Pulsatile Administration of Agents Using ALZET® Osmotic Pumps

16337 Figge, D. A., Eskow Jaunarajs, K. L., Standaert, D. G. Dynamic DNA Methylation Regulates Levodopa-Induced Dyskinesia. J Neurosci 2016; 36(-24-):6514-24. >>> RG108; Cyclodextrin, hydroxypropyl-B-; CSF/CNS (dorsal striatum); Rat; 2004; Controls received mp w/ vehicle; animal info (male Sprague-dawley, 60– 90 days old, 180-200 g); functionality of mp verified by behavioral testing; 5% cyclodextrin used; Plastics One unilateral guide cannula used; post op. care (7 days of care, buprenorphine and wound care for pain management); behavioral testing (forepaw adjusting steps test); tissue perfusion (brain); delayed delivery “additional polyethylene tubing was added to provide a 14 d prime of vehicle before RG-108 administration” (pg. 6515); “rats were given a unilateral dopamine lesion to the left medial forebrain bundle” (pg. 6515); Brain coordinates: anteroposterior, 0 from bregma, -3mmlateral from midline, and -3.5 mm from the dura; Dose (100 uM);.

16152 Pereira, P. A., Rocha, J. P., Cardoso, A., Vilela, M., Sousa, S., Madeira, M. D. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus. Neurotoxicology 2016; 54(--):153-60. >>> Nerve growth factor; Methylene blue; BSA; CSF, artificial; CSF/CNS; Rat; 2002; animal info (male, Wistar); functionality of mp verified by residual volume; ALZET brain infusion kit used; post op. care (SC injections of 0.9% saline (2ml)); pulsed delivery; used PE-60 tubing; used lynch coil;.

16033 Rakesh Kumar,, K. H. Reeta,, Subrata Basu Ray  Indian Journal of Experimental Biology 2014; 52(--):317-322. >>> loperamide; morphine; PEG, saline, ethanol; CSF/CNS (intrathecal); rat; 2ML2; Controls received mp w/ vehicle; animal info (adult male Sprague-dawley rats, 275-350 g); dose-response (pg 319, 320); good methods (pg. 317-318); post op. care (neomycin ointment and perioperative ketoprofen [3 mg/kg, im] given); behavioral testing (stepping placing, righting reflex, and Hargreaves paw withdrawal test); delayed delivery (lynch coil filled with saline used to delay administration of drug by 3 days; ); Dose: Morphine and Loperamide ( 0.5,1, and 2 uL/hr).

13659 Robins, S.C., Villemain, A., Liu, X.H., Djogo, T., Kryzskaya, D., Storch, K.F., Kokoeva, M.V. Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal. Glia 2013; 61(-10-):1735-1747. >>> Uridine, bromodioxy; Ara-C; Cerebrospinal fluid, artificial; CSF/CNS; Mice (transgenic); Animal info (male, NG2-CreER:tomato, 8-12 weeks old); pulsatile delivery (delayed delivery 2 days with vehicle in catheter); brain tissue distribution; cyanoacrylate adhesive used to close catheter tubing; Plastics 1 cannula and catheter.

13642 Howell, K.K., Monk, B.R., Carmack, S.A., Mrowczynski, O.D., Clark, R.E., Anagnostaras, S.G. Inhibition of PKC disrupts addiction-related memory. Frontiers in Behavioral Neuroscience 2014; 8(-;-):U1-U9. >>> Peptide, zeta-inhibitory; chelerythrine; Cerebrospinal fluid, artificial; PBS; CSF/CNS (third ventricle); Mice; 1002; Controls received mp w/ vehicle; animal info (C57BL/6Jx129T2SvEms/J, adult); ALZET brain infusion kit 3 used; post op. care (buprenorphine injection); behavioral testing (locomotion, locomotor sensitization); pulsatile delivery; dependence; peptides; zeta-inhibitory peptide aka ZIP; Lynch coil of ZIP administration for 14.5 hours; used mineral oil; Schematic of pump implantation pg.3 Fig 1A;.

13471 Pereira, P.A., Santos, D., Neves, J., Madeira, M.D., Paula-Barbosa, M.M. Nerve growth factor retrieves neuropeptide Y and cholinergic immunoreactivity in the nucleus accumbens of old rats. NEUROBIOLOGY OF AGING 2013; 34(-8-):1988-1995. >>> Nerve growth factor; Cerebrospinal fluid, artificial; bovine serum albumin; CSF/CNS; SC; Rat; 2002; Animal info (male, Wistar, 6-24 months old); functionality of BIK verified by methylene blue staining; ALZET brain infusion kit used; 0.1% Bovine Serum Albumin used; neurodegenerative (aging); post op. care (SC injections 2ml of 0.9% saline); pulsatile delivery (used coiled Intramedic PE-60; 0.1% methylene blue with air-oil spacer at pump end with agent); peptides;.

12743 Williams, A.M., Reis, D.J., Powell, A.S., Neira, L.J., Nealey, K.A., Ziegler, C.E., Kloss, N.D., Bilimoria, J.L., Smith, C.E., Walker, B.M. The effect of intermittent alcohol vapor or pulsatile heroin on somatic and negative affective indices during spontaneous withdrawal in Wistar rats. Psychopharmacology 2012; 223(-1-):75-88. >>> Heroin; Saline; SC; Rat; 2ML4; Control animals received mp w/ vehicle; animal info (Wistar, male, 70 days old); pulsatile delivery;"By filling the pumps with saline and attaching polyethylene (PE60) tubing to the pump, based on the tubing inner diameter and pump flow rate characteristics, the volume needed for different infusion periods (e.g., 14- or 10-h periods) could be determined"; pulsatile delivery; good methods, pg 78; image of pump with connected Lynch coil; wound clips used; post op. care (Baytril); behavioral testing (elevated plus mazel forced swim test).

12424 Gollamudi, S., Johri, A., Calingasan, N.Y., Yang, L.C., Elemento, O., Beal, M.F. Concordant Signaling Pathways Produced by Pesticide Exposure in Mice Correspond to Pathways Identified in Human Parkinson's Disease. PLoS One 2012; 7(-5-):U341-U353. >>> Paraquat; pyridaben; maneb; PBS; ethanol; M-5 oil; SC; Mice; Controls received mp w/ vehicle;"we administered the pesticides using alzet pumps, which have the advantage of producing a more even exposure, which is more likely to mimic human exposure than the pulsatile effects of i.p. injections"pg 4; neurodegenerative (Parkinson's disease).

12093 Shaffery, J.P., Lopez, J., Roffwarg, H.P. Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices. Neuroscience Letters 2012; 513(-1-):84-88. >>> Brain-derived neurotrophic factor; PBS; BSA; CSF/CNS (visual cortex); Rat; 2002; 1007D; Controls received mp w/ saline; animal info (Long-Evans Hooded, P28; immature, P22-P25); pulsatile delivery; polyethylene tubing contained saline with an air bubble separator for a 5-day drug delay and recovery period; delayed delivery;.

12008 Kudo, S., Mizuta, H., Takagi, K., Hiraki, Y. Cartilaginous repair of full-thickness articular cartilage defects is induced by the intermittent activation of PTH/PTHrP signaling. OSTEOARTHRITIS AND CARTILAGE 2011; 19(-7-):886-894. >>> Parathyroid hormone (1-84), recomb. human; Saline, sterile; Knee (articular cavity); Rabbit; 2002; Controls received mp w/ vehicle; animal info (male, white, adolescent, Japanese, 3-3.4 kg); pulsatile delivery;"The program consisted of alternating segments of 5 ul PTH (50 ug/ml) solution and 5 ul sterile saline interrupted by 1 ul air bubbles."pg 888.

10698 Stockwell, K.A., Scheller, D., Rose, S., Jackson, M.J., Tayarani-Binazir, K., Iravani, M.M., Smith, L.A., Olanow, C.W., Jenner, P. Continuous administration of rotigotine to MPTP-treated common marmosets enhances anti-parkinsonian activity and reduces dyskinesia induction. Experimental Neurology 2009; 219(-2-):533-542. >>> Rotigotine; Saline, sterile; SC; Monkey (marmoset); 2004; Controls received mp w/ vehicle; animal info (adult common, male, female, 354 g); comparison of sc injections vs. mp; neurodegenerative (Parkinson's disease); post op. care (Rimadyl, Synulox);"pumps were removed... and replaced with new minipumps implanted into the opposite flank."pg 534;"These results demonstrate that the anti-parkinsonian benefits associated with a continuous infusion of rotigotine were more sustained compared to pulsatile rotigotine or L-DOPA treatment..."pg 541; long-term study.

10273 Stockwell, K.A., Scheller, D.K.A., Smith, L.A., Rose, S., Iravani, M.M., Jackson, M.J., Jenner, P. Continuous rotigotine administration reduces dyskinesia resulting from pulsatile treatment with rotigotine or L-DOPA in MPTP-treated common marmosets. Experimental Neurology 2010; 221(-1-):79-85. >>> Rotigotine hydrochloride; DMSO; water, sterile; SC; Marmoset; 2004; Comparison of SC injections or PO administration vs. SC mp; animal info (adult, common, male, female, 2-7 years old, 350-500); 50% DMSO used;"These data suggest that dyskinesia induced by pulsatile drug treatment may be improved by switching to continuous rotigotine delivery."pg. 79;"...this study highlights the potential benefits of continuous drug delivery."pg 84.

9500 Wong, J.H., Dukes, J., Levy, R.E., Sos, B., Mason, S.E., Fong, T.S., Weiss, E.J. Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns. Journal of Clinical Investigation 2008; 118(-8-):2969-2978. >>> Growth hormone, recomb. mouse; Saline; NaCO3; Mice; Controls received mp w/ vehicle; comparison of pulsatile injections vs. mp; cardiovascular; peptides; animal info (male, female, C57BL/6J, wt, lit-mt, 6-8 wks old).

7746 Jarukamjorn, K., Sakuma, T., Jaruchotikamol, A., Ishino, Y., Oguro, M., Nemoto, N. Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver. Toxicology 2006; 219(-1-3-):97-105. >>> Growth hormone, recomb. human; Saline, normal; SC; Mice; 1007D; Controls received mp w/ vehicle; comparison of SC injections vs. mp; peptides; animal info (C57BL/6, male and female, 8 wk old);"Continuous GH administration allowed the GH level to be maintained relatively stably in the circulation compared with pulsatile GH administration". (p. 104).

6345 Neumann, I.D. Antisense oligodeoxynucleotide effects on the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis. METHODS 2000; 22(-3-):227-237. >>> Oligodeoxynucleotide, antisense; Ringer's solution; CSF/CNS; Rat (lactating); 1007D; Tissue perfusion (various brain regions); comparison of ICV injections vs. mp; pulsed delivery (various ODN's, air bubble spacer); antisense; ODN's infused were antisense, mixed base, or 21-mer end capped phosphorothioated; the mp was filled with ringer's solution and PE tubing was filled w/ 50 ul of each agent solution. An air bubble was inserted between solutions; 25-g guide cannula and 27-g infusion cannula used together to allow concomitant icv injections.

5035 de Segura, A.G., Castell, T., Vazquez, I., Mata, A., De Miguel, E. Somatostatin antagonism prevents elemental diet-induced intestinal atrophy in the rat. Digestive Diseases and Sciences 2001; 46(-9-):1985-1992. >>> Somatostatin antagonist; Saline; IP; rat; 2ML1; controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; comparison of sc injections vs. mp; peptides; The somatostatin antagonist is cyclo-7-aminoheptanoyl-phe-d-trp-lys-thr (also known as BZL); SC injections examined pulsatile administration of the agent; pump model 2ML1 used (2001 incorrectly listed);.

4683 Sun, Y-N, Lee, H.J, Almon, R.R, Jusko, W.J  The Journal of Pharmacology and Experimental Therapeutics 1999; 289(-3-):1523-1532. >>> Growth hormone, recomb. human; SC;; monkey;; comparison of SC injections vs. mp vs. microspheres; peptides;"Continuous rhGH input delivered by ProLease and osmotic pump is more effective than pulsatile injections in induction of IGF-I, especially when the delivery systems can maintain growth hormone concentration above the SC50"(p. 1531)..

4620 Kostenuik, P.J, Harris, J, Halloran, B.P., Turner, R.T., Morey-Holton, E.R., Bikle, D.D. Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I.. Journal of Bone and Mineral Research 1999; 14(-1-):21-31. >>> Parathyroid hormone (1-34);; NaCl; HCl; Serum, rat; Saline; Sesame oil;; SC;; rat;; 2001;; controls received mp w/vehicle; peptides; pulsatile administration; PE-60 was filled with sesame oil interspersed with PTH or with vehicle; pumps filled with saline; PTH was designed to be delivered for 1 hr per day for 8 days..

3349 Becker, S.E., Johnson, A.L. Effects of gonadotropin-releasing hormone infused in a pulsatile or continuous fashion on serum gonadotropin concentrations and ovulation in the mare. J. Anim. Sci 1992; 70(--):1208-1215. >>> Luteinizing HRH; IV (jugular); horse; 2ML1; controls received no treatment; functionality of mp verified by LH plasma levels; comparison of iv pulsatile infusion vs. mp; peptides.

2829 Hoffman, A., Nyska, A., Avramoff, A., Golomb, G. Continuous versus pulsatile administration of erythropoietin (EPO) via the uterus in anemic rats. Int. J. Pharmaceutics 1994; 111(--):197-202. >>> Erythropoietin; intrauterine; rat; 2002; controls received intrauterine bolus of saline; replacement therapy (gentamicin-induced anemia); comparison of iv bolus and intrauterine bolus vs. mp; peptides; mp implanted subdermally in abdomen;"administration of drug at a constant rate produces considerably greater biological effect than that observed in the pulsatile mode."(pg. 200); tissue perfusion (uterus); recomb. human EPO used.

2549 Huybrechts, L.M., Decuypere, E., Buyse, J., Kuhn, E.R., Tixier-Boichard, M. Effect of recombinant human insulin-like growth factor-1 on weight gain, fat content, and hormonal parameters in broiler chickens. Poult. Sci 1992; 71(--):181-187. >>> Insulin-like growth factor I; Sodium chloride; SC; bird (chicken); 2002; controls received mp w/ saline; good discussion of pulsatile vs. constant infusion effects with GH (pg.185); recomb. bovine IGF-1 used.

2541 Hebert, N.J., Kim, J.H., Lin, R.J., Nicoll, C.S. Restoration of lactation in bromocriptine-treated rats by prolactin replacement: comparison of constant versus pulsatile infusion and intrahepatic versus intrajugular routes of delivery. J. Endocrinol. Invest 1993; 16(--):29-35. >>> Prolactin, ovine; IV (jugular); IV (hepatic portal); rat; 2001; controls received mp w/ solvent; functionality of mp verified by in vitro dye testing of pulsatile release; comparison of pulsed delivery w/ mp vs. continuous infusion w/ mp; pulsed delivery;"Constant infusion of oPRL. . . was, overall, more effective at restoring lactation. . . than was giving pulses, regardless of the site of delivery."(pg. 29).

325 Podbesek, R., Edouard, C., Meunier, P.J., Parsons, J.A., Reeve, J., Stevenson, R.W., Zanelli, J.M. Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds. Endocrinology 1983; 112(-3-):1000-1006. >>> Parathyroid hormone, human 1-34; SC; dog; comparison of pulsatile injec. vs. mp infusion; pump replaced weekly; comparison of human clinical data vs. animal; long-term study; peptides.


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What researchers are saying...

“Mini-pumps were used to eliminate stress associated with multiple daily injections.” Akhter et al., Journal of Orthopaedic Research 2002;21:14-19.