Quinoxaline-based efflux pump inhibitors restore drug susceptibility in drug-resistant nontuberculous mycobacteria.

Nontuberculous mycobacteria (NTM) comprise several ubiquitous, environmentally localized bacteria that may be responsible for serious human diseases. NTM-associated pulmonary infections largely affect individuals with underlying respiratory disease or chronic disease and immunosuppressed patients. Mycobacterium simiae and M.

Levels of different cytokines in women and men with asymptomatic genital infection caused by Chlamydia.

Introduction: Immune response to genital Chlamydia trachomatis infection is involved in both immunity and pathology. The cytokine profile during infection has been implicated in the disease outcome, either resolution or severe sequelae.

Methodology: In total, 3900 patients were analyzed for presence of genital infections caused by Chlamydia using molecular assays.

Enhancement of antimicrobial activity of pump inhibitors associating drugs.

Introduction: with the continuous emergence of pathogenic resistance to conventional drugs through efflux pumps, increasing efforts are directed toward discovering efflux inhibitory molecules.

Methodology: in this study three P-glycoprotein (P13CP, P22CP, P34CP) efflux-inhibitors (EIs), belonging to the series of phenoxymethylquinoxalines capable to restore/potentiate the antiproliferative activity of doxorubicin and vincristine against human tumor cell lines and different antibiotics against clinical isolates, were investigated on 10 clinical strains of Candida and 12 clinical and ATCC strains of Gram positive and Gram-negative bacteria.

Results: MFC values of FLC were reduced in all Candida strains by the P22CP and P34CP inhibitors, and in 5/10 fungal strains by the P13CP inhibitor.

activity of against mycobacterial species.

The increasing incidence of resistance in tuberculosis and in atypical mycobacterial infections has prompted the search for alternative agents. We explored the antimycobacterial activity of essential oil against tubercular and non tubercular mycobacterials isolates. The good activity observed towards indicated that this essential oil might represent a promising antimicrobial agents, particularly in the management of microbial resistance.

Design, synthesis and antitubercular activity of 4-alkoxy-triazoloquinolones able to inhibit the M. tuberculosis DNA gyrase.

A number of new F-triazolequinolones (FTQs) and alkoxy-triazolequinolones (ATQs) were designed, synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv. Five out of 21 compounds exhibited interesting minimum inhibitory concentration (MIC) values (6.6-57.

Tuberculosis in Sardinia: An investigation into the relationship between natives and immigrants.

Objective/background: Tuberculosis (TB) has had a recrudescence in the last few decades in Italy as a result of many factors, among which migration from countries where TB is endemic is one of them. In Sardinia, a major island of Italy, there was no knowledge of the mechanisms of transmission of TB in the immigrant subpopulation and the impact it may have on the native subpopulation and on the community as a whole. Therefore, a molecular epidemiological study was carried out to get a clearer picture of the number and genetic features of Mycobacterium tuberculosis strains isolated from immigrants and from natives in Sardinia.

Effect of teriflunomide on QuantiFERON-TB Gold results.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis.

QuantiFERON-TB Gold Assay on Plasma for Confirmation of Presumed Tuberculosis-Related Uveitis.

The QuantiFERON-TB Gold assay was used to measure interferon gamma levels in plasma from 4 patients with presumed tuberculosis-related uveitis before, during, and after antitubercular therapy. After treatment, all patients showed clinical improvement. The concentrations showed a reversion to an absence of interferon gamma in one case, decreased in two cases, and remained stable in one case.

Could inducible protein-10 and heparin-binding hemagglutinin improve the detection of Mycobacterium tuberculosis-infected subjects in a country with low incidence of tuberculosis?

Background: This study aimed to evaluate inducible protein-10 (IP-10) as a biomarker besides interferon-gamma (IFN-γ) to improve the identification of active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with a low incidence of TB.

Methods: Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with region-of-difference-1 (RD1)-specific peptides and with heparin-binding hemagglutinin (HBHA) to determine the release of IP-10 and IFN-γ.

Results: No statistically significant difference was observed between positive rates of IP-10 and IFN-γ after RD1-specific peptide stimulation in the TB and LTBI groups; a different response was detected in QuantiFERON TB-gold test-negative (QFT-) subjects.

Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries.

Tuberculosis remains one of the major causes of global death from a single infectious agent. This situation is worsened by the HIV/AIDS pandemic because one-third of HIV/AIDS patients are co-infected with Mycobacterium tuberculosis. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely manner, allowing continued M.

Identification of non-tuberculous mycobacteria from clinical samples.

Non-tuberculous mycobacterial infections cause morbidity worldwide. NTM are considered opportunistic pathogens, and several species have been associated with human disease which has typically pulmonary, skin and soft tissue, lymphatic or disseminated presentation. This study evaluated the distribution of non-tuberculous mycobacteria in Sardinia.

Molecular identification of Mycobacterium avium subspecies paratuberculosis in oral biopsies of Crohn's disease patients.

Oral lesions may be found in patients with Crohn's disease (CD), in a percentage up to 20%. The aim of this study was to investigate a possible relationship between Mycobacterium avium subsp. paratuberculosis (MAP) and oral lesions in CD patients.

Tuberculin skin test and QuantiFERON in children.

Until some time ago, the tuberculin skin test was the only available screening test for the diagnosis of tubercular infection. Now the new interferon-? release assay QuantiFERON-TB Gold shows promise of greater accuracy in the detection of Mycobacterium tuberculosis-infected subjects. The aim of our study was to evaluate the use of QuantiFERONTB Gold in children and to verify its agreement with the tuberculin skin test.

Epidemic of tuberculosis in a high school in Northern Sardinia.

The aim of this study was to investigate the Mycobacterium tuberculosis transmission among high school student and teacher populations in a high school in Northern Sardinia. Tuberculin skin-test screening, chest-X-rays, QuantiFERON-TB Gold, microbiological examination, spoligotyping and variable numbers of tandem repeats (VNTR) analysis of M. tuberculosis isolates were performed.

Interaction between Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium subspecies paratuberculosis with the enteric glia and microglial cells.

Background: We investigated the interaction of Mycobacterium avium subspecies paratuberculosis, M. bovis and M. tuberculosis and different glial cells (enteric glial and microglial cells) in order to evaluate the infecting ability of these microorganisms and the effects produced on these cells, such as the evaluation of cytokines expression.

Tuberculosis patients are characterized by a low-IFN-γ/high-TNF-α response to methylated HBHA produced in M. smegmatis.

Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with heparin-binding hemagglutinin (HBHA). Tuberculosis (TB) patients showed an HBHA-specific T-cell response characterized by low-IFN-γ/high-TNF-α secretion, while asymptomatic subjects with latent infection (LTBI) and TB patients under therapy showed a pattern with high IFN-γ/low TNF-α. These results underscore the usefulness of HBHA in helping to distinguish LTBI subjects versus TB patients.

Preliminary data of different methods for the indirect diagnosis of Mycobacterium bovis infection.

We compared the response induced by QuantiFERON-TB Gold antigens to that obtained with the Intradermal Comparative Tuberculin Test and BOVIGAM assay. Our results showed that the QuantiFERON-TB Gold technique used in humans could also be applied for the diagnosis of TB infection in cattle.

Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease among RD1-responders.

Background: A challenge in tuberculosis (TB) research is to develop a new immunological test that can help distinguish, among subjects responsive to QuantiFERON TB Gold In tube (QFT-IT), those who are able to control Mtb replication (remote LTBI, recent infection and past TB) from those who cannot (active TB disease). IFN-γ response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with LTBI, but the cumbersome procedures of purifying the methylated and immunological active form of the protein from Mtb or M. bovis Bacillus Calmette et Guerin (BCG) have prevented its implementation in a diagnostic test.

Evaluation of the Antimicrobial Properties of the Essential Oil of Myrtus communis L. against Clinical Strains of Mycobacterium spp.

Mycobacterium tuberculosis is the etiological agent of tuberculosis. The World Health Organization has estimated that 8 million of people develop active TB every year and the situation is complicated by an increase of Mycobacterium tuberculosis strains resistant to drugs used in antitubercular therapy: MDR and XDR-TB. Myrtle leaf extracts, used as an antiseptic in Sardinian traditional medicine, have strong antibacterial activity as several investigations showed.

Molecular characterization of Sardinian Mycobacterium tuberculosis isolates by IS6110 restriction fragment length polymorphism, MIRU-VNTR and rep-PCR.

An evaluation of the utility of rep PCR typing compared to the 15 loci discriminatory set of MIRU-VNTR was undertaken. Twenty-nine isolates of Mycobacterium tuberculosis from patients were examined. Genomic DNA was extracted from the isolates by standard method.

Usefulness of the QuantiFERON-TB-Gold in tube in a population at risk of bovine tubercular infection.

The effectiveness of the QuantiFERON-TB-Gold in tube was compared with PPD to detect tuberculosis infection in the staff of cattle-farms, as a consequence of an outbreak of bovine tuberculosis in livestock. The data revealed the advantage of the immunological test for the specific detection of subjects infected by Mycobacterium tuberculosis complex.

Phages specific for mycobacterial lipoarabinomannan help serodiagnosis of tuberculosis.

This study evaluated the possibility to use six phages specific to the Mycobacterium tuberculosis lipoarabinomannan (LAM) as tools for tubercular serodiagnosis. We analysed sera samples from 30 subjects with active tuberculosis (TB+), 30 with latent tubercular infection (LTBI) and 60 healthy subjects as controls (K). Our data indicated a good antibody response of the TB+ and LTBI patients against the phage Ri(7)17; the optical density (OD) values obtained from sera patients was statistically significant when compared to the control samples.