Effect of high intensity training on anaerobic capacity of middle gluteal muscle in Thoroughbred horses.

We hypothesize that high intensity training for Thoroughbred horses that have been subjected to conventional training could further improve the metabolic properties of the middle gluteal muscle. Nine well-trained horses were subjected to high intensity (80-100% Vdot;O(2)max, 5 minx2) training for 12 weeks. Biopsy samples were obtained from the muscle before and after 4 and 12 weeks of training. Three of the 9 horses did not complete the training programme. In the remaining 6 horses, activities of succinic dehydrogenase (SDH), phosphofructokinase (PFK) and 3-hydroxy acyl CoA dehydrogenase (HAD), and the composition of myosin heavy chain isoforms were analyzed by biochemical techniques. After 12 weeks of training, a significant increase was found in PFK activity but not in the SDH and HAD activities. There were no significant changes in the composition of myosin heavy chain isoforms. The high intensity training in this study was effective at increasing glycolytic enzyme activity, indicating the possibility to improve anaerobic capacity, which potentially could contribute greatly to performance in Thoroughbred horses. This study also highlighted a fact that high intensity training should be given with the great care to prevent the skeletal muscle injuries.

Effect of controlled exercise on middle gluteal muscle fibre composition in Thoroughbred foals.

REASONS FOR PERFORMING STUDY: Most racehorses are trained regularly from about age 18 months; therefore, little information is available on the effect of training in Thoroughbred foals. HYPOTHESIS: Well-controlled exercise could improve muscle potential ability for endurance running. METHODS: Thoroughbred foals at age 2 months were separated into control and training (treadmill exercise) groups and samples obtained from the middle gluteal muscle at 2 and 12 months post partum. Muscle fibre compositions were determined by histochemical and electrophoretical techniques and succinic dehydrogenase (SDH) activity was analysed in each fibre type. RESULTS: All fibre types were hypertrophied with growth and type I and IIA fibres were significantly larger in the training than the control group at age 12 months. A significant increase of SDH activity was found in type IIX muscle fibres in the training group. CONCLUSIONS: Training in young Thoroughbred horses can facilitate muscle fibre hypertrophy and increase the oxidative capacity of type IIX fibres, which could potentially enhance stamina at high speeds. POTENTIAL RELEVANCE: To apply this result to practical training, further studies are needed to determine more effective and safe intensities of controlled exercise.

Doxorubicin ototoxicity is induced in mice by combination treatment with cyclosporin A.

Although doxorubicin [adriamycin (ADM)] ototoxicity has not been detected to date, it has been reported that neurotoxicity in the central nervous system was induced by chemotherapy with ADM in patients receiving chronic cyclosporin A (CsA) treatment. ADM ototoxicity may be induced by combination therapy with CsA because extrusion of ADM from the inner ear by p-glycoprotein (p-gp), which acts as an extrusion pump and is expressed on the surface of endothelial cells of capillary blood vessels, might be inhibited by CsA. resulting in significant accumulation of ADM in the inner ear. ADM (10 mg/kg) was administered to FVB mice either with or without CsA (200 mg/kg). Auditory brainstem responses (ABRs) were recorded before and after treatment. ABR changes were not observed in mice treated with either ADM or CsA alone. Threshold elevation, elongation of wave I-V latencies and interpeak latencies of waves I-II, I-III, I-IV and I-V were detected in mice treated with ADM in combination with CsA. These changes reached their peak values 3 weeks after treatment, and then recovered to pre-treatment levels. In normal mice, ADM is extruded by p-gp from the inner ear and auditory pathway, thus preventing hearing disorder. However, ADM ototoxicity was induced by combination therapy with CsA, indicating that CsA has an inhibitory action on p-gp function in the auditory pathway, including the inner ear. After organ transplantation, therefore, clinical administration of ADM in combination with CsA should be performed with caution.

Cyclosporin A inhibits the extrusion pump function of p-glycoprotein in the inner ear of mice treated with vinblastine and doxorubicin.

Cyclosporin A (CsA) inhibits the membrane transport protein p-glycoprotein (p-gp) and can enhance the accumulation of vinblastine (VBL) and doxorubicin (Dx) in the inner ear of mice. In mice pretreated with 200 mg/kg of CsA, there were significantly increased VBL and Dx concentrations detected in the inner ear tissue and other organs, with a small but significant increase in the brain. Furthermore, hearing thresholds measured by auditory brainstem responses were significantly elevated 3 weeks after VBL or Dx treatment in combination with CsA. However, the altered thresholds recovered to pretreatment levels 8 weeks after treatment. Pharmacokinetic and functional alterations observed in this study suggest caution in applying these combinations in clinical practice.

Expression of p-glycoprotein is associated with that of multidrug resistance protein 1 (MRP1) in the vestibular labyrinth and endolymphatic sac of the guinea pig.

Expression of p-glycoprotein (p-gp) and multidrug resistance protein 1 (MRP1) was detected in the vestibular labyrinth and endolymphatic sac (ES) of the guinea pig by immunohistochemical staining using anti-p-gp monoclonal antibody (mAb) C219 and anti-MRP mAb MRPr1. P-gp was detected in capillary endothelial cells of the crista ampullaris, utricle, saccule and ES. MRP1 was detected in the epithelial lining of the crista ampullaris, utricle, saccule, and epithelial cells of the ES. Since p-gp and MRP1 act as extrusion pumps, they may coordinate with each other in vestibular organs and ES and play an important role in the blood-labyrinth barrier.

Recent outcome of tympanoplasty in the elderly.

OBJECTIVE: To investigate the outcome of tympanoplasty in the elderly (patients older than 60 years) compared with younger patients. PATIENTS AND STUDY DESIGN: Retrospective review of 87 (28.3%) older patients among a total of 307 patients with chronic otitis media with or without cholesteatoma who were surgically treated at a university hospital by the senior author. Follow-up was systematically provided at the same institution. INTERVENTIONS: Surgery included tympanoplasty with mastoidectomy performed as the primary procedure in 358 ears. Tympanoplasty was performed with canal-wall-up or canal-wall-down with canal wall reconstruction, ossiculoplasty with autologous or homologous ossicle interposition or columella. Mean follow-up was 30 months (range, 12-70 months). MAIN OUTCOME MEASURES: Pre- and postoperative air- and bone-conduction thresholds were calculated as an average of three speech frequencies (0.5, 1, and 2 kHz). Analysis was subsequently carried out on the postoperative air-bone gap, hearing gain, and postoperative problems such as elevation of the bone-conduction threshold, delayed epithelialization, and reperforation of the eardrum. Statistical analysis was performed by chi-square or Student's t-test. A p value less than 0.05 was considered significant. RESULTS: Compared with results from younger patients, there was no particular disadvantage in postoperative hearing results and complications in the elderly, although preoperative bone-conduction thresholds were gradually worsened with age. CONCLUSIONS: There is no contraindication for tympanoplasty in older patients if their physical status is the same or better than what is normal for their chronological age.

Expression of multidrug resistance protein 1 (MRP1) in the rat cochlea with special reference to the blood-inner ear barrier.

Expression of multidrug resistance protein 1 (MRP1) was detected in the rat cochlea by RT-PCR and immunohistochemistry using anti-MRP monoclonal antibody MRPr1. Use of primers specific for rat mrp1 gene resulted in the amplification of an expected 394 bp fragment prepared from brain and cochlear tissues. Immunohistochemically, MRP was found in the choroid plexus, stria vascularis, spiral ligament, spiral prominence and cochlear nerve in the modiolus. From these results, it was suggested that MRP in the rat cochlea might function as an extrusion pump and play an important role in the blood-inner ear barrier.

Long-term follow-up results of electrogustometry and subjective taste disorder after middle ear surgery.

OBJECTIVES: The present study compares the long-term follow-up results of electrogustometry with patient reports of taste dysfunction after middle ear surgery. STUDY DESIGN: Retrospective review of 371 patients who underwent middle ear surgery. METHODS: Patients were divided into the following groups depending on the degree of manipulation or surgical damage to the chorda tympani nerves: the no-touch group (group 1 [n = 109]); the touch group (group 2 [n = 149]); and the severed nerve group (group 3 [n = 113]). Electrogustometry was periodically performed over the course of several years. RESULTS: The incidences of postoperative subjective taste disorder in groups 1, 2, and 3 were 2.8%, 25.5%, and 38.9%, respectively. Although the subjective taste disorder usually recovered within 1 to 2 years after surgery in all groups, it persisted for more than 2 years in 2.7% of the touch group and 5.3% of the severed nerve group. Concerning postoperative electrogustometric results, in the no-touch group, 8.3% of patients showed threshold elevation on electrogustometry, but the elevated thresholds completely recovered in all cases. In the touch group, 45% of patients exhibited elevated electrogustometric thresholds on their first postoperative test, including 32.9% who subsequently had complete electrogustometric recovery, 10.1% who subsequently had incomplete recovery, and 2% who failed to recover during the follow-up period. In the severed nerve group, none of the patients was responsive to the electrical stimulus on the first postoperative test, including 8.8% of patients who subsequently exhibited complete electrogustometric recovery, 32.7% who later had incomplete electrogustometric recovery, and 58.4% who never recovered any electrogustometric responsiveness. Nerve repair in the severed nerve group produced better recovery, as measured electrically. CONCLUSIONS: The incidence of postoperative subjective taste disorder was low, although inconsistent with the high incidence of threshold elevation on electrogustometry, especially in the severed nerve group. Preservation or repair of the chorda tympani nerve is recommended in order to maintain or recover gustatory function.

Neuronal pathways from low-threshold muscle and cutaneous afferents innervating tail to trunk muscle motoneurons in the cat.

We studied neuronal pathways from low-threshold muscle (group I, II) and cutaneous afferents (group A(alpha)beta) innervating the tail to motoneurons innervating trunk muscles (m. iliocostalis lumborum and m. obliquus externus abdominus) in 18 spinalized cats. Stimulation of group I muscle afferents produced excitatory postsynaptic potentials or excitatory postsynaptic potentials followed by inhibitory postsynaptic potentials in all motoneurons innervating the m. iliocostalis lumborum which showed effects (32%), and predominantly inhibitory postsynaptic potentials in motoneurons innervating the m. obliquus externus abdominus (47%). Stimulation of group I+II afferents produced significant increases of the incidence of motoneurons showing postsynaptic potentials (the notoneurons innervating the m. iliocostalis lumborum, 87%; the motoneurons innervating the m. obliquus externus abdominus, 82%). The effects of low threshold cutaneous afferents were bilateral, predominantly producing inhibitory postsynaptic potentials in motoneurons innervating both muscles. These results suggest that neuronal pathways from muscle afferents to back muscle motoneurons mainly increase the stiffness of the trunk to maintain its stability, while those to abdominal muscles help to extend the dorsal column by decreasing their activities. The results also indicate that neuronal pathways from cutaneous afferents to trunk motoneurons functionallY disconnect the tail from the trunk.

Spinal projections of cat primary afferent fibers innervating caudal facet joints.

The spinal projections of afferent fibers innervating the facet joints between caudal vertebrae were examined by the use of anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Experiments were performed on 5 adult cats in which spinal dorsal roots below the 2nd sacral segment (S2) on the right side were cut. Injections of WGA-HRP into the caudal facet joints gave rise to extensive cranio-caudal distribution of WGA-HRP positive products along the spinal cord, indicating that many afferent fibers innervating unilateral facet joints terminate bilaterally in laminae I-II, V-VI and X of the thoracic, lumbar, sacral and caudal spinal cord. These afferent fibers may convey a series of sensory information from the caudal facet joints to the spinal cord.

Electromyographic and kinematic studies of tail movements during falling in cats.

When falling from an inverted position, EMG activities of tail muscles (the m. extensor caudae lateralis, m. abductor caudae externus, m. flexor caudae longus) and tail movements were recorded in 7 long-tailed adult cats. After being released from an elevated position, cat rotates the tail in a reverse direction to rotation of other parts of the cat's body then lands on four legs. Rotation of the tail was started by EMG activities of the tail muscles on one side. Both synchronized and alternating groups of discharge occur between its left and right side, while extensor and flexor movements and displacements of its tail appear in the air. After transection of ventral roots from the coccygeal spinal segments innervating tail muscles, cats often fail to land on four legs. These facts suggest that that tail movements control body balance in the air when falling from an inverted position.

Use of an instrument sandwiched between the hoof and shoe to measure vertical ground reaction forces and three-dimensional acceleration at the walk, trot, and canter in horses.

OBJECTIVE: To develop an instrument that could be sandwiched between the hoof and shoe of horses and that would reliably measure vertical ground reaction forces and three-dimensional acceleration at the walk, trot, and canter. ANIMALS: 5 clinically sound Thoroughbreds. PROCEDURES: The recording instrument (weight, 350 g) consisted of 2 metal plates, 2 bolts, 4 load cells, and 3 accelerometers. It was mounted to the hoof with a glue-on shoe and devised to support as much load exerted by a limb as possible. The load cells and accelerometers were wired to a 16-channel transmitter, and transmitted signals were received and amplified with a telemetry receiver. RESULTS: The recording instrument could measure in real time the 4 components of the ground reaction force or their resultant force along with acceleration in 3 dimensions as horses walked, trotted, or cantered on a treadmill. Patterns of force-time curves recorded for consecutive strides were similar to each other and to those previously reported, using a force plate. CONCLUSIONS AND CLINICAL RELEVANCE: The recording instrument developed for use in the present study allowed us to record vertical ground reaction force and acceleration in 3 dimensions in horses at the walk, trot, and canter.

Effects of a canine Elizabethan collar on ambulatory electrocardiogram recorded by a Holter recording system and spontaneous activities measured continuously by an accelerometer in Beagle dogs.

Ambulatory electrocardiogram (ECG) has been recorded in dogs wearing a jacket to protect a Holter recording system, but the jacket was often damaged by dogs. We compared ECG recorded by a Holter recording system and spontaneous activity measured by an accelerometer in Beagle dogs with or without an Elizabethan collar. There were few significant differences in mean values (per hr) of the heart rate and the amount of spontaneous activity between dogs with or without the Elizabethan collar. Mean values (per 23 hr) of them had no significant difference between them. We concluded that the Elizabethan collar did not have any effect on ambulatory ECG and canine movements and was effective to protect the recording apparatus.

Spontaneous activities measured continuously by an accelerometer in beagle dogs housed in a cage.

Spontaneous activities in 10 beagle dogs housed in an individual cage were recorded continuously for 2 hr by an accelerometer fixed to dogs and by a video camera. The responses of the accelerometer were compared to movements identified from the video tapes. We found that gross differentiation of quantitative spontaneous activities might be possible by using only the accelerometer if the threshold of the accelerometer and the amount of acceleration volume were set adequately: the responses of the accelerometer at the threshold of 0.10 G with the acceleration number of 251 or more revealed only movements of the whole-body, and those at the threshold of 0.02 G all movements including changes of the part(s) of the body.

The effect of pyramidal stimulation upon tail muscle motoneurons in the decerebrate cat.

This study aimed to determine the effects of the corticospinal tract (CST) on the motoneurons innervating the tail muscles in cats. The stimulation of the pyramidal tract predominantly evoked excitatory postsynaptic potentials (EPSPs; 48/90 motoneurons: 53%). Single-pulse stimulation produced EPSPs in 18 of 48 motoneurons, but double shocks evoked postsynaptic potentials in most of the remaining cells (26/48). Monosynaptic excitatory connections between pyramidal tract fibers and tail motoneurons were confirmed in 4 motoneurons. Inhibitory postsynaptic potentials (IPSPs) were recorded from motoneurons innervating long tendinous tail muscles (7/90: 8%) and the shortest neuronal pathways of IPSPs were shown to be disynaptic pathways. Interactions between the CST and reflex pathways from low-threshold muscle and cutaneous afferents innervating the tail and hindlimbs were observed.

An intracellular study of pudendal afferent inputs onto tail motoneurons in the spinalized cat.

Postsynaptic potentials, elicited by stimulation of the sensory pudendal (SPud) and superficial perineal nerves (SPeri) on both sides, were recorded from motoneurons innervating tail muscles in the non-anaesthetized and spinalized cat. The stimulation of SPud and SPeri on both sides predominantly produced excitatory postsynaptic potentials (EPSPs) in all kinds of tail motoneurons (70-95%). The inhibitory postsynaptic potentials (IPSPs) were often observed in motoneurons innervating ventral tail muscles (30-33%). The means of averaged central latencies of EPSPs and IPSPs ranged from 4.3 to 7.3 ms, and from 4.6 to 8.4 ms, respectively. The findings suggests that polysynaptic neuronal pathways from pudendal nerve to tail motoneurons produce tonic activities of all tail muscles to raise the tail in micturation, defecation and sexual movements which are induced by stimulation of pudendal nerves.

Neuronal pathways from low-threshold hindlimb cutaneous afferents to motoneurons innervating trunk muscles in low-spinal cats.

Postsynaptic potentials (PSPs) evoked in motoneurons innervating the back and abdominal muscles in the lumbar part of the body by stimulating hindlimb cutaneous afferents were investigated in unanesthetized decerebate and spinal cats. Various types of PSP: pure excitatory postsynaptic potential (EPSP), pure inhibitory postsynaptic potential (IPSP), and mixed PSP (i.e., EPSP followed by IPSP, EPSP/IPSP; and IPSP followed by EPSP, IPSP/EPSP) were observed. The weak stimulation at 2 times threshold (2T) produced predominantly the EPSP, while at 5T the incidence of IPSP or EPSP followed by IPSP was increased. In about 20-50% of the various groups of motoneurons, PSPs evoked by ipsi- and contralateral nerves were qualitatively and quantitatively similar. For the other motoneurons, PSPs evoked by ipsi- and contralateral nerves were markedly different with respect to magnitude and/or polarity. These findings suggest that, within each motoneuron pool, some neurons act to increase stiffness of the trunk or to move vertically in response to an increased activity of cutaneous afferents, while the other motoneurons act to produce lateral bending of the trunk.

Age-related changes in the brainstem auditory evoked potentials of the marmoset.

Changes in brain-stem auditory evoked potentials (BAEPs) with age were recorded in common marmosets (Callithrix jacchus) at the age of 1-2, 6-8 and 10-12 years. The auditory function was assessed by thresholds, latencies and amplitudes of BAEPs evoked by use of tone burst stimulations with audible frequencies ranging from 1 to 99 kHz. Prolongation of the latencies of later waves was observed in the animals at the age of 6-8 and 10-12 years at high frequencies, suggesting that aging in marmosets, as reported previously in humans and other animals, may cause earlier hearing loss at high frequency than at low frequency within the hearing range. At 10-12 years of age, the elevations of BAEP thresholds and the declines of BAEP amplitudes in older animals were also observed. As the differences in the parameters are small, it was suggested that only a moderate hearing loss occurred with onset late in life in common marmoset similar to that in CBA/Ca mice. Based on the results obtained in this study, BAEP latencies appear to be more sensitive indicators than BAEP thresholds and amplitudes for the early detection of hearing impairment.