IgE-reactivity to seven Malassezia species

BACKGROUND: Malassezia yeasts play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). The revised genus Malassezia includes several species which all are natural habitants of the human skin. In this study, we evaluated the presence of immunoglobulin E (IgE) antibodies to different Malassezia spp. in AEDS patients to allow optimization of the characterization of the IgE antibody profile of IgE-associated AEDS. METHODS: Ninety-six adult patients, with a clinical diagnosis of AEDS, were included in the study. Seventeen of the patients had IgE antibodies to M. sympodialis, ATCC 42132 (m70 ImmunoCAP, Pharmacia, Diagnostic AB, Uppsala, Sweden). The IgE antibodies to seven Malassezia spp. were measured and inhibition immunoblotting was performed to investigate whether M. sympodialis contains all the allergen components present in the other Malassezia spp. RESULTS: Twenty per cent of 79 AEDS patients with a negative m70 ImmunoCAP test had IgE antibodies to at least one of the other six Malassezia spp. tested. Our inhibition studies indicated that Malassezia spp. to a great extent, share allergenic determinants. However, Malassezia species also contained species-specific allergens. CONCLUSION: The use of only one species of Malassezia is not sufficient to detect all patients IgE sensitized to Malassezia. To obtain an optimal allergen preparation both common allergenic components as well as species-specific allergens have to be considered.     

Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress,caspase-3 and NF-kB activity in BALB/c mice

Cyclophosphamide (CP), as a chemotherapeutic agent, with the generation of oxidative stress leads to testicular toxicity. Sinapic acid (SA), as a phenylpropanoid compound has therapeutic activities. This research was planned to evaluate the improving effects of SA versus testicular injury induced by CP. Forty-eight mice were distributed into six groups: untreated, SA (5 and 10 mg/kg), CP (200 mg/kg) and CP + SA (5 and 10 mg/kg). SA was administrated for 7 successive days and CP was administered intraperitoneally on the 3rd day of study. On the 10th day of research, testicular toxicity was evaluated by sperm parameters test, tissue (oxidative stress parameters) and serum (testosterone) biochemical, histopathological, and immunohistochemical (Caspase-3 and NF-kB) assays. The findings illustrated that CP induces atypical appearance in tissue structure, disorder of sperm parameters dysfunction, decrease of testosterone, oxidative stress (an increase of MDA and decrease of GSH), apoptosis and inflammation in testicular tissue. SA administration protected testis from oxidative stress and improves testosterone level and structure. Moreover, immunohistochemical findings also showed that SA can inhibit Caspase-3 and NF-kB activity. Data have confirmed that SA could protect testis structure and its functions against CP-induced injury through antioxidant, anti-inflammatory and anti-apoptotic activities.     

Identification of allergen components of the opportunistic yeast Pityrosporum orbiculare by monoclonal antibodies

The yeast Pityrosporum orbiculare (P. orbiculare) is a member of the normal human cutaneous flora, but it is also associated with several clinical manifestations of the skin. We have previously observed IgE-binding components in P. orbiculare extracts, using sera from patients with atopic dermatitis. In the present study, we raised several monoclonal antibodies (MoAbs) against P. orbiculare to characterize some of its antigens, and used Candida albicans (C. albicans) as a control. We obtained several IgGI MoAbs which specifically recognized P. orbiculare in ELISA. Two of these were selected for immunoblotting studies on P. orbiculare and two patterns of reactivity emerged. Firstly, one MoAb showed a distinct band at a molecular mass of 67 kDa. In the second pattern, a sharp band at about 37 kDa appeared. In contrast, the IgM antibodies raised reacted with a 14-kDa component; but they reacted with C. albicans in addition to P. orbiculare The IgGI antibodies seemed to react with proteins, as their ability to react in ELISA with extract pretreated with protease was greatly reduced. In contrast, IgM MoAbs were much less affected, suggesting that they recognized nonprotein components. To determine whether these MoAbs-binding components were also recognized by human IgE, we adopted a radioimmunoassay (RIA) using the MoAbs as catcher antibodies. Both the 67-kDa and the 37-kDa components were IgE-binding proteins. P. orbicular RAST positive sera were scored as positive in the RIA, whereas the control serum was not.     

Passive immunisation against Pseudomonas aeruginosa recombinant flagellin in an experimental model of burn wound sepsis

Background

This study was aimed to investigate whether anti-recombinant flagellin type A (anti r-fla-A) immunoglobulin G (IgG) provides protection in a mouse burn model of infection, and to determine the role of anti r-fla-A IgG as an opsonin and motility inhibitor in local and systemic infections.

Methods

Following the preparation of r-flagellin type A, rabbit polyclonal IgG was prepared. Specificity of anti r-flagellin for r-flagellin was evaluated by immunoblot analysis. After burn and challenge, mortality rate was screened in the mice treated with anti r-fla-A IgG. The ability of antiserum to promote phagocytosis of bacteria was assessed by the opsonophagocytosis testing. Functional activity of anti r-fla-A IgG was assessed in vitro by motility inhibition assay. Bacterial quantity in skin and internal organs was evaluated to study systemic infection.

Results

In vivo administration of anti r-fla-A IgG resulted in a significant improvement in survival in mice infected by a homologous strain of Pseudomonas aeruginosa from 16.6% to 75% compared with the control IgG. By contrast, this rate was 33.3% in the mice infected by the heterologous strain, PAO1 (type B flagellated strain). Protection was improved by giving a second treatment of r-flagellin antisera at 24-h post-burn and infection. Furthermore, anti r-fla-A IgG enhanced considerably the phagocytosis of the homologous strain but it was slight in the heterologous strain. The antiserum against r-flagellin type A was able to inhibit the motility of the PAK strain (type A flagellated strain), but slight inhibition was observed against PAO1. Meanwhile, anti r-fla-A IgG inhibited the systemic spread of PAK strain from the site of infection to internal organs.

Conclusion

In this study, passive immunisation with anti r-fla-A IgG was active against a homologous strain of infecting P. aeruginosa, but lost most of its efficiency against a heterologous strain. Therefore, passive treatment with anti r-fla-A IgG might protect burned mice against local and systemic infection of P. aeruginosa.     

Efficient IL-2R signaling differentially affects the stability,function, and composition of the regulatory T-cell pool

Signaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25^Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25^Y129H Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with the maintenance, heterogeneity, and suppressive function of the Treg cell pool.     

Acute idiopathic frosted branch angiitis.

This is a case of acute idiopathic frosted branch angiitis in a 4-year-old African American girl with history of sickle cell trait. She developed bilateral, subacute vision loss attributed to acute idiopathic frosted branch angiitis and was treated with systemic corticosteroids with a good recovery of vision. Acute idiopathic frosted branch angiitis is a rare disease, usually with a good prognosis. This is, to our knowledge, the 10th reported case in the United States.     

Cutaneous adverse reactions to hydroxyurea in patients with intermediate thalassemia

Although the cutaneous effects of hydroxyurea have been described for patients with sickle cell anemia, myeloproliferative disorders, and psoriasis, there are no reports of cutaneous adverse effects from hydroxyurea when used for patients with intermediate thalassemia. Therefore 43 patients with intermediate thalassemia treated with hydroxyurea were examined by a dermatologist, and pertinent cutaneous findings were recorded. These patients had received hydroxyurea for a mean of 15.5 months. Nineteen had cutaneous hyperpigmentation, eight had xerosis, and three were found to have one cafe au lait macule each. Eleven patients had nail abnormalities, including nail ridging, partial leukonychia, and longitudinal melanonychia. There were no cases of leg ulceration. It was concluded that the risk of developing leg ulcers and pigmentary disorders appears to be related to the underlying disease being treated, as well as to a patient's age, gender, and pigmentation.     

Effects of family conversation on health care practices in Ethiopia: a propensity score matched analysis

Background

Maternal and newborn mortality rates in Ethiopia are among the highest in sub-Saharan Africa. The majority of deaths take place during childbirth or within the following 48 h. Therefore, ensuring facility deliveries with emergency obstetric and newborn care services available and immediate postnatal follow-up are key strategies to increase survival. In early 2014, the Family Conversation was implemented in 115 rural districts in Ethiopia, covering about 17 million people. It aimed to reduce maternal and newborn mortality by promoting institutional delivery, early postnatal care and immediate newborn care practices. More than 6000 Health Extension Workers were trained to initiate home-based Family Conversations with pregnant women and key household decision-makers. These conversations included discussions on birth preparedness, postpartum and newborn care needs to engage key household stakeholders in supporting women during their pregnancy, labor and postpartum periods. This paper examines the effects of the Family Conversation strategy on maternal and neonatal care practices.

Methods

We used cross-sectional data from a representative sample of 4684 women with children aged 0–11 months from 115 districts collected between December 2014 and January 2015. We compared intrapartum and newborn care practices related to the most recent childbirth, between those who reported having participated in a Family Conversation during pregnancy, and those who had not. Propensity score matched analysis was used to estimate average treatment effects of the Family Conversation strategy on intrapartum and newborn care practices, including institutional delivery, early postnatal and immediate breastfeeding.

Results

About 17% of the respondents reported having had a Family Conversation during their last pregnancy. Average treatment effects of 7, 12, 9 and 16 percentage-points respectively were found for institutional deliveries, early postnatal care, clean cord care and thermal care of the newborn (p < 0.05).

Conclusion

We found evidence that Family Conversation, and specifically the involvement of household members who were major decision-makers, was associated with better intrapartum and newborn care practices. This study adds to the evidence base that involving husbands and mothers-in-law, as well as pregnant women, in behavior change communication interventions could be critical for improving maternal and newborn care and therewith lowering mortality rates.