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Challenges experienced in early life cause an enduring phenotypical shift of immune cells towards a sensitised state that may lead to an exacerbated reaction later in life and contribute to increased vulnerability to neurological diseases. Peripheral and central inflammation may affect neuronal function through cytokines such as IL-1. The extent to which an early life challenge induces long-term alteration of immune receptors organization in neurons has not been shown. We investigated whether a single episode of maternal deprivation (MD) on post-natal day (PND) 9 affects: (i) the synapse distribution of IL-1RI together with subunits of NMDA and AMPA receptors; and (ii) the interactions between IL-1RI and the GluN2B subunit of the NMDAR in the long-term, at PND 45. MD increased IL-1RI levels and IL-1RI interactions with GluN2B at the synapse of male hippocampal neurons, without affecting the total number of IL-1RI or NMDAR subunits. Although GluN2B and GluN2A were slightly but not significantly changed at the synapse, their ratio was significantly decreased in the hippocampus of the male rats who had experienced MD; the levels of the GluA1 and GluA2 subunits of the AMPAR were also decreased. These changes were not observed immediately after the MD episode. None of the observed alterations occurred in the hippocampus of the females or in the prefrontal cortex of either sex. These data reveal a long-term, sex-dependent modification in receptor organisation at the hippocampal post-synapses following MD. We suggest that this effect might contribute to priming hippocampal synapses to the action of IL-1β., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Appendicitis in the neonatal period is extremely rare. Its low incidence together with non-specific clinical symptoms often mean the diagnosis is delayed, leading to increased rates of peritonitis and mortality. We report the case of a 33-week premature infant, small for gestational age (1180 g at birth), clinically stable and receiving exclusive enteral feeding, who presented clinical manifestations of necrotizing enterocolitis at 14 days of life. Acute phase reactants were elevated and abdominal radiography showed pneumoperitoneum. Laparotomy revealed acute perforated appendicitis without intestinal involvement and purulent fluid in the peritoneum, for which appendectomy was performed. Neonatal acute appendicitis should be considered in the differential diagnosis of abdominal sepsis since early diagnosis and treatment significantly reduce associated morbidity and mortality.

Unlabelled: Early-life stress is associated with an increased risk of developing affective disorders and chronic pain conditions. This study examined the effect of maternal deprivation (MD) on nociceptive responding prior to and following peripheral nerve injury (L5-L6 spinal nerve ligation [SNL]). Because neuroimmune signaling plays an important role in pain and affective disorders, associated alterations in glial and cytokine expression were assessed in key brain regions associated with emotional and nociceptive responding, the hippocampus and prefrontal cortex. MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia compared with control (non-MD) counterparts. SNL resulted in mechanical and cold allodynia in MD and control rats of both sexes. However, MD females exhibited enhanced SNL-induced allodynic responding compared with non-MD counterparts. Interleukin 6 (IL-6) expression was reduced in the prefrontal cortex of MD-SNL males when compared with non-SNL counterparts. Glial fibrillary acidic protein and IL-1β expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced tumor necrosis factor alpha in the prefrontal cortex with a concomitant increase in IL-6 and tumor necrosis factor alpha expression in the hippocampus, compared with either MD or SNL alone. In conclusion, MD female, but not male, rats exhibit enhanced nociceptive responding following peripheral nerve injury, effects that may relate to the distinct neuroinflammatory profile observed in female versus male rats., Perspective: This study demonstrates that females rats exposed to early-life stress exhibit enhanced neuropathic pain responding, effects that are associated with alterations in neuroinflammatory mediators. Increased understanding of the interactions among early-life stress, gender, and pain may lead to the identification of novel therapeutic targets for the treatment of chronic pain disorders., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: The aim of our study is to evaluate the correlation between gynecological examination and magnetic resonance (MRI) findings for the assessment of local response in cervical cancer patients treated with radiotherapy/chemotherapy (RT/ChT)., Patients and Methods: This study is a retrospective review of 75 consecutive cervical cancer patients from April 2004 to November 2009 treated with RT/ChT. Clinical and radiological data were subsequently analyzed. Patient's median age was 51 with a FIGO stage from Ib to IVb. Individualized RT/ChT was administered with a median dose of 45 Gy. Sixty-three patients received a complementary brachytherapy. Seventy-one patients received chemotherapy on a weekly basis. Gynecological exam was performed 3 months and 6 months after treatment and these findings were compared to MRI results at the same time., Statistic Analysis: We used the Spearman's Rho test to determine the correlation level between the clinical and radiological methods., Results: A correlation of 0.68 (60%) was observed between the clinical and MRI findings at 3 months with a further increase of up to 0.86 (82.6%) at 6 months. In the few cases with a poor correlation, the subsequent assessment and the natural history of the disease showed a greater value of the clinical exam as compared with the MRI findings., Conclusions: Physical exam remains an essential tool to evaluate the local response to RT/ChT for cervical cancer. The optimal clinical radiological correlation found at 6 months after treatment suggests that the combination of gynecological examination and MRI are probably adequate in patient monitoring.

The low-cost in-home distribution of full-standard digital TV jointly with high-bitrate data using 50 m long 1 mm core diameter graded-index plastic optical fiber (GI-POF) is proposed and experimentally demonstrated. Discrete multitone (DMT) modulation is demonstrated to provide an adaptive bitrate which can spectrally coexist with digital video broadcasting-terrestrial (DVB-T) signals in 470-862 MHz. A 3 Gb/s DMT signal and two DVB-T channels are generated, transmitted and received exhibiting excellent performance.

The simultaneous transmission of four orthogonal frequency-division multiplexing (OFDM)-based signals used to provide quintuple-play services along wavelength division multiplexing (WDM) long-reach passive optical networks (LR-PONs) is demonstrated experimentally. Particularly, the transmission performance of custom signal bearing Gigabit Ethernet data, Worldwide Interoperability for Microwave Access, Long Term Evolution and Ultra Wideband (sub-bands 2 and 3) signals is evaluated for different LR-PONs reaches, considering single-wavelength and WDM transmission, and using a centralized impairment compensation technique at the central office that is transparent to the services provided.It is shown that error vector magnitude-compliant levels are obtained for all the OFDM-based signals in WDM LR-PONs reaching 100 km and that negligible inter-channel crosstalk is obtained for a channel spacing of 100 GHz regardless the OFDM-based signal considered. The successful multi-format OFDM transmission along the 100 km-long WDM LR-PON is achieved in the absence of optical dispersion compensation or single sideband modulation, and it is enabled by the performance improvement provided by the centralized impairment compensation realized.

Radio-over-fiber (RoF) schemes offer the possibility of permitting direct access to native format services for the domestic user. A low power requirement and cost effectiveness are crucial to both the service provider and the end user. Here, we present an ultra-low cost and power RoF scheme using direct modulation of commercially-available 1344 nm and 1547 nm VCSELs by band-group 1 UWB wireless signals (ECMA-368) at near broadcast power levels. As a result, greatly simplified electrical-optical-electrical conversion is accomplished. A successful demonstration over a transmission distance of 20.1 km is described using a SSMF, CWDM optical network. EVMs of better than -18.3 dB were achieved., (© 2011 Optical Society of America)

A dual-drive LiNbO(3) architecture modulator with chirp management is proposed and developed offering SFDR > 25 dB in a 1.4 V bias excursion compared to only 0.5 V bias excursion in a conventional Mach-Zehnder electro-optical modulator (MZ-EOM). The architecture effectively extends the linear regime and enables the optical transmission of wireless systems employing orthogonal division multiplexing (OFDM) modulation such as ultra-wide band (UWB) which require high linearity over a broad frequency range due to their high peak-to-average power ratio (PARP). Radio-over-fiber UWB transmission in a passive optical network is experimentally demonstrated employing this technique, exhibiting an enhancement of 2.2 dB in EVM after 57 km SSMF when the dual-drive developed modulator is employed., (© 2011 Optical Society of America)

The paper addresses the problem of distribution of high-definition video over fiber-wireless networks. The physical layer architecture with the low complexity envelope detection solution is investigated. We present both experimental studies and simulation of high quality high-definition compressed video transmission over 60 GHz fiber-wireless link. Using advanced video coding we satisfy low complexity and low delay constraints, meanwhile preserving the superb video quality after significantly extended wireless distance., (© 2011 Optical Society of America)

We propose and analyze a novel (to our knowledge) approach to implement the spectral self-imaging effect of optical frequency combs. The technique is based on time-domain multilevel phase-only modulation of a periodic optical pulse train. The method admits both infinite- and finite-duration periodic pulse sequences. We show that the fractional spectral self-imaging effect allows one to reduce by an integer factor the comb frequency spacing. Numerical simulation results support our theoretical analysis.

Maternal deprivation (MD) has numerous outcomes, including modulation of neuroendocrine functions. We previously reported that circulating leptin levels are reduced and hypothalamic cell-turnover is affected during MD, with some of these effects being sexually dimorphic. As leptin modulates the development of hypothalamic circuits involved in metabolic control, we asked whether MD has long-term consequences on body weight, leptin levels and the expression of neuropeptides involved in metabolism. Rats were separated from their mother for 24h starting on postnatal day (PND) 9 and sacrificed at PNDs 13, 35 and 75. In both sexes MD reduced body weight, but only until puberty, while leptin levels were unchanged at PND 35 and significantly reduced at PND 75. Adiponectin levels were also reduced at PND 75 in females, while testosterone levels were reduced in males. At PND 13, MD modulated cell-turnover markers in the hypothalamus of males, but not females and increased nestin, a marker of immature neurons, in both sexes, with males having higher levels than females and a significantly greater rise in response to MD. There was no effect of MD on hypothalamic mRNA levels of the leptin receptor or metabolic neuropeptides or the mRNA levels of leptin and adiponectin in adipose tissue. Thus, MD has long-term effects on the levels of circulating hormones that are not correlated with changes in body weight. Furthermore, these endocrine outcomes are different between males and females, which could be due to the fact that MD may have sexually dimorphic effects on hypothalamic development., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Early maternal deprivation (MD) in rats (24h, PND 9-10) is a model for neurodevelopmental stress. Our previous data showed that MD altered the hippocampal levels of the endocannabinoid 2-AG and the expression of hippocampal cannabinoid receptors in 13-day-old rats, with males being more markedly affected. The aim of this study was to analyze the impact of MD on the enzymes involved in 2-AG biosynthesis (DAGLalpha and DAGLbeta) and degradation (MAGL) in relevant areas (DG, CA1, CA3) of the hippocampus in 13-day-old neonatal rats. The expression of the enzymes was evaluated by quantitative RT-PCR, immunohistochemistry, and densitometry. MD induced a significant increase in DAGLalpha immunoreactivity in both males and females, which was mainly associated with fibers in the polymorphic cell layer of the dentate gyrus and in the stratum pyramidale of CA3. In contrast, the molecular layer of the dentate gyrus showed a significant decrease in DAGLalpha immunoreactivity in MD males and females. No changes were observed in DAGLbeta immunoreactivity. MD induced a significant decrease in MAGL immunoreactivity in hippocampal CA3 and CA1 areas, more marked in males than in females, and that was mainly associated with fibers in all strata of CA3 and CA1. The results also showed a significant decrease of MAGL mRNA levels in MD males. These data support a clear association between neurodevelopmental stress and dysregulation of the endocannabinoid system. This association may be relevant for schizophrenia and other neurodevelopmental psychiatric disorders., (Copyright 2010 Elsevier B.V. All rights reserved.)

Rats subjected to a single prolonged episode of maternal deprivation (MD) [24h, postnatal days 9-10] show, later in life, behavioural alterations that resemble specific signs of schizophrenia and other neuropsychiatric signs including increased levels of impulsivity and an apparent difficulty to cope with stressful situations. Some of these behavioural modifications are observable in the periadolescent period. However there is no previous information regarding the possible underlying neurochemical correlates at this critical developmental period. In this study we have addressed the effects of MD on the levels of serotonin (5-HT), dopamine (DA) and their respective metabolites in prefrontal cortex, hippocampus, striatum, midbrain and cerebellum of male and female periadolescent Wistar rats. MD rats showed significantly increased levels of 5-HT in all regions studied with the exception of cerebellum. In addition, MD animals showed increased levels of DA in PFC as well as increased levels of DA and a decrease of DOPAC/DA and HVA/DA ratios in striatum. The effect of MD on the monoaminergic systems was in several cases sex-dependent., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system. Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse. Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis. Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration. WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol. These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.

We review here our latest results regarding short- and long-term effects of a neonatal maternal deprivation (MD) stress [24h at postnatal day (PND) 9] on diverse psychoneuroimmunoendocrine parameters, pointing out the existence of numerous sexual dimorphisms. Behavioral changes observed in MD animals might be at least in part attributable to neurodevelopmental effects of MD-induced elevated corticosterone levels. Our findings of short-term effects of MD on hippocampal and cerebellar neurons and glial cells appear to support this hypothesis. However, it is important to note that these cellular effects were more marked in males than in females. Moreover, in analyzing the effects of this neonatal stress on the endocannabinoid system (hippocampal endocannabinoid levels and CB1 receptors) we have also found that males were more affected by MD. Since all these sexual dimorphisms were found at an early neonatal age (PND 13), they are attributable to organizational effects of gonadal steroids. We discuss the potential implications of the elevated corticosterone and decreased leptin levels shown by MD animals in their diverse functional alterations, including the above mentioned neural effects as well as the intriguing persistent deficit in their immunological system. We also emphasize the necessity of analyzing the important influence of sex as regards the specific consequences of early life stress.

Early maternal deprivation (MD) in rats (24 h, postnatal day 9-10) is a model for neurodevelopmental stress. There are some data proving that MD affects the endocannabinoid system (ECS) in a gender-dependent manner, and that these changes may account for the proposed schizophrenia-like phenotype of MD rats. The impact of MD on cannabinoid receptor distribution in the hippocampus is unknown. The aim of this study is to evaluate the expression of CB(1) and CB(2) receptors in diverse relevant subregions (DG, CA1, and CA3) of the hippocampus in 13-day-old rats by immunohistochemistry and densitometry. MD induced a significant decrease in CB(1) immunoreactivity (more marked in males than in females), which was mainly associated with fibers in the strata pyramidale and radiatum of CA1 and in the strata oriens, pyramidale, and radiatum of CA3. In contrast, MD males and females showed a significant increase in CB(2) immunoreactivity in the three hippocampal areas analyzed that was detected in neuropil and puncta in the stratum oriens of CA1 and CA3, and in the polymorphic cell layer of the dentate gyrus. A marked sex dimorphism was observed in CA3, with females exhibiting higher CB(1) immunoreactivity than males, and in dentate gyrus, with females exhibiting lower CB(2) immunoreactivity than males. These results point to a clear association between developmental stress and dysregulation of the ECS. The present MD procedure may provide an interesting experimental model to further address the role of the ECS in neurodevelopmental mental illnesses such as schizophrenia., ((c) 2008 Wiley-Liss, Inc.)

Adult animals submitted to a single prolonged episode of maternal deprivation [24h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. According to the neurodevelopmental theory, these behavioral deficits might be mediated by detrimental neurodevelopmental processes that might be associated, at least partially, with stress-induced corticosterone responses. In order to address this hypothesis, we have focused on the hippocampus and cerebellar cortex, two brain regions that show high density of glucocorticoid receptors, and analyzed possible neuronal and glial alterations by immunohistochemical techniques. To evaluate the presence of degenerated neurons we used Fluoro-Jade-C (FJ-C) staining and for the study of astrocytes we employed glial fibrillary acidic protein (GFAP). Within control animals, females showed significantly more GFAP positive cells than males and a trend towards more FJ-C positive cells. Maternal deprivation induced neuronal degeneration and astroglial changes in the hippocampus and cerebellar cortex of neonatal rats that, in general, were more marked in males. This differential effect may be attributable to a greater vulnerability of males to this kind of early environmental insult and/or to sex-dependent differences in the onset and/or progression of the effects. The present experimental procedure may be instrumental in elucidating sex-dependent mechanisms of neurodevelopmental psychiatric disorders with a basis in early environmental insults.

Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation (MD), consisting of a single 24-h maternal deprivation episode during early neonatal life, has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. Despite first onset of mental disorders usually occur during adolescence, characterization of MD has been mostly developed in adult animals. We review here a series of experiments that were conducted on rats and mice, in which we analyzed the psychoimmunoendocrine outcomes of MD at both adolescence and adulthood. As a whole our results indicate that MD might promote a depressive-like trait that may be present from adolescence to maturity. Maternally deprived adolescent animals also displayed altered locomotor responses, a reduced interest for social investigation and seemed prone for impulsive behavior. Therefore, MD in rodents is further confirmed as a suitable animal model for the study of neuropsychiatric disorders that might become evident during adolescence. Given the increasing consumption of cannabis derivatives among the juvenile population and the reported comorbidity of neuropsychiatric symptoms with cannabis abuse, we also discuss our results indicating altered responses of maternally deprived adolescent animals to cannabinoid compounds.

Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. Accordingly, this experimental procedure has been proposed as an animal model of schizophrenia based on the neurodevelopmental hypothesis. We have recently reported that MD-induced sex-dependent alterations in the hippocampus of neonatal rats. In view of recent evidence for important implications of the cerebellum in neurodevelopmental psychiatric diseases, we have now addressed possible degenerative changes in the cerebellar cortex of neonatal Wistar rats of both genders. To evaluate the presence of degenerated nerve cells, we used Fluoro-Jade C staining and for the study of astrocytes, we employed glial fibrillary acidic protein. Further, we analyzed the modulatory actions of two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin, AA-5-HT, and the endocannabinoid reuptake inhibitor, OMDM-2 (daily subcutaneous injections during the postnatal period 7-12). The animals were sacrificed at postnatal Day 13. MD induced significant increases in the number of Fluoro-Jade C positive cells (indicative of degenerating neurons) and in the number of glial fibrillary acidic protein positive cells, only in males. The two cannabinoid compounds reversed or attenuated these effects. The present results provide new insights regarding the psychopathological implications of the cerebellum, the role of the endocannabinoid system in neural development, and the possible neurodevelopmental basis of gender differences in schizophrenia., ((c) 2008 Wiley Periodicals, Inc.)

Adult animals submitted to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days (PND) 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. These behavioral impairments may be related to neuronal loss in the hippocampus triggered by elevated glucocorticoids. Furthermore, our previous data suggested functional relationships between MD stress and the endocannabinoid system. In this study, we addressed the effects of MD on hippocampal glial cells and the possible relationship with changes in plasma corticosterone (CORT) levels. In addition, we investigated the putative involvement of the endocannabinoid system by evaluating (a) the effects of MD on hippocampal levels of endocannabinoids (b) The modulation of MD effects by two inhibitors of endocannabinoids inactivation, the fatty acid amide hydrolase inhibitor N-arachidonoyl-serotonin (AA-5-HT), and the endocannabinoid reuptake inhibitor, OMDM-2. Drug treatments were administered once daily from PND 7 to PND 12 at a dose of 5 mg/kg, and the animals were sacrificed at PND 13. MD induced increased CORT levels in both genders. MD males also showed an increased number of astrocytes in CA1 and CA3 areas and a significant increase in hippocampal 2-arachidonoylglycerol. The cannabinoid compounds reversed the endocrine and cellular effects of maternal deprivation. We provide direct evidence for gender-dependent cellular and biochemical effects of MD on developmental hippocampus, including changes in the endocannabinoid system., (Copyright (c) 2008 Wiley Periodicals, Inc.)

Tobacco smoking and obesity are worldwide important health problems with a growing impact in adolescent and young adults. One of the consequences of nicotine withdrawal is an increase in body weight that can act as a risk factor to relapse. Experimental therapies with a cannabinoid receptor antagonist have been recently proposed for both cigarette smoking and complicated overweight. In the present study, we aimed to investigate metabolic and hormonal effects of chronic nicotine treatment (during treatment and in abstinence) in an animal model of adolescence as well as to address the pharmacological effects of the novel selective CB1 cannabinoid receptor antagonist, SR 147778 (Surinabant). Adolescence (postnatal days 37-44) and/or post-adolescence (postnatal days 45-59) administration of Surinabant reduced body weight gain, as well as plasma glucose levels and triglycerides. The drug also reduced insulin and leptin secretion, and increased adiponectin and corticosterone levels. The effects showed sexual dimorphisms and, in general, were more pronounced in females. Chronic exposure to nicotine (0.8 mg/kg), from postnatal days 30-44 did not result in overt effects on food intake or body weight gain. However, it altered certain responses to the administration of Surinabant, both when the two drugs were given simultaneously and when Surinabant was administered during the post-adolescence period, along nicotine withdrawal. The present results indicate that the endogenous cannabinoid system is active as a metabolic modulator during adolescence and that nicotine exposure can induce long-lasting effects on metabolic regulation, altering cannabinoid modulation of energy expenditure and metabolism.

The endocannabinoid system is involved in the regulation of behavioural and physiological stress-related responses. Nicotine exerts complex effects on emotional behaviour, and its withdrawal may result in depressive and anxiogenic-like symptoms. Cannabinoid receptor agonists and nicotine induce biphasic effects in diverse tests of unconditioned anxiety, alter adrenocortical activity and affect hippocampus-dependent contextual fear conditioning. Upon exposure to stressful stimuli, central endocannabinoid and cholinergic systems appear to be activated in key limbic areas such as hippocampus and amygdala, which might contribute to adaptive cognitive and emotional strategies to cope with aversive situations. Numerous studies indicate the existence of functional interactions between nicotine and cannabinoids, particularly in relation to anxiety-related processes. An overlapping distribution of CB1 and nicotinic acetylcholine receptors in the hippocampus is observed and the endocannabinoid system exerts a modulatory role over the hippocampal cholinergic system. In this review, we point to the hippocampus as a relevant neural substrate for cannabinoid-nicotine interactions, notably as regards emotional responses. After a general description of the cannabinoid and nicotinic systems, we review their implications in unconditioned anxiety, depressive-like behaviour and fear conditioning. Then we discuss the role of both systems in modulating stress-induced changes at cellular, endocrine and behavioural levels and their possible involvement in hippocampal neurogenesis. Although we mainly focus on animal data, some relevant human studies are also discussed.

Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses.

There is evidence for the existence of functional interactions between nicotine and cannabinoids and opioid compounds in adult experimental animals. However, there is scarce information about these relationships in young animals. In the present study we evaluated short and long-term effects of a subchronic nicotine treatment [0.4 mg/kg daily i.p. injections from postnatal day (PND) 34 to PND 43], upon hippocampal and striatal cannabinoid-CB(1) and mu-opioid receptors in Wistar rats of both genders. Rats were sacrificed 2 h after the last nicotine injection (short-term effects, PND 43) or one month later (long-term effects, PND 75). Hippocampal and striatal cannabinoid CB(1) and mu-opioid receptors were quantified by Western blotting. The subchronic nicotine treatment induced a region-dependent long-lasting effect in cannabinoid CB(1) receptor: a significant increase in hippocampal cannabinoid CB(1) receptors and a significant decrease in striatal cannabinoid CB(1) receptors, with these effects being similar in males and females. With respect to mu-opioid receptors, subchronic nicotine induced a significant down-regulation in hippocampal and striatal mu-opioid receptors in the long-term, and within the striatum the effects were more marked in adult males than in females. The present results indicate that juvenile nicotine taking may have implications for the endocannabinoid and endogenous opioid function and for the behaviors served by those systems, this includes possible modification of the response of adults to different psychotropic drugs, i.e. cannabis and morphine/heroin when taken later in life.

The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long-term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

We have studied functional interactions between nicotine and the cannabinoid receptor agonist CP 55,940 (CP) in the modulation of behavioural and corticosterone responses of male and female adolescent Wistar rats. The animals underwent a subchronic nicotine treatment (0.4 mg/kg i.p., once daily) during the periadolescent period (postnatal days 34-43). Twenty-four hours after the last injection of nicotine an acute dose of CP (1 or 100 microg/kg i.p.) was administered. Thirty minutes after the cannabinoid injection, the animals were tested individually in the holeboard immediately followed by the elevated plus-maze. We also measured corticosterone levels by radioimmunoassay. In males, neither CP (1 microg/kg) nor nicotine induced any modification in anxiety when administered alone. However, the combination of the two drugs resulted in a significant anxiogenic-like effect. In females, the lower dose of CP was anxiogenic and nicotine, which did not induce any effect per se, prevented this response. In the holeboard, subchronic nicotine and the acute cannabinoid treatment interacted in the modulation of horizontal activity and the nature of this interaction also showed a clear sexual dimorphism. Both, the cannabinoid agonist and nicotine increased corticosterone concentrations and the animals receiving the two drugs showed higher levels than the animals receiving the cannabinoid alone. The data provide evidence for the existence of functional interactions between nicotine and cannabinoids in the modulation of behavioural responses and adrenocortical activity in adolescent rats.

Objective: We summarize our experience of endoscopic treatment of gastrointestinal fistulas with fibrin glue., Patients and Method: We retrospectively reviewed the outcome of 30 patients with gastrointestinal fistulas (9 internal and 21 external) refractory to standard conservative treatment for at least 10 days. Once the fistula was endoscopically located, 4 to 8 ml of reconstituted fibrin glue (Tissucol 2.0) at 37 degrees C was injected through a Duplocath catheter on a weekly basis., Results: The mean age was 59 years (32-87) and 63% were men. A total of 21.9% of the patients had high output fistulas. We were able to find all fistular orifices what were located close to the surgical anastomosis. Healing time was 17 days (4-90); 2.8 sessions were required per patient (1-5) but only 2.3 sessions were required in responders. Complete sealing of fistulas was achieved in 75%; (80% in low-output, 25% in high-output and 55.5% in internal fistulas). The frequency of fistula recurrence was 3.3%. No complications related to the sealing procedure were found. Overall mortality was 10%, but only 6.6% was related to persistence of the fistula., Conclusions: Endoscopic treatment of fistulas with biological glue has a high success rate in sealing without complications, helping to speed up the healing process and reduce costs, particularly in low-output enterocutaneous fistulas.

Background and Study Aims: An ideal treatment for choledocholithiasis in the laparoscopic era has not been established. The objective of this study was to elucidate whether a treatment strategy of performing intraoperative endoscopic retrograde cholangiopancreatography (ERCP) during laparascopic cholecystectomy (when choledocholithiasis is confirmed by intraoperative cholangiography) is better for patients with suspected common bile duct stones than the current strategy (preoperative ERCP followed by laparoscopic cholecystectomy)., Patients and Methods: This was a prospective randomized study to evaluate which of these two approaches was most benefit- and cost-effective for patients with intermediate risk of choledocholithiasis. Patients underwent either preoperative ERCP followed by a laparoscopic cholecystectomy a few weeks later (the "preoperative ERCP" group) or intraoperative ERCP (the "intraoperative ERCP" group). Intraoperative ERCP was performed using the rendezvous technique., Results: There were 64 patients in the preoperative ERCP group and 59 patients in the intraoperative ERCP group. The demographic and clinical characteristics of the two groups were similar, except that the bilirubin and gamma-glutamyl transferase (GGT) levels and the number of patients treated on an inpatient basis were higher in the preoperative ERCP group. Success rates were similar (96.6 % in the preoperative ERCP group vs. 90.2 % in the intraoperative ERCP group in the per-protocol study). Total morbidity, post-ERCP morbidity, and post-ERCP acute pancreatitis rates were higher in the preoperative ERCP group, but there were no differences between the two groups in the frequency of residual common bile duct stones, the conversion rate to open cholecystectomy, or surgical morbidity. The length of hospital stay and costs were lower in the intraoperative ERCP group despite the longer surgical times in this group. Univariate analysis did not find any relationship between morbidity and total bilirubin or GGT. Logistic regression analysis confirmed that morbidity was related only to the treatment group and the time spent in the operating room: the relative risk (RR) was 4.37 for morbidity and 1.015 for the time spent in the operating room); the RR for papillotomy was 5.49., Conclusions: Both treatment approaches were equally effective but the intraoperative ERCP group had less morbidity, a shorter hospital stay, and reduced costs. The lower morbidity in the intraoperative ERCP group resulted from the lower rate of papillotomy and lower rates of post-ERCP pancreatitis and cholecystitis. Total morbidity was principally related to the type of treatment approach used.

Background: Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance., Aim: To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy., Methods: One hundred and thirty patients (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts with omeprazole, clarithromycin and amoxicillin were treated for 12 days with rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg t.d.s., Results: The intention-to-treat and per-protocol eradication rates were 90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant impact on H. pylori eradication rates. A higher overall eradication rate of 96.6% (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing 1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects reported in 40% of patients were mild., Conclusion: A 12-day course of low dose of rifabutin with an increased dose of amoxicillin and pantoprazole is well-tolerated and highly effective against dual-resistant H. pylori infection after failure of triple therapy.

The kappa (kappa) opioid system appears to interact with nicotine in the modulation of locomotion and addiction related processes. In this study we have investigated the possible implication of the kappa-opioid system in the effects of nicotine on anxiety and adrenocortical activity. In two different experiments, we analysed the possible interaction between nicotine (0.5 mg/kg i.p.) and either the kappa-opioid receptor antagonist nor-binaltorphimine (5 mg/kg i.p.) or the kappa-opioid receptor agonist U50,488H (1 mg/kg s.c.). Behavioural and endocrine experiments were performed in different groups of animals. Animals were exposed to the holeboard immediately followed by the plus-maze. Serum corticosterone levels were determined by radioimmunoassay. Nicotine induced an anxiogenic-like effect in the plus-maze and a significant decrease of holeboard activity. The anxiogenic-like effect in the plus-maze was not modified by any of the kappa-opioid receptor ligands. Nicotine also induced a significant increase in the corticosterone levels, and the kappa antagonist, which did not exert any effect per se, antagonised this effect. The kappa-agonist U50,488H induced a significant increase in corticosterone concentration when administered alone. We provide the first evidence for the involvement of the kappa-opioid receptor in the stimulatory effect of nicotine on adrenocortical activity.

The present article focuses on psychoneuroendocrine effects of cannabinoids in developing animals, with special emphasis on the perinatal, periweanling and periadolescent periods. We describe and discuss published data dealing with acute and long-term effects of exposure to cannabinoid agonists in such critical periods. Human studies have demonstrated that the consumption of marijuana by women during pregnancy affects the neurobehavioural development of their children. Investigations using animal models provide useful information for a better understanding of the long-lasting deleterious consequences of cannabis exposure during pregnancy and lactation. The increasing use of cannabis among adolescents and its associated public health problems have led to a parallel increase in basic research on appropriate animal models. Chronic administration of cannabinoid agonists during the periadolescent period causes persistent behavioural alterations in adult animals. Some of these alterations may be related to a possible increased risk of psychosis and other neuropsychiatric disorders in early onset cannabis users.

The effects of a sodium dodecyl sulfate, SDS, micellar solution on the coupling rates of two arenediazonium ions, ArN(2)(+), with the hydrophobic 1-naphthylamine, 1NA and N-(1-naphthyl) ethylenediamine, NED, coupling agents and with the hydrophilic Na salt of 2-naphthol-6-sulfonic acid, 2N6S, have been studied. First, we explored the micellar effects on the thermal decomposition of the arenediazonium ions. The observed rate constants are slightly depressed or increased, depending on the nature of ArN(2)(+), compared to those in pure water upon increasing [SDS]. Estimations of the corresponding association constant to the micelle indicate that a significant fraction of the arenediazonium ions are incorporated into the micelles even at low surfactant concentrations. The sulfonate group in 2N6S prevents its incorporation into the micellar aggregate due to the electrostatic barrier imposed by the micelles and, in consequence, the coupling reaction is inhibited. In contrast, when employing the naphthylamine derivatives, the observed rate constant increase rapidly up to a maximum at [SDS]

The rate of the spontaneous decomposition of 4-methylbenzenediazonium tetrafluoroborate, 4MBD, was determined. The effects of solvent composition (MeOH/H2O) on its electrochemical processes and on those of the derivatized 2-naphthol-6-sulfonate-4-toluene (6S2NPT) azo dye were investigated by Differential Pulse Polarography (DPP). This electrochemical technique shows an effective sensitivity for detecting arenediazonium ions and derivatized azo dyes.