Long-Term Sustained Release of Salicylic Acid from Cross-Linked Biodegradable Polyester Induces a Reduced Foreign Body Response in Mice

There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 x 10(-4) h(-1) over similar to 1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-alpha and IL-1 beta), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

IFN-gamma inhibits growth of WISH cells in a cell cycle phase-specific manner

Treatment of WISH (human amnion) cells with interferon-gamma (IFN-gamma) inhibits their growth. Release of the cells from IFN-gamma-mediated growth inhibition led to a rapid and significant increase in DNA synthesis, followed by doubling of cell numbers. The DNA synthesis profile was strikingly similar to that shown by WISH cells released from growth arrest by the G(1)/S phase inhibitor, aphidicolin, This strongly suggested that IFN-gamma treatment leads to growth inhibition of WISH cells at the G(1)/S boundary of the cell cycle. In contrast, IFN-alpha blocked growth of these cells at the G(0)/G(1) boundary.

AE energy release during the fracture of HSC beams

An attempt has been made experimentally to investigate the acoustic emission (AE) energy release in high-strength concrete (HSC) beams subjected to monotonically increasing load. Acoustic emission energy release during the fracture process of the HSC beams is measured. Stress waves released during the fracture process in materials cause acoustic emissions. AE energy released during the fracture of a notched three-point bend plain concrete beam specimens having 28-day compressive strengths of 50.0 MPa, 69.0 MPa and 78.0 MPa and mortar (cement: sand (1: 4) by weight) specimens are studied. Mortar consists of one part cement and four parts sand by weight. The specimens were tested by a material testing system of 1200 kN capacity employing crack mouth opening displacement control at the rate of 0.0004 mm/s. The fracture energy and the AE energy released during the fracture process of all the tested TPB and mortar specimens are compared and discussed. The observations made in the present experimental study have some applications for monitoring the integrity of structures.

Prolactin suppresses release of luteinising hormone during lactation in the monkey

STUDIES with rats have shown that during lactation there is an inhibition of luteinising hormone (LH)-dependent physiological events, such as implantation1, and a return to oestrus cyclicity2. This inhibition has been shown to occur only during the intense suckling phase and it has been correlated with the high levels of prolactin present in the circulation at this time. Although exogenous prolactin could substitute for the effects of intense suckling, it could do so only under the permissive influence of minimal suckling stimulus. We have shown that there is, in these conditions, a lowering of LH levels, and that this is due to interference by prolactin with the pituitary responsiveness to LH-releasing hormone (LHRH) (K. Muralidhar, R. M. and N. R. M., unpublished). Using the lactating monkey, we have now demonstrated a similar inhibitory effect of prolactin on pituitary responsiveness to LHRH, suggesting a mechanism by which amenorrhoeic conditions are maintained during lactation.

Encapsulation and release of rifampicin using poly(vinyl pyrrolidone)-poly (methacrylic acid) polyelectrolyte capsules

Poly(vinyl pyrrolidone) and poly(methacrylic acid) multilayer capsules based on hydrogen bonding have been prepared by the layer-by-layer approach and used to encapsulate and release rifampicin, an antituberculosis drug. Removal of silica core using a buffer of ammonium fluoride and hydrofluoric acid at about pH 3 was found to produce better capsules than hydrofluoric acid alone. An eight-layered capsule had a wall thickness of 20 rim. Maximum encapsulation was found to be about 86 mu g at 40 degrees C with 1 +/- 0.2 x 10(6) capsules. Release studies showed a burst kind of release and maximum release was obtained above pH 7 where the capsules disintegrate rapidly thereby releasing the drug in a short period. Interactions studies with Mycobacterium smegmatis showed that the capsules were cytocompatible and the released drug functioned with the same efficacy as the free drug.

Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled (proportional to time(-0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs.

Cu2+-induced room temperature hydrogen release from ammonia borane

Mechanical stirring of ammonia borane with CuCl2 in the solid state resulted in the release of hydrogen at room temperature through the intermediacy of [NH4](+)[BCl4](-).

CD4+ alpha beta T cell and gamma delta T cell responses to Mycobacterium tuberculosis. Similarities and differences in Ag recognition, cytotoxic effector function, and cytokine production.

CD4+ and gamma delta T cells are activated readily by Mycobacterium tuberculosis. To examine their role in the human immune response to M. tuberculosis, CD4+ and gamma delta T cells from healthy tuberculin-positive donor were studied for patterns of Ag recognition, cytotoxicity, and cytokine production in response to M. tuberculosis-infected mononuclear phagocytes. Both T cell subsets responded to intact M. tuberculosis and its cytosolic Ags. However, CD4+ and gamma delta T cells differed in the range of cytosolic Ags recognized: reactivity to a wide m.w. range of Ags for CD4+ T cells, and a restricted pattern for gamma delta T cells, with dominance of Ags of 10 to 15 kDa. Both T cell subsets were equally cytotoxic for M. tuberculosis-infected monocytes. Furthermore, both CD4+ and gamma delta T cells produced large amounts of IFN-gamma: mean pg/ml of IFN-gamma in supernatants was 2458 +/- 213 for CD4+ and 2349 +/- 245 for gamma delta T cells. By filter-spot ELISA (ELISPOT), the frequency of IFN-gamma-secreting gamma delta T cells was one-half of that of CD4+ T cells in response to M. tuberculosis, suggesting that gamma delta T cells on a per cell basis were more efficient producers of IFN-gamma than CD4+ T cells. In contrast, CD4+ T cells produced more IL-2 than gamma delta T cells, which correlated with diminished T cell proliferation of gamma delta T cells compared with CD4+ T cells. These results indicate that CD4+ and gamma delta T cell subsets have similar effector functions (cytotoxicity, IFN-gamma production) in response to M. tuberculosis-infected macrophages, despite differences in the Ags recognized, IL-2 production, and efficiency of IFN-gamma production.

Effects of compressibility and heat release on entrainment processes in mixing layers

Characteristics of the process of entrainment in plane mixing layers, and the changes with compressibility and heat release, were studied using temporal DNS with simultaneous fluid packet tracking. Convective Mach numbers of the simulations are 0.15, 0.7 and 1.1. The Reynolds number is quite high (between 11 000 and 37 000 based on layer width and velocity difference), and is above the mixing transition. The study agrees with recent findings in round jets: first, engulfed fluid volume and its growth rate are both very small compared with the volume of the turbulent region and its growth rate, respectively. Secondly, most often, the process occurs close to the turbulent-nonturbulent boundaries. A new finding is that both compressibility and heat release retard the entrainment process so that it takes an O(1) time for vorticity or scalar levels to grow even after growth has been initiated. This delay is manifested as the fall in mixing layer growth rates as compressibility and heat release levels increase.

A real coded genetic algorithm for data partitioning and scheduling in networks with arbitrary processor release time

The problem of scheduling divisible loads in distributed computing systems, in presence of processor release time is considered. The objective is to find the optimal sequence of load distribution and the optimal load fractions assigned to each processor in the system such that the processing time of the entire processing load is a minimum. This is a difficult combinatorial optimization problem and hence genetic algorithms approach is presented for its solution.

Minimizing total weighted tardiness on a batch-processing machine with non-agreeable release times and due dates

This study considers the scheduling problem observed in the burn-in operation of semiconductor final testing, where jobs are associated with release times, due dates, processing times, sizes, and non-agreeable release times and due dates. The burn-in oven is modeled as a batch-processing machine which can process a batch of several jobs as long as the total sizes of the jobs do not exceed the machine capacity and the processing time of a batch is equal to the longest time among all the jobs in the batch. Due to the importance of on-time delivery in semiconductor manufacturing, the objective measure of this problem is to minimize total weighted tardiness. We have formulated the scheduling problem into an integer linear programming model and empirically show its computational intractability. Due to the computational intractability, we propose a few simple greedy heuristic algorithms and meta-heuristic algorithm, simulated annealing (SA). A series of computational experiments are conducted to evaluate the performance of the proposed heuristic algorithms in comparison with exact solution on various small-size problem instances and in comparison with estimated optimal solution on various real-life large size problem instances. The computational results show that the SA algorithm, with initial solution obtained using our own proposed greedy heuristic algorithm, consistently finds a robust solution in a reasonable amount of computation time.

Thyroidal control of hepatic release and metabolism of vitamin A

The inverse relationship that exists between thyroxine and the vitamin A level of plasma has been examined in chicken. Thyroxine treatment leads to a decrease in the level of vitamin A carrier proteins, retinol-binding protein and prealbumin-2 in plasma and liver. There is an accumulation of vitamin A in the liver, with a greater proportion of vitamin A alcohol being present compared to that of control birds. In thyroxine treatment there is enhanced plasma turnover of retinol-binding protein and prealbumin-2, while their rates of synthesis are marginally increased. Amino acid supplementation partially counteracts effects of thyroxine treatment. Amino acid supplementation of thyroxine-treated birds does not alter the plasma turnover rates of retinol-binding protein and prealbumin-2 but increases substentially their rates of synthesis. The release of vitamin A into circulation is interfered with in hyperthyroidism due to inadequate availability of retinol-binding protein being caused by enhanced plasma turnover rate not compensated for by synthesis.