A new route for synthesis of silver:gold alloy nanoparticles loaded within phosphatidylcholine liposome structure as an effective antibacterial agent against Pseudomonas aeruginosa.

Ag:Au alloy nanoparticles were successfully synthesized through the new route using co-reduction method with silver nitrate, chloroauric acid, cetyl trimethyl ammonium bromide (CTAB) and sodium borohydride at room temperature. The Ag:Au alloy nanoparticles were then loaded within the phosphatidylcholine (97%) liposome structure. Various molar ratios of phosphotidylcholine and CTAB to the total metals were investigated showing its importance on the stability of nanocomposites suspension. The size distribution and morphology of encapsulated nanoparticles within the liposome structure were studied via ultraviolet (UV)-visible spectrum, transmission electron microscope (TEM) micrographs, and dynamic light scattering data. The synthesis of alloy nanoparticles were confirmed with formation of single band at 430, 465 and 500 nm for 75:25, 50:50 and 25:75 Ag:Au mole ratios, respectively. The TEM micrographs of different samples indicated formation of three various nanocomposite structures with size of 82-300 nm. The antibacterial activities of Ag:Au nanocomposites were studied against Pseudomonas aeruginosa through well-diffusion agar. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by Broth microdilution method. The results showed that 10 ppm nanocomposite reasonably killed the above bacteria.

Aerococcus viridans native valve endocarditis.

Aerococcus viridans is an infrequent human pathogen and few cases of infective endocarditis have been reported. A case involving a 69-year-old man with colon cancer and hemicolectomy 14 years previously, without recurrence, is reported. A diagnosis of native mitral valve endocarditis was established on the basis of clinical presentation, characteristic echocardiographic findings and pathological specimen examination after urgent valve replacement. A viridans endocarditis appears to be particularly virulent, requiring a surgical approach in four of 10 cases reported and death in one of nine. Given the aggressive nature of A viridans endocarditis and the variable time to diagnosis (a few days to seven months), prompt recognition of symptoms and echocardiography, in addition to blood cultures, should be performed when symptoms persist.

L'Aerococcus viridans est un pathogène humain peu fréquent qui s'associe à peu de cas déclarés d'endocardite infectieuse. Les auteurs présentent le cas d'un homme de 69 ans atteint d'un cancer du côlon et ayant subi une hémicolectomie 14 ans auparavant, sans récurrence depuis. Les médecins ont posé un diagnostic d'endocardite de la valvule mitrale naturelle d'après la présentation clinique, les observations échocardiographiques caractéristiques et l'examen des échantillons pathologiques après un remplacement valvulaire d'urgence. L'endocardite à A viridans semble particulièrement virulente. Elle a exigé une approche chirurgicale dans quatre des dix cas déclarés, et a suscité un décès dans un cas sur neuf. Étant donné le caractère agressif de l'endocardite à A viridans et le délai variable avant le diagnostic (de quelques jours à quelques mois), il faut en reconnaître rapidement les symptômes et ajouter une échocardiographie aux hémocultures en cas de persistance des symptômes.

Primary Peritoneal Cancer Two Decades after a Bilateral Salpingo-Oophorectomy.

Bilateral salpingo-oophorectomy (BSO) is increasingly employed as a risk-reducing strategy for epithelial ovarian cancer (EOC). We report the third case of a patient developing primary peritoneal cancer two decades after a bilateral salpingo-oophorectomy. This 66-year-old female underwent a hysterectomy for pelvic pain at age 28 and a subsequent bilateral salpingo-oophorectomy (BSO) at age of 45 for a pelvic mass. Presenting with a 6-month history of increasing abdominal girth, decreased energy, and a reduction in appetite, she was consented for a unilateral salpingo-oophorectomy, omentectomy, and cytoreductive surgery. Pathology specimens revealed a high grade metastatic papillary serous carcinoma consistent with a primary gynecologic origin. It is unlikely that an occult malignancy was missed at the time of pathologic assessment following her previous BSO; therefore it provides evidence that primary peritoneal cancers can arise through the malignant transformation of benign endosalpingiosis.

AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70.

We describe a group of small-molecule inhibitors of Jun kinase (JNK)-dependent apoptosis. AEG3482, the parental compound, was identified in a screening effort designed to detect compounds that reduce apoptosis of neonatal sympathetic neurons after NGF withdrawal. We show that AEG3482 blocks apoptosis induced by the p75 neurotrophin receptor (p75NTR) or its cytosolic interactor, NRAGE, and demonstrate that AEG3482 blocks proapoptotic JNK activity. We show that AEG3482 induces production of heat shock protein 70 (HSP70), an endogenous inhibitor of JNK, and establish that HSP70 accumulation is required for the AEG3482-induced JNK blockade. We show that AEG3482 binds HSP90 and induces HSF1-dependent HSP70 mRNA expression and find that AEG3482 facilitates HSP70 production while retaining HSP90 chaperone activity. These studies establish that AEG3482 inhibits JNK activation and apoptosis by a mechanism involving induced expression of HSP proteins.

Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of Bad.

The p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and after injury to the CNS. The signaling cascades activated by p75NTR that result in apoptosis remain poorly understood. In this study, we show that overexpression of p75NTR in primary cortical neurons, in pheochromocytoma cell line (PC12) cells, and in glioma cells results in activation of Jun kinase (JNK), accumulation of cytochrome c within the cytosol, and activation of caspases 9, 6, and 3. To link p75NTR-dependent JNK activation to mitochondrial cytochrome c release, regulation of BH3-domain-only family members was examined. Transcription of BH3-domain-only family members was not induced by p75NTR, but p75NTR-dependent JNK activation resulted in phosphorylation and oligomerization of the BH3-domain-only family member Bad. Loss of function experiments using Bad dominant negatives or RNA interference demonstrated a requirement for Bad in p75NTR-induced apoptosis. Together, these studies provide the first data linking apoptosis induced by p75NTR to the phosphorylation of BH3-domain-only family members.

Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall.

Intraoperative assessment of sentinel lymph nodes at time of surgical excision of primary breast carcinoma is a crucial step in the determination of cancer extent and the need for further axillary dissection. Benign epithelial inclusions in axillary lymph nodes can mimic metastatic carcinoma and are a well-known pitfall during examination of these nodes in frozen or permanent sections. Most often, these inclusions consists of heterotopic mammary glands and are familiar to the practicing pathologist. Here, however, we present a rare case of endosalpingiosis in the axillary lymph nodes of a breast cancer patient and describe our experience and effort to characterize the lesion. Simulating a metastatic focus of invasive ductal carcinoma, the glandular inclusions lacked myoepithelial cells and failed to stain with myoepithelial markers. However, consistent with a Mullerian origin, the inclusions demonstrated strong staining with PAX-8 and WT-1. Although endosalpingiotic inclusions are not uncommonly encountered in subdiaphragmatic lymph nodes, they are an extremely rare finding above the diaphragm. Pathologists must be aware of these lesions and their ability to imitate metastatic gland-forming carcinoma during frozen section or permanent examination of axillary lymph nodes.

NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway.

The p75 neurotrophin receptor (p75NTR) mediates signaling events leading to activation of the JNK pathway and cell death in a variety of cell types. We recently identified NRAGE, a protein that directly interacts with the p75NTR cytosolic region and facilitates p75NTR-mediated cell death. For the present study, we developed an inducible recombinant NRAGE adenovirus to dissect the mechanism of NRAGE-mediated apoptosis. Induced NRAGE expression resulted in robust activation of the JNK pathway that was not inhibited by the pharmacological mixed lineage kinase (MLK) inhibitor CEP1347. NRAGE induced cytosolic accumulation of cytochrome c, activation of Caspases-3, -9 and -7, and caspase-dependent cell death. Blocking JNK and c-Jun action by overexpression of the JNK-binding domain of JIP1 or dominant-negative c-Jun ablated NRAGE-mediated caspase activation and NRAGE-induced cell death. These findings identify NRAGE as a p75NTR interactor capable of inducing caspase activation and cell death through a JNK-dependent mitochondrial apoptotic pathway.