Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells

Demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacterial attachment, whereas nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers. During M. leprae-induced demyelination, Schwann cells proliferate significantly both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby securing the intracellular niche for M. leprae.     

A family with severe insulin resistance and diabetes due to a mutation in AKT2

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.     

Electrochemotherapy in treatment of canine oral non‐tonsillar squamous cell carcinoma. A case series report

Non‐tonsillar squamous cell carcinoma (ntSCC) is a common and locally aggressive oral tumour in dogs. The treatments of choice are currently surgery and radiotherapy. Electrochemotherapy (ECT) is a local ablative anti‐tumour technique using electric pulses to enhance the intracellular diffusion of cytotoxic drugs. The aim was to retrospectively evaluate the outcome of patients with oral ntSCC treated with ECT. Twelve dogs with ntSCC were retrospectively enrolled. ECT was combined with IV bleomycin (15 000 UI/m²) alone in 11 cases and post‐surgery in 1. Parameters considered were: tumour site and size, electroporation parameters, response rate (complete remission [CR], partial remission [PR]), median survival time (MST), recurrence rate (RR), median disease‐free interval (DFI) and treatment toxicity (6‐point scale). Median tumour size was 1.65 cm (range 0.3‐8.0 cm) and the response rate was 90.9% (10/11; 8 CR and 2 PR). Two dogs underwent a second ECT. MST for dogs dead with tumour (n = 2) was 110 days and for dogs dead without tumour (n = 3) was 831 days. Among five surviving dogs, one experienced tumour recurrence and four were in CR. Results from two dogs were analysed separately. Overall RR was 27.3%. DFI and MST for dogs with recurrence were 50 and 115 days, respectively. Treatment toxicity was very low. We noticed that all dogs with tumours smaller than 1‐2 cm achieved CR without recurrence suggesting a favourable prognosis when using ECT. ECT for canine ntSCC could be considered a valid treatment option especially for smaller tumours, but a larger caseload would be needed to confirm this statement.