Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer

In search of an efficient transdermal drug delivery system (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also the first report of the application of PHA and dendrimer to the TDDS.     

Properties of Injectable Apatite-Forming Premixed Cements

Previous studies reported premixed calcium phosphate cements (CPCs) that were stable in the package and form hydroxyapatite (HA) as the product after exposure to an aqueous environment. These cements had setting times of greater than 60 min, which are too long to be useful for some clinical applications. The present study investigated properties of fast-setting HA-forming premixed CPCs that initially consisted of two separate premixed pastes: (1) finely ground (1.0 μm in median size) dicalcium phosphate anhydrous (DCPA) mixed with an aqueous NaH(2)PO(4) solution, 1.5 mol/L or 3.0 mol/L in concentration, and (2) tetracalcium phosphate consisting of combinations of particles of two different size distributions, 5 μm (TTCP5) and 17 μm (TTCP17) in median size, mixed with glycerin. Equal volume of Pastes 1 and 2 were injected with the use of atwo-barrel syringe fitted with a static mixer into sample molds. The molar Ca/P ratio of combined paste was approximately 1.5. Cements were characterized in terms of setting time (Gilmore needle), diametral tensile strength (DTS), and phase composition (powder x-ray diffraction, XRD). Setting times were found to range from (4.3 ± 0.6 to 68 ± 3) min (mean ± sd; n = 3), and 1-d and 7-d DTS values were from (0.89 ± 0.08 to 2.44 ± 0.16) MPa (mean ± sd; n = 5). Both the NaH(2)PO(4) concentration and TTCP particle size distribution had significant (p < 0.01) effects on setting time and DTS. Powder XRD analysis showed that low crystallinity HA and unreacted DCPA were present in the 1-day specimens, and the extent of HA formation increased with increasing amount of TTCP5 in the TTCP paste. CONCLUSION: Injectable HA-forming premixed CPCs with setting times from 4 to 70 min can be prepared by using DCPA and TTCP as the ingredients. Compared to the conventional powder liquid cements, these premixed CPCs have the advantages of being easy to use and having a range of hardening times.     

Acute ingestion of yerba mate infusion (Ilex paraguariensis) inhibits plasma and lipoprotein oxidation

Yerba mate extract (Ilex paraguariensis) is a source of phenolic compounds that possesses in vitro antioxidant activities and may contribute to a reduction in the risk of cardiovascular disease. In this study we examined the acute effects of the consumption of mate infusion on ex vivo plasma and low-density lipoprotein (LDL) oxidation, plasma antioxidant capacity, and platelet aggregation. Twelve healthy fasted subjects ingested 500 mL of mate infusion and blood samples were collected before and 1 h after mate intake. Lipid peroxidation of plasma and LDL was monitored by the measurement of cholesteryl-ester hydroperoxides (CE-OOH) and cholesterol oxides. The plasma antioxidant capacity was measured as ferric-reducing antioxidant potential (FRAP). Platelet aggregation was evaluated in platelet-rich plasma stimulated with adenosine diphosphate and coagulation was tested in platelet-poor plasma. Ingestion of mate infusion diminished the ex vivo oxidizability of both plasma and LDL particles. After mate intake, the CE-OOH levels were around 50% lower in plasma oxidized with copper or 2,2′-azobis[2-amidine-propane-hydrochloride] (AAPH) and the lag time to plasma oxidation increased 2-fold (P < 0.05). Copper- and AAPH-induced LDL peroxidation were also inhibited by around 50% and 20%, respectively, after mate consumption (P < 0.05). The levels of various oxysterols were significantly reduced in oxidized-plasma and LDL (P < 0.05) and FRAP increased by 7.7% after mate intake (P < 0.01). However, mate consumption did not inhibit platelet aggregation or blood coagulation. In summary, intake of yerba mate infusion improved the antioxidant capacity and the resistance of plasma and LDL particles to ex vivo lipid peroxidation.     

六角形布置反应堆高保真物理计算方法研究与验证

俄罗斯商用压水堆VVER和大多数实验堆均采用了六角形紧凑型栅格布置,为了实现VVER和六角形实验堆的高保真数值模拟分析,本文基于数值反应堆物理计算程序（NECP-X）开展了六角形堆芯高保真计算方法研究和程序开发。首先,将全局-局部耦合共振自屏计算方法拓展至六角形堆芯,实现六角形堆芯燃料棒的全堆芯高精度共振计算;其次,基于2D/1D耦合输运计算方法研究了六角形堆芯的高保真计算方法;最后,为了提高全堆芯计算的计算效率,研究了基于区域分解松耦合的非结构网格的粗网有限差分（CMFD）加速方法,可以实现以矩形、六角形和其他多边形栅元为基础的pin-by-pin CMFD 加速。为了验证六角形堆芯高保真计算方法的精度和效率,计算了六角形C5G7基准问题,并分析了六角形输运计算方法的计算精度和CMFD方法的加速效果;将NECP-X程序应用于西安脉冲堆的2D全堆芯计算,与蒙特卡罗程序的结果对比表明NECP-X程序计算得到的特征值和功率分布均具有较高精度。因此,本文建立的六角形堆芯高保真计算方法可以应用于六角形堆芯的分析计算。      

4-O-Methylascochlorin-Mediated BNIP-3 Expression Controls the Balance of Apoptosis and Autophagy in Cervical Carcinoma Cells

4-O-methylascochlorin (MAC) is a 4-fourth carbon-substituted derivative of ascochlorin, a compound extracted from a phytopathogenic fungus Ascochyta viciae. MAC induces apoptosis and autophagy in various cancer cells, but the effects of MAC on apoptosis and autophagy in cervical cancer cells, as well as how the interaction between apoptosis and autophagy mediates the cellular anticancer effects are not known. Here, we investigated that MAC induced apoptotic cell death of cervical cancer cells without regulating the cell cycle and promoted autophagy by inhibiting the phosphorylation of serine-threonine kinase B (Akt), mammalian target of rapamycin (mTOR), and 70-kDa ribosomal protein S6 kinase (p70S6K). Additional investigations suggested that Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP-3), but not Hypoxia-inducible factor 1 alpha (HIF-1α), is a key regulator of MAC-induced apoptosis and autophagy. BNIP-3 siRNA suppressed MAC-induced increases in cleaved- poly (ADP-ribose) polymerase (PARP) and LC3II expression. The pan-caspase inhibitor Z-VAD-FMK suppressed MAC-induced cell death and enhanced MAC-induced autophagy. The autophagy inhibitor chloroquine (CQ) enhanced MAC-mediated cell death by increasing BNIP-3 expression. These results indicate that MAC induces apoptosis to promote cell death and stimulates autophagy to promote cell survival by increasing BNIP-3 expression. This study also showed that co-treatment of cells with MAC and CQ further enhanced the death of cervical cancer cells.     

Stabilization of poly(vinyl chloride). X. Synergisms between epoxidized polybutadienes and metal soaps on the stabilization of poly(vinyl chloride)

Effects of epoxidized 1,2- or 1,4-polybutadienes on the zinc stearate/calcium stearate synergetic soap-induced thermal stabilization of poly(vinyl chloride) (PVC) were investigated by colorimetry. The remarkable stabilization effects of epoxidized polybutadienes could not be observed on the PVC films without synergetic soaps, while the stabilization of PVC was markedly enhanced by combined use of epoxidized polybutadienes with synergetic soaps. Excessive coloration of cool color-producing zinc chloride-polyene complexes that were the source of abrupt discoloration of stabilized PVC was retarded by using epoxidized polybutadienes together with synergetic soap. The synergism of epoxidized polybutadienes was enhanced with increasing epoxy contents. Moreover, the effect is also clearly dependent on degree of dispersion of epoxidized polybutadienes in PVC. Further colorimetries, infrared (IR), and X-ray photoelectron spectroscopies on the various PVC-containing epoxidized polybutadienes and zinc chloride indicated that the epoxy groups capture the zinc chloride. The synergistic effect between epoxidized polybutadienes and metal soap was ascribed to epoxidized polybutadienes serving as acceptors for the excessive cool color-producing zinc chloride produced by zinc stearate to retard the abrupt discoloration of stabilized PVC. The plate-out phenomenon appeared during the molding process of PVC-containing epoxy compounds was considerably retarded by epoxidized polybutadienes which modified polyols. The polyol-modifying epoxidized polybutadienes also exhibited a marked effect on PVC stabilization with metal soap.     

Anomalous properties of poly(γ-benzyl L-glutamate) film composed of unusual 7/2 helices

Poly(γ-benzyl L-glutamate) film composed of unusual 7-residue 2-turn (7/2) helices was prepared by slow casting from chloroform solution. The 7/2 helical conformation was irreversibly transformed at 84°C to the normal 18/5 conformation. In d.s.c. thermograms the transformation appeared as an endothermic first order transition with an enthalpy change of 3.4 cal g⁻¹. The viscoelastic and dielectric measurements indicated that the loss peak due to the side chain motion in this film was reduced to a great extent compared to the film of 18/5 helices. The dielectric relaxation strength dictated that there was a motional restriction in three quarters of the side chains. By comparison to a racemic mixture of poly(γ-benzyl glutamate), these anomalous properties were attributed to the stack of terminal benzyl groups of side chains (ormed in an alternating manner between neighbouring chains). The first order transition arises from the cooperative fusion of the stack and the side chains with their benzyl groups which are restricted in thermal motion. Such stacks may be facilitated by the precise ‘knob (side chain) and hole (space between side chains)’ packing which can be attained between neighbouring 7/2 helices.     

Measurement of heat of mixing for ammonium chloride + ammonia system at 25 °c

Heat of mixing for ammonium chloride in liquid ammonia at 25°C was determined in the concentration range 0-50 wt% NH₄Cl. It was calculated from the differential heat of solution observed in this work and the differential heat of dilution estimated from activities of solvent. A twin isoperibol calorimeter consisting of two stainless Dewar vessels was used at a relatively high pressure (up to 1.5 MPa). The accuracy of this calorimetry was examined by measuring the heat of solution for tris-(hydroxymethyl)aminomethane(THAM) in 0.1 kmol/m³ HCl at 25°C, and satisfactory agreement within 1.1% between experimental and literature value was obtained. The reproducibility for the experiment was within 2.8%.