Ad libitum (AL) feeding of rats leads to obesity and increased result variability, as well as premature morbidity and mortality. It may also alter metabolism and responses to foreign compounds. Moderate dietary restriction (DR) reduces these untoward effects without compromising the sensitivity of rodent bioassays. The diet board (DB) is a novel method for achieving moderate DR in group housing. Food pellets are firmly attached into grooves in an aspen board, and rats have to gnaw the wood in order to eat. Food is available continuously, but due to the effort involved rats eat less. This study simulated a chronic safety test to assess the long-term effects of DB feeding. A total of 146 male and female outbred Sprague-Dawley rats, nine weeks old at onset, were housed in groups of three and fed either AL or with DBs for two years. Food and water consumption were measured at six time points. The rats were weighed every one to two weeks. Body and tibial lengths and epididymal fat weight were measured at necropsy. Modified body mass index was calculated at five time points after one year of age. DB feeding reduced body weight and fat tissue moderately, more so in males. DB males ate less than AL males, but no differences were seen in the total food consumption in the females. There was no consistent difference in the within-group variations of the measured parameters. DB is a workable DR method, albeit some modification could enhance and standardize its DR effects, especially in female rats. Keywords diet board, dietary restriction, rats, reduction, refinementExcessive morbidity and shortened lifespans of rodents involved in long-term safety studies were first recognized decades ago. This phenomenon has largely been attributed to ad libitum (AL) feeding of high-quality food, although other factors, such as the tendency to favour fast growing animals in breeding, have also been recognized.1 Unrestricted feeding has even been named as the least controlled variable in rodent bioassays, as it can lead to excessive and uneven energy intake, obesity and increased variation of animal size, as well as influencing the metabolism and the effects of foreign substances.2-5 AL feeding and the associated increase in body weight (BW) have pathological consequences, e.g. increased susceptibility to cardiac and circulatory diseases, progressive kidney failure, hormonal disturbances, early developing tumours and decreased longevity.2,3,5 Some of these adverse effects may even be seen in young animals and short-term experiments; but the consequences of AL feeding may create serious problems, particularly in long-term studies. If a considerable number of rats, even in control groups, do not survive to the end of an experiment, any late emerging study effects become difficult to discern.2,3

Objectives: The structure of the mandibular condylar cartilage (MCC) is regulated by dynamic and multifactorial processes. The aim of this study was to examine the effects of altered dietary loading, estrogen level, and aging on the structure of the condylar cartilage and the expressions of matrix metalloproteinase (MMP) -3 and MMP-8 of rat MCC.Methods: In this study, Crl:CD (SD) female rats were randomly divided into 3 groups according to dietary hardness: hard diet (diet board), normal diet (pellet), and soft diet (powder). In each group, the rats were further divided into 2 subgroups by ovariectomy at the age of 7 weeks. The rats were sacrificed at 5-and 14-month-old.Histomorphometric analysis of the MCC thickness was performed after toluidine blue staining. Immunochemical staining was done for MMP-3 and MMP-8. A linear mixed model was used to assess the effects of dietary loading, estrogen level, and aging.Results: Increased dietary loading was the main factor to increase the MMP-3 expression and the anterior and central thickness of the MCC. Lack of estrogen was the main factor associated with decreased MMP-8. Aging was associated with the thickness changes of the whole condylar cartilage and the reduced expression of MMP-8. Conclusion:The condylar cartilage structure and metabolism of the female rats are 2 sensitive to dietary loading changes, estrogen level as well as aging. The proper balance of these factors seems to be essential for the maintenance of the condylar cartilage.

Condylar cartilage is sensitive to the interplay between loading, aging, and sex of middle-aged and older rats. High loading of condylar cartilage increased the thickness of cartilage in younger rats.

Fentanyl is used for pain treatment during pregnancy in human beings and animals. However, fentanyl pharmacokinetics during pregnancy has not been fully established. The aim of this study was to characterize fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal dosing during surgical procedure performed to ewe and foetus. Pharmacokinetic parameters reported for non-pregnant sheep and nominal transdermal dose rate were utilized for a priori calculation to achieve analgesic fentanyl concentration (0.5-2 ng/ml) in maternal plasma. A total of 20 Aland landrace ewes at 118-127 gestational days were used. In the first protocol, 1 week before surgery, 10 animals received 2 lg/kg fentanyl intravenous bolus, and on the operation day, transdermal fentanyl patches at nominal dose rate of 2 lg/kg/hr were applied to antebrachium, and ewes were then given a 2 lg/kg intravenous bolus followed by an intra-operative 2.5 lg/kg/hr infusion. In the second protocol, 10 animals received fentanyl only as transdermal patches on the operation day and oxycodone for rescue analgesia. The data were analysed with population pharmacokinetic modelling. Intra-and post-operative fentanyl concentrations were similar and slightly lower than the a priori predictions, and elimination and distribution clearances appeared slower during than before or after the surgery. Transdermal patches provided sustained fentanyl absorption for up to 5 days, but the absorption rate was slower than the nominal dose rate and showed a high interindividual variability. Further research is warranted to evaluate the clinical relevance of the observations made in sheep.Opioids are commonly used to treat pain during labour and caesarean section, and also for pregnant women for surgical procedures and other severe pain conditions. Fentanyl, a synthetic opiate derivative, has a rapid onset and short half-life [1]. It is metabolized to inactive metabolites. These properties make fentanyl a feasible compound for labour analgesia. During labour, fentanyl is commonly administered spinally, epidurally, intravenously or intramuscularly. Transdermal delivery of fentanyl has been studied in other populations, but the pharmacokinetics of transdermal fentanyl in pregnant women is not known. Furthermore, possible impact of labouror caesarean section-induced transient changes in physiology on pharmacokinetics of fentanyl is not established.In animal studies, intravenous and transdermal fentanyl pharmacokinetics has been studied in several species, including llamas, non-pregnant sheep and horses [2][3][4][5]. Pharmacokinetics of intravenously administered fentanyl in pregnant sheep has been studied by Craft et al. [6] with radioimmunoassay. However, the results may be confounded by cross-reaction of radioimmunoassay with fentanyl metabolites in plasma as shown in horses [7]. Furthermore, the fentanyl concentrations were monitored only up to 120 min. after administration during which the fentanyl kinetics are mainly governed by distribution processes, t...

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