References on the Administration of Immunosuppressants Using ALZET^® Osmotic Pumps

1. Cyclosporin

R0244 Gruber,S.A., Shirbacheh,M.V., Jones,J.W., Barker,J.H., Breidenbach,W.C. Local drug delivery to composite tissue allografts. MICROSURGERY 2000; 20(-8-):407-411. >>> Cyclosporin A; FK-506; IA (brachial); Rabbit; 6 days; Dose-response; review, see pg. 409.

P9116 Kwun,J., Hazinedaroglu,S.M., Schadde,E., Kayaoglu,H.A., Fechner,J., Hu,H.Z., Roenneburg,D., Torrealba,J., Shiao,L., Hong,X., Peng,R., Szewczyk,J.W., Sullivan,K.A., DeMartino,J., Knechtle,S.J. Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients. AMERICAN JOURNAL OF TRANSPLANTATION 2008; 8(-8-):1593-1603. >>> Cyclosporin; SC; Mice; 1002; ; Animal info (male, C57BL/6, 6-8 wks old, Cxcr3-/-).

P8737 Addy,N.A., Fornasiero,E.F., Stevens,T.R., Taylor,J.R., Picciotto,M.R. Role of calcineurin in nicotine-mediated locomotor sensitization. Journal of Neuroscience 2007; 27(-32-):8571-8580. >>> Cyclosporin; FK-506; rapamycin; PBS; Tween 20; DMSO; ethanol; cremaphor; CSF/CNS (ventral tegmental area); CSF/CNS (nucleus accumbens); Rat; 2004; 3-4 weeks; Controls received mp w/ vehicle; no stress (see pg. 8573); animal info (male, Sprague-Dawley, 200-250g); 25% DMSO.

P8541 Muramatsu,Y., Furuichi,Y., Tojo,N., Moriguchi,A., Maemoto,T., Nakada,H., Hino,M., Matsuoka,N. Neuroprotective efficacy of FR901459, a novel derivative of cyclosporin A, in in vitro mitochondrial damage and in vivo transient cerebral ischemia models. Brain Research 2007; 1149(--):181-190. >>> Cyclosporin A; FR901459; Cremophor EL; saline;; CSF/CNS; Rat; 1003D; 48 hours; Dose-response (fig. 7); comparison of IV bolus injections vs. mp; ischemia (cerebral); animal info (male, Wistar, 9-10 weeks old, 274-280 grams, MCAO).

P8446 Coenen,J.J.A., Koenen,H.J.P.M., van Rijssen,E., Kasran,A., Boon,L., Hilbrands,L.B., Joosten,I. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplantation 2007; 39(-9-):537-545. >>> Cyclosporin A; SC; Mice; 2004; 7,14,28 days; Controls received mp w/PBS; dose-response (fig. 1); cardiovascular; immunology; animal info (C3H (H-2K), BALB/C (H-2d), 8-12 wks old).

P8367 Wranning,C.A., El-Akouri,R.R., Groth,K., Moelne,J., Parra,A.K., Braennstroem,M. Rejection of the transplanted uterus is suppressed by cyclosporine A in a semi-allogeneic mouse model. Human Reproduction 2007; 22(-2-):372-379. >>> Cyclosporin A; Propylene glycol; SC; Mice; 1007D; 7-10 days; Controls received mp w/ vehicle, or no treatment; functionality of mp verified by serum CyA levels; dose-response (Table 1); immunology; post op.care (buprenorphin, carprofen, cefuroxine); animal info (female, C57BL/6, B6CBAF1, 6-8 wks old, uterine transplant).

P8173 Marchal,F., Tran,N., Marchal,S., Leroux,A., Marchal,C., Bolotine,L., Guillemin,F.O., Villemot,J.P. Development of an HT29 liver metastases model in nude rats. Oncology Reports 2005; 14(-5-):1203-1207. >>> Cyclosporin A; IP; Rat (nude); 2ML4; 4 weeks; Controls received no treatment; no stress (see pg. 1204); cancer (colorectal); peptides; animal info (male, athymic Rowett nude, 300 grams).

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

P6785 Luckow,B., Joergensen,J., Chilla,S., Li,J.P., Henger,A., Kiss,E., Wieczorek,G., Roth,L., Hartmann,N., Hoffmann,R., Kretzler,M., Nelson,P.J., de Lema,G.P., Maier,H., Wurst,W., Balling,R., Pfeffer,K., Groene,H.J., Schloendorff,D., Zerwes,H.G. Reduced intragraft mRNA expression of matrix metalloproteinases Mmp3, Mmp12, Mmp13 and Adam8, and diminished transplant arteriosclerosis in Ccr5-deficient mice. European Journal of Immunology 2004; 34(-9-):2568-2578. >>> Cyclosporin A; SC; Mice; 2002; ; Heart transplant; cardiovascular.

P6525 Bai,S., Stepkowski,S.M., Kahan,B.D., Brunner,L.J. Metabolic interaction between cyclosporine and sirolimus. Transplantation 2004; 77(-10-):1507-1512. >>> Cyclosporin; sirolimus; Sandimmune IV solution; dimethylacetamide, N-N-; Tween 80; PEG 400; IV (femoral); Rat; 2002; 14 days; Controls received mp w/ vehicle; multiple pumps per animal (2); CSA was purchased as sandimmune IV solution (cremophor or castor oil and 33% ethanol); SRL was dissolved in Tween 80 (10%), PEG 400 (70%), and dimethyl acetamide, N-N- (20%); Immunology.

P6171 Nikolovski,Z., Hof,A., Baumlin,Y., Hof,R.P. Efficacy of SDZ RAD compared with CsA monotherapy and combined RAD/FTY720 treatment in a murine cardiac allotransplantation model. TRANSPLANT IMMUNOLOGY 2001; 9(--):43-49. >>> SDZ RAD; cyclosporin A; Propanediol propylene glycol, 1,2-; SC; Mice; 2002; 8 weeks; Controls received mp w/ vehicle; pumps replaced every two weeks; cardiovascular; SDZ RAD (everolimus or certican) is an immunosuppresant; "SDZ RAD has a shorter half-life than rapamycin; CsA was dissolved in sandimmune IV solution.

P5887 Matsumoto,Y., Hof,A., Baumlin,Y., Hof,R.P. Differential effect of cyclosporine A and SDZ RAD on neointima formation of carotid allografts in apolipoprotein E-deficient mice. Transplantation 2003; 76(-8-):1166-1170. >>> SDZ RAD; cyclosporin A; Propylene glycol; SC; Mice (knockout); 2002; 8 weeks; Dose-response (survival dose response) p. 1168; pumps replaced every 2 weeks; immunology; (RAD) is a novel rapamycin derivative and is an immunosuppresant, aka everolimus or certican; sandimmun IV solution used; "CSA&RAD were administered by ALZET minipumps, which we prefer because of the well-defined drug exposure." p. 1168.

P5496 Haouzi,D., Cohen,I., Vieira,H.L.A., Poncet,D., Boya,P., Castedo,M., Vadrot,N., Belzacq,A.S., Fau,D., Brenner,C., Feldmann,G., Kroemer,G. Mitochondrial permeability transition as a novel principle of hepatorenal toxicity in vivo. Apoptosis 2002; 7(-5-):395-405. >>> Cyclosporin A; Ethanol; SC; Mice; 1003D; .

P4669 Ramirez,C, Olmo,A, O'Valle,F, Masseroli,M, Aguilar,M, Gomez-Morales,M, Revelles,F, Garcia-Chicano,M.J, Arrebola,F, Reguero,J.E, del Moral,R.G. Role of intrarenal endothelin 1, endothelin 3, and angiotensin II expression in chronic cyclosporin A nephrotoxicity in rats.. Experimental Nephrology 2000; 8(--):161-172. >>> Cyclosporin A; Endothelin-1; Endothelin-3;; Saline; Propylene glycol;; SC;; rat;; 2ML4;; 56 days;; Controls received mp w/ vehicle; functionality of mp verified by whole blood CsA levels; long-term study, pumps replaced after 28 days; antihypertensive; cardiovascular; secretion in nephrotoxicity, relationship with Angiotensin II in renal expression propylene glycol used as vehicle for CsA..

P4577 Shirbacheh,M.V, Harralson,T.A, Jones,J.W, Breidenbach,W.C, Jevans,A.W, Maldonado,C, Barker,J.H, Gruber,S.A. Pharmacokinetic advantage of intra-arterial cyclosporin A delivery to vasculary isolated rabbit forelimb. II. Dose dependence. The Journal of Pharmacology and Experimental Therapeutics. 1999; 289(-3-):1191-1195. >>> Cyclosporin A;; Cremophor;; IA (brachial);; rabbit;; 2ML1;; 6 days;; dose-response (p. 1192-1194); immunology; sandimmune (CSA) solution used; intramedic PE-60/PE-10 infusion catheter used; to acheive highest dose; two pumps were implanted and catheters were joined via a Y-connector;.

P4576 Shirbacheh,M.V, Ren,X, Jones,J.W, Breidenbach,W.C, Jevans,A.W, Fernandez-Botran,G.R, Maldonado,C, Barker,J.H, Gruber,S.A. Pharmacokinetic advantage of intra-arterial cyclosporin A delivery to vascularly isolated rabbit forelimb. I. Model development. The Journal of Pharmacology and Experimental Therapeutics. 1999; 289(-3-):1185-1190. >>> Cyclosporin A; IA (brachial); IV (jugular);; rabbit;; 2ML1;; 6 days; good surgical methods (p. 1186); immunology; diagram of pump/catheter system (p. 1186); PE-60 tubing was glued to PE-10 tubing; Sandimmune (CSA) solution used;.

P3997 Brandle,D., Joergensen,J., Zenke,G., Burki,K., Hof,R.P. Contribution of donor-specific antibodies to acute allograft rejection. Transplantation 1998; 65(-11-):1489-1493. >>> Cyclosporin A; SC; mice; no duration posted; dose-response (0, 3, 10 mg/kg/d); immunology.

P3995 Oliver,S.J., Cheng,T.P., Banquerigo,M.L., Brahn,E. Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF). Cellular Immunol. 1995; 166(--):196-206. >>> Cyclosporin A; PEG 300; SC; rat; 2ML4; no duration posted; photo of rat showing implanted pump (pg. 204); no stress (see pp. 199, 204, 205); immunology; controls received sham surgeries.

P3901 Stepkowski,S.M., Wang,M.E., Amante,A., Kalinin,D., Qu,X., Blasdel,T., Condon,T., Kahan,B.D., Bennett,F.C. Antisense ICAM-1 oligonucleotides block allograft rejection in rats. Transplant.Proc. 1997; 29(--):1285-. >>> Cyclosporin; Oligodeoxynucleotide, antisense; Cremophor; IV; rat; 7, 14 days; immunology; antisense; controls received scrambled antisense.

P3900 Wehr,S., Rudin,M., Joergensen,J., Hof,A., Hof,R.P. Allo- and autotransplantation of carotid artery - a new model of chronic graft vessel disease. Transplantation 1997; 64(-1-):20-27. >>> Cyclosporin; SC; rat; 2ML4; 2ML2; 8 weeks; controls received mp w/vehicle; functionality of mp verified by CsA blood levels at 1 and 8 weeks; immunology.

P3899 Sandberg,J.-O., Benda,B., Lycke,N., Korsgren,O. Xenograft rejection of porcine islet-like cell clusters in normal, interferon-gamma, and interferon-gamma receptor deficient mice. Transplantation 1997; 63(-10-):1446-1452. >>> Cyclosporin; SC; mice; 2002; 6, 12 days; controls received mp w/vehicle; functionality of mp verified by blood CsA levels and visual inspection at study end; immunology.

P3611 Tice,D.G., Bruch,D., Ikramuddin,S. Anti-VLA-4 and cyclosporine synergistically prolong rat heterotopic small bowel allografts. Transplant.Proc. 1996; 28(-5-):2496-. >>> Cyclosporin A; rat; 20 days; immunology.

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.

P3239 Larsen,C.P., Elwood,E.T., Alexander,D.Z., Ritchie,S.C., Hendrix,R., Tucker-Burden,C., Cho,H.R., Aruffo,A., Hollenbaugh,D., Linsley,P.S. Long-term acceptance of skin and cardiac allografts after blocking CD 40 and CD 28 pathways. Nature 1996; 381(-6581-):434-438. >>> Cyclosporin A; SC; Mice; 2002; 14 days; No stress (see pg. 437); immunology; animal info (C57BL/6).

P2982 Ferraresso,M., Rigotti,P., Stepkowski,S.M., Chou,T.-C., Kahan,B.D. Immunosuppressive effects of defibrotide. Transplantation 1993; 56(-4-):928-933. >>> Defibrotide; Cyclosporin A; PBS; Cremophor; IA (innominate); IV (lumbar); rat; 2002; 2ML1; no duration posted; Controls were untreated; comparison of ip injections or oral gavage vs. mp; defibrotide infused into artery of graft or recipient vein; defibrotide is an immunosuppressant w/ antithrombotic and profibrinolytic activities.

P2264 Ferraresso,M., Ghobrial,R., Stepkowski,S.M., Kahan,B.D. The mechanism of unresponsiveness to allografts induced by rapamycin and rapamycin/cyclosporine treatment in rats. Transplantation 1993; 55(-4-):888-894. >>> Cyclosporin; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween 80; IV (lumbar); rat; 2002; 14 days; immunology.

P2246 DiJoseph,J.F., Mihatsch,M.J., Sehgal,S.N. Influence of rat strain on rapamycin's kidney effects. Transplant.Proc. 1993; 25(-1-):714-715. >>> Cyclosporin A; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween; IV (jugular); rat; 2002; 2 weeks; controls received mp w/vehicle; functionality of mp verified by HPLC analysis; immunology.

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".

P2016 Stepkowski,S.M., Chen,H.F., Wang,M.E., Daloze,P., Kahan,B.D. Inhibition of host-versus-graft and graft-versus-host responses after small bowel transplantation in rats by rapamycin. Transplantation 1992; 53(-2-):258-264. >>> Cyclosporin; Rapamycin; Dimethylacetamide; PEG 400; Tween; IV (lumbar); rat; 2002; 14 days; tissue perfusion (allograft); immunology.

P1958 Brahn,E., Peacock,D.J., Banquerigo,M.L. Suppression of collagen-induced arthritis by combination cyclosporin A and methotrexate therapy. Arthritis Rheum. 1991; 34(-10-):1282-1288. >>> Cyclosporin A; PEG 300; rat; 2ML4; 28 days; dose response (graph, p. 1284); immunology.

P1941 Bernareggi,A., Rowland,M. Physiologic modeling of cyclosporin kinetics in rat and man. J.Pharmacokinet.Biopharm. 1991; 19(-1-):21-49. >>> Cyclosporin; Cremophor; Ethanol; SC; rat; 6 days; blood and tissue concentrations, volume of distribution on blood and tissues.

P1822 Pereira,G.M.B., Miller,J.F., Shevach,E.M. Mechanism of action of cyclosporine A in vivo. J.Immunol. 1990; 144(-6-):2109-2116. >>> Cyclosporin A; PBS; mice; 2001; 7 days; functionality of mp verified by measuring CsA plasma levels (HPLC); used Sandimmune iv formulation.

P1729 Textor,S.C., Smith-Powell,L., Telles,T. Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats. Am.J.Physiol.(Heart Circ.Physiol.27) 1990; 258(-3-):H854-H860. >>> Cyclosporin A; Olive oil; IP; rat; 2 weeks; controls received pumps with olive oil only; two doses infused.

P1691 Lee,Y.B., Lee,Y.K. The effect of continuous injection of cyclosporine A on the cardiac allograft in the rats. J.Catholic Med.College 1989; 42(-2-):459-469. >>> Cyclosporin A; IV; rat; 2002; 11 days; comparison of daily IV injections vs. mp; graft survival: heart transplant; Japanese with English summary, English captions on graphs and tables.

P1688 Pereira,G.M.B., Furtado,G.de C., Yokoyama,W.M., Kipnis,T.L., Shevach,E.M. Comparative aspects of T cell activation in vivo following stimulation with anti-CD3 MAB, allogenic cells and trypanosoma cruzi. Mem.Inst.Oswaldo Cruz 1988; 1(-83-):284-291. >>> Cyclosporin A; SC; mice; 2001; no duration posted; immunology.

P1567 Stepkowski,S.M., Goto,S., Ito,T., Reynolds,K., Didlake,R., Kim,E.K., Kahan,B.D. Prolongation of heterotropic heart allograft survival by local delivery of continuous low-dose cyclosporine therapy. Transplantation 1989; 47(-1-):17-23. >>> Cyclosporin; Cremophor; IA (innominate); IV; rat; 2002; 14 days; dose-response; comparison of gavage vs. mp infusion; functionality of mp verified by blood levels; tissue perfusion (heart allograft).

P0880 Ruers,T.J., van der Linden,C.J., Buurman,W.A., Kootstra,G. 2'Deoxycoformycin: a new immunosuppressive drug with a potency comparable to cyclosporine. Transplant.Proc.XVII 1985; 17(-1-):1333-1335. >>> Cyclosporin A; Deoxycoformycin, 2'-; Ethanol; Saline; IP; rat; 2ML2; 12 days; controls received mp w/saline; comparison of agents effects; animals rec'd skin grafts; comparison of ip injections vs. mp infusion; immunology.

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2. Deoxyspergualin

P3365 Suzuki,S., Nishimori,H., Kido,K., Arita,S., Tashiro,H., Ohdan,H., Quinones,D., Amemiya,H. Continuous administration of methyldeoxyspergualin prolongs xenograft survival in hamster-to-rat cardiac transplantation. Transplant.Proc. 1993; 25(-1-):430-431. >>> Methyldeoxyspergualin; IP; rat; 2001; 2ML2; 8, 14 days; immunology.

P2065 Nishikawa,K., Shibasaki,C., Takahashi,K., Takeuchi,T. Treatment schedule dependency of antitumor effect of deoxyspergualin. Jpn.J.Antibiot. 1991; 44(-9-):917-925. >>> Deoxyspergualin; Saline; IP; mice; 2001; 1,2,4, or 8 days; comparison of injections vs. mp; cancer; detailed formulation information; time-dependent systemic toxicity characterized; 'continuous infusion produced higher efficacy' over injections.

P0971 Plowman,J., Harrison,Jr.S.D., Trader,M.W., Griswold Jr,D.P., Chadwick,M., McComish.M.F., Silveira,D.M., Zaharko,D. Preclinical antitumor activity and pharmacological properties of deoxyspergualin. Cancer Res. 1987; 47(--):685-689. >>> Deoxyspergualin; Saline; SC; mice; 2001; 24, 48, 72, and 96 hours; dose-response; mps primed in saline at 37C prior to implant; mice w/sc L1210 leukemia cells; comparison of bolus injections vs. mp infusion; functionality of mp verified by plasma conc.; cancer.

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3. FK-506

P8737 Addy,N.A., Fornasiero,E.F., Stevens,T.R., Taylor,J.R., Picciotto,M.R. Role of calcineurin in nicotine-mediated locomotor sensitization. Journal of Neuroscience 2007; 27(-32-):8571-8580. >>> Cyclosporin; FK-506; rapamycin; PBS; Tween 20; DMSO; ethanol; cremaphor; CSF/CNS (ventral tegmental area); CSF/CNS (nucleus accumbens); Rat; 2004; 3-4 weeks; Controls received mp w/ vehicle; no stress (see pg. 8573); enzyme inhibitor (calcineurin); animal info (male, Sprague-Dawley, 200-250g); 25% DMSO.

P8021 Zen,K., Okigaki,M., Hosokawa,Y., Adachi,Y., Nozawa,Y., Takamiya,M., Tatsumi,T., Urao,N., Tateishi,K., Takahashi,T., Matsubara,H. Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response. Journal of Molecular and Cellular Cardiology 2006; 40(-6-):799-809. >>> FK-506; SC; Hamster; 2004; ; Cardiovascular; animal info (8 weeks 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.

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

P6217 Leamey,C.A., Ho-Pao,C.L., Sur,M. Role of calcineurin in activity-dependent pattern formation in the dorsal lateral geniculate nucleus of the ferret. Journal of Neurobiology 2003; 56(-2-):153-162. >>> FK-506; DMSO; saline; CSF/CNS (dorsal lateral geniculate nucleus); Ferret (kit); 2002; 12 days; Controls received mp w/ vehicle; teratology; post op. care (prophylactically treated with amoxycillin); 50% DMSO used; 14-15 day told ferret kits received pumps.

P5470 Kiyama,T., Tajiri,T., Tokunaga,A., Yoshiyuki,T., Barbul,A. Tacrolimus enhances colon anastomotic healing in rats. Wound Repair and Regeneration 2002; 10(-5-):308-313. >>> FK-506; SC; Rat; 1003D; 3 days; Dose-response; FK506 also called tacrolimus.

R0244 Gruber,S.A., Shirbacheh,M.V., Jones,J.W., Barker,J.H., Breidenbach,W.C. Local drug delivery to composite tissue allografts. MICROSURGERY 2000; 20(-8-):407-411. >>> Cyclosporin A; FK-506; IA (brachial); Rabbit; 6 days; Dose-response; review, see pg. 409.

P5285 Shirbacheh,M.V., Jones,J.W., Harralson,T.A., Edelstein,J., Tecimer,T., Breidenbach,W.C., Jevans,A.W., Maldonado,C., Barker,J.H., Gruber,S.A. Pharmacokinetics of intra-arterial delivery of tacrolimus to vascularly isolated rabbit forelimb. J Pharmacol Exp.Ther 1999/6; 289(-3-):1196-1201. >>> FK-506; IA (brachial); Rabbit; 2ML1; 6 days; Functionality of mp verified by FK506 blood levels via ELISA; dose-response (p.1198); FK506 also known as tacrolimus; continuous systemic vs. local administration; immunology; transplantation.

P2848 Motoyama,K., Kamei,T., Arima,T., Ueki,M., Hirano,T., Nakafusa,Y., Tanaka,M. Pretransplant intrathymic inoculation of donor antigen combined with FK506 treatment: prolongation of survival of cardiac, but not renal, allografts in rats. World J.Surg. 1995; 19(--):299-302. >>> FK-506; Ethanol; SC; rat; 2001; 7 days; immunology; 70% ethanol used as a vehicle.

P1966 Ryu,S., Yasunami,Y. The necessity of differential immunosuppression for prevention of immune rejection by FK506 in rat islet allografts transplanted into the liver or beneath the kidney capsule. Transplantation 1991; 52(-4-):599-605. >>> FK-506; Ethanol; SC; rat; 2001; 7, 14, 21, 28 days; pumps replaced each week for 4 weeks; immunology; 70% ETOH; immunosuppressant.

P1923 Ryu,S., Yasunami,Y. Prevention of immune rejection in rat islet allografts by continuous sc administration of FK 506 using a mini-osmotic pump. Transplant.Proc. 1991; 23(-1-):760-. >>> FK-506; Ethanol; SC; rat; 2001; 7 days; 70% ethanol used, immunology.

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4. Methyldeoxyspergualin

P3365 Suzuki,S., Nishimori,H., Kido,K., Arita,S., Tashiro,H., Ohdan,H., Quinones,D., Amemiya,H. Continuous administration of methyldeoxyspergualin prolongs xenograft survival in hamster-to-rat cardiac transplantation. Transplant.Proc. 1993; 25(-1-):430-431. >>> Methyldeoxyspergualin; IP; rat; 2001; 2ML2; 8, 14 days; immunology.

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5. Rapamycin

P8737 Addy,N.A., Fornasiero,E.F., Stevens,T.R., Taylor,J.R., Picciotto,M.R. Role of calcineurin in nicotine-mediated locomotor sensitization. Journal of Neuroscience 2007; 27(-32-):8571-8580. >>> Cyclosporin; FK-506; rapamycin; PBS; Tween 20; DMSO; ethanol; cremaphor; CSF/CNS (ventral tegmental area); CSF/CNS (nucleus accumbens); Rat; 2004; 3-4 weeks; Controls received mp w/ vehicle; no stress (see pg. 8573); enzyme inhibitor (calcineurin); animal info (male, Sprague-Dawley, 200-250g); 25% DMSO.

P7922 Segrelles,C., Moral,M., Lara,M.F., Ruiz,S., Santos,M., Leis,H., Garcia-Escudero,R., Martinez-Cruz,A.B., Martinez-Palacio,J., Hernandez,P., Ballestin,C., Paramio,J.M. Molecular determinants of Akt-induced keratinocyte transformation. ONCOGENE 2006; 25(-8-):1174-1185. >>> Rapamycin; PBS; BSA; SC; Mice (nude); 2002; 2 weeks; Cancer; animal info (nude, 5-6 weeks old, female).

P7354 Krahe,T.E., Medina,A.E., De Bittencourt-Navarrete,R.E., Colello,R.J., Ramoa,A.S. Protein synthesis-independent plasticity mediates rapid and precise recovery of deprived eye responses. Neuron 2005; 48(-2-):329-343. >>> Cycloheximide; rapamycin; tetrodotoxin; PBS; Ferret; 4 days; Controls received mp w/ vehicle; 0.25 ul model pump used.

P7287 Guba,M., Koehl,G.E., Neppl,E., Doenecke,A., Steinbauer,M., Schlitt,H.J., Jauch,K.W., Geissler,E.K. Dosing of rapamycin is critical to achieve an optimal antiangiogenic effect against cancer. TRANSPLANT INTERNATIONAL 2005; 18(-1-):89-94. >>> Rapamycin; DMSO; IP; Mice; 2002; 7-35 days; Controls received mp w/ vehicle; comparison of IP injections vs. mp; cancer (colon adenocarcinoma); "The most effective inhibition of tumor growth occurred in rapamycin-treated mice on the continuous pumping system.;" "Survival data also show the most positive effect with continuous drug delivery." P. 91.

P4566 Luo,H., Chen,H., Qi,S, Loh,D., Daloze,P., Veillette,A, Xu,D., Wu,J. De novo-developed T cells have compromised response to existing alloantigens: Using Ld-specific transgenic 2C T cells as tracers in a mouse heart transplantation model. The Journal of Immunology 1998; 161(--):73-82. >>> Rapamycin; IP; Mice; 14 days;; Immunology; heart transplantation.

P3996 Thompson,P., Xu,D., Brunette,I., Chen,H. Combined effect of rapamycin and cyclosporine in the prevention of rat corneal allograft rejection. Transplant.Proc. 1998; 30(--):1033-1035. >>> Rapamycin; Tween 80; IV (lumbar); rat; 2002; 14 days; transplantation; dose-response (p. 1034); immunology.

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.

P2508 Ferraresso,M., Tian,L., Ghobrial,R., Stepkowski,R., Kahan,B.D. Rapamycin inhibits production of cytotoxic but not noncytotoxic antibodies and preferentially activates T helper 2 cells that mediate long-term survival of heart allografts in rats. J.Immunol. 1994; 153(--):3307-3318. >>> Rapamycin; Dimethylacetamide, N, N-; PEG 400; Tween 80; IV (lumbar); rat; 2002; 14 days; immunology; serum from rats treated with RAPA via minipumps used to inoculate secondary recipients.

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".

P3013 Di Joseph,J.F., Russo,R.J., Cochran,D.W. Osmotic pump delivery of rapamycin. Transplantation 1993; 55(-2-):450-452. >>> Rapamycin; Dimethylacetamide, N, N-; Tween 80; PEG 400; in vitro; 2002; 2 weeks; stability verified by in vitro testing and HPLC for 14 days; in vitro validation of functionality and rapamycin stability.

P2417 Roberge,F.G., Xu,D., Chan,C.-C., de Smet,M.D., Nussenblatt,R.B., Chen,H. Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction. Curr.Eye Res. 1993; 12(-2-):197-203. >>> Rapamycin; PEG 400; Tween 80; Dimethylacetamide, N, N-; IV (lumbar); rat; 2002; 14 days; Immunology.

P2309 Hamashima,T., Yoshimura,N., Ohsaka,Y., Oka,T., Stepkowski,S.M., Kahan,B.D. In vivo use of rapamycin suppresses neither IL-2 production nor IL-2 receptor expression in rat transplant model. Transplant.Proc. 1993; 25(-1-):723-724. >>> Rapamycin; IV (lumbar); rat; 7 days; Immunology.

P2289 Chen,H.J., Xu,D., Luo,H., Daloze,P.M. Reversal of ongoing heart, kidney, and pancreas allograft rejection and suppression of accelerated heart allograft rejection in the rat by rapamycin. Transplantation 1993; 56(-3-):661-666. >>> Rapamycin; DMA; PEG 400; Tween 80; IV (lumbar); Rat; 2002; 14 days; Immunology.

P2264 Ferraresso,M., Ghobrial,R., Stepkowski,S.M., Kahan,B.D. The mechanism of unresponsiveness to allografts induced by rapamycin and rapamycin/cyclosporine treatment in rats. Transplantation 1993; 55(-4-):888-894. >>> Cyclosporin; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween 80; IV (lumbar); rat; 2002; 14 days; immunology.

P2246 DiJoseph,J.F., Mihatsch,M.J., Sehgal,S.N. Influence of rat strain on rapamycin's kidney effects. Transplant.Proc. 1993; 25(-1-):714-715. >>> Cyclosporin A; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween; IV (jugular); rat; 2002; 2 weeks; controls received mp w/vehicle; functionality of mp verified by HPLC analysis; immunology.

P2245 Daloze,P.J., Chen,H., Luo,H., Xu,D., Shan,X., Wu,J. Rapamycin's long-term effects on humoral and cellular immune responses in the rat. Transplant.Proc. 1993; 25(-1-):721-722. >>> Rapamycin; PEG; IV (lumbar); rat; 28 days; controls received mp w/PEG; pumps replaced at day 14; immunology.

P2229 Chen,H., Wu,J., Xu,D., Luo,H., Daloze,P. Rapamycin reverses acute heart, kidney, and pancreas allograft rejection and prevents accelerated heart allograft rejection in the rat. Transplant.Proc. 1993; 25(-1-):719-720. >>> Rapamycin; Dimethylacetamide, N, N-; PEG 400; Tween; IV; rat; 2002; 14,28 days; controls received mp w/vehicle; immunology.

P2228 Chen,H., Wu,J., Luo,H., Daloze,P. Synergistic effect of rapamycin and cyclosporine in pancreaticoduodenal transplantation in the rat. Transplant.Proc. 1992; 24(-3-):892-893. >>> Rapamycin; IV (lumbar); rat; 14 days; immunology.

P2016 Stepkowski,S.M., Chen,H.F., Wang,M.E., Daloze,P., Kahan,B.D. Inhibition of host-versus-graft and graft-versus-host responses after small bowel transplantation in rats by rapamycin. Transplantation 1992; 53(-2-):258-264. >>> Cyclosporin; Rapamycin; Dimethylacetamide; PEG 400; Tween; IV (lumbar); rat; 2002; 14 days; tissue perfusion (allograft); immunology.

R0106 Chang J.Y., Sehgal,S.N., Bansbach,C.C. FK506 and rapamycin: novel pharmacological probes of the immune response. TIPS 1991; 12(--):218-223. >>> Rapamycin; rat; 14 days; immunology.

P3156 Chen,H.F., Wu,J.P., Luo,H.Y., Daloze,P.M. Reversal of ongoing rejection of allografts by rapamycin. Transplant.Proc. 1991; 23(-4-):2241-2242. >>> Rapamycin; Tween; Dimethylacetamide, N-N-; PEG 400; IV (lumbar); rat; 14 days; immunology.

P2015 Stepkowski,S.M., Chen,H., Daloze,P., Kahan,B.D. Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat. Transplantation 1991; 51(-1-):22-26. >>> Rapamycin; Dimethylacetamide; PEG 400; Tween 80; IA (innominate); IV (lumbar); rat; 2002; 14 days; tissue perfusion (allograft).

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