Expression of the Antiapoptotic Protein BAG3 Is a Feature of Pancreatic Adenocarcinoma and Its Overexpression Is Associated With Poorer Survival.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, being the fourth leading cause of cancer-related deaths. Long-term survival reaching 15% is achieved in less than 5% of patients who undergo surgery, and median survival is only 6 months in those with inoperable lesions. A deeper understanding of PDAC biologic characteristics as well as novel prognostic markers are therefore required to improve outcomes. Herein we report that BAG3, a protein with recognized anti-apoptotic activity, was expressed in 346 PDACs analyzed, but was not expressed in the surrounding nonneoplastic tissue. In a cohort of 66 patients who underwent radical resection (R0), survival was significantly shorter in patients with high BAG3 expression (median, 12 months) than in those with low BAG3 expression (median, 23 months) ( P = 0.001). Furthermore, we report that BAG3 expression in PDAC-derived cell lines protects from apoptosis and confers resistance to gemcitabine, offering a partial explanation for the survival data. Our results indicate that BAG3 has a relevant role in PDAC biology, and suggest that BAG3 expression level might be a potential marker for prediction of patient outcome

Ultrabiomicroscopy anterior segment evaluation of ocular contusive trauma caused by pressurized bottled drink caps. a case report

We report the case of a patient presented to the emergency department because of a contu-sive trauma from a pressurized bottled drink cap. During the visit, the patient indicated that he had been hit in his left eye by a cork while he was opening a sparkling wine bottle. He underwent a total ophthalmology examination. He had an important reduction of visual acuity, corneal swelling, Descemet’s folds, and hyphema. Therefore, we decided to perform ultrabio-microscopy (UBM) of the anterior segment to study the endothelial damage and Descemet’s membrane. UBM images confirmed the direct biomicroscopy, highlighting the damaged loca-tion

Ocriplasmin in the treatment of vitreomacular traction in a patient with central retinal vein occlusion. a case report

Aim: To investigate the efficacy of intravitreal injection of ocriplasmin (JETREA®) in the treat-ment of vitreomacular traction (VMT). Materials and Methods: An 81-year-old man with VMT associated with central retinal vein occlusion in his left eye, was treated with a single intravitreal injection of ocriplasmin (25 μg). Best corrected visual acuity (BCVA), ocular fundus, and optical coherence tomography were examined before and after treatment. Results: Complete release of VMT produced a reduction of central macular thickness, ranging from 459 to 141 μm. BCVA remained stable. Discussion and Conclusions: The use of ocriplasmin was effective in the treatment of VMT. Ocriplasmin represents a valid alternative to conventional pars plana vitrec-tomy

Evidence for BAG3 modulation of HIV-1 gene transcription.

A family of co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are involved in a number of cellular processes, including proliferation and apoptosis. Among these proteins, BAG3 has received increased attention due to its high levels in several disease models and ability to associate with Hsp70 and a number of other molecular partners. BAG3 expression is stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, and certain drugs. Here, we demonstrate that BAG3 expression is elevated upon HIV-1 infection of human lymphocytes and fetal microglial cells. Furthermore, BAG3 protein was detectable in the cytoplasm of reactive astrocytes in HIV-1-associated encephalopathy biopsies, suggesting that induction of BAG3 is part of the host cell response to viral infection. To assess the impact of BAG3 upregulation on HIV-1 gene expression, we performed transcription assays and demonstrated that BAG3 can suppress transcription of the HIV-1 long terminal repeat (LTR) in microglial cells. This activity was mapped to the kappaB motif of the HIV-1 LTR. Results from in vitro and in vivo binding assays revealed that BAG3 suppresses interaction of the p65 subunit of NF-kappaB with the kappaB DNA motif of the LTR. Results from binding and transcriptional assay identified the C-terminus of BAG3 as a potential domain involved in the observed inhibitory effect of BAG3 on p65 activity. These observations reveal a previously unrecognized cell response, that is, an increase in BAG3, elicited by HIV-1 infection, and may provide a new avenue for the suppression of HIV-1 gene expression

Immunomodulation of fucosyl-lactose and lacto-N-fucopentaose on mononuclear cells from multiple sclerosis and healthy subjects

The 1,2-fucosyl-oligosaccharides, and among these the 2’-fucosyl-lactose (2’-FL) and lacto-N-fucopentaose (LNFP)-I, are quantitatively the most represented oligosaccharides of human milk. They are also seen to represent an important immune device to prevent nursing infants from severe infectious diarrhoea. Recent evidences show that the appearance of 2’-FL and LNFP-I in human colostrums is synchronised with the macrophage inhibition and that LNFP-III induces a Th2 response from the mouse peripheral immune system. Since mannosyl-fucosyl receptors are described on the macrophage surface, all these evidences allow us to investigate on the possible immune function of human 2’-FL and LNFP-I in vitro on LPS-activated mononuclear cells (MNC) from 12 patients with multiple sclerosis (MS) and 20 matched health controls (HC). We found that 2’-FL and LNFP-I significantly decrease, to a different extent, the MNC proliferation from both HC and MS patients, in a linear and dose-dependent manner. 2’-FL and LNFPI also reduce the production of IL-12 and IFN-γ, particularly in MS patients as compared to HC (p=0.01 and p<0.001, respectively), while increasing that of IL- 10. The overall immunomodulatory effect of 2’-FL and LNFP I here presented may represent a future therapeutic option for the abnormal immune response found in some monocyte-mediated diseases

predictive factors of intraocular pressure level evolution over time and glaucoma severity in fuchs heterochromic iridocyclitis

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Somatotropic gene response to recombinant growth hormone treatment in buffalo leucocytes

The use of recombinant bovine growth hormone (rbGH) to increase milk yield in cows is banned in some countries. In others, where it is authorised, it has triggered harsh debates on labelling of dairy products. If many studies have been performed on bovines, there is a lack of information on buffaloes, which are sometimes treated with rbGH and re­present an important economical resource for dairy products in some countries. Analytical methods with legal value for surveillance of rbGH treatments do not yet exist. Research on gene expression biomarkers is one of the most promising approaches to this purpose. For this reason, we treated five buffaloes for 10 weeks with a sustained-release formulation of rbGH and analysed the response of 20 somatotropic axis genes in leucocytes by real-time polymerase chain reaction. Overall changes in gene expression levels were of low magnitude and sometimes affected by the ‘time’ factor. Only the IGFBP-1 gene showed a significant under-expression (about two-fold; p <0.001) in treated animals. Taken together, these results give evidence that expression analysis of the somatotropic axis genes in leuco­cytes is little helpful for discrimination of rbGH-treated buffaloes, but do not exclude that another array of genes could provide useful patterns of variation

Development of a PCR assay for the detection of animal tissues in ruminant feeds.

The European Community ban on use of meat and bone meal in ruminant feed, as a consequence of the spread of bovine spongiform encephalopathy in Europe, has prompted a number of investigations about the possibility of detecting animal tissues in feedstuff. In this paper, a study on vertebrate primers, designed in the 16S rRNA gene of mitochondrial DNA, is described. These primers were able to amplify fragments that contained between 234 and 265 bp. The fragments were specific for bovine, porcine, goat, sheep, horse, rabbit, chicken, trout, and European pilchard and were confirmed by sequence analysis amplicons. The primers were used in a PCR assay applied to five samples of meat and blood meals of different species and subjected to severe rendering treatments (134.4 to 141.9 degrees C and 3.03 to 4.03 bar for 24 min). The presence of vertebrate tissues was detected in all samples. The assay proved to be rapid and sensitive (detection limit 0.0625%). It can be used as a routine method to detect animal-derived ingredients in animal feedstuff

Simulation of the Impact on the Workload of the Enlargement of the Clinical Staff of a Specialistic Reference Center.

Quality of care and patient satisfaction are important aspects of high standard care. If clinical staff is subject to an elevated workload there is a possible decrease of both. This justifies the development of tools to quantify the workload and to find organizational changes that will normalize it. We have previously developed a simulation system to quantify the workload of the staff working in a regional reference center for the treatment of bleeding and hemorrhagic disorders. The goal of this new work is to simulate, through an agent-based model, the impact of adding a physician to the staff. Ten sets of initial parameters were defined to simulate ten typical weeks. Results show that the introduction of the new physician together with a second ambulatory room can reduce the workload of all the staff to the expected 8-hour. In this situation, in which the staff workload does not exceed the daily capacity, we may suppose that an increase in the quality of care and patient satisfaction will be possible