Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells.

BACKGROUND: Allergic reactions to ß-lactams are among the most frequent causes of drug allergy and constitute an important clinical problem. Drug covalent binding to endogenous proteins (haptenation) is thought to be required for activation of the immune system. Nevertheless, neither the nature nor the role of the drug protein targets involved in this process is fully understood. Here, we aim to identify novel intracellular targets for haptenation by amoxicillin (AX) and their cellular fate. METHODS: We have treated B lymphocytes with either AX or a biotinylated analog (AX-B). The identification of protein targets for haptenation by AX has been approached by mass spectrometry and immunoaffinity techniques. In addition, intercellular communication mediated by the delivery of vesicles loaded with AX-B-protein adducts has been explored by microscopy techniques. RESULTS: We have observed a complex pattern of AX-haptenated proteins. Several novel targets for haptenation by AX in B lymphocytes have been identified. AX-haptenated proteins were detected in cell lysates and extracellularly, either as soluble proteins or in lymphocyte-derived extracellular vesicles. Interestingly, exosomes from AX-B-treated cells showed a positive biotin signal in electron microscopy. Moreover, they were internalized by endothelial cells, thus supporting their involvement in intercellular transfer of haptenated proteins. CONCLUSIONS: These results represent the first identification of AX-mediated haptenation of intracellular proteins. Moreover, they show that exosomes can constitute a novel vehicle for haptenated proteins, and raise the hypothesis that they could provide antigens for activation of the immune system during the allergic response.

Hypersensitivity reactions to ß-lactams: relevance of hapten-protein conjugates.

ß-Lactams (BL) are the drugs most frequently involved in allergic reactions. They are classified according to their chemical structure as penicillins, cephalosporins, monobactams, carbapenems, and clavams. All BL antibiotics have a BL ring that is fused to a 5-member or 6-member ring (except in monobactams) and has 1, 2 or 3 side chains (except in clavams). Differences in chemical structure mean that a wide range of BLs are recognized by the immune system, and patients may experience clinical reactions to one BL while tolerating others. Diagnosis is based on skin and in vitro testing, although both display low sensitivity, possibly because they are based on drugs or drug conjugates that are not optimally recognized by the immune system. BLs are haptens that need to bind to proteins covalently to elicit an immune response. These drugs have a high capacity to form covalent adducts with proteins through nucleophilic attack of amino groups in proteins on the BL ring. Allergenic determinants have been described for all BLs, although benzylpenicillin is the most widely studied. Moreover, formation of BL-protein adducts is selective, as we recently demonstrated for amoxicillin, which mainly modifies albumin, transferrin, and immunoglobulin heavy and light chains in human serum. Given the complexity of BL allergy, understanding the immunological mechanisms involved and optimization of diagnostic methods require multidisciplinary approaches that take into account the chemical structures of the drugs and the carrier molecules, as well as the patient immune response.

[Resolution with vascular endoprosthesis after first angioplasty failure in the treatment of post-transplant stenosis of the renal artery]. / Resolución con endoprótesis vascular tras primera angioplastia fallida en el tratamiento de la estenosis de la arteria renal post-trasplante.

We report a case of renal artery stenosis after a living transplant kidney, treated successfully with percutaneous transluminal angioplasty (PTA) and vascular endoprosthesis. PTA is the initial treatment of choice for most patients with high grade transplant renal artery stenosis. Surgical revascularization is indicated if PTA cannot be done or is unsuccessful.

Modified endoscopic left inguinal lymphadenectomy.

INTRODUCTION: Endoscopic Inguinal Lymphadenectomy is an evolution of laparoscopic surgery thanks to background in these techniques. This is a new technique and the indications in the field of penile tumors today are expanding. The technique aims at reducing the morbidity of the procedure without compromising the cancer control or reducing the template of the dissection. MATERIAL AND METHODS: We present the modified endoscopic inguinal lymphadenectomy in a 70 years-old male patient with penile melanoma and positive sentinel lymph node in left inguinal limb. Intraoperative data, pathology, post operatory evolution and oncological follow-up is described RESULTS: Operative time was 120 min. Nine lymph nodes were retrieved and none of then showed positivity at pathology. There were no complications. The drain was kept for five days. After 12 months of follow up, no signs of disease progression were noted. CONCLUSION: The endoscopic inguinal lymphadenectomy is feasible in clinical practice. New studies with a greater number of patients and long-term follow-up may confirm the oncological efficacy and possible lower morbidity of these new approach.