On the secondary stability of coated cementless hip replacement: parameters that affected interface strength

Unlike primary stability of coated cementless implants, their secondary stability has been poorly studied. This paper considers some theoretical aspects of the secondary stability of a coated cementless hip implant in a human femur. The bone is separated from the implant by a thin layer of microscopic peaks and troughs formed on the surface of the coating. The size of the peaks and troughs is very small compared with the macrosize of the implant stem and bone in contact. The study of the bone–stem contact by direct application of the finite element method is prohibitively costly. A two-scale asymptotic homogenisation procedure that takes into account the microgeometry of the interface layer and mechanical properties of bone and the implant material is applied to obtain effective, homogenised contact parameters. These parameters can be used in finite element analyses involving smooth interfaces, which require hundreds of times fewer finite elements. With the homogenisation technique and finite element analyses for a simplified design, two parameters were found to be most important—the normal contact stiffness and the friction coefficient. They both increase several times as bone grows into the rough surface of the implant and mineralises, thus providing a stronger interface and resulting in reduced micromotions.     

False aneurysm of ascending aorta due to pericardial mesothelioma

Ascending aortic false aneurysm is a rare but serious complication of pericardial mesothelioma. We report a case of ascending aortic pseudoaneurysm due to spindle cell pericardial mesothelioma. In this case, the first symptoms of the disease appeared 18 months before surgery. The final diagnosis was determined only when severe late complications occurred. Palliative tumour excision, aortoplasty and aortic valve prosthesis were performed with subsequent adjuvant chemotherapy. Over 10 months after surgery, the patient is alive and a significant reduction of the tumour mass has been achieved. This case demonstrates that timely lifetime diagnosis of malignant pericardial tumour remains very difficult and effective adjuvant chemotherapy is needed to improve the results of surgery.     

Gene expression changes in dorsal root ganglia following peripheral nerve injury: roles in inflammation,cell death and nociception

Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.     

A lentivirally delivered photoactivatable GFP to assess continuity in the endoplasmic reticulum of neurones and glia

The endoplasmic reticulum (ER) is the largest intracellular membranous organelle. Functions of the ER are many and diverse, which include various biosynthetic, transport and signalling roles, central to cellular physiology, such as the biosynthesis of membrane and secretory proteins and the regulation of intracellular calcium. Its continuous lumen also serves as a highway for the distribution of proteins and ions to different regions of the cell, independent of the cytosol. The ER is an excitable organelle, capable of generating a regenerative wave of calcium release, which can propagate along the endomembrane throughout the entire cell, serving as a system of intracelluar communication in polarised cells. Nowhere is this feature of ER function more crucial than in neurones. The extremely polarised nature of nerve cells presents a unique challenge for the global co-ordination of localised physiological events such as growth cone guidance and synaptic plasticity. Clearly, the physical continuity of the neuronal ER lumen is central to its functionality as a conduit for communication. To further probe the continuity of ER in neurones and glia, we developed LV-PA-pIN-KDEL, a photoactivatable analogue of our recently described vector LV-pIN-KDEL, a lentivirally delivered ER-targeting soluble GFP. We demonstrate the ability of this vector to transduce astrocytes and neurones in culture and in cortical explants. Furthermore, we exploit the photoactivatable attributes of the vector together with a focal laser photoactivation protocol to reveal the continuous nature of the ER lumen in these cell types, presenting the first direct evidence of an astrocytic ER luminal continuum and providing more data to support the existence of a single ER lumen in neurones. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Anticonvulsant effect of retigabine during postnatal development in rats

Retigabine is a new-generation antiepileptic drug that exerts therapeutic action through the activation of KCNQ channel dependent M-type potassium currents. While retigabine has been extensively studied in adult animals using a wide variety of seizure models, its effects in developing animals have not been examined. There has only been one previous report of retigabine efficacy in juvenile rats (Mazarati et al., 2008), which examined efficacy against kindled seizures and did not examine ages younger than postnatal day (P) 14. To determine the efficacy of retigabine during brain development we pretreated rats with retigabine (0-30 mg/kg) at three ages corresponding to the neonatal period through late childhood/early adolescence (i.e., P7, P14, or P25). Seizures were induced 30 min later using a chemoconvulsant (pentylenetetrazol, PTZ) model, which has been widely used to determine anticonvulsant efficacy of many other antiepileptic drugs in neonatal animals. In a dose and age-dependent manner, retigabine reduced the severity of PTZ evoked seizures, increased the latency to seizure onset, and decreased the incidence of full maximal seizures. The minimum effective dose was found to be 5mg/kg for P7 animals, 2.5mg/kg for P14 animals, and 1mg/kg for P25 animals. These findings allow a direct comparison between retigabine and previously studied antiepileptic drugs against PTZ seizures during development, and provide the first report of the effective dose range of retigabine in neonatal animals.     

Basic presynaptic functions in hippocampal neurons are not affected by acute or chronic lithium treatment

Lithium is an effective mood-stabilizer in the treatment of bipolar affective disorder. While glycogen synthase kinase 3-mediated and inositol depletion-dependent effects of lithium have been described extensively in literature, there is very little knowledge about the consequences of lithium treatment on vesicle recycling and neurotransmitter availability. In the present study we have examined acute and chronic effects of lithium on synaptic vesicle recycling using primary hippocampal neurons. We found that exocytosis of readily releasable pool vesicles as well as recycling pool vesicles was unaffected by acute and chronic treatment within the therapeutic range or at higher lithium concentrations. Consistent with this observation, we also noticed that the network activity and number of active synapses within the network were also not significantly altered after lithium treatment. Taken together, as lithium treatment does not affect synaptic vesicle release at even high concentrations, our data suggest that therapeutic effects of lithium in bipolar affective disorder are not directly related to presynaptic function.