In the Leishmania major mouse model of cutaneous leishmaniasis inducible nitric oxide synthase (iNOS) is crucial for the killing of the parasite in the skin and draining lymph node. However, the effector mechanism operating against L. major in the spleen is unknown. As reactive oxygen intermediates might play a role, we analyzed macrophages and mice lacking the gp91phox subunit of the phagocyte NADPH oxidase (phox) for their ability to combat an infection with L. major. Macrophages from wild-type and gp91phox -/-mice had an equal capacity to kill L. major after activation by cytokines. Unlike iNOS, the activity of phox was dispensable for the resolution of the acute skin lesions and exerted only a limited effect on the containment of the parasites in the draining lymph node, but was essential for the clearance of L. major in the spleen. During the chronic phase of infection, parasites persisted at high levels in gp91phox -/-mice, and cutaneous lesions re-emerged in approximately 60% of these mice. gp91phox deficiency did not impair the expression of iNOS or the production of TNF and IFN-+ . These results demonstrate that iNOS and phox are both required for the control of L. major in vivo and display unexpected organ-and stage-specific anti-leishmanial effects.

The functional expression of TLRs on placental cells may play an important role in the initiation of an immune response in the developing fetus.

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Leptin is a circulating hormone that is secreted primarily by adipose tissue. However, recent studies have demonstrated leptin production by other tissues, including placenta, stomach, kidney, liver, and lung, a process not only activated by stimuli such as insulin or corticosteroids, but also by hypoxia, which is mediated by the hypoxia inducible factor-1. In contrast to this fact, smokers have lower plasma leptin levels. The purpose of this study was to determine whether tissue hypoxygenation [induced by lack of oxygen] or inhalation of carbon monoxide (CO) are sufficient to up-regulate leptin in fat cells as well as in peripheral organs such as lung, liver, and kidney of rats. In hypoxic rats, leptin expression was unchanged or even reduced in adipose tissue. In contrast, in liver, kidney, and lung we observed an increase in leptin expression compared with normoxic controls, whereas plasma levels were unchanged. When animals were exposed to CO, generating a functional anemia known to activate the HIF-1-dependent transcription, a significant decrease in leptin gene expression in adipose tissue and in all organs tested was observed. Plasma leptin concentrations after CO exposure were significantly diminished compared with those in control animals. These findings suggest that tissue hypoxygenation up-regulates leptin expression in nonadipose tissue. However, this is not sufficient to raise plasma leptin levels in rats. Inhalation of CO leads to a significant decrease in leptin mRNA and protein concentration in the plasma of the animals, suggesting a negative effect of CO on leptin transcription.

Fusiogenic glycoprotein syncytin-1, expressed in human placenta, is a promising candidate for acquiring a basic knowledge of placental syncytialization. However, its cellular mode of action is unidentified. We investigated whether syncytin-1 may exert influence on apoptotic processes. Therefore, we incubated CHO cells after stable transfection with syncytin-1 (CHO-52) in the presence or absence of staurosporine (STS), a kinase inhibitor well characterized to induce apoptosis. When testing the phenotype of CHO-52 cells, we could demonstrate that the induction of apoptosis by STS was delayed over a period of up to 24 h. Furthermore, the cell death rate was decreased by approx 75% following transfection of syncytin-1 in CHO-52 compared to mock-treated cells. In detail, after 18h of incubation with 500 nM STS, 64 +/- 2% of CHO-52 cells were viable compared to 16 +/- 1% of CHO-mocks, after 24 h 43 +/- 3% vs 5 +/- 2%, respectively. CHO-52 cells exhibited a lower expression of active caspase 3 and anti-apoptotic Bcl-2 was found to be increased in CHO-52 cells at baseline and following STS treatment. Our study provides first evidence that syncytin-1 serves anti-apoptotic function under certain conditions. A lessened activation of caspase 3 and an increased expression of Bcl-2 are possible mechanisms.

The objective of our study was to evaluate hemodynamic effects and the cardiac function after very early extubation within the first 6 hours after open-heart surgery in children. During a 12-month period, we performed a retrospective study of 50 children (ages 3 months to 7 years) admitted to the pediatric intensive care unit immediately after minor cardiac surgery. All children were extubated within the first 6 hours after their arrival. Arterial blood and central venous pressure were monitored, and arterial blood gas analysis was performed. Cardiac index, stroke volume index, systemic vascular resistance index, and extravascular lung water index were measured by thermodilution. Early extubation of children after minor open-heart surgery with cardiopulmonary bypass is safe and does not affect cardiac functions. A slight decrease of arterial oxygen tension not resulting in respiratory or metabolic acidosis or reintubation was noted. Very early extubation in children after open-heart surgery does not promote cardiodepressive effects. It is a safe procedure that helps to reduce the unnecessary and prolonged mechanical ventilation of children after cardiopulmonary bypass surgery.