Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 Macmillan Publishers Ltd.No abstract available (Letter to the editor).The Leukaemia Research Fun

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Insights into maternal diet for the prevention of childhood leukaemia

Nutrition plays a crucial role in wellbeing and is being increasingly recognised as an environmental factor in the development of disease. During pregnancy, maternal diet influences foetal development, playing a role not only in the prevention of neural tube defects and malformations, but also in the susceptibility to disease later in life. Certain micronutrients, such as folates, are involved in the maintenance of genome integrity, which is compromised in cancer. A deficiency in these nutrients can therefore be relevant in carcinogenic processes. The early onset of childhood leukaemia implies that it originates already in utero, where environmental factors can interfere with the healthy development of the foetus. Population studies have found an association between maternal intake of folic acid and multivitamins and a reduced risk in the development of leukaemia in the offspring. Although the supplementation of vitamins is recommended during pregnancy, the adequate dosage and nutrient combinations need to be further elucidated to fully maximise their protective role

PDGF-BB Does Not Accelerate Healing in Diabetic Mice with Splinted Skin Wounds

Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used

Guidelines for the therapeutic use of botulinum toxin in movement disorders. Italian Study Group for Movement Disorders, Italian Society of Neurology.

Since its introduction in the early '80s the use of botulinum toxin has improved the quality of life of the patients affected by movement disorders. Toxin's neuromuscular blocking action allows a symptomatic treatment of those clinical conditions characterised by excessive muscular activity. Although the dosages used are safe and the side-effects are reversible, a correct use of botulinum toxin depends on the knowledge of its clinical pharmacology and of the anatomy of the body segments to be injected. In addition, the treatment of more complex conditions, i.e. laringeal dystonia, imposes an inter-disciplinary approach and specialised injection techniques. In this review, the Italian Study Group on Movement Disorders presents the consensus guidelines for the therapeutic use of botulinum toxin in movement disorders. The main toxin types, their use and administration modalities, and the training guidelines will be presented