862 research outputs found
Translational tuberculosis research: immune profile as biomarker of tuberculosis infection
No full textMtb is able to establish a chronic asintomatically infection mainly in the lung and the balance between host immune response and the mycobacteria plays a fundamental role in the control of the Mtb replication . Although the immune response to Mtb has been deeply studied, as described in the previously chapters, the host factors that leads to the development to active TB disease are not fully understood. However, on the base of immunogical findings on Mtb infection, it is possible to speculate that the containment of the latent Mtb needs an acquired cellular response with specific characteristics of immune surveillance, differently contrasting the replicating Mtb requires effector and cytotoxic proprierty.
Objective of the present study is to take a picture of the immunological status of patients with Mtb infection, characterizing their Mtb specific immune response, in order to find a correlation with the different stages of Mtb infection.
In the chapter 5 it is described the use of several cytometric approaches to evaluate the surface expression of the activation marker CD27 on Mtb-specific CD4+ T-cells, as a tool to diagnose active TB and LTBI.
The chapter 6 is focused on flow cytometric characterization of the specific CD4 and CD8 T-cell responses to Mtb antigens contained within the QuantiFERON®-TB Gold Plus (QFT-Plus). QFT-Plus is the new generation of QuantiFERON-TB Gold In-Tube test (QFT-GIT) to identify the latent tuberculosis infection, it includes two tubes called TB1 and TB2 tubes which contain selected Mtb peptides designed to stimulate both CD4 and CD8 T-cells. Aim of the study was to analyze if the immune response to TB1 and TB2 stimulation could or not highlight differences between different TB stages.
In the chapter 7, QFT-Plus performance was compared with that one of QFT-GIT in a cross sectional study of individuals with LTBI, active TB or treated for TB in the past. In this study, we wanted also to evaluate if the different ability t
Pharmacokinetics and pharmacogenetics of anti-tubercular drugs: a tool for treatment optimization?
No full textWHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Areas covered: This review discusses available pharmacokinetic and pharmacogenetic data of first and second-line antitubercular agents in relation to efficacy and toxicity. Pharmacodynamic implications of optimized drugs and new options regimens are reviewed. Moreover a specific session describes innovative investigations on drug penetration. Expert opinion: The optimal use of available antitubercular drugs is paramount for tuberculosis control and eradication. Whilst trials are still on-going, higher rifampicin doses should be reserved to treatment for tubercular meningitis. Therapeutic Drug Monitoring with limiting sampling strategies is advised in patients at risk of failure or with slow treatment response. Further studies are needed in order to provide definitive recommendations of pharmacogenetic-based individualization: however lower isoniazid doses in NAT2 slow acetylators and higher rifampicin doses in individuals with SLCO1B1 loss of function genes are promising strategies. Finally in order to inform tailored strategies we need more data on tissue drug penetration and pharmacological modelling
Infezione da HIV: trattamento del paziente naïve
No full textRecently, the approach to initial therapy in naive patients has profoundly changed. The trend in 2008 suggests that HAART be started earlier than previously held. HAART should also be considered in selected patients with a CD4(+) count falling in the range 350-400 cells/microliter and in all subjects with a TCD4 (+) lower than 350 cells/microliter. Initial HAART provides a sufficiently broad range of choices, undoubtedly destined to further improve in the near future. However, such a choice has to take into account the patient's specific requirements and clinical picture, including comorbidity, risk factors for cardiovascular metabolic complications, simplicity and convenience of therapeutic regimen, and long-term tolerability
Organizing through and for the urban space. Experiencing of and reflecting on Marghera (mainland Venice)
No full textThe present paper represents an exploration of how alternative forms of organizing perform spatial practices to accomplish their social and cultural missions. By analyzing three different case studies of organizations based in the same urban context, we manage to shed light on differences and similarities of the activities made through and towards the spatial dimension, when alternative organizing aims at altering or criticizing how social relations and communities are ruled by dominant power structures. Our study contributes to the literature by showing how alternative organizations enact spatial practices managing to deform their organizational boundaries, expand their reach and scaling through relational networks, and take distance from others’ influence to recreate safe spaces and conduct their activities without external contaminations. All of these spatial practices, we observe, are linked to a peculiar attention to everydayness, both in the sense that they hinge on mundane activities to persist and that entail apparently trivial interaction rituals that imbue organizational spaces with symbolic and emotional valence transforming them into lived spaces
Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare
No full textMycobacterium abscessus complex is a group of rapidly growing non-Tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d,d-Transpeptidases and l,d-Transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies
Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients
No full textRaltegravir was the first available integrase inhibitor for treating HIV-positive patients. This review aims to provide an overview of its role in the management of HIV-1 infection, highlighting its key pharmacokinetic and pharmacodynamic properties
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