Background: Immunosuppressant blood levels should be measured at regular periods in order to keep them within the therapeutic index. Although LC-MS/MS is preferred as a reliable method, some molecules like radiopaque agents in blood matrix may lead to false results. The aim of this study is to investigate the effect of seven different radiopaque agents on immunosuppressant drugs. Methods: Seven different radiopaque agents were added into control materials containing tacrolimus, everolimus, sirolimus and cyclosporine A drugs. Measurements were performed by LC-MS/MS instrument. The amount of deviations from target values were calculated. Results: Immunosuppressant blood levels significantly changed after the administration of radiopaque agents. Seven different radiopaque products led to false negative results in tacrolimus and cyclosporine A levels at a rate of 19.77% to 44.45%. The smallest deviations were seen in everolimus levels with administration of RM6 (gadodiamide) and in sirolimus levels with RM1 (gadobutrol) at rates of 4.04% and 2.11%, respectively. The highest deviations were observed with RM3 (iohexol) administration in everolimus and sirolimus levels at rates of 153.72% and 171.41%, respectively. Conclusions: False immunosuppressant results associated with radiopaque agents may result in organ rejection. Preferring radiopaque agents that cause the least interference risk is important to reduce the organ rejection risk. However, the least risky method is to obtain samples for drug levels before contrast-enhanced imaging.

Aims: To review canine rabies, mass parental vaccination, human post-exposure prophylaxis, gene therapy and costs for fighting rabies. Place and Duration of Study: Department of Animal Science – Other, Nelwan Institution for Human Resource Development, Indonesia, between December 2017 and March 2018. Methodology: The author searched the Pubmed Database at NCBI for articles on rabies disease published between 2007 and 2018. All articles were open access and in English. For rabies virus examination, Seller’s test was used. In this article, references written by the author and other relevant publications were included. The author reviewed a rabies dog case kept at Nelwan Institution for Human Resource Development. Results: The dog showed clinical signs such as inappetance, urinary frequency and soaking in a small, juicy drain. Currently, to treat rabies, no drugs are available. For rabies prevention, vaccination is the best way. To eradicate rabies, mass vaccination in dogs, post-exposure prophylaxis, and gene therapy should be used. Fort rabies disease eradication, minimum of 70% of the dog population should receive the vaccination. In addition, humans with category II exposure should receive a rabies vaccine and rabies immunoglobulin. Conclusion: To eradicate rabies, vaccinations are required. In addition, gene therapy can eliminate rabies from the infected neurons by using rAAV-N796. CRISPR/Cas9 system in combination with the MMEJ-based method. Furthermore, mass parental vaccination, post-exposure prophylaxis, and gene therapy can reduce costs in controlling rabies disease.

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.

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

Babchi (Psoralea corylifolia) oil is an important essential oil used in several traditional medicines to cure various disorders. This phytotherapeutic agent possesses number of pharmacological activities including antibacterial, antifungal, antioxidant, anti-inflammatory, immunomodulatory and antitumor. However, volatile nature, poor stability and solubility of babchi oil (BO) restrict its pharmaceutical applications. Hence, the aim of the present work was to encapsulate this oil in β-cyclodextrin nanosponges (NS) in order to overcome above limitations. To fabricate nanosponges, β-cyclodextrin was crosslinked with diphenyl carbonate in different molar ratios viz.1:2, 1:4, 1:6, 1:8 and 1:10. The blank nanosponges were loaded with babchi oil using freeze-drying method. Particle size of the babchi oil loaded nanosponges was found to lie between 200-500 nm, with low polydispersity index. Further, zeta potential, Fourier transform infrared spectroscopy, X-ray diffraction, thermal analysis and electron microscopy were carried out for characterization of babchi oil nanosponges. Results obtained from spectral analysis ascertained the formation of inclusion complexes. Additionally, solubilisation efficiency of the babchi oil was checked in distilled water and found enhanced by 4.95 times with optimized β-cyclodextrin nanosponges. The cytotoxicity study was carried out by MTT assay using HaCaT cell lines. A significant improvement in photostability of essential oil was also observed by inclusion in nanosponges. Lastly, the optimized formulation was tested for antibacterial activity using Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Hence, encapsulation of BO in nanosponges resulted in efficacious carrier system in terms of solubility, photostability as well as safety of this oil along with handling benefits.

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.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

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.

Background: Meniere's disease (MD) has been recently linked to gluten assumption. Approximately 75% of MD patients show positive skin test to food and about 50% of the positive responses are specific to the gliadin acid extract fraction. Aim of this study was to investigate the humoral immune responses to wheat antigens and related autoantigens in MD patients. Methods. We assessed the reactivity of sera from 28 patients with definite MD and 100 healthy controls against a repertoire of 51 antigens usually associated with immune reaction to gluten. Results. MD patients showed an increase of anti-wheat IgA, anti-cerebellar peptide IgA and anti-glutamic acid decarboxylase (GAD) 65 IgM compared to healthy controls. In particular, the increase of anti-wheat IgA and GAD 65 IgM has been confirmed in a subgroup of MD patients symptomatically responding to a gluten free diet (GFD). Conclusion. In MD patients, an increase of the antibody production against gluten biomarkers was observed; in particular, anti-wheat IgA seems to be associated to clinical response to GFD.

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.

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.

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.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.