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[Display omitted] • Orally administered S -allyl- L -cystine sulfoxide (ACSO/alliin) suppressed melanoma growth in xenografted mice. • ACSO suppressed B16F1 melanoma cells viability in vitro. • Only ACSO exhibited both in vivo and in vitro effects, different from other garlic odor precursors. Certain foods modify the risk of developing melanoma. Various garlic compounds, including odor precursors and their derivatives, inhibit tumor growth; thus, garlic could protect against melanoma. However, it is unclear if S -allyl- L -cystine sulfoxide (ACSO/alliin), which is the most abundant (>10 mg/g) odor precursor in fresh raw garlic, has anti-melanoma effect. We investigated if ACSO and the related compounds suppress tumor growth in vivo and in vitro. We orally administered ACSO, S -methyl- L -cystine sulfoxide (MCSO), and S -allyl- L -cystine (ACS) to mice with xenografted melanoma and observed the effect of these administrations on tumor size and lactate dehydrogenase activity. The effect of ACSO, MCSO, and ACS on B16F1 melanoma cells viability was also studied. We found that only ACSO suppressed tumor growth in vivo and in vitro. In addition, the sera collected from rats after oral administration of ACSO suppressed melanoma proliferation in vitro. ACSO may be the key anti-melanoma compound in garlic. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: A whole blood flow-chamber system, the Total Thrombus-formation Analysis System (T-TAS), was developed for quantitative analysis of platelet thrombus formation (PTF) using microchips with thrombogenic surfaces (collagen, PL chip; collagen plus tissue thromboplastin, AR chip) under shear stress conditions. We evaluated the usefulness of the T-TAS for assessing individual thrombogenicity compared with other platelet function tests. Materials and Methods: Blood samples from 31 healthy volunteers were applied to the T-TAS to measure PTF starting time (T10: time to reach 10 kPa), occlusion time (T60 for PL chip; T80 for AR chip), and area under the curve (AUC10, area under curve until10 min for PL chip; AUC30, 30min for AR chip) under various shear rates (1000, 1500, 2000s−1 for PL chip; 300s−1 for AR chip). Platelet functions were also tested using platelet aggregometry, the PFA-100 (collagen and epinephrine [C/EPI], collagen and adenosine diphosphate [C/ADP]), and the VerifyNow P2Y12 assay. Results: Individual pressure waveforms, including PTF starting and ending points, varied among healthy subjects. In the PL chip, T10 and AUC10 showed a shear-dependent correlation with C/EPI or C/ADP. VerifyNow P2Y12 values were not significantly associated with the parameters of the T-TAS. Platelet counts were correlated with all AR measurements, and mostly with PL measurements. Conclusion: The results of the T-TAS were associated with those of the PFA-100 in many respects, indicating that its characteristics are related to shear-induced PTF. The T-TAS showed few correlations with platelet aggregometry and the VerifyNow P2Y12 assay. The T-TAS may allow for the measurement of comprehensive parameters of individual thrombogenicity under whole blood flow conditions. [Copyright &y& Elsevier]

Abstract: Introduction: Autoantibodies to ADAMTS13 have a pivotal role in the pathogenesis of acquired thrombotic thrombocytopenic purpura (TTP). By decreasing the function of ADAMTS13, autoantibodies impair the cleavage of ultra-large von Willebrand factor (UL-VWF) multimers into smaller sizes, leading to lethal platelet-VWF thrombi in the microcirculation. We therefore aimed to determine the sites of autoantibody recognition on ADAMTS13. Materials and Methods: In this study, IgG purified from 13 acquired TTP patients were examined to determine their binding sites on ADAMTS13. Immobilized IgG on microtiter plate or proteinG beads was screened by phage library expressing various peptides of ADAMTS13. Results: In screening, diverse peptide sequences were obtained from almost all of the ADAMTS13 domains, including the spacer domain, which is considered a major binding site. In particular, we detected an identical amino-acid sequence in the C-terminus of the spacer domain from Gly662 to Val687 that was recognized by autoantibodies from 5 TTP patients. The specific autoantibody was expected to be associated with the plasma levels of the ADAMTS13 antigen or activity, and with the quantity of ADAMTS13 autoantibodies or the inhibitory autoantibody titer in TTP patient plasma. These measurements, however, did not seem to be related to the presence or absence of the specific autoantibody. Conclusions: These findings indicate that the specific autoantibody might be a feature of acquired TTP, although its clinical significance remains to be elucidated. [Copyright &y& Elsevier]

• Rice albumin was digested to indigestible HMP (14 kDa) and LMP (<2 kDa) by trypsin. • HMP and LMP suppressed the blood glucose and insulin elevation in rats (OGTT). • HMP adsorbed glucose and retarded its diffusion rate like dietary fibers. • LMP suppressed the expression of sodium-dependent glucose transporter-1 (SGLT1). The mechanism of the suppressive effect of rice albumin (RA) on postprandial hyperglycemia after glucose loading was investigated. In order to examine if small peptides derived from RA are responsible for prevention of postprandial hyperglycemia, RA was hydrolysed to indigestible high-molecular-weight peptides (HMP) and low-molecular-weight peptides (LMP) by trypsin, HMP and LMP being fractionated by gel-filtration chromatography. In oral glucose tolerance test (OGTT), both HMP and LMP suppressed the increase in blood glucose levels. In vitro diffusion test results showed that HMP adsorbed glucose and retarded its diffusion rate like dietary fibers. On the other hand, LMP suppressed the expression of sodium-dependent glucose transporter-1 (SGLT1) in STC-1 cells. Therefore, the suppressive effect of RA on postprandial hyperglycemia would be due to the dual actions of HMP and LMP. Our results demonstrated the potential use of RA as a functional food material to prevent diabetes. [ABSTRACT FROM AUTHOR]

A model for describing the rate of glucose diffusion through a dialysis membrane was developed. The diffusion coefficient of glucose in the dialysis membrane, D , was constant, regardless of the glucose concentration. The data on the diffusion rate of glucose both in the presence and absence of water-soluble dietary fibres were well described by the model, and the amounts of glucose adsorbed on different fibres were evaluated. The amount of adsorbed glucose increased linearly with an increase in the glucose concentration. A decrease in diffusion rate was caused by adsorption of glucose on water-soluble dietary fibre but not by viscosity. Since the rate of desorption of glucose from dietary fibres is slow enough, the amount of glucose adsorbed is considered to be kept almost constant during the dialysis experiment. [Display omitted] • The model to describe the diffusion of glucose through the membrane was developed. • The Amount of glucose adsorbed onto soluble dietary fibers was evaluated. • The adsorbed glucose increased linearly with increasing glucose concentration. • The decrease in diffusion rate was caused by adsorption of glucose onto dietary fiber. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: von Willebrand factor (VWF) cleavage by ADAMTS13 is mediated by multi-step interactions between their multi-domain structures. To clarify the relationship between inhibitory effects of monoclonal antibodies and epitopes on each ADAMTS13 domain, we analyzed how each ADAMTS13 domain contributes to catalyze VWF using a mouse anti-ADAMTS13 monoclonal antibody panel. Materials and Methods: FRETS-VWF73 assay was used to examine the effects of 14 anti-ADAMTS13 monoclonal antibodies on the catalytic activity of plasma ADAMTS13. Epitope mapping was performed using phage surface display. Libraries expressing peptide fragments of ADAMTS13 were screened with the monoclonal antibodies. Results: Eleven epitopes of 14 monoclonal antibodies were successfully defined. Three monoclonal antibodies recognizing metalloprotease or disintegrin-like domains strongly inhibited the catalytic activity and their epitopes were on Gln159-Asp166, Tyr 305-Glu327, and Asn308-Glu376. Five monoclonal antibodies recognizing TSP1-3 to -7 repeats showed weak inhibitory effects, and their epitopes were on Pro744-Ala806, Pro856-Cys864, Gln892-Gly940, Cys1007-Cys1072, and Gln1163-Asn1185. Four monoclonal antibodies recognizing the TSP1-1, TSP1-2, CUB1 or CUB2 domains had no inhibitory effects, and their epitopes, except that for TSP1-1, were Pro682-Cys742, Thr1200-Cys1213, and Gln1409-Glu1414. Two monoclonal antibodies recognizing cysteine-rich and spacer domains showed moderate inhibitory effects, but their epitopes were not determined. Conclusions: We revealed the epitopes of 11 monoclonal anti-ADAMTS13 antibodies on each of the domains and clarified their association with inhibitory effects on VWF catalysis under static conditions. Catalytic activity correlated strongly with the epitopes on metalloprotease and disintegrin-like domains, weakly with those on TSP1-3 to -7 repeats, and negatively with those on TSP1-1, -2, and CUB domains. [Copyright &y& Elsevier]