bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different Sites of Action for α2-Adrenoceptor Antagonists in the Modulation of Noradrenaline Release and Contraction Response in the Vas Deferens of the Rat
Authors: Harsing L G , Vizi E S 
Published: April 2011

Abstract
Rat vas deferens was prepared, loaded with [3H]noradrenaline, and superfused to measure the release of tritium in resting conditions and in response to electrical field stimulation. The α2-adrenoceptor antagonists yohimbine, CH-38083 (7,8-(methylenedioxi)-14α-hydroxyalloberbane HCl), and idazoxan increased the electrically induced release of tritium in a concentration-dependent manner, whereas noradrenaline and the α2-adrenoceptor agonist xylazine exerted opposite effects. The inhibitory effect of noradrenaline on electrically induced tritium release was antagonized by yohimbine, CH-38083, and idazoxan. Of the α2-adrenoceptor antagonists tested, yohimbine and CH-38083 reversed the xylazine-induced inhibition of tritium release, and idazoxan was found to be completely ineffective against xylazine. Idazoxan, yohimbine and CH-38083 antagonized the inhibitory effect of xylazine on electrical stimulation-induced contractions of the vas deferens, as was evidenced by the apparent pA2 values. We conclude from the present experiments that noradrenaline and xylazine inhibit noradrenaline release by acting on distinct prejunctional α2-adrenoceptors and that the receptor subtype that responds to xylazine is insensitive to idazoxan. In addition, inhibition by xylazine of contractility but not of noradrenaline release was antagonized by idazoxan, suggesting that besides noradrenergic neurotransmission, other motor transmitter systems (purinergic) may also be involved in the inhibition by α2-adrenoceptor antagonists of mechanical responses in the rat vas deferens.
Renal clearance–lipophilicity relationships of some organic acids in rabbits, rats and mice
Authors: Lázníček Milan 
Published: April 2011

Abstract
The effect of lipophilicity on the renal clearance for a group of weak organic acids (benzoic, phenylacetic and hippuric acid derivatives) was studied in rabbits, rats and mice. These compounds are eliminated in the kidney by glomerular filtration and undergo both tubular secretion and tubular reabsorption. For quantification of the effect of lipophilicity, an equation
log(ERPF/CLR − 1) = a + b log D
was employed, where CLR represents renal clearance of the parent drug, ERPF is effective renal plasma flow, D is the partition coefficient of the acids between octanol and water, and a and b are constants. In interspecies comparison, the values of parameters a and b are similar indicating no significant interspecies differences in this route of elimination.
Haemolytic action of N-alkylpolymethylenediamines
Authors: Miyamoto Etsuko , Murata Yoshifumi , Kawashima Susumu , Ueda Michihiro 
Published: April 2011

Abstract
The haemolytic action of various N-alkyl derivatives (lauryl; C12H25-, myristyl; C14H29-, palmityl; C16H33-) of 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane, 1,7-diaminoheptane, 1,8-diaminooctane was examined using rabbit red blood cells. The activities of the various derivatives were compared with those of antiplaque agents commonly used as mouthwashes; cetylpyridinium chloride (CP) and chlorhexidine acetate (CH). The haemolytic activities of these agents were dependent on the length of the N-alkyl chain, whereas the number of methylene groups between the nitrogen atoms had little effect. The order of potency was CP, N-palmityl derivatives, N-myristyl derivatives &gt; N-lauryl derivatives &gt; CH which was similar to the order of the antiplaque effect evaluated in-vitro.
Effects of morphine: an electrophysiological study on guinea-pig papillary muscle
Authors: Alarcón S , Hernández J , Laorden M L 
Published: April 2011

Abstract
Intracellular microelectrodes were used to study the electrophysiological effects of morphine on guinea-pig papillary muscle. Morphine (5 × 10−4 m) caused a significant decrease in the maximum rate of depolarization. At high concentrations (5 × 10−3 m) morphine induced a decrease in the action potential amplitude and a prolongation of the action potential duration. The administration of naloxone (10−7 m) partially antagonized the cardiac electrophysiological effects of morphine. These results suggest that the electrophysiological effects of morphine may be due to an interaction with opioid receptors.
Bile Salt- and Lysophosphatidylcholine-induced Membrane Damage in Human Erythrocytes
Authors: Martin Gary P , El-Hariri Linda M , Marriott Christopher 
Published: April 2011

Abstract
The interaction of bile salts and lysophosphatidylcholine (LPC) with membranes has implications both in understanding the aetiology of a number of gastrointestinal disorders, including gastritis, gastric ulcers and colonic cancer, and in enhancing drug absorption by various epithelia. The membrane toxicity of nine bile salts (the sodium (S) salts of chenodeoxycholate (CDC), deoxycholate (DC) and cholate (C) and their glycine (G) and taurine (T) conjugates) and LPC was determined using erythrocyte haemolysis as a model parameter. Washed human erythrocytes were incubated for 15–60 min at 20°C with media buffered at pH 8, 7 and 6. Bile salt toxicity was shown to be a function of type, concentration, pH and contact time with the membrane. At pH 7 toxicity decreased in the order LPC &gt; unconjugated dihydroxy salts (SDC and SCDC) &gt; conjugated deoxycholates (SGDC and STDC) &gt; conjugated chenodeoxycholates (SGCDC and STCDC) &gt; unconjugated trihydroxy salt (SC) &gt; conjugated trihydroxy salts (SGC and STC). Incubation with equimolar combinations of bile salts (SDC + SCDC; STCDC + SGDC; SDC + STDC) indicated that the resultant damage was an additive function of the damage induced by the individual bile salts.
Adsorption of Paracetamol and Chloroquine Phosphate by Some Antacids
Authors: Iwuagwu M A , Aloko K S 
Published: April 2011

Abstract
The adsorption of paracetamol and chloroquine phosphate onto some antacids with adsorptive properties, has been studied. Dissolution of the drugs from commercial tablets was significantly retarded in the presence of the antacids. The adsorption and retardation of dissolution of both drugs by the adsorbent antacids studied followed the rank order magnesium trisilicate &gt; magnesium oxide &gt; aluminium hydroxide &gt; edible clay. The concomitant administration of the drugs and antacid formulations containing any of these should be discouraged.
Effect of compressional forces on piroxicam polymorphs
Authors: Ghan G A , Lalla J K 
Published: April 2011

Abstract
The effect of compressional force on the polymorphic transition in piroxicam has been examined, using pure polymorph, by differential scanning calorimetery, powder X-ray diffractometry and by determination of dissolution rates from tablets of the individual polymorphs. The needle shaped polymorph was found to undergo transition to the cubic polymorph during compression.
Improvement of Intestinal Absorption of Thyrotropin-releasing Hormone by Chemical Modification with Lauric Acid
Authors: Yamada Keigo , Murakami Masahiro , Yamamoto Akira , Takada Kanji , Muranishi Shozo 
Published: April 2011

Abstract
Intestinal absorption of 125I-labelled lauryl thyrotropin-releasing hormone (Lau-TRH), a novel lipophilic derivative of TRH, was examined by rat in-situ closed intestinal loops. At a dose of 1 μmol per rat into the small intestine, a significant increase in percent of dose in plasma radioactivity of Lau-TRH was observed in comparison with that of TRH. A dose-dependent decrease in percent of dose in plasma radioactivity of TRH was noted, suggesting a saturable process of TRH transport. In contrast, the percent of dose in plasma radioactivity of Lau-TRH increased with increasing dose of Lau-TRH. The stability of TRH and Lau-TRH was studied in plasma and rat small intestinal homogenates. Lau-TRH was more stable than TRH in rat plasma. These results suggest that chemical modification of TRH with lauric acid may not only increase the lipophilicity of TRH but also reduce the degradation of TRH, resulting in the increased plasma radioactivity of TRH. On the other hand, Lau-TRH was gradually converted to TRH in the intestinal mucosal homogenate. These findings indicate that chemical modification of TRH with lauric acid might be a useful approach for improving the intestinal absorption of this peptide.
Relationship Between Paracetamol Plasma Levels and its Analgesic Effect in the Rat
Authors: Granados-Soto Vinicio , Flores-Murrieta Francisco J , López-Muñoz Francisco J , Salazar Luis A , Villarreal Julian E , Castañeda-Hernández Gilberto 
Published: April 2011

Abstract
The relationship between plasma levels of paracetamol and its analgesic effect was studied in the rat using a model of pain-induced functional impairment (PIFI). Female Wistar rats received an intraarticular injection of 30% uric acid in the knee of the right hind limb, inducing its dysfunction. Animals then received oral paracetamol at doses of 178, 316 or 562 mg kg−1and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol plasma levels were determined by HPLC. Results showed that there is a direct relationship between paracetamol plasma levels and its analgesic effect that follows a sigmoidal model according to the Hill equation. The PIFI model appears to be a useful tool to establish pharmacokinetic/pharmacodynamic relationships for non-narcotic analgesics.
Single- and Multiple-dose Pharmacokinetics of Nefiracetam, a New Nootropic Agent, in Healthy Volunteers
Authors: Fujimaki Y , Sudo K , Hakusui H , Tachizawa H , Murasaki M 
Published: April 2011

Abstract
The pharmacokinetic profile of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-l-pyrrolidinyl)acetamide), a new nootropic agent, was studied in healthy Japanese male volunteers. Nefiracetam was administered orally at doses of 10–200 mg in the single-dose studies, and at doses of 200 mg three times a day for seven days in the multiple-dose study. An HPLC method was used to determine the concentrations of nefiracetam in serum, urine and faecal samples. Linear kinetic behaviour was obtained after single oral administration. Serum concentrations of nefiracetam reached maximum values (Cmax) within 2 h for all dosage groups, and declined monophasically after Cmax with half-lives of 3–5 h. The area under the concentration-time curve (ALTC∞) and Cmax were linearly related to the dose. The apparent clearance (CL) values were 94·4–140·3 mL min−1. Urinary excretion of nefiracetam was independent of the administered dose, and less than 10% of the dose was recovered in urine as the unchanged form within 24 h after administration. Renal clearance (CLR) did not change significantly as dose increased from 10 to 1200 mg. Faecal excretion of nefiracetam was less than 0·1% of the dose up to 24 h after a 300 mg oral dose. Food intake delayed the absorption of nefiracetam but did not significantly modify its pharmacokinetics. No clinically significant accumulation of nefiracetam in the body was observed during and after multiple doses.
Dissolution and absorption of caffeine from guarana
Authors: Bempong Daniel K , Houghton Peter J 
Published: April 2011

Abstract
The rate of release of caffeine from capsules of guarana was compared with that from capsules containing an equivalent amount of caffeine using the British Pharmacopoeia dissolution test apparatus. Determinations were carried out in media of pH 2 and 6·8 and caffeine concentrations in the dissolution fluid were determined by HPLC. No significant differences in release rates were found between the two preparations at either pH. The rate of absorption of caffeine across rat intestine using the everted gut was also compared for a guarana suspension and a solution containing an equivalent amount of caffeine. Experiments were carried out using fluids of pH 4·0 and 7·4. No significant differences in absorption between the two preparations were observed. These results show that the release and uptake of caffeine from guarana is the same as for preparations containing free caffeine.
The influence of β-cyclodextrin on the solubility and dissolution rate of paracetamol solid dispersions
Authors: Tasić LJ M , Jovanović M D , Djurić Z R 
Published: April 2011

Abstract
The effect of cyclodextrin (β-CD) on the solubility and dissolution rate of various paracetamol dispersion powders (1:1 w/w), and tablets was studied. Lower solubility was exhibited by a spray dried solid dispersion made from paracetamol-Ethocel-Macrogol 6000 (95:2:3). The improvement in solubility was influenced by complexation with β-CD and the crystalline nature of the powder products made by different procedures. The difference in crystallinity was confirmed by X-ray powder diffraction patterns. The dissolution rate of paracetamol from tablets made from the solid dispersions was satisfactory compared with paracetamol alone. The differences between the dissolution rate from the examined paracetamol tablets resulted from the different solubility of each powder and from the structural changes of particles which influenced the consolidation of the tablet mass.
Salivary excretion of mexiletine after bolus intravenous administration in rats
Authors: Nagasako Sadao , Hayashibara Masakazu , Katagiri Yoshihiro , Iwamoto Kikuo 
Published: April 2011

Abstract
Salivary excretion of mexiletine was investigated following bolus intravenous administration (10 mg kg−1) in rats. Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (3 mg kg−1 h−1). The mexiletine levels in blood plasma and parotid and mandibular saliva declined biexponentially with time in almost parallel fashion. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva. Significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (P &lt; 0·001). The saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large extent (0·56 ± 0·10 for parotid saliva, 0·21 ± 0·06 for mandibular saliva), but there was a consistent tendency for the higher plasma drug levels in the distribution phase to produce relatively high S/P ratios for both parotid and mandibular saliva. Moreover, the plasma mexiletine levels calculated by the equation of Matin et al (1974) employing the observed values for the saliva drug level, saliva pH and free fraction of mexiletine in plasma were significantly higher than the observed drug levels. Therefore, it is suggested that the salivary excretion of mexiletine could not be explained quantitatively by simple, passive secretion based on pH-partition theory.
Torasemide, but not frusemide, increases intracellular cAMP and cGMP content in the aorta of the renal hypertensive rat
Authors: Yamanaga Katsumi , Uchida Takeshi , Kido Hideaki , Hayashi Kazutaka , Watanabe Masahiro 
Published: April 2011

Abstract
Repeated oral administration of the novel loop diuretic torasemide (3 mg kg−1) and frusemide (30 mg kg−1) for 7 days, elicited a significant fall in the systolic blood pressure in the one-kidney, one-clip Goldblatt renal hypertensive rat (RHR). The hypotensive action was greater in the torasemide group than in the frusemide group. Furthermore torasemide increased intracellular cAMP and cGMP content in aorta of RHR. Frusemide caused no effect. It is hypothesized that the increase in adenosine- or guanosine-nucleotides is involved in the antihypertensive action of torasemide, but not in that of frusemide.
Locomotor effects of nitrous oxide in mice: requirement of newly-synthesized and main intraneuronal storage pools of dopamine
Authors: Dorris Roy L , Truong Vi 
Published: April 2011

Abstract
Nitrous oxide increases locomotor activity in mice. Other locomotor stimulants are thought to act via central dopaminergic mechanisms and can be divided into two groups as determined by their antagonism by tyrosine hydroxylase inhibitors or by reserpine pretreatment. The purpose of the present study was to determine if nitrous oxide fits one or the other of the groups. Mice were acclimatized for 1 h to exposure chambers (4 L filtration flasks), in air, delivered at 4 L min−1 and then exposed to N2O:O2 (50:50), also delivered at 4 L min−1. Locomotor activity was evaluated at 10 min intervals throughout the experiment. Racemic α-methyltyrosine methyl ester HCl (200 mg kg−1), administered at the beginning of acclimatization, almost totally eliminated the nitrous oxide effect but not that of methylphenidate HCl (20 mg kg−1). Reserpine pretreatment (5 mg kg−1 18 h) totally eliminated the nitrous oxide effect but not that of amphetamine (5 mg kg−1). The results suggest that nitrous oxide requires both the newly synthesized and the main storage pools of dopamine and do not allow assignment of the agent, specifically, to either of the groups.
Effect of Environmental Humidity on the Transformation Pathway of Nitrofurantoin Modifications During Grinding and the Physicochemical Properties of Ground Products
Authors: Otsuka Makoto , Matsuda Yoshihisa 
Published: April 2011

Abstract
The effect of humidity on the physicochemical properties of nitrofurantoin anhydrate and monohydrate during grinding in a humidity-controlled system was investigated using X-ray diffraction analysis, IR spectroscopy, thermal analysis and scanning electron microscopy. Anhydrate and monohydrate were transformed into a noncrystalline solid and a stable monohydrate, respectively, during grinding in a closed system. During grinding in an open system, in which the humidity level of the air was controlled (5, 50 and 75% r.h.), the anhydrate absorbed moisture from the supplied air and water content was increased at 75% r.h.; thereafter the compound was transformed into monohydrate II. The anhydrate did not absorb at 5 or 50% r.h. and was transformed into a noncrystalline solid. Monohydrate I desorbed crystal water during grinding at 5% r.h. and was transformed into a noncrystalline solid. However, monohydrate I was transformed into monohydrate II at 50 and 75% r.h. without desorption of crystal water. These results suggest that the solid-state transformation of nitrofurantoin during grinding depends upon the environmental humidity.
The Transport Mechanism of an Organic Cation, Disopyramide, by Brush-border Membranes. Comparison Between Renal Cortex and Small Intestine of the Rat
Authors: Takahashi Yasushi , Itoh Tatsuya , Kobayashi Michiya , Sugawara Mitsuru , Saitoh Hiroshi , Iseki Ken , Miyazaki Katsumi , Miyazaki Shozo , Takada Masahiko , Kawashima Yoshiaki 
Published: April 2011

Abstract
The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H+ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H+ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H+ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (Km and Vmax of 680 μm and 1·25 nmol (mg protein)−1/30 s, respectively). The stimulation of disopyramide uptake by an outward H+ gradient in rat intestinal brush-border membrane was due to an interior negative H+-diffusion potential. A K+-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.
In-vivo Binding of (+)-[3H]PN 200–110 to Peripheral Tissues and Brain of Spontaneously Hypertensive Rats: Effect of Lacidipine
Authors: Mennini T , Taddei C , Uslenghi A , Cagnotto A , Micheli D , Trist D , Gaviraghi G , Ratti E 
Published: April 2011

Abstract
The time-course of dihydropyridine receptor occupancy by lacidipine and its relationship with pharmacological activity has been studied in spontaneously hypertensive rat (SHR), as measured by the inhibition of specific (+)-[3H]PN 200–110 binding in-vivo. After oral administration of doses active in reducing blood pressure, lacidipine did not show tissue target differences in respect to binding sites labelled by (+)-[3H]PN 200–110 in cerebral cortex, heart, ileum, bladder and thoracic aorta. The relative occupancy of receptors in heart 60 min after oral administration of 1 mg kg−1 lacidipine was 75%. After 12 h, when lacidipine was still effective in reducing blood pressure in SHR, a low (15%) but detectable proportion of receptors was still occupied by the drug. The percentage decrease of blood pressure was linear with the percentage of receptor occupancy obtained by different doses of lacidipine; that is, there was a close correspondence between ED25 for decrease in blood pressure (0·33 mg kg−1) and ED25 for inhibition of (+)-[3H]PN 200–110 specific binding in the heart (0·36 mg kg−1). The long-lasting effect of lacidipine on blood pressure might be explained by its selective interaction with dihydropyridine binding sites labelled in-vivo by (+)-[3H]PN 200–110.
Influence of the sterilization process on alginate dispersions
Authors: Vandenbossche Geert M R , Remon Jean-Paul 
Published: April 2011

Abstract
The influence of different sterilization procedures on alginate dispersions was studied by measuring viscosity and molecular weight changes. Autoclaving caused a 64% decrease in viscosity. Heating at a low temperature over several cycles was less efficient in sterilizing alginates and there was a progressive breakdown of the alginate chain over the succeeding cycles. Heating during ethylene oxide sterilization also resulted in reduced viscosity and breakdown. Membrane filtration yielded a sterile product with no significant reduction in viscosity or mol. wt.
Role of Polymorphonuclear Leucocytes and Oxygen-derived Free Radicals in the Formation of Gastric Lesions Induced by HCl/ethanol, and a Possible Mechanism of Protection by Anti-ulcer Polysaccharide
Authors: Matsumoto T , Moriguchi R , Yamada H 
Published: April 2011

Abstract
This study examined the role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions induced by HCl/ethanol. Superoxide dismutase, and catalase, and their combination reduced gastric lesion formation in mice. Gastric lesions were also reduced in mice treated with cyclophosphamide or anti-neutrophils, but not in mice treated with allopurinol or desulphated-carrageenan. Cobra venom factor did not reduce lesion formation. These results suggested that oxygen-free radicals may contribute to the formation of gastric mucosal lesions induced by HCl/ethanol, and that oxygen radicals were generated from neutrophils but not from xanthine oxidase. Anti-ulcer pectic polysaccharide, bupleuran 2IIc, which was recently isolated from the roots of Bupleurum falcatum L., showed potent inhibition of HCl/ethanol-induced gastric lesions in mice. Bupleuran 2IIc seemed to scavenge hydroxyl radical effectively. It was suggested that this anti-ulcer polysaccharide may provide protection to the gastric mucosa by scavenging oxygen-free radicals.