Persistent luminescence behavior of materials doped with Eu2+ and Tb3+

In this work, the persistent luminescence mechanisms of Tb3+ (in CdSiO3) and Eu2+ (in BaAl2O4) based on solid experimental data are compared. The photoluminescence spectroscopy shows the different nature of the inter- and intraconfigurational transitions for Eu2+ and Tb3+, respectively. The electron is the charge carrier in both mechanisms, implying the presence of electron acceptor defects. The preliminary structural analysis shows a free space in CdSiO3 able to accommodate interstitial oxide ions needed by charge compensation during the initial preparation. The subsequent annealing removes this oxide leaving behind an electron trap. Despite the low band gap energy for CdSiO3, determined with synchrotron radiation UV-VUV excitation spectroscopy of Tb3+, the persistent luminescence from Tb3+ is observed only with UV irradiation. The need of high excitation energy is due to the position of F-7(6) level deep below the bottom of the conduction band, as determined with the 4f(8)-> 4f(7)5d(1) and the ligand-to-metal charge-transfer transitions. Finally, the persistent luminescence mechanisms are constructed and, despite the differences, the mechanisms for Tb3+ and Eu2+ proved to be rather similar. This similarity confirms the solidity of the interpretation of experimental data for the Eu2+ doped persistent luminescence materials and encourages the use of similar models for other persistent luminescence materials. (C) 2012 Optical Society of America

Periaqueductal gray matter modulates the hypercapnic ventilatory response

The periaqueductal gray (PAG) is a midbrain structure directly involved in the modulation of defensive behaviors. It has direct projections to several central nuclei that are involved in cardiorespiratory control. Although PAG stimulation is known to elicit respiratory responses, the role of the PAG in the CO2-drive to breathe is still unknown. The present study assessed the effect of chemical lesion of the dorsolateral and dorsomedial and ventrolateral/lateral PAG (dlPAG, dmPAG, and vPAG, respectively) on cardiorespiratory and thermal responses to hypercapnia. Ibotenic acid (IBO) or vehicle (PBS, Sham group) was injected into the dlPAG, dmPAG, or vPAG of male Wistar rats. Rats with lesions outside the dlPAG, dmPAG, or vPAG were considered as negative controls (NC). Pulmonary ventilation (Ve), mean arterial pressure (MAP), heart rate (HR), and body temperature (Tb) were measured in unanesthetized rats during normocapnia and hypercapnic exposure (5, 15, 30 min, 7 % CO2). IBO lesioning of the dlPAG/dmPAG caused 31 % and 26.5 % reductions of the respiratory response to CO2 (1,094.3 +/- 115 mL/kg/min) compared with Sham (1,589.5 +/- 88.1 mL/kg/min) and NC groups (1,488.2 +/- 47.7 mL/kg/min), respectively. IBO lesioning of the vPAG caused 26.6 % and 21 % reductions of CO2 hyperpnea (1,215.3 +/- 108.6 mL/kg/min) compared with Sham (1,657.3 +/- 173.9 mL/kg/min) and NC groups (1,537.6 +/- 59.3). Basal Ve, MAP, HR, and Tb were not affected by dlPAG, dmPAG, or vPAG lesioning. The results suggest that dlPAG, dmPAG, and vPAG modulate hypercapnic ventilatory responses in rats but do not affect MAP, HR, or Tb regulation in resting conditions or during hypercapnia.

Antinociception induced by acute oral administration of sweet substance in young and adult rodents: The role of endogenous opioid peptides chemical mediators and mu(1)-opioid receptors

The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the mu(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely pre-treated with 500 mu L. of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats (250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during 20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different doses (0.25, 1 or 4mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective pi-opioid receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentrations in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating endogenous opioid peptide and mu(1)-opioid receptor actions. (C) 2011 Elsevier Inc. All rights reserved.

Endogenous opioid peptide-mediated neurotransmission in central and pericentral nuclei of the inferior colliculus recruits mu(1)-opioid receptor to modulate post-ictal antinociception

Background: The aim of the present work was to investigate the involvement of the mu(1)-endogenous opioid peptide receptor-mediated system in post-ictal antinociception. Methods: Antinociceptive responses were determined by the tail-flick test after pre-treatment with the selective mu(1)-opioid receptor antagonist naloxonazine, peripherally or centrally administered at different doses. Results: Peripheral subchronic (24 h) pre-treatment with naloxonazine antagonised the antinociception elicited by tonic-clonic seizures. Acute (10 min) pre-treatment, however, did not have the same effect. In addition, microinjections of naloxonazine into the central, dorsal cortical and external cortical nuclei of the inferior colliculus antagonised tonic-clonic seizure-induced antinociception. Neither acute (10-min) peripheral pre-treatment with naloxonazine nor subchronic intramesencephalic blockade of mu(1)-opioid receptors resulted in consistent statistically significant differences in the severity of tonic-clonic seizures shown by Racine's index (1972), although the intracollicular specific antagonism of mu(1)-opioid receptor decreased the duration of seizures. Conclusion: mu(1)-Opioid receptors and the inferior colliculus have been implicated in several endogenous opioid peptide-mediated responses such as antinociception and convulsion. The present findings suggest the involvement of mu(1)-opiate receptors of central and pericentral nuclei of the inferior colliculus in the modulation of tonic-clonic seizures and in the organisation of post-ictal antinociception. (C) 2011 Elsevier Ltd. All rights reserved.

Previous Exposure to Cigarette Smoke Aggravates Experimental Cyclosporine-Induced Nephrotoxicity

Background/Aims: The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity. Methods: Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal alpha-smooth muscle actin (SMA), nitrotyrosine, and vimentin. Results: CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular alpha-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and alpha-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure. Conclusion: CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity. Copyright (C) 2012 S. Karger AG, Basel

Anti-Aversive Effects of Cannabidiol on Innate Fear-Induced Behaviors Evoked by an Ethological Model of Panic Attacks Based on a Prey vs the Wild Snake Epicrates cenchria crassus Confrontation Paradigm

Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect. Neuropsychopharmacology (2012) 37, 412-421; doi:10.1038/npp.2011.188; published online 14 September 2011

Fish Oil Supplementation Reduces Cachexia and Tumor Growth While Improving Renal Function in Tumor-Bearing Rats

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FENa+) of FO rats was similar to C. Proximal Na+ reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B-2 (TXB2) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

DIFFERENTIAL INVOLVEMENT OF DORSAL RAPHE SUBNUCLEI IN THE REGULATION OF ANXIETY- AND PANIC-RELATED DEFENSIVE BEHAVIORS

A wealth of evidence indicates that the dorsal raphe nucleus (DR) is not a homogenous structure, but an aggregate of distinctive populations of neurons that may differ anatomically, neurochemically and functionally. Other findings suggest that serotonergic neurons within the mid-caudal and caudal part of the DR are involved in anxiety processing while those within the lateral wings (IwDR) and ventrolateral periaqueductal gray (vIPAG) are responsive to panic-evoking stimuli/situations. However, no study to date has directly compared the activity of 5-HT and non-5HT neurons within different subnuclei of the DR following the expression of anxiety- and panic-related defensive responses. In the present investigation, the number of doubly immunostained cells for Fos protein and tryptophan hydroxylase, a marker of serotonergic neurons, was assessed within the rat DR, median raphe nucleus (MRN) and PAG following inhibitory avoidance and escape performance in the elevated T-maze, behaviors associated with anxiety and panic, respectively. Inhibitory avoidance, but not escape, significantly increased the number of Fos-expressing serotonergic neurons within the mid-caudal part of the dorsal subnucleus, caudal and interfascicular subnuclei of the DR and in the MRN. Escape, on the other hand, caused a marked increase in the activity of non-5HT cells within the IwDR, vIPAG, dorsolateral and dorsomedial columns of the PAG. These results strongly corroborate the view that different subsets of neurons in the DR are activated by anxiety- and panic-relevant stimuli/situations, with important implications for the understanding of the pathophysiology of generalized anxiety and panic disorders. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuropathology and behavioral impairments after three types of global ischemia surgery in Meriones unguiculatus: Evidence in motor cortex, hippocampal CA1 region and the neostriatum

The effects of three types of global ischemia by occlusion of carotid artery on motor and exploratory behaviors of Gerbils were evaluated by the Activity Cage and Rota rod tests. Animals were divided based on two surgical criteria: unilateral (UNI) or bilateral (BIL) carotid occlusion, with (REP) or without (OCL) reperfusion; and their behavior was evaluated on the fourth (4) or sixth (6) day. There was reduction of cell number in striatum, motor cortex M1 area, and hippocampal CA1 area in all groups in comparison to control animals. For M1 area and striatum, the largest reduction was observed in UNI6, UNI4, and BIL4 groups. Neuronal loss was also observed in CA1 area of BIL4 rodents. There was a decrease in crossings and rearings in all groups in activity cage test, compared to control. Reperfusion, unilateral and bilateral occlusion groups showed decrease in crossings. Only the BIL4 showed a decrease of rearing. In the Rota rod test, except the UNIOCL6, the groups showed a decrease in the balance in comparison to control. Both groups with REP4 showed a major decrease in balance. These findings suggest that both unilateral and bilateral carotid occlusions with reperfusion produce impairments of motor and exploratory behavior. (C) 2011 Elsevier B.V. All rights reserved.

Consequences of pilocarpine-induced status epilepticus in immunodeficient mice

Systemic injection of pilocarpine in rodents induces status epilepticus (SE) and reproduces the main characteristics of temporal lobe epilepsy (TLE). Different mechanisms are activated by SE contributing to cell death and immune system activation. We used BALB/c nude mice, a mutant that is severely immunocompromised, to characterize seizure pattern, neurochemical changes, cell death and c-Fos activation secondarily to pilocarpine-induced SE. The behavioral seizures were less severe in BALB/c nude than in BALB/c wild type mice. However, nude mice presented more tonic clonic episodes and higher mortality rate during SE. The c-Fos expression was most prominent in the caudate-putamen, CA3 (p < 0.05), dentate gyrus, entorhinal cortex (p < 0.001), basolateral nucleus of amygdala (p < 0.01) and piriform cortex (p < 0.05) of BALB/c nude mice than of BALB/c. Besides, nude mice subjected to SE presented high number of Fluorojade-B (FJB) stained cells in the piriform cortex, amygdala (p < 0.05) and hilus (p < 0.05) in comparison with BALB/c mice. A significant increase in the level of glutamate and GABA was found in the hippocampus and cortex of BALB/c mice presenting SE in comparison to controls. However, the level of glutamate was higher in the brains of BALB nude mice than in the brains of BALB/c wild type mice, while the levels of GABA were unchanged. These results indicate that the brains of immunodeficient nude mice are more vulnerable to the deleterious effects of pilocarpine-induced SE as they present intense activation, increased glutamate levels and more cell death. Published by Elsevier B.V.

Platelet-rich plasma stimulates cytokine expression and alkaline phosphatase activity in osteoblast-derived osteosarcoma cells

Objective: The aim of this study was to investigate the effects of PRP on SAOS-2 cells in terms of cytokine expression, cell activity and oxidative stress. Design: Cell line SAOS-2 (1 x 10(5) cells/mL) were grown in culture medium alpha-MEM with 10% FBS for 24 h and stimulated (or not) with PRP at concentrations of 3, 10 and 20%, LPS (E. coli, 10 g/mL) and IL-1 beta (1 mg/mL) for 24 h. The supernatant was collected and analyzed for the expression of cytokines in a panel array, ALP using a commercial kit and NO2- with Griess reaction method. Also, the cells were analyzed using Western blot for RANKL and slot blotting for nitrotyrosine expression. Result: There were no significant differences amongst the groups in terms of NO2-, protein nitrotyrosine content and RANKL expression. However, all stimuli increased ALP activity and in case of PRP, it was in a dose-dependent manner (p < 0.001). Also, all stimuli induced an increase in cytokines and chemokines expression, but only PRP promoted an increase of component C5, sICAM-1 and RANTES expression. Whilst IL-1 receptor antagonist (IL-1ra) expression was down-regulated by PRP, both LPS and IL-1 beta caused up-regulation of this cytokine. Conclusions: PRP can stimulate osteoblast activity and cytokine/chemokine release, as well as indicate some of the mediators that can (and cannot) be involved in this activation. (C) 2012 Elsevier Ltd. All rights reserved.

Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center

Background: Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment. Methods: This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined. Results: D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%). Conclusion: N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.

Lipopolysaccharide-Induced Sickness Behaviour Evaluated in Different Models of Anxiety and Innate Fear in Rats

The fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as sickness behaviour (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 mu g/kg, i.p.) in young male Wistar rats (weighing 180200 g; 89 weeks old) on the ethological and spatiotemporal parameters of the elevated plus maze, light-dark box, elevated T maze, open-field tests and emission of ultrasound vocalizations. There was a dose-dependent increase in anxiety-like behaviours caused by LPS, forming an inverted U curve peaked at LPS 200 mu g/kg dose. However, these anxiety-like behaviours were detected only by complementary ethological analysis (stretching, grooming, immobility responses and alarm calls), and these reactions seem to be a very sensitive tool in assessing the first signs of sickness behaviour. In summary, the present work clearly showed that there are resting and alertness reactions induced by opposite neuroimmune mechanisms (neuroimmune bias) that could lead to anxiety behaviours, suggesting that misunderstanding data could occur when only few ethological variables or single doses of LPS are analysed. Finally, it is hypothesized that this bias is an evolutionary tool that increases animals security while the body recovers from a systemic infection.

Does anti-hepatitis B virus vaccine make any difference in long-term number of liver transplantation?

Background: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B infection is associated with an increased risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Our aim is to analyze, through a mathematical model, the potential impact of anti-HBV vaccine in the long-term (that is, decades after vaccination) number of LT. Methods: The model simulated that the prevalence of HBV infection was 0.5% and that approximately 20% of all the liver transplantation carried out in the state of Sao Paulo are due to HBV infection. Results: The theoretical model suggests that a vaccination program that would cover 80% of the target population would reach a maximum of about 14% reduction in the LT program. Conclusion: Increasing the vaccination coverage against HBV in the state of Sao Paulo would have a relatively low impact on the number of liver transplantation. In addition, this impact would take several decades to materialize due to the long incubation period of liver failure due to HBV.

HYDROGEN SULFIDE AS A CRYOGENIC MEDIATOR OF HYPDXIA-INDUCED ANAPYREXIA

Hypoxia causes a regulated decrease in body temperature (Tb), a response that has been aptly called anapyrexia, but the mechanisms involved are not completely understood. The roles played by nitric oxide (NO) and other neurotransmitters have been documented during hypoxia-induced anapyrexia, but no information exists with respect to hydrogen sulfide (H(2)S), a gaseous molecule endogenously produced by cystathionine beta-synthase (CBS). We tested the hypothesis that HA production is enhanced during hypoxia and that the gas acts in the anteroventral preoptic region (AVPO; the most important thermosensitive and thermointegrative region of the CNS) modulating hypoxia-induced anapyrexia. Thus, we assessed CBS and nitric oxide synthase (NOS) activities [by means of H2S and nitrite/nitrate (NO(x)) production, respectively] as well as cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) levels in the anteroventral third ventricle region (AV3V; where the AVPO is located) during normoxia and hypoxia. Furthermore, we evaluated the effects of pharmacological modifiers of the H2S pathway given i.c.v. or intra-AVPO. I.c.v. or intra-AVPO microinjection of CBS inhibitor caused no change in Tb under normoxia but significantly attenuated hypoxia-induced anapyrexia. During hypoxia there were concurrent increases in H2S production, which could be prevented by CBS inhibitor, indicating the endogenous source of the gas. cAMP concentration, but not cGMP and NOR, correlated with CBS activity. CBS inhibition increased NOS activity, whereas H2S donor decreased NO. production. In conclusion, hypoxia activates H2S endogenous production through the CBS-H(2)S pathway in the AVPO, having a cryogenic effect. Moreover, the present data are consistent with the notion that the two gaseous molecules, H(2)S and NO, play a key role in mediating the drop in Tb caused by hypoxia and that a fine-balanced interplay between NOS-NO and CBS-H(2)S pathways takes place in the AVPO of rats exposed to hypoxia. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.