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.     

Impact of source and level of calcium fortification on the heat stability of reconstituted skim milk powder

Calcium enrichment of food and dairy products has gained interest with the increased awareness about the importance of higher calcium intake. Calcium plays many important roles in the human body. Dairy products are an excellent source of dietary calcium, which can be further fortified with calcium salts to achieve higher calcium intake per serving. However, the addition of calcium salts can destabilize food systems unless conditions are carefully controlled. The effect of calcium fortification on the heat stability of reconstituted skim milk was evaluated, using reconstituted skim milks with 2 protein levels: 1.75 and 3.5% (wt/wt) prepared using low and high heat powders. Calcium carbonate, phosphate, lactate, and citrate were used for fortification at 0.15, 0.18, and 0.24% (wt/wt). Each sample was analyzed for solubility, heat stability, and pH. The addition of phosphate and lactate salts lowered the pH of milk, citrate did not have any major effect, and carbonate for the 1.75% protein samples increased the pH. In general, changes in solubility and heat stability were associated with changes in pH. Calcium addition decreased the solubility and heat stability. However, interestingly, the presence of carbonate salt greatly increased the heat stability for 1.75% protein samples. This is due to the neutralizing effect of calcium carbonate when it goes into solution. The results suggested that the heat stability of milk can be affected by the type of calcium salt used. This may be applied to the development of milk-based calcium enriched beverages.     

Simultaneous MSMR and SSM/I observations and analysis of sea‐ice characteristics over the Antarctic region

Polar sea ice has been monitored quasi‐continuously over the last 30 years using passive microwave radiometers onboard three satellites in polar orbit, namely Nimbus‐5, Nimbus‐7 and Defense Meteorological Satellite Program (DMSP) series. A short overlap between Scanning Multichannel Microwave Radiometer (SMMR) on Nimbus‐7 and Special Sensor Microwave Imager (SSM/I) onboard DMSP allowed inter‐calibration of the two sensors leading to a consistent series of long‐term sea‐ice measurements since 1978. With the launch of Multifrequency Scanning Microwave Radiometer (MSMR) onboard OCEANSAT‐1 in the polar sun‐synchronous orbit during 1999, India developed the capability to monitor the polar sea ice on a regular basis. The concurrent availability of SSM/I and MSMR over the last few years presents a valuable opportunity to attempt an inter‐comparison of MSMR with SSM/I measurements and derived sea‐ice parameters.

In this paper, we present an indirect validation of the brightness temperatures (T _b) observed by MSMR with near‐simultaneous measurements from SSM/I over the Antarctic and Southern Polar Ocean regions. Simultaneous MSMR and SSM/I data from two contrasting seasons—summer and winter—for the 1999–2000 period have been used. Analysis includes a comparison of T _b scatterograms to achieve confidence in the quantitative use of the T _b data to derive various geophysical parameters, e.g. sea‐ice concentration and extent. Additionally, the T _b images produced by the two sensors are compared to establish the capability of MSMR in reliable two‐dimensional portrayal of all the sea and continental ice features over the Antarctic Region. Based on a regression analysis between MSMR observed T _b in different frequency channels and polarizations, and SSM/I‐derived sea‐ice concentration (SIC) values, we have developed algorithms to estimate SIC over the Southern Polar Ocean from MSMR data. The MSMR algorithms allow estimation of SIC with better than 10% rms error. MSMR SIC images faithfully capture the observed distribution of sea ice in all the sectors of the Southern Ocean both during summer and winter periods. Using the MSMR‐derived SIC, we have also derived monthly sea‐ice extent (SIE) estimates for a period extending for about 20 months from the beginning of the launch of MSMR. These estimates show excellent agreement with values derived from SSM/I. These analyses bring out the very high level of compatibility in the measurements and derived sea‐ice parameters produced by the two sensors.     

Antioxidant activity and protective effect against plasmid DNA strand scission of leaf, bark, and heartwood extracts from Acacia catechu

The antioxidant activity of methanol extract/fractions of leaf, bark, and heartwood of Acacia catechu was evaluated by various antioxidant assays, including free radical, superoxide and hydroxyl radical, reducing power, metal ion chelation, as well as hydroxyl radical induced DNA strand scission. The leaf, bark, and heartwood powder was extracted in methanol and the lyophilized methanol extract was fractionated with different solvents in the order of increasing polarity. The results indicate that ethyl acetate fraction of heartwood has the highest antioxidant capacities, presenting lower EC(50) values particularly in free radical scavenging activity, including DPPH radicals (4.76 ± 0.14 μg/mL), superoxide anions (26.21 ± 0.79 μg/mL), and hydroxyl radicals (33.69 ± 1.42 μg/mL), in direct assay systems. Reducing power was also highest in ethyl acetate fraction of heartwood (EC(50) of 79.05 ± 1.02 μg/mL). As for the chelating power on ferrous ions, leaf extract was more effective than bark and heartwood extracts. Furthermore, the ethyl acetate and acetone fractions of heartwood significantly protected pBR322 supercoiled plasmid DNA against strand scission induced by hydroxyl radicals in a Fenton's reaction mixture. PRACTICAL APPLICATION: The present investigation suggests that the three organs of A. catechu differ significantly in their antioxidant potential as seen in the DPPH radical scavenging assay, reducing power assay, metal ion chelating assay, superoxide radical scavenging assay and hydroxyl radical scavenging assay. Further, our results showed that crude methanol extract and ethyl acetate fraction of heartwood of A. catechu might have a good potential as a source for natural health products due to its antioxidant and DNA protective activities.     

A computational framework for automating generation of sizing function in assembly meshing via disconnected skeletons

This paper proposes a framework for generating mesh sizing functions for assembly models. Size control is crucial in obtaining a high-quality mesh with a reduced number of elements. The reduction in the number of elements will decrease computation time and memory use during mesh generation and analysis. The framework consists of a background octree lattice for storing the sizing function, a set of source entities for providing sizing information based on geometric information, and an interpolation module for calculating the sizing on the background octree lattice using the source entities. Source entities are generated by performing a detailed systematic study to identify all the geometric factors of an assembly. Disconnected skeletons are extracted and used as tools to measure 3D proximity and 2D proximity, which are two of the geometric factors. The framework facilitates the generation of a variety of meshes with a low computational cost, to meet industry needs. The framework has been tested on many industrial parts, and sizing control on a few typical assemblies has been presented to demonstrate the effectiveness of the proposed framework.     

Ordinal Representation of Numeric Quantities by Brown Capuchin Monkeys (Cebus apella).

Using techniques established by E. M. Brannon and H. S. Terrace (2000) with rhesus macaques (Macaca mulatta), the authors tested the ability of brown capuchins (Cebus apella) to order arrays of items ranging in quantity from 1 to 9. Three monkeys were trained on a touch screen to select the quantities 1-4 in ascending order. The monkeys exhibited successful transfer of this ability to novel representations of the quantities 1-4 and to pairs of the novel quantities 5-9. Patterns of responding with respect to numeric distance and magnitude were similar to those seen in human subjects, suggesting the use of similar psychological processes. The capuchins demonstrated an ordinal representation of quantity equivalent to that shown in Old World monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Site-specific frame-shift mutagenesis by the 1-nitropyrene-DNA adduct N-(deoxyguanosin-8-y1)-1-aminopyrene located in the (CG)3 sequence: effects of SOS, proofreading, and mismatch repair

1-Nitropyrene (1-NP), the predominant nitropolycyclic hydrocarbon found in diesel exhaust, is a mutagen and tumorigen. Nitroreduction is a major pathway by which 1-NP is metabolized. Reductively activated 1-NP forms a major DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene (dGAP), both in vitro and in vivo. In Salmonella typhimurium 1-NP induces a CpG deletion in a CGCGCGCG sequence. In Escherichia coli, however, mostly -1 and +1 frame-shifts are observed, which occur predominantly in 5'-CG, 5'-GC, and 5'-GG sequences. In order to determine the mechanism of mutagenesis by dGAP in a CpG repetitive sequence, we constructed a single-stranded M13 genome containing the adduct at the underscored deoxyguanosine of an inserted CGCGCG sequence. In E. coli strains with normal repair capability the adduct induced approximately 2% CpG deletions, which was 20-fold that of the control. With SOS, the frequency of frame-shift mutations increased to 2.6%, even though the frequency of CpG deletion accompanied 50% reduction. The enhancement in mutagenesis was due to a +1 frame-shift that occurred at a high frequency. In strains with a defect in methyl-directed mismatch repair, 50-70% increase in mutation frequency was observed. When these strains were SOS induced, frame-shift mutagenesis increased by approximately 100%. When transfections were carried out in dnaQ strains that are impaired in 3'-->5'exonuclease activity of DNA polymerase III, frame-shift mutagenesis increased 5-7-fold. dGAP-induced frame-shifts in the (CG)3 sequence, therefore, varied from 2% to 17% depending on the state of repair of the host cells. We conclude that dGAP induces both -2 and +1 frame-shifts in a CpG repetitive sequence and that these two mutagenic events are competing pathways. The CpG deletion does not require SOS functions, whereas the +1 frame-shifts are SOS-dependent. On the basis of the data in repair-deficient strains, it appears that both types of frame-shifts occurred as a result of misalignment, which are corrected primarily by the proofreading exonuclease of the DNA polymerase. Misaligned structures that escape the exonuclease are repaired by the methyl-directed mismatch repair, albeit with limited efficiency.