bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Testing of Bioadhesive, Fluoride-containing Slow-release Tablets for Oral Use
Authors: Bottenberg P , Cleymaet R , De Muynck C , Remon J P , Coomans D , Michotte Y , Slop D 
Published: April 2011

Abstract
The bioadhesive characteristics of tablets for oral use made from modified starch, polyacrylic acid (PAA), polyethylene glycol (PEG) and sodium carboxymethylcellulose (CMC) were investigated. Adhesion force and energy were determined in-vitro and maximal adhesion time was evaluated in-vivo in human subjects. In-vitro, PAA showed the best bioadhesive properties, followed by modified maize starch and PEG with a mol. wt of 300 000–400 000 daltons. The presence of 0·1 mg of fluoride as NaF did not lead to significant differences in adhesion force and energy for the same formulation. The in-vivo bioadhesion was not strongly correlated to the in-vitro data. PAA, despite its excellent adhesion, proved to be irritating to the mucosa. PEG with a mol. wt of 200000 daltons was subject to erosion. CMC showed good bioadhesive properties but the mechanical strength of the tablets was low. Modified maize starch tablets containing 5% (w/w) PAA and PEG with a mol. wt of 300 000 daltons proved to be the most suitable formulations for a fluoride-slow-release tablet with bioadhesive properties. In-vitro, the tablets released all of the fluoride within the 8 h period, with a high initial release. The release rate was related to the water absorption rate of the tablets. The PAA-containing formulations and the CMC formulations had the fastest release. In-vivo, fluoride levels with a minimum of 150 and a maximum of 1000 μg mL−1 were maintained for 8 h in the oral cavity. These fluoride levels were sustained significantly longer than those obtained with the administration of fourfold the amount of fluoride in the form of a fluoride-containing toothpaste. The release characteristics in-vivo exhibited a high variation. The use of bioadhesive polymers in oral pharmacotherapy seems promising.
5-Oxygenated N-Alkyl-and N,N-Dialkyl-2-amino-1-methyltetralins. Effects of Structure and Stereochemistry on Dopamine-D2-receptor Affinity
Authors: Grol Cor J , Nordvall Gunnar , Johansson Anette M , Hacksell Uli 
Published: April 2011

Abstract
The ability of a series of stereochemically well-defined 5-oxygenated 2-aminotetralins, consisting of dopamine-receptor agonists and antagonists, to displace [3H]spiperone and [3H]N-propylnorapomor-phine (NPA) from calf-caudate dopamine receptor sites has been evaluated in-vitro. In addition, the partition coefficients of the compounds were determined to measure their lipophilicity. The data were compared with previously obtained in-vivo biochemical data (dopa accumulation in reserpine pretreated or non-pretreated rats). Compounds with 2S-configuration and a C5-hydroxy substituent have the highest affinity for NPA-binding sites and such derivatives also have the highest potency in-vivo. The 2R-derivatives are less efficacious and their affinity for NPA- and spiperone binding sites is influenced by their lipophilicity. On the basis of these results, a model is proposed in which the antagonists form two, and the agonists form three, strong intermolecular bonds with the D2-receptor. According to this model, the agonists, but not the antagonists, are able to donate a hydrogen bond from the phenolic hydroxyl to the receptor.
The Fluoroquinolones Exert a Reduced Rate of Kill Against Enterococcus faecalis
Authors: Lewin C S , Morrissey I , Smith J T 
Published: April 2011

Abstract
The bactericidal activities of ciprofloxacin, ofloxacin and DR-3355 have been investigated against Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis over 24 h. The three fluoroquinolones were found to be rapidly bactericidal against the staphylococci, killing over 99% of the bacteria during the first 3 h of exposure with a further reduction in viability of approximately one logarithm occurring over the next 21 h. In contrast, the fluoroquinolones displayed a much slower rate of kill against E. faecalis, as little or no bactericidal activity was detected over the first 3 h for both E. faecalis ATCC 19433 and a clinical isolate. At 6 h all three of the drugs were bactericidal against the enterococci although the amount of kill was not as great as against the staphylococci. However, at 24 h the amount of kill obtained with all three drugs was similar to that obtained for staphylococci exposed to these drugs. Ciprofloxacin, ofloxacin and DR-3355 were not active against E. faecalis ATCC 19433 in phosphate buffered saline and therefore require cell division for their bactericidal activity against this species.
Cardiovascular Effects of Intracerebroventricular Injections of (±)-Nebivolol and its Enantiomers—a Comparison with those of Metoprolol in the Rat
Authors: Midol-Monnet M , Davy M , Heimburger M , Beslot F , Cohen Y 
Published: April 2011

Abstract
The cardiovascular effects of (±)-nebivolol, a potent β1-adrenoceptor antagonist, and its enantiomers, (+)-nebivolol (SRRR) and (–)-nebivolol (RSSS) in normotensive anaesthetized rats, have been investigated using metoprolol as a reference substance. The drugs decreased blood pressure and heart rate immediately after i.c.v. injection. These effects paralleled the β-blocking potencies ((+)- &gt; (±)- &gt; (–)-nebivolol). Metoprolol induced a weaker hypotension than (±)-nebivolol, and a long-lasting reduction in stroke volume. As reported after i.v. administration, (±)-nebivolol and isomers by the i.c.v. route decreased peripheral vascular resistance following i.c.v. administration while metoprolol increased it. These effects are centrally mediated since cardiovascular responses to isoprenaline i.v. remained unchanged.
The use of electron spin resonance to measure micro viscosity
Authors: Gebre-Mariam Tsige , Armstrong N Anthony , James Kenneth C , Evans Jeffrey C , Rowlands Christopher C 
Published: April 2011

Abstract
The viscosities of a series of mixtures of glycerol and water were measured by electron spin resonance (ESR), photon correlation spectroscopy and Ostwald viscometry. Close agreement was obtained between the last two methods but viscosity as measured by ESR was always significantly lower. The difference, the magnitude of which depended on the spin probe used, was attributed to interaction between water and glycerol. Similar results were obtained using water-sorbitol and water-sucrose mixtures.
Salivary excretion of mexiletine in normal healthy volunteers
Authors: Katagiri Yoshihiro , Nagasako Sadao , Hayashibara Masakazu , Iwamoto Kikuo 
Published: April 2011

Abstract
To investigate the kinetics and correlation between serum and saliva levels of mexiletine, serum (total and unbound) and saliva drug concentration-time courses have been analysed in five normal healthy volunteers after administration of a single oral dose (200 mg) of the drug. Mexiletine levels in saliva were always higher than those in serum. The drug concentration-time curve in each sample was analysed according to the non-linear least squares regression program MULTI, for a two-compartment model with first-order absorption. The saliva drug concentration in the post-absorption phase was found to be well correlated with either corresponding serum total or serum unbound drug level in four of the subjects. Although there was a large inter-individual variation in the ratio of saliva to serum drug concentrations as well as in the pharmacokinetic parameters, an almost consistent ratio was obtained in each individual.
The effect of a 5-HT3-antagonist on the ileal brake mechanism in the rat
Authors: Brown Nicola J , French S J , Rumsey R D E , Read N W 
Published: April 2011

Abstract
Studies have been carried out on 7 male adult rats to investigate how the action of the selective 5-HT3 receptor antagonist, granisetron, influences gastrointestinal transit under control conditions and when it is delayed by ileal infusion of lipid. Stomach to caecum transit time (SCTT) was measured using environmental hydrogen analysis. Subcutaneous administration of granisetron (BRL 43694, 40 μg kg−1) significantly delayed the passage of the head of the baked bean meal through the stomach and the small intestine under control conditions (P &lt; 0·05). The same compound, however, significantly reversed the delay in SCTT induced by ileal infusion of lipid (P &lt; 0·001). These apparently paradoxical results may be rationalized by postulating inhibition of receptors on afferent nerves initiating reflexes that both accelerate and delay transit.
The effect of 8-cyclopentyl-1,3-dipropylxanthine on the development of cyclosporin-induced acute renal failure
Authors: Panjehshahin M R , Chahil R S , Collis M G , Bowmer C J , Yates M S 
Published: April 2011

Abstract
The effect of the selective A1-adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX, 0·1 mg kg−1 i.v.) administered twice daily to rats has been assessed on the development of renal dysfunction induced by four daily injections of cyclosporin (60 mg kg−1 i.p.). The series of cyclosporin injections resulted in a polyuria accompanied by a 64–70% increase in plasma urea and creatinine concentrations and a 50% reduction in inulin clearance. However, cyclosporin administration resulted in no change in p-aminohippurate clearance nor was there any evidence of tubular necrosis or vascular damage. CPX treatment did not improve any index of renal function perturbed by cyclosporin. The findings provide evidence that adenosine does not play a role in the pathophysiology of cyclosporin nephrotoxicity.
Calcium Antagonism by KB-2796, a New Diphenylpiperazine Analogue, in Dog Vascular Smooth Muscle
Authors: Iwamoto T , Morita T , Sukamoto T 
Published: April 2011

Abstract
The effects of KB-2796, a new diphenylpiperazine analogue, on [3H]nitrendipine ([3H]NTD) binding, KCl-induced contraction and 45Ca influx has been examined in dog vascular smooth muscle, and compared with those of other diphenylpiperazines. In the binding study, [3H]NTD was found to bind with a high affinity to a single class of sites on aortic membranes (Kd = 0·41 Nm and Bmax = 31 fmol(mg protein)−1). KB-2796 inhibited specific [3H]NTD binding in a concentration-dependent manner, with a Ki value of 0·34 μm. The other diphenylpiperazine derivatives such as flunarizine and cinnarizine also inhibited binding in the same manner. Also, in the contraction study, all the diphenylpiperazines antagonized the 50 Mm KCl-induced contraction of isolated mesenteric arteries concentration-dependently. The IC50 values of the compounds for KCl-induced contraction correlated strongly with the respective Ki values obtained in the [3H]NTD binding study. In the 45Ca influx study, KB-2796 also effectively inhibited KCl-induced 45Ca influx in mesenteric arteries, with an IC50 value of 0·14 μm. This was close to the IC50 value found in the KCl-induced contraction study. These findings suggest that calcium antagonism by KB-2796 is responsible for its vasorelaxing action in vascular smooth muscle.
The Effect of α1-Acid Glycoprotein on the Pharmacological Activity of α1-Adrenergic Antagonists in Rabbit Aortic Strips
Authors: Chiang Janie , Hermodsson Görel , Øie Svein 
Published: April 2011

Abstract
The pharmacological activity of three α1-adrenergic antagonists, prazosin, tiodazosin and WB4101 has been studied in the presence and absence of 20 μ m α1-acid glycoprotein (AAG) in rabbit aortic strips, and measured as the ability to increase the EC50 value of the α1-adrenergic agonist phenylephrine. For all three drugs, the presence of AAG diminished the pharmacological activity when compared with equivalent unbound concentrations in the absence of AAG. In the presence of AAG the EC50 value of phenylephrine at 5·69 Nm unbound prazosin was on average 47% lower than in the absence of AAG (P &lt; 0·002), at 122 Nm unbound tiodazosin, 39% lower (P &lt; 0·01), and at 25·6 Nm unbound WB4101, 68% lower (P &lt; 0·002). Albumin showed no ability to modify the α1-adrenergic blocking activity of prazosin (P &gt; 0·1). The EC50 value for phenylephrine in the absence of antagonists was not affected by AAG. The effect of AAG on the antagonistic activity of prazosin was concentration-dependent with a maximum suppression of prazosin activity of 79% and with a half-maximum concentration of 1·1 μm AAG. AAG significantly decreased prazosin's ability to reduce α1adrenergic stimulation of calcium influx (P &lt; 0·05), while it had no effect on prazosin's ability to decrease α1-adrenergic-stimulated formation of inositol phosphate. These results suggest that the effect of AAG on adrenoceptors appears to act selectively via α1a-receptors. Consistent with these observations was the observation that WB4101, a selective α1a-antagonist was more affected by AAG than was prazosin or tiodazosin.
The Design of Analytical Methods for Use in Topical Epidermal Growth Factor Product Development
Authors: DiBiase M D , Rhodes C T 
Published: April 2011

Abstract
Data from a reverse phase gradient elution HPLC assay for human epidermal growth factor (EGF) was compared and correlated with data obtained from a competitive heterogeneous radioimmunoassay (RIA). The RIA was established to measure very low concentrations of EGF in formulation drug release and compatibility studies. The HPLC assay, capable of resolving parent and possible modified or fragmented forms of EGF isolated from human urine, was studied as a potential development tool for stability and final product evaluation. As independent analytical methods, the HPLC and the RIA procedures produced correlated results when quantifying freshly prepared and certain degraded samples of EGF. The capacity of the HPLC method to serve as a stability indicating assay was examined. Degradation of EGF was induced by storage in 0·05 m phosphate buffer pH 7·4 at 25, 37 or 50°C. The same three degradation products were detected at each temperature by the HPLC method, one of which was identified as l-isoaspartyl EGF.
Effect of Imipramine on the Membrane Anisotropy and on the Phospholipid Methylation in the Central Nervous System of the Rat
Authors: Melzacka Miroslawa , Nocon Halina 
Published: April 2011

Abstract
An ex-vivo and in-vitro study of the effects of imipramine on the membrane anisotropy and phospholipid methylation in the rat cortical membranes was carried out. A comparative study of the membrane fluidity in various brain regions indicated different basal anisotropy of the areas and different reaction of these membranes to imipramine. It was found that imipramine when given to rats chronically (14 × 10 mg kg−1, i.p.) or added externally to the cortical membranes of naive rats or rats treated with a single dose of imipramine (10 mg kg−1, i.p.) decreased the anisotropy of cortical membranes. Chronic imipramine produced some changes of the membrane architecture in the cortex, whereas imipramine in different concentrations did not fluidize these membranes in-vitro. Imipramine in concentrations corresponding to its mean concentration in the rat brain after administration at a dose of 10 mg kg−1 i.p., potentiated phospholipid methylation in the cortical membranes of naive rats and rats receiving imipramine in a single dose of 10 mg kg−1 i.p. in an in-vitro study, whereas the prolonged administration of imipramine decreased the sensitivity of phospholipid methyltransferases to the stimulating effect of the drug in-vitro.
Impaired Prednisolone Sensitivities of the Endocrine System and Peripheral-blood Lymphocytes are Closely Related to Clinical Incidence in Renal Transplantation
Authors: Hirano Toshihiko , Oka Kitaro , Sakurai Etsuo , Tamaki Tohru , Kozaki Masami 
Published: April 2011

Abstract
Endocrine- and immune-responses to prednisolone and their relation to clinical incidence were assessed in 19 renal transplant recipients. All of the patients were treated with prednisolone and cyclosporin. Response of the hypothalamic-pituitary-adrenal (HPA) system to prednisolone was evaluated by measuring serum Cortisol concentration. Cortisol concentration before transplantation was 126·7 ± 38·6 ng mL−1, while it decreased to 4·1 ±2·5 ng mL−1 within the period characterized by a cumulative dose of prednisolone from 300 to 700 mg. A statistically significant high incidence (P &lt; 0·01) of acute rejections was observed in low HPA responders; (mean Cortisol concentration during prednisolone treatment exceeded 3·0 ng mL−1), 6 of 12 with a low HPA response to prednisolone showed signs of rejection, while none of the 7 with a high HPA response showed signs of rejection. The concentrations of prednisolone suppressing the in-vitro response of pretransplant lymphocytes to concanavalin A by 50% (ID50) were determined. Lymphocytes from 8 patients were extremely insensitive (ID50 &gt; 500 ng mL−1), and 5 of the 8 showed signs of rejection. Lymphocytes from the other 11 patients showed high sensitivity (ID50 &lt; 500 ng mL−1), and only one of those showed signs of rejection. Thus, a significantly high incidence of rejection was observed in low lymphocyte-responders to prednisolone (P &lt; 0·05). The results suggest that an insensitive endocrine response to prednisolone correlates with an impaired lymphocyte response to the steroid, and that both of the indices are related to occurrence of rejection. Evaluation of these pharmacodynamic parameters in combination may serve as a guideline for successful immunosuppressive therapy in renal transplantation.
In-vitro Interaction of a Novel Immunosuppressant, FK 506, and Antacids
Authors: Steeves M , Abdallah H Y , Venkataramanan R , Burckart G J , Ptachcinski R J , Abu-Elmagd K , Jain A K , Fung F , Todo S , Starzl T E 
Published: April 2011

Abstract
The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2–5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Turns resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.
The Effect of Pimobendan on Myocardial Mechanical Function and Metabolism in Dogs: Comparison with Dobutamine
Authors: Ichihara Kazuo , Abiko Yasushi 
Published: April 2011

Abstract
The effect of pimobendan, a newly developed cardiotonic agent, on myocardial mechanical function and energy metabolism has been examined in the dog heart, and compared with that of dobutamine. Either saline, vehicle for pimobendan, dobutamine (0·3 and 1 μg kg−1), or pimobendan (0·3 and 1 mg kg−1) was injected intravenously. Dobutamine and pimobendan both increased the first derivative of left ventricular pressure and percent segment shortening, indicating their positive inotropic action. After 2 min of dobutamine injection, or after 20 min of pimobendan injection, the myocardium was removed, and used for determination of the tissue levels of metabolites of energy and carbohydrate metabolism. In genera), all metabolic parameters measured were not changed by either dobutamine or pimobendan injection. In animals with aortic constriction for 10 months, dobutamine and pimobendan injections did not alter the myocardial energy and carbohydrate metabolism. Although dobutamine and pimobendan increased the cardiac mechanical function, they did not disturb the myocardial energy and carbohydrate metabolism.
Influence of Intravenous Administration Set Composition on the Sorption of Isosorbide Dinitrate
Authors: De Muynck C , Colardyn F , Remon J P 
Published: April 2011

Abstract
The influence of the composition of administration sets on the sorption of isosorbide dinitrate was investigated in-vitro. Isosorbide dinitrate solutions (250 μg mL−1) in 0·9% NaCl or 10% glucose were stored in glass containers and administered at a flow rate of 20 mL h−1. The influence of the concentration of different plasticizers (di-ethylhexylphthalate, tri-ethylhexyltrimelitate) in polyvinylchloride tubings was determined. Polybutadiene tubings of different mol. wt coextruded laminates of these polybutadienes with PVC of different composition and a polyethylene tubing were evaluated. The higher the Shore hardness of the PVC tubing, the lower the sorption. The infusion fluid played an additional role only for the tubings with high Shore hardness (&gt; 70). The sorption of isosorbide dinitrate to polybutadiene tubings of different mol. wt was less than 2·5% after 5 h and was comparable with the sorption to the polyethylene tubing. When polybutadiene/PVC laminates were used, the sorption increased significantly and was in most cases dependent on the Shore hardness of the PVC (higher Shore hardness gave lower sorptions) and on the mol. wt of the polybutadiene (lower mol. wt resulted in higher sorption). Sorption was not dependent on the type of PVC plasticizer.
Development and Evaluation of an Intracutaneous Depot Formulation of Corticosteroids Using Transcutol as a Cosolvent: In-vitro, Ex-vivo and In-vivo rat Studies
Authors: Panchagnula R , Ritschel W A 
Published: April 2011

Abstract
A topical delivery system has been developed using 50% Transcutol (diethylene glycol monoethyl ether) to decrease the body burden of topically administered dexamethasone and hydrocortisone. The delivery system was evaluated in-vitro using a dissolution apparatus to measure the release of steroid from the gel. In 10 h, 29·6±0–39% dexamethasone and 45·5 ±0·84% hydrocortisone was released from the formulation compared with 23·0 ±0·48 and 39·9 ±0·77%, respectively, from control formulations without Transcutol. Ex-vivo evaluation was made using rat whole skin in a diffusion cell; the amount of steroid reaching the acceptor cell was significantly less from the formulation containing Transcutol compared with controls. There was also a 2-fold increase in the retention of dexamethasone and a 3-fold increase in the retention of hydrocortisone in the skin at the end of the permeation experiments compared with control experiments. In-vivo studies were made using a formulation containing [3H]hydrocortisone applied to rat skin, followed by measurement of total radioactivity in the blood. For the Transcutol formulation the area under the blood concentration-time curve (0–96 h) was 6·06± 1·27 compared with 2·52 ± 0·43 × 106 d min−1 mL−1 h for the control formulation, indicating a 58% reduction in body burden.