Management of concurrent corneal diseases and cataract

Cataract surgery is the most common surgical procedure in the United States, and the likelihood of encountering complications from concurrent corneal disease and cataract surgery is great. The rise of pseudophakic bullous keratopathy as an indication for corneal transplantation reflects the current trend toward increasing corneal pathology arising from cataract surgery and intraocular lens complications. Attitudes regarding astigmatism have changed drastically. Cataract surgery, coupled with astigmatic procedures, is becoming the procedure of choice for visual rehabilitation. Congenital corneal conditions and systemic disease processes are also considered in this review.     

A Phase 2 open label study of ledipasvir/sofosbuvir for 12 weeks in subjects with hepatitis B virus infection

Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log₁₀ IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination.     

Current Status of the VU MFEL Compton X-Ray Program

The Vanderbilt University medical FEL (free electron laser) Compton x-ray program is close to being operational. The FEL modifications necessary for this new capability are near completion. The transport and detection systems for electron and IR beams have been designed, delivered, and tested. We initially expect to produce 108 x-ray photons per second in the 15- to 20-keV region.     

Serotonergic mechanisms of cocaine effects in humans

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine high were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.     

An anchoring factor targets protein phosphatase 2A to brain microtubules

Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase composed of a heterodimeric core enzyme that associates with a variety of regulatory subunits. A fraction of brain PP2A associates with microtubules and may play a role in regulating phosphorylation of microtubule-associated proteins. We examined the isoform specificity and the mechanism involved in the association of PP2A with brain microtubules. Only the R2alpha (B/PR55alpha) and R2beta (B/PR55beta) regulatory subunits associated with endogenous neural microtubules. Neither the R2gamma (B/PR55gamma) nor members of the R5 (B'/PR56) family of regulatory subunits co-sedimented with microtubules, although abundant amounts of these proteins were detected in brain. The efficient association of PP2A with microtubules in vitro was dependent on an anchoring activity present in a brain protein fraction containing microtubule-associated and microtubule-interacting proteins. Anchoring factor-dependent association of PP2A with microtubules was specific for the heterotrimeric form of PP2A. The core dimer and the isolated subunits of PP2A had very little affinity for microtubules. Characterization of a fraction enriched in the anchoring factor showed that the activity was a heat labile protein that does not correspond to classical microtubule-associated proteins. The anchoring factor associated with microtubules independently of PP2A. These results indicate the association of PP2A with microtubules can be mediated by an anchoring factor that interacts in an isoform-specific manner with heterotrimeric forms of the phosphatase.