bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Enzyme-linked Immunosorbent Assays to Study the Plasma Disposition of Sheep Polyclonal and Rat Monoclonal Digoxin-specific Fab Fragments in the Rabbit
Authors: Timsina M P , Hewick D S 
Published: April 2011

Abstract
The plasma disposition of sheep polyclonal digoxin-specific Fab (fragment antigen-binding) fragments has been studied in rabbits after their intravenous injection (1 mg kg−1) using enzyme-linked immunosorbent assays exploiting both the species-specificity (ELISAi) and the digoxin-specificity (ELISA2) of digoxin-specific Fab fragments. The log concentration versus time profiles were best described by a biexponential plasma disposition when either assay was used. Although the plasma concentrations determined by ELISA, and ELISA2 at each sampling time were not significantly different, there was a tendency for certain ELISA2 values to be higher. This resulted in the ELISA2-derived data giving a significantly longer distribution half-life (t 1/2α), but similar values for elimination half-life (t 1/2β), apparent volume of distribution at steady state (Vdss), and clearance. Using ELISA2, which was generally the more sensitive assay, to compare the plasma disposition of the sheep polyclonal digoxin-specific Fab fragments with rat monoclonal digoxin-specific Fab fragments, it was shown that the rat product had a shorter t 1/2α (11 vs 22 min), a t 1/2β which was not significantly different (253 vs 168 min), but a faster clearance (1.2 vs 0.7 mL kg−1 min−1), associated with a much larger Vdss (321 vs 108 mL kg−1). The extracellular fluid volume, using thiocyanate as a marker, was about 216 mL kg−1 for the nine rabbits used. This suggests that the rat preparation penetrates more extensively into the extracellular space and may indicate that some degree of extracellular binding or cell penetration is occurring.
The importance of nucleus accumbens in nicotine-induced locomotor activity
Authors: Fung Yiu K 
Published: April 2011

Abstract
Bilateral injections of either nicotine (200 μg) or cytisine (30 or 60 μg) into the nucleus accumbens elicited locomotor hyperactivity in rats. Pretreatment with mecamylamine (2 mg kg−1, s.c.) was effective in attenuating the stimulatory effect of either nicotine or cytisine. This study suggests that nicotinic agonists such as nicotine and cytisine produce their locomotor excitatory effects through stimulation of the mesolimbic dopaminergic pathway.
Release of Chlorpheniramine Maleate from Fatty Acid Ester Matrix Disks Prepared by Melt-extrusion
Authors: Prapaitrakul W , Sprockel O L , Shivanand P 
Published: April 2011

Abstract
Chlorpheniramine maleate was incorporated into disks consisting of glyceryl fatty acid esters, polyethylene glycol fatty acid esters or a combination of the two. A melt-extrusion process was used to prepare the matrix disks containing the drug. The release of the drug into distilled water, pH 1·2 buffer, and pH 7·5 buffer showed the expected square root of time dependence. An increase in the fatty acid ester hydrophilic-lipophilic balance (HLB) from 1 to 14 resulted in a 10-fold increase in the drug release rate from 0·25 ± 0·01 to 25·84 ± 1·29 mg cm−2 h−½ The maximum release rate was seen from the fatty acid ester with a melting point of 44°C. The pH of the dissolution medium had a small impact on the rate of drug release, but the rate of agitation had no significant influence on the rate of drug release. By blending a fatty acid ester of a high melting point (64°C) and a low HLB value of 2 with esters of lower melting points (33 to 50°C) or higher HLB values (10 to 14), it was possible to modify the release from 10·0 ± 0·70 to 21·5 ± 0·57 mg cm−2 h−½
Absorption of Iron from Iron Succinyl-protein Complexes by Mouse Small Intestine
Authors: Simpson R J , Raja K B , Peruzzi M , Cremonesi P 
Published: April 2011

Abstract
The absorption of iron from iron succinyl-protein complexes was investigated in mice. 59Felabelled succinyl-casein and -albumin complexes, [59Fe]ferritin and 59FeSO4, at doses of 20 or 200 μg of iron, were administered orally to normal mice or mice with absorption enhanced by chronic hypoxia. 59Fe from iron succinyl-protein was well absorbed in normal mice (&gt; 10% of dose) and showed enhanced absorption in hypoxic mice (&gt; 40% of dose). Intestinal uptake was predominantly by the duodenum for all compounds studied. In-vivo absorption of 59Fe from an iron succinyl-protein complex was studied using tied-off segments of mouse duodenum, jejunum or ileum of normal or hypoxic mice. Incubation for up to 15 min in duodenum or 60 min in ileum showed very little absorption of 59Fe. No enhancement of absorption was seen in hypoxic mice. It was concluded that absorption of the intact iron succinyl-protein complex cannot explain absorption seen after oral dosing.
Role of the Endothelium and Smooth Muscle Tone in the Dilator Response of the Rabbit Coeliac Artery to Histamine
Authors: Tayo ‘Fola 
Published: April 2011

Abstract
The role of the endothelium and vascular tone was studied on histamine-induced relaxation and contraction of the rabbit coeliac artery. Histamine contracted the tissue via the release of noradrenaline (NA), an action blocked by prazosin and mepyramine but not influenced by endothelial removal. Tachyphylaxis readily developed to histamine-induced contractions. After a moderate tone (40–55%) was induced with NA, histamine relaxed the tissues concentration-dependently. This relaxation was absent when the endothelium was removed indicating that the receptors involved are located on the endothelium. When the tone was increased to 80–85% with NA, relaxation could only be demonstrated after blocking H1-receptors. Removal of the endothelium did not influence this response. The relaxant effect of histamine in both preparations, however, was blocked by metiamide indicating that it is H2-receptor mediated. In the rabbit coeliac artery, endothelial H2-receptors are readily activated at moderate tone while muscular H2-receptors are stimulated at high tone after blocking H1-receptors. The predominance of H2-receptors in this artery may serve the physiological function of vasodilation in the blood vessels of the stomach.
The Effect of Nifedipine Alone or Combined with Cytotoxic Chemotherapy on the Mouse NC Carcinoma In-vitro and In-vivo
Authors: Gaffen J D , Stamford I F , Chambers E , Tavares I A , Bennett A 
Published: April 2011

Abstract
Effects of the calcium antagonist nifedipine on the response of the murine NC carcinoma has been examined alone and together with cytotoxic chemotherapy in-vitro and in-vivo. The cytotoxic drug combination of methotrexate and melphalan, or nifedipine alone (0·2–25 μg mL−1), caused a concentration-related reduction of NC cell growth in culture. At the lower concentrations, combination of the cytotoxic drugs with nifedipine resulted in an addition of the separate drug effects, but with drug concentrations that on their own approached maximal effectiveness the combined response was less than additive. NC tumours were excised from mice 14 days after inoculation s.c. with NC cells, weighed, and extracted for prostanoids. Mouse survival was determined up to day 121, and cancer spread was recorded postmortem. Nifedipine 1, 5 or 10 mg kg−1 had little or no effect on the tumour weight, tumour prostanoid content, metastasis to the lymph nodes or lungs, or on the increase of mouse longevity by the cytotoxic drugs.
Characterization of the variation between batches of Fast-Flo lactose using low frequency dielectric spectroscopy
Authors: Craig Duncan Q M , Davies Carole F , Boyd James C , Hakes Linda B 
Published: April 2011

Abstract
The dielectric response of four batches of lactose has been measured over a frequency range of 104 to 10−2 Hz. The spectra corresponding to three of the batches were identical, while the fourth showed a marked reduction in response. This particular batch has also been reported to exhibit longer disintegration times than the other three when formulated as a tablet. The potential use of dielectric spectroscopy as a means of screening batches of pharmaceutical materials is discussed.
Sulphate conjugation enhances reversible binding of drug to human serum albumin
Authors: Mizuma Takashi , Komori Michiyo , Ueno Masaharu , Horikoshi Isamu 
Published: April 2011

Abstract
Reversible binding of model compounds, their conjugated metabolites (sulphates and glucuronides), and also derivatives of the compounds, to human serum albumin (HSA) has been examined using an ultrafiltration method. p-Nitrophenol (P-NP), α-naphthol (α-NA) and β-naphthol (β-NA) were used as model compounds. Reversible binding of 500 μm p-NP sulphate to 4% HSA (96·6 ± 0·35%, mean ± s.d. n = 3) was significantly higher (P &lt; 0·001), whereas reversible binding of p-NP glucuronide to 4% HSA (33·3 ± 9·82%) was much lower (P &lt; 0·001) than that of 500 μm p-NP (90·9 ± 0·60%). Reversible binding of 500 μm p-NP glucopyranoside to 4% HSA (25·8 ±2·82%) was comparable with that of the glucuronide, with which it is structurally similar. In contrast, reversible binding of 500 μm p-NP phosphate, an anionic compound like p-NP sulphate, to 4% HSA (61·4 ± 5·28%) was significantly lower than that of p-NP (P &lt; 0·001). Similar results were observed in reversible binding of sulphates of α-NA and β-NA. Significant differences of dissociation constants for HSA binding were observed between the parent compound (α- or β-NA) and its sulphate conjugate (P &lt; 0·005 for α-NA and α-NA sulphate, P &lt; 0·001 for β-NA and β-NA sulphate), but the number of binding sites was the same. These results indicated that sulphate conjugation enhances reversible binding of a parent compound to HSA by increasing the binding affinity of the parent compound to HSA. This enhancement appeared to be advantageous for preventing random distribution of this metabolite to organs in the body.
Inhibition of Dapsone-Induced Methaemoglobinaemia by Cimetidine in the Rat During Chronic Dapsone Administration
Authors: Coleman M D , Tingle M D , Park B K 
Published: April 2011

Abstract
Dapsone undergoes N-acetylation to monoacetyl dapsone as well as N-hydroxylation to a hydroxylamine which is responsible for the haemotoxicity (i.e. methaemoglobinaemia; Met Hb) of the drug. Since dapsone is always given chronically, we have investigated the ability of cimetidine to inhibit Met Hb formation caused by repeated dapsone administration. The drug was given (i.p.) to four groups (n = 6 per group) of male Wistar rats, 300–360 g. Group I received 10 mg kg−1 at 1, 24, 48 and 72 h. Group II received 10 mg kg−1 at 1, 8, 24, 32, 48, 56, 72 and 80 h. Groups III and IV received the drug as for groups I and II, respectively, as well as cimetidine (50 mg kg−1) 1 h before each dose of dapsone. Twice daily dapsone administration (Group II) resulted in a significantly greater (P &lt; 0.05) Met Hb AUC (757 ± 135 vs 584 ± 115% Met Hb h), dapsone AUC (140 ± 17.5 vs 113 ± 130 μg h mL−1) and monoacetyl dapsone AUC (48.2 ± 18.3 vs 10.8 ± 4.6 μg h mL−1) compared with a single daily dapsone dose (group I). The administration of cimetidine before the once daily dose of dapsone (group III) resulted in a significant (P &lt; 0.05) fall in Met Hb (302 ± 179 vs 584 ± 115% Met Hb h) and an increase in both the dapsone (151 ± 22.2 vs 113 ± 13.0 μg h mL−1) and monoacetyl dapsone AUC values (33.6 ± 5.8 vs 10.8 ± 4.0 μg h mL−1) compared with a single daily dose of dapsone (group I). Administration of cimetidine before the twice daily dose of dapsone (group IV) resulted in no significant change in Met Hb or monoacetyl dapsone levels, despite a marked increase in the AUC after dapsone compared with control (303 ± 53.2 vs 140 ± 17.5 μg h mL−1 P &lt; 0.05; group II). The administration of a single dose of monoacetyl dapsone alone resulted in rapid production of methaemoglobinaemia (17.1 ± 7.2%) at 1 h; however, prior administration of cimetidine did not significantly affect methaemoglobin levels over 24 h (287.6 ± 77.9 vs 316.4 ± 120.2% Met Hb h). These studies indicate that although cimetidine may reduce Met Hb formation during chronic dapsone administration, dose reduction of dapsone is required to avoid haemotoxicity because of the increased accumulation of both parent drug and its monoacetyl metabolite.
Effects of Tableting Pressure on Hydration Kinetics of Theophylline Anhydrate Tablets
Authors: Otsuka Makoto , Kaneniwa Nobuyoshi , Kawakami Katsumi , Umezawa Osamu 
Published: April 2011

Abstract
The effects of tableting pressure on hydration kinetics of types I and II theophylline anhydrate tablets at 95% relative humidity, 35°C, have been studied by using various kinetic equations. Relations between tablet expansion and hydration were studied. Samples of 2 cm diameter tablets (1 g) were compressed at 5, 10 and 20 MPa. The hydration of types I and II tablets decreased with increased tableting pressure. The time required for 50% hydration of 2 cm diameter tablets, compressed at various pressures suggests that the tablet hydration rate was affected by the tableting pressure. Types I and II tablets expanded 11.37-16.75% in volume during hydration to the monohydrate. The thickness expansion of the tablets exceeded the diameter expansion as the tablet structure was not uniform owing to the orientation of particles during the compression. The final expansion ratio of the tablets increased with increased tableting compression pressure. The Hancock Sharp constant (m) and fitting of the kinetic data to a suitable model suggested that the hydration of theophylline anhydrate tablets followed the two-dimensional phase boundary equation (type I tablets) or the three-dimensional phase boundary equation (type II tablets).
Response of canine cerebral arteries to endothelin-1
Authors: Garcia J L , Monge L , Gómez B , Diéguez G 
Published: April 2011

Abstract
The effects of endothelin-1 (10−10-10−7 M) were isometrically recorded in 4 mm cylindrical segments from the middle cerebral artery of dogs. Cumulative application of endothelin-1 produced marked, sustained contraction of arteries in a concentration-dependent-manner, the maximal response being about 2.6 times higher than that achieved with KCl (50 mM). The contraction by endothelin-1 was unaffected either by endothelium removal or by the cyclo-oxygenase inhibitors indomethacin (10−6 M) and meclofenamate (10−6 M). In a Ca2+ -low (25 μM) solution the endothelin-1-induced arterial contraction was decreased. Therefore, the cerebral vasoconstriction induced by endothelin-1 could be caused by activation of specific receptors located on smooth muscle cells which would lead to the influx of extracellular calcium and vascular musculature contraction.
Comparison of the effects of hydralazine and nifedipine on contractions and 45Ca influx of rat aorta
Authors: Orallo Francisco , Gil-Longo José , Bardán Belén , Calleja José M 
Published: April 2011

Abstract
The effect of the vasodilator hydralazine has been compared with nifedipine on KCl-(K+) (60 mM) and noradrenaline-(NA) (10 μM) induced 45Ca uptake and contractile responses in rat aorta arterial strips without endothelium. Hydralazine (0.5–10 mM) was equally effective in relaxing K+ - (IC50 = 2.2 ± 0.17 mM) and NA-(IC50 = 3.06 ± 0.25 mM) induced tension, the degree of relaxation depending on the dose. Nifedipine totally inhibited K+-(IC50 = 3.16 ± 0.28 nM) induced contractions with lower doses than were necessary to relax (up to 54.0 ± 4.1% with supramaximal concentrations) NA-induced contractions (IC50 = 1.48 ± 0.12 μM). In the experiments in a calcium-free medium, nifedipine (1 μM) had no effect on the NA-(10 μM) induced contractions whereas hydralazine (1 mM) strongly inhibited them. Nifedipine did not affect the basal uptake of 45Ca but the induced uptakes were reduced to 66.3 ± 3.2% (K+) and 65.5 ± 4.1% (NA) of their basal values. Hydralazine did not affect the basal uptake of 45Ca nor that induced by the two vascoconstrictor agents. These results suggest that nifedipine acts on the cell membrane by blocking the movements of calcium through the voltage-dependent and receptor-operated calcium channels, whilst hydralazine has an intracellular effect.
Plasma volumes, blood volumes, and plasma protein concentrations after moderate haemodilution with Fluosol-DA or normal saline in the rat
Authors: Shrewsbury Robert P 
Published: April 2011

Abstract
Plasma volumes, blood volumes, and plasma total protein, albumin, and bilirubin concentrations have been determined in rats for 72 h following 20 or 40 mL kg−1 haemodilution with Fluosol-DA or 0.9% Nad. Haemodilution with 20 mL kg−1 of either haemodiluent had no influence on the measured values. Plasma and blood volumes did not change after Fluosol-DA haemodilution at 40 mL kg−1, but albumin and bilirubin concentrations were decreased for 72 h. Only bilirubin concentrations were decreased for 72 h following haemodilution with 40 mL kg−1 of 0.9% NaCl. It was concluded that changes in a drug's plasma protein binding, and not the plasma or blood volume, are responsible for the reported alterations in a drug's apparent volume of distribution after haemodilution.
Effect of Chronic Nicotine Treatment and Withdrawal on Rat Striatal D1 and D2 Dopamine Receptors
Authors: Kirch Darrell G , Taylor Timothy R , Creese Ian , Xu Shou-Xi , Wyatt Richard Jed 
Published: April 2011

Abstract
The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12 mg kg−1 day−1), and after withdrawal from chronic nicotine (12 mg kg−1 day−1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal. Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2 ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0·3 Mm GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters.
Calcium-calmodulin-dependent Activation of Adenylate Cyclase in Prostaglandin-induced Electrically-monitored Intestinal Secretion in the Rat
Authors: Hardcastle J , Hardcastle P T , Ayton B , Chapman J , Macneil S 
Published: April 2011

Abstract
The calcium-calmodulin antagonist 5-iodo-C8-W7 inhibited the PGE2-induced stimulation of cAMP production by isolated enterocytes from rat small intestine. It also reduced the secretory response of intestinal sheets to PGE2, measured as a rise in short-circuit current. It did not however, inhibit the electrical responses to forskolin and dibutyryl cAMP, nor to acetylcholine, a secretagogue whose effect is not mediated by cAMP. It is concluded that the receptor-mediated activation of adenylate cyclase and the subsequent secretory response are dependent upon calcium-calmodulin.
Time Course of PAF Formation by Gastrointestinal Tissue in Rats After Castor Oil Challenge
Authors: Pintoy A , Autore G , Mascolo N , Sorrentino R , Biondi A , Izzo A A , Capasso F 
Published: April 2011

Abstract
When castor oil was administered by gavage to rats, the duodenum and jejunum, but not the stomach, produced large amounts of platelet activating factor 3–7 h after oil challenge with a peak at 3 h. Intraluminal release of acid phosphatase was also markedly increased in the duodenum and jejunum of castor oil-treated rats, especially 3–5 h after oil challenge. No increase was observed in the stomach. There was a correlation between elevated release of acid phosphatase and intestinal hyperaemia.
Effect of Calcium Channel Blockers on Postprandial Gastrointestinal Motility in the Dog
Authors: De Ponti Fabrizio , Einaudi Arturo , Cosentino Marco , D'Angelo Luigi , Frigo Gian Mario , Crema Antonio 
Published: April 2011

Abstract
We have compared the ability of nifedipine and lacidipine, a new 1,4-dihydropyridine, to interfere with postprandial gastrointestinal motility. Five conscious dogs, fitted with 8 bipolar electrodes along the gastrointestinal tract, were studied. Gastrointestinal spike activity was evaluated by means of a computer system. Lacidipine (8 μg kg−1) was administered as an i.v. bolus immediately followed by a 10 μg kg−1 h−1 i.v. infusion for 3 h, starting 30 min before a standard meal. This dose of lacidipine decreased systolic blood pressure by approximately 20%. Nifedipine was used at equihypotensive doses (30 μg kg−1 i.v. bolus followed by 300 μg kg−1 h−1 i.v. infusion). Lacidipine had no effect on either gastric or intestinal postprandial spike activity. Nifedipine significantly delayed the appearance of the fed pattern and reduced the number of spikes in the small bowel, while it had no effect on gastric spike activity. We conclude that equihypotensive doses of lacidipine and nifedipine differ in their effects on the gastrointestinal tract, lacidipine having a better cardiovascular selectivity profile than nifedipine, and that the sensitivity to nifedipine varies in different parts of the gut.
Investigation of the 5-HT receptor mediating relaxation in guinea-pig proximal colon
Authors: Elswood C J , Bunce K T 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) induced concentration-related relaxations (EC50 = 9·1 μm) of guinea-pig proximal colon pretreated with ketanserin (1 μm) and ondansetron (10 μm). This 5-HT-induced effect was neuronally mediated since it was blocked by tetrodotoxin (0·3 μm). 5-Carboxamidotryptamine was a full agonist and ten times more potent than 5-HT. α-Methyl-5-HT was a partial agonist. 2-Methyl-5-HT was without effect. Methysergide and metergoline were antagonists of 5-HT producing parallel shifts at 0·1 μm but unsurmountable antagonism at higher concentrations. pKB values of 8·0 and 7·3 were calculated for methysergide and metergoline, respectively. This study has identified a 5-HT-induced relaxation of guinea-pig proximal colon which is mediated via a neuronal 5-HT1-like receptor. However, the subtype has yet to be established.
Inhibition by diltiazem of left ventricle collagen proliferation during renovascular hypertension development in rats
Authors: Baxter C F 
Published: April 2011

Abstract
Diltiazem administered in drinking water (0·7 mg mL−1) to Goldblatt two kidney-one clip rats over 16 weeks did not prevent the development of hypertension and left ventricular hypertrophy (LVH). When the collagen content of the left ventricles was assayed (as hydroxyproline), it was found that the fibrosis, characteristic of LVH, was inhibited by diltiazem treatment, despite the fact that hypertension and LVH had developed. This study provides some indirect evidence for the notion that the collagen and myocyte compartments of the myocardium are under separate influences during LVH development in renovascular hypertension.