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1
Braund, David. "Laches at Acanthus: Aristophanes, Wasps 968–9." Classical Quarterly 49, no. 1 (May 1999): 321–25. http://dx.doi.org/10.1093/cq/49.1.321.
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Kovács, Péter. "Once again about Constantius heros – In response to J.P.W. Wijnendaele." Acta Archaeologica Academiae Scientiarum Hungaricae 73, no. 1 (June 3, 2022): 121–26. http://dx.doi.org/10.1556/072.2022.00010.
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Abstract In his paper the author re-examines the lost funerary inscription of Constantius ‘dux’ following his earlier study and the subsequent study written by J.W.P. Wijnendaele and M. Hanaghan. In their study, the authors used the results of Kovács's earlier paper but several times they misinterpreted the author's conclusions. According to the author, their work was unnecessary and there is no need to re-evaluate the suggested date (420s) and identification given by him.
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Storey, Ian C. "Philoxenos … of Doubtful Gender." Journal of Hellenic Studies 115 (November 1995): 182–84. http://dx.doi.org/10.2307/631660.
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The date of Phrynichos' Satyroi is not known, but it seems fair to assume that in the late 420s a certain Philoxenos ‘enjoyed’ a vogue in comedy as an alleged effeminate and catamite (note the descriptions of him as θήλεια, καταπύγων, πόρνος, οὐκ ἄρρην. Both Dover and Henderson comment that καταπύγων in can mean just ‘worthless’, but here the more precise and homosexual meaning of the term is meant. Dover is very probably right that in Cl. 686 the poet has selected as male names those of ‘three men whose masculinity could be called in question’.
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Edwards, Michael J. "Antiphon and the Beginnings of Athenian Literary Oratory." Rhetorica 18, no. 3 (2000): 227–42. http://dx.doi.org/10.1525/rh.2000.18.3.227.
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Abstract: The development of an oratorical literary genre is connected with the work of Antiphon, the first in the canon of ten Attic orators. This paper argues against the modern view that the beginnings of literary oratory date to the 420s B.C. when Antiphon began publishing his speeches. It argues that this view depends on a mistaken conception of literacy in the ancient world and that Antiphon's speech-writing activities began much earlier. The argument is based on references to Antiphon in contemporary and later sources, the dating of his speeches, the authenticity and dating of the Tetralogies, and Antiphon's reputation in antiquity as the first logographer.
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Wilson, Andrew. "The Walls of Carthage and the Date of Augustine’s De Trinitate." Journal of Theological Studies 70, no. 2 (April 14, 2019): 680–705. http://dx.doi.org/10.1093/jts/flz027.
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Abstract This article calls attention to a hitherto overlooked piece of evidence that securely dates the completion of Book IX and subsequent books of Augustine’s De Trinitate to ad 424/425 or later: in it Augustine refers to having seen the moenia (defensive walls) of Carthage, which were not built until ad 424/425. The essay reviews the evidence for and previous scholarship on the chronology of the composition and completion of the De Trinitate, and considers the implications of the new dating for the circumstances of its completion, situating it within the production of Augustine’s other major works in the mid- to late 420s.
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Storey, Ian C., and Norma P. Miller. "Domestic Disharmony in Euripides' Andromache." Greece and Rome 36, no. 1 (April 1989): 16–27. http://dx.doi.org/10.1017/s0017383500029296.
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The Andromache of Euripides has not had a good press. Sandwiched between more immediately attractive plays such as Medea and Hippolytos and the more controversial dramas such as Elektra and Herakles, it has for the most part languished in obscurity with the other less appealing plays of the 420s (e.g. Herakleidai, Hekabe). More than one critic has been overtly hostile, and what interest has been shown has tended to focus on its odd tripartite structure, the elegiacs unique to tragedy in Andromache's lament (103–16), 1 the possibility of its production other than at Athens (Σ ad v. 445, evidence of a most doubtful kind), and the two well-known anti-Spartan diatribes (445–63, 595–604).
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Eisen, LewisA, YaJ Chang, and SamuelO Acquah. "A PATIENT PRESENTING WITH LUNG CAVITIES, ENDOBRONCHIAL NODULES, DIFFUSE ALVEOLAR HEMORRHAGE, MICROTHROMBI AND A POSITIVE C-ANCA." Chest 128, no. 4 (October 2005): 420S. http://dx.doi.org/10.1378/chest.128.4_meetingabstracts.420s.
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Zaganas, Dimitrios. "Traces de l’influence de Cyrille d’Alexandrie sur le De Trinitate du Pseudo-Didyme." Augustinianum 62, no. 1 (2022): 189–204. http://dx.doi.org/10.5840/agstm20226219.
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This article further examines the literary relationship between the De Trinitate falsely attributed to Didymus the Blind and the works of Cyril of Alexandria, aside from their common philosophical citations. The highlighted similarities of these two authors cannot be explained by a common source; on the contrary, they indicate a direct dependence of one author upon the other. Their analysis shows that words, turns of phrase and ideas which are typical of Cyril and often occur in his writings are each used only once by Pseudo-Didymus. This evidence weighs heavily in favour of Cyril’s antecedence. In fact, the anonymous author of the De Trinitate has been influenced, in addition to fourth-century doctrinal treatises, by Cyril’s De sancta Trinitate dialogi, an anti-Arian work dating from the 420s. He also assimilated several other Cyrillian features, and was even inspired by Cyril’s anti-Arian Christology in his doctrine on the Holy Spirit. Cyril of Alexandria, therefore, has priority over Pseudo-Didymus, both chronologically and theologically.
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Krupa, Paweł, Jarosław Bystroń, Magdalena Podkowik, Joanna Empel, Aneta Mroczkowska, and Jacek Bania. "Population Structure and Oxacillin Resistance ofStaphylococcus aureusfrom Pigs and Pork Meat in South-West of Poland." BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/141475.
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The genotypes and oxacillin resistance of 420S. aureusisolates from pigs (n=203) and pork (n=217) were analyzed. Among 18spatypes detected inS. aureusfrom pig t011, t021, t034, t091, t318, t337, and t1334 were the most frequent. Among 30spatypes found inS. aureusisolates from pork t084, t091, t499, t4309, t12954, and t13074 were dominant. The animalS. aureusisolates were clustered into MLST clonal complexes CC7, CC9, CC15, CC30, and CC398 and meat-derived isolates to CC1, CC7, and CC15. Thirty-six MRSA were isolated exclusively from pigs. All MRSA were classified tospat011 SCCmecV. BORSA phenotype was found in 14%S. aureusisolates from pigs and 10% isolates from pork meat.spat034 dominated among BORSA from pigs and t091 among meat-derived BORSA. This is the first report onspatypes and oxacillin resistance ofS. aureusstrains from pigs and pork meat in Poland. BesidesS. aureusCC9, CC30, and CC398 known to be distributed in pigs, the occurrence of genotype belonging to CC7 in this species has been reported for the first time. To our knowledge it is also the first report concerning CC398 BORSA isolates from pigs and pork meat.
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Parsia, SamS, RobertL Smith, and KevinJ Felner. "EXTRAGONADAL GERM CELL TUMOR PRESENTING WITH RESPIRATORY FAILURE." Chest 128, no. 4 (October 2005): 420S. http://dx.doi.org/10.1378/chest.128.4_meetingabstracts.420s-a.
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Hood, John Y. B. "Did Augustine Abandon His Doctrine of Jewish Witness in Aduersus Iudaeos?" Augustinian Studies 50, no. 2 (2019): 171–95. http://dx.doi.org/10.5840/augstudies20195752.
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Augustine’s doctrine of Jewish witness maintains that, although Christianity has superseded Judaism as the one true religion, it is God’s will that the Jews continue to exist because they preserve and authenticate the Old Testament, divinely-inspired texts which foretold the coming of Jesus. Thus, Christian rulers are obligated to protect the religious liberties of the Jewish people, and the church should focus its missionary efforts on pagans rather than Jews. Current scholarly consensus holds that Augustine adhered consistently to this doctrine from its first iteration in Contra Faustum in 398 until his death in 430. However, this essay argues that, when Augustine spoke his last words on the subject in the Tractatus Aduersus Iudaeos (427–430), the doctrine was no longer his primary guide in thinking about how Christians should interact with Jews. In marked contrast to his earlier views, here, Augustine passionately urges Jews to accept Christ and encourages his congregation to try to convert them. This reading of the Tractatus Aduersus Iudaeos calls for a re-examination of the development of Augustine’s teaching, particularly in the context of dramatic changes in imperial policy toward Jews in the 420s.
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Heiden, Bruce. "Tragedy and Comedy in the Frogs of Aristophanes." Ramus 20, no. 1 (1991): 95–111. http://dx.doi.org/10.1017/s0048671x00002848.
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Whenever we discuss the Frogs of Aristophanes we find ourselves discussing Athenian tragedy in the Frogs, because Frogs is the play that sends Dionysos down to Hades to recall the tragedian Euripides to Athens, the play that pits Aeschylus and Euripides against one another in a contest that provides one of the earliest specimens of Western literary criticism, and the play in which Aeschylus is finally resurrected to bring the Athenians the teaching that will save the city in its hour of distress. Athenian comedy in Frogs, in contrast, is a much less urgent topic, for while Frogs is a comedy, it does not seem to be about comedy in the same way that it is about tragedy. It includes no comic poets among its characters, it makes no mention whatsoever of comedy in the agōn of the tragic poets, and it even lacks the section of the parabasis praising Aristophanes' art, so familiar from the plays of the 420s. The few references to comedy that do appear in Frogs all occur in the first third of the play; after the parodos, there is silence.
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Evans, Joshua M. "Augustine and the Problem of Bodily Desire." Augustinian Studies 52, no. 2 (2021): 161–83. http://dx.doi.org/10.5840/augstudies202181267.
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In what sense did Augustine attribute desires to the human body itself? Scholars disagree substantially about how to answer this question, yet it has rarely been treated as anything approaching a scholarly quaestio disputata. Some hold that bodily desire is in principle impossible according to Augustine’s anthropology. Others hold that bodily desire is of marginal significance in Augustine’s system. Still others hold that bodily desire is a central problem in human life according to Augustine. This essay is an intervention intended to prompt further exchange about the interpretation of Augustine’s thought on the issue of bodily desire. To achieve that goal, the essay closely examines two texts from Augustine’s writings against Julian of Eclanum in the early 420s. In book I of De nuptiis et concupiscentia, Augustine argues that the body does have its own desires and they are an extensive problem in human life. Furthermore, in Contra Iulianum we find that Augustine himself responds to three crucial objections that might be raised against my interpretation. In short, late in his life Augustine treated bodily desire as a grave and pervasive problem. The essay does not address his views in his earlier works. As an intervention, the essay inevitably prompts important questions it cannot fully address, especially around Augustine’s philosophy of mind, the development of Augustine’s thought, and the implications of Augustine’s claims about the body for other elements of his theological project. Future investigations will hopefully take up these topics in the scholarly exchange this intervention intends to foster.
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Sun, Xiao, and Qiu Hui Zhang. "Study on the Optimum Hot-Pressing Process and Surface Decoration of Waste Tetra Pak/Sawdust Composite Board." Advanced Materials Research 710 (June 2013): 147–51. http://dx.doi.org/10.4028/www.scientific.net/amr.710.147.
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To improve the way of efficient recycling of waste Tetra Pak package, save wood materials and develope new packaging materials, this article studied on the optimum hot-pressing process and surface decoration of waste Tetra Pak/sawdust composite board. Using the orthogonal experimental method, we studied the effect of that four factors, such as resin content, hot-pressing temperature, hot-pressing time and Tetra Pak/sawdust mass ratio, on MOR, MOE, TS for 2h of waste Tetra Pak/sawdust composite board. And according to the measurement and analysis of these three test indicators of the board, we obtained the optimum hot-pressing process of waste Tetra Pak/sawdust composite board. The results showed the optimization of process parameters for the board was that: resin content for 14%, hot-pressing temperature for 150°C, hot-pressing time for 420s and Tetra Pak/sawdust mass ratio for 4:6 were suitable to product this board. At this point, the maximum MOR of the board was up to 23.1MPa, the maximum MOE of the board was up to 2917MPa, the minimum TS for 2h of the board was down to 6.1%. In the processing of PVC surface decoration, by using comparison tests, the results figured out that hot-pressing temperature for 50°C-60°C, hot-pressing time for 10s-20s, hot-pressing pressure beyond 0.02MPa were good for PVC to decorate this kind of board. The formaldehyde emission of this veneer composite board was 0.3mg/L, the surface abrasion resistance of it could reach 900r, besides, its performance of surface pollution resistance has reached the national standard.
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Henriksen, N. G., O. Z. Andersen, M. S. Jellesen, T. L. Christiansen, and M. A. J. Somers. "Influence of Laser Marking on Microstructure and Corrosion Performance of Martensitic Stainless Steel Surfaces for Biomedical Applications." HTM Journal of Heat Treatment and Materials 77, no. 3 (June 1, 2022): 177–96. http://dx.doi.org/10.1515/htm-2022-1010.
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Abstract The medical device industry demands unique device identification (UDI) tags on metallic components applied via laser marking. A common issue is that the visual appearance of the marking becomes poorly legible over time due to loss of contrast. Nanosecond pulsed laser irradiation was used to grow an oxide layer on two different martensitic stainless steels AISI 420F mod and 420B to compare the influences of the chemical composition of the steel (with and without S), power density, and energy input. The corrosion behavior was found to depend strongly on laser energy input. The presence of sulfur negatively affected the corrosion resistance and narrowed the applicable window for the laser processing parameters significantly. For the sulfur-containing AISI 420F steel, 3‒5 μm wide craters formed on the surface after laser marking, which is interpreted as thermal degradation of protruding MnS inclusions resulting from the laser marking process. Also, substantial cracking in the oxide layer was observed. The marked specimens suffered from corrosion in a thin zone below the formed oxide layer. This behavior is attributed to Cr-depletion in the zone adjacent to the oxide layer, resulting from providing Cr to the growing oxide layer.
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Tebas, Pablo, Kimberly A. Kraynyak, Ami Patel, Joel N. Maslow, Matthew P. Morrow, Albert J. Sylvester, Dawson Knoblock, et al. "Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers." Journal of Infectious Diseases 220, no. 3 (March 19, 2019): 400–410. http://dx.doi.org/10.1093/infdis/jiz132.
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AbstractBackgroundNonlive vaccine approaches that are simple to deliver and stable at room temperature or 2–8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery.MethodsTwo DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices.ResultsThe safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen.ConclusionsID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations.Clinical Trials Registration. NCT02464670.
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H. Khan, Amir. "The Impact of Human Resource Practices on Employees’ Intention to Stay and Organisational Commitment in the IT Firms." HELIX 8, no. 6 (October 31, 2018): 4202–5. http://dx.doi.org/10.29042/2018-4202-4205.
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Kumar Saini, Tejosh. "Every Moment Matters: Study of Employee Engagement at Radisson Hotel Group, Nagpur." HELIX 8, no. 6 (October 31, 2018): 4206–9. http://dx.doi.org/10.29042/2018-4206-4209.
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Ruzin, Alexey, and Richard P. Novick. "Glycerol Monolaurate Inhibits Induction of Vancomycin Resistance in Enterococcus faecalis." Journal of Bacteriology 180, no. 1 (January 1, 1998): 182–85. http://dx.doi.org/10.1128/jb.180.1.182-185.1998.
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ABSTRACT Glycerol monolaurate (GML) is a surfactant that has been found to inhibit the post-exponential phase activation of virulence factor production and the induction of β-lactamase in Staphylococcus aureus. It has been suggested that signal transduction is the most probable target for GML (S. J. Projan, S. Brown-Skrobot, P. M. Schlievert, F. Vandenesch, and R. P. Novick, J. Bacteriol. 176:4204–4209, 1994). We found that GML suppresses growth of vancomycin-resistant Enterococcus faecalis on plates with vancomycin and blocks the induction of vancomycin resistance, which involves a membrane-associated signal transduction mechanism, either at or before initiation of transcription. Given the surfactant nature of GML and the results of previous experiments, we suggest that GML blocks signal transduction. In contrast, GML has no effect on the induction of erythromycin-inducible macrolide resistance in S. aureus, which does not involve signal transduction.
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Sekino, Masaki, Yusuke Inoue, and Shoogo Ueno. "Correction to "Magnetic Resonance Imaging of Electrical Conductivity in the Human Brain" [Oct 05 4203-4205]." IEEE Transactions on Magnetics 45, no. 7 (July 2009): 3031. http://dx.doi.org/10.1109/tmag.2009.2016418.
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Kim, Jaehwan, Sungryul Yun, and Zoubeida Ounaies. "Discovery of Cellulose as a Smart Material. Volume 39, Number 12, June 13, 2006, pp 4202−4206." Macromolecules 39, no. 16 (August 2006): 5583. http://dx.doi.org/10.1021/ma0614489.
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Kutty, R. Krishnan, Reynold F. Daniel, Dene E. Ryan, Wayne Levin, and Mahin D. Maines. "Rat liver cytochrome P-450b, P-420b, and P-420c are degraded to biliverdin by heme oxygenase." Archives of Biochemistry and Biophysics 260, no. 2 (February 1988): 638–44. http://dx.doi.org/10.1016/0003-9861(88)90492-4.
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Wang, Xiao-Yun, and Xu-Rong Chen. "Discovery Potential for the Neutral Charmonium-LikeZ0(4200)byp-pAnnihilation." Advances in High Energy Physics 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/918231.
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Inspired by the observation of charmonium-likeZ(4200), we explore the discovery potential of the neutralZ0(4200)production by antiproton-proton annihilation with an effective Lagrangian approach. By investigating thep-p→J/ψπ0process including theZ0(4200)signal and background contributions, it is found that the center of mass energyEc.m.≃4.0–4.5 GeV is the best energy window for searching the neutralZ0(4200), where the signal can be clearly distinguished from background. The relevant calculations not only are helpful to search for the neutralZ0(4200)in the future experiment but also will promote the understanding of the nature and production mechanism of neutralZ0(4200)better.
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Blasius, Amanda, William Vermi, Anne Krug, Fabio Facchetti, Marina Cella, and Marco Colonna. "A cell-surface molecule selectively expressed on murine natural interferon–producing cells that blocks secretion of interferon-alpha." Blood 103, no. 11 (June 1, 2004): 4201–6. http://dx.doi.org/10.1182/blood-2003-09-3108.
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Abstract Natural interferon (IFN)-producing cells (IPCs) recognize certain viruses and DNA containing deoxycytidylate-phosphatedeoxyguanylate (CpG) motifs through the toll-like receptor (TLR) 9, resulting in secretion of IFN-α, interleukin 12 (IL-12), and proinflammatory chemokines. Human IPCs are found mainly in inflamed lymph nodes, where they are presumably recruited from the blood to activate both innate and adaptive responses to microbial infections. Demonstrating IPC recruitment and function in murine infection models has been difficult because multiple antibodies are required to distinguish IPCs from other immune cells and very few IPCs can be recovered from lymph nodes. Here we describe a monoclonal antibody (mAb) that exclusively detects murine IPCs in all lymphoid organs under both normal and inflammatory conditions. Using this antibody, we demonstrate that IPCs are normally present in the T-cell zone of lymph nodes and spleen and that inoculation of peripheral tissues with inflammatory stimuli triggers recruitment of IPC into sentinel lymph nodes, whether the stimuli are able to directly stimulate IPCs through TLR or not. Remarkably, we show that incubation of IPCs with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-α in response to CpG DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-α secretion. (Blood. 2004;103:4201-4206)
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Kraynyak, Kimberly Ann, Dinah Amante, Pablo Tebas, Dawson Knoblock, Albert J. Sylvester, Matthew P. Morrow, Naseem Prostak, et al. "Intradermal Delivery of INO-4201 Drives Robust Ebola Glycoprotein Specific Humoral and Cellular Immune Responses in Healthy Volunteers in an Open Label Phase I Trial." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 225.9. http://dx.doi.org/10.4049/jimmunol.198.supp.225.9.
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Abstract The most recent Ebola outbreak in West Africa resulted in over 28,000 suspected cases of infection and over 11,000 deaths. As no specific immune correlate has been associated with protection against Ebola to date, the development of a vaccine that generates robust humoral and cellular immune responses may be the best approach to achieve full protection. INO-4201 is a plasmid-based prophylactic vaccine targeting Zaire Ebola glycoprotein (GP), designed to prevent Ebola infection. INO-4201 encodes a consensus antigen that encompasses genetic variability from previous outbreak strains to broaden immune coverage for divergent Ebola virus variants. Intradermal (ID) administration of a 2 or 3-dose regimen of INO-4201 followed by in vivo electroporation with the CELLECTRA® device was well tolerated in 140 healthy volunteers with no related Grade 3 or Grade 4 SAEs reported. INO-4201 induced robust Ebola GP-specific antibody and T cell responses in the healthy volunteers. The majority of patients seroconverted, as gauged by binding ELISA after only 2 doses of INO-4201. EBOV GP specific T cell response were assessed by Interferon gamma (IFNγ) ELISpot revealing a mean peak response magnitude of 295 SFU per 106 PBMCs. Intracellular cytokine staining indicated that immunization with INO-4201 drove statistically significant increases in the production of IFNγ or Tumor Necrosis Factor alpha in both the CD8+ T cell compartment (p=0.001) and CD4+ T cell compartment (p=0.004). ID administration of INO-4201 using the CELLECTRA® device was well tolerated and immunogenic as assessed by both humoral and cellular EBOV GP-specific immunoassays supporting INO-4201 as a strong candidate for further clinical development of a prophylactic Ebola vaccine.
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Kalfa, Theodosia A., Frans A. Kuypers, Marilyn J. Telen, Punam Malik, Diamantis G. Konstantinidis, Jeremy H. Estepp, Hyon J. Kim, et al. "Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Studies of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, in Healthy and Sickle Cell Disease Subjects." Blood 134, Supplement_1 (November 13, 2019): 616. http://dx.doi.org/10.1182/blood-2019-121889.
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Background: The hallmark of sickle cell disease (SCD) is hemoglobin S (HbS) polymerization upon deoxygenation, resulting in red blood cell (RBC) sickling, oxidative damage, membrane damage, hemolysis, chronic anemia, vaso-occlusions and inflammation. Exacerbating the pathogenesis of SCD, the HbS RBC has 1) increased (↑) 2,3-DPG with decreased (↓) oxygen affinity (↑ P50) and 2) ↓ RBC ATP. FT-4202 is a novel, small molecule allosteric activator of erythrocyte pyruvate kinase (PKR) that increases the activity of both wild type and mutated PKR enzymes, resulting in ↓ 2,3-DPG levels and ↑ ATP levels in RBC. In preclinical safety studies, FT-4202 had no effect on steroidogenesis, low risk of drug-to-drug interactions (DDI) and was well tolerated in vivo at the maximum doses administered. In vitro FT-4202 treatment of RBCs from patients with SCD increased oxygen affinity and shifted the point of sickling by oxygen scan. After 1-week of dosing in vivo Berkeley SCD mouse-models, FT-4202 increased the oxygen affinity of HbS RBC, resulting in reduction of sickling and improved hemoglobin. Based on these results, a first-in-human Phase 1 study evaluating FT-4202 in healthy subjects and subjects with SCD was initiated. The key objectives of this randomized, double-blind, placebo-controlled single (SAD), multiple ascending dose (MAD), and food effects (FE) study are to evaluate the safety and pharmacokinetics/pharmacodynamics (PK/PD) of FT-4202, in healthy and SCD subjects [NCT03815695]. Herein we report the effects of FT-4202 on healthy subjects in this ongoing study. Methods: SAD cohorts were randomized to receive a single oral dose of FT-4202 or placebo (P). Four healthy SAD cohorts were evaluated (n=8 each; 6 FT-4202, 2 P), at increasing doses of 200, 400, 700, and 1000 mg. Four healthy MAD cohorts (n=12 each; 9 FT-4202, 3 P) received 200 to 600 mg total daily dose for 14 days at QD or BID dosing. In the FE cohort, 10 subjects received 200 mg FT-4202 QD with and without food. Safety assessments included adverse events (AEs), vital signs, ECGs and laboratory parameters. Rich PK/PD blood sampling was performed on Day1 (SAD/MAD/FE) and Day 14 (MAD), up to 72h after the last dose and at the end of study visit. PD parameters included 2,3-DPG, ATP, and P50. Safety data are summarized in a blinded fashion pending enrollment of SCD subjects. To maintain study blind, PK/PD analysis was performed by an unblinded pharmacologist using dummy subject identifiers. Results: No serious adverse events (SAEs) or AEs leading to withdrawal were reported. In the SAD cohorts, 32 subjects (20 males [M] and 12 females [F]; median age 46 yrs) were enrolled and completed the study. A total of 7 treatment-emergent AEs occurred in 6/32 (19%) subjects during the study: 3 Grade (Gr) 1 and 3 Gr 2 in severity while 1 subject in the 1000 mg FT-4202/P dose cohort experienced an isolated, asymptomatic lipase increase (Gr 3 AE) that occurred 4 days post dose and normalized within 24 hrs. In the MAD cohorts, 48 subjects (28 M; 20 F; median age 46 yrs), were enrolled and completed dosing. 18/48 (38%) of subjects receiving FT-4202/P experienced 31 Gr 1 AEs with the most frequent AE of headache (n=12). In PK assessments, FT-4202 was rapidly absorbed with a median Tmax of 1 hr post-dose. Single dose exposure increased in greater than dose-proportional manner at doses ≥700 mg. In multiple-doses delivered BID or QD, linear PK was observed across all dose levels (100-300 mg BID, 400 mg QD), and exposure remained steady up to day 14, without cumulative effect. FT-4202 exposure under fed/fasted conditions was similar. PD activity was demonstrated at all dose levels evaluated in FT-4202-treated subjects (Table 1). Within 24 hr of a single dose of FT-4202, ↓ 2,3-DPG with a corresponding ↓ P50 was observed. After 14 days of FT-4202 dosing these PD effects were maintained along with ↑ ATP over baseline. PK/PD modeling demonstrated that exposures achieved with FT-4202 150-200 mg BID will result in maximum/sustained PD effect. Conclusions: FT-4202 has a favorable safety profile in healthy subjects based on preliminary analysis of subjects receiving a single dose up to 1000 mg or multiple doses up to 600 mg/day for 14 days. FT-4202 demonstrated linear and time-independent PK with proof of mechanism (POM) demonstrated based on PD effects. Studies in SCD subjects are ongoing to confirm safety and POM of FT-4202 at doses predicted to achieve maximum PD effect (↓ 2,3-DPG/↓ P50 and ↑ ATP) in the HbS RBC. Disclosures Kalfa: FORMA: Other: sponsored research agreement; Agios: Other: local PI of clinical research trial. Kuypers:FORMA Therapeutics: Research Funding. Telen:Forma Therapeutics: Research Funding; Novartis: Other: Member of a safety monitoring committee; Pfizer: Other: Member of a clinical trial steering committee. Estepp:Global Blood Therapeutics, FORMA Therapeutics, Pfizer, Eli Lilly and Co: Research Funding; Daiichi Sankyo, Esperion, Global Blood Therapeutics: Consultancy; ASH, NHLBI: Research Funding. Saraf:Pfizer: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wilson:FORMA Therapeutics: Employment. Ribadeneira:FORMA Therapeutics: Employment. Forsyth:FORMA Therapeutics: Employment. Schroeder:FORMA Therapeutics: Employment. Drake:FORMA Therapeutics: Employment. Polyanskaya:FORMA Therapeutics: Employment. Kelly:FORMA Therapeutics: Employment. Biernat:Medpace, Inc.: Employment.
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Shrestha, Archana, Mengna Chi, Kimberly Wagner, Astha Malik, Jennifer Korpik, Adam Drake, Keertik Fulzele, Sylvie Guichard, and Punam Malik. "FT-4202, an oral PKR activator, has potent antisickling effects and improves RBC survival and Hb levels in SCA mice." Blood Advances 5, no. 9 (May 4, 2021): 2385–90. http://dx.doi.org/10.1182/bloodadvances.2020003604.
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Abstract Sickle cell anemia (SCA) results from an abnormal sickle hemoglobin (HbS). HbS polymerizes upon deoxygenation, resulting in red blood cell (RBC) sickling and membrane damage that cause vaso-occlusions and hemolysis. Sickle RBCs contain less adenosine triphosphate and more 2,3-diphosphoglycerate than normal RBCs, which allosterically reduces hemoglobin (Hb) oxygen (O2) affinity (ie, increases the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen [P50]), potentiating HbS polymerization. Herein, we tested the effect of investigational agent FT-4202, an RBC pyruvate kinase (PKR) activator, on RBC sickling and membrane damage by administering it to Berkeley SCA mice. Two-week oral FT-4202 administration was well tolerated, decreasing HbS P50 to levels similar to HbA and demonstrating beneficial biological effects. In FT-4202–treated animals, there was reduced sickling in vivo, demonstrated by fewer irreversibly sickled cells, and improved RBC deformability, assessed at varying shear stress. Controlled deoxygenation followed by reoxygenation of RBCs obtained from the blood of FT-4202–treated mice showed a shift in the point of sickling to a lower partial pressure of oxygen (pO2). This led to a nearly 30% increase in RBC survival and a 1.7g/dL increase in Hb level in the FT-4202–treated SCA mice. Overall, our results in SCA mice suggest that FT-4202 might be a potentially useful oral antisickling agent that warrants investigation in patients with SCA.
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Kubota, N., H. Takigawa, X. Ri, and K. Yasui. "792 PB 036 EFFECT OF ROOTSTOCKS ON SHOOTGROWTH. BERRY QUALITY. AND YIELD OF “FUJIMINORI” GRAPES TREATED WITH GIBBERELLIC ACID." HortScience 29, no. 5 (May 1994): 546e—546. http://dx.doi.org/10.21273/hortsci.29.5.546e.
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Shoot and berry growth, sugar. titratable acidity, and anthocyanin contents of berries and crop yields of “Fujiminori” grapes (Vitis vinifera × V. labruscana) were determined in vines grafted 10 eight different rootstocks: 3309, 3306, 101-14. 5BB. 5C, 8B. SO4, and 420A. Three-year-old vines of 5BB stock and S-year-old vines of each of the other stocks grown in an unheated plastic house were used for this investigation. Shoot growth was more vigorous on vines grafted to 5BB compared to 3309, SO4, and 8B. The highest yield per unit area was observed in vines grafted to 3306. followed in order by 5BB, 3309, 101-14, SO4, 5C, 8B, and 420A. The largest berry size was observed in vines grafted to 3306, followed by 5BB, 101-14, 3309, 8B, 5C, SO4, and 420A. Berries of vines grafted to 420A and 5BB had the highest tota1 soluble solids, followed in descending order by 8B, 101-14. and 5C. Titratable acidity of berry juice was lowest in vines grafted to 420A. The anthocyanin content of berry skin was higher in vines grafted to 420A and 101-14 than in berries of other stocks. GA-treatment did not increase the percentage of seedless berries of this cultivar to a commercially acceptable level for any of the rootstocks used.
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Ten, Leonid N., Sang-Hun Baek, Wan-Taek Im, Liudmila L. Larina, Jung-Sook Lee, Hee-Mock Oh, and Sung-Taik Lee. "Bacillus pocheonensis sp. nov., a moderately halotolerant, aerobic bacterium isolated from soil of a ginseng field." International Journal of Systematic and Evolutionary Microbiology 57, no. 11 (November 1, 2007): 2532–37. http://dx.doi.org/10.1099/ijs.0.64491-0.
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A Gram-positive, non-motile, endospore-forming bacterial strain, designated Gsoil 420T, was isolated from soil of a ginseng field in Pocheon Province, South Korea, and was characterized, using a polyphasic approach, in order to determine its taxonomic position. The novel isolate consisted of strictly aerobic, rod-shaped cells and was able to grow in medium supplemented with up to 12 % NaCl at 25 °C and pH 6.5–7.0. Comparative 16S rRNA gene sequence analysis showed that strain Gsoil 420T fell within the radiation of the cluster comprising Bacillus species and formed a coherent cluster with Bacillus niacini (16S rRNA gene sequence similarity, 98.6 %), Bacillus bataviensis (98.6 %), Bacillus soli (98.3 %), Bacillus drentensis (98.0 %), Bacillus novalis (98.0 %), Bacillus vireti (97.9 %), Bacillus foraminis (97.6 %), Bacillus fumarioli (97.4 %) and Bacillus jeotgali (97.0 %). The levels of 16S rRNA gene sequence similarity with respect to other Bacillus species with validly published names were less than 96.8 %. Strain Gsoil 420T had a genomic DNA G+C content of 44.9 mol% and the predominant respiratory quinone was MK-7. The major fatty acids were anteiso-C15 : 0 (33.9 %), iso-C15 : 0 (24.5 %) and iso-C14 : 0 (19.9 %). These chemotaxonomic results supported the affiliation of strain Gsoil 420T to the genus Bacillus. However, low DNA–DNA relatedness values and distinguishing phenotypic characteristics allowed genotypic and phenotypic differentiation of strain Gsoil 420T from recognized Bacillus species. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain Gsoil 420T represents a novel species of the genus Bacillus, for which the name Bacillus pocheonensis sp. nov. is proposed. The type strain is Gsoil 420T (=KCTC 13943T=DSM 18135T).
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Shrestha, Archana, Mengna Chi, Kimberly Wagner, Adam Drake, Keertik Fulzele, Sylvie Guichard, and Punam Malik. "Oral Administration of FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Has Potent Anti-Sickling Effects in a Sickle Cell Anemia (SCA) Mouse Model, Resulting in Improved RBC Survival and Hemoglobin Levels." Blood 136, Supplement 1 (November 5, 2020): 21–22. http://dx.doi.org/10.1182/blood-2020-140875.
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Introduction: Sickle cell anemia (SCA) results from a mutant β-globin gene that produces abnormal hemoglobin S (HbS). HbS polymerizes upon deoxygenation, resulting in red blood cell (RBC) sickling and membrane damage, leading to vaso-occlusions and hemolysis. Additionally, sickle RBCs contain less ATP and more 2,3-diphosphoglycerate (2,3-DPG) than normal RBCs; 2,3,DPG allosterically reduces hemoglobin (Hb) oxygen (O2)-affinity [i.e. increases P50], promoting faster unloading of O2, which potentiates HbS polymerization and RBC sickling. FT-4202, a selective and orally bioavailable allosteric activator of RBC pyruvate kinase (PKR), decreases 2,3-DPG and increases ATP in normal human RBCs (Blood, 2019, 134, Supplement 1:616). We hypothesized that oral administration of FT-4202 to SCA mice will increase HbS O2-affinity, and thereby decrease RBC sickling and membrane damage. Methods: Berkeley SCA mice were given 500-1000 mg/kg/day FT-4202 in chow (FT-4202 group) or control chow (control group) in 4 cohorts for 2 weeks (total 17-18 mice/group). In all cohorts, the health status, weight, and average chow consumption of each mouse was determined 3 times/week. Three cohorts were injected with sulfo-NHS-biotin 1 week into treatment (10-11 mice/group), and RBC survival assessed over the next week with serial micro-bleeds while on treatment. The 4th cohort was only bled at 2 week time-point to obtain P50 (Hemox Analyzer) and Hb levels (Hemavet). At experiment termination, all cohorts were terminally bled to determine (a) RBC levels of 2,3-DPG and ATP, (c) plasma levels of FT-4202 by LC-MS/MS, (d) the proportion of irreversibly sickled RBC (ISC) on blood smears (Image-J analysis), (e) the kinetics of experimentally-induced sickling (Lorrca®Oxygenscan) and (f) membrane deformability (Lorrca®Ektacytometry). Results: SCA mice on FT-4202 consumed a similar amount of food, and had similar weights and survival, compared to SCA mice on control chow throughout the 2-week period. As hypothesized, HbS O2 affinity increased, reflected by a decrease in P50 from 29.6 ± 0.62 mmHg (mean ± SEM) in the control group to 27.6 ± 0.58 mmHg in the FT-4202 group (p<0.03). Determinations of 2,3-DPG, ATP and FT-4202 are ongoing and will be presented. As expected, this increased HbS O2-affinity in the FT-4202 group reduced RBC sickling and membrane damage. At 2 weeks, the proportion of ISCs on blood smears was reduced in the FT-4202 group to 2.4 ± 0.3% vs. 5.9 ± 1.4% in the control group (p<0.02). The sickle RBC half-life increased to 1.8 ± 0.07 days in FT-4202 group vs. 1.4 ± 0.1 days in the control group, a 28% increase in RBC survival (p<0.01, Figure 1A). Hence, Hb levels in the FT-4202 group increased from 9.1 ± 0.2 g/dL before treatment, to 10.8 ± 0.3 g/dL 2 weeks after treatment (p<0.001), while Hb levels in the control group remained unchanged (Figure 1B). The reticulocytes remained unchanged in both groups before and after treatment. When sickle RBCs were de-oxygenated from an ambient pO2 of ~150 mmHg to a pO2 of 10-15 mmHg, followed by their re-oxygenation to ambient pO2 at a constant shear stress of 30 Pa (Oxygenscan), the point of sickling (PoS; pO2 level when the EI becomes 95% of the EI at ambient O2) decreased on average from 37% pO2 in the control group, to 30% pO2 in the FT-4202 group (p<0.002, Figure 1C), with a significantly improved Elongation Index at the point of minimum pO2 (EImin), (p<0.05). Next, RBC membrane deformability was measured under ambient pO2 (normoxic conditions), but varying shear stress after the de-oxygenation/re-oxygenation cycle on the Oxygenscan. Sickle RBCs from the FT-4202 group were significantly more deformable [i.e. had a higher Elongation Index (EI)] compared to control sickle RBCs (p<0.01, Figure 1D), as shear stress increased to ≥3 Pa, demonstrating that FT-4202 sickle RBCs sustained significantly less membrane damage following sickling and un-sickling. Conclusion: A 2-week oral FT-4202 administration was well tolerated by SCA mice and demonstrated beneficial biological effects: improved RBC membrane deformability and sickling parameters, with a shift in the PoS to lower pO2, and increased RBC survival and Hb levels. A parallel human phase-I study in healthy subjects and sickle cell disease patients to assess the safety and PK/PD of FT-4202 is ongoing (NCT03815695). Overall, our results suggest that FT-4202 can be a potentially useful orally available agent with significant anti-sickling effect. Disclosures Drake: Forma Therapeutics: Other: Shareholder of Forma Therapeutics. Fulzele:FORMA Therapeutics, Inc: Current Employment, Other: Shareholder of Forma Therapeutics. Guichard:FORMA Therapeutics, Inc: Current Employment, Other: Shareholder of Forma Therapeutics; AstraZeneca: Other: Shareholder. Malik:Aruvant Sciences, Forma Therapeutics, Inc.: Consultancy; Aruvant Sciences, CSL Behring: Patents & Royalties.
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Moyer, Cassandra, Jamal Hill, Darian Coleman, Shizuko Sei, Altaf Mohammed, Martin Sanders, Powel Brown, and Abhijit Mazumdar. "Abstract P004: Targeting the RXR pathway for the prevention of triple-negative breast cancer." Cancer Prevention Research 16, no. 1_Supplement (January 1, 2023): P004. http://dx.doi.org/10.1158/1940-6215.precprev22-p004.
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Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive cancer that lacks expression of the estrogen receptor (ER), progesterone receptor, and Erb-B2 receptor tyrosine kinase 2. TNBC patients exhibit a poor prognosis, even if treated with chemotherapy. Although studies using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have shown that breast cancer prevention is feasible, these drugs do not prevent ER-negative or TNBC tumors. It has been shown by our laboratory and others that retinoid X receptor (RXR)-specific ligands (rexinoids) can prevent breast cancers that are both ER-positive and ER-negative in mice. In our previous studies in MMTV-erbB2 mice, IRX-4204, a fourth generation rexinoid, prevented the development of most HER2/erbB2-positive tumors in these mice. For this study, we hypothesized that by targeting RXR pathway, we can prevent the development of triple negative, BRCA1-mutant mammary tumors in mice. To test the hypothesis, we treated MMTV-Cre/BRCA1co/co/p53+/- mice prior to their developing tumors with IRX-4204 to determine whether this RXR agonist effectively prevents triple-negative breast tumors. Methods: We tested the tumor preventative effect of IRX-4204 using the established MMTV-Cre/BRCA1co/co/p53+/- mouse model. These mice were produced by breeding MMTV-Cre/BRCA1co/co/p53+/- males and MMTV-Cre/BRCA1co/co/p53+/+ females, and female pups were PCR genotyped. All mice were separated into 4 groups: 1) sesame oil control, 2) IRX-4204 (10 mg/kg), 3) IRX-4204 (20 mg/kg) and 4) 9-cis-UAB-30 (5 mg/kg). All treatments were given by oral gavage, five days a week from 4 months of age. Mice were observed daily for tumor formation and toxicity. The percentage of tumor free mice were recorded, from which tumor incidence and time to tumor formation was visualized using Kaplan Meier curves and analyzed using the Log-rank test. Results: In MMTV-Cre/BRCA1co/co/p53+/- mice, IRX-4204 reduced tumor incidence and was associated with an increase in median tumor free survival time from 209 days to 336 days at 10 mg/kg dose (p=0.005). At the higher dose (20 mg/kg) IRX-4204 also delayed tumor formation with median tumor free survival from 209 days to 260 days (p=0.039). The rexinoid 9-cis-UAB 30 also significantly delayed tumor formation in MMTV-Cre/BRCA1co/co/p53+/- mice with median survival from 209 days to 270 days (p=0.04). Long term treatment of IRX-4204 was not associated with any toxicity. Conclusion: RXR agonist IRX-4204 delayed ER-negative mammary tumor formation in BRCA1co/co; MMTV-Cre; p53+/- mice. Based on our results, IRX-4204 is an effective cancer preventive drug without observed toxicity. Our results suggest that studies with reduced IRX-4204 dose alone or in combination with other targeted therapies such as selective estrogen receptor modulators are warranted. In the future, clinical trials of the IRX-4204 should be considered for the prevention of breast cancer in high-risk patients. (Supported by NCI-PREVENT contract to P. Brown and A. Mazumdar HHSN26100008). Citation Format: Cassandra Moyer, Jamal Hill, Darian Coleman, Shizuko Sei, Altaf Mohammed, Martin Sanders, Powel Brown, Abhijit Mazumdar. Targeting the RXR pathway for the prevention of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P004.
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Bantia, Shanta, Cynthia Parker, Ramanda Upshaw, John Michael Kilpatrick, Amanda Cunningham, Jianwen Zhang, Pravin Kotian, Philip Morris, Pooran Chand, and Yarlagadda S. Babu. "BCX-4208 (RO5092888), a Purine Nucleoside Phosphorylase (PNP) Inhibitor, Is a Novel, Potent Orally Active Anti-T-Cell and B-Cell Agent." Blood 112, no. 11 (November 16, 2008): 1547. http://dx.doi.org/10.1182/blood.v112.11.1547.1547.
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Abstract The profound suppression of T-cell immunity seen in patients with an inherited PNP deficiency supports the potential application of inhibitors of this purine salvage enzyme in the therapy of T-cell malignancies and T-cell mediated autoimmune diseases. About thirty percent of PNP deficient patients also show evidence of B-cell dysfunction. BCX-4208 is a novel potent transition state analog inhibitor of PNP (IC50 ~ 0.0005 μM) and in the presence of 10 μM deoxyguanosine (dGuo), inhibits human lymphocyte proliferation induced by MLR, IL-2 or Con-A with IC50s of 0.159, 0.26 and 0.73 μM, respectively. The IC50 for dGuo in the same assays in the presence of 1 μM BCX-4208 ranges from 1–3 μM. Neither BCX-4208 alone nor dGuo alone inhibits proliferation of lymphocytes. In the presence of PNP inhibitor, dGuo is converted to dGMP and then to dGTP. Accumulation of dGTP results in the alteration of deoxynucleotide (dNTP) pools, causing death of cells via a mechanism characteristic of apoptosis. In vitro data demonstrates that following exposure to BCX-4208 and dGuo, dGTP in human lymphocytes is elevated and a 5–8 fold increase in dGTP results in 50% inhibition of lymphocyte proliferation. Flow cytometric analyses of human lymphocytes using annexin-V staining reveal that BCX-4208 in the presence of dGuo induces cellular apoptosis not only in T cells (CD3+), but also in B cells (CD20+; CD19+) (Table 1). BCX-4208 is orally bioavailable in mice, can achieve maximal inhibition of PNP, and elevates plasma dGuo levels to 3–5 μM (predose levels < 0.004 μM), which is similar to levels seen in PNP deficient patients and to levels needed to cause apoptosis in T and B-cells. These data support the evaluation of BCX-4208 in the treatment of not only T-cell mediated diseases but also B-cell mediated diseases. BCX- 4208 is currently undergoing early clinical investigation in patients with psoriasis. Table 1. Cell subsets % Apoptotic cells mean ± SEM (n = 4–7) Vehicle Treatment group *p ≤ 0.01 compared to vehicle CD3+ 7.2 ± 0.9 18.3 ± 3.7* CD20+ 24.0 ± 3.6 41.8 ± 6.2* CD19+ 25.0 ± 3.1 51.6 ± 7.4*
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Keerthana, K., S. Chitra, and T. Naveenkumar. "Screening of finger millet genotypes for sodicity tolerance using the Na+/K+ ratio as a major physiological trait." Journal of Applied and Natural Science 14, SI (July 15, 2022): 73–76. http://dx.doi.org/10.31018/jans.v14isi.3571.
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Sodicity affects a larger area than salinity, but research on the sodicity tolerance mechanism is limited. The study was carried out to screen 120 finger millet genotypes under sodic soil conditions and identify sodicity-tolerant genotypes. The experimental field soil conditions were sandy clay loam with pH 8.9, electrical conductivity (EC) 0.94 dSm-1 and exchangeable sodium percentage (ESP) 21.5, which was naturally sodic. Grain yield per plant and Na+/K+ ratio were recorded for each genotype to screen sodicity tolerance among the genotypes. A significantly higher grain yield per plant than that of the sodicity-tolerant check variety TRY 1 (23.10 g) was observed in 30 finger millet genotypes. The analysis of sodium and potassium revealed that these 30 finger millet genotypes also recorded a significantly lower Na+/K+ ratio, which is comparatively lower than that of the sodicity-tolerant check variety TRY 1 (0.23 Na+/K+ ratio). The genotypes (FIN 3045, FIN 2875, FIN 3077, FIN 3015, FIN 3063, FIN 2861, FIN 3028, FIN 2867, FIN 2854, FIN 2860, FIN 2872, FIN 2896, FIN 4268, FIN 3034, FIN 3928, FIN 3104, FIN 3965, FIN 3091, FIN 2960, FIN 3994, FIN 4198, FIN 3174, FIN 3078, FIN 4288, FIN 4202, FIN 4238, FIN 3089, FIN 4205, FIN 3966 and FIN 3182) that recorded higher grain yield per plant and lower Na+/K+ ratio can be considered sodicity tolerant. These genotypes with a high grain yield per plant and a low Na+/K+ ratio could be utilized in stress breeding programs to develop sodicity-tolerant finger millet varieties.
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Yilmaz, Fatma Ozlem, Esra Meltem Koc, Meryem Askin, Rabia Kahveci, and Musa Ozata. "The Attitudes About Law Number 4207 Among Health Administration Students." Eurasian Journal of Family Medicine 9, no. 2 (June 26, 2020): 87–95. http://dx.doi.org/10.33880/ejfm.2020090204.
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Aim: ‘National Tobacco Control Program’ had developed in Turkey by the Ministry of Health in 2009 with amendment of Law 4207 and all closed places became smoke-free. The National Media Campaign has been initiated with the “Smoke Free Air-Zone” slogan for raising public awareness. The aim of our study is to determine the smoking status and attitude of Health Management students about Law 4207 in a university in Turkey, four years after the application of Smoke Free Air-Zone. Methods: In this study we used a questionnaire with 33 questions, which was developed by researchers and Fagerstrom Nicotine Dependent Test to obtain the addiction level of the smokers. Results: Sixty-two percent of 244 students were female. 3.3% were ex-smokers and 10.7% were active smokers. 5.2% of females and 19.3% of males were smoking. 87.5% of smokers think smoking habbit is harmful. 41.4% of the students thought that Law 4207 was generally accepted by the society. Conclusion: Reducing the smoking prevalence and increasing the awareness about the Law 4207 among health administrators is very important for the imlementation of health policy. So our research has an importance to highlight this subject and increase the awareness of the campaign. Keywords: administrators, Law 4207, smoking cessation, tobacco use cessation
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Kikkawa, Shintaro, Kazuyuki Sogawa, Mamoru Satoh, Hiroshi Umemura, Yoshio Kodera, Kazuyuki Matsushita, Takeshi Tomonaga, Masaru Miyazaki, Osamu Yokosuka, and Fumio Nomura. "Identification of a Novel Biomarker for Biliary Tract Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry." International Journal of Proteomics 2012 (July 25, 2012): 1–8. http://dx.doi.org/10.1155/2012/108609.
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Early diagnosis of biliary tract cancer (BTC) is important for curative surgical resection. Current tumor markers of BTC are unsatisfactory in terms of sensitivity and specificity. In a search for novel biomarkers for BTC, serum samples obtained from 62 patients with BTC were compared with those from patients with benign biliary diseases and from healthy controls, using the MALDI-TOF/TOF ClinProt system. Initial screening and further validation identified a peak at 4204 Da with significantly greater intensity in the BTC samples. The 4204 Da peak was partially purified and identified as a fragment of prothrombin by amino acid sequencing. The sensitivity of the 4204 Da peptide for detection of stage I BTC cancer was greater than those for CEA and CA19-9. Also, serum levels of the 4204 Da peptide were above the cut-off level in 15 (79%) of 19 cases in which the CEA and CA19-9 levels were both within their cut-off values. Receiver operating characteristic analysis showed that the combination of the 4204 Da peptide and CA19-9 was significantly more sensitive for detection of stage I BTC cancer compared to CEA and CA19-9. These results suggest that this protein fragment may be a promising biomarker for biliary tract cancer.
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Zhu, Li Hua, Xiao Jing Xu, Xiao Ya Niu, Ting Zhuo Chen, and Min Liu. "Surface Properties of TiNi Alloy Treated by Micro-Arc Oxidation under Different Voltages." Advanced Materials Research 1053 (October 2014): 21–29. http://dx.doi.org/10.4028/www.scientific.net/amr.1053.21.
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The effects of micro-arc oxidation (MAO) voltage (370V, 400V, 420V) on the surface morphology, adhesion of film/substrate, corrosion resistance and fretting friction and wear properties after micro-arc oxidation and heat-treatment for 48h of TiNi alloy were investigated. The results show that, as the voltage gradually increases: (1) micro-arc oxidation coatings form, when the voltage increase to 420V, the coating shows a significant micro-arc oxidized porous characteristics; (2) the Ca/P ratio in the coatings also increases, so the Ca/P ratio can be controlled by adjusting the voltage of micro-arc oxidation; (3) the corrosion resistance of MAO coatings can be significantly improved by increasing the output voltage, the corrosion rate and the corrosion potential of 420V are smaller two magnitude than 370V’s; (4) the coating of 420V shows lower friction coefficient with higher resistance, narrower wear scar width; (5) the MAO coatings have formed different types of hydroxyapatite crystals (HA) after immersed in high temperature and pressure reactor for 48h, and the phase composition of the coating are mainly apatite.
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Hong, Min, Min Lu, Yimin Qian, Liping Wei, Yaqun Zhang, Xueying Pan, Hua Li, Huaying Chen, and Naping Tang. "A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats." INQUIRY: The Journal of Health Care Organization, Provision, and Financing 58 (January 2021): 004695802110560. http://dx.doi.org/10.1177/00469580211056044.
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Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.
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Wang, Daqing, Melissa Precopio, Michael J. Reardon, Tao Lan, Jimmy X. Tang, Ekambar R. Kandimalla, Alice Bexon, Nicola La Monica, and Sudhir Agrawal. "IMO-4200, a Novel TLR7 and TLR8 Dual Agonist, Enhances Antitumor Effect of Ofatumumab, Rituximab and Cytotoxics in Preclinical Models of Hematological Malignancies,." Blood 118, no. 21 (November 18, 2011): 3724. http://dx.doi.org/10.1182/blood.v118.21.3724.3724.
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Abstract Abstract 3724 Background Toll-like receptors (TLR) are ideal targets for combination therapy of hematological malignancies as they modulate immune responses and can influence the tumor microenvironment through cytokine and chemokine induction. TLR-targeted agents have potential to treat hematological tumors by regulating the innate and acquired immune responses to cancer cells. We have previously shown that IMO-4200, a TLR7 and TLR8 dual agonist enhanced the antibody-dependent cell cytotoxicity (ADCC) of rituximab on Raji and Granta human lymphoma cell lines in vitro. Furthermore, we demonstrated that combining the agonist with rituximab resulted in long-term tumor-free survival of mice implanted i.v. with Raji B cell lymphoma or HBL-2 mantle cell lymphoma xenografts. Materials and methods In a first study, we evaluated the antitumor effect of IMO-4200 and ofatumumab, a fully human anti-CD20 antibody, in mice challenged with Raji tumor xenografts. SCID mice implanted i.v. with Raji cells were treated with 50mg/kg agonist (s.c., twice weekly for 5 weeks), 10mg/kg ofatumumab (i.p. 5 times in 3 weeks) or PBS. Treatment was initiated at day 8. In a second experiment we evaluated IMO-4200 in combination with rituximab and bendamustine or rituximab and fludarabine in human lymphoma xenograft models. Mice implanted i.v. with Ramos cells were treated with 50 mg/kg of IMO-4200 (s.c., every other day for 5 times), 10 mg/kg rituximab (i.p., every other day for 5 times), the combination of the two agents or PBS starting at day 8. Lastly, we repeated the fludarabine study design using bendamustine, 15 mg/kg, i.p., daily for 3 days, as the cytotoxic agent. Results – ofatumumab combination – The control group that received PBS developed disseminated systemic disease with a median survival of 21 days and all died within 26 days. Treatment with ofatumumab alone led to moderate tumor growth inhibition with a median survival of 31 days (p=0.0036); however, all of these mice developed lymphoma and died within 34 days. Treatment of mice with the combination of agonist and ofatumumab resulted in increased survival of 45% of mice (p=0.003 compared to antibody alone) with a median survival of 56 days. Results – rituximab/chemotherapy combinations – Mice that received PBS developed systemic disease with a median survival of 23 days. The median survival of mice treated with IMO-4200 did not differ significantly (25 days, p = 0.233), whereas rituximab increased median survival to 36 days (p < 0.01). In contrast, the combination of IMO-4200 and rituximab extended median survival to 45 days (p = 0.0121 compared to rituximab alone). Similarly, rituximab and bendamustine increased median survival to 49 days. The triple combination of IMO-4200, rituximab and bendamustine augmented median survival to 59 days (p = 0.023 compared to rituximab plus IMO-4200; p =0.026 compared to rituximab plus bendamustine). Similar enhancement of antitumor activity was observed in human B-cell lymphoma Raji xenografts when IMO-4200 was combined with rituximab and fludarabine. Conclusions Our data suggest that IMO-4200, a novel dual agonist of TLR7 and TLR8 has the potential to increase the efficacy of rituximab as well as other novel and standard agents in the treatment of non-Hodgkins lymphoma and other hematological malignancies. Disclosures: No relevant conflicts of interest to declare.
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Kayanne, Hajime, Teruaki Ishii, Eiji Matsumoto, and Nobuyuki Yonekura. "Late Holocene Sea-Level Change on Rota and Guam, Mariana Islands, and Its Constraint on Geophysical Predictions." Quaternary Research 40, no. 2 (September 1993): 189–200. http://dx.doi.org/10.1006/qres.1993.1071.
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AbstractHolocene emergent reefs and notches are well distributed on Rota and Guam. Relative sea-level changes at these islands are reconstructed based on geomorphological observations and borings on present and emergent reefs, together with 54 radiocarbon dates. Sea level rose gradually to a maximum of 1.8 m between 6000 and 4200 yr B.P. and reached its highest level by 4200 yr B.P. on both islands. After 3200 yr B.P. abrupt uplift caused emergence of the reef. By subtracting the tectonic effect, we obtained the sea-level change in the Marianas: sea level reached its present level by 4200 yr B.P. and has remained almost stable since then. Reconstructed late Holocene sea-level change in the Mariana Islands provides constraints on geophysical models of sea-level variations.
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Brown, R. Clark, Kimberly Cruz, Theodosia A. Kalfa, Frans A. Kuypers, Santosh L. Saraf, Jeremie H. Estepp, Luke R. Smart, et al. "FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease." Blood 136, Supplement 1 (November 5, 2020): 19–20. http://dx.doi.org/10.1182/blood-2020-134269.
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I NTRODUCTION: The hallmark of sickle cell disease (SCD) is hemoglobin S (HbS) polymerization upon deoxygenation, resulting in red blood cell (RBC) sickling, oxidative damage, membrane damage, hemolysis, cell adhesion, and vaso-occlusion. Exacerbating the pathogenesis of SCD, the HbS RBC has [1] increased (↑) 2,3-DPG with decreased (↓) O2 affinity (↑ P50) and [2] ↓ RBC ATP. FT-4202, a small molecule allosteric activator of erythrocyte pyruvate kinase (PKR), increases PKR activity resulting in ↓ 2,3-DPG levels and ↑ ATP levels in RBCs. In healthy volunteer (HV) studies (Kalfa et al. Blood 2019), FT-4202 was well tolerated, demonstrating physiologic responses (↓ 2,3-DPG and ↑ ATP) with biologic effects including ↑ O2 affinity, ↓ reticulocytes (P<.001) and ↑ Hb (ns). Based on the safety and pharmacokinetic/pharmacodynamic (PK/PD) profile in HV studies, FT-4202 is being evaluated in patients (pts) with SCD, first in a single dose (SD) cohort and then in multiple-dose (MD) cohorts (14-day and 12-week) [NCT03815695]. METHODS: In the SD and 14-day MD cohorts, pts with SCD were randomized 3:1 to FT-4202 or placebo. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, ECGs and laboratory parameters. PK/PD blood sampling was performed for up to 72h after the last dose and at the end-of-study visit; PD parameters included 2,3-DPG, ATP, P50, RBC deformability with controlled deoxygenation and reoxygenation (Lorrca® oxygenscan) and varying osmolality (Lorrca® osmoscan). To maintain study blind, pt identifiers were removed when needed. RESULTS: As of 17-July-2020, the SD (700 mg FT-4202) cohort is complete and the 1st MD cohort (MD-1, 300 mg once daily) is enrolling. Unblinded data from the SD and blinded data from the MD-1, 3 pt safety lead-in (randomized 2:1) are summarized. No serious adverse events (SAEs) or TEAEs leading to pt withdrawal were reported. In the SD cohort, 7 pts (2 males, 5 females, all HbSS) received 700 mg FT-4202 (n=5) or placebo (n=2). Six transient Grade 1 TEAEs occurred in 4 of 7 (57%) pts, including 3 TEAEs (arthralgia, headache, palpitations) in 2 of 5 (40%) pts receiving FT-4202 and 3 TEAEs (back pain, myalgia, pruritis) in 2 of 2 (100%) pts receiving placebo. RBC ATP concentrations increased by 30% and RBC 2,3-DPG concentrations decreased by 26% 24h after FT-4202. Increased O2 affinity (↓P50) with a decreased point of sickling (PoS) and improved HbS RBC deformability were observed in all FT-4202-treated pts. Improved HbS RBC membrane function was also demonstrated with a shift of the osmoscan results towards normal. Improved hematologic parameters, including ~0.9 g/dL Hb increase compared with placebo, were also observed 24h after a single dose of FT-4202. In 3 pts with SCD (3 females, all HbSS) who thus far completed MD-1, 14 days of 300 mg FT-4202 or placebo daily was well tolerated, with 1 pt reporting transient, unrelated Grade 2 TEAEs of nausea/vomiting at the end of the 14-day dosing period. Laboratory changes relative to pretreatment for each pt are shown in Table 1. In 2 of 3 SCD MD-1 pts treated with FT-4202/placebo (currently blinded), Hb increased by > 1 g/dL, % reticulocytes decreased, and markers of hemolysis were improved after 14 days of treatment (compared to pre-treatment levels). Hematologic parameters returned to pre-treatment levels 4 to 7 days post-treatment (data not shown) without clinical AEs. Functional studies in the 2 pts with increased Hb showed improved RBC deformability (↓ PoS) and improved RBC membrane function while on study treatment relative to pre-treatment and/or post-treatment. CONCLUSION: FT-4202 has a favorable safety profile in pts with SCD receiving a single dose or up to 14 days of dosing. A single dose of FT-4202 led to decreased 2,3-DPG and increased ATP, resulting in increased O2 affinity, decreased PoS, improved RBC deformability, and improved RBC membrane function. Initial blinded results of daily dosing with 300 mg FT-4202/placebo over 14 days show improvement in both hematologic and hemolytic parameters in 2 of 3 pts with SCD, along with improved RBC functional studies, suggesting the pharmacodynamic consequences of PKR activation may be of clinical benefit in SCD. Multiple-dose cohorts are ongoing to further evaluate the safety, PK/PD, and biological activity of FT-4202 following daily administration in pts with SCD; updated data will be presented. Disclosures Brown: Imara, Inc.: Consultancy, Research Funding; Forma Therapeutics, Inc,: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis, Inc.: Consultancy, Research Funding. Kalfa:Agios Pharmaceuticals, Inc: Consultancy, Research Funding; Forma Therapeutics, Inc: Research Funding. Kuypers:Forma Therapeutics, Inc.: Research Funding. Saraf:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer, Global Blood Therapeutics, Novartis: Research Funding. Estepp:Global Blood Therapeutics, Forma Therapeutics, Pfizer, Eli Lilly and Co: Research Funding; Daiichi Sankyo, Esperion, Global Blood Therapeutics: Consultancy; ASH, NHLBI: Research Funding. Malik:Aruvant Sciences, CSL Behring: Patents & Royalties; Aruvant Sciences, Forma Therapeutics, Inc.: Consultancy. Ribadeneira:Forma Therapeutics, Inc.: Current Employment. Forsyth:Forma Therapeutics, Inc.: Current Employment. Schroeder:Forma Therapeutics, Inc.: Current Employment. Wu:Forma Therapeutics, Inc.: Current Employment. Kelly:Forma Therapeutics, Inc.: Current Employment. Telen:Forma Therapeutics: Research Funding; GlycoMimetics Inc.: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Mahmoudi, Touraj, Khatoon Karimi, Maral Arkani, Hamid Farahani, Mohsen Vahedi, Reza Dabiri, Hossein Nobakht, et al. "Resistin -420C>G Promoter Variant and Colorectal Cancer Risk." International Journal of Biological Markers 29, no. 3 (July 2014): 233–38. http://dx.doi.org/10.5301/jbm.5000079.
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Purposes Obesity is associated with an increased risk of colorectal cancer (CRC), and ghrelin (GHRL) and resistin (RETN) are thought to be related to obesity. Our aim was to investigate whether GHRL and RETN gene variants are associated with CRC risk. Materials and Methods All 414 subjects, including 197 cases with CRC and 217 controls, were genotyped for the GHRL (rs26802) and RETN (rs1862513) or -420C>G gene variants using the PCR-RFLP method. Results Our findings indicated that the RETN -420C>G “CC” genotype, compared with the “GG” and “GC” genotypes, was a marker of decreased CRC susceptibility; the difference remained significant after adjustment for age, BMI, gender, smoking status, NSAID use, and family history of CRC (p=0.020; OR=0.52, 95% CI=0.30-0.90). Furthermore, after adjustment for confounding factors, the -420C>G “CC” genotype, compared with the “GG” genotype, was associated with a decreased risk for CRC (p=0.044; OR=0.53, 95% CI=0.29-0.98). In addition, no significant difference was observed for the GHRL (rs26802) gene variant. Conclusions To our knowledge, this is the first study suggesting that the RETN -420C>G “CC” genotype is a marker of decreased CRC susceptibility. This observation is relevant from a scientific perspective and deserves further investigations.
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Vali Nurullayev, Vali Nurullayev, Bуybala Usubaliyev Bуybala Usubaliyev, Gusein Gurbanov Gusein Gurbanov, Zeynab Abdullayeva Zeynab Abdullayeva, and Hasanova Matanat Hasanova Matanat. "STUDY OF THE EFFECT OF ADDITIVES ON THE RHEOLOGICAL PROPERTIES OF CRUDE OILS AND ASPHALTENE-RESİN-PARAFFINE COMPOUNDS." PAHTEI-Procedings of Azerbaijan High Technical Educational Institutions 12, no. 01 (January 22, 2022): 41–52. http://dx.doi.org/10.36962/pahtei1201202241.
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Studies of the rheological properties of oil during transportation depending on the content of resinous components and on the intensity of asphalten-rezin-parphine deposits (ARPD). Exploitation and development of heavy oil fields requires the use of non-traditional methods of their extraction, collection and transportation by pipeline. The rheological properties of the oil are used as the primary source information for design and operation issues during field development and subsequent pipeline transportation. In practice, chemical, thermal and mechanical methods are often used together to clean the ARPD. In this case, the technological and economic effect is achieved as a result of the complete elimination of ARPD and the acceleration of the process. It is important to follow safety rules when using chemical methods in combination with mechanical and thermal methods. One of the main tasks of rheological research is to determine the relationship between the force acting on the environment under study and the deformation forces that occur under the influence of this force. The results of experimental studies of low-paraffinic and high-paraffinic oils show that the presence in the oil of a dispersed system of asphaltenes and resins can lead to depressant effects. In the process of completing the graduation qualification work were overview of ARPD, mechanism of formation and factors, influencing the formation of ARPD. Detailed description is given existing ARPD control technologies with results of pilot tests at various fields and presented comparative analysis of control methods. The study revealed the most effective technologies for prevention and removal of asphalt-resin-paraffin sediments, as well as proposed improvement of one of the methods combating ARPD. The conclusion concluded on the prospects of application technologies during operation of complicated well stock Azerbaijani. These technologies are useful for fields with high content of asphalt-resin-paraffin substances in oil, which leads to a decrease in production of well products. Effective viscosity and tensile strength were measured in a rotary rheometer REOTEST-2 using a measuring system in accordance with GOST 26581-85. The results of electron microscopic studies of the oil sample extracted from the Balakhani field show that only with the addition of BAF-1 reagent, the asphaltene-resin-paraffin associations are completely dissolved and dissolved in the volume of oil. According to the obtained results, it was found that asphalteno-resinous components are natural depressants that reduce the crystallization temperature of paraffin depending on the type of oil. Difron-4201 and BAF-1 were used in different proportions as additives in the article. BAF-1 and Difron 4201 reagents were added to the 1:1:1 ratio of paraffin-resin-asphaltene mixture in Balakhani heavy oil, respectively, in a 1:1 ratio of Difron 4201 and BAF-1 reagents. As a result of the 1:1 ratio of Difron 4201 and BAF-1 reagents to the mixture, the uniform distribution of parasite-resin-asphaltene asociates was observed, which is one of the main conditions for improving the oil relog. The effect of Difron-4201 and BAF-1 additives on the properties of the oil sample extracted from the higher paraffin Bulla field was studied. Difron-4201 and BAF-1 composites consisting of a 1:1 mixture were found to be more effective among the studied ARD additives, which reduces the freezing temperature of the oil sample in the range of 200-800 kg/ton. The optimal density of Difron-4201 and BAF-1 composites was determined to be 600 kg/ton. Similar studies were conducted on Balakhani heavy and Surakhani oil samples. After exposure of BAF-1 and Difron-4201 to resin-asphaltene-paraffin compounds separated from Bulla and Balakhani oil samples by their additives, their electron microscopic studies were studied. According to the research, it is more expedient to use a composite made of a mixture of reagents BAF-1 and Difron-4201 to improve the rheological properties of paraffin, resin, asphaltene oils. Keywords: viscosity, asphaltene, resin, paraffin, association, additive, Difron-4201, BAF-1.
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Lefer, Allan M., and Harald Darius. "Taprostene (CG-4203)." Cardiovascular Drug Reviews 7, no. 1 (March 1989): 39–51. http://dx.doi.org/10.1111/j.1527-3466.1989.tb00387.x.
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Suriyaprom, Kanjana, Rungsunn Tungtrongchitr, and Pisit Namjuntra. "Associations of Resistin Levels with Resistin Gene Polymorphism and Metabolic Syndrome in Thais / Asocijacija Nivoa Rezistina Sa Polimorfizmom Gena Za Rezistin I Metaboličkim Sindromom Kod Tajlanđana." Journal of Medical Biochemistry 34, no. 2 (April 1, 2015): 170–78. http://dx.doi.org/10.2478/jomb-2014-0034.
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Summary Background: Metabolic syndrome (MS) is a clinical constellation comprising risk factors associated with developing cardiovascular disease and type 2 diabetes. Resistin has been suggested as a linkage between obesity, inflammation and type 2 diabetes. This study aimed to investigate resistin concentrations and hematological-biochemical parameters in MS subjects and controls, and to determine whether two resistin gene (RETN) polymorphisms (-420C>G & +299G>A) are linked to resistin levels and MS among Thais. Methods: This case-control study was performed with 322 Thai volunteers: 160 MS subjects and 162 controls. Anthropometric parameters and hematological-biochemical variables were determined. The RETN -420C>G (rs1862513) and +299G>A (rs3745367) polymorphisms were genotyped by PCR-RFLP technique. Results: The resistin levels of the MS group were significantly higher than those of the control group. Resistin levels were positively correlated with anthropometric parameters and WBC count in the MS group. According to RETN -420C>G polymorphism, MS subjects with the G allele (CG/GG) (3.9 mg/L) had significantly higher resistin con- centrations than in subjects with the CC genotype (2.4 mg/L); with regard to RETN +299G>A polymorphism, carriers with the A allele (GA/AA) (3.8 mg/L) had significantly higher resistin levels than subjects with the GG genotype (2.7 mg/L), after adjusting for potential covariates. How - ever, the RETN -420C>G and +299G>A poly morphisms were not found to be associated with MS, hematologicalbiochemical parameters and anthropometric variables. Conclusions: These findings suggest resistin levels are linked with MS and the RETN -420C>G and +299G>A polymorphisms have impacted the circulating resistin concentrations. However, these two RETN polymorphisms pro - bably do not influence susceptibility to MS among Thais.
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Maurin, N. "The in vitro Bleeding Time While Using a Stable Prostacyclin Analogue during Hemodialysis." International Journal of Artificial Organs 11, no. 4 (July 1988): 243–48. http://dx.doi.org/10.1177/039139888801100406.
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A serious disadvantage of preventing clot formation by using prostacyclin (PGI2) to inhibit thrombocyte function during dialysis is that there exists no rapidly measurable monitoring parameter. The “in vitro bleeding time” fin vitro BT) is a new method for measuring primary hemostasis in vitro. Five chronic dialysis patients each underwent two dialyses: 1) with conventional full heparinization, and 2) with the stable PGI2 analogue CG 4203 and additional “low-dose” heparin. The predialytic in vitro BT is longer than normal values and values 1 h after the end of dialysis. While heparin has no significant effect on the in vitro BT, CG 4203 prolongs it concentration-dependently. Infusing CG 4203 at a rate of 25 ng/kg/min, the in vitro BT is extended beyond the measurable range of 800 μl during the first approx. 150 min of dialysis. During the next approx. 90 min it steadily decreases.
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Lin, Han-Syuan, Yi-Luen Huang, Yi-Rui Stefanie Wang, Eugene Hsiao, Tsu-An Hsu, Hui-Yi Shiao, Weir-Torn Jiaang, et al. "Identification of Novel Anti-Liver Cancer Small Molecules with Better Therapeutic Index Than Sorafenib via Zebrafish Drug Screening Platform." Cancers 11, no. 6 (May 28, 2019): 739. http://dx.doi.org/10.3390/cancers11060739.
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Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths worldwide. Sorafenib was the only U.S. Food and Drug Administration (FDA) approved drug for treating advanced HCC until recently, so development of new target therapy is urgently needed. In this study, we established a zebrafish drug screening platform and compared the therapeutic effects of two multiple tyrosine kinase inhibitors, 419S1 and 420S1, with Sorafenib. All three compounds exhibited anti-angiogenesis abilities in immersed fli1:EGFP transgenic embryos and the half inhibition concentration (IC50) was determined. 419S1 exhibited lower hepatoxicity and embryonic toxicity than 420S1 and Sorafenib, and the half lethal concentration (LC50) was determined. The therapeutic index (LC50/IC50) for 419S1 was much higher than for Sorafenib and 420S1. The compounds were either injected retro-orbitally or by oral gavage to adult transgenic zebrafish with HCC. The compounds not only rescued the pathological feature, but also reversed the expression levels of cell-cycle-related genes and protein levels of a proliferation marker. Using a patient-derived-xenograft assay, we found that the effectiveness of 419S1 and 420S1 in preventing liver cancer proliferation is better than that of Sorafenib. With integrated efforts and the advantage of the zebrafish platform, we can find more effective and safe drugs for HCC treatment and screen for personalized medicine.
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Delistraty, D. A., and B. J. Noble. "420." Medicine & Science in Sports & Exercise 19, Supplement (April 1987): S70. http://dx.doi.org/10.1249/00005768-198704001-00420.
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Parke, Rachael, Shay McGuinness, Andrew Jull, and Robyn Dixon. "420." Critical Care Medicine 40 (December 2012): 1–328. http://dx.doi.org/10.1097/01.ccm.0000424638.61392.c3.
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Jeong, Jin-Heon, Sung-Jin Nam, Jun Young Chang, In-Ae Song, Young-Jae Cho, Yoon-suk Jeon, and Sang-Heon Park. "420." Critical Care Medicine 41 (December 2013): A101. http://dx.doi.org/10.1097/01.ccm.0000439564.55857.a6.
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Case, James, Michael Delrahim, Jasmina Dizdarevic, Nasreen Khan, Akram Khan, Martin Schreiber, Dane Nichols, and Thomas DeLoughery. "420." Critical Care Medicine 42 (December 2014): A1461. http://dx.doi.org/10.1097/01.ccm.0000457917.80100.cb.
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