Alcohol induced conformational transitions of proteins and polypeptides

Integral enthalpies of solution of diglycine in tert.-butyl alcohol + water and of diglycine and β-alanine in ethanol + water mixtures were measured at 298.15 K as a function of alcohol concentration. Enthalpies of transfer of the solutes from water to aqueous alcohol mixtures were evaluated from these data. Entropies of transfer of a peptide backbone unit (CH₂CONH) and peptide group (CONH) from water to aqueous ethanol solutions were derived from the enthalpy of transfer data and the free energies of transfer of glycine, α-alanine, β-alanine and diglycine. The thermodynamic transfer functions are discussed in terms of “water structure” mediated solute-solute interactions. The observed trends in the thermodynamic transfer functions have also been utilized to rationalize the effect of alcohols on the conformational stability of proteins and polypeptides in aqueous solutions     

Interactions of beta- and hydroxypropyl-beta-cyclodextrin with some purine alkaloids: thermodynamic study

The effect of native and hydroxypropylated beta-cyclodextrin on the solubility and activity of some purine alkaloids was examined. For this purpose, the solubility of purine alkaloids in pure water and in aqueous solutions of mentioned beta-cyclodextrins was determined at 298.15 K. Stability constants of inclusion complexes and their stoichiometry were obtained from solubility diagrams. Enthalpic characteristics of interactions occurring between beta-cyclodextrins and purine alkaloids in aqueous solution were calculated from the direct calorimetric measurements. It was found, that beta-cyclodextrin forms with purine alkaloids weak complexes which are stabilized only by the entropy term. Due to very low complexing affinity of both beta-cyclodextrins to studied purine alkaloids their solubilizing effect is insignificant. The influence of structure of purine alkaloids and beta-cyclodextrin on the thermodynamic parameters of interaction was discussed.     

The effect of urea on the solubility of methyl p-hydroxybenzoate in aqueous sodium chloride solutions

The effects of sodium chloride and urea, separately and together, on the solubility of methyl p-hydroxybenzoate in water have been studied. Sodium chloride decreases and urea increases the solubility. Observed and calculated “salting-out” parameters have been obtained for addition of sodium chloride to the benzoate-urea-water systems. Good agreement was observed between calculated and observed values, and the change in the “salting-out” parameters as the concentration of urea altered may indicate dipole-ion interaction between urea and sodium chloride.     

Solvation of human serum albumin in aqueous alkylurea solutions

Solvation of human serum albumin in aqueous solutions of urea, methyl-, N,N′ -dimethyl-, and ethylurea was studied by density measurements. From the densities at constant molality and constant chemical potential, the preferential solvation parameters of human serum albumin were determined. In all solutions the denaturant is preferentially bound. From preferential solvation data, Gibbs free energies of transfer from water to alkylurea solutions were calculated. Since the enthalpies of transfer were determined previously the entropies of transfer would also be obtained. Based on these and model compound data an attempt is made to identify various interactions involved in solvation. The total binding of denaturant to protein could also be calculated from preferential solvation data. The following major binding sites have been identified: ionic groups on the surface of protein molecules, peptide groups and aromatic side-chains. The correlation between the total number of sites and the number of urea molecules bound is satisfactory.     

Closantel nano-encapsulated polyvinyl alcohol (PVA) solutions

The influence of closantel on the rheological and physicochemical properties (particle size and by UV–Vis absorption spectroscopy) of PVA aqueous solutions is studied here. About 1% PVA aqueous solutions were prepared by varying the closantel content. The increase of closantel content led to a reduction in the particle size of final solutions. All the solutions were buffered at pH?7.4 and exhibited shear-thinning behavior. Furthermore, in oscillatory flow, a “solid-like” type behavior was observed for the sample containing 30?μg/mL closantel. Indicating a strong interaction between the dispersed and continuous phases and evidencing an interconnected network between the nanoparticle and PVA, this sample also showed the highest shear viscosity and higher shear thinning slope, indicating a more intrincate structure disrupted by shear. In conclusion, PVA interacts with closantel in aqueous solution and the critical concentration for closantel encapsulation by PVA was about 30?μg/mL; above this concentration, the average particle size decreased notoriously which was associated to closantel interacting with the surface of the PVA aggregates and thus avoiding to some extent direct polymer–polymer interaction.     

The swelling properties of poly(2-hydroxyethyl methacrylate) hydrogels polymerized by gamma-irradiation and chemical initiation

The swelling behaviour of polyHEMA hydrogels in aqueous solutions of various compounds has been investigated. Gels polymerized using a chemical initiator attained a higher equilibrium hydration in aqueous solutions than those polymerized by ionizing radiation. The difference in equilibrium hydration has been explained in terms of the effect of residual initiator on swelling. Aqueous solutions of sodium chloride, sucrose and glucose were found to dehydrate the gels, while solutions of phenol, urea, acetic acid, acetamide, ethanol, sodium acetate and ethyl urea caused swelling. The extent of swelling was a function of the osmotic activity, size, lipophilicity and number of hydrogen bonding groups of the solute molecule. A linear relationship was found between the swelling rate and the concentration of cross-linking agent in the gel.     

Dynamic swelling behavior of gamma-radiation induced polyelectrolyte poly(AAm-co-CA) hydrogels in urea solutions

The aim of this study was to investigate the equilibrium swelling properties in urea solutions of gamma-radiation induced polyelectrolyte copolymeric hydrogels consisting of acrylamide (AAm) and crotonic acid (CA). Poly(acrylamide-co-crotonic acid), poly(AAm-co-CA) hydrogels containing different amounts of CA were obtained in the form of rods after radiation. Swelling experiments were performed in aqueous urea solutions at 25 degrees C, gravimetrically. The hydrogels showed large extents of swelling in aqueous (urea/water) media the swelling being highly dependent on the chemical composition of the hydrogels and irradiation dose. The percentage swelling of poly(AAm-co-CA) hydrogels was between 1160 and 4250%, while that of the AAm hydrogels was between 670 and 900%. The diffusional exponent values (n) are between 0.51 and 0.66, hence the diffusion of urea/water into the hydrogels is non-Fickian. Equilibrium urea/water contents of the hydrogel systems were changed between 0.870 and 0.977.     

Spontaneous Self-Assembly of Polymeric Nanoparticles in Aqueous Media: New Insights From Microfluidics,In Situ Size Measurements,and Individual Particle Tracking

Supramolecular cyclodextrin-based nanoparticles (CD-NPs) mediated by host-guest interactions have gained increased popularity because of their “green” and simple preparation procedure, as well as their versatility in terms of inclusion of active molecules. Herein, we showed that original CD-NPs of around 100 nm are spontaneously formed in water, by mixing 2 aqueous solutions of (1) a CD polymer and (2) dextran grafted with benzophenone moieties. For the first time, CD-NPs were instantaneously produced in a microfluidic interaction chamber by mixing 2 aqueous solutions of neutral polymers, in the absence of organic solvents. Whatever the mixing conditions, CD-NPs with narrow size distributions were immediately formed upon contact of the 2 polymeric solutions. In situ size measurements showed that the CD-NPs were spontaneously formed. Nanoparticle tracking analysis was used to individually follow the CD-NPs in their Brownian motions, to gain insights on their size distribution, concentration, and stability on extreme dilution. Nanoparticle tracking analysis allowed to establish that despite their non-covalent nature, and the CD-NPs were remarkably stable in terms of concentration and size distribution, even on extreme dilution (concentrations as low as 100 ng/mL).     

The effect of temperature on the solubilities of testosterone propionate in low polarity solvents

The solubilities of testosterone propionate have been determined between 25 and 100° in 15 solvents and compared with theoretical values obtained from regular solution theory. Entropy considerations show that solvent-solute interactions occur in some solvents, increasing the solubility and resulting in deviations from regular solution behaviour. “Regular solutions” are obtained only in saturated hydrocarbon solvents, and the solubility is more accurately predicted as the temperature approaches the melting point, and as the molar volumes of solvent approach that of the solute.     

Influence of hashish extract on the social behaviour of encountering male baboons (Papio c. anubis)

The effects of hashish extract (2 mg Δ⁹-THC/kg)on the social behaviour of encountering male baboons were tested by ethological methods. In the “approaching” male the drug reduced “approach” and the aggressive elements “hit-ground”, “brows-back” and “attack” but increased the frequency of “retreat”. Social interactions were generally diminished. In the “retreating” male friendly social interactions as “lipsmack” and “touch-back/handle-genitals” were suppressed but thethreatening elements “open-mouth” and “tooth-grind” were stimulated. “Retreat” was additionally more frequent. Non-social activities and locomotion were not affected in either of the males. Treating both subjects with hashish resulted in a reduction of “lipsmack”, “approach”, “fight” and “chase” in the approaching and “lipsmack”, “touch-back/handle-genitals”, “chase”, “retreat” and “flee” in the retreating male. Social activities were generally reduced in both animals. Comparing the behavioural effects of hashish in male baboons to those described in other non-human primates, in rodents but also in man revealed analogous effects in all species. The drug generally impaired social interactions, induced social withdrawal and led to social isolation of the drugged subject.     

Alcohol Consumption and Alcohol-Related Problems: Prevalence amongst a General Practice Population

Abstract: The prevalence of “at risk” levels of alcohol consumption and of alcohol-related problems in a sample of general practice patients was examined. Consumption was measured using both Quantity Frequency (N = 2066) and retrospective diary (N = 808) measures. The two measures yielded similar results. The proportion of females drinking “at risk” levels (40 gms a day) ranged from 0.6% to 1.2% and between 4.1% and 5.8% of males were classified “at risk” (60gms/day). Using the SMAST to measure alcohol-related problems, 8.6% of females and 12.1% of males were classified as “probable alcoholic”, while “possible alcoholism” was present in a further 15.1% of females and 20.1% of males. Only a weak relationship was found between being at physical risk on the basis of excessive consumption and being identified as having alcohol-related problems by the SMAST. Logistic regression was used in an attempt to delineate predictors of alcohol-related problems. Smoking status, alcohol consumption, age and report of skin problems entered the final model, but the prediction from this model was poor (X² = 322.67, df = 204, p = 0.122). The results are discussed in terms of strategies for general practitioner detection and intervention with patients with alcohol-related problems.     

THE HAEM-ACCESSIBILITY IN LEGHAEMOGLOBIN OF LUPINUS LUTEUS AS OBSERVED BY PROTON MAGNETIC RELAXATION

Using the solvent-protons' longitudinal magnetic relaxation rates (p.m.r.) for Lupinus luteus leghaemoglobin derivatives the accessibility of the haem has been evaluated by our “stereo-chemical p.m.r. titration” method with nonexchangeable protons of aliphatic lower alcohols in otherwise deuterated solutions. The haem in leghaemoglobin is more accessible and its protein environment more flexible compared with vertebrate haemoglobins. The correlation time in aquometleghaemoglobin aqueous solution has been determined by measuring the frequency dispersion of the p.m.r. rates between 6.1 and 93 MHz. Taking into account the measured value of τ_c = (7.7 ± 0.5) × 10^-10 s the iron-to-proton inter-spin distances have been calculated. The significance of these distances as well as the electronic g-factor anisotropy for elucidation of fine structural details of the haem-environment are discussed.     

Influence of chlordiazepoxide on alcohol consumption in mice

In a free-choice situation, chlordiazepoxide (CDP; 12.5 or 25 mg/100 ml; groups B or C), when incorporated in ethanol solutions (2 to 20%, v/v), caused a significant decrease in ethanol preference index (P.I.). This was probably due to the combined CNS effects of both drugs rather than a taste effect, since the mice did not discriminate between aqueous CDP solutions and water. However, when the mice had prior exposure to ethanol and CDP was incorporated intermittently, no significant decreases in P.I. resulted. In a no-choice situation, ethanol intake was increased only on the first day of each intermittent incorporation of CDP (3 days for each 6-day cycle), being more persistent in group B (2 to 15% ethanol) than in group C (2 to 6.5%). Ethanol intake decreased in group C when alcohol concentrations exceeded 10%. The “first-day” CDP effect also occurred in the no-choice situation of an ethanolic liquid diet. Possible factors for this effect are discussed. Thus the effects of CDP on alcohol consumption in non-deprived mice vary with experimental designs.     

Evaluation of community pharmacists’ knowledge about drug–drug interaction in Central Saudi Arabia

IntroductionAlthough all implemented and ongoing initiatives, drug-drug interactions (DDIs) are still a global problem. Most published studies about DDIs in Saudi Arabia are carried out in hospital settings. In addition, assessing the knowledge of drug interactions in Saudi Arabia is limited. The aim of our study is to evaluate the knowledge of potential common drug-drug interactions among community pharmacists particularly in Saudi Arabia.MethodologyA crosses-sectional study utilizing a self- administered questionnaire was conducted among community pharmacy in Riyadh city Saudi Arabia. DDIs' knowledge was assessed by 26 drug pairs. Community pharmacists were asked to select the DDIs as “contraindication”, “may be used together with monitoring”, “no interaction” and “not sure”.ResultsA total of 283 of community pharmacists completed the survey with response rate of 80.9%. Among the 26 drug pairs only 5 of them were identified correctly by most of the participants. To add more 3 out of the 5 pairs had a cutoff of less than 10% between the correct and wrong answer, meaning there still a majority that couldn't identify the correct answer. All the 26 pairs had a statistically significant difference between the correct and incorrect answer.ConclusionThe results of this study showed that knowledge of community pharmacists about DDIs was inadequate. Community pharmacist should have specific courses in drug interactions to cover the most possible interactions that can be seen in this setting.     

修订“药品”定义时必须重视的几个关键性问题

目的:为修订"药品"定义提供建设性建议。方法:依据国家的有关法律、法规和行政规章,研究问题、分析原因、探讨对策。结果与结论:"药品"定义的可修订空间十分有限。当前最紧迫的工作应该是将解决现有违反"药品"定义的某些原则性问题,列为先于修订"药品"定义的前置性工作,展开深入研究,并尽早妥善解决。同时,修订"药品"定义时应该阐明"药品"与药物(包括试验用药品)的关系,以便合法地规范用词。     

Nutraceutical-definition and introduction

Dr Stephen DeFelice coined the term “Nutraceutical” from “Nutrition” and “Pharmaceutical” in 1989. The term nutraceutical is being commonly used in marketing but has no regulatory definition. An attempt to redefine nutraceuticals and functional foods is made in this article. The proposed definitions can help distinguish between functional foods, nutraceuticals, and dietary supplements. The advantages and disadvantages of nutraceuticals are also briefly discussed.     

Studies on photostability of phenazone in aqueous solutions

Investigations of the Photostability of Phenazone in Aqueous Solutions The photostability of phenazone in aqueous solutions is very slightly diminished in the presence of oxygen. In alkaline medium photo-destruction occurs – as was shown by the use of diethyl amine –, with the production of N-phenyl-N-acetonyl-N′,N′-diethyl urea; N-phenyl-N′,N′-diethyl urea and 1-phenyl-3,4-dimethyl-5(H)-imidazolone (2).     

Solubilization of indomethacin using hydrotropes for aqueous injection.

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that exhibits analgesic, antipyretic and anti-inflammatory activities. It is practically insoluble in water. The effect of various hydrotropes such as urea, nicotinamide, resorcinol, sodium benzoate and sodium p-hydroxy benzoate on the solubility of indomethacin was investigated. The solubility enhancement of indomethacin by the hydrotropes was observed in decreasing order as sodium p-hydroxy benzoate>sodium benzoate>nicotinamide>resorcinol>urea. In order to elucidate the probable mechanism of solubilization, various solution properties of hydrotropes such as viscosity, specific gravity, surface tension, refractive index and specific conductance of hydrotropic solutions were studied at 25+/-2 degrees C. Each solubilized product was characterized by ultraviolet, infrared, powder X-ray diffraction and differential scanning calorimetry techniques. The hydrotropic solubilization of indomethacin at lower hydrotrope concentration may be attributed to weak ionic interactions while that at higher hydrotrope concentration may be due to molecular aggregation. Aqueous injectable formulations using sodium p-hydroxy benzoate, sodium benzoate and nicotinamide as hydrotropes were developed and studied for physical and chemical stability.     

Characterization of protein-solvent interactions with NMR-spectroscopy: The role of urea in the unfolding of proteins

Multidimensional NMR techniques for the investigation of interactions between biological macromolecules and solvent molecules are discussed. Examples for the use of these techniques for the study of the interactions between urea and the DNA-binding domain of the 434-repressor which lead to unfolding of the polypeptide are given. These investigations show, that at low temperatures interaction between urea and the hydrophobic side chains of the protein can be detected. However, at temperatures above 293 K no binding of urea molecules to the polypeptide chain can be observed. Moreover, titration experiments with salts and non-ionic compounds show, that chemicals which act as kosmotropes can refold the protein even in 7 M urea. All these results suggest, that water molecules play an active role in the unfolding process of proteins.     

Photo- und Radiolyse des Chloramphenicols

Photolysis and Radiolysis of Chloramphenicol In aqueous solution chloramphenicol undergoes decomposition into an aromatic (I) and an aliphatic (II) radical through photo-β-cleavage. I stabilizes itself to p-nitrobenzaldehyde, II to glycol aldehyde and dichloroacetamide. Through a sequence of photosensitized and non photosensitized reactions, p-nitrobenzaldehyde is reduced to p,p′-azoxybenzoic acid, p-aminobenzaldehyde and p-amino-benzoic acid; through “oxygen quenching” it undergoes oxidation, mainly to p-nitrobenzoic acid. In presence of 1,3-butandiol the primarily formed p-nitrobenzaldehyde is transformed to 2-(p-nitrophenyl)-4-methyl-1,3-dioxane. If aqueous chloramphenicol solutions are subjected to γ-rays, degradation products similar to those produced through photolysis are formed. Chloramphenicol is more stable in the crystalline state; also here photoinduced β-cleavage takes place to a limited extent.