430 research outputs found
A nucleoside-sparing regimen of dolutegravir plus ritonavir-boosted atazanavir in HIV-1-infected patients with virological failure: the DOLATAV study
No full textVincenzo Spagnuolo,1,2 Laura Galli,2 Andrea Poli,2 Alba Bigoloni,2 Luca Fumagalli,2 Nicola Gianotti,2 Silvia Nozza,2 Davide Ferrari,3 Massimo Locatelli,3 Adriano Lazzarin,2 Antonella Castagna1,2 1Vita-Salute San Raffaele University, Faculty of Medicine and Surgery, Milan, Italy; 2Clinic of Infectious Diseases, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy; 3Laboratory Medicine Service, IRCCS San Raffaele Hospital, Milan, Italy IntroductionThe increased exposure of dolutegravir (DTG) when given with atazanavir/ritonavir (ATV/r), as well as the acceptable safety profile, may suggest the use of this combination as a two-drug regimen both in virologically suppressed and treatment-failing subjects.1–5 This nucleoside reverse transcriptase inhibitors (NRTIs)-sparing regimen, characterized by a high genetic barrier, may represent an option in patients who have failed previous regimens and developed pharmacoresistance mutations to NRTIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs). However, no data on DTG plus boosted ATV in patients with virological failure are currently available. Therefore, the aim of the DOLATAV study was to investigate the efficacy, safety, and pharmacokinetics of ATV/r 300/100 mg once-daily plus DTG 50 mg once-daily  
Improved thymopoietic potential in aviremic HIV-infected individuals treated with HAART by intermittent IL-2 administration
No full textObjective: In HIV-positive individuals administration of intermittent interleukin (IL)-2 in addition to highly active antiretroviral therapy (HAART) induces expansion of the peripheral T cell pool with dilution of signal joint T cell receptor excision circles (sjTREC) that cannot be used to measure thymic output. We analysed whether in vitro thymopoiesis could be used to predict in viva thymic output in IL-2 treated subjects. Design and methods: We correlated the relative variation of peripheral CD4 T cells over 12 months in HIV-positive subjects on HAART or HAART + IL-2 with the mean levels of both sjTREC and T cells developed in chimeric murine foetal thymic organ cultures (FTOC) reconstituted with circulating progenitors. Results: In contrast with HAART treated individuals in which these values were directly correlated, in subjects receiving HAART + IL-2 the increase of CD4 T cells in viva was correlated to neither sjTREC number nor to reconstitution of FTOC, probably reflecting a main effect of IL-2 in the expansion of the peripheral T cell pool. Nevertheless, addition of IL-2 to HAART determined a significant increase of in vitro thymopoietic potential in individuals with undetectable viraemia. Conclusions: The increased T cell development in vitro after addition of IL-2 to HAART suggests that intermittent IL-2 administration may exert a positive influence on lymphopoiesis. In two subjects with positive viraemia treated with IL-2 we observed reduced in vitro development of T cell precursors suggesting that the positive influence of IL-2 on thymopoiesis could be secondary to the control of viral replication by HAART. These observations provide novel evidence in support of the potential beneficial use of lL-2 in HAART treated individuals
Rhus coriaria l. Fruit extract prevents UV-A-induced genotoxicity and oxidative injury in human microvascular endothelial cells
No full textRhus coriaria L. (sumac) is a small plant widely diffused in the Mediterranean region. Its fruit are often consumed as a spice but are also present in traditional medicine of several countries. Recently, interest in this plant has increased and many scientific works reported its beneficial effects including antioxidant and anti-inflammatory properties. Plant extracts can be successfully used against ultraviolet rays, which are able to reach and damage the human skin; however, sumac extracts were never applied to this usage. Thus, in this study, we used a macerated ethanol extract of Rhus coriaria L. dried fruit (mERC) to demonstrate its preventive role against the damage induced by ultraviolet-A rays (UV-A) on microvascular endothelial cells (HMEC-1). In vitro effects of the extract pre-treatment and UV-A exposure were evaluated in detail. The antioxidant capacity was assessed by reactive oxygen species (ROS) formation and cellular antioxidant activity measurement. Genoprotective effects of mERC were investigated as well. Our findings indicate that the extract acts as a cell cycle inhibitor or apoptosis inducer, according to the level of damage. The present work provides new insights into the usage of Rhus coriaria extracts against skin injuries
Highlights on HIV eradication in 2013
No full textAlmost 20 years after the introduction of HAART,
scientific community, doctors and patients are still
struggling with the absence of effective strategies aimed
at eradicating HIV infection, or at preventing it through
a vaccin
Screening of maize germplasm for nutritional and technological parameters
No full textIn many countries maize is largely grown as food for humans, whereas in Italy it is mostly used for animal feed or industrial uses. However, the diffusion of gluten intolerance or celiac disease among consumers in recent years suggested introducing larger amount of maize, a gluten-free cereal, into diets. In this context, it is important to identify the characteristics which contribute to the identification of the most suitable raw materials, from a nutritional and technological point of view. Consequently, a set of 28 maize inbreds (comprising both old and recent Italian inbred lines and public line B73) were chosen for a preliminary screening of maize genotypes. The lines were multiplied in Bergamo during 2014 and reproduced by self-pollination. After harvest, their ears were dried, shelled and ground with a laboratory mill by a 0.5 mm sieve. Chemical analyses were carried out for the following parameters: crude protein, crude lipid, total starch, soluble phenols (SPs) and total antioxidant capacity (TAC), as measured by ABTS assay. Pasting properties and calorimetry analyses were also carried out, in order to evaluate the potential value of these flours for the food industry.
The results of the chemical descriptors indicated the presence of a large variability among the lines for all the considered parameters. The older inbreds and the two amylose extender genotypes were characterized by the highest percentages of protein and lipid, whereas public line B73, which has almost black kernels, showed the highest values for SPs and TAC. Even the rheological properties showed a high variability among the samples. The most interesting characteristics, in terms of pasting properties (MicroViscoAmilograph test), were observed for lines Lo1481 and Lo1530. These samples showed the highest values for peak viscosity and setback indices, suggesting the formation of hard gels that make the flours suitable for pasta making. On the contrary, flours from lines Lo1501 or Lo1550 presented lower setback and could be used as an ingredient for bread and biscuits. The two amylose extender flours were characterized by an unusual trend, without viscosity increase and gelatinization peak.
In general, the genetic variability present in maize germplasm for many compounds and technological parameters can be exploited, through the activation of specific breeding programs, for the selection of raw materials with a potential, innovative application in the food industry
Use of a novel implantable cardioverter-defibrillator multisensor algorithm for heart failure monitoring in a COVID-19 patient: A case report
No full textWe report the case of a patient implanted with an implantable defibrillator endowed with a multisensor algorithm for heart failure monitoring. Automatic measurement of multiple clinical variables allowed to detect impending heart failure decompensation and showed its ability to facilitate differential diagnosis in the context of the current COVID-19 pandemic
Identification and experimental validation of an HIV model for HAART treated patients
No full textThe objective of this paper is to identify the parameters of a human immunodeficiency virus (HIV) evolution model from a clinical data set of patients treated with two different highly active antiretroviral therapy (HAART) protocols. After introducing a model with six state variables, a preliminary step considers the reduction of the number of parameters to be identified by means of sensitivity analysis, and then identifiability items are discussed. A nonlinear optimization-based procedure for identification is developed, which divides the unknown parameters into two families: the group dependent and the patient dependent parameters. Numerical results show that the identified model can be individually adapted to each patient and this result is promising for predicting the effects (e.g., failures or successes) of therapeutic actions
Scanning the Escherichia coli chromosome by random transposon mutagenesis and multiple phenotypic screening
No full textAnalysis of the complete DNA sequences of many microbial genomes available reveals a fair number of putative ORFs without an
identified function. A systematic scan of the Escherichia coli chromosome was achieved by random transposition with a newly developed Tn5 minitransposon derivative carrying the arabinose-inducible araPBAD promoter oriented outward at one end (Tn5–araPBAD). The transposon insertion mutants obtained were assayed for conditional lethal phenotypes (arabinose dependence or sensitivity), for growth at two temperatures (37 and 15 ◦C) and in different media (rich and minimal medium). The Tn5–araPBAD-tagged genes were identified by sequencing the transposon insertion points. In this way we found a new essential gene cluster (yhbN–yhbG), produced conditional lethal (arabinose-dependent) mutations in already known essential genes (folD, frr, plsC, thiL, serS, thrS, and trpS) and provided a new phenotype (cold sensitivity) to other known genes (holD, ahpC, and tolA). Moreover, we identified eight putative ORFs (kch, ycaM, ycbQ, yddA, yddB,
ydeK, ydeX, and yliF) that appear to be required in optimum growth conditions (rich medium at 37 ◦C) but not in the cold and in minimal medium
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