ARTICLE Download: 108| View: 225| Comments: 0 | doi:10.20944/preprints202004.0102.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Medicinal plants; Mpro; 3CLpro; spike (S) glycoprotein; COVID-19; SARS-CoV-2
Online: 7 April 2020 (12:08:57 CEST)
Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19.
Mon, 9 March 2020
CASE REPORT Download: 416| View: 909| Comments: 2
Online: 9 March 2020 (10:34:58 CET)
An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.
Mon, 2 March 2020
ARTICLE Download: 637| View: 1246| Comments: 0 | doi:10.20944/preprints202003.0024.v1
Subject: Medicine & Pharmacology, Allergology Keywords: SARS-CoV-2; nonstructural proteins (NSP); NSP12; NSP7; NSP8; virtual screening; inhibitor
Online: 2 March 2020 (03:11:33 CET)
A novel coronavirus (SARS-CoV-2) that is initially found to trigger human severe respiratory illness in Wuhan City of China in 2019, has killed 2,718 people in China by February 26, 2020, and which has been recognized as a public health emergency of international concern as well. And the virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS-Cov-2 infection. NSP12-NSP7-NSP8 complex of SARS-CoV-2, essential for viral replication and transcription, is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7-NSP8 complex (PDB ID: 6NUR) structure of SARS, two homologous models were established for virtual screening in the present study, namely NSP12-NSP7 interface model and NSP12-NSP8 interface model. Seven compounds (Saquinavir, Tipranavir, Lonafarnib, Tegobuvir, Olysio, Filibuvir, and Cepharanthine) were selected for binding free energy calculations based on virtual screening and docking scores. All seven compounds can combine well with NSP12-NSP7-NSP8 in the homologous model, providing drug candidates for the treatment and prevention of SARS-CoV-2.
Thu, 27 February 2020
CASE REPORT Download: 173| View: 428| Comments: 0
Online: 27 February 2020 (12:05:30 CET)
An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to February 21, 2020, at least 75570 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.
Wed, 26 February 2020
CASE REPORT Download: 2892| View: 4943| Comments: 1
Subject: Medicine & Pharmacology, Allergology Keywords: Coronavirus; SARS-CoV-2; COVID-19; Thalidomide; pneumonia
Online: 26 February 2020 (12:31:47 CET)
A novel coronavirus strain (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in December 2019 and can cause acute respiratory distress syndrome and death. However, there are only limited therapy choices and no vaccine for SARS-CoV-2 is currently available. Here we report about a case of a SARS-CoV-2 caused pneumonia successfully treated with thalidomide. Thalidomide is an immunomodulatory and anti-inflammatory agent and was combined with a low-dose glucocorticoid. We suggest, that the effects of thalidomide might be related to regulating immunity, inhibiting the inflammatory cytokine surge, alleviating anxiety to reduce oxygen consumption, relieving vomit and lung exudation.
Fri, 24 January 2020
REVIEW Download: 63| View: 137| Comments: 0 | doi:10.20944/preprints202001.0277.v1
Subject: Medicine & Pharmacology, Allergology Keywords: statin; arthroplasty; revision; failure; osseointegration; osteolysis; loosening
Online: 24 January 2020 (10:54:30 CET)
Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognised disease limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and the proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol modulating drugs widely used for cardiovascular risk reduction, which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. Epidemiological and experimental research have demonstrated that there may be a biological and population-wide effect of statins in reducing the risk of revision arthroplasty. This work summarises the current breadth of evidence for this phenomenon including in vitro, in vivo and epidemiological research.
Tue, 29 October 2019
REVIEW Download: 76| View: 69| Comments: 0 | doi:10.20944/preprints201910.0331.v1
Subject: Medicine & Pharmacology, Allergology Keywords: allergic reaction; CD158d; IgE receptor; KIR2DL4; KIT; mast cell; pregnancy
Online: 29 October 2019 (10:26:12 CET)
Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK-cell-specific protein but its expression has also been demonstrated in human mast cells. Mast cells are involved in allergic reactions via their KIT-mediated and IgE receptor-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), a human mast cell line (LAD2), and non-neoplastic mast cells, including pathological specimens. An agonistic antibody against KIR2DL4 negatively regulates the KIT- and IgE-receptor-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion from these cells of leukemia inhibitory factor and serine proteases, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.
Wed, 23 October 2019
ARTICLE Download: 95| View: 89| Comments: 0 | doi:10.20944/preprints201910.0270.v1
Subject: Medicine & Pharmacology, Allergology Keywords: apelin; galectin-3; Preeclampsia; insulin resistance; lipid profile
Online: 23 October 2019 (17:31:26 CEST)
Preeclampsia (PE) is a common pregnancy complication. It is associated with high maternal morbidity and mortality rates and intrauterine foetal growth restriction. This condition is characterised by high blood pressure and urinary protein levels. Apelin and galectin-3 (Gal- 3) are peptides involved in the regulation of body fluid homeostasis, inflammation and cardiovascular functions. This study aimed to determine the correlations amongst serum apelin and Gal-3 levels and insulin resistance (IR) in women with PE. Sixty patients with PE and 30 healthy controls participated in this study. The PE group had significantly lower apelin levels (p < 0.01) and higher Gal-3 levels (p < 0.05) than the control group. The PE group had higher serum glucose levels and β-cell functions than the control group. Moreover, patients with PE exhibited dyslipidaemia. Correlation analysis indicated that apelin and Gal-3 levels were not significantly correlated. Moreover, no correlation existed between the apelin levels and any measured parameters of the PE group. In conclusion, the elevations in serum Gal-3 levels with increments in IR-related parameters and lipid profiles reflect the possible contribution of Gal-3 to the harmful effects of IR and dyslipidemia levels on women with PE.
Thu, 26 September 2019
ARTICLE Download: 69| View: 223| 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: 83| View: 205| 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: 156| View: 319| 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: 109| View: 322| 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: 73| View: 155| 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: 864| View: 194| 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: 322| View: 1284| 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: 648| View: 674| 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: 682| View: 657| 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: 522| View: 549| 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: 763| View: 611| 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.