Oxidative stress in patients with laryngeal carcinoma

Background : Cancer is a multifactorial disease. Repetitive cumulative damage of cellular organelles by oxy-free radicals are few of the important causative factors. Aim : To assess the role of oxidative stress in the laryngeal cancer patients in Indian population. Setting and Design : Case control study. Materials and Methods : Level of malondialdehyde (MDA) as a marker of oxidative stress was examined in large cohort of control (50) and laryngeal carcinoma patients (155) from North India. Both the controls and laryngeal carcinoma patients were smokers. Results : In control healthy subjects MDA levels were 0.102±0.07 (0.080- 0.303, 95% CI) n mol/ml, as compared to 0.329±0.16 (0.124-0.354, 95% CI) n mol/ml in the cases of laryngeal carcinoma patients. Three times higher serum MDA levels indicated that there was significant oxidative stress in the subjects having laryngeal carcinoma lesions. In addition patients with secondaries were having MDA levels of 0.4±0.02 (0.391-0.408 95% CI) n mol/ml, as compared to 0.57±0.03 (0.558-0.582 95% CI)n mol/ml in group of patients without secondaries. These two values were statistically significant as compared to control values (P< 0.01). Conclusion : These findings suggest that in case of laryngeal carcinoma patients, there is increase in the level of oxidative enzyme MDA. The oxidative stress might be due to the modulation of pro-oxidant or anti-oxidant systems in laryngeal carcinoma

Oxidative stress in patients with laryngeal carcinoma

Background : Cancer is a multifactorial disease. Repetitive cumulative damage of cellular organelles by oxy-free radicals are few of the important causative factors. Aim : To assess the role of oxidative stress in the laryngeal cancer patients in Indian population. Setting and Design : Case control study. Materials and Methods : Level of malondialdehyde (MDA) as a marker of oxidative stress was examined in large cohort of control (50) and laryngeal carcinoma patients (155) from North India. Both the controls and laryngeal carcinoma patients were smokers. Results : In control healthy subjects MDA levels were 0.102\ub10.07 (0.080- 0.303, 95% CI) n mol/ml, as compared to 0.329\ub10.16 (0.124-0.354, 95% CI) n mol/ml in the cases of laryngeal carcinoma patients. Three times higher serum MDA levels indicated that there was significant oxidative stress in the subjects having laryngeal carcinoma lesions. In addition patients with secondaries were having MDA levels of 0.4\ub10.02 (0.391-0.408 95% CI) n mol/ml, as compared to 0.57\ub10.03 (0.558-0.582 95% CI)n mol/ml in group of patients without secondaries. These two values were statistically significant as compared to control values (P&lt; 0.01). Conclusion : These findings suggest that in case of laryngeal carcinoma patients, there is increase in the level of oxidative enzyme MDA. The oxidative stress might be due to the modulation of pro-oxidant or anti-oxidant systems in laryngeal carcinoma

Effects of oral and oropharyngeal cancer on speech intelligibility using acoustic analysis: Systematic review

Background: The development of automatic tools based on acoustic analysis allows to overcome the limitations of perceptual assessment for patients with head and neck cancer. The aim of this study is to provide a systematic review of literature describing the effects of oral and oropharyngeal cancer on speech intelligibility using acoustic analysis. Methods: Two databases (PubMed and Embase) were surveyed. The selection process, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, led to a final set of 22 articles. Results: Nasalance is studied mainly in oropharyngeal patients. The vowels are mostly studied using formant analysis and vowel space area, the consonants by means of spectral moments with specific parameters according to their phonetic characteristic. Machine learning methods allow classifying “intelligible” or “unintelligible” speech for T3 or T4 tumors. Conclusions: The development of comprehensive models combining different acoustic measures would allow a better consideration of the functional impact of the speech disorder

Altered miRNA expression network in locus coeruleus of depressed suicide subjects

Norepinephrine (NE) is produced primarily by neurons in the locus coeruleus (LC). Retrograde and ultrastructural examinations reveal that the core of the LC and its surrounding region receives afferent projections from several brain areas which provide multiple neurochemical inputs to the LC with changes in LC neuronal firing, making it a highly coordinated event. Although NE and mediated signaling systems have been studied in relation to suicide and psychiatric disorders that increase the risk of suicide including depression, less is known about the corresponding changes in molecular network within LC. In this study, we examined miRNA networks in the LC of depressed suicide completers and healthy controls. Expression array revealed differential regulation of 13 miRNAs. Interaction between altered miRNAs and target genes showed dense interconnected molecular network. Functional clustering of predicated target genes yielded stress induced disorders that collectively showed the complex nature of suicidal behavior. In addition, 25 miRNAs were pairwise correlated specifically in the depressed suicide group, but not in the control group. Altogether, our study revealed for the first time the involvement of LC based dysregulated miRNA network in disrupting cellular pathways associated with suicidal behavior

MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects

<div><h3>Background</h3><p>Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases.</p> <h3>Methodology/Principal Findings</h3><p>The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5′-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group.</p> <h3>Conclusions/Significance</h3><p>The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).</p> </div

DendroBlast: approximate phylogenetic trees in the absence of multiple sequence alignments

The rapidly growing availability of genome information has created considerable demand for both fast and accurate phylogenetic inference algorithms. We present a novel method called DendroBLAST for reconstructing phylogenetic dendrograms/trees from protein sequences using BLAST. This method differs from other methods by incorporating a simple model of sequence evolution to test the effect of introducing sequence changes on the reliability of the bipartitions in the inferred tree. Using realistic simulated sequence data we demonstrate that this method produces phylogenetic trees that are more accurate than other commonly-used distance based methods though not as accurate as maximum likelihood methods from good quality multiple sequence alignments. In addition to tests on simulated data, we use DendroBLAST to generate input trees for a supertree reconstruction of the phylogeny of the Archaea. This independent analysis produces an approximate phylogeny of the Archaea that has both high precision and recall when compared to previously published analysis of the same dataset using conventional methods. Taken together these results demonstrate that approximate phylogenetic trees can be produced in the absence of multiple sequence alignments, and we propose that these trees will provide a platform for improving and informing downstream bioinformatic analysis. A web implementation of the DendroBLAST method is freely available for use at http://www.dendroblast.com/

Human depression: a new approach in quantitative psychiatry

The biomolecular approach to major depression disorder is explained by the different steps that involve cell membrane viscosity, Gsα protein and tubulin. For the first time it is hypothesised that a biomolecular pathway exists, moving from cell membrane viscosity through Gsα protein and Tubulin, which can condition the conscious state and is measurable by electroencephalogram study of the brain's γ wave synchrony

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus