bluuebunny/crossref_metadata_2025_split huggingface dataset:
Force-time Curves of a Rotary Tablet Press. Interpretation of the Compressibility of a Modified Starch Containing Various Amounts of Moisture
Authors: Leitritz M , Krumme M , Schmidt P C 
Published: April 2011

Abstract
On a rotary tablet press, the force-time curves are segmented into three phases: the compression phase, the dwell phase during which both stress and strain are variable for plastically deforming materials and the decompression phase. The following seven parameters were investigated: the compression area (A1) and the compression slope (Slc) describing the initial phase, the area ratio (AR) and the peak offset time (toff) characterizing the dwell time, the decompression area (A4) and the decompression slope (Sld) describing the terminal phase and the total area under the force-time curve (Atot). AR, toff, Slc and A1 (the last with limitations) are used for phase-specific allocation of the occurrence of plastic flow, which is found to be a function of compression force and moisture content. Tablet strength, tablet porosity and in-die bulk porosity provide additional information for comprehensive interpretation.
The values of A4 for the four starch batches are not significantly different. Sld provides somewhat better information about the elastic compact recovery. In general, however, the short decompression phase seems to be inappropriate for characterization by force-time curve parameters, because it is difficult to separate machine recovery from that of the tablet.
Porosity above the porosity limit of the material was found to be a prerequisite for plastic flow within the compact. When the porosity limit is reached, further densification remains elastic and leads to a reduced compact strength during expansion. The area ratio, as a robust in-process control parameter for plastically flowing formulations, is suggested as a means of preventing this effect.
Synthesis, Physical Properties, Toxicological Studies and Bioavailability of L-Pyroglutamic and L-Glutamic Acid Esters of Paracetamol as Potentially Useful Prodrugs
Authors: Bousquet E , Marrazzo A , Puglisi G , Spadaro A , Tirendi S 
Published: April 2011

Abstract
Paracetamol ester prodrugs with L-pyroglutamic and L-glutamic acid, biosynthetic precursors of glutathione, have been synthesized to reduce paracetamol hepatotoxicity and improve bioavailability.
The toxicological studies of paracetamol esters show that only L-5-oxo-pyrrolidine-2-paracetamol carboxylate reduces toxicity after administration of an overdose. The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg−1 and the intraperitoneal LD50 was 1900 mg kg−1.
These results taken together with hydrolysis and bioavailability data show that ester is a potential candidate as a prodrug of paracetamol.
The Disposition of Morphine and Morphine-3-glucuronide in the Isolated Perfused Rat Liver: Effects of Altered Perfusate Flow Rate
Authors: O'Brien Josephine A , Nation Roger L , Evans Allan M 
Published: April 2011

Abstract
The rat single-pass isolated perfused liver preparation was used to study the effects of altered perfusate flow rate on the hepatic disposition of morphine and its polar metabolite morphine-3-glucuronide (M3G). Using a balanced, cross-over design, livers of female Sprague-Dawley rats (n = 6) were perfused at 15 and 30 mL min−1 with erythrocyte- and protein-free perfusion medium containing a constant concentration of morphine (2.7 μM). After reaching steady-state, inflow and outflow perfusate and bile samples were collected and morphine and M3G were measured by HPLC.
Doubling of perfusate flow rate was associated with a significant increase (P &lt; 0.05) in the availability of morphine (mean ±s.d. of 0.19± 0.06 at 15 mL min−1 and 0.29 ± 0.08 at 30 mL min−1). The magnitude of the change in morphine availability was consistent with the predictions of the well-stirred model of hepatic elimination.
The fate of hepatically generated M3G was assessed by the biliary extraction ratio of M3G; alterations in perfusate flow rate had no significant effect on this ratio (mean ± s.d. of 0.49 ± 0.14 at a perfusate flow rate of 15 mL min−1 and 0.47 ± 0.22 at 30 mL min−1).
A physiologically-based mathematical model, in which the vascular and intracellular spaces of the liver were represented by two well-mixed compartments, was utilized to derive an equation for the biliary extraction ratio of M3G. According to the model, the value of this extraction ratio will become insensitive to changes in perfusate flow rate when the permeability for M3G of the membrane separating the intracellular and vascular compartments is low compared with perfusate flow rate. Hence, the experimental results are consistent with the concept that the hepatic sinusoidal membrane represents a diffusional barrier to M3G.
A High-performance Liquid-chromatographic Microanalytical Procedure for the Rapid Estimation of Piracetam in Plasma or Cerebrospinal Fluid
Authors: Doheny M H , O'Connell M T , Patsalos P N 
Published: April 2011

Abstract
Presently available GC and HPLC methods for analysis of piracetam, require large samples and suffer from interference.
A micro scale, isocratic high-performance liquid-chromatographic method is described for the determination of piracetam in plasma (25 μL) or cerebrospinal fluid (10 μL) using ultraviolet absorbance at 215 nm. The limit of quantitation is 4 μg mL−1 and the within-batch and between-batch coefficients of variation are less than 10%. No interference from other commonly prescribed antimyoclonic or antiepileptic drugs was observed and thus the method can be used to monitor piracetam in patients on polytherapy antimyoclonic or antiepileptic drug regimens.
Because of the sensitivity and rapidity of the method it is suitable for pharmacokinetic and mechanistic studies and for analysis of paediatric samples.
Uptake Mechanism of Trientine by Rat Intestinal Brush-border Membrane Vesicles
Authors: Tanabe Ryou , Kobayashi Michiya , Sugawara Mitsuru , Iseki Ken , Miyazaki Katsumi 
Published: April 2011

Abstract
The uptake characteristics of trientine by rat intestinal brush-border membrane vesicles were studied.
The uptake characteristics of trientine were similar to those of the physiological polyamines with respect to the excessive accumulation in vesicles, the pH dependency, the temperature dependency and the ineffectiveness of K+ diffusion potential (inside negative). The initial uptake of trientine was saturable with a Km value of 1.13 mM, which was larger than that of spermine and spermidine. Furthermore, the uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Spermine competitively inhibited the uptake of trientine with a Ki value of 18.6 μM, and it was close to the Km value for spermine (30.4 μM).
These data suggested that the uptake of trientine was similar to that of spermine and spermidine in rat small intestinal brush-border membrane vesicles, and these polyamines seem to inhibit the absorption of trientine from the gastrointestinal tract.
Selective Cyclodextrin Inhibition of Alfaxolone-induced Ataxia
Authors: Koetzner Lee , Riggs Raine L , Mastropaolo John , Deutsch Stephen I 
Published: April 2011

Abstract
The effect of the use of a number of popular solubility treatments was examined on alfaxolone- and diazepam-induced ataxia.
The effects of diazepam were not significantly altered by solution in cyclodextrin, Alkamuls EL-620 or a mixture of propylene glycol and ethanol. The effects of alfaxolone were not altered by solution in Alkamuls EL-620, but were significantly lessened by solution in cyclodextrin. In a dose-response experiment, the ED50 of alfaxolone increased from 15.3 mg kg−1 (in Alkamuls EL-620) to 25.6 mg kg−1 (in hydroxypropyl-β-cyclodextrin).
The results suggest that although cyclodextrins are popular and effective solubilizers, their use must be considered carefully in the context of the experiments in which they are to be used.
Evaluation of the Relaxant Activity of some United Arab Emirates Plants on Intestinal Smooth Muscle
Authors: Tanira M O M , Ali B H , Bashir A K , Wasfi I A , Chandranath I 
Published: April 2011

Abstract
Although medicinal plants are used as antispasmodic agents in folk medicine there have been no scientific studies of the phytochemical composition and usefulness of these plants for such treatment. Extracts of 23 plants used in the traditional medicine of the United Arab Emirates were tested for their effects on intestinal smooth muscle activity.
Most of the plants tested caused stimulation followed by inhibition of the motility of the rabbit jejunum and guinea-pig ileum. The inhibitory effect of plants that had EC50 values &lt; 1 mg was confirmed in-vivo using the gastrointestinal transit time test. These plants were phytochemically screened for their secondary constituents. The effect of Rhazya stricta was investigated, particularly in relation to acetylcholine effect.
The results indicated the potential of some of the plants, especially Rhazya stricta, as a source of antispasmodic agents.
Animal Pharmacokinetics and Interspecies Scaling from Animals to Man of Lamifiban, a New Platelet Aggregation Inhibitor
Authors: Lave Thierry , Saner Alphonse , Coassolo Philippe , Brandt R , Schmitt-Hoffmann Anne H , Chou Ruby C 
Published: April 2011

Abstract
Relating pharmacokinetic information obtained in animal species to man (interspecies scaling) can play an important role in enabling understanding of the differences and similarities between species, and helping to predict the kinetic profile of a new compound in man.
Interspecies scaling techniques have been applied to lamifiban (Ro 44–9883), a new selective and potent nonpeptidic inhibitor of human glycoprotein IIb-IIIa intended for use in clinical treatment of, for example, acute coronary syndrome. The pharmacokinetic profile of lamifiban in man was predicted from animal data (in rats, dogs and cynomolgus monkeys) by using allometric scaling and concentration-time transformations. These extrapolations for lamifiban were performed prospectively, to help design the first pharmacokinetic studies in man. The approach based on equivalent time was preferred for our prospective predictions, in view of the high values found for the allometric exponents. Using allometric scaling, clearance (CL), half-life(t1/2) and volume of distribution (Vd) were overestimated by approximately two-to fourfold. Compared with allometric scaling, the transformation based on equivalent time improved the prediction for all human pharmacokinetic parameters. For t1/2 and CL, the observed values for man were within the range predicted from the various animal species.
Of the individual animal species, the cynomolgus monkey gave the most reliable predictions of these two parameters, as well as accurately predicting the Vd value.
Adrenomedullin is Inactivated in the Lungs of Neonatal Piglets
Authors: Sabates Braulio , Granger Tommie , Choe Ella , Pigott John , Lippton Howard , Hyman Albert , Flint Lewis , Ferrara John 
Published: April 2011

Abstract
Adrenomedullin, a novel 52 amino acid peptide normally present in adult human plasma, has been shown to induce systemic hypotension in the adult rat, pig and cat, and in the new-born piglet. Little is known about the site(s) of adrenomedullin inactivation in adults or neonates.
Groups of five 0–2-day old and 2-week old anaesthetized piglets were prepared to enable continuous monitoring of cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, mean systemic vascular resistance and mean pulmonary vascular resistance. In both age groups, injections of human adreno-medullin1–52 into the left atrium produced significant (P &lt; 0.05) reductions in mean systemic arterial pressure and mean pulmonary artery pressure. Although injections of similar doses of human adrenomedullin1–52 into the right atrium produced significant (P &lt; 0.05) decreases in mean pulmonary artery pressure, there were no appreciable alterations in mean systemic arterial pressure in either age group.
These results suggest that the systemic vasodilator properties of human adrenomedullin1–52 are reduced upon first pass through the pulmonary circulation in 2-week old piglets, a phenomenon that is present at birth.
Twenty-eight-day Double-blind Safety Study of an HFA-134a Inhalation Aerosol System in Healthy Subjects
Authors: Harrison Lester I , Donnell David , Simmons Jean L , Ekholm Bruce P , Cooper Katherine M , Wyld Peter J 
Published: April 2011

Abstract
A 28-day double-blind parallel group study has been conducted to compare the safety and tolerability of HFA-134a, a chlorofluorocarbon-free propellant in a pressurized metered-dose inhaler (MDI A), with a chlorofluorocarbon propellant (MDI C).
Sixteen subjects were randomly assigned to receive one of the two MDIs, either four inhalations four times per day for 14 days or eight inhalations four times a day for 14 days, and were then crossed over to the alternative exposure regime with the same propellant for the next 14-day period. No clinically significant changes occurred in blood pressure, heart rate, electrocardiograms, pulmonary function (FEV1, FVC, FEF25–75%), haematology or serum chemistry. One subject in the MDI A group had elevated eosinophil counts throughout the study; there were no other remarkable clinical laboratory data. Fifty six adverse events were related to the study propellants; 34 of these occurred in the MDI C group and 22 in the MDI A group. For each adverse event no statistically significant differences were detected between propellant systems or between exposure levels. The most frequent adverse event was headache, which was reported by four subjects with each propellant system. Blood samples for HFA-134a in the MDI A group were collected on day 28 to measure systemic absorption. Blood levels of HFA-134a were detected in all subjects given this propellant within 1 min post-exposure, and these levels decreased to one-tenth of the original value by 18 min after the start of exposure.
The safety and tolerability of an HFA-134a chlorofluorocarbon-free system was demonstrated over 28 days of exposure in healthy subjects. These negative results are clinically important because they indicate it will be safe to proceed with the study of this chlorofluorocarbon-free system in asthmatic patients.
Pharmacodynamics of ZM 241385, a Potent A2a Adenosine Receptor Antagonist, after Enteric Administration in Rat, Cat and Dog
Authors: Poucher S M , Keddie J R , Brooks R , Shaw G R , Mckillop D 
Published: April 2011

Abstract
4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) is currently the most selective for the A2a adenosine receptor antagonist. This paper describes the in-vivo activity of ZM 241385 after administration by both oral and intraduodenal routes.
In conscious spontaneously hypertensive rats, ZM 241385 (1–10 mg kg−1) selectively attenuated the mean arterial blood pressure response produced by exogenous adenosine (1 mg kg−1 min−1, i.v.) by up to 45% after oral administration. Activity of ZM 241385 was maintained for at least 6 h after 3 and 10 mg kg−1 (p.o.). In conscious normotensive cats, ZM 241385 attenuated the blood pressure responses to adenosine (0.6–10 mg kg−1, i.v.) by 94% after 10 mg kg−1 (p.o.) and by up to 74% after 0.3 mg kg−1 (i.v.). Duration of action of ZM 241385 up to 12 h (36% inhibition) was observed after 3 mg kg−1 (p.o.). In anaesthetized dogs and cats, ZM 241385, after intraduodenal administration (1–10 mg kg−1), produced a rapid (dose ratio 100-fold 15 min after administration of 10 mg kg−1 in the cat) and prolonged (dose ratio of 14 at 6 h after administration of 10 mg kg−1) attenuation of the vasodilatation responses to adenosine receptor stimulation. When administered by this route ZM 241385 was six times more potent than theophylline in the cat and at least twice as potent as theophylline in the dog.
In conclusion, ZM 241385 is a potent, selective A2a adenosine receptor antagonist which is orally active, with a good duration of action by the enteric route in cat, rat and dog. It could therefore be used to evaluate the role of adenosine A2a receptors in the action of adenosine in-vivo.
Dexamethasone Reduced Clonidine-induced Hypoactivity in Mice
Authors: Capasso A , Di Giannuario A , Loizzo A , Pieretti S , Sorrentino L 
Published: April 2011

Abstract
Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to investigate the effects of dexamethasone pretreatment on locomotor hypoactivity, another example of clonidine-induced behaviour in mice.
Dexamethasone administered intraperitoneally (0.1, 1.0, 10 mg kg−1) 30 min before clonidine reduced clonidine-induced locomotor hypoactivity in the activity cage to an extent which was dose-dependent. Dexamethasone administered centrally (10 ng/mouse) 30 min before clonidine was also able to reduce clonidine-induced locomotor hypoactivity. Cycloheximide administered at a dose of 10 mg kg−1 2 h before clonidine did not change the effects of clonidine but was able to prevent the effects of dexamethasone on clonidine-induced hypoactivity. The glucocorticoid receptor antagonist RU38486 administered centrally at the dose of 1 ng/mouse did not change the effects of clonidine, whereas it was able to block the effects of dexamethasone on clonidine-induced locomotor hypoactivity.
These results suggest that the effects of dexamethasone on clonidine-induced locomotor hypoactivity depend on the stimulating effects that dexamethasone exerts on the protein synthesis via the glucocorticoid receptor in the brain.
Sympathomimetic Effects of Scoparia dulcis L. and Catecholamines Isolated from Plant Extracts
Authors: Freire Sonia Maria De Farias , Torres Luce Maria Brandão , Souccar Caden , Lapa Antonio José 
Published: April 2011

Abstract
The herb Scoparia dulcis L. is used in Brazilian folk medicine to treat bronchitis, gastric disorders, haemorrhoids, insect bites and skin wounds, and in oriental medicine to treat hypertension. A previous study has shown that extracts of S. dulcis have analgesic and anti-inflammatory properties; in this work the sympathomimetic activity of an ethanolic extract of Scoparia dulcis L. has been investigated in rodent preparations in-vivo and in-vitro.
Administration of the extract (0.5-2 mg kg−1, i.v.) to anaesthetized rats produced dose-related hypertension blocked by the α-adrenoceptor antagonist prazosin (1 mg kg−1). Partition of the extract in chloroform-water yielded an aqueous phase 20 times more potent than the extract; this produced hypertension in either reserpine-treated or pithed rats. In untreated and reserpine-treated rats the same fraction (1–3 × 103 μg mL−1) produced concentration-dependent contractions of the vas deferens musculature parallel to those obtained with noradrenaline (10−8-10−4 m). Prazosin (10−7 m) reduced the maximum contractile effect of the aqueous fraction, and shifted the concentration-response curves for noradrenaline to the right. The aqueous fraction (25 and 50 μg mL−1) increased the inotropism of electrically driven left atria of rats, the effect being blocked by propranolol (0.4 μg mL−1). In preparations of guinea-pig tracheal rings the aqueous fraction (1–3 × 103 μg mL−1) relaxed the muscle contraction induced by histamine (10−4 m) in proportion to the concentration. The effect was antagonized competitively by propranolol (1.5 μm). High-performance liquid-chromatographic analysis of the aqueous fraction revealed the presence of both noradrenaline and adrenaline in the plant extract.
The results indicated that both catecholamines may account for the hypertensive and inotropic effects obtained after parenteral administration of S. dulcis extracts. This sympathomimetic activity is, however, unrelated to the previously reported analgesic and anti-inflammatory properties of the plant extract, but may explain its effectiveness upon topical application in the healing of mucosal and skin wounds.
Interactions of Cephradine and Cefaclor with the Intestinal Absorption of D-Galactose
Authors: Idoate Isabel , Mendizábal M Victoria , Urdaneta Elena , Larralde Jesús 
Published: April 2011

Abstract
Oral cephalosporins are frequently prescribed β-lactam antibiotics. Although it has been well established that cephalosporins compete with dipeptides for absorption in the intestine, using the same transport mechanism, little is known about the action of the drugs on the absorption of other nutrients. In this work the effect of cephradine and cefaclor on the absorption of d-galactose has been studied. Intestinal sugar uptake was measured in-vitro in pieces of intestine (50 mg) and brush-border membrane vesicles, and in-vivo in intestinal loops.
Galactose uptake was inhibited by cephalosporins in a dose-related, time-dependent manner. In-vivo the inhibition appeared when the antibiotics were on the luminal side of the enterocyte and when they reached the gut from the basolateral side. Only the active transport of the sugar was modified; passive transfer did not change in the presence of cephalosporins. In brush-border membrane vesicles, cephradine and cefaclor did not alter sugar uptake in either sodium or potassium gradients. Both antibiotics non-competitively inhibited basolateral Na+,K+-ATPase activity.
These findings show that cephradine and cefaclor inhibit the active-transport component of galactose absorption because they reduce the activity of the basolateral Na+,K+-ATPase.
Elcatonin Raises Levels of Vasoactive Intestinal Peptide in Human Plasma
Authors: Takeyama Masaharu , Ikawa Kazuro , Nagano Toshiaki , Mori Kazuo 
Published: April 2011

Abstract
Elcatonin, used for treatment of hypercalcaemia, Paget's disease and osteoporosis, causes flushing of the face and hands. To determine whether this was because of increased levels of vasoactive intestinal peptide, which is known to induce vasodilation, the effect of elcatonin on the plasma levels of vasoactive intestinal peptide was studied in five healthy volunteers.
After a single intramuscular administration of elcatonin (20 int. units), peak plasma elcatonin levels (approx. 30 pg mL−1) were achieved 30 min after injection. Plasma vasoactive intestinal peptide concentrations rose similarly with peak levels of about 17 pg mL−1 after 30 min. Side-effects such as cutaneous flushing (most obvious in the face and hands) occurred to an extent dependent on the amount of elcatonin administered, and declined over 45 min in parallel with the fate of plasma vasoactive intestinal peptide.
The side-effects of elcatonin, especially cutaneous flushing, seem to be closely connected with vasoactive intestinal peptide.