Targeted Delivery of Agents Using ALZET^® Osmotic Pumps

ALZET pumps allow researchers to understand and optimize the key determinants of drug action. These determinants are the level of drug exposure and its duration, and the spatial distribution of drug relative to the target tissue. By manipulating these variables, drug effects can be optimized early in preclinical development, allowing clinical studies to be conducted at lower cost and with better results. Accumulated literature offers numerous examples of targeted delivery in which ALZET pumps expose a specific, limited region to a compound. Through a catheter introduced into the arterial blood supply of an organ, or affixed within or adjacent to the target tissue, the pump provides continuous and controlled input of a compound. A variety of organs and tissues have become target sites for drug delivery using this method.

Targeted infusion offers significant advantages over systemic administration. Daemen et al. (Trends Pharmacol Sci 1988;9:138) assert that "for the clinician, drug delivery should ideally be direct to its target tissue. Its distribution should be confined to the target site (thus avoiding any systemic drug effects), where it should reach high concentration." This ideal has two key facets:

• achieving sufficiently high concentrations at the target site
• minimizing systemic concentrations

 

To demonstrate a drug's efficacy, it must reach the target tissue at a concentration sufficient to elicit a therapeutic effect. There are many obstacles that can make it difficult to achieve sufficient concentration at the target site, such as drug metabolism, drug excretion, and permeability barriers. Infusing drug to the target tissue can circumvent these barriers, and can improve the drug's efficacy as compared with systemic administration.

Even if the concentration at the target site is sufficient, the desired effect may or may not be recognized. If the drug is administered such that significant systemic concentrations are also produced, simultaneous or cascading drug effects in multiple tissues may result. These systemic effects may alter the effect from the target tissue by diminishing, antagonizing, or simply obscuring it. Additionally, unwanted systemic effects may be toxic to the target tissue or even lethal, thus preventing the desired effect from ever developing.

References in which the following organs or tissues were infused via ALZET pumps are included in this list, with the exception of brain infusion. (References on brain infusion can be obtained at www.alzet.com or by contacting ALZET Technical Support at 1-800-692-2990 or by email at alzet@durect.com.)

Representative List of Areas Targeted Using ALZET Osmotic Pumps with a Catheter

Arterial Wall	Mammary Gland
Articular Cavity	Muscle
Bladder	Nerve
Bone	Ovary
Brain (Solid Tissue)	Pericadial Space
Brain (Ventricles)	Prostate
Ear	Skin
Eye	Spleen
Gallbladder	Stomach
Intestine	Testis+
Kidney*	Tumor
Liver*	Trachea
Lymph Node	Uterus
* Perfused via arterial blood supply. + Perfused directly and via arterial supply

The technical notes following each reference detail the substance(s) infused, route of administration, animal model studied, infusion vehicle, model of pump used, duration of infusion, and notable technical achievements or results obtained. For a more complete discussion of the capabilities of solid tissue microperfusion, consult the following reference:

R0051 Urquhart, J., Fara, J., and Willis, K.L. Rate§]controlled delivery systems in drug and hormone research. Ann. Rev. Pharmacol. Toxicol. 24, 199§]236, 1984.

Note: This listing does not contain abstracts in this category, nor references for every year. To obtain abstracts or additional references, contact ALZET Technical Services at (800) 692-2990 or by email at alzet@durect.com.

P8536 Joyce,M.M., Burghardt,J.R., Burghardt,R.C., Hooper,R.N., Jaeger,L.A., Spencer,T.E., Bazer,F.W., Johnson,G.A. Pig conceptuses increase uterine interferon-regulatory factor 1 (IRF1), but restrict expression to stroma through estrogen- induced IRF2 in luminal epithelium. Biology of Reproduction 2007; 77(-2-):292-302. >>> Conceptus secretory proteins, porcine; Albumin, porcine serum; dye, india ink; PBS; Intrauterine (uterine horn); Pig; 2ML1; 4 days; Controls received mp w/ PSA; tissue perfusion (uterus); peptides; multiple pumps per animal (2); animal info (female, pseudopregnant); india ink used to confirm agent distribution in uterus; tissue perfusion (uterine horn).

P8496 Sun,Z.Y., Rafferty,K.L., Egbert,M.A., Herring,S.W. Masticatory mechanics of a mandibular distraction osteogenesis site: Interfragmentary micromovement. Bone 2007; 41(-2-):188-196. >>> Amikacin; Sub-masseteric tunnel; Pig; 2ML2; 14 days; Bone healing; x-ray image showing pump adjacent to mandible bone (p. 189); pump positioned near mandible bone to deliver antibiotics for infection control; tissue perfusion (sub-masseteric tunnel).

P8429 Frederiksen,B.L., Caye-Thomasen,P., Lund,S.P., Wagner,N., Asal,K., Olsen,N.V., Thomsen,J. Does erythropoietin augment noise induced hearing loss?. Hearing Research 2007; 223(-1-2-):129-137. >>> Erythropoietin; Ear (round window); Guinea-Pig; 1007D; 1 week; Controls received mp w/ saline; replacement therapy (noise-induced hearing impairment); comparison of acute admin. vs. mp; peptides; animal info (male, Dunkin-Hartley); mp primed 6 hours in 37 Celsius saline; correct catheter placement confirmed; tissue perfusion (round window).

P8402 Maruyama,J., Yamagata,T., Ulfendahl,M., Bredberg,G., Altschuler,R.A., Miller,J.M. Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs. NEUROBIOLOGY OF DISEASE 2007; 25(-2-):309-318. >>> Trolox; neomycin; ascorbic acid; Perilymph, artificial; sodium bicarbonate; Ear (cochlea); Guinea-Pig; 2002; 26 days; Controls received mp w/ vehicle; pumps replaced after 14 days; post op. care (doxycycline); animal info (male, pigmented, 250-400g., neomycin deafening); cannula primed with 10% neomycin solution followed by a small air bubble spacer to allow neomycin infusion for first 2 days; trolox, a vitamin F analogue, and ascorbic acid delivered together in 1 mp; tissue perfusion (cochlea).

P8368 Wang,J., Ruel,J., Ladrech,S., Bonny,C., Van de Water,T.R., Puel,J.L. Inhibition of the c-Jun N-terminal kinase-mediated mitochondrial cell death pathway restores auditory function in sound-exposed animals. MOLECULAR PHARMACOLOGY 2007; 71(-3-):654-666. >>> Jun, c-, N-Terminal kinase Inhibitor-1, D-; peptide, D-TAT; Jun, c-, N-Terminal kinase Inhibitor-1-mutant; Perilymph, artificial; PBS; Ear (round window membrane); Guinea-Pig; 2001; 7 days; Controls received mp w/ vehicle, or inactive JNKI-1-mutant or TAT-empt peptide or contralateral untreated ear; dose-response (fig 6); comparison of acute infusion vs. hyaluronic acid gel vs.; enzyme inhibitor (c-Jun N-terminal kinase); peptides; animal info (pigmented, 250-300g.; sound trauma); D-JNKI-1 peptide contains a 10-amino acid HIV-TAT transporter sequece to facilitate its entry into cells; tissue perfusion (round window membrane).

P8366 Dorrell,M.I., Aguilar,E., Scheppke,L., Barnett,F.H., Friedlander,M. Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-3-):967-972. >>> Vascular endothelial growth factor, aptamer; EMD472523; T2-TrpRS; PBS; CSF/CNS (intratumoral); Rat; 2001D; 2ML2; 2ML4; 3,6 days; 24 hours; Controls received mp w/ vehicle; cancer (gliosarcoma); animal info (male, Fischer, 344); EMD472523 is an integrin antagonist, VEGF aptamer is chemically identical to Macugen; T2 is a proteolytic fragment of tryptophan tRNA synthetase; all agents have angiostatic activity; tissue perfusion (tumor).

P8252 Lee,Y., Gaskins,D., Anand,A., Shekhar,A. Glia mechanisms in mood regulation: a novel model of mood disorders. Psychopharmacology 2007; 191(-1-):55-65. >>> PDC; CSF, artificial; CSF/CNS (basolateral amygadala); Rat; 1002; 4, 7, 8 days; Controls received mp w/ vehicle; dose-response (fig. 1); animal info (male, Wistar, 275-300g.); L-trans-pyrrolidine-2, 4-dicarboxylic acid, a glial&neuronal glutamate transport inhibitor; cannulae location verified with cresyl violet staining; mood disorder model; tissue perfusion (basolateral amygadala).

P8149 Kovacs,P., Morales,J.C., Karkanias,G.B. The effect of diabetes and centrally administered insulin on anterior hypothalamic estrogen receptor alpha immunoreactivity. ACTA DIABETOLOGICA 2007; 44(-1-):38-44. >>> Insulin, human; Saline; CSF/CNS (third ventricle); Rat; 2002; 14 days; Controls received mp w/ vehicle; replacement therapy (STZ-induced Diabetes, ovariectomy); peptides; animal info (female, Sprague-Dawley, 175-200g.); tissue perfusion (ventricle).

P8132 Haruta,M., Hata,Y. Experience-driven axon retraction without binocular imbalance in developing visual cortex. CURRENT BIOLOGY 2007; 17(-1-):37-42. >>> Muscimol; Saline; CSF/CNS (visual cortex, area 17); Cat (kitten); 2002; 2 weeks; Brain tissue distribution; post op. care (enrofloxacin); animal info (4 wks old, vision deprivation by eyelid suture); tissue perfusion (visual cortex).

P7978 Engelhardt,M., Di Cristo,G., Berardi,N., Maffei,L., Wahle,P. Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period. European Journal of Neuroscience 2007; 25(-2-):529-540. >>> Nerve growth factor, mouse; NT-4, human recomb.; brain-derived neurotrophic factor, recomb. human; CSF/CNS (visual cortex); Rat; 1007D; 8 days; Post op. care (antibiotics and local anesthetics); animal info (Long-Evans); dental cement used; 30 G cannula used; tissue perfusion (visual cortex).

P7968 Wang,Y.L., Wang,D.Z., Nie,X., Lei,D.L., Liu,Y.P., Zhang,Y.J., Suwa,F., Tamada,Y., Fang,Y.R., Jin,Y. The role of bone morphogenetic protein-2 in vivo in regeneration of peripheral nerves. BRITISH JOURNAL OF ORAL&MAXILLOFACIAL SURGERY 2007; 45(-3-):197-202. >>> Bone morphogenetic protein-2; Saline; CSF/CNS (facial nerve); Rabbit; 2ML4; 10 days; Controls received mp w/ vehicle; animal info (New Zealand, 1.6-2.3 kg); total daily infused volume incorrect; tissue perfusion (facial nerve).

P8388 Sendowski,I., Abaamrane,L., Raffin,F., Cros,A., Clarencon,D. Therapeutic efficacy of intra-cochlear administration of methylprednisolone after acoustic trauma caused by gunshot noise in guinea pigs. Hearing Research 2006; 221(-1-2-):119-127. >>> Methylprednisolone; perilymph, artificial; Perilymph, artificial; Ear (scala tympani); Guinea-Pig; 2001; 14 days; Controls received mp w/ vehicle, or non-implanted ear; dose-response (fig. 1); pumps replaced after 7 days of artifical perilymph; animal info (pigmented, 400-500g., acoustic trauma, gunshot); tissue perfusion (scala tympani).

P8208 Martens,T., Schmidt,N.O., Eckerich,C., Fillbrandt,R., Merchant,M., Schwall,R., Westphal,M., Lamszus,K. A novel one-armed anti-c-met antibody inhibits glioblastoma growth in vivo. Clinical Cancer Research 2006; 12(-20-):6144-6152. >>> Antibody, anti-c-Met, OA5D5; Histidine; CSF/CNS (intratumoral); Mice (nude); 2004; 12, 21, 28 days; Controls received mp w/ vehicle; cancer (glioblastoma); ALZET brain infusion kit 2 used; animal info (male, NMRI-nu/nu, 6-8 wks old); "Because the OA-5D5 antibody is a relatively large but stable molecule, convection-enhanced drug delivery (by mp) was ideally suited to deliver it in our orthotopic model." (p.6151); tissue perfusion (tumor).

P8195 Mccoy,M.K., Martinez,T.N., Ruhn,K.A., Szymkowski,D.E., Smith,C.G., Botterman,B.R., Tansey,K.E., Tansey,M.G. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease. Journal of Neuroscience 2006; 26(-37-):9365-9375. >>> Endotoxin, LPS; XENP345; Saline, sterile; CSF/CNS (striatum); Rat; 2002; 2 weeks; Controls received mp w/ vehicle; animal info (female, Sprague-Dawley, 200-225 grams, male, CDF, 200-240 grams); neurodegenerative (Parkinson's disease); dominant-negative TNF inhibitor; tissue perfusion (striatum).

P8176 Radeloff,A., Smolders,J.W.T. Brain-derived neurotrophic factor treatment does not improve functional recovery after hair cell regeneration in the pigeon. Acta Oto-laryngologica 2006; 126(-5-):452-459. >>> Brain-derived neurotrophic factor, recomb. human; PBS; albumin, chicken; Hank's solution; Ear (scala tympani); Bird (pigeon); 2002; 8 weeks; Controls received mp w/ vehicle or no treatment to contralateral ear; long-term study; pumps replaced every 14 days; ALZET brain infusion kit used; peptides; animal info (Columba livia, 6 months old, 320-580 grams); deafening of both ears; tissue perfusion (scala tympani).

P8152 Abizaid,A., Liu,Z.W., Andrews,Z.B., Shanabrough,M., Borok,E., Elsworth,J.D., Roth,R.H., Sleeman,M.W., Picciotto,M.R., Tschoep,M.H., Gao,X.B., Horvath,T.L. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal of Clinical Investigation 2006; 116(-12-):3229-3239. >>> BIM28163; Saline; CSF/CNS (ventral tegmental area); Mice; 1002; 7 days; Controls received mp w/ vehicle; animal info (C57BL/6); cannula placement confirmed by histological exam w/ cresyl violet; tissue perfusion (ventral tegmental area).

P8145 Grommes,C., Landreth,G.E., Sastre,M., Beck,M., Feinstein,D.L., Jacobs,A.H., Schlegel,U., Heneka,M.T. Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. MOLECULAR PHARMACOLOGY 2006; 70(-5-):1524-1533. >>> Pioglitazone; DMSO; PBS; CSF/CNS (intratumoral); Rat; 2ML4; 3, 6, 9, 14, 21 days; Controls received mp w/ vehicle; comparison of oral admin. vs. mp; no stress (see p.1532); stability verified by in vitro incubation at 37 celsius for 21 days; cancer (glioma); ALZET brain infusion kit used; animal info (Sprague-Dawley, 200-250g.); 0.1% DMSO; Antineoplastic; tissue perfusion (tumor).

P8141 Huang,Q.L., Timofeeva,E., Richard,D. Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress. Journal of Endocrinology 2006; 191(-1-):179-188. >>> Leptin, recomb. murine; CSF/CNS (third ventricle); Rat; 2001; 5 days; Controls received mp w/ PBS; peptides; animal info (male, Wistar, 270-290g.); tissue perfusion (ventricle).

P8129 Heinrich,C., Nitta,N., Flubacher,A., Muller,M., Fahrner,A., Kirsch,M., Freiman,T., Suzuki,F., Depaulis,A., Frotscher,M., Haas,C.A. Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus. Journal of Neuroscience 2006; 26(-17-):4701-4713. >>> Antibody, monoclonal, CR-50; immunoglobulin G, mouse; DMEM; CSF/CNS (hippocampus); Mice; 1007D; 7 days; Controls received mp w/ mouse IgG; ALZET brain infusion kit use; brain tissue distribution; animal info (male, C57BL/6, 8-10 wks old); Reelin-neutralizing antibody; DMEM is Dulbecco's modified eagle medium; tissue perfusion (hippocampus).

P8081 de Yebra,L., Malpesa,Y., Ursu,G., Pugliese,M., Lievens,J.C., Goff,L.K.L., Mahy,N. Dissociation between hippocampal neuronal loss, astroglial and microglial reactivity after pharmacologically induced reverse glutamate transport. NEUROCHEMISTRY INTERNATIONAL 2006; 49(-7-):691-697. >>> PDC; CSF/CNS (hippocampus); Rat; 1007D; 14 days; Controls received mp w/ PBS; dose-response (fig.2); animal info (male, Wistar, 220-240g.); L-trans-pyrrolidine-2, 4-dicarboxylate; tissue perfusion (hippocampus).

P8078 Hoe,H.S., Pociuausek,A., Dai,H.N., Chakraborty,G., Harris,D.C., Rebeck,G.W. Effects of apoE on neuronal signaling and APP processing in rodent brain. Brain Research 2006; 1112(-;-):70-79. >>> Apolipoprotein E; apolipoprotein E3, recomb human; apolipoprotein E4, recomb human; Saline; CSF/CNS (dorsal hippocampus); Rat; 2001; 1 week; Controls received mp w/ vehicle; comparison of icv injections vs. mp; peptides; animal info (Sprague-Dawley, 230-250g.); correct infusion sites confirmed post mortem; tissue perfusion (hippocampus).

P8071 Morrey,J.D., Siddharthan,V., Olsen,A.L., Roper,G.Y., Wang,H., Baldwin,T.J., Koenig,S., Johnson,S., Nordstrom,J.L., Diamond,M.S. Humanized monoclonal antibody against West Nile virus envelope protein administered after neuronal infection protects against lethal encephalitis in hamsters. Journal of Infectious Diseases 2006; 194(-9-):1300-1308. >>> Antibody, monoclonal hE16; CSF, artificial; CSF/CNS (parenchyma); Hamster; 2001D; 24 hours; Controls received mp w/ vehicle, or saline; comparison of ip injections vs. mp; brain tissue distribution; animal info (female, Syrian golden, 7 wks. old, 116g., infected w/ West Nile Virus); hE16 is specific for WNV envelope protein domain III "this delivery system facilitated broad delivery of Ab into the brain, with highest levels near the site of cannulation." (p.1305); tissue perfusion (parenchyma).

P8062 Gelling,R.W., Morton,G.J., Morrison,C.D., Niswender,K.D., Myers,MG Jr, Rhodes,C.J., Schwartz,M.W. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metabolism 2006; 3(-1-):67-73. >>> LY294002; CSF/CNS (third ventricle); Rat; 2002; 9 days; Controls received mp w/ vehicle; comparison of icv injections vs. mp; enzyme inhibitor (phosphatidylinositol 3-kinase); animal info (male, Sprague-Dawley, 250-350g); cannula placement confirmed; tissue perfusion (ventricle).

P8053 Bruno,M.A., Cuello,A.C. Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006; 103(-17-):6735-6740. >>> Neuroserpin; GM6001; CSF, artificial, PBS; CSF/CNS (parietal cortex); Rat; 2001; 72 hours; Controls received mp w/ vehicle into contralateral side; enzyme inhibitor (tpa, metalloproteinase); multiple pumps per animal (2); animal info (Fischer 344, 6 month old); Lynch coil with air-oil spacer at mp end of tubing; bilateral infusion cannulae; tissue perfusion (parietal cortex).

P8036 Yasuhara,T., Matsukawa,N., Hara,K., Yu,G.L., Xu,L., Maki,M., Kim,S.U., Borlongan,C.V. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease. Journal of Neuroscience 2006; 26(-48-):12497-12511. >>> Stem cell factor, human recomb.; PBS; CSF/CNS (striatum); Rat; 2004; 4 weeks; Animal info (Sprague-Dawley, 200-250 grams); neurodegenerative (Parkinson's Disease); behavioral study; tissue perfusion (striatum).

P8017 Kawai,T., Takagi,N., Mochizuki,N., Besshoh,S., Sakanishi,K., Nakahara,M., Takeo,S. Inhibitor of vascular endothelial growth factor receptor tyrosine kinase attenuates cellular proliferation and differentiation to mature neurons in the hippocampal dentate gyrus after transient forebrain ischemia in the adult rat. Neuroscience 2006; 141(-3-):1209-1216. >>> Vascular endothelial growth factor receptor tyrosine kinase inhibitor; DMSO; CSF/CNS (dentate gyrus); Rat; 2001; 7 days; Controls received mp w/ vehicle; dose-response (fig. 4); enzyme inhibitor (VEGF receptor tyrosine kinase); ischemia (transient forebrain); animal info (male, Wistar, 8 weeks old, carotid artery occlusion); 0.5% DMSO; agent also known as 4-[(4'-chloro-2'-fluoro) phenylamino]-6,7-dimethoxyquinazoline; tissue perfusion (dentate gyrus).

P8009 Niimura,M., Takagi,N., Takagi,K., Mizutani,R., Ishihara,N., Matsumoto,K., Funakoshi,H., Nakamura,T., Takeo,S. Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia. Journal of Cerebral Blood Flow and Metabolism 2006; 26(-11-):1354-1365. >>> Hepatocyte growth factor; Saline; CSF/CNS (right hippocampal region); Rat; 1003D; 3 days; Animal info (male, Wistar, 200-250 grams); ischemia (cerebral); tissue perfusion (hippocampal region).

P8008 Niimura,M., Takagi,N., Takagi,K., Mizutani,R., Tanonaka,K., Funakoshi,H., Matsumoto,K., Nakamura,T., Takeo,S. The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. Neuroscience Letters 2006; 407(-2-):136-140. >>> Hepatocyte growth factor; CSF/CNS (right hippocampal region); Rat; 1003D; 3 days; Animal info (male, Wistar, 200-250 grams); ischemia (cerebral); tissue perfusion (hippocampal region).

P7994 Vavrek,R., Girgis,J., Tetzlaff,W., Hebert,G.W., Fouad,K. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain 2006; 129(--):1534-1545. >>> Brain-derived neurotrophic factor; NT-3; Albumin, rat serum; CSF/CNS (left motor cortex, intrathecal, cisterna magna); Rat; 2002; 14 days; Controls received mp w/ vehicle; ALZET brain infusion kit used; SCI (spinal cord injury); dental cement used to secure cannula; NT-3 delivered intrathecally; tissue perfusion (left motor cortex).

P7988 Wang,X.Y., Engisch,K.L., Teichert,R.W., Olivera,B.M., Pinter,M.J., Rich,M.M. Prolongation of evoked and spontaneous synaptic currents at the neuromuscular junction after activity blockade is caused by the upregulation of fetal acetylcholine receptors. Journal of Neuroscience 2006; 26(-35-):8983-8987. >>> Tetrodotoxin; Saline; CSF/CNS (sciatic nerve); Mice; 1002; ; Controls received mp w/ vehicle; animal info (2-4 months old); silastic nerve cuff; tissue perfusion (sciatic nerve).

P7971 Sosenko,I.R.S., Kallapur,S.G., Nitsos,I., Moss,T.J.M., Newnham,J.P., Ikegami,M., Jobe,A.H. IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs. PEDIATRIC RESEARCH 2006; 60(-3-):294-298. >>> Interleukin-1, alpha, recomb. ovine; Intratracheal; Sheep (fetus); 2001D; ; Controls received mp w/ saline; animal info (merino, ewes + fetuses); silicone tubing used to collect lung fluid; vinyl tubing for intratracheal infusion; tissue perfusion (trachea).

P7938 Bartlett,C.S., Rapuano,B.E., Lorich,D.G., Wu,T., Anderson,R.C., Tomin,E., Hsu,J.F., Lane,J.M., Helfet,D.L. Early changes in prostaglandins precede bone formation in a rabbit model of heterotopic ossification. Bone 2006; 38(-3-):322-332. >>> AH 6809; cyclic AMP, Rp-; IM (vastus intermedius); Rabbit; 2ML2; 14 days; Functionality of mp verified by residual volume; no stress (see pg. 326); animal info (New Zealand); plain and high resolution (Faxitron) radiographs; fig 7 and 9; tissue perfusion (vastus intermedius); agent is a PGE2/PGD receptor antagonist.

P7937 Bartoli,M.A., Parodi,F.E., Chu,J., Pagano,M.B., Mao,D.L., Baxter,B.T., Buckley,C., Ennis,T.L., Thompson,R.W. Localized administration of doxycycline suppresses aortic dilatation in an experimental mouse model of abdominal aortic aneurysm. Annals of Vascular Surgery 2006; 20(-2-):228-236. >>> Doxycycline hydrochloride; Saline; SC; IP; aorta; Mice; 1002; 14 days; Controls received mp w/ vehicle; tissue perfusion (aorta); dose-response (table 1); comparison of oral vs. mp; half-life (p. 234), 26.5 hours; cardiovascular; animal info (C57BL/6J, male, 8-10 weeks old, 20-35 grams); catheter secured to a polyvinyl alcohol sponge positioned over the anterior surface of the aorta and secured to retroperitoneal tissues; (quote p. 233).

P7905 Shir,A., Ogris,M., Wagner,E., Levitzki,A. EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLOS MEDICINE 2006; 3(-1-):125-135. >>> RNA, double stranded; polyinosine-cytosine (poly IC) dsRNA; Non-viral vector; SC; Mice; 2001D; 2 days; Per communication with author on 8/11/07, "We did not have any particular problems with the anesthesia exposure. For the pump replacement procedure Ketamine/Xylazine 2% (0.85ml/0.15ml), 40-50 ul IP per mouse (25 gram) was used. Replacing of the pump was not problematic either. The skin was closed with a surgical clips which are less traumatic to the mice and are easily applied and removed." 2001D pump replaced every day for two days total duration; synthetic dsRNA was attached to a non-viral vector (PEI-PEG-EGF beta PEI-Mel complexes) with specificity to the epidermal growth factor receptor (EGFR); controls received vector only (no poly IC); tissue perfusion (intratumoral); cancer (glioblastoma, breast, adenocarcinoma).

P7849 Sanada,H., Yatabe,J., Midorikawa,S., Katoh,T., Hashimoto,S., Watanabe,T., Xu,J., Luo,Y.J., Wang,X.Y., Zeng,C.Y., Armando,I., Felder,R.A., Jose,P.A. Amelioration of genetic hypertension by suppression of renal G protein-coupled receptor kinase type 4 expression. Hypertension 2006; 47(-6-):1131-1139. >>> Oligodeoxynucleotide, phosphorothioate antisense; oligodeoxy nucleotide, missense; Ringer's solution, lactated; Kidney; Rat; 2001; 2004; 5 weeks; Controls received mp w/ vehicle, or missense oligos; tissue perfusion (kidney); pumps replaced after 1 week of vehicle; no stress (see pg. 1135); antisense (GRK4); cardiovascular; animal info (male, Wistar-Kyoto, SHR, 4 wk. old).

P8287 Manabe,T., Okino,H., Maeyama,R., Mizumoto,K., Tanaka,M., Matsuda,T. New infusion device for trans-tissue, sustained local delivery of anticancer agent to surgically resected tissue: Potential use for suppression of local recurrence of pancreatic cancer. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS 2005; 73B(-1-):203-207. >>> Gemcitabine; SC; Mice (nude); 1007D; 7 days; Tissue perfusion (intratumoral); comparison of IP injections; cancer (pancreatic); animal info (five week old); pump used as part of a novel infusion device; pictures of device p. 205; PE tubing used to connect pump to perfusion device; continuous infusion resulted in macroscopically undetectable tumors after day 6.

P8059 Hara,H., Takeno,K., Shimogori,H., Yamashita,H. CGRP expression in the vestibular periphery after transient blockage of bilateral vestibular input. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2005; 67(-5-):259-265. >>> Tetrodotoxin; Ear (cochlea perilymphatic space); Guinea-pig; 2002; 7 days; Controls received mp w/ sterile saline; post op. care (piperacillin sodium); animal info (male, Hartley, 600g.); tissue perfusion (cochlea).

P7975 Pyrko,P., Wang,W., Markland,F.S., Swenson,S.D., Schmitmeier,S., Schonthal,A.H., Chen,T.C. The role of contortrostatin, a snake venom disintegrin, in the inhibition of tumor progression and prolongation of survival in a rodent glioma model. Journal of Neurosurgery 2005; 103(-3-):526-. >>> Contortrostatin; CSF/CNS (intratumorally); Mice; 2 weeks; Controls received mp w/ PBS; plasma levels taken; cancer (glioma); brain tissue distribution; snake venom disintegrin; "agent was well tolerated by animals and lacks obvious neurotoxic side effects. All the contortrostatin treated mice survived the entire treatment period and continued to do well for seven more days after the termination." p. 533; tygon tubing used; tissue perfusion (tumor).

P7765 Richardson,R.T., O'Leary,S., Wise,A., Hardman,J., Clark,G. A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support. Hearing Research 2005; 204(-1-2-):37-47. >>> NT-3, recomb. human; brain-derived neurotrophic factor; Ringer's solution; Ear (scalatympani); Guinea-pig; 2004; 28 days; Comparison of bolus infusion vs. mp; peptides; animal info (adult, pigmented Dunkin-Hartley, 455g.); tissue perfusion (scala tympani).

P7629 Li,Y., Wo,J.M., Su,R.F.R., Ray,M.B., Jones,W., Martin,R.C.G. Esophageal injury with external esophageal perfusion. Journal of Surgical Research 2005; 129(-1-):107-113. >>> Bile; Saline; Intra-esophageal; Rat; 2ML1; 2ML2; 2ML4; 1,2,4 weeks; Controls received mp w/ vehicle; no stress (see pg. 109 and 111); good methods (p. 108); animal info (8 weeks old, Sprague-Dawley); pump/catheter schematic (p. 108); pump used in a novel, external esophageal perfusion model to induce esophageal injury; PE-50 used to cannulate the esophageal wall and connect pumps; surgical technique described in detail (p. 108); 0.5% bovine bile, pH 7.4; tissue perfusion; pump implanted on back of neck and connected to the tubing.

P7529 Tanaka,K., Takemoto,T., Sugahara,K., Okuda,T., Mikuriya,T., Takeno,K., Hashimoto,M., Shimogori,H., Yamashita,H. Post-exposure administration of edaravone attenuates noise-induced hearing loss. European Journal of Pharmacology 2005; 522(-1-3-):116-121. >>> Edaravone; saline; Water; NaOH; Ear (cochlea); Guinea-pig; 2002; 12 hours; Controls received no treatment to left ear; pumps replaced, mp w/ saline used then replaced with mp with agent; stability verified for 24 hours; post op. care (antibiotic ointment); animal info (male, Hartley, 300-450 g); tissue perfusion (cochlea).

P7331 Wise,A.K., Richardson,R., Hardman,J., Clark,G., O'Leary,S. Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3. Journal of Comparative Neurology 2005; 487(-2-):147-165. >>> Brain-derived neurotrophic factor, recomb. human; NT-3; Ear (scala tympani); Guinea-Pig; 2004; 28 days; Controls received mp w/ Ringer's solution; cannula patency ascertained by visual inspection; tissue perfusion (scala tympani).

P7306 Shepherd,R.K., Coco,A., Epp,S.B., Crook,J.M. Chronic depolarization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss. Journal of Comparative Neurology 2005; 486(-2-):145-158. >>> Brain-derived neurotrophic factor, recomb. human; perilymph, artificial; Ringer's solution; albumin, recomb. guinea-pig; Ear (scala tympani); Guinea-Pig; 2004; 28 days; Controls received mp w/ artificial perilymph or untreated contralateral cochlea; functionality of mp verified by residual fluid, cannula connection and patency; no stress (see pg. 155); good methods; peptides; post op. care (carprofen, Baytril); mp primed 36-48 hours in 37 degrees celsius Ringer's solution; Electrode array also inserted into scala tympani; "We observed no evidence of mechanical trauma to cochlea following long-term implantation and AP or BDNF delivery." (p. 155); tissue perfusion (scala tympani).

P7197 MacKay,J.A., Deen,D.F., Szoka,FC Jr  Brain Research 2005; 1035(-2-):139-153. >>> Liposomes; FITC-dextran-lysine; Saline; tris buffer; CSF/CNS (caudate putamen); CSF/CNS (intratumoral); Rat; 2001D; 24 hours; Tissue perfusion (intratumoral); comparison of acute CSF/CNS injection vs. mp; half-life (p. 151) 9.9 hours; cancer (glioblastoma); ALZET brian infusion kit 2 used; brain tissue distribution; post op. care (buprenophine).

P7209 Wimmer,C., Mees,K., Stumpf,T., Welsch,U., Reichel,O., Suckfuell,M. Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity. OTOLOGY&NEUROTOLOGY 2004; 25(-1-):33-40. >>> Methionine, D-; filoblast growth factor 2; thiosulfate, sodium petahydrate; brain-derived neurotrophic factor; Water; PBS; Ear (round window membrane); Guinea-Pig; 2001; 6 days; Controls received mp w/ saline; mp primed > 12 hours in saline; tissue perfusion (round window membrane).

P7105 Roberson,D.W., Alosi,J.A., Cotanche,D.A. Direct transdifferentiation gives rise to the earliest new hair cells in regenerating avian auditory epithelium. Journal of Neuroscience Research 2004; 78(-4-):461-471. >>> Uridine, bromodeoxy-; Ear (cochlea); Bird (chicken); 2002; 3-11 days; Controls received untreated contralateral ear; functionality of mp verified by (epithelial immunohistochemistry); stability verified by epithelial immunohistochemistry; tissue perfusion (cochlea).

P7104 Minami,S.B., Yamashita,D., Schacht,J., Miller,J.M. Calcineurin activation contributes to noise-induced hearing loss. Journal of Neuroscience Research 2004; 78(-3-):383-392. >>> FK-506; cyclosporin A; Perilymph, artificial; Ear (cochlea); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle, or contralateral untreated cochlea; dose-response (fig. 3); stress/adverse reaction: (see pg. 385) 4 of 43 animals developed middle ear infections; 4 of 43 animals had post surgical hearing loss; calcineurin inhibitors; "Systematic application may therefore have unwanted side effects that may be avoided by intracochlear perfusion by osmotic pump. The use of an osmotic pumps also allows relatively precise control over the timing and concertration of drugs applied to the tissues of the inner ear." (pg. 389); tissue perfusion (cochlea).

P7101 Le Prell,C.G., Yagi,M., Kawamoto,K., Beyer,L.A., Atkin,G., Raphael,Y., Dolan,D.F., Bledsoe,SC Jr, Moody,D.B. Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions. Journal of the Acoustical Society of America 2004; 116(-2-):1044-1056. >>> AMPA; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2002; 2004; 14-56 days; Controls received mp w/ vehicle; dose-response (fig. 2); long-term study; pumps replaced at 14 or 28 day intervals; stress/adverse reaction: (see pg. 1045) middle ear infections; tissue perfusion (scala tympani).

P7069 Jing,W., Ladrech,S., Pujol,R., Brabet,P., Van de Water,T.R., Puel,J.L. Caspase inhibitors, but not c-Jun NH2-terminal kinase inhibitor treatment, prevent cisplatin-induced hearing loss. Cancer Research 2004; 64(-24-):9217-9224. >>> z-DEVD-fmk; z-IETD-fmk; z-LEHD-fmk; z-FA-fmk; JNKI-1, D-; Perilymph, artificial; Ear (cochlea); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (caspases (-3,-8,-9), cathepsinB, JNK); peptides; tissue perfusion (cochlea).

P6930 Gillespie,L.N., Clark,G.M., Marzella,P.L. Delayed neurotrophin treatment supports auditory neuron survival in deaf guinea pigs. NeuroReport 2004; 15(-7-):1121-1125. >>> Brain-derived neurotrophic factor; nerve growth factor; NT-3; NT-4/5; Ear (scala tympani, cochlea); Guinea-pig; 2004; 28 days; Tissue perfusion.

P6921 Love,D.A., Lietman,S.A. The effect of osteogenic protein-1 dosing regimen on ectopic bone formation. Clinical Orthopaedics and Related Research 2004; (-423-):264-267. >>> Osteogenic protein-1; Lactic acid; Bone (matrix); Rat; 1002; 14 days; comparison of bolus injections vs. mp; stability verified by in vitro incubation study; silastic tubing used to target the SC implanted bone matrix; tissue perfusion (bone matrix).

P6918 Li,M., Ding,D.L., Zheng,X.Y., Salvi,R. Vestibular destruction by slow infusion of gentamicin into semicircular canals. Acta Oto-laryngologica 2004; 124(--):35-41. >>> Gentamicin; Hank's solution; Ear (semicircular canals); Chinchilla; 1007D; 7 days; Controls received mp w/ vehicle; Meniere's disease; microcatheter used; 27 gauge tubing used for cannulation; tissue perfusion (semicircular canals).

P6793 Stocks,R.M.S., Gould,H.J., Bush,A.J., Dudney,BW Jr, Pousson,M., Thompson,J.W. Ototoxic protection of sodium thiosulfate: Daily vs constant infusion. OTOLARYNGOLOGY-HEAD AND NECK SURGERY 2004; 131(-1-):115-119. >>> Thiosulfate, sodium; Ear (middle ear space); Guinea-pig; 2002; 18 days; Controls received no treatment to right ear; comparison of daily middle ear space injections vs. mp; pumps replaced after 7 days; multiple pumps per animal (2); "Continuous infusion of STS is the preferred method of administration." (p. 118) "STS continuously infused into the middle ear system provides a greater protective function than daily injection." (p. 119); tissue perfusion (middle ear space).

P6764 Frewert,S., Stockhammer,F., Warschewske,G., Zenclussen,A.C., Rupprecht,S., Volk,H.D., Woiciechowsky,C. Intratumoral infusion of interleukin-1 beta and interferon-gamma; induces tumor invasion with macrophages and lymphocytes in a rat glioma model. Neuroscience Letters 2004; 364(-3-):145-148. >>> Interleukin-1, beta recomb. rat; Interferon-gamma, recomb. rat; Saline, physiological; albumin, human serum; CSF/CNS (intratumoral); Rat; 1003D; 48 hours; Controls received mp w/ vehicle; tissue perfusion (tumor); cancer (glioma).

P6720 Gondi,C.S., Lakka,S.S., Dinh,D.H., Olivero,W.C., Gujrati,M., Rao,J.S., Rao,J.S. RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas. ONCOGENE 2004; 23(--):8486-8496. >>> RNA, small interfering; EV/SV vector; PBS; CSF/CNS (intratumoral); Mice (nude); ; Controls received mp w/ vehicle; tissue perfusion (tumor); cancer (glioma); gene therapy; antiangiogenesis; siRNA (cathepsin B); pump model not stated (0.25 ul/hr); "...local intracranial delivery of pcu using mini-osmotic pumps effectively inhibited human malignant glioma growth.".

P6629 Davies,J.E, Tang,X, Dennis,J.W., Archibald,S.J., Davies,S.J.A  European Journal of Neuroscience 2004; 19(--):1226-1242. >>> Decorin, recomb. human; PBS; CSF/CNS (spinal cord, intrathecal); Rat; 2001; 8 days; Controls received mp w/ vehicle; tissue perfusion (spinal lesion); enzyme inhibitor (tyrosine kinase); decorin is known to inhibit TGF beta and is an antagonist to EGF receptor tyrosine kinase.

P6543 Svetlecic,J., Molteni,A., Herndon,B. Bronchiolitis obliterans induced by intratracheal papaverine: A novel animal model. Lung 2004; 182(-2-):119-134. >>> Papaverine; Saline; Intratracheal; Rat; 2004; 28 days; Controls received mp w/ vehicle; no stress (see pg. 123); good methods p. 121; "All the rats survived for the length of the experiments. The intratracheal pump was well tolerated and the procedure produced no overt complications." p. 123; papaverine is an alkaloid in sauropus plants and is responsible for human toxicant-induced CBO (constrictive bronchiolitis obliterans); good picture showing the implantation/cannulation site p. 122; tissue perfusion (trachea).

P6536 Sugahara,K., Shimogori,H., Okuda,T., Takemoto,T., Hashimoto,M., Yamashita,H. Cochlear administration of adenosine triphosphate facilitates recovery from acoustic trauma (temporary threshold shift). ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2004; 66(-2-):80-84. >>> Adenosine triphosphate; PPADS; Ear (cochlea); Guinea-pig; 2002; ; Post op. care (antibiotic ointment applied); PE-10 used to target the inner ear and fixed with dental cement; for recover period, pumps and catheters were filled with saline, then pumps replaced with reagent filled pumps; infusion of agents was 12 hours post pump replacement to allow for saline in catheter to be infused; PPADS is pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid solution; tissue perfusion (cochlea).

P6535 Fischer,W., Gustafsson,L., Mossberg,A.K., Gronli,J., Mork,S., Bjerkvig,R., Svanborg,C. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Research 2004; 64(-6-):2105-2112. >>> Lactalbumin, alpha; HAMLET; radio-isotopes; 125I tracer; saline; CSF/CNS (intratumoral); Rat (nude); 2001D; 1 day; Tissue perfusion (tumor); functionality of mp verified by autoradiography on brain sections; no stress (see pg. 2108); cancer (glioblastoma); brain tissue distribution; agent is called HAMLET or (human alpha lact albumin made lethal to tumor cells); "...there were no signs of edema or tissue damage in the surrounding brain, including the cortex, which had been penetrated by the [26 gauge] infusion cannula." p. 2108.

P6462 Takemoto,T., Sugahara,K., Okuda,T., Shimogori,H., Yamashita,H. The clinical free radical scavenger, edaravone, protects cochlear hair cells from acoustic trauma. European Journal of Pharmacology 2004; 487(-1-3-):113-116. >>> Edaravone; saline; NaOH; water; HCL; Ear (cochlea); Guinea-pig; 2002; 17 days; Controls received no treatment to contralateral ear; animals received mp w/saline for 3 days; then pumps replaced for mp w/edaravone; no stress (see pg. 115); post op. care (antibiotic ointment); edaravone is a free radical scavenger; tissue perfusion (cochlea).

P6458 Olivius,P., Alexandrov,L., Miller,J.M., Ulfendahl,M., Bagger-Sjoebaeck,D., Kozlova,E.N. A model for implanting neuronal tissue into the cochlea. BRAIN RESEARCH PROTOCOLS 2004; 12(-3-):152-156. >>> Brain-derived neurotrophic factor; ciliary neurotrophic factor Ax1, human; Ear (scala tympani); Guinea-pig; 2002; 21-22 days; Pump replaced on days 11-12; post op. care (cyclosporine, doxycycline); tissue perfusion (scala tympani).

P6437 Wenk,G.L., gann-Gramling,K., Hauss-Wegrzyniak,B. The presence of the APPswe mutation in mice does not increase the vulnerability of cholinergic basal forebrain neurons to neuroinflammation. Neuroscience 2004; 125(-3-):769-776. >>> Tumor necrosis factor-alpha; memantine; CSF, artificial; saline; CSF/CNS (basal forebrain); Mice (transgenic); 1002; 20 days; Controls received mp w/ vehicle; tissue perfusion (basal forebrain); multiple pumps per animal (2); Plastics One cannula used with tygon tubing; secured with dental cement; second pump contained memantine/saline and was implanted on the other side of the spine.

P6392 Okuda,T., Sugahara,K., Shimogori,H., Yamashita,H. Inner ear changes with intracochlear gentamicin administration in guinea pigs. Laryngoscope 2004; 114(-4-):694-697. >>> Gentamicin; Saline; Ear (cochlea); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle; pumps replaced at day 7; pump contained saline only for the first seven days ; PE-10 used; tissue perfusion (cochlea).

P6374 Souweidane,M.M., Occhiogrosso,G., Mark,E.B., Edgar,M.A., Dunkel,I.J. Interstitial infusion of carmustine in the rat brain stem with systemic administration of O(6)-benzylguanine. Journal of Neuro-oncology 2004; 67(-3-):319-326. >>> Carmustine; Dextrose water; CSF/CNS (brain stem); Rat; 2001D; 24 hours; Tissue perfusion (brain stem); good methods p. 321; cancer; carmustine (BCNU) was dissolved in 5% dextrose water; pump incorrectly listed as a 2001 model; 30 g Plastics One cannula used with vinyl tubing by DURECT.

P6373 Souweidane,M.M., Occhiogrosso,G., Mark,E.B., Edgar,M.A. Interstitial infusion of IL13-PE38QQR in the rat brain stem. Journal of Neuro-oncology 2004; 67(-3-):287-293. >>> Interleukin-13,PE38QQR; Saline; serum albumin; CSF/CNS (brain stem); Rat; 2001D; 24 hours; Tissue perfusion (brain stem); stability verified (7 days at 37 degrees Celsius); good methods p. 288; cancer; cyanoacrylate adhesive; pump incorrectly labeled as a 2001; IL13-PE38QQR is a tumor specific, chimeric cytotoxin; 30 g Plastics One Cannula used; vinyl catheter tubing from DURECT used.

P6265 Tepel,J., Kruse,M.L., March,C., Fiedler,A., Kapischke,M., Ketterer,T., Sipos,B., Kremer,B., Kalthoff,H. Terminally modified oligodeoxynucleotides directed against p53 in an orthotopic xenograft model: A novel adjuvant treatment strategy for pancreatic ductal carcinoma. Pancreas 2004; 28(-1-):1-12. >>> Oligodeoxynucleotide, antisense; SC; Mice (SCID); 14 days; Tissue perfusion (intratumoral); comparison of IP injections vs. sc mp; cancer (pancreatic ductal carcinoma); transplantation; 200 ul pump used.

P6703 Wang,J., Faulconbridge,R.V.L., Fetoni,A., Guitton,M.J., Pujol,R., Puel,J.L. Local application of sodium thiosulfate prevents cisplatin-induced hearing loss in the guinea pig. Neuropharmacology 2003; 45(-3-):380-393. >>> Thiosulfate, sodium; Perilymph, artificial; water, sterile distilled; Ear (cochlea); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; stress/adverse reaction: (see pg.381) "Seven animals died during the course of the CDDP treatment (probably from the toxic effects of CDDP)" (p.381); cancer; "Perfusion of STS into the cochlea via an osmotic minipump completely prevented CDDP-induced hearing loss" (p.391); pump/catheter schematic (p.381); tissue perfusion (cochlea).

P6666 Kawaminami,M., Shibata,Y., Yaji,A., Kurusu,S., Hashimoto,I. Prolactin inhibits annexin 5 expression and apoptosis in the corpus luteum of pseudopregnant rats: Involvement of local gonadotropin-releasing hormone. Endocrinology 2003; 144(-8-):3625-3631. >>> Cetrorelix; Intraovarian; Rat (psuedo pregnant); 1003D; 2 days; Tissue perfusion (hemilateral ovarian bursa); GnRH antagonist.

P6540 Grossi,P.M., Ochiai,H., Archer,G.E., McLendon,R.E., Zalutsky,M.R., Friedman,A.H., Friedman,H.S., Bigner,D.D., Sampson,J.H. Efficacy of intracerebral microinfusion of trastuzumab in an Athymic rat model of intracerebral metastatic breast cancer. Clinical Cancer Research 2003; 9(-15-):5514-5520. >>> Herceptin; antibody, anti-Her2 monoclonal; radio-isotopes; Saline; 125I tracer; IP; CSF/CNS (intratumoral); Rat (athymic); 2ML1; 7 days; Tissue perfusion (tumor); herceptin serum levels (p. 5516); comparison of systemic IP mp vs. intracerebral mp infusion; cancer (breast); brain tissue distribution; radiolabeled herceptin (transtuzumab) was also infused intratumorally, peritumorally, and i.p to study tissue distribution.

P6405 Kirk,S.P., Oldham,J.M., Jeanplong,F., Bass,J.J. Insulin-like growth factor-II delays early but enhances late regeneration of skeletal muscle. JOURNAL OF HISTOCHEMISTRY&CYTOCHEMISTRY 2003; 51(-12-):1611-1620. >>> Insulin-like growth factor-II; Acetic acid; culture medium, RPMJ 1640; IM; Rat; 1007D; 7 days; Tissue perfusion (femoris muscle); peptides; IGF-II was recomb. human; vinyl catheter used for IM delivery.

P6159 Ekborn,A., Laurell,G., Ehrsson,H., Miller,J. Intracochlear administration of thiourea protects against cisplatin-induced outer hair cell loss in the guinea pig. Hearing Research 2003; 181(-1-2-):109-115. >>> Thiourea; Perilymph, artificial; water, sterile; Ear (cochlea); Guinea-pig; 2002; 14 days; good methods p. 111; microtip catheter was held in place using cyanoacrylate glue at the bulla defect, which was then sealed with dental cement; cites a detailed cannulation method; tissue perfusion (cochlea).

P6130 Wang,J., Van de Water,T.R., Bonny,C., de Ribaupierre,F., Puel,J.L., Zine,A. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. Journal of Neuroscience 2003; 23(-24-):8596-8607. >>> D-JNKI-1; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (JNK); D-JNKI-1 is a C-JUN N-terminal kinase (JNK); glass pipette was glued to PE-50 and pressed against cochlea; tissue perfusion (scala tympani).

P6098 Takeda,T., Sawada,S., Takeda,S., Kitano,H., Suzuki,M., Kakigi,A., Takeuchi,S. The effects of V(2) antagonist (OPC-31260) on endolymphatic hydrops. Hearing Research 2003; 182(-1-2-):9-18. >>> OPC-31260; Saline; Ear (cochlea); Guinea-pig; 2002; ; Controls received mp w/ vehicle; OPC-31260 is a vasopressin type-2 antagonist; insertion site of the cannula was sealed with biobonde (biomedical adhesive); tissue perfusion (cochlea).

P6080 Wenk,G.L., McGann,K., Hauss-Wegrzyniak,B., Rosi,S. The toxicity of tumor necrosis factor-alpha; upon cholinergic neurons within the nucleus basalis and the role of norepinephrine in the regulation of inflammation: Implications for Alzheimer's disease. Neuroscience 2003; 121(-3-):719-729. >>> Tumor necrosis factor, alpha; CSF, artificial; CSF/CNS (basal forebrain); Mice; 1002; 14 days; Controls received mp w/ vehicle; tissue perfusion (basal forebrain); Plastics One cannula used; "A volume overload to the brain tissue is minimal using this procedure because the 0.25 ul/hr administered contributes only about 0.2% of the total CSF volume produced by the mouse each hour..." p. 720; post op. care (1.0 ml of sterile saline (S.C) injected to prevent dehydration); neurodegenerative (Alzheimer's disease).

P6077 Lang,H., Schulte,B.A., Schmiedt,R.A. Effects of chronic furosemide treatment and age on cell division in the adult gerbil inner ear. JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY 2003; 4(-2-):164-175. >>> Furosemide; Ear (cochlea); Gerbil; 2004; 1 week; No stress (p. 165); tissue perfusion (cochlea).

P6047 Ekdahl,C.T., Claasen,J.H., Bonde,S., Kokaia,Z., Lindvall,O. Inflammation is detrimental for neurogenesis in adult brain. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2003; 100(-23-):13632-13637. >>> Endotoxin, E. coli; CSF, artificial; CSF/CNS (hippocampus); Rat; 2004; 4 weeks; 6 days; Controls received mp w/ vehicle; ALZET brain infusion kit used; tissue perfusion (cerebral tissue); endotoxin was from e. coli (serotype 055:B5).

P5991 Rubin,J.B., Kung,A.L., Klein,R.S., Chan,J.A., Sun,Y.P., Schmidt,K., Kieran,M.W., Luster,A.D., Segal,R.A. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2003; 100(-23-):13513-13518. >>> AMD 3100; PBS; SC; Mice; 21 days; Controls received mp w/ vehicle; tissue perfusion (intratumoral); comparison of 2x daily injections vs. mp; cancer (glioblastoma); CXCR4 antagonist; 0.5 ul/hr pumps used; In vivo tumor imaging performed with IVIS imaging system (Xenogen); bioluminescence imaging (BLI).

P5983 Zou,J., Bretlau,P., Pyykkoe,I., Toppila,E., Olovius,N.P., Stephanson,N., Beck,O., Miller,J.M. Comparison of the protective efficacy of Neurotrophins and antioxidants for vibration-induced trauma. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2003; 65(-3-):155-161. >>> Brain-derived neurotrophic factor; ciliary neurotrophic factor; Ear (scala tympani); Guinea-pig; 2002; 14 days; tissue perfusion (cochlea); comparison of RWM injections vs. mp; peptides.

P5967 Boyd,J.G., Gordon,T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Experimental Neurology 2003; 183(-2-):610-619. >>> Glial-derived neurotrophic factor; brain-derived neurotrophic factor; Saline; CSF/CNS (tibial nerve); Rat; 2001; 2ML4; 7,28 days; Controls received mp w/ vehicle; tissue perfusion (nerve repair site); good methods (p. 611,612); silastic cuff used; pumps used for a 1 week and 4 week study.

P5966 Roguin,A., Avivi,A., Nitecki,S., Rubinstein,I., Levy,N.S., Abassi,Z.A., Resnick,M.B., Lache,O., Melamed-Frank,M., Joel,A., Hoffman,A., Nevo,E., Levy,A.P. Restoration of blood flow by using continuous perimuscular infiltration of plasmid DNA encoding subterranean mole rat Spalax ehrenbergi VEGF. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES O F AMERICA 2003; 100(-8-):4644-4648. >>> DNA, naked; vascular endothelial growth factor, DNA; Water; IM; Mice; 2001; 7 days; Controls received mp w/ saline; tissue perfusion (quadriceps muscle); gene therapy; fenestrated catheter; pump implanted IP; "we have shown that when using plamid DNA, continuous administration is superior to multiple simultaneous IM injections." (p. 4647).

P5906 Nadeau,S., Rivest,S. Glucocorticoids play a fundamental role in protecting the brain during innate immune response. Journal of Neuroscience 2003; 23(-13-):5536-5544. >>> Tumor necrosis factor-alpha; L-NAME; endotoxin, LPS; Saline; BSA; ascorbic acid; PIPES; DMSO; CSF/CNS (cortex, dorsal basal ganglia); Rat; 2004; 3,7,14,21 days; Controls received mp w/ vehicle; tissue perfusion (cerebral tissue&dorsal ganglia); enzyme inhibitor (nitric oxide); brain tissue distribution; guid cannula used; TNF-a was dissolved in saline + 0.1% BSA + 0.01% ascorbic acid; L-NAME was dissolved in PIPES&10% DMSO&infused into the dorsal basal ganglia.

P5872 Wang,X.B., Truong,T., Billings,P.B., Harris,J.P., Keithley,E.M. Blockage of immune-mediated inner ear damage by etanercept. OTOLOGY&NEUROTOLOGY 2003; 24(-1-):52-57. >>> Etanercept; PBS; keyhole limpet hemocyanin; Ear (scala tympani); Guinea-pig; 2001; 7 days; Controls received mp w/ PBS or KLH; Etanercept is a TNF receptor; keyhole limpet hemocyanin is (KLH); tissue perfusion (scala tympani).

P5835 Svechnikova,I., Gray,S.G., Kundrotiene,J., Ponthan,F., Kogner,P., Ekstrom,T.J. Apoptosis and tumor remission in liver tumor xenografts by 4-phenylbutyrate. INTERNATIONAL JOURNAL OF ONCOLOGY 2003; 22(-3-):579-588. >>> Verapamil; Perilymph, artifical; Ear (cochlea); guinea-pig; 2002; 7 days; Pumps replaced every two weeks; 2 week stability verified by high pressure liquid chromatography p. 220; good methods p.220; 3 day recovery post implant; tissue perfusion (cochlea).

P5819 Giussani,C., Carrabba,G., Pluderi,M., Lucini,V., Pannacci,M., Caronzolo,D., Costa,F., Minotti,M., Tomei,G., Villani,R., Carroll,R.S., Bikfalvi,A., Bello,L. Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in vivo. Cancer Research 2003; 63(-12-):2499-2505. >>> Platelet factor-4; MMP-2 (hemopexin fragment); PBS; SC; CSF/CNS (intratumoral); Mice; 2004; 28 or 94 days; Controls received mp w/ PBS; tissue perfusion (tumor); dose-response (p.2502); comparison of IP injections SC systemic mp infusion vs. local intracranial mp infusion; long-term study; pumps replaced after 28 days in some groups; stability verified by in vitro assay; cancer (glioma); Angiogenesis inhibitors; COOH terminal fragment of PF-4 used; In vitro activity of agents confirmed for up to 16 days; "In conclusion, our data demonstrates that local intracerebral delivery of endogenous inhibitors by osmotic minipumps is a very effective modality for the treatment of aggressive tumors..." (p.2505); tissue perfusion (tumor);.

P5811 Du,X.P., Yoo,T.J., Mora,R. Distribution of beta-tubulin in guinea pig inner ear. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2003; 65(-1-):7-16. >>> Tubulin, beta; PBS; Ear (scala tympani); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle; tissue perfusion (cochlea); peptides.

P5774 Torrente,Y., El Fahime,E., Caron,N.J., Del Bo,R., Belicchi,M., Pisati,F., Tremblay,J.P., Bresolin,N. Tumor necrosis factor-alpha (TNF-alpha) stimulates chemotactic response in mouse myogenic cells. CELL TRANSPLANTATION 2003; 12(-1-):91-100. >>> Tumor necrosis factor-a; Saline; IM; Mice; 2002; 5 days; Controls received mp w/ vehicle; tissue perfusion (tibialis anterior muscle); dose-response (p.95 fig M); perforated PE tubing used.

P5712 Fukaya,K., Hasegawa,M., Mashitani,T., Kadoya,T., Horie,H., Hayashi,Y., Fujisawa,H., Tachibana,O., Kida,S., Yamashita,J. Oxidized galectin-1 stimulates the migration of Schwann cells from both proximal and distal stumps of transected nerves and promotes axonal regeneration after peripheral nerve injury. Journal of Neuropathology and Experimental Neurology 2003; 62(-2-):162-172. >>> Cisplatin; Saline; Ear (cochlea); Guinea-pig; 2002; 14 days; Tissue perfusion (cochlea).

P5672 Chelikh,L., Teixeira,M., Martin,C., Sterkers,O., Ferrary,E., Couloigner,V. High variability of perilymphatic entry of neutral molecules through the round window. Acta Oto-laryngologica 2003; 123(-2-):199-202. >>> Mannitol; Inulin;; Radio-isotopes; 3H tracer; saline; ethanol; Ear (round window); Guinea-pig; 1007D; 7 days; Tissue perfusion (round window).

P5670 Eckardt,H., Bundgaard,K.G., Christensen,K.S., Lind,M., Hansen,E.S., Hvid,I. Effects of locally applied vascular endothelial growth factor (VEGF) and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis. Journal of Orthopaedic Research 2003; 21(-2-):335-340. >>> Vascular endothelial growth factor; vascular endothelial growth factor R2/FC chimera; Phosphate buffer; BSA; Bone (tibia); Rabbit; 2ML2; 14 days; Controls received mp w/ vehicle; tissue perfusion (osteotomy site); replacement therapy (distraction osteogenesis); stability verified by in vitro assay for 2 weeks at 37 C. (p. 336);.

P5669 Gillespie,L.N., Clark,G.M., Bartlett,P.F., Marzella,P.L. BDNF-induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects. Journal of Neuroscience Research 2003; 71(-6-):785-790. >>> Brain-derived neurotrophic factor; Ear (cochlea); Guinea-pig; 2004; 4 weeks; Peptides; BDNF was recombinant human; tissue perfusion (cochlea).

P5659 Horiike,O., Shimogori,H., Ikeda,T., Yamashita,H. Protective effect of edaravone against streptomycin-induced vestibulot oxicity in the guinea pig. European Journal of Pharmacology 2003; 464(-1-):75-78. >>> Streptomycin; Saline; Ear (cochlea); Guinea-pig; 2002; 24 hours; tissue perfusion (round window).

P5649 Norrholm,S.D., Bibb,J.A., Nestler,E.J., Ouimet,C.C., Taylor,J.R., Greengard,P. Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5. Neuroscience 2003; 116(-1-):19-22. >>> Roscovitine; Sodium phosphate; sodium chloride; DMSO; CSF/CNS (nucleus accumbens); Rat; 2004; 28 days; Controls received mp w/ vehicle; tissue perfusion (nucleus accumbens); enzyme inhibitor (cyclin dependent kinase-5); roscovitine is a potent Cdk5 inhibitor; bilateral cannula used; 50% DMSO used.

R0213 Duan,M.L., Ulfendahl,M., Laurell,G., Counter,A.S, Pyykko,I., Borg,E., Rosenhall,U. Protection and treatment of sensorineural hearing disorders caused by exogenous factors: experimental findings and potential clinical application. Hearing Research 2002; 169(--):169-178. >>> Liposomes, cationic; Ear (cochlea); Guinea-pig; ; Gene therapy; tissue perfusion (cochlea).

R0183 Lalwani,A.K., Jero,J., Mhatre,A.N. Developments in cochlear gene therapy. GENETIC HEARING IMPAIRMENT: ITS CLINICAL PRESENTATIONS 2002; 61(-;-):28-33. >>> ; Ear; ; Gene therapy; review of gene vectors and routes of delivery for cochlear gene therapy; tissue perfusion (cochlea).

R0164 Lalwani,A.K., Jero,J., Mhatre,A.N. Current issues in cochlear gene transfer. Audiol.Neurootol. 2002/5; 7(-3-):146-151. >>> Gene vectors; Ear (cochlea); Guinea-pig; 1007D; ; Gene therapy; review of various cochlear gene delivery methods; diagram of the various delivery methods (p. 147); tissue perfusion (cochlea).

P6148 Leaver,H.A., Wharton,S.B., Bell,H.S., Leaver-Yap,I.M.M., Whittle,I.R. Highly unsaturated fatty acid induced tumor regression in glioma pharm acodynamics and bioavailability of gamma linolenic acid in an implanta tion glioma model: effects on tumour biomass, apoptosis and neuronal t issue histology. PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS 2002; 67(-5-):283-292. >>> Linolenic acid, gamma; PBS; CSF/CNS (intratumoral); 2001; 3-7 days; Controls received mp w/ vehicle; tissue perfusion (tumor); cancer (glioma); ALZET brain infusion kit used.

P5820 Sorensen,D.R., Leirdal,M., Iversen,P.O., Sioud,M. Combination of endostatin and a protein kinase C alpha DNA enzyme improves the survival of rats with malignant glioma. NEOPLASIA 2002; 4(-6-):474-479. >>> Platelet factor 4 peptides; PBS; CSF/CNS (intratumoral); Mice (nude); 2004; 28 days; Controls received mp w/ vehicle; tissue perfusion (intratumoral); dose-response (p. 6888; fig 6); cancer; peptides; glioma; antiangiogenesis..

P5587 Lefranc,F., Camby,I., Belot,N., Bruyneel,E., Chaboteaux,C., Brotchi,J., Mareel,M., Salmon,I., Kiss,R. Gastrin significantly modifies the migratory abilities of experimental glioma cells. Lab.Invest. 2002; 82(-9-):1241-1252. >>> Gastrin; SC; rat; 1002; 14 days; controls received mp with saline; tissue perfusion (tumor resection cavity); cancer.

P5579 Foster,P.K., Luebke,A.E. A model for perilymphatic fistula induced hearing loss in the guinea pig cochlea. Hearing Research 2002; 167(-1-2-):175-179. >>> Perilymph, artificial; Ear (scala tympani); guinea-pig; ; some animals also received an air bubble ~1.5-2 microliters infused into the scala tympani; tissue perfusion (scala tympani).

P5571 Germinario,E., Esposito,A., Midrio,M., Betto,R., Danieli-Betto,D. Expression of sarco(endo)plasmic reticulum Ca2+-ATPase slow (SERCA2) i soform in regenerating rat Soleus skeletal muscle depends on nerve impulses. Experimental Physiology 2002; 87(-5-):575-583. >>> Tetrodotoxin; CSF/CNS (sciatic nerve); rat; 2002; 14 days; tissue perfusion (nerve cuff); PE catheter connected to a silicon nerve cuff.

P5542 Fernandez-Botran,R., Gorantla,V., Sun,X.C., Ren,X.P., Perez-Abadia,G., Crespo,F.A., Oliver,R., Orhun,H.I., Quan,E.E., Maldonado,C., Ray,M., Barker,J.H. Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in allotransplantation. Transplantation 2002; 74(-5-):623-629. >>> MC-2; Saline; IA (profunda femoris artery); Rat; 2ML2; ; Controls received mp w/ vehicle; tissue perfusion (skin flap allograft); immunology; peptides; MC-2 is derived from mouse interferon gamma; transplant.

P5540 Lalwani,A.K., Han,J.J., Castelein,C.M., Carvalho,G.J., Mhatre,A.N. In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. Laryngoscope 2002; 112(-8-):1325-1334. >>> Virus, adeno-associated; Gene, green fluorescent protein; Gene, brain-derived neurotrophic factor; PBS; Ear (cochlea); Guinea-pig; 1007D; 1 week; Gene therapy; cochlea cannulated with PE10 attached to PE50; virus contained gene for brain-derived neurotrophic factor and/or green fluorescent protein; tissue perfusion (cochlea).

P5531 Chen,Y., Lin,S.M., Lai,H.S., Tseng,S.H., Chen,W.J. Effects of irradiated tumor vaccine and continuous localized infusion of granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice. Journal of Pediatric Surgery 2002; 37(-9-):1298-1304. >>> Colony-stimulating factor, GM; PBS; BSA; SC (tumor vaccine injection site); Mice; 1002; 14 days; Controls received mp w/ PBS; immunology; GM-CSF is recombinant murine; tissue perfusion.

P5489 Cuevas,P., Carceller,F., Diaz-Gonzalez,D., Cuevas,B., Fernandez,A., Garcia-Gomez,I., Dujovny,M. Inhibition of rat glioma growth by neomycin. Preliminary report. NEUROLOGICAL RESEARCH 2002; 24(-6-):522-524. >>> Dexamethasone; Perilymph, artificial; Ear (cochlea); guinea-pig; 2002; 26 days; Controls received mp w/ vehicle; pumps replaced after 14 days; no stress (see pg. 67); "The current study indicates that intra-cochlear administration using osmotic pumps can provide a stable and continuous delivery of Dexamethasone without causing functional changes or tissue damage." (p. 67); tissue perfusion (cochlea).

P5473 Erami,C., Zhang,H., Ho,J.G., French,D.M., Faber,J.E. Alpha 1-adrenoceptor stimulation directly induces growth of vascular wall in vivo. American Journal of Physiology-Heart and Circulatory Physiology 2002; 283(-4-):H1577-H1587. >>> Norepinephrine; benoxathian; prazosin; KMD-3213; AH11110A; BMY-7378; propranolol; RX-821002; Ringer's, lactated; ascorbate; Perivascular; Rat; 2ML2; 14, 28 days; Tissue perfusion (left carotid wall); pumps replaced after 14 days for prazosin; catheter constructed from thin walled vinyl tubing and fenestrated at end placed near vessel; norepinephrine is a catecholamine; propranolol is a beta adrenoceptor antagonist; all other agents are antagonists alpha antagonists.

P5452 Matsuoka,H., Kwon,S.S., Yazawa,Y., Barbieri,M., Yoo,T.J. Induction of endolymphatic hydrops by directly infused monoclonal antibody against type II collagen CB11 peptide. Annals of Otology Rhinology and Laryngology 2002; 111(-7-):587-592. >>> Antibody, anti-CB11 monoclonal; Ear (scala tympani); Guinea-pig; 2002; 14 days; Controls received mp w/ mouse serum; tissue perfusion (scala tympani).

P5448 Schmiedt,R.A., Okamura,H.O., Lang,H., Schulte,B.A. Ouabain application to the round window of the gerbil cochlea: A model of auditory neuropathy and apoptosis. JARO 2002; 3(-3-):223-233. >>> Ouabain; Saline; Ear (round window); Gerbil; 2004; 2, 4, 8 days; 2, 24 hours; Tissue perfusion (round window).

P5373 Takahashi,M., Fukami,S., Iwata,N., Inoue,K., Itohara,S., Itoh,H., Haraoka,J., Saido,T.C. In vivo glioma growth requires host-derived matrix metalloproteinase 2 for maintenance of angioarchitecture. Pharmacological Research 2002; 46(-2-):155-163. >>> TIMP-1; TIMP-2; PBS; CSF/CNS (intratumoral); Rat; 2002; 3, 7, or 14 days; Controls received mp w/ vehicle; tissue perfusion (tumor); functionality of mp verified by immunohistochemistry of agents; cancer; enzyme inhibitor; ALZET brain infusion kit used; MMP inhibitors (tissue inhibitors of metalloprotease = TIMP); rat glioma model.

P5370 Spiess,A.C., Lang,H.N., Schulte,B.A., Spicer,S.S., Schmiedt,R.A. Effects of gap junction uncoupling in the gerbil cochlea. Laryngoscope 2002; 112(-9-):1635-1641. >>> Proadifen; Ear (round window niche); Gerbil; 2001; 2002; 6-7 or 11-14 days; Tissue perfusion (bulla); no stress (see pg. 1637); Proadifen, also called SKF-525A, is a gap junction uncoupler; the pump and cannula were gas-sterilized prior to filling (note: manufacturer does not recommend sterilizatioin of pumps); "The animals experienced no long-term trauma from either the surgery or the extra bulk of the pump." (p. 1637).

P5357 Walker,T.L., Dass,C.R., Burton,M.A. Enhanced In Vivo tumour response from combination of carboplatin and low-dose c-myc antisense oligonucleotides. Anticancer Research 2002; 22(-4-):2237-2245. >>> Neomycin; Kanamycin; Furosenide; PBS; ear (scala tympani); Guinea-pig; 2004; 86 hours; Tissue perfusion (round window); functionality of mp verified by residual volume; diagram of pump and electrode assembly (p. 94); catheter patency assessed by passing fluid through the line at the end of the experiment; Neomycin infused in pilot study; Kanamycin and furosenide were co-infused in a second study.

P5271 Davies,M.M., Mathur,P., Carnochan,P., Saini,S., Allen-Mersh,T.G. Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model. Br.J Cancer 2002/1/7; 86(-1-):123-129. >>> Fibroblast growth factor, basic; Saline; IV (jugular); Intratumoral; Rat; 2004; 28 days; Controls received mp w/ vehicle; tissue perfusion (intratumoral); cancer; peptides; bFGF delivered either by systemic IV infusion or intratumorally.

P5248 Wongtrakul,S., Bishop,A.T., Friedrich,P.F. Vascular endothelial growth factor promotion of neoangiogenesis in conventional nerve grafts. J Hand Surg.[Am.] 2002/3; 27(-2-):277-285. >>> Vascular endothelial growth factor; PBS; Albumin, rabbit serum; CSF/CNS (sciatic nerve); Rabbit; 1003D; 3 days; Controls received mp w/ vehicle; tissue perfusion (sciatic nerve graft); peptides; human recomb. VEGF used; transplantation;.

P5186 Gordon,T., Boyd,J.G., Gordon,T. A dose-dependent facilitation and inhibition of peripheral nerve regeneration by brain-derived neurotrophic factor. European Journal of Neuroscience 2002; 15(--):613-626. >>> Brain-derived neurotropic factor; PBS; Tween 20; CSF/CNS (tibial nerve); Rat; 2ML4; 28 days; Controls received gelfoam or mp w/ saline; tissue perfusion (tibial nerve); stability verified by in vitro assay on embryonic chick neurons (p. 614); good methods (p. 614-5); peptides; silastic tubing used; graphic showing nerve perfusion (p. 615); "pump, nerve cuff and drug delivery catheter did not interfere with regeneration of the TIB motor axons" (p. 617).

P5178 Iwase,M., Kim,K.J., Kobayashi,Y., Itoh,M., Itoh,T. A novel bisphosphonate inhibits inflammatory bone resorption in a rat osteolysis model with continuous infusion of polyethylene particles. Journal of Orthopaedic Research 2002; 20(--):499-505. >>> Polyethylene particles, HDPE; Knee (articular cavity); Rat; 2002; 4-8 weeks; Tissue perfusion (diagram p.501); Arthritis; functionality verified by residual volume; pumps replaced every 2 weeks.

P5102 Skovseth,D.K., Yamanaka,T., Brandtzaeg,P., Butcher,E.C., Haraldsen,G. Vascular morphogenesis and differentiation after adoptive transfer of human endothelial cells to immunodeficient mice. American Journal of Pathology 2002; 160(-5-):1629-1637. >>> Interferon-gamma; Abdominal wall; mice; 2004; ; tissue perfusion (abdominal wall); immunology; peptides; pump implanted SC, catheter tube perfused matrigel plug in abdominal wall..

P5087 Dufourcq,P., Couffinhal,T., Alzieu,P., Daret,D., Moreau,C., Duplaa,C., Bonnet,J. Vitronectin is up-regulated after vascular injury and vitronectin blockade prevents neointima formation. Cardiovascular Research 2002; 53(--):952-962. >>> Antibody, monoclonal anti-vitronectin; Antibody, monoclonal anti-B3 integrin; Antibody, monoclonal anti-avB5 integrin; PBS; Immunoglobulin G, non-immune; perivascular (carotid artery adventitia); rat; 7 days; controls received control immunoglobulin; tissue perfusion (corotid adventitia); cardiovascular; peptides.

P5086 Hirotani,H., Ohtsuka-Isoya,M., Mori,S., Sakai,R., Eto,Y., Echigo,S., Shinoda,H. Activin A Increases the Bone Mass of Grafted Bone in C3H/HeJ Mice. Calcif.Tissue Int. 2002/4; 70(--):330-338. >>> Activin A; Saline; Bone (tibia graft); mice; 2001; 2002; 2004; 1, 2, or 4 weeks; controls received mp w/ vehicle; tissue perfusion (tibial bone graft); graphic of pump setup (p. 331); Activin A was recombinant human; multiple pumps per animal (2): one containing Activin, one containing saline (control).

P5065 Tanaka,H, Wakisaka,A, Ogasa,H, Kawai,S  Journal of Endocrinology 2002; 174(--):63-70. >>> Platelet-derived growth factor; Insulin-like growth factor I; SC; bone (femur); rat; 5 days; controls received mp w/ vehicle; tissue perfusion (bone); functionality of mp verified by residual aspiration (p. 64); peptides; growth factors were human recombinant; agents infused separately or concomitantly;.

P5061 Moss,T.J.M., Newnham,J.P., Willett,K.E., Kramer,B.W., Jobe,A.H., Ikegami,M. Early gestational intra-amniotic endotoxin - Lung function, surfactant, and morphometry. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2002; 165(--):805-811. >>> Endotoxin, E. coli; Saline; Amniotic sac; sheep (lamb, fetus); 2ML4; 4 weeks; controls received mp w/ vehicle; tissue perfusion (amniotic sac); comparison of intra-amniotic injections vs. mp; immunology; teratology; pre-natal lung development.

P5059 Davies,M.M., Burke,D., Carnochan,P., Glover,C., Kaur,S., Allen-Mersh,T.G. Basic fibroblast growth factor infusion increases tumour vascularity, blood flow and chemotherapy uptake. Acta Oncologica 2002; 41(-1-):84-90. >>> AG-041R; DMSO; saline; knee (articular cavity); rabbit; 2002; 10, 14, or 28 days; controls received mp w/ vehicle; tissue perfusion (knee joint).

P5043 Wang,J., Dib,M., Lenoir,M., Vago,P., Eybalin,M., Hameg,A., Pujol,R., Puel,J.L. Riluzole rescues cochlear sensory cells from acoustic trauma in the guinea-pig. Neuroscience 2002; 111(-3-):635-648. >>> Riluzole; Perilymph, artificial; Ear (cochlea); guinea-pig; 2001; 7 days; controls received mp w/ vehicle; tissue perfusion (cochlea); 2-day recovery period. Schematic of pump infusing to inner ear (p. 636). Riluzole is a neoroprotective agent (also called 1-amino-6-trifluoromethoxy benzothiazole). Paper states the use of 1003D, but specifications indicate model 2001 was used.

P5009 Shinohara,T., Bredberg,G., Ulfendahl,M., Pyykko,I., Olivius,N.P, Kaksonen,R., Lindstrom,B., Altschuler,R., Miller,J.M. Neurotrophic factor intervention restores auditory function in deafened animals. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2002; 99(-3-):1657-1660. >>> Brain-derived neurotrophic factor; Ciliary neurotrophic factor; Neomycin;; Perilymph, artificial; Ear (scala tympani); guinea-pig; 2002; 26 days; controls received mp w/ vehicle; tissue perfusion (cochlea, scala tympani); pumps replaced at day 15; peptides; catheter filled with perilymph and 10% neomycin; pump filled with vehicle or neurotrophic factor solution; 48-hr infusion of neomycin to cause deafness followed by 12 or 26 day infusion of neurotrophic factor pump reservoir..

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