Long term success of percutaneous implants is dependent on soft tissue attachment to prevent infection and epithelial downgrowth, which leads to failure of the implant. Fibronectin coatings are known to enhance fibroblast attachment in vitro, but are subject to desorption from serum protein competition in vivo. This paper quantifies the binding of fibronectin to titanium alloy by silanization and the durability of this attachment when soaked in protein-rich fluid compared with adsorbed fibronectin. The biological activity of fibronectin bound to silanized titanium alloy was confirmed by analyzing cell area, morphology, immunolocalization of focal contacts, and metabolism of dermal fibroblasts. This was compared with both adsorbed fibronectin and uncoated titanium alloy. Silanized titanium alloy bound over twice the amount of fibronectin compared to untreated titanium alloy. On soaking in fetal calf serum there was no significant loss of fibronectin (p = 0.589) from the silanized surface but a significant 44% loss (p = 0.002) from untreated surfaces. Fibroblasts on silanized fibronectin had significantly larger cell areas and more vinculin focal contact markers when compared to untreated surfaces (p < 0.005). The results confirm the durability of silanized fibronectin from protein competition and bioactive effect on fibroblasts.
Parkinson's disease (PD) is associated with loss of dopaminergic signalling, and affects not just movement, but also vision. As both mammalian and fly visual systems contain dopaminergic neurons, we investigated the effect of LRRK2 mutations (the most common cause of inherited PD) on Drosophila electroretinograms (ERGs). We reveal progressive loss of photoreceptor function in flies expressing LRRK2-G2019S in dopaminergic neurons. The photoreceptors showed elevated autophagy, apoptosis and mitochondrial disorganization. Head sections confirmed extensive neurodegeneration throughout the visual system, including regions not directly innervated by dopaminergic neurons. Other PD-related mutations did not affect photoreceptor function, and no loss of vision was seen with kinase-dead transgenics. Manipulations of the level of Drosophila dLRRK suggest G2019S is acting as a gain-of-function, rather than dominant negative mutation. Increasing activity of the visual system, or of just the dopaminergic neurons, accelerated the G2019S-induced deterioration of vision. The fly visual system provides an excellent, tractable model of a non-autonomous deficit reminiscent of that seen in PD, and suggests that increased energy demand may contribute to the mechanism by which LRRK2-G2019S causes neurodegeneration.
Background:The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies.
modes of variability in the Southern Hemisphere, such as ENSO. This implies that several factors, possibly more localised, may modulate the spatial and temporal frequency of severe thunderstorms across the region.
Stump ulcers are common problems in amputees. Temporary discontinuation of prosthetic limb use is frequently employed to facilitate healing. Inevitably, this limits activity and may, for instance, prevent an amputee from going to work. A survey of clinical practice was carried out based on the premise that controlled continued prosthetic limb use in patients with stump ulcers will not adversely affect the ulcer nor prevent healing. The survey would also form a basis for developing future guidelines in the management of stump ulcers. All consecutive patients attending the Chapel Allerton Hospital prosthetic clinic between January 2003 and May 2004 with stump ulcers were recruited into the study. Primary outcome measures were changes in the surface area of the ulcers and in clinical photographs taken on 2 occasions 6 weeks apart. Some 102 patients with a mean age 60 years (range 18 -88 years) were recruited. Eight patients who were established prosthetic limb users did not complete the study and were excluded from the analysis. Of the patients 52 were newly referred patients with delayed surgical wound healing while 42 were established prosthetic limb users for at least 1 year. Continued prosthetic limb was associated with a significant reduction in ulcer size (p 5 0.05). Mean sizes of the ulcers at first and second observations were 3.30 cm 2 (range 0.06 -81) and 0.70 cm 2 (range 0.00 -13.00) respectively. The ulcers improved in 83 cases while two were unchanged. Deterioration was observed in nine cases. The current clinical practice is to allow most of the patients to commence or continue prosthetic limb wearing despite the presence of stump ulceration. This observational study found that, despite prosthetic use, 60 (64%) cases healed completely within the six-week study period and 23 (25%) ulcers reduced in size. The ulcers were unchanged in 2% of the cases. Deterioration was observed in nine (9%) cases. This survey suggests that the current practice of allowing patients to use their prostheses is safe. A clinical trial is now needed to establish whether this practice alters healing rate or has any other disadvantages for new or established amputees.
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