DOCSLIB.ORG

United States Patent (10) Patent No.: US 9,687,573 B2 Reb Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent (10) Patent No.: US 9,687,573 B2 Reb Et Al US009687573B2 (12) United States Patent (10) Patent No.: US 9,687,573 B2 Reb et al. (45) Date of Patent: Jun. 27, 2017 (54) COMPOSITIONS AND ASSOCIATED 5,762.903. A 6/1998 Parket al. METHODS FOR RADIOSOTOPE-BINDING 3. A 3. E. et al. e MCROPARTICLES 5,885,547 A 3/1999 Gray 5,888,546 A 3, 1999 Ji et al. (71) Applicant: Biosphere Medical, Inc., South Jordan, 5,894,022 A 4/1999 Ji et al. UT (US) 5,942,209 A 8, 1999 Leavitt et al. 6,015,541 A 1/2000 Greff et al. (72) Inventors: Philippe Reb, Themericourt (FR): 6,039,970 A 3/2000 Callegaro et al. Celine Chaix, Clichy la Garenne (FR) 6,060,040 A * 5/2000 Tournier ................ A61K424/9.364 49,06 6,083,495 A 7/2000 Holmes-Farley et al. (73) Assignee: Biosphere Medical, Inc., South Jordan, 6,099.457 A 8, 2000 Good UT (US) 6,103,295 A 8, 2000 Chan et al. 6,106,454. A 8/2000 Berg et al. (*) Notice: Subject to any disclaimer, the term of this 6,168,777 B1 1/2001 Greff et al. patent is extended or adjusted under 35 4.2.95. r. I R $39. St.reff et al. U.S.C. 154(b) by 0 days. 6,231,615 B1 5/2001 Preissman 6,241,962 B1 6/2001 Nicolini (21) Appl. No.: 14/207,219 6.248,057 B1 6/2001 Mavity et al. 6,258.338 B1 7/2001 Gray (22) Filed: Mar 12, 2014 6,273,851 B1 8, 2001 Slater et al. 9 6,296,831 B1 10/2001 Weller et al. (65) Prior Publication Data (Continued) US 2014/0271461 A1 Sep. 18, 2014 FOREIGN PATENT DOCUMENTS CA 2307190 5, 1999 Related U.S. Application Data CA 230719.1 5, 1999 (60) Provisional application No. 61/779,712, filed on Mar. (Continued) 13, 2013. OTHER PUBLICATIONS (51) Int. C. A6 IK 5L/12 (2006.01) O'Leary, 2000, Periodic Table Groups http://www.ucc.ie/academic? A6 IK 5/06 (2006.01) chem dolchem/html/elem?group.html, 1-6. (52) U.S. C. Scranton et al., BioMedical Applications of Polyelectrolykes'. Adv. CPC ..... A61K 51/1244 (2013.01); Y10T 428/2982 Polymer. Sci., 1995, 122, 1-54. DeMar et al., “Comparison of Gas Clearance and Radioactive (2015.01) Microspheres for Pancreatic Blood Flow Measurement. Pancreas, (58) Field of Classification Search vol. 4, No. 2, pp. 161-168, 1989. CPC ....... A61K 49/00; A61K 51/065; A61K 51/12 Ehrhardt et al., “Therapeutic Use of 90Y Microspheres'. Nucl. Med. USPC ............................. 424/1.11, 1.29, 1.37, 9.34 Biol., vol. 14, No. 3, pp. 233-242, 1987. See application file for complete search history. Ercan, Radioactive Microparticles, Part I: Preparation. MML Series, vol. 2, pp. 283-307, 1999. (56) References Cited Ercan, Radioactive Microparticles, Part II: Medical Applications'. U.S. PATENT DOCUMENTS MML Series, vol. 2, pp. 313-342, 1999. (Continued) 3,334,050 A 8, 1967 Grothenhuis et al. 4,123,396 A 10, 1978 Rembaum et al. 4,224,177 A 9, 1980 Macedo et al. Primary Examiner — Jake Vu 4,224427 A 9, 1980 Mueller et al. Assistant Examiner — Jagadishwar Samala 4,789,501 A 12/1988 Day et al. (74) Attorney, Agent, or Firm — Stoel Rives LLP 4,889,707 A 12/1989 Day et al. 4,994,013 A 2, 1991 Suthanthiran et al. 5,011,677 A 4/1991 Day et al. (57) ABSTRACT 5,011,797 A 4/1991 Day et al. 5,030, 195 A 7, 1991 Nardi The present disclosure relates to polymeric materials that 5,039,326 A 8/1991 Day et al. may be labeled with a radioisotope, to processes for pro 5,069,816 A 12/1991 DeSantis et al. ducing the labeled polymeric material, and to methods of 5,162,267 A 11/1992 Smyth 5,163,896 A 1 1/1992 Suthanthiran et al. using the materials in analytical and therapeutic applica 5, 182,051 A 1/1993 Bandy et al. tions. Specifically, the disclosure relates to injectable and 5,302.369 A 4/1994 Day et al. implantable microparticles, such as microspheres, which are 5,342,283 A 8, 1994 Good 5,424,288 A 6, 1995 Order associated with radioisotopes such that the microparticles 5,496,545 A 3/1996 Holmes-Farley et al. are both therapeutic and detectable. The radioisotope-con 5,514,379 A 5, 1996 Weissleder et al. 5,614,652 A 3, 1997 Filler et al. taining microparticles are useful for embolization and other 5,635,215 A 6, 1997 Boschetti et al. therapeutic medical applications. 5,648,100 A 7, 1997 Boschetti et al. 5,667,775 A 9/1997 Holmes-Farley et al. 16 Claims, 11 Drawing Sheets US 9,687,573 B2 Page 2 (56) References Cited Schafer et al., “Physical and Chemical Characterization of a Porous Phosphate-Modified Zirconia Substrate'. Journal of Chromatogra U.S. PATENT DOCUMENTS phy, 587(2): 137-147, Dec. 20, 1991. International Search Report dated May 16, 2007 for PCT/US2005/ 6,328,700 B1 12/2001 Rheinhardt O25.645. 6,333,020 B1 12/2001 Wallace et al. van Es et al., Tumour Embolization of the Vx2 Rabbit Head and 6,335,028 B1 1/2002 Vogel et al. Neck Cancer Model with Dextran Hydrogel and Holmium-Poly 6,348,184 B1 2/2002 Nicolini (L-Lactic Acid) Microspheres: A Radionuclide and Histological 6,352,682 B2 3, 2002 Leavitt et al. Pilot Study, Journal of Cranio-Maxillogacial Surgery, Oct. 2001, 6,355,275 B1 3, 2002 Klein 29, p. 289-297. 6,368,586 B1 4/2002 Jacob et al. Business Wire, Biosphere Medical Launches New EmboGold 6,379,648 B1 4/2002 Day et al. Microspheres'. Sep. 6, 2001. 6,436,424 B1 8/2002 Vogel et al. Notice of Abandonment dated Mar. 30, 2009 for U.S. Appl. No. 6,589,502 B1 7/2003 Coniglione et al. 10/688,768. 6,660,301 B1 12/2003 Vogel et al. Office Action dated Sep. 8, 2008 for U.S. Appl. No. 10/688,768. 6,680,046 B1 1/2004 Boschetti Office Action dated Jul. 27, 2007 for U.S. Appl. No. 10/688,768. 6,746,661 B2 6/2004 Kaplan Office Action dated Dec. 19, 2006 for U.S. Appl. No. 10/688,768. 6,818, 199 B1 1 1/2004 Hainfeld et al. Office Action dated Nov. 12, 2008 for U.S. Appl. No. 1 1/185.449. 2002fOO68089 A1 6/2002 Vogel et al. Office Action dated Aug. 11, 2009 for U.S. Appl. No. 1 1/185.449. 2002/0114763 A1 8/2002 Glajch et al. Office Action dated Apr. 9, 2010 for U.S. Appl. No. 11/185.449. 2002fO187172 A1* 12, 2002 Reb ........................ A61K 49.18 Office Action dated Sep. 27, 2010 for U.S. Appl. No. 1 1/185.449. 424/401 Office Action dated Aug. 9, 2011 for U.S. Appl. No. 11/185.449. 2002fO197326 A1 12/2002 Vogel et al. Mumper et al., Neutron-Activated Holmium-166-Poly (L-Lactic 2003/0118658 A1 6/2003 Trogolo et al. Lactic Acid) Microspheres: A Potential Agent for the Internal 2003/O120355 A1* 6/2003 Hafeli ................ A61K 51.1251 Radiation Therapy of Hepatic Tumors. Journal of Neclear Medi TOOf1 cine, vol. 32 No. 11, Nov. 1991, (Nov. 1991), pp. 2139-2143. 2003/0215519 A1 11/2003 Schwarz et al. Hafeli et al., Hepatic Tumor Radioembolization in a Rat Model 2004/0091425 A1 5, 2004 Boschetti Using Radioactive Themium (186RE/188RE) Glass Microspheres'. 2004/0258614 A1* 12/2004 Line ..................... A61K 51,065 Int. J. Radiation Oncology Biol. Phys., vol. 44, No. 1, Apr. 1999 424/1.11 (Apr. 1999), pp. 189-199. 2006/0067883 A1 3f2006 Krom ................. A61K 51.1255 Campbell et al., Tumour Dosimetry in Human Liver Following 424,129 Hepatic Yttrium-90 Microsphere Therapy, Phys. Med. Biol. 46: 487-498, 2001. FOREIGN PATENT DOCUMENTS Campbell et al., “Analysis of the Distribution of Intra-Arterial Microspheres in Human Liver Following Hepatic Yttrium-90 CA 2369983 11, 2000 Microsphere Therapy, Phys. Med. Biol. 45:1023-1033, 2000. CA 2370,124 11 2000 Ho et al., Intrahepatic 90 Y-Microspheres for Hepatocellular Car CA 2393539 6, 2001 cinoma, The Journal of Nuclear Medicine 42(10): 1587-1588, Oct. EP 1371365 12/2003 2001. WO WOOOf 661.83 11 2000 WO WOO2.34300 5, 2002 Lin et al., “Effects of 90Y-Microspheres on Liver Tumors: compari WO WOO3,OO4930 11/2003 Son of Intratumoral Injection Method and Intra-Arterial Injection WO WO2004/04O972 5, 2004 Method. The Journal of Nuclear Medicine 41(11): 1892-1897, Nov. WO WO2005/035.005 4/2005 2000. WO WO2005/061009 7/2005 Loehman, Preparation and Properties of Yttrium-Silicon-Alumi WO 2006036269 4/2006 num. Oxynitride Glasses'. The Journal of the American Ceramic WO 2008034911 3, 2008 Society 62(9-10): 491-494, 1979. Stubbs et al., 'Selective Internal Radiation Therapy with 90Yttrium Microspheres for Extensive Colorectal Liver Metastases, J. OTHER PUBLICATIONS Gastrointest. Surg. 5(3): 294.302, 2001. Stubbs et al., 'Selective Internal Radiation Therapy (SIRT) with Gray et al., “Randomised Trial of SIR-Spheres(R Plus Chemo 90Yttrium Microspheres for Extensive Colorectal Liver Metasta therapy vs. Chemotherapy Alone for Treating Patients with Liver ses'. Hepato-Gastroenterology 48: 333-337, 2001. Metastases from Primary Large Bowel Cancer. Annals of Oncol Notice of Abandonment dated Sep. 27, 2007 for U.S. Appl. No. ogy, vol. 12, pp. 1711-1720, 2001.
Load more

Recommended publications
  • Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus
    The Journal of Neuroscience, October 2, 2013 • 33(40):15675–15685 • 15675 Cellular/Molecular Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus Andrea Rahel Sieber,1 Rogier Min,1 and Thomas Nevian1,2 1Department of Physiology and 2Center for Cognition, Learning and Memory, University of Bern, 3012 Bern, Switzerland The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices.WefoundthatspecificactivitypatternsinthepostsynapticTCcellinducedinhibitorylong-termpotentiation(iLTP).ThisiLTPwas non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsyn- aptic burst activity alone. iLTP required postsynaptic dendritic Ca 2ϩ influx evoked by low-threshold Ca 2ϩ spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (Ϫ50 mV), which suppressed these low-threshold Ca 2ϩ spikes, induced no plasticity. The postsynaptic dendritic Ca 2ϩ increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylylcyclase,resultinginthepresynapticexpressionofiLTP.ThedependenceofiLTPonthemembranepotentialandthereforeonthe
    [Show full text]
  • Feeding Acetyl-L-Carnitine and Lipoic Acid to Old Rats Significantly Improves Metabolic Function While Decreasing Oxidative Stress
    Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress Tory M. Hagen*, Jiankang Liu†‡, Jens Lykkesfeldt§, Carol M. Wehr†, Russell T. Ingersoll‡, Vladimir Vinarsky†, James C. Bartholomew¶, and Bruce N. Ames†‡ʈ *Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331; †Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; ‡Children’s Hospital Oakland Research Institute, Oakland, CA 94609; §Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Copenhagen DK-1870, Denmark; and ¶Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Contributed by Bruce N. Ames, December 28, 2001 Mitochondrial-supported bioenergetics decline and oxidative antioxidants or mitochondrial bioenergetics (13–15). Feeding stress increases during aging. To address whether the dietary old rats acetyl-L-carnitine (ALCAR), a mitochondrial metabo- addition of acetyl-L-carnitine [ALCAR, 1.5% (wt͞vol) in the drinking lite, reverses the age-related decline in tissue carnitine levels and water] and͞or (R)-␣-lipoic acid [LA, 0.5% (wt͞wt) in the chow] improves mitochondrial fatty acid ␤-oxidation in the tissues improved these endpoints, young (2–4 mo) and old (24–28 mo) studied (15–18). ALCAR supplementation also reverses the F344 rats were supplemented for up to 1 mo before death and age-related alterations in fatty acid profiles and loss in cardio- ؉ hepatocyte isolation. ALCAR LA partially reversed the age-related lipin levels, an essential phospholipid required for mitochondrial decline in average mitochondrial membrane potential and signif- substrate transport (15–17). We demonstrated that ALCAR ؍ icantly increased (P 0.02) hepatocellular O2 consumption, indi- supplementation reverses the age-associated decline in meta- cating that mitochondrial-supported cellular metabolism was -؉ bolic activity in rats, suggesting that ALCAR improves mito markedly improved by this feeding regimen.
    [Show full text]
  • Fe2+-Induced Lysis and Lipid Peroxidation of Chromaffin Granules
    Journal of Neurochemisrry Raven Press, New York 0 1985 International Society for Neurochemistry Fe2’-Induced Lysis and Lipid Peroxidation of Chromaffin Granules Ronald M. Spears and Ronald W. Holz Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan, U.S.A Abstract: Chromaffin granules, the catecholaminergic by trace amounts of reducible polyvalent cation. Lysis storage granules from adrenal chromaffin cells, lysed in sometimes occurred when Ca2+ was added with EGTA 10-9-10-7M Fez+. Lysis was accompanied by the pro- (10 pLM free Ca2+ concentration) and was consistently duction of malondialdehyde which results from lipid per- observed together with malondialdehyde production in oxidation. Both chromaffin granule lysis and malondi- the presence of Ca2+,EGTA, and 10 pM Fez+(total con- aldehyde production were inhibited by the free radical centration). The apparent Ca2+ dependency for chro- trapping agent butylated hydroxytoluene but not by cat- maffin granule lysis and malondialdehyde production was alase and/or superoxide dismutase. The results suggest probably caused by a trace reducible polyvalent ion dis- that lysis resulted from a direct transfer of electrons from placed by Ca2+from EGTA and not by a Ca2+-dependent Fe2+to a component of the chromaffin granule membrane reaction involving the chromaffin granule. Key Words: without the participation of either superoxide or hy- Chrornaffin granules- Fe2+- Malondialde hyde- Lipid drogen peroxide and may have resulted from lipid per- peroxidation-Ca2+. Spears R. M. and Holz R. W. oxidation. In some experiments, ascorbate alone induced Fe2+-induced lysis and lipid peroxidation of chromaffin chromaffin granule lysis which was inhibited by EDTA, granules.
    [Show full text]
  • Targeted EDTA Chelation Therapy with Albumin Nanoparticles To
    Clemson University TigerPrints All Dissertations Dissertations 8-2019 Targeted EDTA Chelation Therapy with Albumin Nanoparticles to Reverse Arterial Calcification and Restore Vascular Health in Chronic Kidney Disease Saketh Ram Karamched Clemson University, [email protected] Follow this and additional works at: https://tigerprints.clemson.edu/all_dissertations Recommended Citation Karamched, Saketh Ram, "Targeted EDTA Chelation Therapy with Albumin Nanoparticles to Reverse Arterial Calcification and Restore Vascular Health in Chronic Kidney Disease" (2019). All Dissertations. 2479. https://tigerprints.clemson.edu/all_dissertations/2479 This Dissertation is brought to you for free and open access by the Dissertations at TigerPrints. It has been accepted for inclusion in All Dissertations by an authorized administrator of TigerPrints. For more information, please contact [email protected]. TARGETED EDTA CHELATION THERAPY WITH ALBUMIN NANOPARTICLES TO REVERSE ARTERIAL CALCIFICATION AND RESTORE VASCULAR HEALTH IN CHRONIC KIDNEY DISEASE A Dissertation Presented to the Graduate School of Clemson University In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Bioengineering by Saketh Ram Karamched August 2019 Accepted by: Dr. Narendra Vyavahare, Ph.D., Committee Chair Dr. Agneta Simionescu, Ph.D. Dr. Alexey Vertegel, Ph.D. Dr. Christopher G. Carsten, III, M.D. ABSTRACT Cardiovascular diseases (CVDs) are the leading cause of death globally. An estimated 17.9 million people died from CVDs in 2016, with ~840,000 of them in the United States alone. Traditional risk factors, such as smoking, hypertension, and diabetes, are well discussed. In recent years, chronic kidney disease (CKD) has emerged as a risk factor of equal importance. Patients with mild-to-moderate CKD are much more likely to develop and die from CVDs than progress to end-stage renal failure.
    [Show full text]
  • Deferiprone and Efonidipine Mitigated Iron-Overload Induced Neurotoxicity
    Life Sciences 239 (2019) 116878 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Deferiprone and efonidipine mitigated iron-overload induced neurotoxicity T in wild-type and thalassemic mice Jirapas Sripetchwandeea,b, Juthamas Khamseekaewb, Saovaros Svastic, Somdet Srichairatanakoold, Suthat Fucharoenc, Nipon Chattipakorna,b, ∗ Siriporn C. Chattipakorna,b,e, a Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand b Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand c Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand d Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 50200, Thailand e Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand ARTICLE INFO ABSTRACT Keywords: Aims: We previously demonstrated that iron-overload in non-thalassemic rats induced neurotoxicity and cog- Iron-overload nitive decline. However, the effect of iron-overload on the brain of thalassemic condition has never beenin- Oxidative stress vestigated. An iron chelator (deferiprone) provides neuroprotective effects against metal toxicity. Furthermore, a Iron chelator T-type calcium channels blocker (efonidipine) effectively attenuates cardiac dysfunction in thalassemic mice T-type calcium channel blockers with iron-overload. However, the effects of both drugs on brain of iron-overload thalassemia has notbeen Mitochondria determined. We hypothesize that iron-overload induces neurotoxicity in Thalassemic and wild-type mice, and not only deferiprone, but also efonidipine, provides neuroprotection against iron-overload condition. Main methods: Mice from both wild-type (WT) and β-thalassemic type (HT) groups were assigned to be fed with a standard-diet or high-iron diet containing 0.2% ferrocene/kg of diet (HFe) for 4 months consecutively.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0222294 A1 Pele (43) Pub
    US 2010O222294A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0222294 A1 Pele (43) Pub. Date: Sep. 2,9 2010 (54) FORMULATIONS OF ATP AND ANALOGS OF Publication Classification ATP (51) Int. Cl. A 6LX 3L/7076 (2006.01) (75) Inventor: Amir Pelleg, Haverford, PA (US) A6IP35/00 (2006.01) Correspondence Address: 39t. 87, C FSH & RICHARDSON P.C. (2006.01) P.O. BOX 1022 A6IP 9/00 308: MNNEAPOLIS. MN 55440-1022 US A6IP II/06 2006.O1 9 (US) A6IP II/08 (2006.01) (73) Assignee: DUSKA SCIENTIFIC CO., CI2N 5/02 (2006.01) Philadelphia, PA (US) AOIN I/02 (2006.01) (52) U.S. Cl. ................................ 514/47; 435/375; 435/2 (21) Appl. No.: 12/715,170 (57) ABSTRACT (22) Filed: Mar. 1, 2010 This disclosure provides solutions and compositions (e.g., O O pharmaceutical solutions and compositions) containing Related U.S. Application Data adenosine 5'-triphosphate (ATP) or an analog thereof. In (60) Provisional application No. 61/156.263, filed on Feb. addition, it features methods of making and using the solu 27, 2009. tions and compositions. Patent Application Publication Sep. 2, 2010 US 2010/0222294 A1 Figure , NH N O O. O. a'rn HO-P-O-PYo-E-40. O-P-O- o, 's-slNYN Ohi Oi O US 2010/0222294 A1 Sep. 2, 2010 FORMULATIONS OF ATP AND ANALOGS OF N-Tris(hydroxymethyl)methylglycine (Tricine); glycine; ATP Diglycine (Gly-Gly); N,N-Bis(2-hydroxyethyl)glycine (Bi cine); N-(2-Hydroxyethyl)piperazine-N'-(4-butanesulfonic acid) (HEPBS); N-Tris(hydroxymethyl)methyl-3-amino 0001.
    [Show full text]
  • Nitric Oxide Modulation of Interleukin-1Я-Evoked Intracellular
    The Journal of Neuroscience, December 15, 2000, 20(24):8980–8986 Nitric Oxide Modulation of Interleukin-1␤-Evoked Intracellular Ca2؉ Release in Human Astrocytoma U-373 MG Cells and Brain Striatal Slices Antonella Meini,1 Alberto Benocci,1 Maria Frosini,1 Gianpietro Sgaragli,1 Gianpaolo Pessina,2 Carlo Aldinucci,2 Gise` le Tchuisseu Youmbi,1 and Mitri Palmi1 1Istituto di Scienze Farmacologiche and 2Istituto di Fisiologia, Universita` di Siena, 53100 Siena, Italy Intracellular Ca 2ϩ mobilization and release into mammal CSF Ca 2ϩ release induced by 2.5 but not 10 ng/ml IL-1␤. Ruthenium plays a fundamental role in the etiogenesis of fever induced by red (50 ␮M) and, to a lesser extent, heparin (3 mg/ml) antagonized the proinflammatory cytokine interleukin-1␤ (IL-1␤) and other IL-1␤-induced Ca 2ϩ release, and both compounds administered pyrogens. The source and mechanism of IL-1␤-induced intracel- together completely abolished this response. Similar results were lular Ca 2ϩ mobilization was investigated using two experimental obtained in human astrocytoma cells in which IL-1␤ elicited a models. IL-1␤ (10 ng/ml) treatment of rat striatal slices preloaded delayed (30 min) increase in intracellular Ca 2ϩ concentration 45 2ϩ 2ϩ Ϯ with Ca elicited a delayed (30 min) and sustained increase ([Ca ]i ) (402 71.2% of baseline), which was abolished by 1 45 2ϩ (125–150%) in spontaneous Ca release that was potentiated mML-NAME. These data indicate that the NO/cGMP-signaling by L-arginine (300 ␮M) and counteracted by N-␻-nitro-L-arginine pathway is part of the intracellular mechanism transducing IL- 2ϩ methyl ester (L-NAME) (1 and 3 mM).
    [Show full text]
  • Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems
    Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 640754, 26 pages http://dx.doi.org/10.1155/2014/640754 Review Article Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems Bechan Sharma,1 Shweta Singh,2 and Nikhat J. Siddiqi3 1 Department of Biochemistry, University of Allahabad, Allahabad 211002, India 2 Department of Genetics, SGPGIMS, Lucknow 226014, India 3 Department of Biochemistry, King Saud University, Riyadh 11451, Saudi Arabia Correspondence should be addressed to Bechan Sharma; [email protected] Received 28 February 2014; Revised 28 May 2014; Accepted 10 July 2014; Published 12 August 2014 Academic Editor: Hartmut Jaeschke Copyright © 2014 Bechan Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis.
    [Show full text]
  • Transcriptomic Analysis of Synergy Between Antifungal Drugs and Iron Chelators for Alternative Antifungal Therapies
    Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies Yu-Wen Lai School of Life and Environmental Sciences (SoLES) Faculty of Science The University of Sydney 2017 A thesis submitted in fulfilment of the requirements of the degree of Doctor of Philosophy. Declaration of originality I certify that this thesis contains no materials which have been accepted for award of any other degree or diploma at any other university. To the best of my knowledge, this thesis is original and contains no material previously published or written by any other person, except where due reference has been made in the text. Yu-Wen Lai August 2016 i Acknowledgements This whole thesis and the years spent into completing it would not have been possible without the help and support of a lot of people. I am thankful and grateful to my supervisor Dee Carter and also to my co-supervisor Sharon Chen for giving me the opportunity to work on this project. I am also thankful to our collaborator Marc Wilkins and his team. This project has been very challenging and your inputs and advice have really helped immensely. A big thank you goes to past and present honours students, PhD candidates and post-docs. Your prep talks, stimulating discussions, humour, baked goods and cider making sessions were my staples for keeping me mostly sane. To Kate Weatherby and Sam Cheung, we started honours and PhDs together and even travelled together in Europe. There were major ups and downs during the course of our projects, but were finally getting to the end! Thank you Katherine Pan and Mia Zeric for always offering chocolate and snacks, I swear I mostly go over to your side of the office just to eat your food.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0271461 A1 Reb Et Al
    US 20140271461A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0271461 A1 Reb et al. (43) Pub. Date: Sep. 18, 2014 (54) COMPOSITIONS AND ASSOCATED Publication Classification METHODS FOR RADIOSOTOPE-BINDING MCROPARTICLES (51) Int. Cl. A615 L/2 (2006.01) (71) Applicant: Biosphere Medical, Inc., South Jordan, (52) U.S. Cl. UT (US) CPC .................................. A61K 51/1244 (2013.01) USPC ........................... 424/1.37: 525/360; 428/402 (72) Inventors: Philippe Reb, Themericourt (FR); Celine Chaix, Clichy la Garenne (FR) (57) ABSTRACT (73) Assignee: Biosphere Medical, Inc., South Jordan, The present disclosure relates to polymeric materials that UT (US) may be labeled with a radioisotope, to processes for produc ing the labeled polymeric material, and to methods of using (21) Appl. No.: 14/207,219 the materials in analytical and therapeutic applications. Spe cifically, the disclosure relates to injectable and implantable (22) Filed: Mar 12, 2014 microparticles. Such as microspheres, which are associated with radioisotopes such that the microparticles are both thera Related U.S. Application Data peutic and detectable. The radioisotope-containing micropar (60) Provisional application No. 61/779,712, filed on Mar. ticles are useful for embolization and other therapeutic medi 13, 2013. cal applications. Patent Application Publication Sep. 18, 2014 Sheet 1 of 11 US 2014/0271461 A1 FIG. 1 Patent Application Publication Sep. 18, 2014 Sheet 2 of 11 US 2014/0271461 A1 FIG. 2 Patent Application Publication Sep. 18, 2014 Sheet 3 of 11 US 2014/0271461 A1 FIG 3 Patent Application Publication Sep. 18, 2014 Sheet 4 of 11 US 2014/0271461 A1 FIG.
    [Show full text]
  • Mechanisms and Effects of Intracellular Calcium Buffering on Neuronal Survival in Organotypic Hippocampal Cultures Exposed to Anoxia/Aglycemia Or to Excitotoxins
    The Journal of Neuroscience, May 15, 1997, 17(10):3538–3553 Mechanisms and Effects of Intracellular Calcium Buffering on Neuronal Survival in Organotypic Hippocampal Cultures Exposed to Anoxia/Aglycemia or to Excitotoxins Khaled M. Abdel-Hamid1 and Michael Tymianski1,2 1Playfair Neuroscience Unit and 2Division of Neurosurgery, University of Toronto, Toronto, Ontario M5T-2S8, Canada Neuronal calcium loading attributable to hypoxic/ischemic in- survival after OGD were identical, indicating that increased jury is believed to trigger neurotoxicity. We examined in orga- buffer content is necessary for the observed protective effect. notypic hippocampal slice cultures whether artificially and re- Protection by Ca21 buffering originated presynaptically be- versibly enhancing the Ca21 buffering capacity of neurons cause BAPTA-AM was ineffective when endogenous transmit- reduces the neurotoxic sequelae of oxygen–glucose depriva- ter release was bypassed by directly applying NMDA to the tion (OGD), whether such manipulation has neurotoxic poten- cultures, and because pretreatment with the low Ca21 affinity tial, and whether the mechanism underlying these effects is pre- buffer 2-aminophenol-N,N,O-triacetic acid acetoxymethyl es- or postsynaptic. Neurodegeneration caused over 24 hr by 60 ter, which attenuates excitatory transmitter release, attenuated min of OGD was triggered largely by NMDA receptor activation neurodegeneration. Thus, in cultured hippocampal slices, en- and was attenuated temporarily by pretreating the slices with hancing neuronal Ca21 buffering unequivocally attenuates or cell-permeant Ca21 buffers such as 1,2 bis(2- delays the onset of anoxic neurodegeneration, likely by atten- aminophenoxy)ethane-N,N,N9,N9-tetra-acetic acid acetoxym- uating the synaptic release of endogenous excitatory neuro- ethyl ester (BAPTA-AM).
    [Show full text]
  • Guidelines for Monitoring Autophagy in Higher Eukaryotes
    Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (2nd edition) Daniel J Klionsky,1,2,* Kotb Abdelmohsen, Akihisa Abe, Md. Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M Adams, Peter D Adams, Khosrow Adeli, Peter J. Adhihetty, Sharon G Adler, Galila Agam, Rajesh Agarwal, Manish K Aghi, Maria Agnello, Patrizia Agostinis, Julio Aguirre-Ghiso, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T Akporiaye, Mohamed Al-Rubeai, Guillermo M Albaiceta, Diego Albani, Matthew L Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Emad S Alnemri, Covadonga Alonso, Dario C Altieri, Lydia Alvarez-Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Amal O Amer, Mohamed Amessou, Angelika Amon, Frank A. Anania, Stig U Andersen, Usha P Andley, Catherine K Andreadi, Nathalie Andrieu-Abadie, Alberto Anel, David K Ann, Shailendra Anoopkumar-Dukie, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R Ariosa, Thierry Arnould, Ivica Arsov, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Julie D Atkin, Laura D Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Laura Avagliano, Limor Avrahami, Tiziana Bachetti, Jonathan M Backer, Dong-Hun Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Seung-Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna,
    [Show full text]