Negative effects of chronic oral chlorpromazine and olanzapine treatment on the performance of tasks designed to assess spatial learning and working memory in rats.

Learning potential and memory capacity are factors that strongly predict the level of rehabilitation and the long-term functional outcome in patients with schizophrenia. Unfortunately, however, the effects of antipsychotic drugs (i.e. the primary treatments for schizophrenia) on these components of cognition are unclear, particularly when they are administered chronically (i.e. a standard clinical practice). In this rodent study we evaluated the effects of different time periods (ranging from 2 weeks to 6 months) of oral treatment with the first generation antipsychotic chlorpromazine (10.0 mg/kg/day), or the second generation antipsychotic olanzapine (10.0 mg/kg/day) on the repeated acquisition of a water maze task (i.e. a method of assessing spatial learning potential in a repeated testing format). We assessed locomotor function (in an open field) and employed a radial arm maze (RAM) task to assess antipsychotic effects (5.0 and 10.0 mg/kg/day doses) on spatial working memory during the treatment period between 15 days and 2 months. Finally, we conducted experiments using liquid chromatography/tandem mass spectrometry (LC-MS/MS) to evaluate the therapeutic relevance of our method of drug delivery (oral administration in drinking water). In the water maze experiments, both antipsychotics were associated with impairments in acquisition in the earlier test sessions that could eventually be overcome with repeated testing while olanzapine also impaired retention in probe trials. Both antipsychotics were also associated with impairments in delayed non-match-to-position trials in the RAM and some impairments of motor function (especially in the case of olanzapine) as indicated by slightly reduced swim speeds in the water maze and decreased activity in some components of the open field assessment. Finally, LC-MS/MS studies indicated that the method of antipsychotic administration generated clinically relevant plasma levels in the rat. These animal data indicate that chronic oral treatment with chlorpromazine or olanzapine can impair the performance of tasks designed to assess specific components of cognition that are affected in schizophrenia.

Oral haloperidol or risperidone treatment in rats: temporal effects on nerve growth factor receptors, cholinergic neurons, and memory performance.

First and second generation antipsychotics (FGAs and SGAs) ameliorate psychotic symptoms of schizophrenia, however, their chronic effects on information processing and memory function (i.e. key determinants of long term functional outcome) are largely unknown. In this rodent study the effects of different time periods (ranging from 2 weeks to 6 months) of oral treatment with the FGA, haloperidol (2.0 mg/kg/day), or the SGA, risperidone (2.5 mg/kg/day) on a water maze repeated acquisition procedure, the levels of nerve growth factor receptors, and two important cholinergic proteins, the vesicular acetylcholine transporter and the high affinity choline transporter were evaluated. The effects of the antipsychotics on a spontaneous novel object recognition procedure were also assessed during days 8-14 and 31-38 of treatment. Haloperidol (but not risperidone) was associated with impairments in water maze hidden platform trial performance at each of the time periods evaluated up to 45 days, but not when tested during days 83-90. In contrast, risperidone did not impair water maze task performance at the early time periods and it was actually associated with improved performance during the 83-90 day period. Both antipsychotics, however, were associated with significant water maze impairments during the 174-180 day period. Further, haloperidol was associated with decrements in short delay performance in the spontaneous novel object recognition task during both the 8-14 and 31-38 day periods of treatment, while risperidone was associated with short delay impairment during the 31-38 day time period. Both antipsychotics were also associated with time dependent alterations in the vesicular acetylcholine transporter, the high affinity choline transporter, as well as tyrosine kinase A, and p75 neurotrophin receptors in specific brain regions. These data from rats support the notion that while risperidone may hold some advantages over haloperidol, both antipsychotics can produce time-dependent alterations in neurotrophin receptors and cholinergic proteins as well as impairments in the performance of tasks designed to assess spatial learning and episodic memory.

Adaptations in cortical and trabecular bone in response to mechanical loading with and without weight bearing.

Exercise that imparts rapid, high-magnitude mechanical loading is considered to be advantageous to bone health. Previous rodent studies have suggested that swimming may also be beneficial to bone. We investigated the differential effects of exercise with and without weight bearing on cortical and trabecular bone. Forty female Sprague-Dawley rats (120 days) were weight-stratified and randomized into four groups: swim control (Cs, n = 10), swim (S, n = 10), treadmill control (Ct, n = 10), and treadmill (T, n = 10). Treadmill speed was adjusted to match the average limb loading frequency used for swimming, and all training progressed to 1 hour/day, 5 days/week, for 12 weeks. Femurs and humeri were assessed for cortical morphometry by peripheral quantitative computed tomography, areal bone mineral density (BMD) by peripheral dual-energy X-ray absorptiometry, mineral content by ashing, strength by three-point bending, and trabecular volume (BV/TV) by micro-computed tomography. Swimming was associated with increases in cortical thickness and BMD in the humerus midshaft and trabecular BV/TV in the distal femur and proximal humerus compared with age-matched controls. Compared to swimming, treadmill training was associated with increases in percent ash of the femur and humerus and Young's modulus of the femur. Swimming appears to engender novel bone strains and osteogenic adaptations in the humerus and femur, which are different from those induced by normal cage activity. In summary, our findings suggest that when limb loading frequency is matched, swimming may afford greater benefits to cortical and trabecular bone than uphill treadmill work in rats.

Dual-energy X-ray absorptiometry of birds: an examination of excised skeletal specimens.

The ability of dual-energy X-ray absorptiometry (DXA) to measure bone mineral content and density of bird bones has received little attention. This paper represents the first comprehensive study of the methods, precision, and reproducibility of DXA (GE-Lunar DPX-L) for the uniquely shaped, thin and pneumatic bones of birds. Skeletal elements and portions represented by 26 regions of interest (ROIs) are presented and evaluated for the gallinaceous bird species, wild turkey (Meleagris gallopavo), ruffed grouse (Bonasa umbellus) and bobwhite quail (Colinus virginianus). Using Lunar small animal software and the methods described in this paper, photodensitometry of bird bones is possible and opens new opportunities for using birds in clinical models in veterinarian science, osteoporosis studies, space biology, and even archaeological and paleontological research.

Bone mineral density of competitive male mountain and road cyclists.

The purpose of this study was to compare the bone mineral density (BMD) of two types of trained male cyclists (n = 30) with recreationally active men (n = 15), aged 20-40 years. Sixteen of the cyclists regularly trained for, and competed in, cross-country mountain bike races. The other 14 cyclists trained and raced on the road. The cyclists had trained an average of 11 +/- 3 hours per week for 8 +/- 4 years. Fifteen recreationally active men volunteered as controls. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD of the proximal femur, lumbar spine, and total body. Anthropometric, muscle strength and power, aerobic fitness, and sex hormone data assessments were conducted on all participants. Mountain cyclists were younger and weighed less than road cyclists and controls. BMD at all sites was comparable among the three groups (p > 0.05). When adjusted for body weight and controlled for age, BMD was significantly higher at all sites in the mountain cyclists compared with the road cyclists and controls. Some anthropometric, physical fitness, and sex steroid variables were predictive of BMD, but of these variables, only total body weight, total body fat, and aerobic fitness were different between the groups. In conclusion, endurance road cycling does not appear to be any more beneficial to bone health than recreational activity in apparently healthy men of normal bone mass. Higher BMD in the mountain cyclists suggests that mountain cycling may provide an osteogenic stimulus that is not inherent to road cycling.

Comparison of accelerometers with oxygen consumption in older adults during exercise.

PURPOSE: The purpose of this study was to compare two commercially available accelerometers with indirect calorimetry in a group of older adults (x +/- SD; 70.6+/-3.7 yr; N = 86, 44 males and 42 females). METHODS: The accelerometers (Caltrac and Tritrac, Hemokinetics, Madison, WI) were worn while performing three submaximal, discontinuous (5 min exercise, 2 min recovery), progressive levels of treadmill walking and bench stepping. The treadmill exercise averaged 3.4 mph, at 0.4% grade, 3.0% grade, and 5.1% grade, while the stepping work rates (24 steps x min(-1)) were performed on 15.2-, 20.3-, and 25.4-cm steps. Estimated energy expenditure (EE) from the two accelerometers was compared with EE as measured by indirect calorimetry. RESULTS: The Caltrac significantly (P < 0.05) overestimated EE at the three treadmill work rates (10-52% difference) and underestimated EE at the three stepping work rates (-19% to -28% difference). When comparing the changes in EE between work rates one, two and three, the Caltrac was not sensitive to the changes (increase in EE) that occurred during graded treadmill walking but did detect some changes in the stepping exercise. The Tritrac significantly (P < 0.05) underestimated EE for the three work rates of both the treadmill and stepping exercise when compared with indirect calorimetry but did detect differences in EE among work rates during stepping exercise (P < 0.05). CONCLUSIONS: These data indicate that the magnitude of the differences between measured and estimated EE is affected by exercise mode and intensity and that caution is warranted when using the accelerometers in an attempt to quantify EE in older adults.

The diffusion of medical technology: free enterprise and regulatory models in the USA.

The diffusion of technology in the US has taken place in an environment of both regulation and free enterprise. Each has been subject to manipulation by doctors and medical administrators that has fostered unprecedented ethical dilemmas and legal challenges. Understanding these developments and historical precedents may allow a more rational diffusion policy for medical technology in the future.