Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein

Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.

[Only a denture sore? Causes of a possible denture sore from a maxillary complete denture]

This case presentation documents the treatment sequence of a 74 years old patient who complained about a sore spot of the palatal mucosa underneath the complete denture. The intraoral examination revealed a dark spot, redness and swelling of the mucosa around this spot and halitosis. The mucosa exhibited a perforation of 3 x 10 mm in diameter. A radiographic 3-D picture showed an impacted canine tooth, which was partly covered by the palatal bone. Firstly the denture base was relieved and the swelling gradually disappeared. Then a biopsy was taken for histological analysis to exclude any malignant process. In local anesthesia the tooth was extracted, which exhibited a deep carious lesion of the entire crown. After surgery a visible collapse of the jaw crest was observed. During a period of two months the denture was relined with a soft material to improve its fit and to enhance the healing process. With a final rebasement, the existing denture could be adapted again and the patient continued to wear it.

[Acute myocardial infarction: importance of the networking in the initial management]

Early reperfusion with prompt re-establishment of coronary blood flow improves survival in patients suffering from acute ST-elevation myocardial infarction (STEMI). Leaving systemic thrombolysis for primary percutaneous coronary intervention (PCI) is justified by clinical results in favor of PCI. Nevertheless, primary PCI necessitates additional transfer time and requires an efficient territorial networking. The present article summarizes the up-to-dated management of patients with acute STEMI and/or overt cardiogenic shock.

[A Swiss multicentric project to improve the prevention of cardiovascular event recurrence after acute coronary syndromes]

Recurrence of cardiovascular events and mortality remain high after acute coronary syndromes. A Swiss multicentric study, "Inflammation and acute coronary syndromes (ACS)--Novel strategies for prevention and clinical managements", is currently underway with the support of the Swiss National Science Foundation. The study includes a clinical research subproject of which the aim is to assess the impact of the ELIPS program (multi-dimEnsionaL prevention Program after acute coronary Syndrome) on the recurrence of cardiovascular events after an ACS. The basic research sub-projects aim to investigate novel cardiovascular risk biomarkers and genetic determinants of recurrence and to study the role of stem cells after an ACS. Another sub-project will evaluate intracoronary imaging techniques and the efficacy of different types of stents.

[Laparoscopic management of genital prolapse by lateral suspension using mesh: a series of 377 patients]

Genital prolapse is frequent and can be found in about 50% of parous women. Its etiology is complex and multifactorial. Predisposing factors include: genetics (connective tissue disorders, family history); general state (age, parity, weight, smoking, obstructive pulmonary disease); trauma (carrying heavy loads, intense physical exercise); or iatrogenic (post hysterectomy). Treatment can be conservative or surgical and depends mainly on the severity of symptoms. Developments in surgical techniques and synthetic material in the last 20 years enabled us to use minimally invasive procedures with improved post operative course and decreased recurrence rates.

TNFα inhibits the development of osteoclasts through osteoblast-derived GM-CSF

Inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) are potent stimulators of osteoclast formation and bone resorption and are frequently associated with pathologic bone metabolism. The cytokine exerts specific effects on its target cells and constitutes a part of the cellular microenvironment. Previously, TNFα was demonstrated to inhibit the development of osteoclasts in vitro via an osteoblast-mediated pathway. In the present study, the molecular mechanisms of the inhibition of osteoclastogenesis were investigated in co-cultures of osteoblasts and bone marrow cells (BMC) and in cultures of macrophage-colony stimulating factor (M-CSF) dependent, non-adherent osteoclast progenitor cells (OPC) grown with M-CSF and receptor activator of NF-κB ligand (RANKL). Granulocyte-macrophage colony stimulating factor (GM-CSF), a known inhibitor of osteoclastogenesis was found to be induced in osteoblasts treated with TNFα and the secreted protein accumulated in the supernatant. Dexamethasone (Dex), an anti-inflammatory steroid, caused a decrease in GM-CSF expression, leading to partial recovery of osteoclast formation. Flow cytometry analysis revealed that in cultures of OPC, supplemented with 10% conditioned medium (CM) from osteoblasts treated with TNFα/1,25(OH)(2)D(3), expression of RANK and CD11c was suppressed. The decrease in RANK expression may be explained by the finding, that GM-CSF and the CM from wt osteoblasts were found to suppress the expression of c-Fos, Fra-1, and Nfatc-1. The failure of OPC to develop into CD11c(+) dendritic cells suggests that cell development is not deviated to an alternative differentiation pathway, but rather, that the monocytes are maintained in an undifferentiated, F4/80(+), state. The data further implies possible interactions among inflammatory cytokines. GM-CSF induced by TNFα acts on early hematopoietic precursors, inhibiting osteoclastogenesis while acting as the growth factor for M-CSF independent inflammatory macrophages. These in turn may condition a microenvironment enhancing osteoclast differentiation and bone resorption upon migration of the OPC from circulation to the bone/bone marrow compartment.

[Oral health as the mirror of health: the primary care medicine's poor relative?]

Oral health (OH) is indivisible from general health. Several studies have established the link between morbi-mortality, especially cardiovascular, and bad OH, particularly in the case of edentation. Regrettably, part of the population choses dental care renunciation for financial reasons. The primary care physician (PCP), as the health professionnal with the most frequent and intense contacts with the patients, plays an important role to reinforce prevention measures, OH maintenance and to detect oral pathologies. To fulfill this mission, he has to be trained to endo-buccal examination. Furthermore, both the PCP and the dentist have to proactively build an interprofessional approach to promote patients' OH.

[Endoscopic decompression of the ulnar nerve in the cubital tunnel syndrome: about 55 patients]

Sulcus ulnaris syndrome is the second most common neurocompression syndrome in the upper limb after carpal tunnel syndrome. Its severity can be appreciated by the Dellon Classification. We present our experience and results after endoscopic decompression.

[Thirty years of laser-assisted microvascular anastomosis (LAMA): what are the clinical perspectives?]

Since the first studies by Jain and Gorisch (1979), laser-assisted anastomoses have been steadily developed to a stage where clinical use is within reach. The laser-assisted vascular microanastomosis (LAMA) procedure is performed more quickly than conventional anastomosis, the surgically induced vessel damage is limited, and reduced bleeding after unclamping is observed.

[Historical review and future orientations of the conventional vascular microanastomoses]

Microvascular surgery has become an important method for reconstructing surgical defects due to trauma, tumors or after burn. The most important factor for successful free flap transfer is a well-executed anastomosis. The time needed to perform the anastomosis and the failure rate are not negligible despite the high level of operator's experience. During the history, many alternatives were tried to help the microsurgeon and to reduce the complications. A Medline literature search was performed to find articles dealing with non-suture methods of microvascular anastomosis. Many historical books were also included. The non-suture techniques can be divided into four groups based on the used mechanism of sutures: double intubation including tubes and stents, intubation-eversion including simple rings, double eversion including staples and double rings, and wall adjustement with adhesives or laser. All these techniques were able to produce a faster and easier microvascular anastomosis. Nevertheless, disadvantages of the suturless techniques include toxicity, high cost, leakage or aneurysm formation. More refinement is needed before their widespread adoption. Thus, laser-assisted microvascular anastomosis using 1,9 μm diode laser appeared to be a safe and reliable help for the microsurgeon and may be further developed in the near future.

[Prosthetic rehabilitation of a traumatic occlusion due to bulimia nervosa. Case report]

Because of the typical localisation of erosions in anorectic/bulimic patients, the dentist is frequently the first medical person to discern this general illness (anorexia and bulimia nervosa). From the dental viewpoint, the aim should be to preserve sound dental tissue and to prevent further toothwear. A restorative treatment is to be carried out only after causal therapy and after resolving the basic disease. By means of this procedure a good long-term prognosis can be expected. Considering the patient's young age, dentistry should be preservative using the adhesive technique. This case report documents the systematic procedure of the functional and esthetic rehabilitation of an eroded dentition and shows factors essential to the treatment.

[The image of dentistry. Part 2: The ideal dentist]

Our second part of the publication entitled "The image of Dentistry" discusses the properties that correspond to the ideal image of dentistry or even the ideal scientist such as the management of the dental practice, the dentist-patient relationship and the appropriate handling of the patient's emotions such as anxiety or pain. The quality of treatment and the friendly, honest and compassionate attitude of the dentist can immediately affect the image of dentistry. Therefore, the dental professional must try to keep the balance between practice profit, staffing and patient well-being in order to fulfill both social and public health responsibilities.