Sera from Trypanosoma b. gambiense infected patients cross-react with a Trypanosoma cruzi recombinant protein

In previous studies, we and others have shown utility of a 24-kDa #Trypanosoma cruzi recombinant antigen (rTc24) for serological diagnosis of Chagas' disease. Also, this molecule has been proved useful to evaluate cure of chagasic patients who submit to specific treatment. However, in all the studies done so far, the 24-kDa protein was used as a fusion with a Gluthatione-S-transferase (GST) of #Schistosoma japonicum, therefore, parallel assays to determine the anti-GST responses of all sera were required to deduce the GST noise in serological tests. Here, we show the subcloning by polymerase chain reaction of the cDNA encoding the #T. cruzi$ 24-kDa antigen in a vector system (pQE) allowing us to obtain Tc24 recombinant protein as a single molecule. The highly reactivity of chagasic sera from Colombia, Ecuador, Brazil and Bolivia in ELISA against the recombinant antigen is confirmed. However, sera from patients infected with African trypanosomes recognize rTc24 in ELISA and blot. The relevance of these findings in the context of Chagas' disease diagnosis and/or the relationship with African trypanosomes is analyzed. (Résumé d'auteur

Pancreatico-jejunostomy decreases post-operative pancreatic fistula incidence and severity after central pancreatectomy

BACKGROUNDS: Central pancreatectomy (CP) is an alternative to pancreaticoduodenectomy and distal pancreatectomy in benign tumours of pancreatic isthmus management. It is known for a high post-operative pancreatic fistula (POPF) rate. The purpose of this study was to compare POPF incidence between pancreatico-jejunostomy (PJ) and pancreatico-gastrostomy (PG). METHODS: Fifty-eight patients (mean age 53.9 ± 1.9 years) who underwent a CP in four French University Hospitals from 1988 to 2011 were analysed. The distal pancreatic remnant was either anastomosed to the stomach (44.8%, n = 25) or to a Roux-en-Y jejunal loop (55.2%, n = 35) with routine external drainage allowing a systematic search for POPF. POPF severity was classified according to the International Study Group on Pancreatic Fistula (ISGPF) and Clavien-Dindo classifications. RESULTS: The groups were similar on sex ratio, mean age, ASA score, pancreas texture, operative time and operative blood loss. Mean follow-up was 36.2 ± 3.9 months. POPF were significantly more frequent after PG (76.9 versus 37.5%, P = 0.003). PG was associated with significantly higher grade of POPF both when graded with ISGPF classification (P = 0.012) and Clavien-Dindo classification (P = 0.044). There was no significant difference in post-operative bleeding (0.918) and delayed gastric emptying (0.877) between the two groups. Hospital length of stay was increased after PG (23.6 ± 3.5 days versus 16.5 ± 1.9 days, P = 0.071). There was no significant difference in incidence of long-term exocrine (3.8 versus 19.2%, P = 0.134) and endocrine (7.7 versus 9.4%, P = 0.575) pancreatic insufficiencies. CONCLUSION: PG was associated with a significantly higher POPF incidence and severity in CP. We recommend performing PJ especially in older patients to improve CP outcomes

Metastase axillaire d'un carcinome papillaire de la thyroïde: À propos d'un cas

Les métastases axillaires dans le cadre d'un cancer de la thyroïde sont extrêmement rares. Plusieurs hypothèses expliquent ce drainage. Nousrapportons le cas d'un patient de 78 ans ayant pour antécédents  chirurgicaux une lobo-isthmectomie en 1987, puis une totalisation chirurgicale en 1997 non documentés, admis en septembre 2008 pour exploration d'une masse latéro-cervicale gauche. Le reste de l'examen clinique révèle la présence de multiples adénopathies axillaires bilatérales. La biopsie exérèse d'une adénopathie axillaire droite (côté controlatéral) retrouve une métastase ganglionnaire d'un carcinome papillaire de la thyroïde avec effraction capsulaire. La tomodensitométrie cervico-thoracique note la présence d'un processus tumoral latéro-cervical gauche, un lobe thyroïdien droit siège de multiples nodules hypodenses, des adénopathies cervicales et axillaires et des lésions suspectes au niveau du parenchyme pulmonaire. Une thyroïdectomie totale avec curage  ganglionnaire cervical est décidée, complétée par une ablation des ganglions axillaires macroscopiquement atteints. Des cures d'iode  radioactif (IRA-thérapie) sont indiquées. Bien qu'exceptionnelle, la  présence de métastases axillaires d'un carcinome thyroïdien est de  pronostic péjoratif. On se demande alors si ces patients ne nécessitent pas une prise en charge particulière. Une réflexion à une stratégie  thérapeutique est donc nécessaire

Impairment of T Cell Function in Parasitic Infections

In mammals subverted as hosts by protozoan parasites, the latter and/or the agonists they release are detected and processed by sensors displayed by many distinct immune cell lineages, in a tissue(s)-dependent context. Focusing on the T lymphocyte lineage, we review our present understanding on its transient or durable functional impairment over the course of the developmental program of the intracellular parasites Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Trypanosoma cruzi in their mammalian hosts. Strategies employed by protozoa to down-regulate T lymphocyte function may act at the initial moment of naïve T cell priming, rendering T cells anergic or unresponsive throughout infection, or later, exhausting T cells due to antigen persistence. Furthermore, by exploiting host feedback mechanisms aimed at maintaining immune homeostasis, parasites can enhance T cell apoptosis. We will discuss how infections with prominent intracellular protozoan parasites lead to a general down-regulation of T cell function through T cell anergy and exhaustion, accompanied by apoptosis, and ultimately allowing pathogen persistence.Work supported by an FCT (Fundaçao para a Ciência e Tecnologia) grant nu PTDC/SAU-FCF/100749/2008. JE thanks the Canada Research Chair program for financial assistance. JE and KA were supported by a Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). VR is supported by a doctoral fellowship from FCT code SFRH/BD/64064/2009. RS is supported by the FCT program Ciência 2008. The research has received funding from the European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Prise En Charge Des Anévrismes Artériels Dans Un Centre Africain Non Spécialisée

Introduction: Arterial aneurysms affect 7 to 8% of people over 65 in the West and are the 2nd leading cause of death in these countries. In Africa this frequency is poorly evaluated. The objective of this work is to report the management of arterial aneurysms at the National Hospital of Niamey (HNN). Patients and methods: This was a retrospective, descriptive study over a period of eight (8) years from January 2009 to December 2016, performed in the surgical departments of the National Hospital of Niamey. Included in the study were patients of both sexes, hospitalized and / or operated for arterial aneurysm. Not included were patients treated for arterial aneurysm with incomplete records or those concerning the neurosurgical sphere. Results: During the study period, 17,748 patients were hospitalized in the general surgery departments, including 16 patients for arterial aneurysm, or 0.09% of surgical pathologies. There were 13 men (81.25%) and 3 women (18.75%), or a sex ratio of 4.33. The average age was 55.75 years with extremes ranging from 25 years old to 90 years old. The circumstances of discovery of the aneurysms were swelling of the antero-internal aspect of the thigh in 7 cases (43.75%), abdominal mass 6 cases (37.50%), then 2 cases (12.50%) of chest pain and incidental discovery in 1cas (6.25%). The most common risk factor was high blood pressure with 43.75% (7 cases). The aneurysm sat on the femoral artery in 43.75% (n = 7), of which 6 on the deep femoral and 1 on the superficial femoral, on the infrarenal aorta in 31.25% (n = 5), on thoracic aorta 12.50% (n = 2), on the iliac artery 12.50% (n = 2). For the diagnosis the angioscanner is realized in all the patients and in addition Doppler ultrasound in 43, 75% of cases. Twelve (12) patients benefited from curative surgical intervention by prosthetic graft by PTFE in 58.33% of cases and by Dacron in 41.66%. The average stay was 29.75 days and the immediate operative followup was complicated by thrombosis in 12.5% and parietal suppurations in 6.25%. We recorded two (2) deaths, ie 12.5% among non-operated patients. Conclusion: Arterial aneurysms are rare diseases at the HNN. Conventional surgery is the treatment performed in our patients. The postoperative course was simple in most cases

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Cathepsin B-like and cell death in the unicellular human pathogen Leishmania

In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H2O2), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes