Friction in Total Hip Joint Prosthesis Measured In Vivo during Walking

Friction-induced moments and subsequent cup loosening can be the reason for total hip joint replacement failure. The aim of this study was to measure the in vivo contact forces and friction moments during walking. Instrumented hip implants with Al₂O₃ ceramic head and an XPE inlay were used. In vivo measurements were taken 3 months post operatively in 8 subjects. The coefficient of friction was calculated in 3D throughout the whole gait cycle, and average values of the friction-induced power dissipation in the joint were determined. On average, peak contact forces of 248% of the bodyweight and peak friction moments of 0.26% bodyweight times meter were determined. However, contact forces and friction moments varied greatly between individuals. The friction moment increased during the extension phase of the joint. The average coefficient of friction also increased during this period, from 0.04 (0.03 to 0.06) at contralateral toe off to 0.06 (0.04 to 0.08) at contralateral heel strike. During the flexion phase, the coefficient of friction increased further to 0.14 (0.09 to 0.23) at toe off. The average friction-induced power throughout the whole gait cycle was 2.3 W (1.4 W to 3.8 W). Although more parameters than only the synovia determine the friction, the wide ranges of friction coefficients and power dissipation indicate that the lubricating properties of synovia are individually very different. However, such differences may also exist in natural joints and may influence the progression of arthrosis. Furthermore, subjects with very high power dissipation may be at risk of thermally induced implant loosening. The large increase of the friction coefficient during each step could be caused by the synovia being squeezed out under load.     

Total Hip Replacement in Inflammatory Hip Disease using the Charnley Prosthesis

The Charnley low-friction arthroplasty was performed on 73 hips in 55 patients with inflammatory joint disease, usually for intolerable pain. Sixty-five of these operations were reviewed at a special clinic or by postal questionnaire; 57 hips were painfree or gave rise to only occasional discomfort, in 58 there was an increased range of movement, and in 46 of the 59 hips assessed clinically, the results were excellent or good. The most serious complication was deep infection, which occurred in 7 operations.     

Total Hip Replacement in Osteoarthrosis using the Charnley Prosthesis

Charnley low-friction arthroplasty was performed on 352 osteoarthritic hips, usually because of severe pain. Three hundred and twenty hips were reviewed at a special follow-up clinic or by postal questionnaire. After operation 89% of hips were pain-free or caused only occasional discomfort, and in 76% there was an increased range of movement. Of those patients actually seen for review 79% were judged to have a good or excellent result. The most frequent single complication was deep infection, which occurred in 5·3% of hips.     

大直径陶瓷假体用于全髋关节置换术的稳定性和安全性

目的:探讨大直径陶瓷-陶瓷假体对髋关节置换患者术后假体磨损,稳定性和髋关节功能的影响。方法:选取我院2010年1月-2014年1月间采用大直径陶瓷-陶瓷假体行关全髋置换的股骨头坏死患者46例作为研究组。另选40例采用标准金属-聚乙烯假体手术患者作为对照组。观察并比较两组患者假体磨损情况、髋关节稳定性和功能评分。结果:研究组患者术后无一例脱位,发生假体松动1例,Harris评分为(82.04±1.92)分;对照组术后发生假体脱位4例,松动4例,Harris评分为(81.37±1.27)分;研究组假体稳定性和磨损程度优于对照组,差异具有统计学意义(P0.05),但两组髋关节功能评分无显著差异(P0.05)。发生假体松动的患者术后血沉、IL-1和IL-6浓度均高于正常值,差异具有统计学意义(P0.05)。结论:与标准假体相比,大直径陶瓷-陶瓷假体稳定性好,磨损率低,是全髋置换手术的良好假体。     

Wear Testing of Moderate Activities of Daily Living Using In Vivo Measured Knee Joint Loading

Resumption of daily living activities is a basic expectation for patients provided with total knee replacements. However, there is a lack of knowledge regarding the impact of different activities on the wear performance. In this study the wear performance under application of different daily activities has been analyzed. In vivo load data for walking, walking downstairs/upstairs, sitting down/standing up, and cycling (50 W & 120 W) has been standardized for wear testing. Wear testing of each activity was carried out on a knee wear simulator. Additionally, ISO walking was tested for reasons of comparison. Wear was assessed gravimetrically and wear particles were analyzed. In vivo walking produced the highest overall wear rates, which were determined to be three times higher than ISO walking. Moderate wear rates were determined for walking upstairs and downstairs. Low wear rates were determined for standing up/sitting down and cycling at power levels of 50 W and 120 W. The largest wear particles were observed for cycling. Walking based on in vivo data has been shown to be the most wear-relevant activity. Highly demanding activities (stair climbing) produced considerably less wear. Taking into account the expected number of loads, low-impact activities like cycling may have a greater impact on articular wear than highly demanding activities.     

Torsion and Antero-Posterior Bending in the In Vivo Human Tibia Loading Regimes during Walking and Running

Bending, in addition to compression, is recognized to be a common loading pattern in long bones in animals. However, due to the technical difficulty of measuring bone deformation in humans, our current understanding of bone loading patterns in humans is very limited. In the present study, we hypothesized that bending and torsion are important loading regimes in the human tibia. In vivo tibia segment deformation in humans was assessed during walking and running utilizing a novel optical approach. Results suggest that the proximal tibia primarily bends to the posterior (bending angle: 0.15°–1.30°) and medial aspect (bending angle: 0.38°–0.90°) and that it twists externally (torsion angle: 0.67°–1.66°) in relation to the distal tibia during the stance phase of overground walking at a speed between 2.5 and 6.1 km/h. Peak posterior bending and peak torsion occurred during the first and second half of stance phase, respectively. The peak-to-peak antero-posterior (AP) bending angles increased linearly with vertical ground reaction force and speed. Similarly, peak-to-peak torsion angles increased with the vertical free moment in four of the five test subjects and with the speed in three of the test subjects. There was no correlation between peak-to-peak medio-lateral (ML) bending angles and ground reaction force or speed. On the treadmill, peak-to-peak AP bending angles increased with walking and running speed, but peak-to-peak torsion angles and peak-to-peak ML bending angles remained constant during walking. Peak-to-peak AP bending angle during treadmill running was speed-dependent and larger than that observed during walking. In contrast, peak-to-peak tibia torsion angle was smaller during treadmill running than during walking. To conclude, bending and torsion of substantial magnitude were observed in the human tibia during walking and running. A systematic distribution of peak amplitude was found during the first and second parts of the stance phase.     

Light Dependence of Calcium and Membrane Potential Measured in Blowfly Photoreceptors In Vivo

Light adaptation in insect photoreceptors is caused by an increase in the cytosolic Ca²⁺ concentration. To better understand this process, we measured the cytosolic Ca²⁺ concentration in vivo as a function of adapting light intensity in the white-eyed blowfly mutant chalky. We developed a technique to measure the cytosolic Ca²⁺ concentration under conditions as natural as possible. The calcium indicator dyes Oregon Green 1, 2, or 5N (Molecular Probes, Inc., Eugene, OR) were iontophoretically injected via an intracellular electrode into a photoreceptor cell in the intact eye; the same electrode was also used to measure the membrane potential. The blue-induced green fluorescence of these dyes could be monitored by making use of the optics of the facet lens and the rhabdomere waveguide. The use of the different Ca²⁺-sensitive dyes that possess different affinities for Ca²⁺ allowed the quantitative determination of the cytosolic Ca²⁺ concentration in the steady state. Determining the cytosolic Ca²⁺ concentration as a function of the adapting light intensity shows that the Ca²⁺ concentration is regulated in a graded fashion over the whole dynamic range where a photoreceptor cell can respond to light. When a photoreceptor is adapted to bright light, the cytosolic Ca²⁺ concentration reaches stable values higher than 10 μM. The data are consistent with the hypothesis that the logarithm of the increase in cytosolic Ca²⁺ concentration is linear with the logarithm of the light intensity. From the estimated values of the cytosolic Ca²⁺ concentration, we conclude that the Ca²⁺-buffering capacity is limited. The percentage of the Ca²⁺ influx that is buffered gradually decreases with increasing Ca²⁺ concentrations; at cytosolic Ca²⁺ concentration levels above 10 μM, buffering becomes minimal.     

Tubulin Sorting during Dimerization In Vivo

We demonstrate sorting of beta-tubulins during dimerization in the Drosophila male germ line. Different beta-tubulin isoforms exhibit distinct affinities for alpha-tubulin during dimerization. Our data suggest that differences in dimerization properties are important in determining isoform-specific microtubule functions. The differential use of beta-tubulin during dimerization reveals structural parameters of the tubulin heterodimer not discernible in the resolved three-dimensional structure. We show that the variable beta-tubulin carboxyl terminus, a surface feature in the heterodimer and in microtubules, and which is disordered in the crystallographic structure, is of key importance in forming a stable alpha-beta heterodimer. If the availability of alpha-tubulin is limiting, alpha-beta dimers preferentially incorporate intact beta-tubulins rather than a beta-tubulin missing the carboxyl terminus (beta 2 Delta C). When alpha-tubulin is not limiting, beta 2 Delta C forms stable alpha-beta heterodimers. Once dimers are formed, no further sorting occurs during microtubule assembly: alpha-beta 2 Delta C dimers are incorporated into axonemes in proportion to their contribution to the total dimer pool. Co-incorporation of beta 2 Delta C and wild-type beta 2-tubulin results in nonmotile axonemes because of a disruption of the periodicity of nontubulin axonemal elements. Our data show that the beta-tubulin carboxyl terminus has two distinct roles: 1) forming the alpha-beta heterodimer, important for all microtubules and 2) providing contacts for nontubulin components required for specific microtubule structures, such as axonemes.     

Risk Factors for Periprosthetic Joint Infection after Total Hip Arthroplasty and Total Knee Arthroplasty in Chinese Patients

Purpose

The purpose of this hospital-based case–control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.

Method

From January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Demographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77–16.97; p = 0.003), age (65–75 vs. 45–65 years) (OR = 3.36, 95% CI: 1.30–8.69; p = 0.013), BMI (≥28 vs. 18.5–28 kg/m²) (OR = 2.77, 95% CI: 1.20–6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13–6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06–8.23; p = 0.039).

Conclusion

Patients with diabetes, older age, BMI of ≥28 kg/m² and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.     

Deducing the Kinetics of Protein Synthesis In Vivo from the Transition Rates Measured In Vitro

The molecular machinery of life relies on complex multistep processes that involve numerous individual transitions, such as molecular association and dissociation steps, chemical reactions, and mechanical movements. The corresponding transition rates can be typically measured in vitro but not in vivo. Here, we develop a general method to deduce the in-vivo rates from their in-vitro values. The method has two basic components. First, we introduce the kinetic distance, a new concept by which we can quantitatively compare the kinetics of a multistep process in different environments. The kinetic distance depends logarithmically on the transition rates and can be interpreted in terms of the underlying free energy barriers. Second, we minimize the kinetic distance between the in-vitro and the in-vivo process, imposing the constraint that the deduced rates reproduce a known global property such as the overall in-vivo speed. In order to demonstrate the predictive power of our method, we apply it to protein synthesis by ribosomes, a key process of gene expression. We describe the latter process by a codon-specific Markov model with three reaction pathways, corresponding to the initial binding of cognate, near-cognate, and non-cognate tRNA, for which we determine all individual transition rates in vitro. We then predict the in-vivo rates by the constrained minimization procedure and validate these rates by three independent sets of in-vivo data, obtained for codon-dependent translation speeds, codon-specific translation dynamics, and missense error frequencies. In all cases, we find good agreement between theory and experiment without adjusting any fit parameter. The deduced in-vivo rates lead to smaller error frequencies than the known in-vitro rates, primarily by an improved initial selection of tRNA. The method introduced here is relatively simple from a computational point of view and can be applied to any biomolecular process, for which we have detailed information about the in-vitro kinetics.     

Changes in Leaf Nitrate Reductase Activity In Vivo and In Vitro During Light-Dark Transitions

Nitrate reductase activity in the leaves of a number of plants after transfer from light to dark was assayed both by in vivo and in vitro methods. The initial activity persisted during the dark phase for a considerable length of time and declined gradually. After exposure to light again, the NR activity increased rapidly. The possibility of nitrate assimilation in complete darkness is discussed.     

Surgical Site Infections and Other Postoperative Complications following Prophylactic Anticoagulation in Total Joint Arthroplasty

Background

Anticoagulants reduce the risk of venous thromboembolism (VTE) after total joint replacement. However, concern remains that pharmacologic VTE prophylaxis can lead to bleeding, which may impact on postoperative complications such as infections and reoperations.

Methods and Findings

From the Global Orthopedic Registry (GLORY), we reviewed 3,755 patients in US who elected for primary total hip or knee arthroplasty, received either warfarin or low molecular weight heparin (LMWH) as VTE prophylactics, and had up-to-90-day follow-up after discharge. We compared incidence rates of VTE, infections and other complications between LMWH and warfarin groups, and used multivariate analyses with propensity score weighting to generate the odds ratio (OR). Patients receiving LMWH tended to be older and higher in the American Society of Anesthesiologists grade scores. In contrast, warfarin was used more frequently for hip arthroplasty with longer duration among patients with more pre-existing comorbidity (all P<0.02). A weight variable was created with propensity score to account for differences in covariate distributions. Propensity score-weighted analyses showed no differences in VTE complications. However, compared to warfarin, LMWH was associated with significantly higher rates of bleeding (6.2% vs. 2.1%; OR = 3.82, 95% confidence interval [CI], 2.64 to 5.52), blood transfusion (29.4% vs. 22.0%; OR = 1.75, 95% CI, 1.51 to 2.04), reoperations (2.4% vs. 1.3%; OR = 1.77, 95% CI, 1.07 to 2.93) and infections (1.6% vs. 0.6%; OR = 2.79, 95% CI, 1.42 to 5.45). Similar results were obtained from compliant uses of warfarin (26%) and LMWH (62%) according to clinical guidelines. While surgical site infections were mostly superficial, current study was underpowered to compare incidence rates of deep infections (<1.0%).

Conclusions

Surgical site infections and reoperations in 3 months following primary total joint arthroplasty may be associated with anticoagulant use that exhibited higher bleeding risk. Long-term complications and deep wound infections remain to be studied.     

AMPK Mediates Autophagy during Myocardial Ischemia In Vivo

We have recently shown that autophagy is induced by ischemia and reperfusion in the mouse heart in vivo. Ischemia stimulates autophagy through an AMP activated protein kinase (AMPK)-dependent mechanism, whereas reperfusion after ischemia stimulates autophagy through a Beclin 1-dependent, but AMPK-independent, mechanism. Autophagy plays distinct roles during ischemia and reperfusion: autophagy may be protective during ischemia, whereas it may be detrimental during reperfusion. We will discuss the role of AMPK in mediating autophagy during myocardial ischemia in vivo.

Addendum to:

Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion: Roles of AMP-Activated Protein Kinase and Beclin 1 in Mediating Autophagy

Y. Matsui, H. Takagi, X. Qu, M. Abdellatif, H. Sakoda, T. Asano, B. Levine and J. Sadoshima

Circ Res 2007; 100:914-22     

Extracellular Hypothalamic Monoamines Measured by In Vivo Microdialysis in a Rat Model of Dietary Fat-Induced Obesity

We tested two hypotheses about monoamine neurotransmitters in two strains of rats that differ in their sensitivity to obesity when eating a high-fat diet; 1) that the concentrations of norepinephrine and serotonin and of their metabolites differ in the extracellular fluid of tlie ventromedial hypothalamus of conscious, unrestrained Osborne-Mendel and S 5B/PI rats, and 2) that these monoamines are altered differently between strains by a high-fat diet. The monoamines were measured by HPLC in dialysate collected by in vivo microdialysis in rats eating a semisyntlietic low-fat diet (10% of kcal as fat) and again after either two or seven days of eating a high-fat diet (56 % of kcal as fat). Norepinephrine, serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) were lower in Osborne-Mendel rats than in S 5BR1 rats eating the low-fat diet. Norepinephrine and serotonin both increased in Osborne-Mendel rats with the onset of tlie high-fat diet so that Osborne-Mendel and S 5B/PI rats no longer differed in these neurotransmitters. By day 7 of high-fat feeding, the concentrations of 3-methoxy-4-hydroxyplienylglycol (MHPG), 5-HIAA and the 5-HIAA/5-HT ratio rose in both strains. Ambient extracellular monoamines in the medial hypothalamus are lower in Osborne-Mendel rats than in S 5B/PI rats and the response of these catecholamines to dietary fat was greater in Osborne-Mendel rats than in S 5B/PI rats.     

Terminal Autoreceptor Control of 5-Hydroxytryptamine Release as Measured by In Vivo Microdialysis in the Conscious Guinea-Pig

In vivo microdialysis in the frontal cortex of the freely moving guinea-pig was used to measure extracellular 5-hydroxytryptamine (5-HT) and study terminal autoreceptor control of its release. The indoleamine levels were determined by HPLC with electrochemical detection. Release of extracellular 5-HT and, to a lesser extent, 5-hydroxyindoleacetic acid was sensitive to tetrodotoxin, confirming the neuronal origin of measured neurotransmitter levels. Both systemic and local administration of the 5-HT1 agonist 5-carboxamidotryptamine caused inhibition of extracellular 5-HT levels, confirming the regulatory role of the terminal, and possibly also the somatodendritic, 5-HT autoreceptor on neuronal 5-HT release. Levels of extracellular 5-hydroxyindoleacetic acid were not affected by 5-carboxamidotryptamine following either central or peripheral administration.     

Determination and Modulation of Total and Surface Calcium-Sensing Receptor Expression in Monocytes In Vivo and In Vitro

Expression of the calcium-sensing receptor (CaSR) has previously been demonstrated in human circulating monocytes (HCM). The present study was designed to measure CaSR expression in HCM and to examine its potential modulation by pro-inflammatory cytokines, Ca2+, vitamin D sterols in U937 cell line. Twenty healthy volunteers underwent blood sampling with subsequent isolation of peripheral blood mononuclear cells (PBMC) at 3 visits. Flow cytometry analysis (FACS) was performed initially (V1) and 19 days later (V2) to examine intra- and intersubject fluctuations of total and surface CaSR expression in HCM and 15 weeks later (V3) to study the effect of vitamin D supplementation. In vitro experiments were conducted to assess the effects of pro-inflammatory cytokines, calcidiol, calcitriol and Ca2+ on CaSR expression in U937 cell line. By FACS analysis, more than 95% of HCM exhibited cell surface CaSR staining. In contrast, CaSR staining failed to detect surface CaSR expression in other PBMC. After cell permeabilization, total CaSR expression was observed in more than 95% of all types of PBMC. Both total and surface CaSR expression in HCM showed a high degree of intra-assay reproducibility (<3%) and a moderate intersubject fluctuation. In response to vitamin D supplementation, there was no significant change for both total and surface CaSR expression. In the in vitro study, U937 cells showed strong total and surface CaSR expression, and both were moderately increased in response to calcitriol exposure. Neither total nor surface CaSR expression was modified by increasing Ca2+ concentrations. Total CaSR expression was concentration dependently decreased by TNFα exposure. In conclusion, CaSR expression can be easily measured by flow cytometry in human circulating monocytes. In the in vitro study, total and surface CaSR expression in the U937 cell line were increased by calcitriol but total CaSR expression was decreased by TNFα stimulation.     

Leg and Joint Stiffness in Children with Spastic Diplegic Cerebral Palsy during Level Walking

Individual joint deviations are often identified in the analysis of cerebral palsy (CP) gait. However, knowledge is limited as to how these deviations affect the control of the locomotor system as a whole when striving to meet the demands of walking. The current study aimed to bridge the gap by describing the control of the locomotor system in children with diplegic CP in terms of their leg stiffness, both skeletal and muscular components, and associated joint stiffness during gait. Twelve children with spastic diplegia CP and 12 healthy controls walked at a self-selected pace in a gait laboratory while their kinematic and forceplate data were measured and analyzed during loading response, mid-stance, terminal stance and pre-swing. For calculating the leg stiffness, each of the lower limbs was modeled as a non-linear spring, connecting the hip joint center and the corresponding center of pressure, with varying stiffness that was calculated as the slope (gradient) of the axial force vs. the deformation curve. The leg stiffness was further decomposed into skeletal and muscular components considering the alignment of the lower limb. The ankle, knee and hip of the limb were modeled as revolute joints with torsional springs whose stiffness was calculated as the slope of the moment vs. the angle curve of the joint. Independent t-tests were performed for between-group comparisons of all the variables. The CP group significantly decreased the leg stiffness but increased the joint stiffness during stance phase, except during terminal stance where the leg stiffness was increased. They appeared to rely more on muscular contributions to achieve the required leg stiffness, increasing the muscular demands in maintaining the body posture against collapse. Leg stiffness plays a critical role in modulating the kinematics and kinetics of the locomotor system during gait in the diplegic CP.     

Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements

The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered key markers of neurological function in animal models of stress-induced sleep perturbation.