References on the Administration of Antivirals Using ALZET® Osmotic Pumps

1. Acyclovir

16030 Ito, N., Ito, K., Koshimichi, H., Hisaka, A., Honma, M., Igarashi, T., Suzuki, H. Contribution of protein binding, lipid partitioning, and asymmetrical transport to drug transfer into milk in mouse versus human. Pharm Res 2013; 30(-9-):2410-22. >>> acetaminophen, cephalothin sodium salt, clindamycin hydrochloride, disopyramide phosphate salt, labetalol hydrochloride, nitrofurantoin +-propranolol hydrochloride, terbutaline hemisulfate salt, verapamil hydrochloride, Acyclovir, alprazolam, atenolol, anhydrous caffeine, cefotaxime sodium salt, cephapirin sodium salt, diltiazem hydrochloride, metronidazole, nitrazepam, prednisolone, 6-propyl-2-thiouracil, trazadone hydrochloride, chloramphenicol, cimetidine, theophylline, fluconazole, metoprolol, mirtazapine, praziquantel, quetiapine fumarate, triprolidine hydrochloride, metformin, moclobemide.; DMSO; water; IP; mice; 1003D; animal info: lactating mice, postnatal age of 14 days; functionality of mp verified by measurement of drug concentration in milk and plasma; mp were used to infuse study lactational drug transfer..

14228 Ito, N., Ito, K., Ikebuchi, Y., Kito, T., Miyata, H., Toyoda, Y., Takada, T., Hisaka, A., Honma, M., Oka, A., Kusuhara, H., Suzuki, H., Ito, K. Organic Cation Transporter/Solute Carrier Family 22a is Involved in Drug Transfer into Milk in Mice. Journal of Pharmaceutical Sciences 2014; 103(--):3342-3348. >>> Acyclovir; cimetidine; clindamycin; metformin; terbutaline; verapamil;; IP; Mice; 1003D; Animal info (female, lactating, Bcrp KO or WT FVB); functionality of mp verified by plasma and milk concentrations; no stress"All mice survived the surgical procedure and appeared to be lactating normally, and all pups thrived throughout the course of the experiment."(see pg. 3343);.

379 Myerson, D., Hsiung, G.D. Prophylactic and therapeutic treatment with acyclovir of genital herpes in the guinea pig (41717). Proc. Soc. Exp. Biol. Med 1983; 174(--):147-152. >>> Acyclovir, sodium; Saline; SC; guinea-pig; 2ML2; comparison of ip inject vs. mp infusion; article states incorrectly that 2ML2 is spent after 7 days.

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2. Amantadine

13572 Huang, E.Y.K., Tsui, P.F., Kuo, T.T., Tsai, J.J., Chou, Y.C., Ma, H.I., Chiang, Y.H., Chen, Y.H. Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury. PLoS One 2014; 9(-1-):U118-U131. >>> Amantadine; Saline; SC; Rat; 2006; Control animals received mp w/ vehicle; animal info (male, Sprague Dawley, 200-250 g, 6 wks old); long-term study.

4422 Hesselink, M.B., De Boer, A.G., Breimer, D.D., Danysz, W. Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.. Journal of Neural Transmission 1999; 106(--):409-421. >>> MK-801; Memantine; Amantadine;; Water;; SC;; rat;; 2ML2;; controls received sham surgeries; comparison of S.C. injections vs. mp; half-life (p. 411);"In the clinical situation, depending on dosing schedule, only minor fluctuations in the steady-state plasma levels of the aminoadamantanes is observed. The only way to mimic this in animals is by continuous infusion of the drug using ALZET osmotic minipumps."(p. 411);.

4327 Hesselink, M.B., De Boer, B.G., Breimer, D.D., Danysz, W. Brain penetration and in vivo recovery of NMDA receptor antagonists amantadine and memantine: a quantitative microdialysis study. Pharmaceut. Res 1999; 16(-5-):637-642. >>> Memantine; Amantadine; Water; SC; rat; 2ML2; dose-response; serum levels.

15427 Stitz, L., Planz, O., Bilzer, T. Lack of antiviral effect of amantadine in borna disease virus infection. Med Microbiol Immunol 1998; 186(--):195-200. >>> Adamantane, 1-amino-; Water, sterile distilled; SC; rat; 2ML2; functionality of mp verified by serum levels; comparison of oral doses vs. mp; immunology; agent is NMDA antagonist also called amantadine or 1-adamantanamide.

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3. Azidothymidine

2202 Tarantal, A.F., Spanggord, R.J., Hendrickx, A.G. Pre and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine: I. fetal studies. Pediatr. Aids HIV Infection: Fetus to Adolescent 1994; 5(-1-):10-19. >>> Azidothymidine; Sodium hydroxide; SC; monkey (pregnant); 2ML4; controls received mp w/vehicle; functionality of mp verified by plasma levels of AZT; teratology; AZT is azidothymidine, also known as zidovudine; multiple pumps per animal (3-4);"Circulating levels of AZT remained constant during the course of treatment and were achieved by the first (24 hr.) sample (p. 11)..

2089 Sinet, M., Harcouet, L., Desforges, B., Colin, J.N., Farinotti, R., Pocidalo, J.J. Efficacy of continuous zidovudine infusion at early stages of retroviral infection in mice. J. Acquir. Immune Defic. Syndr 1992; 5(--):577-582. >>> Azidothymidine; Propylene glycol; Water; SC; mice; 2001; functionality of mp verified by plasma AZT levels; comparison of b.i.d. s.c. injections vs. mp; good methods; also called zidovudine; pK; half-life (p.577); continuous infusion significantly more effective than bolus injection.

1924 Bilello, J.A., MacAuley, C., Fredrickson, T.N., Bell, M.M., McKissick, C., Shapiro, S.G., Personette, R., Eiseman, J.L. Use of a neonatal murine retrovirus model to evaluate the long-term efficacy and toxicity of antiviral agents. Ann. N. Y. Acad. Sci 1990; 616(--):238-251. >>> Azidothymidine; mice (pregnant); 2001; Pumps replaced after each week to achieve 3 weeks duration; immunology; teratology; oral delivery of AZT resulted in highly variable plasma levels.

1641 Gallo, J.M., Clark, L.N., Rubino, J.T. Pump delivery of azidothymidine: potential for constant concentrations and improved brain delivery. J. Controlled Release 1989; 9(--):249-253. >>> Azidothymidine; IA (carotid); rat; 2001; Dose-response; blood levels; comparison of IV injections vs. mp; good methods; antiviral; alkaline pH of 11 increased solubility and stability of AZT.

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4. Ganciclovir

16267 Varvel, N. H., Grathwohl, S. A., Degenhardt, K., Resch, C., Bosch, A., Jucker, M., Neher, J. J. Replacement of brain-resident myeloid cells does not alter cerebral amyloid-beta deposition in mouse models of Alzheimer's disease. J Exp Med 2015; 212(-11-):1803-9. >>> Valganciclovir; PBS; CSF/CNS (ventricle); mice; 2004; Controls received mp w/ vehicle; animal info (Female hemizygous TK mice crossed w/ male hemizygous APPPS1 or hemizygous APP23); ALZET brain infusion kit 3 used; good methods (pg. 11807); post op. care (paracetamol, i.p. 5 mg/kg daily; acetaminophen i.p. 5 mg/kg daily); brain tissue distribution; Dental cement used; Cannula placement verified via staining; anesthetized using ketamine and xylazine; Brain coordinates; from bregma: +0.1 mm anteroposterior, 1.0 mm lateral, and 2.5 mm dorsoventral; Dose (50 mg/ml);.

16232 Prokop, S., Miller, K. R., Drost, N., Handrick, S., Mathur, V., Luo, J., Wegner, A., Wyss-Coray, T., Heppner, F. L. Impact of peripheral myeloid cells on amyloid-beta pathology in Alzheimer's disease-like mice. J Exp Med 2015; 212(-11-):1811-8. >>> Ganciclovir; CSF, artificial; CSF/CNS (lateral ventricles); mice; 2001; Controls received mp w/ vehicle; animal info (APPPS1 transgenic mice); brain infusion cannula used; neurodegenerative (Alzheimer’s); Dose (2.5 mg/ml); Therapeutic indication (Alzheimer’s Disease);.

15909 Grathwohl, S. A., Jucker, M. Replacement of osmotic minipumps to extend the intracerebral infusion time of compounds into the mouse brain. Biotechniques 2013; 55(-2-):75-8. >>> Ganciclovir; PBS; CSF/CNS; mice; controls received mp w/ PBS; paper introduces Y-shaped connection piece between infusion cannula and pump reservoir. It is used to prolong ICV infusion, serves as a channel to modulate pressure that is released;.

15782 Andriana G Kotini, Elisa de Stanchina, Maria Themeli, Michel Sadelain, Eirini P Papapetrou. Escape Mutations, Ganciclovir Resistance, and Teratoma Formation in Human iPSCs Expressing an HSVtk Suicide Gene. MOLECULAR THERAPY 2016; 5(--):. >>> Ganciclovir; PBS; SC; Mice (NSG); 1007D; animal info (female, NSG, 8 weeks old); pumps replaced every week; cancer (teratoma); Dose (5 mg/kg/day);.

15072 Schneider, U., Davids, A.M., Brandenburg, S., Mueller, A., Elke, A., Magrini, S., Atangana, E., Turkowski, K., Finger, T., Gutenberg, A., Gehlhaar, C., Brueck, W., Heppner, F., Vajkoczy, P., Vajkoczy, P. Microglia inflict delayed brain injury after subarachnoid hemorrhage. ACTA NEUROPATHOLOGICA 2015; 130(--):215-231. >>> Ganciclovir; CSF/CNS; Mice; Animal info (CD11b-HSVTK, 14-14 weeks old, 22-25g); ALZET brain infusion kit used; immunology; noted 230 ul reservoir;.

15019 Dixon, K.J., Theus, M.H., Nelersa, C.M., Mier, J., Travieso, L.G., Yu, T.S., Kernie, S.G., Liebl, D.J., Liebl, D.J. Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury. JOURNAL OF NEUROTRAUMA 2015; 32(--):753-764. >>> Ganciclovir sodium; SC; Mice; 1002; Controls received mp w/ vehicle; animal info (CD1 nestin TK, adult); pumps replaced every 2 weeks; behavioral testing (motor function/rotarod test); traumatic brain injury;.

14887 Cho, K.O., Lybrand, Z.R., Ito, N., Brulet, R., Tafacory, F., Zhang, L., Good, L., Ure, K., Kernie, S.G., Birnbaum, S.G., Scharfman, H.E., Eisch, A.J., Hsieh, J., Hsieh, J. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nature Communications 2015; 6(--):U1-U13. >>> Ganciclovir; Water, distilled; SC; Mice; 2004; Controls received mp w/ vehicle; animal info (C57BL6 or Nestin-TH, 6 weeks old); behavioral testing (epilepsy behavior, open field, memory); pumps removed after 4 weeks; epilepsy;.

14860 Bustos, M.L., Mura, M., Hwang, D., Ludkovski, O., Wong, A.P., Keating, A., Waddell, T.K., Waddell, T.K. Depletion of Bone Marrow CCSP-Expressing Cells Delays Airway Regeneration. MOLECULAR THERAPY 2015; 23(--):561-569. >>> Ganciclovir; SC; Mice; Animal info (CCtk or WT);.

14807 Rolon-Reyes, K., Kucheryavykh, Y.V., Cubano, L.A., Inyushin, M., Skatchkov, S.N., Eaton, M.J., Harrison, J.K., Kucheryavykh, L.Y., Kucheryavykh, L.Y. Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway. PLoS One 2015; 10(--):U2306-U2323. >>> Ganciclovir; CSF/CNS (intratumoral); Mice (transgenic); 2004; Controls received mp w/ saline, normal; animal info (male, CD11b-HSVTK trangenic); ALZET brain infusion kit used; cancer (glioma GL261);.

14774 Seo, D.O., Carillo, M.A., Lim, S.C.H., Tanaka, K.F., Drew, M.R., Drew, M.R. Adult Hippocampal Neurogenesis Modulates Fear Learning through Associative and Nonassociative Mechanisms. JOURNAL OF NEUROSCIENCE 2015; 35(--):11330-11345. >>> Ganciclovir; PBS; CSF/CNS; Mice; 1002; Control animals received mp w/ vehicle; animal info (8 wks old, DCX-TK transgenic, wt); ALZET brain infusion kit 3 used.

14667 Bennett, R.E., Brody, D.L., Brody, D.L. Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury. Journal of Neurotrauma 2014; 31(--):1647-1663. >>> Valganciclovir; Saline, sterile; Mice; 1002; 2004; Controls received mp w/ vehicle; animal info (CD11b-TK +/-,6-8 weeks); post op. care (antibacterial ointment; heating pad); cyanoacrylate adhesive; Cannula placement verified via histological analysis; used Plastics One Cannula; pumps primed at 37C for 36-48 hours; pumps removed after 7 days and reimplanted after two closed-skull injuries; traumatic brain injury;.

13918 Sachewsky, N., Leeder, R., Xu, W., Rose, K.L., Yu, F., van der Kooy, D., Morshead, C.M., Morshead, C.M. Primitive Neural Stem Cells in the Adult Mammalian Brain Give Rise to GFAP-Expressing Neural Stem Cells. STEM CELL REPORTS 2014; 2(--):810-824. >>> Ganciclovir; AraC; PBS; saline; CSF/CNS; Mice (transgenic); 1007D; Animal info (GFAP-TK); ischemia (cerebral); 2% AraC; 200uM GCV;.

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5. Interferons

15995 Hoyo-Becerra, C., Liu, Z., Yao, J., Kaltwasser, B., Gerken, G., Hermann, D. M., Schlaak, J. F. Rapid Regulation of Depression-Associated Genes in a New Mouse Model Mimicking Interferon-alpha-Related Depression in Hepatitis C Virus Infection. Mol Neurobiol 2015; 52(-1-):318-29. >>> Interferon-a, murine; polyinosinic/polycytidylic acid; PBS; CSF/CNS; Mice; 1002; Controls received mp w/ vehicle; animal info (C57BL6J); behavioral testing (open field test; tail suspension test; forced swimming test); polyinosinic/polycytidylic acid is a toll-like receptor-3 agonist; Dose (mIFN-a 250 IU/day; poly(I:C) 1 ug/day);.

15270 Alfredo Q. Antoniazzi. Endocrine Delivery of Interferon Tau Protects the Corpus Luteum from Prostaglandin F2 Alpha-Induced Luteolysis in Ewes. Biology of Reproduction 2013; 88(-6-):1-12. >>> interferon-tau, recombinant ovine; BSA; IV (jugular, intrauterine); ewe; 2001D, 1003D; controls received mp w/ vehicle; functionality of mp verified by serum antiviral activity; pumps were anchored in the s.c. space with cyanoacrylate glue; 200 ug/day (uterine vein); 200 ug/day (jugular vein).

15056 Pereira, L., Medina, R., Baena, M., Planas, A.M., Pozas, E., Pozas, E. IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult SVZ niche. Frontiers in Cellular Neuroscience 2015; 9(--):U1-U10. >>> Interferon, gamma; Saline; CSF/CNS (third ventricle); Mice; 1007D; Controls received mp w/ vehicle; animal info (male, STAT2 KO or 129S6/SvEv); immunology;.

14264 Lee, J., Stanley, J.A., McCracken, J.A., Banu, S.K., Arosh, J.A., Arosh, J.A. Intrauterine Coadministration of ERK1/2 Inhibitor U0126 Inhibits Interferon TAU Action in the Endometrium and Restores Luteolytic PGF(2alpha) Pulses in Sheep. Biology of Reproduction 2014; 91(--):U177-U185. >>> U0126; serum protein, ovine; interferon tau, recombinant ovine; DMSO; Intrauterine (uterine horn); Sheep (ewe); 2ML1; Controls received mp w/ vehicle; animal info (female, Suffolk Ovis aries); 3% DMSO used; tissue perfusion (uterine horn); cyanoacrylate adhesive; used cyanoacrylate glue to anchor pump; interferon tau aka IFNT;.

13823 Johnson, T.S., Terrell, C.E., Millen, S.H., Katz, J.D., Hildeman, D.A., Jordan, M.B. Etoposide Selectively Ablates Activated T Cells To Control the Immunoregulatory Disorder Hemophagocytic Lymphohistiocytosis. Journal of Immunology 2014; 192(-1-):84-91. >>> Interferon, gamma; Saline; SC; Mice; Controls received mp w/ vehicle; animal info (prf -/- or WT, lymphocytic choriomeningitis virus infected); functionality of mp verified by serum levels; immunology; murine model of hemophagocytic lymphohistiocytosis;.

12869 Dorniak, P., Welsh, TH Jr, Bazer, F.W., Spencer, T.E. Cortisol and Interferon Tau Regulation of Endometrial Function and Conceptus Development in Female Sheep. Endocrinology 2013; 154(-2-):931-941. >>> Cortisol; PF915275; meloxicam; interferon, tau, recomb. ovine; Ethanol; Intrauterine (uterine horn); Sheep (ewe); 2ML1; Control animals received mp w/ vehicle; animal info (mature, rambouillet, female, ewe); 2% ethanol used; vinyl catheter used (0007760);"Our previous studies found that infusion of that amount of IFNT in the uterine lumen each day mimics effects of the conceptus on endometrial expression of hormone receptors and IFNT-stimulated genes during early pregnancy in ewes"pg 932.

12680 Kimura, A., Ishida, Y., Inagaki, M., Nakamura, Y., Sanke, T., Mukaida, N., Kondo, T. Interferon-gamma is protective in cisplatin-induced renal injury by enhancing autophagic flux. Kidney International 2012; 82(-10-):1093-1104. >>> Interferon, gamma, recomb. mouse; SC; Mice; 1007D; Animal info (BALB/c, male, 8-10 wks old).

12343 Dorniak, P., Bazer, F.W., Wu, G.Y., Spencer, T.E. Conceptus-Derived Prostaglandins Regulate Endometrial Function in Sheep. Biology of Reproduction 2012; 87(-1-):U80-U86. >>> Interferon, tau, recomb. ovine; meloxicam; PGE2, ovine serum; PGF2a, ovine serum; PGI2, ovine serum; Ethanol; saline; Intrauterine (uterine horn); Sheep (ewe); 2ML1; Controls received mp w/ vehicle; animal info (Mature Rambouillet); tissue perfusion (intrauterine); multiple pumps used (2); enzyme inhibitor (prostaglandin synthase two).

12342 Dorniak, P., Welsh, TH Jr, Bazer, F.W., Spencer, T.E. Endometrial HSD11B1 and Cortisol Regeneration in the Ovine Uterus: Effects of Pregnancy, Interferon Tau, and Prostaglandins. Biology of Reproduction 2012; 86(-4-):U106-U115. >>> Interferon, tau, recomb. ovine; meloxicam; PGE2, ovine serum; PGF2a, ovine serum; PGI2, ovine serum; Ethanol; saline; Intrauterine (uterine horn); Sheep (ewe); 2ML1; Controls received mp w/ vehicle; animal info (Mature Rambouillet); good methods (pg 2); vinyl tubing used (0007760); 2% ethanol used; enzyme inhibitor (prostaglandin synthase two); tissue perfusion (intrauterine).

12326 Li, T.X., Shi, Z.D., Rockey, D.C. Preproendothelin-1 expression is negatively regulated by IFNgamma during hepatic stellate cell activation. American Journal of Physiology-Gastrointestinal and Liver Physiology 2012; 302(-9-):G948-G957. >>> Interferon, gamma; PBS; BSA; Rat; 1002; Controls received mp w/ vehicle; animal info (Sprague Dawley).

12269 Yuan, Y., Kasar, S., Underbayev, C., Vollenweider, D., Salerno, E., Kotenko, S.V., Raveche, E. Role of microRNA-15a in autoantibody production in interferon-augmented murine model of lupus. MOLECULAR IMMUNOLOGY 2012; 52(-2-):61-70. >>> Interferon, alpha; interferon, gamma; PBS; BSA; SC; Mice; 2006; Animal info (13 wks old, female, B/W); pumps replaced after 8 weeks; long-term study; stability verified after 8 weeks;"residue IFNs from the pumps at the end of treatment were tested on IFN and IFN responsive cell lines and demonstrated that the in vivo conditions in the pump did not affect bioactivity of both IFNs (data not shown)"pg 63.

11995 Tu, S.P., Quante, M., Bhagat, G., Takaishi, S., Cui, G.L., Yang, X.D., Muthuplani, S., Shibata, W., Fox, J.G., Pritchard, D.M., Wang, T.C. IFN-gamma Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis. Cancer Research 2011; 71(-12-):4247-4259. >>> Interferon-gamma; PBS; BSA; Mice (transgenic); Controls received mp w/ vehicle; animal info (wt B6, IFN-gamma transgenic, 2 mo old).

11623 Tang, Y., Desierto, M.J., Chen, J.C., Young, N.S. The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure. Blood 2010; 115(-3-):541-548. >>> Interferon, gamma; SC; Mice; Animal info (F1, Tbet -/-).

11598 Strickertsson, J.A.B., Dossing, K.B.V., Aabakke, A.J.M., Nilsson, H.O., Hansen, T.V.O., Knigge, U., Kjaer, A., Wadstroem, T., Friis-Hansen, L. Interferon-gamma inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism. WORLD JOURNAL OF GASTROENTEROLOGY 2011; 17(-26-):3117-3125. >>> Interferon, gamma; SC; Mice; 2001; Animal info (C57BL6/J).

11308 Dorniak, P., Bazer, F.W., Spencer, T.E. Prostaglandins Regulate Conceptus Elongation and Mediate Effects of Interferon Tau on the Ovine Uterine Endometrium. Biology of Reproduction 2011; 84(-6-):1119-1127. >>> Meloxicam; interferon, recomb. ovina, tau; Ethanol; saline; Intrauterine (uterine horn); Sheep (ewe); 2ML1; Controls received mp w/ vehicle; animal info (ewe, mature, Rambouillet); cyanoacrylate adhesive; enzyme inhibitor (prostaglandin synthase (PTGS)); vinyl catheter used (0007760);"The Alzet pump was then affixed to the mesometrial ligament between the uterine horn and oviduct by using cyanoacrylate glue... and then secured by sewing the oviduct to the perimetrium of the uterine horn, using 0 coated polyglactin suture."pg 1120; 2% ethanol used; photo of pump and catheter placement, fig. 1;"Intrauterine infusion of that amount of IFNT mimics effects of the conceptus on endometrial expression of hormone receptors and IFNT-stimulated genes during early pregnancy in ewes."pg 1120.

10657 Ryu, H.J., Kim, J.E., Kim, M.J., Kwon, H.J., Suh, S.W., Song, H.K., Kang, T.C. THE PROTECTIVE EFFECTS OF INTERLEUKIN-18 AND INTERFERON-gamma ON NEURONAL DAMAGES IN THE RAT HIPPOCAMPUS FOLLOWING STATUS EPILEPTICUS. Neuroscience 2010; 170(-3-):711-721. >>> Antibody, anti IL-18; IL-18, recomb. rat; interferon, gamma, recomb. rat; antibody, anti interferon, gamma; IL-18 receptor antagonist; interferon, gamma, receptor antagonist; Saline; CSF/CNS; Rat; 1007D; Controls received mp w/ vehicle; animal info (Sprague Dawley, 7 wks old); ALZET brain infusion kit 1 used.

10163 Bott, R.C., Ashley, R.L., Henkes, L.E., Antoniazzi, A.Q., Bruemmer, J.E., Niswender, G.D., Bazer, F.W., Spencer, T.E., Smirnova, N.P., Anthony, R.V., Hansen, T.R. Uterine Vein Infusion of Interferon Tau (IFNT) Extends Luteal Life Span in Ewes. Biology of Reproduction 2010; 82(-4-):725-735. >>> Interferon-tau, recomb, ovine; IV (uterine vein); Sheep (ewe); 2001D; 2ML1; Controls received mp w/BSA or sham surgeries; animal info (white-faced, western range ewe); cyanoacrylate adhesive.

9847 Tzima, S., Victoratos, P., Kranidioti, K., Alexiou, M., Kollias, G. Myeloid heme oxygenase-1 regulates innate immunity and autoimmunity by modulating IFN-beta production. Journal of Experimental Medicine 2009; 206(-5-):1167-1179. >>> Interferon-beta, recomb. human; Mice; 2002; Animal info (Hmox1 KO).

9538 Shinohara, A., Koyanagi, S., Hamdan, A.M., Matsunaga, N., Aramaki, H., Ohdo, S. Dosing schedule-dependent change in the disruptive effects of interferon-alpha on the circadian clock function. LIFE SCIENCES 2008; 83(-15-16-):574-580. >>> Interferon-alpha, recomb. human; Saline; SC; Mice; 2001; Controls received mp w/ vehicle; comparison of SC injections vs. mp; half-life (p. 579)"relatively short"; peptides; animal info (male, ICR, 5 wks old); behavioral testing (locomotor activity).

9066 Rogers, A.B., Theve, E.J., Feng, Y., Fry, R.C., Taghizadeh, K., Clapp, K.M., Boussahmain, C., Cormier, K.S., Fox, J.G. Hepatocellular carcinoma associated with liver-gender disruption in male mice. Cancer Research 2007; 67(-24-):11536-11546. >>> Interferon-gamma, recomb. murine; SC; Mice; Controls received mp w/ vehicle; cancer (tumorigenic hepatitis, liver); peptides; animal info (male, female, A/JCr).

8969 Qiao, X.T., Ziel, J.W., Mckimpson, W., Madison, B.B., Todisco, A., Merchant, J.L., Samuelson, L.C., Gumucio, D.L. Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology 2007; 133(-6-):1989-1998. >>> Interferon-gamma; PBS; BSA; IP; Mice (transgenic); Controls received mp w/ vehicle; comparison of IP injections vs. mp; peptides; animal info (12.4 KVil-EGFP tg; C57BL/6J; 4 months old); long-term study.

8498 Si, Y., Ciccone, S., Yang, F.C., Yuan, J., Zeng, D., Chen, S., van de Vrugt, H.J., Critser, J., Arwert, F., Haneline, L.S., Clapp, D.W. Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice. Blood 2006; 108(-13-):4283-4287. >>> Interferon-gamma, mouse; PBS; SC; Mice; 1007D; Controls received mp w/ vehicle; no stress (see pg. 4286); immunology; peptides; animal info (C57BL/6).

7941 Birk, R.Z., Rubinstein, M. IFN-alpha induces apoptosis of adipose tissue cells. Biochemical and Biophysical Research Communications 2006; 345(-2-):669-674. >>> Interferon-a A/D, recomb. human; Saline; SC; Mice; Controls received mp w/ vehicle; animal info (C57BL/6, diet-induced obese).

7657 Kang, W.Q., Rathinavelu, S., Samuelson, L.C., Merchant, J.L. Interferon gamma induction of gastric mucous neck cell hypertrophy. LABORATORY INVESTIGATION 2005; 85(-5-):702-715. >>> Interferon-gamma, recomb. mouse; IP; Mice; 1002; Controls received PBS; animal info (c57BL/6).

7394 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; Controls received mp w/ vehicle; long-term study; pumps replaced every 2 weeks; immunology.

7350 Brooling, J.T., Campbell, J.S., Mitchell, C., Yeoh, G.C., Fausto, N. Differential regulation of rodent hepatocyte and oval cell proliferation by interferon gamma. Hepatology 2005; 41(-4-):906-915. >>> Interferon-gamma, recomb. mouse; SC; Mice; Controls received mp w/ saline; replacement therapy (hepatectomy).

7251 Li, X.X., Yang, Y.Z., Yuan, J., Hong, P., Freie, B., Orazi, A., Haneline, L.S., Clapp, D.W. Continuous in vivo infusion of interferon-gamma (IFN-gamma) preferentially reduces myeloid progenitor numbers and enhances engraftment of syngeneic wild-type cells in Fancc(-/-) mice. Blood 2004; 104(-4-):1204-1209. >>> Interferon-gamma, murine; PBS; SC; Mice; 1007D; Controls received mp w/ vehicle; dose-response (fig. 7); no stress (pg. 1209); stress/adverse reaction: (see pg. 1205)"modest though not significant rise in peripheral white blood cell count"(pg. 1205);"IFN-gamma was overall well tolerated by both WT and Fancc -/- mice."(pg. 1208); hematology.

6972 Frewert, S., Stockhammer, F., Warschewske, G., Zenclussen, A.C., Rupprecht, S., Volk, H.D., Woiciechowsky, C. Intratumoral infusion of interleukin-1 beta and interferon-gamma; induces tumor invasion with macrophages and lymphocytes in a rat glioma model. Neuroscience Letters 2004; 364(-3-):145-148. >>> Interleukin-1, beta recomb. rat; Interferon-gamma, recomb. rat; Saline, physiological; albumin, human serum; CSF/CNS (intratumoral); Rat; 1003D; Controls received mp w/ vehicle; tissue perfusion (tumor); cancer (glioma).

6306 Koyanagi, S., Ohdo, S. Alteration of intrinsic biological rhythms during interferon treatment and its possible mechanism. MOLECULAR PHARMACOLOGY 2002; 62(-6-):1393-1399. >>> Interferon-alpha; Saline, sterile; SC; Mice; 2001; Controls received mp w/ vehicle; immunology; peptides.

6214 Zavros, Y., Rathinavelu, S., Kao, J.Y., Todisco, A., Del Valle, J., Weinstock, J.V., Low, M.J., Merchant, J.L. Treatment of Helicobacter gastritis with IL-4 requires somatostatin. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2003; 100(-22-):12944-12949. >>> Interleukin-4; interferon-gamma; PBS; IP; Mice; 1007D; Controls received mp w/ vehicle; comparison of IP injections vs. IP mp.

5228 Skovseth, D.K., Yamanaka, T., Brandtzaeg, P., Butcher, E.C., Haraldsen, G. Vascular morphogenesis and differentiation after adoptive transfer of human endothelial cells to immunodeficient mice. American Journal of Pathology 2002; 160(-5-):1629-1637. >>> Interferon-gamma; Abdominal wall; mice; 2004; tissue perfusion (abdominal wall); immunology; peptides; pump implanted SC, catheter tube perfused matrigel plug in abdominal wall..

4782 Jander, S, Schroetter, M, Fischer, J, Stoll, G. Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony-stimulating factors.. Glia 2000; 30(--):401-410. >>> Interferon-gamma; Tumor necrosis factor-a;; PBS, sterile;; CSF/CNS;; rat;; 1007D;; Controls received mp w/ vehicle; immunology; peptides; ALZET brain infusion kit used; proinflammatory cytokines;.

4656 Nedelec, B, Dodd, C.M, Scott, P.G, Ghahary, A., Tredget, E.E. Effect of interferon-alpha 2b on guinea pig wound closure and the expression of cytoskeletal proteins in vivo.. Wound Repair and Regeneration 1998; 6(--):202-212. >>> Interferon-a2b; Saline, sterile; IP; Guinea-pig; 2ML4; Controls received mp w/vehicle; wound healing study.

4758 Voest, E.E, Kenyon, B.M, O'Reilly, M.S, Truitt, G, D'Amato, R.J, Folkman, J. Inhibition of angiogenesis in vivo by interleukin 12.. Journal of the National Cancer Institute 1995; 87(-8-):581-586. >>> Interferon-gamma; Saline; IM; Mice (scid); 2002; Controls received mp w/ saline; functionality of mp verified by checking residual volume; comparison of bolus invections vs. mp; cancer; immunology; angiogenesis inhibitor; recomb. murine interferon-gamma used;"... in comparison with bolus injections, continuous intraperitoneal infusion of IFN gamma achieved enhanced inhibition of angiogenesis ..."(p. 585).

15492 Henke, P.K., Bergamini, T.M., Watson, A.L., Brittian, K.R., Powell, D.W., Peyton, J.C. Bacterial products primarily mediate fibroblast inhibition in biomaterial infection. J. Surg. Res 1998; 74(--):17-22. >>> Antibody, anti-interferon gamma; Antibody, indomethacin; Antibody, anti-TNFa; Antibody, interleukin 1 alpha; PBS, sterile; ETOH; Indomethacin; SC; mice; 1007D; immunology; pump implanted next to Dacron graft; peptides.

4081 Henke, P.K., Bergamini, T.M., Watson, A.L., Brittian, K.R., Powell, D.W., Peyton, J.C. Bacterial products primarily mediate fibroblast inhibition in biomaterial infection. J. Surg. Res 1998; 74(--):17-22. >>> Antibody, anti-interferon gamma; Antibody, indomethacin; Antibody, anti-TNFa; Antibody, interleukin 1 alpha; PBS, sterile; ETOH; Indomethacin; SC; mice; 1007D; immunology; pump implanted next to Dacron graft; peptides.

3830 Galbiati, F., Rogge, L., Guery, J.-C., Smiroldo, S., Adorini, L. Regulation of the IL-12 receptor B2 subunit by soluble antigen and IL-12 in vivo. Eur. J. Immunol 1998; 28(--):209-220. >>> Interleukin-12; Interleukin-2; Lysozyme, hen egg white; Ovalbumin; Interferon-gamma; PBS; Albumin, mouse serum; SC; mice; 2001; controls received mp w/ PBS; comparison of ip injections vs. mp; immunology; peptides; agents infused singly or in combination in the same pump; recomb. human IL-2 used; recomb. mouse IFN-gamma used.

3674 Tsuji-Takayama, K., Harashima, A., Tahata, H., Izumi, N., Nishida, Y., Namba, M., Okuda, Y., Ohta, T., Kurimoto, M. IFN-gamma in combination with IL-3 accelerates platelet recovery in mice with 5-fluorouracil-induced marrow aplasia. J. Interferon and Cytokine Res 1996; 16(--):447-451. >>> Interferon-gamma; Interleukin-3; Albumin, mouse serum; PBS; SC; mice; 1007D; controls received mp w/ vehicle; stability verified after 7 day storage; immunology; peptides; cytokines given singly and together.

3609 Siesjo, P., Visse, E., Sjogren, H.O. Cure of established, intracerebral rat gliomas induced by therapeutic immunizations with tumor cells and purified APC or adjuvant IFN-gamma treatment. J. Immunol 1996; 19(-5-):334-345. >>> Interferon-gamma; SC; CSF/CNS; rat; cancer; immunology; peptides; ALZET brain infusion kit used.

3212 Unemori, E.N., Beck, L.S., Lee, W.P., Xu, Y., Siegel, M., Keller, G., Liggitt, H.D., Bauer, E.A., Amento, E.P. Human relaxin decreases collagen accumulation in vivo in two rodent models of fibrosis. J. Invest. Dermatol 1993; 101(--):280-285. >>> Relaxin; Interferon-gamma; PBS; SC; rat; mice; 2002; controls received mp with vehicle; immunology; multiple pumps per animal (1-2) for relaxin delivery; polyvinyl alcohol sponges implanted subcutaneously in rats for fibrotic infiltration; intentional capsule formation in mice analyzed.

3113 Flynn, J.L., Chan, J., Triebold, K.J., Dalton, D.K., Stewart, T.A., Bloom, B.R. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med 1993; 178(--):2249-2254. >>> Interferon-gamma; PBS; SC; mice; controls received mp w/ PBS or could endogenously produce IFN; replacement therapy (genetic inability to produce IFN-gamma); comparison of im injections vs. mp; circulating half-life of IFN-gamma in mice is about 1 hour; continuous delivery of IFN-gamma prolonged survival longer than did IFN injections (12 vs. 4 days longer than controls); mouse IFN-gamma used.

3051 Curfs, J.H.A.J., van der Meide, P.H., Billiau, A., Meuwissen, J.H.E.Th., Eling, W.M.C. Plasmodium berghei: recombinant interferon-y and the development of parasitemia and cerebral lesions in malaria-infected mice. Exp. Parasitology 1993; 77(--):212-223. >>> Interferon-gamma; Saline, isotonic; IP; Mice; mice (nude); 2002; controls were untreated, or treated but uninfected;". . .daily injection of a bolus of 105 units of IFN-gamma is not lethal, whereas even a lower daily total dose of 2.5 x 104 units of IFN-gamma administered by continuous release is lethally toxic."; only continuous delivery was able to prevent development of cerebral malaria; comparison of ip injections vs. mp; recomb. rat IFN-gamma.

3037 Rapp, J., Dallah, C.N., Schulz-Key, H. Parenteral administration of cytokines and drugs in rodent filariasis via osmotic pumps. Parasite 1994; 1(-1S-):35-37. >>> Interferon-gamma; SC; mice; 2002; controls received mp with PBS or were untreated; no stress (see pg. 37); immunology;"implantation of osmotic pumps is a suitable method for the application of short lived substances like IFN-gamma or other cytokines."; incision heals within three days and animals show no signs of discomfort, making pumps a useful alternative to repeated injections especially for rodents..."; recomb. mouse IFN-gamma used.

2763 Drath, D.B., Do, C., Burd, T., Hong, L.L. Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers. Immunol. Invest 1994; 23(-2-):115-127. >>> Interferon-gamma; S-MDP, free; S-MDP, liposome-encapsulated; SC; rat; comparison of bolus tracheal injections, iv administration and mp; immunology; peptides; IFN-gamma and S-MDP were most effective when delivered either intravenously or via osmotic minipump infusion; S-MDP is lipophilic N-acetylmuramyl-6-0-stearoyl-alanyl-D-isoglutamine; recomb. mouse IFN-gamma used.

2713 Wiranowska, M., Prockop, L.D., Naidu, A.K., Saporta, S., Kori, S., Kulkarni, A.P. Interferon entry through the blood-brain barrier in glioma and its effect on lipoxygenase activity. Anticancer Res 1994; 14(--):1121-1126. >>> Interferon-a/B, mouse; Interferon-gamma; SC; mice; cancer; peptides; recomb. mouse IFN-gamma used.

2621 Rockey, D.C., Chung, J.J. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J. Invest. Med 1994; 42(-4-):660-670. >>> Interferon-gamma; PBS; Albumin, bovine serum; IP; rat; 2ML4; controls received mp w/ vehicle; immunology; peptides; rat IFN-gamma used.

2581 Rosiello, R.A., Merrill, W.W., Rockwell, S., Carter, D., Cooper Jr, J.A.D., Care, S., Amento, E.P. Radiation pneumonitis: bronchoalveolar lavage assessment and modulation by a recombinant cytokine. Am. Rev. Respir. Dis 1993; 148(--):1671-1676. >>> Interferon-gamma; SC; rat; peptides; oncology.

2288 Kuhn, J.A., Wong, J.Y.C., Beatty, B.G., Esteban, J.M., Williams, L.E., Beatty, J.D. Gamma-interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts. J. Immunother 1992; 11(--):257-266. >>> Interferon-gamma; Albumin, bovine serum; PBS; SC; mice; 1007D; functionality of mp verified by residual amounts; dose-response (text p. 259, graph p. 260); comparison of ip injections vs. infusion; cancer; immunology; peptides; biological activity of residual in pump diminished 15% by day 4, 25% by day 6 (p. 262); recomb. human IFN-gamma used.

2115 Wiranowska, M., Gonzalvo, A.A., Saporta, S., Gonzalez, O.R., Prockop, L.D. Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model. J. Neurooncology 1992; 14(--):225-236. >>> Interferon-a/B, mouse; SC; mice; 1003D; cancer; homologous mouse IFN-a/B used.

1995 Denis, M. Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis. J. Leukoc. Biol 1991; 50(--):495-501. >>> Interferon-gamma, inactivated; Tumor necrosis factor-a; Interferon-gamma; Interleukin-2; Interleukin-2, inactivated; Tumor necrosis factor-a, inactivated; IP; mice; 2002; peptides.

1943 Newton, G.R., Martinod, S., Hansen, P.J., Thatcher, W.W., Siegenthaler, B., Gerber, C., Voirol, M.-J. Effect of bovine interferon on acute changes in body temperature and serum progesterone concentration in heifers. J. Dairy Sci 1990; 73(--):3439-3448. >>> Interferon-a1; cattle; 2ML1; peptides; serum IFN-a levels (p. 3445).

1914 Granstein, R.D., Deak, M.R., Jacques, S.L., Margolis, R.J., Flotte, T.J., Whitaker, D., Long, F.H., Amento, E.P. The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wound model. J. Invest. Dermatol 1989; 93(-1-):18-27. >>> Interferon-gamma; PBS; Serum, mouse; IP; SC; mice; 2002; peptides; wound healing.

1841 Denis, M. Recombinant murine beta interferon enhances resistance of mice to systemic mycobacterium avium infection. Infect. Immun 1991; 59(-5-):1857-1859. >>> Interferon-beta; mice; 2002; controls received pumps with heat-inactivated cytokines; peptides.

1715 Murray, H.W. Effect of continuous administration of interferon-y in experimental visceral leishmaniasis. J. Infect. Dis 1990; 161(--):992-994. >>> Stibogluconate, sodium; Interferon-gamma; Albumin, bovine serum; Saline; SC; mice; 2002; comparison of ip injections vs. mp; immunology; some mice received 2 pumps.

1293 Guadagni, F., Schlom, J., Pothen, S., Pestka, S., Greiner, J.W. Parameters involved in the enhancement of monoclonal antibody targeting in vivo with recombinant interferon. Cancer Immunol. Immunother 1988; 26(--):222-230. >>> Interferon-a, recomb. human; Saline; SC; Mice (nude); 2001; dose-response (graph); half-life; comparison of i.m. injections vs. mp infusion; functionality of mp verified by plasma levels; cancer/immunology; peptides.

987 Granstein, R.D., Murphy, G.F., Margolis, R.J., Byrne, M.H., Amento, E.P. Gamma-interferon inhibits collagen synthesis in vivo in the mouse. J. Clin. Invest 1987; 79(-4-):1254-1258. >>> Interferon-gamma; PBS; Serum, mouse; SC; mice; 2002; 2002, 7-14 days; controls received mp w/vehicle; peptides; immunology; stress/adverse reaction (fibrous tissue formation which was used to study effects of gamma-interferon).

957 Drath, D.B. Modulation of pulmonary macrophage superoxide release and tumoricidal activity following activation by biological response modifiers. Immunopharmacology 1986; 12(-2-):117-126. >>> Interferon-gamma; Liposomes; SC; rat; 2001; controls received mp w/empty liposomes; liposome encapsulated agent and free agent; comparison of iv injections vs. mp infusion; cancer/immunology; peptides.

504 Heston, W.D.W., Fleischmann, J., Tackett, R.E., Ratliff, T.L. Effects of a-difluoromethylornithine and recombinant interferon-a2 on the growth of a human renal cell adenocarcinoma xenograft in nude mice. Cancer Res 1984; 44(--):3220-3225. >>> Interferon-a2, recomb. human; SC; Mice (nude); 2002; pump replaced after 2 weeks; immunotherapy; controls received unidentified vehicle in mp; peptides; cancer; recomb. human IF-a2 used.

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6. PMEA

1959 Lee, J.S., Mullaney, S., Bronson, R., Sharpe, A.H., Jaenisch, R., Balzarini, J., De Clercq, E., Ruprecht, R.M. Transplacental antiretroviral therapy with 9-(2-phosphonylmethoxyethyl)adenine is embryotoxic in transgenic mice. J. Acquir. Immune Defic. Syndr 1991; 4(--):833-838. >>> PMEA; Mice; comparison of ip injections vs. mp; teratology; antiviral agent.

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7. R-95288

3819 Agatsuma, T., Abe, K., Furukawa, H., Koga, R., Koizumi, M., Hotoda, H., Kaneko, M. Protection of hu-PBL-SCID/beige mice from HIV-1 infection by a 6-mer modified oligonucleotide, R-95288. Antiviral Res 1997; 34(--):121-130. >>> R-95288; Saline; IP; SC; mice (SCID); 2002; controls received mp w/saline; antisense; mice were transplanted w/human peripheral blood leukocytes; R-95288 protects human chimeric mice against HIV-1 infection; AIDS.

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8. Ribavirin

9369 Georges-Courbot, M.C., Contamin, H., Faure, C., Loth, P., Baize, S., Leyssen, P., Neyts, J., Deubel, V. Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah Virus infection. Antimicrobial Agents and Chemotherapy 2006; 50(-5-):1768-1772. >>> Ribavirin; 6-aza-uridine; SC; Hamster; 2ML2; Controls received mp w/ PBS; toxicology; animal info (2 months old, golden); Ribavirin is an antiviral agent; 6-aza-uridine is a triazmenucleoside.

5586 Charlier, N., Leyssen, P., Paeshuyse, J., Drosten, C., Schmitz, H., Van Lommel, A., De Clercq, E., Neyts, J. Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis. Journal of General Virology 2002; 83(--):1887-1896. >>> Ribavirin; SC; Mice (SCID); 2002; Ribavirin is an antiviral.

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9. SID 791

3692 Datema, R., Rabin, L., Hincenbergs, M., Moreno, M.B., Warren, S., Linquist, V., Rosenwirth, B., Seifert, E., McCune, J.M. Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry. Antimicrob. Agents Chemother 1996; 40(-3-):750-754. >>> SID 791; Saline, sterile; SC; Mice (SCID); mice; 2002; functionality of mp verified by plasma levels; dose-response; comparison of sc injections vs. mp; immunology; SID 791 is a bicyclam which inhibits HIV replication in vivo; human fetal liver&thymus transplanted into SCID mice.

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“Unlike injected nicotine, the infusion of nicotine via osmotic minipumps does not cause any overt signs of hypoxia/ischemia, such as blanching of the skin or cyanosis.” Xu et al., Brain Research 2002; 951:280-292.