Migratory activation of primary cortical microglia upon infection with Toxoplasma gondii

Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites in situ in the brain parenchyma. Toxoplasma gondii tachyzoites were allowed to infect primary microglia and astrocytes in vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia, Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet Toxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells in vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as "Trojan horses," paradoxically facilitating dissemination of Toxoplasma within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.     

A porcine model of massive, totally occlusive, pulmonary embolism

Background

A reliable, animal model of massive, totally occlusive, pulmonary embolism (PE) is lacking.

Objectives

To design an animal model of totally occlusive PE and to challenge the model by a plasminogen activator.

Methods

In eight anaesthetized pigs (~ 90 kg) a massive preformed autologous thrombus was injected into the caval vein. One animal was autopsied to assess the extent of injected clot, whereas in the other animals extracorporeal life support (ECLS) was initiated and continued for three hours. These animals received 100 mg rt-PA. Blood gases, coagulation tests, creatine kinase (CK), lactate dehydrogenase (LDH), end-tidal CO2, systemic and pulmonary artery blood pressures and flow were registered.

Results

All animals went into circulatory arrest within 2 minutes after injection of the thrombus. In the animal where ECLS was not started, autopsy relieved a totally occlusive embolus of the pulmonary artery. The ECLS maintained a systemic blood flow of 6-8 L/min with adequate oxygenation and CO2-removal. However, lactate increased and base-excess became negative. Ddimer increased, fibrinogen decreased, and CK and LDH increased. All seven animals were weaned from ECLS. Despite the rt-PA treatment, the animals had at that time low end tidal CO2/PaCO2 ratio and increased mean pulmonary arterial pressure, suggesting a significant amount of embolic material remaining in the pulmonary artery.

Conclusion

This model of massive, totally occlusive, pulmonary embolism mimics well fatal PE seen in the clinic, and has the potential for use in testing of new therapeutic interventions.     

Finite element analysis of side branch access during bifurcation stenting

Stent implantation has become a widely accepted endovascular intervention for the treatment of stenosed arteries. This minimally invasive technique has shown excellent results in unbranched arteries. However, stenting bifurcation lesions remains a challenge in coronary intervention as it is associated with a lower success rate. Many different techniques have been proposed in medical practice but all the suggested methodologies have specific limitations. Numerical simulations may help to understand and eliminate the shortcomings of current clinical techniques and devices.In this study, one of the currently applied techniques is analysed which involves the implantation of a stent in the main branch, followed by subsequent inflation of a balloon through the side of the stent. This improves the side branch patency and provides access to the side branch for later stent implantations. The impact of using different balloon sizes and stent designs was investigated. The stent cell through which the balloon is inflated increases considerably and as intuitively expected, using a larger balloon results in a larger opening. Furthermore, it was observed that this procedure may compromise the downstream main branch lumen. These observations correspond well with previously reported results, which were based on in vitro studies. The added value of the proposed numerical model is the ability to study many different techniques/stents, without the need for various expensive stent samples.     

Comparative Analysis of Outcomes in Living and Deceased Donor Liver Transplants for Primary Sclerosing Cholangitis

Introduction  Primary sclerosing cholangitits (PSC) is a progressive fibrosing cholangiopathy eventually leading to end-stage liver disease (ESLD). While literature for deceased donor liver transplantation (DDLT) for PSC abounds, only a few reports describe live donor liver transplant (LDLT) in the setting of PSC. We present a single-center experience on survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Aim  The aim of this study was to analyze survival outcomes and disease recurrence for LDLT and DDLT for ESLD secondary to PSC. Patients and Methods  A retrospective review of 58 primary liver transplants for PSC-associated ESLD, performed between May 1995 and January 2007, was done. Patients were divided into two groups based on donor status. Group 1 (n = 14) patients received grafts from living donors, while group 2 (n = 44) patients received grafts from deceased donors. An analysis of survival outcomes and disease recurrence was performed. Recurrence was confirmed based on radiological and histological criteria. Results  Recurrence of PSC was observed in four patients in LDLT group and seven in DDLT group. Retransplantation was required in one patient in LDLT group and nine patients in DDLT group. One patient (7%) among LDLT and six patients (14%) among DDLT died. The difference in patient and graft survival was not statistically significant between the two groups (patient survival, p = 0.60; graft survival, p = 0.24). Conclusion  This study demonstrates equivalent survival outcomes between LDLT and DDLT for PSC; however, the rate of recurrence may be higher in patients undergoing LDLT.