Long-Term Infusion Using ALZET Osmotic Pumps

ALZET pumps range in duration from 24 hours to 4 weeks. Animals can be dosed for periods which exceed the duration of a single pump by serial reimplantation of fresh pumps. This collection of references includes only the most recent citations. However, we do have older references which include infusions of as long as 3 years and in which up to 52 serial implantations have been performed on a single animal. The following table indicates the longest published duration of administration by animal along with a reference. (In some cases, more than one study infused for this duration.)

ANIMAL	DURATION	PUMPS REPLACED	REFERENCE
Mouse	5 months	Every 4 weeks	P6774  Bello, L. et al. Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma. Clinical Cancer Research.   2004; 10(13): 4527-4537
Rabbit	10 weeks	Every 3 weeks	P2297  Sun Y-P, Zhu B-Q, Sievers RE, Glantz SA, Parmley WW. Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke. Circulation 1994; 89:2260-2265.
Rat	1 year	Not stated	P0818  Murphy WM, Blatnik AF, Shelton TB, Soloway MS. Carcinogenesis in mammalian urothelium: changes induced by non-carcinogenic substances and chronic indwelling catheters. J Urol 1986; 135(4):840-844
Dog	18 months	Every 2-4 weeks	P0752  McRae GI, Roberts BB, Worden AC, Bajka A, Vickery BH. Long-term reversible suppression of oestrus in bitches with nafarelin acetate, a potent LHRH agonist. J Reprod Fertil 1985; 74(2):389-397
Guinea-pig	8 weeks	Every 13 days	P4742  Tang W, Seidman MD, Henig JP, Shulman A, Stracher A. The effects of leupeptin on cochlear blood flow, auditory sensitivity, and histology. International Tinnitus Journal 2001; 7(1):4-12
Monkey	3 years	Every 3 weeks	P2083  Ravindranath N, Ramesh V, Krishnamurthy H, Roa AJ, Moudgal RN. Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata). Fertil Steril 1992; 57(3):671-676.

The short abstract following each reference in the attached list details the substance(s) infused, route of administration, animal model studied, solvent(s), model of pump, duration of infusion, and whether stress to the animal was noted.

To obtain a complete list of citations pertaining to extended duration studies published since 1975, please contact ALZET Technical Services at (800) 692-2990 (U.S. & Canada), or (408) 367-4036. You may also contact us via e-mail at alzet@durect.com.

P8567 Zhang,J., Tokui,Y., Yamagata,K., Kozawa,J., Sayama,K., Iwahashi,H., Okita,K., Miuchi,M., Konya,H., Hamaguchi,T., Namba,M., Shimomura,I., Miyagawa,J.I. Continuous stimulation of human glucagon-like peptide-1 (7-36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes. Diabetologia 2007; 50(-9-):1900-1909. >>> Glucagon-like peptide-1; Acetic acid buffer, 5%; SC; Mice; 2004; 4 or 8 weeks; Controls received mp w/ saline; functionality of mp verified by GLP-1 plasma levels; long-term study; pumps replaced after 4 weeks; animal info (female, NOD mice, 8 weeks old); diabetes; "plasma concentrations of active GLP-1...after pump implantation were significantly elevated and about 1.5 fold higher than before the pump implantation. We therefore considered this delivery system to be appropriate for this experiment." (p. 1903).

P8559 Samuel,C.S., Lin,F., Hossain,M.A., Zhao,C.X., Ferraro,T., Bathgate,R.A.D., Tregear,G.W., Wade,J.D. Improved chemical synthesis and demonstration of the relaxin receptor binding affinity and biological activity of mouse relaxin. Biochemistry 2007; 46(-18-):5374-5381. >>> Relaxin, synthetic mouse; SC; Mice; 2004; 4 months; Controls received no treatment; dose-response (fig. 4); long-term study; pumps replaced every month; half-life (p. 5376) 10-15 minutes; peptides; animal info (Rln -/-, 2 months old, male).

P8516 Hong,L.Z., Hsieh,P.S. Hyperinsulinemia Instead of Insulin Resistance Induces Baroreflex Dysfunction in Chronic Insulin-Infused Rats. American Journal of Hypertension 2007; 20(-4-):451-458. >>> Insulin, porcine; Glycerin; ethanol; SC; Rat; 2002; 8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 14 days; post op. care (penicillin); animal info (male, Sprague-Dawley, 200-250 grams); 50% ETOH used [manufacturer suggests 15% or less ETOH; for pump compatibility purposes].

P8513 Gomori,A., Ishihara,A., Ito,M., Matsushita,H., Ito,M., Mashiko,S., Iwaasa,H., Matsuda,M., Bednarek,M.A., Qian,S., MacNeil,D.J., Kanatani,A. Blockade of MCH1 receptor signalling ameliorates obesity and related hepatic steatosis in ovariectomized mice. Br.J.Pharmacol. 2007/7; 151(-6-):900-908. >>> Melanin-concentrating hormone 1, receptor antagonist; Propylene glycol; water, distilled; CSF/CNS; Mice; 2004; 8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced after 4 weeks of vehicle delivery; ALZET brain infusion kit used; post op. care (cefamezin-a); animal info (female, C57BL/6J, 12 weeks old, female Mch1r KD, 14-16 weeks old, 22 g); cannula placement confirmed with Evans Blue dye; obesity.

P8478 Ma,T., Gutnick,J., Salazar,B., Larsen,M.D., Suenaga,E., Zilber,S., Huang,Z., Huddleston,J., Smith,R.L., Goodman,S. Modulation of allograft incorporation by growth factors over a prolonged continuous infusion of duration in vivo. Bone 2007; 41(-3-):386-392. >>> Fibroblast growth factor-2; osteogenic protein-1, recomb. human; Water, distilled; acetate buffer; Bone (tibia); Rabbit; 2004; 4,36 weeks; Controls received no treatment to contralateral side; long-term study; pumps replaced every 4 weeks, with 4 week rest periods between 4 week infusion periods; animal info (New Zealand white, 6-12 months old, 3.5-4.2 kg); peptides; OP-1 also known as bone morphogenic protein-7 (BMP-7); unique drug test chamber and bone harvest chamber used in conjunction with mp.

P8477 Mack,C., Wilson,J., Athanacio,J., Reynolds,J., Laugero,K., Guss,S., Vu,C., Roth,J., Parkes,D. Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2007; 293(-5-):R1855-R1863. >>> Amylin; DMSO; SC; Rat; 2ML4; 4,8,11 weeks; Controls received mp w/ vehicle; functionality of mp verified by plasma amylin concentrations; dose-response (fig 1); comparison of IP injections vs. mp; long-term study; pumps replaced every 4 weeks; half-life (p. R1861) "short;" peptides; animal info (male, Sprague-Dawley, Levin DIOP); 50% DMSO used; endocrinology; "Due to its short half-life, amylin was administered via subcutaneous infusion as a proof of concept for its potential use as an antiobesity agent." (p. R1861).

P8443 Banach-Petrosky,W., Jessen,W.J., Ouyang,X., Gao,H., Rao,J., Quinn,J., Aronow,B.J., bate-Shen,C. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Research 2007; 67(-19-):9089-9096. >>> Testosterone propionate; PEG 400; SC; Mice; 2004; 7 months; Controls received mp w/ vehicle, or no treatment; replacement therapy (castration); dose-response (fig 1A); long-term study; pumps replaced every 28 days; cancer prostate; animal info (male, C57Bl/65X129/SvImJ, 6 wks old).

P8436 Rabbani,Z.N., Batinic-Haberle,I., Anscher,M.S., Huang,J., Day,B.J., Alexander,E., Dewhirst,M.W., Vujaskovic,Z. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 2007; 67(-2-):573-580. >>> AEOL 10150; SC; Rat; 2002; 10 weeks; 8 days; Controls received mp w/ vehicle; functionality of mp verified by plasma AEOL 10150 concentrations; dose-response (fig. 4); long-term study; pumps replaced every 2 weeks; half-life (p. 574), short; cancer; animal info (female, Fisher-344, 150-170 grams); "Osmotic mini-pumps provided consistent and dose-dependent delivery of AEOL 10150," "a continuous availability of antioxidant via osmotic infusion pumps throughout the study." (p. 575).

P8405 Zhang,X.C., Jia,Y.H., Jackson,E.K., Tofovic,S.P. 2-methoxyestradiol and 2-ethoxyestradiol retard the progression of renal disease in aged, obese, diabetic ZSF1 rats. Journal of Cardiovascular Pharmacology 2007; 49(-1-):56-63. >>> Estradiol, 2-hydroxy-; estradiol, 1-methoxy-; PEG 400; Rat; 2ML4; 9 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced after 32 days; no stress (see pg. 58-9); cardiovascular; animal info (male, obese ZSF1,35 wks old, 650-375g.); nephrology.

P8343 Bone,W., Walden,C.M., Fritsch,M., Voigtmann,U., Leifke,E., Gottwald,U., Boomkamp,S., Platt,F.M., van der Spoel,A.C. The sensitivity of murine spermiogenesis to miglustat is a quantitative trait: a pharmacogenetic study. Reproductive Biology and Endocrinology 2007; 5(--):U1-U13. >>> Miglustat; SC; Mice; 2004; 7 weeks; Functionality of mp verified by serum agent levels; comparison of oral vs. mp; long-term study; enzyme inhibitor (ceramide glucosyltransferase); animal info (male, C57BL/6J, BALB/C, FVB/N, 6 weeks old); reproductive endocrinology.

P8323 Shibata,M.A., Morimoto,J., Doi,H., Morishima,S., Naka,M., Otsuki,Y. Electrogene therapy using endostatin, with or without suicide gene therapy, suppresses murine mammary tumor growth and metastasis. Cancer Gene Therapy 2007; 14(-3-):268-278. >>> Ganciclovir; Saline; SC; Mice; 2002; 8 weeks; Controls received mp w/ agent and empty control vector; long-term study; pumps replaced every 14 days; no stress (see pg. 271); cancer (mammary adenocarcinoma); animal info (BALB/C, female, 20-24 grams).

P8282 Birkeland,J.A.K., Sjaastad,I., Brattelid,T., Qvigstad,E., Moberg,E.R., Krobert,K.A., Bjornerheim,R., Skomedal,T., Sejersted,O.M., Osnes,J.B., Levy,F.O. Effects of treatment with a 5-HT4 receptor antagonist in heart failure. British Journal of Pharmacology 2007; 150(-2-):143-152. >>> SB207266; SC; Rat; 2ML4; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced after 3 weeks; stress/adverse reaction: (see pg. 145), 1 animal managed to remove the mp [ALZET: This could be due to the agent being irritating or a number of additional variables]; cardiovascular; animal info (male, Wistar, 320 g, MI by left coronary artery ligation).

P8243 Saxe,M.D., Malleret,G., Vronskaya,S., Mendez,I., Garcia,A.D., Sofroniew,M.V., Kandel,E.R., Hen,R. Paradoxical Influence of hippocampal neurogenesis on working memory. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-11-):4642-4646. >>> Ganciclovir; Saline, sterile; SC; Mice (transgenic); 2004; 8 weeks; Controls received mp w/ agent but did not contain GFAP-Tk Tg; long-term study; pumps replaced after 4 weeks, with 2 weeks in between implantations; no stress (see pg. 4643); animal info (male, C57BL/6-BALB/C, 12-20 weeks old); "Because this system has previously been shown to cause gastrointestinal toxicity at high doses (16), we delivered a constant low dose of GCV for several weeks via SC osmotic minipumps...This modification achieved a nearly complete reduction in hippocampal neurogenesis...but resulted in no effects on activity, body weight, food consumption, or (GI) pathology." (p. 4643).

P8167 Bidani,A.K., Picken,M., Hacioglu,R., Williamson,G., Griffin,K.A. Spontaneously reduced blood pressure load in the rat streptozotocin-induced diabetes model: potential pathogenetic relevance. American Journal of Physiology-Renal Physiology 2007; 292(-2-):F647-F654. >>> Insulin; SC; Rat; 16-20, 36-40 weeks; Replacement therapy (STZ-induced Diabetes); long-term study; pumps replaced every 4 weeks; peptides; animal info (male, Sprague-Dawley, 8 weeks old, 250 grams).

P7996 Viquez,O.M., Valentine,H.L., Friedman,D.B., Olson,S.J., Valentine,W.M. Peripheral nerve protein expression and carbonyl content in N,N-diethlydithiocarbamate myelinopathy. Chemical Research In Toxicology 2007; 20(-3-):370-379. >>> Diethlydithiocarbamate, N, N-; IP; Rat; 2ML4; 8 weeks; Long-term study; pumps replaced every 4 weeks; animal info (adult, male, Sprague-Dawley, 351 grams).

R0239 Richardson,R.T., Noushi,F., O'Leary,S. Inner ear therapy for neural preservation. AUDIOLOGY AND NEURO-OTOLOGY 2006; 11(-6-):343-356. >>> Nerve groth factor; NT-3; adenovirus; brain-derived neurotrophic factor; perilymph, artificial; glial-derived neurotrophic factor; ciliary neurotrophic factor; fibroblast growth factor, acidic; fibroblast growth factor-1; fibroblast growth factor-2; fibroblast growth factor, basic; Ear (cochlea); ear (scala tympani); Guinea-pig; 1,2,4,8 weeks; 15-60, 11-12, 26 days; Comparison of polymers, hydrogels, gene therapy, cell-based therapy, and injections vs. mp; long-term study; pumps replaced; no stress (see pg. 350); half-life (p. 344), short in blood; gene therapy; peptides; animal info (deafened); Table 2; "The mini-osmotic pump device is ideally suited to studying the effects of neurotrophic factors in the cochlea experimentally." (p. 350).

P8397 Park,J.H., Widi,G.A., Gimbel,D.A., Harel,N.Y., Lee,D.H.S., Strittmatter,S.M. Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice. Journal of Neuroscience 2006; 26(-51-):13279-13286. >>> Nogo 66 Receptor (310) Ecto-Fc, rat; immunoglobulin G, rat; PBS; SC; Mice (transgenic); 2004; 12 weeks; Controls received mp w/ rat IgG; long-term study; pumps replaced every 28 days; animal info (APPswe/PSEN-1delta E9, 7-10 months old); neurodegenerative (Alzheimer's disease).

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).

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).

P8161 Balatsouka,D., Gotfredsen,K., Sorensen,L., Lindh,C.H., Berglundh,T. Effect of systemic administration of nicotine on healing in osseous defects. An experimental study in rabbits. Part II. CLINICAL ORAL IMPLANTS RESEARCH 2006; 17(-5-):488-494. >>> Nicotine hydrogen tartrate salt; Water, sterile; SC; Rabbit; 2ML4; 8 weeks; Controls received mp w/ saline; functionality of mp verified by cotinine plasma levels; long-term study; pumps replaced after 4 weeks; multiple pumps per animal (2); animal info (female, New Zealand white, 9-12 months old, 3-4 kg, osseous defects).

P8079 Nakamura,S., Murayama,N., Noshita,T., Katsuragi,R., Ohno,T. Cognitive dysfunction induced by sequential injection of amyloid-beta and ibotenate into the bilateral hippocampus; protection by memantine and MK-801. European Journal of Pharmacology 2006; 548(-1-3-):115-122. >>> Memantine; MK-801; Saline; SC; Rat; 2ML2; 6 weeks; 11 days; Controls received mp w/ vehicle; dose-response (fig.2); long-term study; pumps replaced every 2 weeks; animal info (male, F344/DuCrj, 10 wk old, 220-250g.); neurodegenerative (Alzheimers's disease).

P8042 Wente,W., Efanov,A.M., Brenner,M., Kharitonenkov,A., Koester,A., Sandusky,G.E., Sewing,S., Treinies,I., Zitzer,H., Gromada,J. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes 2006; 55(-9-):2470-2478. >>> Fibroblast growth factor-21; Saline; SC; Mice; 1002; 8 weeks; FGF-21 plasma levels taken; long-term study; pumps replaced every two weeks; animal info (C57BL/6, 8 weeks old); diabetes.

P8020 Ma,T., Nelson,E.R., Mawatari,T., Oh,K.J., Larsen,D.M., Smith,R.L., Goodman,S.B. Effects of local infusion of OP-1 on particle-induced and NSAID-induced inhibition of bone ingrowth in vivo. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 2006; 79A(-3-):740-746. >>> OP-1, recomb. human; Acetate buffer; Bone (tibia); Rabbit; 2004; 6, 24 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 4-6 weeks; stress/adverse reaction (see pg. 742) implant (DTC and mp) infection in one animal [manufacturer note: pumps are provided sterile]; peptides; post op. care (cephalosporin); animal info (male, New Zealand white, 6-12 months old, 3.5-4.2 kg); agent also know as bone morphogenic protein-7; mp implanted with a titanium drug test chamber (DTC).

P7875 Lund,A.K., Goens,M.B., Nunez,B.A., Walker,M.K. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice. TOXICOLOGY AND APPLIED PHARMACOLOGY 2006; 212(-2-):127-135. >>> BQ-123; Saline; SC; Mice; 2004; 7, 28, 58 days; 8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced on day 29; cardiovascular; peptides; animal info (C57B6N, AhR -/-, wt, 2 month old, 5 month old, 20-30g.); ET-A receptor antagonist.

P7866 Lupien,S.B., Bluhm,E.J., Ishii,D.N. Effect of IGF-I on DNA, RNA, and protein loss associated with brain atrophy and impaired learning in diabetic rats. NEUROBIOLOGY OF DISEASE 2006; 21(-3-):487-495. >>> Insulin-like growth factor-I; Acetic acid; SC; Rat; 7-8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 18 days; peptides; neurodegenerative (Alzheimer's disease); animal info (male, Harlan Wistar, 10 wk. old).

P7853 Jesmin,S., Zaedi,S., Maeda,S., Togashi,H., Yamaguchi,I., Goto,K., Miyauchi,T. Endothelin antagonism suppresses plasma and cardiac endothelin-1 levels in SHRSPs at the typical hypertensive stage. EXPERIMENTAL BIOLOGY AND MEDICINE 2006; 231(-6-):919-924. >>> SB209670; Saline; SC; Rat; 2ML4; 12 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 4 weeks; cardiovascular; animal info (male, SHRSP, 6 wk. old, Wistar-Kyoto); ETA/ETB dual receptor antagonist.

P7850 Ichihara,A., Kaneshiro,Y., Takemitsu,T., Sakoda,M., Suzuki,F., Nakagawa,T., Nishiyama,A., Inagami,T., Hayashi,M. Nonproteolytic activation of prorenin contributes to development of cardiac fibrosis in genetic hypertension. Hypertension 2006; 47(-5-):894-900. >>> Prorenin decapeptide, rat; peptides, synthetic; SC; Rat; 2004; 8 weeks; Controls received mp w/ saline; long-term study; pumps replaced after 4 weeks; cardiovascular; peptides; animal info (male, Wistar Kyoto, SHR, 4 wk. old).

P7809 Ma,J., Weisberg,A., Griffin,J.P., Vaughan,D.E., Fogo,A.B., Brown,N.J. Plasminogen activator inhibitor-1 deficiency protects against aldosterone- induced glomerular injury. Kidney International 2006; 69(-6-):1064-1072. >>> Aldosterone, D-; DMSO; SC; Mice; 2004; 12 weeks; Controls received mp w/ vehicle; replacement therapy (uninephrectomy); long-term study; pumps replaced every 4 weeks; cardiovascular; animal info (male, C57BL/6J wt or PAI-1(-/-), 8-10 wk old, 27g.); 3.6% DMSO; nephrology.

P7777 Fan,Y.Y., Baba,R., Nagai,Y., Miyatake,A., Hosomi,N., Kimura,S., Sun,G.P., Kohno,M., Fujita,M., Abe,Y., Nishiyama,A. Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; Renoprotective effects of an ultrahigh dose of olmesartan. HYPERTENSION RESEARCH 2006; 29(-3-):169-178. >>> Aldosterone; Ethanol; SC; Rat; 2002; 3, 6 weeks; Controls received mp w/ vehicle; replacement therapy (uninephrectomy); long-term study; pumps replaced every 2 weeks; cardiovascular; animal info (male, Sprague-Dawley, 162-184g.); 2% ETOH.

P7681 Colpaert,F.C., Deseure,K., Stinus,L., Adriaensen,H. High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning. Journal of Pharmacology and Experimental Therapeutics 2006; 316(-2-):892-899. >>> F13640; morphine, HCl; Saline; SC; Rat; 2ML2; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every two weeks; multiple pumps per animal (2); animal info (male, Sprague-Dawley, 220-240 g); during pump replacement a new incision was made about 1 cm away from the previous incision.

P7756 Shibuya,K., Kanasaki,K., Isono,M., Sato,H., Omata,M., Sugimoto,T., Araki,S.I., Isshiki,K., Kashiwagi,A., Haneda,M., Koya,D. N-acetyl-seryl-aspartyl-lysyl-proline prevents renal insufficiency and mesangial matrix expansion in diabetic db/db mice. Diabetes 2005; 54(-3-):838-845. >>> Peptide, AcSDKP; Balanced salt solution; SC; Mice; 2004; 8 weeks; Controls received mp w/ vehicle, or controld peptide; functionality of mp verified by plasma AC-SDKP levels; replacement therapy (diabetes); long-term study; pumps replaced at 4 weeks; no stress (see pg. 839, 843); peptides; animal info (male, db/db, db/m, 10 wk. old).

P7750 Suzuki,J., Iwai,M., Li,Z., Li,J.M., Min,L.J., Ide,A., Yoshii,T., Oshita,A., Mogi,M., Horiuchi,M. Effect of combination of calcium antagonist, azelnidipine, and AT1 receptor blocker, olmesartan, on atherosclerosis in apolipoprotein E-deficient mice. Journal of Hypertension 2005; 23(-7-):1383-1389. >>> Olmesartan; IP; Mice; 1002; 10 weeks; Dose-response (fig.1); long-term study; pumps replaced every 2 weeks; cardiovascular; animal info (adult, male, ApoE -1-, 6 wk. old, 25-30g.).

P7740 Sekhon,H.S., Song,P.F., Jia,Y.B., Lindstrom,J., Spindel,E.R. Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure. Cell and Tissue Research 2005; 320(-2-):287-297. >>> Nicotine tartrate; Water, bacteriostatic; SC; Monkey (pregnant); 2ML4; 19 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 3 weeks; post op. care (cefazolin); animal info (female, Rhesus, gestation day 26-160); amniocentesis.

P7633 Bao,L.H., Osawe,I., Haas,M., Quigg,R.J. Signaling through up-regulated C3a receptor is key to the development of experimental lupus nephritis. Journal of Immunology 2005; 175(-3-):1947-1955. >>> C3aR; DMSO; Mice; 2001; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every week; half-life (p. 1948), 1.5 hours; animal info (BALB/c, male); 50% DMSO used.

P7621 Narai,H., Nagano,I., Ilieva,H., Shiote,M., Nagata,T., Hayashi,T., Shoji,M., Abe,K. Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SOD(G93A) transgenic mice. Journal of Neuroscience Research 2005; 82(-4-):452-457. >>> Insulin-like growth factor I, recomb. human; CSF, artificial; CSF/CNS (intrathecal, subarachnoid space, lumbar); Mice (transgenic); 2004; 5-10 weeks; Controls received mp w/ vehicle; dose-response (fig 1); long-term study; pumps replaced every 4 weeks; neurodegenerative (Amyotrophic Lateral Sclerosis); animal info (C57BL/6J, female).

P7606 Kadoya,T., Oyanagi,K., Kawakami,E., Hasegawa,M., Inagaki,Y., Sohma,Y., Horie,H. Oxidized galectin-1 advances the functional recovery after peripheral nerve injury. Neuroscience Letters 2005; 380(-3-):284-288. >>> Galectin-1, recomb. human oxidized; CSF/CNS (sciatic nerve); Rat; 2ML4; 12 weeks; Controls received mp w/ PBS; dose-response (fig. 1); long-term study; no stress (see pg. 285); peptides; animal info (male, adult, Sprague-Dawley); "No rats showed any toxic effects or reaction to the administration of rh GAL-1/Ox." (p. 285).

P7602 Iwai,M., Chen,R., Li,Z., Shiuchi,T., Suzuki,J., Ide,A., Tsuda,M., Okumura,M., Min,L.J., Mogi,M., Horiuchi,M. Deletion of angiotensin II type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice. Circulation 2005; 112(-11-):1636-1643. >>> Valsartan; IP; Mice; 1002; 10 weeks; Controls received no treatment; long-term study; cardiovascular; animal info (male); AT1 receptor blocker.

P7575 Zhan,G.X., Serrano,F., Fenik,P., Hsu,R., Kong,L.H., Pratico,D., Klann,E., Veasey,S.C. NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2005; 172(-7-):921-929. >>> Apocynin; DMSO; SC; Mice; 1002; 8 weeks; Controls received mp w/ vehicle or PBS; long-term study; pumps replaced; enzyme inhibitor (NADPH oxidase); animal info (male, C57BL/6J, 10 wk old).

P7554 Lautrette,A., Li,S.Q., Alili,R., Sunnarborg,S.W., Burtin,M., Lee,D.C., Friedlander,G., Terzi,F. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Nature Medicine 2005; 11(-8-):867-874. >>> Angiotensin II; Saline; SC; Mice; mice (transgenic); 2004; 2 months; 7 days; Controls received mp w/ vehicle; replacement therapy (nephrectomy); long-term study; pumps replaced at 1 month; peptides; animal info (C57Bl6, female, 1 week old).

P7401 Donners,M.M.P.C., Bot,I., De Windt,L.J., van Berkel,T.J.C., Daemen,M.J.A.P., Biessen,E.A.L., Heeneman,S. Low-dose FK506 blocks collar-induced atherosclerotic plaque development and stabilizes plaques in ApoE-/- mice. AMERICAN JOURNAL OF TRANSPLANTATION 2005; 5(-6-):1204-1215. >>> FK-506; PBS; SC; Mice; 2004; 4,8 weeks; Controls received mp w/ vehicle; plasma levels taken; long-term study; pumps replaced every 4 weeks.

P7362 McDonald,C.G., Dailey,V.K., Bergstrom,H.C., Wheeler,T.L., Eppolito,A.K., Smith,L.N., Smith,R.F. Periadolescent nicotine administration produces enduring changes in dendritic morphology of medium spiny neurons from nucleus accumbens. Neuroscience Letters 2005; 385(-2-):163-167. >>> Nicotine; Saline; SC; Rat; 1002; 2004; 6 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced at two weeks with the 2004 model; "5.6 mglkglday was chosen to provides plasma nicotine levels comparable to those seen in human smokers." p. 164; bahavioral study.

P7341 Zhou,Y., Chen,R., Catanzaro,S.E., Hu,L.F., Dansky,H.M., Catanzaro,D.F. Differential effects of angiotensin II on atherogenesis at the aortic sinus and descending aorta of apolipoprotein-E-deficient mice. American Journal of Hypertension 2005; 18(-4-):486-492. >>> Angiotensin II; Saline; SC; Mice (knockout); 2004; 8-32 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 4 weeks; cardiovascular; peptides.

P7334 Turrone,P., Remington,G., Kapur,S., Nobrega,J.N. Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats. Biological Psychiatry 2005; 57(-4-):406-411. >>> Haloperidol; olanzapine; SC; Rat; 2ML4; 8 weeks; Controls received mp w/ vehicle; comparison of injections vs. mp; long-term study; pumps replaced every four weeks in a new incision; post op. care (placed in heated plexiglass cage); wound clips and vetbond were used to close incision.

P7328 Kharitonenkov,A., Shiyanova,T.L., Koester,A., Ford,A.M., Micanovic,R., Galbreath,E.J., Sandusky,G.E., Hammond,L.J., Moyers,J.S., Owens,R.A., Gromada,J., Brozinick,J.T., Hawkins,E.D., Wroblewski,V.J., Li,D.S., Mehrbod,F., Jaskunas,S.R., Shanafelt,A.B. FGF-21 as a novel metabolic regulator. Journal of Clinical Investigation 2005; 115(-6-):1627-1635. >>> Fibroblast growth Factor-21; Saline; SC; Mice; 8 weeks; Controls received mp w/ vehicle; replacement therapy (diabetic, db/db); comparison of SC injections vs. mp (minipump used to study mitogenicity during longer exposure); long-term study.

P7320 Balatsouka,D., Gotfredsen,K., Lindh,C.H., Berglundh,T. The impact of nicotine on bone healing and osseointegration - An experimental study in rabbits. CLINICAL ORAL IMPLANTS RESEARCH 2005; 16(-3-):268-276. >>> Nicotine hydrogen tartrate salt; Water, sterile; SC; Rabbit; 2ML4; 8 weeks; Controls received mp w/ saline; functionality of mp verified by plasma cotinine levels; long-term study; pumps replaced after 4 weeks.

P7300 Venken,K., Boonen,S., Van Herck,E., Vandenput,L., Kumar,N., Sitruk-Ware,R., Sundaram,K., Bouillon,R., Vanderschueren,D. Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: Evidence from the aged orchidectomized male rat model. Bone 2005; 36(-4-):663-670. >>> Nortestosterone, 7a-methyl-19-; Propandiol; SC; Rat; 2004; 16 weeks; Controls received mp w/ vehicle; replacement therapy (orchidectomy); dose-response (fig. 1); long-term study; pumps replaced every 4 weeks; animal info (male, 13 month old, Wistar, 600-650 g).

P7286 Balatsouka,D., Gotfredsen,K., Lindh,C.H., Berglundh,T. The impact of nicotine on osseointegration - An experimental study in the femur and tibia of rabbits. CLINICAL ORAL IMPLANTS RESEARCH 2005; 16(-4-):389-395. >>> Nicotine hydrogen tartrate salt; water, sterile; SC; Rabbit; 2ML4; 2 months; Controls received mp w/ saline; functionality of mp verified by plasma cotinine levels; long-term study; pumps replaced at 4 weeks; multiple pumps per animal (2); post op. care (streptocillin, temgesic); titanium implants in femur and tibia.

P7245 Mashiko,S., Ishihara,A., Gomori,A., Moriya,R., Ito,M., Iwaasa,H., Matsuda,M., Feng,Y., Shen,Z., Marsh,D.J., Bednarek,M.A., MacNeil,D.J., Kanatani,A. Antiobesity effect of a melanin-concentrating hormone 1 receptor antagonist in diet-induced obese mice. Endocrinology 2005; 146(-7-):3080-3086. >>> Melanin-concentrating hormone 1 receptor antagonist; Propylene glycol; CSF, artificial; CSF/CNS; CSF/CNS (third ventricle); Mice; 1007D; 2002; 2004; 3, 8 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced after 1 or 4 weeks of vehicle; ALZET brain infusion kit used; peptides; cyanoacrylate adhesive; post op. care (cefamedin); DEXA; cannula placement confirmed by Evans blue dye injection; animal info (C57BL/6); pumps used in lateral ventricle for one group of animals, and third ventricle for others. Third ventricle group used Plastics One cannulae.

P7184 Mathian,A., Weinberg,A., Gallegos,M., Banchereau,J., Koutouzov,S. IFN-alpha induces early lethal lupus in preautoimmune (New Zealand black x New Zealand White)F1 but not in BALB/c mice1. Journal of Immunology 2005; 174(-5-):2499-2506. >>> Interferon, mouse; PBS; BSA; SC; Mice; 1002; 8-10 weeks; Controls received mp w/ vehicle; long-term study; pumps replaced every 2 weeks; immunology.

P7168 Kobayashi,Y., Kim,K.J., Itoh,T. Gene expression of bone-resorbing cytokines in rat osteolysis model. JOURNAL OF ORTHOPAEDIC SCIENCE 2005; 10(-1-):62-69. >>> Polyethylene; Serum, rat; Knee (articular cavity); Rat; 2002; 2, 4, 6, 8, 10 weeks; Controls received mp w/ vehicle, comparison of single injection vs. mp, long-term study; pumps replaced every 2 weeks, "Continuous infusion induced more active fibrous tissue formation with osteoclastic bone resorption than did the single injection... even though the dose of PE particles we used for continuous infusion was one order of magnitude lower." (p. 68).

P7458 Schaefer,S., Schmidts,H.L., Bleich,M., Busch,A.E., Linz,W., Schaefer,S. Nephroprotection in Zucker diabetic fatty rats by vasopeptidase inhibition is partly bradykinin B2 receptor dependent. British Journal of Pharmacology 2004; 143(--):27-32. >>> Icatibant; SC; Rat; 26 weeks; Controls received no treatment; long-term study; pumps replaced every 4 weeks; animal info (ZDF, 21 weeks old, diabetic nephropathy); bradykinin B2 receptor antogonist.

P7070 Foster,HE Jr, Yono,M., Shin,D., Takahashi,W., Pouresmail,M., Afiatpour,P., Latifpour,J. Effects of chronic administration of doxazosin on alpha1-adrenoceptors in the rat prostate. Journal of Urology 2004; 172(-6-):2465-2470. >>> Doxazosin; DMSO; SC; Rat; 8,12 weeks; Controls received mp w/ vehicle; dose-response (table 2); long-term study; cancer (prostatic hyperplasia); 50% DMSO; due to limitations in solubility mp was combined with oral dosing to deliver higher doses.

P7053 Zucker,B., Ludin,D.E., Gerds,T.A., Luecking,C.H., Landwehrmeyer,G.B., Feuerstein,T.J. Gabapentin-lactam, but not gabapentin, reduces protein aggregates and improves motor performance in a transgenic mouse model of Huntington's disease. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2004; 370(-2-):131-139. >>> Gabapentin-lactam; gabapentin; Isobutanol; saline; SC; Rat; mice (transgenic); 2002; 4-8 weeks; Controls received mp w/ vehicle, or no treatment; functionality of mp verified by residual volume; long-term study; pumps replaced every 2 weeks; no stress (see pg. 137); half-life (pg. 134, 136) approx. 2 hours; "The continuous application of both GBP-L and of GBP by ALZET pumps have maintained the plasma levels so that the actions of these drugs at their targets in the CNS were not interrupted due to their rather short half-lives." (pg. 138); neurodegenerative (huntington's disease).

P7031 Hild,S.A., Attardi,B.J., Reel,J.R. The ability of a gonadotropin-releasing hormone antagonist, acyline, to prevent irreversible infertility induced by the indenopyridine, CDB-4022, in adult male rats: The role of testosterone. Biology of Reproduction 2004; 71(-1-):348-358. >>> Acyline; Tween 80; water, bacteriostatic; SC; Rat; 2002; 2004; 2,4,10,14 weeks; Controls received mp w/ vehicle; dose-response (fig. 2); long-term study; pumps replaced every 4 weeks; peptides; multiple pumps per animal (2); in exp.II two rats died at weeks 14 and 16, both had received mp w/ vehicle weeks -4 to 0, mp removed at week 0; GRH antagonist.

P7005 Duncan,R.E., El-Sohemy,A., Archer,M.C. Mevalonate promotes the growth of tumors derived from human cancer cells in vivo and stimulates proliferation in vitro with enhanced cyclin-dependent kinase-2 activity. Journal of Biological Chemistry 2004; 279(-32-):33079-33084. >>> Mevalonate; SC; Mice (nude); 2004; 13 weeks; Controls received mp w/ vehicle, or isotonic saline; long-term study; pumps replaced every 28 days; cancer (MDA-MB-435); MDA-MB-435 is a highly malignant human cancer of either breast adenocarcinoma or occult melanoma (origin uncertain); cancer (breast, melanoma, adenocarcinoma).

P6870 Ferrandi,M., Molinari,I., Barassi,P., Minotti,E., Bianchi,G., Ferrari,P. Organ hypertrophic signaling within caveolae membrane subdomains triggered by ouabain and antagonized by PST 2238. Journal of Biological Chemistry 2004; 279(-32-):33306-33314. >>> Ouabain; SC; Rat; 2002; 2004; 18 weeks; Controls received mp w/ sterile saline; functionality of mp verified by plasma ouabain concentration; long-term study.

P6838 Thordarson,G., Semaan,S., Low,C., Ochoa,D., Leong,H., Rajkumar,L., Guzman,R.C., Nandi,S., Talamantes,F. Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments. Breast Cancer Research and Treatment 2004; 87(-3-):277-290. >>> Insulin-like growth factor I, recomb. human; SC; Rat; 21 weeks; 10 days; Controls received no treatment; replacement therapy (GH deficient, dwarf); long-term study; cancer (mammary); peptides.

P6822 Lee,J.K., Kim,J.E., Sivula,M., Strittmatter,S.M. Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. Journal of Neuroscience 2004; 24(-27-):6209-6217. >>> Antibody, NgR (310) Ecto-Fc; Immunoglobulin G, rat; PBS; CSF/CNS; Rat; 2ML4; 9 weeks; Controls received mp w/ rat IgG; long-term study; pumps replaced after 28 days; good methods (p. 6210); ALZET brain infusion kit 2 used; peptides; cyanoacrylate adhesive; ischemia (cerebral); Nogo-Nogo receptor (NgR); NgR (310) Ecto-Fc is an IgG fusion protein with a soluble ectodomain fragment of NgG; behavioral study.

P6794 Pittner,R.A., Moore,C.X., Bhavsar,S.P., Gedulin,B.R., Smith,P.A., Jodka,C.M., Parkes,D.G., Paterniti,J.R., Srivastava,V.P., Young,A.A. Effects of PYY[3-36] in rodent models of diabetes and obesity. International Journal of Obesity 2004; 28(-8-):963-971. >>> Peptide YY (3-36); PBS; SC; Rat; mice; 2004; 2ML4; 4, 8 weeks; Controls received mp w/ vehicle; dose-response (fig. 1); comparison of IP injections vs. mp; long-term study; pumps replaced after 4 weeks; diabetes; obesity; peptide.

P6787 Yono,M., Foster,HE Jr, Shin,D., Takahashi,W., Pouresmail,M., Latifpour,J. Doxazosin treatment causes differential alterations of alpha1-adrenoceptor subtypes in the rat kidney, heart and aorta. LIFE SCIENCES 2004; 75(-21-):2605-2614. >>> Doxazosin; DMSO; SC; Rat; 12 weeks; Controls received mp w/ vehicle; functionality of mp verified by plasma doxazosin levels; long-term study; antihypertensive; 50% DMSO; doxazosin supplemented orally in drinking water.

P6760 Neves,K.R., Graciolli,F.G., dos Reis,L.M., Pasqualucci,C.A., Moyses,R.M.A., Jorgetti,V. Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure. Kidney International 2004; 66(-6-):2237-2244. >>> Parathyroid hormone, rat 1-34; Cysteine; Rat; 2ML4; 8 weeks; Controls received mp w/ vehicle; replacement therapy (parathyroidectomy, 5/6 nephrectomy); long-term study; pumps replaced at day 28.

P6747 Itoh,T., Nagaya,N., Murakami,S., Fujii,T., Iwase,T., Ishibashi-Ueda,H., Yutani,C., Yamagishi,M., Kimura,H., Kangawa,K. C-type natriuretic peptide ameliorates monocrotaline-induced pulmonary hypertension in rats. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2004; 170(-11-):1204-1211. >>> Natriuretic peptide, C-type; Glucose; SC; Rat; 1,5,8 weeks; Controls received mp w/ vehicle; comparison of IV injections vs. mp; long-term study; pumps replaced every 2 weeks; antihypertensive; peptides; "Continuous infusion of CNP ameliorated MCT - induced pulmonary hypertension and improved survival in rats." (p.1210).

P6742 Ichihara,A., Hayashi,M., Kaneshiro,Y., Suzuki,F., Nakagawa,T., Tada,Y., Koura,Y., Nishiyama,A., Okada,H., Uddin,M.N., Nabi,A.H.M.N., Ishida,Y., Inagami,T., Saruta,T. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle'' region for nonproteolytic activation of prorenin. Journal of Clinical Investigation 2004; 114(-8-):1128-1135. >>> Peptide, prorenin handle region; SC; Rat; 2004; 8, 16, 24 weeks; Controls received mp w/ saline; long-term study; pumps replaced every 28 days; no stress (see pg.1129); enzyme inhibitor (prorenin); peptides; "Continuous infusion of HRP by subcutaneous minipumps did not affect the body weight, BP, or blood glucose levels of either control or diabetic rats during the 24-week treatment period." (p.1129); diabetes.

P6736 Pitkanen,A., Narkilahti,S, Bezvenyuk,Z, Haapalinna,A., Nissinen,J. Atipamezole, an alpha 2-adrenoceptor antagonist, has disease modifying effects on epileptogenesis in rats. Epilepsy Res. 2004; 61(--):119-140. >>> Atipamezole; Saline; SC; Rat; 2ML1; 2ML4; 9 weeks; Controls received mp w/ vehicle; functionality of mp verified by residual volume and plasma levels; long-term study; pumps replaced every 4 weeks and one week (for the 2ML1); epilepsy; 2ML4 pump implanted, then the 2ML1, then the 2ML4 again; memory; behavioral study.

P6721 Hashimoto,N., Maeshima,Y., Satoh,M., Odawara,M., Sugiyama,H., Kashihara,N., Matsubara,H., Yamasaki,Y., Makino,H. Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a mouse remnant kidney model. American Journal of Physiology-Renal Physiology 2004; 286(-3-):F516-F525. >>> PD123319; SC; Mice; 2002; 6 weeks; Long-term study; pumps replaced every two weeks; AT2R specific antagonist.

P6541 Brooks,D.E., Kaellberg,M.E., Cannon,R.L., Komaromy,A.M., Ollivier,F.J., Malakhova,O.E., Dawson,W.W., Sherwood,M.B., Kuekuerichkina,E.E., Lambrou,G.X. Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia. INVESTIGATIVE OPHTHALMOLOGY&VISUAL SCIENCE 2004; 45(-6-):1830-1840. >>> Endothelin; Saline; acetic acid; CSF/CNS (optic nerve); Monkey; 18 months; Controls received mp w/ vehicle; long-term study; pumps replaced every 6 weeks; no stress (see pg. 1833); peptides; "The osmotic minipumps were well tolerated by the monkeys for the length (1.5 years) of the experiment." The long exposure time was used to "mimic more closely the prolonged human glaucomatous condition." p. 1838; pump model not listed; ischemia.

P6528 Sepehrdad,R., Chander,P.N., Singh,G., Stier,CT Jr  American Journal of Physiology-Renal Physiology 2004; 286(-6-):F1185-F1192. >>> Benzamil; dimethylamiloride; Propanediol; Rat; 2002; 8 weeks; long-term study; pumps replaced every 2 weeks.

P6523 Cingolani,O.H., Yang,X.P., Liu,Y.H., Villanueva,M., Rhaleb,N.E., Carretero,O.A. Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats. Hypertension 2004; 43(-5-):1067-1073. >>> Ac-SDKP; Acetic acid; SC; Rat; 4 months; Controls received mp w/ vehicle; Long-term study; pumps replaced every 4 weeks; no stress (see pg.1069); cardiovascular; peptides; Ac-SDKP is N-acetyl-seryl-aspartyl-lysyl-proline and is antifibrotic.

P6255 Moulder,J.E., Fish,B.L., Cohen,E.P. Impact of angiotensin II type 2 receptor blockade on experimental radiation nephropathy. RADIATION RESEARCH 2004; 161(-3-):312-317. >>> PD123319; Saline; SC; Rat; 2ML4; 12 weeks; Comparison of SC injections vs. mp; long-term study; pumps replaced every 4 weeks; PD123319 is an AT2 blocker.

P6708 Huddleston,G.G., Michael,R.P., Zumpe,D., Clancy,A.N. Estradiol in the male rat amygdala facilitates mounting but not ejaculation. PHYSIOLOGY&BEHAVIOR 2003; 79(-2-):239-246. >>> Fadrozole; Saline; SC; Rat; 2004; 8 weeks; Functionality of mp verified by residual volume; long-term study; pumps replaced after 26 days; enzyme inhibitor (aromatase); post op. care (penicillin, banamine); fadrozole is also termed CGS-15949A.

P6602 Tolbert,D.L., Clark,B.R. GDNF and IGF-I trophic factors delay hereditary Purkinje cell degeneration and the progression of gait ataxia. Experimental Neurology 2003; 183(-1-):205-219. >>> Glial-derived neurotrophic factor; insulin-like growth factor I; SC; Rat; 2004; 4,8 weeks; Controls received mp w/ saline; long-term study; pumps replaced at 4 weeks; peptides.

P6365 Turrone,P., Remington,G., Kapur,S., Nobrega,J.N. Differential effects of within-day continuous vs transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats. Neuropsychopharmacology 2003; 28(-8-):1433-1439. >>> Haloperidol; SC; Rat; 2ML4; 8 weeks; Haloperidol plasma levels taken; comparison of SC injections vs. SC mp; long-term study; pumps replaced every 4 weeks; Vetbond glue and wound clips used to close wounds; "...minipump treated animals had stable haloperidol plasma levels throughout the day...subcutaneously [injection] treated rats experienced a dramatic decline over the same period." p. 1437.

P6100 Feeney,S.J., Austin,L., Bennett,T.M., Kurek,J.B., Jean-Francois,M.J.B., Muldoon,C., Byrne,E. The effect of leukaemia inhibitory factor on SOD1 G93A murine amyotrophic lateral sclerosis. Cytokine 2003; 23(-4-5-):108-118. >>> Leukemia inhibitory factor; CSF/CNS (intrathecal); Mice (transgenic); 2004; 13 weeks; Comparison of SC injections vs. IT mp; long-term study; pumps replaced every 4 weeks; ALZET brain infusion kit 1 used (per Dr. Feeney); used the BIK for the IT infusion; glued and sutured the cannula in place; "All mice that entered the study recovered from the surgical procedure and appeared to have no adverse effects." (p. 111); neurodegenerative (Amyotrophic Lateral Sclerosis).

P6082 Hayashi,T., Sohmiya,K., Ukimura,A., Endoh,S., Mori,T., Shimomura,H., Okabe,M., Terasaki,F., Kitaura,Y. Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart. HEART 2003; 89(-10-):1236-1242. >>> Candesartan; IP; Rat; 2002; 6 weeks; Long-term study; pumps replaced every two weeks; diabetes.

P5937 Simon,G., Jackel,M., Illyes,G. Role of angiotensin II, sympathetic stimulation and salt in the development of structural vascular changes in rat kidney. Clinical and Experimental Pharmacology and Physiology 2003; 30(-7-):476-481. >>> Angiotensin II; SC; Rat; 2ML4; 4,12 weeks; Blood pressure taken; long-term study; pumps replaced every 28 days for 12 week study; cardiovascular; peptides.

P5936 Liu,R.L., Liu,I.Y., Bi,X.N., Thompson,R.F., Doctrow,S.R., Malfroy,B., Baudry,M. Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES O F AMERICA 2003; 100(-14-):8526-8531. >>> Euk-189; euk-207; Mannitol; water; SC; Mice; 2004; 3 months; Controls received mp w/ vehicle; long-term study; pumps replaced every 28 days in same location; pumps primed for >40 hours in 5% mannitol; eukarion is a synthetic catalytic scavenger of reactive oxygen species; stress/adverse reaction: in 10% of mice, the pumps were replaced on the other side of hip area due to skin damage of original site of implantation; behavioral study.

P5726 Eder,I.E, Hoffmann,J, Rogatsch,H, Schafer,G, Zopf,D, Bartsch,G, Klocker,H  Cancer Gene Therapy 2003; 9(-2-):117-125. >>> Oligonucleotide, antisense; Water, distilled; SC; Mice (nude); 7 weeks; Controls received mp w/ vehicle; long-term study, pumps replaced every two weeks; no stress (see pg. 122); cancer (prostate); antisense; pumps implanted SC in the vicinity of tumors; ODN w/ specificity to the androgen receptor; "...mice did not show any reaction on the subcutaneously installed ALZET diffusion pumps. These were chosen to guarantee a continuous systemic administration of oligonucleotides, a commonly used method for antisense treatment in vivo." (p 122).

P6220 Pizzo,D.P., Winkler,J., Sidiqi,I., Waite,J.J., Thal,L.J. Modulation of sensory inputs and ectopic presence of Schwann cells depend upon the route and duration of nerve growth factor administration. Experimental Neurology 2002; 178(-1-):91-103. >>> Nerve growth factor, recomb. human; cytochrome c; PBS; CSF/CNS; CSF/CNS (nucleus basalis magnocellularis); Rat; 2004; 3,6 months; Controls received mp w/ vehicle; long-term study; pumps replaced every 4 weeks; stress/adverse reaction: (see pg. 98) minor inflammatory response at cannulation site; brain tissue distribution; peptides.

P5890 Gregorevic,P., Plant,D.R., Leeding,K.S., Bach,L.A., Lynch,G.S. Improved contractile function of the mdx dystrophic mouse diaphragm muscle after insulin-like growth factor-I administration. American Journal of Pathology 2002; 161(-6-):2263-2272. >>> Insulin-like growth factor; HCL; Saline; SC; Mice; 1002; 8 weeks; Functionality of mp verified by residual volume; long-term study; pumps replaced after 2 weeks; no stress (see pg. 2264); good methods p. 2264; muscular dystrophy; partially dipped in paraffin wax to achieve a pumping rate of 0.125 ul/hr for 28 days.

P5330 Ramchandra,R., Barrett,C.J., Guild,S.J., Malpas,S.C. Neural control of the renal vasculature in angiotensin II-induced hypertension. Clinical and Experimental Pharmacology and Physiology 2002; 29(-10-):867-872. >>> Angiotensin II; IV (jugular); Rabbit; 2ML4; 7 weeks; Long-term study, pumps replaced after 4 weeks; cardiovascular.

P5237 Abrahamsen,C.T., Barone,F.C., Campbell,W.G.,Jr., Nelson,A.H., Contino,L.C., Pullen,M.A., Grygielko,E.T., Edwards,R.M., Laping,N.J., Brooks,D.P. The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension. J Pharmacol Exp.Ther. 2002; 301(-1-):21-28. >>> Eprosartan; IP; Rat; 2ML4; 12 weeks; Controls received mp w/ vehicle; long-term study. pumps replaced every 28 days; cardiovascular; antihypertensive; angiotensin type 1 receptor antagonist; ischemia.

P5164 Wang,X., Abdel-Rahman,A.A. Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts. American Journal of Physiology-Heart and Circulatory Physiology 2002; 282(--):H2309-H2315. >>> Estradiol, 17B-; Saline; SC; rat; 2004; 12 weeks; controls received mp w/ vehicle; functionality of mp verified by plasma estradiol levels; replacement therapy (ovariectomy); long-term study, pumps replaced every 4 wks; cardiovascular.

P5100 Loot,A.E., Roks,A.J., Henning,R.H., Tio,R.A., Suurmeijer,A.J., Boomsma,F., van Gilst,W.H. Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats. Circulation 2002/4/2; 105(-13-):1548-1550. >>> Angiotensin-(1-7); Saline; IV; rat; 2004; 8 weeks; controls received mp w/ vehicle; functionality of mp verified by plasma Ang(1-7) levels; long-term study, pumps replaced after 4 weeks; cardiovascular; peptides.

P5097 Garverick,H.A., Baxter,G., Gong,J., Armstrong,D.G., Campbell,B.K., Gutierrez,C.G., Webb,R. Regulation of expression of ovarian mRNA encoding steroidogenic enzymes and gonadotrophin receptors by FSH and GH in hypogonadotrophic cattle. REPRODUCTION 2002; 123(--):651-661. >>> Aldosterone; Saline; SC; rat; 2002; 7.5 weeks; controls received mp w/ vehicle; functionality of mp verified by systolic BP measurement; dose response (graph p. 1446); long-term study, pumps replaced every 2 weeks; cardiovascular; mineralocorticoid hypertension;.

P4945 Rothermund,L., Pinto,Y.M., Vetter,R., Herfort,N., Kossmehl,P., Neumayer,H.H., Paul,M., Kreutz,R. Effects of angiotensin II subtype 1 receptor blockade on cardiac fibrosis and sarcoplasmic reticulum Ca2+ handling in hypertensive transgenic rats overexpressing the Ren2 gene. Journal of Hypertension 2001; 19(--):1465-1472. >>> Eprosartan; Saline; IP; rat; 2ML4; 20 weeks; Controls received mp w/ vehicle; long-term study, pumps replaced every 4 weeks; cardiovascular; antihypertensive; Eprosartan is an Angiotensin II Type 1 receptor antagonist, given at antihypertensive (6 mg/kg/day) or hypertensive (60 mg/kg/day) doses..

P4904 Halonen,T., Nissinen,J., Pitkanen,A. Chronic elevation of brain GABA levels beginning two days after status epilepticus does not prevent epileptogenesis in rats. Neuropharmacology 2001; 40(--):536-550. >>> Vigabatrin; Saline; SC; rat; 2ML2; 10 weeks; controls received mp w/ vehicle; long-term study, pumps replaced every 2 weeks for 10 weeks; epilepsy; seizures..

P4846 Iwaniec,U.T., Fung,Y.K., Akhter,M.P., Haven,M.C., Nespor,S., Haynatzki,G.R., Cullen,D.M. Effects of nicotine on bone mass, turnover, and strength in adult female rats. Calcified Tissue International 2001; 68(--):358-364. >>> Nicotine; Saline; SC; rat; 2004; 3 months; controls received mp w/ vehicle; functionality of mp verified by serum nicotine levels; dose response (graphs p. 360); long-term study, pumps replaced every 30 days..

P4803 Fang,T.-C., Wu,C.C., Huang,W.C. Inhibition of nitric oxide synthesis accentuates blood pressure elevation in hyperinsulinemic rats.. Journal of Hypertension 2001; 19(-7-):1255-1262. >>> Insulin, porcine;; Glycerin; Ethanol;; SC;; rat;; 2002;; 6 weeks;; Controls received mp w/ vehicle; functionality of mp verified by removing, measuring residual volume; long-term study, pumps replaced after 14 days and 28 days; vehicle was 50:50 glycerin, ethanol mix;.

P4775 Weiss,D., Kools,J.J., Taylor,W.R. Angiotensin II-induced hypertension accelerates the development of atherosclerosis in ApoE-deficient mice. Circulation 2001; 103(--):448-454. >>> Angiotensin II; Norepinephrine;; Water; Sodium chloride; Acetic acid;; SC;; mice;; 1002;; 4 or 8 weeks; Functionality of mp verified by plasma angiotensin levels; long-term study, pumps replaced 4 to 8 week study; vehicle solution was 0.15 M NaCl, .01 N acetic acid;.

P4742 Tang,W, Seidman,M.D, Henig,J.P, Shulman,A, Stracher,A  International Tinnitus Journal 2001; 7(-1-):4-12. >>> Leupeptin;; Hank's solution;; ear (round window);; guinea-pig;; 2002;; 8 weeks;; Controls received mp w/ vehicle; tissue perfusion (bulla); long-term study, pumps replaced every 13 days; IntraEAR catheter used; Leupeptin is a potent calpain inhibitor; neuroprotection; buprenorphine given as postoperative analgesic; chloramphenicol given as prophlactic antibiotic;.

P8572 Surwit,R.S., Edwards,C.L., Murthy,S., Petro,A.E. Transient effects of long-term leptin supplementation in the prevention of diet-induced obesity in mice. Diabetes 2000; 49(-7-):1203-1208. >>> Leptin, recomb. mouse; SC; Mice; 2004; 12 weeks; Controls received mp w/ PBS; functionality of mp verified by plasma levels and residual volume; long-term study; pumps replaced every 4 weeks; no stress (see pg. 1205); peptides; animal info (male, C57BL/6J, B6, A/J, 20 grams); obesity.

P4748 Iwaniec,U.T, Fung,Y.K., Cullen,D.M, Akhter,M.P, Haven,M.C, Schmid,M  Calcif.Tissue Int. 2000; 67(--):68-74. >>> Nicotine tartrate;; Saline;; SC;; rat;; 2004;; 2-3 months;; Controls received mp w/ vehicle; functionality of mp verified by serum nicotine levels via gas chromatography; long-term study, pumps replaced every 30 days; low (3.0 mg/kg.day) or high dose (4.5 mg/kg.day); bone density strength;.

P4680 Hieda,Y, Keyler,D.E, Ennifar,S, Fattom,A, Pentel,P.R  International Journal of Immunopharmacology 2000; 22(--):809-819. >>> Nicotine bitartrate;; Saline;; SC;; rat;; 2ML4;; 11 weeks;; Controls received mp w/ vehicle; comparison of chronic bolus injections vs. mp; long-term study, pumps replaced after 4 and 8 weeks; immunology; dependence;.

P4660 Cooper,T.T, Clancy,A.N., Karom,M, Moore,T.O, Albers,H.E. Conversion of testosterone to estradiol may not be necessary for the expression of mating behavior in male Syrian hamsters.. Hormones and Behavior 2000; 37(--):237-245. >>> Fadrozole;; Saline;; SC;; hamster;; 2004; 2002;; 8 weeks;; Controls received empty mp; functionality of mp verified by weighing residual fluid; long-term study, pumps replaced every 2 or 4 weeks; enzyme inhibitor (nonsteroidal aromatase inhibitor);.

P4160 Turner,N.D., Byers,F.M., Kenison,D.C. Plasma kinetics of zeranol in steers receiving variable doses in implant or mini-osmotic pump form. Unknown 1999; (--):71-75. >>> Zeranol; Water; cattle (steer); 56 days; comparison of pellets vs. mp; long-term study, pumps replaced after 28 days.

P4030 Rao,A.J., Ramachandra,S.G., Ramesh,V., Krishnamurthy,H.N., Jayaraman,S., Gopalakrishnan,K., Juneja,H.S. Effect of chronic administration of tamoxifen on fertility in male bonnet monkeys (macaca radiata). Andrologia 1998; 30(--):129-132. >>> Tamoxifen; Ethanol; Propylene glycol; SC; monkey; 90 days; controls received mp w/vehicle; long-term study, pumps replaced every 30 days.

P3775 Robinson,S.E., Maher,J.R., Wallace,M.J., Kunko,P.M. Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat. Neurotoxicol.Teratol. 1997; 19(-4-):295-303. >>> Methadone HCl; SC; rat (pregnant); 42 days; controls received mp w/sterile water; dependence; long-term study, pumps replaced after 4 weeks; teratology.

P3737 Keller,D.A., Marshall,C.E., Lee,K.P. Subchronic nasal toxicity of hexamethylphosphoramide administered to rats orally for 90 days. Fundam.Appl.Toxicol. 1997; 40(--):15-29. >>> Hexamethylphosphoramide; Water; SC; rat; 2ML4; 45, 85 days; comparison of oral dosings vs. mp; long-term study, pumps replaced every 28 days; stability verified by gas chromatography; ALZAID chemical compatibility kit used to test compatibility of agent and vehicle (25% hexamethylphosphoramide); toxicology.

P3706 Basile,A.S., Huang,J.-M., Xie,C., Webster,P., Berlin,C., Skolnick,P. N-Methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss. Nature Medicine 1996; 2(-12-):1338-1343. >>> MK-801; Ifenprodil tartrate; DMSO; Water, deionized; Alkamuls EL620; SC; guinea-pig; 2002; no duration posted; long-term study, pumps replaced after 14 days; agents NMDA antagonists; 40% DMSO used; dizocilpine maleate used.

P3692 Gong,J.G., Campbell,B.K., Bramley,T.A., Gutierrez,C.G., Peters,A.R., Webb,R. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist. Biol.Reprod. 1996; 55(--):68-74. >>> Buserelin; SC; cattle; 2ML4; 48 days; controls received no treatment; long-term study, pumps replaced after 28 days; agent is a GnRH agonist; pumps replaced in opposite shoulder than original placement; researchers compare mp w/ injections from previous study (p. 72).

P3246 Li,H., Helander,H.F. Parietal cell kinetics after administration of omeprazole and ranitidine in the rat. Scand.J.Gastroenterol. 1995; 30(--):205-209. >>> Ranitidine; Thymidine; 3H tracer; Radio-isotopes; SC; rat; 2002; 2ML1; 5-56 days; controls received mp with saline; long-term study, pumps replaced weekly; 1 ranitidine and 1 thymidine pump used concomitantly in each animal.

P2821 Ataya,K., Pydyn,E., Ramahi-Ataya,A., Orton,C.G. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: preliminary observations. J.Clin.Endocrinol.Metab. 1995; 80(-3-):790-795. >>> Leuprolide acetate; NaCl; SC; monkey; 2ML4; 82 days; controls received mp with vehicle and/or no irradiation; long-term study, pumps replaced every 24 days; leuprolide acetate is a luteinizing hormone-releasing hormone (LHRH) agonist.

P2998 DiGregorio,G.B., Gonzalez Reyna,A., Murphy,B.D. Roles of melatonin and prolactin in testicular crudescence in mink (Mustela vison). J.Reprod.Fertil. 1994; 102(--):1-5. >>> Prolactin, ovine; SC; mink; 110 days; controls received no treatment; long-term study, pumps replaced every 4 weeks; peptides.

P2646 Brooks,J., McNeilly,A.S. Regulation of gonadotrophin-releasing hormone receptor mRNA expression in the sheep. J.Endocrinol. 1994; 143(--):175-182. >>> Buserelin; SC; sheep; 2ML4; 42 days; long-term study, pumps replaced after 26 days; peptides; pumps inserted in the flank; buserelin is a synthetic GnRH agonist, [D-Ser(But)] GnRH(1-9) nonapeptide-ethylamide.

P3225 Lyford,G.L., Gutnikov,S.A., Clark,A.M., Rawlins,J.N.P. Determinants of non-spatial working memory deficits in rats given intraventricular infusions of the NMDA antagonist AP5. Neuropsychologia 1993; 31(-10-):1079-1098. >>> AP5, D-; CSF, artificial;; CSF/CNS; rat; 2002; 14-40 days; controls received mp with vehicle; long-term study, pumps replaced every 10 days; sulphonamide powder applied topically to surgical wound.

P3012 Verhofstad,A.A.J  J.Anat. 1993; 183(--):315-326. >>> Uridine, bromodeoxy-;; PBS;; SC;; rat;; 12 hours to 73 days;; comparison of bolus injections vs mp.; long-term study; no stress (see pg. 323);.

P2924 Ronayne,E., Enright,W.J., Roche,J.F. Effects of continuous administration of gonadotropin-releasing hormone (GnRH) or a potent GnRH analogue on blood luteinizing hormone and testosterone concentrations in prepubertal bulls. Domest.Anim.Endocrinol. 1993; 10(-3-):179-189. >>> Luteinizing HRH; Leuprolide acetate; Saline; SC; cattle; 2ML4; 28,56 days; controls received mp with vehicle; functionality of mp verified by plasma levels; long-term study, pumps replaced at 28 days; peptides.

P2880 Robinson,J.J., Wallace,J.M., Aitken,R.P., McNeilly,A.S. Effect of chronic treatment with a GnRH agonist to suppress pulsatile LH secretion on the ability of exogenous melatonin to advance oestrous cyclicity in ewes. J.Reprod.Fertil. 1993; 99(--):601-608. >>> Buserelin; SC; sheep; 2ML4; 50 days; long-term study, pumps replaced on day 25; peptides.

P2606 Ataya,K., Ramahi-Ataya,A. Reproductive performance of female rats treated with cyclophosphamide and/or LHRH agonist. Reprod.Toxicol. 1993; 7(-3-):229-235. >>> Leuprolide; Sodium chloride; SC; rat; 2002; 76-98 days; controls received mp w/ saline and/or sham operations; long-term study, pumps replaced every 12 days; cancer; toxicology.

P2277 Geraci,J.P., Taylor,D.A., Mariano,M.S., Jackson,K.L. Effects of dexamethasone on the development of radiation nephropathy in the rat. Radiat.Res. 1992; 131(--):186-191. >>> Dexamethasone; SC; rat; 2ML4; 166 days; comparison of administration in drinking water vs. mp; long-term study, pumps replaced every 4 weeks; benefits of mp admin, p.190.

P2244 de Bruine,A.P., Dinjens,W.N.M., Zijlema,J.H.L., Lenders,M.-H., Bosman,F.T. Renewal of enterochromaffin cells in the rat caecum. Anat.Rec. 1992; 233(--):75-82. >>> Uridine, bromodeoxy-; Ammonia; PBS; SC; rat; 2001; 2002; 1,2,4,8,16,25,31,73 days; long-term study, pumps replaced every 7 days or 14 days.

P3283 McLaughlin,C.L., Rogan,G.J., Buonomo,F.C., Cole,W.J., Hartnell,G.F., Hudson,S., Kasser,T.R., Miller,M.A., Baile,C.A. Finishing lamb performance responses to bovine and porcine somatotropins administered by ALZET pumps. J.Anim.Sci. 1991; 69(--):4039-4048. >>> Growth hormone, bovine; Growth hormone, porcine; SC; sheep; 6 weeks; controls received no treatment; functionality of mp verified by in vitro testing; long-term study, pumps replaced every 2 weeks; peptides.

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