bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the reactivity of a tertiary allylic alcohol in an acetophenonic series, a model for natural products synthesis
Authors: Hélesbeux J J , Séraphin D , Duval O , Richomme P , Bruneton J 
Published: July 2003

Abstract
The synthesis of benzopyranic simplified analogues of dibenzopyranic natural compounds is described, together with the access to a precursor of a new furobenzopyranic natural product. These natural products have anti-cancer activity. The 1,3-diacetoxy-2-acetyl-4-(3-hydroxy-3-methylbut-1-enyl)benzene synthone is used as a common precursor to these structures.
5-Substituted 3,4-dihydro-3-amino-2H-1-benzopyran derivatives: synthesis and interaction with serotoninergic receptors
Authors: Rezaie R , Joseph B , Bremner J B , Delagrange P , Kopp C , Misslin R , Pfeiffer B , Renard P , Guillaumet G 
Published: July 2003

Abstract
A new series of 3,4-dihydro-3-amino-2H-1-benzopyran derivatives (1 and 2) bearing various substituents on the 5-position was successfully prepared via palladium-mediated cross-coupling reactions. Some of the new compounds showed high affinity for 5-HT1A and 5-HT7 receptors. The best affinity for the 5-HT1A and 5-HT7 receptors was obtained for 2b (Ki = 0.3 nM for 5-HT1A and 3.1 nM for 5-HT7). The anxiolytic activity of compound 2b was evaluated.
Pharmacokinetic study on gastrointestinal absorption of insulinomimetic vanadyl complexes in rats by ESR spectroscopy
Authors: Fugono Jun , Yasui Hiroyuki , Sakurai Hiromu 
Published: July 2003

Abstract
Recently, we have shown that oral administrations of vanadyl (+ 4 oxidation state of vanadium) complexes normalize the blood glucose level of streptozotocin-induced diabetic rats (STZ-rats). To develop clinically useful insulin-mimetic vanadyl complexes, clarification of the pharmacokinetic features of vanadyl compounds is essential. First, we investigated the absorption processes of three compounds, an ionic form of vanadyl sulfate (VS) and the complex forms of bis(picolinato)oxovandium(IV) (VO(pic)2) and bis(6-methylpicolinato)oxovanadium(IV) (VO(6mpa)2), from the gastrointestinal tract of healthy rats. The concentration curves of paramagnetic vanadyl species in the blood of rats after oral administration of these compounds, as monitored by X-band electron spin resonance (ESR) spectroscopy, exhibited biphasic increasing patterns, indicating that these compounds were absorbed from more than two sites in the gastrointestinal tract. The bioavailability of the compounds was enhanced in the following order on both oral and intraperitoneal administration: VO(6mpa)2 &gt; VO(pic)2 &gt; VS. In addition, bioavailability of the VO(6mpa)2 on ileal administration was enhanced compared with that using other administration sites such as the stomach and jejunum, and resulted in an enhancement about 1.8 fold that compared with oral administration. On the basis of these results, we concluded that the bioavailability of the complex is enhanced most effectively by delivery of the VO(6mpa)2 complex to the ileum.
Hexarelin - evaluation of factors influencing oral bioavailability and ways to improve absorption
Authors: Westberg Carina , Benkestock Kurt , Fatouros Angelica , Svensson Marianne , Sjöström Brita 
Published: July 2003

Abstract
Hexarelin, a hexapeptide with growth hormone-releasing activity, has been found in man to have a biological bioavailability (estimated from growth hormone levels) of 0.3 ± 0.1 % after oral administration. The cause of the low oral efficacy of hexarelin and means of improving its absorption have been evaluated. It was found that hexarelin was degraded in the presence of the contents of the intestine. The metabolite was identified as hexarelin deamidated at the lysine residue. The degradation of hexarelin in the contents of rat ileum was inhibited by the addition of chymostatin, Pefabloc SC, EDTA, and EGTA. Furthermore, the presence of pancreatic proteases from pancrease substitute drugs caused a degradation of hexarelin that could be inhibited by the addition of Pefabloc SC. The same hexarelin metabolite that was found with the contents of rat ileum was found in the presence of human, porcine and bovine trypsin. Hexarelin permeability across rat ileum and in Caco-2 cell monolayers was low. An increase in hexarelin permeability was observed in the presence of different permeability enhancing agents.
The use of polymeric solid phase extraction and HPLC analysis for the determination of ranitidine in routine plasma samples obtained from paediatric patients
Authors: Hare L G , Millership J S , Collier P S , McElnay J C , Carson D J , Shields M S 
Published: July 2003

Abstract
A sensitive HPLC method for the determination of ranitidine in small-volume (0.5 mL) paediatric plasma samples is described. Plasma samples were extracted using a simple, rapid solid phase extraction (SPE) technique developed using disposable copolymer packed SPE cartridges. Chromatographic separation was achieved by reverse-phase HPLC with isocratic elution using a μBondapak C18 column and a phosphate buffer (10 mm, pH 3.75)-acetonitrile (87:13 v/v) mobile phase with UV detection at 313 nm. The HPLC system exhibited linearity in the range 8–800 ng mL−1. Intraday % CV and % bias values were in the range 1.28–8.09% (% bias %-4.33 to %-0.87) and interday % CV and % bias values were in the range 0.73–15.28% (% bias %-1.80 to +1.65). The limits of detection and quantitation obtained were 2 ng mL−1 and 8 ng mL−1, respectively, and ranitidine extraction recoveries from plasma ranged from 92.30 to 103.88%. In this study, the developed HPLC and SPE methodologies have been successfully applied to the determination of ranitidine concentrations in 68 paediatric plasma samples. The sampled population was drawn from patients already receiving the study drug therapeutically. Patients recruited had received ranitidine by two main routes - oral and intravenous. The plasma concentrations of ranitidine encountered in paediatric samples following oral or intravenous administration of a range of prescribed doses are presented graphically. These profiles are based on analysis of the first 68 plasma samples obtained from the first 35 patients recruited to the study receiving ranitidine by the oral or intravenous route.
Monoamine oxidase inhibitory activity of some Hypericum species native to South Brazil
Authors: Gnerre Carmela , von Poser Gilsane L , Ferraz Alexandre , Viana Alice , Testa Bernard , Rates Stela M K 
Published: July 2003

Abstract
The total methanol crude extracts and petroleum ether, chloroform, and methanol fractions obtained from Hypericum species, H. caprifoliatum, H. carinatum, H. connatum, H. cordatum, H. myrianthum, H. piriai, H. polyanthemum and H. brasiliense, all native to South Brazil, were assayed for monoamine oxidase A (MAO A) and MAO B inhibitory activity in rat brain mitochondrial preparations at concentrations ranging from 1 to 20 μg mL−1. Three benzo-pyrans, HP1 (6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-iso-butyryl-5-methoxy-2,2-dimethylbenzopyran) and HP3 (5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethylbenzopyran) isolated from H. polyanthemum were also tested at maximal concentrations of 150, 150 and 75 μ, respectively. The lipophilic extracts of H. polyanthemum, H. caprifoliatum and H. piriai displayed MAO A inhibitory activity greater than 50%. Among the benzopyrans, only HP3 showed significant activity, with an IC50 value of 22 μ. The total methanol crude extracts of aerial parts from H. carinatum, H. connatum, H. cordatum, H. polyanthemum and H. piriai were evaluated for antidepressant activity in the Porsolt's forced swimming test in Wistar rats (270 mg kg−1 day−1; i.p); however, none of them showed activity.
In-vitro and in-vivo immunomodulatory effects of syringin
Authors: Cho Jae Youl , Nam Kwon Ho , Kim Ae Ra , Park Jisoo , Yoo Eun Sook , Baik Kyong Up , Yu Young Hyo , Park Myung Hwan 
Published: July 2003

Abstract
Syringin was found to possess immunomodulatory activity by which it inhibited the in-vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea-pig serum through suppression of C3-convertase of the classical complement. In this study, we examined its in-vitro and in-vivo activity on tumour necrosis factor (TNF)-α and nitric oxide (NO) production, CD4 + T cell and CD8+ cytotoxic T cell (CTLL-2) proliferation, and croton oil-, arachidonic acid- and fluorescein-isothiocynate (FITC)-induced mouse ear oedema model. Syringin significantly inhibited both TNF-α production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and CD8+ T cell (CTLL-2) proliferation in a dose-dependent manner, whereas neither NO production nor CD4+ T cell proliferation were blocked even by high concentrations of syringin. In the in-vivo experiments, syringin also significantly suppressed FITC-induced ear oedema in mice but not the ear oedema induced by croton or arachidonic acid. These results suggest that syringin may be implicated as an immunomodulator having an anti-allergic effect rather than an antiinflammatory effect. The anti-allergic effect of syringin seems to be due, in part, to inhibition of TNF-α production and cytotoxic T cell proliferation.
Inhibition of prostaglandin E2 production by 2′-hydroxychalcone derivatives and the mechanism of action
Authors: Kim Yong Pil , Ban Hyun Seung , Lim Soon Sung , Kimura Natsuko , Jung Sang Hoon , Ji Jun , Lee Sanghyun , Ryu Nama , Keum Sam Rok , Shin Kuk Hyun , Ohuchi Kazuo 
Published: July 2003

Abstract
The effects of 14 synthetic 2′-hydroxychalcone derivatives on prostaglandin E2 (PGE2) production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), were examined to clarify the structure-activity relationship. 2′,4-Dihydroxy-4′-methoxychalcone (compound 3), 2′,4-dihydroxy-6′-methoxychalcone (compound 8) and 2′-hydroxy-4′-methoxychalcone (compound 9) suppressed PGE2 production more potently than the other compounds. The IC50 (50 % Inhibitory concentration) value for compounds 3, 8 and 9 was calculated to be 3 μ. The activity of cyclooxygenase (COX)-1 was inhibited slightly by compound 9, but that of COX-2 was not inhibited. At concentrations that inhibited the production of PGE2, compound 9 had no effect on the release of radioactivity from [3H]arachidonic acid-labelled macrophages stimulated by TPA. Western-blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by compound 9 in parallel with the inhibition of PGE2 production. Compounds 3 and 8 had similar effects. These findings suggest that 4′-methoxyl and 6′-methoxyl groups are required for the expression of more potent inhibitory activity against PGE2 production, and that the inhibition of PGE2 production by these 2′-hydroxychalcone derivatives is due to the inhibition of TPA-induced COX-2 protein expression.
The challenge of gene therapy and DNA delivery
Authors: Phillips Anthony J 
Published: July 2003

Abstract
It is 10 years since the first gene therapeutic was administered to patients. Since that time approximately 3500 patients have been treated and although some evidence of gene transfer has been seen it has generally been inadequate for a meaningful clinical response. The major challenges have been delivery of DNA to the target cells and duration of expression. A variety of gene transfer systems have been evaluated and these are summarized with their advantages and disadvantages. Encouraging data have been obtained recentlyby a number of workers and there is some optimism that the enormous potential of gene therapy will be realized in the second decade of its development.
New strategies for polymer development in pharmaceutical science — a short review
Authors: Godwin A , Bolina K , Clochard M , Dinand E , Rankin S , Simic S , Brocchini S 
Published: July 2003

Abstract
We are developing synthetic polymers for pharmaceutical and medical applications. These applications can be broadly grouped on how the polymer will be utilized e.g. material, excipient or molecule. Our focus is to develop polymers with more defined structures that are based on biological, physicochemical and/or materials criteria. Strategies are being developed to more efficiently optimize structure—property correlations during preclinical development. We describe two examples of our research on pharmaceutical polymer development: narrow molecular weight distribution (MWD) homopolymeric precursors which can be functionalized to give families of narrow MWD homo- and co-polymers, and hydrolytically degradable polymers.
Oral sustained delivery of theophylline from thermally reversible xyloglucan gels in rabbits
Authors: Miyazaki Shozo , Kawasaki Naoko , Endo Kumiko , Attwood David 
Published: July 2003

Abstract
Thermally reversible gels formed in-situ following the oral administration of dilute aqueous solutions of an enzyme-degraded xyloglucan to rabbits were evaluated as sustained-release vehicles for the delivery of theophylline. In-vitro release of theophylline from gels formed by warming xyloglucan sols (0.5, 1.0 and 1.5% w/w) to 37°C followed root-time kinetics over a period of 4 h. Gels formed after oral administration to rabbits of chilled 1.5% w/w aqueous solutions of xyloglucan containing dissolved drug showed sustained-release characteristics with a maximum plasma concentration at 4.5 h. The theophylline bioavailability from a 1.5% w/w xyloglucan gel was 1.7–2.5 times that of commercial oral sustained-release liquid dosage forms containing an identical theophylline concentration. It was concluded that dilute solutions of the enzyme-degraded xyloglucan had suitable rheological properties and in-situ gelling characteristics for use as sustained-release vehicles for oral drug delivery. The in-vivo release characteristics of theophylline in a rabbit model suggested the potential for the use of these vehicles in humans for the oral delivery of this drug.
The powder flow and compact mechanical properties of two recently developed matrix-forming polymers
Authors: Hancock Bruno C , Carlson Glenn T , Ladipo Dauda D , Langdon Beth A , Mullarney Matthew P 
Published: July 2003

Abstract
The powder flow and compact mechanical properties of two recently developed matrix-forming polymers were determined. The polymers are cross-linked high-amylose starch (Contramid) and poly(acrylic acid) (Carbopol EX507), and their properties were compared with those of two established matrix-forming polymers, hydroxypropyl methylcellulose (Methocel K100LV) and hydroxypropyl cellulose (Klucel EXF). The particle morphology, size distribution and true density of the four materials were quite different and they exhibited measurable performance differences with respect to powder flow, compact ductility, compact elasticity and compact tensile strength. Recommendations for formulating solid dosage forms with each of these excipients were made, based on a consideration of their physical properties and their anticipated processing performance.
Effectiveness of repeated administration of a new oral naltrexone controlled-release system on morphine analgesia
Authors: Álvarez-Fuentes J , Rojas-Corrales M O , Holgado M A , Sánchez-Lafuente C , Micó J A , Fernández-Arévalo M 
Published: July 2003

Abstract
Naltrexone hydrochloride, an opioid antagonist used as an adjunct to the maintenance of the opioid-free state for detoxified individuals, was introduced into the polymeric structure of Eudragit L30D, ananionic copolymer based on polymethacrylic acid and ethylacrylate. From the results of a preclinical study, this complexation technique can be considered as a useful tool in the design of oral controlled-release systems (naltrexone-Eudragit L) capable of inducing long-lasting effects in-vivo. The biopharmaceutical characterization of the naltrexone-Eudragit L complex in comparison with naltrexone hydrochloride using the mouse hot-plate model has been previously carried out. The results showed a longer effect, an enhancement of 23.47% of the area under the curve of the inhibition of analgesic activity vs time, and a delay of 51.80% in the t1/2 value induced by the complex, compared with those induced by conventional naltrexone. In this study, a regimen of chronic administration of naltrexone-Eudragit L was established. Thus, in an 8-day treatment (4 doses in alternate days) this oral controlled-release system effectively antagonized the analgesic effect of morphine for 8 h, whereas naltrexone hydrochloride has to be administered over 16 days (8 doses in alternate days) to induce the same effect. In the 16-day schedule the complex-induced antagonism lasted over 14 h after administration.
Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats
Authors: Rodriguez Marta , Antúnez José Antonio , Taboada Cristina , Seijo Begoña , Torres Dolores 
Published: July 2003

Abstract
Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmaco-therapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.
Improved activity and stability of lysozyme at the water/CH2CI2 interface: enzyme unfolding and aggregation and its prevention by polyols
Authors: Pérez Caroline , Griebenow Kai 
Published: July 2003

Abstract
Protein inactivation and aggregation at the water/CH2CI2 interface is one of the most detrimental events hindering the encapsulation of structurally unperturbed proteins into poly(lactide-co-glycolide) (PLG) microspheres for their clinical application as sustained release dosage forms. We have investigated the inactivation and aggregation of the model protein hen egg-white lysozyme at this interface and devised methods to prevent both events. When lysozyme was exposed to a large water/CH2CI2 interface achieved by homogenization, lysozyme aggregation occurred. Fourier-transform infrared (FTIR) spectroscopic data demonstrated that the aggregates formed contained intermolecular β-sheets. The aggregates were of a non-covalent nature because they slowly dissolved in D2O and the IR spectral bands typical for the intermolecular β-sheets disappeared at approximately 1617 and 1690 cm−1. The observed loss in specific enzyme activity of soluble lysozyme was caused by the irreversible formation of an unfolded lysozyme species, which was found to be monomeric, and was able to leave the water/CH2CI2 interface and accumulate in the aqueous phase. Polyols were, in a concentration dependent fashion, efficient in ameliorating lysozyme unfolding and aggregation. However, prevention of lysozyme aggregation and activity loss in the various samples were unrelated. Thus, polyols must work by more than one mechanism preventing the two events. For the first time, an excipient effect on the conformational stability of lysozyme has been excluded from contributing to the prevention of lysozyme unfolding and aggregation.
Iontophoretic pulsatile transdermal delivery of human parathyroid hormone (1–34)
Authors: Suzuki Yasuyuki , Iga Katsumi , Yanai Shigeo , Matsumoto Yukihiro , Kawase Masahiro , Fukuda Tunehiko , Adachi Hirotoshi , Higo Naruhito , Ogawa Yasuaki 
Published: July 2003

Abstract
Iontophoretic pulsatile transdermal delivery of hPTH(1–34) was examined in Sprague-Dawley (SD) rats, hairless rats and beagle dogs. Application for 60 min (200 μ 0.1 mA cm−2) showed current-responsive increases in serum hPTH(1–34) levels in all the animals. In SD rats, the area under the curves of serum hPTH(1–34) levels (AUCs) were proportional to the doses (40, 120, 200, 400 and 1000 μg) and current densities (0.05, 0.1 and 0.15 mA cm−2) applied. The absorption rates per 200-μg dose, calculated by a deconvolution method, were 6.7, 2.4 and 3.7 μg h−1 for SD rats, hairless rats and beagle dogs, respectively. These values correlated well with the ratios of the skin porosity to the dermal thickness reported for these animals, which are believed to represent the reciprocal of the electrical resistance of the aqueous channels formed by the hair follicles. From this correlation, we suggested that absorption of hPTH(1–34) occurs mainly via the hair-follicle route, and that the absorption rate in man might be intermediate between those in hairless rats and beagle dogs. Three-fold repetitions of 30 min current with various rest intervals produced current-responsive triple pulses in serum hPTH(1–34) levels in SD rats. Seven-fold repetitions of current also produced similar current-responsive pulsatile serum hPTH(1–34) levels. However, peak serum hPTH(1–34) levels tended to decrease gradually after the fourth current application, possibly due to consumption of the electrodes, suggesting that three-fold repetitions of current might be optimal. These findings suggest that this iontophoretic administration system could create a repeated-pulsatile pattern of serum hPTH(1–34) levels without the necessity for frequent injections, and may be useful for the treatment of osteoporosis with hPTH(1–34).