Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

Downregulation of CD163 in monocytes and its soluble form in the plasma is associated with a pro-inflammatory profile in pregnant women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by a systemic inflammatory response that polarizes peripheral blood monocytes to the M1 phenotype. The classically activated M1 monocytes comprise immune effector cells with an acute inflammatory phenotype. CD163 is a scavenger receptor expressed by monocytes/macrophages that may be shed from their cell membrane after proteolytic cleavage, producing the soluble CD163 molecule (sCD163). This study evaluated CD163 expression by monocytes and sCD163 as well as pro- and anti-inflammatory cytokine concentration in the plasma of pregnant women with PE. Fifty-six women with PE and 28 normotensive pregnant women were included. Plasma levels of sCD163, interleukin-1 beta (IL-1ß), IL-6, IL-10, transforming growth factor beta (TGF-ß1), and tumor necrosis factor-alpha (TNF-α) were determined by ELISA, and CD163 expression by monocytes was assessed by flow cytometry. The expression of CD163 by monocytes was significantly lower in severe and mild PE than in normotensive pregnant. Plasma concentrations of IL-1ß, TGF-ß1, and TNF-α were higher in severe PE than in mild PE and normotensive pregnant women. Both groups of preeclamptic women showed decreased plasma levels of sCD163 and IL-10. Negative correlations between sCD163 and IL-1ß (r = - 0.45; P = 0.014) and between sCD163 and TNF-α concentrations (r = - 0.54; P = 0.001) were observed in the severe PE group. The association between the pro-inflammatory cytokine profile and lower concentrations of sCD163 and IL-10 in plasma from women with severe PE suggests an impairment in the modulation of the systemic inflammatory response in this group of pregnant women with preeclampsia.

Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype.

PROBLEM: This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets. METHOD OF STUDY: Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour necrosis factor-alpha (TNF-α), interleukin-(IL)-12p40, IL-12p70, and IL-10 were evaluated in the supernatant of monocyte cultures by ELISA. RESULTS: Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was significantly higher, while the expression of CD163 and CD206 expression was significantly lower compared with NT pregnant women. Endogenous production of TNF-α, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL-10 was lower in women with PE than in NT pregnant women. CONCLUSIONS: Monocytes from women with PE are classically activated, producing higher levels of pro-inflammatory cytokines, and express surface receptors characteristic of the M1 subset. These results provide evidence that the systemic inflammatory environment in PE may differentiate and polarize these cells to the M1 phenotype.

Pregnancy after renal transplantation: an evaluation of the graft function.

OBJECTIVES: To evaluate pregnancy outcomes and graft function in renal transplant recipients. STUDY DESIGN: Thirty-four pregnancies in 31 patients were evaluated. Graft dysfunction was defined as an increase of 0.3mg/dL (215 µmol/L) or more in serum creatinine (SCr) during pregnancy. Twenty-eight patients were also evaluated at one, six and twelve months after delivery to analyze the evolution of the graft function. RESULTS: Fifteen patients experienced graft dysfunction during pregnancy, 10 related to preeclampsia, two related to rejection, one related to allograft obstruction and one related to urinary tract infection. One patient did not have an identified cause. In one patient, graft rejection ended in graft loss. The mean SCr level in the first trimester was 0.9 mg/dL (range: 0.5-2.1) among women who did not have graft dysfunction and 1.1mg/dL (range: 0.5-1.9) among patients who had graft dysfunction (P=0.66). The mean SCr level one year after delivery was 1.18 mg/dL in the first group and 1.21 mg/dL in the second group (P=0.74). There was no difference in SCr level from the first trimester of pregnancy to one year after delivery in both groups evaluated (P=0.35 and P=0.13). CONCLUSIONS: Although graft dysfunction may occur during pregnancy, it seems to be temporary in the majority of the cases. It is important to emphasize that rejection is still a cause of graft loss during pregnancy.