No abstract

Cat-scratch disease (CSD) is the most frequent presentation of Bartonella henselae infection. It has a worldwide distribution and is associated with a previous history of scratch or bite from a cat or dog. CSD affects children and teenagers more often (80%) than adults, and it usually has a self-limiting clinical course. Atypical clinical course or systemic symptoms are described in 5%–20% of patients. Among them, hepatosplenic (HS) forms (abscess) have been described. The majority of published cases have affected children or immunosuppressed patients. Few cases of HS forms of CSD in immunocompetent adult hosts have been reported, and data about the management of this condition are scarce. Herein, we present 3 new cases of HS forms of CSD in immunocompetent adults and review 33 other cases retrieved from the literature. We propose an approach to clinical diagnosis and treatment with oral azithromycin.

Out of the biomarkers assessed, only CRP ≥ 120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH ≥ 390 UI/L and urea ≥ 25 mg/dL. For allogeneic patients only CRP ≥ 120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea ≥ 25 mg/L was included.

Highly metastatic cells are known to overexpress certain Asn-linked oligosaccharides in the plasmatic membrane. Another phenotypic characteristic of malignant cells consists in the expression of high levels of intracellular glutathione (GSH). The aim of the present work was to demonstrate that the inhibition of N-glycosylation induces changes in intracellular GSH levels, and in turn participates in the inhibition of the metastatic potential of tumor cells by tunicamycin treatment. Firstly, we demonstrated that in comparison to the poorly metastatic cell line F21, the highly metastatic cells S4MH express a higher number of Asn-linked β1–6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins involved in the regulation of the adhesion efficiency of tumor cells on endothelial cells and extracellular matrix. Our results showed that the decrease in S4MH cell adhesion efficiency on endothelial cells and extracellular matrix after the inhibition of N-glycan processing by tunicamycin treatment was caused by: (1) inhibition of the expression of N-glycan structures recognized by endothelial endogenous lectins, including β1–6 branched oligosaccharides and SA and/or chitobiose oligosaccharides, and (2) redistribution of cell surface glycoproteins with β1–6 branched oligosaccharides and/or SA and/or chitobiose oligosaccharides in their structures, caused by the depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cells necessary for anchoring to the substratum.

No abstract

Expression of determined Asn-bound glycans (N-glycans) in cell surface glycoproteins regulates different processes in tumour cell biology. Specific patterns of N-glycosylation are displayed by highly metastatic cells and it has been shown that inhibition of N-glycan processing restrains cell proliferation and induces cell death via apoptosis. However, the mechanisms by which different N-glycosylation states may regulate cell viability and growth are not understood. Since malignant cells express high levels of intracellular glutathione (GSH) and a reduction of intracellular GSH induces cell death via apoptosis, we investigated whether GSH was involved in the induction of apoptosis by removal of cell surface N-glycans. We found that removal of N-glycans from cell surface proteins by treating the rhabdomyosarcoma cell line S4MH with tunicamycin or N-glycosidase resulted in a reduction in intracellular GSH content and cell death via apoptosis. Moreover, GSH depletion caused by the specific inhibitor of GSH synthesis BSO induced apoptosis in S4MH cells. This data indicates that adequate N-glycosylation of cell surface glycoproteins is required for maintenance of intracellular GSH levels that are necessary for cell survival and proliferation.

No abstract

Glutathione (GSH) is involved in many cellular functions, including cell growth and differentiation. GSH also plays an important role in the protection of cells against oxidative damage and hence in determining the sensitivity of cells to the cytotoxicity of anticancer agents. Because of this, induction of GSH depletion has been proposed as a good strategy for sensitizing tumor cells to antitumor agents. The aim of the present work is to study the effect of buthionine sulfoximine (BSO, a specific cellular GSH-depleting agent) in two rat tumor cell lines derived from the same rhabdomyosarcoma tumor model, the moderately differentiated and low metastatic F21 cell line, and the poorly differentiated and high metastatic S4MH cell line, to investigate the influence of the degree of differentiation in the induction of GSH depletion-based therapy. We observed that, whereas in the S4MH cell line BSO induced a dose-dependent inhibition of both cell growth in vitro and tumorigenic potential in vivo, in F21 cells the administration of moderate doses of BSO enhanced tumor growth and only at high doses was there a slight reduction of their tumorigenic potential. These effects were in consonance with the fact that the activity of gamma-glutamyltranspeptidase (gamma-GT) present in the F21 cells was 4 times higher than in the S4MH cells. Indeed, inhibition of gamma-GT activity by acivicin not only abrogated the BSO-induced increase of GSH content and of cell growth, but also the combination of acivicin + BSO significantly decreased intracellular GSH levels and cell proliferation, and induced F21 cells to apoptosis. These studies suggest that, as occurs in the rhabdomyosarcoma tumor model, gamma-GT levels and the degree of differentiation of tumor cells might influence the response of tumor cells to inducers of GSH depletion, and should be taken into account in therapies based on GSH metabolism.