Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle

There is growing evidence that 1,25-dihydroxyvitamin D-3 is involved in normal brain development. The aim of this study was to examine the impact of prenatal and postnatal hypovitaminosis D on prepulse inhibition (PPI) of acoustic startle in adult rats. We compared six groups of rats: control rats with normal vitamin D throughout life and normal litter size (Litter); control rats with normal vitamin D but with a reduced litter size of two (Control); offspring from reduced litters of vitamin D deplete mothers who were repleted at birth (Birth), repleted at weaning (Weaning) or remained on a deplete diet until 10 weeks of age (Life); or control rats that were placed on a vitamin D-deficient diet from 5 to 10 weeks of age (Adult). All rats were tested in acoustic startle chambers at 5 and 10 weeks of age for acoustic startle responses and for PPI. There were no significant group differences at 5 weeks of age on the acoustic startle response or on PPI. At 10 weeks of age, rats in the Life group only had impaired PPI despite having normal acoustic startle responses. We conclude that combined prenatal and chronic postnatal hypovitaminosis D, but not early life hypovitaminosis D, alters PPI. (C) 2004 Elsevier Inc. All rights reserved.

Behavioural characterization of Vitamin D receptor knockout mice

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate horneostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety. (C) 2004 Elsevier B.V. All rights reserved.

Drug utilization evaluation of parenteral proton pump inhibitors

Current evidence supports parenteral infusion of proton pump inhibitors (PPI) after endoscopic treatment of bleeding peptic ulcers and such treatment seems reasonable where there is active bleeding or visible vessel on endoscopy. Parenteral boluses of PPI can be used in patients nil by mouth who cannot tolerate oral therapy. We sought to examine the appropriateness of parenteral PPI use. Drug utilisation evaluation was performed on 94 patients admitted to a 500 bed metropolitan hospital. 39 patients received continuous parenteral infusion of omeprazole (8 mg/ h) over a mean of 60 ± 29 h. 55 patients had parenteral boluses (40 mg bd) of omeprazole over a mean of 5 ± 4 days. Indications for PPI infusion (n = 39) were: major haemorrhage requiring transfusion (23), minor haemorrhage (8), dyspepsia (4) and others (4). 31 of the 39 patients on PPI infusion had upper gastrointestinal (GI) endoscopy. PPI infusion was commenced prior to endoscopy in 26 (84%) patients. 13 patients (33%) had active bleeding or visible non bleeding vessels at endoscopy. Only 11 patients (28%) had endoscopically treated peptic ulcers. Indications for parenteral PPI boluses (n = 55) included patients nil by mouth unable to take maintenance PPI orally (21), minor haemorrhage (8), peptic ulcer prophylaxis in seriously unwell (6), major haemorrhage (4), dyspepsia (2), postoprative period following peptic ulcer surgery (2) and others (12). Endoscopy was performed in 10 patients (18%) with only 1 endoscopically treated peptic ulcer. Our data suggest significant inappropriate use of parenteral PPI, which may be used for minor GI bleeding and dyspepsia and are typically commenced prior to endoscopy. These findings can explain the costly hospital expenditure on PPI.