Notes

Sequence-Selective Safety of Peptides via Proteolysis.
Antihistamines have been in clinical use for more than 70 years to treat allergic and nonallergic symptoms including relief from cold and flu symptoms. Despite their widespread use, pharmacokinetic (PK) data are sparse for older, first-generation antihistamines. This phase 1 single-center open-label, randomized, single-dose, 3-way crossover trial evaluated the PK profiles of 2 doses of film-coated triprolidine caplets (2.5 and 5 mg) compared with a reference combination tablet (triprolidine 2.5 mg + pseudoephedrine 60 mg) in 24 healthy adults. Blood samples were collected predose and at specified intervals across a 24-hour period after administration, and triprolidine was quantified using liquid chromatography-tandem mass spectrometry. Maximum plasma concentration of triprolidine for the 2.5 mg and dose-normalized 5 mg single-agent tablets were comparable (8.4 versus 7.1 ng/mL, respectively) and higher for the combination tablet (9.5 ng/mL). PK parameters, including time to maximum plasma concentration (∼1.5 hours) and elimination half-life (∼4 hours), were comparable between the 3 treatment arms. The safety profile of this sedating antihistamine was as expected; however, adverse effects were reported in a markedly higher proportion of women than men. There were no significant sex differences in any of the measured PK parameters. © 2020 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.Hereditary spherocytosis (HS) is often misdiagnosed due to lack of specific diagnostic methods. Our study summarized clinical characteristics and described the diagnostic workflow for mild and moderate HS in Chinese individuals, using data from 20 adults, 8 of whom presented a familial history for HS. We used scanning electron microscopy (SEM) to diagnose HS. We observed reduced eosin maleimide fluorescence activity (5.50 mean channel fluorescence (MCF) units) in the 10 cases of HS, which differed significantly when compared with 10 normal adults (15.50 units), iron deficiency anemia (15.50 MCF units), and megaloblastic anemia (12.00 MCF units) values (P  less then  .05). Next generation sequencing results revealed that 9 out of 10 patients were found to have mutations in the spectrin alpha chain (SPTB), anchor protein (ANK1), and SLC4A1 genes. These mutations were not reported in the Human Gene Mutation Database (HGMD), 1000 human genome, ExAC, and dbSNP147 databases. Splenectomy proved to be beneficial in alleviating HS symptoms in 10 cases. It was found that for the diagnosis of HS, SEM and next generation gene sequencing method proved to be more ideal than red blood cell membrane protein analysis using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting. © 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.The antimicrobial efficacy of antiseptics used in wound management is tested in vitro under standardised conditions according to DIN EN 13727, with albumin and sheep erythrocytes used as organic challenge. However, these testing conditions do not adequately simulate the wound bed environment. Thus, the aim of this study was to compare the efficacy of different antiseptics such as octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHX), polyhexamethylene biguanide (PHMB), and povidone-iodine under challenge with human wound exudate instead of standardised organic load in an in vitro setting according to DIN EN 13727. Moreover, protein contents, pH, and temperature were compared with standardised testing conditions. The tested antiseptic agents were reduced to different extents based on their bactericidal efficacy, when challenged with human wound exudate compared with standardised conditions. Overall, 0.10% OCT showed the highest effects reaching full efficacy after 30 seconds. selleck kinase inhibitor CHX and PHMB were the least efficient. Next to the protein content, other components of wound exudate, such as the microflora, seem to influence the efficacy of antiseptics. In summary, the optimisation of in vitro testing conditions in future applications, to more adequately simulate the wound bed environment, will allow a more realistic picture on the potential performance of antiseptics in clinical practice. © 2020 Medicalhelplines.com Inc and John Wiley & Sons Ltd.The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) waitlist progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC waitlist progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012-2018. Patients were grouped according to etiology of liver disease HCV(-), HCV(+) never treated with DAAs and HCV(+) treated with DAAs either before or after transplantation. Multivariable competing risk models were conducted for both, HCC waitlist progression adjusted by a propensity score matching (pre-LT DAAs effect) and for post-LT HCC recurrence (pre or post LT DAAs effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs and 16.5% were HCV+ treated with DAAs either before (n=66) or after LT (n=98). Patients treated with DAAs before LT presented similar cumulative incidence of waitlist tumor progression when compared with those HCV+ without DAAs (26.2% vs 26.9%; P=0.47) and a similar HCC related drop-out rate [12.1% (CI 0.4-8.1%) versus 12.9% (CI 3.8-27.2%)], adjusted for baseline tumor burden, AFP values, HCC diagnosis after listing, bridging therapies and by the probability of having received or not DAAs through a propensity score matching [SHR 0.9 (CI 0.6; 1.6); P=0.95]. A lower incidence of post-transplant HCC recurrence among HCV+ treated with pre or post-LT DAAs was observed [0.7% (CI 0.2-4.0%)]; however, this effect was confounded by time to DAAs initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased waitlist tumor progression and HCC recurrence after LT. This article is protected by copyright. All rights reserved.
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