Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation.

A better understanding of the cellular and molecular pathomechanisms of Alzheimer's disease (AD) is a prerequisite for the development of efficient treatments. We have used a novel assay system based on virus-transduced organotypic hippocampal slice cultures that mimics important aspects of tau-driven AD pathology in a short time frame. Human tau P301L, when expressed in pyramidal neurons of hippocampal slice cultures, was increasingly phosphorylated at several disease-relevant epitopes, leading to progressive neuronal dystrophy and formation of RIPA-insoluble tau. AD-like tau hyperphosphorylation was reduced by the tau kinase inhibitors lithium and SRN-003-556, but RIPA-insoluble tau remained unaffected after treatment with any of these substances. Only SRN-003-556 was able to protect hippocampal neurons from synaptic damage that was presumably caused by a toxic soluble tau fraction. These data provide first mechanistic insights towards the functional benefits of SRN-003-556 that have been observed in vivo.

Occipitomental (Waters' view) radiographs from general practice: are they adequate?

Critics maintain that family physicians produce radiographic images of poorer technical quality than radiologists but the impact of lower quality images on patient care is unknown. Two radiologists assessed occipitomental radiographs made in either a general practice or a certified laboratory for 247 patients with clinically diagnosed acute bacterial rhinosinusitis. With an occipitomental radiograph correct positioning is more difficult than with the usual radiographs of chest or extremities commonly made in general practice. Good positioning was less common in radiographs from general practices, with the pyramid projected below the maxillary sinuses in 63% of radiographs from general practice and 79% of radiographs from a certified laboratory. However, a radiographic diagnosis of possible acute maxillary sinusitis was as common in radiographs from general practice (38%) as in radiographs from a certified laboratory (41%). Although routine use is not recommended, family physicians with suitable technical and interpretative skills can use an occipitomental radiograph to rule out acute maxillary sinusitis in difficult cases. With a radiograph that is hard to read the physician should act as if the disease is present or refer the radiograph to a consulting radiologist.