LCBDE during laparoscopic cholecystectomy solves 2 problems during the same anesthesia with high success rates and may be employed successfully.

Tuberculosis (TB) remains the world's leading cause of morbidity and mortality. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine currently in use, its efficacy is highly variable. It has been suggested that early antigenic presentation is a pivotal event leading to a better immune response in TB vaccine models. To investigate this further, we compared in vitro cell-mediated immune responses in the context of early sensitization with TB (i.e. healthy adults vaccinated with BCG when they were young, HD; n = 25) to those in its absence (i.e., newborns with naïve immunity to TB, UV; n = 10) by challenging mononuclear cells with BCG Moreau. After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. In addition, supernatants were assayed for a broad range of cytokines using an array system. The HD group showed robust reactivity to Protein Purified Derivative and BCG while the naïve, UV group did not. Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. Otherwise, only the UV group showed expression of CD25dim+ as an activation marker dependent on BCG infection. In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. Taken together, our results highlight critical roles of early sensitization with TB in mounting cell-mediated immune responses.

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BackgroundTuberculosis (TB) is the second greatest killer worldwide that is caused by a single infectious agent. For its control, studies of TB vaccines are needed. Since Bacillus Calmette-Guerin (BCG) is the only vaccine against TB currently in use, studies addressing the protective role of BCG in the context of inducible inflammatory mediators are urgently required.MethodsIn this study, groups of HIV-negative adult healthy donors (HD; n = 42) and neonates (UV; n = 18) have been voluntarily enrolled, and BCG Moreau strain was used for the in vitro mononuclear cell infections for an initial period of 48 h. Subsequently, harvested conditioned medium (CM) was added to autologous resting cells for an additional 24, 48, and 120 h, and Annexin V, in conjunction with a vital dye, was then used for apoptosis detection. CM was also assayed for nitric oxide (NO), prostaglandin E2 (PGE2), leukotriene B4 (LTB4), interferon (IFN)-β, and transforming growth factor (TGF)-β1 levels. The p values were set up for any differences between two groups of individuals using Student’s t-test and considered significant when ≤ 0.05.ResultsAt 120 h, CM induced the highest apoptosis levels in both group studied, but necrosis was high in UV group only (p-value < 0.05). NO was released equally during BCG infection in both groups, but higher levels were found in HD when compared with UV group (p-value < 0.05). Overall, BCG Moreau triggered high PGE2, LTB4 and IFN-β productions in macrophages from the UV group (p-value ≤ 0.05), whereas the prostanoid PGE2 and TGF-β1 had an opposite pattern in the HD group.ConclusionsThis study uncovers critical roles for endogenous compounds in the instruction of host macrophage cell death patterns. Understanding the regulation of human immune responses is critical for vaccine development and the treatment of infectious diseases. These findings shed new light on the potential condition for a booster immunization in individuals already vaccinated with BCG for TB protection, and further studies are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0105-0) contains supplementary material, which is available to authorized users.

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