Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload.

OBJECTIVE: To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). METHODS: We examined the levels of superoxide anion (O2-), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. RESULTS: Patients with IOL showed higher O2- levels (39.4 MFI) than normal controls (22.7 MFI, p=0.0356) and patients at diagnosis (19.4 MFI, p=0.0049). Antioxidant systems, except SOD activity, exhibited significant changes in IOL patients with respect to controls (CAT: 7.1 vs 2.7nmol/ml/min, p=0.0023; GPx: 50.9 vs 76.4nmol/ml/min, p=0.0291; GSH: 50.2 vs 24.1 MFI, p=0.0060). Furthermore, mitochondrial dysfunction was only detected in IOL cases compared to controls (ΔΨm: 3.6 vs 6.4 MFI, p=0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients. CONCLUSION: Oxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.

Canine leishmaniasis. Immunophenotypic profile of leukocytes in different compartments of symptomatic, asymptomatic and treated dogs.

Canine visceral leishmaniasis (CanL) is an emerging disease, expanding in various parts of the world. The infection caused by Leishmania, an intracellular protozoan parasite, can show different clinical manifestations, from asymptomatic or subclinical to symptomatic dogs, in which a wide spectrum of clinical signs is evident. The fact that the parasite replicates in different organs raises the hypothesis that each organ may have a specific immune response. The local immune responses should be evaluated and taken into consideration when developing prophylactic tools. Therefore, phenotypic characterization of peripheral blood, lymph node and bone marrow lymphocyte populations and the expression of class II molecules of major histocompatibility complex (MHCII) were performed in asymptomatic and symptomatic dogs and in dogs that had been diagnosed and treated for leishmaniasis. Our findings showed that blood and bone marrow lymphocytes from symptomatic dogs were highly activated. In bone marrow of asymptomatic and treated dogs, a high frequency of MHCII(+) lymphocytes was observed, as well as MHCII(+) monocytes in the treated group. These results show increased expression of MHCII molecules giving evidence for antigenic presentation mainly by lymphocytes. The symptomatic and treated dogs showed an expansion of CD4(+) T cells subpopulations in lymph nodes, revealing an important contribution of these cells in controlling local parasite replication. This study also underlines the eventual importance of CD3(+)CD4(-)CD8(-) (double negative) and CD3(+)CD4(+)CD8(+) (double positive) T cell subsets in sensing and controlling latent infections and their possible function in the immune dynamics during CanL. The specific cellular immune responses raised in different compartments where the parasite replicates seem to have variable effects on local parasite control, highlighting the complexity of the cellular immune response developed by the dog infected by Leishmania infantum.

[Regulatory cells]. / Células reguladoras.

The role of regulatory T cells in the induction and maintenance of peripheral tolerance has received growing attention during the last years. Several subsets of regulatory T cells were described based on their surface markers and cytokine production, but nevertheless, there are no specific markers for any subsets and their classification relies on their suppression mechanism. It is unknown which of the subgroups of regulatory T cells is more important in the prevention and control of allergic diseases, being commonly accepted its importance in homeostasis.

The combined effect of platelet storage media and intercept pathogen reduction technology on platelet activation/activability and cellular apoptosis/necrosis: Lisbon-RBS experience.

Platelets are known to undergo shape change, activation, a release reaction and apoptosis/necrosis during processing and storage, all of which are collectively known as the platelet storage lesion. Any additional processing may have some deleterious impact on platelet activability and functional integrity, which need to be investigated. This preliminary investigation was undertaken to establish the combined effects of standard platelet storage media and the intercept pathogen reduction technology on platelet activation and activability during 7 day storage, using buffy-coat derived platelets in standard storage media containing 35% plasma (N=24). P-selectin (CD62p) expression, a classical marker of platelet activation, and phosphatidylserine (PS) exposure on the platelet surface membrane, a hallmark of cellular necrosis/apoptosis, were both measured by flow cytometry. The results reveal significant increases in activation, from an average of 22.7% on day 1 before treatment to 31.6% on day 2 after treatment and 58.7% at the end of storage. Concomitantly, the basal expression of PS was slightly increased from 1.9% to 2.8% at day 2 after treatment and 7.3% at the end of storage. However, the functional reserve of platelets during storage, which reflects their capability to undergo activation and the release reaction when platelets were challenged with either calcium ionophore or thrombin, was relatively well maintained. These preliminary data confirm the earlier data on the use of intercept, and for the first time, based on the assessment of platelet functional integrity, suggest that platelet functional reserve is relatively well maintained, with little change in the formation of apoptotic cells.