Modeling chronic olanzapine exposure using osmotic minipumps: Pharmacological limitations

2011 ◽  
Vol 100 (1) ◽  
pp. 86-89 ◽  
Author(s):  
Gary Remington ◽  
Steve Mann ◽  
Patrick McCormick ◽  
José N. Nobrega ◽  
Margaret Hahn ◽  
...  
Keyword(s):  
Osmotic Minipumps

Effects of Water-Deprivation on Renal-Function and Plasma Arginine Vasotocin in the Feral Chicken, Gallus-Gallus (Phasianidae)

1991 ◽  
Vol 39 (4) ◽  
pp. 439 ◽  
Author(s):  
JR Roberts
Keyword(s):  
Renal Function ◽  
Water Availability ◽  
Filtration Rate ◽  
Water Deprivation ◽  
Arginine Vasotocin ◽  
Constant Infusion ◽  
Osmotic Minipumps ◽  
Diuretic Hormone ◽  
Infusion Method ◽  
Plasma Arginine

Feral chickens occur on a coral atoll off the coast of Queensland, Australia, where the availability of water is limited. Glomerular filtration rate (GFR) was measured in conscious unrestrained feral chickens by means of osmotic minipumps in fully hydrated birds and in birds subjected to a four-day period of water deprivation. Plasma ionic and osmotic concentrations were measured on each day of the experiment. During water deprivation, body weight decreased and plasma ionic and osmotic concentrations increased. Haematocrit was not significantly affected by dehydration. GFR fell on days 2, 3 and 4 of water deprivation to 62% of hydrated values. The plasma levels of the avian diuretic hormone, arginine vasotocin (AVT), increased by a factor of 2.8 over the period of water deprivation. The sensitivity of release of AVT in the feral chicken is higher than that reported for domestic strains of chickens. This may be related to the ability of the feral strain to survive in regions of limited water availability. GFR was measured also by the 'constant infusion' method, which was not significantly different from GFR measured by osmotic minipumps.

Combined use of the chemitrode with osmotic minipumps for experimental brain research

1981 ◽  
Vol 7 (6) ◽  
pp. 719-721 ◽  
Author(s):  
M. Girgis ◽  
J. Kent ◽  
S. Kohlhardt ◽  
J. Rasko ◽  
P. Stobo
Keyword(s):  
Brain Research ◽  
Experimental Brain Research ◽  
Osmotic Minipumps ◽  
Combined Use

Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin

2001 ◽  
Vol 280 (2) ◽  
pp. R331-R337 ◽  
Author(s):  
Mihai Covasa ◽  
Jeremy K. Marcuson ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Peritoneal Cavity ◽  
Dietary Protein ◽  
High Protein ◽  
High Fat ◽  
Low Fat ◽  
Osmotic Minipumps ◽  
Fat Composition

Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released in response to HF meals than low-fat (LF) meals, we hypothesized that increased circulating CCK associated with ingestion of HF diets contributes to the development of decreased CCK sensitivity. To test this hypothesis, we implanted osmotic minipumps filled with either NaCl or CCK octapeptide into the peritoneal cavity. Subsequently, we examined the effect of intraperitoneal NaCl or CCK (0.5 μg/kg) injection on 30-min food intake. CCK significantly reduced 30-min food intake less in rats implanted with CCK-releasing minipumps compared with those with NaCl-releasing minipumps. Because dietary protein is a potent releaser of endogenous CCK, we hypothesized that rats adapted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, whereas both HF and HP markedly increase plasma CCK concentrations. Both doses of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, or body fat composition among LF-, HF-, and HP-fed rats. These results are consistent with the hypothesis that sustained elevation of CCK either by infusion of exogenous CCK or by dietary-induced elevation of plasma CCK contributes to the development of reduced sensitivity to exogenous CCK.

Continuous long-term insulin delivery in diabetic rats utilizing implanted osmotic minipumps

1983 ◽  
Vol 9 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Insulin Delivery ◽  
Diabetic Rats ◽  
Osmotic Minipumps

Catechol oestrogen induced initiation of implantation in the delayed implanting rat

1985 ◽  
Vol 109 (3) ◽  
pp. 418-422 ◽  
Author(s):  
Betsy S. Kantor ◽  
S. K. Dey ◽  
D.C. Johnson
Keyword(s):  
Release Rate ◽  
Capillary Permeability ◽  
Daily Administration ◽  
Osmotic Minipumps ◽  
Delayed Implantation ◽  
Full Complement ◽  
Implantation Process ◽  
Blue Reaction

Abstract. In the rat oestrogen is essential for induction of implantation in a progesterone primed uterus. The ability of the catechol oestrogens, 4-hydroxy-oestradiol (4-OH-E2) and 2-hydroxy-oestradiol (2-OH-E2) to initiate the implantation process (blue reaction, indicative of increased endometrial capillary permeability at the location of the blastocyst) in hypophysectomized delayed implanting rats was compared to that of oestradiol-17β (E2). Delayed implantation was maintained by daily administration of 2 mg of progesterone. A single sc injection of 100 ng of E2 or 400 ng of 4-OH-E2 consistently initiated implantation in all animals. When delivered sc via osmotic minipumps at a constant release rate of 10 ng/μl/h, implantation of a full complement of embryos was obtained with E given for 6 or 24 h. This dose 4-OH-E2 was ineffective when administered for 24 h. However, 25 ng/μl/h for 24 h was effective. When the dose was increased to 50 mg/μl/h implantation was evident in the majority of animals exposed to the hormone for 6 or 8 h; all animals implanted when this dose was given for 24 h. In contrast, 2-OH-E2 given at 50 ng/μl/h for 24 h was totally ineffective. When the dose of the latter steroid was raised to 200 ng/μl/h implantation was achieved in half of the animals when exposure was 24 h. The results suggest that when administered systemically, 4-OH-E2 is less potent than E2, but more potent than 2-OH-E2, for initiating implantation. The lower potency of systemically administered catechol oestrogens probably results from their rapid metabolism and clearance for the circulation and target tissues.

scholarly journals The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mouse model for rheumatoid arthritis

2008 ◽  
Vol 68 (1) ◽  
pp. 124-129 ◽  
Author(s):  
A Knedla ◽  
B Riepl ◽  
S Lefèvre ◽  
S Kistella ◽  
J Grifka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Scid Mouse ◽  
Severe Combined Immunodeficiency ◽  
Protective Effects ◽  
Combined Immunodeficiency ◽  
Human Cartilage ◽  
Osmotic Minipumps ◽  
Osmotic Pumps ◽  
Scid Mouse Model

Objectives:The viral gene transfer of interleukin 1 receptor antagonist (IL1ra) and interleukin 10 (IL10) into rheumatoid arthritis (RA) synovial fibroblasts (RASFs) has shown protective effects on cartilage destruction in the severe combined immunodeficiency (SCID) mouse model of RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost and time intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID mouse model for RA.Methods:Isolated RASFs were cultured for four passages and coimplanted together with human cartilage and an Alzet osmotic miniature pump model 2004, containing 200 μl of IL10 and IL1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL10 and IL1ra in murine serum were measured by ELISA.Results:Release of IL10 and IL1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL10 and IL1ra release showed protective effects towards the coimplanted cartilage, similar to the adenovirally IL10/IL1ra-transduced RASFs. The mean (SD) invasion scores for the implants with the osmotic pumps were: invasion 0.7 (0.5), degradation 0.5 (0.3) (all parameters significant vs controls, p<0.05).Conclusions:The results demonstrate that the combination of osmotic pumps with the SCID mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.

Adrenaline-Induced Hypertension in Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 191s-193s ◽  
Author(s):  
L.-H. Tung ◽  
M. J. Rand ◽  
H. Majewski
Keyword(s):  
Blood Pressure ◽  
Feedback Loop ◽  
Chronic Treatment ◽  
Nerve Terminals ◽  
Concomitant Treatment ◽  
Metoprolol Tartrate ◽  
Osmotic Minipumps ◽  
Pressor Responses ◽  
Induced Hypertension ◽  
Blood Pressures

1. Rats implanted with osmotic minipumps delivering adrenaline intraperitoneally at the rate of 2.9 nmol/h had significantly higher systolic and diastolic pressures from days 2 to 6 after implantation than sham-operated control rats. 2. Concomitant treatment with metoprolol tartrate (2.5 mg/kg, intraperitoneally, twice daily) prevented the elevation in blood pressure induced by adrenaline from osmotic minipumps. Such metoprolol treatment did not affect the blood pressure of control rats. 3. Noradrenaline administered intraperitoneally from osmotic minipumps at the rate of 2.9 nmol/h had no significant effect on blood pressure over a 6-day period of observation. 4. Tachyphylaxis developed to the acute pressor responses to intermittent intravenous infusions of adrenaline in doses of 0.78 μg (4.24 nmol) every 10 min, but after 14 days of such treatment systolic and diastolic blood pressures were significantly greater than in control rats. 5. It is suggested that the increase in blood pressure produced by chronic treatment with adrenaline is due to the uptake and accumulation of adrenaline in noradrenergic nerve terminals, from which it is subsequently released as a cotransmitter that mediates a positive feedback loop on, transmission by acting on prejunctional β-adrenoceptors.

Relaxin acts centrally to inhibit oxytocin release during parturition: an effect that is reversed by naloxone

1986 ◽  
Vol 111 (1) ◽  
pp. 99-102 ◽  
Author(s):  
S. A. Jones ◽  
A. J. S. Summerlee
Keyword(s):  
Jugular Vein ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Opioid System ◽  
Opioid Antagonist ◽  
Unoperated Control ◽  
Osmotic Minipumps ◽  
Oxytocin Release ◽  
Naloxone Treatment

ABSTRACT Experiments were carried out to establish whether infusion of relaxin prolongs gestation and labour in the rat by suppressing release of oxytocin, and whether the effects of relaxin on birth could be reversed by the opioid antagonist naloxone. Female rats were implanted with subcutaneous osmotic minipumps for the infusion of purified porcine relaxin into the jugular vein for 84 h from either day 19 or day 20 of gestation. Infusion of relaxin delayed the onset of labour and in those animals which delivered during relaxin infusion, delivery was longer by approximately 45 min. Plasma oxytocin levels 40 min after delivery of the first fetus were 45·25 ± 3·6 pmol/l (mean ± s.d.) in unoperated controls and significantly (P < 0·01) depressed (23·89 ± 3·9) in rats that delivered during infusion of relaxin. Rats that delivered after the infusion of relaxin had finished, gave birth significantly (P < 0·05) faster than controls and plasma oxytocin levels were significantly (P < 0·01) raised (77·87 ±15·9 pmol/l). Naloxone treatment (1 mg/kg; i.m.) given immediately after the delivery of the first fetus reversed the inhibitory effect of relaxin and the interval between successive deliveries was slightly faster than that of controls. Plasma oxytocin levels in relaxin-infused naloxone-treated rats were significantly (P < 0·01) higher than values in unoperated control rats. The results confirm that relaxin suppresses oxytocin release possibly through an opioid system and this may be important in the control of the timing of birth. J. Endocr. (1986) 111, 99–102

Abstract 461: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yuki Kakio ◽  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Jun Wada
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Ex Vivo ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Osmotic Minipumps ◽  
Abdominal Aortic ◽  
Deficient Mice

Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, it is reported that voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Therefore, we hypothesized that cilnidipine, an N/L-type calcium channel blocker, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in mice. The purpose of this study was to evaluate whether cilnidipine influenced AngII-induced AAAs. Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) each by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. AngII infusion did not alter serum cholesterol concentrations. However, cilnidipine slightly decreased serumcholesterol concentrations in AngII-infused mice. Cilnidipine had no effect on body weights, heart rates, and urine total protein, but mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine did not affect ex vivo measurement of maximal diameter of abdominal aorta (1.04 ± 0.09 mm vs 1.11 ± 0.06 mm, n.s.) in saline infused mice. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas, but was attenuated by cilnidipine (1.79 ± 0.59 mm vs 1.26 ± 0.38 mm, P < 0.05). In addition, cilnidipine significantly reduced the incidence of AngII-induced AAAs (Cilnidipine: 38 %, Vehicle: 88 %; P < 0.05). Furthermore, gelatin zymography demonstrated that cilnidipine diminished AngII-induced increase in aortic MMP-9 protein abundance. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice.

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