Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus ...Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a- DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor alpha, IL-1beta, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.
Mycobacterium tuberculosis induces apoptosis in human monocyte-derived macrophages (MDMs) during the early stages of infection. We investigated the proapoptotic role of cell wall-associated ...mycobacterial 19-kDa lipoprotein and the possible association between 19-kDa lipoprotein signaling and production of proinflammatory cytokines. Purified mycobacterial 19-kDa lipoprotein, 19-kDa lipoprotein-expressing M. smegmatis (M. smegmatis 19+), 19-kDa lipoprotein knockout (KO) M. tuberculosis, and 19-kDa lipoprotein KO M. bovis bacille Calmette-Guérin (BCG) strains were analyzed for their ability to induce apoptosis in MDMs. The 19- kDa lipoprotein and infection with M. smegmatis 19+ induced apoptosis in MDMs. M. tuberculosis and BCG KO strains had significantly decreased abilities to induce apoptosis. The 19-kDa lipoprotein proapoptotic signal was mediated by Toll-like receptor 2 but not by tumor necrosis factor-α. Only the release of interleukin (IL)- 1β was decreased after infection with 19-kDa lipoprotein KO strains. These findings indicate that the 19-kDa lipoprotein is the main signal required to trigger both apoptosis and the release of IL-1β during the early stages of mycobacterial infection.
Executive function disorders are more bound to occur in children with specific learning disorders (SLD). In this population deficits in executive functioning are associated with worse clinical ...conditions, maladaptive behaviors, and problems with school achievement. Here, are reported the effects of the training targeting these higher-order processes through computer games in a child with a diagnosis of SLD treated in our rehabilitation center. Results show an improvement after a 6-month training program for all the executive domains.
To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and subclinical hepatic encephalopathy (SHE).
...Randomised, parallel group, controlled trial.
The study enrolled 31 patients with hepatic cirrhosis resulting from hepatitis C and/or hepatitis B, alcohol abuse and other causes. Patients randomised to active treatment, received oral L-carnitine 6 g/day in two divided doses for 4 weeks. Diagnosis of SHE was based on psychometric tests (subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Neuropsychological Test Battery) carried out at beginning and end of study. Serum ammonia levels were measured before treatment and weekly thereafter.
A total of 27 patients completed the study. Sixteen patients received L-carnitine and 11 served as controls (no treatment). L-carnitine caused rapid and significant reductions in ammonia levels, sustained over the 4-week treatment period (mean reductions 60.1 and 1.4 (μmol/L in the treated and control groups, respectively). Normal ammonia levels were attained in 14 of 16 patients receiving L-carnitine. Based on psychometric test results, seven patients (43.7%) in the L-carnitine group and five (45.5%) in the control group had SHE at baseline. L-carnitine treatment for 4 weeks caused a net overall improvement in psychometric test results compared with controls. No clinically significant adverse events were reported and all patients receiving L-carnitine reported subjective improvements in their condition.
RESULTS of this preliminary study indicate that L-carnitine reduces hyperammonaemia and improves the clinical symptoms of SHE in patients with hepatic cirrhosis.
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