Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids

The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells

Shortening osteotomy for the treatment of spinal neuroarthropathy following spinal cord injury. A case report and literature review

The development of Charcot’s arthropathy of the spine secondary to spinal cord injury is rare and reports in the literature concerning it’s surgical management are limited. Arthrodesis is the recommended treatment for painful and unstable neuropathic joints. Traditionally this involves extensive debridement of the affected joint with anterior and posterior instrumented fusion and autograft to bridge the defect. This paper reviews the reported surgical management of post-traumatic spinal neuroarthropathy in the recent literature and presents a case where sound fusion was achieved by a shortening osteotomy and end-to-end apposition of the fresh bleeding bony surfaces of the adjacent vertebral bodies. The patient reported marked improvement of symptoms post-operatively without any complications of surgery. CT scan at 13 months confirmed successful bony union. Clinical follow up was completed to 3 years. This technique eliminated the need for anterior surgery and extensive autograft thus reducing surgical morbidity

Diabetes dietary management alters responses to food pictures in brain regions associated with motivation and emotion: a functional magnetic resonance imaging study

Aims/hypothesis: We hypothesised that living with type 2 diabetes would enhance responses to pictures of foods in brain regions known to be involved in learnt food sensory motivation and that these stronger activations would relate to scores for dietary adherence in diabetes and to measures of potential difficulties in adherence. Methods: We compared brain responses to food images of 11 people with type 2 diabetes and 12 healthy control participants, matched for age and weight, using functional magnetic resonance imaging (fMRI). Results: Having type 2 diabetes increased responses to pictured foods in the insula, orbitofrontal cortex (OFC) and basal ganglia and, within these regions, the effect of the fat content of the foods was larger in participants with type 2 diabetes than in healthy controls. Furthermore, increased activation to food within the insula and OFC positively correlated with external eating, dietary self-efficacy and dietary self-care. In contrast, responses within subcortical structures (amygdala and basal ganglia) were positively correlated with emotional eating and rated appetite for the food stimuli and negatively correlated with dietary self-care. Conclusions/interpretation: Type 2 diabetes is associated with changes in brain responses to food that are modulated by dietary self-care. We propose that this is linked to the need to follow a life-long restrictive diet