bluuebunny/crossref_metadata_2025 huggingface dataset:
Dextropropoxyphene and Norpropoxyphene in Blood, Muscle, Liver and Urine in Fatal Poisoning
Authors: Christensen Hanne
Published: July 2010

AbstractPost‐mortemconcentrations of dextropropoxyphene (DP) and its major metabolite norpropoxyphene (NP) were determined by combined gas‐liquid chromatography and thin‐layer chromatography in autopsy material from 53 cases of fatal DP poisoning collected over a 1‐year period. Among 11 oral cases without simultaneous ethanol ingestion, the minimal lethal dose was less than 1.5 g DP chloride. The ranges of total drug concentrations (DP + NP) were 1.1‐15 μg/g in blood, 1.3‐23μxg/g in muscle, and 27‐261 μg/g in liver. Among 21 oral cases where ethanol was detected in the blood, the minimal lethal dose was 0.7 g DP chloride (ethanol 2.41 μg/g) and the total drug concentrations was 0.7‐12 μg/g in the blood, 1.3–8.4 μg/g in the muscle and 19‐285μg/g in the liver. The minimal lethal blood concentrations tended to decrease with increasing ethanol concentration. NP constituted roughly half of the total drug levels, somewhat less in muscle and more in the urine, and this pattern was not changed in connexion with ethanol ingestion. Other metabolites were not detected.
Respiratory and Cardiovascular Effects of 3‐MethyIxanthine, a Metabolite of Theophylline
Authors: Persson C. G. A. , Andersson K.‐E.
Published: July 2010

AbstractThe effects of 3‐methylxanthine (3‐MX), a major metabolite of theophylline in man, were studied and compared with those of theophylline in isolated preparations of human and guinea‐pig airways, isolated guinea‐pig hearts, and in anaesthetized cats. 3‐MX was pharmacologically active, producing effects similar to those of theophylline. The guinea‐pig and human airways preparations were relaxed; the rate and force of contraction of guinea‐pig hearts were increased. In anaesthetized cats, 3‐MX decreased the respiratory overflow and arterial blood pressure, and increased the heart rate. Theophylline was always more potent (between 1 and 5 times) than 3‐MX. It is suggested that 3‐MX may contribute to the effects of theophylline during long‐term treatment.
The Metabolism of Benzo(a)pyrene in Isolated Perfused Lungs from Variously‐treated Rats
Authors: Vähäkangas Kirsi , Nevasaari Kaisu , Pelkonen Olavi , Kärki Niilo T.
Published: July 2010

AbstractRats were pretreated either by the injection of 3‐methylcholanthrene (MC) 40 mg/kg intraperitoneally for 3 days or by giving phenobarbitone (PB) 0.5 g/1 in the drinking water for 7 days. Benzo(a)pyrene (BP) and its metabolites were measured by thin‐layer chromatography (TLC) and radiometry in samples of perfusion medium up to two hours. In perfusion medium the half‐life of BP was about 15 min. in the perfusions of lungs from MC‐pretreated rats and 60‐90 min. in the perfusions of lungs from PB‐pretreated and control rats. The appearance of water‐soluble metabolites was most marked in the perfusions of lungs from MC‐pretreated rats being at fifteen minutes 2.5‐fold and at two hours 2‐fold in comparison to the controls. In the perfusions of lungs from PB‐pretreated rats the accumulation was retarded perhaps indicating an inhibition of lung enzymes by PB. Water‐soluble metabolites included glucuronic and sulphuric acid conjugates as well as those conjugates resistant to acid hydrolysis. Phenols were the most pronounced organic‐soluble metabolites at the beginning of perfusion of lungs from MC‐pretreated rats. At fifteen minutes the amount of phenols in the perfusions of lungs from PB‐pretreated rats was 1/6 and in controls 1/3 of that in the perfusions of lungs from MC‐pretreated rats. Towards the end of perfusion phenols decreased in the perfusions of lungs from MC‐pretreated rats. In other perfusions all metabolite fractions increased slowly during the perfusion. Covalently bound radioactivity and BP‐hydroxylase in lung homogenates were studied after perfusions. The covalent binding of radioactivity in the lungs from MC‐pretreated rats was 3.5 times higher than in control lungs and the lungs from PB‐pretreated rats. There was a correlation between covalent binding and the activity of BP‐hydroxylase in lung homogenates. Exposure of rats to cigarette smoke resulted in effects on the BP metabolism resembling those of MC pretreatment.
Pharmacokinetics of 2‐Pivaloylindan‐1,3‐Dione in Dogs
Authors: Fitzek A.
Published: July 2010

AbstractThe pharmacokinetics of 2‐pivaloylindan‐1,3‐dione (Pival±) after administration of a single dose was investigated in dogs. The plasma concentration graph can be described by a one compartment open model. The drug is fairly well absorbed (67%) and the excretion is extremely slow with a half‐life of nearly five days. These kinetics can be explained by the physicochemical properties of the drug, such as strong binding to canine plasma protein, high lipophility and the lack of transformation to polar metabolites. A single oral dose of 5 mg/kg must be regarded as lethal to dogs and the LD50 is assumed to be approximately 4 mg/kg in this species.
Whole Blood Chromium Level and Chromium Excretion in the Rat after Zinc Chromate Inhalation
Authors: Langård Sverre , Gundersen Nils , Tsalev Dimetez L. , Gylseth Bjørn
Published: July 2010

Abstract Studies on absorption and excretion of chromium in the rat exposed to known atmospheric concentrations of zinc chromate in an inhalation chamber and the influence of diurnal variations in physical activity have been carried out. Chromium analyses were performed on samples of blood, urine and faeces using a method for determining chromium in small samples of biological material based on flameless atomic absorption spectrometry. Zinc chromate is absorbed quickly during exposure and excreted mainly via urine. An accumulation of chromium in blood was observed, followed by a slow elimination. It is suggested that chromium from zinc chromate enters the blood in the hexavalent state.
Some Properties of Ca‐Binding Microsomal Subfractions Isolated from Rabbit Colon Muscle
Authors: Nilsson Karin B. , Andersson Rolf G. G. , Mohme‐Lundholm Ella , Lundholm Lennart
Published: July 2010

AbstractFrom a homogenate of rabbit colon smooth muscle a microsomal fraction was isolated, which was divided into subfractions by centrifugation on a discontinuous sucrose gradient. The Ca‐binding properties of the subfractions were investigated under different conditions. In the presence of 0.35 mM ATP the Ca binding of the fractions amounted to 4–8 nmol/mg protein. The 35% fraction bound more Ca per mg protein than the 35–45% fraction. The Ca accumulation was comparatively higher both in the presence of 5 mM ATP and in the presence of 5 mM oxalate. The two fractions showed about the same sensitivity for oxalate. This substance stimulated the Ca uptake at 5 mM but not at lower concentrations. The amount and the rate of Ca binding were more dependent on variations in the exogenous ATP concentration in the 35% fraction than was the case for the 35–45% fraction. The Ca binding was completely inhibited by salyrgan when the microsomal fractions were pretreated with this agent. Sodium azide did not influence the Ca‐binding capacity of the fractions. It is suggested that the microsomal subfractions of the rabbit colon muscle represent physiologically important parts of the Ca sequestering system of the muscle, since Ca binding takes place at Ca‐ and ATP‐concentrations which are believed to be present in the myoplasm.
Methodological Aspects on Drug Receptor Binding Analysis
Authors: Wahlström Agneta
Published: July 2010

Abstract Although drug receptors occur in relatively low concentrations, they can be visualized by the use of appropriate radioindicators. In most cases the procedure is rapid and can reach a high degree of accuracy. Specificity of the interaction is studied by competition analysis. The necessity of using several radioindicators to define a receptor population is emphasized. It may be possible to define isoreceptors and drugs with selectivity for one isoreceptor.
Determination of Thiopental by High Pressure Liquid Chromatography
Authors: Christensen J. Heslop , Andreasen F.
Published: July 2010

AbstractA specific and rapid reverse phase HPLC‐method for the determination of thiopental in serum and in protein free solutions is described. No extraction is used. The detection limit is about 0.090 μg/ml for serum and about 0.030 μg/ml for buffer solutions. The retention time is 3.80 min. No interference is found with drugs commonly used in patients with heart diseases. The method was used to follow the serum concentrations in 7 patients who were given thiopental as an introduction to general anaesthesia.
Pharmacokinetics of Dipyridamole
Authors: Nielsen‐Kudsk F. , Pedersen A. Kirstein
Published: July 2010

AbstractDipyridamole, though originally introduced as a coronary vasodilator, has lately been increasingly investigated in the treatment of thromboembolic diseases because of its inhibitory influence upon blood platelet function. The compound is eliminated from the organism by hepatic biotransformation to the monoglucuronide, which almost exclusively is subjected to biliary and faecal excretion with simultaneous partial enterohepatic circulation taking place. Only minute amounts are excreted through the kidneys. In experiments on four normal human volunteers it was found that the serum concentration curve after intravenous administration of dipyridamole rather closely fits the pharmacokinetics of an open two‐compartment model with first order, linear disposition kinetics and elimination taking place from the central compartment. Experiments with oral ingestion of the compound could be described by the use of a corresponding pharmacokinetic model with two consecutive first order input steps, representing the dissolution and absorption processes. The disposition rate constants (β) were within the range of 0.0051‐0.0083 min.‐1corresponding to biological half‐lives of 84‐145 min. The absorption rate constant was about 0.07 min.‐1, and the systemic availability of an oral dose of 100 mg dipyridamole in tablets varied from 37 to 66%.
Penetration Enhancers and Other Factors Governing Percutaneous Local Anaesthesia with Lidocaine
Authors: Åkerman Bengt , Haegerstam Glenn , Pring Brian G. , Sandberg Rune
Published: July 2010

AbstractThe percutaneous penetration of the local anaestetic lidocaine was investigated in the guinea‐pig. Three different types of composition were employed: lidocaine hydrochloride in aqueous solution, lidocaine base in an aqueous alcoholic solvent mixture and lidocaine base in aqueous solutions of dipolar aprotic solvents. The latter solvents included simple tertiary aliphatic amides, amides related to dimethylacetamide, some cyclic amides as well as a number of miscellaneous compounds. The degree of dermal anaesthesia was noted in each case. In addition, the uptake and distribution of lidocaine in the skin and its absorption into the blood were studied using tritium‐labelled drug. The results show that the percutaneous penetration of lidocaine is dependent on the concentration of the agent, the time of epicutaneous application of the composition, whether the agent was used as salt or free base, and the nature of the solvent medium. Lidocaine base in aqueous dimethylacetamide was most effective in producing percutaneous local anaesthesia.
Naloxone: A Potent Ketobemidone Antagonist in Man
Authors: Holst‐Larsen H. , Aasen A. O. , Rugstad H. E.
Published: July 2010

AbstractNaloxone has been accepted as a potent antagonist towards several narcotic analgesics, e.g. morphine, heroin and pethidin. Its effect as an antagonist and its potency against ketobemidone have not been tested in man. We have described the antagonistic effect of naloxone towards the respiratory depression caused by the administration of ketobemidone to patients anaesthetized with N2O/O2and methohexitone.
The Influence of Selenium on Methyl Mercury Toxicity in Rat Hepatoma Cells, Human Embryonic Fibroblasts and Human Lymphocytes in Culture
Authors: Alexander J. , Høstmark A. T. , Førre Ø. , Bryn M. von Kræmer
Published: July 2010

Abstract The effect of methyl mercury and two selenium compounds have been studied in cell cultures. Methyl mercury in concentrations above 1 μM had a pronounced inhibiting effect on the growth of rat Morris hepatoma cells. Glucose and lactate uptake in relation to cell protein was appreciably stimulated by the organic mercury compound. Selenite in low concentrations (0.5 μM) and seleno‐di‐N‐acetyl glycine in thousandfold higher concentrations offered considerable protection against these effects of methyl mercury. The same selenite concentration (0.5 μM), which did not affect cell growth, caused an appreciable protection against methyl mercury (6 μM), even if it was added 3 days after methyl mercury. The methyl mercury inhibited the growth of human embryonic fibroblasts and the DNA‐synthesis in the human lymphocytes. However, no protective effect of selenite were observed in these cell types. These results suggest that selenium compounds exert their protective effects through cell specific processes rather than by a direct chemical reaction between selenite and methyl mercury.
On the Possible Role of Potassium Ions in the Action of Terbutaline on Skeletal Muscle Contractions
Authors: Holmberg Eva , Waldeck Bertil
Published: July 2010

AbstractThe soleus, a slow‐contracting, and the extensor digitorum longus (EDL), a fast‐contracting muscle from guinea‐pig were prepared for isometric recordingin vitro, and the effect of terbutaline, a β‐adrenoceptor agonist, was studied during various experimental conditions. In the soleus terbutaline caused an initial depression of the force of contraction followed by an increase. The degree of fusion of subtetanic contractions was reduced throughout the experiment. The EDL responded with an increased force only. The force of contraction of the two muscles increased with the K+‐ion concentration of the medium up to 8 mM. Higher concentrations of K+caused a depression which was partly prevented by terbutaline. When the contractions of the soleus muscle had been depressed by excess K+, depletion of K+or by ouabain, terbutaline restored the twitch tension. It is suggested that the contractile machinery of the muscles is controlled by the ionic balance which in turn is changed following β‐adrenoceptor stimulation.
Mechanical Response of Rat Myocardium to Dibutyryl Cyclic AMP in Relation to Effects of α‐ and β‐Adrenoceptor Stimulators
Authors: Skomedal Tor , Osnes Jan‐Bjørn , Øye Ivar
Published: July 2010

Abstract:Dibutyryl cyclic AMP, and α‐ and β‐adrenoceptor stimulators are all able to elicit inotropic effects, α‐ and β‐Adrenoceptor stimulation are known to change each myocardial contraction‐relaxation cycle differently. In order to elucidate the myocardial function of cyclic AMP the effects of dibutyryl cyclic AMP on the contraction‐relaxation cycle of isolated rat heart papillary muscle were examined and compared to the effects of α‐ and β‐adrenoceptor stimulation, respectively. Dibutyryl cyclic AMP (in the presence of propranolol) increased developed tension (Tmax) by 18%, rate of tension rise (T′max) by 46%, rate of tension fall (T′min) by 62% and onset‐rate of relaxation (T″min) by 136%. These changes in the contraction‐relaxation cycle were strikingly similar to those produced by isoprenaline (β‐adrenoceptor stimulation). The response to dibutyryl cyclic AMP, however, developed much slowlier than did the response to isoprenaline. The latter effect was associated with cyclic AMP elevation in a way indicating a trigger function for cyclic AMP. The α‐adrenoceptor stimulation (by phenylephrine combined with propranolol), however, increased measures both for contraction and for relaxation by about the same degree, and the effects occurred without changes of cyclic AMP contents. Phenylephrine alone (combined α‐ and β‐adrenoceptor stimulation) elicited a substantial cyclic AMP elevation but gave mechanical effects only slightly different from the pure α‐adrenergic response. Thus cyclic AMP effects did not seem to be fully expressed in this case. As a whole, the results indicate that the effects of both dibutyryl cyclic AMP and of isoprenaline are mediated by the cyclic AMP‐system while α‐adrenoceptor stimulation involves other mechanisms.
Interaction of Putative Opioid Peptides with Opiate Receptors
Authors: Stengaard‐Pedersen K. , Larsson L.‐I.
Published: July 2010

Abstract:Binding of3H‐enkephalinamide and3H‐naloxone to P2‐fractions of whole rat brain homogenate displayed saturable, stereospecific binding to receptor sites with at least two binding sites for3H‐met‐enkephalinamide (type I: KD= 0.4 nM and Bmax= 35 fmol/mg protein; type II: KD= 5.7 nM and Bmax= 57 fmol/mg protein) and for3H‐naloxone (type I: KD= 1.5 nM and Bmax= 40 fmol/mg protein; type II: KD= 51 nM and Bmax= 255 fmol/mg protein), β‐endorphin and met‐ and leu‐enkephalin produced a concentration‐dependent inhibition of3H‐met‐enkephalinamide and3H‐naloxone binding with dissociation constants in the nanomolar range, but with very different displacement curves. Purified porcine ACTH (1–39) displaced both3H‐met‐enkephalinamide and3H‐naloxone with dissociation constants of 3.4 × 10‐ Mand 1.8 × 10−6M, respectively. The synthetic congeners, ACTH (1–32) and to a lesser extent ACTH (1–28) and ACTH (1–24) showed a similar effect, whereas other fragments of ACTH were inactive in concentrations ranging from 10−10to 10−6M. In the same concentration range cholecystokinin congeners (CCK‐8 and CCK‐4) were without effect. Since ACTH immunoreactive nerves seem also to contain β‐endorphin and furthermore, to show a partially overlapping distribution with the enkephalinergic systems it is possible that the binding of ACTH fragments to opiate receptors is of physiological relevance.
The Kinetics of Citalopram: Single and Multiple Dose Studies in Man
Authors: Kragh‐Sørensen Per , Overø Kerstin Fredricson , Petersen Ove Lindegaard , Jensen Knud , Parnas Witold
Published: July 2010

Abstract: The kinetics of citalopram were studied in a group of volunteers after oral (8 subjects) and intravenous (4 subjects) single doses and repeated oral administration (7 subjects). Inter‐ and intraindividual variation was limited and linearity of kinetics indicated. Systemic and apparent oral clearance estimates (mean 0.42 1 plasma/min.) were similar, indicating roughly complete systemic availability. The presence of unchanged drug in urine, corresponding to 1/7 of the dose, suggests elimination by renal as well as hepatic processes. The data from the intravenous test revealed two compartment kinetics; the total volume of distribution was estimated to about 11501 and that of the central compartment to 1751. Upon repeated administration steady‐state conditions were generally achieved after one week in agreement with the 33 hrs half‐life of elimination. Citalopram peak concentrations were reached within 2–4 hrs after the daily dose and maximally two‐fold variation was recorded in the 24 hrs dose interval. The levels of a main pharmacodynamically active metabolite were roughly half as high as the drug levels.
Imipramine Kinetics in the Single Pass Rat Liver Perfusion Model
Authors: Erlandsen Erland J. , Gram Lars F.
Published: July 2010

Abstract:Imipramine elimination and metabolism was studied in a single‐pass rat liver perfusion model with flow and pressure kept constant for a perfusion‐period of 120–200 min. Imipramine was eliminated from the liver mainly in three ways: unchanged in the outflow medium, by demethylation forming desipramine, and by 2‐hydroxylation and subsequent glucoronide coupling. The formed desipramine was eliminated unchanged (outflow) or by 2‐hydroxylation + glucuronide coupling. The conjugated metabolites were mainly eliminated via the bile. By perfusion with constant imipramine concentration in the inflow medium (10–50 μM), steady state could not be obtained within 120 min. perfusion time, neither in terms of a constant outflow concentration, nor in terms of balance between input and output. Perfusion with imipramine for 20 min. (single‐dose) followed by perfusion with drug‐free medium showed an extensive elimination of imipramine (extraction ratio 0.64–0.97) and rapid disappearance of imipramine from outflow medium (t1/25–10 min). A second single dose imipramine perfusion given 70 to 90 min. after start showed a significant reduction in extraction ratio. At the same time the elimination via bile decreased about 50%, and only a fraction of this decrease was accounted for by a decrease in bile flow. The data thus indicate that a gradual decline in elimination rate may explain the difficulties in reaching a steady state during constant infusion with imipramine. Gradual changes in distribution kinetics could not be excluded though. Results of both types of experiments (continuous or single dose administration) indicated dose dependent elimination compatible with saturation kinetics.
A Study on Inhibition of Cholera Toxin‐induced Intestinal Hypersecretion by Neuroleptics
Authors: Larsen Jens‐Jørgen
Published: July 2010

Abstract:Various types of neuroleptics and other agents were examined for inhibitory effect in cholera toxin‐induced hypersecretion in ligated loops of mice jejunum. Several agents belonging to the phenothiazine group or thioxanthene group were inhibitory. Only three other neuroleptics, loxapin, haloperidol and penfluridol, inhibited the hypersecretion. Among the miscellaneous agents the calcium antagonist nifedipine was inhibitory. The potencies of the neuroleptics did not correlate with the dopamine antagonistic potencies. The results indicate that the site of antisecretory action of the drugs is to be found outside the central nervous system.
Studies on the Effects of Orally Administered Dicyclohexyl Phthalate in the Rat
Authors: Lake Brian G. , Foster John R. , Collins Michael A. , Stubberfield Colin R. , Gangolli Sharat D. , Srivastava S. P.
Published: July 2010

Abstract:The oral administration of 500–2500 mg/kg/day dicyclohexyl phthalate (DCHP) to young male Sprague‐Dawley rats for 7 days resulted in liver enlargement and induction of some parameters of hepatic xenobiotic metabolism. Additional studies indicated that the hepatic enzyme induction resembled that of sodium phenobarbitone rather than that of polycyclic hydrocarbons. Morphological examination of the livers of DCHP treated rats revealed centrilobular cell hypertrophy and ultrastructural examination demonstrated marked proliferation of the smooth endoplasmic reticulum. Mitochondrial structure and numbers of peroxisomes (microbodies) were not affected. DCHP treatment did not affect kidney and testes weights but some histological evidence of testicular damage was obtained with 2500 mg/kg/day of DCHP. The metabolites of DCHP, namely monocyclohexyl phthalate (MCHP) and cyclohexanol, also induced certain parameters of hepatic xenobiotic metabolism. MCHP, but not cyclohexanol also produced marked testicular atrophy. It is concluded that DCHP is a weak drug‐type inducer of hepatic xenobiotic metabolism in the rat and the hepatic effects of this phthalate diester are different from those of di‐(2‐ethylhexyl) phthalate.
Reevaluation of Potency and Pharmacokinetic Properties of some Lipid‐soluble Barbiturates with an EEG‐threshoJd Method
Authors: Bolander Hans G. , Wahlström Göran , Norberg Lennart
Published: July 2010

Abstract:Five lipid‐soluble anaesthetic barbiturates amobarbital, (pentymalum NFN), hexobarbital (en‐hexymalum NFN), pentobarbital (mebumalum NFN), thiopental (thiomebumalum NFN), methohexital (enallynymalum NFN) were investigated for potency and kinetic properties with an EEG‐threshold method. By constant infusion of barbiturate at different dose rates to a well specified EEG‐criterion, the “silent second”, a dose rate curve can be made. This curve has a minimum, “optimal dose rate”, and the amount of barbiturate used to reach the criterion at this dose rate can be used as an accurate measure of potency. The dose to reach the “silent second” at the optimal dose rate was highly correlated to brain concentrations at the criterion for the barbiturates in contrast to the plasma concentrations. This measure of potency is superior to other used measures such as anaesthesia times or AD50, since it is less affected by differences in pharmacokinetic properties. The anaesthesia times after threshold determinations show large variations between different barbiturates which can be dependent both on dose administered and on dose rate. The quotient between brain concentration at the EEG‐criterion and at the time of return of righting reflex for these barbiturates shows variations that can be due to differences in acute tolerance.
Femoxetine Clearance in Patients with Liver Cirrhosis
Authors: Hansen Bent A. , Mengel Helle , Keiding Susanne , Lund Jørgen
Published: July 2010

Abstract: The pharmacokinetics of femoxetine (a 5‐HT uptake inhibitor with antidepressive effect) was studied in 12 patients with üver cirrhosis and in 6 healthy controls after a single oral dose of femoxetine HC1. The average blood concentration of femoxetine, as assessed by the values of AUC (area under the plasma concentration/time curve), was significantly higher in the patients with liver cirrhosis than in the healthy controls in spite of dose reduction in the patients. The elimination half‐life of femoxetine was within the normal limits in most of the patients. The oral clearance of femoxetine was considerably lower in patients, (0.65–4.02 1/hr/kg) than in the controls (8.13‐>50 1/hr/kg). It was not directly related to the metabolic function of the liver, measured as the galactose elimination capacity being 0.015–0.024 mmol/min./kg and 0.033–0.041 mmol/min./kg, respectively. When treating patients with reduced liver function, it is recommended to reduce the doses and to monitor closely the plasma levels
Potassium supplements or potassium‐sparing agents
Authors: Persson Stig
Published: July 2010

Abstract:During diuretic treatment alterations in myocardial cellular excitability due to potassium‐induced dis‐turbances of the membrane potential may arise without obvious changes of total body K. This may be explained by coexisting disturbances of the acid/ base balance and other ions such as magnesium. two factors which independently influence the transport of potassium across the cell membrane. The consequence may be cardiac arihythmias, particularly in the presence of digitalis. On the other hand hypokalemia, induced by diuretics, may also be accompanied by a significant depletion of total body K. bringing about more general consequences. It must be considered essential to maintain a normal general electrolyte balance during diuretic therapy.

Potassium supplements may be used if true depletion of total body K is suspected, e.g. in hypokalemia with acidosis. Its use may, however, otherwise be questioned, as it is only directed towards the potassium situation and neglects the influence of diuretics upon other ions, such as H+and Mg++. The potassium‐sparing agents amiloride and triamterene normalize the general electrolyte situation in the distal tubules and should thus be regarded as drugs of first choice. Spironolactone has identical properties concerning the electrolytes but more serious side effects. It should be preferred when a significant secondary hyperaldosteronism is suspected and/or a more intense diuresis or an accentuated antihypertensive action is desired. The role of captopril in this context has not yet been established.
Comparison of Central Nervous System Actions of Taurine and N–Pivaloyltaurine
Authors: Ahtee Liisa , Auvinen Helinä , Mäenpää Anna‐Riitta , Vahala Maija‐Liisa , Lehtinen Maire , Halmckoski Jaakko
Published: July 2010

Abstract:N–Acetyl, N–propionyl, and N–pivaloyl derivatives of taurine were synthesized by applying a modified Schotten–Bauman method starting from taurine and using the corresponding acid chloride or acid anhydride for direct acylation reactions. The central nervous system actions of these lipid soluble taurine derivatives, which were presumed to pass the blood–brain barrier, were studied and compared to those of taurine in mice. A large dose (15 mmol/kg) of intraperitoneally administered taurine lengthened the pentobarbitone induced sleep by 30%. N–Pivaloyltaurine was 45 times more potent but not more effective than taurine. Neither N–acetyl– nor N–propionyltaurine lengthened the pentobarbitone induced sleep in doses up to 3 mmol/kg. Intraperitoneally administered N–pivaloyltaurine depressed the locomotor activity in a smaller dose and for a longer period than taurine. However, when administered intracerebroventricularly neither N–acetyl– nor N–pivaloyltaurine altered the locomotor activity in three times larger dose than in which taurine clearly depressed it. Intraperitoneally administered N–pivaloyltaurine decreased the rectal temperature slightly more than taurine, whereas intracerebroventricularly administered taurine was clearly more potent in inducing hypothermia than its acyl derivatives. Intraperitoneally administered N–pivaloyltaurine was about three times more potent than taurine in increasing the striatal concentration of dopamine. Intraperitoneally administered N–pivaloyltaurine only in a very large dose (3 × 15 mmol/kg) slightly and transiently increased the cerebral taurine concentration. Carboxylesterase inhibition by bis–p–nitrophenyl phosphate (BNPP) did not modify this increase. Furthermore, BNPP pretreatment modified neither the hypothermic nor the striatal dopamine concentration elevating effects of N–pivaloyltaurine. Our results suggest that N–pivaloyltaurine possesses taurine–like pharmacological actions. It is not converted to taurine to produce these actions. When administered intracerebroventricularly it is less potent than taurine. However, when administered intraperitoneally it is more potent than taurine because it seems to pass the blood–brain–barrier more easily than taurine. Thus N–pivaloyltaurine could be used to study the behavioural and other central nervous system actions of taurine
Effects of Leucine Methylester on guinea–Pig Atria
Authors: Franconi Flavia , Bennardini Federico , Stendardi Isabella , Matucci Rosanna , Dini Germana , Giotti Alberto
Published: July 2010

Abstract: Superfusion of guinea–pig atria with 10 mM 1–leucine methylester leads to a mechanical arrest and to an increase in protein outflow. Homogenate of alria exhibits a decrease in the sedimentability of phosphatase acid activity as compared to control. Morphological studies reveal that leucine methylester causes not only a lysosomal swelling but also a disruption of myofibrils and slight mitochondrial damage
The Effect of Diuretics and Lithium on3H‐Ouabain Binding Site Concentration and Na,K‐Content in Rat Skeletal Muscle
Authors: Nørgaard Aage , Kjeldsen Keld
Published: July 2010

Abstract:Previous studies have shown an increase in3H‐ouabain binding sites or Na,K‐pumpsin vitroin cultured cells in response to incubation in low K, diuretics or lithium. However, in the present study the administrationin vivoof various diuretics or lithium combined with supplementary K was not associated with any significant changes in Na,K‐content or3H‐ouabain binding site concentration in rat skeletal muscle. When the diuretics were administered in combination with only the basal K requirement a decrease in both K‐content and3H‐ouabain binding site concentration was seen. This indicates that the decrease in3H‐ouabain binding site concentration is not caused by these drugsper sebut is secondary to the associated K‐depletion. The discrepancy between the results obtained using isolated cells and rat skeletal muscles could be related to the fact that cultured cells are not subject to the normal growth control of the intact organism. It should be emphasized that results obtained using cultured cells do not necessarily reflect processes taking place in the intact organism.
Rapid HPLC‐Determination of Ibuprofen and Flurbiprofen in Plasma for Therapeutic Drug Control and Pharmacokinetic Applications
Authors: Askholt J. , Nielsen‐Kudsk F.
Published: July 2010

Abstract:Ibuprofen has wide applications in the treatment of rheumatoid arthritis and osteoarthroses as an effective non‐steroidal antiinflammatory drug. The drug is still being investigated regarding its possible ability to reduce myocardial infarct size. The more potent biphenyl propionic analogue, flurbiprofen, has recently been introduced. Both drugs are strong inhibitors of cyclooxygenase. The specific HPLC‐method described requires plasma samples of 100 μl which are deproteinized and simultaneously extracted with acctonitrile containing either of the drugs as internal standard. Aliquots of 25 μl of this primary extract were directly injected on a μBondapack C18column. For elution was used a mixture of 60% methanol and 40% 50 mM phosphate buffer adjusted to pH 4.6. The detection limit (at 214 nm) for both drugs corresponded to plasma concentrations of about 0.2 μg ml−1. The applicability of the method was demonstrated in a pharmacokinetic ibuprofen experiment in an adult person.
Cardioplegia and Myocardial Ischemia during Cardiopulmonary Bypass
Authors: Leijala Mauri A.
Published: July 2010

Abstract: Presently myocardial protection can be obtained in three main ways: 1) energy conservation through chemical induction of rapid and complete diastolic arrest, 2) slowing of the metabolic rate and degradative process through the use of hypothermia, and 3) prevention or reversal of unfavourable ischemic‐induced changes with various protective agents. These methods of myocardial protection and their effectiveness, the calcium metabolism during myocardial ischemia, and the effects of calcium channel blockers are briefly reviewed and discussed. It is stressed that myocardial protection during ischemic arrest is a complex entity, and that new modes of myocardial protection are needed in the future.
Medawar Redux – An Overview on the Use of Farm Animal Models to Elucidate Principles of Reproductive Immunology
Authors: Hansen Peter J.
Published: July 2010

Citation Hansen PJ. Medawar redux – an overview on the use of farm animal models to elucidate principles of reproductive immunology. Am J Reprod Immunol 2010

Farm animals have been important models for the development of reproductive immunology. Two of the major concepts underpinning reproductive immunology, the idea of the fetal allograft and progesterone’s role in regulation of uterine immunity, were developed using the bovine as a model. This volume of the American Journal of Reproductive Immunology is composed of review articles that highlight the continued relevance of farm animals as models for research in mammalian biology. It is important that a diverse array of genotypes are used to elucidate biological principles relevant to mammalian biology and human health because the nature of mammalian evolution has resulted in a situation where the genome of the most commonly used animal model, the laboratory mouse, is less similar to the human than other species like the cow. Moreover, the evolution of placental function has been accompanied by formation of new genes during recent evolution so that orthologs do not exist in any but closely related species. Given the infrastructure needs to study farm animal species, optimal utilization of these animals as models for biomedical research will require significant increases in funding to reverse a historical erosion of resources devoted to animal agricultural research.
Mastocytosis – an update
Authors: Amon Ulrich , Hartmann Karin , Horny Hans‐Peter , Nowak Anna
Published: July 2010

Mastocytosis (MC) encompasses a range of disorders characterized by a clonal, pathological accumulation of mast cells having a somatic activating mutation of the tyrosine kinase receptor Kit (exon 17, codon 816; D816V) in more than 90 % of adult patients. The mutation is much less common in children. Skin and bone marrow are most often affected. Symptoms and clinical course are very heterogeneous due to a variable degree of local or systemic mediator release or organ dysfunction as a result of mast cell infiltrates. Pruritus, wheals, flushing and gastrointestinal symptoms are often reported. The majority of pediatric patients experience spontaneous remission of MC. Adults usually have chronic disease, rarely transforming into an aggressive or lethal type. Indolent systemic MC with involvement of skin and bone is the most common type. In MC the risk for anaphylactic reactions following an insect sting (and other causes of mast cell activation) is increased significantly. Diagnostic hallmarks are biopsies from skin and bone marrow using tryptase antibodies for staining as well as serum tryptase levels. At present a curative treatment for MC is not available. Systemic histamine H1 receptor antagonists are widely used. Aggressive types of MC respond partially to IFN‐α or cladribine. A variety of receptor tyrosine kinase inhibitors is still under critical evaluation for systemic treatment of MC. After introduction of the WHO classification for MC and the development a German MC guideline, as well as the foundation of national and international competence networks for MC, a significantly improved quality of medical care for MC patients can be expected for the future.
The association between self perceptions of psychological well‐being and overweight in Brazilian children
Authors: Alexius Silvia Letícia , Olinto Maria Teresa Anselmo , Henn Ruth Liane , Pattussi Marcos Pascoal
Published: July 2010

Our objective was to estimate the prevalence and test the association between psychological well‐being and overweight in children. We conducted a cross‐sectional study using anthropometrical measures and interviews with 1048 6–10‐year‐old school children from a Brazilian town. Overweight was assessed by the body mass index and included obesity. Psychological data of children and their parents were collected using a face scale. Poisson regression models were used to test the associations and to obtain unadjusted and adjusted prevalence ratios (PR). The prevalence of overweight was of 15.3% (95% CI: 13.2–17.6) and of only obesity was 3.8% (2.8–5.2). After controlling for age, sex, school type and parental overweight, the prevalence of overweight was 52% and 44% higher in children who reported a psychological dissatisfaction in themselves and in their mothers when compared with those with positive self perception (PR = 1.52 95% CI = 1.02–2.28; P = 0.038) and (PR = 1.44 95% CI = 1.00–2.09; P = 0.049), respectively. The study suggests that actions aiming weight control of children should take into account psychological aspects of children and their families.
Physico‐Chemical Properties, Probiotic Survivability, Microstructure, and Acceptability of a Yogurt‐Like Symbiotic Oats‐Based Product Using Pre‐Polymerized Whey Protein as a Gelation Agent
Authors: Walsh Helen , Ross Jane , Hendricks Gregory , Guo Mingruo
Published: July 2010

Abstract:  Consumption of a food product containing prebiotics and probiotics has been recognized as an important factor in lowering risk of intestinal cancer and gastrointestinal diseases and risks associated with high cholesterol. An oats‐based symbiotic yogurt‐like food (Oagurt) was developed using oats and probiotics (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium), with pre‐polymerized whey protein (PWP) as a gelation agent. The product was also fortified with inulin to increase soluble fiber, minerals, and vitamins. Physico‐chemical analyses and 9 wk shelf life for viability of probiotics and changes in pH and viscosity were carried out for formulations with (F) and without (C) fortification. Results of the shelf life study showed that both L. casei and Bifidobacterium remained at therapeutic levels: 4.8 × 106 CFU/g (F), 4.3 × 106 CFU/g (C) and 3.1 × 106 CFU/g (F), 3.17 × 106 CFU/g (C) after 9 wk. However L. acidophilus did not survive after 3 wk. Viscosity and pH decreased significantly during the study with the difference between formulations also significant for pH (P < 0.0001). Scanning electron microscopy of samples revealed that the pre‐polymerized whey protein played a major role in the structure of the gel with an increased protein network structure visible at higher PWP levels. A consumer acceptability study showed that the product was “fair” for all organoleptic attributes.
Diversity of the Predominant Spoilage Bacteria in Water‐Boiled Salted Duck during Storage
Authors: Liu Fang , Wang Daoying , Du Lihui , Zhu Yongzhi , Xu Weimin
Published: July 2010

Abstract:  The spoilage microbiota in water‐boiled salted duck during storage at 4 °C was determined using culture‐dependent and independent methods. Analysis of the denaturing gradient gel electrophoresis (DGGE) patterns of PCR amplicons targeting the V3 region of the 16S rDNA and sequencing of the bands allowed profiling of the microbiota present in the duck. Community DNA extracts were prepared directly from water‐boiled salted duck and from culturable bacterial fractions harvested from both MRS and PCA media. The spoilage bacteria mainly consisted of Staphylococcus saprophyticus, Macrococcus caseolyticus, Weissella, Halomonas sp. or Cobetia sp., and Exiguobacterium sp. based on sequencing and homology search of the DGGE bands. It appeared that both the bacterial counts and diversity increased during storage time. By plating method, bacterial counts in MRS agar increased from 104 to 108 CFU/g from day 1 to 10, while total bacterial counts in PCA agar reached 109 CFU/g after 10 d. Total of 14 strains isolated from PCA and MRS agar were identified as M. caseolyticus (2), S. saprophyticus (7), S. sciuri (1), W. paramesenteroides (2), and W. confusa (2) by 16S rDNA sequencing. The identification of the spoilage‐related microbiota is helpful to better understand the bacteria ecology in water‐boiled salted duck and may lead to the discovery of appropriate preservation strategies.
Relative Efficiency of Price Discovery on an Established New Market and the Main Board: Evidence from Korea
Authors: Eom Kyong Shik , Seon Junghoon , Chang Kook‐Hyun
Published: July 2010

We examine the relative efficiency of price discovery between the new market (KOSDAQ) and the main board (KOSPI) in the Korean stock markets that have the same trading mechanism (i.e. electronic limit‐order book), focusing on the comparisons of each market’s efficiency of price discovery in three aspects: speed, degree, and accuracy. We find that, for our entire firm sample, price discovery on KOSDAQ is less efficient than on KOSPI. However, the price discovery of the most liquid group (top 40 stocks) on KOSDAQ turns out to be as efficient as the lowest group (top 160th–200th stocks) among the top 200 liquid stocks on KOSPI. These two quintiles are comparable in terms of their firm characteristics, so it appears that the greater overall efficiency of price discovery on KOSPI is due to the characteristics of its listed firms, rather than any inherent difference between a main board and a new market. We also find evidence that the speed of price discovery is mainly determined by turnover, whereas the accuracy of price discovery is mainly determined by turnover and intraday volatility. All together, our results provide some policy implications for developing or even developed countries eager to establish a viable new market. First, price discovery in a successful or viable new market in an emerging economy behaves as predicted in the market microstructure literature, even though that literature is based primarily on main boards in advanced stock markets. Second, price discovery in the most liquid group in a new market is more accurate, although slower, than in the lowest group among the liquid stocks on a main board; on balance, the main board and new market are comparable. Finally, the accuracy of price discovery is more (less) impacted by turnover (intraday volatility) on the new market than on the main board.
Automated Manufacturability Analysis of the Draw Bending of Complex Aluminum Profiles
Authors: Johansson Joel
Published: July 2010

Manufacturing companies are required to develop and produce products that meet increased requirements from customers and investors on shortened time spans. One key factor in meeting these requirements is the efficiency of the product development and the production preparation process. Design automation is a powerful tool to increase efficiency in these two processes. The benefits of automating the production preparation process are shortened lead-time, improved product performance, and ultimately decreased cost. Further, automation is beneficial as it increases the ability to adapt products to new product specifications with production preparations done in few or in a single step. During the automation process, knowledge about the production preparation process is collected and stored in the corporation systems, thus allowing full control over the design of production equipments. The contribution of this work is a method for connecting knowledge pieces implemented in auxiliary software applications using an inference engine. The knowledge pieces can control CAD-models and automatically generate, execute, and interpret finite element analyses. The presented method allows the automation of corporation know-how developed by skilled engineers over time. Further, it is possible for the resulting systems to meet criteria for good design automation systems such as low effort of developing, low level of investment, user readable and understandable knowledge, scalability, and flexibility. The method is exemplified by an implementation for analyzing manufacturability of the rotary draw bending of extruded sections of aluminum where the sections are complex. The output from the example system is based on established design practice and heuristic knowledge developed over many years of practical experience, rules analytically derived from fundamental physical laws, and finite element calculations. The system applies knowledge to a given specification that a skilled engineer otherwise would do manually. The method is described along with the example system in this paper.
Kinematics of the Roller Motion and CAM Size Optimization of Disc CAM-Follower Mechanisms With Translating Roller Followers
Authors: Flores Paulo , Machado Gaspar J. B. Q. A. , Pereira Rui M. S. , Claro J. C. Pimenta
Published: July 2010

This paper deals with the kinematic analysis and design optimization of disc cam mechanisms with eccentric translating roller followers. The objective function considered in the present work takes into account the three major parameters that influence the final cam size, namely the base circle radius of the cam, the radius of the roller and the offset of the follower. Furthermore, geometric constraints related to the maximum pressure angle and minimum radius of curvature are included to ensure good working conditions of the system. Finally, an application example is offered.
Knowledge Driven Design Features for the Product Life Cycle of Engine Parts
Authors: Jagenberg Jan Tim , Gilsdorf Erik A. , Anderl Reiner , Bornkessel Thomas
Published: July 2010

The high competitive pressure in the aero-engine market demands higher quality products in shorter time at lower costs. In order to achieve this, a close integration of the product lifecycle with early design stages is necessary. Decisions made in design have an impact on later lifecycle areas like manufacturing and aftermarket, which a design may not foresee without the relevant information. This leads to avoidable iterations in the product development process. This paper illustrates a concept for a design decision support system on feature level. Key knowledge of different design domains is provided within the available design systems during the product development phases.