55 research outputs found
Ephesis against Eubulides (Dem. 57): Legal Arguments against the Sykophantâs Game
This paper analyses Euxitheusâ legal arguments in the trial against Eubulides (Dem. 57) and proposes a new analysis of the ephesis procedure. Within this framework it argues that Euxitheusâ forensic strategy is not only relevant to the question at issue â to prove his status as a legitimate citizen (gnesios polites), as someone born from two citizen parents â but is also characterised by a strict adherence to the laws and procedure involving his case. The relation between rhetoric and law emerging in Euxitheusâ speech reveals a rhetorical strategy grounded on legal evidence and documents. This essay will especially focus on two important arguments in the speech, that is, the use of religious arguments and the theme of the plot against Euxitheus, which prove extremely enlightening in showing the how the relevant procedure shaped Euxitheusâ arguments. To this aim section II compares Dem. 57and other probable cases of ephesis in order to reassess how the ephesis procedure worked when it arose from a diapsephisis. Section III shows that the arguments used by Euxitheus are to be considered relevant to winning an ephesis case in court.The entire speech is effectively constructed to demonstrate âwhat is trueâ against Eubulidesâ âfalse accusationsâ and âdefamatory statementsâ (57.1), that is, to use legal arguments against âthe sykophantâs gameâ: to allege everything but prove nothingâ.This paper analyses Euxitheusâ legal arguments in the trial against Eubulides (Dem. 57) and proposes a new analysis of the ephesis procedure. Within this framework it argues that Euxitheusâ forensic strategy is not only relevant to the question at issue â to prove his status as a legitimate citizen (gnesios polites), as someone born from two citizen parents â but is also characterised by a strict adherence to the laws and procedure involving his case. The relation between rhetoric and law emerging in Euxitheusâ speech reveals a rhetorical strategy grounded on legal evidence and documents. This essay will especially focus on two important arguments in the speech, that is, the use of religious arguments and the theme of the plot against Euxitheus, which prove extremely enlightening in showing the how the relevant procedure shaped Euxitheusâ arguments. To this aim section II compares Dem. 57and other probable cases of ephesis in order to reassess how the ephesis procedure worked when it arose from a diapsephisis. Section III shows that the arguments used by Euxitheus are to be considered relevant to winning an ephesis case in court.The entire speech is effectively constructed to demonstrate âwhat is trueâ against Eubulidesâ âfalse accusationsâ and âdefamatory statementsâ (57.1), that is, to use legal arguments against âthe sykophantâs gameâ: to allege everything but prove nothingâ.This paper analyses Euxitheusâ legal arguments in the trial against Eubulides (Dem. 57) and proposes a new analysis of the ephesis procedure. Within this framework it argues that Euxitheusâ forensic strategy is not only relevant to the question at issue â to prove his status as a legitimate citizen (gnesios polites), as someone born from two citizen parents â but is also characterised by a strict adherence to the laws and procedure involving his case. The relation between rhetoric and law emerging in Euxitheusâ speech reveals a rhetorical strategy grounded on legal evidence and documents. This essay will especially focus on two important arguments in the speech, that is, the use of religious arguments and the theme of the plot against Euxitheus, which prove extremely enlightening in showing the how the relevant procedure shaped Euxitheusâ arguments. To this aim section II compares Dem. 57and other probable cases of ephesis in order to reassess how the ephesis procedure worked when it arose from a diapsephisis. Section III shows that the arguments used by Euxitheus are to be considered relevant to winning an ephesis case in court.The entire speech is effectively constructed to demonstrate âwhat is trueâ against Eubulidesâ âfalse accusationsâ and âdefamatory statementsâ (57.1), that is, to use legal arguments against âthe sykophantâs gameâ: to allege everything but prove nothingâ
Neurochemical characterization of primary sensory neurons in a rat model of bortezomic-induced peripheral neuropathy
Peripheral neuropathies, as the result of nerve damage, are characterized by pain, numbness, and tingling in the extremities and slow nerve conduction. Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of many other commonly used chemotherapeutic agents, including platinum drugs, taxanes, epothilones and vinca alkaloids, but also newer agents such as bortezomib.
Bortezomib (VELCADE) is a boronic acid dipeptide, which causes a selective blockade of proteasome activity. Bortezomib-induced peripheral neuropathy is an important clinical complication, often difficult to manage or reverse, whose treatment usually involves dose reduction, interruption, or cessation of therapy. Though many animal models of chemotherapy-induced peripheral neuropathy have been designed, knowledge concerning the mechanisms that may underlie neurochemical changes accompanying the onset of bortezomib-induced peripheral neuropathy is still poor. In this study, to analyze the possible neurochemical changes occurring in primary sensory neurons, the effects of a single-dose intravenous administration and a well-established âchronicâ schedule (three times/week for 8 weeks) in a rat model of bortezomib-induced peripheral neuropathy have been examined.
The transient.receptor.potential.vanilloid.type.1 (TRPV1) channel and sensory neuropeptides calcitonin.gene-related.peptide (CGRP) and substance.P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord and sciatic nerve using western blot (WB), immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). Behavioral measures, performed at the end of the chronic bortezomib-treatment, confirmed a reduction of the mechanical nociceptive threshold, whereas no difference occurred in the thermal withdrawal latency. In the DRGs, TRPV1-, CGRP- and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. WB analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib-administration. Comparative RT-PCR revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. The characterization of this animal model of peripheral neuropathy suggests that the neurochemical changes occurring in populations of DRG neurons that are likely involved in pain transmission appear to be an important component of the sensory neuropathy induced by the bortezomib-treatment and may represent the outcome of the molecular machine activated by the drug during the onset and persistence of bortezomib-induced neuropathic pain
KniMet: a pipeline for the processing of chromatography-mass spectrometry metabolomics data.
INTRODUCTION: Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow. OBJECTIVES: Merge in the same platform the steps required for metabolomics data processing. METHODS: KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform. RESULTS: The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation. CONCLUSION: KniMet provides the user with a local, modular and customizable workflow for the processing of both GC-MS and LC-MS open profiling data
Effects of forced swimming stress on ERK and histone H3 phosphorylation in limbic areas of Roman high-and low-avoidance rats
Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK) and histone H3 (pH3) in limbic brain areas of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression-like behavior. We demonstrate that FS markedly increased the density of pERK-positive neurons in the infralimbic (ILCx) and the prelimbic area (PrLCx) of the prefrontal cortex (PFCx), the nucleus accumbens, and the dorsal blade of the hippocampal dentate gyrus to the same extent in RLA and RHA rats. In addition, FS induced a significant increase in the intensity of pERK immunoreactivity (IR) in neurons of the PFCx in both rat lines. However, RHA rats showed stronger pERK-IR than RLA rats in the ILCx both under basal and stressed conditions. Moreover, the density of pH3-positive neurons was equally increased by FS in the PFCx of both rat lines. Interestingly, pH3-IR was higher in RHA than RLA rats in PrLCx and ILCx, either under basal conditions or upon FS. Finally, colocalization analysis showed that in the PFCx of both rat lines, almost all pERK-positive cells express pH3, whereas only 50% of the pH3-positive neurons is also pERK-positive. Moreover, FS increased the percentage of neurons that express exclusively pH3, but reduced the percentage of cells expressing exclusively pERK. These results suggest that (i) the distinctive patterns of FS-induced ERK and H3 phosphorylation in the PFCx of RHA and RLA rats may represent molecular signatures of the behavioural traits that distinguish the two lines and (ii) FS-induced H3 phosphorylation is, at least in part, ERK-independent
Transient receptor potential vanilloid type 1 (TRPV1) and neuropeptides in the dorsal root ganglia and spinal cord in a rat model of Bortezomib-induced neuropathy
Neuroplastic changes in c-Fos, ÎFosB, BDNF, trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity
Sexual activity causes differential changes in the expression of markers of neural activation (c-Fos and Delta FosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and Delta FosB) or immunohistochemistry (BDNF, trkB, Arc, and c-Fos), in the hippocam pus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naive than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c-Fos, and Arc levels were similar to those of controls, while Delta FosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals
Immunochemical detection of BDNF in the brain of a rat model of depression
Several lines of evidence show a relationship between alterations in the mechanisms that control the expression of neurotrophic factors and mood disorders (1). In particular, support for the role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of depression and related deficits in neuronal plasticity comes from evidence that a reduction of BDNF expression has been found in postmortem brains and serum of depressed subjects and that the BDNF gene is required for the response to antidepressant drugs. With the aim to contribute to the characterization of the molecular and neuronal systems involved in the pathogenesis of depression and in the mechanism of action of the antidepressant treatments, here we use the outbread Roman High- (RHA) and Roman Low-Avoidance (RLA) rat lines, psychogenetically selected for rapid versus poor acquisition of active avoidance, respectively, and bearing several behavioral characteristics closely resembling the cardinal symptoms of depression (2), to investigate on the immunochemical occurrence of BDNF in selected areas of the RHA and RLA rat brain by means of western blot (WB) and immunohistochemistry. WB analysis indicates that the relative levels of BDNF patently and markedly differed in the hippocampus, where they were significantly lower by 58% in RLA vs RHA rats (p = 0.0014). In the remaining examined areas, namely the prefrontal cortex, the caudate-putamen complex proper, the core and shell regions of the nucleus accumbens and the ventral tegmental area, the relative BDNF levels did not show statistically significant differences. In tissue sections, BDNF-like immunoreactive (LI) material labelled neuronal cell bodies, proximal processes and varicose nerve fibers, with an uneven distribution in telencephalic cerebral cortex, hippocampus, amygdala, nucleus accumbens, caudate-putamen complex proper, thalamus and ventral tegmentum of the midbrain. Densitometric analysis of immunostained brain sections were used to quantify differences among the two rat lines. The results obtained provide a morphological evidence for a differential expression of BDNF in specific areas of RLA vs RHA rat brains and may form the morphological basis to understand the regulation of the trophic machinery in depression
Immunochemical detection of trkB receptor in the brain of a rat model of depression
The outbread Roman High- (RHA) and Roman Low-Avoidance (RLA) rat lines were psychogenetically selected for rapid versus poor acquisition of active avoidance, respectively, and differ in many behavioural traits that closely resemble the cardinal symptoms of depression (1). Beyond the monoamine hypothesis of depression, compelling evidence suggests that mood disorders are characterized by reduced neuronal plasticity. Consistently, it has been shown that exposure to stress and antidepressant treatment modulate the expression of neurotrophic molecules and their relevant receptors, and that these changes show an anatomical specificity (2). With the aim to characterize the molecular and neuronal systems involved in the pathogenesis of depression and in the mechanism of action of the antidepressant treatments, here we investigate on the immunochemical occurrence of trkB, the high affinity tyrosinekinase receptor for brain-derived neurotrophic factor (BDNF), in selected areas of the RHA and RLA rat brain by means of western blot (WB) and immunohistochemistry. WB analysis indicates that the relative levels of trkB patently and markedly differed in the prefrontal cortex and the hippocampus, where they were lower in RLA vs RHA rats, and in the caudate-putamen complex proper where, by contrast, they were higher in RLA vs RHA rats. No statistically significant differences were seen in nucleus accumbens and ventral tegmental area. In tissue sections, trkB-like immunoreactive (LI) labelling was mainly localized to neuronal cell bodies and proximal processes, unevenly distributed in the telencephalic cerebral cortex, the hippocampus, and the ventral tegmentum of the midbrain. Densitometric analysis of immunostained brain sections revealed that differences among the two groups are consistent to a good extent with WB data. As a whole, the finding of a different expression of trkB receptor in the RLA vs RHA rat brains implies the occurrence of an altered neuronal responsiveness to BDNF in specific brain regions and may contribute to outline the molecular and morphological basis for the distinct vulnerability to depression in the two rat lines
Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
<p>Abstract</p> <p>Background</p> <p>Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of <it>Pistacia lentiscus </it>L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma.</p> <p>Methods</p> <p>Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone.</p> <p>Results</p> <p>BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA).</p> <p>Conclusions</p> <p>Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.</p
BDNF, trkB and PSA-NCAM in the hippocampus of Roman rats after forced swimming
The selective breeding of Roman High- (RHA) and Low-Avoidance (RLA) rats are considered as a genetic model of resilience to stress-induced depression and of vulnerability to that trait, respectively1. There is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders. Here, we investigated on immunochemical occurrence of Brain-derived neurotrophic factor (BDNF), tyrosine-kinase receptor trkB and polysialilated form of the neural cell adhesion molecule (PSANCAM) in the hippocampus of the Roman rat lines under baseline conditions and after acute forced swimming (FS). Western blot (WB) analyses showed that, in basal conditions, the relative levels of BDNF, trkB and PSA-NCAM markedly differed, appearing lower by 48%, 25% and 65%, respectively, in RLA vs RHA rats. WB analyses carried out after FST showed no differences between baseline and FST rats. In tissue sections, BDNF-, trkB- and PSA-NCAM-like immunoreactivity (LI) showed a distinctive labelling, mainly localized to proximal neuronal processes and nerve fibers distributed in the Ammonâs horn and dentate gyrus (DG). A number of PSA-NCAM-positive neurons in the subgranular layer of dentate gyrus also occurred. Densitometric analysis further showed differences in the hippocampal subregions. Thus, upon FST, BDNF-LI was less abundant in the CA3 sector of the Ammonâs horn of FST vs control RLA rats (-24%), whereas PSA-NCAM-LI was more abundant in the DG of RHA than RLA rats (+26%). Our findings suggest that an altered neuronal availability of and/or responsiveness to BDNF and inadequate dynamic events related to neuroplasticity may contribute to outline the molecular and morphological basis for the distinct vulnerability to stress-induced depression in the two rat lines
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