Osmotic mini-pumps

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

In parenteral therapy, the subcutaneously implantable, osmotic mini-pumps developed by the Alza Corp. are used widely in experimental animal studies. The DUROS implant pump is a modified version of the Alzet pumps and was developed specifically for the controlled delivery of peptides and proteins (see Section 4.6.1.2). Osmotic mini-pumps, such as the Oros osmotic pump, are also available for controlled... 

In animal studies, pyridostigmine has generally been administered either by subcutaneous or intramuscular injection for studies of acute effects or, in more recent studies, via subcutaneously implanted mini-osmotic pumps which generate sustained release of pyridostigmine for up to 28 days in an attempt to mimic repeated oral administration in field situations. It is acknowledged that such continuous administration is an imperfect, if pragmatic, surrogate for repeated oral administration. 

Subchronic exposure to MnCb for 7 days (total dose 1750 pmol/kg) by means of mini-osmotic pumps inplanted s.c. produced significant reduction in GSH-peroxidase (EC 1.11.1.9) activity in the cytosol and mitochondrial fractions of the whole rat brain and the striatum (Liccione and Maines 1988). The decrease in GSH-peroxidase was most pronounced in the mitochondrial fraction of the striatum where the activity was reduced to 35 % of the control. Catalase (EC 1.11.1.6) activity was also decreased in the striatum of rats treated with Mn but not in the whole brain. GSH content was markedly depleted (20 % of the control) in the striatum, although only modestly decreased in the whole brain (80% of the control). The treatment of rats with Mn also decreased the activity of oxidised glutathione reductase (EC 1.6.4.2) the same treatment increased the activity of y-glutamyltranspeptidase (EC 2.3.2.2). The activity of y-glutamylcysteine synthetase was not altered by Mn. 

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