Name: trans-tympanic drug delivery for the treatment of ototoxicity
Uploaded: 2018-03-16T12:30:00
Description: Watch this Scientific Journal Video about Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity at JoVE.com

Il lavoro descritto in questo articolo è stato supportato da un NCI RO1 CA166907, NIDCD RO1-DC 002396 e RO3 DC011621.

Linee guida e un protocollo approvato dal comitato di utilizzare e Southern Illinois University School di medicina laboratorio Animal Care utilizzare Wistar maschio ratti sono stati trattati in conformità con l'animale di National Institutes of Health. Risposta uditiva del tronco cerebrale (ABR) è stato effettuato su ratti mentre nell'ambito dell'anestesia prima della somministrazione del farmaco e 72 h dopo per verificare l'effetto della veicolazione trans-timpanico.
1. risposta uditive del t...

<ol>
	<li>McKeage, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparative+adverse+effect+profiles+of+platinum+drugs.">Comparative adverse effect profiles of platinum drugs.</a> Drug Saf. 13 (4), 228-244 (1995).</li><li>Boulikas, T., Vougiouka, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cisplatin+and+platinum+drugs+at+the+molecular+level.">Cisplatin and platinum drugs at the molecular level.</a> Oncol Rep. 10 (6), 1663-1682 (2003).</li><li>Fouladi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phase+II+study+of+oxaliplatin+in+children+with+recurrent+or+refractory+medulloblastoma,+supratentorial+primitive+neuroectodermal+tumors,+and+atypical+teratoid+rhabdoid+tumors:+a+pediatric+brain+tumor+consortium+study.">Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study.</a> Cancer. 107 (9), 2291-2297 (2006).</li><li>Pasetto, L. M., D'Andrea, M. R., Rossi, E., Monfardini, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxaliplatin-related+neurotoxicity:+how+and+why.">Oxaliplatin-related neurotoxicity: how and why.</a> Crit Rev Oncol Hematol. 59 (2), 159-168 (2006).</li><li>Ardizzoni, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cisplatin-+versus+carboplatin-based+chemotherapy+in+first-line+treatment+of+advanced+non-small-cell+lung+cancer:+an+individual+patient+data+meta-analysis.">Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.</a> J Natl Cancer Inst. 99 (11), 847-857 (2007).</li><li>Banfi, B., Malgrange, B., Knisz, J., Steger, K., Dubois-Dauphin, M., Krause, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NOX3,+a+superoxide-generating+NADPH+oxidase+of+the+inner+ear.">NOX3, a superoxide-generating NADPH oxidase of the inner ear.</a> J Biol Chem. 279 (44), 46065-46072 (2004).</li><li>Mukherjea, D., Whitworth, C. A., Nandish, S., Dunaway, G. A., Rybak, L. P., Ramkumar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+of+the+kidney+injury+molecule+1+in+the+rat+cochlea+and+induction+by+cisplatin.">Expression of the kidney injury molecule 1 in the rat cochlea and induction by cisplatin.</a> Neuroscience. 139 (2), 733-740 (2006).</li><li>Rybak, L. P., Husain, K., Morris, C., Whitworth, C., Somani, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+protective+agents+against+cisplatin+ototoxicity.">Effect of protective agents against cisplatin ototoxicity.</a> Am J Otol. 21 (4), 513-520 (2000).</li><li>Lee, J. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+reactive+radicals+in+degeneration+of+the+auditory+system+of+mice+following+cisplatin+treatment.">Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment.</a> Acta Otolaryngol. 124 (10), 1131-1135 (2004).</li><li>Lee, J. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+apoptosis+induced+by+cisplatin+in+marginal+cells+in+mouse+stria+vascularis.">Mechanisms of apoptosis induced by cisplatin in marginal cells in mouse stria vascularis.</a> ORL J Otorhinolaryngol Relat Spec. 66 (3), 111-118 (2004).</li><li>Lawenda, B. D., Kelly, K. M., Ladas, E. J., Sagar, S. M., Vickers, A., Blumberg, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Should+supplemental+antioxidant+administration+be+avoided+during+chemotherapy+and+radiation+therapy.">Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy.</a> J Natl Cancer Inst. 100 (11), 773-783 (2008).</li><li>Akil, O., Oursler, A. E., Fan, K., Lustig, L. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+auditory+brainstem+response+testing.">Mouse auditory brainstem response testing.</a> Bio Protoc. 6 (6), 1768 (2016).</li><li>Montgomery, S. C., Cox, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Whole+Mount+Dissection+and+Immunofluorescence+of+the+Adult+Mouse+Cochlea.">Whole Mount Dissection and Immunofluorescence of the Adult Mouse Cochlea.</a> J. Vis. Exp. (107), e53561 (2016).</li><li>Whitlon, D. S., Szakaly, R., Greiner, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cryoembedding+and+sectioning+of+cochleas+for+immunocytochemistry+and+in+situ+hybridization.">Cryoembedding and sectioning of cochleas for immunocytochemistry and in situ hybridization.</a> Brain Res Brain Res Protoc. 6 (3), 159-166 (2001).</li><li>Londos, C., Cooper, D. M., Wolff, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subclasses+of+external+adenosine+receptors.">Subclasses of external adenosine receptors.</a> Proc Natl Acad Sci. 77 (5), 2551-2554 (1980).</li><li>Lohse, M. J., Klotz, K. N., Lindenborn-Fotinos, J., Reddington, M., Schwabe, U., Olsson, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=8-Cyclopentyl-1,3-dipropylxanthine+(DPCPX)--a+selective+high+affinity+antagonist+radioligand+for+A1+adenosine+receptors.">8-Cyclopentyl-1,3-dipropylxanthine (DPCPX)--a selective high affinity antagonist radioligand for A1 adenosine receptors.</a> Naunyn Schmiedebergs Arch Pharmacol. 336 (2), 204-210 (1987).</li><li>Rybak, L. P., Whitworth, C., Scott, V., Weberg, A. D., Bhardwaj, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+as+a+potential+model+for+hearing+loss+in+biotinidase+deficiency.">Rat as a potential model for hearing loss in biotinidase deficiency.</a> Ann Otol Rhinol Laryngol. 100 (4), 294-300 (1991).</li><li>Mukherjea, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NOX3+NADPH+oxidase+couples+transient+receptor+potential+vanilloid+1+to+signal+transducer+and+activator+of+transcription+1-mediated+inflammation+and+hearing+loss.">NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.</a> Antioxid Redox Signal. 14 (6), 999-1010 (2011).</li><li>Kaur, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adenosine+A1+receptor+protects+against+cisplatin+ototoxicity+by+suppressing+the+NOX3/STAT1+inflammatory+pathway+in+the+cochlea.">Adenosine A1 receptor protects against cisplatin ototoxicity by suppressing the NOX3/STAT1 inflammatory pathway in the cochlea.</a> J Neurosci. 36 (14), 3962-3977 (2016).</li><li>Kaur, T., Mukherjea, D., Sheehan, K., Jajoo, S., Rybak, L. P., Ramkumar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Short+interfering+RNA+against+STAT1+attenuates+cisplatin-induced+ototoxicity+in+the+rat+by+suppressing+inflammation.">Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation.</a> Cell Death Dis. 2 (180), (2011).</li></ol>

La via di somministrazione trans-timpanico permette per consegna localizzata di farmaci e di altri agenti alla coclea che altrimenti potrebbe produrre effetti collaterali sistemici significativi se somministrato per via sistemica. Questo metodo di somministrazione del farmaco consente l'accesso rapido di farmaci al sito d'azione alle dosi significativamente più alto di quello che potrebbe essere raggiunto attraverso la via sistemica. Risultati qui presentati e pubblicati precedentemente mostravano che trans-timpanico ge...

Il sistema uditivo periferico è squisitamente sensibile a farmaci quali cisplatino e aminoglycoside antibiotici. Il cisplatino è un agente chemioterapeutico ampiamente usato per il trattamento di una varietà di tumori solidi, quali testa, testicolare e ovarico e cancri del collo. L'ototossicità sperimentato con l'uso di questo farmaco è dose-limitante e abbastanza comune, che colpisce il 75-100% dei pazienti trattati1. Altri farmaci, come carboplatino e oxaliplatino, sono emerse come alternative al cisplatino2,3,4,5, ma la loro utilità è limitata ad alcuni tipi di cancro.
I primi studi hanno dimostrato il ruolo critico di specie reattive dell'ossigeno (ROS) nel mediare l'ototossicità prodotta dal cisplatino e gli aminoglicosidi. Studi successivi hanno mostrato che l'isoforma NOX3 della NADPH ossidasi è la principale fonte di ROS nella coclea e viene attivato da cisplatino6,7. La generazione di compromessi ROS l'antiossidante tampone di cellule, con conseguente aumentata perossidazione lipidica delle membrane cellulari8. Inoltre, cisplatino aumenta la produzione di radicali idrossilici che generano altamente tossico aldeide 4-hydroxynonenal (4-HNE), un iniziatore di cellule morte9,10. Basato su questi risultati, parecchi antiossidanti sono stati esaminati per il trattamento dell'ototossicità del cisplatino. Questi includono N-acetil cisteina (NAC), tiosolfato di sodio (STS), amifostina e D-metionina. Tuttavia, delle principali preoccupazioni della terapia antiossidante è che questi antiossidanti potrebbero ridurre il cisplatino chemioterapeutico efficacia quando somministrato per via sistemica11 attraverso l'interazione di cisplatino con gruppi tiolici in molecole antiossidanti.
In considerazione di questi problemi con la terapia antiossidante, l'obiettivo di questo studio era di esaminare il percorso trans-timpanico di fornire antiossidanti e altri farmaci alla coclea per ridurre la perdita dell'udito. La via trans-timpanico di droga e breve interferire (si) RNA, descritto di seguito, appare particolarmente promettente.

<table border="0" cellpadding="0" cellspacing="0" style="width:1025px;" width="1025">
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		<tr height="19">
			<td height="19" style="height:19px;width:423px;">Ketathesia (100 mg/ml) 10 ml</td>
			<td style="width:192px;">Henry Schein</td>
			<td style="width:127px;">56344</td>
			<td style="width:284px;">Controlled substance&#160;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">AnaSed Injection/Xylazine (20 mg/ml) 20 ml</td>
			<td>Henry Schein</td>
			<td>33197</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">2.5 mm disposable ear specula</td>
			<td>Welch Allyn</td>
			<td>52432</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Surgical Scope</td>
			<td>Zeiss</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">29 G X 1/2 insulin syringe</td>
			<td>Fisher Scientific</td>
			<td>14-841-32&#160;</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">cis-Diammineplatinum(II) dichloride</td>
			<td>Sigma Aldrich</td>
			<td>P4394</td>
			<td>TOXIC - wear proper PPE</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Harvard 50-7103 Homeothermic Blanket Control Unit</td>
			<td>Harvard Apparatus</td>
			<td>Series 863</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Excel International 21 G X 3/4 butterfly needle</td>
			<td>Fisher</td>
			<td>14-840-34&#160;</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">BSP Single Speed Syringe Pump</td>
			<td>Brain Tree Sci, Inc</td>
			<td>BSP-99</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Pulse Sound Measurement System</td>
			<td>Bruel &#38; Kjaer</td>
			<td>Pulse 13 software</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">High-Frequency Module</td>
			<td>Bruel &#38; Kjaer</td>
			<td>3560C</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">1/8&#8243; Pressure-field Microphone &#8212;-Type 4138</td>
			<td>Bruel &#38; Kjaer</td>
			<td>bp2030</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">High Frequency Transducer</td>
			<td>Intelligent Hearing System</td>
			<td>M014600</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Opti-Amp Power Transmitter</td>
			<td>Intelligent Hearing System</td>
			<td>M013010P</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">SmartEP ABR System</td>
			<td>Intelligent Hearing System</td>
			<td>M011110</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Disposable Subdermal EEG Electrodes</td>
			<td>CareFusion</td>
			<td>019-409700</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">16% Formaldehyde, Methanol-free</td>
			<td>Fisher Scientific</td>
			<td>28908</td>
			<td>TOXIC - wear proper PPE&#160;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">7 mL Borosilicate Glass Scintillation Vial</td>
			<td>Fisher Scientific</td>
			<td>03-337-26</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">EDTA</td>
			<td>Fisher Scientific</td>
			<td>BP118-500</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Sucrose</td>
			<td>Fisher Scientific</td>
			<td>S5-500</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Tissue Plus OCT Compound</td>
			<td>Fisher Scientific</td>
			<td>4585</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">CryoMolds (15 mm x 15 mm x 5mm)</td>
			<td>Fisher Scientific</td>
			<td>22-363-553</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Microscope Slides (25mm x 75mm)</td>
			<td>MidSci</td>
			<td>1354W</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Coverslips (22 x 22 x 1)</td>
			<td>Fisher Scientific</td>
			<td>12-542-B</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Poly-L-Lysine Solution (0.01%)</td>
			<td>EMD Millipore</td>
			<td>A-005-C</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">HM525 NX Cryostat</td>
			<td>Thermo Fischer Scientific</td>
			<td>956640</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">MX35 Premier Disposable Low-Profile Microtome Blades</td>
			<td>Thermo Fischer Scientific</td>
			<td>3052835</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Wheaton&#8482;&#160;Glass 20-Slide Staining Dish with Removable Rack</td>
			<td>Fisher Scientific</td>
			<td>08-812</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Super Pap Pen Liquid Blocker</td>
			<td>Ted Pella, Inc.</td>
			<td>22309</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Normal Donkey Serum</td>
			<td>Jackson Immuno Research</td>
			<td>017-000-121</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">TritonX-100</td>
			<td>Acros</td>
			<td>21568</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">BSA</td>
			<td>Sigma Aldrich</td>
			<td>A7906</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Phospho-Stat1 (Ser727) antibody</td>
			<td>Cell Signaling</td>
			<td>9177</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">VR1 Antibody (C-15)</td>
			<td>Santa Cruz</td>
			<td>sc-12503</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">DyLight 488 Donkey anti Rabbit</td>
			<td>Jackson Immuno Research</td>
			<td>711-485-152</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">DyLight 488 Donkey anti Goat</td>
			<td>Jackson Immuno Research</td>
			<td>705-485-003</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Rhodamine (TRTIC) Donkey anti Rabbit</td>
			<td>Jackson Immuno Research</td>
			<td>711-025-152</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">ProLong&#174; Diamond Antifade Mountant w/ DAPI</td>
			<td>Thermo Fisher</td>
			<td>P36971</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">(&#8722;)-N6-(2-Phenylisopropyl)adenosine</td>
			<td>Sigma Aldrich</td>
			<td>P4532</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">8-Cyclopentyl-1,3-dipropylxanthine</td>
			<td>Sigma Aldrich</td>
			<td>C101</td>
			<td></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">siRNA pSTAT1</td>
			<td>Qiagen</td>
			<td>Custome Made</td>
			<td>Kaur et al. 201120</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">siRNA NOX3</td>
			<td>Qiagen</td>
			<td>Custome Made</td>
			<td>Kaur et al. 201120</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">Scrambled Negative Control siRNA</td>
			<td>Qiagen</td>
			<td>1022076</td>
			<td>Kaur et al. 201120</td>
		</tr>
	</tbody>
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trans-tympanic drug delivery for the treatment of ototoxicity

La somministrazione sistemica di agenti protettivi per trattare l'ototossicità indotta da farmaci è limitata dalla possibilità che questi agenti protettivi potrebbero interferire con l'efficacia chemioterapeutica delle droghe primarie. Questo è particolarmente vero per il cisplatino della droga, le cui azioni anticancro sono attenuati dagli antiossidanti che forniscono una protezione adeguata contro perdita dell'udito. Altri agenti attuali o potenziali otoprotective potrebbero rappresentare un problema simile, se somministrato per via sistemica. L'applicazione di vari biologicals o agenti protettivi direttamente alla coclea consentirebbe di alti livelli di questi agenti localmente con limitati effetti collaterali sistemici. In questo rapporto, dimostriamo un trans-timpanico metodo di consegna dei vari farmaci o reagenti biologici alla coclea, che dovrebbe migliorare la ricerca di scienza di base sulla coclea e forniscono un modo semplice di orientare l'utilizzazione di agenti otoprotective nelle cliniche. Questo rapporto Dettagli un metodo di consegna della droga trans-timpanico e fornisce esempi di come questa tecnica è stata utilizzata con successo in animali da esperimento per trattare l'ototossicità del cisplatino.

ABR risposte misurate in ratti a tre giorni dopo somministrazione di cisplatino hanno mostrato un'elevazione significativa in soglie. Elevazione di queste soglie è stata ridotta significativamente in ratti amministrati con trans-timpanico [R] - N - phenylisopropyladenosine (R-PIA), adenosina un1 recettore agonista15, prima del cisplatino. La specificità dell'azione del R-PIA presso l'adenosina un ricevitore1 è sta...

Watch this Scientific Journal Video about Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity at JoVE.com

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Presentiamo una tecnica per somministrazione localizzata di farmaci attraverso la via trans-timpanica nella coclea. Somministrazione di farmaci attraverso questa rotta non avrebbe interferito con l'efficacia anticancro dei farmaci chemioterapici come il cisplatino.

Veicolazione Trans-timpanico per il trattamento dell'ototossicità

The systemic administration of protective agents to treat drug-induced ototoxicity is limited by the possibility that these protective agents could ...

Research

JoVE Journal

Medicine

Thermal Ablation for the Treatment of Abdominal Tumors

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Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

Ricerca

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The pancreas is a bifunctional organ with both endocrine and exocrine components. A number of pathologies can afflict the pancreas, including diabetes, ...

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Migliorato il metodo per la creazione di un In Vitro barriera emato - encefalica modello basato sulle cellule endoteliali Porcine cervello

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

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Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain ...