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Chemical Compound Review

Proxanol     2-methyloxirane; oxirane

Synonyms: POLOXAMER, Poloxalene, Poloxalkol, Therabloat, Poloxamer 188, ...
 
 
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Disease relevance of Poloxalkol

  • ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control) [1].
  • Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity [2].
  • However, although both EVAc and Pluronic release of c-myb antisense oligonucleotide sequences inhibited intimal hyperplasia 2 weeks after injury, only the more prolonged EVAc matrix release of antisense oligonucleotide to c-myc was effective [3].
  • Neither Fluosol nor Pluronic caused mortality without E coli [4].
  • The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection [4].
 

Psychiatry related information on Poloxalkol

 

High impact information on Poloxalkol

  • By electron microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited a two- to threefold increase in large intracellular cytoplasmic lipid globules and the appearance of lamellae in apposition, with a marked decrease in the number of surfactant-like particles overlying the brush border [7].
  • Antisense c-myc applied in a pluronic gel to the arterial adventitia reduced peak c-myc expression by 75% and significantly reduced neointimal formation at 14 d, compared with sense c-myc and gel application alone [8].
  • A parallel decline (60%) in alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated animals [7].
  • CONCLUSIONS: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction [2].
  • Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function [1].
 

Chemical compound and disease context of Poloxalkol

 

Biological context of Poloxalkol

 

Anatomical context of Poloxalkol

 

Associations of Poloxalkol with other chemical compounds

  • Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours [1].
  • Dox was encapsulated within stabilized Pluronic micelles and administered weekly i.v. to the rats starting 6 weeks after the tumor inoculations [18].
  • We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992) [19].
  • In an effort to improve the efficacy of antisense delivery, we evaluated polyethyleneimine (PEI, 2 kDa) alone or grafted with nonionic amphiphilic block copolymer Pluronic (P85) as a carrier for Ku86 antisense oligonucleotide (ASO) delivery [20].
  • RESULTS: TPGS, but not Poloxamer 188, inhibited the P-gp-mediated talinolol transport in Caco-2 cells [21].
 

Gene context of Poloxalkol

 

Analytical, diagnostic and therapeutic context of Poloxalkol

  • INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128) [27].
  • Total particle content (measured by an ELISA using antiserum against purified particle) after Pluronic treatment was decreased in mucosal scrapings, lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%, respectively, at 5 h after fat feeding [7].
  • Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury [2].
  • The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo [2].
  • BACKGROUND: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction [2].

References

  1. Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function. Schaer, G.L., Hursey, T.L., Abrahams, S.L., Buddemeier, K., Ennis, B., Rodriguez, E.R., Hubbell, J.P., Moy, J., Parrillo, J.E. Circulation (1994) [Pubmed]
  2. Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction. Results of a randomized, double-blind, placebo-controlled trial. Schaer, G.L., Spaccavento, L.J., Browne, K.F., Krueger, K.A., Krichbaum, D., Phelan, J.M., Fletcher, W.O., Grines, C.L., Edwards, S., Jolly, M.K., Gibbons, R.J. Circulation (1996) [Pubmed]
  3. c-myc in vasculoproliferative disease. Edelman, E.R., Simons, M., Sirois, M.G., Rosenberg, R.D. Circ. Res. (1995) [Pubmed]
  4. Increased infection mortality and decreased neutrophil migration due to a component of an artificial blood substitute. Lane, T.A., Lamkin, G.E. Blood (1986) [Pubmed]
  5. Pluronic gels for nasal delivery of Vitamin B12. Part I: preformulation study. Pisal, S.S., Paradkar, A.R., Mahadik, K.R., Kadam, S.S. International journal of pharmaceutics. (2004) [Pubmed]
  6. Postabsorptive factors are important for satiation in rats after a lipid meal. Sakata, Y., Fujimoto, K., Ogata, S., Koyama, T., Fukagawa, K., Sakai, T., Tso, P. Am. J. Physiol. (1996) [Pubmed]
  7. A possible role for rat intestinal surfactant-like particles in transepithelial triacylglycerol transport. Mahmood, A., Yamagishi, F., Eliakim, R., DeSchryver-Kecskemeti, K., Gramlich, T.L., Alpers, D.H. J. Clin. Invest. (1994) [Pubmed]
  8. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides. Bennett, M.R., Anglin, S., McEwan, J.R., Jagoe, R., Newby, A.C., Evan, G.I. J. Clin. Invest. (1994) [Pubmed]
  9. Hyperoxic reperfusion is required to reduce infarct size after intravenous therapy with perfluorochemical (Fluosol-DA 20%) or its detergent component (poloxamer 188) in a poorly collateralized animal model. Absence of a role of polymorphonuclear leukocytes. Kolodgie, F.D., Farb, A., Carlson, G.C., Wilson, P.S., Virmani, R. J. Am. Coll. Cardiol. (1994) [Pubmed]
  10. Nonionic block copolymers potentiate activities of drugs for treatment of infections with Toxoplasma gondii. Araujo, F.G., Slifer, T. Antimicrob. Agents Chemother. (1995) [Pubmed]
  11. Polymeric carriers for amphotericin B: in vitro activity, toxicity and therapeutic efficacy against systemic candidiasis in neutropenic mice. Espuelas, M.S., Legrand, P., Campanero, M.A., Appel, M., Chéron, M., Gamazo, C., Barratt, G., Irache, J.M. J. Antimicrob. Chemother. (2003) [Pubmed]
  12. Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer. Alakhov VYu, n.u.l.l., Moskaleva EYu, n.u.l.l., Batrakova, E.V., Kabanov, A.V. Bioconjug. Chem. (1996) [Pubmed]
  13. Pluronic F-68 reduces the endothelial adherence and improves the rheology of liganded sickle erythrocytes. Smith, C.M., Hebbel, R.P., Tukey, D.P., Clawson, C.C., White, J.G., Vercellotti, G.M. Blood (1987) [Pubmed]
  14. The mechanism of facilitated cell membrane resealing. Togo, T., Alderton, J.M., Bi, G.Q., Steinhardt, R.A. J. Cell. Sci. (1999) [Pubmed]
  15. Effects of poloxamer 407 on transfection time and percutaneous adenovirus-mediated gene transfer in native and stented vessels. Van Belle, E., Maillard, L., Rivard, A., Fabre, J.E., Couffinhal, T., Kearney, M., Branellec, D., Feldman, L.J., Walsh, K., Isner, J.M. Hum. Gene Ther. (1998) [Pubmed]
  16. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Lee, R.C., River, L.P., Pan, F.S., Ji, L., Wollmann, R.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  17. Lipid corralling and poloxamer squeeze-out in membranes. Wu, G., Majewski, J., Ege, C., Kjaer, K., Weygand, M.J., Lee, K.Y. Phys. Rev. Lett. (2004) [Pubmed]
  18. Ultrasonically activated chemotherapeutic drug delivery in a rat model. Nelson, J.L., Roeder, B.L., Carmen, J.C., Roloff, F., Pitt, W.G. Cancer Res. (2002) [Pubmed]
  19. The induction of cytotoxic T cells and tumor regression by soluble antigen formulation. Hariharan, K., Braslawsky, G., Black, A., Raychaudhuri, S., Hanna, N. Cancer Res. (1995) [Pubmed]
  20. Polyethyleneimine grafted with pluronic P85 enhances Ku86 antisense delivery and the ionizing radiation treatment efficacy in vivo. Belenkov, A.I., Alakhov, V.Y., Kabanov, A.V., Vinogradov, S.V., Panasci, L.C., Monia, B.P., Chow, T.Y. Gene Ther. (2004) [Pubmed]
  21. P-glycoprotein and surfactants: effect on intestinal talinolol absorption. Bogman, K., Zysset, Y., Degen, L., Hopfgartner, G., Gutmann, H., Alsenz, J., Drewe, J. Clin. Pharmacol. Ther. (2005) [Pubmed]
  22. Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport. Evers, R., Kool, M., Smith, A.J., van Deemter, L., de Haas, M., Borst, P. Br. J. Cancer (2000) [Pubmed]
  23. Sensitization of cells overexpressing multidrug-resistant proteins by pluronic P85. Batrakova, E.V., Li, S., Alakhov, V.Y., Elmquist, W.F., Miller, D.W., Kabanov, A.V. Pharm. Res. (2003) [Pubmed]
  24. Low density lipoprotein (LDL)-mediated suppression of Lewis lung carcinoma in hypercholesterolemic LDL receptor-deficient mice. Trieu, V.N., Uckun, F.M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. Expression of parathyroid hormone-related protein in human and experimental atherosclerotic lesions: functional role in arterial intimal thickening. Ishikawa, M., Akishita, M., Kozaki, K., Toba, K., Namiki, A., Yamaguchi, T., Orimo, H., Ouchi, Y. Atherosclerosis (2000) [Pubmed]
  26. Inhibition of multidrug resistance-associated protein (MRP) functional activity with pluronic block copolymers. Miller, D.W., Batrakova, E.V., Kabanov, A.V. Pharm. Res. (1999) [Pubmed]
  27. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial. Orringer, E.P., Casella, J.F., Ataga, K.I., Koshy, M., Adams-Graves, P., Luchtman-Jones, L., Wun, T., Watanabe, M., Shafer, F., Kutlar, A., Abboud, M., Steinberg, M., Adler, B., Swerdlow, P., Terregino, C., Saccente, S., Files, B., Ballas, S., Brown, R., Wojtowicz-Praga, S., Grindel, J.M. JAMA (2001) [Pubmed]
 
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