bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Albumin Binding of Tamoxifen in the Presence of a Perfluorochemical Erythrocyte Substitute
Authors: Shah I G , Parsons D L 
Published: April 2011

Abstract
The binding of tamoxifen (an HSA site IV ligand) to human serum albumin (HSA) in the presence of a perfluorochemical (PFC) erythrocyte substitute has been examined. Standard centrifugation followed by supernatant ultrafiltration was used to study the binding of 0·1 and 0·5 μg mL−1 tamoxifen at ambient conditions. Tamoxifen was extensively bound (&gt;99%) to the PFC emulsion through an association with the emulsifiers of the droplets. Tamoxifen was also extensively bound (&gt; 99%) to HSA. The percent free tamoxifen increased upon HSA dilution. Tamoxifen was extensively bound by various mixtures of HSA and the PFC emulsion and the percent free drug was similar to those obtained with HSA alone. However, the position of drug binding (PFC emulsion vs HSA) varied significantly with changes in the ratio of PFC emulsion to HSA. This could be important in terms of the different distribution of HSA and PFC emulsion in the body. Studies with PFC emulsion components indicated that any displacement of HSA-bound tamoxifen by the PFC emulsion was due to the oleic acid and, to a much smaller degree, Pluronic F-68 components. Other HSA site IV ligands are expected to be similarly displaced.
Influence of Ion-pair Formation on the Pharmacokinetic Properties of Drugs. Pharmacokinetic Interactions of Bretylium and Hexylsalicylic Acid in Rabbits
Authors: Amlacher Reinhard , Härtl Albert , Neubert Reinhard , Stöckel Ursula , Wenzel Kerstin 
Published: April 2011

Abstract
The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.
Ulcerogenic Mechanism of Ethanol and the Action of Sulphanilyl Fluoride on the Rat Stomach In-vivo
Authors: Cho C H , Pfeiffer C J , Misra H P 
Published: April 2011

Abstract
The effects of ethanol alone and in combination with sulphanilyl fluoride on some of the antioxidant defences in the stomach of rats have been examined. These effects were correlated with lesion formation in the gastric mucosa. Oral administration of ethanol induced gastric lesions which were prevented by sulphanilyl fluoride pre-treatment. N-Ethylmaleimide antagonized the anti-lesion action of sulphanilyl fluoride. Ethanol administration lowered the glucose-6-phosphate dehydrogenase activity in the gastric mucosa, an effect potentiated by N-ethylmaleimide pre-treatment. The total superoxide dismutase activity was unaffected by the drugs used in the present study. Ethanol, however, markedly increased mucosal catalase activity which was reduced by sulphanilyl fluoride pretreatment and reversed by N-ethylmaleimide. It is concluded that the ulcerogenic mechanism of ethanol is mediated at least in part by the depression of the hexose monophosphate shunt and the production of active oxygen species, whereas the anti-lesion action of sulphanilyl fluoride is probably not mediated through these mechanisms.
One-point Feedback Control Method for Phenytoin Dosage Adjustment
Authors: Yukawa Eiji , Higuchi Shun , Aoyama Toshinobu 
Published: April 2011

Abstract
Routine clinical pharmacokinetic data collected from patients receiving phenytoin have been analysed to propose a new and simple equation to aid the dosage adjustment of this drug. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The rate equation for the elimination of phenytoin can be written as Do = kCssn, which fits the steady-state serum concentration (Css) and daily dose data (Do). The parameter n is the kinetic order and the parameter k is an arbitrary rate constant. From the above equation, D2 = D1C1 −nC2n can be derived, which forms the basis of predicting the dosage, D2, to obtain a desired Css, Q2, using one initial Css, C1, obtained with an initial dose, D1 and using a population value of n. The value of n for phenytoin was estimated to be 0·312 in this study. The predictive performance of this equation was compared with the Richens and Dunlop nomogram and Bayesian feedback method using two or more steady-state concentration/dose pairs from each of 78 outpatients. This equation allowed the prediction of a dose needed to produce a desired steady-state concentration with errors comparable with the Bayesian feedback method for therapeutic drug monitoring.
Effect of Crude Extracts from Leonotis nepetaefolia (Labiatae) on Rat and Guinea-pig Smooth Muscle and Rat Cardiac Muscle
Authors: Calixto João B , Yunes Rosendo A , Rae Giles A 
Published: April 2011

Abstract
The actions of hydroalcoholic and tea extracts of stems of Leonotis nepetaefolia on agonist-induced and electrically-evoked contractions have been analysed in-vitro in rat uterus and left atrium and in guinea-pig ileum and trachea. The tea extract (500–2000 μg mL−1) caused parallel and graded rightward shifts of concentration-response curves to bradykinin and BaCl2 in the rat isolated uterus, but antagonized responses to prostaglandin F2α in a typically non-competitive manner. The hydroalcoholic extract also caused rightward displacements of the curves to bradykinin, acetylcholine (ACh), angiotensin II, oxytocin and BaCl2 and reduced their maximal contractile effects. Both extracts (30–3000 μg mL−1) relaxed uterine preparations precontracted with KCl (80 Mm), the hydroalcoholic extract being about 2-fold more potent than the tea extract. The relaxant response to the former was unaffected by propranolol (1 μm) or forskolin (10 Nm), but was potentiated 2-fold by 3-isobutyl-1-methylxanthine (10 μm). In the guinea-pig ileum the hydroalcohplic extract shifted the ACh- and bradykinin-induced contractile curves to the right and markedly inhibited their maximal effects, whereas the tea extract caused a typical non-competitive antagonism of ACh-induced contractile responses. In field-stimulated ileal strips, both extracts (3–3000 μg mL−1) caused contractions and inhibited twitch responses. Guinea-pig tracheal rings precontracted with carbachol (0·3 μm) were relaxed only by concentrations of either extract in excess of 1000 μg mL−1, an action that was unaffected by propranolol (0·1 μm) or by indomethacin (1 μm). Prior incubation of tracheal rings with the hydroalcoholic extract (1000 μg mL−1), which failed to affect responses to ACh, significantly potentiated the relaxations induced by isoprenaline or theophylline (3-fold) of preparations contracted with carbachol. Finally, the hydroalcoholic extract (0·1–1000 μg mL−1) caused a graded long-lasting inotropic effect in the rat electrically-stimulated left atrium. Altogether, these findings provide some experimental support for the reputed folk medicinal anti-asthmatic and anti-diarrhoeal properties of this plant. It is suggested that the pharmacological effects of the extracts of L. nepetaefolia may result from potentiation of the cAMP system.
Protective Effect of Cimetidine on Tannic Acid-induced Gastric Damage in Rats
Authors: Hung Chen-Road , Lee Chau-Hwei 
Published: April 2011

Abstract
The effect of cimetidine on the acidified tannic acid-induced back diffusion of gastric acid and mucosal damage was investigated in the vagotomized rat. After intragastric irrigation for 1 to 3 h, tannic acid (20–500 mg kg−1) produced a dose-related increase in gastric volume and the loss of luminal H+. The change of mucosal permeability to the electrolyte, either the loss of H+ or the gain of Na+, K+, and Ca2+, induced by tannic acid was significantly diminished by the combination with intragastric cimetidine. However, intravenous injection of cimetidine did not protect this damage and back diffusion of acid neutralized intragastric cimetidine did not reduce the back diffusion of acid and Na+, K+, and Ca2+ output provoked by acid solution. Thus, the neutralizing action of cimetidine seems responsible.
Cepharanthine (biscoclaurine alkaloid) treatment in endotoxic shock of suckling rats
Authors: Goto Masakatsu , Zeller W Patrick , Hurley R Morrison 
Published: April 2011

Abstract
Gram-negative sepsis/septic shock causes significant mortality in newborns. However, there has been no established method for newborn endotoxic shock treatment. Prostaglandins play a role in endotoxic shock. Cepharanthine is a biscoclaurine alkaloid that primarily inhibits phospholipase A2. Therefore, the effects of cepharanthine have been studied on endotoxic shock in newborn rats. Cepharanthine decreased the 24 h mortality of endotoxic shock in a dose-related manner. At the dose of 0·2 mg kg−1 it effectively reduced the mortality from 90 to 21 % in newborn rats. It also induced hyperglycaemia in control rats and blunted the hypoglycaemia of endotoxic shock. Cepharanthine did not suppress body weight gain nor did it delay death as seen with glucocorticoid treatment. We conclude that cepharanthine is beneficial in the treatment of newborn endotoxic shock.
The effect of dihydropyridine calcium channel agents on 5-HT metabolism in the CNS of the rat
Authors: Colado M I , Alfaro M J , López F , Del Val V , Martín M I 
Published: April 2011

Abstract
The effects of dihydropyridines on the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indole acetic acid (5-HIAA) in the spinal cord and various brain regions of the rat have been studied. Nimodipine, nitrendipine and nifedipine (10 mg kg−1), nisoldipine (5 mg kg−1), and BAY K8644 (0–2 and 2 mg kg−1) were administered i.p. 1 h before killing. The administration of nifedipine and nitrendipine increased 5-HT turnover in all of the areas studied except for the spinal cord. Nisoldipine increased 5-HT turnover in midbrain, hippocampus and cortex, while the effect of nimodipine was restricted to midbrain. BAY K8644 at 2 mg kg−1 produced the same effects as nifedipine and nitrendipine; however, at low doses (0·2 mg kg−1), this compound increased 5-HT turnover only in midbrain and medulla oblongata. These results indicate that both dihydropyridine calcium channel agonist and antagonists are able to activate the 5-HT-ergic system in the central nervous system of the rat in-vivo. Therefore, it seems likely that such effects could be due to indirect actions or to interactions of the compounds with receptors other than the voltage-sensitive calcium channels.
Effects of khellin on contractile responses and 45Ca2+ movements in rat isolated aorta
Authors: Ubeda Amalia , Tejerina Teresa , Tamargo Juan , Villar Angel 
Published: April 2011

Abstract
The effects of khellin on contractile responses and 45Ca2+ flux have been studied in rat isolated aortae. Khellin (10−5- 3.2 times 10−4M) produced a concentration-dependent inhibition of noradrenaline (10−6 M) and high K+ (80 mM)-induced contractions. At 3.2 times 10−4 M, khellin increased cAMP levels and reduced 45Ca2+ influx in resting tissues and in tissues stimulated by noradrenaline (10−5 M) and high K+ without affecting basal 45Ca2+ efflux or noradrenaline induced 45Ca2+ efflux. It is concluded that in rat isolated aorta, khellin caused a non-specific inhibition of Ca2+ influx but may also exhibit intracellular actions, thus decreasing the availability of Ca2+ required for activation. One or more of these mechanisms may be related to an increase in intracellular cAMP levels.
Solid tumour chemotherapy using implantable collagen-poly (HEMA) hydrogel containing 5-fluorouracil
Authors: Jeyanthi R , Nagarajan B , Panduranga Rao K 
Published: April 2011

Abstract
Implantable collagen-poly(HEMA) hydrogels containing the anticancer drug 5-fluorouracil (5-FU) have been prepared and evaluated for their efficacy towards a solid tumour fibrosarcoma in Wistar rats. The tumour was developed by inoculation of a 10% tumour-cell suspension in the anterior aspect of the hind limb. Four groups were studied—untreated control, intratumoural injection of free 5-FU, subcutaneous implantation of placebo and implantation of 5-FU-bearing hydrogel pellets (10 mm diameter × 1 mm thick) containing the drug in close proximity to the tumour. The hydrogel showed an improved antitumour activity over free 5-FU as evidenced by the gross tumour weight assessments and by [3H]thymidine incorporation in-vitro. This was attributed to the controlled and slow release of 5-FU compared with free 5-FU over the same period of treatment. The implantation of hydrogel could thus be a potential alternative to free 5-FU therapy in the treatment of solid tumours such as fibrosarcoma.
Duration of action and effect on baroreflex function of the anti-arrhythmic α1 antagonist UK-52,046
Authors: Spiers James P , Harron Dean W G , Wilson Richard 
Published: April 2011

Abstract
The effects of acute and chronic oral administration of UK-52,046 (25 μg kg−1) on baroreflex function and its duration of action, were studied in conscious dogs. It was found that UK-52,046 had no effect on blood pressure and heart rate following acute and chronic administration. UK-52,046 shifted the phenylephrine dose response curve to the right, and the PE50 (measure of α1-adrenoceptor antagonism) was increased (P &lt; 0.05) compared to placebo on day 1 (2, 4, 8 and 24 h) and day 8 (2, 4, 8 and 12 h). The antagonism was increased (P &lt; 0.05) on day 8 (0,8 and 12 h) compared with day 1. Evaluation of the effects of UK-52,046 on baroreflex function using phenylephrine to increase blood pressure indicated no significant difference from placebo. It was concluded that at an antiarrhythmic dose, UK-52,046 has no effect on blood pressure, heart rate or baroreflex function. The pressor response curve was shifted to the right indicating a duration of action of at least 12 h on chronic oral administration.
Effects of Temperature and Pressure During Compression on Polymorphic Transformation and Crushing Strength of Chlorpropamide Tablets
Authors: Matsumoto Takahiro , Kaneniwa Nobuyoshi , Higuchi Shigesada , Otsuka Makoto 
Published: April 2011

Abstract
The effects of temperature on the polymorphic transformation of chlorpropamide during compression and on the physical properties of the tablet have been investigated. A heater and liquid nitrogen pool were mounted on the die of a single punch eccentric tableting machine, and the die temperature was controlled by a thermocontroller. A tableting machine with two load cells (upper and lower punches) and a non-contact displacement transducer were used to measure compression stress, distance and energy. The X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The amount of form C transformed from form A at 45°C was about twice that at 0°C with the same compression energy. The amount of form A transformed from form C by compression at 45°C was almost the same as that at 0°C. This suggests that the mechanochemical effect of form A depended on the compression temperature, but that of form C was independent of temperature. The crushing strength of tablets of form A was about twice that of form C, even at the same porosity. The plots of log (crushing strength of tablet) against porosity of form A tablets compressed at 0 and 45°C were linear with the same slope; the slope for form C tablets compressed at 45°C was less than that at 0°C.
Dissolution and relative bioavailability of two carbamazepine preparations for children with epilepsy
Authors: Hartley R , Aleksandrowicz J , Bowmer C J , Cawood A , Forsythe W I 
Published: April 2011

Abstract
The in-vitro dissolution profiles of two carbamazepine formulations (Tegretol and a generic carbamazepine) have been assessed and the bioavailability of carbamazepine compared in 12 epileptic children at steady-state. Dissolution from the generic formulation (100 and 200 mg tablets) tended to be greater than for the proprietary tablets. However, the bioavailability and pharmacokinetics of carbamazepine when assessed at steady-state were similar for the two formulations. It appears, therefore, that the breakthrough seizures and higher incidence of neurological side-effects observed when children were given generic carbamazepine in place of the proprietary formulation cannot be accounted for by differences in bioavailability or pharmacokinetics.
Inhibition of contractions and 45Ca influx by adenosine in rabbit aorta
Authors: Parija S C , Raviprakash V , Mishra S K 
Published: April 2011

Abstract
The effects of adenosine on contractility and 45Ca-uptake in rabbit aorta have been examined and compared with those of nifedipine. Both adenosine (10−5 M) and nifedipine (10−8 M) inhibited contractions caused by CaCl2 (0.1–10 mM) in K+-depolarized preparations. Nifedipine (10−7 M) significantly inhibited the contractions of noradrenaline (NA) at all doses (10−8-10−4 M), while adenosine inhibited the contractions induced only by lower doses of NA (10−8 and 10−7 M) without affecting those at higher doses (&gt; 10−7 M). Adenosine (10−8 M) and nifedipine (10−7 M) inhibited K+-stimulated 45Ca-uptake by aortic strips by 75 and 100%, respectively. Similarly, NA (10−4 M)-stimulated 45Ca influx was inhibited by about 70% by both these agents. The results suggest that adenosine inhibits inward Ca2+ movement involving both voltage-operated and receptor-operated calcium channels in rabbit aortic smooth muscle.
Opioid Properties of Some Derivatives of Pethidine Based on Tropane
Authors: Casy A F , Dewar G H , Pascoe R A 
Published: April 2011

Abstract
The preparation of some tropane analogues of pethidine and its reversed ester, chiefly with preferred 3α-m-hydroxyphenyl chair conformations, is described. The former were secured from tropan-3-one in a sequence of reactions involving cyanide attack, hydrolysis, Grignard attack and then rearrangements. The reversed ester was obtained by treating tropan-3-one with lithium phenyl, followed by acylation. Configurational and conformational assignments follow from NMR analysis. The antinociceptive potencies of these compounds in mice are reported, and discussed in relation to non-phenolic congeners and the 4-arylpiperidine moiety of morphine.
Comparison of the Effects of Cromakalim in Trachea Isolated from Normal and Albumin-sensitive Guinea-pigs
Authors: McCaig Dorothy J , Aitken Susan , De Jonckheere B 
Published: April 2011

Abstract
The effects of the K+-channel activator, cromakalim, on spontaneous tone and constrictor responses to vagal stimulation or acetylcholine were compared in trachea isolated from groups of guinea-pigs that were: untreated; sensitized and chronically exposed to inhaled albumin; or sham sensitized. Responses were assessed as changes in intraluminal pressure in the isolated, Krebs-filled trachea, increases and decreases in intraluminal pressure directly reflecting constriction and dilatation, respectively. Cromakalim reduced resting intraluminal pressure in normal trachea but in sensitized trachea mixed effects occurred, many preparations exhibiting increases in intraluminal pressure, particularly at lower concentrations of cromakalim. Cromakalim attenuated the frequency-dependent increases in intraluminal pressure evoked by stimulation of the vagus nerve in a concentration-dependent manner and to a similar degree in trachea from each of the three groups tested. The degree of attenuation was similar in the absence and presence of the cyclo-oxygenase inhibitor flurbiprofen. In untreated trachea, responses to a range of concentrations of applied acetylcholine were attenuated by cromakalim. In sensitized trachea the response to the lowest concentration of applied acetylcholine was attenuated by cromakalim but responses to higher concentrations of were unaffected. The results indicate that the direct relaxant effect of cromakalim is altered in sensitized trachea, which may indicate abnormal K+-channel behaviour in the smooth muscle cell membrane. Attenuation by cromakalim of vagal responses occurs in both normal and sensitized trachea, due chiefly to a pre-junctional effect on cholinergic neurotransmission which is independent of the generation of cyclo-oxygenase products.
The Interaction between Noradrenaline and ATP upon Polyphosphoinositide Metabolism and Contraction in Tail Arteries from Normo- and Hypertensive Rats
Authors: Guild S B , Jenkinson S , Muir T C 
Published: April 2011

Abstract
The effects of, and interaction between, noradrenaline and α,β-methylene ATP upon polyphosphoinositide (PPI) breakdown, investigated by measuring the accumulation of inositol phosphates, and contraction, were studied in tail arteries from normo- (WKY) and spontaneously-hypertensive (SHR) rats. Noradrenaline (10−7-10−3 m) evoked a prazosin (10−6 m)-sensitive, concentration-dependent increase in total inositol phosphate accumulation in both WKY and SHR rats. No significant differences were observed in either the maximal response or in the concentration range over which noradrenaline evoked this response, between these two populations. Noradrenaline (5 × 10−7-5 × 10−5 m) evoked a concentration-dependent contraction of arteries from both SHR and WKY rats. The responses to noradrenaline were about 2-fold greater at all effective concentrations of noradrenaline in SHR compared with WKY rats. α,β-Methylene ATP (10−6 m) did not alter noradrenaline-stimulated total inositol phosphate accumulation, in arteries from either SHR or WKY rats, measured either as the maximal response or as the EC50. α,β-Methylene ATP (5 × 10−6m), by itself, evoked a contractile response, which was quantitatively similar in SHR and WKY rats, and was additive with the contractile responses to noradrenaline (5 × 10−7–5 × 10−5 m). The maximum response produced by a combination of noradrenaline and α,β-Methylene ATP was quantitatively similar to that produced by noradrenaline alone. No evidence of synergism between α,β-Methylene ATP and noradrenaline upon contraction was observed. Nerve stimulation (50 V, 16 Hz, 0·5 ms for 5 min) evoked a prazosin (10−6 m)-sensitive significant (P &lt; 0·001) increase in total inositol phosphate accumulation in arteries from WKY rats. α,β-Methylene ATP did not modulate noradrenaline-elicited increases in either contraction or PPI metabolism in either SHR or WKY rats. The postsynaptic modifications responsible for the previously reported enhanced contraction to sympathetic nerve stimulation in this tissue are not due to changes in purinergic influence upon either noradrenaline-stimulated PPI metabolism or upon contraction.
Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers
Authors: Mori Kazuo , Asakura Shunji , Morikawa Norifumi , Takeyama Masaharu 
Published: April 2011

Abstract
The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference.