Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia.

Patients with defective ectodysplasin A (EDA) are affected by X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by sparse hair, inability to sweat, decreased lacrimation, frequent pulmonary infections, and missing and malformed teeth. The canine model of XLHED was used to study the developmental impact of EDA on secondary dentition, since dogs have an entirely brachyodont, diphyodont dentition similar to that in humans, as opposed to mice, which have only permanent teeth (monophyodont dentition), some of which are very different (aradicular hypsodont) than brachyodont human teeth. Also, clinical signs in humans and dogs with XLHED are virtually identical, whereas several are missing in the murine equivalent. In our model, the genetically missing EDA was compensated for by postnatal intravenous administration of soluble recombinant EDA. Untreated XLHED dogs have an incomplete set of conically shaped teeth similar to those seen in human patients with XLHED. After treatment with EDA, significant normalization of adult teeth was achieved in four of five XLHED dogs. Moreover, treatment restored normal lacrimation and resistance to eye and airway infections and improved sweating ability. These results not only provide proof of concept for a potential treatment of this orphan disease but also demonstrate an essential role of EDA in the development of secondary dentition.

Dating human skeletal remains using 90Sr and 210Pb: case studies. [Dating human skeletal remains using Sr-90 and Pb-210: Case studies]

In legal medicine, the post mortem interval (PMI) of interest covers the last 50 years. When only human skeletal remains are found, determining the PMI currently relies mostly on the experience of the forensic anthropologist, with few techniques available to help. Recently, several radiometric methods have been proposed to reveal PMI. For instance, (14)C and (90)Sr bomb pulse dating covers the last 60 years and give reliable PMI when teeth or bones are available. (232)Th series dating has also been proposed but requires a large amount of bones. In addition, (210)Pb dating is promising but is submitted to diagenesis and individual habits like smoking that must be handled carefully. Here we determine PMI on 29 cases of forensic interest using (90)Sr bomb pulse. In 12 cases, (210)Pb dating was added to narrow the PMI interval. In addition, anthropological investigations were carried out on 15 cases to confront anthropological expertise to the radiometric method. Results show that 10 of the 29 cases can be discarded as having no forensic interest (PMI>50 years) based only on the (90)Sr bomb pulse dating. For 10 other cases, the additional (210)Pb dating restricts the PMI uncertainty to a few years. In 15 cases, anthropological investigations corroborate the radiometric PMI. This study also shows that diagenesis and inter-individual difference in radionuclide uptake represent the main sources of uncertainty in the PMI determination using radiometric methods.