Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transporter 1 expression and glutamate reuptake. We investigated whether CEF can prevent cognitive decline and neurological deficits and increase neurogenesis in DLB rats. Male Wistar rats infused with viral vector containing human alpha-synuclein (α-syn) gene, SNCA, in the lateral ventricle were used as a rat model of DLB. CEF (100 mg/kg/day, i.p.) was injected in these rats for 27 days. The active avoidance test and object recognition test was performed. Finally, the brains of all the rats were immunohistochemically stained to measure α-syn, neuronal density, and newborn cells in the hippocampus and substantia nigra. The results revealed that DLB rats had learning and object recognition impairments and exhibited cell loss in the nigrostriatal dopaminergic system, and hippocampal CA1, and dentate gyrus (DG). Additionally, DLB rats had fewer newborn cells in the DG and substantia nigra pars reticulata and more α-syn immune-positive cells in the DG. Treatment with CEF improved cognitive function, reduced cell loss, and increased the number of newborn cells in the brain. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of DLB rats. CEF may therefore has clinical potential for treating DLB.

Using a numerical method to precisely evaluate the alpha angle in a hip image.

The alpha angle is a parameter extensively used to assess for cam-type femoroacetabular impingement (FAI) in a 2D image of the hip. As this angle requires estimation of the axis of the femoral neck, the drawing of this axis often results in measurement errors due to subjective judgment, influencing inter-rater and intra-rater agreements. In the present study, sampling points were captured from the edges of a femoral neck and head in the 2D image, and the best curves of the two were fitted respectively by using the curve fitting method. The morphology of the femoral neck was outlined by two polynomials, and the femoral head was represented by an equation of a circle. By means of the proposed method, the results reveal that the inter-rater ICCs in X-ray and MRI were respectively 0.905 and 0.969, and the intra-rater ICCs in X-ray and MRI were respectively 0.892 and 0.840. The Bland-Altman plot shows that the values obtained by the proposed method and the conventional method were not consistent; nevertheless, the linear regression analysis indicated the two measurement results had a significant association (p < 0.001). This study provides a repeatable and agreed α angle measuring method, which contributes to identifying normal and abnormal femoral head-neck morphologies. The proposed numerical method would contribute to diagnose early FAI.

Using nonlinear finite element models to analyse stress distribution during subluxation and torque required for dislocation of newly developed total hip structure after prosthetic impingement.

Dislocation is a serious potential complication of total hip replacement. Previous studies have proposed a newly developed total hip structure that meets the required oscillation angle of 120°, for which the chamfer on the acetabular liner rim was designed to enable the neck to impinge on the chamfer over a large area after impingement occurs. This study adopted the finite element method to further analyse the torque limits leading to dislocation and the contact stresses at the impingement and egress sites of the liner during subluxation. The compressive stress-strain curve for ultra-high molecular weight polyethylene is nonlinear. The results reveal that an adequate chamfer angle of the acetabular cup liner can significantly increase dislocation torque and decrease contact stress on the liner rim. By means of the new design, when the head-neck ratio (HNR) is 2.5 or 3.0, the maximum torque value that a 36-mm head can withstand is 1.38 (8.7 Nm/6.3 Nm) or 1.47 (8.4 Nm/5.7 Nm) times that of a 22-mm head, while the maximum stress of a 36-mm head is 0.41 (14.58 MPa/35.73 MPa) or 0.70 (33.71 MPa/47.90 MPa) times that of a 22-mm head. When the head diameters are identical, the dislocation torque of the HNR = 2.5 structure is slightly greater than that of the HNR = 3.0 structure (3.3-10.5%); thus, the newly developed structure can disperse contact stress, and the structure of a large head with a low HNR exhibits a higher dislocation torque value and lower stress.

Dextromethorphan upregulates osteoblast and osteoclast activity but does not attenuate ovariectomy-induced osteoporosis.

AIMS: Study on the in vivo regulatory role of glutamate in osteoblast (OB) and osteoclast (OC) differentiation is less advanced. The present study investigated the effect of dextromethorphan (DXM), an N-methyl-d-aspartate receptors (NMDARs) antagonist, on osteoporosis development. MAIN METHODS: In order to examine the role of glutamate in bone metabolism, ovariectomized (Ovx) female Wistar rats were injected three times per week for 8weeks with either saline, or 15µg/kg of ß-estrodiol, or DXM (40mg/kg) intraperitoneally. Serum samples were collected every two weeks for measuring osteocalcin and C-terminal telopeptide of type I collagen (CTX-1) level. Rats were then sacrificed at week 8 and the femurs harvested for micro-CT scanning and mechanical strength. KEY FINDINGS: In saline-treated group, osteocalcin level significantly lower than that of sham-operated rats at 8weeks after operation, while CTX-1 levels were not affected. Estrogen treatment, as a positive control, partially inhibited the Ovx-induced reduction of osteocalcin serum level. DXM injection prevented the Ovx-induced reduction of osteocalcin expression and significantly upregulated CTX-1 expression. The micro-CT scan showed that the bone volume density decreased significantly in DXM treated rats compared to the sham-operated rats. In the mechanical strength assay, the maximum failure load for DXM treatment was significantly lower than the other groups. SIGNIFICANCE: Treatment with DXM upregulated OB and OC markers in Ovx rats, however with a greater effect on the OC marker, and had no significant benefit on bone volume density or bone strength.

The study of wear behaviors on abducted hip joint prostheses by an alternate finite element approach.

An acetabular cup with larger abduction angles is able to affect the normal function of the cup seriously that may cause early failure of the total hip replacement (THR). Complexity of the finite element (FE) simulation in the wear analysis of the THR is usually concerned with the contact status, the computational effort, and the possible divergence of results, which become more difficult on THRs with larger cup abduction angles. In the study, we propose a FE approach with contact transformation that offers less computational effort. Related procedures, such as Lagrangian Multiplier, partitioned matrix inversion, detection of contact forces, continuity of contact surface, nodal area estimation, etc. are explained in this report. Through the transformed methodology, the computer round-off error is tremendously reduced and the embedded repetitive procedure can be processed precisely and quickly. Here, wear behaviors of THR with various abduction angles are investigated. The most commonly used combination, i.e., metal-on-polyethylene, is adopted in the current study where a cobalt-chromium femoral head is paired with an Ultra High Molecular Weight Polyethylene (UHMWPE) cup. In all illustrations, wear coefficients are estimated by self-averaging strategy with available experimental datum reported elsewhere. The results reveal that the THR with larger abduction angles may produce deeper depth of wear but the volume of wear presents an opposite tendency; these results are comparable with clinical and experimental reports. The current approach can be widely applied easily to fields such as the study of the wear behaviors on ante-version, impingement, and time-dependent behaviors of prostheses etc.

Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.

Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis.

Effects of chronic treatment with diosgenin on bone loss in a D-galactose-induced aging rat model.

D-galactose is known to cause oxidative stress and induce aging-related diseases. Our previous study demonstrated that diosgenin can prevent osteoporosis in menopausal rats. The aim of the present study was to determine the effects of oral administration of diosgenin on bone loss in a D-galactose-induced aging rat model. Three groups of twelve-week-old male Wistar rats received a daily injection of D-galactose (150 mg/kg/day, i.p.) and orally administered diosgenin (0, 10, or 50 mg/kg/day) for eight weeks, while a control group received saline injection (1 ml/kg/day, i.p.), then the femurs were taken to measure mechanical and morphological properties. The results showed that frame volume and femur volume decreased and porosity and frame density increased in the D-galactose-induced aging rats compared to controls and that these effects were prevented by co-administration of diosgenin. This suggests that diosgenin might prevent bone loss during aging and provide beneficial effects in osteoporosis in the elderly.

Effects of design parameters of total hip components on the impingement angle and determination of the preferred liner skirt shape with an adequate oscillation angle.

The oscillation angle (OsA), which is the sum of the impingement angles on the two sides when the prosthetic neck sways from the neutral axis of the acetabular cup to the liner rim, is one of the most important factors that can affect the range of motion of an artificial hip joint. The aim of this study was to determine the influence of total hip component design on the impingement angle. Our findings show that an increase in cup depth of the liner restricts the motion of the neck and results in a reduced impingement angle, while an increase in chamfer angle increases the impingement angle until it reaches a critical value when a further increase no longer results in an increase in impingement angle. The impingement angle is not only dependent on the head/neck ratio, but also on the head size itself. For most arbitrarily chosen cup depths and chamfer angles, the neck only impacts at one point on the liner. This study proposes a suitable combination of cup depth and chamfer angle and a preferred impact mode, which, if impingement does occur, enables the neck to impinge on the liner rim over a large area. Cup-neck combinations that have an adequate OsA with maximum femoral head coverage are presented.

Wear analysis of chamfered elongated acetabular cup liners.

This study investigated the wear phenomena of chamfered acetabular cup liners. The liners have three parameters at the lengthened rim: the length of the elongation, the depth of the cup and the chamfer angle. Using published wear volume equations for cylindrically elongated liners, this study analysed the volume of the chamfer to obtain the exact theoretical wear volume of the chamfered liner. The criteria described in our previous paper were used to verify the accuracy of the proposed methodology. The results showed that a shallow cup depth (<2 mm) and a chamfer angle of about 30° could significantly reduce the wear volume arising from the elongation. When the chamfer angle was increased further, this effect became progressively less significant. The results suggest that a chamfer angle up to about 30° is appropriate, but the angle should not be larger than required to obtain the minimum femoral range of motion (ROM). The results of this study can also be integrated with the analysis of the kinetics and kinematics of liners. A compromise design incorporating a lower wear volume, sufficient ROM and a lower contact stress should be possible.

Wear patterns of, and wear volume formulae for, cylindrically elongated acetabular cup liners.

This study analyzed the wear patterns of, and wear volume formulae for, cylindrically elongated acetabular cup liners. The geometric patterns of the wear surface were first classified, then wear volume formulae were derived by integral calculus. SolidWorks((R)) software or published formulae were used to verify the accuracy of the proposed formulae. The analytical results showed that the wear shape of the liner can be categorized into seven wear patterns, including the special case of wear at 90 degrees , and the seven corresponding wear formulae were derived. In addition, wear of the cylindrical elongation might add considerably to the volume loss of the liner, depending on the height and shape of the elongation and the depth and direction of the linear penetration, being maximally 21% in the investigated model. The proposed wear formulae and patterns will be useful for more accurate performance evaluation of existing hip components implanted in patients and for the designing of new hip components.

Evaluating the accuracy of wear formulae for acetabular cup liners.

This study proposes two methods for exploring the wear volume of a worn liner. The first method is a numerical method, in which SolidWorks software is used to create models of the worn out regions of liners at various wear directions and depths. The second method is an experimental one, in which a machining center is used to mill polyoxymethylene to manufacture worn and unworn liner models, then the volumes of the models are measured. The results show that the SolidWorks software is a good tool for presenting the wear pattern and volume of a worn liner. The formula provided by Ilchmann is the most suitable for computing liner volume loss, but is not accurate enough. This study suggests that a more accurate wear formula is required. This is crucial for accurate evaluation of the performance of hip components implanted in patients, as well as for designing new hip components.

Vertebral axial rotation measurement method.

This study presents a new method for measuring axial rotation of vertebra. Anatomical landmarks of the vertebral body were first recognized in X-ray film. By employing appropriate geometrical relationships, vertebral body shape parameters and a computer iteration method, the rotation angle of vertebra on the transverse plane can rapidly be obtained. A cadaver lumbar spine axial rotation-fixation device was designed to confirm the accuracy of the proposed methodology. Rotation angles on CT images were adopted as the golden standard and compared with analytical results based on X-ray films. Analytical results demonstrated that the proposed method obtained more accurate and reliable results than previous methods.

Computer simulation on fatigue behavior of cemented hip prostheses: a physiological model.

This paper is concerned with the investigation on the fatigue failure of implant fixation by numerical approaches. A computer algorithm based on finite element analysis and continuum damage mechanics was proposed to quantify the fatigue damage rate of cement mantle under physiological conditions. In examining the interfacial debonding effect, the interface elements were introduced at cement-stem interfaces and calibrated with the increase of loading cycles. Current results reveal that the major sites for failure initiation are in the proximal anterior-medial regions and at the distal prosthesis tip, which clearly demonstrate the same failure scenario as observed in clinical studies. Such fatigue failures not only result in the corruption of cement-stem interfaces, but also greatly affect the cement stress distribution and the damage rate in subsequent loading cycles. Another significant result is that the predicted damage rate increases steadily with gait cycles. This trend in damage development is consistent with the findings obtained from fatigue tests available in literature. It is anticipated that presented methodology can serve as a pre-clinical validation of cemented hip prostheses.

The computer simulation of wear behavior appearing in total hip prosthesis.

Computer algorithms are proposed for the estimation of wear appearing in artificial hip joints using finite element analysis based on the modified Archard's wear law, contact features and an analogue wear process. A pin-on-disk plate experiment is reconstructed to assess the efficiency and validity of the algorithms proposed here. Through the successful verification of wear depth and volume loss of the pin-on-disk plate as well as the artificial hip joint, the current algorithms provide significant agreement with experiments, clinical measurements and numerical calculations and are shown to be both valid and feasible. Further investigation into the effect of femoral heads with various sizes suggests that the larger femoral head may induce larger wear volume but gives a smaller wear depth and that wear depth and volume loss are apparently nonlinearly related to the femoral head diameter. It is shown that the current algorithms are useful and helpful in understanding wear behavior for alternative or new designs of artificial hip joints and even for other analogous structures.

Measurement of polyethylene wear - a new three-dimensional methodology.

Studies in the field of polyethylene wear of the acetabular cup have been generally discussed using a two-dimensional assumption on the coronal plane; significant errors thus appear. The present study proposes a new, advanced methodology in order to accurately estimate the polyethylene wear. Through the usage of the distance between X-ray focus and film and only one follow-up, anteroposterior (AP) radiograph, a three-dimensional (3D) algorithm is introduced here. Here, 91 primary total hip joint replacements in 67 patients have been examined and three findings are obtained. Results show that the mean rate of 3D linear wear of the polyethylene estimated by the current method is 0.230+/-0.036 mm per year, that of the 2D linear wear is 0.148+/-0.028 mm per year. Moreover, the wear depth of the femoral head on the sagittal plane is 0.173+/-0.043 mm per year by the current method. This study also shows that the adoption of only one AP radiograph in the evaluation of the 3D penetration of femoral head is possible. Furthermore, the methodology proposed here is more convenient than others.