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Background: Patients suffering chronic pain are at high risk of suffering long-lasting emotional disturbances characterized by persistent low mood and anxiety. We propose that this might be the result of a functional impairment in noradrenergic circuits associated with locus coeruleus (LC) and prefrontal cortex, where emotional and sensorial pain processes overlap., Methods: We used a chronic constriction injury of sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats to assess the time-dependent changes that might potentially precipitate mood disorders (2, 7, 14, and 28 days after injury). This was measured through a combination of behavioral, electrophysiological, microdialysis, immunohistochemical, and Western blot assays., Results: As expected, nerve injury produced an early and stable decrease in sensorial pain threshold over the testing period. By contrast, long-term neuropathic pain (28 days after injury) resulted in an inability to cope with stressful situations, provoking depressive and anxiogenic-like behaviors, even more intense than the aversiveness associated with pain perception. The onset of these behavioral changes coincided with irruption of noradrenergic dysfunction, evident as: an increase in LC bursting activity; in tyrosine hydroxylase expression and that of the noradrenaline transporter; and enhanced expression and sensitivity of α2-adrenoceptors in the LC., Conclusions: Long-term neuropathic pain leads to anxio-depressive-like behaviors that are more predominant than the aversion of a painful experience. These changes are consistent with the impairment of noradrenergic system described in depressive disorders., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The therapeutic activity of noradrenaline reuptake inhibitors (NaRIs) and serotonin reuptake inhibitors (SSRIs) as antidepressant is based on their ability to increase monoamine concentrations in the synaptic cleft. α(2)-Adrenoceptors inhibit noradrenaline (NA) release, which modulates antidepressant neurochemical activity. The present study assesses the influence of the addition of the selective α(2)-adrenoceptor antagonist RS79948 to the NaRI reboxetine and the SSRI citalopram on brain extracellular NA. Dual-probe microdialysis technique in the locus coeruleus (LC) and prefrontal cortex (PFC) was performed in freely moving rats. Acute reboxetine (3 and 5 mg/kg i.p.) promoted a dose-dependent increase of NA in LC (164 ± 15%; 243 ± 24%) and PFC (140 ± 7%; 181 ± 30%). Acute citalopram (5 mg/kg i.p.) did not change NA in LC or PFC, but at 10 mg/kg i.p. increased NA in LC (144 ± 14%) and decreased it in PFC (-42 ± 7%). An inactive dose of RS79948 (0.1mg/kg i.p.) in rats pretreated with reboxetine (3 mg/kg i.p.) or citalopram (5mg/kg i.p.) induced a significant enhancement of NA in LC (reboxetine: 462 ± 137%; citalopram: 142 ± 11%) and PFC (reboxetine: 281 ± 56%; citalopram: 130 ± 16%). The results indicate that co-administration of selective α(2)-adrenoceptor antagonist drugs might improve the effects of NaRI or SSRI antidepressants by enhancing extracellular NA concentrations in the brain., (Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.)

Protein disulfide isomerase (PDI) enzymes are eukaryotic oxidoreductases that catalyze the correct formation of disulfide bonds during protein folding. Structurally they are characterized by the presence of functional thioredoxin-like (Trx) domains. For the protozoan parasite causative of the human amebiasis (Entamoeba histolytica), the correct formation of disulfide bonds is important for an accurate folding of its proteins, including some virulence factors. However, little is known about the enzymes involved in this mechanism. We undertook a post-genomic approach to identify the PDI family of this parasite. The genome database survey revealed a set of 11 PDI-encoding sequences with predictable protein thiol/disulfide oxidoreductase activities.

Objective: To compare the diagnostic accuracy of the Moorfields regression classification (MRC) and subjective optic disc evaluation in discriminating early to moderate glaucomatous from nonglaucomatous eyes., Design: Cross-sectional observational study., Participants: Two hundred thirty-three patients with glaucoma and 216 normal subjects were included in the analysis. Racial groups were defined by self-description., Methods: All subjects underwent confocal scanning laser ophthalmoscopy, stereophotography, and standard perimetry. Glaucoma was defined by visual field defect alone and confirmed with a second visual field test. Stereo photographs were graded as either normal or glaucomatous appearing in a masked fashion by 2 independent graders and adjudicated by a third grader in cases of disagreement. Mean disc area was compared between patients correctly and incorrectly diagnosed with either technique., Main Outcome Measures: Sensitivity and specificity of MRC and subjective evaluation of stereophotographs in the detection of glaucomatous visual field loss., Results: With the MRC, the sensitivity and specificity were higher using the 95% cutoff than using the 99.9% cutoff. Classification based on subjective photo assessment had a greater agreement with the diagnosis of glaucoma than the MRC for blacks (MRC, sensitivity = 62.5%, specificity = 93.2%; Photo, sensitivity = 76.5%, specificity = 91.5%) and whites (MRC, sensitivity = 67.0%, specificity = 92.2%; photo, sensitivity = 78.4%, specificity = 91.9%). Disc area was significantly larger in patients incorrectly diagnosed with the MRC (P = 0.0289)., Conclusions: Subjective optic disc grading by glaucoma specialists outperformed the MRC with the HRT II in both black and white subjects. Both subjective and objective diagnostic methods were associated with similar sensitivity and specificity between racial groups. The MRC was more likely to provide an incorrect diagnosis in subjects with larger optic discs.

High levels of malate dehydrogenase were found in Trichuris ovis. Two molecular forms of the enzyme, of different cellular location and electrophoretic pattern, were isolated and purified. The activity of soluble malate dehydrogenase was greater than that of mitochondrial malate dehydrogenase. Both forms also displayed different electrophoretic profiles in comparison with purified extracts from goat (Capra hircus) liver. Substrate concentration directly affected enzyme activity. Host and parasite malate dehydrogenase activity were both inhibited by a series of benzimidazoles and pyrimidine-derived compounds, some of which markedly reduced parasite enzyme activity, but not host enzyme activity. Percentage inhibition by some pyrimidine derivatives was greater than that produced by benzimidazoles.