Montree Tungjai

Spectrophotometric Characterization of Behavior and the Predominant Species of Flavonoids in Physiological Buffer: Determination of Solubility, Lipophilicity and Anticancer Efficacy

The objectives of this study were to investigate the behavior of flavonoids in an aqueous physiological buffer and to determine the structural and functional group substitution which is responsible for their anticancer action. The de- protonated anionic form of 7 flavonoids can easily be determined using spectrophotometry, and owing to its charged state, is highly soluble in aqueous physiological buffer and is not prone to aggregation. The protonated form of these 7 flavon- oids is much less soluble and tends to aggregate following precipitation. For all flavonoids studied except catechin and 5,5� -dihydroxy-6,7,3� ,4� -tetramethoxyflavone, it was possible to determine the rates of deprotonation; pKa value of eri- odictyol, apigenin, kaempferol, quercetin, WP 279, and WP 283 was equal to 7.00, 8.72, 7.86, 8.30, 7.70 and 9.90, respec- tively. The methoxyl group substitutions in place of hydrogen atoms and/or hydroxyl groups at various positions of car- bon atoms in ring A, B and C particularly WP 283 resulted in an increase in the solubility, lipophilicity, and specifically its anticancer efficacy (by 60-fold). The neutral forms of flavonoids are predominantly active molecules and the active sites responsible for anticancer activity are found in ring A and C, especially C4=O, C5-OH and C2=C3.

Effects of 100MeV protons delivered at 0.5 or 1cGy/min on the in vivo induction of early and delayed chromosomal damage.

Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of (137)Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p<0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or (137)Cs γ rays (delivered at 1cGy/min) were similar.

Bone mineral density at distal forearm in men over 40 years of age in Mae Chaem district, Chiang Mai Province, Thailand: a pilot study

Abstract Objective: To study the prevalence of bone mineral density (BMD) and osteoporosis in the distal forearm among Thai men over 40 years of age in Mae Chaem District, Chiang Mai Province, Thailand. Methods: The subjects in this study were 194 Thai men, aged between 40 and 87 years who resided in Mae Chaem District, Chiang Mai Province, Thailand. Self-administered questionnaires were used for receiving the demographic characteristics information. BMD was measured by peripheral dual energy X-ray absorptiometry at the nondominant distal forearm in all men. Results: The BMD was highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The average T-score at the distal forearm was also highest in the age-group 40–49 years and lowest in the age-group 70–87 years. The BMD decreased as a function of age-group (p < .05). In contrast, the BMD increased as a function of weight (p < .05). Height had weak impact on the BMD in the distal forearm (p > .05). The percentage of osteopenia and osteoporosis are increased as a function of age-group in, while decreased in that of normal bone density. Conclusions: We found the prevalence of osteoporosis in men who resided in Mae Chaem District, Chiang Mai Province, Thailand.

Proteomic Profiling of Hematopoietic Stem/Progenitor Cells after a Whole Body Exposure of CBA/CaJ Mice to Titanium (48Ti) Ions

Myeloid leukemia (ML) is one of the major health concerns from exposure to radiation. However, the risk assessment for developing ML after exposure to space radiation remains uncertain. To reduce the uncertainty in risk prediction for ML, a much increased understanding of space radiation-induced changes in the target cells, i.e., hematopoietic stem/progenitor cells (HSPCs), is critically important. We used the label-free quantitative mass spectrometry (LFQMS) proteomic approach to determine the expression of protein in HSPC-derived myeloid colonies obtained at an early time-point (one week) and a late time-point (six months) after an acute whole body exposure of CBA/CaJ mice to a total dose of 0, 0.1, 0.25, or 0.5 Gy of heavy-ion titanium (48Ti ions), which are the important component of radiation found in the space environment. Mice exposed to 0 Gy of 48Ti ions served as non-irradiated sham controls. There were five mice per treatment groups at each harvest time. The Trans-Proteomic Pipeline (TPP) was used to assign a probability of a particular protein being in the sample. A proof-of-concept based Ingenuity Pathway Analysis (IPA) was used to characterize the functions, pathways, and networks of the identified proteins. Alterations of expression levels of proteins detected in samples collected at one week (wk) post-irradiation reflects acute effects of exposure to 48Ti ions, while those detected in samples collected at six months (mos) post-irradiation represent protein expression profiles involved in the induction of late-occurring damage (normally referred to as genomic instability). Our results obtained by using the IPA analyses indicate a wide array of signaling pathways involved in response to 1 GeV/n 48Ti ions at both harvest times. Our data also demonstrate that the patterns of protein expression profiles are dose and time dependent. The majority of proteins with altered expression levels are involved in cell cycle control, cellular growth and proliferation, cell death and survival, cell-to-cell signaling and interaction. The IPA analyses indicate several important processes involved in responses to exposure to 48Ti ions. These include the proteosme/ubiquination, protein synthesis, post-translation modification, and lipid metabolism. The IPA analyses also indicate that exposure to 1 GeV/n 48Ti ions affects the development and function of hematological system, immune cell trafficking, including the cytoskeleton. Further, the IPA analyses strongly demonstrate that the NF-κB and MAPKs (ERKs, JNKs, and p38MAPK) pathways play an essential role in signal transduction after exposure to 1 GeV/n 48Ti ions. At an early time-point (1 week), the top networks identified by the IPA analyses are related to metabolic disease, lipid metabolism, small molecule biochemistry, and development disorder. In contrast, the top networks identified in samples collected at a late time-point (6 mos post-irradiation) by the IPA analyses are related to cancer, hematological disorders, and immunological diseases. In summary, the proteomic findings from our study provide a foundation to uncover compounds potentially be highly effective in radiation countermeasures.

Persistent depletion of plasma gelsolin (pGSN) after exposure of mice to heavy silicon ions

Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon (28Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells. We evaluated the levels of pGSN in plasma collected from groups of mice (5 mice in each) at 1 week (wk) and 1 month (1 mo) after exposure whole body to different doses of 28Si ions, i.e. 0, 0.1, 0.25, or 0.5 Gy (2 fractionated exposures, 15 days apart that totaled each selected dose). In the same mouse, the measurements of pGSN levels were coupled with the quantitation of injuries in the lung, determined by (a) the levels of cleaved poly (ADP-ribose) polymerase (cleaved-PARP), a marker of apoptotic cell-death, (b) the levels of activated nuclear factor-kappa B (NF-κB) and selected cytokines, i.e. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, from tissue-lysates of the lung. Further, the ratio of neutrophils and lymphocytes (N/L) was determined in the same mouse. Our data indicated: (i) the magnitude of pGSN depletion was dependent to radiation dose at both harvest times, (ii) a persistent depletion of pGSN up to 1 mo post-exposure to 0.25 or 0.5 Gy of 28Si ions, (iii) an inverse-correlation between pGSN depletion and increased levels of cleaved-PARP, including activated NF-κB/pro-inflammatory cytokines in the lung, and (iv) at both harvest times, statistically significant increases in the N/L ratio in groups of mice exposed to 0.5 Gy only. Our findings suggested that depletion in pGSN levels reflects not only the responses to 28Si-ion exposure at both harvest times but also early and late-occurring damage.

Protein expression profiles in hematopoietic stem/progenitor cells after exposure of mice to silicon (28Si) ions

It has been well recognized that exposure to space radiation is a major challenge to space exploration. To protect astronauts in space environments, improvement in our knowledge of radiation-induced changes in specific target cells that may affect the health of astronauts is required. Cancer of blood cells, in particular myeloid leukemia (ML), is one of the major health concerns from exposure to space radiation. However, the predictions of risks for developing ML post-exposure to space radiation are unsatisfactory. To increase the reliability of predicting risk for ML, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is critically important. In vivo studies of humans are not possible. Thus, controlled and randomized animal experiments are critically important. Most proteomic applications mentioned above have used 2-DE or stable isotope-tagged mass spectrometry. Although the 2-DE has several advantages (e.g. the detection of potential post-translational modifications of proteins which can be readily visualized on the gel, although the exact type of modification requires determination by mass spectrometry), such technology is simply not as comprehensive and reliable as desired. To overcome these limitations, we recently developed a unique label-free quantitative mass spectrometry (LFQMS) platform [ 1]. This is an innovative, experimentally based method that accurately determines peptide peak retention-time and uses multiple filters for exclusion of unqualified peptides by peptide frequency, retention time, intensity coefficient of variation and intensity correlation to enhance protein quantification of qualified peptides and proteins. In this study, we used the LFQMS platform to examine protein expression-profiles in the colonies of HSPCs (the best population of cells for studying in vivo biological effects of radiation on hematopoietic stem cells) obtained at 6 months after exposure (at which radiation-induced genomic instability and chronic inflammation have been detected [ 2]) of CBA/CaJ mice whole-body to a total dose of 0, 0.1, 0.25 or 0.5 Gy of 300 MeV/nucleon 28Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). These doses of 300 MeV/nucleon 28Si ions are comparable to what astronauts encounter in space. Mice exposed to 0 Gy of 28Si ions served as non-irradiated sham controls. The colonies of HSPCs were obtained from BM cells of five mice per treatment group, by means of an in vitro colony forming unit assay (CFU-A) using methylcellulose-based medium. Proteins were extracted from HSPC colonies and protein concentrations were determined by the Bradford Protein Assay. The trans-proteomic pipeline (TPP) was used to assign a probability of a particular protein being in the sample. A total of 1344 unique, non-redundant proteins were identified with ≥90% confidence from 3254 peptides, quantified and their abundances were compared statistically. Among the 1344 proteins, differential expression of 198 proteins was found to be statistically significant in HSPC colonies obtained from treated groups, in relation to those found in non-irradiated sham controls. A proof-of-concept-based Ingenuity Pathway Analysis (IPA, www.ingenuity.com) was used to characterize the functions and pathways of these 198 identified proteins. The majority of these proteins are cancer-related (P < 0.0001). Biochemical analyses of the molecular and cellular functions of these proteins reveal association with perturbation in cell survival, free radical scavenging, cell cycle, DNA repair, cellular assembly, hematological system development and inflammatory responses. These proteins are linked to two major molecular networks that are linked to cancer and inflammatory responses (i.e. nuclear factor-κ B and the protein phosphatase 2 A networks). Our results indicated 28Si ion-induced damage in HSPCs.

An evaluation of the antioxidant properties of iodinated radiographic contrast media: An in vitro study

Graphical abstract

Radiation Shielding Properties of BaO-ZnO-B2O3 Glass for X-Ray Room

This study is to find a parameters that necessary for fabricating a radiation shielding glass in x-ray room. In this study, we performed a comparison of commercial lead glass product commercial window, and developed lead-free glass in the composition of xBaO:20ZnO:(80-x)B2O3 which are applied used for lead glass replacement. The result found that, the linear attenuation coefficients (m) were increased with the increase of BaO concentrations and the decrease of an x-ray tube voltage. The developed glass samples were investigated in terms of half value layer (HVL) and mean free path (MFP) that found to be decreased with the increase of BaO concentrations which the good characteristics for application in a x-ray shielding glass manufacturing.

Effects of Medical Diagnostic Low-dose X Rays on Human Lymphocytes: Mitochondrial Membrane Potential, Apoptosis and Cell Cycle

Abstract Low-dose radiation is widely used across the world for the diagnosis of many diseases by means of a variety of imaging technologies. However, the harmful effects of exposure to low-dose radiation during medical examination remain controversial. The authors studied the effects of medical diagnostic low-dose x rays (i.e., 0.03, 0.05, or 0.1 mGy) after an in vitro exposure of human lymphocytes. Cells with no irradiation served as the non-irradiated control group. Three biological indicators were used to determine the effects of medical diagnostic low-dose x rays at 4, 8, 24, 48, and 72 h post-irradiation. These biological endpoints were mitochondrial membrane potential (&Dgr;&PSgr;m), cell cycle, and apoptosis. Results indicated no changes in the &Dgr;&PSgr;m, number of apoptotic cells, and cell cycle in lymphocytes exposed to these low doses of radiation, as compared to the corresponding non-irradiated lymphocytes at all harvest time-points. These results suggested that there were no harmful effects of the diagnostic low-dose x rays when human lymphocytes were exposed in an in vitro condition.

Mass Attenuation Coefficients and Partial Interactions of BaO-ZnO-B2O3 Glasses System

The mass attenuation coefficients and partial interactions of BaO-ZnO-B2O3 glasses have been investigated using WinXCom program at difference photon energy. BaO-ZnO-B2O3 glasses were prepared in composition xBaO: 20ZnO: (80-x)B2O3 (where x = 15 and 20 mol %) by melt quenching technique under normal atmosphere. The densities of glasses are 3.0052 and 3.1022 g/cm3, respectively. The mass attenuation coefficients at 20% mol are higher than 15% mol of BaO in all energy range. The optical spectra were measured and good transparent behavior was obtained. Half value layer (HVL) of glasses are also report and compared with same standard shielding materials and show better shielding than ordinary concrete.