bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Process and Formulation Variables on the Properties of Spray-dried β-Galactosidase
Authors: Broadhead J , Rouan S K Edmond , Hau I , Rhodes C T 
Published: April 2011

Abstract
The objective of this study was to evaluate the joint effects of various processing and formulation variables on the properties of spray-dried β-galactosidase using statistically designed experiments. The key response variables evaluated were product yield, residual enzymatic activity, moisture content and particle size and appearance. The residual enzymatic activity and product yield were significantly affected by the processing variables. The highest product yields were obtained when the drier outlet temperature was relatively high, resulting in extensive protein denaturation. Subsequent experiments, therefore, compared the relative effectiveness of four stabilizers (mannitol, sucrose, arginine hydrochloride and trehalose) in terms of their ability to preserve enzymatic activity during the spray-drying process and during long-term storage. Trehalose was the most suitable stabilizer. The effect of a number of other formulation variables (total solids level, ratio of stabilizer to protein, presence of surfactant and presence of buffer) was also investigated. A final formulation consisting of 6% β-galactosidase and 10% trehalose in deionized water was selected. Spray-drying at inlet and outlet temperatures of 140 and 95°C, respectively, results in greater than 70% yields of a fully active product with a moisture content of 2–5% and a mean particle size of 2–4 μm.
The Role of the Displacement-time Waveform in the Determination of Heckel Behaviour Under Dynamic Conditions in a Compaction Simulator and a Fully-instrumented Rotary Tablet Machine
Authors: Muller Francis X , Augsburger Larry L 
Published: April 2011

Abstract
The Heckel equation has been used widely to characterize the compression behaviour of pharmaceutical powders, yet very little attention has been paid to the role of the displacement-time profile used to generate this relationship. The objective of this study was to evaluate and compare selected standard waveforms with actual and theoretical tablet press waveforms in the Heckel analysis of representative formulations under dynamic conditions in a compaction simulator and to compare such data with that determined on the same formulation using an actual fully-instrumented rotary tablet press. Increased tableting rate and different programmed displacement-time waveforms with the same gross punch-speed changed the Heckel behaviour of all formulations. The results of this study suggest the pressure-volume relationship determined during powder-bed compression is affected by the instantaneous punch-speed profile of the displacement-time waveform for all materials studied, even though they deform by different mechanisms. It appears that the instantaneous punch-speed profile of the particular displacement-time waveform is a confounding factor of Heckel analysis. Compaction simulators programmed to deliver saw-toothed displacement-time traces have the advantage of constant punch-speed and may be a better choice for characterizing a formulation by Heckel indices and the strain-rate sensitivity index. On the other hand, they also carry the liability of not being a realistic representation of tableting on a rotary tablet press.
The Stability of bFGF Against Thermal Denaturation
Authors: Vemuri Sriram , Beylin Irina , Sluzky Victoria , Stratton Pamela , Eberlein Gert , Wang Y John 
Published: April 2011

Abstract
The influence of sulphated ligand and pH on thermal denaturation of basic fibroblast growth factor (bFGF) was investigated by differential scanning calorimetry (DSC), and verified by fluorescence spectrophotometry. Purity of bFGF before and after heat denaturation was assessed by SDS-PAGE analysis. In DSC studies the samples were heated to 95°C. The midpoint of the temperature change in the thermogram was designated as Tm. Sulphated ligand experiments were undertaken in potassium phosphate (pH 6·5) and sodium acetate buffers. Control thermograms (with no ligand) showed a Tm at 59°C in potassium phosphate buffer. Higher Tm values were noted as sulphated ligand concentration was increased. Similarly when heparin was added, the Tm moved to a higher temperature. A ratio as low as 0·3:1 of heparin to bFGF, increased the Tm to 90°C, which is a 31°C shift in Tm. The effect of pH on thermal denaturation of bFGF was studied in a citrate-phosphate-borate buffer system. A shift in Tm from 46 to 65°C was observed as the pH is changed from 4 to 8. Changes in protein conformation as a function of pH were monitored by fluorescence spectroscopy. It was found that a pH range from 5 to 9 is optimal for the stability of bFGF formulations. In a stability study it was noted that heparin protected bFGF from thermal denaturation only at high temperature.
Induction of the Conversion of Xanthine Dehydrogenase to Oxidase in Rabbit Liver by Cu2+, Zn2+ and Selenium Ions
Authors: Sakuma Satoru , Fujimoto Yohko , Iwai Mimi , Fujimoto Kenjiro , Yasuda Maki , Nishida Hiroko , Fujita Tadashi 
Published: April 2011

Abstract
Effects of Cu2+, Zn2+, Fe2+ and selenium ions on the conversion of xanthine dehydrogenase to oxidase in rabbit liver were examined. Under basal conditions, xanthine oxidase activity represented only 16% of the total xanthine oxidase plus dehydrogenase activity. Cu2+ (2–10 μm), Zn2+ (5–30 μm) and selenium ions (5–100 μm) brought about the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. The concentrations of Cu2+, Zn2+ and selenium ions required for increasing xanthine oxidase activity by 50% was approximately 4, 10 and 20 μm, respectively. On the other hand, Fe2+ had no effect on the conversion of the enzyme up to 100 μm. These results suggest that Cu2+, Zn2+ and selenium ions have the potential to modulate the conversion of xanthine dehydrogenase to oxidase in rabbit liver.
Analysis of Neurogenic Contractions Induced by ML-1035 and Other Benzamides in the Guinea-pig Non-stimulated Isolated Ileum
Authors: Linnik Matthew D , Butler Brent T , Elsea Sarah H , Ahmed Nahed K 
Published: April 2011

Abstract
4-Amino-5-chloro-substituted benzamides have been shown to increase gastric motility in-vivo and enhance field-stimulated and peristaltic contractions in-vitro. The present experiments examined the contractile response to a series of benzamides in the guinea-pig non-stimulated ileum. Four benzamides elicited contractions in the isolated ileum which were expressed as a percentage of the contraction induced by 1 μm acetylcholine (% acetylcholine response = 12 ± 2, 19 ± 3, 26 ± 2, 51 ± 3, n= 13, 8, 17, and 21, with EC50 values of 0·85, 1·8, 5·7, and 14·2 μm for cisapride, zacopride, metocloprarmde, and ML-1035 (4-amino-5-chloro-2-((2-methylsulphinyl)-ethoxy)-N-(2-(diethylamino)-ethyl)-benzamide hydrochloride), respectively). ML-1035 contractions were completely blocked by atropine and tetrodotoxin, while ganglionic blockade with hexamethonium was ineffective. Metoclopramide has been reported to sensitize postjunctional muscarinic receptors, however, ML-1035 did not enhance acetylcholine-induced contractions. Tropisetron (ICS 205–930, 1 μm), caused a parallel rightward shift in the concentration-response curve for both ML-1035 and zacopride (EC50 = 14·2 ± 1·3 and 1·8 ± 0·8 μm in the absence, and 26 ± 2·7 and 6·9 ± 2·3 μm in the presence of tropisetron for ML-1035 and zacopride, respectively) with apparent pKB values of 5·9 and 6·0 for the respective compounds. 5-Hydroxytryptaminergic receptor desensitization by 2-methyl-5-hydroxytryptamine (5-HT3) and 5-methoxytryptamine (5-HT4), attenuated the response to ML-1035. We also examined the effect of the benzamides on [3H]acetylcholine release from longitudinal muscle myenteric plexus preparations; however, these compounds had little effect on basal [3H]acetylcholine release. Thus, the pharmacological data indicate that the benzamides can elicit neurogenic contractions in the non-stimulated ileum by activating postganglionic, cholinergic neurons which is independent of an effect on smooth muscle.
Increased Cardiovascular Responsiveness to Central Cholinergic Stimulation in the Genetically Epilepsy-prone Rat
Authors: Trimarchi G R , Imperatore C , Arcadi F A , Saija A , de Sarro A , de Sarro G B , Costa G 
Published: April 2011

Abstract
We sought to determine whether differences in cardiovascular responsiveness to central stimulation of the cholinergic system existed between the genetically epilepsy-prone and outbred Sprague-Dawley rats. We treated the unanaesthetized, restrained rats with the indirect cholinergic agonist physostigmine (25, 50, 100 and 200 μg kg−1, i.v.) and the direct muscarinic agonist arecoline (50, 100 and 200 μg kg−1, i.v.). Blood pressure and heart rate were evaluated. Genetically epilepsy-prone rats demonstrated to be more susceptible to the action of physostigmine than the outbred Sprague-Dawley rats. Conversely, we did not note any difference between the two strains in the extent of the pressor response induced by arecoline. Moreover, we treated both strains with hemicholinium-3 (34·8 nmol, i.c.v.) to deplete endogenous stores of acetylcholine. This treatment did not affect the pressor response to arecoline, whereas it greatly reduced the response to physostigmine. The present results support an increased cardiovascular responsiveness to central cholinergic stimulation in the genetically epilepsy-prone rat which appears to be related to a pre-synaptic rather than a post-synaptic component.
Topically effective ocular hypotensive acetazolamide and ethoxyzolamide formulations in rabbits
Authors: Loftsson T , Friðriksdóttir H , Stefánsson E , Thórisdóttir S , Guðmundsson ö , Sigthórsson T 
Published: April 2011

Abstract
The effect of topically active 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) eye-drop formulations containing solutions of acetazolamide, ethoxyzolamide or timolol on the intra-ocular pressure (IOP) was investigated in normotensive conscious rabbits. Both acetazolamide and ethoxyzolamide were active but their IOP-lowering effect was less than that of timolol. The IOP-lowering effects of acetazolamide and ethoxyzolamide and that of timolol appeared to be to some extent additive. Combination of acetazolamide and timolol or ethoxyzolamide and timolol in one HP-β-CyD formulation resulted in a significant increase in the duration of activity compared with HP-β-CyD formulations containing only acetazolamide, ethoxyzolamide or timolol. Also, it was possible to increase the IOP-lowering effect of acetazolamide by formulating the drug as a suspension in an aqueous HP-β-CyD vehicle.
In-vivo and in-vitro evaluations of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-β-cyclodextrin and hydroxypropylcelluloses in dogs
Authors: Wang Zheng , Hirayama Fumitoshi , Uekama Kaneto 
Published: April 2011

Abstract
To maintain a suitable blood level of nifedipine for a long period of time, double-layer tablets consisting of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) and 3% nonionic surfactant (HCO-60) as a fast-release portion and hydroxypropylcelluloses (HPCs) with different viscosity grades (low, medium and high) as a slow-release portion were prepared, and their in-vitro and in-vivo release behaviours were investigated. Among the seven formulations, the tablet having the mean dissolution time of 0·8–1·3 h gave prolonged plasma nifedipine levels without decrease of AUC after oral administration to dogs. Consequently, the double-layer tablet consisting of HP-β-CyD with 3% HCO-60/(HPC-low: HPC-medium) in a weight ratio 1/(1·5:1·5) was selected as an appropriate modified-release formulation because it elicited almost comparable retarding effects with superior oral bioavailability compared with those of a commercially available slow-release nifedipine product.
Pertechnetate release from a water/oil microemulsion and an aqueous solution after subcutaneous injection in rabbits
Authors: Bellâ M , Colangelo D , Gasco M R , Maranetto F , Morel S , Podio V , Turco G L , Viano I 
Published: April 2011

Abstract
A water-oil microemulsion and an aqueous solution, both carrying pertechnetate, were injected subcutaneously in rabbits; release was observed by imaging the administration sites with a gamma-camera. Disappearance from the injection site of pertechnetate in aqueous solution was about ten times faster than that of pertechnetate in a microemulsion.
Cardiac response to autonomic drugs in atria of diabetic mouse
Authors: Wong Kai K 
Published: April 2011

Abstract
Comparisons of chronotropic effects of sympathomimetic and parasympathomimetic agents were made in isolated atria from alloxan-induced diabetic and age-matched control mice. In atria from mice rendered diabetic for three months, the cardiac response to bethanechol was potentiated compared with that of the age-matched control atria. However, the cardiac responses of atria from alloxan-treated mice to noradrenaline, 3-isobutyl-1-methylxanthine and 1,1-dimethyl-4-phenyl piperazinium iodide were similar to those of the controls.
The effect of low temperature on the enzyme activities and the level of SH groups in benign gastric ulcer and gastric carcinoma
Authors: Rzymowska J 
Published: April 2011

Abstract
Homogenates of human benign gastric ulcers and gastric carcinomas were stored at a low temperature (4°C). The activities of l-lactate dehydrogenase (LDH), malic dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and the concentrations of SH-containing compounds showed changes. Increased activities of LDH, MDH, G6PDH and GR occurred in the gastric carcinomas stored at 4°C compared with controls at 37°C. In contrast, the activities of G6PDH and GR decreased in the tissues of benign gastric ulcers. On incubation at 4°C the SH-containing compounds incorporated into protein molecules, SH groups binding with protein and non-protein SH groups decreased in both the benign and malignant tissues.
Evaluation of free radical production in an ischaemia-reperfusion model in the rabbit using a tourniquet
Authors: Chopineau J , Sommier M F , Sautou V 
Published: April 2011

Abstract
Use of a tourniquet on a limb to stem blood flow is frequent in surgery. However, this results in an ischaemia-reperfusion effect that causes damage through the production of free radicals. The aim of this work was to evaluate this production of free radicals in an ischaemia-reperfusion model in the rabbit after placement of a tourniquet. Plasma lipoperoxides were measured by high-performance liquid chromatography using the malondialdehyde assay method. We found significant (P &lt; 0·01) production of free radicals 1 min after release of the tourniquet compared with controls; no variation in levels of free radicals was observed during the ischaemia phase.
Rheological Behaviour of Saturated Polyglycolysed Glycerides
Authors: Bourret E , Ratsimbazafy V , Maury L , Brossard C 
Published: April 2011

Abstract
Seven saturated polyglycolysed glycerides (Gelucires) of melting points varying from 42 to 53°C and hydrophilic-lipophilic balance values from 2 to 14 were selected. Their rheological behaviour was determined by adjustment of the flow curves to the Ostwald power-law and by statistical assessment of the flow index. The flow of Gelucires was slightly shear thickening. This shear thickening rose when the temperature and the lipophilic specificity of the Gelucire increased. This behaviour accounted for a reorganization of the particles under the shear which became easier when the temperature increased and when the degree of condensation of the polyethylene glycol chains decreased with lipophilicity of the Gelucires.
The Power-consumption-controlled Extruder: A Tool for Pellet Production
Authors: Kleinebudde P , Sølvberg A J , Lindner H 
Published: April 2011

Abstract
Based on the assumption that there is a link between power consumption of an extruder and pellet properties, a control circuit for power consumption was developed. Powder and granulation liquid are feeded separately into a twin-screw extruder. The power consumption is controlled by varying the pump rate at a given powder-feed rate; consequently each level of power consumption results in a specific water content of the extrudate for a particular formulation. The shape of pellets depends almost entirely on the level of power consumption irrespective of formulation. The size of dry pellets is additionally affected by a shrinking factor which depends on the water content. The power-consumption-controlled extruder is an appropriate tool for the production of pellets. The system is able to adapt the water content for a formulation automatically.
Calcitonin and Insulin in Isobutylcyanoacrylate Nanocapsules: Protection Against Proteases and Effect on Intestinal Absorption in Rats
Authors: Lowe Philip J , Temple Cathy S 
Published: April 2011

Abstract
One of the major limiting steps for the absorption of peptide drugs from the intestine is proteolytic degradation. To slow this degradation, human calcitonin was trapped in polyacrylamide nanoparticles, and human calcitonin and insulin were encapsulated with polyisobutylcyanoacrylate. Human calcitonin trapped in polyacrylamide nanoparticles showed no delayed release characteristics and thus would not provide protection from proteases. Proteolytic degradation of human calcitonin and insulin in polyisobutylcyanoacrylate nanocapsules was slower than the free peptides in solution. The plasma pharmacokinetic profiles were consistent with increased survival time of the peptides in the intestine, with higher plasma concentrations of the peptides in the later time samples compared with the controls. However, the nanocapsules gave no significant overall enhancement of peptide absorption. This led to the conclusion that the nanocapsules released the peptides into the intestinal lumen, with small amounts then being absorbed but the rest largely degraded.
Hepatobiliary Disposition of 3′-Azido-3′-deoxythymidine (AZT) in the Rat: Effect of Phenobarbitone Induction
Authors: Bezek Štefan , Kukan Marián , Bohov Pavol 
Published: April 2011

Abstract
Isolated liver with a recirculating perfusate was used to study 3′-azido-3′-deoxythymidine (AZT) disposition in phenobarbitone-pretreated rats at 68 μm AZT concentration in the reservoir. Clearance of AZT in the livers obtained from control animals was 0·42 ± 0·01 (mean ± s.d.) mL min−1/10 g liver. Over the study period of 105 min, 12·7 ± 2·6% of the dose was excreted in bile and of this 95% was recovered as 3′-azido-3′-deoxy-5′-O-β-d-glucopyranuronosylthymidine (GAZT). The amount of GAZT found in the perfusate after 105 min of liver perfusion was &lt; 1% of the AZT dose introduced into the reservoir. Phenobarbitone pretreatment of rats resulted in a 5·5-fold increase of AZT clearance. In addition, the area under the perfusate concentration-time curve (AUC0–105 min) for 3′-amino-3′-deoxythymidine (AMT) and for a catabolite of unknown structure was increased 3- and 10-fold, respectively, and the amount of AZT dose excreted in the bile was nearly doubled. Thus phenobarbitone was capable of stimulating both detoxification of AZT to GAZT and bioactivation of AZT to AMT, a catabolite known to be highly toxic to human bone marrow cells. This induction was the result of enhancement of AZT catabolism rather than its transport into the cells, since on incubation of AZT (0–250 μm) with rat isolated hepatocytes, a linear relationship between concentration and amount taken up by the cells was shown. In addition, the rate of AZT uptake was not influenced by KCN, dinitrophenol, or temperature, which is consistent with a simple diffusion of AZT through the hepatocellular membrane. Rats dosed intraduodenally with [3H]GAZT excreted 5·8 ± 3·3% of the GAZT dose in bile within 4 h after administration. This suggests that enterohepatic recycling is involved in AZT disposition in the rat.
The Recognition of a Diarylimine as a Metabonate Produced During Incubation of N-Benzyl-4-chloroaniline with Hepatic Microsomal Preparations
Authors: Ulgen Chian-Ming Low M , Gorrod J W 
Published: April 2011

Abstract
Evidence is presented for the formation of N-benzylidene-4-chloroaniline as a metabonate during the metabolism of N-benzyl-4-chloroaniline. Control studies suggest that the diarylimine is formed as a chemical artifact from the debenzylation products (benzaldehyde and 4-chloroaniline). This novel observation indicates a possible pathway to amide formation from N-benzylanilines via diarylimines as intermediates.
Pharmacokinetic and Pharmacodynamic Studies of the Histamine H1-Receptor Antagonist Ebastine in Dogs
Authors: Puigdemont Anna , Queralt Mireia , Jansat Josep M , Martinez-Tobed Antonio 
Published: April 2011

Abstract
The pharmacokinetics and pharmacodynamics of ebastine at single oral doses of 10 and 20 mg were studied in six healthy beagle dogs. Plasma concentrations of the active metabolite of ebastine were measured at predetermined times after the dose. At these times an intradermal injection of 0·01 mL of a 0·2 mg mL−1 histamine diphosphate solution was given, and wheal areas were computed. The plasma elimination half-life of ebastine was 4·38 ± 1·01 h after 10 mg ebastine and 4·09 ± 0·74 h after 20 mg ebastine; the distribution volume was 3·99 ± 0·88 and 3·65 ± 0·75 L kg−1 after 10 and 20 mg of ebastine, respectively; the clearance after the 10 mg dose of ebastine was 0·67 ± 0·24 L h−1 kg−1 and after 20 mg ebastine was 0·63 ± 0·17 L h−1 kg−1. The mean histamine-induced wheal areas were significantly suppressed from 1 to 25 h after the 10 mg dose ebastine and from 1 to 32 h after the 20 mg dose ebastine, compared with the mean predose wheal areas (P &lt; 0·001). Maximum suppression of the wheals was 75 and 82% from 10 and 20 mg ebastine, respectively. A combined pharmacokinetic-pharmacodynamic model was used to analyse the relationship between inhibition of wheal skin reaction and changes in the active metabolite of plasma concentration after ebastine administration. A significant delay of 3–4 h was present between the maximum effect and the peak plasma concentration. Calculated from mean data, the rate constant for equilibration of the drug between plasma and effect site was 0·17 and 0·22 h−1 after 10 and 20 mg ebastine with a half-life of 4·13 and 3·56 h, respectively, and the steady-state plasma concentration resulting in 50% of maximal effect was 18·9 ± 4.8 ng mL−1 after 10 mg and 18·2 ± 5.7 ng mL−1 after 20 mg ebastine.