Diagnostic utility of basophil CD203c expression in ß-lactam allergy.

Background: A diagnosis of immunoglobulin E (IgE) mediated reactions to ß-lactam (BL) antibiotics is still challenging because of the limited availability of skin-prick test (SPT), and standardization issues, particularly with newer BLs, are still ongoing. Because encouraging data are increasingly emerging in the use of basophil activation tests in the diagnosis of IgE-mediated drug hypersensitivity reactions, in this study, we aimed to determine CD203c expression, a basophil surface marker, in the diagnosis of IgE-mediated hypersensitivity to BL antibiotics. Methods: This study included two groups of subjects. The first group (group 1) (n = 20) included patients with a diagnosis of IgE-mediated allergy to BLs as confirmed through STs or drug provocation tests, and the control group consisted of healthy volunteers (group 2) (n = 24). Expression of CD203c by flow cytometry was studied in samples stimulated by two different concentrations of six different BL antibiotics. A stimulation index ≥ 2 was considered a positive response. Results: The study groups had comparable age and sex distribution. In the entire group, the sensitivity and specificity of CD203c were 29.4% (5 out of 17) and 82.6% (19 out of 23), respectively. When considering the single reactors, two among four patients who were allergic to amoxicillin demonstrated upregulation of CD203c with amoxicillin, which makes 50% sensitivity. The specificity was 100%. Conclusion: Our data demonstrated that assessment of CD203c in the diagnosis of IgE-mediated reactions to BLs provided encouraging results, particularly with amoxicillin allergy. However, this finding needs to be verified in a larger number of cases.

Enhancing the Kinetic Stability of Polymeric Nanomicelles (PLGA) Using Nano-Montmorillonite for Effective Targeting of Cancer Tumors.

The toxic profile of chemical cross-linkers used in enhancing the stability of self-assembled nanomicelles made of amphiphilic polymeric materials hinders their use in clinical applications. This study was aimed to use the layered structure of Na-montmorillonite (MMT) as a stabilizer for nanomicelles made of poly(d,l-lactide-co-glycolide) (PLGA) amphiphilic polymer. The size of Na-MMT was reduced below 40 nm (nano-MMT) by processing in an attritor prior to its incorporation with PLGA. Hybrid PLGA nano-MMT (PM) nanoparticles (NPs) were prepared using dialysis nanoprecipitation. The size distribution was measured using dynamic light scattering (DLS). Loading 1250 µg of the model drug molecule curcumin to PM (PMC) resulted in obtaining 88 nm-sized particles, suitable for passive targeting of cancer tumors. The structure of nano-MMT and its position in PMC were investigated using FT-IR, differential scanning chalorimetry (DSC), XRF, XRD, ESEM, and EDAX assays, all of which showed the exfoliated structure of nano-MMT incorporated with both hydrophilic and hydrophobic blocks of PLGA. Curcumin was mutually loaded to PLGA and nano-MMT. This firm incorporation caused a serious extension in the release of curcumin from PMC compared to PLGA (PC). Fitting the release profile to different mathematical models showed the remarkable role of nano-MMT in surface modification of PLGA NPs. The ex vivo dynamic model showed the enhanced stability of PMC in simulated blood flow, while cytotoxicity assays showed that nano-MMT does not aggravate the good toxic profile of PLGA but improves the anticancer effect of payload. Nano-MMT could be used as an effective nontoxic stabilizer agent for self-assembled NPs.

Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke of undetermined cause is a major health issue because of its high frequency and clinical relevance. Histopathologic analysis of human thrombi, retrieved from stroke patients with large-vessel occlusion during mechanical thrombectomy, may provide information about underlying pathologies. This study examines the relationship between stroke causes and histological clot composition to identify specific patterns that might help to distinguish causes of cryptogenic stroke. METHODS: Thrombi of 145 consecutive stroke patients with large-vessel occlusion were collected during intracranial mechanical recanalization. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red and white blood cells and fibrin/platelets). These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the international Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The composition of thrombi from cardioembolic and noncardioembolic stroke patients differed significantly for all main thrombus components. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.009), less erythrocytes (P=0.003), and more leucocytes (P=0.035) than noncardioembolic thrombi. Cryptogenic strokes showed strong overlap with cardioembolic strokes but not with noncardioembolic strokes, in terms of both thrombus histology and interventional and clinical outcome parameters. CONCLUSIONS: Quantitative evaluation of thrombus composition may help to distinguish between different stroke causes. Our findings support the notion that the majority of cryptogenic strokes are cardioembolic.

Regulatory T Cells and Vitamin D Status in Children with Chronic Autoimmune Thyroiditis.

OBJECTIVE: It is suggested that vitamin D is one of the factors that can regulate the function of Treg cells. In this study, the relationships between Treg cells and vitamin D levels was investigated in pediatric chronic autoimmune thyroiditis (CAT) patients. METHODS: Thirty-two children with CAT and 24 healthy subjects were studied. FOXP3 expressing CD4+CD25+high Foxp3+T cells were identified as Treg cells. At diagnosis, 25-hydroxycholecalciferol (25OHD3) levels were determined in all patients. FOXP3 expression was measured before and after vitamin D replacement therapy in patients having low levels of 25OHD3. RESULTS: In the CAT patients, Treg cell levels did not differ from the control group, while the frequency of vitamin D deficiency was higher and FOXP3 molecule expression was lower. FOXP3 molecule expression significantly increased in CAT patients having vitamin D deficiency who were given vitamin D replacement. CONCLUSION: FOXP3 expression is decreased in pediatric CAT patients. This reduction seems to be associated with vitamin D levels. Vitamin D can play a role in enhancing natural Treg cell functions.

Serum IL-13 levels at diagnosis and remission in children with malignant lymphoma.

Interleukin (IL)-13 has been reported to have a role in the pathogenesis of lymphoma through recent molecular studies predominantly in adult patients. As malignant lymphomas in children differ from adult counterparts in terms of histology and response to treatment, we aimed to determine the serum IL-13 levels of patients with lymphoma; its relation with clinical-laboratory parameters and to look for any correlation of serum IL-13 levels with different prognostic factors in children. Twenty-eight patients with malignant lymphoma and 20 age-matched healthy controls were included in the study. The median serum IL-13 level at diagnosis (range 0.59-68 pg/ml, median 3.40 pg/ml) was higher than that in remission (range 0.14-12.2 pg/ml, median 1.60 pg/ml) in the HL group (p < 0.05). Remarkably, median serum IL-13 level of patients with nodular sclerosis at diagnosis was higher than those with mixed-cellularity (p < 0.05) and declined to normal limits during remission (p < 0.05). In Burkitt's lymphoma (BL) subgroup, the median (range 2.94-154 pg/ml, median 4.5 pg/ml) was high and declined to normal levels during remission (range 0.55-11.30 pg/ml, median 1.57 pg/ml) and the difference was significant (p < 0.05). In terms of prognostic factors, serum IL-13 levels were found to be associated with white blood cells counts only in HL group. Although the number of patients is limited in our study, we found that the serum IL-13 levels exhibit variances in different histopathologic groups. IL-13 might have a role in histopathogenesis of lymphoma, but seems to have no prognostic significance. Nevertheless, more molecular studies are needed to evaluate the pathogenesis of HL.

HLA-haploidentical transplantations for primary immunodeficiencies: a single-center experience.

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.