Degradability of the linear azo polymer conjugated 5,5′-azodisalicylic acid segment in the main chain for colon-specific drug delivery

A novel type of linear copolymer composed of poly(ethylene glycol) (PEG) with 5,5′-azodisalicylic acid [olsalazine (OLZ)] was developed for colon-specific drug delivery. These copolymers contained azo bonds that would be degraded by the azoreductase activities in the colon. The resultant condensation polymers were characterized with Fourier transform infrared, nuclear magnetic resonance, and gel permeation chromatography. The degradation behavior of the polymer was evaluated in vitro and in vivo. The in vitro results indicated that the active 5-aminosalicylic acid (5-ASA), one of the degradation products, could be released in the medium of the cecum contents specifically. In an in vivo test, there was a 8-h lag time before 5-ASA could be detected in urine samples, and this indicated that the conjugate could remain intact in the upper part of the gastrointestinal tract. In comparison with OLZ, the release profiles of 5-ASA from PEG–OLZ copolymers were significantly prolonged. In addition, the release profiles of 5-ASA from PEG–OLZ copolymers could be adjusted by changes in the molecular weight of the PEG segment. Because of these advantages of PEG–OLZ copolymers, it could be concluded that PEG–OLZ copolymers could be promising candidates for colon-specific polymeric prodrugs of 5-ASA. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

What is the role of α-linolenic acid for mammals?

This review examines the data pertaining to an important and often underrated EFA, α-linolenic acid (ALA). It examines its sources, metabolism, and biological effects in various population studies, in vitro, animal, and human intervention studies. The main role of ALA was assumed to be as a precursor to the longer-chain n-3 PUFA, EPA and DHA, and particularly for supplying DHA for neural tissue. This paper reveals that the major metabolic route of ALA metabolism is β-oxidation. Furthermore, ALA accumulates in specific sites in the body of mammals (carcass, adipose, and skin), and only a small proportion of the fed ALA is converted to DHA. There is some evidence that ALA may be involved with skin and fur function. There is continuing debate regarding whether ALA has actions of its own in relation to the cardiovascular system and neural function. Cardiovascular disease and cancer are two of the major burdens of disease in the 21st century, and emerging evidence suggests that diets containing ALA are associated with reductions in total deaths and sudden cardiac death. There may be aspects of the action and, more importantly, the metabolism of ALA that need to be elucidated, and these will help us understand the biological effects of this compound better. Additionally, we must not forget that ALA is part of the whole diet and should be seen in this context, not in isolation.     

Identification of the pathway of α-oxidation of cerebronic acid in peroxisomes

Cerebronic acid (2-hydroxytetracosanoic acid), an α-hydroxy very long-chain fatty acid (VLCFA) and a component of cerebrosides and sulfatides, is unique to nervous tissues. Studies were carried out to identify the pathway and the subcellular site involved in the oxidation of cerebronic acid. The results from these studies revealed that cerebronic acid was catabolized by α-oxidation to CO₂ and tricosanoic acid (23:0). Studies with subcellular fractions indicated that cerebronic acid was α-oxidized in fractions having particulate bound catalase and enzyme systems for the β-oxidation of VLCFA (e.g., lignoceric acid), suggesting peroxisomes as the subcellular organelle responsible for α-oxidation of cerebronic acid. Etomoxir, an inhibitor of mitochondrial fatty acid oxidation, had no effect on cerebronic acid α-oxidation. Further, cerebronic acid oxidation was found to be dependent on the presence of NAD⁺ but not FAD, NADPH, ATP, Mg²⁺, or CoASH. Intraorganellar localization studies indicated that the enzyme system for the α-oxidation of cerebronic acid was associated with the peroxisomal limiting membranes. Studies on cultured fibroblasts from normal subjects and patients with peroxisomal disorders indicated an impairment of α-oxidation of cerebronic acid in cell lines that lack peroxisomes [e.g., Zellweger syndrome (ZS)]. On the other hand, α-oxidation of cerebronic acid was found to be normal in cell lines from X-linked adrenoleukodystrophy, adult Refsum disease, and rhizomelic chondrodysplasia punctata. Our results clearly demonstrate that α-oxidation of α-hydroxy VLCFA (cerebronic acid) is a peroxisomal function and that this oxidation is impaired in ZS. Furthermore, this α-oxidation enzyme system is distinct from the one for the α-oxidation of β-carbon branched-chain fatty acids (e.g., phytanic acid).     

Studying the structure of the vapor–liquid equilibrium diagram of the butyl propionate–propionic acid–butyl butyrate–butyric acid system

This article deals with specific structural features of the vapor–liquid equilibrium diagram of the butyl propionate–propionic acid–butyl butyrate–butyric acid four-component system, which is of industrial importance and contains biazeotropic ester–acid constituents. The positions of some isomanifolds in the concentration tetrahedron and in its constituents are reported.     

One-step synthesis of ?-caprolactam via the liquid phase catalytic nitrosation of cyclohexane in the presence of concentrated sulfuric acid

A simple and efficient approach for the synthesis of ?-caprolactam via the liquid phase nitrosation of cyclohexane and nitrosyl sulfuric acid in the presence of concentrated sulfuric acid has been developed. A series of novel AlVPO composites were prepared by an impregnation method and the composites were then employed to catalyze the nitrosation reaction of cyclohexane and nitrosyl sulfuric acid. Compared to the reaction using fuming sulfuric acid, the selectivity for the desired product was significantly improved using this one-step catalytic process. This method affords a shortcut to prepare ?-caprolactam and its analogs from cyclohexane.     

Effects of dietary α-linolenic acid on the conversion and oxidation of13C-α-linolenic acid

The effects of a diet rich in α-linolenic acid vs. one rich in oleic acid on the oxidation of uniformly labeled¹³C-α-linolenic acid and its conversion into longer-chain polyunsaturates (LCP) were investigatedin vivo in healthy human subjects. Volunteers received a diet rich in oleic acid (n=5) or a diet rich in α-linolenic acid (n=7; 8.3 g/d) for 6 wk before and during the study. After 6 wk, subjects were given 45 mg of¹³C-α-linolenic acid dissolved in olive oil. Blood samples were collected att=0, 5, 11, 24, 96, and 336 h. Breath was sampled and CO₂ production was measured each hour for the first 12 h. The mean (±SEM) maximal absolute amount of¹³C-eicosapentaenoic acid (EPA) in plasma total lipids was 0.04 ±0.01 mg in the α-linolenic acid group, which was significantly lower (P=0.01) than the amount of 0.12±0.03 mg¹³C-EPA in the oleic acid group. Amounts of¹³C-docosapentaenoic acid (DPA) and¹³C-docosahexaenoic acid (DHA) tended to be lower as well. The mean proportion of labeled α-linolenic acid (ALA) recovered as¹³CO₂ in breath after 12 h was 20.4% in the ALA and 15.7% in the oleic acid group, which was not significantly different (P=0.12). The cumulative recovery of¹³C from¹³C-ALA in breath during the first 12 h was negatively correlated with the maximal amounts of plasma¹³C-EPA (r=−0.58,P=0.047) and¹³C-DPA (r=−0.63,P=0.027), but not of¹³C-DHA (r=−0.49,P=0.108). In conclusion, conversion of¹³C-ALA into its LCP may be decreased on diets rich in ALA, while oxidation of¹³C-ALA is negatively correlated with its conversion into LCP. In a few pilot samples, low¹³C enrichments of n−3 LCP were observed in a diet rich in EPA/DHA as compared to oleic acid.     

Poly(β,L-malic acid)/Doxorubicin ionic complex: A pH-dependent delivery system

Poly(β,L-malic acid) (PMLA) was made to interact with the cationic anticancer drug Doxorubicin (DOX) in aqueous solution to form ionic complexes with different compositions and an efficiency near to 100%. The PMLA/DOX complexes were characterized by spectroscopy, thermal analysis, and scanning electron microscopy. According to their composition, the PMLA/DOX complexes spontaneously self-assembled into spherical micro or nanoparticles with negative surface charge. Hydrolytic degradation of PMLA/DOX complexes took place by cleavage of the main chain ester bond and simultaneous release of the drug. In vitro drug release studies revealed that DOX delivery from the complexes was favored by acidic pH and high ionic strength.     

Cytotoxicity of a metal–organic framework: Drug delivery

A new Zn(II) metal–organic framework of [Zn₆(L)₃(DMA)₄]·5DMA (1) (H₄L = [1,1′:3′,1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid), was used as a drug carrier of 5-fluorouracil (5-FU) for drug delivery. Drug release behavior was also investigated under different pH condition. 5-FU is released in a highly controlled and progressive manner with 95.8% of the drug release after 96 h at acidic condition and with 91.6% after 96 h at PBS. Vitro cytotoxicity assays indicated that the 1 possesses no obvious cytotoxicity.     

To what extent do the storage conditions of polyether-based polyurethane have an impact on diazepam delivery?

Interactions between medical device material and the drug itself have been evoked for polyurethane and may lead to underdosing. Polyurethane, sterilization mode, and the crosslinking level of the polymer have an influence on sorption. The aim here is to evaluate the impact of polyurethane conservation time and conditions as well as sterilization mode. Two polyurethane extension tubes were tested, one sterilized by ethylene oxide and the second by gamma radiation. Forced degradation experiments were performed. After 3 and 6 months of incubation, thermal properties, diazepam delivery and cytotoxicity of leachates were assessed. Diazepam delivery differs significantly according to the version of polyurethane. Sterilization however has no impact on diazepam delivery. No cytotoxicity was observed whatever the infusion tube and the aging conditions. In conclusion, sterilization procedures do not induce polyurethane degradation, but high temperature/relative humidity/time storage conditions lead to a slight degradation in polyurethane.     

Inhibition by tween-85 of the corrosion of cold rolled steel in 1.0?M hydrochloric acid solution

The inhibition effect of tween-85 on the corrosion of cold rolled steel (CRS) in 1.0 M hydrochloric acid (HCl) was studied by weight loss and potentiodynamic polarization methods. The results show that tween-85 is a good inhibitor in 1.0 M HCl and its maximum inhibition efficiency (IE) is 92% at very low concentration. Its adsorption obeys the Langmuir adsorption isotherm equation. The thermodynamic parameters of adsorption enthalpy (ΔH ⁰), adsorption free energy (ΔG ⁰) and adsorption entropy (ΔS ⁰) were calculated and discussed. Polarization curves show that tween-85 acts as a mixed-type inhibitor in hydrochloric acid. IE values obtained from weight loss and polarization are consistent. The adsorbed film on a CRS surface containing an optimum dose of tween-85 was investigated by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). An inhibitive mechanism is proposed from the viewpoint of adsorption theory.     

Industrial applications of formulation computations: Is the computer the enemy?

The basis of modern computations of colorant formulations is a 1931 article by Kubelka and Munk. Virtually all the subsequent important contributions to the problem were published in the following four decades; if it were the practice for software instructions to include a comprehensive list of published references, it is unlikely that many, if any, would be dated later than the advent of the modern computer. This implies either that no major problems remain unsolved, or that some factor is discouraging further improvements or is inhibiting their publication. This leads to the hypothesis that the accepted practice, in the dissemination of computer documentation, of failing to provide references to relevant published work is a significant basis of stultifying new development. It is accordingly urged that promulgators of software accept the responsibility, universally observed in scientific and technological publication, of disclosing prior work by supplying appropriate lists of relevant published material. The failure to disclose prior published work should be deemed a form of plagiarism. © 1996 John Wiley & Sons, Inc.     

Grafting of sulfamethoxazole on acrylic acid−vinyl methyl ketone copolymer using the schiff base reaction−application as a drug delivery system

A series of poly(acrylic acid-co-methylvinylketone–graft–sulfamethoxazole)(AVMDS) species was synthesized for drug carrier applications. The synthesis involved two steps: copolymerization of acrylic acid(AA) with methyl vinyl ketone(MVK) through the free radical route and subsequent grafting of the sulfamethoxazole (SMX) onto the copolymer via the Schiff base reaction of the primary amine of SMX with the carbonyl groups of the MVK units. The structures and properties of the materials were characterized by nuclear magnetic resonance(NMR), X-ray diffraction(XRD), differential scanning calorimetry(DSC), and scanning electronic microscopy (SEM). An in-vitro cytotoxicity test of the drug-carrier systems via MTT assay revealed no significant cytotoxic effect at concentrations up to 100?µg?·?ml^?1. The dynamic release of SMX from these systems through a retro-imidation reaction (inverse Schiff base reaction) was investigated in depth, where the diffusion through the polymer matrix, the enhancement of the water solubility of SMX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamics were evaluated. The AVMGS4 and AVMGS1 drug carrier systems containing 3.58 and 1.18?wt% of SMX were the best performing systems.     

The effect of α-linolenic acid and linoleic acid on the growth and development of formula-fed infants: A systematic review and meta-analysis of randomized controlled trials

This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: α-linolenic acid (ALA, 18∶3n−3) and linoleic acid (LA, 18∶2n−6)] in the diets of term and preterm infants on DHA (22∶6n−3) status, growth, and developmental outcomes. Only randomized controlled trials (RCT) involving formula-fed term and preterm infants, in which the 18-C PUFA composition of the formula was changed and growth or developmental outcomes were measured, were included. Differences were presented as control (standard formula) and treatment (18-C PUFA-supplemented formula). Primary analyses for term infants were 4 and 12 mon and for preterm infants 37–42 and 57 wk postmenstrual age. Five RCT involving term infants and three RCT involving preterm infants were included in the systematic review. Infants fed ALA-supplemented formula had significantly higher plasma and erythrocyte phospholipid DHA levels than control infants. There was no effect of ALA supplementation on the growth of preterm infants. In term infants, ALA supplementation was associated with increased weight and length at 12 mon, which was at least 4 mon after the end of dietary intervention. Developmental indices of term infants did not differ between groups. There was a transient improvement in the retinal function of preterm infants fed ALA-supplemented diets compared with controls. The findings suggest that ALA-supplemented diets improve the DHA status of infants. Further studies are needed to provide convincing evidence regarding the effects of ALA supplementation of formula on infant growth and development.     

The effect of addition of acrylic acid and thioglycolic acid on the nanostructure and thermal stability of PMMA–montmorillonite nanocomposites

Poly(methyl methacrylate) (PMMA)/organophilic montmorillonite (OMMT) nanocomposites were synthesized by the in situ free radical bulk polymerization of methyl methacrylate. The effect of small amount of acrylic acid as the co-monomer and thioglycolic acid as the chain transfer agent on the nanostructure of these nanocomposites was investigated by X-ray diffraction (XRD) and small-angle X-ray scattering (SAXS) analyses. No reflection was discernible in the XRD patterns of all samples. In SAXS experiments, a great amount of small clay montmorillonite aggregates (less than 40 Å) were observed. The acrylic acid used as the co-monomer increased the affinity between the montmorillonite and the polymer, resulting in better dispersion of the montmorillonite particles. The glass transition temperature of the nanocomposites was evaluated by differential scanning calorimetry (DSC) and the thermal stability was investigated by thermogravimetric studies (TGA). As expected, the presence of the montmorillonite increased the glass transition temperature. The thermal stability of nanocomposites was distinctly higher than of pure PMMA and was increased by the presence of small amounts of acrylic acid as the co-monomer.     

Characterization of the ybdT gene product of Bacillus subtilis: Novel fatty acid β-hydroxylating cytochrome P450

We have characterized the gene encoding fatty acid α-hydroxylase, a cytochrome P450 (P450) enzyme, from Sphingomonas paucimobilis. A database homology search indicated that the deduced amino acid sequence of this gene product was 44% identical to that of the ybdT gene product that is a 48 kDa protein of unknown function from Bacillus subtilis. In this study, we cloned the ybdT gene and characterized this gene product using a recombinant enzyme to clarify function of the ybdT gene product. The carbon monoxide difference spectrum of the recombinant enzyme showed the characteristic one of P450. In the presence of H₂O₂, the recombinant ybdT gene product hydroxylated myristic acid to produce β-hydroxyristic acid and α-hydroxymyristic acid which were determined by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry. The amount of these products increased with increasing reaction period and amount of H₂O₂ in the reaction mixture. The amount of β-hydroxyl product was slightly higher than that of α-hydroxyl product at all times during the reaction. However, no reaction products were detected at any time or at any concentration of H₂O₂ when heat-inactivated enzyme was used. HPLC analysis with a chiral column showed that the β-hydroxyl product was nearly enantiomerically pure R-form. These results suggest that this P450 enzyme is involved in a novel biosynthesis of β-hydroxy fatty acid.     

Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness?

Background  

Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2 × 180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS.     

KMnO4/guanidinium-based sulfonic acid: as an efficient Brønsted acid organocatalyst for the selective oxidation of organic compounds

KMnO₄/guanidinium-based sulfonic acid as a green organocatalytic oxidative system can be used effectively for the selective oxidation of organic compounds in n-hexane as a nonpolar and inert solvent at room temperature in good yields. The use of this approach is described for the oxidation of alkyl arenes, alcohols, and sulfides.     

Influence of acid–base property of support on the toluene combustion activity of palladium

Metal–support interaction in the catalytic combustion of toluene was studied, using metal oxides with different acid–base properties as supports. The combustion activity over Pd loaded on strong acidic or basic support was lower than over Pd on weak acidic or basic metal oxides. The study of Pd surface with X-ray photoelectron spectroscopy and reaction order measurement showed that the affinity for oxygen changed according to the acid–base property of support. It was considered that the combustion activity of Pd was controlled by the acid–base property of support through an electronic interaction. This revised version was published online in July 2006 with corrections to the Cover Date.