Preparation and pharmacodynamic evaluation of liposomes of indomethacin

The side effects of indomethacin, such as ulceration of the kidney and central nervous system (CNS) toxicity, limit its use as a drug for rheumatoid arthritis. Encapsulation of this drug in liposomes may reduce the toxic effects. The aim of this study was to determine the factors influencing encapsulation of indomethacin in liposomes and to determine anti-inflammatory potential of liposomal indomethacin. A series of liposomal formulations of indomethacin were prepared using various phospholipids. The effects of method of preparation, lipid composition, charge, and cholesterol (CH) on encapsulation of indomethacin in liposomes were investigated. A significant variation in encapsulation of the drug in liposomes was observed when prepared by different methods. With all the methods of preparation tried, the favorable lipid composition for high encapsulation of this drug was egg phosphatidyl choline:CH: stearlyamine (PC:CH:SA) at a 1:0.5:0.1 molar ratio. Inclusion of cholesterol did not affect the encapsulation efficiency of the drug in liposomes. The drug release profile from the liposomes was biphasic, and the highest percentage drug release was observed with large unilamellar vesicles (LUVs) (100 nm). Inclusion of stearylamine (PC:CH:SA 1:0.5:0.1) and phosphatidyl glycerol (PG) (PC:CH:PG 1:0.5:0.2) in the liposomes reduced the release of the drug in comparison to the neutral liposomes (PC:CH 1:1). The slow release of the drug from stearylamine-containing liposomes may be explained by the electrostatic interaction between the acid moiety of the drug and the amine moiety of the lipid. It is assumed that the possible hydrogen bonding between--OH groups of phosphatidyl glycerol and the--COOH group of the drug might be the reason for the slow release of the drug from PC:CH:PG (1:0.5:0.2) containing liposomes. Pharmacodynamic evaluation of the liposomes was performed by carrageenan-induced rat paw edema (acute) and adjuvant arthritis (chronic) models. The anti-inflammatory activity was increased from the first to fifth hour PC:CH:PG (1:0.5:0.2) and PC:CH:SA (1:0.5:0.1) liposomes showed the highest percentage inhibition of edema. In both these models, anti-inflammatory activity of liposomal indomethacin was significantly higher than that of free indomethacin (p < .01). The ulcer index of the free drug was about three times more than the encapsulated drug when administered at the same dose intraperitoneally to arthritic rats consecutively for 21 days.     

Epoxidation of natural rubber studied by nmr spectroscopy

Epoxidation of natural rubber with peroxyacids in homogeneous solution (CHCl₃, benzene) and in latex occurs without main chain fission or isomerization of the cis configuration. There are two possible modes of addition of oxygen to the double bond, which gives rise to diastereoisomers in dyad structures, as shown by the occurrence of splitting of ¹³C NMR resonances in 100% epoxidized rubber. In partially epoxidized rubber the ¹³C NMR resonances of the methylene carbon atoms have been fully assigned using pulse sequences and lanthanide shift reagents, in terms of triad sequences. Resonances in the olefinic region of the spectrum require assignment in terms of pentad sequences whereas those from the oxirane region are much more closely spaced and are assigned using triads. Intensity measurements on the methylene carbon NMR resonances show that the epoxidation reaction is a random process in both homogeneous solution and in latex particles.     

Production of bioactive proteins and peptides from the diatom Nitzschia laevis and comparison of their in vitro antioxidant activities with those from Spirulina platensis and Chlorella vulgaris

This research focuses on green production of bioactive proteins and hydrolysates from Nitzschia. A comparison of antioxidant activities was established between protein extracts and hydrolysates from Nitzschia and two other well‐known microalgae, chlorella and spirulina. Protein hydrolysates from these microalgae were produced using Alcalase^®, Flavourzyme^® and Trypsin. The hydrolysis process enhanced the antioxidant activities in general, especially those obtained using Alcalase^®. Nitzschia showed the highest (P < 0.05) total phenolic content/reducing capacity (2.4 ± 0.02 mg GAE/100 g) after 90 min of hydrolysis with Alcalase^®. The ABTS [2,2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid)] radical scavenging activity (66.77 ± 0.00%) was highest (P < 0.05) after 120 min of hydrolysis, but DPPH (2,2‐Diphenyl‐1‐picrylhydrazyl radical) was low (29.59 ± 0.02%). A correlation between ABTS activity and total phenolic contents was the highest (P < 0.05) for protein hydrolysates from all three organisms using Alcalase^®, but superoxide anion radical scavenging activity was intermediate for Nitzschia. Therefore, Nitzschia protein hydrolysates have the potential to be used as antioxidants.     

Physicochemical properties of bread dough and finished bread with added pectin fiber and phenolic antioxidants

Comparative studies were conducted in this paper to investigate the effects of added dietary fiber (DF) and/or phenolic antioxidants on the properties of bread dough and finished bread. Breads were developed in the absence (control bread), or presence of apple pectin and/or fruit phenolic extracts (treated breads), and subjected to quality evaluation (attributes including color, weight, and volume) and characterization of chemical and rheological properties. Chemical analyses revealed that breads with added phenolic extracts had greater antioxidant activity and higher extractable phenolic content, than control bread and the treated breads with added apple pectin(s). The measured antioxidant activity was mainly derived from the phenolics present in bread. Storage modulus G' (elasticity) and loss modulus G″ (viscocity) of the treated bread dough with added pectin(s) only were higher than those of control dough. The G' or G″ of the treated breads incorporated with a combination of a pectin and fruit phenolic extract depended on the type of phenolic extract (that is, apple and blackcurrant extracts behaved differently from kiwifruit extract). The G' and G″ at the final baking step were higher than those of other stages, indicating an increase in cross-linking among polymeric molecules and bread particles of high molecular weight. We conclude that the added pectin and/or phenolic extract had influenced bread dough cross-linking microstructure and bread properties through being involved in the interactions with bread components such as wheat proteins during dough development and bread baking. PRACTICAL APPLICATION: Dietary fibers and phytochemicals (including phenolic antioxidants) have long been recognized as the active nutrients responsible for the health benefits of fruit and vegetables to humans. Interest in incorporating bioactive ingredients such as dietary fiber and phenolic antioxidants into popular foods like bread has grown rapidly, due to the increased consumer health awareness. The added bioactive ingredients may or may not promote the development of bread dough. This paper reports the findings associated with the properties of the functional breads enhanced with apple pectin and apple, blackcurrant, and kiwifruit phenolic extracts. Results of this paper indicate that the success of the development of such functional breads is ultimately determined by the interactions among added bioactive ingredients and other bread components.     

The origin of naturally occurring perchlorate: the role of atmospheric processes

Perchlorate, an iodide uptake inhibitor, is increasingly being detected in new places and new matrices. Perchlorate contamination has been attributed largelyto the manufacture and use of ammonium perchlorate (the oxidizer in solid fuel rockets) and/or the earlier use of Chilean nitrate as fertilizer (approximately 0.1% perchlorate). However, there are regions such as the southern high plains (Texas Panhandle) where there is no clear historical or current evidence of the extensive presence of rocket fuel or Chilean fertilizer sources. The occurrence of easily measurable concentrations of perchlorate in such places is difficult to understand. In the southern high plains groundwater, perchlorate is better correlated with iodate, known to be of atmospheric origin, compared to any other species. We show that perchlorate is readily formed by a variety of simulated atmospheric processes. For example, it is formed from chloride aerosol by electrical discharge and by exposing aqueous chloride to high concentrations of ozone. We report that perchlorate is present in many rain and snow samples. This strongly suggests that some perchlorate is formed in the atmosphere and a natural perchlorate background of atmospheric origin should exist.     

ON PREDICTION WITH FRACTIONALLY DIFFERENCED ARIMA MODELS

Abstract. This paper considers some extended results associated with the predictors of long-memory time series models. These direct methods of obtaining predictors of fractionally differenced autoregressive integrated moving-average (ARIMA) processes have advantages from the theoretical point of view.     

Ozonolysis of epoxidized natural rubber

The epoxidized natural rubber was fragmented by ozonolysis and the ozonolyzed mixture was analyzed by gas chromatography/mass spectroscopy. The peak areas of the analyzed partial chromatograph were used to calculate the ratio of CC, CEC, and CEEC (dyad, triad, and tetrad) compared with the theoretical value calculated assuming random epoxidation of the latex. In this manner the epoxidation reaction was proved to be random.     

A combined stochastic dynamic programming-statistical disaggregation approach applied to multiple reservoir systems

The stochastic dynamic programming (SDP) method faces computational difficulties when used to determine the optimal operation of multiple storages. A new approach, a combined SDP-statistical disaggregation approach is introduced to determine releases for a special situation relating to multiple reservoir systems, that is, for a system of multiple storages where operational data are available. The approach consists of defining an equivalent single reservoir which represents the system of multiple reservoirs. The optimal releases from the equivalent single reservoir are derived by the use of SDP. Disaggregation of the optimal releases from the equivalent single reservoir, to produce the releases from the individual storages is based on historical operational data. The Melbourne (Australia) water supply system is considered as the example. The releases derived from the combined SDP-statistical disaggregation approach are tested by operating a simulation model, and the conclusion is made that the approach produces satisfactory releases for a system of multiple reservoirs where operational data are available. The method cannot be applied to existing systems where insufficient or no operational data are available, or to proposed systems where operational data are not available. The method uses a small amount of computer time.