bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymeric Chitosan-based Vesicles for Drug Delivery
Authors: Uchegbu Ijeoma F , Schätzlein Andreas G , Tetley Laurence , Gray Alexander I , Sludden Julieann , Siddique Soryia , Mosha Erasto 
Published: April 2011

Abstract
A simple carbohydrate polymer glycol chitosan (degree of polymerization 800 approx.) has been investigated for its ability to form polymeric vesicle drug carriers. The attachment of hydrophobic groups to glycol chitosan should yield an amphiphilic polymer capable of self-assembly into vesicles. Chitosan is used because the membrane-penetration enhancement of chitosan polymers offers the possibility of fabricating a drug delivery system suitable for the oral and intranasal administration of gut-labile molecules.
Glycol chitosan modified by attachment of a strategic number of fatty acid pendant groups (11–16mol%) assembles into unilamellar polymeric vesicles in the presence of cholesterol. These polymeric vesicles are found to be biocompatible and haemocompatible and capable of entrapping water-soluble drugs. By use of an ammonium sulphate gradient bleomycin (MW 1400), for example, can be efficiently loaded on to these polymeric vesicles to yield a bleomycin-to-polymer ratio of 0.5 units mg−1.
Previously polymers were thought to assemble into vesicles only if the polymer backbone was separated from the membrane-forming amphiphile by a hydrophilic side-arm spacer. The hydrophilic spacer was thought to be necessary to decouple the random motion of the polymer backbone from the ordered amphiphiles that make up the vesicle membrane. However, stable polymeric vesicles for use in drug delivery have been prepared from a modified carbohydrate polymer, palmitoyl glycol chitosan, without this specific architecture. These polymeric vesicles efficiently entrap water-soluble drugs.
Novel Aryl-bis-quinolines with Antimalarial Activity In-vivo
Authors: Ismail F M D , Dascombe M J , Carr P , Mérette S A M , Rouault P 
Published: April 2011

Abstract
Three rationally designed isomeric aryl-bridged bis-quinolines, N1,Nx-bis(7-chloroquinolin-4-yl)phenylene-1,x-diamines, where x = 2, 3 or 4, i.e. o-, m- and p-substituted analogues respectively, were synthesized and evaluated against Plasmodium berghei in-vivo.
The compound with x = 2 had an ID50 of 30 mg kg−1, whereas the p-substituted analogue (x = 4) was not statistically schizonticidal at either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg kg−1, ID50 = 60 mg kg−1 approx.). When the delivery vehicle was changed to saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50 17mg kg−1). In contrast, the m-substituted analogue had marked antimalarial activity (ID50 1.2 mg kg−1), which compares favourably with that of chloroquine diphosphate (ID50 = 4.3 mg kg−1). The data presented show that the amino-methylene side chain in amodiaquine can be successfully replaced by a 7-halo-4-aminoquinoline, establishing that carbon bridges containing less than four contiguous carbon atoms can be present within highly active aryl-substituted 4-aminoquinoline antimalarials.
These results confirm that the presence of an OH group in the aryl bridge is not necessary for antimalarial activity and substantiate the view that, despite the appearance of resistant strains, new and existing aminoquinolines still have an important role in treating malaria.
Metabolism of Roxithromycin in the Isolated Perfused Rat Liver
Authors: Jarukamjorn Kanokwan , Thalhammer Therese , Gollackner Bernd , Pittenauer Ernst , Jäger Walter 
Published: April 2011

Abstract
Roxithromycin is a macrolide antibiotic with high clinical potency. N-Demethylation is considered to be one of the main pathways of roxithromycin metabolism in rats. We have studied the hepatic metabolism of roxithromycin in the isolated perfused rat liver.
After addition of roxithromycin (30 μM) to the perfusion medium the parent compound and one major metabolite were detected in bile by high-performance liquid chromatography. The metabolite was identified as monodesmethylated roxithromycin by mass spectrometric analysis. Onset of biliary excretion of native roxithromycin was fast, reaching a maximum (130.52 ±43.88 pmol g−1 min−1) after only 10 min, whereas excretion of the metabolite was delayed (maximum 75.83 ± 11.92 pmol g−1 min−1 at 30 min). The cumulative excretion of roxithromycin and its metabolite into bile during the 60 min of application amounted to only 1.09 ± 0.30 and 0.64 ± 0.22% of the roxithromycin cleared from the perfusate during the same time. The liver content was 0.48 μmol (g liver)−1, indicating high retention within the organ. No release of the metabolite into the perfusate was detected.
In conclusion, this study has demonstrated the importance of phase-I metabolism for the biliary excretion of roxithromycin in rat liver. These findings might be predictive of roxithromycin biotransformation and biliary excretion in man.
Effect of D-002 on the Pre-ulcerative Phase of Carrageenan induced Colonic Ulceration in the Guinea-pig
Authors: Noa Miriam , Mas Rosa 
Published: April 2011

Abstract
D-002 is a natural mixture of higher aliphatic primary alcohols, isolated and purified from beeswax which has anti-inflammatory properties, reduces leukotrienes (LTB4) and thromboxane B2 (TXB2) in exudated carrageenan-induced pleurisy, and has anti-ulcer activity in different experimental models. This study was conducted to determine the effect of D-002 on the pre-ulcerative phase of carrageenan-induced colonic ulceration in guinea-pigs.
Animals were randomly distributed among a negative control, a positive control group treated with the vehicle Tween 20 in H2O and two experimental groups receiving D-002 at 25 and 50 mg kg−1. All treated animals received degraded carrageenan for three days for induction of colonic ulceration. Significant reductions in wet weight, wall thickness, counts of infiltrating polymorphonuclear neutrophils and of macrophages, and histological index were observed in colonic mucosa of D-002-treated animals compared with controls.
It is concluded that D-002 has a protective effect on the pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.
Effects of the Ginsenosides Rgl and Rbl on Morphine-induced Hyperactivity and Reinforcement in Mice
Authors: Kim Hack-Seang , Hong Youn-Tack , Jang Choon-Gon 
Published: April 2011

Abstract
Recent studies have demonstrated that ginseng saponin inhibits the hyperactivity and conditioned place-preference response induced by psychostimulants and opiates. This seems to occur by direct or indirect modulation of dopaminergic activity. However, it is not known which components of ginseng saponin are active. These experiments were conducted to determine the effects of the ginsenosides Rb1 and Rg1, major components of the protopanaxadiol and protopanaxatriol fractions of ginseng saponin, on morphine-induced hyperactivity and conditioned place-preference.
Morphine-induced hyperactivity, but not apomorphine-induced climbing behaviour, was inhibited by both Rb1 and Rg1. These findings confirm the hypothesis that ginsenosides modulate catecholaminergic activity preferentially at pre-synaptic sites. Morphine-induced conditioned place-preference was inhibited by Rg1, but not by Rb1. It has previously been shown that at low doses Rb1 and Rg1 are equally effective at inhibition of catecholamine secretion at the pre-synaptic site, but that at high doses Rg1 is a more effective inhibitor. This observation might explain our finding that morphine-induced conditioned place-preference was inhibited by Rg1 only.
Our findings suggest that Rg1, a component of ginseng saponin with appropriate activity, might be a useful agent for prevention and treatment of the adverse effects of morphine.
Variability of Mitomycin C Adsorption by Activated Charcoal
Authors: Shah I A , Lindup W E , Mcculloch P G 
Published: April 2011

Abstract
A saline suspension of mitomycin C adsorbed on activated charcoal and administered intraperitoneally has been reported to be safe and effective in the treatment of gastric carcinoma. Activated charcoal specifically targets tumour and lymph-node tissues and the sustained higher local drug concentration is thought to be beneficial. The charcoal particles used in these suspensions have varied in size from &gt; 147 μm to &lt; 20 nm in diameter, but no data have been published to show how this might affect drug adsorption and delivery. Any variability in drug adsorption could pose a serious clinical risk for drugs with a narrow therapeutic index. We have, therefore, investigated the adsorption of mitomycin C on activated charcoal in-vitro.
Activated charcoal was ground and sieved to yield four size-fractions between 180 and 53 μm. Adsorption isotherms (n ≥ 3) were constructed and applied to the Freundlich model with 0–100 μg mL−1 mitomycin C measured by HPLC with detection at 365 nm. Adsorption of mitomycin C by activated charcoal varied by a factor of three under identical conditions at room temperature (21°C) and at 37°C. The specific adsorption (μg mitomycin C (mg activated charcoal)−1) was generally higher at 37°C than at room temperature. The variability of mitomycin C adsorption was greatly reduced by addition of the surface-active agent polyvinylpyrollidone, used to determine that adsorption of mitomycin C was independent of activated charcoal particle size.
The characteristics of adsorption of mitomycin C by activated charcoal are complex and should be thoroughly investigated to discover the critical controlling factors before submitting the suspensions for further clinical evaluation.
Pharmacokinetic Assessment of the Sites of First-pass Metabolism of BMS- 181101, an Antidepressant Agent, in Rats
Authors: Vachharajani Nimish N , Shyu Wen Chyi , Shah Vinod R , Barbhaiya Rashmi H 
Published: April 2011

Abstract
The relative contribution of the gut and the liver to the first-pass metabolism of BMS-181101 (3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-5-fluoro-1H-indole dihydrochloride), a potential antidepressant agent, has been evaluated in rats.
Nine male Sprague–Dawley rats were divided into three groups of three and each rat received a single 20 mg kg−1 dose of [14C]BMS-181101 via a 30 min constant-rate intravenous infusion, a 30-min constant-rate intraportal infusion or oral gavage. Serial blood samples were collected for 8 h after dosing and plasma was analysed for unchanged BMS-181101 and total radioactivity. Extraction ratios for BMS-181101 by the gut and liver were calculated on the basis of ratios of the area under the plasma BMS-181101 concentration–time curve. The gut had a high intrinsic capacity for metabolizing BMS-181101-extraction ratios were 93% and 10% for the gut and liver, respectively. After oral administration BMS-181101 is sequentially exposed to the gut then the liver. As a result, the contribution of the gut to the overall first-pass effect (ca. 93%) was significantly greater than that of the liver
HPLC on Chiralcel OJ-R for Enantiomer Separation and Analysis of Ketoprofen, from Horse Plasma, as the 9-Aminophenanthrene Derivative
Authors: Aboul-Enein Hassan Y , Van Overbeke An , Weken Guido Vander , Baeyens Willy , Oda Hirofumi , Deprez Piet , De Kruif Aart 
Published: April 2011

Abstract
Racemic ketoprofen is a non-steroidal anti-inflammatory drug used to treat musculoskeletal and colic conditions in horses. The enantioselective chiral inversion of ketoprofen administered to horses has been studied by use of cellulose tris(4-methylbenzoate), also known as Chiralcel OJ-R, as chiral stationary phase; acetonitrile − 0·02 m perchlorate buffer (pH 2·0) - methanol, 60:15:25 (v/v/v) was used as mobile phase. Before chromatography, to effect adequate chiral interaction with the chiral stationary phase ketoprofen was derivatized with 9-aminophenanthrene, under acid conditions, after solid-phase (C18) extraction and then liquid–liquid extraction, to ensure effective removal of endogenous plasma materials. The 9-aminophenanthrene derivative of S-ibuprofen was used as internal standard. The enantiomers of ketoprofen were separated to baseline (Rs = 6·44, α = 1·76) within a short analysis time.
The results indicate that the bio-inversion of R-ketoprofen to the S isomer is significant in equine species. However, considerable differences in pharmacokinetic parameters were observed, indicating large inter-animal variation.
Effect of Mn2+ on the Development of Tension Induced in Guinea-pig Taenia Coli by Bay K 8644
Authors: Nasu Tetsuyuki , Sasaki Miyori 
Published: April 2011

Abstract
We have studied the effects of Mn2+ on the contractile response induced by Bay K 8644, a dihydropyridine Ca2+ agonist, on guinea-pig taenia coli. Mn2+ (5 mm) completely inhibited Bay K 8644 (10−6 m)-induced rhythmic contraction and contracture to baseline values in normal Ca2+ medium; thereafter, the contraction progressively increased to about 90% of the K+ (60 mm)-induced tonic response. In Ca2+-free medium in the presence of Bay K 8644 Mn2+ also evoked contraction and a concomitant increase in Mn2+ influx into the cytoplasm.
These results suggest that during the opening of voltage-dependent Ca2+ channels activated by Bay K 8644, Mn2+ can enter cytoplasm through the channels and induce contraction in taenia coli.
Drug-delivery Products and the Zydis Fast-dissolving Dosage Form
Authors: Seager H 
Published: April 2011

Abstract
Many patients find it difficult to swallow tablets and hard gelatin capsules and do not take their medication as prescribed. It is estimated that 50% of the population is affected by this problem which results in a high incidence of non-compliance and ineffective therapy. The difficulty is experienced in particular by paediatric and geriatric patients, but it also applies to people who are ill in bed and to those active working patients who are busy or travelling, especially those who have no access to water. Such problems can be resolved by means of the Zydis dosage form which does not require water to aid swallowing. The Zydis fast-dissolving dosage form is a unique freeze dried medicinal tablet, made from well known and acceptable materials. When Zydis units are put into the mouth, the freeze dried structure disintegrates instantaneously releasing the drug which dissolves or disperses in the saliva. The saliva containing the dissolved or dispersed medicament is then swallowed and the drug is absorbed in the normal way. Some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. In these cases, the bioavailabilities of drugs from Zydis formulations are significantly greater than those observed from standard dosage forms.
This paper deals with the formulation and process technology of the Zydis dosage form. The bioavailability characteristics of Zydis products are summarized, and in particular, the design of Zydis products for the enhancement of oral bioavailability and the improvement of clinical activity, through transmucosal delivery and pregastric absorption, is discussed.
Kinetic Interaction between Fluoxetine and Imipramine as a Function of Elevated Serum Alpha-1-acid Glycoprotein Levels
Authors: Holladay John W , Dewey Michael J , Yoo Sun D 
Published: April 2011

Abstract
The effect of elevated serum alpha-1-acid glycoprotein (AAG) levels on the pharmacokinetic interaction between imipramine and fluoxetine has been examined by utilizing a novel strain of transgenic mice which express serum AAG levels several times greater than normal.
Before fluoxetine treatment, serum imipramine levels were approximately three times greater in transgenic mice than in control mice. Despite higher serum imipramine levels in transgenic mice, brain drug levels were lower than those found in control mice. Fluoxetine pre-treatment (20mg kg−1 for 5 days) resulted in an increase in serum imipramine levels in both groups of mice and the extent of the increase was greater in transgenic mice than in control mice (4.5-fold increase compared with 3.1-fold). Similarly, fluoxetine pre-treatment resulted in an increase in brain levels of imipramine in both groups of mice and the extent of the increase was greater in transgenic mice than in control mice (3.0-fold increase compared with 2.0-fold). Similar trends were observed for levels of desipramine in the serum and brain. Serum imipramine and desipramine levels did not correlate with their respective brain levels in the presence of elevated serum AAG levels before and after pre-treatment.
These findings indicate that the extent of increases in imipramine and desipramine serum and brain levels are greater during elevated serum AAG states than during normal AAG states when imipramine is co-administered with fluoxetine.
Is Arachis Oil a Solvent Only, or Does it also Have an Effect on the Central Nervous System?
Authors: Erden B Faruk , Ulak GüNer , Gacar Nejat , Özdemirci Sitki 
Published: April 2011

Abstract
Peanut (Archis hypogaea L.) seed, an important oil crop (arachis oil) throughout the world, is grown in large quantities in Africa, India and China. The oil is used in many edible products, including shortenings, margarines and mayonnaise, as a cooking and frying oil and as a salad oil. Arachis oil contains fatty acids and antioxidants. It has been shown to be unexpectedly atherogenic in the diets of experimental animals (Chow 1992).
Synthesis of Thiazolotriazine Derivatives and Their Antinociceptive Effects in Mice
Authors: Issartel Veronique , Coudert Pascal , Rubat Catherine , Nhamias Solange , Couquelet Jacques 
Published: April 2011

Abstract
A series of 2-(4-arylpiperazin-1-yl-methyl)-4-methyl-1-oxo-5,6,8,8a-tetrahydro-thiazolo[3,4-d] [1,2,4]triazines was prepared and tested for antinociceptive activity.
The compounds were prepared by the Mannich reaction from the corresponding 2-unsubstituted thiazolotriazines. When administered intraperitoneally most were found to have potent analgesic activity in the mouse during tests of phenylbenzoquinone-induced abdominal constriction; ED50 values (doses resulting in half the maximum effect) ranged from 10 to 87 mg kg−1. Derivatives with a 3-chloro- or 4-fluorophenylpiperazinylmethyl side-chain in the 2-position of the bicyclic system were, when administered intraperitoneally at doses greater than 25 mg kg−1, also effective in the hot-plate test without associated sedative effects. The compounds have a large therapeutic index; intraperitoneal LD50 values (doses which result in the death of half the animals) were &gt; 700 mg kg−1. Naloxone attenuated the analgesic activity of the 3-chloro derivative, suggesting the participation of μ-receptors in the antinociceptive effects of this drug. In addition, a non-opioid mechanism, probably related to enhancement of the release of 5-hydroxytryptamine and noradrenaline, or inhibition of the neuronal re-uptake of these compounds, has been evinced to explain the analgesic properties of the 3-chloro or 4-fluoro derivatives.
These results provide evidence for the involvement of noradrenergic and 5-hydroxytryptaminergic pathways in the analgesic activity of 3 and 4. Because of their potential effectiveness, the 3-chloro- or 4-fluorophenylpiperazinylmethyl derivatives might be suitable for treatment of a wide variety of painful conditions and could be attractive reserve agents for patients dissatisfied with opioids.
Stereoselective Synthesis of Peptidyl Trifluoromethyl Alcohols and Ketones: Inhibitory Potency Against Human Leucocyte Elastase, Cathepsin G, Porcine Pancreatic Elastase and HIV-1 Protease
Authors: Amour Augustin , Reboud-Ravaux Michèle , de Rosny Eve , Abouabdellah Ahmed , Bégué Jean-Pierre , Bonnet-Delpon Danièle , Gall Marie Le 
Published: April 2011

Abstract
New fluorinated inhibitors have been designed to target two major proteases—human leucocyte elastase and HIV-1 protease.
Two series of β-peptidyl trifluoromethyl alcohols (TFMAs) Z-L-Val-NH-*CH(Y)-*CH(OH)-CF3, where *C is the chiral centre, varied in the nature of the substituent Y, a phenylethyl [-(CH2)2-C6H5] or an isopropyl [-CH(CH3)2] group. These TFMAs were first synthesized as two pairs of the syn and anti diastereoisomers. The inhibitory effects of these mixtures were then assessed on three serine proteases chosen on the basis of the aromatic and aliphatic nature of the substituents—human leucocyte elastase (HLE), human cathepsin G (HCG) and porcine pancreatic elastase (PPE). In the presence of detectable inhibition, each epimer at C2 was separated to determine its inhibition constant (Ki) towards HLE, HCG and PPE. The stereoisomerically pure TFMAs were then oxidized into peptidyl trifluoromethyl ketones = 5·65 × 10−4 M). The tested compounds also had structural properties compatible with recognition by HIV-1 protease. The inhibition of the enzyme was observed with TFMK only (IC50 = 15–200 μM). The phenylethyl substituent promoted inhibition by a factor of 10 (IC50 = 15μM) compared with the isopropyl substituent (IC50 = 200 μM) leading to selective inhibition of HIV-1 protease.
Isomerically pure TFMKs were more potent towards HLE than the alcohols from which they were obtained. However, an enantiomerically pure TFMA selectively inhibited HLE unlike its TFMK analogue which also inhibited PPE. This last result together with the selective inhibition of HIV-1 protease by TFMK with a phenylethyl substituent might be relevant to the design of specific HLE and HIV-1 inhibitors as therapeutic agents.
Effects of Epidermal Growth Factor Dosage Forms on Mice Full-thickness Skin Wound Zinc Levels and Relation to Wound Strength
Authors: Gönül B , Söylemezoglu T , Babül A , Celebi N 
Published: April 2011

Abstract
Epidermal growth factor (EGF) and zinc promote re-epithelization and reparative tissue strength by enhancing deposition of collagen at the site of the wound. In this study two EGF dosage forms were chosen to assess the effect of zinc levels on wound healing and for comparison with wound tear strengths.
A solution of EGF in 0.9% w/v NaCl and an EGF gel in 0.2% Carbopol 940 polymer (5 μL) were applied to full-thickness skin wounds of mice twice a day for 7 and 15 days. Wound zinc levels were higher on day 7 than on day 15, especially in wounds treated with EGF. The wound zinc levels of the gel + EGF group on day 15 were similar to those of normal control skin.
These results imply that there is a close connection, but no direct relationship, between EGF application in both dosage forms and wound zinc levels during healing.
Interrelationship of Cardiovascular Effects, Plasma Levels of Nicorandil, and Vascular cGMP Formation in Conscious Rats
Authors: Sakai Kazushige , Akima Michitaka , Kamachi Shinichi , Moriyasu Matsuko , Kitajima Shunichi 
Published: April 2011

Abstract
The relationship between the dual activity of nicorandil (KATP channel-opening activity and nitrate-like action), plasma levels, and changes in vascular cGMP levels and cardiovascular parameters was investigated in conscious rats.
Nicorandil (3 mg kg−1, p.o.) was rapidly absorbed and caused a significant reduction in blood pressure, lasting for at least 1 h, increases in heart rate and femoral blood flow, and decreases in femoral vascular resistance. These were entirely abolished by intravenous glibenclamide (20 mg kg−1). The plasma concentration of nicorandil reached a maximum 30 min after dosing. After administration of nicorandil, a correlation was observed between blood pressure and plasma nicorandil level or femoral vascular resistance. A significant increase (P &lt; 0.05) in the cGMP content of the thoracic aorta occurred 15 min after administration of nicorandil, and persisted for at least 2 h.
These results imply that nicorandil induces vasodilatation by opening KATP channels in peripheral resistance vessels, leading to overt reduction of blood pressure, but acts on conductance vessels mainly through nitrate-like activity.