bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency Distribution of Candida albicans Blastospores Adhered to Mucosal Epithelial Cells In-vitro
Authors: Gorman S P , Jones D S , Mcgovern J G , Woolfson A D 
Published: April 2011

Abstract
Although several methods are available for examination of microbial adherence to epithelial cells, these do not distinguish between adherence of viable and non-viable micro-organisms. This study reports the use of acridine orange-stained blastospores of Candida albicans in conjunction with direct epifluorescence microscopy to determine viable (orange-fluorescing) and non-viable (green-fluorescing) blastospore adherence to buccal epithelial cells. The method was also employed to examine the effects of chlorhexidine treatment at sub-minimum inhibitory concentrations on the adherence of viable and non-viable blastospores.
There was good correlation in the assessment of blastospore viability between the direct epifluorescence microscopy technique and the standard serial dilution and plating method for viable counting, confirming the reliability of direct epifluorescence microscopy. Chlorhexidine treatment before acridine orange staining did not alter this assessment of viability. Blastospore adherence to buccal epithelial cells resulted in a similarly skewed distribution whether examined using a crystal violet stain in conjunction with light microscopy or using direct epifluorescence microscopy, therefore validating the direct epifluorescence microscopy technique for the enumeration of blastospore adherence. Chlorhexidine treatment (0.0005% v/v, 30 min) of either blastospores or buccal epithelial cells altered the distribution of adherent blastospores per epithelial cell by increasing the number of epithelial cells having no adherent blastospores. No differences in adherence were, however, observed between blastospore or epithelial cells after treatment with this agent. Examination of the adherence of viable and non-viable blastospores to buccal epithelial cells using direct epifluorescence microscopy revealed a greater adherence capacity of non-viable than viable blastospores for buccal epithelial cells. Treatment of blastospores with chlorhexidine altered the frequency distributions of viable and non-viable blastospores with lower numbers of blastospores adherent per epithelial cell. The larger reduction in adherent viable blastospores in comparison with their non-viable counterparts is, however, an important observation which might have clinical relevance.
Microbial cells adhere to epithelial cells resulting in a skewed distribution; study of this distribution gives useful information about the adherence process. Viable and non-viable components of a microbial population have different adherence capabilities and treatment of such populations with an antimicrobial agent exerting anti-adherent activity at sub-minimum inhibitory concentrations reduces the amount of adherence of these viable/non-viable components to different extents.
Bioequivalence and Generic Prescribing: An Industrial View
Authors: Pidgen Alwyn 
Published: April 2011

Abstract
The whole concept of bioequivalence is based upon the existence of a clear relationship between drug concentration and clinical effect.
To date there are insufficient data available in the form of publications to support this concept.
Both the pharmaceutical industry and the regulatory authorities could do more to promote this issue and publish relevant information.
The pharmaceutical industry could provide more information on concentration-effect relationships in volunteers and patients.
Upon expiry of the patent, regulators could provide estimates of the inter- and intra-subject variability in the pharmacokinetics of a drug in volunteers and patients, asessment of therapeutic windows for drugs and drug classes and their impact on bioequivalence acceptance criteria.
Current regulatory guidelines refer to rate and extent of absorption BUT there is no rate parameter which allows products to be compared for both pharmaceutical quality and safety and efficacy.
Antimicrobial Activity of Electrochemical Silver Ions in Nonionic Surfactant Solutions and in Model Dispersions
Authors: Scalzo M , Perazzi M E , Simonetti N , Cerreto F 
Published: April 2011

Abstract
The microbicidal effectiveness against Gram-positive and Gram-negative bacteria and Candida albicans of electrochemical silver ions in aqueous solutions containing nonionic surfactants was investigated. From the perspective of the possible use of anodic silver as a preservative in cosmetic or pharmaceutical preparations, microbicidal efficacy was also studied in oil/water model dispersions.
Surfactants and botanical extracts partially inhibited the microbicidal effectiveness of anodic silver. Nevertheless in all the experimental conditions, silver ions reduced the microbial concentration up to 4 log units of the starting inoculum in less than 6h.
The wide microbicidal spectrum and the high rate of kill of silver ions appear, therefore, attractive enough to suggest a possible utilization of anodic silver as a preserving agent.
Glibenclamide Antagonizes the Inhibitory Effect of Morphine on Gall Bladder Emptying
Authors: Patil B M , Thakker P R 
Published: April 2011

Abstract
Egg yolk-induced gall-bladder emptying in mice was used to investigate the effect of glibenclamide and minoxidil (ATP-dependent K+-channel modulators) on biliary tract effects of morphine.
The inhibitory effect of morphine (1–4 mg kg−l, i.p.) on egg yolk-induced gall-bladder emptying was completely blocked by pretreatment with naloxone (2 mg kg−l, i.p.) or glibenclamide (0.65 mg kg−l, i.p.) whereas, pretreatment with minoxidil (0.65 mg kg−1, i.p.) did not modify the inhibitory effect of morphine on gall-bladder emptying.
Our results suggest that biliary-tract actions of morphine are mediated through glibenclamide-sensitive K+ channels similar to those involved in the analgesic action of morphine.
Modification of Ca2+ Metabolism in the Rabbit Aorta as a Mechanism of Spasmolytic Action of Warifteine, a Bisbenzylisoquinoline Alkaloid Isolated from the Leaves of Cissampelos sympodialis Eichl. (Menispermaceae)
Authors: de Freitas M R , Côrtes S De F , Thomas G , Filho J M Barbosa 
Published: April 2011

Abstract
The regulation of intracellular Ca2+ as a mechanism of spasmolytic activity of a bisbenzylisoquinoline alkaloid, warifteine, isolated from the leaves of Cissampelos sympodialis, Eichl (Menispermaceae) was studied in the rabbit aorta.
Warifteine (pD'2 4.12 ± 0.09) similar to verapamil (pD'2 6.89 · 0.05) antagonized, in a noncompetitive and reversible manner, KCl-induced contractions, mediated by Ca2+ entry through voltage-operated channels. Noradrenaline-induced sustained contractions mediated by Ca2+ entry through receptor-operated channels were also inhibited by warifteine (IC50 6.03 × 10−5 m) and the standard agent sodium nitroprusside (IC50 1.9 × 10−8 m). In Ca2+-free medium, the alkaloid reduced the intracellular Ca2+-dependent transient contraction to noradrenaline by inhibiting the release of Ca2+ (IC50 2.6 × 10−5 m) from the stores and the refilling (IC50 1.9 × 10−5 m) of the intracellular stores. The standard agent, procaine, also inhibited the release of Ca2+ (IC50 3.2 × 10−5 m) but had no significant effect on Ca2+ uptake into the stores. Warifteine failed to affect intracellular Ca2+ stores sensitive to caffeine, while procaine inhibited (IC50 7.9 × 10−4 m) the release of Ca2+ from these stores.
The results indicate that warifteine may cause muscle relaxation by inhibiting Ca2+ channels and by modifying the intracellular Ca2+ stores sensitive to noradrenaline.
The Effect of Surfactant and Solid Phase Concentration on Drug Aggregates in Model Aerosol Propellent Suspensions
Authors: Bower Christopher , Washington Clive , Purewal T S 
Published: April 2011

Abstract
The effect of increasing solid phase concentration on the morphology and flocculation rate of model aerosol suspensions has been investigated. Suspensions of micronized salbutamol sulphate and lactose in trichlorotrifluoroethane (P113) were studied under conditions of increasing shear stress. By use of image analysis techniques, measurement of aggregate size, fractal dimension and rate of aggregation was performed. The effect of the surfactant sorbitan monooleate on morphology and flocculation rate was also studied.
Increased solid phase concentration caused an increase in the rate of aggregation and average aggregate size at a given value of shear stress. Surfactant addition retarded the aggregation rate, and caused a shift from a diffusion-limited cluster aggregation to a reaction-limited cluster aggregation mechanism. The aggregate profiles showed a corresponding change from rugged and crenellated without surfactant, to increasingly smooth and Euclidian with increasing surfactant concentration. The morphological changes were characterized by a decrease in the average boundary fractal dimension which also correlated well with the corresponding reduction in aggregation rate.
Effect of Activated Charcoal and Atropine on Absorption and/or Exsorption of Organophosphorus Compounds in Rats
Authors: Tomimaru Aki , Arimori Kazuhiko , Inotsume Nobuo , Nakano Masahiro 
Published: April 2011

Abstract
Effects of activated charcoal and atropine for the removal of organophosphorus compounds, which remain in the gastrointestinal tract or have already been absorbed into the systemic circulation, were investigated in rats.
Activated charcoal extensively adsorbed the organophosphates fenitrothion, tolclofos methyl, piperophos and salithion, and its immediate administration after oral ingestion of fenitrothion remarkably reduced serum fenitrothion levels, but had no effect on the serum levels of the compound which had been absorbed from the gastrointestinal tract. Thus, all of the organophosphorus compounds were poorly exsorbed (0.002-0.39% of the dose in 120 min) from the blood into the intestinal lumen probably due to their extensive protein binding and large distribution volumes. Atropine inhibited absorption of fenitrothion in the perfusion in-situ and also delayed the absorption of the compound in-vivo, but had no significant effect on exsorption of fenitrothion. The serum fenitrothion levels on treatment with both atropine and charcoal significantly decreased compared with those of the control. We conclude that, oral activated charcoal will not be able to enhance the elimination of organophosphorus compounds which have already been absorbed into the systemic circulation, but constitute a useful method for the removal of the compounds remaining in the gastrointestinal tract because of its excellent adsorptive capacity.
Mechanism of Action of p-Chlorobiphenyl on the Inhibition of Platelet Aggregation
Authors: Ko Feng-Nien , Yeh Ling-Jau , Liang Hsiu-Chuan , Kuo Sheng-Chu , Teng Che-Ming 
Published: April 2011

Abstract
p-Chlorobiphenyl (1–50 μm) concentration-dependently inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 and thrombin. The IC50 values of p-chlorobiphenyl on the arachidonic acid and collagen-induced platelet aggregation were 2.9 ± 0.5 and 12.8 ± 2.3 μm, respectively. The formation of both platelet thromboxane B2 and prostaglandin D2 caused by arachidonic acid was inhibited by p-chlorobiphenyl concentration-dependently. In myo-[3H]inositol-labeled and fura-2-loaded platelets, [3H]inositol monophosphate generation and the rise in intracellular Ca2+ stimulated by arachidonic acid were inhibited by p-chlorobiphenyl. In human platelet-rich plasma, p-chlorobiphenyl and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5′-diphosphate and adrenaline without affecting the primary aggregation.
It is concluded that p-chlorobiphenyl may be a cyclo-oxygenase inhibitor and its antiplatelet action is mainly due to the inhibition of thromboxane formation.
Antithrombotic Activity of a 2-kDa Heparin Fragment in an Experimental Model of Carotid Artery Thrombosis in Rats
Authors: Guarini Salvatore , Bazzani Carla , Botticelli Annibale , Balugani Alessandro , Bertolini Alfio 
Published: April 2011

Abstract
The antithrombotic activity of a 2-kDa heparin fragment was studied in a rat model of common carotid artery thrombosis that causes a completely occlusive thrombus with cessation of the blood flow within 10–15 min.
The compound reduced thrombus formation in a dose-dependent manner, starting from an intravenous dose of 5 mg kg−1. A dose of 20 mg kg−1 completely prevented thrombus formation and apparently induced the almost complete lysis of the already formed occlusive thrombus. At none of the doses used did the compound cause increased bleeding or the formation of haematomas.
The present results indicate that low molecular weight heparins, which have an established, highly beneficial effect in venous thromboembolism, are also highly effective in an animal model of arterial thrombosis.
Inhibition of Lipid Peroxidation by Sesquiterpenoid in Heterotheca inuloides
Authors: Haraguchi Hiroyuki , Saito Takashi , Ishikawa Harumi , Sanchez Yolanda , Ogura Tetsuya , Kubo Isao 
Published: April 2011

Abstract
A sesquiterpenoid, 7-hydroxy-3,4-dihydrocadalin, isolated from a Mexican medicinal plant Heterotheca inuloides was evaluated as an antioxidant.
This sesquiterpenoid inhibited mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH. Furthermore, 7-hydroxy-3,4-dihydrocadalin protected red cells against oxidative haemolysis.
This sesquiterpene was thus shown to be effective in protecting biological systems against oxidative stresses.
Improved Stereospecific Syntheses of Novel 1-alkyl-3-benzoyl-4-hydroxy-4-phenylpiperidines
Authors: Jaffar Mohammed , Upton Christopher 
Published: April 2011

Abstract
The stereoselective synthesis of conformationally restricted 1-alkyl-3-benzoyl-4-hydroxy-4-phenylpiperidine hydrochlorides via the Mannich reaction followed by an intramolecular aldol condensation is reported. The compounds were evaluated by 1H NMR and 13C NMR techniques.
Decomposition Kinetics of Cisplatin in Human Biological Fluids
Authors: Nagai N , Okuda R , Kinoshita M , Ogata H 
Published: April 2011

Abstract
Cisplatin is metabolized to high- and low-molecular mass complexes by exchanging of one or both chloride ligands with nucleophilic species. The decomposition of cisplatin and the formation of its metabolites in human biological fluids was investigated in-vitro.
In nucleophile-free medium, cisplatin was decomposed by a reversible chloride ligand exchange reaction, which was dependent upon both chloride ion concentration and medium pH. The effect of pH was observed in the second-order rate constant for cisplatin re-formation, which was far smaller in neutral and alkaline media than in acidic media. In the medium containing nucleophilic species (glutathione, human albumin and globulin), cisplatin was irreversibly decomposed according to apparent first-order kinetics. The linear relationship between apparent decomposition rate constant and concentration of nucleophilic species suggested that nucleophilic species in biological fluids might react with cisplatin directly. Both high- and low-molecular mass metabolites were formed in human plasma and ascites; however, only a low-molecular mass metabolite was produced in urine. The faster decomposition of cisplatin and the greater ratio of fixed and mobile metabolites formed in plasma were mainly attributed to higher albumin concentration in plasma than in ascites and urine.
The in-vitro decomposition of unchanged cisplatin and formation of high- and low-molecular mass metabolites in human biological fluids were simultaneously evaluated according to the kinetic model which combined both pathways via hydrolysis and by the direct reaction process with nucleophilic species.
Involvement of a Cytochrome P450 System in Microsomal Debromination of α-(Bromisovaleryl)urea
Authors: Oka Koji , Kitamurax Shigeyuki , Tatsumi Kiyoshi 
Published: April 2011

Abstract
The reductive debromination of a hypnotic, (α-bromisovaleryl)urea to (3-methylbutyryl)urea by rat liver microsomes was studied.
Pretreatment of rats with cytochrome P450 inducers such as phenobarbitone, 3-methylcholanthrene, acetone and pregnenolone-16α-carbonitrile enhanced the debromination of (α-bromisovaleryl)urea by liver microsomes. Microsomal debromination was inhibited by cytochrome P450 inhibitors such as metyrapone, α-naphthoflavone, SKF 525-A and carbon monoxide. Microsomal debromination was enhanced by addition of NADPH-cytochrome P450 reductase and inhibited by addition of an antibody against the flavo enzyme to the liver microsomes. A reconstituted cytochrome P450 system containing NADPH-cytochrome P450 reductase, and cytochrome P450 1A1 or P450 2B1 exhibited debrominating activity toward the hypnotic.
These results indicated that a cytochrome P450 system plays an essential role in the microsomal debromination of (α-bromisovaleryl)urea.
Screening for Cytochrome P450 3A in Man: Studies with Midazolam and Nifedipine
Authors: Yeates R A , Scharpf F , Laufen H , Zimmermann T 
Published: April 2011

Abstract
This report describes work directed towards the development of a screening technique for cytochrome P450 3A activity which should be valid for a variety of drugs metabolized by this enzyme.
A significant correlation (P &lt; 001) was found between the ratio of the plasma concentration of nifedipine to that of its oxidized metabolite and the area under the time curve for the plasma concentration of midazolam.
It is suggested that the nifedipine: metabolite ratio might have general predictive value for the metabolism of orally administered cytochrome P450 3A substrates.
Studies on the Toxicity of Analogues of Dapsone In-vitro Using Rat, Human and Heterologously Expressed Metabolizing Systems
Authors: Coleman Michael D , Smith Stephen N , Kelly Diane E , Kelly Steven L , Seydel Joachim K 
Published: April 2011

Abstract
Three metabolizing systems (rat, heterologously expressed CYP3A4 and human liver) were used to evaluate 12 analogues of dapsone (4,4′diaminodiphenylsulphone) in-vitro. Methaemoglobin formation in a two-compartment and cytotoxicity in a single-compartment model were studied using human erythrocytes and neutrophils, respectively, as target cells.
In the two-compartment system using rat microsomes as a generating system and methaemoglobin as an end-point, the least potent methaemoglobin formers tested were the 2-methyl-4-propylamino (AXDD14), 2-hydroxy-4-4′amino (ABDD5) derivatives and a sulphone/trimethoprim derivative (K-130). Dapsone itself, a 2-methoxy-4-ethylamino (W10) and a 2-hydroxyl-4-ethylamino compound (ABDD39) were the most toxic. In the single-compartment cytotoxicity test using rat microsomes, AXDD14 was again among the least toxic, as was a 2-methyl 4-cyclopentyl derivative (AXDD17) and surprisingly ABDD39. The most cytotoxic compounds again included dapsone itself as well as two 2-trifluoromethyl derivatives. The only significant methaemoglobin formation and cytotoxicity shown with the heterologously expressed human CYP 3A4 was with AXDD14, which was extensively activated. Interestingly, metabolism of dapsone was low using the expressed CYP 3A4.
In the two-compartment system using human liver microsomes, AXDD14, K-130 and ABDD5 were oxidized to a significantly lesser extent compared with dapsone and these preliminary findings indicate that future development of these compounds may be worthwhile.
Inhibitory Effects of (±)-Tetrahydropalmatine on Thyrotropin-stimulating Hormone Concentration in Hyperthyroid Rats
Authors: Hsieh Ming-Tsuen , Wu Long-Yuan 
Published: April 2011

Abstract
The effects of (±)-tetrahydropalmatine ((±)-THP) on the hypothalamus-pituitary-thyroid system in rats were investigated.
Thyroid function experiments indicated that (±)-THP produces significant decreases in thyroid function in hyperthyroid rats after 14 days of treatment. These effects were the same as those of propylthiouracil. However, propylthiouracil also decreased thyroid function in normal rats. Measurements of thyrotropin-stimulating hormone (TSH) demonstrated that (±)-THP decreased TSH in hyperthyroid rats after 14 days of treatment; however, propylthiouracil increased TSH in hyperthyroid rats. (±)-THP had no influence on TSH, or thyroid and pituitary weight in normal and hyperthyroid rats.
We conclude that (±)-THP has an antithyroid function and the mechanism of action may be related to the inhibition of TSH in the pituitary.
The Antistaphylococcal Effect of Nisin in a Suitable Vehicle: A Potential Therapy for Atopic Dermatitis in Man
Authors: Valenta Claudia , Bernkop-SchnüRch Andreas , Rigler Hans Peter 
Published: April 2011

Abstract
Staphylococcus aureus plays a central role in the pathogenesis of atopic dermatitis and is the predominant microorganism both in the lesions and in adjacent clinically normal skin. Chronic infection might aggravate the underlying lesion and serve as a source for further S. aureus infection. Nisin is a non-toxic and non-irritant peptide with no antibiotic-like side effects.
In this study the antistaphylococcal activity of nisin in six topical formulations was investigated in diffusion tests and is shown to depend both on the water content and on the technological system. Because topical products often adhere to the stratum corneum for only a short time, the kinetics of antimicrobial activity were examined using a membrane filter technique. Thirty minutes after nisin addition almost no living microorganisms were detectable in different aqueous samples.
The results demonstrate the potential of nisin preparations as an alternative to common antibiotics in the treatment of S. aureus infections in atopic dermatitis.
Chemical Approaches to Improve the Oral Bioavailability of Peptidergic Molecules
Authors: Samanen James , Wilson Glynn , Smith Philip L , Lee Chao-Pin , Bondinell William , Ku Thomas , Rhodes Gerald , Nichols Andrew 
Published: April 2011

Abstract
This review discusses both tools and strategies that may be employed as approaches towards the pursuit of orally active compounds from peptidergic molecules. Besides providing a review of these subjects, this paper provides an example of how these were utilized in a research programme at SmithKline Beecham involving the development of orally active GPIIb/IIIa antagonists. The tools for studying oral drug absorption in-vitro include variants of the Ussing chamber which utilize either intestinal tissues or cultured epithelial cells that permit the measurement of intestinal permeability. Example absorption studies that are described are mannitol, cephalexin, the growth hormone-releasing peptide SK&F 110679 and two GPIIb/ IIIa antagonist peptides SK&F 106760 and SK&F 107260. With the exception of cephalexin, these compounds cross the intestine by passive paracellular diffusion. Cephalexin, on the other hand, crosses the intestine via the oligopeptide transporter. Structure-transport studies are reviewed for this transporter. The tools for studying oral drug absorption in-vivo involve animals bearing in-dwelling intestinal or portal vein catheters. A study of the segmental absorption of SK&F 106760 is provided.
The review concludes with two chemical strategies that may be taken towards the enhancement of oral bioavailability of peptidergic molecules. The first strategy involves the chemical modification of peptides which enhance intestinal permeability, specifically the modification of amide bonds. The second strategy involves the design of compounds bearing nonpeptide templates, which are more amenable to the discovery of compounds with oral activity, from peptide pharmacophore models. An example is given regarding the discovery of SB 208651, a potent orally active GPIIb/IIIa antagonist, designed from the peptides SK&F 106760 and SK&F 107260.