Clinical diversity and treatment results in Tegumentary Leishmaniasis: A European clinical report in 459 patients

BackgroundCutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management.MethodologyDemographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients.Principal findingsCompared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%).Conclusion/SignificanceCL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates.     

4-Mercaptoimidazoles derived from the naturally occurring antioxidant ovothiols 2. Computational and experimental approach of the radical scavenging mechanism

The radical-scavenging mechanism of fourteen 4-mercaptoimidazoles, derived from the natural family of ovothiols, was studied via a QSAR approach, cyclic voltammetry, ESR and NMR spectroscopy. A significant correlation was found between the DPPH scavenging abilities of test compounds and thermodynamic parameters like overall ease of disulphide formation. The production of a disulphide compound via thiyl radical formation is proposed. Upon DPPH scavenging, hydrogen abstraction from thiols yields transient short-lived thiyl radicals, which were characterised by ESR and rapidly dimerise to form a disulphide compound. Cyclic voltammetry showed that the best DPPH scavengers exhibit low oxidation potentials for their oxidation to disulphides.     

Destructive and non-destructive microanalysis of biocarbonates applied to anomalous otoliths of archaeological and modern sciaenids (Teleostei) from Peru and Chile

Anomalous otoliths were discovered among modern and archaeological (8th millennium BP) sciaenids. The two species concerned, Cilus gilberti and Sciaena deliciosa, are common on the Peruvian-Chilean coast and do not seem to be affected by this morphological anomaly that maintained in their populations for thousands of years. The carbonates of the anomalous forms, determined by X-ray diffraction, are different from that of the normal otoliths, i.e. calcite and vaterite instead of aragonite. A method of non-destructive analysis by cathodoluminescence is tested and assumptions on the origin of the anomaly and its possible implications on environmental studies are advanced.     

Endoplasmic reticulum resident, immunoglobulin joining chain, can be secreted by perturbation of the calcium concentration in the endoplasmic reticulum

We established a transient human joining (J)-chain gene expression system in the baby hamster kidney (BHK) cell. The J-chain was detected as a 29-kDa single band on Western blotting. Immunofluorescent staining of the transfectant revealed an exclusive localization of the J-chain in the endoplasmic reticulum (ER). Intracellular transport experiment revealed that incubating conditions favorable for vesicular stomatitis virus glycoprotein (VSV-G) transport did not allow the J-chain to exit from the ER. Analysis of glycosylation status of the J-chain in the transfectant was examined by tunicamycin treatment, endoglycosidase H digestion, and also by treatment with brefeldin A. It was found that an N-glycosylation consensus site of the J-chain was functional, and intracellular J-chain was endoglycosidase H sensitive. These results indicate that, in the absence of any immunoglobulin molecules, J-chain localizes exclusively in the ER. We also tested whether the J-chain could be exported from the ER by perturbing the Ca2+ concentration in the ER. Cultivation of the J-chain transfectant in the presence of ionomycin resulted in the time-dependent secretion of the J-chain. The secreted J-chain was modified by the Golgi resident glycosylation enzymes, indicating that the secreted J-chain passed through the normal exocytic pathway.