Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the degradation of heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The anti-inflammatory and antioxidant properties of HO-1 activity are conferred in part by the release of CO and BV and are extensively characterized. However, iron constitutes an important product of HO-1 activity involved in the regulation of several cellular biological processes. The macrophage-mediated recycling of heme molecules, in particular those contained in hemoglobin, constitutes the major mechanism through which living organisms acquire iron. This process is finely regulated by the activities of HO-1 and of the iron exporter protein ferroportin. The expression of both proteins can be induced or suppressed in response to pro- and anti-inflammatory stimuli in macrophages from different tissues, which alters the intracellular iron concentrations of these cells. As we discuss in this review article, changes in intracellular iron levels play important roles in the regulation of cellular oxidation reactions as well as in the transcriptional and translational regulation of the expression of proteins related to inflammation and immune responses, and therefore, iron metabolism represents a potential target for the development of novel therapeutic strategies focused on the modulation of immunity and inflammation.

Retinoic acid (RA) is a fundamental vitamin A metabolite involved in regulating immune responses through the nuclear RA receptor (RAR) and retinoid X receptor. While performing experiments using THP-1 cells as a model for Mycobacterium tuberculosis infection, we observed that serum-supplemented cultures displayed high levels of baseline RAR activation in the presence of live, but not heat-killed, bacteria, suggesting that M. tuberculosis robustly induces the endogenous RAR pathway. Using in vitro and in vivo models, we have further explored the role of endogenous RAR activity in M. tuberculosis infection through pharmacological inhibition of RARs. We found that M. tuberculosis induces classical RA response element genes such as CD38 and DHRS3 in both THP-1 cells and human primary CD14+ monocytes via a RAR-dependent pathway. M. tuberculosis–stimulated RAR activation was observed with conditioned media and required nonproteinaceous factor(s) present in FBS. Importantly, RAR blockade by (4-[(E)-2-[5,5-dimethyl-8-(2-phenylethynyl)-6H-naphthalen-2-yl]ethenyl]benzoic acid), a specific pan-RAR inverse agonist, in a low-dose murine model of tuberculosis significantly reduced SIGLEC-F+CD64+CD11c+high alveolar macrophages in the lungs, which correlated with 2× reduction in tissue mycobacterial burden. These results suggest that the endogenous RAR activation axis contributes to M. tuberculosis infection both in vitro and in vivo and reveal an opportunity for further investigation of new antituberculosis therapies.

Introdução: A detecção precoce de uma infecção por HPV em amostras cervicovaginais, sem alteração histopatológica, em mu-lheres assintomáticas pode trazer uma possibilidade de prevenção do câncer de colo do útero. Objetivo: Investigar a presença de material genético de HPV em amostras cervicovaginais, sem alterações citológicas. Material e Métodos: Amostras de raspado cervicovaginal de 50 mulheres sexualmente ativas entre 18 e 30 anos, sem lesão uterina à colposcopia. A extração do DNA foi realizada utilizando um sistema comercial baseado em colunas de sílica. A detecção do material genético viral se deu por meio da técnica de PCR qualitativa, com primers GP5 +/GP6+, seguido de amplificação por MY09/MY11 para comprovação de resultados. Os resultados foram avaliados por eletroforese em gel de agarose a 3% com 30 minutos de corrida. Resultados: Foi identificado material genético de HPV em 44% das amostras testadas, e, além disso, verificamos que em 55% dos casos em que a análise citológica foi normal, o DNA viral estava presente. Conclusão: Foi detectado DNA de HPV mesmo em amostras cervicovaginais sem alterações citológicas. Sendo assim, comprova-se a existência de infecções subclínicas que podem ser diagnosticas pelo método de PCR.

This study aimed to evaluate the effectiveness of acepromazine as an adjuvant to ketamine, midazolam and methadone in the chemical restraint and anesthesia of cats undergoing ovariohysterectomy. We allocated 14 cats in two groups: group ketamine (GK), premedicated with ketamine 8 mg/kg, midazolam 0.3 mg/kg and methadone 0.3 mg/kg and group acepromazine (GAK), premedicated with acepromazine 0.05 mg/kg in addition to the above-mentioned drugs. At baseline (T0) and every 5 mins up to 20 mins (T5, T10, T15 and T20) after premedication, the sedation score was evaluated at 0 to 24 points. The sedation score was significantly higher at T5, T10, T15 and T20 in both groups. There were no significant differences in extubation times (3.7 ± 1.3 mins in GK; 5.2 ± 2.6 mins in GAK) and the time to reach a score equal to 0 on the sedation scale (88 ± 63.9 mins in GK; 133 ± 39.7 mins in GAK); however, the time of anesthetic release was significantly higher in the GAK than in GK (19.7 ± 6.5 mins vs 11 ± 5.9 mins) (P = 0.023). Sedation was adequate in both groups. The results indicated that the administration of acepromazine did not contribute to sedation in the protocol and could delay the anesthetic release.