The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus

The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.     

β-carotene ameliorates CUS-induced circadian alternations of locomotor activity and melatonin patterns in rats

Circadian and stress systems have a crucial role in adaptation of organisms to environmental challenges. This study investigates the ability of Oscillatoria brevis (O. brevis) β-carotene extract (βC) in modulating the circadian alternations of locomotor activity (LA) and serum melatonin (M) rhythms under chronic unpredictable stress (CUS) in rats. Twenty rats (5 rats/group) were used in monitoring LA using running wheels. Eighty rats (20 rats/group) were used in observing circadian serum M profile. Rats were randomly divided into four groups, viz. control, βC-treated, CUS-exposed, and “βC-treated&CUS-exposed” groups. CUS-exposure was applied for 21 days. One hour before exposure, βC was daily administered (10 mg/kg), intraperitoneally (IP). Blood was sampled at 6-h intervals for 5 rats/time point at Zeitgeber (ZT) 3, 9, 15, and 21. Results demonstrated that unstressed rats exhibited circadian M pattern and nocturnal LA rhythm with acrophase around ZT 21 and ZT 15, respectively. CUS-exposure revealed a disturbance in these patterns. Phase shifting of M and LA profiles was recorded. A decrease M acrophase and a significant decrease in LA (p < 0.05) were recorded at ZT 9. Daily βC administration in stressed rats modulates the CRs alternation induced by CUS. It may be concluded that βC ameliorated the induced alternations in circadian rhythms.     

Cloacal temperature responses of broiler chickens administered with betaine and ascorbic acid during the hot-dry season

The experiment was performed to evaluate cloacal temperature (CT) responses in broiler chickens, administered with betaine and ascorbic acid (AA) during the hot–dry season. Broilers were divided into four groups: Group I (control) was given sterile water; Group II, betaine at 250 mg/kg; Group III, AA at 50 mg/kg and Group IV, betaine (250 mg/kg) + AA (50 mg/kg). The different solutions were given orally for 42 days. Dry-bulb temperature (DBT), relative humidity (RH) and temperature-humidity index (THI) in the pen, and CT of each broiler chicken were measured bihourly (06:00–18:00 h) on days 28, 35 and 42. DBT, RH and THI values were outside the thermo-neutral zone for broiler chickens. Results showed that AA lowered (p < 0.001) CT, while betaine + AA increased (p < 0.001) CT, compared with controls. In conclusion, betaine + AA or AA alone modulated CT responses of broiler chickens subjected to the thermal stress in the hot–dry season.     

Daily rhythms of leukocytes populations,biochemical and enzymatic blood parameters in a carnivorous freshwater catfish (Lophiosilurus alexandri)

The aim of this study was to investigate the daily rhythms of hematological, biochemical and enzymatic parameters of the blood of a nocturnal model of fish (Lophiosilurus alexandri) bred in the laboratory (F1). Thirty-six juveniles were stocked in six tanks of a recirculation aquaculture system for 20 days. The fish were exposed to a light:dark cycle of 12:12 h and were fed 1% of biomass twice a day with commercial diet. The daily rhythms of hematological, biochemical and enzymatic parameters were then measured at six sampling times “zeitgeber time = ZT” at four-hour intervals under light:dark 12:12 h (lights on = ZT0, at 8.00 a.m). No differences were observed to alkaline phosphatase, glucose, cortisol, aspartate aminotransferase, superoxide dismutase, total protein and hematocrit (p > 0.05). However, white blood cell count, Lymphocytes (LYN), Neutrophils (NEU), Eosinophil and Neutrophils to Lymphocytes ratio were significant different between sample times (p < 0.05). Also, a significant difference in alanine transaminase was observed, with a peak of production at nighttime. In contrast, glutathione peroxidase peaked at 8:00. Uric acid, magnesium and Calcium (Ca⁺⁺) showed statistically significant differences (p < 0.05). A significant difference was observed (p < 0.05), with a peak of albumin at 08:00 and triglycerides at 12:00, while cholesterol was low (p < 0.05) at 08:00 and higher from 12:00 to 04:00. Cosinor analysis revealed also rhythmicity to SOD, UA, Mg and Ca⁺⁺, ALB and CHO (p < 0.05). In conclusion, the time of day must be considered a key factor when using blood parameters as biomarkers for disease, health and welfare in the L. alexandri aquaculture.     

Opuntia ficus-indica juice supplementation: what role it plays on diurnal variation of short-term maximal exercise?

The aim of this study was to investigate the effect of natural Opuntia ficus-indica juice (OFIJ) supplementation on anaerobic performance at two times of day. Twenty-two healthy male subjects (20.91 ± 1.22; 21.00 ± 0.84 years) divided into two groups: Experimental group (EG: n = 11) and a control group (CG: n = 11) performed two tests-sessions (30-s of Wingate test (i.e. Peak power (PP), Mean power (MP)), Sargent jump test (SJT), sprint 10 m), before and after natural OFIJ supplementation at 07:00 h and 17:00 h. T-test showed that the OFIJ has a potent antioxidant capacity for capturing free radicals following the 22-diphenyl-1-picrylhydrazyl (DPPH^●) test (p < 0.05). Likewise, the ANOVA revealed that anaerobic performances were significantly higher at 17:00 h compared to 07:00 h around the peak of the temperature (p < 0.05) in both EG and CG before supplementation. Moreover, OFIJ lead an improvement of performances with (+2.09% at 07:00 h vs.+9.36% 17:00 h) for PP, (+11.29% at 07:00 h vs.+11.77% 17:00 h) for MP, (+9.42% at 07:00 h vs.+7.63% 17:00 h) for SJT in EG. The RPE scores on response to the Wingate test decrease after OFIJ supplementation (p < 0.01). For the sprint values, a significant improvement was after OFIJ (?7.10% at 07:00 h vs. ?6.45% 17:00 h). However, no change was observed for CG after supplementation. In conclusion, the natural OFIJ supplementation for two weeks appears to ameliorate the performance upon two times of day with great improvement observed in the evening during short-term maximal exercise given the higher muscle damage, inflammatory, and oxidative responses at this time of day. Thus, it’s necessary that athletes, coaches, and medical staff consider the positive effects of Opuntia ficus-indica to improve anaerobic performance.     

Altering meal timing to improve cognitive performance during simulated nightshifts

ABSTRACT

Altering meal timing could improve cognition, alertness, and thus safety during the nightshift. This study investigated the differential impact of consuming a meal, snack, or not eating during the nightshift on cognitive performance (ANZCTR12615001107516). 39 healthy participants (59% male, age mean±SD: 24.5 ± 5.0y) completed a 7-day laboratory study and underwent four simulated nightshifts. Participants were randomly allocated to: Meal at Night (MN; n= 12), Snack at Night (SN; n = 13) or No Eating at Night (NE; n = 14). At 00:30 h, MN consumed a meal and SN consumed a snack (30% and 10% of 24 h energy intake respectively). NE did not eat during the nightshift. Macronutrient intake was constant across conditions. At 20:00 h, 22:30 h, 01:30 h, and 04:00 h, participants completed the 3-min Psychomotor Vigilance Task (PVT-B), 40-min driving simulator, post-drive PVT-B, subjective sleepiness scale, 2-choice Reaction Time task, and Running Memory task. Objective sleep was recorded for each of the day sleeps using Actigraphy and for the third day sleep, Polysomnography was used. Performance was compared between conditions using mixed model analyses. Significant two-way interactions were found. At 04:00 h, SN displayed increased time spent in the safe zone (p < .001; percentage of time spent within 10 km/h of the speed limit and 0.8 m of lane center), and decreases in speed variability (p < .001), lane variability (p < .001), post-drive PVT-B lapses (defined as RT > 355 ms; p < .001), and reaction time on the 2-choice reaction time task (p < .001) and running memory task (p < .001) compared to MN and NE. MN reported greater subjective sleepiness at 04:00 h (p < .001) compared to SN and NE. There was no difference in objective sleep between eating conditions. Eating a large meal during the nightshift impairs cognitive performance and sleepiness above the effects of time of night alone. For improved performance, shiftworkers should opt for a snack at night.     

Circadian expression of DNA methylation and demethylation genes in zebrafish gonads

This research aimed at investigating the light synchronization and endogenous origin of daily expression rhythms of eight key genes involved in epigenetic mechanisms (DNA methylation and demethylation) in zebrafish gonads. To this end, 84 zebrafish were distributed into six tanks, each one containing 14 fish (7 males and 7 females). Animals were subjected to 12 h light:12 h dark cycles (LD, lights on at ZT0 h) and fed randomly three times a day during the light phase. Locomotor activity rhythms were recorded in each tank for 20 days to test their synchronization to light. Then, zebrafish were fasted for one day and gonad samples were collected every 4 h during a 24 h cycle (ZT2, 6, 10, 14, 18, and 22 h). The results revealed that most of the epigenetic genes investigated exhibited a significant daily rhythm. DNA methylation genes (dnmt4, dnmt5, dnmt7) exhibited a daily rhythm of expression with a nocturnal acrophase (ZT14:01~ZT22:17 h), except for dnmt7 in males (ZT2:25 h). Similarly, all DNA demethylation genes (tet2, tdg, mb4, gadd45aa, and apobec2b) revealed the existence of statistically significant daily rhythms, except for gadd45aa in females. In females, tdg, mb4, and apobec2b presented a nocturnal peak (ZT14:20 ~ ZT22:04 h), whereas the tet2 acrophase was diurnal (ZT4:02 h). In males, tet2, tdg, and gadd45aa had nocturnal acrophases (ZT18:26~ZT21:31 h), whereas mb4 and apobec2b displayed diurnal acrophases (ZT5:28 and ZT4:02 h, respectively). To determine the endogenous nature of gene expression rhythms, another experiment was performed: 12 groups of 14 fish (7 males and 7 females) were kept in complete darkness (DD) and sampled every 4 h during a 48 h cycle (CT2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46 h). Under DD, most of the genes (7 out of 8) presented circadian rhythmicity with different endogenous periodicities (tau), suggesting that the epigenetic mechanisms of DNA methylation and demethylation in the gonads follow an internal control, functioning as part of the translation network linking the environment into somatic signals in fish reproduction.     

Effects of a diet containing fusarium toxins on the fertility of gilts and on bulbourethral gland weight in barrows

Nine gilts weighing 80 kg at the beginning of the trial were fed a mycotoxin contaminated diet containing 2 mg deoxynivalenol (DON) and 0.4 mg zearalenone (ZON) per kg (Diet M). Their daily weight gain until 103 kg BW was reduced in comparison to the nine control animals fed an uncontaminated diet (Diet C) (763 vs. 912 g; p = 0.02). There was no treatment effect on the age at first observed oestrus. Seven and eight gilts receiving Diet M and C, respectively, became pregnant after being mated once or being again mated three weeks later. The examination of the uteri of gilts slaughtered 35–61 days after mating showed that the exposure to DON and ZON had no effect on the number of foetuses per gilt (p = 0.54), but increased their growth rate (p = 0.003). Thus, low dietary DON and ZON levels had no negative effects on the reproductive parameters examined. The hypothesis that the bulbourethral gland weight of barrows can be used for the bioassay of low dietary ZON levels was rejected since feeding Diet M from 80–103 kg BW did not increase the weight of that accessory sex gland (p = 0.51).     

Effect of napping opportunity at different times of day on vigilance and shuttle run performance

ABSTRACT

The aim of the present study was to examine the effect of a nap opportunity during the daytime realized at different times of day on physical and mental performance. Eighteen physically active males (age: 20.5 ± 3.0 years, height: 175.3 ± 5.9 cm, body-mass: 70.0 ± 8.6 kg) were tested under four experimental conditions: no-nap condition, nap at 13h00, nap at 14h00 and nap at 15h00. All nap durations were of 25-min and all tests were performed at 17h00. They performed a 5-m shuttle run test, which generated measures of the highest distance (HD) and total distance (TD). The rating of perceived exertion (RPE) was recorded after each of the six sprints in the 5-m shuttle run test. Vigilance was measured using a digit cancellation test. The results showed that TD at 17h00 was 4% greater after a nap at 14h00 than in the no-nap condition (+28 m, p < .05) or after the nap at 13h00 (+29 m, p < .05). HD was 8% higher (+9 m, p < .001) after a nap at 14h00 than in the no-nap condition and 7% higher after nap at 15h00 than in the no-nap condition (+7 m, p < .05). In addition, HD was 6% higher after nap at 14h00 (+7 m, p < .01) and 5% higher after nap at 15h00 (+9 m, p < .01) than HD after a nap at 13h00. Napping at 13h00 had no effect on physical performance at 17h00. No significant differences were observed between RPE and vigilance scores in the nap and no-nap conditions. In conclusion, napping for 25 min at 14h00 and 15h00 produces meaningful improvements in responses during repeated short-term maximal exercise tests performed at 17h00. Napping at 13h00 does not. Vigilance, as measured using a digit cancellation test, and RPE scores are not influenced by any of the nap opportunities.     

<Emphasis Type="Italic">Trans</Emphasis>-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model

Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8 mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1β (IL-1β), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced Aβ_1–42 protein accumulation in brain of mice. Remarkably CNM’s effect on IL-1β was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden.     

Daily rhythms after vaccination on specific and non-specific responses in Nile tilapia (Oreochromis niloticus)

ABSTRACT

We evaluated the daily changes in immunological and hematological factors in tilapia (Oreochromis niloticus) after an immunization period with a subsequent challenge. Experiments were divided into two phases: Phase 1 (immunization): 144 fish were distributed into two groups with 72 fish in six tanks. One group (T1) was immunized, comprising six vaccination time points (ZT schedule = ZT2 h, ZT6 h, ZT10 h, ZT14 h, ZT18 h, ZT22 h). The same schedule was applied to the other group, but with saline solution (non-vaccinated: T2). Both groups remained in the laboratory for 30 days (considered the immunization period). Phase 2 (challenge): on day 30, both vaccinated and non-vaccinated groups were challenged with Streptococcus agalactiae (2.0 × 10⁷ CFU mL^?1) following the same ZT schedule to stimulate the immune response without leading to widespread infection and mortality. On day 45, blood and head kidney samples were collected during the same ZT schedule. The variations in time of the following parameters within each group were evaluated: hematology, peroxidase activity, IgM, tnf-α3, tgf-β1, il-1β and il-12 gene expression. No significant mortality was observed for the groups or the ZT schedule (p > 0.05). Daily rhythms with diurnal acrophases were found in T2 for il12, tnf-α3 and tgf-β1 expression gene, while the acrophases of the peroxidase level, hematocrit and thrombocytes were at nighttime (p < 0.05). In contrast, most of the parameters in the vaccinated tilapia showed no daily rhythms (p > 0.05), except IgM. For all the parameters, the interaction effect between time and treatment (vaccinated and non-vaccinated groups) depended on ZT. Our results reveal that the humoral and non-specific immune system displayed a circadian rhythm based on the light-dark cycle, which could be affected by the vaccination procedure in tilapia.     

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 (R ² = 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.     

Toxicity of Chemically Spiked Sediment to the Carpet Shell Clam Ruditapes decussatus Embryos and Larvae

The objective of this research was to assess the toxicity of sediment contaminated with cadmium, DDT, chlorpyrifos, and fluoranthene to embryos and larvae of the European clam Ruditapes decussatus, exposed to two sediment fractions, the whole sediment and elutriate. The percentages of abnormal D-shaped larvae and larval mortality have been investigated. The median effective concentration (EC50) values, reducing 50% of the percentage of D-shaped larvae, in whole sediments and elutriates were, respectively, 1.17 mg/kg and 417.1 μgl^?1 (3.71 μM) for cadmium, 1.66 mg/kg and 97.8 μgl^?1 (0.48 μM) for fluoranthene, 1.71 mg/kg and 384.8 μgl^?1 (1.08 μM) for DDT, and 0.96 mg/kg and 339.5 μgl^?1 (0.96 μM) for chlorpyrifos. The 96h-median lethal concentrations (LC50) reducing larval survival by 50% were 4.04 mg/kg 654.3 μgl^?1 (5.82 μM) for cadmium, 17.41 mg/kg 8666.6 μgl^?1 (42.84 μM) for fluoranthene, 3.93 mg/kg and 457.4 μgl^?1 (1.29 μM) for DDT, and 2.53 mg/kg and 308.06 μgl^?1 (0.87 μM) for chlorpyrifos. Based on EC₅₀ and LC₅₀ comparisons to toxicity data for other marine species, these findings suggest that the R. decussatus embryotoxicity and larvae mortality bioassay were among the most sensitive tools for sediment quality assessment.     

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.     

Effect of Anacyclus pyrethrum on Pentylenetetrazole-Induced Kindling, Spatial Memory, Oxidative Stress and Rho-Kinase II Expression in Mice

Anacyclus pyrethrum (A. pyrethrum) has been reported to exhibit anticonvulsant activity. In the present study, the effect of hydro-alcoholic extract of A. pyrethrum root (HEAP) on pentylenetetrazole (PTZ) induced kindling, spatial memory, oxidative stress and rho kinase (ROCK II) was assessed. Male albino mice (25–30 g) were used in the study. PTZ (35 mg/kg, i.p. on alternate days) was injected to induce kindling and PTZ (70 mg/kg, i.p) challenge was given 7 days post-kindling. HEAP was administered orally daily in the doses of 100, 250 and 500 mg/kg along with PTZ injections during the kindling process and continued till PTZ challenge post kindling. Spatial memory was assessed using Morris water maze test. Oxidative stress parameters [malondialdehyde (MDA) and reduced glutathione (GSH)] and ROCK II expression were estimated in whole brain at the end of the study. Pre-treatment with HEAP (250 and 500 mg/kg) showed significant increase in the myoclonic jerk latency and delay in the development of kindling. A significant decrease in mortality was observed at higher doses of HEAP (250 and 500 mg/kg). Pre-treatment with HEAP significantly increased the number of platform crossings and decreased the escape latency, as opposed to the PTZ group, thus showing protection against memory deficit. HEAP pre-treatment also attenuated the oxidative stress induced by PTZ kindling. PTZ induced kindling increased the ROCK II expression whereas, HEAP pre-treatment attenuated the increase in ROCK II expression. To conclude, HEAP pre-treatment showed antiepileptic effect and also showed protection against cognitive impairment by decreasing oxidative stress and ROCK II expression in PTZ kindled mice.     

Influence of feeding a fish oil-containing diet to young,lean, adult dogs: effects on lipid metabolites,postprandial glycaemia and body weight

The aim of this study was to determine the effect of feeding a fish oil (FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and body weight in young, lean, adult dogs. Eight female Beagles were randomly assigned to one of two isonitrogenous and isoenergetic diets, Control or FO, in a crossover design. At the beginning of the experiment and at 30 and 60 d, a baseline blood sample was collected and the dogs then were fed their daily ration. Nitrogen balance began at 07:00 h on day 63 of each experimental period and ended at 07:00 h on day 69. On day 66 of each period, a single dose (7.5 mg/kg) of ¹⁵N-glycine was administered orally to each dog via gelatin capsule. Postprandial glycaemia did not differ between treatments or among sampling days within treatment. Cholesterol concentration was increased (p < 0.05) on the Control treatment throughout the experiment when compared to values of day 0. Dogs fed the FO treatment had higher plasma triglyceride and ghrelin concentrations than those fed the Control treatment. Body weight and food intake did not differ between dietary treatments. Faecal excretion was increased (p < 0.05) in the FO treatment. Dry matter digestibility was decreased (p < 0.05) and fat digestibility tended (p < 0.10) to decrease in the FO treatment. Overall, feeding a FO-containing diet showed a protective effect against the rise of plasma cholesterol and it increased plasma ghrelin concentration. However, FO supplementation did not appear to affect protein metabolism or postprandial glycaemia in adult lean dogs.     

The effects of 12-week progressive strength training on strength,functional capacity,metabolic biomarkers,and serum hormone concentrations in healthy older women: morning versus evening training

ABSTRACT

Previous findings suggest that performing strength training (ST) in the evening may provide greater benefit for young individuals. However, this may not be optimal for the older population. The purpose of this study was to compare the effects of a 12-week ST program performed in the morning vs. evening on strength, functional capacity, metabolic biomarker and basal hormone concentrations in older women. Thirty-one healthy older women (66 ± 4 years, 162 ± 4 cm, 75 ± 13 kg) completed the study. Participants trained in the morning (M) (07:30, n = 10), in the evening (E) (18:00, n = 10), or acted as a non-training control group (C) (n = 11). Both intervention groups performed whole-body strength training with 3 sets of 10–12 repetitions with 2–3 minutes rest between sets. All groups were measured before and after the 12-week period with; dynamic leg press and seated-row 6-repetition maximum (6-RM) and functional capacity tests (30-second chair stands and arm curl test, Timed Up and Go), as well as whole-body skeletal muscle mass (SMM) (kg) and fat mass (FM-kg, FM%) assessed by bioelectrical impedance (BIA). Basal blood samples (in the intervention groups only) taken before and after the intervention assessed low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), blood glucose (GLU), triglycerides (TG), high-sensitive C-reactive protein (hsCRP) concentrations and total antioxidant status (TAS) after a 12 h fast. Hormone analysis included prolactin (PRL), progesterone (P) estradiol (ESTR), testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH). While C showed no changes in any variable, both M and E significantly improved leg press (+ 46 ± 22% and + 21 ± 12%, respectively; p < 0.001) and seated-row (+ 48 ± 21% and + 42 ± 18%, respectively; p < 0.001) 6-RM, as well as all functional capacity outcomes (p < 0.01) due to training. M were the only group to increase muscle mass (+ 3 ± 2%, p < 0.01). Both M and E group significantly (p < 0.05) decreased GLU (–4 ± 6% and –8 ± 10%, respectively), whereas significantly greater decrease was observed in the E compared to the M group (p < 0.05). Only E group significantly decreased TG (–17 ± 25%, p < 0.01), whereas M group increased (+ 15%, p < 0.01). The difference in TG between the groups favored E compared to M group (p < 0.01). These results suggest that short-term “hypertrophic” ST alone mainly improves strength and functional capacity performance, but it influences metabolic and hormonal profile of healthy older women to a lesser extent. In this group of previously untrained older women, time-of-day did not have a major effect on outcome variables, but some evidence suggests that training in the morning may be more beneficial for muscle hypertrophy (i.e. only M significantly increased muscle mass and had larger effect size (M: g = 2 vs. E: g = 0.5).     

<Emphasis Type="Italic">Arbutus andrachne</Emphasis> L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats

Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P < 0.05). Treatment of animals with A. andrachne fruit extract at all doses prevented long-term memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P < 0.05) induced by chronic sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.     

Post-resistance training detraining: time-of-day effects on training and testing outcomes

The aim of this study was to examine the effects of 3 and 5 weeks of detraining after 14 weeks of resistance training at a specific time of day on performances during the squat jump (SJ) and the maximal voluntary contraction (MVC). Thirty-one healthy male physical education students (age: 23.1 ± 1.0 years; height: 176.1 ± 6.3 cm; weight: 74.9 ± 10.9 kg) were randomly assigned to either a morning training group (MTG, training between 07:00 and 08:00 h, n = 10), an evening training group (ETG, training between 17:00 and 18:00 h, n = 11) or a control group (CG, no training, n = 10). Participants then performed eight test sessions (twice per day, at 07:00 and 17:00 h) over the course of four phases: during pre-training, immediately post-training, and after 3 and 5 weeks of detraining. Before each test session, oral temperature was recorded. During the first 12 weeks of resistance training, participants performed 3 sets of 10 repetitions to failure (10-RM) for 4 exercises (squat, leg press, leg extension and leg curl, with 2 min of recovery between each exercise); during the last two weeks, training intensity increased to 8-RM with 3 min of recovery between each exercise. Oral temperature was significantly higher at 17:00 than 07:00 h during all test periods (p < 0.05). Likewise, SJ and MVC performances were significantly higher at 17:00 h than 07:00 h during all four test days in ETG and CG, and before training and 3 and 5 weeks after training in MTG (p < 0.05). For both training groups, most SJ and MVC performances (except MTG at 07:00 h and ETG at 17:00 h) returned to baseline values after 5, but not after 3, weeks of detraining. This study showed that 14 weeks of training at a specific time of day blunted the diurnal variation of MVC and SJ in the MTG. The improvement in performance brought about by resistance training was partially retained after 3 weeks of detraining (unless training had taken place at a non-habitual time of day) but was lost after 5 weeks of detraining. There was no effect of the time of training on core temperature.     

Evaluation of 5-HT7 Receptor Trafficking on In Vivo and In Vitro Model of Lipopolysaccharide (LPS)-Induced Inflammatory Cell Injury in Rats and LPS-Treated A549 Cells

This study aimed to investigate the effects of the 5-HT7 receptor agonist (LP44) and antagonist (SB269970) on LPS-induced in vivo tissue damage and cell culture by molecular methods. This study was conducted in two steps. For in vivo studies, 24 female rats were divided into four groups. Group I: healthy; II (2nd h): LPS 5 mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5 mg/kg administered i.p.; IV (8th h): LPS 5 mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2–4 h); II LPS: 1 µg/ml E. Coli O55:B5 strain (2–4 h); III agonist (LP44) 10^?9 M (2–4 h); IV antagonist (SB269970) 10^?9 M (2–4 h); V LPS+agonist 10^?9 M (LP44 1 µg/ml) (2–4 h); VI LPS+antagonist 10^?9 M (2–4 h). In molecular analyses, we determined increased TNF-α, IL-1β, NF-κB, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-α, iNOS, and 5-HT7 mRNA expressions in the A549 cell line. In in vitro parameters, LP44 agonist administration-related decrease was observed. Our study showed that lung 5-HT7 receptor expression is increased in LPS-induced endotoxemia. All this data suggest that 5-HT7 receptor overexpression is an important protective mechanism during LPS-induced sepsis-related cell damage.