bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEG-coated Poly(lactic acid) Nanoparticles for the Delivery of Hexadecafluoro Zinc Phthalocyanine to EMT-6 Mouse Mammary Tumours
Authors: Allemann Eric , Brasseur Nicole , Benrezzak Ouhida , Rousseau Jacques , Kudrevich Svetlana V , Boyle Ross W , Leroux Jean-Christophe , Gurny Robert , van Lier Johan E 
Published: April 2011

Abstract
Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in three vehicles: poly(d,l-lactic acid) (PLA) nanoparticles, polyethylene glycol (PEG)-coated nanoparticles and a Cremophor EL (CRM) oil-water emulsion. Nanoparticles were prepared by the salting-out procedure. Biodistribution of the dye was assessed by fluorescence in EMT-6 mammary tumour bearing mice after intravenous injection of 1 μmol kg−1 ZnPcF16.
Plain nanoparticles were rapidly retained by the reticuloendothelial system (RES) as reflected by the low area under the blood concentration-time curve (AUC0–168, 57 μg h g−1). Little tumour uptake of the dye was observed with this formulation. In contrast, PEG-coated nanoparticles displayed a reduced RES uptake, leading to significantly higher blood levels over an extended period (t1/2 30 h; AUC0–168 227 μg h g−1) and enhanced tumour uptake. At 48 h post injection, tumour to skin and tumour to muscle concentration ratios reached 3·5 and 10·8, respectively.
Blood levels of ZnPcF16 after administration as a CRM emulsion decreased faster than with PEG-coated nanoparticles (t1/2 12 h), but since no early liver uptake was observed, the AUC0–168 and the tumour uptake were only slightly lower. However, with the CRM formulation, a late liver uptake was observed, reaching 51% of the injected dose after 7 days.
Iloprost: Intracellular Ca2+-dependent Contractile Effect on Isolated Smooth Muscle Cells from Guinea-pig Ileum
Authors: Botella Alain , Jeanneton Olivier , Delvaux Michel , Frexinos Jacques , Bueno Lionel 
Published: April 2011

Abstract
Prostaglandin E2 (PGE2) and iloprost induced a concentration-dependent contraction of smooth muscle cells isolated from the circular layer of guinea-pig ileum. PGE2- and iloprost-induced contractions were inhibited by the selective EP1-receptor antagonist, SCI9220 (1-acetyl-2-(8-chloro-10, 11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl)-hydrazine), indicating the involvement of the EP1 subtype of the PGE2 receptor. When cells were incubated for 10 min in the presence of strontium (4 mm L−1), an inhibitor of the release of Ca2+ from intracellular store, the contractile effect of PGE2 and iloprost was inhibited. In contrast, incubation of cells in Ca2+-free medium, Ca2+-free medium plus EGTA, or in the presence of nifedipine, an organic Ca2+-channel blocker, did not alter the PGE2- and iloprost-induced contraction. These observations suggest that the myogenic effect of PGE2 and iloprost on intestinal smooth muscle is dependent on the release of intracellular calcium.
Angiostasis and Vascular Regression in Chronic Granulomatous Inflammation Induced by Diclofenac in Combination with Hyaluronan in Mice
Authors: Alam C A S , Seed M P , Willoughby D A 
Published: April 2011

Abstract
Angiostasis and vascular regression in chronic granulomatous inflammation was assessed in mice induced with diclofenac in combination with hyaluronan.
The local injection of 0·1 mL HYAL EX-0001 (0·18% diclofenac in 2·5% hyaluronan) reduced granulomatous development after six days treatment from 150·4 ± 13·8 (0·18 saline) to 117·1 ± 17·8 mg (dry weight, n = 10), but not significantly when compared with 0·1 mL 2·5% hyaluronan alone or diclofenac in 0·1 mL saline. Diclofenac administered in saline had no significant effect when compared with saline control. The vascular density, expressed as carmine content per mg dry weight tissue, in those animals treated with HYAL EX-0001 was also significantly reduced to 5·27 ± 0·55 μg mg−1 (P &lt; 0·1, n = 10) when compared with saline control (7·99 ± 1·0), hyaluronan alone (7·20 ± 1·0), and diclofenac in saline. (7·36 ± 1·28). A similar profile of activity was seen on topical application except that all treatments did not affect granulomatous tissue development.
On therapeutic dosing of mice daily with HYAL EX-0001 from day 7 after induction of the granulomatous tissue, the granulomatous tissue development was dramatically reduced from 111·67 ± 4·40 mg (n = 14 on day 7) to 60·23 ± 7·22 (P &lt; 0·001, n = 8 on day 14) and 54·98 ± 7·88 (P &lt; 0·001, n = 8 on day 21). HYAL EX-0001 after 14 days of application significantly reduced granulomatous tissue mass when compared with the hyaluronan-dosed control on day 21 (89·58 ± 7·49, P = 0·01, n = 8). The granulomatous tissue lost weight on the application of hyaluronan for 14 days by 19·8% (P &lt; 0·01).
The vascular density of the tissues was 15·05 ± 0·63 μg mg−1, which HYAL EX-0001 significantly reduced to 11·96 ± 1·14 (P &lt; 0·05) after 7 days application and 11·25 ± 1·21 μg mg−1 (P &lt; 0·02) after 14 days application. The latter was significantly inhibited when compared with the day 21 hyaluronan control (14·02 ± 1·39 μg mg−1, P &lt; 0·05). The day 7 vascular density was not significantly reduced by the topical application of hyaluronan from day 7 to 21.
The results suggest that hyaluronan is acting as a novel and effective drug delivery system, and may explain the therapeutic effectiveness of HYAL CT-1101 on basal cell carcinoma and actinic keratosis.
Semicarbazide-sensitive Amine Oxidase Activity in White Adipose Tissue of the Insulin-deficient Rat
Authors: Conforti L , Pirisino R , Ignesti G , Banchelli G , Raimondi L 
Published: April 2011

Abstract
We have investigated whether the effects in white adipose tissue due to insulin deficiency might also be related to an alteration of histamine levels which are regulated by semicarbazide-sensitive amine oxidase.
The lack of circulating insulin induced by streptozotocin produced, in rat white adipose tissue, a loss of affinity of the semicarbazide-sensitive amine oxidase for histamine oxidation. In parallel, a decrease of cell transformation, measured by glycerol-3-phosphate dehydrogenase activity and an augmented sensitivity to histamine lipolysis were observed.
These findings could contribute to the understanding of histamine metabolism and function in diabetic rats and to the knowledge concerning amine oxidases in this animal pathology.
Dexamethasone Reduces the Behavioural Effects Induced by Baclofen in Mice
Authors: Capasso A , Di Giannuario A , Loizzo A , Pieretti S , Sorrentino L 
Published: April 2011

Abstract
The present study examines the influence of dexamethasone on the behavioural effects induced by baclofen in mice. The behaviour elements considered were locomotor activity, motor co-ordination, catalepsy, stereotyped behaviour and antinociception.
Baclofen (1·0–4·0–6·0 mg kg−1, i.p.) induced a significant reduction of all behavioural elements studied and an antinociceptive effect was recorded. Dexamethasone alone (0·1–0·5–1·0 mg kg−1, i.p.) did not induce significant changes in the behaviour elements considered. On the other hand, when the steroid was injected immediately before baclofen a significant reduction of baclofen's behavioural effects was found.
Our results suggest a possible link between glucocorticoid and the GABA-ergic system.
Acid-base Properties of Terbutaline in Terms of Protonation Macro- and Microconstants
Authors: Takács-Novák Krisztina , Noszál Béla , Tökes-Kövesdi Márta , Szász György 
Published: April 2011

Abstract
The acid/base chemistry of terbutaline was characterized at the molecular level in terms of protonation macroconstants and microconstants. The macroconstants were measured by potentiometry and calculated by standard evaluation methods.
The stepwise macroconstant values were log K1 = 11·01, log K2 = 9·89, and log K3 = 8·57 at 250°C and 0·2 m ionic strength. The microconstants were deduced using the relationships between macro- and microconstants and an appropriate data set of model compounds (resorcinol and phenylephrine). The molecule of terbutaline contains three ionizable functional groups. In the unprotonated form of the molecule, the two identical phenolate groups are slightly more basic than the secondary amino group, whereas the amino basicity significantly exceeds that of the phenolate site, when the other phenol is protonated. This is due to the large phenolate-phenolate intramolecular interaction. The phenolate-phenolate and the phenolate-amino interactivity parameters were found to be −1·21 and −0·41 log E units, respectively.
Acid-base Equilibria of 1,4-Benzodiazepine 4-Oxides by Spectrophotometry
Authors: Yang Shen K 
Published: April 2011

Abstract
Chlordiazepoxide (a 1,4-benzodiazepine 4-oxide) is an anxiolytic/hypnotic drug in clinical use. It was reported to be predominantly protonated at the N-oxide oxygen in acidic aqueous solutions at pH ≪ 4·6 (pKa). We have studied the acid-base equilibria of three 1,4-benzodiazepine 4-oxides (chlordiazepoxide, diazepam 4-oxide, and nordiazepam 4-oxide) by ultraviolet-visible spectrophotometry. The results indicate that chlordiazepoxide is not protonated at the N-oxide oxygen, but rather at the nitrogen of an imine bond between C2 carbon and its nitrogen substituent in acidic media.
An In-vitro Evaluation of Silicone Elastomer Latex for Topical Drug Delivery
Authors: Li Luk Chiu , Vu Ngocoanh Thi 
Published: April 2011

Abstract
A silicone elastomer latex was evaluated as a topical drug-delivery system.
With the addition of a fumed silica and the removal of water, the latex produced elastomeric solid films. The water vapour permeability of the solid film was found to be a function of the film composition. An increase in silica content and the incorporation of a water-soluble component, PEG 3350, rendered the silicone elastomer-free film even more permeable to water vapour. The release of hydrocortisone from the elastomer film can be described by a matrix-diffusion-controlled mechanism. Drug diffusion is thought to occur through the hydrophobic silicone polymer network and the hydrated hydrophilic silica region in the film matrix. Silicone elastomer film with a higher silica content exhibited a faster drug-release rate. The addition of PEG 3350 to the film further enhanced the drug-release rate.
Pseudo-ternary Phase Diagrams of Lecithin-based Microemulsions: Influence of Monoalkylphosphates
Authors: Trotta Michele , Ugazio Elena , Gasco Maria Rosa 
Published: April 2011

Abstract
The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was delineated, at 25°C, for systems containing water, soybean lecithin, sodium monoalkylphosphate (hexyl or octyl), alcohol and isopropyl myristate. Six straight or branched alcohols (1-butanol, 2-butanol, isobutanol, 1-pentanol, 2-pentanol, 3-pentanol) were investigated as co-surfactants. A constant lecithin/alcohol mixing ratio was used, while the aqueous phase consisted of a solution of alkylphosphates at different concentrations.
An increase of the microemulsion domain was seen by increasing the concentration of the alkylphosphate. With 0·2 m hexylphosphate, as aqueous phase, the microemulsion domain consisted of a single, region, that, in the presence of butylic alcohols, spanded the greater portion of the phase diagram. In the presence of amyl alcohols the area of this region was much smaller. With 0·2 m octylphosphate the realm of existence of the microemulsions, except for 1-pentanol, consisted of two regions separated by a liquid-crystal region. With all the alcohols examined, the liquid-crystal phase solubilized a larger amount of oil in the presence of octylphosphate than in the presence of hexylphosphate.
The stability ranges of microemulsions in systems containing soybean lecithin, alcohol, water, and isopropyl myristate can be greatly increased by using a second hydrophobic amphiphile, such as hexylphosphate, to adjust the hydrophilic-lipophilic balance or the spontaneous peaking properties of lecithin-alcohol systems.
Absorption Enhancement of a Hydrophilic Model Compound by Verapamil After Rectal Administration to Rats
Authors: Noach Arthur B J , Blom-Roosemalen Margret C M , de Boer Albertus G , Breimer Douwe D 
Published: April 2011

Abstract
The use of verapamil as an absorption enhancer for the paracellular route in-vivo was studied using FITC-labelled dextran (molecular weight 4000) (FD-4) as a hydrophilic model compound for transport enhancement.
The kinetics of FD-4 after intravenous doses of 1 or 10mg could be described by a two-compartment model with a systemic clearance of approximately 2mL min−1 and a terminal plasma half-life of approximately 36 min. Rectal administration to rats, performed as a rectal infusion of 10 mg FD-4 together with 7 mm verapamil, resulted in a 10-fold increase in the percentage of the dose absorbed over a 5-h period compared with the control and a 6-fold increase compared with a bolus administration, although the total amount absorbed remained relatively low (approx. 3% maximum). Large inter-animal variation in effect values were noted.
The data indicate that although verapamil is able to enhance the absorption of hydrophilic compounds in-vivo, practical application of verapamil for this purpose does not seem feasible.
Zinc Sulphadiazines: Novel Topical Antimicrobial Agents for Burns
Authors: Lee A R , Huang W H 
Published: April 2011

Abstract
Two new zinc sulphadiazine (Zn(SD)2)-amine complexes, zinc sulphadiazine-methylamine (Zn(SD)2(CH3NH2)2) and zinc sulphadiazine-ethylenediamine (Zn(SD)2(C2H8N2)3·H2O), were prepared and compared with silver sulphadiazine (AgSD). The compounds were readily obtained by reaction of zinc nitrate hexahydrate with sulphadiazine or its salt in methylamine and ethylenediamine, respectively.
Structure was established by X-ray crystallography and ultraviolet-visible, infrared and nuclear magnetic resonance spectroscopy. The products were effective, in-vitro, against Gram-positive and Gram-negative bacteria as well as fungus. However, their activity is partially reversed by p-aminobenzoic acid. Further investigations in burned mice revealed that these compounds displayed a potential value in the prevention and treatment of wound healing, and diminution of mortality and weight loss. The toxicity of Zn(SD)2 derivatives was much lower than that of AgSD. The better aqueous solubility and skin permeability may explain the reason for their superiority over AgSD in the efficacy for topical therapy.
Zn(SD)2(CH3NH2)2 was consistently more potent and was chosen for further development in clinical uses. The similarity in complexation between Zn(SD)2(CH3NH2)2 and AgSD may be significant to distinguish that from any other Zn(SD)2 derivative in bioactivity.
Antitumour Effects and Pharmacokinetics of Combination of Vinblastine with a Staurosporine Derivative, NA-382, in P388/ADR-bearing Mice
Authors: Miyamoto Ken-Ichi , Takeda Keiko , Koga Kenjiro , Ohshima Taeyuki , Wakusawa Shinya 
Published: April 2011

Abstract
The effects of a staurosporine derivative, N-ethoxycarbonyl-7-oxostaurosporine (NA-382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug-resistant P388/ADR-bearing mice.
At first, the in-vitro experiments indicated that NA-382 permeated into the cells better and were more effective in combined cytotoxicity with vinblastine and on accumulation of vinblastine than with verapamil in P388/ADR cells. In combined intraperitoneal injection with vinblastine (200 μ kg−1) into P388/ADR-bearing mice, NA-382 in a suspension form (10 mg kg−1) prolonged the life-span of the mice near to that of P388/S-bearing mice treated with vinblastine alone, but verapamil even at the maximum tolerated dosage (30 mg kg−1) barely affected the in-vivo antitumour effect of vinblastine.
When simultaneously administered with vinblastine to P388/ADR-bearing mice, NA-382 maintained significantly higher vinblastine levels in the tumour cells for 24 h and gave a larger area under the time-intracellular vinblastine concentration curve (0 to 24 h) than those receiving vinblastine alone, with long retention of the agent in ascitic fluid. Verapamil increased the cellular vinblastine content for only 6 h, accompanying a rapid elimination of the agent from the ascitic fluid.
This study indicates that NA-382 is more effective against multidrug-resistance than verapamil, and its suspension is also advantageous for cancer chemotherapy of multidrug-resistant tumours.
Influences of Immobilization and Footshock Stress on Pharmacokinetics of Theophylline and Caffeine in Rats
Authors: Okazaki Masatoshi , Eto Kohei , Furuno Katsushi , Oishi Ryozo , Gomita Yutaka 
Published: April 2011

Abstract
The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg−1) and caffeine (30 mg kg−1) administered orally were examined in rats.
The immobilization stress for 30 min or 1 h immediately after oral administration caused marked immobilization period-related decreases in plasma theophylline concentrations during the absorption phase, but did not affect plasma caffeine concentrations. The ka and Cmax values for theophylline were significantly decreased, and the tmax was significantly increased. On the other hand, when the immobilization stress was loaded for 1 or 3 h before the oral administration, the plasma theophylline or caffeine concentrations were not affected. The footshock stress for 30 min immediately after oral administration did not significantly decrease plasma theophylline concentrations during the absorption phase.
These results suggest that the pharmacokinetics of theophylline are influenced by strong stress, possibly due to the inhibition of its absorption from the gastrointestinal tract, but the pharmacokinetics of caffeine are not influenced by stress, probably due to its central action.
Comparison of Procedures for Measuring the Quaternary N-Glucuronides of Amitriptyline and Diphenhydramine in Human Urine with and without Hydrolysis
Authors: Fischer Dorothee , Breyer-Pfaff Ursula 
Published: April 2011

Abstract
The activities of β-glucuronidases from Helix pomatia, Escherichia coli and rat towards the N-glucuronides of amitriptyline and diphenhydramine were considerably lower than those towards standard substrates.
The two N-glucuronides were analysed in urine samples by the following procedures: HPLC of the intact conjugate after solid-phase extraction on a cation exchanger cartridge or after direct injection of urine; HPLC of the aglycone after hydrolysis with β-glucuronidase from H. pomatia or E. coli or after alkaline hydrolysis. Solid-phase extraction led to the highest recovery and precision, and sensitivity can be improved by extracting a larger volume of urine.
On application to samples from patients under treatment with amitriptyline, the results of all procedures except alkaline hydrolysis were in good agreement. When diphenhydramine N-glucuronide was analysed in urine samples of volunteers, solid-phase extraction, hydrolysis by E. coli glucuronidase and alkaline hydrolysis resulted in similar values.
Compression of Lactose, Glucose and Mannitol Granules
Authors: Juppo Anne Mari , Kervinen Lasse , Yliruusi Jouko , Kristoffersson Eeva 
Published: April 2011

Abstract
The effect of the amount of granulation liquid, compression speed and maximum compression force on the compressibility and compactibility of lactose, glucose and mannitol granules was studied. The porosity based on the geometrical shape and the uniformity of weight of tablets was also studied.
Lactose and mannitol granules showed a greater compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for tablet production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.
Particle Size Studies for Subcutaneous Delivery of Poly(lactide-co-glycolide) Microspheres Containing Ovalbumin as Vaccine Formulation
Authors: Uchida Takahiro , Goto Shigeru , Foster Todd P 
Published: April 2011

Abstract
The primary objectives of the present study were to produce poly(lactide-co-glycolide) (PLGA) microspheres with different diameters, to characterize these microspheres which were loaded with a model antigen, ovalbumin and to evaluate the effect of microsphere particle size on the serum antibody levels following administration to mice.
Four kinds of ovalbumin-loaded PLGA microspheres with different diameters (1·2, 3·5, 7·0 and 14·3 μm as mean volume diameter) were manufactured by a w/o/w emulsion/solvent evaporation method. Low loading percent (0·08%-0·25%w/w) and efficiencies (8–25% w/w) were observed. Examination using scanning electron photomicrographs showed smooth spherical particles. The in-vitro release of ovalbumin from microspheres showed an expected burst release with all batches and the extent of the burst release increased with decreasing diameters of spheres; PLGA microspheres with the smallest diameter (1·2/μm) showed an 80% burst release within one day. Approximately 10–60% of ovalbumin remained unreleased 30 days later.
The single subcutaneous administrations of ovalbumin-loaded PLGA microspheres with different diameters to mice induced good antibody responses above ovalbumin saline negative controls at 3, 6, 9, and 12 weeks after inoculation. Especially, 0·16% ovalbumin-loaded PLGA microspheres having mean volume diameter of 3·5 /μm exhibited the best immune responses with values greater than those obtained after inoculation with adjuvants such as complete Freund's adjuvant or alum as positive control.
The strong adjuvant activity of PLGA microspheres as vaccine formulation was suggested.
The Transfer of Polystyrene Microspheres from the Gastrointestinal Tract to the Circulation after Oral Administration in the Rat
Authors: Eyles J , Alpar H O , Field W N , Lewis D A , Keswick M 
Published: April 2011

Abstract
Factors relating to the transfer of latex microspheres of 0·87 μm mean diameter from the gastrointestinal tract (GIT) to the circulation have been investigated.
The rapidity of appearance and the number of particles increased when the volume of water used as a suspending vehicle was increased. This was probably due to barrier cell integrity being compromised so that the movement of particles across the enterocytes would be enhanced. Particles were swept into these channels by the waterflow. The tonicity of the fluid was important as isotonic and hypertonic saline were not as affective as water in transferring particles. Particles were transferred from GIT segments adjacent to the stomach which may in part explain the rapid appearance of particles in the circulation. Particle uptake was blocked by cytochalasin B which suggests an active component may also be involved.
The Effect of Lysine, a Water-structure Breaker, on the Stability of Phospholipid-stabilized Emulsions
Authors: Lutz O , Groves M J 
Published: April 2011

Abstract
Phospholipid-stabilized emulsion properties were studied in the presence of lysine, a water-structure breaker, using two unrelated procedures, photon correlation spectroscopy and a light obscuration instrument. Commercial Intralipid was used as a control.
Lysine 0·125, 0·25 and 0·5 M induced changes in the size distribution of a non-heated model emulsion system, irrespective of any changes produced by environmental pH. Some of the laboratory-prepared emulsions containing lysine were more stable than the corresponding commercial heat-sterilized product Intralipid, once heated.
The results suggest that lysine is producing an effect on the nascent oil-water interface that controls the physical stability of the system. Once the heat-induced interfacial rearrangement of the individual phospholipid molecules occurs, the influence of lysine becomes diminished.