References on the Administration of Metals Using ALZET® Osmotic Pumps

1. Arsenate

1078 Hanlon, D.P., Ferm, V.H. The concentration and chemical status of arsenic in the early placentas of arsenate-dosed hamsters. Environ. Res 1987; 42(--):546-552. >>> Arsenate, sodium; Radio-isotopes; Arsenic-74 tracer; Water; Radio-isotopes; hamster (pregnant); 2001; functionality of mp verified by radioassay; teratology.

899 Hanlon, D.P., Ferm, V.H. Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis. Environ. Res 1986; 40(--):372-379. >>> Arsenate, sodium; SC; hamster; 2001; teratology; dose-response; functionality of mp verified by radio assay.

673 Ferm, V.H., Hanlon, D.P. Constant rate exposure of pregnant hamsters to arsenate during early gestation. Environ. Res 1985; 37(-2-):425-432. >>> Arsenate, sodium; Water; SC; hamster (pregnant); 2001; teratogenicity; pumps primed in saline 4 hr prior to implant; dose-response data, 4 doses tested; advantage of mp model p.431.

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2. Cadmium

10293 Pedersen, H.C., Loraas, A., Andersen, R.A., Jenssen, B.M. Behavioural effects of cadmium (Cd) in free-living willow ptarmigan (Lagopus lagopus). EUROPEAN JOURNAL OF WILDLIFE RESEARCH 2010; 56(-2-):141-150. >>> Cadmium chloride; SC; Bird (hen); 2002; Controls received mp w/ physiological saline; pumps replaced after 13 days; animal info (willow, ptarmigan, adult, juvenile).

6854 Piasek, M., Laskey, J.W., Kostial, K., Blanusa, M. Assessment of steroid disruption using cultures of whole ovary and/or placenta in rat and in human placental tissue. International Archives of Occupational and Environmental Health 2002; 75(--):S36-S44. >>> Cadmium chloride; SC; Rat (pregnant); 2ML2; Functionality of mp verified by placental cadmium levels; dose-response (fig. 5); teratology.

6194 Piasek, M., Blanusa, M., Kostial, K., Laskey, J.W. Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability. Biometals 2004; 17(-1-):1-14. >>> Cadmium chloride; Saline; SC; Rat (pregnant); 2ML4; Dose-reponse (p. 7, table 2); comparison of SC injections vs. SC mp; teratology.

5962 Kondoh, M., Imada, N., Kamada, K., Tsukahara, R., Higashimoto, M., Takiguchi, M., Watanabe, Y., Sato, M. Property of metallothionein as a Zn pool differs depending on the induced condition of metallothionein. TOXICOLOGY LETTERS 2003; 142(-1-2-):11-18. >>> Cadmium acetate; Saline; SC; Mice; Controls received mp w/ vehicle; no stress (see pg. 12)"None of the animals displayed any evidence of infection or other adverse effects from the procedure."; toxicology.

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3. Copper

8648 Lavoie, N., Peralta, MR III, Chiasson, M., Lafortune, K., Pellegrini, L., Seress, L., Toth, K. Extracellular chelation of zinc does not affect hippocampal excitability and seizure-induced cell death in rats. JOURNAL OF PHYSIOLOGY-LONDON 2007; 578(-1-):275-289. >>> Tricine; EDTA, copper; EDTA, zinc; EDPA; EDTA, calcium; Saline; cresyl violet; CSF/CNS; Rat; 2001D; Controls received mp w/ vehicle; functionality of mp verified by residual volume; brain tissue distribution; animal info (male, Sprague-Dawley,>35 days old); cresyl violet used to verify injection site.

3225 Toyokuni, S., Sagripanti, J.-L. Increased 8-hydroxydeoxyguanosine in kidney and liver of rats continuously exposed to copper. Toxicol. Appl. Pharmacol 1994; 126(--):91-97. >>> Copper chloride; Cupric nitrilotriacetate; Nitrilotriacetic acid; SC; rat; 2001; controls received mp with saline or no treatment; toxicology; Cu-NTA is a copper chelate; copper pump implant sites were marked by tissue necrosis and massive neutrophil infiltration;"...a level of copper that proved to be lethal or highly toxic when delivered in a single bolus dose could be continuously administered with mild histological alterations and without any noticeable modification in the behavior of the rats.".

1990 Ferrell, J.B., Fleisher, L.N., Smith, M.G., McGahan, M.C. Effect of copper loading and depletion on rabbit superoxide dismutase activity. Trace Elements in Medicine 1992; 9(-2-):55-58. >>> Copper sulfate; Saline; SC; rabbit; 2ML4; no comment posted.

1617 McGahan, M.C., Fleisher, L.N., Grimes, A.M. Clinical signs of acute ocular inflammatory response to endotoxin are not altered by increasing antioxidant potency of intraocular fluids. Inflammation 1989; 13(-4-):383-392. >>> Copper sulfate; Saline; SC; rabbit; 2ML4; uveitis model.

890 Veltman, J.C., Maines, M.D. Regulatory effect of copper on rat adrenal cytochrome P-450 and steroid metabolism. Biochem. Pharmacol 1986; 35(-17-):2903-2909. >>> Copper sulfate; Saline; SC; rat; controls received mp w/ saline.

817 Cook, C.S., Grubb, B. Experimental hypercupremia does not result in increases in copper in lens, iris, or ocular fluids. Curr. Eye Res 1986; 5(-2-):171-173. >>> Copper sulfate; SC; rabbit; 2ML4; dose-response data; controls received anesthesia but no surgery or mp.

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4. Desferrioxamine

2668 Kondo, H., Miura, M., Kodama, J., Ahmed, S.M., Itokawa, Y. Role of iron in oxidative stress in skeletal muscle atrophied by immobilization. Pflugers Arch 1992; 421(--):295-297. >>> Desferrioxamine; Desferrioxamine, iron-saturated; Water, double-distilled; SC; rat; 2ML1; controls received mp w/ water.

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5. Magnesium

14616 Johnson, A.C., Tremble, S.M., Chan, S.L., Moseley, J., LaMarca, B., Nagle, K.J., Cipolla, M.J., Cipolla, M.J. Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia. PLoS One 2014; 9(--):U1482-U1492. >>> Magnesium sulfate; SC; Rat (pregnant); Animal info (Sprague Dawley, 14-16 wks old); multiple pumps (3) used; 2ML sized pumps used.

13610 McGuire, J.L., Bergstrom, H.C., Parker, C.C., Le, T., Morgan, M., Tang, H.Y., Selwyn, R.G., Silva, A.C., Choi, K., Ursano, R.J., Palmer, A.A., Johnson, L.R. Traits of fear resistance and susceptibility in an advanced intercross line. European Journal of Neuroscience 2013; 38(-9-):3314-3324. >>> Magnesium chloride; Bicine buffer; Mice; 1003D; Controls received mp w/ vehicle; animal info (fear-susceptible or fear-resistant, 8-10 weeks old); behavioral testing (fear testing); MRI; manganese used to inhance MRI signal.

13551 Muradov, J.M., Hagg, T. Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats. Journal of Neurotrauma 2013; 30(-10-):840-852. >>> Magnesium chloride; PEG; IV (jugular); Rat; 2001D; 1003D; 2001; Controls received mp w/ vehicle; animal info (female, Sprague Dawley, young adult, 180-220g); functionality of mp verified by residual volume; spinal cord injury; post op. care (Bacitracin ointment, saline injection SC, heating pad, twice daily bladder expression); behavioral testing (open field test, grid walk); Primed overnight in saline 37C.

12955 Hoch, T., Kreitz, S., Gaffling, S., Pischetsrieder, M., Hess, A. Manganese-Enhanced Magnetic Resonance Imaging for Mapping of Whole Brain Activity Patterns Associated with the Intake of Snack Food in Ad Libitum Fed Rats. PLoS One 2013; 8(-2-):U277-U286. >>> Magnesium chloride; SC; Rat; 2001; Animal info (Wistar, male, 257 g); PEEK tubing used;"it was concluded that MnCl2 administration by osmotic pumps is a suitable method for mapping activity patterns in the brain specific for different ingested foods."pg e55355.

12642 Korish, A.A. Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis. HYPERTENSION RESEARCH 2012; 35(-10-):1005-1011. >>> Magnesium sulfate; Rat (pregnant); Control animals received mp w/ saline; animal info (Wistar, pregnant, nonpregnant female); 2ML sized pump used.

12606 Mori, K., Yamamoto, T., Nakao, Y., Miyazaki, M., Iwata, J., Tamura, M., Shiroishi, T. Novel neuroprotective effect of cisternal and intra-cerebral magnesium sulfate solution infusion on delayed cerebral death in rat hippocampal neurons after transient global ischemia. Brain Research 2012; 1480(-;-):72-80. >>> Magnesium sulfate; CSF/CNS; CSF/CNS (cisterna magna); CSF/CNS (hippocampus); Rat; 2ML2; 2001; Animal info (Sprague Dawley, male).

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6. Manganese

16331 Dudek, M., Hyytia, P. Alcohol preference and consumption are controlled by the caudal linear nucleus in alcohol-preferring rats. Eur J Neurosci 2016; 43(-11-):1440-8. >>> Manganese Chloride; Saline, Tris-buffered; SC; Rat; 2001; animal info (male alcohol-preferring AA and male Wistar rats; 6 weeks old, 264-413 g); functionality of mp verified by MRI after pump removal; post op. care (carprofen injection); Dose (120 mg/kg/wk);.

16324 Hoch, T., Kreitz, S., Gaffling, S., Pischetsrieder, M., Hess, A. Fat/carbohydrate ratio but not energy density determines snack food intake and activates brain reward areas. Sci Rep 2015; 5(--):10041. >>> Manganese chloride; SC; Rat; animal info (Wistar rats 571 +/-41 g);“To avoid negative side effects on basic physiology and behaviour of the animals due to the injection of the manganese chloride solution in doses sufficient for MEMRI measurement, osmotic pumps served for the gentle, but rather time-consuming continuous application of non-toxic amounts of manganese, which accumulated in the activated brain areas during the whole time course of the 7-day food test phase” (pg. 8); MRI use.

16323 Hoch, T., Kreitz, S., Gaffling, S., Pischetsrieder, M., Hess, A. Manganese-enhanced magnetic resonance imaging for mapping of whole brain activity patterns associated with the intake of snack food in ad libitum fed rats. PLoS One 2013; 8(-2-):e55354. >>> Manganese chloride; SC; Rat; 2001; animal info (Wistar rats, 257 +/- 21 g); good methods (pumps were incubated in isotonic saline for 12 h previous to implantation); For the use in MRI, the stainless steel flow moderator was replaced by a PEEK micro medical tubing;“Osmotic pump-assisted MEMRI proved to be a promising technique for functional mapping of whole brain activity patterns associated to nutritional intake under normal behavior.” (pg 1); “MnCl2 is administered by osmotic pumps, which slowly and continuously release the solution over a time period of up to seven days avoiding adverse effects on motor activity, but providing sufficient manganese accumulation for MRI analysis” (pg. 2); Dose (1 M solution);.

16114 Dudek, M., Abo-Ramadan, U., Hermann, D., Brown, M., Canals, S., Sommer, W. H., Hyytia, P. Brain activation induced by voluntary alcohol and saccharin drinking in rats assessed with manganese-enhanced magnetic resonance imaging. Addict Biol 2015; 20(-6-):1012-21. >>> Manganese Chloride; Saline, Trist-buffered; SC; rat; 2001; animal info: male alcohol-preferring AA rats, 265–335 g; post op. care (subcutaneous injection of carprofen); MRI done after infusion; brain tissue distribution; brain Mn2+ accumulation; Dose: 120 mg/kg/week.

14915 den Hollander, B., Dudek, M., Ojanperae, I., Kankuri, E., Hyytiae, P., Korpi, E.R., den Hollander, B. Manganese-Enhanced Magnetic Resonance Imaging Reveals Differential Long-Term Neuroadaptation After Methamphetamine and the Substituted Cathinone 4-Methylmethcathinone (Mephedrone). INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 2015; 18(--):U118-U126. >>> Manganese chloride; Tris-buffered saline; SC; Rat; 2001; Animal info (Wistar, 6 weeks old); post op. care (SC injection carprofen 5 mg/kg); behavioral testing (locomotor activity, novel object recognition); MRI; pumps primed overnight in 37C saline;.

13903 Poole, D.S., Plenge, E., Poot, D.H.J., Lakke, E.A.J.F., Niessen, W.J., Meijering, E., van der Weerd, L., Poole, D.S. Three-dimensional inversion recovery manganese-enhanced MRI of mouse brain using super-resolution reconstruction to visualize nuclei involved in higher brain function. NMR IN BIOMEDICINE 2014; 27(--):749-759. >>> Manganese chloride; SC; Mice; 1007D; MRI;.

12363 Sepulveda, M.R., Dresselaers, T., Vangheluwe, P., Everaerts, W., Himmelreich, U., Mata, A.M., Wuytack, F. Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl2 administration using osmotic pumps. Contrast Media&Molecular Imaging 2012; 7(-4-):426-434. >>> Manganese chloride; Saline; SC; Mice; 2004; Controls received mp w/ vehicle; animal info (Swiss, 2 mo old); MRI; comparison of SC injections vs SC mp;"The novel method presented in this study in mice, which is based on subcutaneously implanted mini-osmotic pumps filled with MnCl2, appears to be a better system for delivering the agent into the interstitial tissue compared with repeated agent injections."pg 429.

12126 Mok, S.I., Munasinghe, J.P., Young, W.S. Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain. Brain Structure&Function 2012; 217(-1-):107-114. >>> Manganese chloride; SC; Mice; 1003D; 1007D; 1002; Animal info (Oxtr KO, wt, 22-30 g, age-matched adult); MRI.

11324 Eschenko, O., Canals, S., Simanova, I., Beyerlein, M., Murayama, Y., Logothetis, N.K. Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies. NEUROIMAGE 2010; 49(-3-):2544-2555. >>> Manganese chloride; Saline; IP; Rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-300 g); comparison of SC and IP injections vs IP mp; post op. care (Fynadine Essex, Baytril); behavioral testing (running wheel);"The results of this experiment clearly demonstrate the advantage of systemic administration of MnCl2 via osmotic pumps, which provide a long-lasting, continuous and slow release of Mn 2+ into intraperitoneal space... Such release rate likely is readily managed by homeostatic mechanisms, does not produce toxic effects, while allows reaching relatively high cumulative dose."pg 2550;"In contrast (to chronic infusion with ALZET pumps), a single s.c. or i.p. application of MnCl2 in a dose range of 16 - 80 mg/kg resulted in abrupt and long-lasting toxic effects."pg 2552;"we find the osmotic pump-administration protocol described in the present study clearly advantageous for longitudinal behavioral studies."pg 2553.

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What researchers are saying ...

"Utilizing continuous minipump administration enhances the knockdown to 63% of control." (p. 619) This compared with 40% by twice daily administration. "The results of the present study confirm the utility of osmotic minipump administration of antisense oligonucleotides." (p. 621) Falk et al., Pharmacol Biochem Behav 2002;72:617-622.