Chemotherapy with benznidazole and itraconazole for mice infected with different Trypanosoma cruzi clonal genotypes

The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.     

Contribution of routine cardiac biological markers to the etiological workup of ischemic stroke

Background

Optimization of the detection of atrial fibrillation following stroke is mandatory. Unfortunately, access to long-term cardiac monitoring is limited in many centers. The aim of this study was to assess the potential usefulness of three routine biological markers, troponin, D-dimers and BNP, measured in acute stroke phase in the selection of patients at risk of cardio-embolic stroke.

Characterization of main cytokine sources from the innate and adaptive immune responses following primary 17DD yellow fever vaccination in adults

The mechanisms of immune response following yellow fever (YF-17DD) vaccination are still poorly understood. In this study, we have performed a longitudinal investigation (days 0, 7, 15 and 30) to characterize the cytokine profile of innate and adaptive immunity following YF-17DD first-time vaccination. Data from non-stimulated cultures demonstrated a prominent participation of the innate immunity with increased frequency of TNF-α⁺ neutrophils and IFN-γ⁺ NK-cells at day 7 besides TNF-α⁺ monocytes at day 7, day 15 and day 30. Increased frequency of IL-10⁺ monocytes was observed at day 15 and day 30, and decreased percentage of IL-4⁺ NK-cells were detected at day 7, day 15 and day 30. Time-dependent and oscillating cytokine pattern was observed in CD4⁺ T-cells, with low percentage of IL-12⁺, IL-4⁺ and IL-10⁺ cells at day 7 and increased frequency of TNF-α⁺ cells at day 15 besides IFN-γ⁺ and IL-5⁺ cells at day 15 and day 30. Later changes with increased percentage of IL-12⁺ and IL-5⁺CD8⁺ T-cells were observed at day 30. Increased frequency of IL-10⁺ B-cells was observed at day 15, when seroconversion was detected in all vaccinees. The overall cytokine analysis of non-stimulated leukocytes showed a transient shift towards a pro-inflammatory profile at day 7, mainly due to changes in the innate immunity, which draws back toward a mixed/regulatory pattern at day 15 and day 30. The changes induced by the in vitro YF-17DD vaccine-stimulation were mainly observed at day 0 and day 7 (before seroconversion) with minor changes at day 15 and day 30 (after seroconversion). These data support the hypothesis that a complex network with mixed pro/anti-inflammatory cytokine profile is associated with the establishment of the protective immunity following YF-17DD primo-vaccination, free of adverse events.     

The use of IgG antibodies in conventional and non-conventional immunodiagnostic tests for early prognosis after treatment of Chagas disease

Treatment success of chronically infected Chagas disease patients is laborious and a positive prognosis often is made only after repetitive serological and/or parasitological examinations with continuous negative results. Recently, we have developed a non-conventional flow-cytometric method in order to detect immunoglobulin G antibodies against live trypomastigote forms of Trypanosoma cruzi and showed its usefulness in the prognosis of treatment success. In the present study, we investigated the performance of flow-cytometric anti-live trypomastigote IgG antibodies (FC-ALTA) and flow-cytometric anti-fixed epimastigote IgG antibodies (FC-AFEA), as well as conventional serological methods, for early monitoring of benznidazole treated Chagas disease patients, e.g. 5years after treatment. The analysis of individual FC-ALTA reactivity along the titration curve before and after treatment, we were able to show, that between 4% and 13% of treated patients under evaluation presented with reduced serological reactivity and segregated from the other patient groups. Similar results were obtained with semi-quantitative, conventional indirect hemagglutination or indirect immunofluorescence. Our data therefore suggest that the combined use of conventional and non-conventional serological methods could provide more suitable cure criteria in early post-therapeutic prognosis of Chagas disease.     

Management of midcheek masses and tumors of the accessory parotid gland

Tumors of the lateral wall of the mouth have different origins and behaviors. These lesions often arise from salivary tissues, such as the accessory parotid gland, but tumors can also originate from the muscles, buccal fat pad, or other structures. Surgical approaches are limited in this region by the presence of the facial nerve and the Stensen's duct. In this article, we present 9 cases of midcheek masses that were operated on via extra- or intraoral approaches. We discuss the problems related to the diagnosis of such tumors, as well as the indications and rationales for different treatment approaches.     

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.     

Angioplastie carotidienne bilatérale chez une patiente avec infarctus cérébral sur maladie de Horton

Introduction

Giant cell arteritis is the most frequent vasculitis and can cause stroke in about 4% of the patients. The mechanism is often hemodynamic in relation with an arterial stenosis or occlusion. Optimal treatment remains to be defined. Outcome is often poor.

Case report

We report the case of a 78-year-old patient, with giant cell arteritis who developed neurological deterioration after the onset of the corticotherapy. Brain MRI revealed bilateral stroke caused by multiple preocclusive internal carotid stenosis. The patient was treated successfully with angioplasty and stenting.

Conclusion

Endovascular treatment could constitute an interesting alternative for patients with giant cell arteritis associated with neurological deterioration after a first episode of stroke because of hemodynamic instability or at stroke recurrence. For these patients, the usual medical treatment appears to be insufficient.     

Steroid treatment in four cases of anti-GAD cerebellar ataxia

INTRODUCTION: Few neurological diseases are linked with anti-glutamic acid decarboxylase antibodies (GAD-ab); stiff man syndrome is an example. Cerebellar ataxia is a new feature of this expanding spectrum. No therapeutic trial is yet available in these diseases. We here report on four patients suffering from cerebellar ataxia linked with GAD-ab and review the data in the literature on this recently described syndrome. METHOD: We conducted an open trial with monthly pulsed steroids. Steroid pulses were given six months followed with placebo for another six months. Main clinical and biological parameters were monitored monthly (International Cooperative Cerebellar Ataxia Rating Scale [ICARS] and GAD-ab). RESULT: The clinical response was found limited and inconstant. Transient decline in GAD-ab level was noted in two patients. Moreover, GAD-ab level was found highly variable and did not correlate with clinical parameters. DISCUSSION: Cerebellar ataxia with GAD-ab is an increasingly described syndrome. Outcome can be severe, leading to definitive cerebellar atrophy. Diagnosis is supported by high level of serum GAD-ab with intrathecal secretion. Experimental data have suggested a direct excitotoxic effect of GAD-ab on Purkinje cells. Response to various treatments is often disappointing. Improvement has been obtained with veinoglobulins in individual patients. A weak clinical and biological response was associated with monthly steroid pulses.