Evaluation of proanthocyanidin-crosslinked sericin/alginate blend for ketoprofen extended release

Sericin and alginate blend has shown good results for obtaining sustained release dosage forms. In the case of ketoprofen, it was necessary to resort to the use of the proanthocyanidin (PA) as crosslinking agent in order to achieve this same goal. Thus, various formulations were developed by adding different initial amounts of PA to the sericin and alginate blend with incorporated ketoprofen. The best results for drug loading, entrapment efficiency and release prolongation were obtained for the particle with the lowest amount of PA (0.5%). Mathematical modeling has indicated that different mechanisms may be involved in drug release, especially a complex release mechanism, with polymer dissolution and polymer chain relaxation allowing drug release. Particles characterization confirmed the incorporation of ketoprofen into the sericin, alginate and proanthocyanidin blend. It was verified that there was no interaction between them and there were no major changes in the physicochemical properties of the drug.     

Interphase Strain Gradients in Multilayered Steel Composite from Microdiffraction

Multilayered steel composites consisting of alternating martensite and austenite layers and exhibiting a combination of high strength and ductility were successfully fabricated. To understand the microplasticity mechanisms responsible for such exceptional mechanical behavior, 3D X-ray microscopy with a submicron beam size was employed to probe the stress/strain distribution within the top two layers during incremental tensile loading. The 3D depth-dependent strain gradients were monitored in situ near the martensite/austenite interfaces as a function of the load level. It was observed that the strain gradients redistributed during loading. Specifically, large compressive strains developed in the top martensite layer transverse to the loading direction, while small tensile strains were found across the layer interface into the underneath austenite layer.     

Prospective Validation of High-Shear Wet Granulation Process by Wet Granule Sieving Method. II. Utility of Wet Granule Sieving Method

The general utility of a method for determination of high-shear wet granulation end point by monitoring the wet granule particle size distribution was evaluated. Wet granulation was conducted in a 25-liter high-shear mixer using four model drugs with different solubilities and particle sizes (ethenzamide, unmilled and milled acetaminophen, and antipyrine). For each drug formulation, its wet granule particle size fraction and target range for granulation end point determination were selected based on the tablet characteristics that are known to be influenced by the wet granulation process. Granules manufactured under different conditions (i.e., different main and chopper blade speeds and binder supplying rate) but manufactured to the same granulation end point determined by the selected fraction and range showed very similar granule characteristics and subsequently very similar tabler characteristics. From the fact that there was a good correlation between the wet and dry-sized granule particle size distributions even if the drying method was changed from fluid-bed drying to vacuum drying, the general application of the end point determining method was verified. Further, the method was shown to be sensitive to the critical granulation parameters for granulation progression and to be very capable of determining the granulation extent. Thus, it was suggested that the method is applicable to various drugs and formulations for determination of wet granulation end point.     

Creep strength of magnesium-based alloys

The high-temperature creep resistance of magnesium alloys was discussed, with special reference to Mg-Al and Mg-Y alloys. Mg-Al solid-solution alloys are superior to Al-Mg solid-solution alloys in terms of creep resistance. This is attributed to the high internal stress typical of an hcp structure having only two independent basal slip systems. Although magnesium has a smaller shear modulus than aluminum, the inherent creep resistance of Mg alloys is better than that of Al alloys. The creep resistance of Mg alloys is improved substantially by the addition of Y. Solid-solution hardening is the principal mechanism of the strengthening, but the details of the mechanism have not been elucidated yet. Forest dislocation hardening in concentrated alloys and dynamic precipitation in a Mg-2.4 pct Y alloy also contribute to the strengthening. An addition of a very small amount of Zn raises the dislocation density and significantly improves the creep resistance of Mg-Y alloys. This article is based on a presentation made in the symposium entitled “Defect Properties and Mechanical Behavior of HCP Metals and Alloys” at the TMS Annual Meeting, February 11–15, 2001, in New Orleans, Louisiana, under the auspices of the following ASM committees: Materials Science Critical Technology Sector, Structural Materials Division, Electronic, Magnetic & Photonic Materials Division, Chemistry & Physics of Materials Committee, Joint Nuclear Materials Committee, and Titanium Committee.     

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.     

Classifying hepatitis C virus genotypes

Current cytogenetic evaluation of solid tumors is performed on fresh tissue specimens requiring on-call tissue culture facilities. The application of cryopreservation to tumor samples prior to cytogenetic analysis allows collection of tumors to a desired sample size. We evaluated methods of cryopreservation for their effects on growth potential from 11 benign thyroids and one papillary thyroid cancer. Mitotic indices and thyroglobulin expression applying imunocytology were analyzed. Compared to fresh tumors, the revived tumor samples showed unaltered thyroglobulin expression. A statistically significant (p < 0.004) prolongation to develop mitotic activity occurred in samples received after the freezing of dispase digested tissues, but not in samples frozen as thinly cut pieces. In addition, the data show that cytogenetic analysis at the 400-band level can be achieved in cryopreserved thyroid tissues.     

Effectiveness and limitations of the fallback I algorithm for transient supraventricular tachyarrhythmias in DDD pacing

To examine the function of the fallback I algorithm (Chorus I, Ela Medical Inc., Montrouge, France), which automatically changes the DDD mode to VDI during transient supraventricular tachyarrhythmias to prevent high-rate tracking of the venticule, a total of 45 patients who were preoperatively diagnosed with sick-sinus syndrome (SSS) (Group 1; n = 19) or with advanced or complete atrioventricular block (AVB) (Group 2; n = 26) were followed up and analyzed. Mean follow-up times (mean +/- SD) were 22.4 +/- 9.7 and 12.4 +/- 10.9 months, respectively. Each of the groups was further divided into subgroups according to the preoperative existence of of paroxysmal atrial fibrillation (PAF) or paroxysmal supraventricular tachyarrhythmia (PSVT). During follow-up, the fallback started through a given cycle of ventricular pacing at a upper-rate limit (URL) to avoid a continuous high-rate tracking during the arrhythmias specifically in the patients with PSVT (0/4) (p = 0.0004). The fallback, however, sometimes started in the patients who had AVB not associated with either PAF or PSVT (4/21) during normal exercise because the fallback algorithm did not distinguish a normal P wave from the abnormal atrial waves. To further clarify the behavior of the fallback, a treadmill test was conducted in 25 of the 45 patients. The fallback start was observed in 12 of the 17 patients with AVB (Group 2). In such patients, the use of a long fallback delay and/or a high URL setting prevented the fallback starts during normal exercise. These results suggest that, in DDD pacing, the algorithm in Chorus I is useful in patients with SSS or AVB to avoid highrate tracking of the ventricle during transient supraventricular tachyarrhythmias, but special care must be taken to avoid the fallback starts during the normal exercise in AVB patients.     

Running-wheel avoidance learning in rats (Rattus norvegicus): Effects of contingencies and comparisons of different strains.

In Experiment 1, we showed that active- and passive-avoidance responding in a running wheel was learned because of the avoidance contingency. In Experiment 2, strain differences among four commercially bred rats were assessed in an active-avoidance paradigm. Wistar, Donryu, and Fischer rats learned faster than Sprague-Dawleys. In Experiment 3, learning in a multiple active/passive avoidance schedule was examined, and both components of this task were learned. This multiple schedule was used to investigate strain differences in selectively bred rats in Experiments 4 and 5. Tsukuba low-emotional (TLE) rats responded more than Tsukuba high-emotional (THE) rats in both components. However, discrimination of passive components was better in THE than in TLE rats. Syracuse high-avoidance rats were superior in the active component, whereas Syracuse low-avoidance rats showed superior performance in the passive component. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemical association in symbiosis sterol donors in planthoppers

The role of intracellular symbionts contributing to their host has been investigated in the planthoppers,Nilaparvata lugens Stal andLaodelphax striatellus Fallen. We have found that the isolated yeastlike symbionts, identified as a member of the genusCandida, from the host's egg produce ergosterol when cultured. A comparative study of sterols in the cultured symbionts, the host insects, aposymbiotic host insects, and dietary plants demonstrated that ergosterol produced in the symbiotes is provided to the host insects and possibly transformed in the host insects into cholesterol via 24-methylenecholesterol. The conversion of injected 24-methylenecholesterol-d₃ into cholesterol has been shown in the brown planthopper (N. lugens).     

Dust absorption averaged over the Sahara inferred from moderate resolution imaging spectroradiometer

We estimated the average dust single scattering albedo (omega(0)) over the Sahara using four years of moderate resolution imaging spectroradiometer data. The method employed is based on the theory that the critical surface reflectance (rho(c)) for which the reflectance at the top-of-the-atmosphere is not influenced by the variability of dust optical thickness depends on omega(0). The average dust absorption over the Sahara was estimated to be smaller than that previously reported in the literature, and this may be causing the cooling of the climate system. Our method enables one to estimate omega(0) from data with a variety of aerosol optical thickness values using samples in the vicinity of rho(c). Use of satellite data over large areas and for long periods enables quantification of the average dust absorption over the entire Sahara.