Introduction
This study investigated the presence of different Gram-negative bacterial species and the levels of endotoxins found in primary endodontic infection (PEI), determining their stimulation ...ability against macrophages through the levels of interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor alpha (TNF-α), and evaluated their relationship with clinical and radiographic findings.
Material and methods
Samples were taken from 21 root canals with primary endodontic infection with apical periodontitis (PEIAP). Molecular techniques were used for bacterial detection. Limulus amebocyte lysate assay was used to measure endotoxins. Pro-inflammatory cytokines were measured by ELISA assay.
Results
All samples were positive for bacterial DNA (21/21).
Prevotella nigrescens
(57.2 %) was the most frequent species. Higher levels of endotoxins were found in teeth with pain on palpation and exudation (all
p
< 0.05). Positive correlations were found between endotoxins and the levels of TNF-α and IL-1β, whereas a negative correlation was found between endotoxin and the amount of IL-10 (
p
< 0.05). Endotoxin levels were found to be a risk factor for exudation and increased the number of Gram-negative bacterial species for the presence of a larger area of bone destruction (all
p
< 0.05).
Conclusion
A wide variety of Gram-negative bacterial species are involved in primary endodontic infection, with participation of different
Treponema
species. Thus, the levels of endotoxins and the number of Gram-negative bacteria species present in root canals were considered risk factors for the severity of endodontic infection.
Clinical relevance
The present study revealed that Gram-negative bacterial species and endotoxins play an important role in the development of signs/symptoms and the severity of bone destruction, this knowledge is essential for the establishment of an effective therapy.
The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals ...to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of Odontophrynus americanus, as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments. Americanin-1 was isolated and identified as a neutral peptide exhibiting moderate antibacterial activity against E. coli. Its amphipathic sequence including 19 amino acids and showing a propensity for α-helix structure is discussed. Comparisons of the histomorphology of the skin of O. americanus with other previously documented species within the same genus revealed distinctive features in the Patagonian specimen, differing from conspecifics from other Argentine provinces. The presence of the Eberth–Katschenko layer, a prevalence of iridophores, and the existence of glycoconjugates in its serous glands suggest that the integument is adapted to retain skin moisture. This adaptation is consistent with the prevailing aridity of its native habitat.
Objective
This study aims to investigate the role of protease-activated receptor (PAR) 2 and mast cell (MC) tryptase in LPS-induced lung inflammation and neutrophil recruitment in the lungs of ...C57BL/6 mice.
Methods
C57BL/6 mice were pretreated with the PAR2 antagonist ENMD-1068, compound 48/80 or aprotinin prior to intranasal instillation of MC tryptase or LPS. Blood leukocytes, C-X-C motif chemokine ligand (CXCL) 1 production leukocytes recovered from bronchoalveolar lavage fluid (BALF), and histopathological analysis of the lung were evaluated 4 h later. Furthermore, we performed experiments to determine intracellular calcium signaling in RAW 264.7 cells stimulated with LPS in the presence or absence of a protease inhibitor cocktail or ENMD-1068 and evaluated PAR2 expression in the lungs of LPS-treated mice.
Results
Pharmacological blockade of PAR2 or inhibition of proteases reduced neutrophils recovered in BALF and LPS-induced calcium signaling. PAR2 blockade impaired LPS-induced lung inflammation, PAR2 expression in the lung and CXCL1 release in BALF, and increased circulating blood neutrophils. Intranasal instillation of MC tryptase increased the number of neutrophils recovered in BALF, and MC depletion with compound 48/80 impaired LPS-induced neutrophil migration.
Conclusion
Our study provides, for the first time, evidence of a pivotal role for MCs and MC tryptase in neutrophil migration, lung inflammation and macrophage activation triggered by LPS, by a mechanism dependent on PAR2 activation.
Generalized myasthenia gravis (gMG) is an autoimmune disorder in which pathogenic autoantibodies damage the neuromuscular junction, causing disabling or life-threatening muscle weakness. Most ...treatments nonspecifically inhibit aspects of the immune system, do not directly address the causal mechanisms of tissue damage, and often have side-effect profiles that negatively impact patients. Understanding of the central pathogenic role of the complement cascade in gMG is advancing, and a new complement-targeting treatment is under investigation.
We provide an overview of gMG etiology, the complement cascade, current treatments, and the investigational gMG therapy zilucoplan. Zilucoplan is a small, subcutaneously administered, macrocyclic peptide that inhibits cleavage of complement component C5 and the subsequent formation of the membrane attack complex.
In a randomized, double-blind, placebo-controlled, phase 2 clinical trial, zilucoplan demonstrated clinically meaningful complement inhibition in patients with acetylcholine receptor-positive gMG. Zilucoplan, a first-of-its-kind cyclic peptide targeting C5, appears to be a therapeutic option for the treatment of gMG based on available pharmacokinetic/pharmacodynamic data and phase 1 and 2 efficacy, safety, and tolerability data with limited long-term follow-up. Zilucoplan use earlier in the treatment paradigm would be suitable in this population should phase 3 efficacy and safety data be equally favorable.
The modification of the surface characteristics after treatment with plasma in polymeric materials, such as the aging phenomenon, calls the attention of research in the area of nonthermal plasma ...technology. In this work, a direct treatment with dielectric‐barrier discharge plasma was used on the surfaces of ultrafiltration membranes. The measurements of the contact angle with water, attenuated total reflectance accessory, zeta potential, atomic force microscopy and scanning electron microscopy‐MEV were performed on the surfaces to verify changes after plasma treatment and to understand the occurrence and timing of the plasma aging effect. In the analysis of the membrane performance, hydraulic permeation and protein retention tests were performed. The results showed an improvement in wettability and hydrophilic properties in the post‐treated membranes. The study of reversibility/aging of the post‐plasma surface is important for research that deals with the modification of polymeric membranes. Changes in surface morphology, topography and wettability of the membranes were observed up to seven days after treatment, with a tendency to return to the initial characteristics of the membranes.
The Manila clam, Ruditapes philippinarum, is one of the major aquaculture species in the world and a potential sentinel organism for monitoring the status of marine ecosystems. However, genomic ...resources for R. philippinarum are still extremely limited. Global analysis of gene expression profiles is increasingly used to evaluate the biological effects of various environmental stressors on aquatic animals under either artificial conditions or in the wild. Here, we report on the development of a transcriptomic platform for global gene expression profiling in the Manila clam.
A normalized cDNA library representing a mixture of adult tissues was sequenced using a ultra high-throughput sequencing technology (Roche 454). A database consisting of 32,606 unique transcripts was constructed, 9,747 (30%) of which could be annotated by similarity. An oligo-DNA microarray platform was designed and applied to profile gene expression of digestive gland and gills. Functional annotation of differentially expressed genes between different tissues was performed by enrichment analysis. Expression of Natural Antisense Transcripts (NAT) analysis was also performed and bi-directional transcription appears a common phenomenon in the R. philippinarum transcriptome. A preliminary study on clam samples collected in a highly polluted area of the Venice Lagoon demonstrated the applicability of genomic tools to environmental monitoring.
The transcriptomic platform developed for the Manila clam confirmed the high level of reproducibility of current microarray technology. Next-generation sequencing provided a good representation of the clam transcriptome. Despite the known limitations in transcript annotation and sequence coverage for non model species, sufficient information was obtained to identify a large set of genes potentially involved in cellular response to environmental stress.
The liver is a complex organ that performs several functions to maintain homeostasis. These functions are modulated by calcium, a second messenger that regulates several intracellular events. In ...hepatocytes and cholangiocytes, which are the epithelial cell types in the liver, inositol 1,4,5-trisphosphate (InsP
) receptors (ITPR) are the only intracellular calcium release channels. Three isoforms of the ITPR have been described, named type 1, type 2 and type 3. These ITPR isoforms are differentially expressed in liver cells where they regulate distinct physiological functions. Changes in the expression level of these receptors correlate with several liver diseases and hepatic dysfunctions. In this review, we highlight how the expression level, modulation, and localization of ITPR isoforms in hepatocytes and cholangiocytes play a role in hepatic homeostasis and liver pathology.
Suicide is a global public health problem that causes the loss of more than 800,000 lives each year, principally among young people. In Brazil, the average mortality rate attributable to suicide is ...approximately 5.23 per 100,000 population. Although many guidelines have been published for the management of suicidal behavior, to date, there are no recent guidelines based on the principles of evidence-based medicine that apply to the reality of suicide in Brazil. The objective of this work is to provide key guidelines for managing patients with suicidal behavior in Brazil. This project involved 11 Brazilian psychiatry professionals selected by the Psychiatric Emergencies Committee (Comissão de Emergências Psiquiátricas) of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. For the development of these guidelines, 79 articles were reviewed (from 5,362 initially collected and 755 abstracts). In this review, we present definitions, risk and protective factors, assessments, and an introduction to the Safety Plan.
Systematic review registry number:
CRD42020206517
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