bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclophosphamide as a Potential Chemosterilant for Harmful Snails
Authors: Singh Ravindra , Agarwal R. A.
Published: July 2010

Abstract: Cyclophosphamide induced changes in the ovotestis of the snail Lymnaea acuminata, the vector of the giant liverflukes Fasciola hepatica and Fasciola gigantica were studied in order to explore potential of the drug as a chemosterilant for snails. The drug caused a dose dependent reduction in the levels of DNA, RNA and proteins and the activity of the enzyme alkaline phosphatase. It increased the activity of acid phosphatase and the levels of total free amino acids in the ovotestis. While the animals showed nearly total recovery in RNA and DNA levels 7 days after termination of drug treatment, changes produced in protein, amino acid levels and phosphatase activity did not show any recovery. It appears that cyclophosphamide, while affecting its primary targets i.e. DNA and RNA, irreversibly inhibits protein synthesis through other cellular enzymes as well.
Pharmacokinetics of Theophylline and 3‐Methylxanthine in Guinea Pigs. I. Single Dose Administration
Authors: Madsen Søren Munk , Ribel Ulla
Published: July 2010

Abstract:Aminophylline in the doses 6.31 · 10−5mol kg−1and 2.37 · 10−4mol kg−1(corresponding to 13.8 and 52.0 mg kg−1respectively) and 3‐methylxanthine 2.37 · 10−4mol kg−1(39.4 mg kg−1) was administered to guinea pigs by intravenous bolus injection, n = 7, 10, and 6, respectively. The shape of semilogarithmic plots of all measured plasma theophylline concentrations versus time was compatible with the use of an open 2‐compartment pharmacokinetic model assuming first‐order distribution and elimination processes, but in the comparison of the mean values of the pharmacokinetic parameters obtained after the administration of the low and the high theophylline dose, statistical analysis by Student's t‐test showed β and V1to be significantly altered (low dose: β=0.00338 min.−1, V1= 392 ml kg−1; high dose: β = 0.00198 min.−1, V1= 528 ml kg−1; P<0.05). Following the administration of 3‐methylxanthine, the observed plasma concentration time course of this pharmacologically active theophylline metabolite could be adequately described be means of the 2‐compartment open model. The administered 3‐methylxanthine was eliminated unchanged with a first‐order rate constant ten times larger‐than the total elimination rate constant of theophylline itself, the latter being observed after the administration of the equimolar dose of aminophylline (kel 3mx= 0.029 min.−1, kel theophylline= 0.00293 min.−1). Clearance was calculated to 14.4 ml kg−1min.−1for 3‐methylxanthine and 1.50 ml kg−1min.−1for theophylline. When aminophylline 2.37 · 10−4mol kg−1had been administered, 3‐methylxanthine was renally eliminated at a constant rate for the first hours after the injection, but it did only constitute a few per cent of the theophylline‐derived urine products.
Pharmacokinetics of Theophylline and 3‐Methylxanthine in Guinea Pigs. II. Multiple Dose Administration
Authors: Madsen Saren Munk , Ribel Ulla
Published: July 2010

Abstract:Following intravenous bolus injection of theophylline 2.37.10−4mol kg−1to guinea pigs (administered as aminophylline 52.0 mg kg−1), the elimination of the dose was more rapid in a group of 8 guinea pigs that had received theophylline 2.02 · 10−4mol kg−1(aminophylline 44.3 mg kg−1) intraperitoneally twice daily for 12 days prior to the experiment than in a group of 10 non‐pretreated guinea pigs of the same age. The difference was statistically significant in Student's t‐test (P<0.02). The mean values in the group of pretreated animals were: kel0.00457 min.−1, β 0.00296 min.−1, clearance 2.04 ml kg−1min.−1, Vdβ693 ml kg−1. By way of comparison, the values obtained in non‐pretreated guinea pigs were: kel0.00293 min.−1, β 0.00198 min.−1, clearance 1.50 ml kg−1min.−1, Vdβ757 ml kg−1. This result suggests enzyme induction to occur. The pharmacologically active theophylline metabolite 3‐methylxanthine did not accumulate in the plasma during the long‐term theophylline administration. The general plasma concentration level was 0–1.8.10−8mol ml−1(0–3 μg ml−1). In 5 percent of the samples were detected concentrations in the range 1.8 · 10−8‐7.2 · 10−8mol ml−1(3–12 μg ml−1), but the time of occurrence was sporadic.
The Effect of Chronic Lithium Treatment on the Sialic Acid Content in Rat Brain Synaptosomes
Authors: Edelfors Sven
Published: July 2010

Abstract: Rats were fed a lithium‐containing diet for five weeks (40 mmol LiCl/kg fodder). Plasma lithium concentration was 0.44 mmol Li+/1 plasma. The synaptosomes were isolated and incubated with 3H‐glucosamine for 60 min. The glycopeptides and the gangliosides were extracted and the sialic acid content and the 3H‐sialic acid content were measured. The lithium treatment produced an increase in the synaptosomal glycopeptide content. The sialic acid content was simultaneously increased in glycopeptides as well as gangliosides. The specific activity of sialic acid was reduced to 75% of the control value in the sialoglycopeptide fraction.
Influence of Age on in Vitro Effect of Cadmium on Rat Liver Cytochrome P‐450 Concentration and Monooxygenases Activity
Authors: Jahn Florentine , Klinger Wolfgang
Published: July 2010

Abstract: Cadmium++ added in vitro destroys rat liver cytochrome P‐450 (cyt. P‐450) with increasing age by 25–50%. Ethylmorphine N‐demethylation is inhibited only in rats 30‐days old and thereafter. Ethoxycoumarin 0‐deethylation is inhibited even in newborn rats, and the maximal inhibition appears to increase with age. It is concluded that in all age groups cadmium resistent cyt. P‐450 subspecies are present. Ethoxycoumarin 0‐deethylase activity possibly indicates the cadmium sensitive P‐450 fraction.
Effect of Age and Cardiopulmonary Bypass on the Pharmacokinetics of Lorazepam
Authors: Aaltonen Leena , Kanto Jussi , Arola Matti , Iisalo Esko , Pakkanen Antti
Published: July 2010

Abstract: The pharmacokinetics of lorazepam after 0.03 mg/kg intravenous administration was investigated in 14 surgical patients (nasal surgery under local anaesthesia) ranging in age from 25 to 86 years (8 males and 6 females). No statistically significant changes in the kinetics of lorazepam associated with the aging process were found. In these premedicated patients a slow onset of the drug action of lorazepam was assessed both subjectively and objectively with no apparent relationship to the age. These findings are of potential clinical importance, because it is highly desirable to use drugs for which age‐related alterations are of minimum degree. In 5 male patients undergoing surgery with cardiopulmonary bypass, lorazepam disappeared from the plasma after a single 4 mg intravenous injection with an apparent comparable half‐life (10.0 ± 3.2 min.) to that of the above mentioned surgical patients. The concentrations of both unconjugated and conjugated lorazepam dropped abruptly at the start of extracorporeal circulation followed by an increase in the postperfusion period. After this peak effect the mean apparent half‐life of lorazepam was 15.1 ± 5.8 hours indicating no great change in its elimination in comparison with patients operated under local anaesthesia (half‐life 12.1 ± 3.7 hours). Pharmacokinetically, lorazepam appears to be a useful agent in connection with cardiopulmonary bypass operation.
Effect of 3,4‐Dihydroxyphenylpyruvic Acid on the Metabolism of L‐DOPA in Isolated Perfused Rat Liver
Authors: Lindén I.‐B. , Niemi S.
Published: July 2010

Abstract:The effect of 3,4‐dihydroxyphenylpyruvic acid (DHPPA) on the hepatic metabolism of L‐DOPA was investigated in isolated perfused rat liver. DHPPA decreased the initial hepatic extraction and prolonged the elimination half‐life of L‐DOPA when they were added simultaneously at the ratio 1:4 (L‐DOPA: DHPPA) to the perfusate. At the ratio 1:1 DHPPA had no effect on the elimination half‐life, but decreased the initial hepatic extraction of L‐DOPA. When L‐DOPA was added alone the initial loss of L‐DOPA was 30% at 5 min. At that time the perfusion medium had passed the liver 2.5 times. Between 5 to 60 min. about 5% of the dose was extracted in a single pass through the liver. DHPPA added alone or together with L‐DOPA was rapidly converted to L‐DOPA, only about half of the DHPPA dose remained unmetabolized in the “plasma” at 2.5min.The main metabolites in bile of all the compounds tested were conjugates of homovanillinic acid and 3,4‐dihydroxyphenylacetic acid.
Sodium Nitroprusside Inhibits Lactate Formation in Rat Atria: Is Cyclic GMP Involved?
Authors: Laustiola Kai , Vuorinen Pauli , Vapaatalo Heikki , Metsä‐Ketelä Timo
Published: July 2010

Abstract:Sodium nitroprusside (NP) was found to decrease the tissue lactate level under conditions of high (HiOxSa) and low (hypoxia) oxygen saturation in spontaneously beating rat atria. Nitroprusside also increased the level of cyclic GMP (cGMP) in a dose‐dependent manner in both states. The time course and dose dependence of these effects suggest that cGMP might be responsible for the decreased tissue level of lactate demonstrated. The findings suggest that cGMP might inhibite lactate production in HiOxSa and antagonize the hypoxia‐induced acceleration of anaerobic metabolism. It is proposed that a state of low‐rate glycolysis results from this inhibitory effect of cGMP. Furthermore, the possible role of cGMP as a feed‐back regulator of the redox state is discussed in the light of these findings.
LD50 ‐ its value for the pharmaceutical industry in safety evaluation of drugs.
Authors: Malmfors T. , Teiling A.
Published: July 2010

Abstract Does the pharmaceutical industry perform LD50‐determinations in animals just because it is required by the authorities or are there any scientific benefits from counting dead animals and calculating and index of lethal toxicity? This is an important question when discussing LD50 and possible alternatives. We will try to answer this question by presenting data and some views collected during almost ten years at a Swedish pharmaceutical company.

We will describe how we have made use of the LD50‐values in the safety evaluation process. We will compare LD50‐values with the dose levels used in longterm toxicity both after single or repeated administration and with therapeutical dose levels in man for different classes of drugs.

These data will enable us to demonstrate the value of the LD50‐determinations. As we are of the opinion that the LD50‐value itself has a limited value for the total safety evaluation of drugs we will look into the possibility of replacing the LD50‐determination with something else as an indication of lethal toxicity.

In order to minimize the number of animals used and the number of animals dying because of dosing in studies on lethal toxicity we will try to support a proposal to use the maximal nonlethal dose (MNLD) as an indication of lethal toxicity in small animals.
Hepatotoxicity of Hornet's Venom Sac Extract, after Repeatedin Vivoandin VitroEnvenomation
Authors: Neuman Manuela G. , Eshchar Jerachmiel , Cotariu Dita , Ishay Jacob S. , Bar‐Nea Liliane
Published: July 2010

Abstract:The activity of some enzymes involved in hepatic function was measured in rats,in vivo, after one week's repeated envenomation with Hornet's(Vespa orientalis)venom sac extract (VSE) andin vitroin monolayers of tissue culture of rat hepatocytes treated with VSE. The maximal serum enzymatic changes observedin vivowere significant: twenty fold rise of alkaline phosphatase (ALP), a 7–8 fold rise of aspartate aminotransferase (AST) and a 4–5 fold rise in alanine aminotransferase (ALP) activity. Also 2–3x increases of both serum lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were noted. The maximalin vitrochanges were observed after six days of daily envenomation. There were five fold rises of the activity of AST in the medium, as well as of two‐three fold rises of ALT, ALP and LDH. These changes suggest that Hornet's VSE induces enzymatic changes in the liver after prolonged, repeated exposures. They also exclude a general effect, like shock, that might possibly occur in the intact animal, as the cause of the demonstrated hepatic damage.
Studies on Hydragogue Drugs: Light and Electron Microscopic Examination of the Isolated Rat Colonic Mucosa Exposed to Deoxycholic Acid and Synthetic Surfactants
Authors: Landsverk Thor , Oltedal Einar , Sund Reidar Bredo
Published: July 2010

Abstract: Sacs of the stripped and everted, isolated descending rat colon were incubated for 2 hours in presence of the following surfactants at the mucosal side: Dodecylsulphate (DDS), dioctylsulphosuccinate (DOSS), cetrimonium bromide (CTMAB), Triton X100 and deoxycholic acid (DOC). After tissue fixation, the sacs were processed for light microscopy (LM) and for scanning (SEM) and transmission (TEM) electron microscopy. All three methods revealed that DOSS (1.3 × 10‐4 and 2.6 × 10‐4 mol/1), CTMAB (5 × 1‐5 and 1 × 10‐4) and Triton (2 × 10‐5, 5 × 10‐5 and 1 × 10‐4) caused only minor or moderate changes compared to parallel controls, as did also DDS at 1 × 10‐5 and 2 × 10‐5 mol/1. DDS at 2 × 10‐4 and 4 × 10‐4 mol/l and DOC at 1.5 × 10‐4 and 3 × 10‐4 mol/l caused more prominent changes. LM showed swollen, vacuolated cells with pycnotic nuclei; many of these cells seemed to be extruded. According to SEM, cells thus affected were most abundantly localized to the normal extrusion zone at the borders of the crypt‐surface epithelial cell units. DOC tended to cause a more generalized affection within the units than DDS. In spite of these deleterious effects, gaps corresponding to missing epithelial cells were not observed. TEM indicated the mechanism responsible for restoration of epithelial continuity in spite of extensive cell loss: The remaining epithelial cells seemed to flatten out and re‐establish cell‐to‐cell contact by pseudopod formation along the basement lamina. This repair mechanism seemed to operate at a rapid rate; however, incomplete closure of cellular gaps i.e. small denuded parts of the basement lamina were occasionally observed. The results of this study are discussed in relation to a functional study under identical experimental conditions (Gastroenterol. Clin. Biol. 1981, 5, 124), in which these surfactants caused a significant alteration of normal colonic transport function.
Steric Aspects of Agonism and Antagonism at β‐Adrenoceptors: Experiments with the Enantiomers of Terbutaline and Pindolol
Authors: Jeppsson A.‐B. , Johansson U. , Waldeck B.
Published: July 2010

Abstract:The enantiomers of terbutaline, a β2‐selective adrenoceptor agonist, and pindolol, an unselective antagonist with partial agonist activity, were examined with respect to their ability to reactin vitroon adrenoceptors in the trachea (mostly β2) the soleus muscle (β2) and in the papillary muscle of the left ventricle (β1) from the guinea‐pig. (+)‐terbutaline was more than 3,000 times less potent than (—)‐terbutaline in relaxing the trachea and in depressing subtetanic contractions of the soleus muscle. (+)‐terbutaline did not inhibit the effects of (—)‐terbutaline in these tissues. The effect of (—)‐terbutaline on the papillary muscle was about 200 times weaker than on the soleus. (+)‐terbutaline had a negligible inotropic effect on the papillary muscle and it did not inhibit the effect of isoprenaline. The enantiomers of pindolol did not show any consistent agonistic activity under the present experimental conditions. (—)‐pindolol inhibited competetively the effect of isoprenaline to the same extent in all three tissues. (+)‐pindolol was about 200 times less potent in this respect. Our data do not reveal any qualitative differences in the pharmacological properties between the optical isomers of terbutaline and pindolol, respectively.
Effects of Anaesthetics on Protein Synthesis in Isolated Rat Hepatocytes: Inhibition by Diethyl Ether in Contrast to No Influence by Pentobarbital and Fentanyl
Authors: Bessesen Atle , Merland Jørg
Published: July 2010

Abstract:Hepatocytes were isolated from livers of fasted rats by a two–step Ca++–free/collagenase perfusion method. Suspensions of parenchymal liver cells were incubated in the absence and presence of three different anaesthetics, diethyl ether, pentobarbital and fentanyl at various concentrations. Their influence on the hepatocytes was monitored by measuring protein synthesis as the incorporation of L–(U–14C) valine (50 mCi/ mol, 4.2 mM) into liver proteins. Diethyl ether representing anaesthetics mainly affecting cellular membranes unspecifically, inhibited protein synthesis markedly, concentrations of approximately 10, 20 and 30 mM caused 27, 50 and 74 per cent inhibition respectively, of cellular protein synthesis. The rate of synthesis of medium proteins was somewhat more reduced indicating a greater susceptibility of the synthetic process of these proteins or that ether also inhibited protein secretion from cells to media. The effect of diethyl ether was completely reversible when the anaesthetic was removed by changing the medium. Pentobarbital representing barbiturate anaesthetics, reduced the synthesis of cell and medium proteins very little, while the opiate anaesthetic fentanyl had no inhibitory effect. These results demonstrate a potential hepatotoxic mechanism for membrane active drugs like diethyl ether. They also indicate that special precautions should be taken when this type of anaesthesia is used during the study of hepatic protein synthesis
Reduced Cofactor Function of Human High Molecular Weight Kininogen Induced by Rat Plasma Kallikrein
Authors: Hoem Nils‐Ove , Briseid Kjell
Published: July 2010

Abstract: Plasma kallikrein purified from acetone–activated, plasminogen–free rat plasma yielded in polyacrylamide gel electrophoresis protein bands corresponding to Mr values of 143,000 (main band) and 135,000 (lighter band). After SDS treatment without reduction the protein pattern had changed to two strong bands corresponding to Mr values of 87,000 and 78,000. Gel electrophoresis of kallikrein purified from plasma of rats pretreated with clinical dextran (200 mg/kg intravenously) produced main bands corresponding to Mr values of 120,000–130,000 and 78,000–80,000 for native samples and SDS–treated samples respectively (Johansen & Briseid 1983). Both kinds of kallikrein reduced the capacity of human high molecular weight kininogen to function as a cofactor in the surface–mediated activation of factor XII in a crude plasma preparation. The preparation obtained from plasma of dextran–treated rats was significantly more potent than was the normal kallikrein preparation, both as regards the effect against HMrK, and as an activator of plasminogen
Supersensitivity to Methacholine in Rat Urethra Following Hypertrophy or Disuse
Authors: Ekström Jörgen , Malmberg Lars
Published: July 2010

Abstract:It has been possible to sensitize the rat urethra without cutting its nerves. This was achieved by hypertrophy or disuse. Hypertrophy of the urethra (2–4–fold weight increase) was caused by the presence of an intraluminal paraffin bolus. Disuse was caused by diverting the flow of urine from the lower urinary tract. When examinedin vitroafter an experimental period of 1 to 4 weeks the EC50 value of the parasympathomimetic drug methacholine was in both cases half of that of controls. The common cause of the development of supersensitivity in the two types of experiments is thought to be decreases in the local concentration of transmitter at the muscle cells. The present findings favour the idea of a parasympathetic motor control of the rat urethra
Effects of Amiflamine and Related Compounds on the Accumulation of Biogenic Monoamines in Rat Brain Slices in Vitro and ex Vivo in Relation to their Behavioural Effects
Authors: Rényi Lucy , Ross Svante B.
Published: July 2010

The inhibition of the accumulation of serotonin, noradrenaline and dopamine in rat brain (occipital cortex and striatum) slices by amiflamine and its two major metabolites FLA 788(+) and FLA 668(+) was examined and compared with that of amine releasing compounds e.g. p‐chloroamphetamine (PCA) and α‐ethyltryptamine and uptake inhibitors, e.g. alaproclate, citalopram, desipramine, fluoxetine and norzimeldine. It was found that amiflamine and FLA 788(+) inhibited the accumulation of serotonin and noradrenaline but only slightly that of dopamine in vitro and ex vivo with a mechanism similar to that of PCA and α‐ethyltryptamine, i.e. with higher potency in reserpinized rats than in normal animals suggesting amine releasing mechanisms. Similar to α‐ethyltryptamine and PCA, amiflamine and FLA 788(+) caused behavioural changes (serotonin syndrome) which were particularly pronounced in reserpinized rats but also observed after a second administration of amiflamine in normal rats. Upon repeated administration of amiflamine the behavioural changes disappeared which indicates a functional down‐regulation of the serotonin receptors responsible for this syndrome. FLA 668(+) inhibited the accumulation of noradrenaline in vitro and ex vivo but had less effect on the accumulation of dopamine and particularly that of serotonin. It is concluded that amiflamine and FLA 788(+) inhibit the accumulation of serotonin and noradrenaline by releasing mechanisms and that the released serotonin triggers the behavioural changes observed.
Pharmacokinetics of Diltiazem and Other Calcium Entry Blockers
Authors: Hermann Philippe , Morselli Paolo L.
Published: July 2010

Abstract:Diltiazem, as well as other calcium entry blockers, is widely prescribed for the treatment of various types of angina. This review summarizes the current state of knowledge of the pharmacokinetics of diltiazem and of two other calcium entry blockers: verapamil and nifedipine. Although unrelated in their chemical structure, these three drugs have common features. They are highly lipophilic and have a large volume of distribution, are mainly cleared by metabolism and undergo an extensive first‐pass extraction. On the other hand, as expected from their quite dissimilar structures, they have their own particular kinetic characteristics. For example, metabolism of diltiazem and verapamil gives rise to active metabolites; repeated administration influences the kinetic profile of verapamil but not those of diltiazem and nifedipine. Absorption, distribution and elimination of these three drugs are differently affected by age and pathological conditions. The possible drug interactions involving diltiazem and the other calcium entry blockers are discussed, particularly that with digoxin. Due to its large therapeutic index, there is no need for treatment monitoring of diltiazem. Nevertheless, this procedure may provide useful information for optimizing the dosage regimen of each patient as the pathological condition and drug therapy may be quite complex.
Does Dihydroergotamine Reduce Plasma Volume?
Authors: Bergqvist David , Lindblad Bengt
Published: July 2010

Abstract: Indications on a plasma volume reduction by dihydroergotamine (DHE) has been found in earlier studies. This study was made in order to further evaluate such a change. In animal experiments (sheep, n = 10) measurements were performed of red blood cell volume and plasma volume using radioactive labelling techniques. Red blood cell volume was unchanged but a plasma volume decrease of 10% was found after two hours and it persisted for 24 hours. In postoperative patients (n = 9), who had been given an infusion of ringer‐glucose (5.5%) at a rate of 100 ml/hour, DHE caused an increase in diuresis but neither ADH (n = 9) nor aldosterone (n = 3) levels were changed. The data from the present study further support the earlier findings of a reduced plasma volume after DHE administration. The main effect of dihydroergotamine is on the vascular bed and especially on capacitance vessels (increased tonus). The reduced plasma volume by DHE seems to be one additional effect of DHE.
Effect of Serum, α‐1 Acid Glycoprotein, Lipoproteins and Albumin on Human Mononuclear Leucocyte β‐Adrenoceptors
Authors: Sager G. , Sandnes D. , Aakesson I. , Jacobsen S.
Published: July 2010

Abstract:The effects of serum, α‐1 acid glycoprotein (AAG), serum lipoproteins (SLP) and human serum albumin (HSA) on3H‐(‐)‐dihydroalprenolol (3H‐(‐)‐DHA) binding and (‐)‐isoproterenol ((‐)‐IPR) induced cyclic AMP (cAMP) elevation in human peripheral blood mononuclear leucocytes (MNL) were investigated. The saturable binding of3H‐(‐)‐DHA was decomposed into two classes of binding sites with maximum binding capacity of approximately 1400 and 30000 sites/cell and with dissociation constants (Kd) of approximately 0.7 and 65 nM. Stimulation of the MNL β‐adrenoceptors by (‐)‐IPR caused a concentration dependent cAMP accumulation (EC50 ∼0.2 μM) with maximum level approximately 250% above basal. For all single leucocyte preparations, 30–35 min. exposure to serum, AAG and SLP increased the number of β‐adrenoceptors with 100–200% and the maximal responsiveness to (‐)‐IPR with 30–90%. The presence of proteins did not change the Kdor the EC50. (‐)‐Alprenolol inhibited concentration dependently the serum induced increment in (‐)‐IPR‐responsiveness. Serum, AAG and SLP did also increase the number of low affinity binding sites with 25–40% without effect on the Kd. HSA had no consistent effect on β‐adrenergic binding or stimulation. The present study shows that serum, AAG and SLP influence the number and function of MNL β‐adrenoceptorsin vitro.
Toxic Hepatitis Due to Femoxetine
Authors: Aunsholt Niels Aage , Agnholt Jørgen
Published: July 2010

Abstract: A 51‐year old woman treated with femoxetine – a new serotonin reuptake inhibitor with antidepressive effect – developed toxic hepatitis during the treatment. In spite of that, the elimination half‐life of femoxetine in plasma was within normal limits.
Oral Absorption of Flucloxacillin in Infants and Young Children
Authors: Bergdahl Sven , Eriksson Margareta , Finkel Yigael , Lännergren Karin
Published: July 2010

Abstract: The bioavailability of flucloxacillin (Heracillin®) following oral administration was determined in infants and children. After a dose of 12.5 mg/kg, peak concentrations were achieved at 60 min. which declined rapidly and were low in older children only 4 hours afterwards. Infants below 6 months of age showed a better absorption when given the mixture than older children. Older children achieved higher plasma concentrations when given tablets than when given equal doses of the mixture. There was no difference in the concentration when the dose was given to the subject when fasting, or with breakfast.
The Effect of Long‐term Ethanol Treatment on a Metal Binding Protein Fraction in Liver and Kidneys of Mice
Authors: Hopf G. , Böcker R. , Kusch G. , Estler C.‐J.
Published: July 2010

Abstract:In mice 4–12 weeks ingestion of ethanol decreased the concentration of a metallothionein‐like protein fraction in the liver but not in the kidneys. The zinc and copper concentration also tended to decrease in the liver and remained unaffected in the kidneys.
Stability of 7‐Alkyldeoxyguanosines of Trichloropropylene Oxide, Epichlorohydrin and Glycidol
Authors: Hemminki K. , Lax M.
Published: July 2010

Abstract: Deoxyguanosine was reacted with trichloropropylene oxide (TCPO), epichlorohydrin and glycidol in aqueous solution and the products were isolated by high pressure liquid chromatography (HPLC). For each compound 7‐alkyldeoxyguanosine was the main adduct; TPCO reacted about 3 times faster than epichlorohydrin and about 10 times faster than glycidol. The pKa's of the 7‐alkyldeoxyguanosines were 6.7, 6.8 and 6.9 for the TCPO‐, epichlorohydrin‐, and glycidol‐adducts, respectively. The respective half‐lives of imidazole ring‐opening were 6.3, 15 and 27 hrs (pH 8.5, 28°) and those of depurination 1.9, 3.4 and 4.4 hrs (pH 5.5, 28°).
Chronic Treatment with Antidepressant Drugs and the Analgesia Induced by 5‐Methoxy‐N,N‐dimethyltryptamine: Attenuation by Desipramine
Authors: Danysz Wojciech , Minor Bruce G. , Post Claes , Archer Trevor
Published: July 2010

Abstract: The effect of chronic and acute oral or intraperitoneal treatment with the antidepressant drugs, desipramine, amitryptyline, alaproclate and iprindole, upon pain thresholds in the tail flick, hot plate and shock titration tests of nociception in saline‐ and 5‐MeODMT‐treated rats was studied. Chronic desipramine treatment increased the pre‐test tail flick latencies. In the saline‐treated rats, chronic oral desipramine treatment increased tail flick latencies, whereas chronic oral amitryptyline treatment decreased tail flick latencies. In 5‐MeODMT‐treated rats, chronic oral desipramine treatment attenuated the effects of 5‐MeODMT (1 mg/kg) in all three tests of nociception, whereas chronic amitryptyline caused a potentiation in the tail flick and hot plate tests. Chronic oral iprindole treatment attenuated 5‐MeODMT‐induced analgesia in the hot plate test. Chronic intraperitoneal desipramine treatment attenuated 5‐MeODMT analgesia in the tail flick and shock titration tests. In a different chronic treatment experiment, oral desipramine treatment attenuated 5‐MeODMT analgesia in the tail flick test and zimeldine did for both the tail flick and hot plate tests, whereas mianserin potentiated 5‐MeODMT‐induced analgesia in both the tail flick and hot plate tests. In the saline‐treated rats, acute treatment with all four drugs, despiramine, amitryptiline, iprindole and alaproclate, elevated the shock thresholds, whereas in 5‐MeODMT‐treated rats, desipramine and amitryptyline elevated shock thresholds. Two main conclusions can be drawn: chronic desipramine caused a quite consistent attenuation of 5‐MeODMT‐induced analgesia and the effects of acute treatment differed strongly from that of the chronic treatment. The effects of chronic administration with these antidepressants were compared with other findings using different measures of behavioural and receptor function.
In VivoPharmacokinetics of Felodipine Predicted fromin VitroStudies in Rat, Dog and Man
Authors: Bäärnhielm C. , Dahlbäck H. , Skånberg I.
Published: July 2010

Abstract:The elimination of felodipine in liver microsomes from dog and man were characterized by Kmand Vmax. The results were compared with previous data reported for rat. In all species studied, felodipine was primarily metabolized to its corresponding pyridine analogue. The elimination rate order was rat> dog> man. The same species difference was observedin vivofor the oral plasma clearance which was; rat 26 1/hr/kg, dog 7.5 1/hr/kg and man 4.3 1/hr/kg. The intrinsic hepatic clearance of felodipine was predictedin vitrofrom Vmaxover Km. Thein vitrovalues were not significantly different from those observedin vivo. Felodipine is a high‐clearance drug and thein vivoextraction ratios were about the same in all species: rat 0.80, dog 0.83 and man 0.84. The extraction ratios predicted from thein vitrostudies, rat 0.91, dog 0.70 and man 0.80, agreed well with those observedin vivo.
Hemodynamic Effects of Calcium Channel Blockers in Essential Hypertension
Authors: Hulthén Lennart
Published: July 2010

Abstract: Calcium channel blockers decrease blood pressure in essential hypertension due to a marked reduction of systemic vascular resistance (arteriolar tone). They also dilate conducting arteries but have no venodilatory effect in antihypertensive doses. With the dihydropyridines (e.g. nifedipine) and diltiazem there is a transient increase in heart rate and cardiac output but this is not observed with verapamil.

The vasodilatory responsiveness in the resistance vessels to calcium channel blockers is selectively enhanced in patients with established essential hypertension but not in the early borderline phase of hypertension. During treatment with chlorthalidone, atenolol, acebutolol or nitrendipine for four to six weeks the reduction of blood pressure is accompanied by a selective decrease in the vasodilatory responsiveness to calcium channel blockers.
Medicinal leeches for the treatment of venous congestion and hematoma after plastic reconstructive surgery
Authors: Riede Friederike , Koenen Wolfgang , Goerdt Sergij , Ehmke Heimo , Faulhaber Jörg
Published: July 2010

Background: Leeches were used for medical purposes as long as 2 000 years ago in ancient Egypt. In recent years the use of medicinal leeches became rather popular again, e. g. to improve blood circulation in ischemic tissue after reconstructive plastic surgery.

Patients and Methods: In a single center, retrospective study 23 consecutive cases were analyzed in which medicinal leeches had been used therapeutically after plastic reconstructive surgery. All cases were categorized regarding the indication for leech therapy, the onset, the duration, the number of leeches and the number of sessions.

Results: Among the group of patients there were 7 female and 16 male patients with a mean age of 73 ± 14 years (48–94 years) altogether. The main indications were venous congestion (12/23; 52 %) and hematoma (9/23; 39 %). Two cases were diagnosed with a necrosis of the tip of the flap and therefore received leech therapy (2/23; 9 %). The average number of leeches was 2.6 leeches/session, the number of sessions was 1.7 ± 0.8. 20/23 patients (87 %) showed a restitutio ad integrum after leech therapy, in 3/23 patients (13 %) a necrosis of the tip of the flap could not be prevented. A clinical improvement was noticed after an average of 1.1 ± 0.3 days. Conclusions: The early application of medicinal leeches can improve local hemodynamic conditions. Leech therapy is a simple and effective method; the cost efficiency of the treatment is high.
CAPACITY OF GROUP A, B, C, D AND G STREPTOCOCCI TO AGGLUTINATE SENSITIZED SHEEP RED CELLS
Authors: Christensen Poui. , Kronvall Göran
Published: July 2010

The reactivity of streptococci with sheep red cells, sensitized with a subagglutinating dose of rabbit anti‐sheep red cell antibodies was studied; agglutination of sensitized and not non‐sensitized sheep red cells by streptococci was demonstrated in isolates belonging to groups A, B, C, D and G. The frequencies of isolates which had the capacity to agglutinate were 97, 88 and 100 per cent in group A, C and G, but only 47 and 33 in group B and D. The agglutination of sensitized sheep red cells by streptococci diminished after treatment of the streptococci with protease from Streptomyces griseus, but was not affected by pepsin or trypsin treatment. Heating the streptococci at 60°C for 30 minutes and repeated subculturing did not suppress their agglutinating activity. Besides, various streptococcal extracts agglutinated sensitized sheep red cells. The presence of an immunoglobulin G reactivity in streptococci might cause certain difficulties in the serological grouping and typing of streptococci.
TRAGEDY AND THE MEANING OF SCHOOL SHOOTINGS
Authors: Warnick Bryan R. , Johnson Benjamin A. , Rocha Samuel
Published: July 2010

School shootings are traumatic events that cause a community to question itself, its values, and its educational systems. In this article Bryan Warnick, Benjamin Johnson, and Samuel Rocha explore the meanings of school shootings by examining three recent books on school violence. Topics that grow out of these books include (1) how school shootings might be seen as ceremonial rituals, (2) how schools come to be seen as appropriate places for shootings, and (3) how advice to educators relating to school shootings might change the practice of teaching. The authors present various ways of understanding school shootings that may eventually prove helpful, but they also highlight the problems, tensions, and contradictions associated with each position. In the end, the authors argue, the circumstances surrounding school shootings demonstrate the need for the “tragic sense” in education. This need for the tragic sense, while manifest in many different areas of schooling, is exemplified most clearly in targeted school shootings.
How will history judge Gordon Brown?
Authors: Seldon Anthony , Lodge Guy
Published: July 2010

Anthony Seldon and Guy Lodge chart a tale of five movements in the course of Brown's premiership.
Simulation of Combined Best Management Practices and Low Impact Development for Sustainable Stormwater Management1
Authors: Damodaram Chandana , Giacomoni Marcio H. , Prakash Khedun C. , Holmes Hillary , Ryan Andrea , Saour William , Zechman Emily M.
Published: July 2010

Damodaram, Chandana, Marcio H. Giacomoni, C. Prakash Khedun, Hillary Holmes, Andrea Ryan, William Saour, and Emily M. Zechman, 2010. Simulation of Combined Best Management Practices and Low Impact Development for Sustainable Stormwater Management. Journal of the American Water Resources Association (JAWRA) 1‐12. DOI: 10.1111/j.1752‐1688.2010.00462.x

Abstract:  Urbanization causes increased stormwater runoff volumes, leading to erosion, flooding, and the degradation of instream ecosystem health. Although Best Management Practices (BMPs) are used widely as a means for controlling flood runoff events, Low Impact Development (LID) options have been proposed as an alternative approach to better mimic the natural flow regime by using decentralized designs to control stormwater runoff at the source, rather than at a centralized location in the watershed. For highly urbanized areas, LID practices such as rainwater harvesting, green roofs, and permeable pavements can be used to retrofit existing infrastructure and reduce runoff volumes and peak flows. This paper describes a modeling approach to incorporate these LID practices in an existing hydrologic model to estimate the effects of LID choices on streamflow. The modeling approach has been applied to a watershed located on the campus of Texas A&M University in College Station, Texas, to predict the stormwater reductions resulting from retrofitting existing infrastructure with LID technologies. Results demonstrate that use of these LID practices yield significant stormwater control for small events and less control for flood events. A combined BMP‐LID approach is tested for runoff control for both flood and frequent rainfall events.
Musée national de Mongolie, Oulan Bator
Authors: Burnee Julziitiin
Published: July 2010

Les présentations de ce grand musée s'organisent autow de trois composantes majeures: l'histoire humaine, l'histoire naturelle, l'ethnographie. Ce qu'elles perdent en expression de l'histoire globale, elZes le regagnent, en un sens, à la favew des soins, minutieux et rasnés, apportés aux trois parties respectivement.

Avec le palais et les deux monastãres qui lui sont rattachés:a ane centrale de décentralisation B.
Musée d'histoire d'Amsterdam
Authors: Snoep Derk P.
Published: July 2010

Une chose est surprenante, entre toutes, dans la genèse de cet enfant batave: le modèle d'histoire globale en émerge dès 1938, issu de la pensée de grands noms de la muséologie nationale et internationale, feu David Röell et les bien vivants Arthur van Schendel et Willem Sandberg.

La périodisation en est explicite, du site naturel préalable à la prospective d'Amsterdam. Les moyens d'expression sont d'une variété égale à celle du Musée d'histoire allemande. On y met en cause, en la nuançant, l'omniprésence de l'art. Le texte pédagogique y règne d'un bout à l'autre, hiérarchisé.

La confrontation est suggestive, à ce point du sommaire, entre partis respectifs des musées d'histoire de Londres, de Metz, d'Amsterdam, en matière d'architecture. Londres bâtit du neuf au pied d'une tour de bureaux, sur site romain dégagé en surface. Metz se loge en des monuments historiques du moyen âge et des temps modernes, sur site romain dégagé en profondeur. Amsterdam, lui, occupe, en plein cœur de la ville, un édifice baroque, percé lui‐même, à l'initiative du musée, d'une rue piétonne.
Avoidance Powers and Incentives to File for Bankruptcy*
Authors: Kim Jeong‐Yoo , Joo Sang Lyong
Published: July 2010

In this paper, we examine the incentives for a failing debtor and creditors to file for bankruptcy either under Chapter 7 or Chapter 11, and discuss whether avoidance powers can provide proper incentives to file. We show that if the future profitability of a failing firm is known, avoidance powers can eliminate an inefficient delay in bankruptcy filing. However, if profitability is uncertain, in particular, if a creditor is pessimistic, what might result is an inefficient rush to file under Chapter 7. We also demonstrate that the conditional avoidance powers can give creditors a stronger incentive to gather information pertinent to future profitability, thereby enhancing efficiency.
Impact of the Change in Tick Size on Transaction Costs and Liquidity: An Empirical Investigation of the Taiwan Stock Exchange*
Authors: Kuo Su‐Wen , Huang Chin‐Sheng , Chen Chia‐Cheng
Published: July 2010

The minimum price variation on the Taiwan Stock Exchange reduced for most price categories on March 1, 2005. The present paper simultaneously examines the institutional and endogenous impacts of tick size changes on transaction costs, market liquidity, and trading activity. The empirical evidence suggests that following a reduction in tick size, uniform declines are discernible in transaction costs and market liquidity. In particular, those stocks with a larger relative tick size reduction, higher trading volume, and higher order handling cost components have greater reductions in spread and market depth. Moreover, endogenous tick size reductions have an adverse effect on the trading activity for low‐price stocks, due to the relative disadvantage in explicit transaction costs. Finally, the present study observes a general diminution in trade size resulting from a reduction in tick size in the Taiwan Stock Exchange. This study attributes plausible rationales to the fact that after tick size reductions, informed traders employ a smaller trade size to hide private information, or front‐runners place a smaller trade size to avoid market turbulence.
Nano- and Component Level Friction of Rubber Seals in Dispensing Devices
Authors: Prokopovich Polina , Theodossiades Stephanos , Rahnejat Homer , Hodson Darren
Published: July 2010

In many drug dispensing devices, such as syringes and inhalers, a rubber ring is used as a seal. During device actuation the seal is subjected to friction which in turn causes it to deform. This can lead to suboptimal performance of the device and as a consequence variability in the delivered dose. Seal friction is complex, arising from adhesion of rubber in contact with a moving counterface, viscous action of a thin film of entrained fluid into the contact and ploughing of seal asperities. Therefore, the first step in the understanding of the conjunctional behaviour of rubber seals is the fundamental study of these friction mechanisms. A developed model can then be validated against measurements, prior to its use in a multi-body dynamic model of the inhaler valve to predict product performance, robustness and variability due to manufacturing tolerances. This paper undertakes two distinct studies. Firstly, a friction model for the rough elastomeric material, typically used for valve seals is developed. The model is then validated against measurements in nano-scale. Friction data is presented for nitrile rubber, using a silicon nitride AFM tip for nano-scale interactions. The validation is then extended to macro-scale motion of an instrumented trolley, incorporating an elastomeric surface sliding on a polymeric counterface. These tests are carried out for polybutylene terephthalate (PBT). Secondly, the validated friction model is used in an elastomeric seal model in-situ within the valve and in contact with a polymeric stem surface and subject to both global fittment deformation and canister pressure. Reasonable agreement is found between the measurements and model predictions for the nano-scale coefficient of friction of rubber against silicon nitride. Similarly, good agreement has been obtained for the mean coefficient of friction of rubber against PBT. In addition, the mechanism of adhesion between contacting surfaces of gasket and stem is taken into account.
Graphical Interpretation of the Teamology Transformation
Authors: Wilde Douglass J.
Published: July 2010

The “teamology” approach to psychologically constructing and organizing design teams is based on an original transformation of personality questionnaire responses on to the four cognitive mode pairs of C. G. Jung’s underlying personality theory. This article shows how to interpret the transformation as the combination of a pair of square graphs, one for the two information collection (perception) mode pair scores; the other, for the two decision-making (judgment) mode pair scores. Questionnaire data are plotted in each square’s rectangular coordinates. The mode scores in each square are the projections of the questionnaire points on to the two diagonals. To illustrate, example graphs are used to guide the organization of a student trio to identify and strengthen a potential weakness. This can be done whether or not the team was constructed according to teamological principles.
Why Systematic Design Engineering?
Authors: Eder W. Ernst
Published: July 2010

Design engineering is different from other more artistic forms of designing because on one hand it is more constrained by the engineering sciences, economics and other factors, but on the other hand it has more possibilities for abstract modeling in the conceptual phases. Creativity is essential, but in many cases not sufficient to explore the many possible candidate solutions. A more systematic and methodical approach can help to overcome many of the problems that arise during conceptualizing in design engineering. Use of appropriate methods to enhance the search for solutions can expand the solution field. A systematic approach based on engineering design science has been shown to enhance understanding, good record-keeping, and traceability for the design process. Several grounded theories are reviewed and brought into mutual context, they refer to memory and thinking operations, expertise, human action modes, and competencies. The discussion reveals a need for specific instructions for a methodical and systematic engineering design procedure, when the design problem is seen as non-routine, and expertise is lacking.
Identifying Sets of Four and Five Positions That Generate Distinctive Center-Point Curves
Authors: Myszka David H. , Murray Andrew P.
Published: July 2010

The fixed pivots of a planar 4R linkage that can achieve four design positions are constrained to a center-point curve. The curve is a circular cubic function and plots can take one of five different forms. The center-point curve can be generated with a compatibility linkage obtained from an opposite pole quadrilateral of the four design positions. This paper presents a method to identify design positions that generate distinctive shapes of the center-point curves. The form of the center-point curve is dependent on whether the shape of the opposite pole quadrilateral is an open or closed form of a rhombus, kite, parallelogram, or when the sum of two sides equals the other two. Interesting cases of three and five position synthesis are also explored. Four and five position cases are generated that have center points at infinity allowing a PR dyad with line of slide in any direction to achieve the design positions. Further, a center-point curve for five specific design positions is revealed.