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31.
The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF‐α 下载免费PDF全文
Monica Castrichini Pietro Enea Lazzerini Alessandra Gamberucci Pier Leopoldo Capecchi Rossella Franceschini Mariarita Natale Mohamed Hammoud Antonio Moramarco Stefania Zimbone Elena Gianchecchi Cinzia Montilli Gianluca Ricci Enrico Selvi Luca Cantarini Mauro Galeazzi Franco Laghi‐Pasini 《European journal of immunology》2014,44(1):227-238
The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL‐1β release. Since innate immune activation and IL‐1β release seem to be implicated in Behçet's disease (BD), a systemic immune‐inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca2+ permeability induced by the selective P2×7r agonist 2′‐3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL‐1β release from LPS‐primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF‐α‐incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP‐induced Ca2+ intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF‐α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti‐TNF‐α drugs in the treatment of the disease. 相似文献
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Jonathan C. Wilton Mark O. HardinJohn D. Ritchie Kevin K. ChungJames K. Aden Leopoldo C. CancioSteven E. Wolf Christopher E. White 《Burns : journal of the International Society for Burn Injuries》2013
Objective
Adult burn patients who experience in-hospital cardiac arrest (CA) and undergo cardiopulmonary resuscitation (CPR) represent a unique patient population. We believe that they tend to be younger and have the added burden of the burn injury compared to other populations. Our objective was to determine the incidence, causes and outcomes following cardiac arrest (CA) and cardio-pulmonary resuscitation (CPR) within this population.Methods
We conducted a retrospective review at the US Army Institute of Surgical Research (ISR) burn intensive care unit (BICU). Charts from 1st January 2000 through 31st August 2009 were reviewed for study. Data were collected all on adult burn patients who experienced in-hospital CA and CPR either in the BICU or associated burn operating room. Patients undergoing CPR elsewhere in our burn unit were excluded because we could not validate the time of CA since they are not routinely monitored with real-time rhythm strips. The study population included civilian burn patients from the local catchment area and burn casualties from the conflicts in Iraq and Afghanistan, but patients with do-not-resuscitate (DNR) orders were excluded.Results
We found 57 burn patients who had in-hospital CA and CPR yielding an incidence of one or more in-hospital CA of 34 per 1000 admissions (0.34%). Fourteen of these patients (25%) survived to discharge while 43 (75%) died. The most common initial cardiac rhythm was pulseless electrical activity (50.9%). The most common etiology of CA among burn patients was respiratory failure (49.1%). The most significant variable affecting survival to discharge was duration of CPR (P < 0.01) with no patient surviving more than 7 min of CPR.Conclusions
CPR in burn patients is sometimes effective, and those patients who survive are likely to have good neurological outcomes. However, prolonged CPR times are unlikely to result in return of spontaneous circulation and may be considered futile. Further, those who experience multiple CA are unlikely to survive to discharge. 相似文献35.
Teresa Zelante Giuseppe Pieraccini Lucia Scaringi Franco Aversa Luigina Romani 《Seminars in immunopathology》2016,38(2):239-248
Fungal commensals coexist in a complex milieu of bacteria within the human body. An increased understanding of the importance of microbiota in shaping the host’s immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. Metagenomics has revealed the complex interactions between fungal and bacterial commensals that, either directly or through the participation of the host immune system, impact on immune homeostasis at mucosal surfaces that, in turn, lead to secondary fungal infections. Metabolomics has captured the dialogue between the mammalian host and its microbiota. It appears that the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a dominant role in the interplay between tryptophan catabolism by microbial communities, the host’s own pathway of metabolite production, and the activation of the aryl hydrocarbon receptor (AhR)/IL-22 axis, eventually impacting on mucosal immune homeostasis and host/fungal symbiosis. Thus, the regulatory loop involving AhR and IDO1 may be exploited for the development of multi-pronged host- and microbiota-directed therapeutic approaches for mucosal and systemic fungal diseases. 相似文献
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Bianca De Filippis Paola Nativio Alessia Fabbri Laura Ricceri Walter Adriani Enza Lacivita Marcello Leopoldo Francesca Passarelli Andrea Fuso Giovanni Laviola 《Neuropsychopharmacology》2014,39(11):2506-2518
Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG-binding protein 2 gene (MECP2) cause >95% of classic cases, and currently there is no cure for this devastating disorder. The serotonin receptor 7 (5-HT7R) is linked to neuro-physiological regulation of circadian rhythm, mood, cognition, and synaptic plasticity. We presently report that 5-HT7R density is consistently reduced in cortical and hippocampal brain areas of symptomatic MeCP2–308 male mice, a RTT model. Systemic repeated treatment with LP-211 (0.25 mg/kg once/day for 7 days), a brain-penetrant selective 5-HT7R agonist, was able to rescue RTT-related defective performance: anxiety-related profiles in a Light/Dark test, motor abilities in a Dowel test, the exploratory behavior in the Marble Burying test, as well as memory in the Novelty Preference task. In the brain of RTT mice, LP-211 also reversed the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons by mTOR is responsible for the altered protein translational control. Present findings indicate that pharmacological targeting of 5-HT7R improves specific behavioral and molecular manifestations of RTT, thus representing a first step toward the validation of an innovative systemic treatment. Beyond RTT, the latter might be extended to other disorders associated with intellectual disability. 相似文献
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Patients with burn shock can be challenging to resuscitate. Burn shock produces a variety of physiologic derangements: Patients are hypovolemic from volume loss, have a increased systemic vascular resistance, and may have a depressed cardiac output depending on the extent of the thermal injury. Additionally, the burn wound produces a significant inflammatory cascade of events that contributes to the shock state. Fluid resuscitation is foundational for the initial treatment of burn shock. Typical resuscitation is with intravenous lactated Ringer's in accordance with well‐established formulas based on burn wound size. In the past century, as therapies to treat thermal injuries were being developed, plasma was the fluid used for burn resuscitation; in fact, plasma was used in World War II and throughout the 1950s and 1960s. Plasma was abandoned because of infectious risks and complications. Despite huge strides in transfusion medicine and the increased safety of blood products, plasma has never been readopted for burn resuscitation. Over the past 15 years, there has been a paradigm shift in trauma resuscitation: Less crystalloid and more blood products are used; this strategy has demonstrated improved outcomes. Plasma is a physiologic fluid that stabilizes the endothelium. The endotheliopathy of trauma has been described and is mitigated by transfusion strategies with a 1:1 ratio of RBCs to plasma. Thermal injury also results in endothelial dysfunction: the endotheliopathy of burns. Plasma is likely a better resuscitation fluid for patients with significant burn wounds because of its capability to restore intravascular volume status and treat the endotheliopathy of burns. 相似文献
39.
José Alberto de Agustín José Juan Gómez de Diego Pedro Marcos-Alberca Patricia Mahía José Luis Rodrigo María Luaces Iván Javier Núñez-Gil Joaquín Ferreiros Ana Bustos Beatriz Cabeza Miguel Ángel García-Fernández Carlos Macaya Leopoldo Pérez de Isla 《Revista espa?ola de cardiología》2018,71(2):105-109
Introduction and objectives
Multidetector computed tomography (MDCT) has been demonstrated as a feasible alternative to invasive coronary angiography (ICA). However, contradictory results have been reported regarding the effect of coronary artery calcium score (CS) on the diagnostic accuracy of MDCT. Our aim was to assess the agreement of MDCT and ICA and to evaluate the influence of CS on this agreement.Methods
We enrolled 266 consecutive patients who underwent evaluation with 64-slice MDCT and ICA. Standard CS software tools were used to calculate the Agatston score. Stenosis was qualitatively classified as mild, moderate, or severe by 1 blinded observer and the results were compared with those of ICA, which was used as the gold standard.Results
The mean age of the patients was 65.4 ± 11.2 years, and 188 patients (70.3%) were men. A total of 484 segments with coronary stenosis ≥ mild were qualitatively evaluated and quantified with MDCT. Noninvasive measurements were concordant with ICA in 402 stenoses (83.05%; Kappa, 0.684), with no significant differences between vessels and with no statistically significant influence of CS on this agreement (OR, 0.93; 95%CI, 0.76-1.09; P = .21). Multidetector computed tomography had high sensitivity, specificity, positive predictive value, and negative predictive value on a per-segment, per-vessel, and per-patient basis.Conclusions
Non-ICA using MDCT showed good agreement with ICA in the qualitative quantification coronary stenosis and CS had no significant impact on this agreement.Full English text available from: www.revespcardiol.org/en 相似文献40.
Sean M. Griffing Leopoldo Villegas Venkatachalam Udhayakumar 《Emerging infectious diseases》2014,20(10):1691-1696
Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891–1920, malaria was endemic to >600,000 km2 of this country; malaria death rates led to major population decreases during 1891–1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905–1945. Early reports of malaria eradication in Venezuela helped spark the world’s interest in global eradication. We describe early approaches to malaria epidemiology in Venezuela and how this country developed an efficient control program and an approach to eradication. Arnoldo Gabaldón was a key policy maker during this development process. He directed malaria control in Venezuela from the late 1930s to the end of the 1970s and contributed to malaria program planning of the World Health Organization. We discuss how his efforts helped reduce the incidence of malaria in Venezuela and how his approach diverged from World Health Organization guidelines. 相似文献