Effects of floor-feeding and the presence of a foraging substrate on the behaviour and stress physiological response of individually housed gilts

Both restricted feeding and barren housing have a negative influence on sow welfare. The aim of this study was to test whether sows that have to search for their feed in a substrate on the floor show less stereotyped (and other abnormal) behaviour and have a lower physiological stress response. In three batches, 96 gilts were housed individually in two rooms in 3.1 m² pens with 1.9 m² solid floor. In a 2×2 factorial design either wood shavings (S) or no substrate (NS) were provided on the floor, and 900 g of feed was provided twice daily (06:30 and 15:00 h) either in a trough (T) or on the floor (F). In weeks 8–12, behaviour was scan-sampled once in the periods 07:00–09:00 h (P1), 10:00–12:00 h (P2), and 13:00–15:00 h (P3). Data from the 5 weeks were pooled per animal. Video recordings (24 h) in week 12 or 13 were scan-sampled for ‘standing’. Saliva samples were taken in week 11 at 2 h intervals during 24 h and measured for cortisol. Spontaneously voided morning-urine was sampled in weeks 2, 7 and 12 or 13 for determination of ratios of adrenaline (A) and noradrenaline (NA) with creatinine (CR). Most effects that were found were due to substrate presence. Main findings were that compared with S-animals, NS-animals stood more during the dark period (4.8% versus 3.0%; P<0.05) and showed more (visible) oral behaviour in P1 (56.8% versus 47.6%; P<0.05), P2 (35.8% versus 30.8%; tendency) and P3 (44.1% versus 33.8%; P<0.05). This included more sham chewing in P1 (tendency), P2 and P3, more pen manipulation in P3, and more other oral behaviour (e.g. teeth grinding) in P1 (tendency) and P2. They had higher cortisol levels before feeding (peaks) and in the early evening (24 h average: 1.49 ng/ml versus 1.02 ng/ml; P<0.05) and higher NA/CR ratios in weeks 7 (tendency) and 12 (5.5 ng/mg versus 3.7 ng/mg; P<0.05). No treatment effects were found on A/CR ratios. Substantial interactive effects of feeding method and substrate were only found in floor manipulation. In all three periods NS-T-animals manipulated the floor less than other animals, probably because they had no attraction to the floor and were not rewarded for searching. Results imply that the presence of a substrate on the floor improves welfare, whereas provision of feed in the substrate in order to stimulate foraging behaviour is of less importance.     

Circadian Variation in the Intracortical Accumulation Kinetics of Tobramycin in Conscious Rats

The time-dependent variation in the renal accumulation of aminoglycosides has not been extensively investigated. The aim of the present study was to better characterize the temporal variation in the intracortical accumulation kinetics of tobramycin. Female Sprague-Dawley rats weighing 210–254 g were maintained in a 14 h light/10 h dark cycle (light on 06h00–20h00). They were infused for 6 h with tobramycin to achieve individual steady-state serum levels of 0.5–15 μg/ml over four different periods of the day (02h00–08h00; 08h00–14h00; 14h00–20h00; and 20h00–02h00). As previously reported, the steady-state elevation of serum tobramycin concentrations was associated with a linear increase of the cortical concentration in all groups. The tobramycin accumulation rate was significantly lower in animals infused at 20h00–02h00 compared to rats infused at 08h00–14h00 (p < 0.001). The data suggest that the lower rate of tobramycin accumulation during the dark period might be responsible for the lower toxicity observed during this time.     

Dietary nickel improves male broiler (Gallus domesticus) bone strength

The effects of dietary nickel (0, 25, 50, 75, 100, and 150 mg/kg) on the bone strength characteristics and performance parameters of male broilers were investigated. Broilers were housed in either cages or floor pens. At 6 wk of age, the shear fracture energy of the tibia from the caged birds increased when the basal diet was supplemented with 25 mg of dietary nickel per kilogram of feed. The shear force, stress, and fracture energy of the radius from the caged birds also increased at 25 mg/kg nickel. Dietary nickel had no effect on bird body weight, but the caged broilers (2161 g) were heavier than the floor birds (2005 g). Nickel had no effect on the strength characteristics of the tibia from the floor birds. Percent tibia bone ash, a measure of bone density, was not influenced by dietary nickel, but the tibia ash of the floor birds was greater than that of the caged birds. Overall, the data indicates that adding 25 mg/kg of dietary nickel to a poultry diet will have a positive influence on bone strength characteristics and performance.     

A behavioral comparison of New Zealand White rabbits (Oryctolagus cuniculus) housed individually or in pairs in conventional laboratory cages

Despite their gregarious nature, rabbits used for research are often housed individually due to concerns about aggression and disease transmission. However, conventional laboratory cages restrict movement, and rabbits housed singly in these cages often perform abnormal behaviors, an indication of compromised welfare. Pairing rabbits in double-sized cages could potentially improve welfare by providing both increased space and social stimulation. We compared the behavior of female New Zealand White rabbits (Oryctolagus cuniculus) housed either individually (N=4) in cages measuring $\text{61}\text{cm}\text{×76}\text{cm}\text{×41}$ cm or in non-littermate pairs (four pairs) in double-wide cages measuring $\text{122}\text{cm}\text{×76}\text{cm}\text{×41}$ cm. The rabbits were kept under a reversed photoperiod (lights on 22:00–12:00 h). Each rabbit was observed five times per week for 5 months, using 15-min focal animal samples taken between 08:00–09:00, 12:00–13:00, and 16:00–17:00 h. Data were analyzed using a repeated measures General Linear Model (GLM). Over the 5 months, individually housed rabbits showed an increase in the proportion of the total behavioral time budget spent engaged in abnormal behaviors (digging, floor chewing, bar biting), from 0.25 to 1.77%, while pairs remained unchanged at 0.95% (treatment×time interaction, F_1,24=4.60; P≤0.0422). Paired rabbits engaged in more locomotor behavior (F_1,6=16.49; P≤0.0066) than individual rabbits (average proportions of time budget: 2.71 and 0.70% for paired and individual rabbits, respectively), which may be important because caged rabbits are susceptible to osteoporosis and other bone abnormalities due to the restricted ability to move. Time spent feeding and body weights of dominant and subordinate rabbits in a pair did not differ, indicating that food competition was not a problem, and paired rabbits were often observed in physical contact (26.7% of data records) although the size of the cages allowed physical separation. Aggression between pairmates did not increase significantly during the study. However, one pair did have to be separated at the end of the study due to bite wounds from persistent aggression. Thus, although methods for decreasing injurious aggression require further investigation, the beneficial effects of pair housing in decreasing abnormal behaviors and increasing locomotion suggest that pair housing should be considered as an alternative to individual housing for caged laboratory rabbits.     

Chronopharmacokinetic study of gentamicin in dogs

The purpose of this experiment was to determine whether the time of day of single intravenous doses of gentamicin affects the drug's pharmacokinetics in dogs maintained under a 12 h light (08:00 to 20:00 h), 12 h dark (20:00 to 08:00 h) cycle. Using a crossover design, 6 mixed-breed male dogs received a single dose of 2 mg/kg of gentamicin at 8:00 or 20:00 h. Serial blood samples were collected and pharmacokinetic parameters were calculated following each timed dose. The concentration of the antibiotic was lower following the 08:00 h compared to the 20:00 h administration. When gentamicin was administered at 20:00 h, the initial concentration, mean residence time, and area under the disposition curve were significantly higher (p < 0.05) and the apparent volume of distribution of the central compartment, apparent volume of distribution, apparent volume of distribution at steady-state, and total body clearance (1.73+/-0.55 at 20:00 h versus 3.31+/-0.67 L/min/kg at 08:00 h) were significantly lower than for the 08:00 h administration (p < 0.05). Our results show that the pharmacokinetics of gentamicin exhibits significant temporal variation when administered to dogs at different times of day.     

Banana meal for feeding pigs: digestive utilization,growth performance and feeding behavior

The main objective of the present work was to determine the nutritional value and the strategies of using green banana meal (BM) in growing pigs. Two trials involving a total of 96 growing pigs were designed to study the effect of the harvest stage on the nutritional and energy values of BM (trial 1) and to evaluate the consequence of feeding gradual levels of BM on growth performance and feeding behavior in growing pigs (trial 2). In trial 1, the digestive utilization of three diets including 40% BM were compared with a control (C) soybean meal-corn diet in two batches of 12 pigs. BM was obtained from fruits harvested at 750 degrees-days (DD; early harvesting stage), 900 DD (normal harvesting stage) and 1150 DD (late harvesting stage). In trial 2, 72 Large White pigs were grouped in pens of nine animals and were given ad libitum access to one of the four dietary treatments (two pens/diet) differing from the rate of inclusion of 900 DD BM (0%, 20%, 40%, 60%). The estimated energy apparent digestibility coefficients of BM increased with the harvest stage (75.5%, 80.7% and 83.2% for BM at 750, 900 and 1150 DD, respectively). Digestible energy and metabolizable energy values were higher for BM at 1150 DD (13.56 and 13.05 MJ/kg DM, respectively) than at 900 DD (13.11 and 12.75 MJ/kg DM, respectively) or at 750 DD (12.00 and 11.75 MJ/kg DM, respectively). In trial 2, average daily gain and feed conversion ratio were not affected (P>0.05) by the rate of BM inclusion (822 g/day and 2.75 kg/kg on average, respectively). Feed intake and feeding behavior parameters were not significantly influenced by the dietary treatments except for the rate of feed ingestion with a lower value for the diet with 40% of BM (27.4 v. 32.2 g/min on average; P<0.01) when compared with the other diets. Results of this study indicate that the energy value of BM increases with the harvest stage and that BM can be incorporated up to 60% in growing finishing pig diets.     

Chronopharmacokinetic Study of Gentamicin in Dogs

The purpose of this experiment was to determine whether the time of day of single intravenous doses of gentamicin affects the drug's pharmacokinetics in dogs maintained under a 12 h light (08:00 to 20:00 h), 12 h dark (20:00 to 08:00 h) cycle. Using a crossover design, 6 mixed‐breed male dogs received a single dose of 2 mg/kg of gentamicin at 8:00 or 20:00 h. Serial blood samples were collected and pharmacokinetic parameters were calculated following each timed dose. The concentration of the antibiotic was lower following the 08:00 h compared to the 20:00 h administration. When gentamicin was administered at 20:00 h, the initial concentration, mean residence time, and area under the disposition curve were significantly higher (p<0.05) and the apparent volume of distribution of the central compartment, apparent volume of distribution, apparent volume of distribution at steady‐state, and total body clearance (1.73±0.55 at 20:00 h versus 3.31±0.67 L/min/kg at 08:00 h) were significantly lower than for the 08:00 h administration (p<0.05). Our results show that the pharmacokinetics of gentamicin exhibits significant temporal variation when administered to dogs at different times of day.     

Rabbit preference for cages and pens with or without mirrors

Five-week-old Pannon White rabbits were housed in a closed climatized rabbitry and randomly assigned to either pens (56 rabbits) having a basic area of 1 m² with a stocking density of 16 and 12 rabbits/m² or to 18 individual cages (0.24 m²/cage). The pens and the cages were divided into two halves and animals could move freely between the two halves through swing doors. The walls of one half of the pens and cages were completely covered with mirrors while the other half was covered with white plastic panels. A 24 h video recording was made twice a week using infrared cameras and the number of rabbits in each pen and cage was counted every 15 min. The duration of the trial was 6 weeks. The lighting period was 16L/8D. In each half of the cage or pen, a feeder and nipple drinkers were available and feed intake was measured separately. Throughout the entire rearing period, 72% of the individually caged rabbits showed a preference for the cage half enriched with mirrors (P < 0.001). This preference decreased slightly with increasing age. Preference toward the cage half provided with mirror walls was independent of the time of day; in other words, during the active period (23:00–05:00) corresponding to the dark part of the day, rabbits continued to prefer the mirrored half even if the vision of the reflected image was reduced. The presence of conspecifics at different stocking densities (12 vs. 16 rabbits/m²) did not reduce this interest in mirrors: averaging the ages, 66% of animals living at 16 rabbits/m² stocking density and 63% of those living at 12 rabbits/m² density were found in the half pen with mirrors (P < 0.001). Group-penned rabbits showed a marked preference toward mirrors during the active period (73–76% for 12 and 16 rabbits/m² stocking densities, respectively; P < 0.001). The results suggest that the presence of mirrors offers advantages perhaps related to comfort and welfare, and therefore might be used as environmental enrichment for fattening rabbits and advised for rabbits caged individually for long periods.     

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.     

Influence of cage or pen housing on carcass traits and meat quality of rabbit

Carcass traits and meat quality of rabbits reared in conventional cages (0.385 m2), small pens (0.662 m2) or large pens (4.052 m2) at a similar stock density of 15 rabbits/m2 were compared (n = 30 per group). Pens contained an elevated platform. Slaughter weight (SW; P < 0.01) and cold carcass weight (P < 0.05) decreased in the order of Cage < Small pen < Large pen groups. SW and cold carcass weight were 7% lower in rabbits housed in large pens than in cages. Dressing out and meat-to-bone ratio were not influenced by the housing system. Percentage of fat deposits was highest in caged rabbits (+0.15 point for scapular fat and +0.26 point for perirenal fat compared to rabbits reared in large pens P < 0.05). Rabbits housed in large pens had a bigger proportion of hind part (+1 point), and meat colour was shifted towards greater a* values (P < 0.01) compared to caged rabbits. Water holding capacity and shear test parameters in longissimus lumborum muscle, lipid content and shear test parameters of abductor cruralis cranialis, biceps femoris and semitendinosus muscles were not affected by the housing system. Tibia and femur bone moment of inertia increased in the order of Cage < Small pen < Large pen groups (P < 0.05), whereas elastic modulus, which is a measure of intrinsic stiffness, was highest in caged rabbits. This study showed that large pen housing altered carcass traits independently and increased meat redness and fracture resistance of tibia and femur.     

Effects of high dietary fibre diets formulated from by-products from vegetable and agricultural industries on plasma metabolites in gestating sows

The aim of the present study was to examine the biochemical influence of feeding high dietary fibre (DF) diets formulated from by-products from the vegetable and agricultural industries to sows during early to mid-gestation. The effect of feeding frequency (once vs. twice daily) on diurnal plasma metabolites patterns was also examined. The study included a total of 48 gestating sows from four blocks (12 gestating sows in each block). The sows were fed four different diets containing varying levels of starch (304-519 g/kg dry matter (DM)) and DF (171-404 g/kg DM) but with equal amounts of net energy. The low-DF diet (control) was based on barley and wheat, and the three high-DF diets formulated by replacing barley and wheat by pectin residue, sugar beet pulp and potato pulp, respectively. The experimental design comprised two periods of 4 weeks each. Half the sows were fed once daily at 08:00 h in the first period and twice daily at 08:00 and 15:00 h during the second period, and vice versa for the other half of the sows. Plasma samples from vena jugularis were collected by venipuncture at 07:00, 09:00, 12:00 and 19:00 h. Feeding high-DF increased plasma short-chain fatty acids (p = 0.02) and non-esterified fatty acids (p < 0.001). However, there was no clear effect of DF on glucose and insulin responses. A negative correlation between amount of DF in the diets and plasma creatine (R2 = 1.00; diet effect: p = 0.02) suggested that plasma creatine concentrations was an indicator for the level of glucose-glycogen interchange. Furthermore, an explorative approach using nuclear magnetic resonance spectroscopy-based metabonomics identified betaine (p < 0.001), dimethyl sulfone (DMSO2; p < 0.001) and scyllo-inositol (p < 0.001) as biomarkers for the different by-products; pectin residue was related to high plasma levels of DMSO2, sugar beet pulp to plasma betaine, DMSO2 and scyllo-inositol, and potato pulp to plasma DMSO2 and scyllo-inositol. In conclusion, replacing starch by DF affected surprisingly few metabolites in peripheral plasma. No negative effects were found in feeding pectin residue, sugar beet pulp or potato pulp for gestating sows as judged from the minor metabolic changes.     

Chronotoxicity of nedaplatin in rats

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.     

Chronotoxicity of Nedaplatin in Rats

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00 h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00 h or 20:00 h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00 h than 08:00 h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.     

Effect of orally administered l-tryptophan on serotonin,melatonin, and the innate immune response in the rat

To assess the effects of external administration of L-tryptophan on the synthesis of serotonin and melatonin as well as on the immune function of Wistar rats, 300 mg of the amino acid were administered through an oral cannula either during daylight (08:00) or at night (20:00) for 5 days. Brain, plasma, and peritoneal macrophage samples were collected 4 h after the administration. The accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used to measure the rate of tryptophan hydroxylation in vivo. Circulating melatonin levels were determined by radioimmunoassay, and the phagocytic activity of macrophages was measured by counting, under oil-immersion phase-contrast microscopy, the number of particles ingested. The results showed a diurnal increase (p < 0.05) in the brain 5-HTP, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindolacetic acid (5-HIAA) of the animals which had received tryptophan at 08:00 and were killed 4 h later. In the animals which received tryptophan during the dark period, the 5-HT declined but the 5-HT/5-HIAA ratio remained unchanged. There was also a significant increase (p < 0.05) in nocturnal circulating melatonin levels and in the innate immune response of the peritoneal macrophages in the animals which had received tryptophan at 20:00. The results indicated that the synthesis of serotonin and melatonin, as well as the innate immune response, can be modulated by oral ingestion of tryptophan.     

Circadian variations of serotonin in plasma and different brain regions of rats

Most of the physiological processes that take place in the organism follow a circadian rhythm. Serotonin is one of the most important neurotransmitters in our nervous system, and has been strongly implicated in the regulation on the mammalian circadian clock, located in the suprachiasmatic nuclei (SCN). The present study analysed the levels of serotonin over a period of 24 h in the plasma and in different brain regions. The model used was of male Wistar rats, 14 +/- 2 weeks of age (n = 120), maintained under conditions of 12 h light and 12 h dark, and food and water ad libitum. The serotonin levels were measured by ELISA every hour at night (20:00-08:00 h) and every 4 h during the daytime (08:00-20:00 h). Ours results show that the maximum levels of serotonin in plasma were obtained at 09:00 and 22:00 and a minor peak at 01:00 h. In hypothalamus there was a significant peak at 22:00 and two minor peaks at 17:00 and 02:00 h; the same occurred in hippocampus with a significant peak at 21:00, and two secondary peaks at 24:00 and 05:00 h; in cerebellum there were two peaks at 21:00 and 02:00 h, while in striatum and pineal there were peaks at 21:00 h and 23:00, respectively. In conclusion, the higher levels of serotonin were during the phase of darkness, which varies depending on the region in which it is measured.     

Evaluation of Chronopharmacodynamics of Indomethacin by the Kaolin-Induced Pain Model in Mice

We previously showed that the kaolin-induced writhe reaction exhibits 24h variation with a peak at the end of the resting period (14:00–18:00h) in mice maintained under light from 07:00 to 19:00h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.5 mg/kg) was given orally to mice at 02:00, 08:00, 14:00, or 20:00h, and the suppressive effect on kaolin-induced writhing was determined after each timed dosing. After dosing at 08:00h, indomethacin remarkably reduced the number of writhes during the critical span of 14:00–18:00h—the time when writhing reaction was greatest during the 24h, while the suppressive effect of the medicine after dosing at the other clock times was relatively small. These data suggest the analgesic effect of indomethacin in mice with the kaolin-induced writhing is greater after dosing in the early resting period, which is similar to that reported in patients with nocturnal pain. The kaolin-induced pain mouse model seems to be useful for the chronopharmacodynamic evaluation of analgesic agents.     

Evaluation of chronopharmacodynamics of indomethacin by the kaolin-induced pain model in mice

We previously showed that the kaolin-induced writhe reaction exhibits 24h variation with a peak at the end of the resting period (14:00-18:00h) in mice maintained under light from 07:00 to 19:00h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.5 mg/kg) was given orally to mice at 02:00, 08:00, 14:00, or 20:00h, and the suppressive effect on kaolin-induced writhing was determined after each timed dosing. After dosing at 08:00h, indomethacin remarkably reduced the number of writhes during the critical span of 14:00-18:00h—the time when writhing reaction was greatest during the 24h, while the suppressive effect of the medicine after dosing at the other clock times was relatively small. These data suggest the analgesic effect of indomethacin in mice with the kaolin-induced writhing is greater after dosing in the early resting period, which is similar to that reported in patients with nocturnal pain. The kaolin-induced pain mouse model seems to be useful for the chronopharmacodynamic evaluation of analgesic agents.     

Diurnal variations of serum GM-CSF levels

We aimed to investigate the daily variations of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels and to correlate them with peripheral blood cells counts. Venous blood samples from eleven healthy volunteers were taken four times a day, being at 08:00, 14:00, 20:00 and 02:00h and serum GM-CSF levels measured by ELISA. We could not find a significant overall difference among GM-CSF levels at four different times of the day using the Friedman test. On the other hand, serum GM-CSF levels at night (20:00h) were found to be significantly increased when compared to the morning levels (08:00h) using the Wilcoxon test (P=0. 022). The levels of lymphocytes and white blood cells (WBCs) at 20:00h were also higher than the morning levels (08:00h) as expected. While there was a strong relationship between the morning levels of GM-CSF (08:00h) and all measurements of peripheral blood cells during the day, the levels of GM-CSF measured at 02:00, 14:00 and 20:00h were found to be significantly correlated with only the WBC levels. It was concluded that there may be a significant difference between morning and night levels of GM-CSF and morning levels of GM-CSF may be more important in the regulation of WBC counts during the day. These variations warrant further studies about diurnal rhythms of haematopoiesis chronotherapy with CSFs.     

Chronotoxicity of Nedaplatin in Rats

Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00 h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00 h or 20:00 h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00 h than 08:00 h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.     

Spatial distribution and behaviour of laying hens housed in an alternative system

The spatial distribution and behaviour of perchery housed laying hens were compared at a constant stocking density (18.5 birds/m(2)) in eight pens with colonies of five different sizes (323 birds (N=1), 374 birds (N=2), 431 birds (N=2), 572 birds (N=1) and 912 birds (N=2)). The birds were placed in the perchery when they were 12 weeks old. Observations began when they were 26 weeks old and continued at 8 week intervals until 61 weeks of age. Colony size did not appear to affect the spatial distribution of birds, but more standing behaviour and less feeding behaviour were observed in the smallest and largest colony sizes. Older birds spent more time on the floor areas and less time on perches. Young birds (26-28 weeks) spent more time feeding, foraging, drinking and preening, and less time standing idle than older birds. In the afternoons, there were fewer birds on the perches and more on the floor levels, corresponding with less time spent resting and more time spent performing active behaviours. Birds did not distribute themselves evenly throughout their pens: within specific areas of pens densities varied between 9 and 41 birds/m(2). This variation, which reflects the flux of birds from one part of the pen to another, was greatest for the larger colony sizes, and may have adverse implications for welfare in terms of crowding and hysteria.