ARTICLE Download: 25| View: 190| Comments: 0
Subject: Medicine & Pharmacology, Allergology Keywords: mast cell; tryptase; chymase; serine protease; human chymase; cleavage specificity; cytokine; chemokine; th2
Online: 26 September 2019 (12:00:55 CEST)
Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is the tryptase. To look deeper into the question their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting such regulatory functions may involve controlling excessive TH2 mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15 and IL-21 indicating a potent negative feedback loop on TH2 immunity.
Sun, 11 August 2019
ARTICLE Download: 30| View: 163| Comments: 0 | doi:10.20944/preprints201908.0125.v1
Subject: Medicine & Pharmacology, Allergology Keywords: allergy; IgE; IgG2c; anaphylaxis; dendritic cells
Online: 11 August 2019 (07:32:32 CEST)
Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Experimentally, sensitization with alum adjuvant favors IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying TLR-regulation of immunoglobulin production are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. We show that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited when sensitization to OVA was performed in the presence of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This contrasts with previous reports of in vitro regulation IgE where CpG acted directly on B cells via MyD88 pathway. In addition, CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signaling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.
Mon, 29 July 2019
ARTICLE Download: 80| View: 230| Comments: 0 | doi:10.20944/preprints201907.0328.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Dengue virus (DENV); geographical information systems (GIS); public health; travelers; arboviruses; infectious diseases epidemiology; Honduras
Online: 29 July 2019 (04:36:31 CEST)
Background: After serious epidemics of chikungunya (CHIKV) and Zika (ZIKV) in the Americas, dengue (DENV) have reemerged in most countries. We analyzed the incidence, incidence rates, and evolution of DENV cases in Honduras from 2015-2018 and the ongoing 2019 epidemic. Methods: Using epidemiological weeks (EW) surveillance data on the DENV in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental, and municipal levels. Results: From 1 January 2016 to 21 July 2019, a total of 109,557 cases of DENV were reported, 28,603 in 2019, for an incidence rate of 312.32 cases/100,000 pop this year; 0.13% laboratory-confirmed. The highest peak was reached on the EW 28°, 2019 (5,299 cases; 57.89 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortes (8,404 cases, 479.68 cases/100,000 pop in 2019). Discussion: The pattern and evolution of DENV epidemic in 2019 in Honduras has been similar to that which occurred for in 2015. As previously reported, this epidemic involved the north and central areas of the country predominantly, reaching municipality incidences there >1,000 cases/100,000 pop (1%). Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.
Wed, 5 June 2019
ARTICLE Download: 65| View: 272| Comments: 0 | doi:10.20944/preprints201906.0040.v1
Subject: Medicine & Pharmacology, Allergology Keywords: acid, air pollution, allergic diseases, Ca2+, mechanisms of allergy, multimorbidity, nonallergic, nonatopic
Online: 5 June 2019 (10:42:43 CEST)
Inflammatory allergic and nonallergic respiratory pathologies often co-exist. The root cause is not clear. This paper demonstrates that it is ascribable to protons (H+) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation and bronchospasm; b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic responses. Therefore, the intracellular acidification and consequent Ca2+ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may be the causal mechanism of the multimorbidity of these diseases, and environmental acidity may contribute to their spread.
Tue, 28 May 2019
ARTICLE Download: 34| View: 128| Comments: 0 | doi:10.20944/preprints201905.0323.v1
Subject: Medicine & Pharmacology, Allergology Keywords: black carbon; emergency department visits; allergic rhinitis; allergic asthma; case-crossover design; Serbia
Online: 28 May 2019 (09:50:24 CEST)
Background and Objectives: Many epidemiological studies have shown a positive association between black carbon (BC) and the exacerbation of allergic rhinitis and allergic asthma. However, none of the studies in Serbia examined this relationship so far. The aim of this study was to examine the associations between BC and emergency department (ED) visits for allergic rhinitis and allergic asthma in the Užice region of Serbia. Materials and Methods: A time-stratified case-crossover design was applied to 523 ED visits for allergic rhinitis and asthma exacerbation that occurred in the Užice region of Serbia between 2012−2014. Data regarding ED visits were routinely collected in the Health Center of Užice. The daily average concentrations of BC were measured by automatic ambient air quality monitoring stations. Odds ratios and their corresponding 95% confidence intervals were estimated using conditional logistic regression adjusted for the potential confounding influence of weather variables (temperature, humidity, and air pressure). Results: Statistically significant associations were observed between ED visits for allergic rhinitis and 2-day lagged exposure to BC (OR = 3.20; CI = 1.00−10.18; p < 0.05) and allergic asthma and 3-day lagged exposure to BC (OR = 3.23; CI = 1.05−9.95; p < 0.05). Conclusion: Exposure to BC in the Užice region increases the risk of ED visits for allergic rhinitis and asthma, particularly during the heating season.
Wed, 29 August 2018
REVIEW Download: 655| View: 164| Comments: 0 | doi:10.20944/preprints201808.0487.v1
Subject: Medicine & Pharmacology, Allergology Keywords: sex; anxiety disorders; 5-HT; tryptophan; immune system; inflammation
Online: 29 August 2018 (08:58:26 CEST)
Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.
Wed, 4 April 2018
REVIEW Download: 281| View: 1233| Comments: 3 | doi:10.20944/preprints201804.0052.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Th2 immunity; food allergy; allergic sensitization; allergens; alarmins; initiation of allergy; IgE; allergic disease
Online: 4 April 2018 (07:35:35 CEST)
In contrast to Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. Part of the difficulty in identifying universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Indeed, such responses are launched towards harmful macroscopic parasites and noxious substances such as venoms but also against largely innocuous allergens. This suggests that the canonical understanding about sensing and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters that either activate the immune system or lower its threshold activation are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that shapes an adaptive Th2 response.
Sat, 15 July 2017
ARTICLE Download: 593| View: 643| Comments: 0 | doi:10.20944/preprints201707.0039.v1
Subject: Medicine & Pharmacology, Allergology Keywords: diet, gut microbiota, epigenetics, inflammatory bowel diseases
Online: 15 July 2017 (00:46:37 CEST)
Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.
Tue, 25 April 2017
ARTICLE Download: 610| View: 628| Comments: 0 | doi:10.20944/preprints201704.0156.v1
Subject: Medicine & Pharmacology, Allergology Keywords: ranolazine; atrial fibrillation; prevention; pharmacological cardioversion; meta-analysis
Online: 25 April 2017 (07:48:26 CEST)
Introduction Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation.Methods Both randomized controlled trials (RCTs) and non randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy , or assigned to placebo. Efficacy outcomes were the risk of new- onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence(≤ 48 h)of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension.Results Ten studies ( 8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR= 0.60; 95% CI: 0.43–0.83; p = 0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting(CABG) surgery (RR= 0.39; 95% CI: 0.18-0.83; p=0.02) when compared to non- postoperative AF (RR= 0.76; 95% CI: 0.63-0.92; p=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05–1.33; p = 0.004) and significantly decreased the time to cardioversion(SMD= −10.35 h; 95% CI: −18.13 hours to − 2.57 hours; p < 0.001). Overall risks of death, adverse events, and QTc prolongation were shown to be similar in the comparison between patients treated with ranolazine and controls. Conclusions Ranolazine given orally at appropriate doses showed the property to significantly quicken the conversion of AF to sinus rhythm when combined with the iv amiodarone, compared to iv amiodarone alone . Furthermore, in patients in sinus rhythm, ranolazine proved to reduce the frequency of new onset AF as well as of its recurrences, especially in patients undergone CABG surgery, known to be at high risk of developing postoperative AF. In addition, ranolazine use seems to be safe and associated with relatively few adverse events.
Mon, 3 April 2017
REVIEW Download: 466| View: 531| Comments: 0 | doi:10.20944/preprints201704.0006.v1
Subject: Medicine & Pharmacology, Allergology Keywords: fibromyalgia; drugs; NMDA receptor; ketamine; memantine.
Online: 3 April 2017 (16:43:53 CEST)
Activation of the N-methyl D-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly that which relates pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer –term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.
Wed, 28 December 2016
REVIEW Download: 710| View: 589| Comments: 0 | doi:10.20944/preprints201612.0132.v1
Subject: Medicine & Pharmacology, Allergology Keywords: wheat allergy; specific immunoglobulin E; children; gluten-related disorders
Online: 28 December 2016 (10:37:23 CET)
IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.