Marquezblum6353

Drug-induced hypersensitivity syndrome (DiHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction characterized by various symptoms skin rash, fever, lymph node enlargement and internal organ involvement, which starts within 2 weeks to 3 months after drug initiation. It is challenging to diagnose this syndrome due to the variety of cutaneous and visceral symptoms. Different mechanisms have been implicated in its development, including genetic susceptibility associated with human leucocyte antigen (HLA) loci, detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation, and reactivation of human herpes, including Epstein-Barr virus and human herpes virus (HHV)-6 and HHV-7. The most frequently reported causes of DiHS/DRESS are antiepileptic agents, allopurinol and sulfonamides. We report a case of DiHS/DRESS induced by second-line treatment for tuberculosis, prothionamide and para-aminosalicylic acid, and Epstein-Barr virus re-infection. Patch testing, which was performed in this case, is not fully standardized, but it can be helpful and a safe way to evaluate and diagnose DiHS/DRESS.Alpha-gal syndrome is an immunoglobulin E (IgE)-dependent allergy to galactose-α-1,3-galactose, resulting in a delayed anaphylactic reaction to red meat. The syndrome is causally linked to bites from ticks and associated with cross-reactivity to some drugs, e.g. cetuximab. Although cases of alpha-gal allergy have already been reported in a few European countries, to our best knowledge, no cases have been reported so far in Central-Eastern Europe. In the current report, we describe a case of alpha-gal syndrome diagnosed in Poland, to highlight the fact that it may occur in new geographic areas. Within three months, the described patient underwent five anaphylactic reactions with typical clinical manifestations. They developed a few hours after ingestion of red meat (pork, beef or mutton) and were preceded by tick bites. The level of specific IgE antibodies to alpha-gal reached 72.6 kAU/l, whereas the levels of specific IgE antibodies to other food allergens were within the reference range. As the onset of symptoms in this syndrome is usually delayed, numerous cases may be identified as idiopathic anaphylaxis, while early diagnosis is indispensable to avoid potentially life-threatening complications.Hypereosinophilic syndrome (HES) is a group of a rare diseases characterized by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a humanized, monoclonal antibody against interleukin 5 (IL-5) receptor α, which is expressed on human eosinophils. Here, we present the case of a patient with severe HES in whom treatment with benralizumab, an anti-IL-5 receptor monoclonal antibody, was initiated 6 months ago. Prior to benralizumab administration, the patient was treated with glucocorticoids (GS) and mepolizumab. However, instead of the applied treatment and normal level of peripheral eosinophils the patient presented with fluctuating lower respiratory tract symptoms and recurrent exacerbations of HES. Treatment with benralizumab (30 mg s.c. every 4-6 weeks) was started, resulting in significant improvement of respiratory signs and symptoms, normalization of eosinophil count and significant reduction of the methylprednisolone dose (after 5 doses of benralizumab administration). No substantial side effects have been noted during treatment and 6-month follow-up. We argue that in the severe and relapsing course of HES, rescue treatment with benralizumab should be taken into account, particularly in cases of relative inefficacy of GS and mepolizumab.Despite tremendous progress in the treatment of many cancer types, leading to a significant increase in survival, pancreatic ductal adenocarcinoma (PDAC) is still burdened with high mortality rates (5-year survival rate less then 9%) due to late diagnosis, aggressiveness, and a lack of more effective treatment methods. Early diagnosis and new therapeutic approaches based on the adaptive metabolism of the tumor in a nutrient-deficient environment are expected to improve the future treatment of PDAC patients. It was found that blocking selected metabolic pathways related to the local adaptive metabolic activity of pancreatic cancer cells, improving nutrient acquisition and metabolic crosstalk within the microenvironment to sustain proliferation, may inhibit cancer development, increase cancer cell death, and increase sensitivity to other forms of treatment (e.g., chemotherapy). The present review highlights selected metabolic signaling pathways and their regulators aimed at inhibiting the neoplastic process. NLRP3 inhibitor Particular attention is paid to the adaptive metabolism of pancreatic cancer, including fatty acids, autophagy, macropinocytosis, and deregulated cell-surface glycoproteins, which promotes cancer cell development in an oxygen-deficient and nutrient-poor environment.

Although

incubation of various cell types with neutrophil extracellular traps (NETs) is commonly used to investigate the influence of NETs on cellular function, it is unclear which human NET isolation and handling protocol is superior. The present study sought to assess the efficacy (yield and purity) and efficiency (time taken) of different available human NET isolation and handling protocols.

Neutrophils isolated from human blood were stimulated using phorbol 12-myristate 13-acetate. Four distinct protocols were used to isolate NETs, and the yield was quantified using fluorimetry.

Addition of the restriction enzyme AluI prior to centrifugation is unique to the most effective NET isolation method, yielding a NET concentration of 1077.22 ±229.04 ng/ml (at 523 nm) measured with PicoGreen. Immediate centrifugation to pellet neutrophils is unique to the most efficient method.

Balancing protocol efficacy and efficiency, the method incorporating centrifugation for 5 min at 450 × γ to pellet neutrophils is more than adequate.

Balancing protocol efficacy and efficiency, the method incorporating centrifugation for 5 min at 450 × γ to pellet neutrophils is more than adequate.Macrophage migration inhibitory factor (MIF) has been associated with the pathogenesis of several rheumatic diseases. In systemic sclerosis (SSc) it has been shown that MIF expression is dysregulated in serum and skin. However, the MIF receptor, CD74, has been poorly investigated and its potential role in the pathogenesis of SSc remains unknown. This study aimed to analyze mRNA, tissue, and serum expression of MIF and CD74 in patients with limited (lcSSc) and diffuse (dcSSc) systemic sclerosis. A case-control study in 20 SSc patients and 20 control subjects (CS) from southern México was conducted. MIF and CD74 mRNA expression levels were quantified by real-time PCR, MIF serum levels were measured by an ELISA kit, and MIF and its receptor CD74 were evaluated by immunohistochemistry of skin biopsies. MIF mRNA expression was significantly higher in CS than in SSc patients (p = 0.02), while CD74 showed no differences between patients and CS. MIF serum levels were similar between SSc patients and CS dcSSc = 3.82 ng/ml, lcSSc = 3.57 ng/ml, and CS = 3.28 ng/ml. In skin biopsies of SSc, MIF and CD74 were enhanced in keratinocytes, while they showed decreased expression in endothelial cells. On the other hand, the staining of CD74 was high in fibroblasts of dcSSc patients. Our findings show MIF and CD74 deregulation at the transcriptional and translational levels in SSc, which might be associated with the proinflammatory process leading to tissue remodeling and excessive fibrosis in SSc.The aim of this study was to assess the incidence of DNA aneuploidy in Polish children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and the relationship between aneuploidy and immunological phenotype, age, leukocyte count, S-phase fraction (SPF) and early response to induction chemotherapy assessed by the percentage of residual blast cells in bone marrow aspirates. The study group consisted of 267 patients. DNA content and immunophenotype were assessed in the bone marrow before treatment using multicolor flow cytometry (FC). DNA aneuploidy was detected in 50/267 (19%) patients. High hyperdiploidy was found to be associated with lower leukocyte count (p = 0.006) and common ALL immunophenotype. Flow cytometry analysis revealed that high hyperdiploid BCP-ALL patients showed significantly higher expression of CD9, CD20, CD22, CD58, CD66c, CD86 and CD123 antigens as compared to other groups of ploidy. In contrast, CD45 showed decreased expression. The percentage of leukemic blasts at diagnosis was lower in high hyperdiploid BCP-ALL cases than in diploid (79% vs. 85.7%, p = 0.001). The difference in minimal residual disease (MRD) levels on day 15 and 33 of induction therapy between analyzed groups was not significant. This study showed that high hyperdiploidy is associated with lower WBC count and specific immunological phenotype. Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BCP-ALL, before genetic tests results are available. Understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.Antimicrobial peptides (AMPs) are one of the primary mechanisms used by the skin in the early stages of immune defense. link2 AMPs have a broad antibacterial activity and also show antifungal and antiviral attributes. Various studies have also shown that levels of antimicrobial peptides change with the development of neoplasia. The aim of this paper is to assess the associations between the presence of basal cell carcinoma (BCC) and the plasma concentrations of cathelicidin and β-defensins (HBD1-3). We examined 108 patients (56 women, 52 men). The BCC group consisted of 49 patients with mean age 69.8 ±12.3 and the control group consisted of 59 participants with mean age 62.1 ±11.1. A statistical analysis of data was performed. The median serum concentration of cathelicidin was almost 3 times higher and the median concentration of HBD-2 more than 6 times higher in BCC patients than in the control group (p less then 0.001). The logistic regression model revealed in univariate analysis that patients who had a detected cathelicidin level above ~1500 pg/ml had 9.9× higher likelihood of having BCC identified in the histopathology in comparison with the control group. In patients who had a HBD-2 level above ~1.2 ng/ml the OR of having BCC identified in the histopathology was 12.6 (p less then 0.001). Elevated concentrations of cathelicidin and β-defensin 2 are associated with the presence of basal cell carcinoma. Additionally, the specificity of cathelicidin and β-defensin 2 in detecting basal cell carcinoma is high. However, it should be remembered that these factors are not specific only to this condition and further studies are needed.

Lupus nephritis (LN) is considered a serious manifestation of systemic lupus erythematosus (SLE). Therefore, a reliable non-invasive biomarker is a priority for monitoring renal involvement instead of the kidney biopsy. Interleukin 35 (IL-35) has an immunosuppressive and anti-inflammatory role in many autoimmune diseases. However, its role in LN still needs to be elucidated.

To evaluate urine and serum levels of IL-35 in SLE patients with LN and without nephritis identifying their potential as biomarkers of renal involvement.

Urine and serum levels of IL-35 were measured in 42 SLE patients, divided into 22 with LN and 20 without LN, and 20 matched healthy controls using enzyme-linked immunosorbent assay (ELISA). SLE disease activity was assessed for patients by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K).

Levels of serum and urine IL-35 were significantly higher (p < 0.001) in the LN group compared with those without LN and with controls. link3 In LN patients, a strong correlation (p < 0.