Potential Use of C

The photosensitizing ability of C60/2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) nanoparticles under visible light irradiation was studied by electron spin resonance (ESR) and phototoxicity on cancer cells. In addition, the photoinduced antitumor effect to the tumor-bearing mice was evaluated. C60 nanoparticles were prepared by grinding a mixture of HP-β-CyD. The resulting C60/HP-β-CyD nanoparticles were highly-sensitive to visible light and generated higher levels of 1O2 than protoporphyrin IX (PpIX). C60/HP-β-CyD reduced the viability of cancer cells (HeLa cells and A549 cells) in response to irradiation by visible light in a dose-dependent manner. The IC50 values of the C60/HP-β-CyD nanoparticles was 10 μM for HeLa cells and 60 μM for A549 cells at an irradiation level of 35 mW/cm2. The photodynamic effect of C60/HP-β-CyD nanoparticles on the in vivo growth of mouse sarcoma S-180 cells was evaluated after intratumor injection. The outcome of PDT by C60/HP-β-CyD was directly dependent on the dose of irradiated light. Treatment with C60/HP-β-CyD nanoparticles at a C60 dose of 2.0 mg/kg under visible light irradiation at 350 mW/cm2 (63 J/cm2) markedly suppressed tumor growth, whereas that at 30 J/cm2 was less effective. These findings suggest that C60/HP-β-CyD nanoparticles represent a promising candidate for use in cancer treatment by PDT

High Levels of Oxidative Stress Exist in the Brain than Serum or Kidneys in Stroke-Prone Spontaneously Hypertensive Rats at Ten Weeks of Age

10週齢の正常血圧WKYラットと脳卒中易発性高血圧自然発症ラット(SHRSP)の脳、血清および腎における酸化ストレスを測定した。WKYと比べてSHRSPの血清では酸化ストレスの指標である後期蛋白酸化産物(AOPP)、酸化アルブミンおよび酸化蛋白質の濃度が低かった。免疫ブロット法で定量される酸化蛋白質はSHRSPの脳で増加していたが、腎では増加していなかった。リアルタイムPCRで定量されるSODのmRNAおよび免疫ブロット法で定量されるカタラーゼ蛋白質はSHRSPの脳で増加していた。10週齢SHRSPでは血清や腎よりも脳で酸化ストレスが高いが、その原因はSODおよびカタラーゼの低下ではない。10週齢の正常血圧WKYラットと脳卒中易発性高血圧自然発症ラット(SHRSP)の脳、血清および腎における酸化ストレスを測定した。WKYと比べてSHRSPの血清では酸化ストレスの指標である後期蛋白酸化産物(AOPP)、酸化アルブミンおよび酸化蛋白質の濃度が低かった。免疫ブロット法で定量される酸化蛋白質はSHRSPの脳で増加していたが、腎では増加していなかった。リアルタイムPCRで定量されるSODのmRNAおよび免疫ブロット法で定量されるカタラーゼ蛋白質はSHRSPの脳で増加していた。10週齢SHRSPでは血清や腎よりも脳で酸化ストレスが高いが、その原因はSODおよびカタラーゼの低下ではない

Polysaccharides as potential antioxidative compounds for extended-release matrix tablets.

The objective of this study was to identify polysaccharides with antioxidant properties for use as potential antioxidative compounds for extended-release matrix tablets. The antioxidant properties of five different polysaccharides, high molecular weight alginate (H-ALG), low molecular weight alginate (L-ALG), high molecular weight chitosan (H-chitosan), low molecular weight chitosan (L-chitosan), and pectic acid (PA) were examined using N-centered radicals from 1,1\u27-diphenyl-2-picrylhydrazyl (DPPH) and 2,2\u27-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and reducing power, based on their ability to reduce Cu(2+). L-chitosan and PA had acceptable scavenging abilities and were good radical scavengers, with good reducing power, but the H-chitosan and alginate derivatives were much less effective. The results suggest that L-chitosan and PA could be useful in combating oxidative stress. A PA and L-chitosan interpolymer complex (IPC) tablet was prepared and evaluated as an extended-release tablet matrix using theophylline (TPH) as a model drug. The release of TPH from the matrix tablet (TPH/PA/L-chitosan=200 mg:150 mg:50 mg) was slower than that from PA only (TPH/PA/chitosans=200 mg:200 mg:0 mg) or L-chitosan only (TPH/PA/L-chitosan=200 mg:0 mg:200 mg) tablet. Turbidity measurements also indicated the optimum complexation ratio for IPC between PA/L-chitosan to be 1/3, indicating an acceptable relationship between the turbidity of the complex and the release ratio of TPH. These results suggest that an L-chitosan/PA complex would be potentially useful in an extended-release IPC tablet with high antioxidant activity.The objective of this study was to identify polysaccharides with antioxidant properties for use as potential antioxidative compounds for extended-release matrix tablets. The antioxidant properties of five different polysaccharides, high molecular weight alginate (H-ALG), low molecular weight alginate (L-ALG), high molecular weight chitosan (H-chitosan), low molecular weight chitosan (L-chitosan), and pectic acid (PA) were examined using N-centered radicals from 1,1\u27-diphenyl-2-picrylhydrazyl (DPPH) and 2,2\u27-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and reducing power, based on their ability to reduce Cu(2+). L-chitosan and PA had acceptable scavenging abilities and were good radical scavengers, with good reducing power, but the H-chitosan and alginate derivatives were much less effective. The results suggest that L-chitosan and PA could be useful in combating oxidative stress. A PA and L-chitosan interpolymer complex (IPC) tablet was prepared and evaluated as an extended-release tablet matrix using theophylline (TPH) as a model drug. The release of TPH from the matrix tablet (TPH/PA/L-chitosan=200 mg:150 mg:50 mg) was slower than that from PA only (TPH/PA/chitosans=200 mg:200 mg:0 mg) or L-chitosan only (TPH/PA/L-chitosan=200 mg:0 mg:200 mg) tablet. Turbidity measurements also indicated the optimum complexation ratio for IPC between PA/L-chitosan to be 1/3, indicating an acceptable relationship between the turbidity of the complex and the release ratio of TPH. These results suggest that an L-chitosan/PA complex would be potentially useful in an extended-release IPC tablet with high antioxidant activity

Useful Extend-release Chitosan Tablets with High Antioxidant Activity.

The antioxidant properties of different low molecular weight (LMW) chitosans (CS1; 22 kDa, CS2; 38 kDa, CS3; 52 kDa, CS4; 81 kDa) were examined for possible use in extended-release tablets. The criteria used were the ability of the chitosans to reduce Cu2+, and hydroxyl and superoxide radicals and N-centered radicals derived from 1,1\u27-diphenyl-2-picrylhydrazyl, via the use of ESR spectrometry. CS2 showed the highest scavenging activity. CS1 and CS3, however, were much less effective and CS4 was not a viable antioxidant. The results suggest that CS2 could be useful in combating the development of oxidative stress. A series of chitosan tablets were prepared using a spray drying method and evaluated as an extended-release matrix tablet using theophylline (TPH) as a model drug. The release of TPH from the different MW chitosan tablets increased with increasing MW of the chitosan used. CS2, CS3 and CS4 showed a reasonable release activity, but CS1 showed the shortest release activity. Moreover, the CS2-TPH tablet showed the highest scavenging activity of the three chitosan tablets (CS2-CS4) using 2,2\u27-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. These results suggest that a CS2-TPH tablet could be potentially useful in an extended-release matrix tablet with a high antioxidant activity.The antioxidant properties of different low molecular weight (LMW) chitosans (CS1; 22 kDa, CS2; 38 kDa, CS3; 52 kDa, CS4; 81 kDa) were examined for possible use in extended-release tablets. The criteria used were the ability of the chitosans to reduce Cu2+, and hydroxyl and superoxide radicals and N-centered radicals derived from 1,1\u27-diphenyl-2-picrylhydrazyl, via the use of ESR spectrometry. CS2 showed the highest scavenging activity. CS1 and CS3, however, were much less effective and CS4 was not a viable antioxidant. The results suggest that CS2 could be useful in combating the development of oxidative stress. A series of chitosan tablets were prepared using a spray drying method and evaluated as an extended-release matrix tablet using theophylline (TPH) as a model drug. The release of TPH from the different MW chitosan tablets increased with increasing MW of the chitosan used. CS2, CS3 and CS4 showed a reasonable release activity, but CS1 showed the shortest release activity. Moreover, the CS2-TPH tablet showed the highest scavenging activity of the three chitosan tablets (CS2-CS4) using 2,2\u27-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. These results suggest that a CS2-TPH tablet could be potentially useful in an extended-release matrix tablet with a high antioxidant activity

Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin

Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to their anti-inflammatory and anti-oxidant properties. They mainly bind to albumin in plasma. These findings influence their body disposition and biological activities. Spectroscopic analysis using site specific probes on human serum albumin (HSA) clearly indicated that curcumin (Cur), demethylcurcumin (Dmc) and bisdemethoxycurcumin (Bdmc) bind to both Site I (sub-site Ia and Ib) and Site II on HSA. At pH 7.4, the binding constants for Site I were relatively comparable between curcuminoids, while the binding constants for Site II at pH 7.4 were increased in order Cur , Dmc , Bdmc. Binding experiments using HSA mutants showed that Trp214 and Arg218 at Site I, and Tyr411 and Arg410 at Site II are involved in the binding of curcuminoids. The molecular docking of all curcuminoids to the Site I pocket showed that curcuminoids stacked with Phe211 and Trp214, and interacted with hydrophobic and aromatic amino acid residues. In contrast, each curcuminoid interacted with Site II in a different manner depending whether a methoxy group was present or absent. A detailed analysis of curcuminoids-albumin interactions would provide valuable information in terms of understanding the pharmacokinetics and the biological activities of this class of compounds

Cys34-cysteinylated human serum albumin is a sensitive plasma marker in oxidative stress-related chronic diseases

The degree of oxidized cysteine (Cys) 34 in human serum albumin (HSA), as determined by high performance liquid chromatography (HPLC), is correlated with oxidative stress related pathological conditions. In order to further characterize the oxidation of Cys34-HSA at the molecular level and to develop a suitable analytical method for a rapid and sensitive clinical laboratory analysis, the use of electrospray ionization time-of-flight mass spectrometer (ESI-TOFMS) was evaluated. A marked increase in the cysteinylation of Cys34 occurs in chronic liver and kidney diseases and diabetes mellitus. A significant positive correlation was observed between the Cys-Cys34-HSA fraction of plasma samples obtained from 229 patients, as determined by ESI-TOFMS, and the degree of oxidized Cys34-HSA determined by HPLC. The Cys-Cys34-HSA fraction was significantly increased with the progression of liver cirrhosis, and was reduced by branched chain amino acids (BCAA) treatment. The changes in the Cys-Cys34-HSA fraction were significantly correlated with the alternations of the plasma levels of advanced oxidized protein products, an oxidative stress marker for proteins. The binding ability of endogenous substances (bilirubin and tryptophan) and drugs (warfarin and diazepam) to HSA purified from chronic liver disease patients were significantly suppressed but significantly improved by BCAA supplementation. Interestingly, the changes in this physiological function of HSA in chronic liver disease were correlated with the Cys-Cys34-HSA fraction. In conclusion, ESI-TOFMS is a suitable high throughput method for the rapid and sensitive quantification of Cys-Cys34-HSA in a large number of samples for evaluating oxidative stress related chronic disease progression or in response to a treatment

Measurement of low-energy antiproton detection efficiency in BESS below 1 GeV

An accelerator experiment was performed using a low-energy antiproton beam to measure antiproton detection efficiency of BESS, a balloon-borne spectrometer with a superconducting solenoid. Measured efficiencies showed good agreement with calculated ones derived from the BESS Monte Carlo simulation based on GEANT/GHEISHA. With detailed verification of the BESS simulation, the relative systematic error of detection efficiency derived from the BESS simulation has been determined to be $\pm$5%, compared with the previous estimation of $\pm$15% which was the dominant uncertainty for measurements of cosmic-ray antiproton flux.Comment: 13 pages, 7 figure

Precise Measurement of Cosmic-Ray Proton and Helium Spectra with the BESS Spectrometer

We report cosmic-ray proton and helium spectra in energy ranges of 1 to 120 GeV and 1 to 54 GeV/nucleon, respectively, measured by a balloon flight of the BESS spectrometer in 1998. The magnetic-rigidity of the cosmic-rays was reliably determined by highly precise measurement of the circular track in a uniform solenoidal magnetic field of 1 Tesla. Those spectra were determined within overall uncertainties of +-5 % for protons and +- 10 % for helium nuclei including statistical and systematic errors.Comment: 12 pages, 4 figure

Molecular Evolutionary Analysis of the Influenza A(H1N1)pdm, May–September, 2009: Temporal and Spatial Spreading Profile of the Viruses in Japan

BACKGROUND: In March 2009, pandemic influenza A(H1N1) (A(H1N1)pdm) emerged in Mexico and the United States. In Japan, since the first outbreak of A(H1N1)pdm in Osaka and Hyogo Prefectures occurred in the middle of May 2009, the virus had spread over 16 of 47 prefectures as of June 4, 2009. METHODS/PRINCIPAL FINDINGS: We analyzed all-segment concatenated genome sequences of 75 isolates of A(H1N1)pdm viruses in Japan, and compared them with 163 full-genome sequences in the world. Two analyzing methods, distance-based and Bayesian coalescent MCMC inferences were adopted to elucidate an evolutionary relationship of the viruses in the world and Japan. Regardless of the method, the viruses in the world were classified into four distinct clusters with a few exceptions. Cluster 1 was originated earlier than cluster 2, while cluster 2 was more widely spread around the world. The other two clusters (clusters 1.2 and 1.3) were suggested to be distinct reassortants with different types of segment assortments. The viruses in Japan seemed to be a multiple origin, which were derived from approximately 28 transported cases. Twelve cases were associated with monophyletic groups consisting of Japanese viruses, which were referred to as micro-clade. While most of the micro-clades belonged to the cluster 2, the clade of the first cases of infection in Japan originated from cluster 1.2. Micro-clades of Osaka/Kobe and the Fukuoka cases, both of which were school-wide outbreaks, were eradicated. Time of most recent common ancestor (tMRCA) for each micro-clade demonstrated that some distinct viruses were transmitted in Japan between late May and early June, 2009, and appeared to spread nation-wide throughout summer. CONCLUSIONS: Our results suggest that many viruses were transmitted from abroad in late May 2009 irrespective of preventive actions against the pandemic influenza, and that the influenza A(H1N1)pdm had become a pandemic stage in June 2009 in Japan