Intravenous Infusion in the Mouse Using ALZET^® Osmotic Pumps

P8575 Pavco,P.A., Bouhana,K.S., Gallegos,A.M., Agrawal,A., Blanchard,K.S., Grimm,S.L., Jensen,K.L., Andrews,L.E., Wincott,F.E., Pitot,P.A. Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin Cancer Res 2000; 6(-5-):2094-2103. >>> Ribozyme, anti-Flt-1; ribozyme, anti-KDR; ribozyme, attenuated; Saline; IV (jugular); SC; Mice; mice (nude); 2002; 14,28 days; Controls received mp w/ vehicle or attenuated control; dose-response (fig. 2); pumps replaced after 18 days; stress/adverse reaction (see pg. 2096);<10% of animals removed from study due to catheter failure or animal not surviving pump implantation; half-life (p. 2100) IV and SC similar; cancer (lung carcinoma, colorectal carcinoma, liver metastasis); animal info (female, C57BL/6, 6-8 weeks old, male, nude, 6-8 weeks old); antiangiogenic, 80% bioavailable after SC administration; targets VEGF receptor mRNA; anti-Flt-1 ribozyme also known as angiozyme.

P8479 Whalen,E.J., Foster,M.W., Matsumoto,A., Ozawa,K., Violin,J.D., Que,L.G., Nelson,C.D., Benhar,M., Keys,J.R., Rockman,H.A., Koch,W.J., Daaka,Y., Lefkowitz,R.J., Stamler,J.S. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell 2007; 129(-3-):511-522. >>> Isoproterenol; GSNO; PBS; IV (jugular); Mice; ; Cardiovascular; agent is also known as nitrosoglutathione.

P8338 Schaefer,M.B., Ott,J., Mohr,A., Bi,M.H., Grosz,A., Weissmann,N., Ishii,S., Grimminger,F., Seeger,W., Mayer,K. Immunomodulation by n-3- versus n-6-rich lipid emulsions in murine acute lung injury - Role of platelet-activating factor receptor. Critical Care Medicine 2006; 35(-2-):544-554. >>> Saline, physiological; lipoven; omegaven; IV (jugular); Mice; 10 days; Controls received mp w/ saline, physiological; pumps replaced after 7 days of saline infusion; animal info (BALB/C wt, 8-12 weeks old, 18-21 grams, LPS induced acute lung injury and IP inflammation); mp contained an external device tied to the back; lipoven 10% (soybean oil); omegaven 10% (fish oil); lipid emulsion.

P8224 Menon,J., Soto-Pantoja,D.R., Callahan,M.F., Cline,J.M., Ferrario,C.M., Tallant,E.A., Gallagher,P.E. Angiotensin-(1-7) inhibits growth of human lung adenocarcinoma xenografts in nude mice through a reduction in cyclooxygenase-2. Cancer Research 2007; 67(-6-):2809-2815. >>> Angiotensin (1-7); Saline; heparin; IV (jugular); Mice (nude); 2004; 28 days; Controls received mp w/ vehicle; no stress (see pg. 2810); cancer (lung); peptides; animal info (male, athymic, 2-4 weeks old, 15-20 grams); "During the infusion period, the animals maintained their body weight as well as food and water consumption and showed no evidence of reduced motor function. Additionally, no gross pathological abnormalities were observed in major organs..indicating a lack of toxic side effects." (p. 2810).

P7871 Ohtaki,H., Nakamachi,T., Dohi,K., Aizawa,Y., Takaki,A., Hodoyama,K., Yofu,S., Hashimoto,H., Shintani,N., Baba,A., Kopf,M., Iwakura,Y., Matsuda,K., Arimura,A., Shioda,S. Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2006; 103(-19-):7488-7493. >>> Pituitary adenylate cyclase-activating polypeptide, 6-38; pituitary adenylate cyclase-activating polypeptide 38; pituitary adenylate cyclase-activating polypeptide; Saline; BSA; IV (jugular); Mice; 4, 8 hours; Controls received mp w/ vehicle; peptides; ischemia (cerebral); animal info (BALB/C, IL-6 -/-, +/-, wt); partial or total middle cerebral artery occlusion.

P7135 Benlloch,M., Ortega,A., Ferrer,P., Segarra,R., Obrador,E., Asensi,M., Carretero,J., Estrela,J.M. Acceleration of glutathione efflux and inhibition of gamma-glutamyltranspeptidase sensitize metastatic B16 melanoma cells to endothelium-induced cytotoxicity. Journal of Biological Chemistry 2005; 280(-8-):6950-6959. >>> Acivicin; verapamil; IV; Mice; 2001D; 7 hours; Controls received mp w/ physiological saline; cancer (melanoma).

P7052 Alley,M.C., Hollingshead,M.G., Pacula-Cox,C.M., Wand,W.R., Hartley,J.A., Howard,P.W., Gregson,S.J., Thurston,D.E., Sausville,E.A. SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity. Part 2: Efficacy evaluations. Cancer Research 2004; 64(-18-):6700-6706. >>> SJG-136; DMSO; PEG; IV (jugular); Mice (nude); 2001; 5 days; Controls received mp w/ vehicle; comparison of IV injections vs. mp; no stress (see pg. 6706); cancer (melanoma); agent also known as NSC 694501; 50% DMSO; "It is noteworthy that 5-day continuous infusions are highly effective in the LOX IMVI tumor model...continuous infusions were highly active and the lower peak plasma concentrations afforded by them may render infusion a useful mode for SJG-136 delivery in man." (pg. 6704-5).

P6973 Arap,W, Haedicke,M, Bernasconi,M, Kain,R, Rajotte,D  PNAS 2002; 99(-3-):1527-1531. >>> SMSIARL, phage; IV; Mice; ; Comparison of pellets vs. mp; peptides; cancer.

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).

P6131 Tejeda,M., Gaal,D., Csuka,O., Ullrich,A., Schwab,R., Pap,A., Horvath,A., Keri,G. The antitumor effect of the somatostatin analogue TT-232 depends on th e treatment regimen. Cancer Detection and Prevention 2003; 27(-2-):155-162. >>> TT-232; Acetic acid; sodium acetate; mannitol; SC; IV (jugular); Mice; 2001; 2002; 1,2,4 weeks; Comparison of SC + IV injections vs. mp; 2002 pumps replaced after 14 days; cancer (sarcoma colon, breast lymphoma); somatostatin analog; PE-10 tubing used for IV group; "The infusion treatment with ALZET Osmotic Pumps proved to be superior to both twice daily injections or intravenous injections." (p. 155).

P6035 Ameredes,B.T., Otterbein,L.E., Kohut,L.K., Gligonic,A.L., Calhoun,W.J., Choi,A.M.K. Low-dose carbon monoxide reduces airway hyperresponsiveness in mice. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 2003; 285(-6-):L1270-L1276. >>> Rp-8-BrcGMP; Saline; IV (jugular); Mice; 10 days; Rp-8-BrcGMP is an inhibitor of cGMP production; pump model not listed.

P5949 Szende,B., Keri,G. TT-232: a somatostatin structural derivative as a potent antitumor drug candidate. Anti-cancer Drugs 2003; 14(-8-):585-588. >>> TT-232; SC; IV; Mice (SCID); 2002; 14 days; Comparison of SC injections vs. mp; cancer (sarcoma, lymphoid, colon, breast); peptides; TT-232 is a somatostatin analog; "the infusion treatment using implanted ALZET-type osmotic mini-pumps proved to be superior to both S.C. and I.V. infusion applied twice a day for 2 weeks." (p. 586).

P5566 Dono,R., Texido,G., Dussel,R., Ehmke,H., Zeller,R. Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO J. 1998/8/3; 17(-15-):4213-4225. >>> Angiotensin II; IV (jugular); Mice; 1007D; 6 days; Cardiovascular; peptides.

P5554 Bowler,R.P., Sheng,H.X., Enghild,J.J., Pearlstein,R.D., Warner,D.S., Crapo,J.D. A catalytic antioxidant (AEOL 10150) attenuates expression of inflammatory genes in stroke. Free Radical Biology and Medicine 2002; 33(-8-):1141-1152. >>> AEOL 10150; PBS; IV (jugular); Mice; 1003D; 6 hours; Controls received mp w/ vehicle; AEOL 10150 is a catalytic antioxidant metalloporphyrin; ischemia (cerebral).

P5314 Sheng,H.X., Enghild,J.J., Bowler,R., Patel,M., Batinic-Haberle,I., Calvi,C.L., Day,B.J., Pearlstein,R.D., Crapo,J.D., Warner,D.S. Effects of metalloporphyrin catalytic antioxidants in experimental brain ischemia. Free Radical Biology and Medicine 2002; 33(-7-):947-961. >>> AEOL 10150; PBS; IV (jugular); Mice; 1003D; 3 days; Controls received mp w/ vehicle; plasma levels of AEOL 10150 determined by HPLC; ischemia (cerebral).

P5249 Sharkey,E.M., O'Neill,H.B., Kavarana,M.J., Wang,H., Creighton,D.J., Sentz,D.L., Eiseman,J.L. Pharmacokinetics and antitumor properties in tumor-bearing mice of an enediol analogue inhibitor of glyoxalase I. Cancer Chemother.Pharmacol 2000; 46(-2-):156-166. >>> Glutathione, S-(N-p-chlorophenyl-N-hydroxycarbamoyl); Cyclodextrin, B-; IV (jugular); Mice; 2002; 14 days; Comparison of IV injections vs. mp; enzyme inhibitor; 20% hydroxypropyl-beta-cyclodextrin used; CHG (Et)2 is an enediol analog inhibitor of glycoxalase in its ester prodrug form; colon adenocarcinoma and prostate cancer.

P4485 Tejeda,M, Gaal,D., Schwab,R.E, Pap,A, Szúts,T, Keri,GY. Influence of various administration routes on the antitumor efficacy of TT-232, a novel somatostatin analog.. Anticancer Res. 2000; 20(--):1023-1028. >>> TT-232; Acetic acid; Water, distilled; Sodium acetate; Marmite;; SC; IV; Mice; 2001; 2002; 1, 2 weeks; comparison of IV + SC injections vs. mp infusion; cancer; peptides; "continuous infusion using an implantable minipump proved to be the most effective route of treatment in both SC or IV administration against S-180 sarcoma." (P. 1026).

P3363 Tu,Y., Stepkowski,S.M., Chou,T.-C., Kahan,B.D. The synergistic effects of cyclosporine, sirolimus, and brequinar on heart allograft survival in mice. Transplantation 1995; 59(-2-):177-183. >>> Cyclosporin A; Rapamycin; Cremophor; Dimethylacetamide, N, N-; Tween 80; PEG 400; IV (jugular); mice; 1007D; 7, 14 days; pumps replaced after 7 days; immunology; CSA and rapamycin given singly and via same pump.

P2096 Redwood,S.M., Liu,B.C.S., Weiss,R.E., Hodge,D.E., Droller,M.J. Abrogation of the invasion of human bladder tumor cells by using protease inhibitor(s). Cancer 1992; 69(-5-):1212-1219. >>> E-64; PBS; IV (jugular); mice (nude); no duration posted; cancer; immunology; enzyme inhibitor (cysteine protease).

P2048 Stepkowski,S.M., Tu,Y., Condon,T.P., Bennett,C.F. Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities. J.Immunol. 1994; 153(--):5336-5346. >>> Oligodeoxynucleotide, phosphorothioate antisense; Cyclosporin A; Rapamycin; Oligodeoxynucleotide, scrambled; Cremophor; Tween 80; Dimethylacetamide, N, N-; PEG 400; IV (jugular); mice; 7,14 days; oligo of interest was IP-3082; controls received no treatment, unrelated oligo IP-1082, or scrambled oligo IP-4189; immunology; "...this study reports the first example of pharmacologic activity of an antisense PS-oligo by i.v. systemic administration in a model of a complex inflammatory process".

P1464 Nesbitt,T., Davidai,G.A., Drezner,M.K. Abnormal adenosine 3'.5'-monophosphate stimulation of renal 1,25-dihydroxyvitamin D production in Hyp mice: evidence that 25-hydroxyvitamin d-1a-hydroxylase dysfunction results from aberrant intracellular function. Endocrinology 1989; 124(--):1184-1189. >>> Cyclic AMP, N-6-monobutyryl; Water; IV (jugular); mice; 2001; 24 hours; no comment posted.

P1160 Naito,K., Pellis,N.R., Kahan,B.D. Effect of continuous administration of interleukin 2 on active specific chemoimmunotherapy with extracted tumor-specific transplantation antigen and cyclophosphamide. Cancer Res. 1988; 48(--):101-108. >>> Interleukin-2; IP; IV; mice; 1702; 2001; 2002; 2ML2; 10 days; mp connected to catheter; half-life; 2 doses infused; IL-2 infused to potentiate effects of TSTA/CY inject.; comparison of bolus inject. vs. inject. vs. mp infusion; tissue perfusion (spleen); cancer/immunology; peptides; human IL-2 used.

P0963 Ishida,K., Yoshimura,K. Eosinophil responses of permissive and nonpermissive hosts to the young adult worms of Angiostrongylus cantonensis. Z.Parasitenkd 1986; 72(--):661-671. >>> Worm extract -A.cantonensis; Worm secretions -A.cantonensis; IP; IV (jugular); guinea-pig; mice; rat; 2001; 7 days; mice implanted w/mp ip other animals infused iv; host-parasite response; eosinophilia determination; comparison of iv injections vs. mp infusion.