Host co-factors of the retrovirus-like transposon Ty1.

Background: Long-terminal repeat (LTR) retrotransposons have complex modes of mobility involving reverse transcription of their RNA genomes in cytoplasmic virus-like particles (VLPs) and integration of the cDNA copies into the host genome. The limited coding capacity of retrotransposons necessitates an extensive reliance on host co-factors; however, it has been challenging to identify co-factors that are required for endogenous retrotransposon mobility because retrotransposition is such a rare event.

Results: To circumvent the low frequency of Ty1 LTR-retrotransposon mobility in Saccharomyces cerevisiae, we used iterative synthetic genetic array (SGA) analysis to isolate host mutations that reduce retrotransposition.

[Membranous glomerulonephritis secondary to allogeneic stem cell transplant: review of the literature].

Renal injury associated with hematopoietic stem cell transplant (HSCT) may be related to a combination of factors. Chronic graft-versus-host disease (cGVHD) is the most common complication of allogeneic HSCT. Although the kidneys are not considered the primary target organs for GVHD, chronic impairment of renal function may occur in 20% to 60% of HSCT patients.

C-terminal truncation of Vascular Endothelial Growth Factor mimetic helical peptide preserves structural and receptor binding properties.

Vascular Endothelial Growth Factor mimetic peptides have interesting applications in therapeutic angiogenesis. Recently, we described the proangiogenic properties of a 15 mer peptide designed on the N-terminal helix 17-25 of VEGF. The peptide was stabilized introducing well known peptide chemical tools among which N- and C-terminal capping sequence.

Pain management in hematological patients with major organ dysfunctions and comorbid illnesses.

Background: Organ dysfunctions and medical complications, such as renal failure, liver impairment, coagulation disorders, cardiovascular and respiratory illnesses, may hamper an adequate pain management in haematological patients.

Aim: To summarize current knowledge on pain management in hematological patients presenting major organ dysfunctions and comorbidity. We also attempted to provide recommendations to optimize analgesia and to minimize side effects in the setting of medically compromised and frail haematological patients.

Indications for vascular grafts as hemodialysis access: consensus from experience in Italy.

Introduction: In Italy, the use of arteriovenous grafts (AVG) is limited (1-5 %) due to different approaches to vascular access (VA) management as compared to other countries, where guidelines (which may not apply to the Italian setting) have been produced. Therefore, the Study Group (GdS) on VA of the Italian Society of Nephrology produced this position paper, providing a list of 8 recommendations built upon current guidelines.

Methods: The most controversial and innovative issues of existing guidelines have been summed up in 12 different statements.

Transgene expression and local tissue distribution of naked and polymer-condensed plasmid DNA after intradermal administration in mice.

DNA vaccination using cationic polymers as carriers has the potential to be a very powerful method of immunotherapy, but typical immune responses generated have been less than robust. To better understand the details of DNA vaccine delivery in vivo, we prepared polymer/DNA complexes using three structurally distinct cationic polymers and fluorescently labeled plasmid DNA and injected them intradermally into mice. We analyzed transgene expression (luciferase) and the local tissue distribution of the labeled plasmid at the injection site at various time points (from hours to days).

Intravenous or oral vinorelbine plus capecitabine as first-line treatment in HER2- metastatic breast cancer: joint analysis of 2 consecutive prospective phase II trials.

Background: The purpose of this study was to assess the activity and safety of the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC).

Patients And Methods: Patients (42) enrolled in trial A received intravenous (i.v.

Poly(2-aminoethyl methacrylate) with well-defined chain length for DNA vaccine delivery to dendritic cells.

Poly(2-aminoethyl methacrylate) (PAEM) homopolymers with defined chain length and narrow molecular weight distribution were synthesized using atom transfer radical polymerization (ATRP), and a comprehensive study was conducted to evaluate the colloidal properties of PAEM/plasmid DNA polyplexes, the uptake and subcellular trafficking of polyplexes in antigen-presenting dendritic cells (DCs), and the biological performance of PAEM as a potential DNA vaccine carrier. PAEM of different chain length (45, 75, and 150 repeating units) showed varying strength in condensing plasmid DNA into narrowly dispersed nanoparticles with very low cytotoxicity. Longer polymer chain length resulted in higher levels of overall cellular uptake and nuclear uptake of plasmid DNA, but shorter polymer chains favored intracellular and intranuclear release of free plasmid from the polyplexes.

Nanocapsules based on linear and Y-shaped 3-miktoarm star-block PEO-PCL copolymers as sustained delivery system for hydrophilic molecules.

Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL were synthesized by ring-opening polymerization of ε-caprolactone initiated by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur in melt-crystallized copolymers when their segmental lengths were comparable and the PCL content was ≤80 wt %.

Management of Peritoneal Dialysis within a Home Care Program for Hematological Malignancies: Concerns and Perspectives Illustrated by a Case Report.

The case of an 86-year-old man suffering from acute myeloid leukemia and end-stage renal disease, managed at home, with continuous peritoneal dialysis regimen, is described.

Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity.

Direct targeting of dendritic cells is an ideal goal for DNA vaccine delivery in order to stimulate both arms of the immune system. However, dendritic cells are often difficult to transfect using nonviral polyplexes. Here we show that transfecting bystander cells such as fibroblasts with PEI/DNA complexes leads to efficient cross-presentation of a model antigen by dendritic cells and subsequent activation of antigen-specific CD8(+) T cells.

[Opioid analgesics in patients with chronic renal failure: principles for use and current guidelines].

The treatment of pain in patients with impaired renal function may be problematic, especially when opioid drugs need to be used. In the presence of renal failure, significant changes occur in the metabolism and pharmacokinetics of these drugs, which can lead to adverse reactions due to the accumulation of parental compounds and active metabolites. This paper presents and discusses the available evidence concerning the optimal use of the most frequently employed opioid analgesics to treat pain in patients with renal impairment.

Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.

Dendritic cells (DCs) are considered the most efficient antigen-presenting cells and are therefore ideal targets for in vivo delivery of antigen for vaccines. We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses. We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.

A new FcεRI receptor-mimetic peptide (PepE) that blocks IgE binding to its high affinity receptor and prevents mediator release from RBL 2H3 cells.

We have recently reported on a class of IgE-binding peptides designed based on the crystallographic structure of the high affinity FcεRI. Peptides contain receptor key residues located within the two distinct binding sites for IgE and selectively bind IgE with an affinity ranging between 6 and 60 µM. We have here designed and characterized a new molecule containing the receptor loops C'-E and B-C and an optimized linker for joining them made of a Lys side chain and a β-Ala.

Management of hematological malignancies in patients affected by renal failure.

The management of hematological malignancies (HM) in renally impaired patients may be a difficult task. Indeed, the kidney represents a major elimination pathway for many chemotherapeutic agents and their metabolites, whose serum levels are not usually measured in daily clinical practice. In addition, many antineoplastic drugs have a narrow therapeutic index for which they require dose adjustment when administered to patients with renal failure.

Pain in malignant hematology.

Pain is frequently experienced by patients with hematological malignancies, although it often receives little attention. Different underlying causes and mechanisms may sustain several pain syndromes in hematological malignant patients. Pain may be due to disease itself, to disease-related complications, to iatrogenic causes or may be associated with unrelated medical conditions.

The relation between self-reported empathy and motor identification with imagined agents.

Background: In a previous study, we found that when required to imagine another person performing an action, participants reported a higher correspondence between their own handedness and the hand used by the imagined person when the agent was seen from the back compared to when the agent was seen from the front. This result was explained as evidence of a greater involvement of motor areas in the back-view perspective, possibly indicating a greater proneness to put oneself in the agent's shoes in such a condition. In turn, the proneness to put oneself in another's shoes could also be considered as a cue of greater identification with the other, that is a form of empathy.

Developing recommendations for vascular access for hemodialysis: Vascular Access Working Group of the Italian Society of Nephrology.

This paper presents an overview of the project carried out by the Vascular Access (VA) Working Group of the Italian Society of Nephrology with the aim of developing 4 position papers at the national level on how to choose, use, and implant the different, possible types of vascular access. The topics of the project are: 1) recommendations on the use of prosthetic arteriovenous fistulas for vascular access in hemodialysis, 2) recommendations on the use of venous catheters for hemodialysis, 3) infections induced by a venous catheter for hemodialysis, and 4) how to create and maintain a vascular access for hemodialysis. This paper also gives an explanation of the difficulties existing in Italy in the implementation of international guidelines, mostly due to significant differences in the procedures for the creation of VA, compared with the countries where most of the literature on the subject has been published.

Block copolymer micelles with acid-labile ortho ester side-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells.

A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length.

Amphiphilic CCK peptides assembled in supramolecular aggregates: structural investigations and in vitro studies.

Supramolecular aggregates obtained by self-aggregation of five new cationic amphiphilic CCK8 peptides have been obtained in water solution and characterized for: (i) aggregate structure and stability; (ii) CCK8 peptide conformation and bioavailability on the external aggregate surface; and (iii) for their cell binding properties. The cationic amphiphilic CCK8 peptides self-aggregate giving a combination of liposomal and micelle structures, with radii ranging between ~60 nm and ~90 nm, and between ~5 and ~10 nm, respectively. The presence of CCK8 peptide well-exposed on the aggregate surface is demonstrated by fluorescence measurements.

[Indications for vascular grafts as dialysis access; consensus from the Italian experience].

In Italy, the use of arteriovenous grafts (AVGs) is limited (1-4%) due to different approaches to vascular access management compared to other countries, where guidelines that may not apply to the Italian setting have been produced. Therefore, the Vascular Access Study Group of the Italian Society of Nephrology produced this position paper, providing a list of 8 recommendations built upon current guidelines. The most controversial and innovative issues of the existing guidelines have been summed up in 12 different topics.

[Vascular access for hemodialysis: recommendations of the Vascular Access Study Group of the Italian Society of Nephrology].

The Vascular Access Study Group of the Italian Society of Nephrology has scheduled four national studies regarding the choice, implantation and use of vascular access. Study topics will include 1) utilization of vascular grafts for hemodialysis; 2) indications and use of venous catheters; 3) tunneled central venous catheter infection; 4) organization of the implantation and repair of vascular access. After examining the difficulties in implementing international guidelines on vascular access in Italy and the differences in practice patterns between our and other countries (where the most important studies were published), the Study Group set out to prepare four position papers based on discussion of controversial aspects of the international guidelines by nephrologists and surgeons experienced in the Italian practice.

VEGFR1(D2) in drug discovery: Expression and molecular characterization.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Its biological activity is mediated by the binding to the extracellular domain of two tyrosine kinase transmembrane receptors: VEGFR1 and VEGFR2. Deletion studies showed that VEGF binding site resides in the first three domains of VEGFR1 and in domains 2 and 3 of VEGFR2.