ABSTRACT
Apical Lesions of Endodontic Origin (ALEO) are initiated by polymicrobial endodontic canal infection. Porphyromonas gingivalis (Pg) and Porphyromonas endodontalis (Pe) lipopolysaccharides (LPS) can induce a pro-inflammatory macrophage response through their recognition by TLR2 and TLR4. However, polarization responses induced by Pg and/or Pe LPS in macrophages are not fully understood. We aimed to characterize the polarization profiles of macrophages differentiated from THP-1 cells following Pg and/or Pe LPS stimulation from reference strain and clinical isolates. A modified LPS purification protocol was implemented and the electrophoretic LPS profiles were characterized. THP-1 human monocytes differentiated to macrophages were stimulated with Pg and Pe LPS. Polarization profiles were characterized through cell surface markers and secreted cytokines levels after 24 h of stimulation. TLR2 and TLR4 cell surfaces and transcriptional levels were determined after 24 or 2 h of LPS stimulation, respectively. LPS from Pg induced a predominant M1 profile in macrophages evidenced by changes in the expression of the surface marker CD64 and pro-inflammatory cytokine profiles, TNF-α, IL-1ß, IL-6, and IL-12. Pe LPS was unable to induce a significant response. TLR2 and TLR4 expressions were neither modified by Pg or Pe LPS. Pg LPS, but not Pe LPS, induced a macrophage M1 Profile.
Subject(s)
Lipopolysaccharides , Porphyromonas gingivalis , Humans , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Porphyromonas endodontalis/metabolism , Porphyromonas gingivalis/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolismABSTRACT
Three decades ago, the term Apparent Life-Threatening Events (ALTE) was proposed and was gra dually incorporated into the clinical approach of these patients, allowing to determine risks, attribute causes, and perform specific treatments. However, this led to studies and hospitalizations considered unnecessary in many cases, increasing health costs. For this reason, the concept of Brief Resolved Unexplained Events (BRUE) was created, in order to reduce the subjectivity of the event and focus a management strategy according to the risk determination. This article analyzes the differences bet ween ALTE and BRUE according to international and Chilean consensus, deepening the approach and incorporating relevant considerations for the daily clinical practice with infants who present a BRUE.
Subject(s)
Brief, Resolved, Unexplained Event/diagnosis , Brief, Resolved, Unexplained Event/therapy , Terminology as Topic , Consensus , Humans , Infant , Infant, Newborn , Medical History Taking , Practice Guidelines as Topic , Risk AssessmentABSTRACT
Background: Obstructive sleep apnea syndrome (OSAS) affects approximately 10%-20% of adults and is associated with obesity, hypertension and metabolic syndrome. Aim: To assess the prevalence and risk factors associated with OSAS in Chilean adults. Material and Methods: A standardized sleep questionnaire and respiratory polygraphy at home were conducted on adults aged 18 years or more, residing in the Metropolitan Region and enrolled in the 2016/17 National Health Survey. Results: Two-hundred and five people between 18 and 84 years old (46% men, mean age 50 years) underwent overnight respiratory polygraphy at home. The estimated obstructive sleep apnea prevalence was 49% (62% men, 31% women) considering an apnea-hypopnea index ≥ 5 respiratory events/hour, and 16% (21% men, 13% women) considering an apnea-hypopnea index ≥ 15 respiratory events/hour. The prevalence of obstructive sleep apnea continuously increased along with age for men and women, with a later onset for women. Age, gender, body mass index, cervical and waist circumference, snoring, reporting of apnea by proxies, self-reported cardiovascular and metabolic diseases such as hypertension, diabetes and dyslipidemia, were significantly associated with OSAS. No association was found with insomnia and daytime sleepiness. Conclusions: The prevalence and risk factors associated to obstructive sleep apnea syndrome were high among these adults.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Sleep Apnea, Obstructive/epidemiology , Chile/epidemiology , Prevalence , Risk Factors , Health SurveysABSTRACT
Resumen: Hace tres décadas se propuso el término Apparent Life-Threatening Events (ALTE), siendo incorpo rado paulatinamente en el enfrentamiento clínico de estos pacientes; permitiendo determinar riesgos, atribuir causas y realizar tratamientos específicos. Sin embargo, llevó a realizar estudios y hospitalizaciones en muchas instancias considerados innecesarios, generando un aumento de los costos sanitarios. Por estos motivos nace el concepto de Brief Resolved Unexplained Events (BRUE), que pretende disminuir la subjetividad del evento y focalizar una estrategia de manejo según determina ción del riesgo. En el siguiente artículo se analizan diferencias entre ALTE y BRUE según consensos internacionales y chilenos, profundizando en el enfrentamiento e incorporando consideraciones de relevancia para la práctica clínica cotidiana de lactantes que presentan un BRUE.
Abstract: Three decades ago, the term Apparent Life-Threatening Events (ALTE) was proposed and was gra dually incorporated into the clinical approach of these patients, allowing to determine risks, attribute causes, and perform specific treatments. However, this led to studies and hospitalizations considered unnecessary in many cases, increasing health costs. For this reason, the concept of Brief Resolved Unexplained Events (BRUE) was created, in order to reduce the subjectivity of the event and focus a management strategy according to the risk determination. This article analyzes the differences bet ween ALTE and BRUE according to international and Chilean consensus, deepening the approach and incorporating relevant considerations for the daily clinical practice with infants who present a BRUE.
Subject(s)
Humans , Infant, Newborn , Infant , Brief, Resolved, Unexplained Event/diagnosis , Brief, Resolved, Unexplained Event/therapy , Terminology as Topic , Practice Guidelines as Topic , Risk Assessment , Consensus , Medical History TakingABSTRACT
OBJECTIVES: To explore the macrophage profiles in symptomatic and asymptomatic forms of AP through phenotypic and functional analyses. MATERIAL AND METHODS: Cross-sectional study. Apical tissue/lesion samples were collected from patients with clinical diagnosis of AAP (n = 51) or SAP (n = 45) and healthy periodontal ligament (HPL) from healthy patients as controls (n = 14), all with indication of tooth extraction. Samples were digested, cells were stained for CD14, M1 (CD64, CD80), and M2 (CD163, CD206) phenotypic surface markers and analyzed by flow cytometry. Functional cytokine profiles L-6, IL-12, TNF-α, IL-23 (M1), IL-10, and TGF-ß (M2) were determined by qPCR. RESULTS: Higher macrophage M1/M2 ratio (CD64+CD80+/CD163+CD206+) along with lower CD163 mean fluorescence intensity (MFI) were found in SAP compared to AAP and controls (p < 0.05). IL-6, IL-12, TNF-α, IL-23 (M1), and IL-10 mRNA (M2) were upregulated, whereas TGF-ß mRNA (M2) was downregulated in apical lesions compared to controls. Specifically, IL-6 and IL-23 (M1) were upregulated in SAP compared with AAP and controls (p < 0.05). The data were analyzed with Kruskal-Wallis test. CONCLUSIONS: Macrophages exhibited a polarization switch towards M1 in AL. SAP exhibited a reduced M2 differentiation profile based on a reduction of CD163 expression levels in SAP over AAP. Specifically, IL-6 and IL-23 were augmented SAP over AAP, suggesting a role in the severity of apical lesions. CLINICAL RELEVANCE: Deciphering the macrophage polarization and functions in apical periodontitis can contribute to explain AP dynamics, its clinical presentation and systemic impact.
Subject(s)
Periapical Periodontitis , Tooth Apex , Cross-Sectional Studies , Humans , Macrophages , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Obstructive sleep apnea syndrome (OSAS) affects approximately 10%-20% of adults and is associated with obesity, hypertension and metabolic syndrome. AIM: To assess the prevalence and risk factors associated with OSAS in Chilean adults. MATERIAL AND METHODS: A standardized sleep questionnaire and respiratory polygraphy at home were conducted on adults aged 18 years or more, residing in the Metropolitan Region and enrolled in the 2016/17 National Health Survey. RESULTS: Two-hundred and five people between 18 and 84 years old (46% men, mean age 50 years) underwent overnight respiratory polygraphy at home. The estimated obstructive sleep apnea prevalence was 49% (62% men, 31% women) considering an apnea-hypopnea index ≥ 5 respiratory events/hour, and 16% (21% men, 13% women) considering an apnea-hypopnea index ≥ 15 respiratory events/hour. The prevalence of obstructive sleep apnea continuously increased along with age for men and women, with a later onset for women. Age, gender, body mass index, cervical and waist circumference, snoring, reporting of apnea by proxies, self-reported cardiovascular and metabolic diseases such as hypertension, diabetes and dyslipidemia, were significantly associated with OSAS. No association was found with insomnia and daytime sleepiness. CONCLUSIONS: The prevalence and risk factors associated to obstructive sleep apnea syndrome were high among these adults.
Subject(s)
Sleep Apnea, Obstructive , Adolescent , Adult , Aged , Aged, 80 and over , Chile/epidemiology , Female , Health Surveys , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sleep Apnea, Obstructive/epidemiology , Young AdultABSTRACT
Background The diagnosis of obstructive sleep apnea syndrome (OSAS) is based on nocturnal records: polysomnography or respiratory polygraphy. However, their high costs limit their use. Aim To examine the predictive value of three sleep questionnaires (STOP, STOP-Bang, Epworth Sleepiness Scale (ESS) in the screening of OSAS in Chilean adults. Material and Methods During the National Health Survey 2016/17, 205 adults aged 50.7 ± 15.0 years (46% males) living in the Metropolitan Region answered sleep questionnaires and underwent an ambulatory respiratory polygraphy. The sensitivity, specificity, positive and negative predictive values and receiver operating characteristic curves of sleep questionnaires were calculated. Results Fifty nine percent of participants had OSAS which was moderate to severe in 26%. The clinical variables associated with OSAS were age, male gender, hypertension, dyslipidemia, overweight, cervical and waist circumferences, history of regular snoring and witnessed apneas. Daytime somnolence, insomnia and unrefreshing sleep were not associated to OSAS risk. STOP, STOP-Bang and ESS questionnaires classified 64%, 71% and 12% of cases as high risk for OSAS, respectively. The STOP and STOP-Bang questionnaires had the highest sensitivity to predict OSAS (76% and 89%, respectively) while the ESS had the highest specificity (91%). Conclusions The sleep questionnaires allowed to identify the subjects at high risk for OSAS in this sample of adults from the Metropolitan Region.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Surveys and Questionnaires , Sleep Apnea, Obstructive/diagnosis , Urban Population , Cross-Sectional Studies , Reproducibility of Results , Risk Factors , ROC Curve , Sensitivity and Specificity , PolysomnographyABSTRACT
Background The diagnosis of obstructive sleep apnea syndrome (OSAS) is based on nocturnal records: polysomnography or respiratory polygraphy. However, their high costs limit their use. Aim To examine the predictive value of three sleep questionnaires (STOP, STOP-Bang, Epworth Sleepiness Scale (ESS) in the screening of OSAS in Chilean adults. Material and Methods During the National Health Survey 2016/17, 205 adults aged 50.7 ± 15.0 years (46% males) living in the Metropolitan Region answered sleep questionnaires and underwent an ambulatory respiratory polygraphy. The sensitivity, specificity, positive and negative predictive values and receiver operating characteristic curves of sleep questionnaires were calculated. Results Fifty nine percent of participants had OSAS which was moderate to severe in 26%. The clinical variables associated with OSAS were age, male gender, hypertension, dyslipidemia, overweight, cervical and waist circumferences, history of regular snoring and witnessed apneas. Daytime somnolence, insomnia and unrefreshing sleep were not associated to OSAS risk. STOP, STOP-Bang and ESS questionnaires classified 64%, 71% and 12% of cases as high risk for OSAS, respectively. The STOP and STOP-Bang questionnaires had the highest sensitivity to predict OSAS (76% and 89%, respectively) while the ESS had the highest specificity (91%). Conclusions The sleep questionnaires allowed to identify the subjects at high risk for OSAS in this sample of adults from the Metropolitan Region.
Subject(s)
Sleep Apnea, Obstructive/diagnosis , Surveys and Questionnaires , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Polysomnography , ROC Curve , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Urban PopulationABSTRACT
We have previously reported that primary hippocampal neurons exposed to synaptotoxic amyloid beta oligomers (AßOs), which are likely causative agents of Alzheimer's disease (AD), exhibit abnormal Ca2+ signals, mitochondrial dysfunction and defective structural plasticity. Additionally, AßOs-exposed neurons exhibit a decrease in the protein content of type-2 ryanodine receptor (RyR2) Ca2+ channels, which exert critical roles in hippocampal synaptic plasticity and spatial memory processes. The antioxidant N-acetylcysteine (NAC) prevents these deleterious effects of AßOs in vitro. The main contribution of the present work is to show that AßOs injections directly into the hippocampus, by engaging oxidation-mediated reversible pathways significantly decreased RyR2 protein content but increased single RyR2 channel activation by Ca2+ and caused considerable spatial memory deficits. AßOs injections into the CA3 hippocampal region impaired rat performance in the Oasis maze spatial memory task, decreased hippocampal glutathione levels and overall content of plasticity-related proteins (c-Fos, Arc, and RyR2) and increased ERK1/2 phosphorylation. In contrast, in hippocampus-derived mitochondria-associated membranes (MAM) AßOs injections increased RyR2 levels. Rats fed with NAC for 3-weeks prior to AßOs injections displayed comparable redox potential, RyR2 and Arc protein contents, similar ERK1/2 phosphorylation and RyR2 single channel activation by Ca2+ as saline-injected (control) rats. NAC-fed rats subsequently injected with AßOs displayed the same behavior in the spatial memory task as control rats. Based on the present in vivo results, we propose that redox-sensitive neuronal RyR2 channels partake in the mechanism underlying AßOs-induced memory disruption in rodents.
ABSTRACT
Amyloid ß peptide oligomers (AßOs), toxic aggregates with pivotal roles in Alzheimer's disease, trigger persistent and low magnitude Ca2+ signals in neurons. We reported previously that these Ca2+ signals, which arise from Ca2+ entry and subsequent amplification by Ca2+ release through ryanodine receptor (RyR) channels, promote mitochondrial network fragmentation and reduce RyR2 expression. Here, we examined if AßOs, by inducing redox sensitive RyR-mediated Ca2+ release, stimulate mitochondrial Ca2+-uptake, ROS generation and mitochondrial fragmentation, and also investigated the effects of the antioxidant N-acetyl cysteine (NAC) and the mitochondrial antioxidant EUK-134 on AßOs-induced mitochondrial dysfunction. In addition, we studied the contribution of the RyR2 isoform to AßOs-induced Ca2+ release, mitochondrial Ca2+ uptake and fragmentation. We show here that inhibition of NADPH oxidase type-2 prevented the emergence of RyR-mediated cytoplasmic Ca2+ signals induced by AßOs in primary hippocampal neurons. Treatment with AßOs promoted mitochondrial Ca2+ uptake and increased mitochondrial superoxide and hydrogen peroxide levels; ryanodine, at concentrations that suppress RyR activity, prevented these responses. The antioxidants NAC and EUK-134 impeded the mitochondrial ROS increase induced by AßOs. Additionally, EUK-134 prevented the mitochondrial fragmentation induced by AßOs, as previously reported for NAC and ryanodine. These findings show that both antioxidants, NAC and EUK-134, prevented the Ca2+-mediated noxious effects of AßOs on mitochondrial function. Our results also indicate that Ca2+ release mediated by the RyR2 isoform causes the deleterious effects of AßOs on mitochondrial function. Knockdown of RyR2 with antisense oligonucleotides reduced by about 50% RyR2 mRNA and protein levels in primary hippocampal neurons, decreased by 40% Ca2+ release induced by the RyR agonist 4-chloro-m-cresol, and significantly reduced the cytoplasmic and mitochondrial Ca2+ signals and the mitochondrial fragmentation induced by AßOs. Based on our results, we propose that AßOs-induced Ca2+ entry and ROS generation jointly stimulate RyR2 activity, causing mitochondrial Ca2+ overload and fragmentation in a feed forward injurious cycle. The present novel findings highlight the specific participation of RyR2-mediated Ca2+ release on AßOs-induced mitochondrial malfunction.
