Development of a Python-based electron ionization mass spectrometry amino acid and peptide fragment prediction model.

The increased fragmentation caused by harsher ionization methods used during mass spectrometry such as electron ionization can make interpreting the mass spectra of peptides difficult. Therefore, the development of tools to aid in this spectral analysis is important in utilizing these harsher ionization methods to study peptides, as these tools may be more accessible to some researchers. We have compiled fragmentation mechanisms described in the literature, confirmed them experimentally, and used them to create a Python-based fragment prediction model for peptides analyzed under direct exposure probe electron ionization mass spectrometry. This initial model has been tested using single amino acids as well as targeted libraries of short peptides. It was found that the model does well in predicting fragments of peptides composed of amino acids for which the model is well-defined, but several cases where additional mechanistic information needs to be incorporated have been identified.

Aripiprazole-induced atrial fibrillation in a patient with concomitant risk factors.

Aripiprazole is an atypical antipsychotic drug with a polypharmacological mechanism of action and a favorable tolerability profile. Its major indications are schizophrenia and mania in adults and adolescents. Here we present the case of a 43-year-old Caucasian man with schizophrenia who developed atrial fibrillation (AF) after starting aripiprazole treatment. Prior to this treatment, he had never received any antipsychotic drugs. On admission to our inpatient unit, he showed severe psychotic symptoms and was started on aripiprazole with a rapid titration regimen (15 mg on the first day and then 15 mg twice daily thereafter) in combination with lorazepam (2.5 mg thrice a day). On the third day, the patient exhibited vomiting and an irregular pulse. An electrocardiogram (ECG) revealed new-onset AF with rapid ventricular response. Aripiprazole was discontinued and cardioversion was obtained with intravenous amiodarone. A different antipsychotic treatment was thus started (perphenazine 12 mg/d), which led to symptom remission without any relevant adverse effects. During the 2-year follow-up observation, neither psychotic symptoms nor ECG abnormalities were detected. Besides aripiprazole, other co-occurring factors might have contributed to the onset of AF in our patient, namely hypertension, low-grade diastolic dysfunction, chronic inflammatory disease, CYP2D6 polymorphism, corticosteroid and antiulcer treatment, and a family loading for myocardial infarction. In conclusion, our case study suggests that although aripiprazole has fewer cardiovascular effects than other antipsychotic drugs, in the presence of concomitant risk factors, high dose, and rapid titration regimen, regular monitoring of clinical parameters and ECG is highly recommended. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

[Hepatotoxicity induced by new immunosuppressants]. / Toxicidad hepática inducida por los nuevos fármacos inmunosupresores.

Immunosuppressants are among the pharmacological agents with the greatest potential to cause adverse reactions, although induction of hepatotoxicity is paradoxical from the pathogenic point of view, since the response of the innate and acquired immune system is a key element in the chain of events leading to chemical liver damage. Hepatotoxicity induced by immunosuppressants is difficult to evaluate since these drugs are sometimes used to treat liver diseases, or in combination with other drugs that can also cause hepatotoxicity, or in the context of liver transplantation, in which rejection or biliary complications can act as confounding factors. In addition, immunosuppressant therapy can favor the development of infections, which by themselves can cause liver damage, or reactivate latent chronic viral hepatitis. Corticosteroids and calcineurin inhibitors only exceptionally cause hepatotoxicity. Methotrexate at high doses and in patients with risk factors can induce advanced fibrosis and cirrhosis. Thiopurine agents can cause a spectrum of hepatic lesions, including hepatocellular of cholestatic lesions, and hepatic vascular alterations. Leflunomide has high hepatotoxic potential, especially when combined with methotrexate. Anti-tumor necrosis factor-alpha agents have rarely been associated with hepatotoxicity, often with detectable autoantibodies, and most of the reactions - some severe - have been linked to infliximab, especially when used in patients with rheumatological diseases.