Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

Increasing evidence suggests that human epidermal melanocytes play an important role in the skin immune system; however, a role of their pigmentation in immune and inflammatory responses is poorly examined. In the study, the expression of Toll‐like receptor 4 (TLR4) and inflammatory cytokines and chemokines by cultured normal melanocytes derived from lightly and darkly pigmented skin was investigated after cell stimulation with lipopolysaccharide (LPS). The basal TLR4 mRNA level in heavily pigmented cells was higher as compared to their lightly pigmented counterparts. Melanocyte exposure to LPS upregulated the expression of TLR4 mRNA and enhanced the DNA‐binding activity of NF‐κB p50 and p65. We found substantial differences in the LPS‐stimulated expression of numerous genes encoding inflammatory cytokines and chemokines between the cells with various melanin contents. In lightly pigmented melanocytes, the most significantly upregulated genes were nicotinamide phosphoribosyltransferase (NAMPT/visfatin), the chemokines CCL2 and CCL20, and IL6, while the genes for CXCL12, IL‐16 and the chemokine receptor CCR4 were the most significantly upregulated in heavily pigmented cells. Moreover, the lightly pigmented melanocytes secreted much more NAMPT, CCL2 and IL‐6. The results of our study suggest modulatory effect of melanogenesis on the immune properties of normal epidermal melanocytes.     

Congenital toxoplasmosis—prenatal aspects of Toxoplasma gondii infection

Toxoplasma gondii (T. gondii) is the cause of toxoplasmosis. Primary infection in an immunocompetent person is usually asymptomatic. Serological surveys demonstrate that world-wide exposure to T. gondii is high (30% in US and 50–80% in Europe). Vertical transmission from a recently infected pregnant woman to her fetus may lead to congenital toxoplasmosis. The risk of such transmission increases as primary maternal infection occurs later in pregnancy. However, consequences for the fetus are more severe with transmission closer to conception. The timing of maternal primary infection is, therefore, critically linked to the clinical manifestations of the infection. Fetal infection may result in natural abortion. Often, no apparent symptoms are observed at birth and complications develop only later in life. The laboratory methods of assessing fetal risk of T. gondii infection are serology and direct tests.Screening programs for women at childbearing age or of the newborn, as well as education of the public regarding infection prevention, proved to be cost-effective and reduce the rate of infection.The impact of antiparasytic therapy on vertical transmission from mother to fetus is still controversial. However, specific therapy is recommended to be initiated as soon as infection is diagnosed.     

Imaging of non-parabolic velocity profiles in converging flow with optical coherence tomography

The optical coherence tomography method was explored for two-dimensional flow mapping of a highly scattering fluid in flow with complex geometry. Converging flow (capillary entry) with 4:1 constriction was used for demonstration of non-invasive and remote methods of mapping varying velocity profiles. Downstream of the geometry was scanned with approximately 10 x 10 x 10 microm3 spatial resolution and structural imaging of the lumen and images of one particular velocity were acquired. Stable concave, blunted and parabolic profiles are obtained at different distances of the inlet length. Application of the technique for the blood circulation is also discussed.     

Complex modulation of human motor cortex excitability by the specific serotonin re-uptake inhibitor sertraline

Monoamines are powerful modulators of cortical function. Serotonin has complex excitatory and inhibitory effects on animal cortex. Here, the effects of a single oral dose (100mg) of the selective serotonin re-uptake inhibitor sertraline on human motor cortex excitability were investigated in healthy subjects. Transcranial magnetic stimulation was used to test motor threshold, motor evoked potential intensity curve, cortical silent period, paired-pulse inhibition and facilitation and I-wave facilitation. Sertraline resulted in a steeper intensity curve and in depressed paired-pulse facilitation (PPF). All other measures and spinal and neuromuscular excitability remained unaffected. The steeper intensity curve points to an increased excitability of the cortico-spinal neurone, while the depressed PPF suggests an enhanced control of the cortico-spinal neurone by inhibitory interneurones. These features may improve the signal-to-noise ratio of output cells in human motor cortex.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

     

Polymerized tree pollen antigens

Aqueous extracts of tree pollen were partially purified and polymerized with methods previously established for preparation of ragweed and grass polymers. The polymerized tree preparations were antigenic as demonstrated by ability to elicit immediate-type skin reactivity in humans and to induce an immune response in rabbits. The polymerized tree antigen was 100- to 10,000-fold less skin reactive than monomer tree antigen in tree pollen-sensitive patients but both preparations had similar antigenicity in rabbits. These results demonstrate that polymerized tree antigens can be prepared and should have the therapeutic potential already demonstrated for polymerized ragweed preparations.