Radiocontrast Medium-Induced Kounis Syndrome in a Dialysis Patient: A Case Report.

Kounis syndrome is defined as the concurrence of acute coronary syndrome and a condition related to mast cell activation, including anaphylaxis and anaphylactoid. A 58-year-old male hemodialysis patient underwent enhanced computed tomography (CT) using the radiocontrast medium, iopamidol for investigation of a kidney tumor. Two minutes after the administration of iopamidol, he developed respiratory symptoms and chest pain. Five minutes after that, disturbed consciousness and low blood pressure were observed. On the other hand, he did not demonstrate urticaria and swelling of the skin. A 12-lead electrocardiogram (ECG) and echocardiogram suggested the presence of cardiac ischemia. Therefore, he was diagnosed with Kounis syndrome caused by radiocontrast media. Eighteen minutes after this, he received an intramuscular injection of adrenaline (0.3 mg), and his vital signs stabilized and his ECG, echocardiogram, and symptoms improved. Without undergoing emergency coronary angiography (CAG), he was hospitalized and closely monitored. The next day, his symptoms had not worsened, and he underwent hemodialysis at his local hospital. The allergen radiocontrast media could be injurious and not sufficiently excreted if administrated for patients on weekly hemodialysis with radiocontrast medium-induced Kounis syndrome manifesting; hence, indication for emergency CAG in radiocontrast medium-induced Kounis syndrome should be cautiously evaluated by close observation.

One-pot ligation of multiple peptide segments via N-terminal thiazolidine deprotection chemistry.

Peptide ligation chemistries have revolutionized the synthesis of proteins with site-specific modifications or proteomimetics through assembly of multiple peptide segments. In order to prepare polypeptide chains consisting of 100-150 amino acid residues or larger generally assembled from three or more peptide segments, iterative purification process that decreases the product yield is usually demanded. Accordingly, methodologies for one-pot peptide ligation that omit the purification steps of intermediate peptide segments have been vigorously developed so far to improve the efficiency of chemical protein synthesis. In this chapter, we first outline the concept and recent advances of one-pot peptide ligation strategies. Then, the practical guideline for the preparation of peptide segments for one-pot peptide ligation is described with an emphasis on diketopiperazine thioester synthesis. Finally, we disclose the explicit protocols for one-pot four segment ligation via repetitive deprotection of N-terminal thiazolidine by a 2-aminobenzamide type aldehyde scavenger.

Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease.

In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4+ T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.5 with neutralizing antibody for treating CeD may be plausible, yet using pan-HLA-DQ antibody risks affecting systemic immunity, while targeting selected gluten peptide:HLA-DQ2.5 complex (pHLA-DQ2.5) may be insufficient. Here we generate a TCR-like, neutralizing antibody (DONQ52) that broadly recognizes more than twenty-five distinct gluten pHLA-DQ2.5 through rabbit immunization with multi-epitope gluten pHLA-DQ2.5 and multidimensional optimization. Structural analyses show that the proline-rich and glutamine-rich motif of gluten epitopes critical for pathogenesis is flexibly recognized by multiple tyrosine residues present in the antibody paratope, implicating the mechanisms for the broad reactivity. In HLA-DQ2.5 transgenic mice, DONQ52 demonstrates favorable pharmacokinetics with high subcutaneous bioavailability, and blocks immunity to gluten while not affecting systemic immunity. Our results thus provide a rationale for clinical testing of DONQ52 in CeD.