bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biphasic effects of acetaldehyde-biogenic amine condensation products on membrane fluidity
Authors: Tsuchiya Hironori 
Published: July 2003

Abstract
I have studied the effects of four acetaldehyde-biogenic amine condensation products on membrane fluidity of liposomes, consisting of 1-palmitoyl-2-oleoylphosphatidylcholine and cholesterol, by measuring fluorescence polarization using different probes.
The condensation products were 1-methyl-1,2,3,4-tetrahydro-β-carboline (MTBC), 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline (6-OH-MTBC), 3-carboxy-1-methyl-1,2,3,4-tetrahydro-β-carboline (3-C-MTBC) and 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol). They changed the fluidity of the hydrophobic and hydrophilic regions of liposomal membranes at micromolar levels almost corresponding to their antibacterial and antiplatelet concentrations, but their membrane effects varied by structure, concentration and membrane lipid composition. MTBC and salsolinol showed biphasic effects on the inner layers of membranes to enhance the fluidity at 250–1000 μM and reduce the fluidity at 50–100 μM, whereas both of them fluidized the outer layers of the membranes. 3-C-MTBC concentration-dependently fluidized both layers of membranes. 6-OH-MTBC most weakly enhanced and reduced the fluidity of the outer and inner layers, respectively. The membrane effect of MTBC was the greatest of the four condensation products. MTBC (50–1000 nM) significantly reduced the fluidity by exclusively acting on the membrane core, but was less effective in fluidizing the membrane surface. However, the others were not active at low nanomolar levels.
The membrane effects may be partly responsible for the antibacterial and antiplatelet actions of the acetaldehyde-biogenic amine condensation products, although they do not appear to be simple membrane fluidizers.
Vancomycin resistance reversal in enterococci by flavonoids
Authors: Liu Iain X , Durham David G , Richards R Michael E 
Published: July 2003

Abstract
The development of clinical vancomycin-resistant strains of enterococci (VRE) is a major cause for concern. Here we show that a combination of galangin or 3,7-dihydroxyflavone with vancomycin may be used to sensitize resistant strains of Enterococcus faecalis and Enterococcus faecium to the level of vancomycin-sensitive strains.
Minimum inhibitory concentrations (MICs) and viable counts were determined in Iso-sensitest broth using a microtitre method. MICs of vancomycin against 67% of resistant clinical isolates and a type strain of enterococci were lowered from &gt; 250 μg mL−1 to &lt; 4 μg mL−1 in the presence of galangin (12.5 μg mL−1) or 3,7-dihydroxyflavone (6.25 μg mL−1).
Viable counts for type culture E. faecalis ATCC 51299 showed the flavonoids alone significantly lowered numbers of colony forming units (CFUs). CFUs were maintained at low levels (&lt; 103 CFU mL−1) for 24 h by vancomycin/flavone combinations. This combinational action in reversing vancomycin resistance of enterococci highlights novel drug targets and has importance in the design of new therapeutic regimes against resistant pathogens.
The biopharmaceutical aspects of nasal mucoadhesive drug delivery
Authors: Ugwoke Michael Ikechukwu , Verbeke Norbert , Kinget Renaat 
Published: July 2003

Abstract
Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections. Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail.
Nasal drug administration is presently mostly used for local therapies within the nasal cavity. Anti-allergic drugs and nasal decongestants are the most common examples. However, nasal drug administration for systemic effects has been practised since ancient times. Nasally-administered psychotropic drugs by native Americans, the use of tobacco snuffs, and nasal administration of illicit drugs such as cocaine are all well known (Illum & Davis 1992). Nowadays, the nasal cavity is being actively explored for systemic administration of other therapeutic agents, particularly peptides and proteins (Illum 1992; Edman & Bjork 1992), as well as for immunization purposes (Lemoine et al 1998). To better understand the basis for nasal drug absorption and factors that can influence it, a brief review of the anatomy and physiology of the nose is appropriate.
Formulation and release characteristics of poly(lactic-co-glycolic acid) microspheres containing chemically modified protein
Authors: Kim Tae-Kyoung , Burgess Diane J 
Published: July 2003

Abstract
Chemical modification of proteins may influence their formulation into and release from polymeric microspheres. Three chemical modifications of rat serum albumin (RSA) were effected on the amine groups of this protein: conjugation with a polyanion using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, intermolecular cross-linking using glutaraldehyde, and reductive alkylation using propyl aldehyde. The modified proteins had different physicochemical properties as well as improved encapsulation efficiencies compared with native RSA microspheres.
The microspheres were incubated at 37°C for over one month to investigate the influence of protein modification on the release profiles. Microsphere degradation accelerated from the ninth day of the release studies and this coincided with an increase in the release rates. The degradation rates of poly(lactic-co-glycolic acid) microspheres containing either native or crosslinked RSA were more rapid than those containing either heparin conjugated or propylated RSA. This was in agreement with the release data, since the release of the native and crosslinked RSA were more rapid than those of the other modified proteins. The release profiles of the RSA-heparin conjugates and the propylated RSA were approximately zero rather than first order between the tenth and thirtieth day of study.
Chemical modification of protein may be a useful method to increase encapsulation efficiency and to decrease release rates of proteins that are to be used in microsphere formulations of potent therapeutic proteins.
Gastrointestinal transit of dosage forms in the pig
Authors: Davis S S , Illum L , Hinchcliffe M 
Published: July 2003

Abstract
The gastrointestinal transit of liquid, pellet and tablet formulations was measured under fasted conditions in the domestic pig (n = 4) using the technique of gamma scintigraphy.
The mean times for 50% gastric emptying for liquid and pellet systems were 1.4 and 2.2 h, respectively; tablets emptied between 1.5 and 6.0 h. Total transit times were in the order of 50 h. These data conform well to published values for the transit of liquid and solid food materials in the pig. The times are much shorter than those previously published for the transit of solid dosage forms in the pig.
We conclude that the domestic pig would be a good model to study the gastrointestinal transit of pharmaceutical formulations and the absorption of drug compounds.
An investigation into the thermal behaviour of an amorphous drug using low frequency dielectric spectroscopy and modulated temperature differential scanning calorimetry
Authors: He Renren , Craig Duncan Q M 
Published: July 2003

Abstract
The objective of the study was to investigate the use of low frequency dielectric spectroscopy as a means of characterizing the thermal transitions of an amorphous drug substance, indometacin, with particular emphasis on modelling the response using the Dissado-Hill function.
The low frequency dielectric behaviour of indometacin was measured over a temperature range of 10–160°C and a frequency range of 10−3-106 Hz. Modulated temperature differential scanning calorimetry (MTDSC) studies were also performed on equivalent samples, showing a glass transition, recrystallization and melting. Isothermal low frequency dielectric spectra of the sample at temperatures below recrystallization showed the dynamic dielectric relaxation associated with the amorphous phase, while changes in the real and imaginary permittivities were observed that were associated with recrystallization and subsequent melting. A small discontinuity was observed immediately above the recrystallization process in the MTDSC and dielectric data, suggested to correspond to a solid state transformation. The use of the Dissado-Hill function as a means of modelling the dielectric behaviour has also been described.
The study suggests that low frequency dielectric spectroscopy, used in conjunction with MTDSC and Dissado-Hill modelling, maybe a useful tool for the characterization of amorphous and crystalline drugs.
Effect of FITC-dextran molecular weight on its release from floating cetyl alcohol and HPMC tablets
Authors: Xu Guojie , Groves Michael J 
Published: July 2003

Abstract
The release mechanism of high molecular weight fluorescein isothiocyanate dextrans (FITC-dextrans) from HPMC hydrogel matrices was studied.
An anomaly was noted in the release behaviour of a series of high molecular weight FITC-dextrans from a tablet formulation designed to float in stomach contents. The tablets contained sodium bicarbonate and hydroxypropylmethyl cellulose (HPMC) in a cetyl alcohol matrix. When hydrated in an acid medium, this tablet consisted of a mixed solid with a viscous surface layer containing carbon dioxide bubbles through which the active ingredient (FITC-dextran) was released into the aqueous environment. However, it was observed that, above a critical molecular weight (approx. 65 kDa), the FITC-dextran was only released into the medium by an erosion-type mechanism, whereas, below this value, both diffusion and erosion processes took place. The key constraint appearedto bethe apparent gel pore-size of the hydrated HPMC that was approximately 12 nm in diameter, irrespective of the molecular weight of the HPMC samples evaluated.
It was concluded that FITC-dextran release was controlled by both FITC-dextran molecular weight and the HPMC hydrogel structure.
Microparticulate uptake mechanisms of in-vitro cell culture models of the respiratory epithelium
Authors: Foster Kimberly A , Yazdanian Mehran , Audus Kenneth L 
Published: July 2003

Abstract
The objective of this study was to examine the uptake mechanisms of fluorescent polystyrene microspheres of various diameters and surface chemistry by two human cell lines derived from the respiratory epithelium, A549 and Calu-3.
These results suggest that A549 and Calu-3 cells can internalize microspheres and that size and effective charge played an important role in the uptake process.
Pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under different food status
Authors: Yap S P , Yuen K H , Wong J W 
Published: July 2003

Abstract
We have investigated the pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under fed and fasted conditions in eight healthy volunteers.
The volunteers were administered a single oral dose of mixed tocotrienols (300 mg) under fed or fasted conditions. The bioavailability of tocotrienols under the two conditions was compared using the parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC0-∞).
A statistically significant difference was observed between the fed and fasted logarithmic transformed values of Cmax (P &lt; 0.01) and AUC0-∞ (P &lt; 0.01) for all three tocotrienols. In addition, the 90% confidence intervals for the ratio of the logarithmic transformed AUC0-∞ values of α-, γ- and δ-tocotrienols under the fed state over those of the fasted state were found to lie between 2.24-3.40, 2.05-4.09 and 1.59-3.81, respectively, while those of the Cmax were between 2.28-4.39, 2.31-5.87 and 1.52-4.05, respectively. However, no statistically significant difference was observed between the fed and fasted Tmax values of the three homologues. The mean apparent elimination half-life (t1/2) of α-, γ- and δ-tocotrienols was estimated to be 4.4, 4.3 and 2.3 h, respectively, being between 4.5- to 8.7-fold shorter than that reported for α-tocopherol. No statistically significant difference was observed between the fed and fasted t1/2 values. The mean apparent volume of distribution (Vd/f) values under the fed state were significantly smaller than those of the fasted state, which could be attributed to increased absorption of the tocotrienols in the fed state.
Secretory transport of p-aminohippuric acid across intestinal epithelial cells in Caco-2 cells and isolated intestinal tissue
Authors: Naruhashi Kazumasa , Tamai Ikumi , Sai Yoshimichi , Suzuki Nagao , Tsuji Akira 
Published: July 2003

Abstract
The intestinal transport of an organic anion, p-aminohippuric acid (PAH), was studied in Caco-2 cell monolayers and rat intestinal tissue mounted in Ussing chambers.
In both experimental methods, PAH exhibited vectorial transport with significantly greater permeability in the secretory direction than the absorptive direction, indicating net secretion. This secretory transport required metabolic energy, but protons or hydroxyl ions were not involved as the driving force. In Caco-2 monolayers, secretory transport of [3H]PAH was decreased, and the intracellular accumulation of PAH was increased with increasing concentration of unlabelled PAH at the basolateral side. Addition of probenecid and genistein at the basolateral side decreased the secretory transport of [3H]PAH; the accumulation was not changed by probenecid, but was increased by genistein. In addition, the initial uptake rate of [3H]PAH from the basolateral side was decreased by both PAH and probenecid, but not by genistein. Therefore, it is suggested that the transport of PAH in Caco-2 cells is regulated by several transporters: a genistein-sensitive transporter on the apical membrane and probenecid-sensitive transporters on both the basolateral and apical membranes. In rat intestinal tissues, the transport rate of PAH showed regional variation (ileum &gt; jejunum &gt; duodenum), suggesting that secretory transporters with high activity exist predominantly in the lower region of the small intestine.
The results suggest that PAH transport in both Caco-2 cells and rat intestinal tissues is regulated by multiple transporters on the apical and basolateral membranes, and these transporters have different characteristics.
Imidazolines inhibit secretory responses of rat colonic mucosa to calcium-dependent but not cyclic AMP-dependent secretagogues
Authors: Anderson Malcolm , Burleigh David 
Published: July 2003

Abstract
The purpose of this study was to investigate whether imidazolines have an anti-secretory action on intestinal epithelial cells. Muscle-stripped preparations of rat colon and monolayers of T84 human colonic epithelial cells were set up in Ussing chambers for measurement of short-circuit current. In rat colon acetylcholine, histamine, vasoactive intestinal polypeptide and forskolin elicited secretory responses which were recorded as increases in short-circuit current. Secretory responses to acetylcholine were inhibited in a concentration-dependent manner by the imidazolines phentolamine, idazoxan and clonidine. The effect of clonidine was not reversed by pre-incubation of mucosal preparations with yohimbine. Secretory responses to vasoactive intestinal polypeptide were unaffected by the three imidazolines. Phentolamine reduced responses of colonic mucosa to histamine but had no effect on responses to forskolin. Responses to vasoactive intestinal polypeptide and forskolin were significantly reduced in the presence of barium. In T84 cell monolayers phentolamine significantly reduced responses to acetylcholine. Three imidazolines, two with alpha-adrenoceptor-antagonist properties and one with alpha-agonist properties, have anti-secretory effects in rat colonic mucosal preparations. The anti-secretory action appears to discriminate between calcium-dependent and cyclic AMP-dependent secretagogues, inhibiting the former but not the latter.
Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formalin test in rats
Authors: Nayebi A R M , Hassanpour M , Rezazadeh H 
Published: July 2003

Abstract
Serotonergic systems are involved in the central regulation of nociceptive sensitivity. Fluoxetine, a selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT), was administered orally (0.16, 0.32, 0.8 mg kg−1 daily for 7 days), intraperitoneally (0.04, 0.08, 0.16 mg kg−1 day−1 for 7 days and a single dose of 0.32 mg kg−1) and intracerebroventricularly(10 μg/rat) to rats and nociceptive sensitivity was evaluated using the formalin test (50 μL of 2.5% formalin injected subcutaneously). The effect of fluoxetine was also studied in the presence of 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) and after co-administration with morphine. Oral (0.8 mg kg−1), intraperitoneal (0.16 and 0.32 mg kg−1) and intracerebroventricular (10 μg/rat) fluoxetine induced antinociception in the late phase of the formalin test. Furthermore, intrathecal administration of 5-HT (100 μg/rat) induced an analgesic effect. The analgesic effect of fluoxetine (0.16 and 0.32 mg kg−1, i.p.) and 5-HT (100 μg/rat, i.t.) was abolished by pre-treatment with 5,7-DHT (100 μg/rat, i.t.). In addition, the analgesic effect of 5-HT (100 μg/rat, i.t.) was decreased by pre-treatment with naloxone(2 mg kg−1, i.p.). Morphine (5 mg kg−1, i.p.) induced analgesia that was increased by fluoxetine (0.32 mg kg−1, i.p.). These results suggest that fluoxetine has an antinociceptive effect in tonic inflammatory pain through functional alteration of the serotonergic system and also potentiates the analgesic effect of morphine.
Antioxidative effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on peroxidation of phospholipid liposomes
Authors: Yamamoto Atsuko , Ichihara Kazuo , Hoshi Katsuji 
Published: July 2003

Abstract
The antioxidative effect of fluvastatin sodium (fluvastatin), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on lipid peroxidation of phosphatidylcholine (PC) liposomes was investigated in various peroxidizing systems. Fluvastatin markedly inhibited the formation of thiobarbituric acid reactive substances in iron (II)-supported peroxidation of liposomes (IC50 = 1.2 × 10−5 M). The order of magnitude of inhibition of each drug on the peroxidation was: butylated hydroxytoluene &gt; fluvastatin ≥ probucol ≥ pravastatin. Moreover, concentrations of fluvastatin ranging from 1 × 10−6 to 1 × 10−4 M inhibited peroxyl radical-mediated peroxidation of liposomes induced by water-soluble and lipid-soluble radical generators, 2,2-azobis (2-amidinopropane) dihydro-chloride and 2,2-azobis (2,4-dimethylvaleronitrile), respectively. However, pravastatin showed no effect against peroxyl radical-mediated peroxidation. These results indicate that fluvastatin acted non-enzymatically as an effective inhibitor against lipid peroxidation of PC liposomes and that the antioxidative effects of fluvastatin may be due to the scavenging action of fluvastatin on liposomal lipid peroxidation induced by peroxyl radicals generated in the aqueous and lipid phases.
Effects of long-term pretreatment with isoproterenol on inotropic responsiveness to α-adrenoceptor stimulation: study in isolated perfused rat hearts
Authors: Silva Cristina O , Monteiro-Filho Waldo O , Duarte Gloria P , Lahlou Saad 
Published: July 2003

Abstract
The effects of chronic pretreatment with isoproterenol (5 mg kg−1) daily for 10 days on cardiac α-adrenergic responsiveness in Langendorff heart preparations were investigated. Isoproterenol pretreatment caused cardiac hypertrophy (29%) as shown by a significant increase in the ratio of ventricular dry weight to body weight. In preparations from isoproterenol-pretreated rats, both maximum increases in left ventricular systolic pressure and heart rate elicited by isoproterenol (10−12 to 10−4 M) were significantly reduced (the isoproterenol concentration producing 50% of the maximum positive inotropic and chronotropic responses was enhanced almost 32- and 4-fold, respectively), while the positive inotropic response to phenylephrine (10−12 to 10−4 M) was significantly enhanced (the phenylephrine concentration producing 50% of the maximum positive inotropic effect was reduced almost 100-fold), compared with saline-pretreated rats. In preparations from both groups, phenylephrine infusion induced non-significant changes in heart rate and its positive inotropic response was reduced in the presence of propranolol (10−7 M) in the perfusion medium. Even under β-adrenoceptor blockade, the curve for the phenylephrine-induced positive inotropic effect remained shifted upward after isoproterenol pretreatment. Chronic isoproterenol pretreatment induces the expected cardiac β-adrenoceptor desensitization while simultaneously enhancing the positive inotropic responsiveness to phenylephrine in Langendorff heart preparations. These findings support the hypothesis that cardiac α1-adrenoceptor stimulation may contribute to the maintenance of myocardial function under conditions in which β-adrenoceptor function is compromised.
Antioxidants, vitamin C and dithiothreitol, activate membrane-bound guanylate cyclase in PC12 cells
Authors: Chen Zi-Jiang , Che Danian , Chang Chung-Ho 
Published: July 2003

Abstract
Antioxidants and antioxidant enzymes are known to protect against cell death induced by reactive oxygen species. However, apart from directly quenching free radicals, little is known about the effect of antioxidants on hormone-activated second messenger systems. We previously found that antioxidants such as 17-β estradiol and resveratrol activate membrane-bound guanylate cyclase GC-A, the receptor for atrial natriuretic factor (ANF), in PC12 cells. It is possible that other antioxidants may also activate membrane-bound guanylate cyclase GC-A. The aim of this study was to determine if dithiothreitol (DTT), vitamin C, and vitamin E activate membrane-bound guanylate cyclase GC-A in PC12 cells. The results showed that both DTT and vitamin C increased cGMP levels in PC12 cells, whereas vitamin E had no effect. DTT and vitamin C inhibited membrane-bound guanylate cyclase activity stimulated by ANF in PC12 cells. In contrast, DTT and vitamin C had no effect on soluble guanylate cyclase activity stimulated by substance P. Furthermore, NO synthase inhibitors L-NAME and aminoguanidine did not affect DTT- and vitamin C-stimulated guanylate cyclase activity. The results indicate that DTT and vitamin C, but not vitamin E, activate membrane-bound guanylate cyclase GC-A in PC12 cells.