摘要:

AbstractThe effect of triazole antifungal agents on the drug secretion process from the serosal to the mucosal side in small intestine was studied using rat everted intestinal sacs. Rhodamine 123 was used as a model drug mediated by P‐glycoprotein.The effect of inhibitors, verapamil and triazole antifungal agents was investigated by measuring the efflux of rhodamine 123. Efflux was significantly reduced by the addition of verapamil. Fluconazole had no effect on the efflux of rhodamine 123, while the efflux of rhodamine 123 was significantly reduced by oral administration of itraconazole.These results suggest that inhibition of drug secretion by P‐glycoprotein in intestine may be involved in the interaction between various drugs and itraconaz

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00549.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractGossypol has a potent anti‐amoebic effect on bothEntamoeba histolyticaaxenic cultures and experimental amoebic hepatic abscess. However, the margin between the in‐vivo effective dose and the toxic dose in hamsters is relatively small. While metronidazole is widely used as an anti‐amoebic medication, it is considered a possible carcinogen in man.With the aid of the Basic Sequential Analytical Simplex Method we tested the effectiveness of 12 metronidazole‐gossypol blends where the concentration of each drug was systematically varied. Amoebic growth inhibition was observed (33–71% with respect to controls) using blends containing metronidazole (50–154 nM) and gossypol (5–16 nM). The combination containing metronidazole (88.61 nM) and gossypol (9.95 nM) caused 62% amoebic growth inhibition. These concentrations where 50% lower than those required to produce an equivalent effect using metronidazole or gossypol alone.Thus, the actions of metronidazole and gossypol againstE. histolyticaare additive. Accordingly, the in‐vivo application of an appropriate combination of metronidazole and gossypol could be as effective as each drug alone, but less to

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00550.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe anti‐amoebic potency of secnidazole and dimetridazole was compared with three other anti‐amoebic nitroimidazoles—metronidazole, ornidazole, and tinidazole.The analyses were performed in‐vitro, against theEntamoeba histolyticaHM1:IMSS strain. The amoebae were maintained in axenic conditions in PEHPS medium. Secnidazole and dimetridazole showed an anti‐amoebic potency (IC50 0.013 and 0.014 μg mL−1, respectively) ten times higher than metronidazole, ornidazole and tinidazole (IC50 0.131, 0.081, and 0.210 μg mL−1, respectively).These results suggest that secnidazole and dimetridazole are promising candidates f

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00551.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractMany bacterial plasmids encode error‐prone (mutagenic) DNA repair. Some antibacterial drugs, such as the quinolones, damage DNA and induce repair, and the presence of such plasmids may therefore increase clinical mutation frequency to drug resistance.Plasmid R46, which increases mutation frequency and protects strains ofEscherichia coliagainst DNA damage induced by ultraviolet light (UV), together with plasmids R391 and pYD1, which increase mutation frequency, but sensitize to UV, and RP4, which does not affect post‐UV survival, were tested inE. coliTK501umuC uvrBfor their effect on DNA synthesis after UV exposure. Synthesis recovered rapidly in the strain containing R46 compared to the plasmid‐negative and RP4‐containing controls, whereas in the R391 and pYD1‐containing strains it remained lower than in controls for up to five hours.Both R46 and R391 carry genes that are homologues of chromosomal error‐prone repairumuDCgenes, and the data presented in this paper suggest that variation in the control of repair gene expression may account for the different plasmid‐encoded

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00552.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe effect of maltosyl–β‐cyclodextrin (G2‐β‐CyD) on self‐association of insulin was investigated by electrospray ionization mass spectrometry (ESI‐MS) coupled with measurement of hydrogen/deuterium (H/D) exchange rates of the peptide.Bovine insulin (MW 5734) gave three signals at 956, 1147 and 1433 corresponding to the [M + 6H]6+, [M + 5H]5+and [M + 4H]4+ions, respectively. By the addition of G2‐β‐CyD, a new signal was observed at 1438 which corresponds to the 1: 1 adduct of penta‐ionized insulin with G2‐β‐CyD, [M + G2‐β‐CyD + 5H]5+. The H/D exchange rate of insulin was fast in 30% v/v acetic acid solution where the peptide is predominantly in a monomer state, and the rate was unchanged by the addition of G2‐β‐CyD. However, the exchange rate significantly slowed down in pH 2.0 solution where insulin is predominantly in a dimer state, and the rate increased with increasing G2‐β‐CyD concentration, indicating that G2‐β‐CyD shifts the monomer‐dimer equilibrium of insulin in favour of the dissociated form.These results suggest that G2‐β‐CyD inhibits the self‐association of insulin through the interaction with hydrophobic amino acid residues of the peptide, and mass spectroscopic technique is

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00553.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractSodium ascorbate (vitamin C), a compound that is sensitive to photochemical oxidation, was stabilized against UV light 120‐fold (t 1/2 increased from about 0.9 h to 112h) by entrapping the vitamin in the form of an α‐cyclodextrin complex in the aqueous phase of multilamellar liposomes composed of equimolar phosphatidylcholine and cholesterol, and containing the light absorbers oil red O and sulisobenzone in their lipid and aqueous phases respectively.α‐Cyclodextrin, the smallest of the natural cyclodextrins, was found to accommodate sodium ascorbate in its cavity with a stability constant of 112 M−1, calculated kinetically. The identification of the formed inclusion complex was carried out in the solid state by differential scanning calorimetry. Entrapment values for all compounds incorporated in liposomes were calculated simultaneously by derivative spectrop

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00554.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe mammalian lignans enterolactone and enterodiol have gained reputation as cancer‐protective agents. These substances are produced in man by a gut microfloral‐promoted transformation of opportune plant lignan precursors such as secoisolariciresinol diglucoside (3). This lignan is largely contained in flaxseed in the form of a more complex glucoside of still undisclosed structure and thus unsuitable for direct quantitative procedures. Since flaxseed‐supplemented diets are usually employed to investigate the cancer‐protective effect of a high mammalian lignan producing diet, a rapid and reliable analytical method for assaying3yield in flaxseed would be highly desirable.Acid hydrolysis of defatted flaxseed gives rise to 3,4‐bis[(3‐methoxy‐4‐hydroxy‐phenyl)methyl] tetrahydrofuran (5), a degradation product readily amenable to gas chromatography resulting from the quantitative secoisolariciresinol‐carrying complex glucoside cleavage. A gas chromatography‐based internal standard method was then set up to derive the true content of3from the quantitative determination of the hydrolysis product5. The method can reliably quantitate5with good linearity, a

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00555.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe release characteristics of diltiazem were modified by short‐ and long‐chain peracylated β‐cyclodextrins, peracetyl‐β‐cyclodextrin (TA‐β‐CyD) and peroctanoyl‐β‐cyclodextrin (TO‐β‐CyD), and their combination in different molar ratios.The release rates of diltiazem from both powder and compressed tablets consisting of diltiazem/TA‐β‐CyD/TO‐β‐CyD decreased in the order of diltiazem alone (t 1/2 = 1 min (powder) and 1 min (tablets))

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00556.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractPrevious investigations into the chiral inversion of 2‐arylpropionic acids by the fungusVerticillium lecaniihave suggested that the mechanism of inversion is similar to that found in mammalian systems. The purpose of this investigation was to determine whether chiral inversion could be demonstrated in cell extracts and if the cofactor requirements were the same.Cell extracts were produced by homogenization of a concentrated cell suspension in either buffer A (100 mM sodium phosphate buffer pH 7.4; 10 mM magnesium chloride) or buffer B (100mM sodium phosphate buffer pH 7.4; 10mM magnesium chloride; 0.1% Triton X‐100 v/v), followed by filtration through a 5‐μm nitrocellulose filter. Assays were set up in the presence of ATP and coenzyme A and eitherR,S‐, R‐ orS‐2‐phenylpropionic acid as substrates and it was found that bidirectional chiral inversion occurred using the pure enantiomers after 16 h incubation only using the cell extracts produced in buffer B. This chiral inversion process was found to occur only when an exogenous coenzyme A supply was present suggesting that the chiral inversion process is similar to the mammalian system where coenzyme A plays a key role.The ability to invert the chirality of the substrate was lost on filtering the cell extract through a 0.45‐μm filter and direct evidence was obtained for the presence of active mitochondria in the 5‐muMm filtrate, suggesting that this may be the site of the inversion re

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00557.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractAlkyl, cycloalkyl or aryl ester analogues of nifedipine, in which the ortho‐nitrophenyl group at position 4 is replaced by 1‐methyl‐5‐nitro‐2‐imidazolyl substituent, were synthesized and evaluated as calcium‐channel antagonists using the high K+contraction of guinea‐pig ileal longitudinal smooth muscle.The results for the symmetrical esters showed that increasing the length of methylene chain (n>2) decreases activity. The relative activity profile for asymmetrical esters was cyclopentyl>cyclohexyl>cyclopropyl. Comparison of esters having the same methylene space showed that the cyclohexyl compounds were more active than the corresponding phenyl derivatives. In addition, asymmetrical esters possessing one R2substituent (methyl>ethyl) indicated that increasing the length of methylene chain in the R1‐substituent decreased activity.Our results demonstrate that several compounds were more active than the reference drug nifedipine. The symmetrical cyclohexyl ester (n = 0) and the asymmetrical (R1= cyclohexyl, R2= Me, n = 0) derivatives were the most potent a

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00558.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY