Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty-eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three-point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups.     

Interhemispheric sleep EEG asymmetry in the rat is enhanced by sleep deprivation

Vigilance state-related topographic variations of electroencephalographic (EEG) activity have been reported in humans and animals. To investigate their possible functional significance, the cortical EEG of the rat was recorded from frontal and parietal derivations in both hemispheres. Records were obtained for a 24-h baseline day, 6-h sleep deprivation (SD), and subsequent 18-h recovery. During the baseline 12-h light period, the main sleep period of the rat, low-frequency (<7.0 Hz) power in the non-rapid eye-movement (NREM) sleep EEG declined progressively. Left-hemispheric predominance of low-frequency power at the parietal derivations was observed at the beginning of the light period when sleep pressure is high due to preceding spontaneous waking. The left-hemispheric dominance changed to a right-hemispheric dominance in the course of the 12-h rest-phase when sleep pressure dissipated. During recovery from SD, both low-frequency power and parietal left-hemispheric predominance were enhanced. The increase in low-frequency power in NREM sleep observed after SD at the frontal site was larger than at the parietal site. However, frontally no interhemispheric differences were present. In REM sleep, power in the theta band (5.25-8.0 Hz) exhibited a right-hemispheric predominance. In contrast to NREM sleep, the hemispheric asymmetry showed no trend during baseline and was not affected by SD. Use-dependent local changes may underlie the regional differences in the low-frequency NREM sleep EEG within and between hemispheres. The different interhemispheric asymmetries in NREM and REM sleep suggest that the two sleep states may subserve different functions in the brain.     

Decreased binding to hypothalamic insulin receptors in young genetically obese rats

[125I]insulin binding to partially purified hypothalamic membranes is reduced during prolonged starvation, and changes in hypothalamic insulin binding capacity correlate well with spontaneous variations in energy balance in ground squirrels. To determine whether an insulin binding impairment in the central nervous system can be observed during the early expression of genetic obesity, both obese (fa/fa) and phenotypically lean (Fal-) Zucker rats were studied at 6 weeks of age. Hypothalamic tissue from fa/fa rats bound significantly less hormone than that from the lean animals, but binding was not changed in tissue from cerebral cortex. It is concluded that a defect in insulin binding to hypothalamic receptors in Zucker fatty rats may contribute to the development of weight gain in these animals.     

Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker

A prerequisite to dephosphorylation at Ser–Pro or Thr–Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker.     

Exome sequencing in familial corticobasal degeneration

BackgroundCorticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described.ObjectiveWe aim to characterize the clinical, imaging, pathological and genetic features of two familial cases of CBD.MethodsWe describe two first cousins with CBD associated with atypical MRI findings. We performed exome sequencing in both subjects and in an unaffected first cousin of similar age.ResultsThe cases include a 79-year-old woman and a 72-year-old man of Native American and British origin. The onset of the neurological manifestations was 74 and 68 years respectively. Both patients presented with a combination of asymmetric parkinsonism, apraxia, myoclonic tremor, cortical sensory syndrome, and gait disturbance. The female subject developed left side fixed dystonia. The manifestations were unresponsive to high doses of levodopa in both cases. Extensive bilateral T1-W hyperintensities and T2-W hypointensities in basal ganglia and thalamus were observed in the female patient; whereas these findings were more subtle in the male subject. Postmortem examination of both patients was consistent with corticobasal degeneration; the female patient had additional findings consistent with mild Alzheimer's disease. No Lewy bodies were found in either case. Exome sequencing showed mutations leading to possible structural changes in MRS2 and ZHX2 genes, which appear to have the same upstream regulator miR-4277.ConclusionsCorticobasal degeneration can have a familial presentation; the role of MRS2 and ZHX2 gene products in CBD should be further investigated.     

Modeling and measurement of the detector presampling MTF of a variable resolution x-ray CT scanner

The detector presampling modulation transfer function (MTF) of a 576-channel variable resolution x-ray (VRX) computed tomography (CT) scanner was evaluated in this study. The scanner employs a VRX detector, which provides increased spatial resolution by matching the scanner's field of view (FOV) to the size of an object being imaged. Because spatial resolution is the parameter the scanner promises to improve, the evaluation of this resolution is important. The scanner's pre-reconstruction spatial resolution, represented by the detector presampling MTF, was evaluated using both modeling (Monte Carlo simulation) and measurement (the moving slit method). The theoretical results show the increase in the cutoff frequency of the detector presampling MTF from 1.39 to 43.38 cycles/mm as the FOV of the VRX CT scanner decreases from 32 to 1 cm. The experimental results are in reasonable agreement with the theoretical data. Some discrepancies between the measured and the modeled detector presampling MTFs can be explained by the limitations of the model. At small FOVs (1-8 cm), the MTF measurements were limited by the size of the focal spot. The obtained results are important for further development of the VRX CT scanner.     

Changes in stretch reflex excitability are related to "giving way" symptoms in patients with anterior cruciate ligament rupture

A rupture of the anterior cruciate ligament (ACL) usually leads to an altered stretch reflex excitability of the thigh muscles that stabilize the knee. The purpose of this study was to quantitatively assess reflex activity in the m. semitendinosus/semimembranosus after anterior tibial translation in 21 patients with isolated ACL ruptures. The patients were divided into a group with "giving way" symptoms (noncopers, n = 12) and a group without "giving way" symptoms (copers, n = 9). While the patients were standing upright with 30 degrees knee flexion, a force of 300 N was applied to the knee to induce posterior-anterior tibial translation. Activity of m. semitendinosus/semimembranosus was measured using surface electromyography (EMG). A linear potentiometer was placed on the tibial tuberosity and measured maximum tibial translation during standing (i.e., functional condition). In addition, knee laxity was assessed with a KT1000 arthrometer under passive conditions. After ACL rupture, the short-latency response (SLR) latency remained unchanged (P = 0.21), whereas for the medium-latency response (MLR) it was significantly longer (P < 0.001). Significantly longer MLR latencies were noted for noncopers compared with copers (P < 0.01), whereas SLR latencies were similar. Significant differences between healthy and injured legs were noted after tibial translations using KT1000 (P < 0.001) and during stance (P < 0.001). Mechanical knee instability was found to be unchanged between copers and noncopers (KT1000: P = 0.97; tibial translation: P = 0.31). These results indicate that ACL rupture is associated with altered stretch reflex excitability, which may lead to "giving way" symptoms, and that altered stretch reflex excitability may be more important for the development of "giving way" than the mechanical instability of the knee.     

Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines

There is an increasing recognition that mitochondrial dysfunction is associated with autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction and how mitochondrial abnormalities might interact with other physiological disturbances such as oxidative stress. Reserve capacity is a measure of the ability of the mitochondria to respond to physiological stress. In this study, we demonstrate, for the first time, that lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS). Ten (44%) of 22 AD LCLs exhibited abnormally high reserve capacity at baseline and a sharp depletion of reserve capacity when challenged with ROS. This depletion of reserve capacity was found to be directly related to an atypical simultaneous increase in both proton-leak respiration and adenosine triphosphate-linked respiration in response to increased ROS in this AD LCL subgroup. In this AD LCL subgroup, 48-hour pretreatment with N-acetylcysteine, a glutathione precursor, prevented these abnormalities and improved glutathione metabolism, suggesting a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction. The results of this study suggest that a significant subgroup of AD children may have alterations in mitochondrial function, which could render them more vulnerable to a pro-oxidant microenvironment as well as intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxins. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors.