Staurosporine‐induced collapse of cochlear hair bundles

Early postnatal mouse cochlear cultures were treated with a small panel of kinase inhibitors to elucidate the mechanisms underlying the maintenance of hair‐bundle structure in the developing inner ear. At low concentrations (1–10 nM), staurosporine causes the collapse and loss of hair bundles without provoking hair‐cell death, as judged by lack of terminal transferase dUTP nick end labeling (TUNEL) labeling or reactivity to anti‐activated caspase‐3. Staurosporine exposure results in the fusion of the hair bundle's stereocilia, a resorption of the parallel actin bundles of the stereocilia into the cytoplasm of the hair cell, a detachment of the apical, non‐stereociliary membrane of the hair cell from the underlying cuticular plate, and a severing of the hair‐bundle's rootlets from the actin cores of the stereocilia. It does not block membrane retrieval at the apical pole of the hair cells, nor does it elicit the externalization of phosphatidylserine. Staurosporine treatment causes a reduction in levels of the phosphorylated forms of ezrin, radixin, and moesin in cochlear cultures during the period of hair‐bundle loss, indicating the integrity of the hair bundle may be actively maintained by the phosphorylation status of these proteins. J. Comp. Neurol. 522:3281–3294, 2014. © 2014 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.     

Strategy-based semantic priming in Alzheimer's dementia

The ability to engage semantic search strategies was assessed in a group of patients with dementia of the Alzheimer's type (DAT) (n = 11) and a group of age-matched control subjects (n = 13). The subjects performed a semantic priming task in which attentional priming was induced by manipulating the expected relationship between the primes and targets. Older control subjects were able to predict target words on the basis of expectancy, regardless of the semantic relationship between the prime and target. The DAT patients were also able to predict targets on the basis of expectancy, but only when the prime and target were semantically related. These results suggest that the structure of semantic memory remains intact in DAT, and that semantic memory retrieval may be facilitated by providing DAT patients with appropriate search strategies.     

Measuring the anticoagulant effects of target specific oral anticoagulants—reasons, methods and current limitations

To simplify and optimize oral anticoagulation, new target-specific oral anticoagulants (TSOAs) have been developed. The direct thrombin-inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban are the first such compounds to receive approval in certain countries for various indications. Due to the predictable pharmacokinetic and pharmacodynamic profiles of these drugs, routine monitoring of patients receiving TSOA therapy has not been considered necessary. However, it has now been realized that in routine clinical settings, there are several situations where it may be prudent to assess the level of TSOA anticoagulation. Several studies evaluating the influence of TSOAs on various coagulation assays have been performed to identify systems that can be used to monitor these drugs. With a particular focus on dabigatran and rivaroxaban, we will describe and discuss the potential of several methods for measuring the anticoagulant effect of TSOAs, as well as their methodological limitations and the restrictions in transferring their results into clinical context.     

Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes

With the increasing incidence of multiple sclerosis (MS) in women and the earlier use of disease modifying therapy (DMT), issues surrounding DMT and pregnancy are a regular subject of discussion with regards to optimal management. Current recommendations are to withdraw DMT prior to conception, leaving patients exposed to an uncertain period of untreated disease. The objective of this study is to report preliminary experience on glatiramer acetate (GA) exposure through conception, pregnancy and the post-partum period in a series of 13 patients with previously highly active relapsing-remitting MS. This is a prospective observational case series. Fourteen pregnancies of 13 women resulted in 13 live births (one twin pregnancy), nine exposed to GA throughout pregnancy. There were no birth defects and treatment was well tolerated. No relapses occurred during pregnancy in those continuing on treatment. In conclusion, our early experience suggests that when considering the risks and benefits of treatment withdrawal prior to pregnancy, it may be reasonable to continue GA in those patients with previously highly active disease. Consideration should also be given to the initiation of a birth register, similar to such initiatives in epilepsy, to generate more robust safety data in this controversial area.     

Aggregatibacter actinomycetemcomitans–Induced Bone Loss and Antibody Response in Three Rat Strains

Background: The aim of this study is to compare the colonization, immunoglobulin (Ig) G response, and alveolar bone loss in Aggregatibacter actinomycetemcomitans (Aa)–inoculated Fawn Hooded Hypertensive (FHH), Dahl Salt‐Sensitive (DSS), and Brown Norway (BN) rats. Methods: Each rat strain was divided into wild‐type Aa‐inoculated and non‐inoculated control groups. Blood taken at 12 weeks after inoculation was assessed for Aa‐specific IgG antibodies by an enzyme‐linked immunosorbent assay. Colonization was assessed 12 weeks postinoculation. Bone loss was estimated by measuring the distance from the cemento‐enamel junction (CEJ) to the alveolar bone crest (ABC) at 20 molar sites. Colonization and antibody levels were compared by using the Student t test. Diseased rats were defined as having two sites per quadrant with CEJ–ABC distances that were significantly greater than the control CEJ–ABC distances. Results: The Aa colonization of FHH rats was significantly higher than in other strains (P <0.05). The Aa‐specific IgG levels in the DSS Aa‐inoculated group were significantly higher than in its control group (P <0.05). Only FHH rats showed Aa disease‐associated bone loss (P = 0.0021). Conclusions: Aa colonized and caused more disease in FHH rats than in the other rat strains. The rat strains each responded differently to the same Aa strain.