A Case of Culture-Negative Endocarditis Due to Bartonella henselae and Cat Scratch Disease.

This report describes the case of a 73-year-old female with a history of a prosthetic mitral valve and breast cancer who presented with fever and confusion. Brain imaging revealed multiple ischemic infarcts, and abdominal imaging demonstrated splenic infarcts. Workup with transesophageal echocardiogram revealed a vegetation on the aortic valve, but several blood cultures had no bacterial growth. Further history revealed a recent exposure to a stray cat, and the patient was found to have positive antibodies for Bartonella henselae, the organism implicated in cat scratch disease. She was treated with the appropriate course of antibiotics, and she made a full recovery to her baseline functional status. This report emphasizes the importance of a comprehensive patient history and a broad differential diagnosis.

Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.

Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonstrate that TNBC cells express TLR9 and are responsive to TLR9 ligands, and treatment of TNBC cells with chemotherapy increases the release of nucleic-acid-containing damage-associated molecular patterns (NA DAMPs) in cell culture. Such culture-derived and breast cancer patient-derived NA DAMPs increase TLR9 activation and TNBC cell invasion in vitro. Notably, treatment with the polyamidoamine dendrimer generation 3.0 (PAMAM-G3) behaved as a nucleic acid scavenger (NAS) and significantly mitigates such effects. In mice that develop spontaneous BC induced by polyoma middle T oncoprotein (MMTV-PyMT), treatment with PAMAM-G3 significantly reduces lung metastasis. Thus, NAS treatment mitigates cancer-induced inflammation and metastasis and represents a novel therapeutic approach for combating breast cancer.

The role of metal ion binding in the antioxidant mechanisms of reduced and oxidized glutathione in metal-mediated oxidative DNA damage.

The antioxidant activity of glutathione in its reduced (GSH) and oxidized (GSSG) forms against metal-mediated oxidative DNA damage was studied by monitoring production of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from calf-thymus DNA. GSH and GSSG were combined with Fe(ii) and Cu(ii) before and after addition of DNA to investigate the role of metal coordination in the antioxidant mechanism. The antioxidant behavior of GSH and GSSG was also compared to the known radical scavenger DMSO. GSH and GSSG lower oxidative DNA damage for Fe(ii) and Cu(ii) reactions. GSH only exhibited appreciable antioxidant behavior when combined with Fe(ii) prior to adding DNA, and GSH and GSSG were slightly more effective against Cu(ii)-mediated damage when combined with Cu(ii) prior to adding DNA. Raman spectra of GSH in the presence of Cu(ii) indicate that Cu(ii) oxidizes GSH and raises the possibility that the antioxidant activity of GSH against Cu(ii) reactions may be attributed to its ability to form GSSG. No evidence of GSH oxidation in the presence of Fe(ii) was observed. The fluorescent probe dichlorofluorescein diacetate (DCF-DA) shows that the presence of GSH (for Cu(ii) reactions) and GSSG (for Fe(ii) and Cu(ii) reactions) lowers levels of reactive oxygen species (ROS) in bulk solution. Overall, the results suggest that the mechanism of antioxidant activity for GSH and GSSG against Fe(ii) and Cu(ii)-mediated oxidative damage involves metal coordination, and isothermal titration calorimetry (ITC) studies of the Cu(ii)-GSSG system show an enthalpically favored complexation reaction with an apparent 1 : 1 stoichiometry.