Effect of <i>CYP3A5*3</i> genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

Park, P.-W.,Seo, Y. H.,Ahn, J. Y.,Kim, K.-A.,Park, J.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.5

<P>Abstract</P><P>Background and Objective: </P><P>Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the <I>CYP3A5*3</I> genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the <I>CYP3A5*3</I> genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients.</P><P>Method: </P><P>The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their <I>CYP3A5</I> genotype was determined. Fourteen patients were <I>CYP3A5</I> expressors (two for <I>CYP3A5*1/*1</I> and 12 for <I>CYP3A5*1/*3</I>) and 21 patients were <I>CYP3A5</I> non-expressors (<I>CYP3A5*3/*3</I>). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for <I>CYP3A5</I> expressors and 13·1 ± 4·5 ng/mL/mg for <I>CYP3A5</I> non-expressors (<I>P</I> = 0·032). The oral clearance of CBZ was significantly higher in <I>CYP3A5</I> non-expressors than that of <I>CYP3A5</I> expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, <I>P</I> = 0·004). The <I>CYP3A5</I> genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.</P>

Isostructural metal-insulator transition in VO₂

Lee, D.,Chung, B.,Shi, Y.,Kim, G.-Y.,Campbell, N.,Xue, F.,Song, K.,Choi, S.-Y.,Podkaminer, J. P.,Kim, T. H.,Ryan, P. J.,Kim, J.-W.,Paudel, T. R.,Kang, J.-H.,Spinuzzi, J. W.,Tenne, D. A.,Tsymbal, E. Y. American Association for the Advancement of Scienc 2018 Science Vol.362 No.6418

<P><B>Separating structure and electrons in VO<SUB>2</SUB></B></P><P>Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO<SUB>2</SUB>) is a metal. But as soon as the material is cooled below 341 kelvin, VO<SUB>2</SUB> turns into an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee <I>et al.</I> studied the peculiar behavior of a heterostructure consisting of a layer of VO<SUB>2</SUB> placed underneath a layer of the same material that has a bit less oxygen. In the VO<SUB>2</SUB> layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO<SUB>2</SUB> was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.</P><P><I>Science</I>, this issue p. 1037</P><P>The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.</P>

BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

Lee, Y-K,Choi, E,Kim, M A,Park, P-G,Park, N-H,Lee, H Nature Publishing Group 2009 The British journal of cancer Vol.101 No.3

<P><B>Background:</B></P><P>Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A.</P><P><B>Methods:</B></P><P>We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment.</P><P><B>Results:</B></P><P>The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (<I>P</I><0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed.</P><P><B>Conclusion:</B></P><P>BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers.</P>

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Westhovens, R,Robles, M,Ximenes, A C,Nayiager, S,Wollenhaupt, J,Durez, P,Gomez-Reino, J,Grassi, W,Haraoui, B,Shergy, W,Park, S-H,Genant, H,Peterfy, C,Becker, J-C,Covucci, A,Helfrick, R,Bathon, J BMJ Group 2009 Annals of the Rheumatic Diseases Vol.68 No.12

<P><B>Objectives:</B></P><P>To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.</P><P><B>Methods:</B></P><P>In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.</P><P><B>Results:</B></P><P>At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone.</P><P><B>Conclusions:</B></P><P>In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.</P>

Factors Affecting Reproductive Performance in the Nepalese Pakhribas Pig: Effects of Nutrition and Housing during Lactation

Shrestha, N.P.,Edwards, S.A.,English, P.R.,Robertson, J.F. Asian Australasian Association of Animal Productio 2003 Animal Bioscience Vol.16 No.5

The effects of housing and nutrition on the performance of first lactation sows of the Nepalese Pakhribas breed were investigated. A total of 36 sows, from a previous experiment on nutrition during gilt rearing, were allocated according to a factorial design with 2 levels of nutrition, 60 or 80% of the calculated lactation requirement, and two types of housing, traditional or improved. The mean live weight loss of sows during lactation was reduced to a slightly greater extent by improved housing (p<0.05) than by better nutrition (p<0.10). There was also a significantly lower loss of $P_2$ backfat thickness (p<0.05) and mean body condition score (p<0.05) for sows on the higher plane of nutrition. Piglet weight gain in early and mid lactation was influenced by gestation feeding of the gilt (p<0.10) and by housing (p<0.05). Late lactation gain was influenced only by lactation feeding (p<0.05). In consequence, piglet weight at 42 day weaning was increased to a similar extent by improved housing (p<0.05) and better lactation nutrition (p<0.01). Significantly more sows were remated by day 10 after weaning from a higher level of rearing nutrition ($x^2=13.57$, p=0.001), and from improved housing and improved lactation (both $x^2=4.57$, p=0.033). It is concluded that, under Nepalese village conditions, improvements in housing may be a more cost effective way of improving sow performance than expenditure on additional feed resources.

The Effects of Phytase Supplementation on Performance and Phosphorus Excretion from Broiler Chickens Fed Low Phosphorus-Containing Diets Based on Normal or Low-phytic Acid Barley

Thacker, P.A.,Haq, Inam,Willing, B.P.,Leytem, A.B. Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.3

A total of 240 day-old broiler chicks were used to study the effects of phytase on performance and phosphorus (P) excretion from birds fed diets containing low phytate barleys formulated without inorganic P. A positive control based on Harrington barley (HB) was formulated to meet requirements for total P. Three experimental diets, based on either HB (0.39% total P with 0.28% phytate P) or the low phytate varieties LP 422 (0.36% total P with 0.14% phytate P) and LP 955 (0.40% total P with 0.01% phytate P), were formulated to be below requirements for total P by removing all the inorganic P from the diet. The four diets were fed with and without 1,000 FTU/kg phytase. Apparent P digestibility was significantly higher (p<0.01) for birds fed the low phytate barleys than for birds fed HB either supplemented or un-supplemented with inorganic P. P excretion was significantly lower (p<0.01) for birds fed HB without inorganic P than with inorganic P. P excretion was further reduced by the use of the low phytate barleys LP 422 and LP 455 (p<0.01). Phytase supplementation did not affect P excretion (p = 0.39). Body weight gain and feed intake were highest for birds fed the HB diet with inorganic P and lowest for birds fed the HB diet without inorganic P (p<0.01). Among the three low P diets, body weight gain and feed intake of broilers increased as the level of phytate in the barley declined (p<0.01). Phytase modestly increased body weight gain (p = 0.08) and feed intake (p = 0.04). The overall results of this study indicate that it may be possible to reduce the amount of inorganic P used when formulating diets with low phytate barley compared with the levels needed when formulating diets with normal phytate barley. However, it is not possible to completely replace the inorganic P in diets containing low phytate barley without impairing poultry performance. Feeding diets devoid of supplementary inorganic P in combination with low phytate barley resulted in a significant reduction in P excretion by poultry.

Growth Mechanism and Electronic Structure of Zn₃P₂ on the Ga-Rich GaAs(001) Surface

Jeon, Seokmin,Bosco, Jeffrey P.,Wilson, Samantha S.,Rozeveld, Steve J.,Kim, Hyungjun,Atwater, Harry A. American Chemical Society 2014 The Journal of Physical Chemistry Part C Vol.118 No.24

<P>The growth of epitaxial Zn<SUB>3</SUB>P<SUB>2</SUB> films on III–V substrates unlocks a promising pathway toward high-efficiency, earth-abundant photovoltaic devices fabricated on reusable, single-crystal templates. The detailed chemical, structural, and electronic properties of the surface and interface of pseudomorphic Zn<SUB>3</SUB>P<SUB>2</SUB> epilayers grown on GaAs(001) were investigated using scanning tunneling microscopy/spectroscopy and high-resolution X-ray photoelectron spectroscopy. Two interesting features of the growth process were observed: (1) vapor-phase P<SUB>4</SUB> first reacts with the Ga-rich GaAs surface to form an interfacial GaP layer with a thickness of several monolayers, and (2) a P-rich amorphous overlayer is present during the entire film growth process, beneath which a highly ordered Zn<SUB>3</SUB>P<SUB>2</SUB> crystalline phase is precipitated. These features were corroborated by transmission electron micrographs of the Zn<SUB>3</SUB>P<SUB>2</SUB>/GaAs interface as well as density functional theory calculations of P reactions with the GaAs surface. Finally, the valence-band offset between the crystalline Zn<SUB>3</SUB>P<SUB>2</SUB> epilayer and the GaAs substrate was determined to be Δ<I>E</I><SUB>V</SUB> = 1.0 ± 0.1 eV, indicating the formation of a hole-depletion layer at the substrate surface which may inhibit formation of an ohmic contact.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2014/jpccck.2014.118.issue-24/jp4127804/production/images/medium/jp-2013-127804_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp4127804'>ACS Electronic Supporting Info</A></P>

Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from <i>Sargassum binderi</i> (Sonder ex J. Agardh)

Fernando, I.P. Shanura,Jayawardena, Thilina U.,Kim, Hyun-Soo,Lee, Won Woo,Vaas, A.P.J.P.,De Silva, H.I.C.,Abayaweera, G.S.,Nanayakkara, C.M.,Abeytunga, D.T.U.,Lee, Dae-Sung,Jeon, You-Jin Academic Press 2019 Environmental research Vol.172 No.-

<P><B>Abstract</B></P> <P>Particulate matter (PM) air pollution has gradually become a widespread problem in East Asia. PM may cause unfamiliar inflammatory responses, oxidative stress, and pulmonary tissue damage, and a comprehensive understanding of the underlying mechanisms is required in order to develop effective anti-inflammatory agents. In this study, fine dust collected from Beijing, China (CPM) (size < PM13 with majority < PM2.5) was evaluated for its oxidative stress- and inflammation-inducing effects, which cause cell damage, in A459 human lung epithelial cells. Oxidative stress was marked by an increase in intracellular ROS levels and the production of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1). Upon induction of oxidative stress, a marked increase was observed in the expression of key inflammatory mediators such as COX-2 and PGE<SUB>2</SUB> and the pro-inflammatory cytokines TNF-α and IL-6 via NF-kB and MAPK pathways. Cellular damage was marked by a reduction in viability, increased lactate dehydrogenase (LDH) release, formation of apoptotic and necrotic bodies, accumulation of sub-G1 phase cells, and DNA damage. Apoptosis was found to be mediated via the activation of caspases through the mitochondria-mediated pathway. Fucosterol, purified from the brown alga <I>Sargassum binderi</I> (Sonder ex J. Agardh) by bio-assay-guided fractionation and purification, exhibited potential therapeutic effects against CPM-induced detrimental effects. Further studies could focus on developing fucosterol, in forms such as steroidal inhalers, against PM-induced pulmonary tissue inflammation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Fine dust air pollution is a major reason of pulmonary complications in East Asia. </LI> <LI> Dust particles induce oxidative stress and inflammation damaging the lung epithelial cells. </LI> <LI> Fucosterol suppressed the dust induced cell damage by inhibiting oxidative stress and inflammation. </LI> <LI> Fucosterol may have beneficial effects in alleviating adverse respiratory effects of air pollution. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Physico-chemical properties of late-incubation egg amniotic fluid and a potential in ovo feed supplement

A.A. Omede,M.M. Bhuiyan,A.F. Islam,P.A. Iji 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.8

Objective: This study explored the physico-chemical properties of late-incubation egg amniotic fluid and a potential in ovo feed (IOF) supplement. Methods: Amniotic fluid was collected from broiler breeders (Ross 308, 51 weeks and Cobb 500, 35 weeks) on day 17 after incubation. A mixture of high-quality soy protein supplement – Hamlet Protein AviStart (HPA) was serially diluted in MilliQ water to obtain solutions ranging from 150 to 9.375 mg/mL. The mixtures were heat-treated (0, 30, 60 minutes) in a waterbath (80°C) and then centrifuged to obtain supernatants. The amniotic fluid and HPA supernatants were analysed for their physico-chemical properties. Results: Only viscosity and K+ were significantly (p<0.05) different in both strains. Of all essential amino acids, leucine and lysine were in the highest concentration in both strains. The osmolality, viscosity and pCO2 of the supernatants decreased (p<0.05) with decreasing HPA concentration. Heat treatment significantly (p<0.05) affected osmolality, pH, and pCO2, of the supernatants. The interactions between HPA concentration and heat treatment were significant with regards to osmolality (p<0.01), pH (p<0.01), pCO2 (p<0.05), glucose (p<0.05), lactate (p<0.01) and acid-base status (p<0.01) of HPA solutions. The Ca2+, K+, glucose, and lactate increased with increasing concentration of HPA solution. The protein content of HPA solutions decreased (p<0.05) with reduced HPA solution concentrations. The supernatant from 150 mg/mL HPA solution was richest in glutamic acid, aspartic acid, arginine and lysine. Amino acids concentrations were reduced (p<0.05) with each serial dilution but increased with longer heating. Conclusion: The values obtained in the primary solution (highest concentration) are close to the profiles of high-protein ingredients. This supplement, as a solution, hence, may be suitable for use as an IOF supplement and should be tested for this potential.

P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc

Kim, Cuk-Seong,Jung, Saet-Byel,Naqvi, Asma,Hoffman, Timothy A.,DeRicco, Jeremy,Yamamori, Tohru,Cole, Marsha P.,Jeon, Byeong-Hwa,Irani, Kaikobad Ovid Technologies Wolters Kluwer -American Heart A 2008 Circulation research Vol.103 No.12

<P>The transcription factor, p53, and the adaptor protein, p66shc, both play essential roles in promoting oxidative stress in the vascular system. However, the relationship between the two in the context of endothelium-dependent vascular tone is unknown. Here, we report a novel, evolutionarily conserved, p53-mediated transcriptional mechanism that regulates p66shc expression and identify p53 as an important determinant of endothelium-dependent vasomotor function. We provide evidence of a p53 response element in the promoter of p66shc and show that angiotensin II-induced upregulation of p66shc in endothelial cells is dependent on p53. In addition, we demonstrate that downregulation of p66shc expression, as well as inhibition of p53 function in mice, mitigates angiotensin II-induced impairment of endothelium-dependent vasorelaxation, decrease in bioavailable nitric oxide, and hypertension. These findings reveal a novel p53-dependent transcriptional mechanism for the regulation of p66shc expression that is operative in the vascular endothelium and suggest that this mechanism is important in impairing endothelium-dependent vascular relaxation.</P>