Gabapentin for tinnitus: a systematic review.

PURPOSE: The main aim of this study was to assess the effect of gabapentin on tinnitus via a systematic review. METHOD: An electronic search of literature as well as a hand search were conducted. Only double-blind randomized controlled trials (RCTs) that met all of the inclusion criteria were included in this review. The Cochrane Collaboration tool for risk of bias assessment was used to investigate the validity of the included studies. Meta-analysis was not appropriate due to inadequate details in reporting the data in the included studies. Hence, qualitative synthesis and interpretation of the data were carried out. RESULTS: Two studies that met the inclusion criteria were included in the review. Fourteen studies were excluded. There were substantive within-study clinical heterogeneities with regard to the baseline tinnitus handicap scores, duration of tinnitus, and severity of hearing loss in the included double-blind RCTs. CONCLUSION: The authors of both studies reported that gabapentin was not superior to placebo in their primary outcomes. However, following the assessment of risk of bias and within-study clinical heterogeneities, this review concludes that there is insufficient evidence regarding the effect of gabapentin on tinnitus

Knocking-Down Cyclin A2 by siRNA Suppresses Apoptosis and Switches Differentiation Pathways in K562 Cells upon Administration with Doxorubicin

Cyclin A2 is critical for the initiation of DNA replication, transcription and cell cycle regulation. Cumulative evidences indicate that the deregulation of cyclin A2 is tightly linked to the chromosomal instability, neoplastic transformation and tumor proliferation. Here we report that treatment of chronic myelogenous leukaemia K562 cells with doxorubicin results in an accumulation of cyclin A2 and follows by induction of apoptotic cell death. To investigate the potential preclinical relevance, K562 cells were transiently transfected with the siRNA targeting cyclin A2 by functionalized single wall carbon nanotubes. Knocking down the expression of cyclin A2 in K562 cells suppressed doxorubicin-induced growth arrest and cell apoptosis. Upon administration with doxorubicin, K562 cells with reduced cyclin A2 showed a significant decrease in erythroid differentiation, and a small fraction of cells were differentiated along megakaryocytic and monocyte-macrophage pathways. The results demonstrate the pro-apoptotic role of cyclin A2 and suggest that cyclin A2 is a key regulator of cell differentiation. To the best of our knowledge, this is the first report that knocking down expression of one gene switches differentiation pathways of human myeloid leukemia K562 cells

Metabolic Regulation in Progression to Autoimmune Diabetes

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

Nature meets nurture: molecular genetics of gastric cancer

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed

Avaliação do perfil auditivo de militares de um quartel do Exército Brasileiro Audiometric assessment for military personnel

No serviço militar, os sujeitos estão expostos a ruídos contínuos em oficinas e a ruídos de impacto provenientes de armas de fogo e detonações. Estes ruídos indesejáveis são capazes de causar lesão ao sistema auditivo, muitas vezes irreversível, além de outros efeitos em todo o organismo. OBJETIVO: Avaliar os perfis auditivos de um grupo de militares e, em face dos resultados, incentivar a implementação de medidas preventivas para perdas auditivas, como programa de conservação auditiva. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Avaliação auditiva de 97 sujeitos que trabalham em uma organização militar do Exército, por meio de entrevista, otoscopia e exames audiométricos. RESULTADOS: 38,1% dos militares examinados apresentaram alterações audiométricas supostamente induzidas por ruído, predominantemente nos artilheiros, com predomínio da perda auditiva unilateral. 64,5% dos militares examinados não utilizava proteção adequada. CONCLUSÃO: A grande ocorrência da perda auditiva entre os militares e a falta de proteção adequada à exposição ao ruído indica a necessidade de se implantarem, nesta categoria, medidas de prevenção de perda auditiva.<br>The individuals rendering the military service are often liable to frequent noise in factories and discharge sounds deriving from firearms and detonations. These sort of undesirable sounds cause lesions the auditory system, which are sometimes irreversible, besides provoking bad effects to the body as a whole. AIM: Evaluating the auditory profiles from a specific group of military personnel, and according to the achieved results to promote the incentive towards the implantation of preventive measures related to auditory losses, such as auditory preservation programs. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: Auditory evaluation of 97 individuals working in a military organization, which included interviews, as well as otoscopic and audiometric tests. RESULTS: From the total examined personnel, 38,1% presented audiometric changes supposedly noise-induced since these changes prevailed in the artillerymen, being the unilateral hearing loss predominant. The use of no proper protection equipment was observed in 64,5% of the total examined military personnel. CONCLUSION: The high level of hearing loss occurrences found between the military personnel joined to the absence of proper protection equipment for the exposition to noises, indicate the need of implanting prevention measures to avoid hearing losses among theses professionals