1,721,006 research outputs found
The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception
The brain derived neurotrophic factor (BDNF) is a crucial neuromodulator in pain transmission both in peripheral and central nervous system (CNS). Despite evidence of a pro-nociceptive role of BDNF, recent studies have reported contrasting results, including anti-nociceptive and anti-inflammatory activities. Moreover, BDNF polymorphisms can interfere with BDNF role in pain perception. In Val66Met carriers, the Met allele may have a dual role, with anti-nociceptive actions in normal condition and pro-nociceptive effects during chronic pain. In order to elucidate the main effects of BDNF in nociception, we reviewed the main characteristics of this neurotrophin, focusing on its involvement in pain
Organizzazione della cromatina: interazioni tra DNA topoisomerasi I e sequenze ripetute semplici e complesse in S.cerevisiae
Trigeminal satellite cells express functional calcitonin gene-related peptide receptors, whose activation enhances interleukin-1β pro-inflammatory effects.
Primary cultures of microglial cells for testing toxicity of anticancer drugs
Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 muM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved
Validation of Extensive Next-Generation Sequencing Method for Monogenic Disorder Analysis on Cell-Free Fetal DNA: Noninvasive Prenatal Diagnosis
During pregnancy, a percentage of the cell-free DNA circulating in the maternal blood is represented by the cell-free fetal DNA (cffDNA), constituting an accessible source for noninvasive prenatal genetic screening. The coexistence of the maternal DNA, the dominant fraction of cell-free DNA, together with the cffDNA component and the scarcity of the cffDNA itself make applying traditional methods of genetics and molecular biology impossible. Next-generation sequencing methods are widely used to study fetal aneuploidies. However, in monogenic disorders, there have been relatively few studies that analyzed single mutations. We present a method for the analysis of an extended group of gene variants associated with recessive and dominant autosomal disorders using next-generation sequencing. The proposed test should allow a complete analysis of common genetic disorders and pathogen-associated variants for diagnostic use. The analysis of cffDNA for single gene disorders may replace invasive prenatal diagnosis methods, associated with the risk of spontaneous abortion and psychological stress for patients. The proposed test should assess reproductive risk for both genetic family disorders and de novo occurrences of the disease. The application of this method to a case of beta-thalassemia is also discussed
Analysis of Endodontic Successes and Failures in the Removal of Fractured Endodontic Instruments during Retreatment: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis
This study presents a systematic review with meta-analysis to evaluate the success rates of endodontic retreatments in teeth where separated instruments are located within the roots. The search and selection of studies were conducted across two databases, SCOPUS and PubMed, as well as the Cochrane Library registry, yielding a total of 1620 records. Following the selection process, 11 studies were included in the systematic review. Overall, out of 1133 retreated teeth, there were 172 failures in instrument removal and 55 perforations. The meta-analysis results indicate that failures are more frequent when instruments are located in the apical third, with a failure rate of 21%, compared to an 8.8% failure rate in the middle/coronal third. The anatomy of the root canals, particularly the location of the separated instruments, significantly influences the success rates
Detection of HLA-B*57:01 in Real-Time PCR: Implementation into Routine Clinical Practice, and Additional Validation Data
Antiretroviral agents increase NO production in gp120/IFNγ-stimulated cultures of rat microglia via an arginase-dependent mechanism
In the present study we carried out a screening of different Antiretroviral drugs (ARVs) for their potential pro-inflammatory effects on microglial cells. Efavirenz, neviparine, darunavir and atazanavir increased nitric oxide (NO) production in microglial cells activated with Gp120CN54 and interferon-γ. The stimulatory effect on NO production appeared to be mediated by inhibition of arginase (ARG) I activity. Consistently the ARG inhibitor, Nω-hydroxy-nor-arginine, mimicked the effects of ARVs. Take together these data suggest that ARG is an additional molecular target of different ARVs, whose inhibition can contribute to their pharmacological activity as well as explain the neurotoxic potential
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