,S‐trimethyl phosphorodithioate (OSSMe) to rats was found to result, 24 hours after treatment, in a dose‐related metabolic alkalosis. Non‐invasive indices of kidney damage revealed that during the first 4 hours after OSSMe administration there was a fourfold increase in urine flow with increases in albumin, β2‐microglobulin and N‐acetyl‐glucosaminidase excretion. These results suggest that OSSMe‐induced metabolic alkalosis may result from early renal functional disturbances.
Differential Effects of the Dopamine Antagonist Remoxipride on Apomorphine Induced Behaviour in the Rat
Authors: Ståhle Lars , Ljungberg Tomas , Rodebjer Anders , Ögren Sven‐Ove , Ungerstedt Urban
Published: March 2009

Abstract: The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.
Comparison of the Effect of Antidepressant Drugs on Arrhythmias in the Isolated Rat Heart Subjected to Myocardial Ischaemia and Reperfusion
Authors: Bril A. , Rochette L.
Published: March 2009

Abstract:Rat isolated hearts were perfused according to the Langendorff's method. The hearts were prelabelled with3H‐noradrenaline (3H‐NA) and the left coronary artery was occluded during 10 min. The liberation of3H‐NA and the development of ventricular arrhythmias were investigated during ischaemia and the following reperfusion period. In control preparations, reperfusion was followed by ventricular fibrillation and a sudden release of radioactivity in the coronary effluent. Antidepressants such as imipramine, metapramine, mianserin and nomifensine prevented reperfusion arrhythmias in a concentration‐dependent manner and caused bradycardia. Amineptine, however, was ineffective in preventing reperfusion arrhythmias even in a high concentration, this agent did not decrease heart rate. Nevertheless none of the antidepressants changed the rate of liberation of3H‐NA during the ligation and reperfusion periods. A quinidine like action seems the most appropriate explanation for the cardiac effects of these antidepressant drugs.
Binding of the Aliphatic Halides 1,2‐Dihromoethane and Chloroform in the Rodent Vaginal Epithelium
Authors: Brittebo Eva B. , Kowalski Bogdan , Brandt Ingvar
Published: March 2009

Abstract: Whole‐body and light microscopic autoradiography were used to study the binding of 1,2‐dibromo(14C)ethane (14C‐DBE) and 14C‐chloroform (14C‐CF) in the mouse and rat vaginal epithelium in vitro and in vivo. In pregnant mice, mice pretreated with pregnant mare's serum gonadotropin (PMSG) or ovariectomized mice primed with medroxyprogesterone, a high level of bound 14C‐DBE metabolites were present in the epithelium, while in ovariectomized oestradiol‐primed mice or intact oestradiol‐primed mice, the binding was low. Similar results were obtained with 14C‐CF, although the level of binding generally was lower than that observed after 14C‐DBE‐exposure. No binding of 14C‐DBE‐metabolites was observed in the juvenile rat vaginal epithelium, whereas a high binding was present in the PMSG‐primed adult rat vaginal epithelium. Collectively, these data show that 14C‐DBE and 14C‐CF are transformed in situ to metabolites that are irreversibly bound to the vaginal epithelium. The results also suggest that the activating enzyme is under endocrine control and has a low activity in the juvenile and oestradiol‐primed adult animal.
Chronic Salt Loading and Adrenergic Mechanisms in the Sprague‐Dawley Rat
Authors: Gradin Kathryn , Persson Bengt
Published: March 2009

Abstract:The effect of chronic salt loading on adrenergic mechanisms was evaluated in Sprague‐Dawley rats (and NMRI mice) maintained on a high sodium (8%) or normal sodium (0.3%) regime for 4 weeks. The basal blood pressure (carotid artery) was not influenced by the high salt diet but the heart rate and blood pressure increases to mental stress (jet air) were larger in the salt loaded rats. There were indications of an increased sympathetic tone in rats on the high salt diet since in these rats sympathoinhibitory treatment with ganglionic blockade or clonidine induced larger falls in blood pressure and heart rate than in the controls. Central catecholamines (brain stem, striatum, hemispheres) were determined spectrofluorimetrically after cation exchange chromatography. The high salt diet influenced neither the endogenous levels of noradrenaline nor central noradrenaline turnover (disappearance of noradrenaline after synthesis inhibition by α‐methyltyrosine and accumulation of dihydroxyphenylalanine after decarboxylase inhibition by 3‐hydroxybenzylhydrazine). There were no changes in central α2‐adrenoceptor responsiveness when assessed as clonidine‐induced deceleration of noradrenaline turnover in the brain and in central α1‐adrenoceptor responsiveness (clonidine‐induced increase of flexor reflex in spinalized rats and clonidine‐induced increase of motor activity in reserpinized mice). Peripheral sympathetic function was assessed in pithed rats. The pressor responses to intravenously administered noradrenaline (0.01‐10 μg/kg) and electrical stimulation of the spinal sympathetic nerves (SNS, 0.25‐2 Hz) were similar in the two groups, suggesting that salt did not influence vascular α‐adrenoceptor responsiveness or transmitter release. In contrast, there seemed to be an upregulation of cardiac β‐adrenoceptors in the salt loaded rats since the chronotropic responses to noradrenaline, isoprenaline, tyramine and SNS were increased. It is concluded that a high salt diet in the Sprague‐Dawley rat increases the responsiveness of cardiac β‐adrenoceptors and increases sympathetic nerve activity.