Multifaceted Aspects of HIV-1 Nucleocapsid Inhibition by TAR-Targeting Peptidyl-Anthraquinones Bearing Terminal Aromatic Moieties.

2,6-dipeptidyl-anthraquinones are polycyclic planar systems substituted at opposite ring positions by short aminoacyl side chains. Derivatives with positively charged terminal amino acids showed in vitro inhibition of HIV-1 nucleocapsid (NC) protein correlating with threading intercalation through nucleic acid substrates. We found that the variation of the terminal amino acid into an aromatic moiety has profound effects on the NC inhibition of TAR-RNA melting, granting enhanced interaction with the protein.

Competition between Allowed and First-Forbidden β Decay: The Case of ^{208}Hg→^{208}Tl.

The β decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{β} window, only three negative parity states are populated directly in the β decay.

Multiple Inhibition of HIV-1 Proteins by 2,6-Dipeptidyl-anthraquinone Conjugates Targeting the PBS RNA.

We recently reported a series of 2,6-dipeptidyl-anthraquinone conjugates (AQs) as Trans-Activation Response element (TAR) RNA-binding agents able to inhibit the HIV-1 nucleocapsid (NC) protein-mediated processes. Because NC is a highly adaptable nucleic acid chaperone assisting several crucial steps along reverse transcription, in this study we investigate the ability of AQs to interact with other virus-derived nucleic acid structures thus potentially inhibiting multiple NC functions. Focusing on the HIV-1 Primer Binding Site (PBS) RNA sequence, we demonstrate that properly substituted dipeptidyl-anthraquinone conjugates efficiently inhibit the NC-mediated primer annealing in the low micromolar range.

Non-Natural Linker Configuration in 2,6-Dipeptidyl-Anthraquinones Enhances the Inhibition of TAR RNA Binding/Annealing Activities by HIV-1 NC and Tat Proteins.

The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of anti-retrovirals by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle. Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidyl-anthraquinones as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to the basic side chains.

Identification of novel 2-benzoxazolinone derivatives with specific inhibitory activity against the HIV-1 nucleocapsid protein.

In this report, we present a new benzoxazole derivative endowed with inhibitory activity against the HIV-1 nucleocapsid protein (NC). NC is a 55-residue basic protein with nucleic acid chaperone properties, which has emerged as a novel and potential pharmacological target against HIV-1. In the pursuit of novel NC-inhibitor chemotypes, we performed virtual screening and in vitro biological evaluation of a large library of chemical entities.

Detection of the serogoups and serotypes causing bacterial meningitidis in Bangui, 2012.

Objective: The aim of this study was to identify the serogroup and serotypes causing bacterial meningitidis and to determine their prevalence in Bangui, Central African Republic.

Materials And Methods: Cerebrospinal fluid (CSF) from patients with suspected meningitis were collected and tested with cell counts, Gram staining, cultures, the latex agglutination test (LAT), and real-time PCR that used specific primers and probes for S. pneumoniae, N.

Synthesis and in Vitro Screening of New Series of 2,6-Dipeptidyl-anthraquinones: Influence of Side Chain Length on HIV-1 Nucleocapsid Inhibitors.

2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives interact preferentially with noncanonical structures of TAR and cTAR, stabilize their dynamics, and interfere with NC chaperone activity.

Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation.

[Integrated screening for HIV, syphilis, and toxoplasmosis among pregnant women in the Central African Republic].

Objective: The aim of this study was to determine the prevalence of syphilis and toxoplasmosis infection in pregnant women in the Central African Republic who were and were not HIV-infected, in the framework of HIV surveillance.

Methods: This case-control study included 270 HIV(+) and 217 HIV(-) pregnant women among 4 750 women who attended prenatal-care clinics throughout the Central African Republic from November 2011 through January 2012. Blood specimens were collected and serological evidence of HIV1/2 was analyzed by ELISA1 and ELISA2.

Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program.

We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis.

Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi.

Purpose: To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old patients with advanced follicular lymphoma responding to brief first-line chemoimmunotherapy followed by rituximab consolidation.

Patients And Methods: A total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy with four monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation. Of these, 210 patients completed the planned treatment, and 202 responders were randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2 months for a total of four doses, or to observation (arm B).

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics.

The anti-CD20 antibody rituximab (RTX; Rituxan®, MabThera®) was the first anti-cancer antibody approved by the US Food and Drug Administration in 1997 and it is now the most-studied unconjugated therapeutic antibody. The knowledge gained over the past 15 y on the pharmacodynamics (PD) of this antibody has led to the development of a new generation of anti-CD20 antibodies with enhanced efficacy in vitro. Studies on the pharmacokinetics (PK) properties and the effect of factors such as tumor load and localization, antibody concentration in the circulation and gender on both PK and clinical response has allowed the design of optimized schedules and novel routes of RTX administration.

Fludarabine, cyclophosphamide, and rituximab in patients with advanced, untreated, indolent B-cell nonfollicular lymphomas: phase 2 study of the Italian Lymphoma Foundation.

Background: Indolent nonfollicular non-Hodgkin B-cell lymphomas (INFLs) are clonal mature B-cell proliferations for which treatment has not been defined to date.

Methods: In this phase 2 study of patients with advanced INFL, the authors evaluated the efficacy and safety of first-line rituximab, fludarabine, and cyclophosphamide (FCR) as induction immunochemotherapy (rituximab 375 mg/m(2) intravenously on day 1 of each cycle and on days 1 and 14 of cycles 4 and 5; fludarabine 25 mg/m(2) intravenously on days 2-4, cyclophosphamide 250 mg/m(2) intravenously on Days 2-4) every 28 days for 6 cycles followed by a maintenance phase with 4 infusions of rituximab (375 mg/m(2) intravenously on day 1) every 2 months for responders.

Results: Forty-seven patients were enrolled.

Assessment of the scientific-technological production in molecular biology in Brazil (1996-2007): the contribution of genomics programs.

Several genome sequencing programs were launched in Brazil by the end of the nineties and the early 2000s.The most important initiatives were supported by the ONSA program (http://watson.fapesp.

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia.

Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 x 10(9)/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2) rituximab weekly for 4 weeks.

Deficient alpha smooth muscle actin expression as a cause of intestinal pseudo-obstruction: fact or fiction?

Aims: To test the hypothesis that deficient alpha smooth muscle actin (ASMA) expression in intestinal smooth muscle, as assessed by immunohistochemistry, is specifically associated with clinical evidence of intestinal pseudo-obstruction.

Methods: Seventeen archival, formalin fixed, paraffin wax embedded samples of small intestine and 12 samples of large intestine were studied. Two of the small bowel samples and one large bowel sample were from patients with symptoms of intestinal pseudo-obstruction.

Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma.

Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m(2) intravenously, weekly for 4 weeks).

[Reactivity differences between serums of patients infected with HIV-2 and HIV-1 antigens according to the patients' geographic origin].

We tested 98 sera from HIV-2-infected patients for cross-reactivity with HIV-1 antigens in a competitive EIA test and western blotting. The sera were obtained during epidemiological surveys in Cape Verde Islands (n = 47) and Mali (n = 51). There were significantly more cross reactions with sera from Mali.

Cellular and plasma viral load in patients infected with HIV-2.

Objective: To determine circulating viral load in HIV-2-infected individuals.

Methods: Viral load was determined in 40 HIV-2-infected adults using standardized quantitative cell and qualitative plasma viraemia assays. We also tested for proviral HIV-2 DNA using single and nested polymerase chain reaction (PCR) in fresh lymphocytes from 27 subjects.

[A ergonomic chair on an oscillating pivot with an electrical motor for the prevention of occupational lumbar pathology due to the seated posture].

It is described an ergonomic chair of new conception, because it is not a static one, but slowly swinging in all planes, with a motion activated by an electrical engine. This chair is patented. The clinical experimentation on cases of "minor" lumbar pathology, as it is found more and more frequently in prolonged seated working situations, confirm the benefit of this instrument, already tested in cases of manifest lumbar pathology.