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.     

Validating for Liveness in Hidden Adversary Systems

Multi-stream interactive systems can be seen as “hidden adversary” systems (HAS), where the observable behaviour on any interaction channel is affected by interactions happening on other channels. One way of modelling HAS is in the form of a multi-process I/O automata, where each interacting process appears as a token in a shared state space. Constraints in the state space specify how the dynamics of one process affects other processes. We define the “liveness criterion” of each process as the end objective to be achieved by the process. The problem now for each process is to achieve this objective in the face of unforeseen interferences from other processes. In an earlier paper, it was proposed that this uncertainty can be mitigated by collaboration among the disparate processes. Two types of collaboration philosophies were also suggested: altruistic collaboration and pragmatic collaboration. This paper addresses the HAS validation problem where processes collaborate altruistically.     

Influence of elastic constants on mode I stress-intensity factors in three-dimensional crack problems

Plates with V-through edge notches subjected to pure bending and specimens with rectangular edge-through-notches subjected to combined bending and axial pull were investigated (under live-load and stress-frozen conditions) in a completely nondestructive manner using scattered-light photoelasticity. Stress-intensity factors (SIFs) were evaluated by analysing the singular stress distributions near crack-tips. Improved methods are suggested for the evaluation of SIFs. The thickness-wise variation of SIFs is also obtained in the investigation. The results obtained are compared with the available theoretical solutions.     

Differences in prevalence of tobacco use among Indian urban youth: the role of socioeconomic status

This study examined whether the distribution of tobacco use and related psychosocial risk factors among youth in urban India vary by socioeconomic status (SES). Data were derived from a cross-sectional survey of students enrolled in the 6th and 8th grades in 32 schools in Delhi and Chennai (N = 11,642). The survey was conducted in 2004, before the implementation of a program designed to prevent and reduce tobacco use (MYTRI). Mixed-effect regression models were used (a) to determine the prevalence of tobacco use among private (higher SES) and government (lower SES) school students, (b) to investigate whether certain psychosocial factors were associated with increased tobacco use, and (c) to determine how these factors varied by school type. Ever-use of multiple forms of tobacco (e.g., gutkha, bidis, and cigarettes) was more prevalent among government school students than private school students. After adjusting for city, gender, grade, and age, we found the prevalence rate for ever-use of any tobacco product to be 18.9% for government school students, compared with 12.2% for private school students (p<.01). Students in government schools scored lower than private school students on most psychosocial risk factors for tobacco use studied here, indicating higher risk. Government school students scored the lowest for refusal skills, self-efficacy, and reasons not to use tobacco. Social susceptibility to chewing tobacco and social susceptibility to smoking were strong correlates of current tobacco use among government school students. Exposure to tobacco advertising was also a strong correlate of current tobacco use for government school students but not private school students. In two large cities of India, students attending government schools are using many forms of tobacco at higher rates than private school students. The psychosocial risk profile of government school students suggests they are more vulnerable to initiation and use and to outside influences that encourage use.     

Effect of organoclay addition on the two-body abrasive wear characteristics of polyamide 6 nanocomposites

Polymer clay nanocomposites (PCN) exhibit improved mechanical properties due to nanolevel dispersion of clay in the polymer matrix. They also exhibit good tribological performance under dry sliding conditions. Abrasive wear behaviour of these materials would be different from dry sliding behaviour as the mechanisms of the both are entirely different. Hence the abrasive wear behaviour of these materials needs to be investigated. The abrasive wear characteristics of polyamide 6 nanocomposites, with 1, 3 and 5% (wt.) clay prepared by melt intercalation technique, under two-body abrasive wear conditions have been reported. Abrasive wear tests were conducted using a pin-on-disc tribometer containing an abrasive counterface. All the polyamide nanocomposites investigated exhibited a low abrasive wear resistance compared with pristine Nylon. The wear performance of the nanocomposites was correlated with the mechanical properties. Dominant ploughing and cutting wear were observed in polymer clay nanocomposites. The amount of clay present alters the wear mechanism.     

Impression creep of monolithic and composite lead free solders

Even though several EMS (Electronic manufacturing services) companies are currently producing “lead free” products, a general notion of apprehension still exists in the industry, primarily due to the lack of sufficient mechanical reliability data supporting the use of lead free alloys. The current study was an effort to generate an understanding of the mechanisms of creep deformation in monolithic and composite (Ag and Cu reinforced) Sn–3.5Ag and Sn–3.0Ag–0.5Cu lead free alloys in the high stress high temperature regime. Small volume solder samples were reflowed using a custom built computer controlled resistance furnace. Impression creep testing was employed to determine the activation energy and stress exponent. A careful analysis of the collected data revealed the underlying creep mechanisms and the following conclusions could be made. Both Sn–3.5Ag and Sn–3.0Ag–0.5Cu exhibited higher creep resistance as compared to the eutectic tin–lead solder under all tested conditions, with the ternary lead free alloy marginally outperforming the binary lead free alloy. Composite solders performed better as compared to monolithic solders. Furthermore, Cu reinforced solders demonstrated higher creep resistance as compared to Ag reinforced solders.     

Gelcast Tooling: Net Shape Casting and Green Machining

Gelcasting is an advanced powder forming process. It is most commonly used to form ceramic or metal powders into complex, near-net shapes. Turbine rotors, gears, nozzles, and crucibles have been successfully gelcast in silicon nitride, alumina, nickel-based superalloy, and several steels. Gelcasting can also be used to make blanks that can be green machined to near-net shape and then high fired. Green machining has been successfully applied to both ceramic and metal gelcast blanks. Recently, we have used gelcasting to make toolinj; for metal casting applications. Most of the work has centered on H13 tool steel. We have demonstrated an ability to gelcast and sinter H13 to near net shape for metal casting tooling. We have also been successful in green machining gelcast blanks using a three-axis CNC milling machine.     

A waveguide-based acoustic microscope

A new instrument is presented which is capable of high resolution acoustic imaging at relatively low frequencies. This approach results in increased complexity of the signal processing required and reduced throughput of the instrument. However, these disadvantages are amply compensated by the ability to create velocity scan images of materials with either high attenuation or low material velocities. These measurements are not possible using traditional/acoustic microscopes. The initial performance of the new instrument is demonstrated using thin samples of shim materials to show that acceptable spatial resolution and highly accurate time delay measurements are possible. An application is then shown using the instrument to evaluate subchondral sclerosis in horse bones. It has been hypothesized that changes in the elastic modulus may be associated with fatigue-induced microdamage. The modulus change may further represent bone damage which precedes the development of microcracking. Thin samples are used to allow complementary microradiography to be performed on the bone slices. Because of the low material velocity, surface wave interference methods (so called V(z) curves) are not well suited for use in some bone samples. The thickness of the samples eliminates the potential for the samples to be evaluated using pulse-echo time delay measurements. The new instrument is thus unique in its ability to create velocity scans of these samples.     

Criteria for stability of a class of multiplicative nonlinear systems

The problem of bounded-input bounded-output stability of a class of systems with multiplicative nonlinearity which arise from a generalization of the Lur'e problem is considered. Sufficient conditions in the frequency domain are presented for the stability of the system when the multiplicative nonlinearity belongs to particular classes.     

Stability of a class of multiplicative nonlinear systems

The problem of input-output stability of a class of systems with multiplicative nonlinearities that arise from a generalization of the Luré problem is considered. Some results are presented that are believed to be new.