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Aim: To examine rat molar pulp innervation and identify complex cellular signalling systems involving nerve growth factor (NGF) and its p75 receptors (NGFR) at different stages of development, maturation and ageing. Methodology: Decalcified mandibular first molar mesial cusps from Wistar rats of ages 0 day; 1, 2, 3, 4, 6, 9, 12 and 24 weeks (n = 5 per group) were sectioned (10 μm) and incubated with antibodies for NGF, NGFR, calcitonin gene‐related peptide (CGRP) and neurofilament. Nerve densities in worn and intact regions of 3‐ to 24‐week‐old rats were compared by anova, Bonferroni and t‐tests. Results: During odontogenesis, differences in NGF and NGFR expression were observed, with no evidence of nerve fibres, suggesting a signalling mechanism controlling cellular differentiation and dentine formation. Tooth wear in 4‐week rats was associated with reduced NGF expression and significantly decreased CGRP axons within affected odontoblast regions. The underlying subodontoblasts started expressing NGF which continued until 9 weeks. This may promote a significant increase in CGRP nerve density in affected regions. Nerve density in intact odontoblast regions increased gradually and reached significant levels in 12‐week rats. Reduction in nerve densities within worn and intact regions of cusps was observed at 24 weeks. Conclusions: Age‐related changes and responses to tooth wear may be controlled by the NGF signalling mechanism, with roles in odontoblast/subodontoblast communication and control of sensory innervation at different stages of tooth development, maturation and ageing. Greater understanding of cellular and nerve regulation in the injured pulp may promote therapeutic strategies for pulp survival. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The effects of dehydration on muscle performance in human are still contradictory, notably regarding muscle force. The effect of water deprivation (WD) on mechanical properties of skeletal muscle, and more precisely its impact on slow and fast muscles, remains largely unknown. The aim of this study was to determine for the first time whether WD leads to changes in contractile properties of skeletal muscle and whether these changes were muscle‐type‐specific. Methods: Sixteen‐week‐old male rats were assigned to either a control group (C) with water or a 96‐hour WD group. At the end of the period, twitch and tetanus properties, as well as biochemical and structural analysis, were performed on soleus (SOL) and extensor digitorum longus (EDL) muscles. Results: Absolute twitch (Pt) and tetanic (P0) tension were, respectively, 17% and 14% lower in EDL of WD rats as compared with C rats, whereas unexpected increases of 43% and 25% were observed in SOL. Tensions normalized with respect to muscle mass were not affected by WD in EDL, whereas they were increased by more than 40% in SOL. A 96‐hour WD period leads to a decrease in fibre cross‐sectional area and absolute myofibrillar content only in EDL. Conclusion: It is hypothesized that differences in the results between slow and fast muscles may come from (i) a muscle‐type‐specific effect of WD on protein balance, EDL showing a greater myofibrillar protein breakdown and (ii) a greater sensitivity to osmolality changes induced by WD in EDL than in SOL. [ABSTRACT FROM AUTHOR]

Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 ( SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. [ABSTRACT FROM AUTHOR]

Key points 5-HT is a neuromodulator released from carotid body (CB) chemoreceptor (type I) cells and facilitates the sensory discharge following chronic intermittent hypoxia (CIH)., In the present study, we show that, in addition to type I cells, adjacent glial-like type II cells express functional, ketanserin-sensitive 5-HT2 receptors, and their stimulation increases cytoplasmic Ca2+ derived from intracellular stores., In type II cells, 5-HT activated a ketanserin-sensitive inward current ( I5-HT) that was similar to that ( IUTP) activated by the P2Y2R agonist, UTP., As previously shown for IUTP, I5-HT was inhibited by BAPTA-AM and carbenoxolone (5 μ m), a putative blocker of ATP-permeable pannexin (Panx)-1 channels; IUTP was reversibly inhibited by the specific Panx-1 mimetic peptide channel blocker, 10Panx peptide., Paracrine stimulation of type II cells by 5-HT, leading to ATP release via Panx-1 channels, may contribute to CB excitability, especially in pathophysiological conditions associated with CIH (e.g. obstructive sleep apnoea)., Abstract Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-HT and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca2+]i) and activating carbenoxolone-sensitive, ATP-permeable, pannexin (Panx)-1-like channels. In the present study, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca2+]i responses in a subpopulation of type I cells, as well as in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP. The 5-HT-induced Ca2+ response in type II cells was dose-dependent (EC50 ∼183 n m) and largely inhibited by the 5-HT2A receptor blocker, ketanserin (1 μ m), and also arose mainly from intracellular stores. 5-HT also activated an inward current ( I5-HT) in type II cells (EC50 ∼200 n m) that was reversibly inhibited by ketanserin (1-10 n m), the Ca2+ chelator BAPTA-AM (5 μ m), and low concentrations of carbenoxolone (5 μ m), a putative Panx-1 channel blocker. I5-HT reversed direction at approximately −11 mV and was indistinguishable from the UTP-activated current ( IUTP). Consistent with a role for Panx-1 channels, IUTP was reversibly inhibited by the specific Panx-1 mimetic peptide blocker 10Panx (100 μ m), although not by its scrambled control peptide (scPanx). Because ATP is an excitatory CB neurotransmitter, it is possible that the contribution of enhanced 5-HT signalling to the increased sensory discharge during CIH may occur, in part, by a boosting of ATP release from type II cells via Panx-1 channels. [ABSTRACT FROM AUTHOR]

Key points Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes., Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring., Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning., Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet., Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation., Abstract Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring. [ABSTRACT FROM AUTHOR]

Key points Ligating the femoral artery of a rat for 72 h, a model for peripheral artery disease, causes an exaggerated exercise pressor reflex in response to muscle contraction., Likewise, the hindlimb muscles of rats with ligated femoral arteries show increased levels of reactive oxygen species., Infusion of tiron, a superoxide scavenger, attenuated the exaggerated pressor reflex and reduced reactive oxygen species production in rats with ligated femoral arteries., Conversely, we found no effect of tiron infusion on the pressor reflex in rats with patent femoral arteries., These results suggest a role of reactive oxygen species with respect to causing the exaggerated pressor response to contraction seen in rats with ligated arteries and peripheral artery disease., Abstract Contraction of muscle evokes the exercise pressor reflex (EPR), which is expressed partly by increases in heart rate and arterial pressure. Patients with peripheral artery disease (PAD) show an exaggerated EPR, sometimes report pain when walking and are at risk for cardiac arrthymias. Previous research suggested that reactive oxygen species (ROS) mediate the exaggerated EPR associated with PAD. To examine the effects of ROS on the EPR, we infused a superoxide scavenger, tiron, into the superficial epigastric artery of decerebrated rats. In some, we simulated PAD by ligating a femoral artery for 72 h before the experiment. The peak EPR in 'ligated' rats during saline infusion averaged 31 ± 4 mmHg, whereas the peak EPR in these rats during tiron infusion averaged 13 ± 2 mmHg ( n = 12; P < 0.001); the attenuating effect of tiron on the EPR was partly reversed when saline was reinfused into the superficial epigastric artery (21 ± 2 mmHg; P < 0.01 vs. tiron). The peak EPR in 'ligated' rats was also attenuated ( n = 7; P < 0.01) by infusion of gp91ds-tat, a peptide that blocks the activity of NAD(P)H oxidase. Tiron infusion had no effect on the EPR in rats with patent femoral arteries ( n = 9). Western blots showed that the triceps surae muscles of 'ligated' rats expressed more Nox2 and p67phox, which are components of NADPH oxidase, compared to triceps surae muscles of 'freely perfused' rats. Tiron added to muscle homogenates reduced ROS production in vitro. The results of the present study provide further evidence indicating that ROS mediates the exaggeration of EPR in rats with simulated PAD. [ABSTRACT FROM AUTHOR]

Key points The brainstem dorsal column nuclei (DCN) process sensory information arising from the body before it reaches the brain and becomes conscious., Despite significant investigations into sensory coding in peripheral nerves and the somatosensory cortex, little is known about how sensory information arising from the periphery is represented in the DCN., Following stimulation of hind-limb nerves, we mapped and characterised the evoked electrical signatures across the DCN surface., We show that evoked responses recorded from the DCN surface are highly reproducible and are unique to nerves carrying specific sensory information., Abstract The brainstem dorsal column nuclei (DCN) play a role in early processing of somatosensory information arising from a variety of functionally distinct peripheral structures, before being transmitted to the cortex via the thalamus. To improve our understanding of how sensory information is represented by the DCN, we characterised and mapped low- (<200 Hz) and high-frequency (550-3300 Hz) components of nerve-evoked DCN surface potentials. DCN surface potentials were evoked by electrical stimulation of the left and right nerves innervating cutaneous structures (sural nerve), or a mix of cutaneous and deep structures (peroneal nerve), in 8-week-old urethane-anaesthetised male Wistar rats. Peroneal nerve-evoked DCN responses demonstrated low-frequency events with significantly longer durations, more high-frequency events and larger magnitudes compared to responses evoked from sural nerve stimulation. Hotspots of low- and high-frequency DCN activity were found ipsilateral to stimulated nerves but were not symmetrically organised. In conclusion, we find that sensory inputs from peripheral nerves evoke unique and characteristic DCN activity patterns that are highly reproducible both within and across animals. [ABSTRACT FROM AUTHOR]

Background and Objective Doxycycline is an antibiotic agent that inhibits the activity of matrix metalloproteinases ( MMPs) present in the extracellular matrix. In this study, the rat incisor was submitted to a hypofunctional condition, and the effects of doxycycline (80 mg/kg/d) on the expression and activity of MMP-2, as well as on eruption rate, were determined in the odontogenic region and in the periodontal ligament for 14 d. Material and Methods Rats were distributed into four groups: normofunctional ( NF); doxycyline normofunctional ( DNF); hypofunctional ( HP); and doxycyline hypofunctional ( DHP). The left lower incisors of 10 rats were shortened every 2 d, using a high-rotation drill, to produce the HP and DHP groups, after starting doxycycline treatment (80 mg/kg) by gavage. Eruption was measured using a millimeter ocular, from the gingival margin to the top of the tooth in the HP and DHP groups, and also by a mark made in the tooth previously, in the NF and DNF groups. The hemimandibles were removed and the teeth were extracted to collect the periodontal and odontogenic tissues for immunohistochemical analyses and zymography. Results The eruption rates were higher in the HP and the DHP groups than in the NF and DNF groups, respectively ( p < 0.05). In the odontogenic region, neither of the treatments changed the expression and activity of MMP-2. In the HP group, the shortening treatment decreased the expression, but not the activity, of MMP-2, while doxycycline was able to inhibit the increase of expression and activity of MMP-2. Conclusion We conclude that the inhibition of MMP-2 by doxycycline, during incisor shortening, was not enough to alter the eruption rate, which suggests that MMP-2 may have an important role in the turnover of extracellular matrix of the periodontal ligament during the tooth-eruption process. [ABSTRACT FROM AUTHOR]

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system ( CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist ( SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol ( PTZ)-kindled rats. Kindling was induced by repeated intraperitoneal ( IP) injections of PTZ (32 mg/kg) with two-day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular ( ICV) injections of SB-334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure-related behaviors were monitored for 30 min following PTZ administration. The anxiety-like behaviors were also assessed using elevated plus-maze in the first and last days of the study. The results revealed that ICV injection of SB-334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ-induced anxiety-like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders. [ABSTRACT FROM AUTHOR]

Stress contributes, as a risk factor, to such psychological disorders as anxiety. The effects of electrical lesions in the basolateral amygdala nucleus ( BLA) were investigated on the locomotor activity and anxiety-like behaviour in different stress durations. For this purpose, rats were randomly allocated to control, sham, and experimental groups, the latter including groups with and without BLA nucleus subjected to acute, sub-chronic, and chronic stress conditions for 1, 7, and 21 days, respectively, applied 6 h/d. The induced anxiety behaviour was evaluated using the open field test ( OFT) while other variables were measured. Findings revealed that sub-chronic stress led to significantly reduced ( P<.05) anxiety behaviours as measured by entries into and the time spent in the centre area while it also led to significant impairments in exploratory and locomotor activities, indicating intensified anxiety-like behaviour. BLA lesion affected rat behaviour differently such that it significantly ( P<.05) decreased fear under sub-chronic and chronic stress conditions as evidenced by the subjects' greater tendency to enter the centre area in the open field test and their increased number of rearing events ( P<.01). However, BLA lesion led to no significant decrease in the locomotor activity of subjects exposed to sub-chronic or chronic stress conditions as compared with those in similar groups but without BLA lesion. Finally, BLA lesion was found not only to decrease significantly ( P<.01) adrenal gland and body weights, particularly under sub-chronic stress, but also to play a critical role in modulating adrenal functions by decreasing adrenal gland weight, and thereby reducing depression-like symptoms. [ABSTRACT FROM AUTHOR]

The typical cause of death in pulmonary hypertension (PH) is right ventricular (RV) failure, with females showing better survival rates than males. Recently, metabolic shift and mitochondrial dysfunction have been demonstrated in RV failure secondary to PH. In light of evidence showing that estrogen protects mitochondrial function and biogenesis in noncardiovascular systems, we hypothesized that the mechanism by which estrogen preserves RV function is via protection of mitochondrial content and oxidative capacity in PH. We used a well-established model of PH (Sugen+Hypoxia) in ovariectomized female rats with/without estrogen treatment. RV functional measures were derived from pressure-volume relationships measured via RV catheterization in live rats. Citrate synthase activity, a marker of mitochondrial density, was measured in both RV and LV tissues. Respiratory capacity of mitochondria isolated from RV was measured using oxygraphy. We found that RV ventricular-vascular coupling efficiency decreased in the placebo-treated SuHx rats (0.78 ± 0.10 vs. 1.50 ± 0.13 in control, P < 0.05), whereas estrogen restored it. Mitochondrial density decreased in placebo-treated SuHx rats (0.12 ± 0.01 vs. 0.15 ± 0.01 U citrate synthase/mg in control, P < 0.05), and estrogen attenuated the decrease. Mitochondrial quality and oxidative capacity tended to be lower in placebo-treated SuHx rats only. The changes in mitochondrial biogenesis and function paralleled the expression levels of PGC-1a in RV. Our results suggest that estrogen protects RV function by preserving mitochondrial content and oxidative capacity. This provides a mechanism by which estrogen provides protection in female PH patients and paves the way to develop estrogen and its targets as a novel RV-specific therapy for PH. [ABSTRACT FROM AUTHOR]

ABSTRACT Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017. [ABSTRACT FROM AUTHOR]

Aim The translationally controlled tumor protein (TCTP) has been reported to promote progression of many physiological processes. However, whether TCTP is involved in liver regeneration has been rarely studied. This study aimed to investigate the potential role of serum TCTP in liver regeneration after two-thirds partial hepatectomy. Methods The synthesis rate and accumulated expression of TCTP was assessed by phosphor imaging and Western blot analysis, respectively. The mRNA expression of tctp was analyzed by quantitative real-time PCR. The effect of serum TCTP on hepatocyte proliferation was investigated by bromodeoxyuridine incorporation, liver/body weight ratio, albumin concentration, and histological examination of liver following treatment of rat with anti-TCTP antibody or prokaryotic TCTP protein before hepatectomy. The MTT assay was used to examine effect of TCTP on hepatocyte proliferation in vitro. Results The results showed that the expression of intracellular and serum TCTP protein was significantly increased in rats after two-thirds partial hepatectomy. In vivo bromodeoxyuridine labeling assay suggested that treatment with anti-TCTP antibody before hepatectomy significantly decreased hepatocyte proliferation and liver/body weight ratio. The prokaryotic TCTP had a potential promoting effect on hepatocyte proliferation both in vivo and in vitro, although prokaryotic TCTP given to rats prior to hepatectomy did not increase the proliferation ratio or liver/body weight ratio. Furthermore, anti-TCTP antibody pretreatment decreased the expression of cyclin E, cdk2, and interleukin-6 in rat liver. Conclusion These findings suggest serum TCTP is involved in rat liver regeneration through promoting hepatocyte proliferation. [ABSTRACT FROM AUTHOR]

Previous studies have documented that rapid juvenile growth is accompanied by functional changes in the arteriolar endothelium, but much less is known about functional changes in arteriolar smooth muscle over this period. In this study, we investigate the possible contribution of epithelial sodium channels ( ENaC) to the myogenic behaviour of arterioles at two stages of juvenile growth. The effects of the ENaC inhibitor benzamil on different levels of myogenic tone were studied in isolated gracilis muscle arterioles from rats aged 21-28 days ('weanlings') and 42-49 days ('juveniles'). ENaC subunit expression in the arteriolar wall was also determined, and the interaction between ENaC and nitric oxide ( NO) in regulating vascular tone was explored by combined use of benzamil and NG-monomethyl- l-arginine ( l- NMMA). At physiological pressures, both steady-state myogenic tone and the dynamic adjustments in this tone triggered by acute pressure changes were less in juvenile arterioles than in weanling arterioles. α, β and γ ENaC protein was present in arterioles at both ages, but benzamil only had an effect on myogenic tone in weanling arterioles. In these vessels, benzamil increased, rather than decreased, myogenic tone, and this effect was prevented by l- NMMA or endothelial removal. These findings suggest that although ENaC is present in gracilis muscle arterioles of both weanling and juvenile rats, it is not obligatory for the genesis of myogenic activity in these vessels at either age. However, ENaC activity can significantly modulate the level of myogenic tone through stimulation of endothelial NO release at an early stage of growth. [ABSTRACT FROM AUTHOR]

The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real-time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways. [ABSTRACT FROM AUTHOR]

The current treatment of choice for attention deficit hyperactivity disorder (ADHD) is pharmacotherapy. A search for new treatment options is underway, however, as the wide application of drugs to the general population of patients with ADHD is limited by side effects and the variance of pharmacokinetic effects of the drugs in each patient. In the present study, we applied repetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment used in a number of other psychiatric disorders, to spontaneously hypertensive rats (SHRs), an animal model of ADHD, in order to assess the efficacy of the treatment in modifying behavioural symptoms as well as levels of dopamine, noradrenaline, serotonin, and brain-derived neurotrophic factor (BDNF). A total of fifteen sessions of high-frequency rTMS treatment were administered. Behavioural symptoms were observed using open field, Y-maze, and elevated plus-maze tests. Upon completion of the experiments, rats were sacrificed, and the neurochemical changes in brain tissue were analysed using high performance liquid chromatography and Western blotting. The SHRs treated with rTMS tended to exhibit less locomotor activity in the open field test over the course of treatment, but there was no improvement in inattention as measured by the Y-maze test. Furthermore, BDNF concentration increased and noradrenaline concentration decreased in the prefrontal cortex of SHRs treated with rTMS. The results of the present preclinical study indicate that rTMS may constitute a new modality of treatment for patients with ADHD, through further evaluation of specific treatment parameters as well as safety and efficacy in humans are required. [ABSTRACT FROM AUTHOR]

BACKGROUND The aim was to study the effects of Pu-erh theabrownin ( TB) ( Mw > 50 kDa) on the metabolism of rat serum by nuclear magnetic resonance ( NMR)-based metabolomics and identify candidate marker metabolites associated with Pu-erh TB, and thus provide fundamental information for a better understanding of the metabolism of Pu-erh tea in animals. RESULTS TB infusion induced different changes in endogenous serum metabolites depending on the type of diet. Compared with the control group, the TB infusion group showed significantly reduced serum glycine and choline levels, as well as significantly increased taurine, carnitine and high-density lipoprotein (all P < 0.05). Compared with the high-lipid group, the high-lipid TB infusion group exhibited significantly reduced low-density lipoprotein and acetate levels, as well as significantly increased inositol, carnitine and glycine levels (all P < 0.05). CONCLUSION Examination of the variations of these differential expressed metabolites and their individual functions revealed that the TB extract accelerated lipid catabolism in rats and might affect glucose metabolism. Of these, carnitine level significantly increased after intragastric infusion of TB regardless of the type of diet, and activities of carnitine palmitoyltransferases I and II changed significantly, suggesting carnitine may be a candidate serum marker for tracking the metabolism of TB in rats. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This study investigated the effect of sevoflurane postconditioning on post-ischaemic cardiac function, infarct size, myocardial mitochondrial ATP-sensitive potassium channel (mito KATP) function and apoptosis in ageing rats to determine the possible mechanism underlying the cardioprotective property of sevoflurane. Ageing rat hearts were isolated and attached to a Langendorff apparatus. The hearts were then exposed or not to sevoflurane postconditioning in the presence or absence of 100 μmol/L 5-hydroxydecanoate (5- HD), a selective mito KATP inhibitor. The infarct size was measured by triphenyltetrazolium chloride ( TTC) staining. Mitochondrial morphology was observed by electron microscopy and scored using FlaMeng semiquantitative analysis. In addition, the expression levels of Bax, Bcl-2, and cytochrome-C (Cyt-C) were determined by Western blot analysis at the end of reperfusion. Sevoflurane postconditioning increased coronary flow, improved functional recovery, reduced Bax/Bcl-2 and Cyt-C phosphorylation levels, and decreased mitochondrial lesion severity and the extent of apoptosis. The protective effects of sevoflurane postconditioning were prevented by the mito KATP inhibitor 5- HD. Sevoflurane postconditioning significantly protected the function of ageing hearts that were subjected to ischaemia and reperfusion, and these protective effects were mediated by mito KATP opening. [ABSTRACT FROM AUTHOR]

Enriched environments are beneficial to neurobiological development; specifically, rodents exposed to complex, rather than standard laboratory, environments exhibit evidence of neuroplasticity and enhanced cognitive performance. In the present study, the nature of elements placed in the complex environment was investigated. Accordingly, rats (n = 8 per group) were housed either in a natural environment characterised by stimuli such as dirt and rocks, an artificial environment characterised by plastic toys and synthetic nesting materials, a natural/artificial environment characterised by a combination of artificial and natural stimuli or a laboratory standard environment characterised by no enrichment stimuli. Following exposure to emotional and cognitive behavioural tasks, including a cricket hunting task, a novel object preference task and a forced swim task, brains were processed for glial fibrillary acidic protein ( GFAP)-, neuronal nuclei (NeuN)- and brain-derived neurotrophic factor ( BDNF) immunoreactivity. Baseline and stress foecal samples were collected to assess corticosterone ( CORT) and dehydroepiandrosterone ( DHEA). Natural environment animals exhibited shorter diving latencies and increased diving frequencies in the second forced swimming task, along with higher DHEA/ CORT ratios, and higher GFAP immunoreactivity in the hippocampus. The type of environmental enrichment did not influence levels of BDNF immunoreactivity in the CA1, CA3 and dentate gyrus of the hippocampus; however, natural environment animals exhibited higher levels of NeuN immunoreactivity in the retrosplenial cortex, an area involved in spatial memory and other cognitive functions. These results suggest that, in addition to enhancing behavioural and endocrinological variables associated with resilience, exposure to natural stimuli might alter plasticity in brain areas associated with cortical processing and learning. [ABSTRACT FROM AUTHOR]

Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml−1 Triton-X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12-month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15- and 0.38-mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364-day study period (<0.04 mg per liver, < 0.006 mg per brain). Copyright © 2015 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Epidemiological studies show a positive correlation between the air levels of fine particulate matter (PM2.5) and cardiovascular disorders, but how PM2.5 affects cardiomyocytes has not been studied in great deal. The aim of the present study was to obtain an insight into the links among intracellular levels of reactive oxygen species (ROS), apoptosis and mitogen-activated protein kinases (MAPKs) in rat cardiac H9c2 cells exposed to PM2.5. H9c2 cells were incubated with PM2.5 at 100-800 µg ml-1 to evaluate the effects of PM2.5 on cell viability, cell apoptosis, intracellular levels of ROS and expression of apoptosis-related proteins as well as activation of MAPKs. PM2.5 decreased cell viability, increased the cell apoptosis rate and intracellular ROS production in a concentration-dependent manner. PM2.5 decreased the Bcl-2/Bax ratio and increased cleaved caspase-3 levels. A Western blots study showed up-regulation of phosphorylated MAPKs including extracellular signal-regulated protein kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAPK in the PM2.5-treated cells. The p38 MAPK inhibitor SB239063 attenuated whereas the ERKs inhibitor PD98059 augmented the effects of PM2.5 on apoptosis and the expression of related proteins. In conclusion, PM2.5 decreases cell viability and increases apoptosis by enhancing intracellular ROS production and activating the MAPKs signaling pathway in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5-induced cardiac injury. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Effect of water dispersible single-walled carbon nanotubes on the medullary cardiovascular control was studied in normotensive (control) and spontaneously hypertensive rats using physiological and biochemical approaches. We have shown for the first time the possible contribution of nitric oxide (NO) to single-walled carbon nanotube-induced effects in the cardiovascular nuclei of the medulla oblongata (the lateral reticular nucleus and nucleus ambiguous). The data of biochemical experiments indicate that single-walled carbon nanotubes added to the medulla oblongata homogenates induce an enhancement of constitutive nitric oxide-synthase (cNOS) activity, which is mostly neuronal nitric oxide-synthase (nNOS) in the brain, and an increase in the level of nitrite (NO-2), a stable nitric oxide metabolite which serves nitric oxide bioavailability marker. In physiological experiments, it has been revealed that effects of single-walled carbon nanotube injection in the cardiovascular nuclei under study are attenuated after preliminary nNOS inhibiting. An analysis of single-walled carbon nanotube-induced changes in the levels of malonic dialdehyde, an oxidative stress marker, as well as the levels of reactive nitrogen species (pools of nitrate anions), and the activity of Ca2+-independent inducible nitric oxide synthase (iNOS) has indicated that single-walled carbon nanotubes used in the study do not promote oxidative and nitrosative stress in control and spontaneously hypertensive rats. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Does an acute bout of exercise alter vitamin D receptor expression in rat skeletal muscle?, What is the main finding and its importance? Resistance exercise but not endurance exercise increased intramuscular vitamin D receptor expression. Thus, resistance exercise may be an effective way to increase muscle vitamin D receptor expression., Vitamin D and vitamin D receptor (VDR) are involved in the maintenance of skeletal muscle mass and function. Although resistance exercise is well known to enhance muscle growth and improve muscle function, the effect of resistance exercise on VDR has been unclear. We investigated intramuscular VDR expression in response to an acute bout of resistance exercise or endurance exercise. Male adult Sprague-Dawley rats were subjected to either resistance exercise (isometrically exercised via percutaneous electrical stimulation for five sets of ten 3 s contractions, with a 7 s interval between contractions and 3 min rest intervals between sets) or endurance exercise (treadmill at 25 m min−1 for 60 min). Rats were killed immediately or 1, 3, 6 or 24 h after completion of the resistance or endurance exercise, and gastrocnemius muscles were removed. Non-exercised control animals were killed in a basal state (control group). Intramuscular VDR expression was significantly higher immediately after resistance exercise and elevated for 3 h after exercise compared with the control group ( P < 0.05), and the resistance exercise significantly increased phosphorylated ERK1/2 and Mnk1 expression ( P < 0.05), which may be associated with VDR expression, immediately after exercise. Additionally, intramuscular expression of cytochrome P450 27B1, an enzyme related to vitamin D metabolism, was significantly higher at 1 and 3 h after exercise ( P < 0.05) compared with the control group. In contrast, endurance exercise had no effect on any of the measured proteins. Our results indicate that resistance exercise may be an efficient way to increase intramuscular VDR and related enzyme expression. [ABSTRACT FROM AUTHOR]

BACKGROUND In São Paulo city, rodent infestation is considered to be a serious public health problem and is the object of a municipal rodent control programme. One of the most important routine methods involves baiting in sewers, using bromadiolone block bait in a pulsed baiting strategy. It has been observed that, after each pulse, bait is not always consumed, and its appearance is altered, which has led to concerns about efficacy. We assessed whether exposure to sewer conditions influences the palatability and efficacy of rodenticide baits to Norway rats ( Rattus norvegicus). Baits containing bromadiolone as active ingredient were placed in sewers, removed after 30 days and offered to rats in a two-choice food trial and a no-choice food trial. RESULTS The appearance of the rodenticide baits changed after 30 days exposure to sewer conditions, but they continued to be palatable and effective against rats. The level of mortality was considered to be satisfactory, 75% in the two-choice food trial and 100% in the no-choice food trial. CONCLUSION Results support the reuse of rodenticide block bait in rodent control. It seems to be justified to continue using/reuse baits even when their appearance has changed after 30 days exposure in sewer systems. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This study was undertaken to explore interactions between c-Src kinase and the N-cadherin-β-catenin complex in seminiferous tubules of flutamide-treated rats. An anti-androgen flutamide (50 mg/kg bw) was injected daily into adult rats from postnatal days 82 to 88. Testes from 90-day-old control and flutamide-treated rats were used for experiments. Flutamide did not affect testis morphology, but impaired connexin43 immunoexpression between Sertoli cells at the blood-testis barrier ( BTB) region, indicating the BTB as a sensitive target for flutamide. Real-time RT- PCR and western blot analyses revealed upregulation of N-cadherin at the mRNA and protein level after flutamide exposure ( p < 0.05), whereas no changes in β-catenin and c-Src expression were observed. Notably, membranous β-catenin immunolocalization indicated its involvement in the cell adhesion complex rather than its contribution to the Wnt signaling pathway. As we used an exposure regime which avoided germ cell loss, it is likely that changes in the N-cadherin-β-catenin complex are a primary effect of androgen signaling disruption by flutamide. Immunohistochemistry revealed a diffusion of N-cadherin and β-catenin signals away from the BTB with concomitant disruption of c-Src staining pattern. As detected by immunofluorescence and coimmunoprecipitation, flutamide promoted disassembly of the N-cadherin-ß-catenin complex, induced N-cadherin to dissociate from c-Src at the BTB site, and altered interactions between the cell junction proteins and/or c-Src. Equally important, increased levels of p-N-cadherin-Tyr860 and p-β-catenin-Tyr654 ( p < 0.05) pointed to a mechanism related to adhesion complex disassembly and suggested a potential role of c-Src in the control of the protein-protein dynamics. Overall, for the first time we have shown that flutamide alters the distribution of c-Src and affects N-cadherin-β-catenin interactions at the BTB. Understanding mechanism(s) by which anti-androgens can affect intercellular adhesion within the testis is relevant for predicting and preventing reproductive disorders affecting male fertility. [ABSTRACT FROM AUTHOR]

Aim Geographic spread and range expansion of species into novel environments may merge originally separated species assemblages, yet the possible drivers of geographic heterogeneity in host-parasite associations remain poorly understood. Here, we examine global patterns in the parasite assemblages of two rat species and explore the role of parasite acquisition from local pools of host species. Location Global. Methods We compiled a global data set of helminth parasites (n = 241 species) from two rat species (Rattus rattus species complex, R. norvegicus) and, concomitantly, from all other mammal species known to be infected by the same parasites. We used an inverse Bayesian modelling approach to explicitly link species-level to community-level infestation probabilities at different geographic scales and alleviate the shortcoming of sampling bias. Results Patterns of species richness and turnover of parasites in the two focal rat species revealed clear biogeographic structure with lowest species richness and most distinct assemblages in Madagascar and highest species richness and least distinct assemblages in the Palaearctic region. Parasite species richness and turnover across regions were correlated for the two focal hosts, although they were associated with distinct assemblages within regions. Infection probability of a focal host with any given parasite was clearly related to infection probability of the local species pool of wildlife hosts with that same parasite. Infection probability of other mammal species infected with these parasite species, in turn, decreased with their taxonomic distance to the genus Rattus. Main conclusions Our study demonstrates the importance of spillover of parasites from local wildlife hosts to invasive rats on global patterns of host-parasite associations. Considering both changes in local pools of host species and the global distributions of parasite and pathogen diversity in consistent model frameworks may therefore advance the forecasting of species-level infestation patterns and the possible risk of disease emergence from local to global scale. [ABSTRACT FROM AUTHOR]

Seasonal or photoperiodically sensitive animals respond to altered day length with changes in physiology (growth, food intake and reproductive status) and behaviour to adapt to predictable yearly changes in the climate. Typically, different species of hamsters, voles and sheep are the most studied animal models of photoperiodism. Although laboratory rats are generally considered nonphotoperiodic, one rat strain, the inbred Fischer 344 ( F344) rat, has been shown to be sensitive to the length of daylight exposure by changing its physiological phenotype and reproductive status according to the season. The present study aimed to better understand the nature of the photoperiodic response in the F344 rat. We examined the effects of five different photoperiods on the physiological and neuroendocrine responses. Young male F344 rats were held under light schedules ranging from 8 h of light/day to 16 h of light/day, and then body weight, including fat and lean mass, food intake, testes weights and hypothalamic gene expression were compared. We found that rats held under photoperiods of ≥ 12 h of light/day showed increased growth and food intake relative to rats held under photoperiods of ≤ 10 h of light/day. Magnetic resonance imaging analysis confirmed that these changes were mainly the result of a change in lean body mass. The same pattern was evident for reproductive status, with higher paired testes weight in photoperiods of ≥ 12 h of light/day. Accompanying the changes in physiological status were major changes in hypothalamic thyroid hormone ( Dio2 and Dio3), retinoic acid ( Crabp1 and Stra6) and Wnt/β-Catenin signalling genes ( sFrp2 and Mfrp). Our data demonstrate that a photoperiod schedule of 12 h of light/day is interpreted as a stimulatory photoperiod by the neuroendocrine system of young male F344 rats. [ABSTRACT FROM AUTHOR]

The article reports on the effects of terpinyl acetate on the percutaneous absorption of caffeine in rats. Topics discussed include absolute percutaneous bioavailability in rats; primary metabolites in caffeine; and the effect of terpinyl acetate on pharmacokinetics in rats. Also mentioned is the role of ethanol in structural modifications of stratum corneum.

Background The 14-3-3 proteins family consists of seven proteins that are highly conserved molecular chaperones with roles in the regulation of metabolism, signal transduction, cell cycle control, protein trafficking and apoptosis. Their role in several pathologies has been reported. In this study, we investigated the mRNA and protein expression of the 14-3-3s in rat brain and liver in the early stage of Type-1 diabetes (T1D). Material and methods Diabetes was induced by a single intraperitoneal injection (70 mg/kg bw) of freshly prepared streptozotocin (STZ), and, after 3 weeks of treatment, brain and liver nuclei and cytosolic extracts were prepared. Quantitative real-time PCR and Western blotting analyses were performed to evaluate mRNA and protein expression for each of the seven 14-3-3s. Results In nondiabetic control rats, the expression profile of 14-3-3s revealed a tissue-specific distribution, and the expression level of each isoform was found higher in the brain than in the liver. In the diabetic brain, mRNA and protein levels of the 14-3-3β, ε, ζ, η and θ were lower; 14-3-3σ mRNA significantly increased while its protein level decreased. In the diabetic liver, the mRNA of 14-3-3γ, 14-3-3θ and 14-3-3σ significantly increased, but only the 14-3-3γ protein level increased. Overall, in diabetic animals, the changes in the expression levels of brain 14-3-3s were much more pronounced than in the liver. Conclusion Our results indicate that during the early phase of STZ-induced T1D, the 14-3-3 proteins are affected in an isoform- and tissue-specific way. [ABSTRACT FROM AUTHOR]

Neuropeptide W ( NPW) is produced in neurons located in hypothalamus, brain stem and antral G cells and its receptors are present in the hypothalamus, in particular in the paraventricular nucleus ( PVN). There are two forms of the peptide, designated as neuropeptide W-23 ( NPW23) and neuropeptide W-30 ( NPW30). Neuropeptide W is an endogenous ligand for G-protein-coupled receptor, GPR7 and GPR8 receptors ( R), which in humans are expressed in the hypothalamus and probably involved in the control of energy homoeostasis and neuroendocrine axes. We conducted this study to investigate the effects of NPW on feeding intake and energy expenditure in Wistar rats. Systemic (icv) injection of both forms of neuropeptide W ( NPW23 and NPW30) to ad libitum feeding Wistar rats decreased dark feeding and fasting-induced feeding. One week of systemic treatment with NPW23 decreased feeding intake and weight gain during the treatment period. On the other hand, systemic treatment with antineuropeptide W antibody increased feeding intake. Moreover, systemic treatment with neuropeptide W-23 raised body temperature and consequently thermogenesis. These results strongly suggest that neuropeptide W may play an important central role in the feeding intake and energy balance control in mammals. [ABSTRACT FROM AUTHOR]

Supplementation of branched-chain amino acid ( BCAA) is often used to attenuate exercise-induced skeletal muscle damage and promote adaptation, but no definitive conclusion on the benefits of BCAA on muscle recovery after injurious exercise can be drawn. Exploration of the systematic BCAA alteration in muscular injury-repair stage per se without any BCAA supplement should provide some useful information in favour of BCAA application in muscle regeneration after injury. One bout of 90-min downhill-running exercise was performed to cause rat skeletal muscle injury. After exercise, myofibrillar BCAA concentrations showed minor changes compared with exercise before, while serum concentrations of BCAA were lower after exercise. Especially, serum leucine, isoleucine and total BCAA concentrations 2 weeks post-run were significantly lower than normal values of exercise before (p = 0.008, p = 0.041, p = 0.015). The data demonstrate that a single eccentric exercise can significantly decrease the serum BCAA concentrations, which mean high utilization of BCAA for myogenesis after injurious exercise. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether orally ingested ovine serum Ig G partly resists digestion in the growing rat. Fifteen Sprague- Dawley male rats were allocated to one of three diets for a 3-week study: a control diet ( CON) and two test diets containing either freeze-dried ovine serum immunoglobulin ( FDOI) or inactivated ovine serum immunoglobulin ( IOI). Samples of stomach chyme and intestinal digesta from the ad libitum-fed rats were subjected to ELISA and Western blot analysis. Amounts of intact ovine Ig G for the FDOI diet were found to be 13.9, 20.0, 34.1, 13.0 and 36.9 μg in the total wet digesta from the stomach chyme, duodenal, jejunal, ileal and colonic digesta respectively. Qualitative detection by Western blot revealed the presence of intact ovine serum Ig G with a ~150 kDa MW. This was detected in all of the gut segments (stomach chyme, duodenal, jejunal, ileal and colonic digesta) for growing rats fed the FDOI diet. No ovine Ig G was detected in the chyme or digesta from rats fed the CON or the IOI diets. Ovine serum Ig G partly resisted digestion in the growing rat fed the FDOI diet and was found throughout the digestive tract. These results provide a basis to explain the reported biological effects of orally administered immunoglobulin. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effects of cold exposure on rat skeletal muscle fiber type, according to myosin heavy chain ( MyHC) isoform and metabolism-related factors. Male Wistar rats (7 weeks old) were housed individually at 4 ± 2°C as a cold-exposed group or at room temperature (22 ± 2°C) as a control group for 4 weeks. We found that cold exposure significantly increased the slow-type MyHC1 content in the soleus muscle (a typical slow-type fiber), while the intermediate-type MyHC2A content was significantly decreased. In contrast to soleus, MyHC composition of extensor digitorum longus ( EDL, a typical fast-type fiber) and gastrocnemius (a mix of slow-type and fast-type fibers) muscle did not change from cold exposure. Cold exposure increased mRNA expression of mitochondrial uncoupling protein 3 ( UCP3) in both the soleus and EDL. Cold exposure also increased mRNA expression of myoglobin, peroxisome proliferator-activated receptor gamma coactivator 1α ( PGC1α) and forkhead box O1 ( FOXO1) in the soleus. Upregulation of UCP3 and PGC1α proteins were observed with Western blotting in the gastrocnemius. Thus, cold exposure increased metabolism-related factors in all muscle types that were tested, but MyHC isoforms changed only in the soleus. [ABSTRACT FROM AUTHOR]

Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism. [ABSTRACT FROM AUTHOR]

The use of medium-chain triglycerides ( MCTs) has been studied for years in an attempt to elucidate their effects in food intake and body weight in animals. The aim of this study was to determine whether there is evidence that the use of MCT reduces consumption and body weight gain in rats, a species chosen as it has been widely used as an animal model in different surveys. A search of scientific work was performed in November 2011 on two bases: 'Web of Science' and ' PubMed'. The terms sample size and homogeneity, randomisation, food consumption and weight gain, body composition, enzyme activity and hormonal activity in rats were used as selection criteria. Thirteen papers were selected after the refinement of the research. Twelve studies measured weight gain and among these, seven detected a decrease in weight gain and five found no differences. Twelve papers also measured food intake and among these, four detected a decrease in consumption, one detected an increase and seven found no differences. Based on established criteria for the ranking of scientific papers, it is concluded that there is strong evidence that MCTs can effectively reduce the consumption and subsequent weight gain of animals. However, in the long term, there may not be differences in results depending on the phenotypic adaptation of animals to a new metabolic condition. [ABSTRACT FROM AUTHOR]

The first aim of the present work was to assess the caloric value of low-calorie cocoa butter (LCCB) prepared by enzymatic transesterification. A growth method on restricted diet was utilized for the assessment with cocoa butter (CB) as a caloric control. Thirty weanling Wistar male rats were divided into six groups and fed for 3 weeks. The estimated caloric value of LCCB was 4.70 kcal/g, exhibited a decrement of 31%. Furthermore, a growth experiment using pair-feeding protocol was performed to evaluate whether high LCCB diet could have any effect on the biochemical and physiological parameters, such as TAG, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, enzymatic activities of superoxide dismutase and catalase, Lee's index, liver index, the atherosclerosis index, and the risk of coronary heart disease. The results revealed that high LCCB dietary intake did not significantly alter the biochemical parameters except for the LDL-c. The fatty acid compositions of plasmas and feces demonstrated that caprylic acid was completely consumed through hepatic portal vein for energy supply, while most behenic acid was excreted. These results suggest that the calorie of CB has been lowered by transesterification and the high LCCB diet do not readily induce obesity or oxidative stress. Practical applications: A method to evaluate the caloric value of fats and oils is presented. A low-calorie cocoa butter may be useful for the chocolate industry. [ABSTRACT FROM AUTHOR]

Contents Numerous experimental models in different species have been developed for the study of polycystic ovarian syndrome. In this study, we used a model of induction of polycystic ovaries ( PO) in rats by exposure to constant light to study the distribution and variations of glycosylated residues present in the different ovarian structures. Seven biotinylated lectins were used ( Con- A, WGA, DBA, SBA, PNA, RCA and UEA- I) on tissue sections, and detection was performed using the streptavidin/peroxidase method. In tissue sections was observed an increase in affinity for Con- A in the granulosa and theca interna of growing follicles and cysts in animals with PO in relation to the control group. Follicular cysts showed higher affinity for WGA and RCA- I which growing follicles in the same group, and there was a decrease in affinity for PNA in the cysts in relation to the growth of follicles in both groups. Atretic follicles in both groups showed greater labelling with lectins PNA, SBA and RCA- I in relation to healthy follicles. It could also be noted that the zona pellucida of cystic follicles lost the affinity for the lectin Con- A. There was no staining on follicles in any category with the lectins DBA and UEA-I, although it was staining in the corpus luteum (control group) and in the mesothelium and interstitial glands of both groups with DBA. These observations probably reflect changes in the glycosaminoglycans present in the different ovarian compartments or in the glycosylation of cellular components essential for proper follicular dynamics. [ABSTRACT FROM AUTHOR]

Apocynin is a naturally occurring acetophenone widely used as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Recent data suggested that apocynin might exert NADPH oxidase-independent pharmacological properties. Among them, vasorelaxant properties have been described, but the mechanisms still give rise to debates. The present study investigated the mechanisms involved in the vasorelaxant effect of apocynin on the in vitro model of rat isolated thoracic aortic rings. Apocynin (30 μ m to 10 m m) induced a dose-dependent relaxation in both endothelium-intact and endothelium-denuded aortic rings with respective EC50 values of 0.78 ± 0.08 and 1.91 ± 0.21 m m. Endothelium removal or inhibition of nitric oxide (NO) synthase with Nω-nitro- l-arginine-methyl ester ( l-NAME) significantly decreased but did not abolish the effect of apocynin. By contrast, apocynin-induced relaxation was unchanged after incubation with indomethacin or charybdotoxin plus apamin. In endothelium-denuded aortas, the vasorelaxant effect of apocynin was significantly reduced by glibenclamide but not by 4-aminopyridine nor by iberiotoxin. Apocynin significantly decreased Ca2+-induced contraction and inhibited intracellular Ca2+mobilization after contraction with phenylephrine. Finally, the acute intravenous injection of apocynin led to an immediate and transient hypotensive effect in spontaneously hypertensive rats (SHR). In conclusion, our data demonstrated that apocynin induces both endothelium-independent relaxant effects involving inhibition of Ca2+mobilization and activation of KATP channels in vascular smooth muscle cells and endothelium-dependent effects mediated by NO. These results should provide a basis for caution when interpreting results on the vascular effects of apocynin. [ABSTRACT FROM AUTHOR]

We examined animal species differences in the postprandial thermic effect of meat and investigated the postprandial thermic effect of mutton in rats. After intake of experimental diets containing each meat, body temperatures of rats fed mutton or venison were significantly higher than that of rats fed rabbit meat. After intake of experimental diets containing fractionized mutton, the body temperatures of rats fed diets containing lean mutton protein were higher than those of rats fed diets without lean mutton protein. In a two-dimensional fluorescence difference gel electrophoresis study of brown adipose tissue, it was shown that the intake of mutton up-regulated the expression of many signaling molecules that are involved in energy metabolism. The postprandial thermic effect of mutton seems to be due not to catecholamine and adrenocorticotropic hormone but to thyroid hormones. The results suggest that intake of lean mutton protein stimulates the secretion of thyroid hormones and facilitates energy metabolism in rats. [ABSTRACT FROM AUTHOR]

Background Novel threads of discovery provide the basis for optimism for the development of a stem-cell-based strategy for the treatment of retinal blindness. Accordingly, achievement to suitable cell source with potential-to-long-term survival and appropriate differentiation can be an effective step in this direction. Methods After derivation of human adipose-derived mesenchymal stem cells ( HAD- MSCs), they were stably transfected with a vector containing Turbo-green fluorescent protein ( GFP) and JRed to be able to trace them after transplantation. Labeled HAD- MSCs were transplanted into the intact adult rat eye and their survival, integration, and migration during 6 months post-transplantation were assessed. Results The transplanted cells were traceable in the rat vitreous humor ( VH) up until 90 days after transplantation, with gradual reduction in numbers, their adhesion and expansion capacity after recovery. These cells were also integrated into the ocular tissues. Nonetheless, some of the implanted cells succeeded to cross the blood-retina barrier ( BRB) and accumulate in the spleen with time. Conclusions The survival of the HAD- MSCs for a period of 90 days in VH and even longer period of up to 6 months in other eye tissues makes them a promising source to be considered in regenerative medicine of eye diseases. However, the potency of crossing the BRB by the implanted cells suggests that use of HAD- MSCs must be handled with extreme caution. [ABSTRACT FROM AUTHOR]

Background Reactive oxygen species ( ROS) and nitric oxide species ( NOS) are pivotal after ischemia-reperfusion. However, the role of different cells on the formation of free radical species after xenotransplantation remains elusive. We hypothesized that ROS and NOS formed during hyperacute rejection are dependent on leukocytes, erythrocytes, activated thrombocytes, and Kupffer cells ( KCs). To address this issue, we developed a model of xenoperfused rat liver and assessed the relationship between free radical production and graft dysfunction. Methods Livers from Sprague- Dawley rats were isolated, flushed with cold Ringer solution, and perfused at physically flow rates for 120 min after 1 h of ischemia. The control group was perfused with rat whole blood (n = 9). In the study groups, the livers were perfused with human whole blood, human plasma with erythrocytes, and plasma with erythrocytes and isolated thrombocytes (n = 9/group). In an additional group, gadolinium chloride ( Gd Cl3), a selective Kupffer cell ( KC) toxic agent, was applied. Liver damage, hyperacute rejection, and the depletion of KCs were monitored histologically. Liver damage and function were determined by means of liver enzymes, portal pressure, and bile production. Malondialdehyde ( MDA), nitric oxide formation, and peroxynitrite concentration, as well as total glutathione (t GSH) level, were measured as indicators for free radical formation and anti-oxidative status. Results Significant differences in the MDA, NO, peroxynitrite levels, and GSH levels after reperfusion with various cell populations were observed. Markedly high ROS/ RNS production was evident in the KCs and the xenogeneic whole-blood group. The oxidative stress was mainly caused by leukocytes and to lower extent by KCs, but only in combination with leukocytes. Neither erythrocytes, thrombocytes, nor hepatocytes had an effect on the release of ROS and RNS, as we could not observe significant differences in the MDA, peroxynitrite, and NO levels in these groups compared with control. Tissue injury and hyperacute rejection were more evident in the KC and whole-blood livers. No sign of damage was observed for the control, erythrocyte, and thrombocyte group. Removal of leukocytes from the perfusate by filtration had a major protective effect on the liver function and the grade of hyperacute rejection, whereas KC depletion reduced the ROS production, but did not have an impact on the hyperacute rejection and liver damage. In all xenogeneic perfused groups, the activation of the complement was histologically observed by positive C3c and C9b. Neither KC depletion nor the removal of leukocytes or thrombocytes from the perfusate had an effect on the activation of the complement system. Damage of the rat liver by the complement system was only observed in association with leukocytes. Conclusion Our data revealed that various cell populations contribute to the formation of free radicals in our model. The production of free radicals was mainly linked to leukocytes and to a minor extent to KCs, but only in combination with leukocytes. Free radicals critically contribute to injury, rejection, and dysfunction of the xenotransplanted liver. Furthermore, hyperacute rejection in the xenogeneic perfused liver is triggered by the complement system only in the presence of leukocytes and free radical formation. [ABSTRACT FROM AUTHOR]

Key points Each segment along arterial vessels adapts to different circumstances, such as high blood pressure in the central and low pressure in the peripheral arteries and high sympathetic innervation in the peripheral and low innervation in the central arteries., We tested, using pharmacological tools, whether the amplitude and time course of each signalling pathway varies dynamically between arterial segments in rat., In small mesenteric arteries, α1-agonist produced a contraction and myosin light chain phosphorylation through sequential activation of α1A-subtype receptors, Ca2+, PKC and protein kinase C-potentiated protein phosphatase inhibitor protein 17 kDa (CPI-17)., In large aorta, α1-agonist-induced contraction and phosphorylation were produced through activation of α1D receptors followed by a Ca2+ increase and constitutively active Rho-kinase in an independent manner. The results for midsized arteries were intermediate., Our findings provide insights into the development of new therapeutic agents controlling the size-dependent vasoconstriction., Abstract Each segment along arterial vessels adapts to different circumstances, including blood pressure and sympathetic innervation. PKC and Rho-associated kinase (ROCK) Ca2+-sensitizing pathways leading to myosin phosphatase inhibition are critically involved in α1-adrenoceptor-mediated vascular smooth muscle contraction in distinctive time-dependent manners. We tested whether the amplitude and time course of each pathway varies dynamically between arterial segments. Using pharmacological approaches, we determined the time-dependent roles of Ca2+ release, Ca2+ influx, PKC and ROCK in α1-agonist-induced contraction and phosphorylation of key proteins in denuded rat small mesenteric artery, midsized caudal artery and thoracic aorta. SR Ca2+ release and voltage-dependent Ca2+ influx were essential for the initial rising and late sustained phases, respectively, of phenylephrine-induced contraction, regardless of arterial size. In small mesenteric arteries, α1A-subtype-specific antagonists and inhibitors of PKC, but not ROCK, markedly reduced the initial and late phases of contraction in a non-additive manner and suppressed phosphorylation of myosin light chain (MLC) and CPI-17, but not myosin targeting subunit of myosin light chain phosphatase (MYPT1). In aorta, an α1D-specific antagonist reduced both the initial and late phases of contraction with a significant decrease in MLC but not CPI-17 or MYPT1 phosphorylation. ROCK inhibitors, but not PKC inhibitors, suppressed the sustained phase of contraction with a decrease in MLC and MYPT1 phosphorylation in the aorta. The effect of ROCK inhibitors was additive with the α1D-antagonist. The results for midsized arteries were intermediate. Thus, the PKC-CPI-17 Ca2+-sensitizing pathway, which is dependent on PKC subtype and a Ca2+-handling mechanism, and is downstream of α1A receptors, plays a major role in α1-agonist-induced contraction of small resistance arteries in the splanchnic vascular beds. The effect of PKC and ROCK increases and decreases, respectively, with decreasing arterial size. [ABSTRACT FROM AUTHOR]

The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies. [ABSTRACT FROM AUTHOR]

Content Spermatogenesis is a complex biological process that requires precise regulation of gene expression in the germ cells and their surrounding somatic cells. Some testis-specific genes are involved in different stages of spermatogenesis; however, the precise mechanisms of stage-specific spermatogenesis are still not elucidated. In this study, we first examined the expression patterns of SYCP3, Tnp2, CDH1, glial cell-line-derived neurotropic factor (GDNF) and GFRA1 mRNAs on post-natal days (PNDs) 2, 4, 6, 8, 10, 12, 15, 20, 25 and 30 in rat testis. SYCP3 mRNA was firstly detected from PND 15, while Tnp2 transcript was only found on PND 30. CDH1 mRNA was highly expressed before PND 6, but decreased dramatically on PND 8, then gradually increased until it started to decrease after 12 dpp. Low GDNF and GFRA1 mRNAs were found before PND 6, but gradually increased to the peak on PND 12, then gradually decreased to low level. According to the expression patterns of CDH1, GDNF and GFRA1, we hypothesized that PNDs 6-10 are critical period in the early spermatogenesis. We, therefore, explored gene expression pattern on PNDs 6, 8 and 10 using cDNA microarray. 700 (PND 8 vs PND 6), 4519 (PND 10 vs PND 8), and 4298 (PND 10 vs PND 6) differentially expressed genes (≥2-fold) were identified from the comparisons, which cover thousands of gene ontology categories (GO terms) and hundreds of signalling pathways. High consistency between microarray data and quantative real-time PCR (qRT-PCR) was verified from five genes (LOC686076, Trib3, Cxcl6, LOC682508 and C2cd4d). These data provide more information to understand the precisely regulatory mechanism at the early stage of spermatogenesis. [ABSTRACT FROM AUTHOR]

To test the hypothesis that early intervention of vitamin A-enriched diet contains the development of obesity and improves insulin resistance, 50-day-old male lean and obese rats of WNIN/Ob strain were given either stock diet (2.6 mg vitamin A/kg diet) or vitamin A-enriched diet (129 mg vitamin A/kg diet) for 3 months. Compared with stock diet-fed obese rats, vitamin A-enriched diet-fed obese rats had reduced body weight gain, visceral adiposity and improved insulin sensitivity as evidenced by decreased fasting plasma insulin and unaltered glucose levels, which could possibly be due to higher phosphorylation of soleus muscle insulin receptor. This in turn is explained by decreased protein tyrosine phosphatase 1B (PTP1B) levels. Most of these changes were not observed in lean rats. In conclusion, chronic feeding of vitamin A-enriched diet to obese rats at an early age ameliorates visceral adiposity and improves the insulin sensitivity, possibly by decreasing soleus muscle PTP1B levels. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes. Methods: DIO rats were acutely given a single dose of oral sCT (0.5 and 2 mg/kg), its oral vehicle N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC) or injectable sCT (5 and 10 µg/kg) (n = 8), followed by oral glucose tolerance test (OGTT). Other DIO rats were chronic treated twice daily with oral vehicle 5-CNAC (n = 6), oral sCT (0.5 and 2 mg/kg) or injectable sCT (10 µg/kg) (n = 8). Fasting and postprandial glucose and pancreatic hormones, body weight and insulin sensitivity were assessed. Results: A single dose of oral sCT acutely reduced glucose and insulin area under the curve during OGTT by approximately 65 and 85%, respectively, compared with vehicle (p < 0.001). Chronic treatment with oral sCT significantly reduced both fasting and postprandial glucose and insulin levels by approximately 1.5 mM and 65%, respectively, compared with vehicle. Oral sCT concomitantly improved insulin sensitivity (homeostatic model assessment, HOMA). In contrast, injectable sCT resembling higher systemic exposure did not improve glycaemic control, either acutely or during chronic treatment. Furthermore, both oral and injectable sCT reduced body weight by 15% compared with vehicle (p < 0.05). Conclusion: A novel oral form of sCT showed antidiabetic effects in DIO rats by improving glycaemic control, glucose homeostasis, insulin sensitivity and body weight. [ABSTRACT FROM AUTHOR]

Yawning appears to be involved in arousal, state change, and activity across vertebrates. Recent research suggests that yawning may support effective changes in mental state or vigilance through cerebral cooling. To further investigate the relationship between yawning, state change, and thermoregulation, 12 Sprague-Dawley rats ( Rattus norvegicus) were exposed to a total of 2 h of ambient temperature manipulation over a period of 48 h. Using a repeated measures design, each rat experienced a range of increasing (22°C → 32°C), decreasing (32°C → 22°C), and constant temperatures (22°C; 32°C). Yawning and locomotor activity occurred most frequently during initial changes in temperature, irrespective of direction, compared to more extended periods of temperature manipulation. The rate of yawning also diminished during constant high temperatures (32°C) compared to low temperatures (22°C). Unlike yawning, however, stretching was unaffected by ambient temperature variation. These findings are compared to recent work on budgerigars ( Melopsittacus undulatus), and the ecological selective pressures for yawning in challenging thermal environments are discussed. The results support previous comparative research connecting yawning with arousal and state change, and contribute to refining the predictions of the thermoregulatory hypothesis across vertebrates. [ABSTRACT FROM AUTHOR]

To characterize the features of radiographic abnormalities of the tibial bone in Wistar rats which have been fed T-2 toxin and Kashin-Beck disease (KBD) epidemic district food. Ninety Wistar rats were divided into five groups. Group A was fed with a normal diet as control; group B was fed with a normal diet and T-2 toxin; group C was fed with a low-nutrition diet and T-2 toxin; group D was fed with a low-nutrition diet; and group E was fed with a KBD-affected diet. At 4, 8 and 12 weeks, six rats from each group were radiographed. After radiographic examination, samples of left knees were harvested and stained with hematoxylin and eosin. At 8 and 12 weeks, there were radiological changes in the epiphyseal plate. Abnormal radiological signs of blurring, thinning and irregularity were seen in groups C and E rats, and the length of tibial bones showed significant difference in the KBD-fed rats and low-nutrition diet combined T-2 toxin rats, compared to the control group rats ( P < 0.05). The epiphyseal plates showed more obvious necrosis of chondrocytes in groups C and E. A rat model of KBD can be established by a KBD-affected diet; proximal epiphyseal plate and metaphyseal bone of the tibia abnormalities on radiographs and histopathology were present in KBD model rats. A low nutrition diet may be involved the aetiology of KBD, and determination of this should be studied in the future. [ABSTRACT FROM AUTHOR]

Disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. The present study tested the hypothesis that perinatal triclosan exposure of dams decreases thyroxine in dams and offspring prior to weaning. Pregnant Long-Evans rats received triclosan by oral gavage (0-300 mg/kg/d) in corn oil from gestational day (GD)6 through postnatal day (PND)21. Serum was obtained from pups on PND4, 14, and 21, and from dams on PND22. Serum thyroxine (T4) was reduced 31% in dams on PND22. In pups, a unique pattern of hypothyroxinemia was observed; serum T4 decreased 27% in PND4 pups with no significant reduction observed on PND14 or PND21. Comparable reductions of approximately 30% in serum T4 at 300 mg/kg/d for dams and PND4 neonates and a lack of effect at PND14 and PND21 suggest that toxicokinetic or toxicodynamic factors may have contributed to a reduced exposure or a reduced toxicological response during the lactation period. Environ. Toxicol. Chem. 2010;29:2840-2844. © 2010 SETAC [ABSTRACT FROM AUTHOR]