bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of the Neuropeptide Galanin on the Contractility and the Effective RefractoryPeriod of Guinea-pig Heart Papillary Muscle Under Normoxic and Hypoxic Conditions
Authors: Kocic Ivan 
Published: April 2011

Abstract
The aim of this study was to discover the effects of galanin, a neuropeptide comprising 29 amino acids capable of activating inward-rectifier K+ channels (IK1) in cardiomyocytes, on the force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (—dF/dt) and effective refractory period (ERP) of guinea-pig heart. The influence of galanin on the time-course of hypoxia-induced disturbances in contractility and ERP was also examined. Experiments were performed on the isolated right ventricle papillary muscle of guinea-pig heart.
In the concentration range 0.001–0.01μM, galanin had no significant effect on the measured parameters. At 0.03 and 0.1 μM, galanin exerted a positive inotropic action and prolonged ERP. Further increasing the concentration led to a negative inotropic action and significant shortening of ERP. Although simulated hypoxia induced a significant drop in Fc, +dF/dt and —dF/dt, and a significant shortening of ERP, recovery of all the measured parameters was complete after 10min reperfusion. In the presence of 0.03 and 0.1 μM galanin the effect of hypoxia on the contractility of papillary muscle was more profound and reperfusion did not result in complete recovery. In contrast, addition of 1 μM galanin to the hypoxic solution significantly protected the muscle and recovery of the tissues during reperfusion was rapid and complete (in 5 min).
One can conclude that galanin at lower concentrations induced a positive inotropic action and a prolongation of ERP, but increased the sensitivity of heart muscle to hypoxia. At higher concentrations however, galanin exerted a negative inotropic action but protected the muscle against hypoxia-induced disturbances in contractility.
Gastroprotective Effect of l-Phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en- 1 -one in Rats
Authors: Rao P N Praveen , Rao Mahadev , Rao M N A 
Published: April 2011

Abstract
1-Phenyl-3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-2-en-1-one (PHP), an antioxidant, has been studied for gastroprotective activity in-vitro and in-vivo, more specifically for its capacity to inhibit in-vitro iron- and copper-driven oxidant damage at acidic pH values mimicking intragastric conditions in the clinical setting.
Our studies showed significant inhibition of both iron- and copper-driven oxidant damage at pH 3.5 and 5.3. Intragastric and intraperitoneal administration of PHP (250mgkg−1) reduced gastric mucosal haemorrhagic lesions in stress-induced and ethanol-induced rat models. The gastroprotective effect of PHP against ethanol was reversed significantly by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis, indicating a possible role of prostaglandins in its gastroprotective effect. Treatment of PHP replenished reduced levels of gastric mucosal non-protein sulphydryls in ethanol-treated rats, suggesting the mediation of its effect through sulphydryls.
These results indicate that PHP was active at acidic pH. This is an interesting observation because highly acidic pH is known to be important in the development of gastric ulcers. Our study suggests that PHP might protect gastric mucosa by its capacity to scavenge free radicals.
Disposition of 4-Methylbenzoylglycine in Rat Isolated Perfused Kidney and Effects of Hippurates on Renal Mitochondrial Metabolism
Authors: Masereeuw Rosalinde , Moons Miek M , Russel Frans G M 
Published: April 2011

Abstract
Hippurates tend to accumulate within proximal tubule cells during renal secretion. High intracellular concentrations can alter proximal tubular function or lead to tubular toxicity. In this study we examined the renal disposition of the hippurate 4-methylbenzoylglycine, a compound known for its high renal intrinsic clearance in-vivo. The effect of intracellular accumulation on mitochondrial respiration was also measured in-vitro and compared with that of the 2-methyl and 4-amino analogues.
Experiments were performed with either 2.5% pluronic or a combination of 2.2% pluronic and 2% bovine serum albumin (BSA) as oncotic agents. Within the concentration range studied (1–200 μg mL−1) tubular secretion seemed to be a function of the amount of unbound drug in the perfusate. Renal excretion data were best fitted by a model in which a Michaelis-Menten term was used to describe active secretion. Parameters obtained after the analysis of renal excretion data were the maximum transport velocity (TM = 55 ± 2 μg min−1) and the Michaelis-Menten constant for tubular transport (KT = 4.2 ± 0.8 μg mL−1). The compound accumulated extensively in kidney tissue, ratios up to 600 times the perfusate concentration were reached. Accumulation could be explained by active tubular uptake and data were analysed best by a model similar to the model used to describe renal excretion. Calculated parameters were theoretical maximum capacity (RM = 300 ± 210 μg g−1) and affinity constant for renal accumulation (KA = 5.0 ± 4.4 μg mL−1). The high intracellular concentrations of 4-methylbenzoylglycine had no effect on kidney function and mitochondrial oxygen consumption. The 2-methyl analogue reduced mitochondrial respiration slightly, but 4-aminobenzoylglycine (p-amino-hippurate) caused a significant reduction.
In conclusion, this study shows that renal accumulation of a hippurate is determined by the efficiency of its tubular secretion. Whether the high intracellular concentrations affect tubular cell functioning depends on the analogue involved.
Ultrastructural Localization of Nicorandil in the Heart of Rats
Authors: Kitajima Shunichi , Tsuchiya Yoko , Sakai Kazushige 
Published: April 2011

Abstract
To examine the intracellular localization of nicorandil in the heart, [14C]nicorandil and [3H]nicorandil (3 mg kg−1) were given orally to rats.
The maximum concentration (Cmax) of nicorandil in the myocardium was reached 15 min after the oral dosing. At this time subcellular localization of nicorandil was examined. Nicorandil and its denitrated metabolite, SG-86 were found in mitochondrial fractions and in cytosolic and microsomal fractions of the heart. Electron-microscopic autoradiograms recorded 15 min after oral dosing of 3 mg kg−1 [3H]nicorandil to rats also showed the presence of silver grains generated by the radioactive nicorandil or its metabolites in the mitochondria of the heart.
We conclude that nicorandil given orally to rats is distributed in mitochondria of the heart.
Hydroxylated Metabolites of Thalidomide: Formation In-vitro and In-vivo in Man
Authors: Eriksson Tommy , Björkman Sven , Roth Bodil , Björk Henrik , Höglund Peter 
Published: April 2011

Abstract
There is renewed interest in the clinical use of thalidomide, because of its unique immunomodulating action. Because data on the metabolism of thalidomide in man are very sparse, the aim of this study was to develop HPLC assays for the 5-hydroxy, 5,6-dihydroxy, 4,5-dihydroxy and 5′-hydroxy metabolites of thalidomide and to investigate their possible formation in man—in-vitro in liver homogenates and in-vivo in healthy volunteers.
Reversed-phase HPLC assays with UV detection were developed for quantification of the metabolites in the low ng mL−1 range in plasma and incubate samples. The stability of the metabolites was investigated and degradation was avoided by rapid chilling and acidification of the samples. After incubation of thalidomide with fraction S9 from human liver, formation of the 5-hydroxy and 5′-hydroxy metabolites could be demonstrated. The 5′-hydroxy metabolite was found, in low concentrations, in plasma samples from eight healthy male volunteers who had received thalidomide orally. The other three metabolites could not be found by HPLC with detection limits of 1–2 ng mL−1.
Thus the formation of two hydroxylated metabolites of thalidomide in the liver in man was demonstrated, but only one of these could be detected in the circulation.
Antinociceptive Effect in Mice of a Hydroalcoholic Extract of Neurolaena lobata (L.) R. Br. and its Organic Fractions
Authors: Gracioso Juliano S , Paulo Marçal Q , Lima Clélia A Hiruma , Brito Alba R M Souza 
Published: April 2011

Abstract
An infusion of the aerial parts of Neurolaena lobata (L.) R. Br. (Compositae-Asteraceae) is used in Caribbean folk medicine to treat several kinds of pain. In this investigation we studied the acute oral toxicity of the hydroalcoholic extract of the plant and the antinociceptive effect of the extract and of its hexane- and chloroform-partitioned fractions, given orally, in nociception and inflammatory models in mice.
No signs of toxicity were observed for oral doses up to 5000 mg kg−1 in mice. Morphine hydrochloride (10 mg kg−1), dipyrone sodium (200 mg kg−1), the hydroalcoholic extract (1000 mg kg−1), and its chloroform- and hexane-partitioned fractions (100 mg kg−1) significantly inhibited acetic acid-induced abdominal constriction in mice (100, 95, 47, 62 and 60% inhibition, respectively when compared with the negative control). In the hot-plate test in mice, morphine hydrochloride, the chloroform- and hexane-partitioned fractions, but not the hydroalcoholic extract, resulted in a significant latency increase in all observation times. In the acetic acid-induced abdominal constriction in mice, pretreatment of the animals with naloxone significantly reversed the analgesic effect of morphine, but not that of the hydroalcoholic extract or of its hexane- and chloroform-partitioned fractions. Finally, administration of the hexane- and chloroform-partitioned fractions (100 mg kg−1) had a significant anti-oedematogenic effect on carrageenan-induced oedema in mice.
These data show that the hydroalcoholic extract of N. lobata and, in particular, its partitioned fractions have significant analgesic properties when assessed through these pain models. Their antinociceptive effect might be the result of interference with the inflammatory process.
Optimization of Sustained-release Diltiazem Formulations in Man by use of an In-vitro/In-vivo Correlation
Authors: Yu K , Gebert M , Altaf S A , Wong D , Friend D R 
Published: April 2011

Abstract
In-vitro/in-vivo correlations (IVIVC) are useful for predicting in-vivo results from in-vitro data. An IVIVC has been used to optimize a hydrocolloidal-based matrix tablet designed to be bioequivalent to an existing once-daily diltiazem HCl*** product (Dilacor XR 240 mg; Rhone-Poulenc Rorer).
Data from a preliminary formulation dosed to fasted and fed subjects were used to establish the IVIVC. The correlation was then used during reformulation of the dosage forms to predict changes in the maximum plasma concentration (Cmax) and the area under the plasma-concentration-time curve (AUC) for fasted and fed subjects using in-vitro dissolution data.
The IVIVC adequately predicted plasma profiles of two optimized formulations in studies with fasted and fed subjects.
Prediction of Serum Vancomycin Concentrations using One-, Two- and Three-compartment Models with Implemented Population Pharmacokinetic Parameters and with the Bayesian Method
Authors: Wu Guang , Furlanut Mario 
Published: April 2011

Abstract
Although previous studies have shown that vancomycin has a complicated pharmacokinetic profile requiring description using a two- or, better, three-compartment model, until recently predictions of serum vancomycin concentrations have been mainly based on one- or two-compartment models using computer software packages. In this study, we have predicted serum vancomycin concentrations in 59 patients using one-, two- and three-compartment models with implemented population pharmacokinetic parameters in the Abbott PKS program and by use of the Bayesian method.
The percentage errors of predictions made using the one-compartment model were smaller when either the Bayesian method or implemented population pharmacokinetic parameters were used (medians of −8·61% and −9·49%, respectively). Predictions using the one-compartment model with the Bayesian method were less biased (median of −1·52 μgmL−1). The best predictions were those made using the three-compartment model with the Bayesian method—they were most accurate (median of 3·40 μg mL−1) and highly precise (median of 11·53 μg2mL−1).
The results suggest that predictions made using the one-compartment model with implemented population pharmacokinetic parameters are preferable if no samples are available, otherwise predictions made using the three-compartment model with the Bayesian method are preferable. The results also supported our previous argument that the greater the number of compartments involved in individualization, the better the predictions obtained using the Bayesian method.
Effects of Tetramethylpyrazine on Portal Hypertensive Rats
Authors: Chang Fang-Chi , Chen Ke-Ji , Lin Jaung-Geng , Hong Chuang-Ye , Huang Yi-Tsau 
Published: April 2011

Abstract
The effects of tetramethylpyrazine, an alkaloid isolated from a Chinese herb Ligusticum wallichii Franch have been assessed in portal hypertensive rats.
Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state had stabilized, rats were anaesthetized after an overnight fast and cannulated for measurement of mean arterial pressure, portal venous pressure, cardiac index and heart rate. Tetramethylpyrazine (3·0, 9·9 and 30mgkg−1) induced dose-dependent reductions of portal venous pressure and mean arterial pressure after intravenous infusion. The maximum percentage reduction of portal venous pressure after tetramethylpyrazine was 6·0±0·8, 9·3±1·6 and 20±2% of baseline for doses of 3·0, 9·9 and 30·0mgkg−1, respectively. Also, total peripheral resistance was significantly reduced by tetramethylpyrazine and cardiac index was slightly increased.
Our results showed that tetramethylpyrazine induced portal pressure reduction in portal hypertensive rats.
Prejunctional Control of pH 6-Induced Bronchoconstriction by NK1, NK2, μ-Opioid, β2-Adrenoceptor and Glucocorticoid Receptors in Guinea-pig Isolated Perfused Lung
Authors: Auberson Serge , Lacroix Jean S , Kordestani Rouzbeh K , Lundberg Jan M 
Published: April 2011

Abstract
This study investigated the release of calcitonin-gene related peptide-like (CGRP) immunoreactivity and bronchoconstriction induced by pH 6 buffer in guinea-pig isolated perfused lung.
Both pH 6-induced CGRP-like immunoreactivity and bronchoconstriction were completely abolished after systemic pretreatment with capsaicin. Pretreatment with the NK2 receptor antagonist SR 48968 (5 times 10−7M) completely inhibited bronchoconstriction and significantly reduced the immunoreactivity induced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 times 10−7M) and, to a lesser extent the NK1 antagonist CP 96345, morphine (5 times 10−6M), the α2-adrenoceptor agonist UK 14304 (10−7M) and betamethasone (10−6M) significantly reduced both pH 6-induced bronchial response and CGRP-like immunoreactivity overflow. The effects of morphine and UK14304 were partially reversed by naloxone (5 times 10−5M) and idazoxan (5 times 10−5M).
Therefore, NK1, NK2, μ-opioid, α2-adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-like immunoreactivity and bronchoconstriction.
Use of Protease Inhibitors to Improve Calcitonin Absorption from the Small and Large Intestine in Rats
Authors: Tozaki Hideyuki , Odoriba Tomokazu , Iseki Tomoya , Taniguchi Toshio , Fujita Takuya , Murakami Masahiro , Muranishi Shozo , Yamamoto Akira 
Published: April 2011

Abstract
The objective of this study was to examine the effects of protease inhibitors on the absorption of calcitonin from different regions of the intestine in rats. The absorption experiments were investigated by in-situ use of closed intestinal loops in rats and stability of calcitonin was examined in mucosal homogenates and intestinal fluids. The intestinal absorption of calcitonin was evaluated by measurement of its hypocalcaemic effect.
No substantial hypocalcaemic response was observed when calcitonin was administered into the jejunum or colon. A slight hypocalcaemic effect was observed after administration of calcitonin into the ileum. Of the co-administered protease inhibitors, bacitracin (20 mM) strongly promoted calcitonin absorption from the jejunum, ileum and colon. A significant hypocalcaemic effect was also obtained after intestinal administration of calcitonin with soybean trypsin inhibitor (10mgmL−1), camostat mesylate (20mM) or aprotinin (2mgmL−1). In the stability experiment, bacitracin reduced the degradation of calcitonin in the different intestinal homogenates. Soybean trypsin inhibitor significantly reduced the degradation of calcitonin in the fluids of the small intestine. We also examined the different endopeptidases in gut luminal fluids and the different exopeptidases in gut mucosal homogenates of rats. The ranking order for the total endopeptidase activity of the intestinal fluids was jejunum &gt; ileum &gt; colon. That for total exopeptidase activity of the intestinal mucosa was jejunum &gt; ileum &gt; colon.
These results suggest that endo- and exopeptidases might be responsible for the hydrolysis of calcitonin and that protease inhibitors might usefully improve absorption of calcitonin to the systemic circulation from the large intestine.
Delayed Healing of Chronic Gastric Ulcer after Helicobacter pylori Infection in Mice
Authors: Makino Mitsuko , Koga Tetsufumi , Ito Keiichi , Kawada Harumi , Tabata Keiichi 
Published: April 2011

Abstract
It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice.
H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mg kg −1 daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing.
In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.
A Comparative Study of the Effects of Sparteine, Lupanine and Lupin Extract on the Central Nervous System of the Mouse
Authors: Pothier J , Cheav S-L , Galand N , Dormeau C , Viel C 
Published: April 2011

Abstract
Lupin is toxic because of its alkaloid content, sparteine and lupanine in particular. Although the pharmacological properties of sparteine are well known those of lupanine have not been much studied. This paper reports procedures for extraction, purification and crystallization of lupanine, and methods for the preparation of an extract for injection of Lupinus mutabilis Sweet, and for the determination of the acute toxicity and maximum non-lethal dose (DL0) of lupanine, sparteine and lupin extract in the mouse.
The three substances were tested on the central nervous system (CNS) for locomotor activity, for interaction with specific drugs used for treatment of the CNS (the stimulant drugs amphetamine and pentetrazol and the depressant drugs pentobarbital and chlorpromazine) and for analgesic activity.
The results indicate that lupanine and lupin extract are less toxic than sparteine and that at the doses studied the three products have a weak sedative effect on the CNS.
Spectrophotometric and Spectrofluorimetric Determination of Fluorouracil in the Presence of its Degradation Products
Authors: Amer M M , Hassan S S M , El-Fatah S A Abd , El-Kosasy A M 
Published: April 2011

Abstract
Three reliable spectrophotometric and spectrofluorimetric procedures are described for the determination of fluorouracil in bulk powder and ampoules in the presence of its degradation products.
One spectrophotometric procedure, based on measurement at 555 nm of the violet-coloured complex formed by fluorouracil with cobalt(II), has a detection limit of 0.03 mg mL−1. Two sensitive spectrofluorimetric procedures are also proposed. One is based on measurement of the intrinsic fluorescence of the liberated fluorouracil at 375 nm, after precipitation as its cobalt(II) complex, decomposition of the precipitate with sulphuric acid and excitation at 295 nm. The second depends on excitation of the fluorouracil-cobalt(II) complex at 395 nm and measuring its fluorescence at 483 nm. The limits of detection of the two spectrofluorimetric procedures are 0.5 and 2 μg mL−1, respectively.
The three procedures have been used successfully for the determination of fluorouracil ampoules. The validity of the methods has been assessed by applying the standard addition technique.
Transdermal Delivery and Accumulation of Indomethacin in Subcutaneous Tissues in Rats
Authors: Mikulak Stephen A , Vangsness C Thomas , Nimni Marcel E 
Published: April 2011

Abstract
Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective pharmacotherapy for a wide variety of painful, inflammatory disorders. Development of an efficient means of topical administration of NSAIDs could increase local soft-tissue and joint concentrations while reducing systemic distribution of the drug, thereby reducing side-effects. With this in mind we studied the effects of a novel topical penetration enhancer for lipophilic compounds, a trans-phase delivery system (TPDS), a solution of benzyl alcohol, iso-propanol and acetone, on the distribution of indomethacin in various tissues locally and remote from the site of application. We compared the TPDS with a 50:50 (v/v) mixture of propylene glycol and ethanol, a commonly used penetration enhancer, and with oral administration.
We found that the TPDS was significantly superior to the other approaches at achieving high local-tissue concentrations in the vicinity of the site of application. In addition, comparison of these two carrier systems seems to clarify the different aqueous and hydrophobic pathways of drug penetration which emerge from various experimental findings and theoretical considerations.
Our results suggest that this non-aqueous solvent system, and benzyl alcohol in particular, because of its unique physicochemical and solvating characteristics, might be able to deliver therapeutic levels of indomethacin to tissues close to the site of application in a safer and more effective manner than presently accepted forms of delivery.