1,206 research outputs found
Role of Disputed Mutations in the <i>rpoB</i> Gene in Interpretation of Automated Liquid MGIT Culture Results for Rifampin Susceptibility Testing of Mycobacterium tuberculosis
No full textABSTRACT
Low-level rifampin resistance associated with specific
rpoB
mutations (referred as “disputed”) in
Mycobacterium tuberculosis
is easily missed by some phenotypic methods. To understand the mechanism by which some mutations are systematically missed by MGIT phenotypic testing, we performed an
in silico
analysis of their effect on the structural interaction between the RpoB protein and rifampin. We also characterized 24 representative clinical isolates by determining MICs on 7H10 agar and testing them by an extended MGIT protocol. We analyzed 2,097 line probe assays, and 156 (7.4%) cases showed a hybridization pattern referred to here as “no wild type + no mutation.” Isolates harboring “disputed” mutations (L430P, D435Y, H445C/L/N/S, and L452P) tested susceptible in MGIT, with prevalence ranging from 15 to 57% (overall, 16 out of 55 isolates [29%]). Our
in silico
analysis did not highlight any difference between “disputed” and “undisputed” substitutions, indicating that all
rpoB
missense mutations affect the rifampin binding site. MIC testing showed that “undisputed” mutations are associated with higher MIC values (≥20 mg/liter) compared to “disputed” mutations (4 to >20 mg/liter). Whereas “undisputed” mutations didn't show any delay (Δ) in time to positivity of the test tube compared to the control tube on extended MGIT protocol, “disputed” mutations showed a mean Δ of 7.2 days (95% confidence interval [CI], 4.2 to 10.2 days;
P
< 0.05), providing evidence that mutations conferring low-level resistance are associated with a delay in growth on MGIT. Considering the proved relevance of L430P, D435Y, H445C/L/N, and L452P mutations in determining clinical resistance, genotypic drug susceptibility testing (DST) should be used to replace phenotypic results (MGIT) when such mutations are found.
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Reclamações ambientais em Aveiro, Portugal: atores, preocupações, padrão territorial e resoluções
No full textThis paper presents an environmental diagnosis based on public complaints on environmental
issues submitted to the Environmental Department of the Aveiro City Council, Portugal, between
2000 and 2005. It discusses the potential influences of these in local environmental planning
and governance. The paper has been organised into five sections. The first of these introduces
the study. The second section focuses on the conceptual approaches relating to environmental
grassroots movements, the main actors involved in these movements and the role played by
local government. It also contains a brief review of the most recent urban environmental
quality challenges in the European context together with a description of the main features of
the associated political and legal framework in Portugal. The third section describes the case
study and the methodology used. The results of the empirical study are detailed in the fourth
section. The final section critically analyses these results with emphases on the temporal
evolution of the submission of complaints, the actors involved, the local environmental problems
and their associated spatial pattern as well as the responses given by the City Council. This
information may then be used to provide a useful indicator for the perception of environmental
quality as well as a credible instrument for the visualisation and evaluation of local performance
in terms of environmental planning and management.AlBan Programme - n. E05M053040B
Sublingual immunotherapy induces spirometric improvement associated with IL-10 production: preliminary reports.
No full textEstrogen-like activity of seafood related to environmental chemical contaminants
No full textAbstract Background A wide variety of environmental pollutants occur in surface waters, including estuarine and marine waters. Many of these contaminants are recognised as endocrine disrupting chemicals (EDCs) which can adversely affect the male and female reproductive system by binding the estrogen receptor and exhibiting hormone-like activities. In this study the estrogenic activity of extracts of edible marine organisms for human consumption from the Mediterranean Sea was assayed. Methods Marine organisms were collected in two different areas of the Mediterranean Sea. The estrogenic activity of tissues was assessed using an in vitro yeast reporter gene assay (S. cerevisiae RMY 326 ER-ERE). Concentrations of polychlorinated biphenyls (PCBs) (congeners 28, 52, 101, 118, 138, 153, 180) in fish tissue was also evaluated. Results Thirty-eight percent of extracts showed a hormone-like activity higher than 10% of the activity elicited by 10 nM 17b-estradiol (E2) used as control. Total PCB concentrations ranged from 0.002 up to 1.785 ng/g wet weight. Chemical analyses detected different levels of contamination among the species collected in the two areas, with the ones collected in the Adriatic Sea showing concentrations significantly higher than those collected in the Tyrrhenian Sea (p Conclusion The more frequent combination of chemicals in the samples that showed higher estrogenic activity was PCB 28, PCB 101, PCB 153, PCB 180. The content of PCBs and estrogenic activity did not reveal any significant correlation.</p
Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report
No full textBackground: Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin 10 (IL-10) plays a crucial role in inducing allergen-specific tolerance; however, no previous studies have examined IL-10 production after sublingual immunotherapy (SLIT).
Objective: To evaluate T-cell proliferation and IL-10 production in patients successfully treated with SLIT for house dust mites (HDMs).
Methods: Peripheral blood mononuclear cells were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic patients and healthy control subjects. After 3 and 6 days of in vitro stimulation with phytohemagglutinin (PHA), Candida albicans, and Dermatophagoides farinae, proliferation and production of IL-10 were measured.
Results: Patients treated with SLIT showed a significant reduction of proliferation induced by C albicans compared with untreated atopic patients (P < .001), but a significant reduction was also demonstrated in healthy controls compared with untreated atopic patients (P < .001). Patients treated with SLIT also showed a significant increase of IL-10 production after Candida and PHA stimuli compared with patients with untreated rhinitis (P < .001 for both). Patients with untreated rhinitis did not produce IL-10.
Conclusion: This preliminary study confirms reduced T-cell proliferation and preliminarily provides the first evidence, to our knowledge, of peripheral IL-10 production in allergic patients successfully treated with HDM SLIT
La TAC nelle demenze secondarie.
No full textIn questo capitolo verranno trattate le Demenze Secondarie, o non Alzheimer, secondo il criterio di classificazione su base etiologica, con l'eccezione di quelle vascolari e cioe i deterioramenti cognitivi
associati ad altre patologie identificabili, aventi fattori causali ben precisi, potenzialmente curabili e talvolta regredibili
Transcriptional regulation and drug resistance in Mycobacterium tuberculosis
No full textBacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against Mycobacterium tuberculosis. Drug resistance in this species is usually due to point mutations in the drug target or in proteins required to activate prodrugs. However, another interesting and underexplored aspect of bacterial physiology with important impact on drug susceptibility is represented by the changes in transcriptional regulation following drug exposure. The main regulators involved in this phenomenon in M. tuberculosis are the sigma factors, and regulators belonging to the WhiB, GntR, XRE, Mar and TetR families. Better understanding the impact of these regulators in survival to drug treatment might contribute to identify new drug targets and/or to design new strategies of intervention
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