Amyloid-β oligomer synaptotoxicity is mimicked by oligomers of the model protein HypF-N

Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-β peptide play a central role in Alzheimer's disease pathogenesis, being implicated in synaptic dysfunction. Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control nontoxic oligomers had none of such effects. These results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer's disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid β peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease.     

Effects of 980-nm diode laser on the ultrastructure and fracture resistance of dentine

Few reports have addressed the effects of diode laser irradiation at 980 nm on the morphology and fracture resistance of dentine. The purpose of this study is to evaluate the effects of 980-nm diode laser on the ultrastructure and fracture resistance of root dentine. The roots of 90 extracted canine teeth were divided into three groups according to the type of irrigating solution (water, NaOCl, and NaOCl/EDTA) and subdivided into three subgroups (n?=?10) according to the amount of laser irradiation (without irradiation, 1.5 W/100 Hz and 3.0 W/100 Hz). The roots were filled with an epoxy resin-based sealer and gutta-percha and then subjected to a fracture resistance test. Data were analyzed by ANOVA and the Tukey test (p?<?0.05). Additionally, 18 canine teeth were prepared using the same irrigation/irradiation protocols and evaluated by scanning electron microscopy (SEM). The SEM showed greater changes when the laser power increased, and the changes also varied according to the irrigating solution. A modified smear layer was observed in specimens that were treated with water and then laser-irradiated. The laser treatment did not alter the fracture resistance of roots treated with 1.5 W/100 Hz (246.3?±?29.5 N) and 3.0 W/100 Hz (215.3?±?25.1 N) laser power. The roots treated with NaOCl were more susceptible to fracture (199.4?±?15.1 N) than those irrigated with water (254.2?±?23.0 N) (p?<?0.05). The 980-nm diode laser altered the morphology of the dentine but did not affect the fracture resistance of the roots.     

Fluoxetine and inappropriate antidiuretic hormone secretion in elderly patients: a case report

Elderly people are more likely to be affected by hyponatremia related to the use of specific inhibitors of serotonin recaptation. Doctors who treat old patients should be aware of this adverse effect which can be serious but is reversible. The observation of a new case of SIADH induced by fluoxetine in a 65 years-old patient is the opportunity to point out the main aspects of this pathological entity which must be suspected in case with hyponatraemia, blood hypoosmolality and high urinary osmolarity.     

Kidney vasculitis connected to cryoglobulinemia IIA and hepatitis B

We report the case of a 70 years old patient hospitalized for renal insufficiency and deterioration of the general state. The electrophoresis of serum proteins on freezing of agarose reveals the presence of a discrete peak of monoclonal pace on the level of the gammaglobulines identified by serum immunofixation like IgM of the kappa type. The research of the cryoglobulinemia carried out in a laboratory of city was made positive and typified like a monoclonal cryoglobulinemia IgM kappa, thus directing the diagnosis towards a disease of Waldenstr?m. However, the result of the biopsy medullary made exclude any lymphoprolifératif syndrome. The positivity of the serology of hepatitis B justified a second request for study of the cryoglobulinemia, carried out within our laboratory. The cryoglobuline was typified like mixed (IgM kappa monoclonal and IgG polyclonales). This result associated with the immunological assessment and the renal biopsy made retain for our patient the diagnosis of a kidney vasculitis connected to an infection chronicle by the virus of hepatitis B. This observation points out the interest of the preanalytic, analytic and post analytic phases in the study of the cryoglobulinemias. A good technical control is today the only guarantee of the quality of the result of this examination which has large importance in internal medicine in the etiologic assistance with the diagnosis of certain clinical demonstrations.     

B-cell memory in malaria: Myths and realities

B-cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long-lasting B-cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long-lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B-cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype-switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B-cell responses to Plasmodium infections.