Botox Injections in Paraspinal Muscles Result in Low Maximal Specific Force and Shortening Velocity in Fast but Not Slow Skinned Muscle Fibers.

STUDY DESIGN: Basic science, experimental animal study. OBJECTIVE: To determine the effects of Botulinum toxin type A (BTX-A) injections on the mechanical properties of skinned muscle fibers (cells) of rabbit paraspinal muscles. SUMMARY OF BACKGROUND DATA: BTX-A has been widely used in the treatment of disorders of muscle hyperactivity, such as spasticity, dystonia, and back pain. However, BTX-A injection has been shown to cause muscle atrophy, fat infiltration, and decreased force output in target muscles, but its potential effects on the contractile machinery and force production on the cellular level remain unknown. METHODS: Nineteen-month-old, male New Zealand White Rabbits received either saline or BTX-A injections into the paraspinal muscles, equally distributed along the left and right sides of the spine at T12, L1, and L2 at 0, 8, 12, 16, 20, and 24 weeks. Magnetic resonance imaging was used to quantify muscle crosssectional area and structural changes before and at 28 weeks following the initial injection. Skinned fibers isolated from the paraspinal muscles were tested for their active and passive force-length relationships, unloaded shortening velocity, and myosin heavy chain isoforms. RESULTS: BTX-A injections led to significant fat infiltration within the injected muscles and a greater proportion of IIa to IIx fibers. Isolated fast fibers from BTX-A injected animals had lower active force and unloaded shortening velocity compared with fibers from saline-injected control animals. Force and velocity properties were not different between groups for the slow fibers. CONCLUSION: Injection of BTX-A into the paraspinal rabbit muscles leads to significant alterations in the contractile properties of fast, but not slow, fibers.Level of Evidence: N/A.

In vivo study of paraspinal muscle weakness using botulinum toxin in one primate model.

BACKGROUND: It has been generally speculated that paraspinal muscle weakness is related to the spinal degeneration including intervertebral disc failure. The purpose of this study was to investigate the effects of paraspinal muscle weakness induced by the botulinum toxin type-A on the lumbar spine and behavior pattern in an in-vivo primate model which has an upright locomotion similar to that of humans. METHODS: Botox injections into paraspinal muscle of one cynomolgus monkey were conducted biweekly up to 19 weeks at L2-L3, L3-L4 and L4-L5. MRIs were performed for measurement of muscle cross-sectional areas and behavioral data were collected using a high-resolution portable digital video camera. FINDINGS: The cross-sectional areas of the paraspinal muscles at L2-L3, L3-L4 and L4-L5 decreased by 8%, 12% and 8% at 21 weeks after the Botox injection, respectively. Intervertebral disc thickness at L2-L3, L3-L4 and L4-L5 decreased by 6%, 8% and 5% at 21 weeks after initial Botox injection, respectively. After the Botox injections, locomotion and movement activity of the monkey was decreased. The duration of sitting increased from 21% to a maximum of 97% at 9 weeks after the Botox injection, while stance time decreased from 9% to a minimum of 1% at 11 weeks post Botox injection. INTERPRETATION: The findings of this study revealed that paraspinal muscle atrophy affects intervertebral disc morphology and locomotion activity of a primate and may lead to an onset of intervertebral disc degeneration.

Optimized balance rehabilitation training strategy for the elderly through an evaluation of balance characteristics in response to dynamic motions.

Balance is important in daily activities and essential for maintaining an independent lifestyle in the elderly. Recent studies have shown that balance rehabilitation training can improve the balance ability of the elderly, and diverse balance rehabilitation training equipment has been developed. However, there has been little research into optimized strategies for balance rehabilitation training. To provide an optimized strategy, we analyzed the balance characteristics of participants in response to the rotation of a base plate on multiple axes. Seven male adults with no musculoskeletal or nervous system-related diseases (age: 25.5±1.7 years; height: 173.9±6.4 cm; body mass: 71.3±6.5 kg; body mass index: 23.6±2.4 kg/m(2)) were selected to investigate the balance rehabilitation training using customized rehabilitation equipment. Rotation of the base plate of the equipment was controlled to induce dynamic rotation of participants in the anterior-posterior, right-diagonal, medial-lateral, and left-diagonal directions. We used a three-dimensional motion capture system employing infrared cameras and the Pedar Flexible Insoles System to characterize the major lower-extremity joint angles, center of body mass, and center of pressure. We found statistically significant differences between the changes in joint angles in the lower extremities in response to dynamic rotation of the participants (P<0.05). The maximum was greater with anterior-posterior and medial-lateral dynamic rotation than with that in other directions (P<0.05). However, there were no statistically significant differences in the frequency of center of body mass deviations from the base of support (P>0.05). These results indicate that optimizing rotation control of the base plate of balance rehabilitation training equipment to induce anterior-posterior and medial-lateral dynamic rotation preferentially can lead to effective balance training. Additional tests with varied speeds and ranges of angles of base plate rotation are expected to be useful as well as an analysis of the balance characteristics considering a balance index that reflects the muscle activity and cooperative characteristics.

Use of the Microsoft Kinect system to characterize balance ability during balance training.

The risk of falling increases significantly in the elderly because of deterioration of the neural musculature regulatory mechanisms. Several studies have investigated methods of preventing falling using real-time systems to evaluate balance; however, it is difficult to monitor the results of such characterizations in real time. Herein, we describe the use of Microsoft's Kinect depth sensor system to evaluate balance in real time. Six healthy male adults (25.5±1.8 years, 173.9±6.4 cm, 71.4±6.5 kg, and 23.6±2.4 kg/m(2)), with normal balance abilities and with no musculoskeletal disorders, were selected to participate in the experiment. Movements of the participants were induced by controlling the base plane of the balance training equipment in various directions. The dynamic motion of the subjects was measured using two Kinect depth sensor systems and a three-dimensional motion capture system with eight infrared cameras. The two systems yielded similar results for changes in the center of body mass (P>0.05) with a large Pearson's correlation coefficient of γ>0.60. The results for the two systems showed similarity in the mean lower-limb joint angle with flexion-extension movements, and these values were highly correlated (hip joint: within approximately 4.6°; knee joint: within approximately 8.4°) (0.40<γ<0.74) (P>0.05). Large differences with a low correlation were, however, observed for the lower-limb joint angle in relation to abduction-adduction and internal-external rotation motion (γ<0.40) (P<0.05). These findings show that clinical and dynamic accuracy can be achieved using the Kinect system in balance training by measuring changes in the center of body mass and flexion-extension movements of the lower limbs, but not abduction-adduction and internal-external rotation.

Comparative study of mechanical properties of dental restorative materials and dental hard tissues in compressive loads.

There are two objectives. One is to show the differences in the mechanical properties of various dental restorative materials compared to those of enamel and dentin. The other is to ascertain which dental restorative materials are more suitable for clinical treatments. Amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy were processed as dental restorative material specimens. The specimens (width, height, and length of 1.2, 1.2, and 3.0 mm, respectively) were compressed at a constant loading speed of 0.1 mm/min. The maximum stress (115.0 ± 40.6, 55.0 ± 24.8, 291.2 ± 45.3, 274.6 ± 52.2, 2206.0 ± 522.9, and 953.4 ± 132.1 MPa), maximum strain (7.8% ± 0.5%, 4.0% ± 0.1%, 12.7% ± 0.8%, 32.8% ± 0.5%, 63.5% ± 14.0%, and 45.3% ± 7.4%), and elastic modulus (1437.5 ± 507.2, 1548.4 ± 583.5, 2323.4 ± 322.4, 833.1 ± 92.4, 3895.2 ± 202.9, and 2222.7 ± 277.6 MPa) were evident for amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy, respectively. The reference hardness value of amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy was 90, 420, 130-135, 86.6-124.2, 1250, and 349, respectively. Since enamel grinds food, its abrasion resistance is important. Therefore, hardness value should be prioritized for enamel. Since dentin absorbs bite forces, mechanical properties should be prioritized for dentin. The results suggest that gold alloy simultaneously has a hardness value lower than enamel (74.8 ± 18.1), which is important in the wear of the opposing natural teeth, and higher maximum stress, maximum strain, and elastic modulus than dentin (193.7 ± 30.6 MPa, 11.9% ± 0.1%, 1653.7 ± 277.9 MPa, respectively), which are important considering the rigidity to absorb bite forces.

Changes in microarchitectural characteristics at the tibial epiphysis induced by collagen-induced rheumatoid arthritis over time.

BACKGROUND: Little is known about the time course of changes in the microarchitecture of the tibial epiphysis with rheumatoid arthritis (RA), although such information would be valuable in predicting risk of fracture. Therefore, we used in vivo microcomputed tomography (µ-CT) to assess patterns of microarchitectural alterations in the tibial epiphysis using collagen-induced RA in an animal model. METHODS: Bovine type II collagen was injected intradermally into the tails of rats for induction of RA. The tibial joints were scanned by in vivo µ-CT at 0, 4, and 8 weeks following injection. Microarchitectural parameters were measured to evaluate alteration patterns of bone microarchitecture at the tibial epiphysis. RESULTS: The microarchitectural alterations in an RA group were significantly different from those in a control group from 0 to 4 weeks and from 4 to 8 weeks following injection (P < 0.05). The distribution of trabecular bone thickness and trabecular bone separation from 0 weeks to 8 weeks differed significantly (P < 0.05). CONCLUSION: These results indicate that the patterns of microarchitectural alterations at the tibial epiphysis are strongly affected by collagen-induced progression of RA and entail a severe risk of fracture at the tibial epiphysis. This study represents a valuable first approach to tracking periodic and continuous changes in the microarchitectural characteristics of the tibial epiphysis with collagen-induced RA.

Alteration patterns of trabecular bone microarchitectural characteristics induced by osteoarthritis over time.

Information regarding the alteration of trabecular bone microarchitecture, which is one of the important criteria to estimate bone condition, induced by osteoarthritis (OA) is sparse. The current study therefore aimed to identify and quantify patterns of alterations in trabecular bone microarchitectural characteristics at tibial epiphysis induced by OA using in vivo microcomputed tomography. Fourteen 8-week-old female Sprague Dawley rats were randomly divided into control (n = 7) and OA (n = 7) groups. Rats in the OA group were administered monoiodoacetate into the knee-joint cavity. The tibial joints were scanned by in vivo microcomputed tomography at 0, 4, and 8 weeks after administration. Two-way analysis of variance with Tukey's honestly significant difference post hoc test was carried out for statistical analyses. The results showed that patterns of alterations in the trabecular bone microarchitectural characteristics in the OA group were not different from those in the control group from 0 to 4 weeks (P > 0.05), but differed from 4 to 8 weeks (P < 0.05). In particular, both trabecular bone thickness and trabecular bone separation distributions over time (4-8 weeks) differed significantly (P < 0.05). These findings suggest that the patterns of bone microarchitecture changes brought about by OA should be periodically considered in the diagnosis and management of arthritic symptoms over time. Improved understanding of the alteration pattern on trabecular bone microarchitecture may assist in developing more targeted treatment interventions for OA.

Low-intensity ultrasound stimulation prevents osteoporotic bone loss in young adult ovariectomized mice.

Osteoporosis is a disease characterized by low bone mass, increased bone fragility, and a greater risk for bone fracture. Currently, pharmacological intervention can generally aid in the prevention and treatment of osteoporosis, but these therapies are often accompanied by undesirable side effects. Therefore, alternative therapies that minimize side effects are necessary. Biophysical stimuli, especially low-intensity ultrasound stimulation (LIUS), may be potential alternatives to drug-based therapies for osteoporosis. Hence, we sought to address whether LIUS therapy can effectively prevent or treat osteoporotic bone loss induced by estrogen deficiency. LIUS (1.5 MHz frequency, 1.0 kHz pulse repetition on frequency, 30 mW/cm(2) intensity, 200 µs pulse length) was applied to right tibiae of eight 14-week-old ovariectomized virgin ICR female mice for 20 min per day, 5 days per week, over a 6-week period. Changes in 3D structural bone characteristics were detected using in vivo micro-computed tomography. Left tibiae served as controls. Structural characteristics including bone volume/tissue volume, trabecular number, trabecular bone pattern factor, and mean polar moment inertia were significantly enhanced 6 weeks after LIUS compared to the control, nonstimulated group (p < 0.05). In particular, the bone volume/tissue volume in the region exposed directly to LIUS was significantly higher in the treated group (p < 0.05). These findings indicate that new bone formation may be activated or that bone structure may be maintained by LIUS, and that LIUS may be effective for preventing estrogen deficiency-induced bone loss.

A comparative study of histogram-based thresholding methods for the determination of cell-free layer width in small blood vessels.

We have recently proposed a computer-based method utilizing a thresholding algorithm (the Otsu method) to provide a convenient way of measuring the cell-free layer width in vivo and in vitro. However, this method does not seem to be a universal method that can be applied to all microvascular studies. Thus, we examined four different histogram-based thresholding algorithms (Otsu, intermode, minimum and second peak) to provide a technical suggestion on the selection of a suitable thresholding algorithm for the cell-free layer measurement. All the measurements were taken in microvascular flows in the rat cremaster muscle recorded with a high-speed camera. The width of the cell-free layer manually measured was compared with that determined by the automated method utilizing the four thresholding algorithms. With our experimental system, results showed that the cell-free layer width determined by the minimum algorithm was in best accordance with the manual measurement. We concluded that the accuracy of the automated methods for determination of the cell-free layer width would depend on the image quality, in particular on the contrast between the red blood cell core and background, which might differ due to the different microscopic setup. Therefore, one may need to examine several appropriate thresholding methods when selecting the best suitable algorithm for the experimental conditions.