bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin is a potent inhibitor of interleukin 1 induced cartilage proteoglycan resorption in-vitro
Authors: Rainsford K D 
Published: April 2011

Abstract
Since interleukin 1 (IL-1) induces the transcriptional synthesis of enzymes responsible for cartilage resorption it was decided to examine the effects of the antitumour drug, doxorubicin, a DNA transcriptional inhibitor, on αIL-1-induced cartilage—resorption in-vitro. Doxorubicin inhibited the resorption in a concentration-dependent fashion, an effect which was shown to be reversible. Fine structure of the chondrocytes was preserved by the doxorubicin treatment with IL-1 in contrast to the extensive cellular destruction evident in cartilage treated with IL-1 alone. [14C]doxorubicin was bound to cartilage proteoglycans, and this effect was promoted by treatment of the cartilage with IL-1. This binding of the drug may prevent access of the proteoglycans to destructive enzymes during the resorptive process induced by IL-1.
Difference spectrophotometric assay of nitrazepam in tablet formulations
Authors: Davidson A G , Li H W 
Published: April 2011

Abstract
A difference spectrophotometric procedure is described for the assay of nitrazepam in tablet formulations. The method is based on the measurement of absorbance at 282 nm of a solution of the tablet extract in 0·1 M hydrochloric acid (pH 1) relative to that of an equimolar solution in 0·1 M sodium hydroxide (pH 13). The method is precise and selective for nitrazepam in the presence of the tablet excipients and 2-amino-5-nitrobenzophenone, the principal hydrolysis product of nitrazepam. The absence of a constant isosbestic point in the difference spectrum of nitrazepam during hydrolysis in alkaline solution indicates the presence of a previously unrecognized intermediate hydrolysis product.
SK&F 93574, a histamine H2-receptor antagonist, releases histamine in the dog
Authors: Jones C A , Conybeare G , Mortensen A , Catto L C , Atterwill C K 
Published: April 2011

Abstract
This study was designed to establish whether SK&F 93574 releases histamine in dogs. Three female beagle dogs each received single infusions (on separate days) of each of SK&F 93574 (2·5 mg kg−1), polyvinylpyrrolidone (PVP, 20 mg kg−1) and sterile saline. The treatments were given at 14 day intervals by rapid intravenous infusion at 0·5 mL kg−1 min−1 for 2 minutes. Dogs showed clinical signs of histamine release such as vasodilation, licking lips, head drooping and increased gut movement after treatment with the known histamine releaser PVP or the test compound SK&F 93574. These signs were of similar severity and duration for the two compounds. No such changes were observed when the dogs received vehicle alone. Treatment with PVP or SK&F 93574 also resulted in markedly elevated plasma histamine concentrations (&gt; 10-fold increase over control). It is concluded that intravenous administration of SK&F 93574 to dogs is associated with histamine release.
Effects of the Mechanical Energy of Multi-tableting Compression on the Polymorphic Transformations of Chlorpropamide
Authors: Otsuka Makoto , Matsumoto Takahiro , Kaneniwa Nobuyoshi 
Published: April 2011

Abstract
The effects of the mechanical energy of tableting compression on the polymorphic transformation of chlorpropamide have been examined. A single-punch eccentric tableting machine with a load cell and a non-contact displacement transducer were used to measure compression stress, distance and energy. An amount of 100 mg of the stable form A or the meta-stable form C of the drug was loaded into the press and the sample compressed with a compression stress of 196 MPa at room temperature (20°C). The compression cycle was repeated from 1 to 30 times. The powder X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The results on forms A and C suggested that both forms were transformed into each other in the solid state by mechanical energy during tableting. The contents of forms A and C reached equilibrium at a constant value above 100 J g−1 of compression energy after more than 10 cycles. After 30 tableting cycles of forms A and C., the contents of A, C and the non-crystalline solid were almost constant at about 45, 25 and 30%, respectively. The compression energies were estimated to be about 500–600 J g−1. From the results it seems that the transformation mechanism of forms A and C during tableting were as follows. The crystal form of A or C was converted to a non-crystalline solid by the mechanical energy, and the solid was then transformed into form A or C.
Thermodynamics of the Binding of Phenothiazines to Human Plasma, Human Serum Albumin and α1-Acid Glycoprotein: A Calorimetric Study
Authors: Aki Hatsumi , Yamamoto Magobei 
Published: April 2011

Abstract
A flow microcalorimetric study has been carried out to investigate the interactions between phenothiazine derivatives and human plasma, human serum albumin (HSA) and α1acid glycoprotein (AGP) at pH 7·4 and 37°C. The direct analyses of enthalpic titration curves allowed the determination of the binding enthalpy change (δH), the apparent binding constant (K), and the number of the binding sites (n), as well as the evaluation of the apparent free energy (δG), and entropy (δS) changes. The overall binding of phenothiazines was exothermic with negative δH, which was compensated for by changes in δS. The values of δG were relatively insensitive to variation in the molecular details of the binding reaction. HSA possessed two classes of binding sites for phenothiazines. The first (n1 = 1), with high affinity (K1 = 105–106 M−1) was characterized by small negative δH and positive δS values due to hydrophobic interaction. The second class of sites had a low affinity (K2 = 103-104 M−1) and high capacity (n2 = 3–8) and contributed to the negative δH and δS values. The binding and thermodynamic parameters were influenced by the aliphatic side chain moieties on the phenothiazine nucleus. On the other hand, the drugs were bound to AGP at a single common binding site with a binding affinity of the order of 104M−1, characterized by negative δH and δS values, which partially reflected the effect of a van der Waals' interaction. In plasma the drugs were bound as a result of an enthalpy-driven type of reaction having large negative δH and a large binding capacity resulting from the presence of AGP and HSA.
Use of Strips Containing Tetracycline Hydrochloride or Metronidazole for the Treatment of Advanced Periodontal Disease
Authors: Deasy P B , Collins Augusta E M , Maccarthy Denise J , Russell R J 
Published: April 2011

Abstract
Strips containing tetracycline hydrochloride or metronidazole 25% in polyhydroxybutyric acid as a biodegradable polymer matrix, showed sustained release in simulated gingival fluid pH 6·6 at 37°C. When evaluated in patients suffering from advanced periodontal disease, the greatest response to therapy was observed with tetracycline hydrochloride strips inserted into periodontal pockets at four-day intervals for 16 days, compared with an untreated control group. A reduction in plaque index, gingival index and pocket depth was observed. A favourable alteration occurred in the microbial flora of treated pockets with an increase in the proportion of cocci and decrease in gram-negative rods, fusiforms and spirochetes. Metronidazole strips or root-planing tended not to be as effective. The clinical improvement produced by each treatment was not maintained when treatment was terminated.
The influence of changes in buccal potential difference on the buccal absorption of propranolol
Authors: Hitoglou-Makedou A , Hedges A , Turner P 
Published: April 2011

Abstract
A buccal potential difference (b.p.d.) exists across the mucous membrane of the mouth, which can be made less negative by contact with aspirin. The influence of changing the b.p.d. with aspirin on the buccal absorption of propranolol from a series of buffers of pH5–10 has been studied in eight volunteers. The study confirmed that the buccal absorption of propranolol was markedly pH dependent, but pretreatment of the buccal membrane with aspirin had no influence on the absorption of propranolol.
α1-Adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites
Authors: Hanft G , Gross G , Beckeringh J J , Korstanje C 
Published: April 2011

Abstract
Recently, it has been demonstrated that two distinct α1-adrenoceptor binding sites showing high and low affinity for WB-4101 (2-(2,6-dimethoxyphenoxy)ethyl-aminomethyl-1,4-benzodioxane) and 5-methyl-urapidil can be distinguished. In the present study we examined the ability of several agonists and antagonists to discriminate between these α1-adrenoceptor binding sites. [3H]Prazosin binding to membranes of rat liver, heart, cerebral cortex and hippocampus was inhibited monophasically by butanserine, I-BE 2254 (2-(3-(4-hydroxy-3-iodophenyl)ethylaminomethyl)tetralone-hydrochloride), prazosin, rauwolscine and verapamil. In contrast, competition curves of adrenaline, oxymetazoline, amidephrine and YM-12617 (5-[2-[[2-(o-ethoxy-phenoxy)ethyl]-amino]propyl]-2-methoxybenzenesulfonamide HCl)were best described by a model of two binding sites. Chloroethylclonidine (CEC), a compound shown to irreversibly eliminate binding sites with low affinity for WB-4101, increased the proportion of high affinity binding sites for oxymetazoline and amidephrine, whereas the binding data for prazosin and adrenaline remained unchanged. These results indicate that amidephrine, oxymetazoline and YM-12617, but not the other drugs tested discriminate between different α1-adrenoceptor recognition sites labelled by [3H]prazosin.
Assessment of topical non-steroidal anti-inflammatory drugs
Authors: Poelman M C , Piot B , Guyon F , Deroni M , Leveque J L 
Published: April 2011

Abstract
A new non-invasive technique for assessing the efficacy of topical non-steroidal anti-inflammatory drugs (NSAID) in man is proposed. The NSAID are initially applied to the skin under occlusion before inflammation is induced by a methyl nicotinate solution. The inflammatory response is quantified in terms of cutaneous blood flow by a laser Doppler velocimeter (LDV). The efficacy of NSAID preparations is calculated by comparing the responses of the LDV to the methyl nicotinate challenge on the pretreated and the non-treated skin sites. This protocol has been used to investigate the effect of three different NSAID preparations (indomethacin, niflumic acid, palmitoyl collagenic acid) and the influence of the vehicle on the efficacy of indomethacin. The three preparations tested gave positive results but with different amplitudes in response. The efficacy of indomethacin varied with the vehicle used.
Amino acids dilate resistance blood vessels of the perfused rat mesentery
Authors: Al-Swayeh O A , Moore P K 
Published: April 2011

Abstract
The vasodilator effect of several L-amino acids in the perfused, noradrenaline-preconstricted rat mesentery preparation has been investigated. N-α-Benzoyl-L-arginine ethyl ester (BAEE) (ED50, 1·4 ± 0·09 μmol) and L-alanine methylester (ED50, 0·9 ± 0·007 μmol) were the most potent although L-arginine methylester, hydroxamate and hydrochloride, N-α-benzoyl-L-arginine methyl ester (BAME), L-methionine methylester, L-lysine hydroxamate and L-glutamic acid methylester exhibited similar potency with ED50 values in the range 2·4–3·7 μmol. L-Homoarginine chloride was inactive at doses up to 20 μmol. D-Arginine hydrochloride and D-lysine hydroxamate were inactive at doses up to 50 μmol whilst D-methionine methylester (50 μmol) produced small falls in perfusion pressure in only 3 out of 7 preparations studied. Responses to BAEE, BAME, L-arginine hydrochloride, L-alanine methylester, L-methionine methylester, L-lysine hydroxamate and acetylcholine (but not nitroprusside) were significantly inhibited by CHAPS (4·7 mg mL−1, 30 s) de-endothelialization as well as pretreatment of mesentery preparations with gossypol (3 μM). Responses to BAEE, BAME, L-arginine hydrochloride, L-alanine methylester and acetylcholine were similarly selectively reduced by NDGA (10 μM) pretreatment. We propose that these L-amino acids exhibit vasodilator activity in the perfused rat mesentery by virtue of releasing endothelium-derived nitric oxide (EDNO).
An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits
Authors: Prakongpan S , Sirimai S , Edwards G , Mcgrath C S , White N J 
Published: April 2011

Abstract
Intramuscular chloroquine is rapidly absorbed, even in severe falciparum malaria, and may cause potentially lethal hypotension. Less rapidly absorbed formulations should be safer. A chloroquine phosphate solution containing 2% methylcellulose 1500 released chloroquine 2·6 times more slowly than a commercial aqueous solution in an in-vitro absorption simulator. There was a log linear relationship between viscosity and release rate. The absorption pharmacokinetics of the more viscous chloroquine phosphate solution were then compared with those of a commercial solution after intramuscular injection to eight rabbits in an open cross over comparison. The rate of absorption was over three times slower with the viscous solution; median time to peak whole blood concentration with the commercial aqueous solution was 10 (range 5–20) min compared with 30 (range 10–60) min for the more viscous formulation (P &lt; 0·05). Peak whole blood concentrations were 66% (95% CI 50–82%) of those with the commercial preparation, but the acute bioavailability of the two solutions was similar. This simple new formulation may be safer than currently available chloroquine preparations and should now be evaluated in man.
Studies on the effects of omeprazole on thyroid function in the rat
Authors: Atterwill C K , Brown C G , Fowler K L , Jones C A 
Published: April 2011

Abstract
The effects of omeprazole (an H+, K+-ATPase inhibitor) on thyroid parameters in rats have been examined. SK&F Wistar rats were dosed orally with omeprazole (up to 500 mg kg−1) or vehicle. Treatment for 7 or 14 days resulted in generally decreased plasma T3 concentrations in males (with little change or slight increases in females) and increased serum TSH concentrations (22%–68% increases). No changes were detected in thyroid 125I uptake or organification. Liver 5′-deiodinase activity was decreased in male rats after 7 days treatment. Thyroxine clearance was not altered after a single dose of omeprazole. In-vitro studies showed omeprazole to be only a weak inhibitor of TSH-stimulated 125I organification in cultured porcine thyrocytes. It is concluded that omeprazole has weak effects on the pituitary-thyroid-liver axis, its main action being to inhibit the peripheral deiodination of thyroid hormones.
The In-vitro pH-Dissolution Dependence and In-vivo Bioavailability of Frusemide-PVP Solid Dispersions
Authors: Doherty C , York P 
Published: April 2011

Abstract
The dependence of the dissolution rate on the pH of the buffered medium, using constant surface area discs, has been examined for crystalline frusemide, a semi-crystalline frusemide-polyvinylpyrrolidone (PVP) solid dispersion and an X-ray amorphous frusemide-PVP dispersion. The marked changes observed in the pH-dissolution profiles indicate that differing dissolution mechanisms operate in the amorphous regions. This conclusion was further supported by the comparison of pH-dissolution and pH-equilibrium solubility profiles that suggested a supersaturation effect to be the relevant term in describing the dissolution enhancing effects of amorphous regions. A marked dissolution enhancement, relative to crystalline frusemide, was shown by the X-ray amorphous solid dispersion in weakly acidic solutions. A similar effect was observed in the dissolution characteristics of gelatin capsule formulations in simulated gastric and intestinal media. In a human bioavailability study, the X-ray amorphous frusemide-PVP solid dispersion exhibited a significant reduction in the time for maximum effect in comparison to crystalline frusemide and a semi-crystalline solid dispersion. This effect, demonstrated by the primary end organ response in seven healthy subjects, concurred with the in-vitro prediction of dissolution enhancement in weakly acidic media.
Topical Application of Penetration Enhancers to the Skin of Nude Mice: a Histopathological Study
Authors: Lashmar Ulla T , Hadgraft Jonathan , Thomas Norman 
Published: April 2011

Abstract
Eighteen potential penetration enhancers, some at concentrations that might be used for that purpose, have been examined to evaluate their irritancy potential on nude mouse skin. A biopsy technique was employed followed by histological examination. Up to 50% glycerol, 10% hydroxyethyl lactamide (HELA), 10% oleyl alcohol, 10% Solketal, 10% glycofurol, 100% tetrahydrofurfuryl alcohol (THFA) and 10% urea induced no discernible change in the histological appearance of the skin whereas 100% dimethyl sulphoxide (DMSO), 100% dimethyl formamide (DMF), 100% N-methyl-2-pyrrolidone, 10% Azone, 10% oleic acid, 10% methyl laurate, 10% benzyl alcohol and 10% glycerol formal caused severe skin irritation.
Thermodynamics of the binding of salicylate to human serum albumin: evidence of non-competition with imidazole
Authors: Matias I , Ceballos A , Gonzalez-Velasco F , Cachaza J M 
Published: April 2011

Abstract
The thermodynamic characteristics of the binding of salicylate to human serum albumin have been studied using a technique based on the variation of the quantum yield of fluorescence of salicylate when it binds to the protein. The binding constants, number of sites and the values of ΔG°, ΔH° and Δ° were determined. The results are consistent with a model that proposes two equal and independent types of binding site with a predominantly ionic interaction and an important hydrophobic contribution in one of the sites. The technique was also used to demonstrate that imidazole and salicylate (that can be found simultaneously in plasma following administration of imidazole-2-hydroxybenzoate) do not compete for the same binding sites on the protein.
Enhancement of phenytoin binding to tissues in rats by heat treatment
Authors: Kato Yoshiteru , Hirate Junji , Sakaguchi Kazuo , Horikoshi Isamu 
Published: April 2011

Abstract
Phenytoin binding to heat-treated tissue homogenates has been examined to characterize the phenytoin binding to tissues. The binding to the heat-treated tissue homogenates was enhanced in all tissues studied compared with controls. The heating might produce the changes in conformation of proteins in tissues and then enhance phenytoin binding to tissue homogenates.
Effect of some penicillins on the sensitivity of limulus amoebocyte lysate test
Authors: Al-Khalifa Issa J , Naidu N V , Nallari V R , Raut H I 
Published: April 2011

Abstract
A group of penicillins have been tested for their effect on the sensitivity of limulus amebocyte lysate test (LAL). Cloxacillin, cephalothin and cefuroxime inhibited the gel formation at concentrations above 2 mg mL−, while ampicillin, methicillin and mecillinam showed no inhibitory effects upto concentrations of 10 mg mL−1. For benzylepenicillin the maximum non-inhibitory concentration was 10,000 units mL−1. However, the dilutions required to overcome inhibition were within the limits of maximum valid dilutions computed for each product showing that LAL test is valid for these products at their non-inhibitory concentrations.
Determination of cephalosporin-C amidohydrolase activity with fluorescamine
Authors: Reyes F , Martinez M-J , Soliveri J 
Published: April 2011

Abstract
A spectrophotometric procedure for the assay of cephalosporin-C amidohydrolase activity, based on the determination of the 7-aminocephalosporanic acid (7-ACA) produced in the hydrolysis of cephalosporin-C by the enzyme, is described. This procedure can be used to detect 7-ACA over a range of 10 to 200 μg mL−1. The same method can be used as a fluorometric procedure with a 100-fold greater sensitivity. At pH 4·5 7-ACA produces a strong fluorophor with fluorescamine, detectable spectrophotometrically at 378 nm and fluorometrically at an excitation of 378 nm and emission of 495 nm. At this pH the fluorophors formed with cephalosporin-C, proteins and aminoadipic acid present minimal absorbance values. The conditions for maximal detection of 7-ACA in the presence of proteins, cephalosporin-C and aminoadipic acid have been determined.
The Effect of Some Preservatives Used in Nasal Preparations on Mucociliary Clearance
Authors: Batts A H , Marriott C , Martin G P , Bond S W 
Published: April 2011

Abstract
The effect of methyl-ρ-hydroxybenzoate, propyl-ρ-hydroxybenzoate, chlorbutol, chlorocresol, EDTA, benzalkonium chloride, chlorhexidine, phenylmercuric nitrate and phenylmercuric borate on mucociliary transport rate of the frog palate has been examined. Following a variable number of applications all these preservatives halted transport, the first three reversibly. However, applications of thiomersal (0·01%) were well tolerated. The frog palate possesses a ciliated epithelium protected by mucus, since some of our findings are at variance with those previously reported results where the protective effect of mucus was negligible in the in-vitro model (usually trachea) employed, it would appear that the contribution of mucus to effective mucociliary clearance should not be underestimated.
Phorbol Esters of Different Biological Activities May Preferentially Act as Mitogens of Human Suppressor T-Cells and are Equi-effective Mitogens of IL-2 Dependent Cells
Authors: Edwards Mary C , Tudor Evans A , Evans Fred J 
Published: April 2011

Abstract
The actions of tetradecanoylphorbolacetate (TPA) and 12-deoxyphorbolphenylacetate-20-acetate (DPPAA) together with a phytohaemagglutinin (PHA) have been examined on the proliferative responses of human mononuclear cells (MNC) depleted of specific cell subsets by the use of monoclonal antibodies. PHA-induced proliferation was found to be reduced when monocytes/macrophages and T-helper cells were depleted from MNC, but enhanced compared with MNC responses when T-suppressor cells were depleted. In contrast, TPA- and DPPAA-induced proliferation was unchanged or slightly enhanced following macrophage/monocyte depletion, and whereas TPA-induced proliferation was largely independent of subtype constitution, the non-tumour promoting DPPAA appeared to selectively enhance proliferation of the T8+ suppressor subset. Indomethacin increased the proliferative MNC responses of phorbol esters whilst having little effect upon the PHA response, an effect antagonized by addition of PGE2. The addition of interleukin-2 (IL-2) increased the proliferative response, as well as resistance to inhibition induced by cyclosporin A and dexamethasone and partially abolished the selective actions of DPPAA and PHA. In IL-2 dependent cultures PHA induced stimulation was more sensitive to inhibition by cyclosporin than were the phorbol esters. The results suggest that, although induction of lymphocyte proliferation by phorbol esters is not a correlate for tumour promotion itself, non-promoting phorbol esters may have a more restricted ability to induce proliferation than TPA.