Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy

A 17‐year‐old female was diagnosed with Wilson disease and commenced on oral zinc therapy. She re‐presented 6 months later with a fall and had classical signs of subacute combined degeneration of the spinal cord confirmed on nerve conduction studies, as a result of zinc‐induced copper deficiency. After 6 months of copper therapy, she made a complete recovery with no residual neurological deficits. Early detection of zinc‐induced copper deficiency and stringent follow‐up mechanisms are crucial. Early initiation of copper replacement may both limit and completely reverse neurological deficits.     

Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Bone morphogenetic protein- and mating-dependent secretory cell growth and migration in the Drosophila accessory gland

The paired male accessory glands of Drosophila melanogaster enhance sperm function, stimulate egg production, and reduce female receptivity to other males by releasing a complex mixture of glycoproteins from a secretory epithelium into seminal fluid. A small subpopulation of about 40 specialized secretory cells, called secondary cells, resides at the distal tip of each gland. We show that these cells grow via mechanisms promoted by mating. If aging males mate repeatedly, a subset of these cells delaminates from and migrates along the apical surface of the glandular epithelium toward the proximal end of the gland. Remarkably, these secretory cells can transfer to females with sperm during mating. The frequency of this event increases with age, so that more than 50% of triple-mated, 18-d-old males transfer secondary cells to females. Bone morphogenetic protein signaling specifically in secondary cells is needed to drive all of these processes and is required for the accessory gland to produce its normal effects on female postmating behavior in multiply mated males. We conclude that secondary cells are secretory cells with unusual migratory properties that can allow them to be transferred to females, and that these properties are a consequence of signaling that is required for secondary cells to maintain their normal reproductive functions as males age and mate.     

Case involving CAD/CAM-generated, screw-retained bridge demonstrates dentistry's scientific progression

The patient in the case presented had successfully used a maxillary overdenture for more than three decades. However, the time had come for the prosthetic appliance to be replaced. This case, which involved the use of a titanium understructure that was designed and fabricated using CAD/CAM technology, illustrates how far dentistry has come since the patient first presented to the clinician some 35 years ago when dental science had not yet included such innovations as bone grafting and CT scans.