Enhanced expression of PD-L1 and IFN-γ on dendritic cells is associated with BCG-induced Th2 inhibition.

Accumulating evidence indicates that the exposure to Mycobacterium bovis bacillus Calmette-Guérin (BCG) prevents the development of allergy and the airway dendritic cells (DCs) may be involved in this protective effect. However, studies to better characterize the specific interactions between BCG and DCs and their role in this mycobacteria-mediated Th2 cell suppression are still ongoing. This study aimed to evaluate the effect of the neonatal BCG vaccination in the innate immune response in a mouse model of ovalbumin (OVA)-induced airway inflammation. BCG treated neonatal BALB/c mice were sensitized and challenged with aerosolized OVA. Twenty-four hours after the last challenge, samples were collected for analysis. The intranasal BCG treatment inhibited the allergic Th2-response by decreasing the allergen-induced eosinophilic inflammation, EPO activity, CCL11, IL-25, TSLP, IL-4 and IL-5 lung levels, and serum levels of IgE. Mycobacteria treatment increased lung levels of IL-10 and TGF-ß, and the TLR2 and TLR4 expressions by pulmonary CD11c+CD103+CD8α+ DCs. Additionally an enhanced expression of PD-L1 was observed besides an increased production of IFN-γ by these cells. These results indicated that neonatal BCG vaccination inhibits key features of allergic airway inflammation, probably by promoting T regulatory immune response via an enhanced expression of TLR2, TLR4 and PD-L1 on DCs.

Severe Paracoccidioidomycosis in a 14-Year-Old Boy.

Paracoccidioidomycosis (PCM) is the most important systemic mycoses in Latin America. We describe a severe case of paracoccidioidomycosis in a 14-year-old boy, with a rapid disease progression. The fungal strain was isolated and inoculated into a T and/or B cell immunocompromised mice, which revealed a highly virulent strain. The case report presented herein emphasizes the importance of considering PCM in the differential diagnosis of patients with other infectious diseases in endemic areas and highlights a novel isolate.

Recovery of renal function in heart transplantation patients after conversion from a calcineurin inhibitor-based therapy to sirolimus.

BACKGROUND: Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. METHODS: The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. CONCLUSION: The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Mitracarpus frigidus aerial parts exhibited potent antimicrobial, antileishmanial, and antioxidant effects.

The crude extract and the hexane, CH(2)Cl(2), EtOAc, n-BuOH, and hydromethanolic fractions of the aerial parts of Mitracarpus frigidus were evaluated against promastigote forms of two species of Leishmania (L. chagasi and L. amazonensis), 11 strains of bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica sorovar Tythimurium, Shigella sonnei, Klebsiella pneumoniae, Escherichia coli, Micrococcus luteus, Enterococcus faecalis, Enterobacter cloacae, Streptococcus pyogenes and Bacillus cereus) and two yeasts (Candida albicans and Cryptococcus neoformans). The antioxidant activity (DPPH radical scavenging activity and reducing power), cytotoxicity against mammalian cells, and the contents of phenolics and flavonoids were determined. Phytochemical analysis of the major groups of phytoconstituents is also reported. All samples showed antioxidant activity which was positively correlated to the content of phenolic compounds. S. sonnei, B. cereus and C. neoformans were susceptible to all extracts tested, except for the n-BuOH and hydromethanolic fractions, which demonstrated no antimicrobial activity. The lowest MIC was recorded for the CH(2)Cl(2) fraction against C. neoformans (MIC of 10 microg/ml), followed by B. cereus, S. sonnei, and E. cloacae (MIC of 20, 39 and 39 microg/ml, respectively). The CH(2)Cl(2) fraction was the most effective against L. chagasi (IC(50) of 6.7 microg/ml), and the hydromethanolic fraction exhibited the best activity against L. amazonensis (IC(50) of 9 microg/ml). A cytotoxic effect on mammalian cells was observed only for the crude extract and CH(2)Cl(2) fraction at the concentrations of 130 and 31 microg/ml, respectively. These results suggest that M. frigidus has interesting antimicrobial, antileishmanial and antioxidant activities.