A Case of Extranodal Metastasis of Primary Bone Lymphoma in the Lower Extremity.

Primary bone lymphoma is a rare disease, accounting for less than 5% of all extranodal lymphoma. Although the femur is cited as being the most common site, primary bone lymphoma is rare, accounting for less than 1% of all non-Hodgkin's lymphoma. Herein we present a case of diffuse B-cell-type malignant lymphoma manifested as a large soft-tissue mass of the leg, via metastasis of primary non-Hodgkin's lymphoma of the femur, which went untreated. We highlight the advantages of various imaging modalities used throughout the process of diagnosis and treatment because accurate and early diagnosis are essential. This case gives us a unique opportunity to witness the rapid progression of metastasis and an atypical location.

Lower-Extremity Infections Caused by Serratia marcescens A Report of Three Cases and a Literature Review.

Serratia marcescens is a ubiquitous, facultatively anaerobic, gram-negative bacillus that has been cited to cause infection in immunocompromised populations. In the literature, S marcescens infections of the lower extremity have presented as granulomatous ulceration, abscess, bullous cellulitis, and necrotizing fasciitis. Herein we present a series of three cases of lower-extremity infections in which S marcescens was the sole or a contributing pathogen. We discuss the commonalities of these three cases as well as with those previously cited. All three patients presented with some combination of a similar set of clinical characteristics, including bullae formation, liquefactive necrosis, and black necrotic eschar. All three patients were diabetic and had peripheral vascular disease.

Exposure of Staphylococcus aureus to silver(I) induces a short term protective response.

The Ag(I) ion has well established anti-bacterial and antifungal properties. Exposure of Staphylococcus aureus to MIC(80) AgNO(3) (3 µg/ml) lead to an increase in the activity of superoxide dismutase, glutathione reductase and catalase at 30 min but activity declined by 60 min. In addition, exposure of cells to this metal ion for 1 h lead to increased expression of a number of proteins such as elongation factors Ts, Tu and G, fructose-bisphosphate aldolase and triosephosphate isomerase but their expression declined following 4 h exposure. ATP binding cassette transporter protein and oligoendopeptidase F showed increased expression at 4 h. While Ag(I) is a potent antimicrobial agent this work demonstrates that S. aureus can mount a short-term protective response to exposure to the metal ion but that this is eventually overcome.

Analysis of the response of Candida albicans cells to Silver(I).

The response of the pathogenic yeast Candida albicans to the silver(I) perchlorate salt (AgClO(4)) was assessed. By employing an anti-phospho-p38 MAPK antibody, dual phosphorylation of a high osmolarity protein (Hog1p) in C. albicans in the presence of AgClO(4) was demonstrated. Phosphorylation of C. albicans Hog1p in response to hydrogen peroxide or AgClO(4) resulted in the translocation of this mitogen-activated protein (MAP) kinase to the nucleus. Nuclear translocation of C. albicans activating protein-1 (Cap1p) was demonstrated by Western blot analysis and detected using polyclonal anti-Cap1p antibody. Upon AgClO(4)-induced translocation of Cap1p there was a concomitant activation of genes coding for glutathione reductase-1 and Mn-superoxide dismutase but no increase in the expression of flavin oxidoreductase or mitochondrial processing protease was recorded. In addition, exposure to AgClO(4) increased the activity of superoxide dismutase, glutathione reductase and catalase. The activation of C. albicans oxidative stress response genes and enzymes following exposure to AgClO(4) is evidence of the generation of oxidative stress within this medically important yeast.

Exposure to caspofungin activates Cap and Hog pathways in Candida albicans.

Caspofungin is a member of the echinocandin group of antifungals and inhibits the activity of beta-glucan synthase thus disrupting cell wall formation and function. While the potent antifungal activity of this agent is well established, this paper analyzed the response of Candida albicans to caspofungin. Exposure of yeast cells to 0.19 microg/ml caspofungin for 1 to 4 h induced nuclear translocation of Cap1p which was confirmed by Western blotting and confocal microscopy. Caspofungin-treated cells demonstrated increased expression of a number of genes associated with the oxidative stress response, including glutathione reductase (GLR1), mitochondrial processing protease (MAS1) and manganese-superoxide dismutase (SOD2) as well as elevated activity of glutathione reductase and superoxide dismutase. Caspofungin treatment also leads to the nuclear localization of Hog1p as visualized by Western blot using anti-phospho-p38 MAPK (Thr180/Tyr182) antibody. This translocation event lead to increased mRNA levels of catalase (CAT1) but not alkyl hydroperoxide reductase (AHP1). The activity of catalase was increased and reached a maximum at 2 h. In addition, pre-exposure of C. albicans to hydrogen peroxide (0.5 mM, 60 min) conferred an increased tolerance to caspofungin. The data presented here highlight the potent antifungal activity of caspofungin and demonstrate that upon exposure to this agent, C. albicans activates the Cap and Hog pathways in an attempt to limit the oxidative and osmotic stresses associated with this drug.

Use of Galleria mellonella larvae to evaluate the in vivo anti-fungal activity of [Ag2(mal)(phen)3].

Larvae of the insect Galleria mellonella were employed to assess the in vivo antifungal efficacy of ([Ag(2)(mal)(phen)(3)]), AgNO(3) and 1,10-phenanthroline. Larvae pre-inoculated with these compounds were protected from a subsequent lethal infection by the yeast Candida albicans while larvae inoculated 1 and 4 h post-infection showed significantly increased survival (P < 0.01) compared to control larvae. Administration of these compounds resulted in an increase over 48 h in the density of insect haemocytes (immune cells) but there was no widespread activation of genes for antimicrobial peptides. This work demonstrates that G. mellonella larvae may be employed to ascertain the antifungal efficacy of silver(I) compounds and offers a rapid and effective means of assessing the in vivo activity of inorganic antimicrobial compounds.

Mechanism of action of coumarin and silver(I)-coumarin complexes against the pathogenic yeast Candida albicans.

The anti-fungal activity and mode of action of a range of silver(I)-coumarin complexes was examined. The most potent silver(I)-coumarin complexes, namely 7-hydroxycoumarin-3-carboxylatosilver(I), 6-hydroxycoumarin-3-carboxylatosilver(I) and 4-oxy-3-nitrocoumarinbis(1,10-phenanthroline)silver(I), had MIC80 values of between 69.1 and 4.6 microM against the pathogenic yeast Candida albicans. These compounds also reduced respiration, lowered the ergosterol content of cells and increased the trans-membrane leakage of amino acids. A number of the complexes disrupted cytochrome synthesis in the cell and induced the appearance of morphological features consistent with cell death by apoptosis. These compounds appear to act by disrupting the synthesis of cytochromes which directly affects the cell's ability to respire. A reduction in respiration leads to a depletion in ergosterol biosynthesis and a consequent disruption of the integrity of the cell membrane. Disruption of cytochrome biosynthesis may induce the onset of apoptosis which has been shown previously to be triggered by alteration in the location of cytochrome c. Silver(I)-coumarin complexes demonstrate good anti-fungal activity and manifest a mode of action distinct to that of the conventional azole and polyene drugs thus raising the possibility of their use when resistance to conventional drug has emerged or in combination with such drugs.