Studies Including Information on the Stability of Agents in ALZET® Osmotic Pumps

Q0707 Tange,Y., Miyazaki,M., Iwata,J., Aiko,Y., Sakamoto,S., Mori,K. Novel Antitumor Effect of Carboplatin Delivered by Intracerebral Microinfusion in a Rat Malignant Glioma Model. NEUROLOGIA MEDICO-CHIRURGICA 2009; 49(-12-):572-579. >>> Carboplatin; Glucose, D-; Evans blue; CSF/CNS (intratumoral); Rat; 2001; 3, 7 days; Animal info (male, F344/N Slc, Fischer 220-260 g); brain tissue distribution; ALZET brain infusion kit used; stability verified (4 weeks) pg 573; cancer (glioma); MRI; brain tissue distribution; "... continuous intracerebral microinfusion using the osmotic mini-pump can provide broader distribution of agents than growth of the brain tumor."; "intracerebral microinfusion can attain clinically favorable drug distribution from a single infusion point." pg 576.

Q0671 Szentirmai,E., Kapas,L., Sun,Y.X., Smith,R.G., Krueger,J.M. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2009; 106(-33-):14069-14074. >>> Obestatin; Saline, isotonic; SC; Mice; 1002; 14 days; Controls received mp w/ vehicle; animal info (preproghrelin KO); peptides; half-life (22 min) pg 14072; replacement therapy (obestatin); "Replacement of obestatin by bolus injection is problematic because of the short half-life (24) of the peptide (22 +/- 2 min), and disturbing the animals by the injection procedure interferes with the thermoregulatory response. Osmotic minipumps also have limitations because of the unknown stability of stored obestatin and unknown dose-response relationship." pg 14072.

Q0586 Dilda,P.J., Decollogne,S., Weerakoon,L., Norris,M.D., Haber,M., Allen,J.D., Hogg,P.J. Optimization of the Antitumor Efficacy of a Synthetic Mitochondrial Toxin by Increasing the Residence Time in the Cytosol. Journal of Medicinal Chemistry 2009; 52(-20-):6209-6216. >>> Phenylarsonous acid; PBS; SC; Mice (nude); 1004; ; Controls received mp w/ vehicle; animal info (BalbC, nude, Female 7-9 week old); stability verified in vitro for at least 2 weeks at 4 or 37 degrees C; "There was a small accumulation of connective tissue at the delivery site of the osmotic pump in 7 of the 10 mice at the higher dose of PENAO. This is likely the result of a local inflammatory response triggered by the high concentrations of PENAO at the delivery site." pg 6213; Phenylarsonous acid (PENAO) is a cysteine mimetic analogue of CAO; cancer.

Q0562 Bennett,S.P., Boyd,T.D., Norden,M., Padmanabhan,J., Neame,P., Wefes,I., Potter,H. A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease. Journal of Neuroscience Methods 2009; 184(-2-):320-326. >>> Antichymotrypsin, alpha-1; CSF, artificial; CSF/CNS; CSF/CNS (hippocampal parenchyma); Mice; 1004; 28 days; Controls received mp w/ vehicle; animal info (PS/APP, PS/APP/ACT, 10 mo old); functionality of mp verified by residual volume; cyanoacrylate adhesive; multiple pumps per animal (2); stability verified ("minimal degradation" after 28 days); custom catheter solution for simultaneous bilateral brain infusions; nitrile cap used to affix custom catheters to the skull; pump plus custom catheter assembly Fig 3e; "entire catheters and pumps we used can be completely removed without terminating the life of the animal" pg 326.

Q0450 Marino,P., Norreel,J.C., Schachner,M., Rougon,G., Amoureux,M.C. A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury. Experimental Neurology 2009; 219(-1-):163-174. >>> PR-21; Water; Rat; 1007D; ; Animal info (9 wks old, female, Wistar); peptides; half-life (p. 166) approximately 14 days in vitro at 37 degrees C; stability verified by ELISA; PR-21 also known as PSA-mimetic peptide; "We verified that PR-21 remained stable in the vehicle (WFI) during 14 days." pg 166; spinal cord injury.

Q00379 Lada-Moldovan,L., Kaloustian,S., Bah,T.M., Girard,S.A., Dery,M.A., Rousseau,G. Chronic Pretreatment With Celecoxib Reduces Infarct Size. Journal of Cardiovascular Pharmacology 2009; 54(-1-):31-37. >>> Celecoxib; DMSO; ethanol; water, distilled; IP; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; animal info (Sprague-Dawley, male, 325-350 g); 50% DMSO used; 15% ethanol used; "...limitation of this study is the lack of assessment of celecoxib stability in the osmotic pump after 28 days. However, since we observed a significant reduction of MI, subepicardial apoptosis and platelet aggregation, we believe that there is enough active compound at 28 days to induce beneficial effects." pg 36.

Q00258 Pathipati,P., Surus,A., Williams,C.E., Scheepens,A. Delayed and chronic treatment with growth hormone after endothelin-induced stroke in the adult rat. Behavioural Brain Research 2009; 204(-1-):93-101. >>> Growth hormone, rat; NaCl; tween 20; NaHCO3; Na2CO3; CSF/CNS; Rat; 2002; 6 weeks; Controls received mp w/ vehicleanimal info (adult, male, Sprague-Dawley, 280-350 g); pumps replaced every 2 weeks; stability verified by for 2 weeks in vitro.

Q00222 Campanella,C., Jamali,F. Influence of prolonged exposure of a short half life non-steroidal anti-inflammatory drugs on gastrointestinal safety. INFLAMMOPHARMACOLOGY 2009; 17(-4-):205-210. >>> Flurbiprofen; PEG 400; IP; Rat; 2002; 7 days; Comparison of IP injections vs. mp; stability verified in vitro test for 14 days; animal info (male, Sprague Dawley, adult, 300-350 g.); "There was no significant difference between the two i.p. groups in the post-mortem plasma R or S-flurbiprofen concentration or in the percent of the dose excreted as glucoronidated flurbiprofen in urine on days 1 and 7" pg 207.

P9959 Vinkers,C.H., Korte-Bouws,G.A.H., Torano,J.S., Mirza,N.R., Nielsen,E.O., Ahring,P.K., de Jong,G.J., Olivier,B. The rapid hydrolysis of chlordiazepoxide to demoxepam may affect the outcome of chronic osmotic minipump studies. Psychopharmacology 2010; 208(-4-):555-562. >>> Chlordiazepoxide; In vitro; ; "When the cumulative CDP concentration over time was corrected for its hydrolysis, drug release from the minipumps followed the theoretical release profile over time (white symbols), suggesting that CDP hydrolysis completely accounted for the declined CDP release over time." pg 558; "In general, the use of osmotic minipumps presents a valid and attractive alternative to the labor-intensive daily injections. However, the issue of drug stability and release should always be carefully investigated before initiating chronic minipump experiments." pg 562.

P9867 Thakker,D.R., Weatherspoon,M.R., Harrison,J., Keene,T.E., Lane,D.S., Kaemmerer,W.F., Stewart,G.R., Shafer,L.L. Intracerebroventricular amyloid-beta antibodies reduce cerebral amyloid angiopathy and associated micro-hemorrhages in aged Tg2576 mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2009; 106(-11-):4501-4506. >>> Immunoglobulin G1; 6E10; CSF/CNS; Mice (transgenic); 2004; ; Functionality of mp verified in vitro for 5 weeks; stability verified in vitro for 5 weeks; animal info (male, 16-18 months old, Tg2576); neurodegenerative (Alzheimer's Disease); 6E10 is a mouse monoclonal IgG1; brain tissue distribution.

P9790 Joosen,M.J.A., Jousma,E., van den Boom,T.M., Kuijpers,W.C., Smit,A.B., Lucassen,P.J., Van Helden,H.P.M. Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning. Neurotoxicology 2009; 30(-1-):72-80. >>> Olanzapine; Acetic acid, glacial; SC; Rat; 2ML4; 4 weeks; Functionality of mp verified by residual volume; animal info (male, Sprague Dawley); stability verified for 4 weeks by electrospray MS/MS.

P9766 Mueller,M.C., Osswald,M., Tinnes,S., Haeussler,U., Jacobi,A., Foerster,E., Frotscher,M., Haas,C.A. Exogenous reelin prevents granule cell dispersion in experimental epilepsy. Experimental Neurology 2009; 216(-2-):390-397. >>> Reelin, recomb.; CSF/CNS (hippocampus); Mice; 2002; 2 weeks; Negative controls received mp w/saline; stability verified by western blot analysis (2 wks); brain tissue distribution; ALZET brain infusion kit 3 used; animal info (C57BL/6NCrI, male, 8-10 wks old); reelin is an extracellular matrix protein important for neuronal positioning.

P9632 Ortiz,M.A., Campana,G.L., Woods,J.R., Boguslawski,G., Sosa,M.J., Walker,C.L., Labarrere,C.A. Continuously-infused Human C-Reactive Protein Is Neither Proatherosclerotic Nor Proinflammatory in Apolipoprotein E-Deficient Mice. EXPERIMENTAL BIOLOGY AND MEDICINE 2009; 234(-6-):624-631. >>> C-reactive protein, human; IP; Mice; 2004; 28 days; Controls received mp w/placebo solution; stability verified by non-denaturing Western blotting; animal info (apoE -/-, male, 12 wks old), IP catheter used.

P9513 Harvey,P.A., Lee,D.H.S., Qian,F., Weinreb,P.H., Frank,E. Blockade of Nogo Receptor Ligands Promotes Functional Regeneration of Sensory Axons after Dorsal Root Crush. Journal of Neuroscience 2009; 29(-19-):6285-6295. >>> Nogo receptor, soluble fragment; CSF/CNS; Rat; 2004; 28 days; Controls received mp w/ vehicle; stability verified by "separate tests" (up to 1 month, pg 6286); ALZET brain infusion kit 2 used; peptides; animal info (male, Sprague Dawley, 200-250 g.); sNGR.

P9487 Bloch-Shilderman,E., Rabinovitz,I., Egoz,I., Raveh,L., Allon,N., Grauer,E., Gilat,E., Weissman,B.A. Subchronic-exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies. TOXICOLOGY AND APPLIED PHARMACOLOGY 2008; 231(-1-):17-23. >>> VX; Propylene glycol; SC; Rat; 2004; 1, 3 months; Controls received mp w/ vehicle; pumps replaced every 10 days; no stress (see pg. 19); stability verified by AChE inhibition in vitro @ -20, 25, 38 degrees Celsius @ 24h, 48h, and 1 week; animal info (male, Sprague Dawley, 260-300 g.); VX, a nerve agent, also known as O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate; toxic organophosphorous; "when pumps were replaced the new incision was made in an adjacent dorsal area." pg. 18; enzyme inhibitor (ACE); long-term study.

P9416 Isa,K., Garcia-Espinosa,M.A., Arnold,A.C., Pirro,N.T., Tommasi,E.N., Ganten,D., Chappell,M.C., Ferrario,C.M., Diz,D.I. Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2) 27 hypertensive rats. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2009; 297(-1-):R111-R115. >>> Antibody, rabbit anti-rat ANG (1-12); immunoglobulin G, rabbit; CSF, artificial; CSF/CNS; Rat (transgenic); 2ML2; 14 days; Controls received mp w/ IgG; functionality of mp verified by residual volume; no stress (see pg. R111, R112); stability verified by activity of agent in residual volume, 91-98% on day 13; antihypertensive; ALZET brain infusion 2 kit; animal info (male, (mRen2)27 Tg, 22-28 wks old, 550g.); cannula placement confirmed at end of each study.

P9248 Poesen,K., Lambrechts,D., Van Damme,P., Dhondt,J., Bender,F., Frank,N., Bogaert,E., Claes,B., Heylen,L., Verheyen,A., Raes,K., Tjwa,M., Eriksson,U., Shibuya,M., Nuydens,R., Van den Bosch,L., Meert,T., D'Hooge,R., Sendtner,M., Robberecht,W., Carmeliet,P. Novel Role for Vascular Endothelial Growth Factor (VEGF) Receptor-1 and Its Ligand VEGF-B in Motor Neuron Degeneration. Journal of Neuroscience 2008; 28(-42-):10451-10459. >>> Vascular endothelial growth factor-B186, recomb. mouse; CSF, artificial; CSF/CNS; Rat; 2004; 100 days; Controls received mp w/ vehicle; long-term study; pumps replaced every 25 days; no stress (see pg. 10456); stability verified by 4 weeks in mp at 37 degrees Celsius; animal info (HAN-Wistar x Sprague Dawley-hSOD1G93A, 60 days old); behavioral testing (Rotarod test); "this delivery route was chosen because previous studies demonstrated that intracerebroventricularly delivered VEGF diffuses from the CSF into the neural parenchyma, where it reaches it's target motor neurons." (p. 10456).

P9237 Galvao,R.P., Garcia-Verdugo,J.M., varez-Buylla,A. Brain-Derived Neurotrophic Factor Signaling Does Not Stimulate Subventricular Zone Neurogenesis in Adult Mice and Rats. Journal of Neuroscience 2008; 28(-50-):13368-13383. >>> Ara-C; brain-derived neurotrophic factor; Saline; BSA; CSF/CNS; Rat; mice; 1007D; 2002; 6, 14 days; Controls received mp w/ vehicle; functionality of mp verified by weight loss due to BDNF's appetite suppression (p. 13377), residual volume; stability verified by testing activity of residual BDNF volume after 14 days/37 degrees Celsius; brain tissue distribution; peptides; post op. care (Buprenorphine); animal info (male, Sprague Dawley, 250 g., male CD-1 3 mo old); mp/cannula placement visually confirmed after brain sectioning.

P9209 Ohta,Y., Kamiya,T., Nagai,M., Nagata,T., Morimoto,N., Miyazaki,K., Murakami,T., Kurata,T., Takehisa,Y., Ikeda,Y., Asoh,S., Ohta,S., Abe,K. Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience Research 2008; 86(-13-):3028-3037. >>> TAT-GFP; TAT-Bcl-XL; CSF, artificial; CSF/CNS (intrathecal); Mice; mice (transgenic); 2001; 2004; 7, 28 days; Controls received mp w/ vehicle; stability verified by antiapoptotic effect at 7, 14, and 28 days at 37 degree Celsius (p. 3031); peptides; animal info (male, B6SJL, wt, G93A SOD1 Tg, 91 days old); neurodegenerative (ALS); behavioral testing (Rotarod test, wheel running test); "intrathecal infusion of TAT-infused proteins using an osmotic minipump is a better method of delivering therapeutic proteins into the spinal cord." (p. 3035).

P8979 Susic,D., Zhou,X.Y., Frohlich,E.D., Lippton,H., Knight,M. Cardiovascular effects of prorenin blockade in genetically spontaneously hypertensive rats on normal and high-salt diet. American Journal of Physiology-Heart and Circulatory Physiology 2008; 295(-3-):H1117-H1121. >>> PRAM-1; Water, distilled; SC; Rat; 2ML4; 4, 8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced after 4 weeks; stability verified; cardiovascular; peptides; animal info (male, SHR, 20 wks old); PRAM-1 is a custom synthesized prorenin inhibitor; "no degradation products of the peptide were observed".

P8953 Knedla,A., Riepl,B., Lefevre,S., Kistella,S., Grifka,J., Straub,R.H., Gay,S., Schoelmerich,J., Mueller-Ladner,U., Neumann,E. The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mouse model for rheumatoid arthritis. Annals of the Rheumatic Diseases 2008; 68(-1-):124-129. >>> Interleukin-10; interleukin-1 receptor antagonist; Saline; DMSO; SC; Mice (SCID); 2004; 40 days; Controls received mp w/ vehicle; functionality of mp verified by plasma levels; good methods (p.125); peptides; animal info (female, SCID, 4-5 wks old); Rheumatoid arthritis; pump and technique schematics p. 125; stability (with an excellent description of methods) was verified for 40 days @ 37C; 50% DMSO used; "... the application of proteins via osmotic pumps is an affective tool to evaluate the effects of cytokines and inhibitors in vitro." p. 128.

P8928 Tejeda,M., Gaal,D., Hullan,L., Csuka,O., Schwab,R., Szokolocz,O., Keri,G. A comparison of the tumor growth inhibitory effect of intermittent and continuous administration of the somatostatin structural derivative TT-232 in various human tumor models. Anticancer Research 2006; 26(-4B-):3011-3015. >>> TT-232; Water, distilled; acetic acid; sodium acetate; mannitol; SC; Mice (SCID); 2002; 14, 28 days; Comparison of IP, SC injections vs. SC mp; stability verified by 3 weeks at 37 degree Celsius by HPLC analysis for agent + degradation products; cancer (epidermoid carcinoma, breast carcinoma); peptides; animal info (female, SCID, 22-24 g.); somatostate structural derivative; "The comparative experiments (injection and infusion) confirmed that continuous treatments and long-term administration were associated with the best treatment responses" (p. 3014); "Continuous infusion administration of TT-232 significantly inhibited the growth of the tumor when compared with intraperitoneal (ip) and subcutaneous (sc) intermittent injection treatments." (p. 3011).

P8852 Wang,H.Y., Ghosh,A., Baigude,H., Yang,C.S., Qiu,L.H., Xia,X.G., Zhou,H.X., Rana,T.M., Xu,Z.S. Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progression. Journal of Biological Chemistry 2008; 283(-23-):15845-15852. >>> RNA, small interfering, modified; RNA, small interfering; PBS; CSF/CNS (intrathecal, subarachnoid space); Mice (transgenic); 1007D; 2004; 7, 28 days; 72 hours; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (Fig. 3); no stress (see pg. 15846, 15849); stability verified by 28 days in vivo (see Fig. 2); half-life (p. 15846) "short"; gene therapy; brain tissue distribution; animal info (SOD1G93A Tg); neurodegenerative (ALS); mp + catheter positioning confirmed; Target (SOD1); "when infused at disease onset at the therapeutic dose for 4 weeks, this siRNA slows disease progression without detectable adverse effects." The catheter was implanted between the L5 and L6 vertebra and connected to a primed Alzet osmotic pump with the PE50 tube. The catheter was stitched to the surface muscle, and the Alzet osmotic pumps were placed under the skin on the back of the mouse..

P8775 Roa,J., Vigo,E., Garcia-Galiano,D., Castellano,J.M., Navarro,V.M., Pineda,R., Dieguez,C., Aguilar,E., Pinilla,L., Tena-Sempere,M. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2008; 294(-6-):E1088-E1096. >>> Kisspeptin-10; Leptin; Saline, physiological; CSF/CNS; Rat; 2001; 7 days; Controls received mp w/ vehicle; functionality of mp verified by response duration and examination; stability verified by persistent FSH response; peptide; animal info (female, Wistar, 205-275 g., adult, 110-120g., 30 days old).

P8639 Palaniyandi,S.S., Nagai,Y., Watanabe,K., Ma,M., Veeraveedu,P.T., Prakash,P., Kamal,F.A., Abe,Y., Yamaguchi,K., Tachikawa,H., Kodama,M., Aizawa,Y. Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. EXPERIMENTAL BIOLOGY AND MEDICINE 2007; 232(-9-):1213-1221. >>> TY-51469; Phosphate buffer; NaOH; IV (jugular); Rat; 2ML4; 4 weeks; Controls received mp w/ vehicle; dose-response (fig. 2); stability verified by study in rat plasma at 40oC for 1 hour; enzyme inhibitor (chymase); cardiovascular; animal info (male, Lewis, 9 wks old).

P8606 Hagg,T., Baker,K.A., Emsley,J.G., Tetzlaff,W. Prolonged local neurotrophin-3 infusion reduces ipsilateral collateral sprouting of spared corticospinal axons in adult rats. Neuroscience 2005; 130(-4-):875-887. >>> Neurotrophin-3, recomb. human; PBS; gentamicin; albumin, rat serum; CSF/CNS (intrathecal); Rat; 2002; 14 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (fig. 4); stability verified by activity assay of residual mp content after 14 days in vivo; ALZET brain infusion kit used; peptides; post op. care (Penicillin G, buprenorphine); animal info (Sprague-Dawley, 3 months old, 200-220 grams, partial resection of corticospinal tract); schematic of mp p. 877 fig 2.

P8437 Henke,E., Perk,J., Vider,J., de Candia,P., Chin,Y., Solit,D.B., Ponomarev,V., Cartegni,L., Manova,K., Rosen,N., Benezra,R. Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. NATURE BIOTECHNOLOGY 2008; 26(-1-):91-100. >>> Oligonucleotide, antisense, peptide conjugated; oligonucleotide, phosphorothioate antisense; peptide, F3; TBS; SC; Mice (nude); mice; 1007D; 1002; 14, 21 days; Controls received mp w/ vehicle or control peptide and oligo in non-conjugated form, or rcId1-PCAO; comparison of IV injections vs. mp; pumps replaced after 14 days; no stress (see pg. 95, 97); stability verified after 24 hours in 37 C, plasma up to 28 days in 37 C saline; antisense (Id1, rcId1); cancer (breast, lung carcinoma); peptides; toxicology; animal info (female, nude NCR; male, C57J/B6); antisense oligos covalently coupled to address peptide that targets tumor endothelial cells; "no adverse effects on treated mice have been observed." (p. 97).

P8419 Jiang,G.L., Nieves,A., Im,W.B., Old,D.W., Dinh,D.T., Wheeler,L. The prevention of colitis by E prostanoid receptor 4 agonist through enhancement of epithelium survival and regeneration. Journal of Pharmacology and Experimental Therapeutics 2007; 320(-1-):22-28. >>> AGN205203; DMSO; saline, normal; SC; Mice; 1002; 9 days; Controls received mp w/ vehicle; metabolic&chemical stability verified; animal info (femal, C57BL/6, 8 wks old); EP4 agonist.

P8406 Zeevalk,G.D., Manzino,L., Sonsalla,P.K., Bernard,L.P. Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: Relevance to Parkinson's disease. Experimental Neurology 2007; 203(-2-):512-520. >>> Glutathione, monoethyl ester; MPP+; Saline; SC; CSF/CNS; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; dose-response (fig. 6); stability verified by incubation for 0-28 days at 37 celsius, assessed by HPLC; half-life (pg. 515) 10-14 hours in culture; brain tissue distribution; toxicology; animal info (Sprague-Dawley, 300g.); neurodegenerative (Parkinson's disease).

P8305 Mook,O.R., Baas,F., de Wissel,M.B., Fluiter,K. Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. MOLECULAR CANCER THERAPEUTICS 2007; 6(-3-):833-843. >>> RNA, small interfering; RNA, small interfering, LNA-modified; Radio-isotopes, 3H-; SC; Mice (nude); 1007D; 7 days; 48 hours; Controls received mp w/ mismatch siRNA or saline; comparison of IV injections vs. mp; stability verified by incubation in mouse serum; half-life (p. 837) increased in LNA-modified; unmodified completely degraded in<5 hours; cancer (pancreatic); animal info (NMRI nu/nu, 8-10 weeks old); siRNA against RNA polymerase II, enhanced GFP, or mismatch.

P8302 Zhang,X.F., Connolly,C., Duquette,M., Lawler,J., Parangi,S. Continuous administration of the three thrombospondin-1 type 1 repeats recombinant protein improves the potency of therapy in an orthotopic human pancreatic cancer model. Cancer Letters 2007; 247(-1-):143-149. >>> Thrombospondin-1, three type 1 repeats; PBS; SC; Mice (SCID); 1007D; 7 days; Controls received mp w/ vehicle; comparison of IP injections vs. mp; stability verified by incubation in pump, 7 days; cancer (pancreatic); peptides; animal info (female, SCID, 4-6 weeks old); antiangiogenesis therapy; 3TSR; "Continuous administration of 3TSR reduced dosage and improved therapeutic potency." p. 146.

P8289 Banach-Petrosky,W., Ouyang,X.S., Gao,H., Nader,K., Ji,Y., Suh,N., DiPaola,R.S., bate-Shen,C. Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in Nkx3.1; Pten mutant mice. Clinical Cancer Research 2006; 12(-19-):5895-5901. >>> Vitamin D3, 1,25-dihydroxy-; Propylene glycol; SC; Mice; 2004; 1-4 months; Controls received mp w/ vehicle; long-term study; pumps replaced every 4 weeks; stability verified by serum calcium levels; cancer (prostate); animal info (4-7 months old, male).

P8284 Yazdani,U., German,D.C., Liang,C.L., Manzino,L., Sonsalla,P.K., Zeevalk,G.D. Rat model of Parkinson's disease: Chronic central delivery of 1-methyl-4-phenylpyridinium (MPP+). Experimental Neurology 2006; 200(-1-):172-183. >>> MPP+; Saline-iodine; CSF/CNS; Rat; 2ML4; 14 days; Stability verified by HPLC, 28 days; animal info (male, Sprague-Dawley, 300-350 grams); neurodegenerative (Parkinson's Disease); "This study presents a chronic model of PD in rats that encompasses the desirable components of current chronic models while reducing their less desirable aspects." P. 181.

P8266 Urushitani,M., bou Ezzi,S., Julien,J.P. Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-7-):2495-2500. >>> Antibody, mouse anti hSOD1; antibody, rabbit polyclonal anit-hSOD1-FITC; Saline; CSF/CNS; Mice; 2004; 16, 28 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; stability verified by Western Blot w/ residual volume AB after 18 days infusion; brain tissue distribution; animal info (G93A SOD1, 85 days old); neurodegenerative (ALS).

P8236 Lecanu,L., Greeson,J., Papadopoulos,V. Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain. Pharmacology 2006; 76(-1-):19-33. >>> Amyloid protein, beta 42; ferrous sulfate; buthionine sulfoximine; CSF, artificial; water, distilled; CSF/CNS; Rat; 2ML4; 4 weeks; Controls received mp w/ vehicle; stability verified by 14 days in mp at 37 C; animal info (male, Long-Evans, 3-4 month old, 300-325 grams); neurodegenerative (Alzheimer's disease).

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).

P8096 Gosain,A., Matthies,A.M., Dovi,J.V., Barbul,A., Gamelli,R.L., DiPietro,L.A. Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression. Journal of Surgical Research 2006; 135(-2-):218-225. >>> Vascular endothelial growth factor 164, recomb.; platelet-dreived growth factor; fibroblast growth factor-2; Wound site; Mice; 2002; 11 days; Controls received mp w/ PBS; functionality of mp verified by VEGF levels in wound sponges, residual volume; stability verified by activity of residual VEGF in endothelial cell cord formation assay (fig.4); cardiovascular; peptides; animal info (female, BALB/c, 8-9 wks old, implanted sponge wounds); "The activity of VEGF isolated from the pump was comparable to fresh recombinant VEGF 164, confriming that the recombinant growth factors present in the mini-osmotic pump retain robust biological activity." (p.221).

P8052 Brown,J.R., Fuster,M.M., Li,R.X., Varki,N., Glass,C.A., Esko,J.D. A disaccharide-based inhibitor of glycosylation attenuates metastatic tumor cell dissemination. Clinical Cancer Research 2006; 12(-9-):2894-2901. >>> Disaccharide, AcGnG-NM; DMSO; propylene glycol; SC; Mice; 2004; 2, 4 weeks; Controls received mp w/ vehicle; stability verified by incubation in mouse serum; cancer (lung carcinoma, B16Bl6 melanoma); animal info (c57BL/6 Es1(e); 8-12 wk old, lung metastases); 50% DMSO used; 50% propylene glycol used.

P8015 Vrang,N., Madsen,A.N., Tang-Christensen,M., Hansen,G., Larsen,P.J. PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity. Am.J.Physiol Regul.Integr.Comp Physiol 2006/8; 291(-2-):R367-R375. >>> Peptide YY (3-36); Saline, isotonic; SC; Mice; rat; 2004; 2ML4; 28 days; Stability verified by in vitro test, degradation was<0.5%/day; peptides; animal info (C57BL/6, DIO and rats, Wistar and Sprague-Dawley); gut hormone; SC administration of PYY (3-36) for 28 days reduced body weight and improved glycemic control.

P7973 Bartolomucci,A., La Corte,G., Possenti,R., Locatelli,V., Rigamonti,A.E., Torsello,A., Bresciani,E., Bulgarelli,I., Rizzi,R., Pavone,F., D'Amato,F.R., Severini,C., Mignogna,G., Giorgi,A., Schinina,M.E., Elia,G., Brancia,C., Ferri,G.L., Conti,R., Ciani,B., Pascucci,T., Dell'Omo,G., Muller,E.E., Levi,A., Moles,A. TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006; 103(-39-):14584-14589. >>> TLQP-21, synthetic; CSF, artificial; CSF/CNS; Mice; 1002; 14 days; Controls received mp w/ vehicle; stability verified by HPLC after 14 days at 37 C; ALZET brain infusion kit 1 used; peptides; animal info (male, CD1); obesity.

P7956 Di,Cristo G., Berardi,N., Cancedda,L., Pizzorusso,T., Putignano,E., Ratto,G.M., Maffei,L. Requirement of ERK activation for visual cortical plasticity. Science 2001/6/22; 292(-5525-):2337-2340. >>> U0126; PD-98059; SB203580; CSF/CNS (visual cortex); Rat; 1 week; Controls received mp w/ vehicle; stability verified by inhibition of ERK activation by picrotoxin; enzyme inhibitor (p38 MAP kinase); animal info (Dark-reared, P28); tissue perfusion (visual cortex).

P7942 Berni,R., Cacciani,F., Zaniboni,M., Savi,M., Bocchi,L., Lapucci,S., Razzetti,R., Pastore,F., Musso,E., Stilli,D. Effects of the alpha 2-adrenergic/DA2-dopaminergic agonist CHF-1024 in preventing ventricular arrhythmogenesis and myocyte electrical remodeling, in a rat model of pressure-overload cardiac hypertrophy. Journal of Cardiovascular Pharmacology 2006; 47(-2-):295-302. >>> CHF-1024; Saline; ascorbic acid; SC; Rat; 2ML4; 1 month; Controls received mp w/ vehicle; functionality of mp verified by plasma levels; dose-response (table 1); stability verified for at least 1 month (pg. 296); cardiovascular; post op. care (gentamicin); animal info (male, Wistar, 6 months old); "a clear dose dependency was found in CHF-1024 plasma levels, indicating a good performance of the osmotic pumps in drug release." (p. 299).

P7940 Ambati,J., Gragoudas,E.S., Miller,J.W., You,T.T., Miyamoto,K., Delori,F.C., Adamis,A.P. Transscleral delivery of bioactive protein to the choroid and retina. Invest Ophthalmol.Vis.Sci. 2000/4; 41(-5-):1186-1191. >>> Immunoglobulin G, FITC-, rabbit; antibody, monoclonal mouse anti-ICAM-1; immunoglobulin, mouse IgG2a; Eye (superotemporal scleral surface, transscleral); Rabbit; 2001D; 2ML4; 3,5,13,20,28 days; 24 hours; Controls received mp w/ control Ab; functionality of mp verified by fluorescence in occular tissues and plasma mAb levels; stability verified by efficacy experiments, FITC linkage timing; half-life (p. 1188), 3 days; ALZET brain infusion kit used; animal info (dutch-belted, pigmented); "We have developed a minimally invasive transscleral drug delivery modality that can deliver therapeutic concentrations of bioactive proteins to the choroid and retina without significant systemic absorption or tissue damage." (P. 1186-87).

P7900 Thompson,E.L., Murphy,K.G., Patterson,M., Bewick,G.A., Stamp,G.W.H., Curtis,A.E., Cooke,J.H., Jethwa,P.H., Todd,J.F., Ghatei,M.A., Bloom,S.R. Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2006; 291(-5-):E1074-E1082. >>> Kisspeptin-54; Saline; SC; Rat; 2001D; 2001; 2002; 1, 2, 3, 13 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; comparison of SC injection vs. mp; no stress (see pg. E1078); stability verified by 14 days in mp in 37 celsius saline (see fig. 2); good methods pg. E1075; peptides; post op. care (flucloxacillin, amoxicillin); animal info (male, Wistar, 275-325g.); mp primed for 3hrs. (2001D) or overnight (2001, 2002) in 37 celsius saline; "animals were healthy throughout the study period. No adverse behaviors were observed in any of the treatment groups at any point during the study." (pg. E1078).

P7844 Royo,N.C., Conte,V., Saatman,K.E., Shimizu,S., Belfield,C.M., Soltesz,K.M., Davis,J.E., Fujimoto,S.T., McIntosh,T.K. Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection. European Journal of Neuroscience 2006; 23(-5-):1089-1102. >>> Neurotrophin-4/5; PBS; BSA; CSF/CNS (somatosensory cortex); Rat; 1007D; 1 week; Controls received mp w/ vehicle; no stress (see pg. 1095); stability verified by activity after 14 days in mp at 37 celsius; ALZET brain infusion kit II used; peptides; animal info (male, Sprague-Dawley, 350-400g., traumatic brain injury by lateral fluid percussion); mp primed 18 hours at 37 celsius.

P7843 Yamaguchi,Y., Miyashita,H., Tsunekawa,H., Mouri,A., Kim,H.C., Saito,K., Matsuno,T., Kawashima,S., Nabeshima,T. Effects of a novel cognitive enhancer, spiro[imidazo[1,2-a]pyridine-3,2- indan]-2(3H)-one (ZSET1446), on learning impairments induced by amyloid-beta (1-40) in the rat. Journal of Pharmacology and Experimental Therapeutics 2006; 317(-3-):1079-1087. >>> Amyloid protein, beta (1-40); amyloid protein, beta (40-1); Acetonitrile; trifluoroacetic acid; CSF/CNS; Rat; 2002; 15 days; Controls received mp w/ vehicle, or AB (40-1); stability verified by testing in solution at 37 celsius (pg. 1080); neurodegenerative (alzheimer's disease); animal info (male, Wistar, 7 wk. old); "An animal model induced by chronic intracerebroventricular (i.c.v.) infusion of AB is particularly attractive for evaluation of drugs for AD because change is similar to those known for AD patients" (pg. 1080); 35% acetonitrile used.

P7817 Igwe,O.J. Agents that act by different mechanisms modulate the activity of protein kinase C beta II isozyme in the rat spinal cord during peripheral inflammation. Neuroscience 2006; 138(-1-):313-328. >>> L-703606 oxalate; dextrorphan tartrate; oligodeoxynucleotide, phosporothioate antisense; phosporothioate missense; Propylene glycol; water, sterile; saline; oligofectamine; SC; Rat; 2001; 7 days; Controls received mp w/ vehicle; dose-response (fig 1); stability verified; antisense (protein kinase C, beta); animal info (male, Sprague-Dawley, 200-300 grams); "mini osmotic pumps were used to administer all agents in order to reduce animal handling after CFA-induced inflammation." (p. 315).

P7757 Winaver,J., Ovcharenko,E., Rubinstein,I., Gurbanov,K., Pollesello,P., Bishara,B., Hoffman,A., Abassi,Z. Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure. American Journal of Physiology-Heart and Circulatory Physiology 2006; 290(-5-):H2007-H2014. >>> Y-27632; Saline; IP; Rat; 2001; 7 days; Controls received mp w/ vehicle; stability verified by assesment in saline and plasma at 37celsius for up to 500 min.; enzyme inhibitor (Rho Kinase); cardiovascular; animal info (male, Wistar, 280-350g., CHF).

P7702 Guarnieri,M., Biser-Rohrbaugh,A., Tyler,B.M., Gabikian,P., Bunton,T.E., Wu,Q.Z., Weingart,J., Carson Sr,B.S. Toxicity of intracranial and intraperitoneal O6-benzyl guanine in combination with BCNU delivered locally in a mouse model. Cancer Chemother.Pharmacol. 2002/11; 50(-5-):392-396. >>> Benzylguanine, 06-; Propylene glycol; ethanol; IP; CSF/CNS (parietal lobe); Mice; 2001; 7 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (table 2); comparison of IP injection vs. mp; stability verified by 14 days at 37 C, UV spectra analysis; good methods (p. 393); cancer (glioma brain); toxicology; animal info (female, BALB/C, 6-12 weeks old); 10% ethanol used.

P7563 Ikegami,T., Nakamura,M., Yamane,J., Katoh,H., Okada,S., Iwanami,A., Watanabe,K., Ishii,K., Kato,F., Fujita,H., Takahashi,T., Okano,H.J., Toyama,Y., Okano,H. Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury. European Journal of Neuroscience 2005; 22(-12-):3036-3046. >>> Chondroitinase ABC; Saline, physiological; CSF/CNS (intrathecal, subarachnoid space); Rat; 2001; 1 week; Controls received mp w/ heat inactivated agent; stability verified by ALZAID chemical compability test kit for 7 days; animal info (adult, female, Sprague-Dawley 230-250 g); mp primed overnight in 37 C saline; spinal cord injury.

P7559 Chan,C.C.M., Khodarahmi,K., Liu,J., Sutherland,D., Oschipok,L.W., Steeves,J.D., Tetzlaff,W. Dose-dependent beneficial and detrimental effects of ROCK inhibitor Y27632 on axonal sprouting and functional recovery after rat spinal cord injury. Experimental Neurology 2005; 196(-2-):352-364. >>> Y-27632; streptomycin; PBS, sterile; penicillin; CSF/CNS (intrathecal); Rat; 2002; 2 weeks; 2, 4 days; Controls received mp w/ vehicle; functionality of mp verified by ROCK inhibitory activity in CSF; dose-response (fig. 3); stability of Y27632 verified by ROCK inhibitory activity after 13 days in mp at 37 C; enzyme inhibitor (RHO Kinase); animal info (male, Sprague-Dawley); cervical 4/5 dorsal column transection; spinal cord injury.

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).

P7519 Kennedy,D.J., Vetteth,S., Periyasamy,S.M., Kanj,M., Fedorova,L., Khouri,S., Kahaleh,M.B., Xie,Z.J., Malhotra,D., Kolodkin,N.I., Lakatta,E.G., Fedorova,O.V., Bagrov,A.Y., Shapiro,J.I. Central role for the cardiotonic steroid marinobufagenin in the pathogenesis of experimental uremic cardiomyopathy. Hypertension 2006; 47(-3-):488-495. >>> Marinobufagenin; Rat; 2004; 4 weeks; Controls received sham operation; functionality of mp verified by agent plasma levels; comparison of partial nephrectomy vs. mp; stability verified for 4 weeks at 37 C by comparable inhibition of 86Rb uptake; cardiovascular; animal info (male, Sprague-Dawley).

P7500 Lotinun,S., Sibonga,J.D., Turner,R.T. Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts. Endocrinology 2005; 146(-9-):4074-4081. >>> Parathyroid hormone, human 1-34; thymidine, methyl -3H; Sodium chloride; HCl; serum, rat; ethanol; SC; Rat; 1, 2, 4 weeks; 1, 3, 5 days; Controls received mp w/ vehicle; functionality of mp verified by serum PTH; pumps replaced after 2 weeks; stability verified; peptides; multiple pumps per animal (2); animal info (female, Sprague-Dawley, 260 g); 2% ethanol.

P7497 Elitok,S., Brodsky,S.V., Patschan,D., Orlova,T., Lerea,K.M., Chander,P., Goligorsky,M.S. Cyclic arginine-glycine-aspartic acid peptide inhibits macrophage infiltration of the kidney and carotid artery lesions in apo-E-deficient mice. American Journal of Physiology-Renal Physiology 2006; 290(-1-):F159-F166. >>> Peptide, CRGD; peptide, CRAD; SC; Mice; 1002; 2004; 14, 28 days; Controls received mp w/ PBS; functionality of mp verified by platelet aggregation inhibitory properties and residual volume; dose-response (fig. 3); stability verified by mass spec of residual volume; half-life (p. F160); peptides; animal info (female, C57BL6, 7 weeks, 290 g); cartoid artery ligation.

P7467 Oldroyd,S.D., Miyamoto,Y., Moir,A., Johnson,T.S., El Nahas,A.M., Haylor,J.L. An IGF-I antagonist does not inhibit renal fibrosis in the rat following subtotal nephrectomy. American Journal of Physiology-Renal Physiology 2006; 290(-3-):F695-F702. >>> Insulin-like growth factor I, receptor antagonist; SC; Rat; 2002; 2004; 10, 90 days; Controls received mp w/ vehicle, or sham operation; dose-response (fig. 3); long-term study; pumps replaced every 4 weeks; stability verified by storage in mp for 4 weeks; peptides; animal info (male, wistar, chronic kidney disease, 200-300 g); IGF-I receptor antagonist (JB3); mp primed 4 hr in 37C isotonic saline.

P7394 Guarnieri,M., Carson,B.S., Khan,A., Penno,M., Jallo,G.I. Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues. Journal of Neuroscience Methods 2005; 144(-2-):147-152. >>> Doxorubicin; carboblatin; Dextrose solution; saline; CSF/CNS (parenchyma); Rat; 2001; ; Animal info (F, Fischer, 220 g); Functionality of mp verified by pump examination, post infusion; stability verified by previous studies, 14 days; good methods (p. 148); cancer (glioma); brain tissue distribution; Plastics One cannula used (stainless steel); "replacement of rigid infusion tubes [cannulae] with flexible tubing increases the reliability of local CNS drug infusions. Rigid catheters [cannulae] may allow backflow of the infused drug along the path of the catheters into the subdural space." (P. 147).

P7267 Fluiter,K., Frieden,M., Vreijling,J., Rosenbohm,C., de Wissel,M.B., Christensen,S.M., Koch,T., Orum,H., Baas,F. On the in vitro and in vivo properties of four locked nucleic acid nucleotides incorporated into an anti-H-Ras antisense oligonucleotide. CHEMBIOCHEM 2005; 6(-6-):1104-1109. >>> Oligodeoxynucleotide, antisense; oligodeoxynucleotide, amino-LNA antisense; oligodeoxynucleotide, thio-LNA antisense; oligodeoxynucleotide, LNA antisense; oligodeoxynucleotide, missense; SC; Mice (nude); 1002; 11 days; 48 hours; Controls received mp w/ saline; dose-response (fig. 4); no stress (see pg. 1106); stability verified by incubation in human serum; antisense (H-Ras); cancer (prostate).

P7265 Ji,B.X., Li,M.W., Budel,S., Pepinsky,R.B., Walus,L., Engber,T.M., Strittmatter,S.M., Relton,J.K. Effect of combined treatment with methylprednisolone and soluble Nogo-66 receptor after rat spinal cord injury. European Journal of Neuroscience 2005; 22(-3-):587-594. >>> Nogo-66 receptor (27-310) ecto-Fc; immunoglobulin G, rat; PBS; CSF/CNS (intrathecal); Rat; 2004; 28 days; Controls received mp w/ vehicle rat IgG; functionality of mp verified by residual volume; stability verified by analysis of remaining mp contents; post op. care (buprenorphine/buprenex, ampicillin); spinal cord injury.

P7264 Boesen,E.I., Anderson,W.P., Kett,M.M. Role of endothelin in noradrenaline-induced hypertension in rats. Journal of Hypertension 2005; 23(-5-):987-993. >>> Noradrenalin; TAK-044; heparin; Saline, heparinized; ascorbic acid; saline; IV (vena cava); Rat; 2ML2; 24 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (fig. 2); pumps replaced at day 10; no stress (see pg. 989); stability verified by acute pressor activity after 14 days at 37 degrees celsius in mp; cardiovascular; multiple pumps per animal (2); 10 IU/ml of heparin.

P7183 Migneault,A., Sauvageau,S., Villeneuve,L., Thorin,E., Fournier,A., Leblanc,N., Dupuis,J. Chronically elevated endothelin levels reduce pulmonary vascular reactivity to nitric oxide. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2005; 171(-5-):506-513. >>> Endothelin-1; Water; IV (jugular); Rat; 7, 20 days; Controls received sham surgery; functionality of mp verified by plasma E7-1 levels; stability verfied by 7 and 28 day incubation at 37 degrees celsius and HPLC; cardiovascular; peptides.

P7137 Baker,S.A., Baker,K.A., Hagg,T. D3 dopamine receptors do not regulate neurogenesis in the subventricular zone of adult mice. NEUROBIOLOGY OF DISEASE 2005; 18(-3-):523-527. >>> DPAT, 7-hydroxy-U-99194A maleate; Saline; CSF/CNS; CSF/CNS (neostriatum); Rat; mice; 1002; 14 days; Controls received mp w/ vehicle; dose-response; comparison of IP injections vs. mp; stability verified by BrdU labeling; cyanoacrylate adhesive used.

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).

P7099 Benn,S.C., Ay,I., Bastia,E., Chian,R.J., Celia,S.A., Pepinsky,R.B., Fishman,P.S., Brown,RH Jr, Francis,J.W. Tetanus toxin fragment C fusion facilitates protein delivery to CNS neurons from cerebrospinal fluid in mice. Journal of Neurochemistry 2005; 95(-4-):1118-1131. >>> Toxin, tetanus fragment C; tempol, toxin tetanus fragment C; CSF/CNS; Mice; 2001; 7 days; Stability verified by incubation at 37C for 7 days; brain tissue distribution; post op. care (bupivicaine and betadine in wound); animal info (C57BL/6, male, 25-30 g); dental cement used for cannula adhesion, agent also know as TTC; compounds were also distributed to further brain sites such as the hypothalamus and the thalamus.

P7077 Lefranc,F., Mijatovic,T., Mathieu,V., Rorive,S., Decaestecker,C., Debeir,O., Brotchi,J., Van Ham,P., Salmon,I., Kiss,R. Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells. Clinical Cancer Research 2004; 10(-24-):8250-8265. >>> Gastrin-17; Saline; CSF/CNS (intratumoral); Rat (nude); 1002; 7 days; Controls received mp w/ vehicle; stability verified; cancer (glioma).

P7068 Harris-White,M.E., Balverde,Z., Lim,G.P., Kim,P., Miller,S.A., Hammer,H. Role of LRP in TGFbeta2-mediated neuronal uptake of A beta and effects on memory. Journal of Neuroscience Research 2004; 77(-2-):217-228. >>> Amyloid protein, beta; transforming growth factor-B2; receptor-associated protein; HEPES buffer; CSF/CNS; Mice; 1002; 2 weeks; Controls received mp w/ vehicle; stability verified by incubation at 37 degree Celsius for 2,4 weeks; peptides; RAP is a LRP (lipoprotein receptor-related protein) antagonist; memory.

P7008 DeKosky,S.T., Abrahamson,E.E., Taffe,K.M., Dixon,C.E., Kochanek,P.M., Ikonomovic,M.D. Effects of post-injury hypothermia and nerve growth factor infusion on antioxidant enzyme activity in the rat: implications for clinical therapies. Journal of Neurochemistry 2004; 90(-4-):998-1004. >>> Nerve growth factor; CSF, artificial; CSF/CNS; Rat; 2002; 1,3 days; Controls received mp w/ vehicle; stability verified by increased ChAT activity.

P6953 Thaete,L.G., Kushner,D.M., Dewey,E.R., Neerhof,M.G. Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. PLACENTA 2005; 26(-2-3-):242-250. >>> L-NAME; A-127722; Saline; ethyl alcohol; NaOH; water; propylene glycol; SC; Rat (pregnant); 2ML1; 1,4,7 days; Functionality of mp verified by residual volume; stability verified by prior experiment (24 days); multiple pumps per animal (2); drugs infused in separate pumps; A-127722 (ETA receptor antagonist) was dissolved in 20% alcohol, 40% PG and 0.04 M of NaOH.

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).

P6894 Tejeda,M, Gaal,D., Csuka,O., Keri,G.Y. Growth Inhibitory Effect of the Somatostatin Structural Derivative (TT-232) on Leukemia Models. Anticancer Research 2005; 25(--):325-330. >>> TT-232; Acetic acid; sodium acetate; water; mannitol; IV; SC; Mice; 2002; 14, 28 days; Dose-response (p. 328, fig 1); comparison of IP/SC injections vs. SC/IV mp; pumps replaced at day 14 for 28 day group; stability verified, 37 degrees Celsius for over 3 weeks; cancer (leukemia); TT-232 is a novel somatostatin analog; "The IV infusion for 28 days resulted in 82% growth inhibition." (p. 328); "The infusion of TT-232 by ALZET osmotic minipump resulted in 70-80% tumor growth inhibition and 20% tumor free survival." (p. 329); "…serial injections represent significant stress to the animals…" "To reduce and eliminate the above mentioned problem [stress] we used an ALZET osmotic minipump…" "Infusion from inserted ALZET minipumps maintains a constant drug level, resulting in a well defined, consistent pattern of drug exposure throughout the period of drug administration." "These studies suggest that TT-232 is a potent inhibitor of leukemia tumor in vitro and in vivo and suggest infusion treatment as a beneficial application in clinical practice." (p. 330); oligopeptide; enzyme inhibitor (tyrosine kinase); animal info (CBA/ca, immunosuppressed, female).

P6599 Guimaraes,M.A.M., Nikolovski,J., Pratt,L.M., Greive,K., Comper,W.D. Anomalous fractional clearance of negatively charged Ficoll relative to uncharged Ficoll. American Journal of Physiology-Renal Physiology 2003; 285(-6-):F1118-F1124. >>> Ficoll, 3H-carboxymethyl; Rat; 2001; 7 days; Functionality of mp verified by GFR and UFR; comparison of IV injections vs. mp; stability verified by ion exchange chromatography of 3H-carboxymethyl ficoll collected on day 7.

P6559 Skuladottir,G.V., Olason,P.I., Jonsson,L., Skarphedinsson,J.O., Eriksdottir,V.H., Atlason,P.T., Franzson,L., Schioeth,H.B. Hyperphagia modifies FA profiles of plasma phospholipids, plasma FFA, and adipose tissue TAG. Lipids 2003; 38(-11-):1127-1132. >>> HS024; CSF, artificial; CSF/CNS; Rat; 2004; 8,28 days; Controls received mp w/ vehicle; stability verified by HPLC&MS weekly; ALZET brain infusion kit; peptides; Melanocortin receptor antagonist.

P6539 Locher,C.P., Witt,S.A., Ashlock,B.M., Levy,J.A. Evaluation of genetic immunization adjuvants to improve the effectiveness of a human immunodeficiency virus type 2 (HIV-2) envelope DNA vaccine. DNA and Cell Biology 2004; 23(-2-):107-110. >>> DNA, plasmid; Gene, HIV-2 gpl40; SC; Mice; 2004; 28 days; 28 day stability verified by agarose gel electrophoresis; immunology; different methods of immunization used; genetic immunization; DNA did not adhere to the osmotic minipump after 1 month since DNA concentration remained stable and intact.

P6497 Tejeda,M., Gaal,D., Barna,K., Csuka,O., Keri,G. The antitumor activity of the somatostatin structural derivative (TT-232) on different human tumor xenografts. Anticancer Research 2003; 23(-5A-):4061-4066. >>> TT-232; Acetic acid; sodium acetate; water, distilled; mannitol; SC; Mice; 2002; 14,28 days; Dose-response (fig.2); comparison of daily SC injections vs. mp; pumps replaced at day 14; stability verified over 3 weeks; cancer (prostate, breast, colon, melanoma, leukemia); peptides; "a significant antitumor activity of TT-232 was observed following long-term infusion using osmotic minipumps" (p. 4064).

P6378 Monassier,L., Greney,H., Thomas,L., Bousquet,P. Chronic treatment with rilmenidine in spontaneously hypertensive rats: Differences between two schedules of administration. Journal of Cardiovascular Pharmacology 2004; 43(-3-):394-401. >>> Rilmenidine; Saline; IP; Rat; 2002; 1 month; Comparison of IP injections vs. IP mp; pumps replaced at 15 days; stability verified (30 days at 37 degrees Celsius); cardiovascular; antihypertensive.

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; 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.

P6245 Froidevaux,S., Eberle,A.N. Homologous regulation of melanocortin-1 receptor (MC1R) expression in melanoma tumor cells in vivo. JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH 2002; 22(-1-4-):111-121. >>> Melanocyte-stimulating hormone, a-; Citric Acid; sodium chloride; SC; Mice (SCID); 1002; 3-14 days; Comparison of IV injections vs. mp; stability verified by HPLC analysis after 2 week peptide incubation @ 37ºC; cancer (melanoma); peptides.

P6192 Dunaiski,V., Belford,D.A. Contribution of circulating IGF-I to wound repair in GH-treated rats. GROWTH HORMONE&IGF RESEARCH 2002; 12(-6-):381-387. >>> Insulin-like growth factor I; Acetic acid; IP; Rat; 2001; 7 days; Controls received mp w/ vehicle; stability verified by daily animal weight gain; imunology; peptides.

P6188 Debeir,T., Marien,M., Chopin,P., Martel,J.C., Colpaert,F., Raisman-Vozari,R. Protective effects of the alpha2-adrenoceptor antagonist, dexefaroxan, against degeneration of the basalocortical cholinergic system induced by cortical devascularization in the adult rat. Neuroscience 2002; 115(-1-):41-53. >>> Dexefaroxan; Water, distilled; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; stability verified by independent exp for 28d; neurodegenerative (Alzheimer's disease); neurology.

P6129 Seeds,N.W., Basham,M.E., Ferguson,J.E. Absence of tissue plasminogen activator gene or activity impairs mouse cerebellar motor learning. Journal of Neuroscience 2003; 23(-19-):7368-7375. >>> Plasminogen activator inhibitor-1; tissue plasminogen activator, STOP; CSF, artificial; CSF/CNS (cerebellum); Mice; 1007D; 7 days; Controls received mp w/ vehicle; stability verified by amidolytic assays (tpa-STOP); good methods (p. 7369); half-life (p. 7369, 145 hours); ALZET brain infusion kit 1 used; recovery period; PAI-1 was recomb. mutant; "pump implantation and subsequent infusion of either aCSF or PAI-1 did not impair the mice's ability to perform a previously learned motor task." p. 7372; behavioral study.

P6115 Wang,H., White,R., Leenen,F.H.H. Stimulation of brain Na(+) channels by FMRFamide in Dahl SS and SR rats. American Journal of Physiology-Heart and Circulatory Physiology 2003; 285(-5-):H2013-H2018. >>> FMRFamide; CSF, artificial; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle; blood pressure taken; stability verified by keeping solution at room temp. for 1 wk; cardiovascular; peptides; CSF production rate mentioned (p. H2014); FMRFamide dissolved in aCSF with a pH of 7.4 and stored at -20 celsius was found to be stable for 1 yr of storage.

P5850 Richardson,R.D., Omachi,K., Kermani,R., Woods,S.C. Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2002; 283(-6-):R1321-R1326. >>> Insulin, porcine; CSF, artifical; CSF/CNS (third ventricle); Rat; 2002; 14 days; Controls received mp w/ vehicle; stability verified by past experiment >11 days stable p.322; peptides; two cannulae used, one in the 3rd ventricle&the other in the right ventricle; 3 day recovery; two cannula systems used so that acute administration of compounds (via lateral ventricle) would not interfere w/ continuous infusion of a second solution (via the third ventricle).

P5832 Miller,A.L., Prieskorn,D.M., Altschuler,R.A., Miller,J.M. Mechanism of electrical stimulation-induced neuroprotection: effects of verapamil on protection of primary auditory afferents. Brain Research 2003; 966(-2-):218-230. >>> Verapamil; Perilymph, artifical; Ear (cochlea); guinea-pig; 2002; 6 weeks; 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);.

P5817 Shinkai,N., Takasuna,K., Takayama,S. Inhibitory effects of formoterol on lipopolysaccharide-induced premature delivery through modulation of proinflammatory cytokine production in mice. REPRODUCTION 2003; 125(-2-):199-203. >>> Endothelin-1; IV (femoral); Rat; 2002; ; Funcionality of mp verified by pump assessment; 2-week stability verified by previous studies by other groups; ET-1 plasma levels measured.

P5688 Abella,A., Marti,L., Camps,M., Claret,M., Fernandez-Alvarez,J., Gomis,R., Guma,A., Viguerie,N., Carpene,C., Palacin,M., Testar,X., Zorzano,A. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats. Diabetes 2003; 52(-4-):1004-1013. >>> Benzylamine hydrochloride; SC; Rat; 2 weeks; 2-week stability verified by in vitro glucose transport assay; diabetes..

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);.

P5619 Yin,D.H., Xu,H.P., He,Y.L., Kirkovsky,L.I., Miller,D.D., Dalton,J.T. Pharmacology, pharmacokinetics, and metabolism of acetothiolutamide, a novel nonsteroidal agonist for the androgen receptor. Journal of Pharmacology and Experimental Therapeutics 2003; 304(-3-):1323-1333. >>> Testosterone propionate; acetothiolutamide; bicalutamide, R-; PEG 300; SC; Rat; 2002; 2 weeks; Controls received mp w/vehicle; functionality of mp verified by residual volume; replacement therapy (orchidectomy); comparison of bolus IV injections vs. mp (p. 1327); stability verified by preliminary experiments (14 days at 37 C. of acetothiolutamide; half-life (p. 1327) acetothiolutamide (26 min); bicalutamide is a nonsteroidal androgen; acetothioluthamide is a nonsteroidal androgen receptor ligand; agents in seperate pumps for seperate groups..

P5575 Gangula,P.R.R., Dong,Y.L., Wimalawansa,S.J., Yallampalli,C. Infusion of pregnant rats with calcitonin gene-related peptide (CGRP)( 8-37), a CGRP receptor antagonist, increases blood pressure and fetal mortality and decreases fetal growth. Biology of Reproduction 2002; 67(-2-):624-629. >>> Calcitonin gene-related peptide (8-37); saline; SC; rat (pregnant); 2ML2; ; controls received mp with saline; stability verified by mass spectrometry for 14 days (p. 625); peptides; agent is a potent vasodilator.

P5476 Carson,BS Sr, Wu,Q.Z., Tyler,B., Sukay,L., Raychaudhuri,R., Dimeco,F., Clatterbuck,R.E., Olivi,A., Guarnieri,M. New approach to tumor therapy for inoperable areas of the brain: chronic intraparenchymal drug delivery. Journal of Neuro-oncology 2002; 60(-2-):151-158. >>> Carboplatin; bis-chlorethyl nitrosourea; Propylene glycol; dextrose; CSF/CNS (brain stem); Rat; 2001; 7 days; Controls received mp w/ vehicle; stability verified by HPLC (p. 151); half-life (p. 154) for BCNU is<1 hr; cancer; brain tissue distribution; study evaluated effects of various infusion rates from 1-10 ul/hr to the brainstem and cortex.

P5391 Sahu,A. Resistance to the satiety action of leptin following chronic central leptin infusion is associated with the development of leptin resistance in neuropeptide Y neurones. Journal of Neuroendocrinology 2002; 14(-10-):796-804. >>> Leptin; PBS; CSF/CNS; Rat; 2002; 28 days; Controls received mp w/ vehicle; pumps replaced 14 days; stability verified by plasma leptin levels; peptides; 7-day aCSF infusion followed by 28-day leptin infusion followed by another period of aCSF infusion.

P5337 Slot,L.A.B., Tarayre,J.P., Koek,W., Ribet,J.P., Colpaert,F.C. Experimental conditions for the continuous subcutaneous infusion of four central analgesics in rats. Pharmacology Biochemistry and Behavior 2002; 72(-4-):943-951. >>> Morphine HCl; Ketamine HCl; Imipramine HCl; gabapentin; Water, distilled; SC; Rat; 2ML2; 2 weeks; Controls received mp w/ saline; no stress (see pg. 947); 14 day stability verified by HPLC on all agents; the site of pump placement was massaged daily to avoid tissue adherance; opioid and non-opioid analgesics; body weight gain information provided.

P5336 Schmiedt,R.A., Lang,H.N., Okamura,H., Schulte,B.A. Effects of furosemide applied chronically to the round window: A model of metabolic presbyacusis. Journal of Neuroscience 2002; 22(-21-):9643-9650. >>> Apomorphine; Saline; SC; Mice; 28 days; Controls received mp w/ vehicle; comparison of sc bolus injections vs. mp; 20-day stability verified by HPLC (p.368); neurodegenerative (Parkinson's disease); "The neurorescue effect of continuous subcutaneous infusion of apomorphine is particularly promising from a clinical standpoint." (p.372).

P5270 Suga,M., Maclean,A.A., Keshavjee,S., Fischer,S., Moreira,J.M., Liu,M. RANTES plays an important role in the evolution of allograft transplant- induced fibrous airway obliteration. Am.J Respir.Crit Care Med. 2000/11; 162(-5-):1940-1948. >>> Antibody, polyclonal anti-rat RANTES; Immunoglobulin G, rabbit; RANTES; Saline; PBS; BSA; Tracheal graft; Rat; 1007D; 2002;; 7, 14, 24 days; Controls received mp w/ vehicle; pumps replaced after 14 days; 14-day stability verified by RANTES ELISA (p.1944); Immunology; peptides; transplantation; RANTES is a chemokine; concentration of RANTES in mp measured before and after delivery (p.1945).

P5269 Qiu,J., Cai,D., Dai,H., McAtee,M., Hoffman,P.N., Bregman,B.S., Filbin,M.T. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002/6/13; 34(-6-):895-903. >>> H89; Saline; CSF/CNS (intrathecal); Rat; 1 week; Controls received mp w/ vehicle; 1 week stability verified (results not shown); enzyme inhibitor; H89 is a protein kinase A inhibitor.

P5207 Hamilton,B.S., Doods,H.N. Chronic application of MTII in a rat model of obesity results in sustained weight loss. Obes.Res 2002/3; 10(-3-):182-187. >>> MTII; Saline; SC; Rat; 2ML4; 17 or 28 days; Controls received mp w/ vehicle; stability verified by HPLC (p.183); MTII is a non-specific melanocortin agonist; pumps left in animal for aprox. 38 days; effects of MTII were noted up until day 38.

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).

P5052 te Velde,E.A., Voest,E.E., van Gorp,J.M., Verheem,A., Hagendoorn,J., Gebbink,M.F., Rinkes,I.H.B. Adverse effects of the antiangiogenic agent angiostatin on the healing of experimental colonic anastomoses. ANNALS OF SURGICAL ONCOLOGY 2002; 9(-3-):303-309. >>> Angiostatin; PBS; SC; mice; 2001; 4-7 days; controls received mp w/ vehicle; stability by mouse cornea neovascularization assay (p. 304); cancer; wound healing; angiogenesis inhibitor.

P5046 Scharstuhl,A., Glansbeek,H.L., van Beuningen,H.M., Vitters,E.L., van der Kraan,P.M., Van Den Berg,W.B. Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair. Journal of Immunology 2002; 169(--):507-514. >>> Transforming Growth Factor-B2, soluble receptor; Polymyxin B; IP; mice; 1007D; 2002; 7,14 or 21 days; Arthritis; controls received empty pumps or mp w/ vehicle; functionality of mp verified by residual aspiration; pumps replaced after 14 days; stability verified by ELISA after infusion (p. 508, 510); soluble TGF-B RII selectively inhibits transforming growth factor-B; peptides; polymyxin B included as endotoxin inhibitor; 2002 pumps used for 7 and 14 day administration, 21-day group received a 1007D pump for final 7 days.

P5040 Rohner-Jeanrenaud,F., Craft,L.S., Bridwell,J., Suter,T.M., Tinsley,F.C., Smiley,D.L., Burkhart,D.R., Statnick,M.A., Heiman,M.L., Ravussin,E., Caro,J.F. Chronic central infusion of cocaine- and amphetamine-regulated transcript (CART 55-102): effects on body weight homeostasis in lean and high -fat-fed obese rats. International Journal of Obesity 2002; 26(--):143-149. >>> Endostatin; Sodium citrate; Sodium phosphate; IP; mice (SCID); mice; 2001; 6 days; controls received mp w/ vehicle; functionality of mp verified by serum endostatin levels; dose-response (p.7673, Fig. 4); comparison of SC and IP bolus injections vs. continuous infusion w/ mp; pumps replaced every 7 days; endostatin stability verified by in vitro biologic activity after 1-7 day implantation; half-life (p. 7669) of endostation in mice after SC bolus is ~10 hrs.; cancer; angiogenesis inhibitor; recomb. human endostatin used; continuous administration of human endostatin resulted in increased efficacy and an 8-10-fold decrease in dose required to achieve the same effect as daily bolus administration.

P4957 Peeling,J., Del Bigio,M.R., Corbett,D., Green,A.R., Jackson,D.M. Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonat e N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke. Neuropharmacology 2001; 40(--):433-439. >>> NXY-059; Saline; SC; rat; 2ML1; 3 days; controls received mp w/ vehicle; functionality of mp verified by plasma NXY-059 levels; dose-response (p. 436 section 3.1); stability verified by checking concentration of remaining drug p. 436); multiple pumps per animal (2); NXY-059 traps free radicals in the brain and may reduce brain injury in hemorrhagic stroke; ischemia (cerebral).

P4902 Jelic,M., Pecina,M., Haspl,M., Kos,J., Taylor,K, Maticic,D, McCartney,J, Yin,S., Rueger,D., Vukicevic,S. Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 2001; 19(--):101-113. >>> Osteogenic protein-1; Acetate buffer; knee (articular cavity); sheep; 2002; 14 days; controls received mp w/ vehicle; tissue perfusion (knee joint defect); functionality of mp verified by aspiration of residual volume after explant; stability verified by in vitro compatibility tests, ELISA, HPLC; good methods (in vitro bio-compatibility table 1 p. 106); OP-1 is also known as BMP-7. Pump was stapled to femoral shaft, PE-60 catheter tubing perfused knee joint; "Results of this study suggest that a recombinant BMP delivered via a mini-osmotic pump into the joint fluid stimulate the repair of articular cartilate defects in sheep." p. 106;.

P4873 Marti,L., Abella,A., Carpene,C., Palacin,M., Testar,X., Zorzano,A. Combined treatment with benzylamine and low dosages of vanadate enhances glucose tolerance and reduces hyperglycemia in streptozotocin-induced diabetic rats. Diabetes 2001; 50(--):2061-2068. >>> Benzylamine; PBS; SC; rat; 2 weeks; controls received sham operation; functionality of mp verified by plasma insulin levels; dose response (table 4 p. 2065-66); comparison of SC injections vs. mp; stability verified by preliminary studies-- benzylamine stable for 2 weeks; rats were diabetic; benzylamine encourages glucose uptake..

P4782 Yang,H.T., Yan,Z., Abraham,J.A., Terjung,R.L. VEGF121- and bFGF-induced increase in collateral blood flow requires normal nitric oxide production.. American Journal of Physiology-Heart and Circulatory Physiology 2001; 280(--):H1097-H1104. >>> Vascular endothelial growth factor 121; Fibroblast growth factor, basic;; PBS; Sodium citrate; Glycerol;; IA (femoral);; rat;; 2002;; 14 days;; Controls received mp w/ vehicle; cardiovascular; peptides; vehicle was PBS w/ 10% sodium citrate and 1.6% glycerol; sodium citrate used to prevent coagulation; glycerol used to enhance protein stability;.

P4771 Perez-Romero,A., De Lama,M.A.R., Granados,B., Vara,E., Gonzalez,I.V., Ariznavarreta,C., Tresguerres,J.A.F. Growth hormone response to long-term GH-RH administration in lambs. Journal of Physiology and Biochemistry 2000; 56(-2-):107-115. >>> Transforming growth factor-B1; Bone (tibia); Rabbit; 2ML4; 4 weeks;; Controls received mp w/ vehicle; tissue perfusion (osteotomy site via catheter); functionality of mp verified by aspirate residual volume after pump removal; no stress (see pg. 620); stability verified by fibroblast cell growth compared w/ fresh solution 7, 14, 21; peptides; dosage of TGF-b1 was 0, 10, 20, or 40 mg/day; delayed drug delivery for 7 days;.

P4764 Larsen,P.J, Vrang,N, Petersen,P.C, Kristensen,P  Obesity Research 2000; 8(-8-):590-596. >>> CART (42-89);; PBS;; CSF/CNS;; rat;; 2001; 2002;; 7, 10 days;; Controls received mp w/ vehicle; dose-response (graph p. 592); pulsed delivery 24 hr. delay for recovery; stability verified by aspire 5 mL of pump contents, inject ICV into naive animals to verify biological activity; peptides; ALZET brain infusion kit used; recombinant CART (42-89) is a hypothalamic neuropeptide; CART (42-89) stands for cocaine-amphetamine-regulated transcript; low dose was 4.8 mg/day for 7 days, high dose was 12 mg/day for 10 days.; delayed delivery;.

P4687 Galuske,R.A.W., Kim,D.-S, Castren,E., Singer,W. Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex.. European Journal of Neuroscience 2000; 12(--):3315-3330. >>> Brain-derived neurotrophic factor; Nerve growth factor;; PBS; BSA; Cytochrome C;; CSF/CNS (visual cortex);; cat; cat (kitten);; 2001; 2002;; 7, 14 days;; Controls received mp w/ vehicle; stress/adverse reaction (see pg. 3319) necrosis develops around the tip of the cannulae; 1 week stability of BDNF verified by bioassay; ALZET brain infusion kit used; peptides; brain tissue distribution; 2001 pump model used in kittens; 2002 pump model used in adult cats; location of cannulae placement confirmed at end of experiment by cresyl violet staining;.

P4672 Nickola,T.J., Ignatowski,T.A., Spengler,R.N. Antidepressant drug administration modifies the interactive relationship between a2-adrenergic sensitivity and levels of TNF in the rat brain.. Journal of Neuroimmunology 2000; 107(--):50-58. >>> Tumor necrosis factor-a; CSF, artificial;; CSF/CNS;; rat;; 14 days;; Stability verified by WEHI-13 VAR fibroblast cylotoxicity assay; peptides; ALZET brain infusion kit used; recomb. rat TNF used;.


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What researchers are saying...

“Commercially available mini-osmotic pumps were pre-tested in vitro and proved to be a reliable method of slowly releasing the protein that was biologically active... The continuous presence of BMP-7 during the 2-4 weeks following surgery seemed to have attracted surrounding mesenchymal-like cells from the synovium into the defect area, and then transformed into chondrocytes.” Pecina et al. International Orthopaedics 2002; 26:131-136.