The Jarisch-Herxheimer reaction (JHR) is a syndrome observed after antimicrobial treatment of some infectious diseases. The syndrome has clinical characteristics of an inflammatory reaction to antibiotic treatment. A prospective study of patients with a clinical and laboratory diagnosis of syphilis was conducted at a sexually transmitted diseases clinic in Rio de Janeiro, Brazil. Patients were treated with benzathine penicillin and observed for the JHR. A total of 115 patients were included in this study. Fifty-one patients (44%) had secondary syphilis; 37 (32%), primary; 26 (23%), latent; and one (1%), tertiary syphilis. Ten patients (9%) developed the JHR. All JHRs occurred in patients with secondary and latent syphilis. No patients experienced an allergic reaction to penicillin. The JHR occurred less frequently than in previous studies. It is important that health-care professionals recognize the clinical characteristics of the JHR so that it is not misinterpreted as an allergic reaction to penicillin.

Herein we describe the antiproliferative effects of two natural dibenzo[b,f]oxepines, pacharin (PAC) and bauhiniastatin-1 (BAU), isolated from Bauhinia acuruana on breast cancer cell line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by MTT assay and IC50 values ranged from 7.8 to 45.1 μM, including upon human breast adenocarcinoma (MCF-7) cells. In contrast, none of the compounds was cytotoxic on normal human peripheral blood mononuclear cells (IC50>100 μM). Then, MCF-7 cells treated with PAC and BAU 20 µM during 24h presented a reduction in cell volume and intensification of chromatin condensation, DNA fragmentation and apoptotic cells, whose findings became more evident after 48h of exposure. Anti-apoptotic B-cell lymphoma-2 (BCL-2) family members, such as Myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma-extra large (Bcl-xL) are important targets in cancer cell, since their overexpression confer resistance to cancer treatments. A significant reduction of the MCL-1 protein levels in MCF-7 cells after 24h of treatment with PAC and BAU at 20 μM was observed, while the Bcl-xL protein content was reduced in BAU-treated cells at 40 μM only. The cytotoxic effects of PAC and BAU are likely linked to the MCL-1 inhibition, which leads to the apoptosis of breast adenocarcinoma cells.