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Autores: Krislainy De Sousa Corrêa , Adeliane Castro Da Costa , Ana Paula Perillo Ferreira Carvalho , José Laerte Rodrigues Da Silva Júnior , Maria Rosedália De Moraes , Ana Paula Junqueira-Kipnis and Marcelo Fouad Rabahi
Introduction: COPD (chronic obstructive pulmonary disease) presents a low degree of systemic inflammation responsible for the disease’s extra pulmonary consequences. Its inflammatory profile can be altered by acute exercise. However, acute effects of a sub maximum test, capable of reproducing activities of daily living (ADL) in sedentary COPD individuals, are not well-known
Objective: To evaluate if the six-minute walk test (6MWT) is capable of altering interleukin-6 (IL-6) blood levels, tumoral necrosis factor alfa (TNF-α) and hypersensitive C reactive protein (hs-CRP) in relation to the basal level of COPD individuals.
Methods: 21 individuals with moderate and severe COPD and 8 healthy individuals, with no history of smoking, sedentary, matched by age were assessed regarding plasma levels of IL-6, TNF-α and hs-CRP before and right after a 6MWT. They also did spirometry and body composition analysis.
Results: 6MWT did not provoke significant alteration in IL-6 levels in COPD individuals (pre=4.53 ± 9.0 pg/ml vs. post=7.14 ± 11.31 pg/ml, p=0.11), whereas in healthy individuals this increase was significant (pre=1.56 ± 6.45 pg/ml vs. post=4.37 ± 8.0 pg/ml, p<0.01). COPD individuals present higher hs-CRP blood levels when compared to healthy subjects both in rest (8.15 ± 9.68 pg/ml vs. 2.60 ± 1.88 pg/ml, p=0.02), and after exercise (8.18 ± 9.08 pg/ml vs. 2.62 ± 1.85 pg/ml, p=0.02. TNF-α did not present difference between groups during rest (COPD=2.13 ± 1.03 pg/ml vs. healthy=2.00 ± 0.59 pg/ml, p>0.05) as well as after 6MWT (COPD=2.48 ± 1.92 pg/ml vs. healthy=1.89 ± 0.69 pg/ml, p>0.05), and their intragroup focus was not affected by the effort (p>0.05).
Conclusions: In COPD patients, 6MWT does not induce acute inflammatory response of IL-6 at the same proportion of that of healthy subjects. Hs-CRP’s and TNFα’s response to 6MWT was similar between groups. COPD patients presented higher concentrations of hs-CRP than healthy individuals.
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Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB.
Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB.
Patients with pulmonary TB had higher titers of IgM (OD = 0.502 ± 0.281) than healthy controls (OD = 0.200 ± 0.125). The cutoff for IgM-ELISA was determined using ROC curve analyzes (AUC = 0.868) with a sensitivity of 80.1% and a specificity of 78.2%. Patients with pulmonary TB also had higher titers of IgG (OD = 0.525 ± 0.391) than healthy controls (OD = 0.215 ± 0.077). The cutoff for IgG-ELISA was determined using ROC curve analyzes (AUC = 0.864) with a sensitivity of 81.7% and a specificity of 74.7%.
The results suggest that the recombinant protein CMX can be used in a serological test to complement the screening of individuals suspected of having active pulmonary TB.
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Autores: Nascimento IP, Rodriguez D, Santos CC, Amaral EP, Rofatto HK, Junqueira-Kipnis AP, Gonçalves EDC, D'Império-Lima MR, Hirata MH, Silva CL, Winter N, Gicquel B, Mills KHG, Pizza M, Rappuoli R, Leite LCC.
In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0-3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.
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Resistance to antimicrobial agents is increasing worldwide and imposes significant life-threatening risks to several different populations, especially those in intensive care units (ICUs). Bacteria can quickly develop or acquire resistance to antimicrobial drugs, and combined with their intrinsic potential to cause disease in humans, these bacteria can become deadly. Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients, and understanding the genetic basis of A. baumannii resistance to beta-lactams among patients in ICUs will result in better protocols to prevent the development of resistance as well as improved treatment regimens. In this study, we assessed 1333 patients in five ICUs, 56 of whom developed A. baumannii infections. Most of the A. baumannii isolates were resistant to beta-lactam antimicrobial drugs, specifically, 3rd- and 4th-generation cephalosporins and carbapenems, and 91.1% of the isolates were multi-drug resistant (MDR). The most frequent OXA gene present was OXA-23 (55.1%), which is significantly associated with MDR strains. Most of the A. baumannii isolates (76.8%) were capable of forming a biofilm. The antimicrobial drug classes that were effective against most of these isolates were polymyxins and tigecycline. The molecular profile of the isolates allowed detection of 12 different clusters comprising 2 to 8 isolates each. In conclusion, our data indicate a high incidence of resistance to carbapenems as well as MDR strains among the observed A. baumannii isolates, most of which exhibited a high prevalence of OXA-23 gene expression. Only a few selective drugs were effective, reinforcing the notion that bacterial resistance is an emerging problem that should be prioritized in every healthcare facility.
Mycobacterium bovis Bacillus Calmette–Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses. The results demonstrate that rCMX protein expressed by BCG (rBCG-CMX) activates pulmonary macrophages; increases the expression of activation molecules, cytokines, and MHC-II. The interaction with rCMX activates the transcription factor NF-κB and induces the production of the cytokines TGF-β, TNF-α, and IL-6. The in vitro stimulation of bone marrow-derived macrophages (BMMs) from TLR-4 or TLR-2 KO mice showed that in the absence of TLR-4, IL-6 was not produced. rBCG-CMX was unable to induce CMX-specific Th1 and Th17 cells in TLR-4 and TLR-2 KO mice, suggesting that these receptors participate in their induction. We concluded that both the rBCG-CMX vaccine and the rCMX protein can activate macrophages and favor the specific immune response necessary for this vaccine.